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39545691
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Sub-chronic nicotine exposure influences methamphetamine self-administration and dopamine overflow in a sex-and genotype-dependent manner in humanized CHRNA6 3'-UTR SNP (rs2304297) adolescent rats.
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The role of anterior insula-brainstem projections and alpha-1 noradrenergic receptors for compulsion-like and alcohol-only drinking.
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Neural representations of phonological information in bilingual language production.
|
<b
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Compulsion-like alcohol drinking (CLAD), where consumption continues despite negative consequences, is a major obstacle to treating alcohol use disorder. The locus coeruleus area in the brainstem and norepinephrine receptor (NER) signaling in forebrain cortical regions have been implicated in adaptive responding under stress, which is conceptually similar to compulsion-like responding (adaptive responding despite the presence of stress or conflict). Thus, we examined whether anterior insula (aINS)-to-brainstem connections and alpha-1 NERs regulated compulsion-like intake and alcohol-only drinking (AOD). Halorhodopsin inhibition of aINS-brainstem significantly reduced CLAD, with no effect on alcohol-only or saccharin intake, suggesting a specific aINS-brainstem role in aversion-resistant drinking. In contrast, prazosin inhibition of alpha-1 NERs systemically reduced both CLAD and AOD. Similar to systemic inhibition, intra-aINS alpha-1-NER antagonism reduced both CLAD and AOD. Global aINS inhibition with GABAR agonists also strongly reduced both CLAD and AOD, without impacting saccharin intake or locomotion, while aINS inhibition of calcium-permeable AMPARs (with NASPM) reduced CLAD without impacting AOD. Finally, prazosin inhibition of CLAD and AOD was not correlated with each other, systemically or within aINS, suggesting the possibility that different aINS pathways regulate CLAD versus AOD, which will require further study to definitively address. Together, our results provide important new information showing that some aINS pathways (aINS-brainstem and NASPM-sensitive) specifically regulate compulsion-like alcohol consumption, while aINS more generally may contain parallel pathways promoting CLAD versus AOD. These findings also support the importance of the adaptive stress response system for multiple forms of alcohol drinking.</AbstractText
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Previous research has explored the neural mechanisms of bilinguals' language production, but most studies focused on neural mechanisms of cognitive control during language production. Therefore, it is unclear which brain regions represent lexical information (especially phonological information) during production and how they are affected by language context. To address those questions, we used representational similarity analysis to explore neural representations of phonological information in native (L1) and second languages (L2) in the single- and mixed-language contexts, respectively. Results showed that Chinese-English bilinguals behaviorally performed worse and exhibited more activations in brain regions associated with language processing and cognitive control in the mixed-language context relative to the single-language context. Further representational similarity analysis revealed that phonological representations of L1 were detected in the left pars opercularis, middle frontal gyrus, and anterior supramarginal gyrus, while phonological representations of L2 were detected in the bilateral occipitotemporal cortex regardless of the target language. More interestingly, robust phonological representations of L1 were observed in brain areas related to phonological processing during L2 production regardless of language context. These results provide direct neuroimaging evidence for the nonselective processing hypothesis and highlight the superiority of phonological representations in the dominant language during bilingual language production.</AbstractText
|
Sub-chronic nicotine exposure influences methamphetamine self-administration and dopamine overflow in a sex-and genotype-dependent manner in humanized CHRNA6 3'-UTR SNP (rs2304297) adolescent rats. <b
|
The role of anterior insula-brainstem projections and alpha-1 noradrenergic receptors for compulsion-like and alcohol-only drinking. Compulsion-like alcohol drinking (CLAD), where consumption continues despite negative consequences, is a major obstacle to treating alcohol use disorder. The locus coeruleus area in the brainstem and norepinephrine receptor (NER) signaling in forebrain cortical regions have been implicated in adaptive responding under stress, which is conceptually similar to compulsion-like responding (adaptive responding despite the presence of stress or conflict). Thus, we examined whether anterior insula (aINS)-to-brainstem connections and alpha-1 NERs regulated compulsion-like intake and alcohol-only drinking (AOD). Halorhodopsin inhibition of aINS-brainstem significantly reduced CLAD, with no effect on alcohol-only or saccharin intake, suggesting a specific aINS-brainstem role in aversion-resistant drinking. In contrast, prazosin inhibition of alpha-1 NERs systemically reduced both CLAD and AOD. Similar to systemic inhibition, intra-aINS alpha-1-NER antagonism reduced both CLAD and AOD. Global aINS inhibition with GABAR agonists also strongly reduced both CLAD and AOD, without impacting saccharin intake or locomotion, while aINS inhibition of calcium-permeable AMPARs (with NASPM) reduced CLAD without impacting AOD. Finally, prazosin inhibition of CLAD and AOD was not correlated with each other, systemically or within aINS, suggesting the possibility that different aINS pathways regulate CLAD versus AOD, which will require further study to definitively address. Together, our results provide important new information showing that some aINS pathways (aINS-brainstem and NASPM-sensitive) specifically regulate compulsion-like alcohol consumption, while aINS more generally may contain parallel pathways promoting CLAD versus AOD. These findings also support the importance of the adaptive stress response system for multiple forms of alcohol drinking.</AbstractText
|
Neural representations of phonological information in bilingual language production. Previous research has explored the neural mechanisms of bilinguals' language production, but most studies focused on neural mechanisms of cognitive control during language production. Therefore, it is unclear which brain regions represent lexical information (especially phonological information) during production and how they are affected by language context. To address those questions, we used representational similarity analysis to explore neural representations of phonological information in native (L1) and second languages (L2) in the single- and mixed-language contexts, respectively. Results showed that Chinese-English bilinguals behaviorally performed worse and exhibited more activations in brain regions associated with language processing and cognitive control in the mixed-language context relative to the single-language context. Further representational similarity analysis revealed that phonological representations of L1 were detected in the left pars opercularis, middle frontal gyrus, and anterior supramarginal gyrus, while phonological representations of L2 were detected in the bilateral occipitotemporal cortex regardless of the target language. More interestingly, robust phonological representations of L1 were observed in brain areas related to phonological processing during L2 production regardless of language context. These results provide direct neuroimaging evidence for the nonselective processing hypothesis and highlight the superiority of phonological representations in the dominant language during bilingual language production.</AbstractText
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19686455
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17848191
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19322192
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Prejudice control and interracial relations: the role of motivation to respond without prejudice.
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Neuroimaging revolutionizes therapeutic approaches to chronic pain.
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18S rRNA processing requires base pairings of snR30 H/ACA snoRNA to eukaryote-specific 18S sequences.
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A decade of research indicates that individual differences in motivation to respond without prejudice have important implications for the control of prejudice and interracial relations. In reviewing this work, we draw on W. Mischel and Y. Shoda's (1995, 1999) Cognitive-Affective Processing System (CAPS) to demonstrate that people with varying sources of motivation to respond without prejudice respond in distinct ways to situational cues, resulting in differing situation-behavior profiles in interracial contexts. People whose motivation is self-determined (i.e., the internally motivated) effectively control prejudice across situations and strive for positive interracial interactions. In contrast, people who respond without prejudice to avoid social sanction (i.e., the primarily externally motivated) consistently fail at regulating difficult to control prejudice and respond with anxiety and avoidance in interracial interactions. We further consider the nature of the cognitive-affective units of personality associated with motivation to respond without prejudice and their implications for the quality of interracial relations.</AbstractText
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An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain - it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS.</AbstractText
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The H/ACA RNAs represent an abundant, evolutionarily conserved and functionally diverse class of non-coding RNAs. Many H/ACA RNAs direct pseudouridylation of rRNAs and snRNAs, while members of the rapidly growing group of 'orphan' H/ACA RNAs participate in pre-rRNA processing, telomere synthesis and probably, in other nuclear processes. The yeast snR30 'orphan' H/ACA snoRNA has long been known to function in the nucleolytic processing of 18S rRNA, but its molecular role remained unknown. Here, we provide biochemical and genetic evidence demonstrating that during pre-rRNA processing, two evolutionarily conserved sequence elements in the 3'-hairpin of snR30 base-pair with short pre-rRNA sequences located in the eukaryote-specific internal region of 18S rRNA. The newly discovered snR30-18S base-pairing interactions are essential for 18S rRNA production and they constitute a complex snoRNA target RNA transient structure that is novel to H/ACA RNAs. We also demonstrate that besides the 18S recognition motifs, the distal part of the 3'-hairpin of snR30 contains an additional snoRNA element that is essential for 18S rRNA processing and that functions most likely as a snoRNP protein-binding site.</AbstractText
|
Prejudice control and interracial relations: the role of motivation to respond without prejudice. A decade of research indicates that individual differences in motivation to respond without prejudice have important implications for the control of prejudice and interracial relations. In reviewing this work, we draw on W. Mischel and Y. Shoda's (1995, 1999) Cognitive-Affective Processing System (CAPS) to demonstrate that people with varying sources of motivation to respond without prejudice respond in distinct ways to situational cues, resulting in differing situation-behavior profiles in interracial contexts. People whose motivation is self-determined (i.e., the internally motivated) effectively control prejudice across situations and strive for positive interracial interactions. In contrast, people who respond without prejudice to avoid social sanction (i.e., the primarily externally motivated) consistently fail at regulating difficult to control prejudice and respond with anxiety and avoidance in interracial interactions. We further consider the nature of the cognitive-affective units of personality associated with motivation to respond without prejudice and their implications for the quality of interracial relations.</AbstractText
|
Neuroimaging revolutionizes therapeutic approaches to chronic pain. An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain - it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS.</AbstractText
|
18S rRNA processing requires base pairings of snR30 H/ACA snoRNA to eukaryote-specific 18S sequences. The H/ACA RNAs represent an abundant, evolutionarily conserved and functionally diverse class of non-coding RNAs. Many H/ACA RNAs direct pseudouridylation of rRNAs and snRNAs, while members of the rapidly growing group of 'orphan' H/ACA RNAs participate in pre-rRNA processing, telomere synthesis and probably, in other nuclear processes. The yeast snR30 'orphan' H/ACA snoRNA has long been known to function in the nucleolytic processing of 18S rRNA, but its molecular role remained unknown. Here, we provide biochemical and genetic evidence demonstrating that during pre-rRNA processing, two evolutionarily conserved sequence elements in the 3'-hairpin of snR30 base-pair with short pre-rRNA sequences located in the eukaryote-specific internal region of 18S rRNA. The newly discovered snR30-18S base-pairing interactions are essential for 18S rRNA production and they constitute a complex snoRNA target RNA transient structure that is novel to H/ACA RNAs. We also demonstrate that besides the 18S recognition motifs, the distal part of the 3'-hairpin of snR30 contains an additional snoRNA element that is essential for 18S rRNA processing and that functions most likely as a snoRNP protein-binding site.</AbstractText
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23418301
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19070668
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23762813
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UP-BEAT (Upper Limb Baby Early Action-observation Training): protocol of two parallel randomised controlled trials of action-observation training for typically developing infants and infants with asymmetric brain lesions.
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Machine learning classifiers and fMRI: a tutorial overview.
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Diagnosis of ACL and meniscal injuries: MR imaging of knee flexion versus extension compared to arthroscopy.
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Infants with asymmetric brain lesions are at high risk of developing congenital hemiplegia. Action-observation training (AOT) has been shown to effectively improve upper limb motor function in adults with chronic stroke. AOT is based on action observation, whereby new motor skills can be learnt by observing motor actions. This process is facilitated by the Mirror Neuron System, which matches observed and performed motor actions. This study aims to determine the efficacy of AOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb activity of infants with asymmetric brain lesions.</AbstractText This study design comprises two parallel randomised sham-controlled trials (RCTs) in: (1) typically developing infants (cohort I) and (2) infants with asymmetric brain lesions (eg, arterial stroke, venous infarction, intraventricular haemorrhage or periventricular leukomalacia; cohort II). Cohort II will be identified through a neonatal ultrasound or neonatal MRI. A sham control will be used for both RCTs, taking into consideration that it would be unethical to give no intervention to an at-risk population. Based on a two-tailed t test of two independent means, with a significance (α) level of 0.05, 80% power, predicted effect size of 0.8 and a 90% retention rate, we require 20 participants in each group (total sample of 40) for cohort I. The sample size for cohort II was based on the assumption that the effect size of the proposed training would be similar to that found by Heathcock et al in preterm born infants (n=26) with a mean effect size of 2.4. Given the high effect size, the calculation returned a sample of only four participants per group, on a two-tailed t test, with a significance (α) level of 0.05 and 80% power. As cohort II will consist of two subgroups of lesion type (ie, arterial stroke and venous infarction), we have quadrupled the sample to include 16 participants in each group (total sample of 32). Infants will be randomised to receive either AOT or standard Toy Observation Training (TOT). Both interventions will be of 4 weeks' duration, from the infant's 9th-13th post-term week of age. Three sessions of 5 min each will be performed each day for 6 days/week (total of 6 h over 28 days). Parents of the AOT group will repeatedly show the infant a grasping action on a set of three toys, presented in random order. Parents of the TOT group will show the infant the same set of three toys, in random order, without demonstrating the grasping action. At 14, 16 and 18 weeks, the quantity and quality of reaching and grasping will be measured using the Grasping and Reaching Assessment of Brisbane; symmetry of reaching and grasping will be measured using the Hand Assessment of Infants (HAI) and pressure of grasping for each hand with a customised pressure sensor. At 6 months' corrected age, the primary outcome measures will be the HAI and Bayley Scales of Infant and Toddler Development (third edition; BSID III), to measure cognitive and motor development. At 8 months, HAI and EEG will be used to measure brain activity and cortical coherence. At 12 months, the primary outcome measures will again be HAI and BSID III.</AbstractText This paper outlines the theoretical basis, study hypotheses and outcome measures for two parallel RCTs comparing the novel intervention Action-observation training with standard TOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb motor activity of infants with asymmetric brain lesions.</AbstractText ACTRN1261100991910. Web address of trial http://www.ANZCTR.org.au/ACTRN12611000991910.aspx.</AbstractText
|
Interpreting brain image experiments requires analysis of complex, multivariate data. In recent years, one analysis approach that has grown in popularity is the use of machine learning algorithms to train classifiers to decode stimuli, mental states, behaviours and other variables of interest from fMRI data and thereby show the data contain information about them. In this tutorial overview we review some of the key choices faced in using this approach as well as how to derive statistically significant results, illustrating each point from a case study. Furthermore, we show how, in addition to answering the question of 'is there information about a variable of interest' (pattern discrimination), classifiers can be used to tackle other classes of question, namely 'where is the information' (pattern localization) and 'how is that information encoded' (pattern characterization).</AbstractText
|
The aim of the study was to evaluate whether MR Imaging of the knee at 30° and 55° of flexion can improve the diagnosis of anterior cruciate ligament and menisci injuries compared to arthroscopy and imaging during extension of the knee joint. Knee joints from 40 patients with clinical suspicion of an anterior cruciate ligament (ACL) rupture were examined using MRI while the knee joint was either extended or flexed at 30° and 55° of knee flexion. A standard MR knee coil was used at extension, whereas at 30° and 55° of flexion a non-metallic positioning device and a flexible surface coil was placed ventral to the patella. Sagittal T2-weighted TSE sequences were acquired. In 29 of 40 patients, arthroscopy results were compared to the MRI examinations. Image quality of MRI examinations was evaluated using a three-point rating scale in a blinded fashion. Images were compared between groups and rated as better quality, same quality, or worse quality. Additionally, each angle MRI was compared to arthroscopy results. Partial ACL ruptures were diagnosed with 63% accuracy using MR imaging at 30° and 55° of knee flexion compared to 50% accuracy during knee extension. MRI imaging of complete ACL ruptures resulted in 83% accuracy of diagnosis when imaged at 30° flexion, 93% accuracy at 55° flexion, and 83% accuracy at extension. The accuracy of diagnosing medial meniscus lesions was 73% at extension, 64% at 30° flexion and 73% at 55° of flexion. MR imaging was only able to diagnose lateral meniscus tears with 55% accuracy in all three knee positions. The diagnosis of meniscal tears was more difficult due to small peripheral tears. The improved results in the diagnosis of ACL tears in response to 30° flexion and in particular in response to 55° flexion were based on the fact that the anterior cruciate ligament moved further away from the intercondylar roof with increased knee flexion. During flexion the ligament tension decreased, which causes the anterior cruciate ligament to have cylindrical shape and therefore made visualization of the injury easier. In conclusion, MR Imaging of the knee at 55° of flexion and less at 30° of flexion allows an improved diagnosis of injuries to the anterior cruciate ligament as compared to MRI examinations at extension. The diagnosis of meniscal injuries, however, was not superior at both flexion positions compared to commonly performed examinations at knee extension.</AbstractText
|
UP-BEAT (Upper Limb Baby Early Action-observation Training): protocol of two parallel randomised controlled trials of action-observation training for typically developing infants and infants with asymmetric brain lesions. Infants with asymmetric brain lesions are at high risk of developing congenital hemiplegia. Action-observation training (AOT) has been shown to effectively improve upper limb motor function in adults with chronic stroke. AOT is based on action observation, whereby new motor skills can be learnt by observing motor actions. This process is facilitated by the Mirror Neuron System, which matches observed and performed motor actions. This study aims to determine the efficacy of AOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb activity of infants with asymmetric brain lesions.</AbstractText This study design comprises two parallel randomised sham-controlled trials (RCTs) in: (1) typically developing infants (cohort I) and (2) infants with asymmetric brain lesions (eg, arterial stroke, venous infarction, intraventricular haemorrhage or periventricular leukomalacia; cohort II). Cohort II will be identified through a neonatal ultrasound or neonatal MRI. A sham control will be used for both RCTs, taking into consideration that it would be unethical to give no intervention to an at-risk population. Based on a two-tailed t test of two independent means, with a significance (α) level of 0.05, 80% power, predicted effect size of 0.8 and a 90% retention rate, we require 20 participants in each group (total sample of 40) for cohort I. The sample size for cohort II was based on the assumption that the effect size of the proposed training would be similar to that found by Heathcock et al in preterm born infants (n=26) with a mean effect size of 2.4. Given the high effect size, the calculation returned a sample of only four participants per group, on a two-tailed t test, with a significance (α) level of 0.05 and 80% power. As cohort II will consist of two subgroups of lesion type (ie, arterial stroke and venous infarction), we have quadrupled the sample to include 16 participants in each group (total sample of 32). Infants will be randomised to receive either AOT or standard Toy Observation Training (TOT). Both interventions will be of 4 weeks' duration, from the infant's 9th-13th post-term week of age. Three sessions of 5 min each will be performed each day for 6 days/week (total of 6 h over 28 days). Parents of the AOT group will repeatedly show the infant a grasping action on a set of three toys, presented in random order. Parents of the TOT group will show the infant the same set of three toys, in random order, without demonstrating the grasping action. At 14, 16 and 18 weeks, the quantity and quality of reaching and grasping will be measured using the Grasping and Reaching Assessment of Brisbane; symmetry of reaching and grasping will be measured using the Hand Assessment of Infants (HAI) and pressure of grasping for each hand with a customised pressure sensor. At 6 months' corrected age, the primary outcome measures will be the HAI and Bayley Scales of Infant and Toddler Development (third edition; BSID III), to measure cognitive and motor development. At 8 months, HAI and EEG will be used to measure brain activity and cortical coherence. At 12 months, the primary outcome measures will again be HAI and BSID III.</AbstractText This paper outlines the theoretical basis, study hypotheses and outcome measures for two parallel RCTs comparing the novel intervention Action-observation training with standard TOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb motor activity of infants with asymmetric brain lesions.</AbstractText ACTRN1261100991910. Web address of trial http://www.ANZCTR.org.au/ACTRN12611000991910.aspx.</AbstractText
|
Machine learning classifiers and fMRI: a tutorial overview. Interpreting brain image experiments requires analysis of complex, multivariate data. In recent years, one analysis approach that has grown in popularity is the use of machine learning algorithms to train classifiers to decode stimuli, mental states, behaviours and other variables of interest from fMRI data and thereby show the data contain information about them. In this tutorial overview we review some of the key choices faced in using this approach as well as how to derive statistically significant results, illustrating each point from a case study. Furthermore, we show how, in addition to answering the question of 'is there information about a variable of interest' (pattern discrimination), classifiers can be used to tackle other classes of question, namely 'where is the information' (pattern localization) and 'how is that information encoded' (pattern characterization).</AbstractText
|
Diagnosis of ACL and meniscal injuries: MR imaging of knee flexion versus extension compared to arthroscopy. The aim of the study was to evaluate whether MR Imaging of the knee at 30° and 55° of flexion can improve the diagnosis of anterior cruciate ligament and menisci injuries compared to arthroscopy and imaging during extension of the knee joint. Knee joints from 40 patients with clinical suspicion of an anterior cruciate ligament (ACL) rupture were examined using MRI while the knee joint was either extended or flexed at 30° and 55° of knee flexion. A standard MR knee coil was used at extension, whereas at 30° and 55° of flexion a non-metallic positioning device and a flexible surface coil was placed ventral to the patella. Sagittal T2-weighted TSE sequences were acquired. In 29 of 40 patients, arthroscopy results were compared to the MRI examinations. Image quality of MRI examinations was evaluated using a three-point rating scale in a blinded fashion. Images were compared between groups and rated as better quality, same quality, or worse quality. Additionally, each angle MRI was compared to arthroscopy results. Partial ACL ruptures were diagnosed with 63% accuracy using MR imaging at 30° and 55° of knee flexion compared to 50% accuracy during knee extension. MRI imaging of complete ACL ruptures resulted in 83% accuracy of diagnosis when imaged at 30° flexion, 93% accuracy at 55° flexion, and 83% accuracy at extension. The accuracy of diagnosing medial meniscus lesions was 73% at extension, 64% at 30° flexion and 73% at 55° of flexion. MR imaging was only able to diagnose lateral meniscus tears with 55% accuracy in all three knee positions. The diagnosis of meniscal tears was more difficult due to small peripheral tears. The improved results in the diagnosis of ACL tears in response to 30° flexion and in particular in response to 55° flexion were based on the fact that the anterior cruciate ligament moved further away from the intercondylar roof with increased knee flexion. During flexion the ligament tension decreased, which causes the anterior cruciate ligament to have cylindrical shape and therefore made visualization of the injury easier. In conclusion, MR Imaging of the knee at 55° of flexion and less at 30° of flexion allows an improved diagnosis of injuries to the anterior cruciate ligament as compared to MRI examinations at extension. The diagnosis of meniscal injuries, however, was not superior at both flexion positions compared to commonly performed examinations at knee extension.</AbstractText
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36449221
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33194932
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37454656
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Perceived negative consequences of dyslexia: the influence of person and environmental factors.
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From Schools to Scans: A Neuroeducational Approach to Comorbid Math and Reading Disabilities.
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Preliminary Experience with a Four-Lead Implantable Pulse Generator for Deep Brain Stimulation.
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Perceived negative consequences of dyslexia entail the degree to which an individual perceives negative outcomes, such as low academic achievement or feelings of anxiety and depression, and attributes these experiences to the disorder. In the current study, we examined how perceived consequences of dyslexia are influenced by person and environmental factors. Perceived consequences were evaluated for the academic domain and the domain of mental health (depression, anxiety). Participants were 123 Dutch students with dyslexia. Cognitive person factors (literacy skills and verbal IQ), socio-emotional person factors (self-perceived literacy skills and coping ability), and environmental factors (literacy demands, support from the institution, reactions of teachers and peers) were included as predictors. Results indicated that perceived negative consequences were not related to cognitive person factors. In contrast, better self-perceived literacy skills were associated with less perceived negative consequences in all domains (academic, depression, anxiety) and coping contributed to depression consequences. With respect to environmental factors, negative reactions in the academic environment contributed to perceived negative consequences of depression and anxiety. As such, findings indicate that individuals with dyslexia perceive negative consequences in the academic, anxiety, and depression domains which cannot be fully accounted for by their objective reading and writing problems. These factors should feature more prominently in future studies on dyslexia and should be addressed in treatment of dyslexia as well.</AbstractText
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We bridge two analogous concepts of comorbidity, dyslexia-dyscalculia and reading-mathematical disabilities, in neuroscience and education, respectively. We assessed the cognitive profiles of 360 individuals (mean age 25.79 ± 13.65) with disability in reading alone (RD group), mathematics alone (MD group) and both (comorbidity: MDRD group), with tests widely used in both psychoeducational and neuropsychological batteries. As expected, the MDRD group exhibited reading deficits like those shown by the RD group. The former group also exhibited deficits in quantitative reasoning like those shown by the MD group. However, other deficits related to verbal working memory and semantic memory were exclusive to the MDRD group. These findings were independent of gender, age, or socioeconomic and demographic factors. Through a systematic exhaustive review of clinical neuroimaging literature, we mapped the resulting cognitive profiles to correspondingly plausible neuroanatomical substrates of dyslexia and dyscalculia. In our resulting "probing" model, the complex set of domain-specific and domain-general impairments shown in the comorbidity of reading and mathematical disabilities are hypothesized as being related to atypical development of the left angular gyrus. The present neuroeducational approach bridges a long-standing transdisciplinary divide and contributes a step further toward improved early prediction, teaching and interventions for children and adults with combined reading and math disabilities.</AbstractText
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Implantable pulse generators (IPGs) store energy and deliver electrical impulses for deep brain stimulation (DBS) to treat neurological and psychiatric disorders. IPGs have evolved over time to meet the demands of expanding clinical indications and more nuanced therapeutic approaches.</AbstractText The aim of this study was to examine the workflow of the first 4-lead IPG for DBS in patients with complex disease.</AbstractText The engineering capabilities, clinical use cases, and surgical technique are described in a cohort of 12 patients with epilepsy, essential tremor, Parkinson's disease, mixed tremor, and Tourette's syndrome with comorbid obsessive-compulsive disorder between July 2021 and July 2022.</AbstractText This system is a rechargeable 32-channel, 4-port system with independent current control that can be connected to 8 contact linear or directionally segmented leads. The system is ideal for patients with mixed disease or those with multiple severe symptoms amenable to &gt;2 lead implantations. A multidisciplinary team including neurologists, radiologists, and neurosurgeons is necessary to safely plan the procedure. There were no serious intraoperative or postoperative adverse events. One patient required revision surgery for bowstringing.</AbstractText This new 4-lead IPG represents an important new tool for DBS surgery with the ability to expand lead implantation paradigms for patients with complex disease.</AbstractText
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Perceived negative consequences of dyslexia: the influence of person and environmental factors. Perceived negative consequences of dyslexia entail the degree to which an individual perceives negative outcomes, such as low academic achievement or feelings of anxiety and depression, and attributes these experiences to the disorder. In the current study, we examined how perceived consequences of dyslexia are influenced by person and environmental factors. Perceived consequences were evaluated for the academic domain and the domain of mental health (depression, anxiety). Participants were 123 Dutch students with dyslexia. Cognitive person factors (literacy skills and verbal IQ), socio-emotional person factors (self-perceived literacy skills and coping ability), and environmental factors (literacy demands, support from the institution, reactions of teachers and peers) were included as predictors. Results indicated that perceived negative consequences were not related to cognitive person factors. In contrast, better self-perceived literacy skills were associated with less perceived negative consequences in all domains (academic, depression, anxiety) and coping contributed to depression consequences. With respect to environmental factors, negative reactions in the academic environment contributed to perceived negative consequences of depression and anxiety. As such, findings indicate that individuals with dyslexia perceive negative consequences in the academic, anxiety, and depression domains which cannot be fully accounted for by their objective reading and writing problems. These factors should feature more prominently in future studies on dyslexia and should be addressed in treatment of dyslexia as well.</AbstractText
|
From Schools to Scans: A Neuroeducational Approach to Comorbid Math and Reading Disabilities. We bridge two analogous concepts of comorbidity, dyslexia-dyscalculia and reading-mathematical disabilities, in neuroscience and education, respectively. We assessed the cognitive profiles of 360 individuals (mean age 25.79 ± 13.65) with disability in reading alone (RD group), mathematics alone (MD group) and both (comorbidity: MDRD group), with tests widely used in both psychoeducational and neuropsychological batteries. As expected, the MDRD group exhibited reading deficits like those shown by the RD group. The former group also exhibited deficits in quantitative reasoning like those shown by the MD group. However, other deficits related to verbal working memory and semantic memory were exclusive to the MDRD group. These findings were independent of gender, age, or socioeconomic and demographic factors. Through a systematic exhaustive review of clinical neuroimaging literature, we mapped the resulting cognitive profiles to correspondingly plausible neuroanatomical substrates of dyslexia and dyscalculia. In our resulting "probing" model, the complex set of domain-specific and domain-general impairments shown in the comorbidity of reading and mathematical disabilities are hypothesized as being related to atypical development of the left angular gyrus. The present neuroeducational approach bridges a long-standing transdisciplinary divide and contributes a step further toward improved early prediction, teaching and interventions for children and adults with combined reading and math disabilities.</AbstractText
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Preliminary Experience with a Four-Lead Implantable Pulse Generator for Deep Brain Stimulation. Implantable pulse generators (IPGs) store energy and deliver electrical impulses for deep brain stimulation (DBS) to treat neurological and psychiatric disorders. IPGs have evolved over time to meet the demands of expanding clinical indications and more nuanced therapeutic approaches.</AbstractText The aim of this study was to examine the workflow of the first 4-lead IPG for DBS in patients with complex disease.</AbstractText The engineering capabilities, clinical use cases, and surgical technique are described in a cohort of 12 patients with epilepsy, essential tremor, Parkinson's disease, mixed tremor, and Tourette's syndrome with comorbid obsessive-compulsive disorder between July 2021 and July 2022.</AbstractText This system is a rechargeable 32-channel, 4-port system with independent current control that can be connected to 8 contact linear or directionally segmented leads. The system is ideal for patients with mixed disease or those with multiple severe symptoms amenable to &gt;2 lead implantations. A multidisciplinary team including neurologists, radiologists, and neurosurgeons is necessary to safely plan the procedure. There were no serious intraoperative or postoperative adverse events. One patient required revision surgery for bowstringing.</AbstractText This new 4-lead IPG represents an important new tool for DBS surgery with the ability to expand lead implantation paradigms for patients with complex disease.</AbstractText
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34205072
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34168340
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40649912
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Improvement of the Similarity Spectral Unmixing Approach for Multiplexed Two-Photon Imaging by Linear Dimension Reduction of the Mixing Matrix.
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Cerebellar granule cell axons support high-dimensional representations.
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Kinetics of Phase Transitions in Amorphous Carbamazepine: From Sub-T(g) Structural Relaxation to High-Temperature Decomposition.
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Two-photon microscopy enables monitoring cellular dynamics and communication in complex systems, within a genuine environment, such as living tissues and, even, living organisms. Particularly, its application to understand cellular interactions in the immune system has brought unique insights into pathophysiologic processes in vivo. Simultaneous multiplexed imaging is required to understand the dynamic orchestration of the multiple cellular and non-cellular tissue compartments defining immune responses. Here, we present an improvement of our previously developed method, which allowed us to achieve multiplexed dynamic intravital two-photon imaging, by using a synergistic strategy. This strategy combines a spectrally broad range of fluorophore emissions, a wave-mixing concept for simultaneous excitation of all targeted fluorophores, and an unmixing algorithm based on the calculation of spectral similarities with previously measured fluorophore fingerprints. The improvement of the similarity spectral unmixing algorithm here described is based on dimensionality reduction of the mixing matrix. We demonstrate its superior performance in the correct pixel-based assignment of probes to tissue compartments labeled by single fluorophores with similar spectral fingerprints, as compared to the full-dimensional similarity spectral unmixing approach.</AbstractText
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In classical theories of cerebellar cortex, high-dimensional sensorimotor representations are used to separate neuronal activity patterns, improving associative learning and motor performance. Recent experimental studies suggest that cerebellar granule cell (GrC) population activity is low-dimensional. To examine sensorimotor representations from the point of view of downstream Purkinje cell 'decoders', we used three-dimensional acousto-optic lens two-photon microscopy to record from hundreds of GrC axons. Here we show that GrC axon population activity is high dimensional and distributed with little fine-scale spatial structure during spontaneous behaviors. Moreover, distinct behavioral states are represented along orthogonal dimensions in neuronal activity space. These results suggest that the cerebellar cortex supports high-dimensional representations and segregates behavioral state-dependent computations into orthogonal subspaces, as reported in the neocortex. Our findings match the predictions of cerebellar pattern separation theories and suggest that the cerebellum and neocortex use population codes with common features, despite their vastly different circuit structures.</AbstractText
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Thermokinetic characterization of amorphous carbamazepine was performed utilizing non-isothermal differential scanning calorimetry (DSC) and thermogravimetry (TGA). Structural relaxation of the amorphous matrix was described in terms of the Tool-Narayanaswamy-Moynihan model with the following parameters: Δ<i
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Improvement of the Similarity Spectral Unmixing Approach for Multiplexed Two-Photon Imaging by Linear Dimension Reduction of the Mixing Matrix. Two-photon microscopy enables monitoring cellular dynamics and communication in complex systems, within a genuine environment, such as living tissues and, even, living organisms. Particularly, its application to understand cellular interactions in the immune system has brought unique insights into pathophysiologic processes in vivo. Simultaneous multiplexed imaging is required to understand the dynamic orchestration of the multiple cellular and non-cellular tissue compartments defining immune responses. Here, we present an improvement of our previously developed method, which allowed us to achieve multiplexed dynamic intravital two-photon imaging, by using a synergistic strategy. This strategy combines a spectrally broad range of fluorophore emissions, a wave-mixing concept for simultaneous excitation of all targeted fluorophores, and an unmixing algorithm based on the calculation of spectral similarities with previously measured fluorophore fingerprints. The improvement of the similarity spectral unmixing algorithm here described is based on dimensionality reduction of the mixing matrix. We demonstrate its superior performance in the correct pixel-based assignment of probes to tissue compartments labeled by single fluorophores with similar spectral fingerprints, as compared to the full-dimensional similarity spectral unmixing approach.</AbstractText
|
Cerebellar granule cell axons support high-dimensional representations. In classical theories of cerebellar cortex, high-dimensional sensorimotor representations are used to separate neuronal activity patterns, improving associative learning and motor performance. Recent experimental studies suggest that cerebellar granule cell (GrC) population activity is low-dimensional. To examine sensorimotor representations from the point of view of downstream Purkinje cell 'decoders', we used three-dimensional acousto-optic lens two-photon microscopy to record from hundreds of GrC axons. Here we show that GrC axon population activity is high dimensional and distributed with little fine-scale spatial structure during spontaneous behaviors. Moreover, distinct behavioral states are represented along orthogonal dimensions in neuronal activity space. These results suggest that the cerebellar cortex supports high-dimensional representations and segregates behavioral state-dependent computations into orthogonal subspaces, as reported in the neocortex. Our findings match the predictions of cerebellar pattern separation theories and suggest that the cerebellum and neocortex use population codes with common features, despite their vastly different circuit structures.</AbstractText
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Kinetics of Phase Transitions in Amorphous Carbamazepine: From Sub-T(g) Structural Relaxation to High-Temperature Decomposition. Thermokinetic characterization of amorphous carbamazepine was performed utilizing non-isothermal differential scanning calorimetry (DSC) and thermogravimetry (TGA). Structural relaxation of the amorphous matrix was described in terms of the Tool-Narayanaswamy-Moynihan model with the following parameters: Δ<i
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28270025
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25897875
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29304174
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A Scalable Weight-Free Learning Algorithm for Regulatory Control of Cell Activity in Spiking Neuronal Networks.
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Plasticity of cortical excitatory-inhibitory balance.
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Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons.
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Recent developments in neural stimulation and recording technologies are providing scientists with the ability of recording and controlling the activity of individual neurons in vitro or in vivo, with very high spatial and temporal resolution. Tools such as optogenetics, for example, are having a significant impact in the neuroscience field by delivering optical firing control with the precision and spatiotemporal resolution required for investigating information processing and plasticity in biological brains. While a number of training algorithms have been developed to date for spiking neural network (SNN) models of biological neuronal circuits, exiting methods rely on learning rules that adjust the synaptic strengths (or weights) directly, in order to obtain the desired network-level (or functional-level) performance. As such, they are not applicable to modifying plasticity in biological neuronal circuits, in which synaptic strengths only change as a result of pre- and post-synaptic neuron firings or biological mechanisms beyond our control. This paper presents a weight-free training algorithm that relies solely on adjusting the spatiotemporal delivery of neuron firings in order to optimize the network performance. The proposed weight-free algorithm does not require any knowledge of the SNN model or its plasticity mechanisms. As a result, this training approach is potentially realizable in vitro or in vivo via neural stimulation and recording technologies, such as optogenetics and multielectrode arrays, and could be utilized to control plasticity at multiple scales of biological neuronal circuits. The approach is demonstrated by training SNNs with hundreds of units to control a virtual insect navigating in an unknown environment.</AbstractText
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Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.</AbstractText
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Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore on host transport factors to ensure specific nuclear import of viral and host components. While some import cargoes bind directly to certain transport factors, most recruit importin β1 via importin α. We identified importin α1 in a small targeted siRNA screen to be important for herpes simplex virus (HSV-1) gene expression. Production of infectious virions was delayed in the absence of importin α1, but not in cells lacking importin α3 or importin α4. While nuclear targeting of the incoming capsids, of the HSV-1 transcription activator VP16, and of the viral genomes were not affected, the nuclear import of the HSV-1 proteins ICP4 and ICP0, required for efficient viral transcription, and of ICP8 and pUL42, necessary for DNA replication, were reduced. Furthermore, quantitative electron microscopy showed that fibroblasts lacking importin α1 contained overall fewer nuclear capsids, but an increased proportion of mature nuclear capsids indicating that capsid formation and capsid egress into the cytoplasm were impaired. In neurons, importin α1 was also not required for nuclear targeting of incoming capsids, but for nuclear import of ICP4 and for the formation of nuclear capsid assembly compartments. Our data suggest that importin α1 is specifically required for the nuclear localization of several important HSV1 proteins, capsid assembly, and capsid egress into the cytoplasm, and may become rate limiting in situ upon infection at low multiplicity or in terminally differentiated cells such as neurons.</AbstractText
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A Scalable Weight-Free Learning Algorithm for Regulatory Control of Cell Activity in Spiking Neuronal Networks. Recent developments in neural stimulation and recording technologies are providing scientists with the ability of recording and controlling the activity of individual neurons in vitro or in vivo, with very high spatial and temporal resolution. Tools such as optogenetics, for example, are having a significant impact in the neuroscience field by delivering optical firing control with the precision and spatiotemporal resolution required for investigating information processing and plasticity in biological brains. While a number of training algorithms have been developed to date for spiking neural network (SNN) models of biological neuronal circuits, exiting methods rely on learning rules that adjust the synaptic strengths (or weights) directly, in order to obtain the desired network-level (or functional-level) performance. As such, they are not applicable to modifying plasticity in biological neuronal circuits, in which synaptic strengths only change as a result of pre- and post-synaptic neuron firings or biological mechanisms beyond our control. This paper presents a weight-free training algorithm that relies solely on adjusting the spatiotemporal delivery of neuron firings in order to optimize the network performance. The proposed weight-free algorithm does not require any knowledge of the SNN model or its plasticity mechanisms. As a result, this training approach is potentially realizable in vitro or in vivo via neural stimulation and recording technologies, such as optogenetics and multielectrode arrays, and could be utilized to control plasticity at multiple scales of biological neuronal circuits. The approach is demonstrated by training SNNs with hundreds of units to control a virtual insect navigating in an unknown environment.</AbstractText
|
Plasticity of cortical excitatory-inhibitory balance. Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.</AbstractText
|
Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons. Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore on host transport factors to ensure specific nuclear import of viral and host components. While some import cargoes bind directly to certain transport factors, most recruit importin β1 via importin α. We identified importin α1 in a small targeted siRNA screen to be important for herpes simplex virus (HSV-1) gene expression. Production of infectious virions was delayed in the absence of importin α1, but not in cells lacking importin α3 or importin α4. While nuclear targeting of the incoming capsids, of the HSV-1 transcription activator VP16, and of the viral genomes were not affected, the nuclear import of the HSV-1 proteins ICP4 and ICP0, required for efficient viral transcription, and of ICP8 and pUL42, necessary for DNA replication, were reduced. Furthermore, quantitative electron microscopy showed that fibroblasts lacking importin α1 contained overall fewer nuclear capsids, but an increased proportion of mature nuclear capsids indicating that capsid formation and capsid egress into the cytoplasm were impaired. In neurons, importin α1 was also not required for nuclear targeting of incoming capsids, but for nuclear import of ICP4 and for the formation of nuclear capsid assembly compartments. Our data suggest that importin α1 is specifically required for the nuclear localization of several important HSV1 proteins, capsid assembly, and capsid egress into the cytoplasm, and may become rate limiting in situ upon infection at low multiplicity or in terminally differentiated cells such as neurons.</AbstractText
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31783975
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25204450
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31777416
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Rapid improvement in carotid adventitial angiogenesis and plaque neovascularization after rosuvastatin therapy in statin treatment-naïve subjects.
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Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging: a histogram analysis approach.
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A dissociation between syntactic and lexical processing in Parkinson's disease.
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Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied.</AbstractText The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).</AbstractText Forty-three lipid treatment-naïve subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5-20 mg/d) to lower low-density lipoprotein cholesterol to <80 mg/dL for 24 months. Carotid DCE-MRI was performed at baseline, 3, 12 and 24 months. Vascularity (V<sub Adventitia V<sub Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.</AbstractText
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Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.</AbstractText MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.</AbstractText In DCE, the skewness of transfer constant (k(trans)) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).</AbstractText Histogram parameters from k(trans) (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.</AbstractText
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Parkinson's disease (PD), which involves the degeneration of dopaminergic neurons in the basal ganglia, has long been associated with motor deficits. Increasing evidence suggests that language can also be impaired, including aspects of syntactic and lexical processing. However, the exact pattern of these impairments remains somewhat unclear, for several reasons. Few studies have examined and compared syntactic and lexical processing within subjects, so their relative deficits remain to be elucidated. Studies have focused on earlier stages of PD, so syntactic and lexical processing in later stages are less well understood. Research has largely probed English and a handful of other European languages, and it is unclear whether findings generalize more broadly. Finally, few studies have examined links between syntactic/lexical impairments and their neurocognitive substrates, such as measures of basal ganglia degeneration or dopaminergic processes. We addressed these gaps by investigating multiple aspects of Farsi syntactic and lexical processing in 40 Farsi native-speaking moderate-to-severe non-demented PD patients, and 40 healthy controls. Analyses revealed equivalent impairments of syntactic comprehension and syntactic judgment, across different syntactic structures. Lexical processing was impaired only for motor function-related objects (e.g., naming 'hammer', but not 'mountain'), in line with findings of PD deficits at naming action verbs as compared to objects, without the verb/noun confound. In direct comparisons between lexical and syntactic tasks, patients were better at naming words like 'mountain' (but not words like 'hammer') than at syntactic comprehension and syntactic judgment. Performance at syntactic comprehension correlated with the last levodopa equivalent dose. No other correlations were found between syntactic/lexical processing measures and either levodopa equivalent dose or hypokinesia, which reflects degeneration of basal ganglia motor-related circuits. All critical significant main effects, interactions, and correlations yielded large effect sizes. The findings elucidate the nature of syntactic and lexical processing impairments in PD.</AbstractText
|
Rapid improvement in carotid adventitial angiogenesis and plaque neovascularization after rosuvastatin therapy in statin treatment-naïve subjects. Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied.</AbstractText The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).</AbstractText Forty-three lipid treatment-naïve subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5-20 mg/d) to lower low-density lipoprotein cholesterol to <80 mg/dL for 24 months. Carotid DCE-MRI was performed at baseline, 3, 12 and 24 months. Vascularity (V<sub Adventitia V<sub Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.</AbstractText
|
Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging: a histogram analysis approach. Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.</AbstractText MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.</AbstractText In DCE, the skewness of transfer constant (k(trans)) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).</AbstractText Histogram parameters from k(trans) (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.</AbstractText
|
A dissociation between syntactic and lexical processing in Parkinson's disease. Parkinson's disease (PD), which involves the degeneration of dopaminergic neurons in the basal ganglia, has long been associated with motor deficits. Increasing evidence suggests that language can also be impaired, including aspects of syntactic and lexical processing. However, the exact pattern of these impairments remains somewhat unclear, for several reasons. Few studies have examined and compared syntactic and lexical processing within subjects, so their relative deficits remain to be elucidated. Studies have focused on earlier stages of PD, so syntactic and lexical processing in later stages are less well understood. Research has largely probed English and a handful of other European languages, and it is unclear whether findings generalize more broadly. Finally, few studies have examined links between syntactic/lexical impairments and their neurocognitive substrates, such as measures of basal ganglia degeneration or dopaminergic processes. We addressed these gaps by investigating multiple aspects of Farsi syntactic and lexical processing in 40 Farsi native-speaking moderate-to-severe non-demented PD patients, and 40 healthy controls. Analyses revealed equivalent impairments of syntactic comprehension and syntactic judgment, across different syntactic structures. Lexical processing was impaired only for motor function-related objects (e.g., naming 'hammer', but not 'mountain'), in line with findings of PD deficits at naming action verbs as compared to objects, without the verb/noun confound. In direct comparisons between lexical and syntactic tasks, patients were better at naming words like 'mountain' (but not words like 'hammer') than at syntactic comprehension and syntactic judgment. Performance at syntactic comprehension correlated with the last levodopa equivalent dose. No other correlations were found between syntactic/lexical processing measures and either levodopa equivalent dose or hypokinesia, which reflects degeneration of basal ganglia motor-related circuits. All critical significant main effects, interactions, and correlations yielded large effect sizes. The findings elucidate the nature of syntactic and lexical processing impairments in PD.</AbstractText
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39209765
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33212018
|
39703232
|
Association between psychological traits and occlusal tactile acuity of healthy individuals.
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Fundamental Differences in Visual Perceptual Learning between Children and Adults.
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Insights into the regulation of CHIP E3 ligase-mediated ubiquitination of neuronal protein BNIP-H.
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Tactile acuity is a somatosensory measure of the extent to which humans can discern tactile stimuli. It is influenced by how peripheral signals are processed centrally. In the oral cavity, Occlusal Tactile Acuity (OTA) is the ability to perceive minimal thicknesses between antagonist teeth. The aim of the current study was to assess the association between psychological traits and OTA of otherwise healthy individuals.</AbstractText Sixty-three volunteers (32 males; mean age ± SD: 24.6 ± 2.7 years) participated in this study. Somatosensory amplification, anxiety, depression, physical symptoms and pain catastrophizing were scored using questionnaires, and subgroups of severity were created per variable based on cut-offs. OTA was measured using 9 aluminium foils with thickness (ranging from 8 to 72 μm) and one sham test (without foil). Each thickness was tested 10 times in random order, the participants were instructed to report whether they felt the foil between their molars and the mean percentage of correct answers was computed. A linear mixed model was used with OTA as a dependent variable and psychological domain as an independent variable.</AbstractText Significantly different OTA was observed among the anxiety subgroups (p = .003), supporting a decreased perception of thicknesses 24 and 32 μm (p = .018 and p < .001, respectively) in participants with moderate/severe anxiety compared to those with no/mild anxiety. Significantly different OTA was also observed among the pain catastrophizing subgroups (p = .008), showing decreased perception of thicknesses 32 and 40 μm (p < .001 and p = .007, respectively) in severe catastrophizing levels, compared to no/mild catastrophizing levels. No significant differences were observed for the other variables.</AbstractText Healthy adults with increased anxiety or pain catastrophizing levels show decreased interdental acuity as compared to participants with minor or no psychological impairment.</AbstractText
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It has remained uncertain whether the mechanisms of visual perceptual learning (VPL)<sup
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BCL2/adenovirus E1B 19-kDa protein-interacting protein 2 homolog (BNIP-H or Caytaxin), a pivotal adaptor protein that facilitates cerebellar cortex growth and synaptic transmission, is posttranslationally modified to regulate neuronal function. This study reports the ubiquitination of BNIP-H by Carboxyl terminus of Hsc70-Interacting Protein (CHIP), a U-box containing E3 ligase that is also regulated <i
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Association between psychological traits and occlusal tactile acuity of healthy individuals. Tactile acuity is a somatosensory measure of the extent to which humans can discern tactile stimuli. It is influenced by how peripheral signals are processed centrally. In the oral cavity, Occlusal Tactile Acuity (OTA) is the ability to perceive minimal thicknesses between antagonist teeth. The aim of the current study was to assess the association between psychological traits and OTA of otherwise healthy individuals.</AbstractText Sixty-three volunteers (32 males; mean age ± SD: 24.6 ± 2.7 years) participated in this study. Somatosensory amplification, anxiety, depression, physical symptoms and pain catastrophizing were scored using questionnaires, and subgroups of severity were created per variable based on cut-offs. OTA was measured using 9 aluminium foils with thickness (ranging from 8 to 72 μm) and one sham test (without foil). Each thickness was tested 10 times in random order, the participants were instructed to report whether they felt the foil between their molars and the mean percentage of correct answers was computed. A linear mixed model was used with OTA as a dependent variable and psychological domain as an independent variable.</AbstractText Significantly different OTA was observed among the anxiety subgroups (p = .003), supporting a decreased perception of thicknesses 24 and 32 μm (p = .018 and p < .001, respectively) in participants with moderate/severe anxiety compared to those with no/mild anxiety. Significantly different OTA was also observed among the pain catastrophizing subgroups (p = .008), showing decreased perception of thicknesses 32 and 40 μm (p < .001 and p = .007, respectively) in severe catastrophizing levels, compared to no/mild catastrophizing levels. No significant differences were observed for the other variables.</AbstractText Healthy adults with increased anxiety or pain catastrophizing levels show decreased interdental acuity as compared to participants with minor or no psychological impairment.</AbstractText
|
Fundamental Differences in Visual Perceptual Learning between Children and Adults. It has remained uncertain whether the mechanisms of visual perceptual learning (VPL)<sup
|
Insights into the regulation of CHIP E3 ligase-mediated ubiquitination of neuronal protein BNIP-H. BCL2/adenovirus E1B 19-kDa protein-interacting protein 2 homolog (BNIP-H or Caytaxin), a pivotal adaptor protein that facilitates cerebellar cortex growth and synaptic transmission, is posttranslationally modified to regulate neuronal function. This study reports the ubiquitination of BNIP-H by Carboxyl terminus of Hsc70-Interacting Protein (CHIP), a U-box containing E3 ligase that is also regulated <i
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35944422
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21031030
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34840531
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Altered dynamic functional connectivity of striatal-cortical circuits in Juvenile Myoclonic Epilepsy.
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Disrupted modularity and local connectivity of brain functional networks in childhood-onset schizophrenia.
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Challenging the clinically-situated emotion-deficient version of empathy within medicine and medical education research.
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To investigate whether the dynamic functional connectivity (dFC) of striatal-cortical circuits changes in juvenile myoclonic epilepsy (JME).</AbstractText The resting-state EEG-fMRI and the sliding-window approach were adopted to explore the dynamic striatal-cortical circuitry in thirty JME patients compared with 30 well-matched health controls (HCs). Six pairs of striatal seeds were selected as regions of interests. The correlation analysis was performed to reveal the relationship between the altered dFC variability and clinical variables in JME group.</AbstractText JME patients exhibited increased dFC variability mainly involved in fronto-striatal and striatal-thalamic networks; decreased dFC variability between striatum subdivisions and default mode network (DMN) regions compared with HCs (p<0.05, GRF corrected). In addition, the hypervariability between left ventral-rostral putamen and left medial superior frontal gyrus was positively (r= 0.493, p=0.008) correlated with the mean frequency score of myoclonic seizures in JME group.</AbstractText JME presented altered dFC variability in striatal-cortical circuits. The pattern of altered circuits showed increased variability in fronto-striatal and striatal-thalamic networks and decreased variability in striatal-DMN. These results provide novel information about the dynamic neural striatal-cortical circuitry of JME.</AbstractText
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Modularity is a fundamental concept in systems neuroscience, referring to the formation of local cliques or modules of densely intra-connected nodes that are sparsely inter-connected with nodes in other modules. Topological modularity of brain functional networks can quantify theoretically anticipated abnormality of brain network community structure - so-called dysmodularity - in developmental disorders such as childhood-onset schizophrenia (COS). We used graph theory to investigate topology of networks derived from resting-state fMRI data on 13 COS patients and 19 healthy volunteers. We measured functional connectivity between each pair of 100 regional nodes, focusing on wavelet correlation in the frequency interval 0.05-0.1 Hz, then applied global and local thresholding rules to construct graphs from each individual association matrix over the full range of possible connection densities. We show how local thresholding based on the minimum spanning tree facilitates group comparisons of networks by forcing the connectedness of sparse graphs. Threshold-dependent graph theoretical results are compatible with the results of a k-means unsupervised learning algorithm and a multi-resolution (spin glass) approach to modularity, both of which also find community structure but do not require thresholding of the association matrix. In general modularity of brain functional networks was significantly reduced in COS, due to a relatively reduced density of intra-modular connections between neighboring regions. Other network measures of local organization such as clustering were also decreased, while complementary measures of global efficiency and robustness were increased, in the COS group. The group differences in complex network properties were mirrored by differences in simpler statistical properties of the data, such as the variability of the global time series and the internal homogeneity of the time series within anatomical regions of interest.</AbstractText
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In this paper, we argue that the notion of a clinically-situated empathy (e.g. physician empathy), is potentially problematic as it perpetuates an emotion-deficient version of empathy within medicine and medicine education research. Utilizing classic and contemporary empathy theory from various social science disciplines, we discuss how empathy in the general sense differs conceptually from clinically-situated empathy-paying particular attention to the role of emotional contagion. To highlight this contrast, we draw upon Hojat et al.'s model of physician empathy and how this body of work reflects broader medical-cultural norms that problematize the role and impact of emotions within the clinical encounter. Alternatively, we present a more encompassing model of empathy drawing upon the fields of social-psychology and social-neuroscience in order to bring the notion of "feeling with" and emotional contagion more specifically, into medical education, medical education research, and medicine more generally.</AbstractText
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Altered dynamic functional connectivity of striatal-cortical circuits in Juvenile Myoclonic Epilepsy. To investigate whether the dynamic functional connectivity (dFC) of striatal-cortical circuits changes in juvenile myoclonic epilepsy (JME).</AbstractText The resting-state EEG-fMRI and the sliding-window approach were adopted to explore the dynamic striatal-cortical circuitry in thirty JME patients compared with 30 well-matched health controls (HCs). Six pairs of striatal seeds were selected as regions of interests. The correlation analysis was performed to reveal the relationship between the altered dFC variability and clinical variables in JME group.</AbstractText JME patients exhibited increased dFC variability mainly involved in fronto-striatal and striatal-thalamic networks; decreased dFC variability between striatum subdivisions and default mode network (DMN) regions compared with HCs (p<0.05, GRF corrected). In addition, the hypervariability between left ventral-rostral putamen and left medial superior frontal gyrus was positively (r= 0.493, p=0.008) correlated with the mean frequency score of myoclonic seizures in JME group.</AbstractText JME presented altered dFC variability in striatal-cortical circuits. The pattern of altered circuits showed increased variability in fronto-striatal and striatal-thalamic networks and decreased variability in striatal-DMN. These results provide novel information about the dynamic neural striatal-cortical circuitry of JME.</AbstractText
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Disrupted modularity and local connectivity of brain functional networks in childhood-onset schizophrenia. Modularity is a fundamental concept in systems neuroscience, referring to the formation of local cliques or modules of densely intra-connected nodes that are sparsely inter-connected with nodes in other modules. Topological modularity of brain functional networks can quantify theoretically anticipated abnormality of brain network community structure - so-called dysmodularity - in developmental disorders such as childhood-onset schizophrenia (COS). We used graph theory to investigate topology of networks derived from resting-state fMRI data on 13 COS patients and 19 healthy volunteers. We measured functional connectivity between each pair of 100 regional nodes, focusing on wavelet correlation in the frequency interval 0.05-0.1 Hz, then applied global and local thresholding rules to construct graphs from each individual association matrix over the full range of possible connection densities. We show how local thresholding based on the minimum spanning tree facilitates group comparisons of networks by forcing the connectedness of sparse graphs. Threshold-dependent graph theoretical results are compatible with the results of a k-means unsupervised learning algorithm and a multi-resolution (spin glass) approach to modularity, both of which also find community structure but do not require thresholding of the association matrix. In general modularity of brain functional networks was significantly reduced in COS, due to a relatively reduced density of intra-modular connections between neighboring regions. Other network measures of local organization such as clustering were also decreased, while complementary measures of global efficiency and robustness were increased, in the COS group. The group differences in complex network properties were mirrored by differences in simpler statistical properties of the data, such as the variability of the global time series and the internal homogeneity of the time series within anatomical regions of interest.</AbstractText
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Challenging the clinically-situated emotion-deficient version of empathy within medicine and medical education research. In this paper, we argue that the notion of a clinically-situated empathy (e.g. physician empathy), is potentially problematic as it perpetuates an emotion-deficient version of empathy within medicine and medicine education research. Utilizing classic and contemporary empathy theory from various social science disciplines, we discuss how empathy in the general sense differs conceptually from clinically-situated empathy-paying particular attention to the role of emotional contagion. To highlight this contrast, we draw upon Hojat et al.'s model of physician empathy and how this body of work reflects broader medical-cultural norms that problematize the role and impact of emotions within the clinical encounter. Alternatively, we present a more encompassing model of empathy drawing upon the fields of social-psychology and social-neuroscience in order to bring the notion of "feeling with" and emotional contagion more specifically, into medical education, medical education research, and medicine more generally.</AbstractText
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38246861
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38634744
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38409793
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Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a cardiac magnetic resonance correlation study.
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Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review.
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Stereotactic Awake Basal Ganglia Electrophysiological Recording and Stimulation (SABERS): A Novel Staged Procedure for Personalized Targeting of Deep Brain Stimulation in Pediatric Movement and Neuropsychiatric Disorders.
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Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR).</AbstractText One-hundred fifty-eight patients [73 (68-77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction: 5.0% (2.0-9.7)]. Native T1 was above normal [1053 ms (1024-1071)] and T2 within the normal range [39.3 ms (37.3-42.0)]. Median MF was 11.9% (6.54-19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125).</AbstractText Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.</AbstractText
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Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (≥18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries <i
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Selection of targets for deep brain stimulation (DBS) has been based on clinical experience, but inconsistent and unpredictable outcomes have limited its use in patients with heterogeneous or rare disorders. In this large case series, a novel staged procedure for neurophysiological assessment from 8 to 12 temporary depth electrodes is used to select targets for neuromodulation that are tailored to each patient's functional needs. Thirty children and young adults underwent deep brain stimulation target evaluation with the new procedure: Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation (SABERS). Testing is performed in an inpatient neuromodulation monitoring unit over 5-7 days, and results guide the decision to proceed and the choice of targets for permanent deep brain stimulation implantation. Results were evaluated 3-6 months postoperatively with the Burke-Fahn-Marsden Dystonia Rating Scale and the Barry-Albright Dystonia Scale. Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation testing allowed modulation to be tailored to specific neurologic deficits in a heterogeneous population, including subjects with primary dystonia, secondary dystonia, and Tourette syndrome. All but one subject were implanted with 4 permanent deep brain stimulation leads. Results showed significant improvement on both scales at postoperative follow-up. No significant adverse events occurred. Use of the Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation protocol with evaluation in the neuromodulation monitoring unit is feasible and results in significant patient benefit compared with previously published results in these populations. This new technique supports a significant expansion of functional neurosurgery to predict effective stimulation targets in a wide range of disorders of brain function, including those for which the optimal target is not yet known.</AbstractText
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Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a cardiac magnetic resonance correlation study. Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR).</AbstractText One-hundred fifty-eight patients [73 (68-77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction: 5.0% (2.0-9.7)]. Native T1 was above normal [1053 ms (1024-1071)] and T2 within the normal range [39.3 ms (37.3-42.0)]. Median MF was 11.9% (6.54-19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125).</AbstractText Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.</AbstractText
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Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review. Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (≥18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries <i
|
Stereotactic Awake Basal Ganglia Electrophysiological Recording and Stimulation (SABERS): A Novel Staged Procedure for Personalized Targeting of Deep Brain Stimulation in Pediatric Movement and Neuropsychiatric Disorders. Selection of targets for deep brain stimulation (DBS) has been based on clinical experience, but inconsistent and unpredictable outcomes have limited its use in patients with heterogeneous or rare disorders. In this large case series, a novel staged procedure for neurophysiological assessment from 8 to 12 temporary depth electrodes is used to select targets for neuromodulation that are tailored to each patient's functional needs. Thirty children and young adults underwent deep brain stimulation target evaluation with the new procedure: Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation (SABERS). Testing is performed in an inpatient neuromodulation monitoring unit over 5-7 days, and results guide the decision to proceed and the choice of targets for permanent deep brain stimulation implantation. Results were evaluated 3-6 months postoperatively with the Burke-Fahn-Marsden Dystonia Rating Scale and the Barry-Albright Dystonia Scale. Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation testing allowed modulation to be tailored to specific neurologic deficits in a heterogeneous population, including subjects with primary dystonia, secondary dystonia, and Tourette syndrome. All but one subject were implanted with 4 permanent deep brain stimulation leads. Results showed significant improvement on both scales at postoperative follow-up. No significant adverse events occurred. Use of the Stereotactic Awake Basal ganglia Electrophysiological Recording and Stimulation protocol with evaluation in the neuromodulation monitoring unit is feasible and results in significant patient benefit compared with previously published results in these populations. This new technique supports a significant expansion of functional neurosurgery to predict effective stimulation targets in a wide range of disorders of brain function, including those for which the optimal target is not yet known.</AbstractText
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39151325
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30064328
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39109111
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The utility of Multicentre Epilepsy Lesion Detection (MELD) algorithm in identifying epileptic activity and predicting seizure freedom in MRI lesion-negative paediatric patients.
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Fast gray matter acquisition T1 inversion recovery MRI to delineate the mammillothalamic tract for preoperative direct targeting of the anterior nucleus of the thalamus for deep brain stimulation in epilepsy.
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The Prevalence of Fibromyalgia in Rheumatoid Arthritis Patients Using the Fibromyalgia Assessment Screening Tool (FAST 4) Based on the Multidimensional Health Assessment Questionnaire (MDHAQ).
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Paediatric patients with drug-resistant focal epilepsy (DRFE) who have no clear focal lesion identified on conventional structural magnetic resonance imaging (MRI) are a particularly challenging cohort to treat and form an increasing part of epilepsy surgery programs. A recently developed deep-learning-based MRI lesion detection algorithm, the Multicentre Lesion Detection (MELD) algorithm, has been shown to aid detection of focal cortical dysplasia (FCD). We applied this algorithm retrospectively to a cohort of MRI-negative children with refractory focal epilepsy who underwent stereoelectroencephalography (SEEG) to determine its accuracy in identifying unseen epileptic lesions, seizure onset zones and clinical outcomes.</AbstractText We retrospectively applied the MELD algorithm to a consecutive series of MRI-negative patients who underwent SEEG at our tertiary Paediatric Epilepsy Surgery centre. We assessed the extent to which the identified MELD cluster or lesion area corresponded with the clinical seizure hypothesis, the epileptic network, and the positron emission tomography (PET) focal hypometabolic area. In those who underwent resective surgery, we analysed whether the region of MELD abnormality corresponded with the surgical target and to what extent this was associated with seizure freedom.</AbstractText We identified 37 SEEG studies in 28 MRI-negative children in whom we could run the MELD algorithm. Of these, 14 (50 %) children had clusters identified on MELD. Nine (32 %) children had clusters concordant with seizure hypothesis, 6 (21 %) had clusters concordant with PET imaging, and 5 (18 %) children had at least one cluster concordant with SEEG electrode placement. Overall, 4 MELD clusters in 4 separate children correctly predicted either seizure onset zone or irritative zone based on SEEG stimulation data. Sixteen children (57 %) went on to have resective or lesional surgery. Of these, only one patient (4 %) had a MELD cluster which co-localised with the resection cavity and this child had an Engel 1 A outcome.</AbstractText In our paediatric cohort of MRI-negative patients with drug-resistant focal epilepsy, the MELD algorithm identified abnormal clusters or lesions in half of cases, and identified one radiologically occult focal cortical dysplasia. Machine-learning-based lesion detection is a promising area of research with the potential to improve seizure outcomes in this challenging cohort of radiologically occult FCD cases. However, its application should be approached with caution, especially with regards to its specificity in detecting FCD lesions, and there is still work to be done before it adds to diagnostic utility.</AbstractText
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When medically intractable epilepsy is multifocal or focal but poorly localized, neuromodulation can be useful therapy. One such technique is deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT). Unfortunately, the ANT is difficult to visualize in standard MRI sequences and its indirect targeting is difficult because of thalamic variability and atrophy in patients with epilepsy. The following study describes the novel use of the fast gray matter acquisition T1 inversion recovery (FGATIR) MRI sequence to delineate the mammillothalamic tract for direct targeting of the ANT through visualizing the termination of the mammillothalamic tract in the ANT. The day prior to surgery in a 19-year-old, right-handed woman with a 5-year history of epilepsy, MRI was performed on a 3-T Siemens Prisma scanner (Siemens AG, Healthcare Sector) using a 64-channel head and neck coil. As part of the imaging protocol, noncontrast magnetization-prepared rapid gradient echo (MP-RAGE) and diffusion tensor imaging (DTI) sequences were obtained for targeting purposes. The ANT was directly targeted using the FGATIR sequence, and bilateral Medtronic 3389 leads were placed. At the last follow-up (2 months), the patient reported an approximate 75% decrease in seizure frequency, as well as a decrease in seizure severity.</AbstractText
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Introduction Fibromyalgia (FM) is characterized by widespread pain and fatigue, accompanied by symptoms such as decreased concentration, autonomic dysfunction, and abdominal pain. It can be either primary or secondary, notably to rheumatoid arthritis (RA). The Fibromyalgia Assessment Screening Tools (FAST 4), derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), is a composite tool allowing for the rapid screening of FM. Our primary objective is to determine the prevalence of FM among RA patients using the FAST 4 index. Secondary objectives include comparing the FAST 4 index with the FiRST score and describing the correlation between FM and RA activity and different factors associated with FM in RA patients. Methods This was an observational cross-sectional study including patients diagnosed with RA according to the ACR/EULAR criteria. The FAST questionnaire comprises four sections assessing pain and fatigue on a visual analog scale, painful joints reported by the patient, and a list of 60 symptoms. A FAST 4 score of ≥ 3/4 indicates a positive screening for FM. Demographics and disease features were compared using descriptive statistics. Univariate and multivariate analyses using logistic regression models were performed to calculate odds ratios (ORs) with 95% CI. The sensitivity and specificity of the FAST 4 index were evaluated, and Fagan's nomograms were used to illustrate post-test probability. Statistically significant results were considered for p-values less than 0.05. Results The study enrolled 97 patients diagnosed with RA. The mean age of the patients was 56 ± 12.7 years, with a predominance of females (90.7%, N=88). The mean duration of RA was 13.5 ± 8.69 years. RA activity measured by DAS 28-ESR showed that 40.2% (N=39) had high disease activity, 38.1% (N=37) had moderate disease activity, 11.3% (N=11) had low disease activity, and 10.3% (N=10) were in remission. The prevalence of comorbid FM, according to the FAST 4 index, was 30.9% (N=30). Based on the Multidimensional Health Assessment Questionnaire (MDHAQ), depression was observed in 66.7% (N=20) patients with FM, while anxiety was reported in 60% (N=18). Moreover, 30.4% of patients screened positive for FM using the FiRST score. The FAST 4 index detected FM patients defined by FiRST with a sensitivity of 78.6% and a specificity of 87.1%. The positive predictive value (PPV) was 73.3%, and the negative predictive value (NPV) was 90%. Univariate analysis revealed that a positive FAST 4 index was associated with the number of painful and swollen joints (p<0.001 and 0.03, respectively). Additionally, patients with a positive FAST 4 index showed higher DAS 28 scores (p=0.002). No significant association was found with CRP levels (p=0.328), ESR (p=0.499), or the use of biological treatments (p=0.146) or corticosteroids (p=0.940). In multivariate analysis, only depression remained a risk factor, increasing the risk sixfold with an OR of 5.917, 95% CI (1.91-18.3), p=0.002. Conclusion Our study suggests a high prevalence of concomitant FM in our population, highlighting the importance of screening for FM, particularly using the FAST 4 index based solely on the MDHAQ questionnaire.</AbstractText
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The utility of Multicentre Epilepsy Lesion Detection (MELD) algorithm in identifying epileptic activity and predicting seizure freedom in MRI lesion-negative paediatric patients. Paediatric patients with drug-resistant focal epilepsy (DRFE) who have no clear focal lesion identified on conventional structural magnetic resonance imaging (MRI) are a particularly challenging cohort to treat and form an increasing part of epilepsy surgery programs. A recently developed deep-learning-based MRI lesion detection algorithm, the Multicentre Lesion Detection (MELD) algorithm, has been shown to aid detection of focal cortical dysplasia (FCD). We applied this algorithm retrospectively to a cohort of MRI-negative children with refractory focal epilepsy who underwent stereoelectroencephalography (SEEG) to determine its accuracy in identifying unseen epileptic lesions, seizure onset zones and clinical outcomes.</AbstractText We retrospectively applied the MELD algorithm to a consecutive series of MRI-negative patients who underwent SEEG at our tertiary Paediatric Epilepsy Surgery centre. We assessed the extent to which the identified MELD cluster or lesion area corresponded with the clinical seizure hypothesis, the epileptic network, and the positron emission tomography (PET) focal hypometabolic area. In those who underwent resective surgery, we analysed whether the region of MELD abnormality corresponded with the surgical target and to what extent this was associated with seizure freedom.</AbstractText We identified 37 SEEG studies in 28 MRI-negative children in whom we could run the MELD algorithm. Of these, 14 (50 %) children had clusters identified on MELD. Nine (32 %) children had clusters concordant with seizure hypothesis, 6 (21 %) had clusters concordant with PET imaging, and 5 (18 %) children had at least one cluster concordant with SEEG electrode placement. Overall, 4 MELD clusters in 4 separate children correctly predicted either seizure onset zone or irritative zone based on SEEG stimulation data. Sixteen children (57 %) went on to have resective or lesional surgery. Of these, only one patient (4 %) had a MELD cluster which co-localised with the resection cavity and this child had an Engel 1 A outcome.</AbstractText In our paediatric cohort of MRI-negative patients with drug-resistant focal epilepsy, the MELD algorithm identified abnormal clusters or lesions in half of cases, and identified one radiologically occult focal cortical dysplasia. Machine-learning-based lesion detection is a promising area of research with the potential to improve seizure outcomes in this challenging cohort of radiologically occult FCD cases. However, its application should be approached with caution, especially with regards to its specificity in detecting FCD lesions, and there is still work to be done before it adds to diagnostic utility.</AbstractText
|
Fast gray matter acquisition T1 inversion recovery MRI to delineate the mammillothalamic tract for preoperative direct targeting of the anterior nucleus of the thalamus for deep brain stimulation in epilepsy. When medically intractable epilepsy is multifocal or focal but poorly localized, neuromodulation can be useful therapy. One such technique is deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT). Unfortunately, the ANT is difficult to visualize in standard MRI sequences and its indirect targeting is difficult because of thalamic variability and atrophy in patients with epilepsy. The following study describes the novel use of the fast gray matter acquisition T1 inversion recovery (FGATIR) MRI sequence to delineate the mammillothalamic tract for direct targeting of the ANT through visualizing the termination of the mammillothalamic tract in the ANT. The day prior to surgery in a 19-year-old, right-handed woman with a 5-year history of epilepsy, MRI was performed on a 3-T Siemens Prisma scanner (Siemens AG, Healthcare Sector) using a 64-channel head and neck coil. As part of the imaging protocol, noncontrast magnetization-prepared rapid gradient echo (MP-RAGE) and diffusion tensor imaging (DTI) sequences were obtained for targeting purposes. The ANT was directly targeted using the FGATIR sequence, and bilateral Medtronic 3389 leads were placed. At the last follow-up (2 months), the patient reported an approximate 75% decrease in seizure frequency, as well as a decrease in seizure severity.</AbstractText
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The Prevalence of Fibromyalgia in Rheumatoid Arthritis Patients Using the Fibromyalgia Assessment Screening Tool (FAST 4) Based on the Multidimensional Health Assessment Questionnaire (MDHAQ). Introduction Fibromyalgia (FM) is characterized by widespread pain and fatigue, accompanied by symptoms such as decreased concentration, autonomic dysfunction, and abdominal pain. It can be either primary or secondary, notably to rheumatoid arthritis (RA). The Fibromyalgia Assessment Screening Tools (FAST 4), derived from the Multidimensional Health Assessment Questionnaire (MDHAQ), is a composite tool allowing for the rapid screening of FM. Our primary objective is to determine the prevalence of FM among RA patients using the FAST 4 index. Secondary objectives include comparing the FAST 4 index with the FiRST score and describing the correlation between FM and RA activity and different factors associated with FM in RA patients. Methods This was an observational cross-sectional study including patients diagnosed with RA according to the ACR/EULAR criteria. The FAST questionnaire comprises four sections assessing pain and fatigue on a visual analog scale, painful joints reported by the patient, and a list of 60 symptoms. A FAST 4 score of ≥ 3/4 indicates a positive screening for FM. Demographics and disease features were compared using descriptive statistics. Univariate and multivariate analyses using logistic regression models were performed to calculate odds ratios (ORs) with 95% CI. The sensitivity and specificity of the FAST 4 index were evaluated, and Fagan's nomograms were used to illustrate post-test probability. Statistically significant results were considered for p-values less than 0.05. Results The study enrolled 97 patients diagnosed with RA. The mean age of the patients was 56 ± 12.7 years, with a predominance of females (90.7%, N=88). The mean duration of RA was 13.5 ± 8.69 years. RA activity measured by DAS 28-ESR showed that 40.2% (N=39) had high disease activity, 38.1% (N=37) had moderate disease activity, 11.3% (N=11) had low disease activity, and 10.3% (N=10) were in remission. The prevalence of comorbid FM, according to the FAST 4 index, was 30.9% (N=30). Based on the Multidimensional Health Assessment Questionnaire (MDHAQ), depression was observed in 66.7% (N=20) patients with FM, while anxiety was reported in 60% (N=18). Moreover, 30.4% of patients screened positive for FM using the FiRST score. The FAST 4 index detected FM patients defined by FiRST with a sensitivity of 78.6% and a specificity of 87.1%. The positive predictive value (PPV) was 73.3%, and the negative predictive value (NPV) was 90%. Univariate analysis revealed that a positive FAST 4 index was associated with the number of painful and swollen joints (p<0.001 and 0.03, respectively). Additionally, patients with a positive FAST 4 index showed higher DAS 28 scores (p=0.002). No significant association was found with CRP levels (p=0.328), ESR (p=0.499), or the use of biological treatments (p=0.146) or corticosteroids (p=0.940). In multivariate analysis, only depression remained a risk factor, increasing the risk sixfold with an OR of 5.917, 95% CI (1.91-18.3), p=0.002. Conclusion Our study suggests a high prevalence of concomitant FM in our population, highlighting the importance of screening for FM, particularly using the FAST 4 index based solely on the MDHAQ questionnaire.</AbstractText
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38175548
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27381481
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36566124
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[Seizures in pregnancy: not always eclamptic seizures].
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Epilepsy in cerebrovascular diseases: Review of experimental and clinical data with meta-analysis of risk factors.
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Strategy for genetic analysis in hereditary neuropathy.
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The differential diagnosis of seizures during pregnancy is extensive and includes potentially fatal underlying diagnoses. Both pregnancy and non-pregnancy related aetiologies should be considered.</AbstractText A 38-years old pregnant woman presented to the emergency department at 31 weeks and 5 days with generalized tonic-clonic seizures. Initial an eclamptic seizure was suspected. Because the seizures lasted despite treatment with magnesium sulphate and anti-epileptic medication. Imaging of the head was performed and a brain tumour was suspected and a biopsy revealed the presence of a high-grade glioma. At 37 weeks of gestation, labour was induced and the patient delivered a healthy daughter. The patient was then palliatively treated with antiepileptic drugs and chemotherapy.</AbstractText Structural brain changes caused by a high-grade gliomas represent a rare cause of seizure during pregnancy, emphasizing the importance of considering non-obstetric causes of seizures in pregnant women.</AbstractText
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Seizures may occur in close temporal association with a stroke or after a variable interval. Moreover, epilepsy is often encountered in patients with leukoaraiosis. Although early post-stroke seizures have been studied extensively, less attention has been paid to post-stroke epilepsy (PSE) and to epilepsy associated with leukoaraiosis (EAL). The aim of this paper is to review data concerning pathophysiology, prognosis, and treatment of PSE and EAL.</AbstractText We performed an extensive literature search to identify experimental and clinical articles on PSE and EAL. We also conducted a systematic review of risk factors for PSE and EAL among eligible studies.</AbstractText PSE is caused by enhanced neuronal excitability within and near the scar. The role played by white matter changes in EAL remains to be elucidated. Meta-analysis showed that cortical involvement (odds ratio [OR] 3.71, 95% confidence interval [CI] 2.34-5.90, p < 0.001), cerebral hemorrhage (OR 2.41, 95% CI 1.57-3.70, p < 0.001), and early seizures (OR 4.43, 95% CI 2.36-8.32, p < 0.001) are associated with an increased risk of PSE. As regards EAL, no prospective, population-based studies evaluated the role of different variables on seizure risk. Studies about the management of PSE are limited. PSE is generally well controlled by drugs. Data about risk factors, prognosis, and treatment of EAL are lacking.</AbstractText Pathophysiology and risk factors are well defined for PSE but need to be elucidated for EAL. Management of PSE and EAL relies on the clinician's judgment and should be tailored on an individual basis.</AbstractText
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Inherited neuropathies are a heterogeneous group of slowly progressive disorders affecting either motor, sensory, and/or autonomic nerves. Peripheral neuropathy may be the major component of a disease such as Charcot-Marie-Tooth disease or a feature of a more complex multisystemic disease involving the central nervous system and other organs. The goal of this review is to provide the clinical clues orientating the genetic diagnosis in a patient with inherited peripheral neuropathy. This review focuses on primary inherited neuropathies, amyloidosis, inherited metabolic diseases, while detailing clinical, neurophysiological and potential treatment of these diseases.</AbstractText
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[Seizures in pregnancy: not always eclamptic seizures]. The differential diagnosis of seizures during pregnancy is extensive and includes potentially fatal underlying diagnoses. Both pregnancy and non-pregnancy related aetiologies should be considered.</AbstractText A 38-years old pregnant woman presented to the emergency department at 31 weeks and 5 days with generalized tonic-clonic seizures. Initial an eclamptic seizure was suspected. Because the seizures lasted despite treatment with magnesium sulphate and anti-epileptic medication. Imaging of the head was performed and a brain tumour was suspected and a biopsy revealed the presence of a high-grade glioma. At 37 weeks of gestation, labour was induced and the patient delivered a healthy daughter. The patient was then palliatively treated with antiepileptic drugs and chemotherapy.</AbstractText Structural brain changes caused by a high-grade gliomas represent a rare cause of seizure during pregnancy, emphasizing the importance of considering non-obstetric causes of seizures in pregnant women.</AbstractText
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Epilepsy in cerebrovascular diseases: Review of experimental and clinical data with meta-analysis of risk factors. Seizures may occur in close temporal association with a stroke or after a variable interval. Moreover, epilepsy is often encountered in patients with leukoaraiosis. Although early post-stroke seizures have been studied extensively, less attention has been paid to post-stroke epilepsy (PSE) and to epilepsy associated with leukoaraiosis (EAL). The aim of this paper is to review data concerning pathophysiology, prognosis, and treatment of PSE and EAL.</AbstractText We performed an extensive literature search to identify experimental and clinical articles on PSE and EAL. We also conducted a systematic review of risk factors for PSE and EAL among eligible studies.</AbstractText PSE is caused by enhanced neuronal excitability within and near the scar. The role played by white matter changes in EAL remains to be elucidated. Meta-analysis showed that cortical involvement (odds ratio [OR] 3.71, 95% confidence interval [CI] 2.34-5.90, p < 0.001), cerebral hemorrhage (OR 2.41, 95% CI 1.57-3.70, p < 0.001), and early seizures (OR 4.43, 95% CI 2.36-8.32, p < 0.001) are associated with an increased risk of PSE. As regards EAL, no prospective, population-based studies evaluated the role of different variables on seizure risk. Studies about the management of PSE are limited. PSE is generally well controlled by drugs. Data about risk factors, prognosis, and treatment of EAL are lacking.</AbstractText Pathophysiology and risk factors are well defined for PSE but need to be elucidated for EAL. Management of PSE and EAL relies on the clinician's judgment and should be tailored on an individual basis.</AbstractText
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Strategy for genetic analysis in hereditary neuropathy. Inherited neuropathies are a heterogeneous group of slowly progressive disorders affecting either motor, sensory, and/or autonomic nerves. Peripheral neuropathy may be the major component of a disease such as Charcot-Marie-Tooth disease or a feature of a more complex multisystemic disease involving the central nervous system and other organs. The goal of this review is to provide the clinical clues orientating the genetic diagnosis in a patient with inherited peripheral neuropathy. This review focuses on primary inherited neuropathies, amyloidosis, inherited metabolic diseases, while detailing clinical, neurophysiological and potential treatment of these diseases.</AbstractText
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36644002
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23286107
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35089235
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Lossless Compressed Sensing of Photon Counts for Fast Diffuse Correlation Spectroscopy.
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Accelerated diffusion spectrum imaging with compressed sensing using adaptive dictionaries.
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Delayed gait recovery by resolution of limb-kinetic apraxia in a chronic hemiparetic stroke patient: A case report.
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Diffuse Correlation Spectroscopy (DCS), a noninvasive optical technique, measures deep tissue blood flow using avalanche photon counting modules and data acquisition devices such as FPGAs or correlator boards. Conventional DCS instruments use in-processor counter modules that consume 32 bits/channel which is inefficient for low-photon budget situations prevalent in diffuse optics. Scaling these photon counters for large-scale imaging applications is difficult due to bandwidth and processing time considerations. Here, we introduce a new, lossless compressed sensing approach for fast and efficient detection of photon counts. The compressed DCS method uses an array of binary-coded-decimal counters to record photon counts from 8 channels simultaneously as a single 32-bit number. We validate the compressed DCS approach by comparisons with conventional DCS in experiments on tissue simulating phantoms and in-vivo arm cuff occlusion. Lossless compressed DCS was implemented with 87.5% compression efficiency. In tissue simulating phantoms, it was able to accurately estimate a tissue blood flow index, with no statistically significant difference compared to conventional DCS. Compressed DCS also recorded blood flow in vivo, in human forearm, with signal-to-noise ratio and dynamic range comparable to conventional DCS. Lossless 87.5% efficient compressed sensing counting of photon counts meets and exceeds benchmarks set by conventional DCS systems, offering a low-cost alternative for fast (~100 Hz) deep tissue blood flow measurement with optics.</AbstractText
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Diffusion spectrum imaging (DSI) offers detailed information on complex distributions of intravoxel fiber orientations at the expense of extremely long imaging times (1 hour). It is possible to accelerate DSI by sub-Nyquist sampling of the q-space followed by nonlinear reconstruction to estimate the diffusion probability density functions (pdfs). Recent work by Menzel et al. imposed sparsity constraints on the pdfs under wavelet and total variation (TV) transforms. As the performance of Compressed Sensing (CS) reconstruction depends strongly on the level of sparsity in the selected transform space, a dictionary specifically tailored for sparse representation of diffusion pdfs can yield higher fidelity results. To our knowledge, this work is the first application of adaptive dictionaries in DSI, whereby we reduce the scan time of whole brain DSI acquisition from 50 to 17 min while retaining high image quality. In vivo experiments were conducted with the novel 3T Connectome MRI, whose strong gradients are particularly suited for DSI. The RMSE from the proposed reconstruction is up to 2 times lower than that of Menzel et al.'s method, and is actually comparable to that of the fully-sampled 50 minute scan. Further, we demonstrate that a dictionary trained using pdfs from a single slice of a particular subject generalizes well to other slices from the same subject, as well as to slices from another subject.</AbstractText
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This paper reports on a chronic hemiparetic stroke patient who showed delayed gait recovery due to resolution of limb-kinetic apraxia (LKA).</AbstractText A 49-year-old man underwent comprehensive rehabilitation at a local rehabilitation hospital since 3 weeks after spontaneous intracerebral haemorrhage. However, he could not walk independently because of severe motor weakness in his right leg until 19 months after the onset.</AbstractText At the beginning of rehabilitation at our hospital (19 months after onset), we thought that he had the neurological potential to walk independently because the unaffected (right) corticospinal tract and corticoreticulospinal tract were closely related to the gait potential, representing intact integrities. As a result, we assumed that the severe motor weakness in the right leg was mainly ascribed to LKA.</AbstractText At our hospital, he underwent comprehensive rehabilitation including increased doses of dopaminergic drugs (pramipexole, ropinirole, amantadine, and carbidopa/levodopa).</AbstractText After 10 days to our hospital, he could walk independently on an even floor with verbal supervision, concurrent with motor recovery of the right leg. After 24 days after hospital admission, he could walk independently on an even floor.</AbstractText We believe that the resolution of LKA in his right leg by the administration of adequate doses of dopaminergic drugs was the main reason for the delayed gait recovery in this patient. The results suggest the importance of detecting the neurological potential for gait ability of a stroke patient who cannot walk after the gait recovery phase and the causes of gait inability for individual patients.</AbstractText
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Lossless Compressed Sensing of Photon Counts for Fast Diffuse Correlation Spectroscopy. Diffuse Correlation Spectroscopy (DCS), a noninvasive optical technique, measures deep tissue blood flow using avalanche photon counting modules and data acquisition devices such as FPGAs or correlator boards. Conventional DCS instruments use in-processor counter modules that consume 32 bits/channel which is inefficient for low-photon budget situations prevalent in diffuse optics. Scaling these photon counters for large-scale imaging applications is difficult due to bandwidth and processing time considerations. Here, we introduce a new, lossless compressed sensing approach for fast and efficient detection of photon counts. The compressed DCS method uses an array of binary-coded-decimal counters to record photon counts from 8 channels simultaneously as a single 32-bit number. We validate the compressed DCS approach by comparisons with conventional DCS in experiments on tissue simulating phantoms and in-vivo arm cuff occlusion. Lossless compressed DCS was implemented with 87.5% compression efficiency. In tissue simulating phantoms, it was able to accurately estimate a tissue blood flow index, with no statistically significant difference compared to conventional DCS. Compressed DCS also recorded blood flow in vivo, in human forearm, with signal-to-noise ratio and dynamic range comparable to conventional DCS. Lossless 87.5% efficient compressed sensing counting of photon counts meets and exceeds benchmarks set by conventional DCS systems, offering a low-cost alternative for fast (~100 Hz) deep tissue blood flow measurement with optics.</AbstractText
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Accelerated diffusion spectrum imaging with compressed sensing using adaptive dictionaries. Diffusion spectrum imaging (DSI) offers detailed information on complex distributions of intravoxel fiber orientations at the expense of extremely long imaging times (1 hour). It is possible to accelerate DSI by sub-Nyquist sampling of the q-space followed by nonlinear reconstruction to estimate the diffusion probability density functions (pdfs). Recent work by Menzel et al. imposed sparsity constraints on the pdfs under wavelet and total variation (TV) transforms. As the performance of Compressed Sensing (CS) reconstruction depends strongly on the level of sparsity in the selected transform space, a dictionary specifically tailored for sparse representation of diffusion pdfs can yield higher fidelity results. To our knowledge, this work is the first application of adaptive dictionaries in DSI, whereby we reduce the scan time of whole brain DSI acquisition from 50 to 17 min while retaining high image quality. In vivo experiments were conducted with the novel 3T Connectome MRI, whose strong gradients are particularly suited for DSI. The RMSE from the proposed reconstruction is up to 2 times lower than that of Menzel et al.'s method, and is actually comparable to that of the fully-sampled 50 minute scan. Further, we demonstrate that a dictionary trained using pdfs from a single slice of a particular subject generalizes well to other slices from the same subject, as well as to slices from another subject.</AbstractText
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Delayed gait recovery by resolution of limb-kinetic apraxia in a chronic hemiparetic stroke patient: A case report. This paper reports on a chronic hemiparetic stroke patient who showed delayed gait recovery due to resolution of limb-kinetic apraxia (LKA).</AbstractText A 49-year-old man underwent comprehensive rehabilitation at a local rehabilitation hospital since 3 weeks after spontaneous intracerebral haemorrhage. However, he could not walk independently because of severe motor weakness in his right leg until 19 months after the onset.</AbstractText At the beginning of rehabilitation at our hospital (19 months after onset), we thought that he had the neurological potential to walk independently because the unaffected (right) corticospinal tract and corticoreticulospinal tract were closely related to the gait potential, representing intact integrities. As a result, we assumed that the severe motor weakness in the right leg was mainly ascribed to LKA.</AbstractText At our hospital, he underwent comprehensive rehabilitation including increased doses of dopaminergic drugs (pramipexole, ropinirole, amantadine, and carbidopa/levodopa).</AbstractText After 10 days to our hospital, he could walk independently on an even floor with verbal supervision, concurrent with motor recovery of the right leg. After 24 days after hospital admission, he could walk independently on an even floor.</AbstractText We believe that the resolution of LKA in his right leg by the administration of adequate doses of dopaminergic drugs was the main reason for the delayed gait recovery in this patient. The results suggest the importance of detecting the neurological potential for gait ability of a stroke patient who cannot walk after the gait recovery phase and the causes of gait inability for individual patients.</AbstractText
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39596523
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22190648
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39068917
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In Vitro Cell Model Investigation of Alpha-Synuclein Aggregate Morphology Using Spectroscopic Imaging.
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Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2.
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Randomized Controlled Trial of Remimazolam Compared with Placebo in Japanese Patients Undergoing Colonoscopy: A Phase III, Investigator-Initiated Trial.
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Recently, it has been hypothesized that alpha-synuclein protein strain morphology may be associated with clinical subtypes of alpha-synucleinopathies, like Parkinson's disease and multiple system atrophy. However, direct evidence is lacking due to the caveat of conformation-specific characterization of protein strain morphology. Here we present a new cell model based in vitro method to explore various alpha-synuclein (αsyn) aggregate morphotypes. We performed a spectroscopic investigation of the HEK293 cell model, transfected with human wildtype-αsyn and A53T-αsyn variants, using the amyloid fibril-specific heptameric luminescent oligomeric thiophene h-FTAA. The spectral profile of h-FTAA binding to aggregates displayed a blue-shifted spectrum with a fluorescence decay time longer than in PBS, suggesting a hydrophobic binding site. In vitro spectroscopic binding characterization of h-FTAA with αsyn pre-formed fibrils suggested a binding dissociation constant K<sub
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Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of "indigestible" prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1-secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.</AbstractText
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We conducted an investigator-initiated clinical trial in which remimazolam was used to achieve sedation in patients undergoing colonoscopies.</AbstractText This multicenter, double-blind, placebo-controlled, phase III investigator-initiated trial included patients who underwent colonoscopy under sedation with remimazolam (initial dose: 3 mg; additional dose: 1 mg) or normal saline (placebo). The primary endpoint of the study was the successful sedation rate during colonoscopy, defined as achieving a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of ≤4 before the procedure, maintaining this score throughout colonoscopy, and requiring no more than five additional drug doses per 15 min.</AbstractText The sedation success rate was 95.0% (38/40 patients) in the remimazolam group and 0.0% (0/11 patients) in the placebo group (p < 0.01). The time from the end of procedure to regaining consciousness was 0.0 (interquartile range: 0.0-0.0) min in both groups. The time from the end of the procedure to ambulation was 5.0 (interquartile range: 0.0-10.0) min in the remimazolam group and 0.0 (interquartile range: 0.0-0.0) min in the placebo group (p = 0.02). Serious adverse events were not observed.</AbstractText The use of remimazolam to achieve sedation in Japanese patients undergoing colonoscopy was more effective than placebo.</AbstractText
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In Vitro Cell Model Investigation of Alpha-Synuclein Aggregate Morphology Using Spectroscopic Imaging. Recently, it has been hypothesized that alpha-synuclein protein strain morphology may be associated with clinical subtypes of alpha-synucleinopathies, like Parkinson's disease and multiple system atrophy. However, direct evidence is lacking due to the caveat of conformation-specific characterization of protein strain morphology. Here we present a new cell model based in vitro method to explore various alpha-synuclein (αsyn) aggregate morphotypes. We performed a spectroscopic investigation of the HEK293 cell model, transfected with human wildtype-αsyn and A53T-αsyn variants, using the amyloid fibril-specific heptameric luminescent oligomeric thiophene h-FTAA. The spectral profile of h-FTAA binding to aggregates displayed a blue-shifted spectrum with a fluorescence decay time longer than in PBS, suggesting a hydrophobic binding site. In vitro spectroscopic binding characterization of h-FTAA with αsyn pre-formed fibrils suggested a binding dissociation constant K<sub
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Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of "indigestible" prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1-secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.</AbstractText
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Randomized Controlled Trial of Remimazolam Compared with Placebo in Japanese Patients Undergoing Colonoscopy: A Phase III, Investigator-Initiated Trial. We conducted an investigator-initiated clinical trial in which remimazolam was used to achieve sedation in patients undergoing colonoscopies.</AbstractText This multicenter, double-blind, placebo-controlled, phase III investigator-initiated trial included patients who underwent colonoscopy under sedation with remimazolam (initial dose: 3 mg; additional dose: 1 mg) or normal saline (placebo). The primary endpoint of the study was the successful sedation rate during colonoscopy, defined as achieving a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of ≤4 before the procedure, maintaining this score throughout colonoscopy, and requiring no more than five additional drug doses per 15 min.</AbstractText The sedation success rate was 95.0% (38/40 patients) in the remimazolam group and 0.0% (0/11 patients) in the placebo group (p < 0.01). The time from the end of procedure to regaining consciousness was 0.0 (interquartile range: 0.0-0.0) min in both groups. The time from the end of the procedure to ambulation was 5.0 (interquartile range: 0.0-10.0) min in the remimazolam group and 0.0 (interquartile range: 0.0-0.0) min in the placebo group (p = 0.02). Serious adverse events were not observed.</AbstractText The use of remimazolam to achieve sedation in Japanese patients undergoing colonoscopy was more effective than placebo.</AbstractText
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40340220
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37525862
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40503475
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[Study on the role and mechanism of Biochanin A in inflammatory response and cardiac remodeling after myocardial infarction in mice].
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Pathophysiology, Diagnosis, and Management of Takayasu Arteritis: A Review of Current Advances.
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Harnessing artificial intelligence to address immune response heterogeneity in low-dose radiation therapy.
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<b <b
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Takayasu arteritis (TA) is a rare, chronic, inflammatory vasculitis that primarily affects large arteries, causing significant morbidity and mortality. This review provides an overview of the pathophysiology, diagnosis, and management of TA based on current advances in the field. TA is characterized by autoimmune-mediated inflammation, vascular remodeling, and endothelial dysfunction. The disease progresses through three stages (active, chronic, and healing phase) each presenting distinct clinical features. Diagnosis of TA can be challenging due to non-specific clinical manifestations and the lack of specific diagnostic tests. Various imaging modalities, such as angiography, ultrasound, and Doppler techniques, play a crucial role in the diagnosis of TA by visualizing arterial involvement and assessing disease extent. Management of TA involves a multidisciplinary approach, with disease-modifying anti-rheumatic drugs (DMARDs) as the cornerstone of medical therapy. Synthetic and biologic DMARDs are used to induce remission, control inflammation, and prevent complications. Non-pharmacologic interventions, such as resistance exercises and curcumin supplementation, show potential benefits. Invasive interventions, including endovascular therapy and open surgery, are used for managing vascular lesions. However, challenges remain in disease understanding and management, including the heterogeneity of disease presentation and the lack of standardized treatment guidelines. The future of TA management lies in precision medicine, utilizing biomarkers and molecular profiling to personalize treatment approaches and improve patient outcomes. Further research is needed to unravel the underlying mechanisms of TA and develop targeted therapies.</AbstractText
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Low-dose radiation therapy has emerged as a promising modality for cancer treatment because of its ability to stimulate antitumor immune responses while minimizing damage to healthy tissues. However, the significant heterogeneity in immune responses among patients complicates its clinical application, hindering outcome prediction and treatment personalization. Artificial intelligence (AI) offers a transformative solution by integrating multidimensional data such as immunomics, radiomics, and clinical features to decode complex immune patterns and predict individual therapeutic outcomes. This editorial explored the potential of AI to address immune response heterogeneity in low-dose radiation therapy and proposed an AI-driven framework for precision immunotherapy. While promising, challenges, including data standardization, model interpretability, and clinical validation, must be overcome to ensure successful integration into oncological practice.</AbstractText
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[Study on the role and mechanism of Biochanin A in inflammatory response and cardiac remodeling after myocardial infarction in mice]. <b <b
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Pathophysiology, Diagnosis, and Management of Takayasu Arteritis: A Review of Current Advances. Takayasu arteritis (TA) is a rare, chronic, inflammatory vasculitis that primarily affects large arteries, causing significant morbidity and mortality. This review provides an overview of the pathophysiology, diagnosis, and management of TA based on current advances in the field. TA is characterized by autoimmune-mediated inflammation, vascular remodeling, and endothelial dysfunction. The disease progresses through three stages (active, chronic, and healing phase) each presenting distinct clinical features. Diagnosis of TA can be challenging due to non-specific clinical manifestations and the lack of specific diagnostic tests. Various imaging modalities, such as angiography, ultrasound, and Doppler techniques, play a crucial role in the diagnosis of TA by visualizing arterial involvement and assessing disease extent. Management of TA involves a multidisciplinary approach, with disease-modifying anti-rheumatic drugs (DMARDs) as the cornerstone of medical therapy. Synthetic and biologic DMARDs are used to induce remission, control inflammation, and prevent complications. Non-pharmacologic interventions, such as resistance exercises and curcumin supplementation, show potential benefits. Invasive interventions, including endovascular therapy and open surgery, are used for managing vascular lesions. However, challenges remain in disease understanding and management, including the heterogeneity of disease presentation and the lack of standardized treatment guidelines. The future of TA management lies in precision medicine, utilizing biomarkers and molecular profiling to personalize treatment approaches and improve patient outcomes. Further research is needed to unravel the underlying mechanisms of TA and develop targeted therapies.</AbstractText
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Harnessing artificial intelligence to address immune response heterogeneity in low-dose radiation therapy. Low-dose radiation therapy has emerged as a promising modality for cancer treatment because of its ability to stimulate antitumor immune responses while minimizing damage to healthy tissues. However, the significant heterogeneity in immune responses among patients complicates its clinical application, hindering outcome prediction and treatment personalization. Artificial intelligence (AI) offers a transformative solution by integrating multidimensional data such as immunomics, radiomics, and clinical features to decode complex immune patterns and predict individual therapeutic outcomes. This editorial explored the potential of AI to address immune response heterogeneity in low-dose radiation therapy and proposed an AI-driven framework for precision immunotherapy. While promising, challenges, including data standardization, model interpretability, and clinical validation, must be overcome to ensure successful integration into oncological practice.</AbstractText
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39241971
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38150045
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40698103
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Effects and mechanisms of harmine on ameliorating ethanol-induced memory impairment.
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Roles of Macrophages and Their Interactions with Schwann Cells After Peripheral Nerve Injury.
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Orbital venous lymphatic malformations: case series on minimally invasive treatment approach.
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Peganum harmala L., a traditional Uyghur ethnic medicine widely used in China, is commonly used in the treatment of conditions such as hemiplegia, forgetfulness, cough, and asthma. Harmine and other β-carboline alkaloids, one of the main active ingredients in P. harmala, have exhibited various pharmacological activities, including anti-Alzheimer's, antidepressant, anti-inflammatory, and antioxidant effects. However, the effects and underlying mechanisms of harmine on improving ethanol-induced memory impairment remain unclear.</AbstractText This study aimed to investigate the effects of harmine on ameliorating ethanol-induced memory impairment, and to explore potential mechanisms.</AbstractText Ethanol (30%, i. g.) was used to induce memory impairment model. The effect of harmine on memory impairment was evaluated by Morris water maze (MWM). The histopathological analysis, immunofluorescence staining, RT-qPCR and UHPLC-MS/MS methods were performed to further investigate the underlying mechanisms.</AbstractText MWM experiments showed that harmine significantly improved ethanol-induced spatial learning memory deficit. Harmine exhibited anti-inflammatory effect by downregulating inflammatory factors such as IL-6, IL-1β and tumor necrosis factor-α (TNF-α) induced by ethanol. Harmine also upregulated brain-derived neurotrophic factor (BDNF) levels to exert neuroprotective effect. Moreover, harmine protected neuronal cells and increased the protein expression of myelin basic protein (MBP). The cellular results indicated that harmine protected SH-SY5Y cells from ethanol-induced cytotoxicity and upregulated the relative mRNA expression of synaptosome associated protein 25 (SNAP25), syntaxin 1 A (STX1A), vesicle associated membrane protein 2 (VAMP2), synaptotagmin 1 (SYT1) and synaptophysin (SYP).</AbstractText Harmine improved ethanol-induced memory impairment by ameliorating inflammation, increasing BDNF levels, promoting synaptic vesicle fusion, protecting myelin sheath, and modulating neurotransmitter levels. These findings provided a scientific basis for development of therapeutic drugs for alcohol-induced memory impairments and other related disorders.</AbstractText
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The adult peripheral nervous system has a significant ability for regeneration compared to the central nervous system. This is related to the unique neuroimmunomodulation after peripheral nerve injury (PNI). Unlike the repair of other tissues after injury, Schwann cells (SCs) respond immediately to the trauma and send out signals to precisely recruit macrophages to the injured site. Then, macrophages promote the degradation of the damaged myelin sheath by phagocytosis of local debris. At the same time, macrophages and SCs jointly secrete various cytokines to reconstruct a microenvironment suitable for nerve regeneration. This unique pathophysiological process associated with macrophages provides important targets for the repair and treatment of PNI, as well as an important reference for guiding the repair of other nerve injuries. To understand these processes more systematically, this paper describes the characteristics of macrophage activation and metabolism in PNI, discusses the underlying molecular mechanism of interaction between macrophages and SCs, and reviews the latest research progress of crosstalk regulation between macrophages and SCs. These concepts and therapeutic strategies are summarized to provide a reference for the more effective use of macrophages in the repair of PNI.</AbstractText
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Orbital venous lymphatic malformations or lymphangiomas are choristomas of the orbit. Common in the pediatric population, the lesion is notorious for spreading into various anatomical spaces due to its infiltrative nature. Additionally, the vascular nature poses challenges to complete removal. Hemorrhages are not uncommon in the lesion, which may result in permanently compromised ocular function. Medical management involves injecting sclerosant into the cystic areas of the lesion, resulting in shrinkage and collapse, followed by total excision, which is the most suitable treatment option. The authors present a series of cases in which lymphangiomas have been completely excised using this minimal manipulative approach.</AbstractText
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Effects and mechanisms of harmine on ameliorating ethanol-induced memory impairment. Peganum harmala L., a traditional Uyghur ethnic medicine widely used in China, is commonly used in the treatment of conditions such as hemiplegia, forgetfulness, cough, and asthma. Harmine and other β-carboline alkaloids, one of the main active ingredients in P. harmala, have exhibited various pharmacological activities, including anti-Alzheimer's, antidepressant, anti-inflammatory, and antioxidant effects. However, the effects and underlying mechanisms of harmine on improving ethanol-induced memory impairment remain unclear.</AbstractText This study aimed to investigate the effects of harmine on ameliorating ethanol-induced memory impairment, and to explore potential mechanisms.</AbstractText Ethanol (30%, i. g.) was used to induce memory impairment model. The effect of harmine on memory impairment was evaluated by Morris water maze (MWM). The histopathological analysis, immunofluorescence staining, RT-qPCR and UHPLC-MS/MS methods were performed to further investigate the underlying mechanisms.</AbstractText MWM experiments showed that harmine significantly improved ethanol-induced spatial learning memory deficit. Harmine exhibited anti-inflammatory effect by downregulating inflammatory factors such as IL-6, IL-1β and tumor necrosis factor-α (TNF-α) induced by ethanol. Harmine also upregulated brain-derived neurotrophic factor (BDNF) levels to exert neuroprotective effect. Moreover, harmine protected neuronal cells and increased the protein expression of myelin basic protein (MBP). The cellular results indicated that harmine protected SH-SY5Y cells from ethanol-induced cytotoxicity and upregulated the relative mRNA expression of synaptosome associated protein 25 (SNAP25), syntaxin 1 A (STX1A), vesicle associated membrane protein 2 (VAMP2), synaptotagmin 1 (SYT1) and synaptophysin (SYP).</AbstractText Harmine improved ethanol-induced memory impairment by ameliorating inflammation, increasing BDNF levels, promoting synaptic vesicle fusion, protecting myelin sheath, and modulating neurotransmitter levels. These findings provided a scientific basis for development of therapeutic drugs for alcohol-induced memory impairments and other related disorders.</AbstractText
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Roles of Macrophages and Their Interactions with Schwann Cells After Peripheral Nerve Injury. The adult peripheral nervous system has a significant ability for regeneration compared to the central nervous system. This is related to the unique neuroimmunomodulation after peripheral nerve injury (PNI). Unlike the repair of other tissues after injury, Schwann cells (SCs) respond immediately to the trauma and send out signals to precisely recruit macrophages to the injured site. Then, macrophages promote the degradation of the damaged myelin sheath by phagocytosis of local debris. At the same time, macrophages and SCs jointly secrete various cytokines to reconstruct a microenvironment suitable for nerve regeneration. This unique pathophysiological process associated with macrophages provides important targets for the repair and treatment of PNI, as well as an important reference for guiding the repair of other nerve injuries. To understand these processes more systematically, this paper describes the characteristics of macrophage activation and metabolism in PNI, discusses the underlying molecular mechanism of interaction between macrophages and SCs, and reviews the latest research progress of crosstalk regulation between macrophages and SCs. These concepts and therapeutic strategies are summarized to provide a reference for the more effective use of macrophages in the repair of PNI.</AbstractText
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Orbital venous lymphatic malformations: case series on minimally invasive treatment approach. Orbital venous lymphatic malformations or lymphangiomas are choristomas of the orbit. Common in the pediatric population, the lesion is notorious for spreading into various anatomical spaces due to its infiltrative nature. Additionally, the vascular nature poses challenges to complete removal. Hemorrhages are not uncommon in the lesion, which may result in permanently compromised ocular function. Medical management involves injecting sclerosant into the cystic areas of the lesion, resulting in shrinkage and collapse, followed by total excision, which is the most suitable treatment option. The authors present a series of cases in which lymphangiomas have been completely excised using this minimal manipulative approach.</AbstractText
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40766112
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37735106
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40519252
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Enhancing Radiation Oncology Training through Patient Advocate Integration.
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'We are suffering. Nothing is changing.' Black mother's experiences, communication, and support in the neonatal intensive care unit in the United States: A Qualitative Study.
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Human Neural Stem Cells Reduce Hypoxia-Ischemic Neurological Impairment Through the Regulation of Inflammatory M1/M2 Microglias in Rats.
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Patient advocates represent the voice of the patient community and bring a unique perspective to research. We hypothesized that including patient advocates in research training would increase trainees ability to communicate their science, understand the impact of their work and increase their empathy for patients.</AbstractText An IRB-approved survey was administered to assess the impact of patient advocate feedback on trainees who presented their research via posters at our Radiation Oncology Research Symposium. Trainees reported demographics and self-assessed their use of lay language, changes in empathy, understanding the impact of their research, and potential future implications. The binomial proportion test and Fisher's exact test were used to determine significance.</AbstractText The survey was completed by 80% (28/35) of trainees who participated in the poster session and interacted with patient advocates. Trainees were predominantly younger (60.7% under 30yo) and people of color (60.7%). Almost all trainees (96.4%) were comfortable talking to advocates but only 89.29% were comfortable using lay language. Trainees agreed (75%) that interacting with advocates increased their empathy. Most trainees (71.4%) believed patient advocates helped them understand the significance of their research and 64.3% believed advocates helped them develop new research ideas. Most trainees would like advocates at future poster presentations (85.7%), but did not want them to participate in study design or analysis. Gender and training level did not affect trainees' ability to communicate in lay language, their empathy for patients, or understanding of their work's clinical relevance.</AbstractText Including patient advocates in poster sessions may improve trainees ability to present their research in lay language, increase their empathy and understand the clinical impact of their research. Future radiation oncology training should consider including the patient advocate voice to improve the tangible connection between research and real-world impact.</AbstractText
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Black mothers experience markedly disproportionate maternal morbidity and mortality in the United States, with racism often cited as the root cause manifesting through several pathways. The study examined Black mothers' perceived provider communication, support needs, and overall experiences in the neonatal intensive care unit (NICU).</AbstractText This study used grounded theory embedded in the Black feminist theoretical (BFT) framework to generate new ideas grounded in the data. Data was collected through semi-structured interviews using videoconferencing, with questions related to the mother's overall NICU experiences, communication within the NICU, and perceived support needs. Data were analyzed using thematic analysis.</AbstractText Twelve mothers participated in the study; most were married (<i The study adds to the growing literature championing Black maternal health equity and multilevel quality improvement strategies to foster equitable maternal health. Our study reinforces the need for racially congruent interventions and policy reformations to protect Black birthing people regardless of socioeconomic factors and social class using life course, holistic approaches, and intersectionality mindset. Importantly, using the BFT, this study calls for culturally sensitive research to capture the nuances associated with the multiplicity of experiences of Black people.</AbstractText
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This study aims to investigate the therapeutic efficacy and migration of human neural stem cell (hNSC) therapy in a rat model of moderate to severe Hypoxic-ischemic encephalopathy (HIE).</AbstractText hNSCs were transplanted into the brain ventricle of HIE-induced rats. The levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), immunohistochemistry of M1 and M2 cells counts, as well as the apoptosis of hNSCs were conducted after 10 days transplantation. Furthermore, Hematoxylin-eosin (HE) staining and neurological function was assessed at 12 weeks post-implantation.</AbstractText After implantation, hNSCs survived for a duration of 12 weeks. After 10 days post-implantation, extensive migration of hNSCs was observed, with a higher concentration detected in the injured hemisphere of the brain. This study also noted an upregulation in the expression levels of VEGF and BDNF in rats treated with hNSCs (<i hNSCs exerted beneficial effects on brain damage recovery and apoptosis suppression via paracrine actions of VEGF and BDNF, M1/M2 microglial balance regulation, cell differentiation promotion. The study underlined the potential of hNSC implantation as a prospective neonatal HIE treatment strategy.</AbstractText
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Enhancing Radiation Oncology Training through Patient Advocate Integration. Patient advocates represent the voice of the patient community and bring a unique perspective to research. We hypothesized that including patient advocates in research training would increase trainees ability to communicate their science, understand the impact of their work and increase their empathy for patients.</AbstractText An IRB-approved survey was administered to assess the impact of patient advocate feedback on trainees who presented their research via posters at our Radiation Oncology Research Symposium. Trainees reported demographics and self-assessed their use of lay language, changes in empathy, understanding the impact of their research, and potential future implications. The binomial proportion test and Fisher's exact test were used to determine significance.</AbstractText The survey was completed by 80% (28/35) of trainees who participated in the poster session and interacted with patient advocates. Trainees were predominantly younger (60.7% under 30yo) and people of color (60.7%). Almost all trainees (96.4%) were comfortable talking to advocates but only 89.29% were comfortable using lay language. Trainees agreed (75%) that interacting with advocates increased their empathy. Most trainees (71.4%) believed patient advocates helped them understand the significance of their research and 64.3% believed advocates helped them develop new research ideas. Most trainees would like advocates at future poster presentations (85.7%), but did not want them to participate in study design or analysis. Gender and training level did not affect trainees' ability to communicate in lay language, their empathy for patients, or understanding of their work's clinical relevance.</AbstractText Including patient advocates in poster sessions may improve trainees ability to present their research in lay language, increase their empathy and understand the clinical impact of their research. Future radiation oncology training should consider including the patient advocate voice to improve the tangible connection between research and real-world impact.</AbstractText
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'We are suffering. Nothing is changing.' Black mother's experiences, communication, and support in the neonatal intensive care unit in the United States: A Qualitative Study. Black mothers experience markedly disproportionate maternal morbidity and mortality in the United States, with racism often cited as the root cause manifesting through several pathways. The study examined Black mothers' perceived provider communication, support needs, and overall experiences in the neonatal intensive care unit (NICU).</AbstractText This study used grounded theory embedded in the Black feminist theoretical (BFT) framework to generate new ideas grounded in the data. Data was collected through semi-structured interviews using videoconferencing, with questions related to the mother's overall NICU experiences, communication within the NICU, and perceived support needs. Data were analyzed using thematic analysis.</AbstractText Twelve mothers participated in the study; most were married (<i The study adds to the growing literature championing Black maternal health equity and multilevel quality improvement strategies to foster equitable maternal health. Our study reinforces the need for racially congruent interventions and policy reformations to protect Black birthing people regardless of socioeconomic factors and social class using life course, holistic approaches, and intersectionality mindset. Importantly, using the BFT, this study calls for culturally sensitive research to capture the nuances associated with the multiplicity of experiences of Black people.</AbstractText
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Human Neural Stem Cells Reduce Hypoxia-Ischemic Neurological Impairment Through the Regulation of Inflammatory M1/M2 Microglias in Rats. This study aims to investigate the therapeutic efficacy and migration of human neural stem cell (hNSC) therapy in a rat model of moderate to severe Hypoxic-ischemic encephalopathy (HIE).</AbstractText hNSCs were transplanted into the brain ventricle of HIE-induced rats. The levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), immunohistochemistry of M1 and M2 cells counts, as well as the apoptosis of hNSCs were conducted after 10 days transplantation. Furthermore, Hematoxylin-eosin (HE) staining and neurological function was assessed at 12 weeks post-implantation.</AbstractText After implantation, hNSCs survived for a duration of 12 weeks. After 10 days post-implantation, extensive migration of hNSCs was observed, with a higher concentration detected in the injured hemisphere of the brain. This study also noted an upregulation in the expression levels of VEGF and BDNF in rats treated with hNSCs (<i hNSCs exerted beneficial effects on brain damage recovery and apoptosis suppression via paracrine actions of VEGF and BDNF, M1/M2 microglial balance regulation, cell differentiation promotion. The study underlined the potential of hNSC implantation as a prospective neonatal HIE treatment strategy.</AbstractText
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39462660
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26973458
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39437792
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[Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice].
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Enrichment of GABAA Receptor α-Subunits on the Axonal Initial Segment Shows Regional Differences.
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Increased cholesterol synthesis drives neurotoxicity in patient stem cell-derived model of multiple sclerosis.
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Ischemic stroke often leads to cognitive dysfunction, which delays the recovery process of patients. However, its pathogenesis is not yet clear. In this study, the cerebral ischemia-reperfusion model was built as the experimental object, and the hippocampal dentate gyrus (DG) was the target brain area. TTC staining was used to evaluate the degree of cerebral infarction, and nerve cell membrane potentials and local field potentials (LFPs) signals were collected to explore the mechanism of cognitive impairment in ischemia-reperfusion mice. The results showed that the infarcted area on the right side of the brain of the mice in the model group was white. The resting membrane potential, the number of action potential discharges, the post-hyperpolarization potential and the maximum ascending slope of the hippocampal DG nerve cells in the model mice were significantly lower than those in the control group ( <i 缺血性卒中常会引起认知功能障碍，从而延缓了患者的康复进程，然而，其发病机制尚未明确。本文以脑缺血再灌注模型为实验对象，以海马齿状回（DG）为目标脑区，TTC染色评估脑梗死程度，采集神经元膜电位和局部场电位（LFPs）信号，旨在探究脑缺血再灌注小鼠认知功能的损伤机制。结果发现，模型组小鼠大脑右侧梗死区呈白色；该模型小鼠海马DG神经元静息膜电位、动作电位放电个数、后超极化电位和最大上升斜率显著低于对照组（ <i
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Although it is generally recognized that certain α-subunits of γ-aminobutyric acid type A receptors (GABAARs) form enriched clusters on the axonal initial segment (AIS), the degree to which these clusters vary in different brain areas is not well known. In the current study, we quantified the density, size, and enrichment ratio of fluorescently labeled α1-, α2-, or α3-subunits aggregates co-localized with the AIS-marker ankyrin G and compared them to aggregates in non-AIS locations among different brain areas including hippocampal subfields, basal lateral amygdala (BLA), prefrontal cortex (PFC), and sensory cortex (CTX). We found regional differences in the enrichment of GABAAR α-subunits on the AIS. Significant enrichment was identified in the CA3 of hippocampus for α1-subunits, in the CA1, CA3, and BLA for α2-subunits, and in the BLA for α3-subunits. Using α-subunit knock-out (KO) mice, we found that BLA enrichment of α2- and α3-subunits were physiologically independent of each other, as the enrichment of one subunit was unaffected by the genomic deletion of the other. To further investigate the unique pattern of α-subunit enrichment in the BLA, we examined the association of α2- and α3-subunits with the presynaptic vesicular GABA transporter (vGAT) and the anchoring protein gephyrin (Geph). As expected, both α2- and α3-subunits on the AIS within the BLA received prominent GABAergic innervation from vGAT-positive terminals. Further, we found that the association of α2- and α3-subunits with Geph was weaker in AIS versus non-AIS locations, suggesting that Geph might be playing a lesser role in the enrichment of α2- and α3-subunits on the AIS. Overall, these observations suggest that GABAARs on the AIS differ in subunit composition across brain regions. As with somatodendritic GABAARs, the distinctive expression pattern of AIS-located GABAAR α-subunits in the BLA, and other brain areas, likely contribute to unique forms of GABAergic inhibitory transmission and pharmacological profiles seen in different brain areas.</AbstractText
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Senescent neural progenitor cells have been identified in brain lesions of people with progressive multiple sclerosis (PMS). However, their role in disease pathobiology and contribution to the lesion environment remains unclear. By establishing directly induced neural stem/progenitor cell (iNSC) lines from PMS patient fibroblasts, we studied their senescent phenotype in vitro. Senescence was strongly associated with inflammatory signaling, hypermetabolism, and the senescence-associated secretory phenotype (SASP). PMS-derived iNSCs displayed increased glucose-dependent fatty acid and cholesterol synthesis, which resulted in the accumulation of lipid droplets. A 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR)-mediated lipogenic state was found to induce a SASP in PMS iNSCs via cholesterol-dependent transcription factors. SASP from PMS iNSC lines induced neurotoxicity in mature neurons, and treatment with the HMGCR inhibitor simvastatin altered the PMS iNSC SASP, promoting cytoprotective qualities and reducing neurotoxicity. Our findings suggest a disease-associated, cholesterol-related, hypermetabolic phenotype of PMS iNSCs that leads to neurotoxic signaling and is rescuable pharmacologically.</AbstractText
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[Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice]. Ischemic stroke often leads to cognitive dysfunction, which delays the recovery process of patients. However, its pathogenesis is not yet clear. In this study, the cerebral ischemia-reperfusion model was built as the experimental object, and the hippocampal dentate gyrus (DG) was the target brain area. TTC staining was used to evaluate the degree of cerebral infarction, and nerve cell membrane potentials and local field potentials (LFPs) signals were collected to explore the mechanism of cognitive impairment in ischemia-reperfusion mice. The results showed that the infarcted area on the right side of the brain of the mice in the model group was white. The resting membrane potential, the number of action potential discharges, the post-hyperpolarization potential and the maximum ascending slope of the hippocampal DG nerve cells in the model mice were significantly lower than those in the control group ( <i 缺血性卒中常会引起认知功能障碍，从而延缓了患者的康复进程，然而，其发病机制尚未明确。本文以脑缺血再灌注模型为实验对象，以海马齿状回（DG）为目标脑区，TTC染色评估脑梗死程度，采集神经元膜电位和局部场电位（LFPs）信号，旨在探究脑缺血再灌注小鼠认知功能的损伤机制。结果发现，模型组小鼠大脑右侧梗死区呈白色；该模型小鼠海马DG神经元静息膜电位、动作电位放电个数、后超极化电位和最大上升斜率显著低于对照组（ <i
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Enrichment of GABAA Receptor α-Subunits on the Axonal Initial Segment Shows Regional Differences. Although it is generally recognized that certain α-subunits of γ-aminobutyric acid type A receptors (GABAARs) form enriched clusters on the axonal initial segment (AIS), the degree to which these clusters vary in different brain areas is not well known. In the current study, we quantified the density, size, and enrichment ratio of fluorescently labeled α1-, α2-, or α3-subunits aggregates co-localized with the AIS-marker ankyrin G and compared them to aggregates in non-AIS locations among different brain areas including hippocampal subfields, basal lateral amygdala (BLA), prefrontal cortex (PFC), and sensory cortex (CTX). We found regional differences in the enrichment of GABAAR α-subunits on the AIS. Significant enrichment was identified in the CA3 of hippocampus for α1-subunits, in the CA1, CA3, and BLA for α2-subunits, and in the BLA for α3-subunits. Using α-subunit knock-out (KO) mice, we found that BLA enrichment of α2- and α3-subunits were physiologically independent of each other, as the enrichment of one subunit was unaffected by the genomic deletion of the other. To further investigate the unique pattern of α-subunit enrichment in the BLA, we examined the association of α2- and α3-subunits with the presynaptic vesicular GABA transporter (vGAT) and the anchoring protein gephyrin (Geph). As expected, both α2- and α3-subunits on the AIS within the BLA received prominent GABAergic innervation from vGAT-positive terminals. Further, we found that the association of α2- and α3-subunits with Geph was weaker in AIS versus non-AIS locations, suggesting that Geph might be playing a lesser role in the enrichment of α2- and α3-subunits on the AIS. Overall, these observations suggest that GABAARs on the AIS differ in subunit composition across brain regions. As with somatodendritic GABAARs, the distinctive expression pattern of AIS-located GABAAR α-subunits in the BLA, and other brain areas, likely contribute to unique forms of GABAergic inhibitory transmission and pharmacological profiles seen in different brain areas.</AbstractText
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Increased cholesterol synthesis drives neurotoxicity in patient stem cell-derived model of multiple sclerosis. Senescent neural progenitor cells have been identified in brain lesions of people with progressive multiple sclerosis (PMS). However, their role in disease pathobiology and contribution to the lesion environment remains unclear. By establishing directly induced neural stem/progenitor cell (iNSC) lines from PMS patient fibroblasts, we studied their senescent phenotype in vitro. Senescence was strongly associated with inflammatory signaling, hypermetabolism, and the senescence-associated secretory phenotype (SASP). PMS-derived iNSCs displayed increased glucose-dependent fatty acid and cholesterol synthesis, which resulted in the accumulation of lipid droplets. A 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR)-mediated lipogenic state was found to induce a SASP in PMS iNSCs via cholesterol-dependent transcription factors. SASP from PMS iNSC lines induced neurotoxicity in mature neurons, and treatment with the HMGCR inhibitor simvastatin altered the PMS iNSC SASP, promoting cytoprotective qualities and reducing neurotoxicity. Our findings suggest a disease-associated, cholesterol-related, hypermetabolic phenotype of PMS iNSCs that leads to neurotoxic signaling and is rescuable pharmacologically.</AbstractText
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39800126
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26925435
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39880153
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3DSlicer software-assisted neuroendoscopic surgery compared with traditional surgery on surgical effects, complications, and safety evaluation in patients with intracerebral hemorrhage: A systematic review and meta-analysis.
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Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration.
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Constructal thermodynamics and its semantic ontology in autopoietic, digital, and computational architectural and urban space open systems.
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This study aims to comprehensively evaluate the complications, effectiveness, and safety of neuroendoscopic surgery (NS) assisted by 3DSlicer software, compared to traditional surgery in patients with intracerebral hemorrhage (IH).</AbstractText We searched for case-control trials from the Chinese Biomedical Literature data (CBM) online database, Wanfang Database, EMBASE, VIP Full-text Database, China National Knowledge Infrastructure (CNKI), Science Direct, Cochrane Library, and PubMed. The studies, published since January 2010, involved NS or traditional surgery for IH patients assisted by 3DSlicer software. Data were independently retrieved by two researchers, and the risk of bias in each study was evaluated using the Cochrane Handbook 5.3 standard.</AbstractText A total of 591 patients from seven controlled clinical studies were included. Fixed-effect model analysis revealed a significantly higher treatment effectiveness rate in the study group (SG) (P < 0.05). Random-effects model (REM) analysis indicated that the operation time in the SG was significantly shorter (P < 0.05). Furthermore, the SG group experienced significantly shorter hospitalization time (P < 0.05). NIHSS scores in the SG were notably lower (P < 0.05). Fixed-effect model analysis also showed that the incidence of postoperative complications in the SG was significantly lower (P < 0.05).</AbstractText Neuroendoscopic surgery assisted by 3DSlicer software is more effective in treating IH, enhancing prognosis, improving neurological function, and reducing complication rates. This approach appears to be a promising candidate for clinical adoption.</AbstractText
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There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by <i
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This paper explores the intersections of constructal thermodynamics, and its semantic ontology within the context of autopoietic, digital and computational design in protocell inspired numerical architectural and urban narratives that are examined here as open systems. Constructal law is the thermodynamic theory based on the analysis of fluxes across the boundaries of an open system. Protocells, as dynamic, autopoietic and adaptive open finite size systems, serve in this paper as a compelling metaphor and design model for responsive and sustainable manmade architectural and urban environments. The ability of protocells to harness energy, minimize entropy, and adapt to environmental changes mirrors the principles of constructal thermodynamics, which govern the flow and distribution of resources in complex self-organizing information open systems in nature. By applying these principles to digital architecture, this study investigates how relational dynamics between spaces, materials, and functions can create adaptive designs that "go with the flow" of ecological and cultural systems. The research demonstrates using the Gouy-Stodola theorem as a variational principle, how protocell-inspired processes facilitate exergy-efficient designs, minimizing waste while maximizing resilience and flexibility. The present paper argues -through an applied case study- for a paradigm where protocell digital architecture serves not only as an ecological and material model but mainly as a spatial narrative driver, blending constructal and digital tools with cultural mythos. Finally, this paper exploring simultaneously the semantic complexity and ontology of such systems, in turn, connects these constructal driven digital designs to broader poly-narratives, embedding cultural, symbolic, philosophical and functional predicates into architectural forms.</AbstractText
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3DSlicer software-assisted neuroendoscopic surgery compared with traditional surgery on surgical effects, complications, and safety evaluation in patients with intracerebral hemorrhage: A systematic review and meta-analysis. This study aims to comprehensively evaluate the complications, effectiveness, and safety of neuroendoscopic surgery (NS) assisted by 3DSlicer software, compared to traditional surgery in patients with intracerebral hemorrhage (IH).</AbstractText We searched for case-control trials from the Chinese Biomedical Literature data (CBM) online database, Wanfang Database, EMBASE, VIP Full-text Database, China National Knowledge Infrastructure (CNKI), Science Direct, Cochrane Library, and PubMed. The studies, published since January 2010, involved NS or traditional surgery for IH patients assisted by 3DSlicer software. Data were independently retrieved by two researchers, and the risk of bias in each study was evaluated using the Cochrane Handbook 5.3 standard.</AbstractText A total of 591 patients from seven controlled clinical studies were included. Fixed-effect model analysis revealed a significantly higher treatment effectiveness rate in the study group (SG) (P < 0.05). Random-effects model (REM) analysis indicated that the operation time in the SG was significantly shorter (P < 0.05). Furthermore, the SG group experienced significantly shorter hospitalization time (P < 0.05). NIHSS scores in the SG were notably lower (P < 0.05). Fixed-effect model analysis also showed that the incidence of postoperative complications in the SG was significantly lower (P < 0.05).</AbstractText Neuroendoscopic surgery assisted by 3DSlicer software is more effective in treating IH, enhancing prognosis, improving neurological function, and reducing complication rates. This approach appears to be a promising candidate for clinical adoption.</AbstractText
|
Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration. There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by <i
|
Constructal thermodynamics and its semantic ontology in autopoietic, digital, and computational architectural and urban space open systems. This paper explores the intersections of constructal thermodynamics, and its semantic ontology within the context of autopoietic, digital and computational design in protocell inspired numerical architectural and urban narratives that are examined here as open systems. Constructal law is the thermodynamic theory based on the analysis of fluxes across the boundaries of an open system. Protocells, as dynamic, autopoietic and adaptive open finite size systems, serve in this paper as a compelling metaphor and design model for responsive and sustainable manmade architectural and urban environments. The ability of protocells to harness energy, minimize entropy, and adapt to environmental changes mirrors the principles of constructal thermodynamics, which govern the flow and distribution of resources in complex self-organizing information open systems in nature. By applying these principles to digital architecture, this study investigates how relational dynamics between spaces, materials, and functions can create adaptive designs that "go with the flow" of ecological and cultural systems. The research demonstrates using the Gouy-Stodola theorem as a variational principle, how protocell-inspired processes facilitate exergy-efficient designs, minimizing waste while maximizing resilience and flexibility. The present paper argues -through an applied case study- for a paradigm where protocell digital architecture serves not only as an ecological and material model but mainly as a spatial narrative driver, blending constructal and digital tools with cultural mythos. Finally, this paper exploring simultaneously the semantic complexity and ontology of such systems, in turn, connects these constructal driven digital designs to broader poly-narratives, embedding cultural, symbolic, philosophical and functional predicates into architectural forms.</AbstractText
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35557617
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31976837
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37143993
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Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality.
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Current and Future Neuropharmacological Options for the Treatment of Essential Tremor.
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Cervical vestibular evoked myogenic potentials in healthy children: Normative values for bone and air conduction.
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Sleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET.</AbstractText We enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted.</AbstractText Global network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (<i Our findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.</AbstractText
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Essential Tremor (ET) is likely the most frequent movement disorder. In this review, we have summarized the current pharmacological options for the treatment of this disorder and discussed several future options derived from drugs tested in experimental models of ET or from neuropathological data.</AbstractText A literature search was performed on the pharmacology of essential tremors using PubMed Database from 1966 to July 31, 2019.</AbstractText To date, the beta-blocker propranolol and the antiepileptic drug primidone are the drugs that have shown higher efficacy in the treatment of ET. Other drugs tested in ET patients have shown different degrees of efficacy or have not been useful.</AbstractText Injections of botulinum toxin A could be useful in the treatment of some patients with ET refractory to pharmacotherapy. According to recent neurochemical data, drugs acting on the extrasynaptic GABAA receptors, the glutamatergic system or LINGO-1 could be interesting therapeutic options in the future.</AbstractText
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To characterize cervical vestibular evoked myogenic potentials (c-VEMPs) in bone conduction (BC) and air conduction (AC) in healthy children, to compare the responses to adults and to provide normative values according to age and sex.</AbstractText Observational study in a large cohort of healthy children (<i In children, the amplitude ratios of AC and BC c-VEMP were correlated (<i The present study provides age- and sex-specific normative data for c-VEMP for children (6 months to 15 years of age) for AC and BC stimulation. Up to the age of 15 years, c-VEMP responses can be obtained equally well with both stimulation modes. Thus, BC represents a valid alternative for vestibular otolith testing, especially in case of air conduction disorders.</AbstractText
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Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality. Sleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET.</AbstractText We enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted.</AbstractText Global network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (<i Our findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.</AbstractText
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Current and Future Neuropharmacological Options for the Treatment of Essential Tremor. Essential Tremor (ET) is likely the most frequent movement disorder. In this review, we have summarized the current pharmacological options for the treatment of this disorder and discussed several future options derived from drugs tested in experimental models of ET or from neuropathological data.</AbstractText A literature search was performed on the pharmacology of essential tremors using PubMed Database from 1966 to July 31, 2019.</AbstractText To date, the beta-blocker propranolol and the antiepileptic drug primidone are the drugs that have shown higher efficacy in the treatment of ET. Other drugs tested in ET patients have shown different degrees of efficacy or have not been useful.</AbstractText Injections of botulinum toxin A could be useful in the treatment of some patients with ET refractory to pharmacotherapy. According to recent neurochemical data, drugs acting on the extrasynaptic GABAA receptors, the glutamatergic system or LINGO-1 could be interesting therapeutic options in the future.</AbstractText
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Cervical vestibular evoked myogenic potentials in healthy children: Normative values for bone and air conduction. To characterize cervical vestibular evoked myogenic potentials (c-VEMPs) in bone conduction (BC) and air conduction (AC) in healthy children, to compare the responses to adults and to provide normative values according to age and sex.</AbstractText Observational study in a large cohort of healthy children (<i In children, the amplitude ratios of AC and BC c-VEMP were correlated (<i The present study provides age- and sex-specific normative data for c-VEMP for children (6 months to 15 years of age) for AC and BC stimulation. Up to the age of 15 years, c-VEMP responses can be obtained equally well with both stimulation modes. Thus, BC represents a valid alternative for vestibular otolith testing, especially in case of air conduction disorders.</AbstractText
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17222724
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15163813
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17934605
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MRI of tarantulas: morphological and perfusion imaging.
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Quantitative analysis of focal masses at MR imaging: a plea for standardization.
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[Cochlear implant: hearing and language in pre-lingual deaf children].
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This paper describes a study performed to evaluate the feasibility of using a 1.5-T whole-body magnetic resonance imaging (MRI) equipment, in combination with pharmacokinetic modeling, to obtain in vivo information about the morphology and perfusion of tarantulas (Eurypelma californicum). MRI was performed on three tarantulas using spin-echo sequences for morphological imaging and a rapid spoiled gradient-echo sequence for dynamic imaging during and after contrast medium (CM; Gd-DTPA) injection. Signal enhancement in dynamic measurements was evaluated with a pharmacokinetic two-compartment model. Spin-echo images showed morphological structures well. Dynamic images were of sufficient quality and allowed a model analysis of CM kinetics, which provides information about regional perfusion. In conclusion, morphological and dynamic contrast-enhanced MRI of tarantulas is feasible with a conventional clinical scanner. Studies of this kind are therefore possible without a dedicated high-field animal scanner.</AbstractText
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To assess the effects of changing analytic method variables on the signal intensity (SI) difference-to-noise ratios (SDNRs) for the contrast between lesions and background organs depicted on magnetic resonance (MR) images and to propose a standardized analytic method for the quantitative analysis of focal masses seen at MR imaging.</AbstractText The SIs of 48 liver metastases (originating from colorectal cancer) in 20 patients, the surrounding liver parenchyma, and the background noise were measured on T2-weighted MR images. All 2000 and 2001 issues of the American Journal of Roentgenology, the Journal of Magnetic Resonance Imaging, Magnetic Resonance Imaging, and Radiology were searched for articles describing quantitative analyses. SDNRs were calculated by using formulas from these articles and various region-of-interest (ROI) locations to measure metastasis and background noise SIs. The Wilcoxon signed rank test was used to compare the various SDNR calculations.</AbstractText In 34 articles in which quantitative analyses of focal masses are described, the reported SDNRs were calculated with four different formulas. The SDNRs for our study material calculated with the four formulas reported in the literature differed grossly in both number and unit. The SDNRs for ROIs encompassing the entire metastasis differed significantly (P =.034) from the SDNRs for ROIs in a homogeneous area of the metastasis margin. Differences in SDNRs between various noise ROI locations were significant (P <.022).</AbstractText Slight changes in the variables of quantitative analysis of focal masses had marked effects on reported SDNRs. To overcome these effects, the use of a standardized method involving one formula, a lesion ROI in a homogeneous area at the metastasis margin, and a background noise ROI along the phase-encoding axis in the air (including systematic noise) is proposed for the quantitative analysis of findings on magnitude MR images.</AbstractText
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Cochlear implant in children, speech perception and oral language, hearing and oral language performance in children with pre-lingual profound sensory-neural hearing impairment, users of cochlear implant.</AbstractText To study the hearing and oral language performance of children with pre-lingual bilateral profound sensory neural hearing impairment, users of multi-channel cochlear implant considering the following aspects: age of the child when the research was carried out, time of hearing sensorial privation, time of cochlear implant use, type of cochlear implant, type of speech coding strategy used, familial permeability level in relation to the therapeutic process and cognitive style of the child.</AbstractText Participants of this study were 60 children who were assessed according to hearing and language categories. All of the variables were statistically analyzed. Psycho-social aspects, considering the child's cognitive style and the family's permeability level were also assessed.</AbstractText Regarding the hearing and language performance with the use of cochlear implant, the intermediate and advanced hearing categories were accomplished by more than half of the children. The statistically significant aspects in the performance of hearing and oral language were: the age of the child upon evaluation, time of hearing sensorial privation, time of cochlear implant use, type of implant, speech sounds coding strategy and familial permeability.</AbstractText The cochlear implant as a treatment for children with pre-lingual sensory-neural hearing impairment is highly effective, although complex, owing to the interaction of variables which interfere in the implanted child's performance. Further studies are needed for the understanding of the implantation complexity in young children.</AbstractText
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MRI of tarantulas: morphological and perfusion imaging. This paper describes a study performed to evaluate the feasibility of using a 1.5-T whole-body magnetic resonance imaging (MRI) equipment, in combination with pharmacokinetic modeling, to obtain in vivo information about the morphology and perfusion of tarantulas (Eurypelma californicum). MRI was performed on three tarantulas using spin-echo sequences for morphological imaging and a rapid spoiled gradient-echo sequence for dynamic imaging during and after contrast medium (CM; Gd-DTPA) injection. Signal enhancement in dynamic measurements was evaluated with a pharmacokinetic two-compartment model. Spin-echo images showed morphological structures well. Dynamic images were of sufficient quality and allowed a model analysis of CM kinetics, which provides information about regional perfusion. In conclusion, morphological and dynamic contrast-enhanced MRI of tarantulas is feasible with a conventional clinical scanner. Studies of this kind are therefore possible without a dedicated high-field animal scanner.</AbstractText
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Quantitative analysis of focal masses at MR imaging: a plea for standardization. To assess the effects of changing analytic method variables on the signal intensity (SI) difference-to-noise ratios (SDNRs) for the contrast between lesions and background organs depicted on magnetic resonance (MR) images and to propose a standardized analytic method for the quantitative analysis of focal masses seen at MR imaging.</AbstractText The SIs of 48 liver metastases (originating from colorectal cancer) in 20 patients, the surrounding liver parenchyma, and the background noise were measured on T2-weighted MR images. All 2000 and 2001 issues of the American Journal of Roentgenology, the Journal of Magnetic Resonance Imaging, Magnetic Resonance Imaging, and Radiology were searched for articles describing quantitative analyses. SDNRs were calculated by using formulas from these articles and various region-of-interest (ROI) locations to measure metastasis and background noise SIs. The Wilcoxon signed rank test was used to compare the various SDNR calculations.</AbstractText In 34 articles in which quantitative analyses of focal masses are described, the reported SDNRs were calculated with four different formulas. The SDNRs for our study material calculated with the four formulas reported in the literature differed grossly in both number and unit. The SDNRs for ROIs encompassing the entire metastasis differed significantly (P =.034) from the SDNRs for ROIs in a homogeneous area of the metastasis margin. Differences in SDNRs between various noise ROI locations were significant (P <.022).</AbstractText Slight changes in the variables of quantitative analysis of focal masses had marked effects on reported SDNRs. To overcome these effects, the use of a standardized method involving one formula, a lesion ROI in a homogeneous area at the metastasis margin, and a background noise ROI along the phase-encoding axis in the air (including systematic noise) is proposed for the quantitative analysis of findings on magnitude MR images.</AbstractText
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[Cochlear implant: hearing and language in pre-lingual deaf children]. Cochlear implant in children, speech perception and oral language, hearing and oral language performance in children with pre-lingual profound sensory-neural hearing impairment, users of cochlear implant.</AbstractText To study the hearing and oral language performance of children with pre-lingual bilateral profound sensory neural hearing impairment, users of multi-channel cochlear implant considering the following aspects: age of the child when the research was carried out, time of hearing sensorial privation, time of cochlear implant use, type of cochlear implant, type of speech coding strategy used, familial permeability level in relation to the therapeutic process and cognitive style of the child.</AbstractText Participants of this study were 60 children who were assessed according to hearing and language categories. All of the variables were statistically analyzed. Psycho-social aspects, considering the child's cognitive style and the family's permeability level were also assessed.</AbstractText Regarding the hearing and language performance with the use of cochlear implant, the intermediate and advanced hearing categories were accomplished by more than half of the children. The statistically significant aspects in the performance of hearing and oral language were: the age of the child upon evaluation, time of hearing sensorial privation, time of cochlear implant use, type of implant, speech sounds coding strategy and familial permeability.</AbstractText The cochlear implant as a treatment for children with pre-lingual sensory-neural hearing impairment is highly effective, although complex, owing to the interaction of variables which interfere in the implanted child's performance. Further studies are needed for the understanding of the implantation complexity in young children.</AbstractText
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40629690
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36209059
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40682349
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A coarse-grained model for simulations of phosphorylated disordered proteins.
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Anti-aging effect of β-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process.
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Painless ruptured pyomyoma causing an abdominal abscess in a postmenopausal woman with abdominal hypoesthesia.
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Protein phosphorylation is a common and essential post-translational modification that affects biochemical properties and regulates biological activities. Phosphorylation is particularly common for intrinsically disordered proteins and can significantly modulate their function and potential to interact with binding partners. To understand the biophysical origins of how phosphorylation of disordered proteins influences their function, it is valuable to investigate how the modifications lead to changes in their conformational ensembles. Here, we have used a top-down data-driven approach to develop a coarse-grained molecular dynamics model compatible with the CALVADOS protein simulation model to study the effects of serine and threonine phosphorylation on the global structural properties of disordered proteins. We parameterize the model using experimental data on the effects of phosphorylation on global dimensions. By comparing with baseline models and simulations using the phosphomimetics aspartate and glutamate, we show that the effect of phosphorylation on the global dimensions of disordered proteins is mostly driven by the additional charge. We envisage that our model can be applied to study the effects of phosphorylation of disordered proteins at the proteome scale as well as to study the important roles of protein phosphorylation on phase separation.</AbstractText
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Research on aging is growing as the elderly make up a greater share of the population, focusing on reversing and inhibiting the aging process. The exhaustion and senescence of stem cells are the fundamental drivers behind aging. β-Carotene has been depicted to have many biological functions, and we speculate that it may have an anti-aging effect.</AbstractText Firstly, the anti-aging property of β-carotene was investigated in vitro using mesenchymal stem cells (MSCs) induced by H<sub The in vitro experiment revealed that β-carotene could relieve the aging of MSCs, as evidenced by a series of aging marker molecules such as p16 and p21. β-Carotene appeared to inhibit aging by regulating the KAT7-P15 signaling axis. The in vivo experiment revealed that β-carotene treatment has significantly down-regulated the aging level of tissues and organs.</AbstractText In this work, we explored the anti-aging effect of β-carotene in vivo and in vitro. The experimental results indicate that β-carotene may be an important potential anti-aging molecule, which can be used as a drug or in functional food to treat aging in the future.</AbstractText
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Pyomyoma is a rare condition caused by an infection within a uterine leiomyoma. When ruptured, it can cause peritonitis with continuous abdominal pain, potentially leading to life-threatening conditions. However, abdominal pain may be absent in patients with abdominal hypoesthesia. We report a case of painless ruptured pyomyoma causing an abdominal abscess in a 60-year-old woman with abdominal hypoesthesia. The patient with a T4-level sensory deficit due to an acute disseminated encephalomyelitis sequela presented with persistent fever but no abdominal pain. She was initially diagnosed with appendicitis and received antibiotics; however, the inflammatory response and fever persisted. Further investigations revealed a ruptured pyomyoma forming an intra-abdominal abscess. Additional antibiotic administration and extensive surgeries, including hysterectomy, bilateral salpingo-oophorectomy, and ileocecal excision, resolved the severe peritonitis. The postoperative course was uneventful without any relapse. Lack of abdominal pain related to abdominal hypoesthesia can mask the severity of peritonitis.</AbstractText
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A coarse-grained model for simulations of phosphorylated disordered proteins. Protein phosphorylation is a common and essential post-translational modification that affects biochemical properties and regulates biological activities. Phosphorylation is particularly common for intrinsically disordered proteins and can significantly modulate their function and potential to interact with binding partners. To understand the biophysical origins of how phosphorylation of disordered proteins influences their function, it is valuable to investigate how the modifications lead to changes in their conformational ensembles. Here, we have used a top-down data-driven approach to develop a coarse-grained molecular dynamics model compatible with the CALVADOS protein simulation model to study the effects of serine and threonine phosphorylation on the global structural properties of disordered proteins. We parameterize the model using experimental data on the effects of phosphorylation on global dimensions. By comparing with baseline models and simulations using the phosphomimetics aspartate and glutamate, we show that the effect of phosphorylation on the global dimensions of disordered proteins is mostly driven by the additional charge. We envisage that our model can be applied to study the effects of phosphorylation of disordered proteins at the proteome scale as well as to study the important roles of protein phosphorylation on phase separation.</AbstractText
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Anti-aging effect of β-carotene through regulating the KAT7-P15 signaling axis, inflammation and oxidative stress process. Research on aging is growing as the elderly make up a greater share of the population, focusing on reversing and inhibiting the aging process. The exhaustion and senescence of stem cells are the fundamental drivers behind aging. β-Carotene has been depicted to have many biological functions, and we speculate that it may have an anti-aging effect.</AbstractText Firstly, the anti-aging property of β-carotene was investigated in vitro using mesenchymal stem cells (MSCs) induced by H<sub The in vitro experiment revealed that β-carotene could relieve the aging of MSCs, as evidenced by a series of aging marker molecules such as p16 and p21. β-Carotene appeared to inhibit aging by regulating the KAT7-P15 signaling axis. The in vivo experiment revealed that β-carotene treatment has significantly down-regulated the aging level of tissues and organs.</AbstractText In this work, we explored the anti-aging effect of β-carotene in vivo and in vitro. The experimental results indicate that β-carotene may be an important potential anti-aging molecule, which can be used as a drug or in functional food to treat aging in the future.</AbstractText
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Painless ruptured pyomyoma causing an abdominal abscess in a postmenopausal woman with abdominal hypoesthesia. Pyomyoma is a rare condition caused by an infection within a uterine leiomyoma. When ruptured, it can cause peritonitis with continuous abdominal pain, potentially leading to life-threatening conditions. However, abdominal pain may be absent in patients with abdominal hypoesthesia. We report a case of painless ruptured pyomyoma causing an abdominal abscess in a 60-year-old woman with abdominal hypoesthesia. The patient with a T4-level sensory deficit due to an acute disseminated encephalomyelitis sequela presented with persistent fever but no abdominal pain. She was initially diagnosed with appendicitis and received antibiotics; however, the inflammatory response and fever persisted. Further investigations revealed a ruptured pyomyoma forming an intra-abdominal abscess. Additional antibiotic administration and extensive surgeries, including hysterectomy, bilateral salpingo-oophorectomy, and ileocecal excision, resolved the severe peritonitis. The postoperative course was uneventful without any relapse. Lack of abdominal pain related to abdominal hypoesthesia can mask the severity of peritonitis.</AbstractText
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29289980
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19727753
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30203704
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Magnetic resonance elastography can monitor changes in medullary stiffness in response to treatment in the swine ischemic kidney.
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Diagnostic value of MR elastography in addition to contrast-enhanced MR imaging of the breast-initial clinical results.
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Closely Related Fruit Fly Species Living at Different Latitudes Diverge in Their Circadian Clock Anatomy and Rhythmic Behavior.
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Low-energy shockwave (SW) therapy attenuates damage in the stenotic kidney (STK) caused by atherosclerotic renal artery stenosis (ARAS). We hypothesized that magnetic resonance elastography (MRE) would detect attenuation of fibrosis following SW in unilateral ARAS kidneys.</AbstractText Domestic pigs were randomized to control, unilateral ARAS, and ARAS treated with 6 sessions of SW over 3 consecutive weeks (n = 7 each) starting after 3 weeks of ARAS or sham. Four weeks after SW treatment, renal fibrosis was evaluated with MRE in vivo or trichrome staining ex vivo. Blood pressure, single-kidney renal-blood-flow (RBF) and glomerular-filtration-rate (GFR) were assessed.</AbstractText MRE detected increased stiffness in the STK medulla (15.3 ± 2.1 vs. 10.1 ± 0.8 kPa, p < 0.05) that moderately correlated with severity of fibrosis (R<sup MRE might be a tool for noninvasive monitoring of medullary fibrosis in response to treatment in kidney disease.</AbstractText
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The purpose of the study was to assess the additional value of magnetic resonance (MR) elastography (MRE) to contrast-enhanced (ce) MR imaging (MRI) for breast lesion characterisation.</AbstractText Fifty-seven suspected breast lesions in 57 patients (mean age 52.4 years) were examined by ce MRI and MRE. All lesions were classified into BI-RADS categories. Viscoelastic parameters, e.g. alpha0 as an indicator of tissue stiffness, were calculated. Histology of the lesions was correlated with BI-RADS and viscoelastic properties. The positive predictive value (PPV) for malignancy, and the sensitivity and specificity of ce MRI were calculated. Receiver-operating characteristics (ROC) curves were separately calculated for both ce MRI and viscoelastic properties and conjoined to analyse the accuracy of diagnostic performance.</AbstractText The lesions (mean size 27.6 mm) were malignant in 64.9% (n = 37) of cases. The PPV for malignancy was significantly (p < 0.0001) dependent on BI-RADS classification. The sensitivity of ce MRI for breast cancer detection was 97.3% (36/37), whereas specificity was 55% (11/20). If ce MRI was combined with alpha0, the diagnostic accuracy could be significantly increased (p < 0.05; AUC(ce MRI) = 0.93, AUC(combined) = 0.96).</AbstractText In this study, the combination of MRE and ce MRI could increase the diagnostic performance of breast MRI. Further investigations of larger cohorts and smaller lesions (in particular those only visible on MRI) are necessary to validate these results.</AbstractText
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Recently, we reported differences in the expression pattern of the blue light-sensitive flavoprotein cryptochrome (CRY) and the neuropeptide pigment-dispersing factor (PDF) in the neuronal clock network of high-latitude Drosophila species, belonging to the Drosophila subgenus ( virilis-repleta radiation), compared with cosmopolitan D. melanogaster flies, belonging to the Sophophora subgenus. Alterations in rhythmic patterns of activity due to these differences might have adaptive significance for colonizing high-latitude habitats and, hence, adjusting to long photoperiods. Here, we show that these differing CRY/PDF expression patterns are only present in those species of the virilis-repleta radiation that colonized high latitudes. The cosmopolitan species D. mercatorum and D. hydei have a D. melanogaster-like clock network and behavior despite belonging to the virilis-repleta radiation. Similarly, 2 species of the holotropical Zaprionus genus, more closely related to the Drosophila subgenus than to the Sophophora subgenus, retain a D. melanogaster-like clock network and rhythmic behavior. We therefore suggest that the D. melanogaster-like clock network is the "ancestral fly clock phenotype" and that alterations in the CRY/PDF clock neurochemistry have allowed some species of the virilis-repleta radiation to colonize high-latitude environments.</AbstractText
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Magnetic resonance elastography can monitor changes in medullary stiffness in response to treatment in the swine ischemic kidney. Low-energy shockwave (SW) therapy attenuates damage in the stenotic kidney (STK) caused by atherosclerotic renal artery stenosis (ARAS). We hypothesized that magnetic resonance elastography (MRE) would detect attenuation of fibrosis following SW in unilateral ARAS kidneys.</AbstractText Domestic pigs were randomized to control, unilateral ARAS, and ARAS treated with 6 sessions of SW over 3 consecutive weeks (n = 7 each) starting after 3 weeks of ARAS or sham. Four weeks after SW treatment, renal fibrosis was evaluated with MRE in vivo or trichrome staining ex vivo. Blood pressure, single-kidney renal-blood-flow (RBF) and glomerular-filtration-rate (GFR) were assessed.</AbstractText MRE detected increased stiffness in the STK medulla (15.3 ± 2.1 vs. 10.1 ± 0.8 kPa, p < 0.05) that moderately correlated with severity of fibrosis (R<sup MRE might be a tool for noninvasive monitoring of medullary fibrosis in response to treatment in kidney disease.</AbstractText
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Diagnostic value of MR elastography in addition to contrast-enhanced MR imaging of the breast-initial clinical results. The purpose of the study was to assess the additional value of magnetic resonance (MR) elastography (MRE) to contrast-enhanced (ce) MR imaging (MRI) for breast lesion characterisation.</AbstractText Fifty-seven suspected breast lesions in 57 patients (mean age 52.4 years) were examined by ce MRI and MRE. All lesions were classified into BI-RADS categories. Viscoelastic parameters, e.g. alpha0 as an indicator of tissue stiffness, were calculated. Histology of the lesions was correlated with BI-RADS and viscoelastic properties. The positive predictive value (PPV) for malignancy, and the sensitivity and specificity of ce MRI were calculated. Receiver-operating characteristics (ROC) curves were separately calculated for both ce MRI and viscoelastic properties and conjoined to analyse the accuracy of diagnostic performance.</AbstractText The lesions (mean size 27.6 mm) were malignant in 64.9% (n = 37) of cases. The PPV for malignancy was significantly (p < 0.0001) dependent on BI-RADS classification. The sensitivity of ce MRI for breast cancer detection was 97.3% (36/37), whereas specificity was 55% (11/20). If ce MRI was combined with alpha0, the diagnostic accuracy could be significantly increased (p < 0.05; AUC(ce MRI) = 0.93, AUC(combined) = 0.96).</AbstractText In this study, the combination of MRE and ce MRI could increase the diagnostic performance of breast MRI. Further investigations of larger cohorts and smaller lesions (in particular those only visible on MRI) are necessary to validate these results.</AbstractText
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Closely Related Fruit Fly Species Living at Different Latitudes Diverge in Their Circadian Clock Anatomy and Rhythmic Behavior. Recently, we reported differences in the expression pattern of the blue light-sensitive flavoprotein cryptochrome (CRY) and the neuropeptide pigment-dispersing factor (PDF) in the neuronal clock network of high-latitude Drosophila species, belonging to the Drosophila subgenus ( virilis-repleta radiation), compared with cosmopolitan D. melanogaster flies, belonging to the Sophophora subgenus. Alterations in rhythmic patterns of activity due to these differences might have adaptive significance for colonizing high-latitude habitats and, hence, adjusting to long photoperiods. Here, we show that these differing CRY/PDF expression patterns are only present in those species of the virilis-repleta radiation that colonized high latitudes. The cosmopolitan species D. mercatorum and D. hydei have a D. melanogaster-like clock network and behavior despite belonging to the virilis-repleta radiation. Similarly, 2 species of the holotropical Zaprionus genus, more closely related to the Drosophila subgenus than to the Sophophora subgenus, retain a D. melanogaster-like clock network and rhythmic behavior. We therefore suggest that the D. melanogaster-like clock network is the "ancestral fly clock phenotype" and that alterations in the CRY/PDF clock neurochemistry have allowed some species of the virilis-repleta radiation to colonize high-latitude environments.</AbstractText
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35847578
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34928414
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36119086
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Dexamethasone does not affect endolymphatic hydrops (EH) in patients with Meniere's disease within 24 h, and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min.
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Visualization of the saccule and utricle with non-contrast-enhanced FLAIR sequences.
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MS4A6A is a new prognostic biomarker produced by macrophages in glioma patients.
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Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops (EH) using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min. The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.</AbstractText In an in vitro study, the potential impact of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography (HPLC) after mixing with Gd-DTPA. Ten patients with definite Meniere's disease (MD) were recruited to study the potential interference of dexamethasone on MRI visualization of EH, and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation (hT<sub The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA. EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone. Excellent inner ear images were obtained from all patients, and EHs with various grades were displayed. There were significant correlations between diagnosis and cochlear EH (p < 0.01, Spearman's Rho), between diagnosis and vestibular EH (p < 0.01, Spearman's Rho), and between cochlear and vestibular EH (p < 0.01, Spearman's Rho). The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH. Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.</AbstractText Intratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application. Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work.</AbstractText 3.</AbstractText
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3D-fluid attenuation inversion recovery (FLAIR) collected 4 h after intravenous gadolinium injection can delineate the perilymphatic space (PLS) from the endolymphatic space (ELS) to capture endolymphatic hydrops, the pathological counterpart of Ménière's disease. We aimed to optimize visualization of such inner ear internal anatomy using 3D-FLAIR without injection.</AbstractText 3D-FLAIR signal from different fluid compartments such as PLS and ELS was first simulated. Then, twenty-two healthy subjects were scanned at 3.0-T MRI with non-injected 3D-FLAIR using variable T2 preparations (T2Preps) (OFF, 200, 400, and 600 ms) and variable inversion times (TIs) (from 224 to 5000 ms) and different resolutions (1.0 × 1.0 × 1.5, 0.6 × 0.6 × 0.8, and 0.6 × 0.6 × 0.6 mm<sup The PLS and ELS were differentiated when T2Prep was used but not without. The relative contrast was larger with T2Prep at 400 ms than at 200 or 600 ms (0.72 ± 0.22 vs. 0.44 ± 0.11, p = 0.019; and 0.72 ± 0.22 vs. 0.46 ± 0.28, p = 0.034, respectively). The saccule and utricle were best delineated in 87. % cases with T2Prep = 400 and TI = 2100 ms at the highest resolution. Visualization of the saccule and utricle in the optimized non-injected 3D-FLAIR was similar to conventional injected 3D-FLAIR in a patient.</AbstractText Combining a specific T2Prep and TI in non-injected 3D-FLAIR could separate PLS and ELS and even the saccule and utricle, paving the way toward future application to diagnose Ménière's disease.</AbstractText • MRI can capture the internal anatomy of inner ear without injection of contrast media. • Specific parameters consisting of a T2 preparation of 400 ms and an inversion time of 2100 ms must be used to visualize the saccule and utricle on non-injected 3D-FLAIR.</AbstractText
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MS4A6A has been recognized as being associated with aging and the onset of neurodegenerative disease. However, the mechanisms of MS4A6A in glioma biology and prognosis are ill-defined. Here, we show that MS4A6A is upregulated in glioma tissues, resulting in unfavorable clinical outcomes and poor responses to adjuvant chemotherapy. Multivariate Cox regression analysis suggested that MS4A6A expression can act as a strong and independent predictor for glioma outcomes (CGGA1: HR: 1.765, <i
|
Dexamethasone does not affect endolymphatic hydrops (EH) in patients with Meniere's disease within 24 h, and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min. Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops (EH) using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min. The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.</AbstractText In an in vitro study, the potential impact of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography (HPLC) after mixing with Gd-DTPA. Ten patients with definite Meniere's disease (MD) were recruited to study the potential interference of dexamethasone on MRI visualization of EH, and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation (hT<sub The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA. EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone. Excellent inner ear images were obtained from all patients, and EHs with various grades were displayed. There were significant correlations between diagnosis and cochlear EH (p < 0.01, Spearman's Rho), between diagnosis and vestibular EH (p < 0.01, Spearman's Rho), and between cochlear and vestibular EH (p < 0.01, Spearman's Rho). The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH. Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.</AbstractText Intratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application. Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work.</AbstractText 3.</AbstractText
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Visualization of the saccule and utricle with non-contrast-enhanced FLAIR sequences. 3D-fluid attenuation inversion recovery (FLAIR) collected 4 h after intravenous gadolinium injection can delineate the perilymphatic space (PLS) from the endolymphatic space (ELS) to capture endolymphatic hydrops, the pathological counterpart of Ménière's disease. We aimed to optimize visualization of such inner ear internal anatomy using 3D-FLAIR without injection.</AbstractText 3D-FLAIR signal from different fluid compartments such as PLS and ELS was first simulated. Then, twenty-two healthy subjects were scanned at 3.0-T MRI with non-injected 3D-FLAIR using variable T2 preparations (T2Preps) (OFF, 200, 400, and 600 ms) and variable inversion times (TIs) (from 224 to 5000 ms) and different resolutions (1.0 × 1.0 × 1.5, 0.6 × 0.6 × 0.8, and 0.6 × 0.6 × 0.6 mm<sup The PLS and ELS were differentiated when T2Prep was used but not without. The relative contrast was larger with T2Prep at 400 ms than at 200 or 600 ms (0.72 ± 0.22 vs. 0.44 ± 0.11, p = 0.019; and 0.72 ± 0.22 vs. 0.46 ± 0.28, p = 0.034, respectively). The saccule and utricle were best delineated in 87. % cases with T2Prep = 400 and TI = 2100 ms at the highest resolution. Visualization of the saccule and utricle in the optimized non-injected 3D-FLAIR was similar to conventional injected 3D-FLAIR in a patient.</AbstractText Combining a specific T2Prep and TI in non-injected 3D-FLAIR could separate PLS and ELS and even the saccule and utricle, paving the way toward future application to diagnose Ménière's disease.</AbstractText • MRI can capture the internal anatomy of inner ear without injection of contrast media. • Specific parameters consisting of a T2 preparation of 400 ms and an inversion time of 2100 ms must be used to visualize the saccule and utricle on non-injected 3D-FLAIR.</AbstractText
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MS4A6A is a new prognostic biomarker produced by macrophages in glioma patients. MS4A6A has been recognized as being associated with aging and the onset of neurodegenerative disease. However, the mechanisms of MS4A6A in glioma biology and prognosis are ill-defined. Here, we show that MS4A6A is upregulated in glioma tissues, resulting in unfavorable clinical outcomes and poor responses to adjuvant chemotherapy. Multivariate Cox regression analysis suggested that MS4A6A expression can act as a strong and independent predictor for glioma outcomes (CGGA1: HR: 1.765, <i
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34677287
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28338470
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33040986
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Sparsity-Based Recovery of Three-Dimensional Photoacoustic Images from Compressed Single-Shot Optical Detection.
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Reducing scan angle using adaptive prior knowledge for a limited-angle intrafraction verification (LIVE) system for conformal arc radiotherapy.
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The Basolateral Amygdala to Nucleus Accumbens Core Circuit Mediates the Conditioned Reinforcing Effects of Cocaine-Paired Cues on Cocaine Seeking.
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Photoacoustic (PA) imaging combines optical excitation with ultrasonic detection to achieve high-resolution imaging of biological samples. A high-energy pulsed laser is often used for imaging at multi-centimeter depths in tissue. These lasers typically have a low pulse repetition rate, so to acquire images in real-time, only one pulse of the laser can be used per image. This single pulse necessitates the use of many individual detectors and receive electronics to adequately record the resulting acoustic waves and form an image. Such requirements make many PA imaging systems both costly and complex. This investigation proposes and models a method of volumetric PA imaging using a state-of-the-art compressed sensing approach to achieve real-time acquisition of the initial pressure distribution (IPD) at a reduced level of cost and complexity. In particular, a single exposure of an optical image sensor is used to capture an entire Fabry-Pérot interferometric acoustic sensor. Time resolved encoding as achieved through spatial sweeping with a galvanometer. This optical system further makes use of a random binary mask to set a predetermined subset of pixels to zero, thus enabling recovery of the time-resolved signals. The Two-Step Iterative Shrinking and Thresholding algorithm is used to reconstruct the IPD, harnessing the sparsity naturally occurring in the IPD as well as the additional structure provided by the binary mask. We conduct experiments on simulated data and analyze the performance of our new approach.</AbstractText
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The purpose of this study is to develop an adaptive prior knowledge guided image estimation technique to reduce the scan angle needed in the limited-angle intrafraction verification (LIVE) system for 4D-CBCT reconstruction. The LIVE system has been previously developed to reconstruct 4D volumetric images on-the-fly during arc treatment for intrafraction target verification and dose calculation. In this study, we developed an adaptive constrained free-form deformation reconstruction technique in LIVE to further reduce the scanning angle needed to reconstruct the 4D-CBCT images for faster intrafraction verification. This technique uses free form deformation with energy minimization to deform prior images to estimate 4D-CBCT based on kV-MV projections acquired in extremely limited angle (orthogonal 3°) during the treatment. Note that the prior images are adaptively updated using the latest CBCT images reconstructed by LIVE during treatment to utilize the continuity of the respiratory motion. The 4D digital extended-cardiac-torso (XCAT) phantom and a CIRS 008A dynamic thoracic phantom were used to evaluate the effectiveness of this technique. The reconstruction accuracy of the technique was evaluated by calculating both the center-of-mass-shift (COMS) and 3D volume-percentage-difference (VPD) of the tumor in reconstructed images and the true on-board images. The performance of the technique was also assessed with varied breathing signals against scanning angle, lesion size, lesion location, projection sampling interval, and scanning direction. In the XCAT study, using orthogonal-view of 3° kV and portal MV projections, this technique achieved an average tumor COMS/VPD of 0.4  ±  0.1 mm/5.5  ±  2.2%, 0.6  ±  0.3 mm/7.2  ±  2.8%, 0.5  ±  0.2 mm/7.1  ±  2.6%, 0.6  ±  0.2 mm/8.3  ±  2.4%, for baseline drift, amplitude variation, phase shift, and patient breathing signal variation, respectively. In the CIRS phantom study, this technique achieved an average tumor COMS/VPD of 0.7  ±  0.1 mm/7.5  ±  1.3% for a 3 cm lesion and 0.6  ±  0.2 mm/11.4  ±  1.5% for a 2 cm lesion in the baseline drift case. The average tumor COMS/VPD were 0.5  ±  0.2 mm/10.8  ±  1.4%, 0.4  ±  0.3 mm/7.3  ±  2.9%, 0.4  ±  0.2 mm/7.4  ±  2.5%, 0.4  ±  0.2 mm/7.3  ±  2.8% for the four real patient breathing signals, respectively. Results demonstrated that the adaptive prior knowledge guided image estimation technique with LIVE system is robust against scanning angle, lesion size, location and scanning direction. It can estimate on-board images accurately with as little as 6 projections in orthogonal-view 3° angle. In conclusion, adaptive prior knowledge guided image reconstruction technique accurately estimates 4D-CBCT images using extremely-limited angle and projections. This technique greatly improves the efficiency and accuracy of LIVE system for ultrafast 4D intrafraction verification of lung SBRT treatments.</AbstractText
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Individuals addicted to cocaine spend much of their time foraging for the drug. Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence, especially when presented response-contingently, acting as conditioned reinforcers that bridge delays to drug use. The acquisition of cue-controlled cocaine seeking has been shown to depend on functional interactions between the basolateral amygdala (BLA) and the nucleus accumbens core (NAcC). However, the precise neuronal circuits underlying the acquisition of cue-controlled cocaine-seeking behavior have not been elucidated.</AbstractText Here, we used a projection-specific Cre-dependent DREADD (designer receptor exclusively activated by designer drugs)-mediated causal approach to test the hypothesis that the direct projections from the BLA to the NAcC are required for the acquisition of cue-controlled cocaine-seeking behavior.</AbstractText In Sprague Dawley rats with Cre-mediated expression of the inhibitory DREADD hM4D(Gi) in the NAcC-projecting BLA neurons, treatment with clozapine N-oxide, but not vehicle, selectively prevented the impact of cocaine-associated conditioned reinforcers on cocaine seeking under a second-order schedule of reinforcement. This effect was attributable to the chemogenetic inhibition of the NAcC-projecting BLA neurons, as it was reversible, and it was absent in clozapine N-oxide-treated rats expressing an empty control virus. In contrast, chemogenetic inhibition of the anterior insula, which receives collateral projections from NAcC-projecting BLA neurons, was without effect.</AbstractText These data demonstrate that the acquisition of cue-controlled cocaine seeking that depends on the conditioned reinforcing effects of cocaine cues requires activity in the direct projections from the BLA to the NAcC.</AbstractText
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Sparsity-Based Recovery of Three-Dimensional Photoacoustic Images from Compressed Single-Shot Optical Detection. Photoacoustic (PA) imaging combines optical excitation with ultrasonic detection to achieve high-resolution imaging of biological samples. A high-energy pulsed laser is often used for imaging at multi-centimeter depths in tissue. These lasers typically have a low pulse repetition rate, so to acquire images in real-time, only one pulse of the laser can be used per image. This single pulse necessitates the use of many individual detectors and receive electronics to adequately record the resulting acoustic waves and form an image. Such requirements make many PA imaging systems both costly and complex. This investigation proposes and models a method of volumetric PA imaging using a state-of-the-art compressed sensing approach to achieve real-time acquisition of the initial pressure distribution (IPD) at a reduced level of cost and complexity. In particular, a single exposure of an optical image sensor is used to capture an entire Fabry-Pérot interferometric acoustic sensor. Time resolved encoding as achieved through spatial sweeping with a galvanometer. This optical system further makes use of a random binary mask to set a predetermined subset of pixels to zero, thus enabling recovery of the time-resolved signals. The Two-Step Iterative Shrinking and Thresholding algorithm is used to reconstruct the IPD, harnessing the sparsity naturally occurring in the IPD as well as the additional structure provided by the binary mask. We conduct experiments on simulated data and analyze the performance of our new approach.</AbstractText
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Reducing scan angle using adaptive prior knowledge for a limited-angle intrafraction verification (LIVE) system for conformal arc radiotherapy. The purpose of this study is to develop an adaptive prior knowledge guided image estimation technique to reduce the scan angle needed in the limited-angle intrafraction verification (LIVE) system for 4D-CBCT reconstruction. The LIVE system has been previously developed to reconstruct 4D volumetric images on-the-fly during arc treatment for intrafraction target verification and dose calculation. In this study, we developed an adaptive constrained free-form deformation reconstruction technique in LIVE to further reduce the scanning angle needed to reconstruct the 4D-CBCT images for faster intrafraction verification. This technique uses free form deformation with energy minimization to deform prior images to estimate 4D-CBCT based on kV-MV projections acquired in extremely limited angle (orthogonal 3°) during the treatment. Note that the prior images are adaptively updated using the latest CBCT images reconstructed by LIVE during treatment to utilize the continuity of the respiratory motion. The 4D digital extended-cardiac-torso (XCAT) phantom and a CIRS 008A dynamic thoracic phantom were used to evaluate the effectiveness of this technique. The reconstruction accuracy of the technique was evaluated by calculating both the center-of-mass-shift (COMS) and 3D volume-percentage-difference (VPD) of the tumor in reconstructed images and the true on-board images. The performance of the technique was also assessed with varied breathing signals against scanning angle, lesion size, lesion location, projection sampling interval, and scanning direction. In the XCAT study, using orthogonal-view of 3° kV and portal MV projections, this technique achieved an average tumor COMS/VPD of 0.4  ±  0.1 mm/5.5  ±  2.2%, 0.6  ±  0.3 mm/7.2  ±  2.8%, 0.5  ±  0.2 mm/7.1  ±  2.6%, 0.6  ±  0.2 mm/8.3  ±  2.4%, for baseline drift, amplitude variation, phase shift, and patient breathing signal variation, respectively. In the CIRS phantom study, this technique achieved an average tumor COMS/VPD of 0.7  ±  0.1 mm/7.5  ±  1.3% for a 3 cm lesion and 0.6  ±  0.2 mm/11.4  ±  1.5% for a 2 cm lesion in the baseline drift case. The average tumor COMS/VPD were 0.5  ±  0.2 mm/10.8  ±  1.4%, 0.4  ±  0.3 mm/7.3  ±  2.9%, 0.4  ±  0.2 mm/7.4  ±  2.5%, 0.4  ±  0.2 mm/7.3  ±  2.8% for the four real patient breathing signals, respectively. Results demonstrated that the adaptive prior knowledge guided image estimation technique with LIVE system is robust against scanning angle, lesion size, location and scanning direction. It can estimate on-board images accurately with as little as 6 projections in orthogonal-view 3° angle. In conclusion, adaptive prior knowledge guided image reconstruction technique accurately estimates 4D-CBCT images using extremely-limited angle and projections. This technique greatly improves the efficiency and accuracy of LIVE system for ultrafast 4D intrafraction verification of lung SBRT treatments.</AbstractText
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The Basolateral Amygdala to Nucleus Accumbens Core Circuit Mediates the Conditioned Reinforcing Effects of Cocaine-Paired Cues on Cocaine Seeking. Individuals addicted to cocaine spend much of their time foraging for the drug. Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence, especially when presented response-contingently, acting as conditioned reinforcers that bridge delays to drug use. The acquisition of cue-controlled cocaine seeking has been shown to depend on functional interactions between the basolateral amygdala (BLA) and the nucleus accumbens core (NAcC). However, the precise neuronal circuits underlying the acquisition of cue-controlled cocaine-seeking behavior have not been elucidated.</AbstractText Here, we used a projection-specific Cre-dependent DREADD (designer receptor exclusively activated by designer drugs)-mediated causal approach to test the hypothesis that the direct projections from the BLA to the NAcC are required for the acquisition of cue-controlled cocaine-seeking behavior.</AbstractText In Sprague Dawley rats with Cre-mediated expression of the inhibitory DREADD hM4D(Gi) in the NAcC-projecting BLA neurons, treatment with clozapine N-oxide, but not vehicle, selectively prevented the impact of cocaine-associated conditioned reinforcers on cocaine seeking under a second-order schedule of reinforcement. This effect was attributable to the chemogenetic inhibition of the NAcC-projecting BLA neurons, as it was reversible, and it was absent in clozapine N-oxide-treated rats expressing an empty control virus. In contrast, chemogenetic inhibition of the anterior insula, which receives collateral projections from NAcC-projecting BLA neurons, was without effect.</AbstractText These data demonstrate that the acquisition of cue-controlled cocaine seeking that depends on the conditioned reinforcing effects of cocaine cues requires activity in the direct projections from the BLA to the NAcC.</AbstractText
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37508383
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32980744
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37542200
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A Novel ENU-Induced Mfn2 Mutation Causes Motor Deficits in Mice without Causing Peripheral Neuropathy.
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The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort.
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The effect of personalized intelligent digital systems for self-care training on type II diabetes: a systematic review and meta-analysis of clinical trials.
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Mitochondrial fission and fusion are required for maintaining functional mitochondria. The mitofusins (MFN1 and MFN2) are known for their roles in mediating mitochondrial fusion. Recently, MFN2 has been implicated in other important cellular functions, such as mitophagy, mitochondrial motility, and coordinating endoplasmic reticulum-mitochondria communication. In humans, over 100 <i
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We aimed to expand the number of currently known pathogenic PNKP mutations, to study the phenotypic spectrum, including radiological characteristics and genotype-phenotype correlations, and to assess whether immunodeficiency and increased cancer risk are part of the DNA repair disorder caused by mutations in the PNKP gene.</AbstractText We evaluated nine patients with PNKP mutations. A neurological history and examination was obtained. All patients had undergone neuroimaging and genetic testing as part of the prior diagnostic process. Laboratory measurements included potential biomarkers, and, in the context of a DNA repair disorder, we performed a detailed immunologic evaluation, including B cell repertoire analysis.</AbstractText We identified three new mutations in the PNKP gene and confirm the phenotypic spectrum of PNKP-associated disease, ranging from microcephaly, seizures, and developmental delay to ataxia with oculomotor apraxia type 4. Irrespective of the phenotype, alpha-fetoprotein is a biochemical marker and increases with age and progression of the disease. On neuroimaging, (progressive) cerebellar atrophy was a universal feature. No clinical signs of immunodeficiency were present, and immunologic assessment was unremarkable. One patient developed cancer, but this was attributed to a concurrent von Hippel-Lindau mutation.</AbstractText Immunodeficiency and cancer predisposition do not appear to be part of PNKP-associated disease, contrasting many other DNA repair disorders. Furthermore, our study illustrates that the previously described syndromes microcephaly, seizures, and developmental delay, and ataxia with oculomotor apraxia type 4, represent the extremes of an overlapping spectrum of disease. Cerebellar atrophy and elevated serum alpha-fetoprotein levels are early diagnostic findings across the entire phenotypical spectrum.</AbstractText
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Type 2 diabetes (T2D) is rising worldwide. Self-care prevents diabetic complications. Lack of knowledge is one reason patients fail at self-care. Intelligent digital health (IDH) solutions have a promising role in training self-care behaviors based on patients' needs. This study reviews the effects of RCTs offering individualized self-care training systems for T2D patients.</AbstractText PubMed, Web of Science, Scopus, Cochrane Library, and Science Direct databases were searched. The included RCTs provided data-driven, individualized self-care training advice for T2D patients. Due to the repeated studies measurements, an all-time-points meta-analysis was conducted to analyze the trends over time. The revised Cochrane risk-of-bias tool (RoB 2.0) was used for quality assessment.</AbstractText In total, 22 trials met the inclusion criteria, and 19 studies with 3071 participants were included in the meta-analysis. IDH interventions led to a significant reduction of HbA1c level in the intervention group at short-term (in the third month: SMD = - 0.224 with 95% CI - 0.319 to - 0.129, p value < 0.0; in the sixth month: SMD = - 0.548 with 95% CI - 0.860 to - 0.237, p value < 0.05). The difference in HbA1c reduction between groups varied based on patients' age and technological forms of IDH services delivery. The descriptive results confirmed the impact of M-Health technologies in improving HbA1c levels.</AbstractText IDH systems had significant and small effects on HbA1c reduction in T2D patients. IDH interventions' impact needs long-term RCTs. This review will help diabetic clinicians, self-care training system developers, and researchers interested in using IDH solutions to empower T2D patients.</AbstractText
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A Novel ENU-Induced Mfn2 Mutation Causes Motor Deficits in Mice without Causing Peripheral Neuropathy. Mitochondrial fission and fusion are required for maintaining functional mitochondria. The mitofusins (MFN1 and MFN2) are known for their roles in mediating mitochondrial fusion. Recently, MFN2 has been implicated in other important cellular functions, such as mitophagy, mitochondrial motility, and coordinating endoplasmic reticulum-mitochondria communication. In humans, over 100 <i
|
The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort. We aimed to expand the number of currently known pathogenic PNKP mutations, to study the phenotypic spectrum, including radiological characteristics and genotype-phenotype correlations, and to assess whether immunodeficiency and increased cancer risk are part of the DNA repair disorder caused by mutations in the PNKP gene.</AbstractText We evaluated nine patients with PNKP mutations. A neurological history and examination was obtained. All patients had undergone neuroimaging and genetic testing as part of the prior diagnostic process. Laboratory measurements included potential biomarkers, and, in the context of a DNA repair disorder, we performed a detailed immunologic evaluation, including B cell repertoire analysis.</AbstractText We identified three new mutations in the PNKP gene and confirm the phenotypic spectrum of PNKP-associated disease, ranging from microcephaly, seizures, and developmental delay to ataxia with oculomotor apraxia type 4. Irrespective of the phenotype, alpha-fetoprotein is a biochemical marker and increases with age and progression of the disease. On neuroimaging, (progressive) cerebellar atrophy was a universal feature. No clinical signs of immunodeficiency were present, and immunologic assessment was unremarkable. One patient developed cancer, but this was attributed to a concurrent von Hippel-Lindau mutation.</AbstractText Immunodeficiency and cancer predisposition do not appear to be part of PNKP-associated disease, contrasting many other DNA repair disorders. Furthermore, our study illustrates that the previously described syndromes microcephaly, seizures, and developmental delay, and ataxia with oculomotor apraxia type 4, represent the extremes of an overlapping spectrum of disease. Cerebellar atrophy and elevated serum alpha-fetoprotein levels are early diagnostic findings across the entire phenotypical spectrum.</AbstractText
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The effect of personalized intelligent digital systems for self-care training on type II diabetes: a systematic review and meta-analysis of clinical trials. Type 2 diabetes (T2D) is rising worldwide. Self-care prevents diabetic complications. Lack of knowledge is one reason patients fail at self-care. Intelligent digital health (IDH) solutions have a promising role in training self-care behaviors based on patients' needs. This study reviews the effects of RCTs offering individualized self-care training systems for T2D patients.</AbstractText PubMed, Web of Science, Scopus, Cochrane Library, and Science Direct databases were searched. The included RCTs provided data-driven, individualized self-care training advice for T2D patients. Due to the repeated studies measurements, an all-time-points meta-analysis was conducted to analyze the trends over time. The revised Cochrane risk-of-bias tool (RoB 2.0) was used for quality assessment.</AbstractText In total, 22 trials met the inclusion criteria, and 19 studies with 3071 participants were included in the meta-analysis. IDH interventions led to a significant reduction of HbA1c level in the intervention group at short-term (in the third month: SMD = - 0.224 with 95% CI - 0.319 to - 0.129, p value < 0.0; in the sixth month: SMD = - 0.548 with 95% CI - 0.860 to - 0.237, p value < 0.05). The difference in HbA1c reduction between groups varied based on patients' age and technological forms of IDH services delivery. The descriptive results confirmed the impact of M-Health technologies in improving HbA1c levels.</AbstractText IDH systems had significant and small effects on HbA1c reduction in T2D patients. IDH interventions' impact needs long-term RCTs. This review will help diabetic clinicians, self-care training system developers, and researchers interested in using IDH solutions to empower T2D patients.</AbstractText
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39955239
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33619789
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40777418
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The stability of the alternative model of personality disorders: Example of the situation related to Covid-19.
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Vulnerable narcissism as beneficial factor for the therapeutic alliance in borderline personality disorder.
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High-density, Identified Cell Recordings from Motor Cortex of Awake Behaving Macaques using 1024-channel SiNAPS-NHP Probes.
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This article aims to explore the relationships between two key levels (Criteria A and B) in the Alternative Model of Personality Disorders (AMPD). Specifically, it examines the articulation between the level of personality functioning (LPF) and the pathological personality dimensions (PPD) to understand their respective contributions to personality disorder (PD) diagnosis.</AbstractText We analyzed data collected through the LPFS-BR and PID-5-BF instruments from two randomized samples of non-clinical participants, gathered both before (n=124) and after (n=126) the COVID-19 pandemic and subsequent lockdown. Mediation analyses were conducted to clarify how LPF and PPD interact in the assessment of PDs.</AbstractText Findings indicate notable intensity differences in LPF levels (P<0.001, Cohen's d>0.92), alongside high stability in both overall PD severity and PPD traits (P>0.05). Regression analysis allowed us to examine the combined effects of Lockdown, Identity, and Detachment on PD severity through mediation modelling. Results suggest that Identity mediates the effects of both Lockdown and Detachment, with Detachment also having a direct impact.</AbstractText These results indicate that while certain aspects of the AMPD are context-sensitive, the PPD may offset these fluctuations through both direct and indirect mechanisms.</AbstractText
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Evidence suggests that narcissism and borderline personality disorder are associated with each other. This naturalistic study investigated the predictive value of grandiose and vulnerable narcissism on the development of the therapeutic alliance in short-term psychodynamic treatment across 12 weeks. The sample consisted of 99 patients with borderline personality disorder. Narcissism was assessed with the Pathological Narcissism Inventory at treatment onset. The therapeutic alliance was rated with the Scale to Assess Therapeutic Relationships by both patient and therapist at four time points during treatment. Results showed a significant predictive value of vulnerable narcissism on the therapeutic alliance, revealing a more beneficial progression for patients with higher vulnerable narcissism. Grandiose narcissism had no predictive value on the therapeutic alliance. The study strengthens the clinical utility of the concept of vulnerable narcissism towards the evaluation of treatment processes in borderline personality disorder.</AbstractText
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Acquiring bioelectric signals from many single neurons in primate brain remains challenging. Chronic implants offer a reasonable channel count (∼100) but sample only a small, fixed region of the cortex. Acutely inserted electrodes can sample from a wider region by making new penetrations each day. The aim of this study was to develop an active dense CMOS probe and experimental procedures to demonstrate acute large-scale single unit recordings from behaving monkeys.</AbstractText A single-shank CMOS probe was specifically designed for intracortical macaque recordings. The device is based on SiNAPS technology, with additional multiplexing circuits to minimize output lines. Synchronous sampling at 20 kHz/channel from >2k electrode-pixels is achieved with multiple probe systems. Experiments were performed in behaving macaques, achieving multiple day insertions in the motor cortex. Methods were developed to extract spontaneous spiking times of antidromically-identified neurons.</AbstractText The probe (10.7 mm in length, 158 μm in width, 50 μm in thickness) provides a regular array of 1024 electrodes (14 × 14 μm <sup This probe configuration can reach the anterior bank of the central sulcus, which contains many corticospinal cells that connect directly to motoneurons.</AbstractText This study is an important advance in the toolkit of primate neurophysiology.</AbstractText
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The stability of the alternative model of personality disorders: Example of the situation related to Covid-19. This article aims to explore the relationships between two key levels (Criteria A and B) in the Alternative Model of Personality Disorders (AMPD). Specifically, it examines the articulation between the level of personality functioning (LPF) and the pathological personality dimensions (PPD) to understand their respective contributions to personality disorder (PD) diagnosis.</AbstractText We analyzed data collected through the LPFS-BR and PID-5-BF instruments from two randomized samples of non-clinical participants, gathered both before (n=124) and after (n=126) the COVID-19 pandemic and subsequent lockdown. Mediation analyses were conducted to clarify how LPF and PPD interact in the assessment of PDs.</AbstractText Findings indicate notable intensity differences in LPF levels (P<0.001, Cohen's d>0.92), alongside high stability in both overall PD severity and PPD traits (P>0.05). Regression analysis allowed us to examine the combined effects of Lockdown, Identity, and Detachment on PD severity through mediation modelling. Results suggest that Identity mediates the effects of both Lockdown and Detachment, with Detachment also having a direct impact.</AbstractText These results indicate that while certain aspects of the AMPD are context-sensitive, the PPD may offset these fluctuations through both direct and indirect mechanisms.</AbstractText
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Vulnerable narcissism as beneficial factor for the therapeutic alliance in borderline personality disorder. Evidence suggests that narcissism and borderline personality disorder are associated with each other. This naturalistic study investigated the predictive value of grandiose and vulnerable narcissism on the development of the therapeutic alliance in short-term psychodynamic treatment across 12 weeks. The sample consisted of 99 patients with borderline personality disorder. Narcissism was assessed with the Pathological Narcissism Inventory at treatment onset. The therapeutic alliance was rated with the Scale to Assess Therapeutic Relationships by both patient and therapist at four time points during treatment. Results showed a significant predictive value of vulnerable narcissism on the therapeutic alliance, revealing a more beneficial progression for patients with higher vulnerable narcissism. Grandiose narcissism had no predictive value on the therapeutic alliance. The study strengthens the clinical utility of the concept of vulnerable narcissism towards the evaluation of treatment processes in borderline personality disorder.</AbstractText
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High-density, Identified Cell Recordings from Motor Cortex of Awake Behaving Macaques using 1024-channel SiNAPS-NHP Probes. Acquiring bioelectric signals from many single neurons in primate brain remains challenging. Chronic implants offer a reasonable channel count (∼100) but sample only a small, fixed region of the cortex. Acutely inserted electrodes can sample from a wider region by making new penetrations each day. The aim of this study was to develop an active dense CMOS probe and experimental procedures to demonstrate acute large-scale single unit recordings from behaving monkeys.</AbstractText A single-shank CMOS probe was specifically designed for intracortical macaque recordings. The device is based on SiNAPS technology, with additional multiplexing circuits to minimize output lines. Synchronous sampling at 20 kHz/channel from >2k electrode-pixels is achieved with multiple probe systems. Experiments were performed in behaving macaques, achieving multiple day insertions in the motor cortex. Methods were developed to extract spontaneous spiking times of antidromically-identified neurons.</AbstractText The probe (10.7 mm in length, 158 μm in width, 50 μm in thickness) provides a regular array of 1024 electrodes (14 × 14 μm <sup This probe configuration can reach the anterior bank of the central sulcus, which contains many corticospinal cells that connect directly to motoneurons.</AbstractText This study is an important advance in the toolkit of primate neurophysiology.</AbstractText
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37657970
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35421548
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37112057
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Pulmonary transit time as a marker of diastolic dysfunction in Takotsubo syndrome.
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Quantitative evaluation of the tibiofemoral joint cartilage by T2 mapping in patients with acute anterior cruciate ligament injury vs contralateral knees: results from the subacute phase using data from the NACOX study cohort.
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Chain Dynamics of Partially Disentangled UHMWPE around Melting Point Characterized by (1)H Low-Field Solid-State NMR.
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To evaluate the pulmonary transit time (PTT) and its derived parameters using cardiac magnetic resonance imaging (CMRI) as markers of diastolic dysfunction in Takotsubo syndrome (TS) and its relationship with transthoracic echocardiography and CMRI parameters.</AbstractText Twenty-two patients with TS, who exhibited diastolic dysfunction as assessed by transthoracic echocardiography, were enrolled retrospectively and the PTT, pulmonary transit time index (PTTI), and pulmonary blood volume index (PBVI) were evaluated using first-pass CMRI. PTT was calculated as the number of cardiac cycles required for a bolus of contrast agent to move from the right ventricle (RV) to the left ventricle (LV), whereas PTTI represents the PTT interval corrected for the heart rate. Finally, PBVI was calculated as the product of PTTI, and RV stroke volume indexed for body surface area. Normal references of PTT, PTTI, and PBVI were evaluated in a cohort of 20 age- and sex-matched healthy controls.</AbstractText Compared with healthy subjects, TS patients showed significantly higher PTT, PTTI, and PBVI (p=0.0001, p=0.0001, and p=0.002, respectively). Using multivariable logistic regression, PBVI provided the best differentiation between TS and controls (AUC 0.84). PBVI was significantly associated with the index of diastolic dysfunction and left atrial strain parameters. In addition, PBVI demonstrated a significant correlation with global T2 mapping (r=0,520, p=0,019).</AbstractText PTT and the derived parameters, as assessed using first-pass CMRI, are potential tools for assessing LV diastolic dysfunction in patients with TS.</AbstractText
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Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee.</AbstractText Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test.</AbstractText T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments.</AbstractText Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA.</AbstractText NCT02931084.</AbstractText
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Melts of ultrahigh molecular weight polyethylene (UHMWPE) entangled significantly, suffering processing difficulty. In this work, we prepared partially disentangled UHMWPE by freeze-extracting, exploring the corresponding enchantment of chain mobility. Fully refocused <sup
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Pulmonary transit time as a marker of diastolic dysfunction in Takotsubo syndrome. To evaluate the pulmonary transit time (PTT) and its derived parameters using cardiac magnetic resonance imaging (CMRI) as markers of diastolic dysfunction in Takotsubo syndrome (TS) and its relationship with transthoracic echocardiography and CMRI parameters.</AbstractText Twenty-two patients with TS, who exhibited diastolic dysfunction as assessed by transthoracic echocardiography, were enrolled retrospectively and the PTT, pulmonary transit time index (PTTI), and pulmonary blood volume index (PBVI) were evaluated using first-pass CMRI. PTT was calculated as the number of cardiac cycles required for a bolus of contrast agent to move from the right ventricle (RV) to the left ventricle (LV), whereas PTTI represents the PTT interval corrected for the heart rate. Finally, PBVI was calculated as the product of PTTI, and RV stroke volume indexed for body surface area. Normal references of PTT, PTTI, and PBVI were evaluated in a cohort of 20 age- and sex-matched healthy controls.</AbstractText Compared with healthy subjects, TS patients showed significantly higher PTT, PTTI, and PBVI (p=0.0001, p=0.0001, and p=0.002, respectively). Using multivariable logistic regression, PBVI provided the best differentiation between TS and controls (AUC 0.84). PBVI was significantly associated with the index of diastolic dysfunction and left atrial strain parameters. In addition, PBVI demonstrated a significant correlation with global T2 mapping (r=0,520, p=0,019).</AbstractText PTT and the derived parameters, as assessed using first-pass CMRI, are potential tools for assessing LV diastolic dysfunction in patients with TS.</AbstractText
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Quantitative evaluation of the tibiofemoral joint cartilage by T2 mapping in patients with acute anterior cruciate ligament injury vs contralateral knees: results from the subacute phase using data from the NACOX study cohort. Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee.</AbstractText Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test.</AbstractText T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments.</AbstractText Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA.</AbstractText NCT02931084.</AbstractText
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Chain Dynamics of Partially Disentangled UHMWPE around Melting Point Characterized by (1)H Low-Field Solid-State NMR. Melts of ultrahigh molecular weight polyethylene (UHMWPE) entangled significantly, suffering processing difficulty. In this work, we prepared partially disentangled UHMWPE by freeze-extracting, exploring the corresponding enchantment of chain mobility. Fully refocused <sup
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40051618
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27068622
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40400301
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Super-resolution of nodal and paranodal disruption in anti-pan-neurofascin-associated autoimmune nodopathy.
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Inherited and acquired disorders of myelin: The underlying myelin pathology.
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Therapeutic Potential of Methylindoline Derivative in Ameliorating Cadmium-Induced Nephritis Experimented in Zebrafish Model.
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In autoimmune nodopathies, autoantibodies target the nodes of Ranvier, impairing saltatory nerve conduction. Understanding the impact of autoantibody binding on protein assembly is crucial for gaining insights into the pathogenicity of different autoantibodies. We investigated nodal, paranodal, and cytoskeletal axonal proteins in teased fibers from a sural nerve biopsy of a patient with anti-pan-neurofascin autoantibodies. Conventional diagnostic tools, including fluorescence microscopy, often miss subtle alterations at the ultrastructural level.</AbstractText We utilized direct stochastic optical reconstruction microscopy (dSTORM), a super-resolution fluorescence imaging technique, to assess the nanoscale architecture of nodal, paranodal, and cytoskeletal axonal proteins.</AbstractText While conventional fluorescence microscopy revealed severe paranodal and nodal damage in 14% of the nodes, with 86% appearing normal at first glance, the super-resolved images revealed a decreased neurofascin-155 and Caspr-1 density, but preserved colocalization of these adhesion proteins in paranodes that initially seemed normal. At the nodes, sodium channel density and distribution remained intact, but neurofascin-186 density was reduced. Axonal beta-IV spectrin was altered only in severely damaged nodes. This indicates that axonal integrity is largely preserved, with a potentially reversible decrease in paranodal and nodal adhesion proteins in patients with nodopathy revealing subtle alterations in nodal integrity that are not apparent with conventional imaging.</AbstractText These likely reversible changes may explain the rapid recovery seen in patients with anti-pan-neurofascin autoantibodies following autoantibody depletion. Conversely, the small percentage of severely and axonally damaged nodes may account for the residual symptoms experienced by most patients.</AbstractText
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Remyelination is a major therapeutic goal in human myelin disorders, serving to restore function to demyelinated axons and providing neuroprotection. The target disorders that might be amenable to the promotion of this repair process are diverse and increasing in number. They range primarily from those of genetic, inflammatory to toxic origin. In order to apply remyelinating strategies to these disorders, it is essential to know whether the myelin damage results from a primary attack on myelin or the oligodendrocyte or both, and whether indeed these lead to myelin breakdown and demyelination. In some disorders, myelin sheath abnormalities are prominent but demyelination does not occur. This review explores the range of human and animal disorders where myelin pathology exists and focusses on defining the myelin changes in each and their cause, to help define whether they are targets for myelin repair therapy.</AbstractText
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Since kidney diseases are a major global concern, their impact on public health makes them an important area of study. The kidneys, as the primary organs responsible for excreting waste, are particularly vulnerable to heavy metal poisoning. Cadmium (Cd), a naturally occurring heavy metal found in contaminated food and water, poses a serious risk to renal health. Due to their remarkable biological properties, methylindoline derivatives are being investigated for a variety of medicinal applications. The primary objective of this study is to screen and assess the anti-inflammatory and anti-nephritic qualities of methylindoline derivatives (IA, IB, IC, ID, IE). Through network pharmacology and molecular docking analyzes, the derivative IC ((E)-3-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-methylindolin-2-one) was identified for further study. In In Vitro screening, IC showed strong antioxidant and anti-inflammatory properties in a dose-dependent manner. It effectively reduced oxidative stress, lipid peroxidation, and apoptosis induced by cadmium in zebrafish. In renal tissues, IC treatment decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while restoring the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). The expression of pro-inflammatory cytokine genes, including TNF-α, IL-1β, IL-6, and NF-κB, was also significantly downregulated by IC. Histopathological analysis of zebrafish kidneys demonstrated the restoration of renal tissue architecture, validating the protective effects of IC. These results highlight IC's therapeutic potential in treating cadmium-induced nephritis.</AbstractText
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Super-resolution of nodal and paranodal disruption in anti-pan-neurofascin-associated autoimmune nodopathy. In autoimmune nodopathies, autoantibodies target the nodes of Ranvier, impairing saltatory nerve conduction. Understanding the impact of autoantibody binding on protein assembly is crucial for gaining insights into the pathogenicity of different autoantibodies. We investigated nodal, paranodal, and cytoskeletal axonal proteins in teased fibers from a sural nerve biopsy of a patient with anti-pan-neurofascin autoantibodies. Conventional diagnostic tools, including fluorescence microscopy, often miss subtle alterations at the ultrastructural level.</AbstractText We utilized direct stochastic optical reconstruction microscopy (dSTORM), a super-resolution fluorescence imaging technique, to assess the nanoscale architecture of nodal, paranodal, and cytoskeletal axonal proteins.</AbstractText While conventional fluorescence microscopy revealed severe paranodal and nodal damage in 14% of the nodes, with 86% appearing normal at first glance, the super-resolved images revealed a decreased neurofascin-155 and Caspr-1 density, but preserved colocalization of these adhesion proteins in paranodes that initially seemed normal. At the nodes, sodium channel density and distribution remained intact, but neurofascin-186 density was reduced. Axonal beta-IV spectrin was altered only in severely damaged nodes. This indicates that axonal integrity is largely preserved, with a potentially reversible decrease in paranodal and nodal adhesion proteins in patients with nodopathy revealing subtle alterations in nodal integrity that are not apparent with conventional imaging.</AbstractText These likely reversible changes may explain the rapid recovery seen in patients with anti-pan-neurofascin autoantibodies following autoantibody depletion. Conversely, the small percentage of severely and axonally damaged nodes may account for the residual symptoms experienced by most patients.</AbstractText
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Inherited and acquired disorders of myelin: The underlying myelin pathology. Remyelination is a major therapeutic goal in human myelin disorders, serving to restore function to demyelinated axons and providing neuroprotection. The target disorders that might be amenable to the promotion of this repair process are diverse and increasing in number. They range primarily from those of genetic, inflammatory to toxic origin. In order to apply remyelinating strategies to these disorders, it is essential to know whether the myelin damage results from a primary attack on myelin or the oligodendrocyte or both, and whether indeed these lead to myelin breakdown and demyelination. In some disorders, myelin sheath abnormalities are prominent but demyelination does not occur. This review explores the range of human and animal disorders where myelin pathology exists and focusses on defining the myelin changes in each and their cause, to help define whether they are targets for myelin repair therapy.</AbstractText
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Therapeutic Potential of Methylindoline Derivative in Ameliorating Cadmium-Induced Nephritis Experimented in Zebrafish Model. Since kidney diseases are a major global concern, their impact on public health makes them an important area of study. The kidneys, as the primary organs responsible for excreting waste, are particularly vulnerable to heavy metal poisoning. Cadmium (Cd), a naturally occurring heavy metal found in contaminated food and water, poses a serious risk to renal health. Due to their remarkable biological properties, methylindoline derivatives are being investigated for a variety of medicinal applications. The primary objective of this study is to screen and assess the anti-inflammatory and anti-nephritic qualities of methylindoline derivatives (IA, IB, IC, ID, IE). Through network pharmacology and molecular docking analyzes, the derivative IC ((E)-3-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-methylindolin-2-one) was identified for further study. In In Vitro screening, IC showed strong antioxidant and anti-inflammatory properties in a dose-dependent manner. It effectively reduced oxidative stress, lipid peroxidation, and apoptosis induced by cadmium in zebrafish. In renal tissues, IC treatment decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while restoring the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). The expression of pro-inflammatory cytokine genes, including TNF-α, IL-1β, IL-6, and NF-κB, was also significantly downregulated by IC. Histopathological analysis of zebrafish kidneys demonstrated the restoration of renal tissue architecture, validating the protective effects of IC. These results highlight IC's therapeutic potential in treating cadmium-induced nephritis.</AbstractText
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39466507
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36129222
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40686908
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Developing a Reproducible Radiomics Model for Diagnosis of Active Crohn's Disease on CT Enterography Across Annotation Variations and Acquisition Differences.
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Detectability of Small Low-Attenuation Lesions With Deep Learning CT Image Reconstruction: A 24-Reader Phantom Study.
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Rapid traceability of Gastrodia elata Blume origins and analysis of key volatile organic components using FTIR and HS-SPME-GC-MS combined with chemometrics.
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To systematically identify radiomics features on CT enterography (CTE) scans which can accurately diagnose active Crohn's disease across multiple sources of variation. Retrospective study of CTE scans curated between 2013 and 2015, comprising 164 subjects (65 male, 99 female; all patients were over the age of 18) with endoscopic confirmation for the presence or absence of active Crohn's disease. All patients had three distinct sets of scans available (full and reduced dose, where the latter had been reconstructed via two different methods), acquired on a single scanner at a single institution. Radiomics descriptors from annotated terminal ileum regions were individually and systematically evaluated for resilience to different imaging variations (changes in dose/reconstruction, batch effects, and simulated annotation differences) via multiple reproducibility measures. Multiple radiomics models (by accounting for each source of variation) were evaluated in terms of classifier area under the ROC curve (AUC) for identifying patients with active Crohn's disease, across separate discovery and hold-out validation cohorts. Radiomics descriptors selected based on resiliency to multiple sources of imaging variation yielded the highest overall classification performance in the discovery cohort (AUC = 0.79 ± 0.04) which also best generalized in hold-out validation (AUC = 0.81). Performance was maintained across multiple doses and reconstructions while also being significantly better (p < 0.001) than non-resilient descriptors or descriptors only resilient to a single source of variation. Radiomics features can accurately diagnose active Crohn's disease on CTE scans across multiple sources of imaging variation via systematic analysis of reproducibility measures. Clinical utility and translatability of radiomics features for diagnosis and characterization of Crohn's disease on CTE scans will be contingent on their reproducibility across multiple types and sources of imaging variation.</AbstractText
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<b
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<i
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Developing a Reproducible Radiomics Model for Diagnosis of Active Crohn's Disease on CT Enterography Across Annotation Variations and Acquisition Differences. To systematically identify radiomics features on CT enterography (CTE) scans which can accurately diagnose active Crohn's disease across multiple sources of variation. Retrospective study of CTE scans curated between 2013 and 2015, comprising 164 subjects (65 male, 99 female; all patients were over the age of 18) with endoscopic confirmation for the presence or absence of active Crohn's disease. All patients had three distinct sets of scans available (full and reduced dose, where the latter had been reconstructed via two different methods), acquired on a single scanner at a single institution. Radiomics descriptors from annotated terminal ileum regions were individually and systematically evaluated for resilience to different imaging variations (changes in dose/reconstruction, batch effects, and simulated annotation differences) via multiple reproducibility measures. Multiple radiomics models (by accounting for each source of variation) were evaluated in terms of classifier area under the ROC curve (AUC) for identifying patients with active Crohn's disease, across separate discovery and hold-out validation cohorts. Radiomics descriptors selected based on resiliency to multiple sources of imaging variation yielded the highest overall classification performance in the discovery cohort (AUC = 0.79 ± 0.04) which also best generalized in hold-out validation (AUC = 0.81). Performance was maintained across multiple doses and reconstructions while also being significantly better (p < 0.001) than non-resilient descriptors or descriptors only resilient to a single source of variation. Radiomics features can accurately diagnose active Crohn's disease on CTE scans across multiple sources of imaging variation via systematic analysis of reproducibility measures. Clinical utility and translatability of radiomics features for diagnosis and characterization of Crohn's disease on CTE scans will be contingent on their reproducibility across multiple types and sources of imaging variation.</AbstractText
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Detectability of Small Low-Attenuation Lesions With Deep Learning CT Image Reconstruction: A 24-Reader Phantom Study. <b
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Rapid traceability of Gastrodia elata Blume origins and analysis of key volatile organic components using FTIR and HS-SPME-GC-MS combined with chemometrics. <i
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39498310
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30318667
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39565860
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Accuracy, repeatability, and reproducibility of water-fat magnetic resonance imaging in a phantom and healthy volunteer.
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Simultaneous fat-free isotropic 3D anatomical imaging and T(2) mapping of knee cartilage with lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses.
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Immune responses drive chorioretinitis and retinal pathology after neonatal CMV infection.
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Bone marrow (BM) damage due to chemoradiotherapy can increase BM fat in cervical cancer patients. Water-fat magnetic resonance (MR) scans were performed on a phantom and a healthy female volunteer to validate proton density fat fraction accuracy, reproducibility, and repeatability across different vendors, field strengths, and protocols. Phantom measurements showed a high accuracy, high repeatability, and excellent reproducibility. Volunteer measurements had an excellent intra- and interreader reliability, good repeatability, and moderate to good reproducibility. Water-fat MRI show potential for quantification of longitudinal vertebral BM fat changes. Further studies are needed to validate and extend these findings for broader clinical applicability.</AbstractText
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Improved knee cartilage morphological delineation and T<sub To develop and assess an isotropic 3D lipid-insensitive T<sub Prospective.</AbstractText Phantoms (n = 6) used in this study were designed to mimic the T<sub A high-resolution isotropic 3D T<sub Numerical simulations and phantom experiments were performed to optimize the LIBRE pulse. Phantom studies were carried out to test the accuracy of the technique against reference standard spin-echo (SE) T<sub A two-tailed paired Student's t-test was used to compare the average T<sub A LIBRE pulse of 1 msec suppressed fat with an RF excitation frequency offset of 1560 Hz and optimal RF excitation angle of 35°. These results were corroborated by phantom and knee experiments. Robust and homogeneous fat suppression was obtained (a fat signal-to-noise ratio (SNR) decrease of 86.4 ± 2.4%). In phantoms, T<sub Homogeneous LIBRE fat signal suppression was achieved with a total RF pulse duration of 1 msec, allowing for the removal of chemical shift artifacts and resulting in improved cartilage delineation and precise T<sub 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1275-1284.</AbstractText
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Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T cell infiltration of the retina and marked gliosis. Blocking immune responses generally, or via targeting the chemokine receptor CXCR3, did not exacerbate retinal disease but instead prevented pathology despite retinal MCMV infection. Thus, our data establish this model for studies of congenital retinal disease and show that the immune system drives pathology in the neonatal eye after MCMV infection.</AbstractText
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Accuracy, repeatability, and reproducibility of water-fat magnetic resonance imaging in a phantom and healthy volunteer. Bone marrow (BM) damage due to chemoradiotherapy can increase BM fat in cervical cancer patients. Water-fat magnetic resonance (MR) scans were performed on a phantom and a healthy female volunteer to validate proton density fat fraction accuracy, reproducibility, and repeatability across different vendors, field strengths, and protocols. Phantom measurements showed a high accuracy, high repeatability, and excellent reproducibility. Volunteer measurements had an excellent intra- and interreader reliability, good repeatability, and moderate to good reproducibility. Water-fat MRI show potential for quantification of longitudinal vertebral BM fat changes. Further studies are needed to validate and extend these findings for broader clinical applicability.</AbstractText
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Simultaneous fat-free isotropic 3D anatomical imaging and T(2) mapping of knee cartilage with lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses. Improved knee cartilage morphological delineation and T<sub To develop and assess an isotropic 3D lipid-insensitive T<sub Prospective.</AbstractText Phantoms (n = 6) used in this study were designed to mimic the T<sub A high-resolution isotropic 3D T<sub Numerical simulations and phantom experiments were performed to optimize the LIBRE pulse. Phantom studies were carried out to test the accuracy of the technique against reference standard spin-echo (SE) T<sub A two-tailed paired Student's t-test was used to compare the average T<sub A LIBRE pulse of 1 msec suppressed fat with an RF excitation frequency offset of 1560 Hz and optimal RF excitation angle of 35°. These results were corroborated by phantom and knee experiments. Robust and homogeneous fat suppression was obtained (a fat signal-to-noise ratio (SNR) decrease of 86.4 ± 2.4%). In phantoms, T<sub Homogeneous LIBRE fat signal suppression was achieved with a total RF pulse duration of 1 msec, allowing for the removal of chemical shift artifacts and resulting in improved cartilage delineation and precise T<sub 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1275-1284.</AbstractText
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Immune responses drive chorioretinitis and retinal pathology after neonatal CMV infection. Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T cell infiltration of the retina and marked gliosis. Blocking immune responses generally, or via targeting the chemokine receptor CXCR3, did not exacerbate retinal disease but instead prevented pathology despite retinal MCMV infection. Thus, our data establish this model for studies of congenital retinal disease and show that the immune system drives pathology in the neonatal eye after MCMV infection.</AbstractText
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40021555
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10607637
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40740483
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The Animal-AI Environment: A virtual laboratory for comparative cognition and artificial intelligence research.
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Internal models for motor control and trajectory planning.
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PI3K/AKT/mTOR Axis in Cancer: From Pathogenesis to Treatment.
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The Animal-AI Environment is a unique game-based research platform designed to facilitate collaboration between the artificial intelligence and comparative cognition research communities. In this paper, we present the latest version of the Animal-AI Environment, outlining several major features that make the game more engaging for humans and more complex for AI systems. These features include interactive buttons, reward dispensers, and player notifications, as well as an overhaul of the environment's graphics and processing for significant improvements in agent training time and quality of the human player experience. We provide detailed guidance on how to build computational and behavioural experiments with the Animal-AI Environment. We present results from a series of agents, including the state-of-the-art deep reinforcement learning agent Dreamer-v3, on newly designed tests and the Animal-AI testbed of 900 tasks inspired by research in the field of comparative cognition. The Animal-AI Environment offers a new approach for modelling cognition in humans and non-human animals, and for building biologically inspired artificial intelligence.</AbstractText
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A number of internal model concepts are now widespread in neuroscience and cognitive science. These concepts are supported by behavioral, neurophysiological, and imaging data; furthermore, these models have had their structures and functions revealed by such data. In particular, a specific theory on inverse dynamics model learning is directly supported by unit recordings from cerebellar Purkinje cells. Multiple paired forward inverse models describing how diverse objects and environments can be controlled and learned separately have recently been proposed. The 'minimum variance model' is another major recent advance in the computational theory of motor control. This model integrates two furiously disputed approaches on trajectory planning, strongly suggesting that both kinematic and dynamic internal models are utilized in movement planning and control.</AbstractText
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The PI3K/AKT/mTOR signaling axis is a pivotal regulator of key cellular functions, including proliferation, metabolism, survival, and immune modulation. In cancer, its dysregulation drives malignant transformation, tumor progression, therapeutic resistance, and immune evasion. Despite numerous studies, an integrated understanding of this pathway's multifaceted role in tumor biology and treatment remains incomplete. This review comprehensively outlines the oncogenic mechanisms governed by the PI3K/AKT/mTOR pathway, including its regulation of epithelial-mesenchymal transition, autophagy, apoptosis, glycolysis, ferroptosis, and lipid metabolism. We emphasize the dual role of autophagy, its interplay with therapeutic resistance, and its contextual impact on cancer dynamics. Moreover, we explore the epigenetic regulation of this axis by noncoding RNAs (miRNAs, lncRNAs, circRNAs) and its influence on tumor hallmarks. The review also highlights the pathway's involvement in modulating responses to chemotherapy, radiotherapy, and immunotherapy, as well as its role in remodeling the tumor microenvironment. We critically evaluate emerging therapeutic strategies targeting the PI3K/AKT/mTOR axis, including small-molecule inhibitors, phytochemicals, and nanoparticle-based systems. By elucidating the integrated landscape of this pathway, our review highlights its value as a central therapeutic target and offers insights into precision oncology approaches aimed at overcoming drug resistance and enhancing treatment efficacy.</AbstractText
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The Animal-AI Environment: A virtual laboratory for comparative cognition and artificial intelligence research. The Animal-AI Environment is a unique game-based research platform designed to facilitate collaboration between the artificial intelligence and comparative cognition research communities. In this paper, we present the latest version of the Animal-AI Environment, outlining several major features that make the game more engaging for humans and more complex for AI systems. These features include interactive buttons, reward dispensers, and player notifications, as well as an overhaul of the environment's graphics and processing for significant improvements in agent training time and quality of the human player experience. We provide detailed guidance on how to build computational and behavioural experiments with the Animal-AI Environment. We present results from a series of agents, including the state-of-the-art deep reinforcement learning agent Dreamer-v3, on newly designed tests and the Animal-AI testbed of 900 tasks inspired by research in the field of comparative cognition. The Animal-AI Environment offers a new approach for modelling cognition in humans and non-human animals, and for building biologically inspired artificial intelligence.</AbstractText
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Internal models for motor control and trajectory planning. A number of internal model concepts are now widespread in neuroscience and cognitive science. These concepts are supported by behavioral, neurophysiological, and imaging data; furthermore, these models have had their structures and functions revealed by such data. In particular, a specific theory on inverse dynamics model learning is directly supported by unit recordings from cerebellar Purkinje cells. Multiple paired forward inverse models describing how diverse objects and environments can be controlled and learned separately have recently been proposed. The 'minimum variance model' is another major recent advance in the computational theory of motor control. This model integrates two furiously disputed approaches on trajectory planning, strongly suggesting that both kinematic and dynamic internal models are utilized in movement planning and control.</AbstractText
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PI3K/AKT/mTOR Axis in Cancer: From Pathogenesis to Treatment. The PI3K/AKT/mTOR signaling axis is a pivotal regulator of key cellular functions, including proliferation, metabolism, survival, and immune modulation. In cancer, its dysregulation drives malignant transformation, tumor progression, therapeutic resistance, and immune evasion. Despite numerous studies, an integrated understanding of this pathway's multifaceted role in tumor biology and treatment remains incomplete. This review comprehensively outlines the oncogenic mechanisms governed by the PI3K/AKT/mTOR pathway, including its regulation of epithelial-mesenchymal transition, autophagy, apoptosis, glycolysis, ferroptosis, and lipid metabolism. We emphasize the dual role of autophagy, its interplay with therapeutic resistance, and its contextual impact on cancer dynamics. Moreover, we explore the epigenetic regulation of this axis by noncoding RNAs (miRNAs, lncRNAs, circRNAs) and its influence on tumor hallmarks. The review also highlights the pathway's involvement in modulating responses to chemotherapy, radiotherapy, and immunotherapy, as well as its role in remodeling the tumor microenvironment. We critically evaluate emerging therapeutic strategies targeting the PI3K/AKT/mTOR axis, including small-molecule inhibitors, phytochemicals, and nanoparticle-based systems. By elucidating the integrated landscape of this pathway, our review highlights its value as a central therapeutic target and offers insights into precision oncology approaches aimed at overcoming drug resistance and enhancing treatment efficacy.</AbstractText
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31183114
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23036449
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31398656
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Synaptic memory devices from CoO/Nb:SrTiO(3) junction.
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Granger causality analysis of fMRI BOLD signals is invariant to hemodynamic convolution but not downsampling.
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Repeated anti-N-methyl-D-aspartate receptor encephalitis coexisting with anti-myelin oligodendrocyte glycoprotein antibody-associated diseases: A case report.
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Non-volatile memristors are promising for future hardware-based neurocomputation application because they are capable of emulating biological synaptic functions. Various material strategies have been studied to pursue better device performance, such as lower energy cost, better biological plausibility, etc. In this work, we show a novel design for non-volatile memristor based on CoO/Nb:SrTiO<sub
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Granger causality is a method for identifying directed functional connectivity based on time series analysis of precedence and predictability. The method has been applied widely in neuroscience, however its application to functional MRI data has been particularly controversial, largely because of the suspicion that Granger causal inferences might be easily confounded by inter-regional differences in the hemodynamic response function. Here, we show both theoretically and in a range of simulations, that Granger causal inferences are in fact robust to a wide variety of changes in hemodynamic response properties, including notably their time-to-peak. However, when these changes are accompanied by severe downsampling, and/or excessive measurement noise, as is typical for current fMRI data, incorrect inferences can still be drawn. Our results have important implications for the ongoing debate about lag-based analyses of functional connectivity. Our methods, which include detailed spiking neuronal models coupled to biophysically realistic hemodynamic observation models, provide an important 'analysis-agnostic' platform for evaluating functional and effective connectivity methods.</AbstractText
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The coexistence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases has been reported. We report the case of a 36-year-old woman who presented with repeated typical anti-NMDAR encephalitis coexisting with unusual symptoms not consistent with anti-NMDAR encephalitis. Apart from the anti-NMDAR encephalitis, her first episode was characterized by balance disability with bilateral medial frontal cortical lesions, suggesting the involvement of the cortico-reticular projections and the basal ganglia-brainstem projections. The second episode presented with Broca's aphasia caused by involvement of the Broca's area and lower part of the precentral gyrus. The detection of MOG-Ab in both episodes suggested the coexistence of MOG-Ab-associated diseases. Thus, an evaluation of MOG-Ab should be considered when anti-NMDAR encephalitis presenting with atypical symptoms is encountered.</AbstractText
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Synaptic memory devices from CoO/Nb:SrTiO(3) junction. Non-volatile memristors are promising for future hardware-based neurocomputation application because they are capable of emulating biological synaptic functions. Various material strategies have been studied to pursue better device performance, such as lower energy cost, better biological plausibility, etc. In this work, we show a novel design for non-volatile memristor based on CoO/Nb:SrTiO<sub
|
Granger causality analysis of fMRI BOLD signals is invariant to hemodynamic convolution but not downsampling. Granger causality is a method for identifying directed functional connectivity based on time series analysis of precedence and predictability. The method has been applied widely in neuroscience, however its application to functional MRI data has been particularly controversial, largely because of the suspicion that Granger causal inferences might be easily confounded by inter-regional differences in the hemodynamic response function. Here, we show both theoretically and in a range of simulations, that Granger causal inferences are in fact robust to a wide variety of changes in hemodynamic response properties, including notably their time-to-peak. However, when these changes are accompanied by severe downsampling, and/or excessive measurement noise, as is typical for current fMRI data, incorrect inferences can still be drawn. Our results have important implications for the ongoing debate about lag-based analyses of functional connectivity. Our methods, which include detailed spiking neuronal models coupled to biophysically realistic hemodynamic observation models, provide an important 'analysis-agnostic' platform for evaluating functional and effective connectivity methods.</AbstractText
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Repeated anti-N-methyl-D-aspartate receptor encephalitis coexisting with anti-myelin oligodendrocyte glycoprotein antibody-associated diseases: A case report. The coexistence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases has been reported. We report the case of a 36-year-old woman who presented with repeated typical anti-NMDAR encephalitis coexisting with unusual symptoms not consistent with anti-NMDAR encephalitis. Apart from the anti-NMDAR encephalitis, her first episode was characterized by balance disability with bilateral medial frontal cortical lesions, suggesting the involvement of the cortico-reticular projections and the basal ganglia-brainstem projections. The second episode presented with Broca's aphasia caused by involvement of the Broca's area and lower part of the precentral gyrus. The detection of MOG-Ab in both episodes suggested the coexistence of MOG-Ab-associated diseases. Thus, an evaluation of MOG-Ab should be considered when anti-NMDAR encephalitis presenting with atypical symptoms is encountered.</AbstractText
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40418702
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32569760
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38313895
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Literature Commentary.
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Therapeutic Hypothermia in Patients with Malignant Ischemic Stroke and Hemicraniectomy-A Systematic Review and Meta-analysis.
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Dual-Target Radiosurgery for Concomitant Continuous Pain Presentation of Trigeminal Neuralgia: Radiomodulation Effect and Dose.
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 In this issue of JNO, Drs. Deborah I. Friedman and Mark L. Moster discuss the following 4 articles. 1. Kim J, Han K, Jung JH, Park KA, Oh SY. Nonarteritic anterior ischemic optic neuropathy and the risk of dementia: a nationwide cohort study. Neurology. 2024;103:e209657.2. Pakravan P, Lai J, Cavuoto KM. Demographics, practice analysis and geographic distribution of neuro-ophthalmologists in the United States in 2023. Ophthalmology. 2024;131:333-340.3. Lema GMC, De Leacy R, Fara MG, Ginsburg RN, Barash A, Banashefski B, Tsai JC, Rosen RB. A remote consult retinal artery occlusion diagnostic protocol. Ophthalmology. 2024;131:724-730.4. Hathaway JT, Shah M, Hathaway DB, Zekavat SM, Krasniqi D, Gittinger JW Jr, Cestari D, Mallery R, Abbasi B, Bouffard M, Chwalisz BK, Estrela T, Rizzo JF III. Risk of non-arteritic ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol 2024:142:732-739.</AbstractText
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Therapeutic hypothermia (TH) offers cerebral protection following ischemic stroke and may improve outcomes in conjunction with decompressive hemicraniectomy (DHC). We aimed to assess the effectiveness of TH in patients with malignant ischemic stroke and DHC.</AbstractText We performed a meta-analysis in patients with malignant ischemic stroke undergoing DHC comparing TH versus normothermia in studies published up to August 2019. Included studies had ≥10 adults with acute ischemic stroke. Primary outcome was functional independence, and secondary outcomes included complications. Effect size was pooled and described by relative risk (RR) ratios and 95% confidence intervals (CIs).</AbstractText Five studies (n = 269 patients; n = 130 TH, n = 139 controls) were included, 4 of which were prospective (n = 2 randomized controlled trials). Median achieved body temperature of TH was 33.6°C (range 33°C-35°C). Median modified Rankin Scale at the study completion was similar between TH and controls (RR 1.08, 95% CI 0.56-2.07, P = 0.8). Three studies reported individual patient modified Rankin Scale outcomes demonstrated a shift toward worse outcomes with TH (unadjusted common odds ratio 1.74; 95% CI 1.05-2.88, P = 0.01). Overall complications were similar between groups (RR 1.20, 95% CI 0.70-2.05, random effects P = 0.5). A suggestion of higher mortality was seen in TH (RR 1.50, 95% CI 0.97-2.32, P = 0.07).</AbstractText Clinical and functional outcomes were not overall different between patients undergoing systemic TH and controls following DHC despite the shift toward worse outcomes with TH observed in some studies.</AbstractText
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Patients with trigeminal neuralgia (TN) experience concomitant continuous pain (CCP) that can be difficult to treat. A dual-target approach delivering a high dose of radiation to the nerve and the contralateral thalamus can develop a fast radiomodulation effect on lowering pain. We sought to determine if this effect was dose dependent.</AbstractText We retrospectively reviewed 21 patients treated with radiosurgery in CCP and severe TN pain, with a visual analog scale (VAS) score of nine out of 10 at the time of treatment. Ten patients were treated with a high dose (>120 Gy) in the thalamus 90 Gy to the nerve, and the rest with a low dose (<120 Gy) to the thalamus and >90 Gy to the nerve.</AbstractText Of those who received the high dose to the thalamus, six patients (60%) received 140 Gy, and four (40%) received 120 Gy, with a median dose to the trigeminal nerve of 90 and 85 Gy, respectively. The high thalamus dose showed a radiomodulation effect from day 1. The low thalamus dose did not produce radiomodulation on any of the first four days. The percentage of VAS score reduction one month after treatment was higher in the high-thalamus dose group than in the low-thalamus dose group. At three months, VAS score was 2 in the high-dose group and 4 in the low-dose group.</AbstractText The radiomodulation effect in pain and dual-target radiosurgery is dose dependent in CCP in TN; a high dose can provide a more consistent clinical result than a lower dose.</AbstractText
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Literature Commentary.  In this issue of JNO, Drs. Deborah I. Friedman and Mark L. Moster discuss the following 4 articles. 1. Kim J, Han K, Jung JH, Park KA, Oh SY. Nonarteritic anterior ischemic optic neuropathy and the risk of dementia: a nationwide cohort study. Neurology. 2024;103:e209657.2. Pakravan P, Lai J, Cavuoto KM. Demographics, practice analysis and geographic distribution of neuro-ophthalmologists in the United States in 2023. Ophthalmology. 2024;131:333-340.3. Lema GMC, De Leacy R, Fara MG, Ginsburg RN, Barash A, Banashefski B, Tsai JC, Rosen RB. A remote consult retinal artery occlusion diagnostic protocol. Ophthalmology. 2024;131:724-730.4. Hathaway JT, Shah M, Hathaway DB, Zekavat SM, Krasniqi D, Gittinger JW Jr, Cestari D, Mallery R, Abbasi B, Bouffard M, Chwalisz BK, Estrela T, Rizzo JF III. Risk of non-arteritic ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol 2024:142:732-739.</AbstractText
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Therapeutic Hypothermia in Patients with Malignant Ischemic Stroke and Hemicraniectomy-A Systematic Review and Meta-analysis. Therapeutic hypothermia (TH) offers cerebral protection following ischemic stroke and may improve outcomes in conjunction with decompressive hemicraniectomy (DHC). We aimed to assess the effectiveness of TH in patients with malignant ischemic stroke and DHC.</AbstractText We performed a meta-analysis in patients with malignant ischemic stroke undergoing DHC comparing TH versus normothermia in studies published up to August 2019. Included studies had ≥10 adults with acute ischemic stroke. Primary outcome was functional independence, and secondary outcomes included complications. Effect size was pooled and described by relative risk (RR) ratios and 95% confidence intervals (CIs).</AbstractText Five studies (n = 269 patients; n = 130 TH, n = 139 controls) were included, 4 of which were prospective (n = 2 randomized controlled trials). Median achieved body temperature of TH was 33.6°C (range 33°C-35°C). Median modified Rankin Scale at the study completion was similar between TH and controls (RR 1.08, 95% CI 0.56-2.07, P = 0.8). Three studies reported individual patient modified Rankin Scale outcomes demonstrated a shift toward worse outcomes with TH (unadjusted common odds ratio 1.74; 95% CI 1.05-2.88, P = 0.01). Overall complications were similar between groups (RR 1.20, 95% CI 0.70-2.05, random effects P = 0.5). A suggestion of higher mortality was seen in TH (RR 1.50, 95% CI 0.97-2.32, P = 0.07).</AbstractText Clinical and functional outcomes were not overall different between patients undergoing systemic TH and controls following DHC despite the shift toward worse outcomes with TH observed in some studies.</AbstractText
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Dual-Target Radiosurgery for Concomitant Continuous Pain Presentation of Trigeminal Neuralgia: Radiomodulation Effect and Dose. Patients with trigeminal neuralgia (TN) experience concomitant continuous pain (CCP) that can be difficult to treat. A dual-target approach delivering a high dose of radiation to the nerve and the contralateral thalamus can develop a fast radiomodulation effect on lowering pain. We sought to determine if this effect was dose dependent.</AbstractText We retrospectively reviewed 21 patients treated with radiosurgery in CCP and severe TN pain, with a visual analog scale (VAS) score of nine out of 10 at the time of treatment. Ten patients were treated with a high dose (>120 Gy) in the thalamus 90 Gy to the nerve, and the rest with a low dose (<120 Gy) to the thalamus and >90 Gy to the nerve.</AbstractText Of those who received the high dose to the thalamus, six patients (60%) received 140 Gy, and four (40%) received 120 Gy, with a median dose to the trigeminal nerve of 90 and 85 Gy, respectively. The high thalamus dose showed a radiomodulation effect from day 1. The low thalamus dose did not produce radiomodulation on any of the first four days. The percentage of VAS score reduction one month after treatment was higher in the high-thalamus dose group than in the low-thalamus dose group. At three months, VAS score was 2 in the high-dose group and 4 in the low-dose group.</AbstractText The radiomodulation effect in pain and dual-target radiosurgery is dose dependent in CCP in TN; a high dose can provide a more consistent clinical result than a lower dose.</AbstractText
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39843799
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40309587
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40731971
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Clinical novel exploration of intractable fever in stroke rehabilitation: a single-center cross-sectional retrospective study.
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Nutritional status of elderly hypertensive patients and its relation to the occurrence of cognitive impairment.
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Diagnostic Approaches for Candida auris: A Comprehensive Review of Screening, Identification, and Susceptibility Testing.
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Fever has long been recognized as one of the earliest clinical indicators of illness and remains a leading reason for seeking medical care worldwide. It is typically classified based on its duration and underlying etiology. In clinical settings, intractable fever is as common as acute fever, particularly in patients with brain injuries. Beyond infectious causes, stroke survivors often experience recurrent intractable fever due to central or neurogenic mechanisms. This study aims to retrospectively investigate the incidence and clinical characteristics of acute and intractable fever in patients undergoing stroke rehabilitation. It explores the associations between these characteristics and the different types of fever. Additionally, the study seeks to identify potential risk factors contributing to the development of intractable fever, aiming to guide clinical management and optimize treatment strategies for stroke-related fever. This study evaluated 1,065 stroke patients in the rehabilitation phase who were admitted to the Neurorehabilitation Center between January 1, 2023, and December 31, 2023. Of these, 230 febrile patients met the inclusion criteria and were included in the analysis, comprising 194 cases of acute fever and 36 cases of intractable fever. Medical records and clinical characteristics were collected, and the data from the two groups of febrile patients were analyzed using t-tests, Mann-Whitney U tests, and chi-square tests. Logistic regression analysis was performed to identify risk factors associated with intractable fever, while receiver operating characteristic (ROC) curves were used to assess the predictive performance of individual and combined risk factors. A p-value of less than 0.05 was considered statistically significant. 15.7% of patients experienced intractable fever, which was significantly associated with brainstem lesions (P < 0.05). Compared to patients with acute fever, those with intractable fever had higher NIHSS scores (33.3% vs. 15.5%, P < 0.05), a greater incidence of consciousness disorders (66.7% vs. 28.9%, P < 0.05), and a higher rate of tracheostomy (55.6% vs. 15.5%, P < 0.05). All patients received antibiotic treatment, and gabapentin was administered to 16 cases. Patients with brainstem lesions were less likely to be treated with gabapentin (37.5% vs. 90%, P < 0.05), while those with intracerebral hemorrhage were more likely to receive gabapentin (87.5% vs. 10%, P < 0.05). Logistic regression analysis revealed that consciousness disorders and tracheostomy status were significant risk factors for intractable fever (P = 0.047, OR 6.691, 95% CI 1.030-43.478; P = 0.021, OR 5.366, 95% CI 1.282-22.465). Brainstem lesions also significantly increased the risk (P = 0.002, OR 9.617, 95% CI 2.277-40.614). Although limited in scope, this retrospective study highlights the increased risk of intractable fever during stroke rehabilitation among patients with consciousness disorders, tracheostomy, and brainstem injuries. The key risk factors identified include higher NIHSS scores, impaired consciousness, tracheostomy status, and brainstem lesions.</AbstractText
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Hypertension is a common chronic disease in the elderly population, and its association with cognitive impairment has been increasingly recognized. Cognitive impairment, including mild cognitive impairment and dementia, can significantly affect the quality of life and independence of elderly individuals. Therefore, identifying risk factors for cognitive impairment in elderly hypertensive patients is crucial for developing effective interventions and improving health outcomes. Nutritional status is one of the potential factors that may influence cognitive function in elderly hypertensive patients. Malnutrition or inadequate nutrition can lead to various health problems, including weakened immune system, increased susceptibility to infections, and impaired physical and mental function. Furthermore, poor nutritional status has been linked to increased risk of cognitive decline and dementia in various populations. In this observational study, we aimed to investigate the nutritional status of elderly hypertensive patients and its relationship to the occurrence of cognitive impairment. By collecting baseline data on general information, body composition, and clinical indicators, we hope to identify risk factors for cognitive impairment in this patient population. The results of this study are expected to provide more scientific basis for the health management of elderly patients with hypertension, particularly in terms of maintaining good nutritional status and reducing the risk of cognitive impairment.</AbstractText To explore the differences between clinical data and cognitive function of elderly hypertensive patients with different nutritional status, analyze the internal relationship between nutritional statuses and cognitive impairment, and build a nomogram model for predicting nutritional status in elderly hypertensive patients.</AbstractText The present study retrospectively analyzed 200 elderly patients admitted to our hospital for a hypertension during the period July 1, 2024 to September 30, 2024 as study subjects, and the 200 patients were divided into a modeling cohort (140 patients) and a validation cohort (60 patients) according to the ratio of 7:3. The modeling cohort were divided into a malnutrition group (26 cases), a malnutrition risk group (42 cases), and a normal nutritional status group (72 cases) according to the patients' Mini-Nutritional Assessment Scale (MNA) scores, and the modeling cohort was divided into a hypertension combined with cognitive impairment group (34 cases) and a hypertension cognitively normal group (106 cases) according to the Montreal Cognitive Assessment Scale (MoCA) scores, and the validation cohort was divided into a hypertension combined with cognitive impairment group (14 cases) and hypertension cognitively normal group (46 cases). The study outcome was the occurrence of cognitive impairment in elderly hypertensive patients. Univariate and multivariate logistic regression was used to explore the relationship between the general information of the elderly hypertensive patients and the influence indicators and the occurrence of cognitive impairment, the roadmap prediction model was established and validated, the patient work receiver operating characteristic curve was used to evaluate the predictive efficacy of the model, the calibration curve was used to assess the consistency between the predicted events and the actual events, and the decision curve analysis was used to evaluate the validity of the model. Pearson correlation analysis was used to explore the relationship between nutrition-related indicators and MoCA scores.</AbstractText In this research, the modeling cohort comprised 140 cases, while the verification cohort consisted of 60 cases, with no notable discrepancy in the data between the two groups. In the modeling cohort, there were significant differences in body mass index (BMI), albumin (ALB), hemoglobin (Hb) and homocysteine levels among the malnourished group, the malnourished risk group and the normal nutritional status group. The results of univariate and multivariate analysis showed that BMI [odds ratio (OR) = 0.830, <i BMI, MNA score, Hb and ALB were independent protective factors for cognitive impairment in elderly hypertensive patients and were positively correlated with MoCA score. ALP was an independent risk factor for cognitive impairment in elderly hypertensive patients and was negatively correlated with the MoCA score. The column line graph model established in the study has a good predictive value.</AbstractText
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<i
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Clinical novel exploration of intractable fever in stroke rehabilitation: a single-center cross-sectional retrospective study. Fever has long been recognized as one of the earliest clinical indicators of illness and remains a leading reason for seeking medical care worldwide. It is typically classified based on its duration and underlying etiology. In clinical settings, intractable fever is as common as acute fever, particularly in patients with brain injuries. Beyond infectious causes, stroke survivors often experience recurrent intractable fever due to central or neurogenic mechanisms. This study aims to retrospectively investigate the incidence and clinical characteristics of acute and intractable fever in patients undergoing stroke rehabilitation. It explores the associations between these characteristics and the different types of fever. Additionally, the study seeks to identify potential risk factors contributing to the development of intractable fever, aiming to guide clinical management and optimize treatment strategies for stroke-related fever. This study evaluated 1,065 stroke patients in the rehabilitation phase who were admitted to the Neurorehabilitation Center between January 1, 2023, and December 31, 2023. Of these, 230 febrile patients met the inclusion criteria and were included in the analysis, comprising 194 cases of acute fever and 36 cases of intractable fever. Medical records and clinical characteristics were collected, and the data from the two groups of febrile patients were analyzed using t-tests, Mann-Whitney U tests, and chi-square tests. Logistic regression analysis was performed to identify risk factors associated with intractable fever, while receiver operating characteristic (ROC) curves were used to assess the predictive performance of individual and combined risk factors. A p-value of less than 0.05 was considered statistically significant. 15.7% of patients experienced intractable fever, which was significantly associated with brainstem lesions (P < 0.05). Compared to patients with acute fever, those with intractable fever had higher NIHSS scores (33.3% vs. 15.5%, P < 0.05), a greater incidence of consciousness disorders (66.7% vs. 28.9%, P < 0.05), and a higher rate of tracheostomy (55.6% vs. 15.5%, P < 0.05). All patients received antibiotic treatment, and gabapentin was administered to 16 cases. Patients with brainstem lesions were less likely to be treated with gabapentin (37.5% vs. 90%, P < 0.05), while those with intracerebral hemorrhage were more likely to receive gabapentin (87.5% vs. 10%, P < 0.05). Logistic regression analysis revealed that consciousness disorders and tracheostomy status were significant risk factors for intractable fever (P = 0.047, OR 6.691, 95% CI 1.030-43.478; P = 0.021, OR 5.366, 95% CI 1.282-22.465). Brainstem lesions also significantly increased the risk (P = 0.002, OR 9.617, 95% CI 2.277-40.614). Although limited in scope, this retrospective study highlights the increased risk of intractable fever during stroke rehabilitation among patients with consciousness disorders, tracheostomy, and brainstem injuries. The key risk factors identified include higher NIHSS scores, impaired consciousness, tracheostomy status, and brainstem lesions.</AbstractText
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Nutritional status of elderly hypertensive patients and its relation to the occurrence of cognitive impairment. Hypertension is a common chronic disease in the elderly population, and its association with cognitive impairment has been increasingly recognized. Cognitive impairment, including mild cognitive impairment and dementia, can significantly affect the quality of life and independence of elderly individuals. Therefore, identifying risk factors for cognitive impairment in elderly hypertensive patients is crucial for developing effective interventions and improving health outcomes. Nutritional status is one of the potential factors that may influence cognitive function in elderly hypertensive patients. Malnutrition or inadequate nutrition can lead to various health problems, including weakened immune system, increased susceptibility to infections, and impaired physical and mental function. Furthermore, poor nutritional status has been linked to increased risk of cognitive decline and dementia in various populations. In this observational study, we aimed to investigate the nutritional status of elderly hypertensive patients and its relationship to the occurrence of cognitive impairment. By collecting baseline data on general information, body composition, and clinical indicators, we hope to identify risk factors for cognitive impairment in this patient population. The results of this study are expected to provide more scientific basis for the health management of elderly patients with hypertension, particularly in terms of maintaining good nutritional status and reducing the risk of cognitive impairment.</AbstractText To explore the differences between clinical data and cognitive function of elderly hypertensive patients with different nutritional status, analyze the internal relationship between nutritional statuses and cognitive impairment, and build a nomogram model for predicting nutritional status in elderly hypertensive patients.</AbstractText The present study retrospectively analyzed 200 elderly patients admitted to our hospital for a hypertension during the period July 1, 2024 to September 30, 2024 as study subjects, and the 200 patients were divided into a modeling cohort (140 patients) and a validation cohort (60 patients) according to the ratio of 7:3. The modeling cohort were divided into a malnutrition group (26 cases), a malnutrition risk group (42 cases), and a normal nutritional status group (72 cases) according to the patients' Mini-Nutritional Assessment Scale (MNA) scores, and the modeling cohort was divided into a hypertension combined with cognitive impairment group (34 cases) and a hypertension cognitively normal group (106 cases) according to the Montreal Cognitive Assessment Scale (MoCA) scores, and the validation cohort was divided into a hypertension combined with cognitive impairment group (14 cases) and hypertension cognitively normal group (46 cases). The study outcome was the occurrence of cognitive impairment in elderly hypertensive patients. Univariate and multivariate logistic regression was used to explore the relationship between the general information of the elderly hypertensive patients and the influence indicators and the occurrence of cognitive impairment, the roadmap prediction model was established and validated, the patient work receiver operating characteristic curve was used to evaluate the predictive efficacy of the model, the calibration curve was used to assess the consistency between the predicted events and the actual events, and the decision curve analysis was used to evaluate the validity of the model. Pearson correlation analysis was used to explore the relationship between nutrition-related indicators and MoCA scores.</AbstractText In this research, the modeling cohort comprised 140 cases, while the verification cohort consisted of 60 cases, with no notable discrepancy in the data between the two groups. In the modeling cohort, there were significant differences in body mass index (BMI), albumin (ALB), hemoglobin (Hb) and homocysteine levels among the malnourished group, the malnourished risk group and the normal nutritional status group. The results of univariate and multivariate analysis showed that BMI [odds ratio (OR) = 0.830, <i BMI, MNA score, Hb and ALB were independent protective factors for cognitive impairment in elderly hypertensive patients and were positively correlated with MoCA score. ALP was an independent risk factor for cognitive impairment in elderly hypertensive patients and was negatively correlated with the MoCA score. The column line graph model established in the study has a good predictive value.</AbstractText
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Diagnostic Approaches for Candida auris: A Comprehensive Review of Screening, Identification, and Susceptibility Testing. <i
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40168936
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36115362
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40429940
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Study of sleep abnormalities in patients with NMOSD-MOG related disorders.
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Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders.
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On the Potential Role of Phytate Against Neurodegeneration: It Protects Against Fe(3+)-Catalyzed Degradation of Dopamine and Ascorbate and Against Fe(3+)-Induced Protein Aggregation.
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Sleep quality and architecture are rarely studied in Neuromyelitis Optica Spectrum disorder (NMOSD) and Myelin Oligodendrocyte associated disorder (MOGAD).</AbstractText To study sleep characteristics in patients with NMOSD and MOGAD.</AbstractText This prospective study (Total:72patients) was carried out in 27-Aquaporin-4positive-NMOSD (AQP4+NMO), 20-MOGAD and 25-dual seronegative NMOSD (SNNMOSD). We assessed sleep characteristics by questionnaires and nocturnal polysomnography in 10 clinically stable patients of each group and 20 healthy controls.</AbstractText The Pittsburgh Sleep Quality Index (PSQI) (7.36±3.73,p = 0.02) and Berlin questionnaire were abnormal in SNNMOSD. Probable (RBD) (1.63±2.02,p = 0.026), anxiety (12.11±8.22,p = 0.047) and depression (9.7 ± 7.58,p = 0.009) scores were predominantly abnormal in AQP4+NMO patients. There was a positive correlation of physical disability with poor sleep quality (r = 0.29,p = 0.01), anxiety (r = 0.28,p = 0.02), depression (r = 0.24,p = 0.046) and development of RLS (r = 0.24,p = 0.04). Periodic limb movements were seen predominantly in SNNMOSD. Supratentorial lesions had higher stage-1 (N1) duration and reduced stage-2 (N2), stage-3 (N3), and REM duration. Voxel-based morphometry revealed a reduction in thalamic volume in all patients compared to healthy controls.</AbstractText Sleep quality and architecture are impaired in NMOSD and MOGAD with significantly reduced thalamic volume. Sleep patterns reflect the extent of damage in NMOSD and MOGAD and would have implications on the comprehensive care.</AbstractText
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Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers.</AbstractText In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding.</AbstractText Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p<0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated.</AbstractText The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention.</AbstractText Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation.</AbstractText
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Myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6) is commonly found in plant-derived foods and has important pharmacological properties against many pathologies. One of them appears to be neurodegeneration, which is notably stimulated by dysregulated metal metabolism. Consequently, we explore the role of IP6 in mitigating neurodegenerative events catalyzed by dysregulated free iron. More precisely, we performed spectrophotometric measurements in aqueous solutions to investigate the ability of IP6 to chelate Fe<sup
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Study of sleep abnormalities in patients with NMOSD-MOG related disorders. Sleep quality and architecture are rarely studied in Neuromyelitis Optica Spectrum disorder (NMOSD) and Myelin Oligodendrocyte associated disorder (MOGAD).</AbstractText To study sleep characteristics in patients with NMOSD and MOGAD.</AbstractText This prospective study (Total:72patients) was carried out in 27-Aquaporin-4positive-NMOSD (AQP4+NMO), 20-MOGAD and 25-dual seronegative NMOSD (SNNMOSD). We assessed sleep characteristics by questionnaires and nocturnal polysomnography in 10 clinically stable patients of each group and 20 healthy controls.</AbstractText The Pittsburgh Sleep Quality Index (PSQI) (7.36±3.73,p = 0.02) and Berlin questionnaire were abnormal in SNNMOSD. Probable (RBD) (1.63±2.02,p = 0.026), anxiety (12.11±8.22,p = 0.047) and depression (9.7 ± 7.58,p = 0.009) scores were predominantly abnormal in AQP4+NMO patients. There was a positive correlation of physical disability with poor sleep quality (r = 0.29,p = 0.01), anxiety (r = 0.28,p = 0.02), depression (r = 0.24,p = 0.046) and development of RLS (r = 0.24,p = 0.04). Periodic limb movements were seen predominantly in SNNMOSD. Supratentorial lesions had higher stage-1 (N1) duration and reduced stage-2 (N2), stage-3 (N3), and REM duration. Voxel-based morphometry revealed a reduction in thalamic volume in all patients compared to healthy controls.</AbstractText Sleep quality and architecture are impaired in NMOSD and MOGAD with significantly reduced thalamic volume. Sleep patterns reflect the extent of damage in NMOSD and MOGAD and would have implications on the comprehensive care.</AbstractText
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Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders. Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers.</AbstractText In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding.</AbstractText Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p<0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated.</AbstractText The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention.</AbstractText Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation.</AbstractText
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On the Potential Role of Phytate Against Neurodegeneration: It Protects Against Fe(3+)-Catalyzed Degradation of Dopamine and Ascorbate and Against Fe(3+)-Induced Protein Aggregation. Myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6) is commonly found in plant-derived foods and has important pharmacological properties against many pathologies. One of them appears to be neurodegeneration, which is notably stimulated by dysregulated metal metabolism. Consequently, we explore the role of IP6 in mitigating neurodegenerative events catalyzed by dysregulated free iron. More precisely, we performed spectrophotometric measurements in aqueous solutions to investigate the ability of IP6 to chelate Fe<sup
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38997145
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26918582
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38194081
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Altered Corticobrainstem Connectivity during Spontaneous Fluctuations in Pain Intensity in Painful Trigeminal Neuropathy.
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Clinical study of cerebrospinal fluid neuropeptides in patients with primary trigeminal neuralgia.
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Risk-taking and self-harm behaviors as markers of adolescent borderline personality disorder.
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Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (<i
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To investigate the expression levels of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and β-endorphin in the cerebrospinal fluid (CSF) and peripheral blood of patients with primary trigeminal neuralgia (TN).</AbstractText We included 20 patients with primary TN who underwent percutaneous radiofrequency thermocoagulation and collected four types of samples from all of them: sample A: CSF samples; sample B: peripheral blood samples; sample C: peripheral blood samples collected one day before the operation; sample D: peripheral blood samples withdrawn one day after the operation. Another 20 CSF samples of patients with nervous system disease or gynecological disease were collected as a control (sample E). Samples A and B were obtained at the same time. We also evaluated the expression of CGRP, SP, β-endorphin, and VIP by visual analog scale (VAS) scores one day before and one day after the operation. In addition, heart rate (HR) at baseline and at the time of sample collection, mean arterial pressure (MAP), and all side effects of the procedure were recorded.</AbstractText Significance were found concerning about CGRP, SP, β-endorphin, and VIP in TN patients and the controls (P<0.001). The expression of CGRP, SP, and VIP in sample A was higher than that in sample E. However, the β-endorphin level in sample A was lower than that in sample E. There was a positive correlation between sample A and B regarding the expression of CGRP, SP, β-endorphin, and VIP (P<0. 01). There was no relationship between the time of disease onset and the expression of CGRP, SP, β-endorphin, and VIP in sample A and sample B (P>0.05). No difference was detected between the neuropeptides levels in samples B and C (P>0.05). Notably, VAS in sample D was significantly lower than that in sample C (P<0.01). Finally, there was no difference between the intraoperative HR and MAP values in the studied samples.</AbstractText In primary TN patients, the blood levels of CGRP, SP, β-endorphin, and VIP were associated with those in CSF samples. There was a significant difference between the levels of the four neuropeptides in CSF and control samples. Our results also indicated that the levels of neuropeptides in blood samples can be tested for those in CSF. The disease onset and duration exerted insignificant effects on the production and release of CGRP, SP, β-endorphin, and VIP.</AbstractText
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Adolescence is a critical period for early identification and intervention of borderline personality disorder (BPD). Risk-taking and self-harm behaviors (RSB) have been identified as promising early markers of BPD and correlates of depression in school-based samples. The present study aimed, first, to examine the association between RSB and BPD in a clinical sample of adolescents and, second, to examine whether RSB are also linked to depression. N = 405 participants (82.7% female) were recruited from an outpatient clinic for adolescents with RSB. RSB assessed included truancy, excessive media use, alcohol, tobacco, and illicit drug use, sexual risk-taking, and self-harm behavior. Regression analyses and generalized linear models were performed to examine the associations between individual RSB or patterns of RSB (identified using latent class analysis, LCA) and a diagnosis and severity of BPD or depression. All RSB (except excessive media use) were positively associated with BPD diagnosis and severity. In contrast, only non-suicidal self-injury (NSSI) and suicide attempts were positively associated with depression diagnosis and severity, while illicit drug use was negatively associated with depression severity. The LCA yielded two classes differing in the occurrence of RSB. The high RSB class was more likely to have a BPD diagnosis and greater BPD severity than the low RSB class. Classes did not differ regarding depression diagnosis or severity. As NSSI and suicide attempts were associated with both BPD and depression, the presence of additional RSB, besides self-harm behavior, may represent a specific risk marker for BPD in adolescents.</AbstractText
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Altered Corticobrainstem Connectivity during Spontaneous Fluctuations in Pain Intensity in Painful Trigeminal Neuropathy. Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (<i
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Clinical study of cerebrospinal fluid neuropeptides in patients with primary trigeminal neuralgia. To investigate the expression levels of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and β-endorphin in the cerebrospinal fluid (CSF) and peripheral blood of patients with primary trigeminal neuralgia (TN).</AbstractText We included 20 patients with primary TN who underwent percutaneous radiofrequency thermocoagulation and collected four types of samples from all of them: sample A: CSF samples; sample B: peripheral blood samples; sample C: peripheral blood samples collected one day before the operation; sample D: peripheral blood samples withdrawn one day after the operation. Another 20 CSF samples of patients with nervous system disease or gynecological disease were collected as a control (sample E). Samples A and B were obtained at the same time. We also evaluated the expression of CGRP, SP, β-endorphin, and VIP by visual analog scale (VAS) scores one day before and one day after the operation. In addition, heart rate (HR) at baseline and at the time of sample collection, mean arterial pressure (MAP), and all side effects of the procedure were recorded.</AbstractText Significance were found concerning about CGRP, SP, β-endorphin, and VIP in TN patients and the controls (P<0.001). The expression of CGRP, SP, and VIP in sample A was higher than that in sample E. However, the β-endorphin level in sample A was lower than that in sample E. There was a positive correlation between sample A and B regarding the expression of CGRP, SP, β-endorphin, and VIP (P<0. 01). There was no relationship between the time of disease onset and the expression of CGRP, SP, β-endorphin, and VIP in sample A and sample B (P>0.05). No difference was detected between the neuropeptides levels in samples B and C (P>0.05). Notably, VAS in sample D was significantly lower than that in sample C (P<0.01). Finally, there was no difference between the intraoperative HR and MAP values in the studied samples.</AbstractText In primary TN patients, the blood levels of CGRP, SP, β-endorphin, and VIP were associated with those in CSF samples. There was a significant difference between the levels of the four neuropeptides in CSF and control samples. Our results also indicated that the levels of neuropeptides in blood samples can be tested for those in CSF. The disease onset and duration exerted insignificant effects on the production and release of CGRP, SP, β-endorphin, and VIP.</AbstractText
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Risk-taking and self-harm behaviors as markers of adolescent borderline personality disorder. Adolescence is a critical period for early identification and intervention of borderline personality disorder (BPD). Risk-taking and self-harm behaviors (RSB) have been identified as promising early markers of BPD and correlates of depression in school-based samples. The present study aimed, first, to examine the association between RSB and BPD in a clinical sample of adolescents and, second, to examine whether RSB are also linked to depression. N = 405 participants (82.7% female) were recruited from an outpatient clinic for adolescents with RSB. RSB assessed included truancy, excessive media use, alcohol, tobacco, and illicit drug use, sexual risk-taking, and self-harm behavior. Regression analyses and generalized linear models were performed to examine the associations between individual RSB or patterns of RSB (identified using latent class analysis, LCA) and a diagnosis and severity of BPD or depression. All RSB (except excessive media use) were positively associated with BPD diagnosis and severity. In contrast, only non-suicidal self-injury (NSSI) and suicide attempts were positively associated with depression diagnosis and severity, while illicit drug use was negatively associated with depression severity. The LCA yielded two classes differing in the occurrence of RSB. The high RSB class was more likely to have a BPD diagnosis and greater BPD severity than the low RSB class. Classes did not differ regarding depression diagnosis or severity. As NSSI and suicide attempts were associated with both BPD and depression, the presence of additional RSB, besides self-harm behavior, may represent a specific risk marker for BPD in adolescents.</AbstractText
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34997717
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33266733
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34383535
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Avian nidopallium caudolaterale mediates decision-making during goal-directed navigation.
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Measuring Integrated Information: Comparison of Candidate Measures in Theory and Simulation.
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A randomized trial comparing group mindfulness-based cognitive therapy with group supportive sex education and therapy for the treatment of female sexual interest/arousal disorder.
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Previous work demonstrates that nidopallium caudolaterale, which is considered to be an analog of the mammalian prefrontal cortex, participates in goal-directed navigation in pigeons. However, its role remains unclear. To clarify its role, two goal-directed navigation tasks in plus-maze were designed, in which the goal location of one is random, and the other is fixed, i.e., the random-goal task and the fixed-goal task. The animals were trained to run from the starting location to the goal location in accordance with the cue in the plus-maze. The goal location is variable for the random-goal task but unchanged for the fixed-goal task. The results have demonstrated that the time point of nidopallium caudolaterale neuron response is consistent with decision-making. During the decision-making, the firing rates significantly increased in two tasks, which can also decode the direction of upcoming movement in the random-goal task. However, the location of decision-making is different between the tasks mentioned above. The decision-making window is at the intersection in the random-goal task, which is a departure in the fixed-goal task. In addition, these results also provide evidence that the neural activities obtained from the nidopallium caudolaterale may contain the decision-making information during goal-directed navigation. These results suggest that the avian nidopallium caudolaterale and the mammalian prefrontal cortex may play a similar role in goal-directed spatial decision-making. Additionally, these also may provide some support to understand the neural mechanism of decision-making for different species.</AbstractText
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Integrated Information Theory (IIT) is a prominent theory of consciousness that has at its centre measures that quantify the extent to which a system generates more information than the sum of its parts. While several candidate measures of integrated information (" Φ ") now exist, little is known about how they compare, especially in terms of their behaviour on non-trivial network models. In this article, we provide clear and intuitive descriptions of six distinct candidate measures. We then explore the properties of each of these measures in simulation on networks consisting of eight interacting nodes, animated with Gaussian linear autoregressive dynamics. We find a striking diversity in the behaviour of these measures-no two measures show consistent agreement across all analyses. A subset of the measures appears to reflect some form of dynamical complexity, in the sense of simultaneous segregation and integration between system components. Our results help guide the operationalisation of IIT and advance the development of measures of integrated information and dynamical complexity that may have more general applicability.</AbstractText
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<b
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Avian nidopallium caudolaterale mediates decision-making during goal-directed navigation. Previous work demonstrates that nidopallium caudolaterale, which is considered to be an analog of the mammalian prefrontal cortex, participates in goal-directed navigation in pigeons. However, its role remains unclear. To clarify its role, two goal-directed navigation tasks in plus-maze were designed, in which the goal location of one is random, and the other is fixed, i.e., the random-goal task and the fixed-goal task. The animals were trained to run from the starting location to the goal location in accordance with the cue in the plus-maze. The goal location is variable for the random-goal task but unchanged for the fixed-goal task. The results have demonstrated that the time point of nidopallium caudolaterale neuron response is consistent with decision-making. During the decision-making, the firing rates significantly increased in two tasks, which can also decode the direction of upcoming movement in the random-goal task. However, the location of decision-making is different between the tasks mentioned above. The decision-making window is at the intersection in the random-goal task, which is a departure in the fixed-goal task. In addition, these results also provide evidence that the neural activities obtained from the nidopallium caudolaterale may contain the decision-making information during goal-directed navigation. These results suggest that the avian nidopallium caudolaterale and the mammalian prefrontal cortex may play a similar role in goal-directed spatial decision-making. Additionally, these also may provide some support to understand the neural mechanism of decision-making for different species.</AbstractText
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Measuring Integrated Information: Comparison of Candidate Measures in Theory and Simulation. Integrated Information Theory (IIT) is a prominent theory of consciousness that has at its centre measures that quantify the extent to which a system generates more information than the sum of its parts. While several candidate measures of integrated information (" Φ ") now exist, little is known about how they compare, especially in terms of their behaviour on non-trivial network models. In this article, we provide clear and intuitive descriptions of six distinct candidate measures. We then explore the properties of each of these measures in simulation on networks consisting of eight interacting nodes, animated with Gaussian linear autoregressive dynamics. We find a striking diversity in the behaviour of these measures-no two measures show consistent agreement across all analyses. A subset of the measures appears to reflect some form of dynamical complexity, in the sense of simultaneous segregation and integration between system components. Our results help guide the operationalisation of IIT and advance the development of measures of integrated information and dynamical complexity that may have more general applicability.</AbstractText
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A randomized trial comparing group mindfulness-based cognitive therapy with group supportive sex education and therapy for the treatment of female sexual interest/arousal disorder. <b
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40375100
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33624238
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40305010
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Trends of antibiotic use for acute upper respiratory infections in Chinese emergency departments and the impact of COVID-19: a cross-sectional study.
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Increased susceptibility to temperature variation for non-accidental emergency ambulance dispatches in Shenzhen, China.
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Positive Emotion Dysregulation in Opioid Use Disorder and Normalization by Mindfulness-Oriented Recovery Enhancement: A Secondary Analysis of a Randomized Clinical Trial.
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The emergence of Coronavirus Disease 2019 (COVID-19) has impacted antibiotic use; however, studies on antibiotic use for acute upper respiratory infections (AURIs) in Chinese emergency department (ED) settings are still scarce.</AbstractText This study aimed to explore trends and patterns in antibiotic use and the impact of COVID-19 in Chinese ED settings.</AbstractText A cross-sectional, retrospective analysis was conducted using prescriptions for ED visits due to AURIs through the Hospital Prescription Analysis Cooperative Project Database between 2018 and 2023. We examined patterns of antibiotic use for AURIs and employed an interrupted time series analysis to assess the impact of the COVID-19 pandemic on antibiotic use. The proportion of antibiotic prescriptions adhering to first-line guideline recommendations was also evaluated.</AbstractText A total of 1,972,270 prescriptions for AURIs from 108 hospitals in EDs were extracted. The antibiotic prescription rate (APR) was 58.44%. The predominant antibiotics prescribed for AURIs were second- and third-generation cephalosporins and azithromycin. Among these prescriptions, only 22.26% adhered to first-line guideline recommendations, while 83.82% involved Watch-group antibiotics. A substantial decrease in antibiotic consumption was observed at the onset of the pandemic, but no significant changes were found in the APR. After the relaxation of anti-COVID-19 measures, both antibiotic consumption and the APR exhibited an upward trend. However, neither returned to pre-pandemic levels.</AbstractText Antibiotic use for AURIs was prevalent in ED settings, with a predominant use of broad-spectrum and Watch-group antibiotics. After the lifting of pandemic control measures, both antibiotic consumption and the APR exhibited an upward trend, underscoring the need to reinforce antimicrobial stewardship, particular targeting broad-spectrum and Watch-group antibiotic use.</AbstractText
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Most studies focused on the temporal trend of mortality risk associated with temperature exposure. The relative role of heat, cold, and temperature variation (TV) on morbidity and its temporal trends are explored insufficiently. This study aims to investigate the temporal trends of emergency ambulance dispatch (EAD) risk and the attributable burden of heat, cold, and hourly temperature variation (HTV). We collected time-series data of daily EAD and ambient temperature in Shenzhen from 2010 to 2017. HTV was calculated as the standard deviation of the hourly temperatures between 2 consecutive days. Quasi-Poisson generalized additive models (GAM) with a time-varying distributed lag nonlinear model (DLNM) were applied to examine temporal trends of the HTV-, heat-, and cold-EAD association. The temporal variation of the attributable fraction (AF%) and attributable number (AN) for different temperature exposures was also calculated. The largest RR was observed in extreme cold [1.30 (95% CI: 1.18, 1.43)] and moderate cold [1.25 (95% CI: 1.17, 1.34)]. Significant increasing trends in HTV-related effects and burden were observed, especially for the extreme HTV effects (P for interaction < 0.05). Decreasing trends were observed in the heat-related effect and burden, though it showed no significance (P for interaction = 0.46). There was no clear change pattern of cold-related effects and burdens. Overall, the three temperature exposure caused 13.7% of EAD, of which 4.1%, 4.3%, and 5.3% were attributed to HTV, heat, and cold, respectively. All the temperature indexes in this study, especially the cold effect, are responsible for the increased risk of EAD. People have become more susceptible to HTV over the recent decade. However, there is no clear evidence to support the temporal change of the population's susceptibility to heat and cold. Thus, in addition to heat and cold, the emergency ambulance service department should pay more attention to HTV under climate change.</AbstractText
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It remains unknown whether difficulties in positive emotion regulation (ER) drive opioid use disorder (OUD) and whether these difficulties may be remediated.</AbstractText To test whether OUD is associated with attenuated positive ER and whether such positive emotion dysregulation may be treated by mindfulness-based intervention.</AbstractText In this mechanistic substudy of a randomized clinical trial, patients with chronic pain who did and did not meet criteria for OUD (OUD+ and OUD-, respectively) were recruited from primary care and pain clinics in Utah from January 2016 to and January 2020 and completed a positive ER task and questionnaires. A subsample of participants at risk for opioid misuse were randomized 1:1 to 8 weeks of Mindfulness-Oriented Recovery Enhancement (MORE) or supportive group (SG) therapy and then completed the ER task at posttreatment and questionnaires through 3-month follow-up. Data were analyzed from December 2022 to June 2024.</AbstractText The primary mechanistic outcome was parietal late positive potential (LPP) and P300 amplitude during positive ER. Secondary outcomes included self-reported anhedonia, positive affect, attention to positive information, and opioid craving.</AbstractText The 160 participants used opioids for a mean (SD) duration of 9.7 (8.4) years, and 98 participants (61.3%) were classified as OUD+. Mean (SD) participant age was 53.7 (11.9) years, and 102 participants (63.8%) were female. A significant group × task strategy (View, Regulate) interaction was observed during positive ER, characterized by the OUD+ group exhibiting lower LPP responses during Regulate compared to View trials relative to the OUD- group (B = 1.91; 95% CI, 0.85-2.96; P < .001). A significant group × strategy interaction was also observed for the P300 (B = 1.40; 95% CI, 0.14-2.67; P = .03). LPP blunting during positive ER mediated the association between OUD status and elevated opioid craving. In the treatment subsample (n = 62), patients treated with MORE showed greater increases in the LPP during Regulate compared with View trials than patients treated with SG (B = 1.53; 95% CI, 0.33-2.73; P = .01). Additionally, MORE improved attention to positive information (B = 1.32; 95% CI, 1.14-5.57; P = .004), positive affect (B = 4.73; 95% CI, 1.22-8.24; P = .01), and anhedonia (B = 2.94; 95% CI, 0.58-5.31; P = .02) while reducing craving (B = -10.88; 95% CI, -21.29 to -0.48; P = .04) to a greater extent than SG. Higher positive ER efficacy predicted lower craving at follow-up (B = -2.38; 95% CI, -4.55 to -0.21; P = .03).</AbstractText OUD among patients with chronic pain is characterized by difficulties in positive ER, evident in neurophysiological markers of salience detection and emotional elaboration. In this study, training in mindfulness and savoring via MORE enhanced positive ER, which in turn reduced craving, indicating that interventions that normalize reward system function may remediate OUD.</AbstractText ClinicalTrials.gov Identifier: NCT02602535.</AbstractText
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Trends of antibiotic use for acute upper respiratory infections in Chinese emergency departments and the impact of COVID-19: a cross-sectional study. The emergence of Coronavirus Disease 2019 (COVID-19) has impacted antibiotic use; however, studies on antibiotic use for acute upper respiratory infections (AURIs) in Chinese emergency department (ED) settings are still scarce.</AbstractText This study aimed to explore trends and patterns in antibiotic use and the impact of COVID-19 in Chinese ED settings.</AbstractText A cross-sectional, retrospective analysis was conducted using prescriptions for ED visits due to AURIs through the Hospital Prescription Analysis Cooperative Project Database between 2018 and 2023. We examined patterns of antibiotic use for AURIs and employed an interrupted time series analysis to assess the impact of the COVID-19 pandemic on antibiotic use. The proportion of antibiotic prescriptions adhering to first-line guideline recommendations was also evaluated.</AbstractText A total of 1,972,270 prescriptions for AURIs from 108 hospitals in EDs were extracted. The antibiotic prescription rate (APR) was 58.44%. The predominant antibiotics prescribed for AURIs were second- and third-generation cephalosporins and azithromycin. Among these prescriptions, only 22.26% adhered to first-line guideline recommendations, while 83.82% involved Watch-group antibiotics. A substantial decrease in antibiotic consumption was observed at the onset of the pandemic, but no significant changes were found in the APR. After the relaxation of anti-COVID-19 measures, both antibiotic consumption and the APR exhibited an upward trend. However, neither returned to pre-pandemic levels.</AbstractText Antibiotic use for AURIs was prevalent in ED settings, with a predominant use of broad-spectrum and Watch-group antibiotics. After the lifting of pandemic control measures, both antibiotic consumption and the APR exhibited an upward trend, underscoring the need to reinforce antimicrobial stewardship, particular targeting broad-spectrum and Watch-group antibiotic use.</AbstractText
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Increased susceptibility to temperature variation for non-accidental emergency ambulance dispatches in Shenzhen, China. Most studies focused on the temporal trend of mortality risk associated with temperature exposure. The relative role of heat, cold, and temperature variation (TV) on morbidity and its temporal trends are explored insufficiently. This study aims to investigate the temporal trends of emergency ambulance dispatch (EAD) risk and the attributable burden of heat, cold, and hourly temperature variation (HTV). We collected time-series data of daily EAD and ambient temperature in Shenzhen from 2010 to 2017. HTV was calculated as the standard deviation of the hourly temperatures between 2 consecutive days. Quasi-Poisson generalized additive models (GAM) with a time-varying distributed lag nonlinear model (DLNM) were applied to examine temporal trends of the HTV-, heat-, and cold-EAD association. The temporal variation of the attributable fraction (AF%) and attributable number (AN) for different temperature exposures was also calculated. The largest RR was observed in extreme cold [1.30 (95% CI: 1.18, 1.43)] and moderate cold [1.25 (95% CI: 1.17, 1.34)]. Significant increasing trends in HTV-related effects and burden were observed, especially for the extreme HTV effects (P for interaction < 0.05). Decreasing trends were observed in the heat-related effect and burden, though it showed no significance (P for interaction = 0.46). There was no clear change pattern of cold-related effects and burdens. Overall, the three temperature exposure caused 13.7% of EAD, of which 4.1%, 4.3%, and 5.3% were attributed to HTV, heat, and cold, respectively. All the temperature indexes in this study, especially the cold effect, are responsible for the increased risk of EAD. People have become more susceptible to HTV over the recent decade. However, there is no clear evidence to support the temporal change of the population's susceptibility to heat and cold. Thus, in addition to heat and cold, the emergency ambulance service department should pay more attention to HTV under climate change.</AbstractText
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Positive Emotion Dysregulation in Opioid Use Disorder and Normalization by Mindfulness-Oriented Recovery Enhancement: A Secondary Analysis of a Randomized Clinical Trial. It remains unknown whether difficulties in positive emotion regulation (ER) drive opioid use disorder (OUD) and whether these difficulties may be remediated.</AbstractText To test whether OUD is associated with attenuated positive ER and whether such positive emotion dysregulation may be treated by mindfulness-based intervention.</AbstractText In this mechanistic substudy of a randomized clinical trial, patients with chronic pain who did and did not meet criteria for OUD (OUD+ and OUD-, respectively) were recruited from primary care and pain clinics in Utah from January 2016 to and January 2020 and completed a positive ER task and questionnaires. A subsample of participants at risk for opioid misuse were randomized 1:1 to 8 weeks of Mindfulness-Oriented Recovery Enhancement (MORE) or supportive group (SG) therapy and then completed the ER task at posttreatment and questionnaires through 3-month follow-up. Data were analyzed from December 2022 to June 2024.</AbstractText The primary mechanistic outcome was parietal late positive potential (LPP) and P300 amplitude during positive ER. Secondary outcomes included self-reported anhedonia, positive affect, attention to positive information, and opioid craving.</AbstractText The 160 participants used opioids for a mean (SD) duration of 9.7 (8.4) years, and 98 participants (61.3%) were classified as OUD+. Mean (SD) participant age was 53.7 (11.9) years, and 102 participants (63.8%) were female. A significant group × task strategy (View, Regulate) interaction was observed during positive ER, characterized by the OUD+ group exhibiting lower LPP responses during Regulate compared to View trials relative to the OUD- group (B = 1.91; 95% CI, 0.85-2.96; P < .001). A significant group × strategy interaction was also observed for the P300 (B = 1.40; 95% CI, 0.14-2.67; P = .03). LPP blunting during positive ER mediated the association between OUD status and elevated opioid craving. In the treatment subsample (n = 62), patients treated with MORE showed greater increases in the LPP during Regulate compared with View trials than patients treated with SG (B = 1.53; 95% CI, 0.33-2.73; P = .01). Additionally, MORE improved attention to positive information (B = 1.32; 95% CI, 1.14-5.57; P = .004), positive affect (B = 4.73; 95% CI, 1.22-8.24; P = .01), and anhedonia (B = 2.94; 95% CI, 0.58-5.31; P = .02) while reducing craving (B = -10.88; 95% CI, -21.29 to -0.48; P = .04) to a greater extent than SG. Higher positive ER efficacy predicted lower craving at follow-up (B = -2.38; 95% CI, -4.55 to -0.21; P = .03).</AbstractText OUD among patients with chronic pain is characterized by difficulties in positive ER, evident in neurophysiological markers of salience detection and emotional elaboration. In this study, training in mindfulness and savoring via MORE enhanced positive ER, which in turn reduced craving, indicating that interventions that normalize reward system function may remediate OUD.</AbstractText ClinicalTrials.gov Identifier: NCT02602535.</AbstractText
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25883585
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28115055
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40098685
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Cognitive rehabilitation in multiple sclerosis: the role of plasticity.
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Dyslexics' faster decay of implicit memory for sounds and words is manifested in their shorter neural adaptation.
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Differences in lower limb co-contraction calculations vary clinical interpretation of aquatic treadmill walking in typically developing and children with cerebral palsy.
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Cognitive deficits are common in multiple sclerosis (MS), documented at many stages of the disease. Both structural and functional neuroimaging have demonstrated a relationship with cognitive abilities in MS. Significant neuroplasticity of cognitive functions in individuals with MS is evident. Homologous region adaptation, local activation expansion, and extra-region recruitment all occur in an effort to maintain cognitive functioning. While much of this neuroplasticity is adaptive, it may also be maladaptive, particularly in individuals that are demonstrating significant cognitive impairment and/or with disease progression. This maladaptive neuroplasticity may come at the cost of other cognitive functions. Studies of cognitive rehabilitation efficacy have also recently applied neuroimaging techniques to establish outcome. Researchers have successfully applied various neuroimaging techniques to study the effects of cognitive rehabilitation in MS including task-based fMRI and resting state functional connectivity across multiple realms of cognition including episodic memory, executive functioning, attention, and processing speed. These studies have demonstrated neuroplasticity in the brains of persons with MS through the documentation of changes at the level of the cerebral substrate from before to after non-invasive, non-pharmacological, behavioral treatment for deficits in cognition. Future research should seek to identify adaptive versus maladaptive neuroplasticity associated with specific cognitive rehabilitation programs within all MS phenotypes to foster the validation of the most effective cognitive rehabilitation interventions for persons with MS.</AbstractText
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Dyslexia is a prevalent reading disability whose underlying mechanisms are still disputed. We studied the neural mechanisms underlying dyslexia using a simple frequency-discrimination task. Though participants were asked to compare the two tones in each trial, implicit memory of previous trials affected their responses. We hypothesized that implicit memory decays faster among dyslexics. We tested this by increasing the temporal intervals between consecutive trials, and by measuring the behavioral impact and ERP responses from the auditory cortex. Dyslexics showed a faster decay of implicit memory effects on both measures, with similar time constants. Finally, faster decay of implicit memory also characterized the impact of sound regularities in benefitting dyslexics' oral reading rate. Their benefit decreased faster as a function of the time interval from the previous reading of the same non-word. We propose that dyslexics' shorter neural adaptation paradoxically accounts for their longer reading times, since it reduces their temporal window of integration of past stimuli, resulting in noisier and less reliable predictions for both simple and complex stimuli. Less reliable predictions limit their acquisition of reading expertise.</AbstractText
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The purposes of this study were to (1) investigate muscle co-contraction during aquatic (Wet) and conventional (Dry) treadmill walking at various speeds in typically developing (TD) and children with cerebral palsy (CP) and (2) explore how the clinical interpretation of co-contraction, using co-contraction indices (CCI), may vary depending on the method employed.</AbstractText Fifteen TD children (30 limbs, 7 M | 8F, 11.3 ± 4.1 yrs., 1.46 ± 0.18 m, 44.2 ± 16.8 kg) and 10 children with CP (20 limbs, 6 M | 4F, 13.1 ± 3.5 yrs., 1.54 ± 0.18 m, 53.2 ± 26.2 kg, 7 GMFCS I and 3 II) participated in this study. Muscle activity of the tibialis anterior (TA), rectus femoris (RF), medial gastrocnemius (MG), and semitendinosus (ST) was recorded during three 3-min walking trials on a Dry treadmill followed by a Wet treadmill. Muscle co-contraction was calculated using three common CCI calculation methods for the RF/ST and TA/MG muscle pairings. Separate linear mixed-effects models examined the influence of population (TD vs. CP), walking speed (Slow, Normal, Fast), and treadmill environment (Dry vs. Wet) on CCI for each equation and muscle pairing.</AbstractText CCI<sub This study shows the potential of aquatic treadmill walking to reduce muscle co-contraction; however, caution is recommended as clinical implications can vary due to the computation method. Future studies should aim to report values from multiple methods to account for the variability within methods and validation of results.</AbstractText
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Cognitive rehabilitation in multiple sclerosis: the role of plasticity. Cognitive deficits are common in multiple sclerosis (MS), documented at many stages of the disease. Both structural and functional neuroimaging have demonstrated a relationship with cognitive abilities in MS. Significant neuroplasticity of cognitive functions in individuals with MS is evident. Homologous region adaptation, local activation expansion, and extra-region recruitment all occur in an effort to maintain cognitive functioning. While much of this neuroplasticity is adaptive, it may also be maladaptive, particularly in individuals that are demonstrating significant cognitive impairment and/or with disease progression. This maladaptive neuroplasticity may come at the cost of other cognitive functions. Studies of cognitive rehabilitation efficacy have also recently applied neuroimaging techniques to establish outcome. Researchers have successfully applied various neuroimaging techniques to study the effects of cognitive rehabilitation in MS including task-based fMRI and resting state functional connectivity across multiple realms of cognition including episodic memory, executive functioning, attention, and processing speed. These studies have demonstrated neuroplasticity in the brains of persons with MS through the documentation of changes at the level of the cerebral substrate from before to after non-invasive, non-pharmacological, behavioral treatment for deficits in cognition. Future research should seek to identify adaptive versus maladaptive neuroplasticity associated with specific cognitive rehabilitation programs within all MS phenotypes to foster the validation of the most effective cognitive rehabilitation interventions for persons with MS.</AbstractText
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Dyslexics' faster decay of implicit memory for sounds and words is manifested in their shorter neural adaptation. Dyslexia is a prevalent reading disability whose underlying mechanisms are still disputed. We studied the neural mechanisms underlying dyslexia using a simple frequency-discrimination task. Though participants were asked to compare the two tones in each trial, implicit memory of previous trials affected their responses. We hypothesized that implicit memory decays faster among dyslexics. We tested this by increasing the temporal intervals between consecutive trials, and by measuring the behavioral impact and ERP responses from the auditory cortex. Dyslexics showed a faster decay of implicit memory effects on both measures, with similar time constants. Finally, faster decay of implicit memory also characterized the impact of sound regularities in benefitting dyslexics' oral reading rate. Their benefit decreased faster as a function of the time interval from the previous reading of the same non-word. We propose that dyslexics' shorter neural adaptation paradoxically accounts for their longer reading times, since it reduces their temporal window of integration of past stimuli, resulting in noisier and less reliable predictions for both simple and complex stimuli. Less reliable predictions limit their acquisition of reading expertise.</AbstractText
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Differences in lower limb co-contraction calculations vary clinical interpretation of aquatic treadmill walking in typically developing and children with cerebral palsy. The purposes of this study were to (1) investigate muscle co-contraction during aquatic (Wet) and conventional (Dry) treadmill walking at various speeds in typically developing (TD) and children with cerebral palsy (CP) and (2) explore how the clinical interpretation of co-contraction, using co-contraction indices (CCI), may vary depending on the method employed.</AbstractText Fifteen TD children (30 limbs, 7 M | 8F, 11.3 ± 4.1 yrs., 1.46 ± 0.18 m, 44.2 ± 16.8 kg) and 10 children with CP (20 limbs, 6 M | 4F, 13.1 ± 3.5 yrs., 1.54 ± 0.18 m, 53.2 ± 26.2 kg, 7 GMFCS I and 3 II) participated in this study. Muscle activity of the tibialis anterior (TA), rectus femoris (RF), medial gastrocnemius (MG), and semitendinosus (ST) was recorded during three 3-min walking trials on a Dry treadmill followed by a Wet treadmill. Muscle co-contraction was calculated using three common CCI calculation methods for the RF/ST and TA/MG muscle pairings. Separate linear mixed-effects models examined the influence of population (TD vs. CP), walking speed (Slow, Normal, Fast), and treadmill environment (Dry vs. Wet) on CCI for each equation and muscle pairing.</AbstractText CCI<sub This study shows the potential of aquatic treadmill walking to reduce muscle co-contraction; however, caution is recommended as clinical implications can vary due to the computation method. Future studies should aim to report values from multiple methods to account for the variability within methods and validation of results.</AbstractText
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39140003
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35998297
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39866391
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Sex-Dependent Effects of Angiotensin Type 2 Receptor-Expressing Medial Prefrontal Cortex Interneurons in Fear Extinction Learning.
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Impairments in Fear Extinction Memory and Basolateral Amygdala Plasticity in the TgF344-AD Rat Model of Alzheimer's Disease Are Distinct from Nonpathological Aging.
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The Impact of Multidisciplinary Team Intervention for Early Mobilization of Patients with Aneurysmal Subarachnoid Hemorrhage in Stroke Care Unit: A Retrospective Cohort Study.
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The renin-angiotensin system has been identified as a potential therapeutic target for posttraumatic stress disorder, although its mechanisms are not well understood. Brain angiotensin type 2 receptors (AT2Rs) are a subtype of angiotensin II receptors located in stress and anxiety-related regions, including the medial prefrontal cortex (mPFC), but their function and mechanism in the mPFC remain unexplored. Therefore, we used a combination of imaging, cre/lox, and behavioral methods to investigate mPFC-AT2R-expressing neurons in fear and stess related behavior.</AbstractText To characterize mPFC-AT2R-expressing neurons in the mPFC, AT2R-Cre/tdTomato male and female mice were used for immunohistochemistry. mPFC brain sections were stained with glutamatergic or interneuron markers, and density of AT2R+ cells and colocalization with each marker were quantified. To assess fear-related behaviors in AT2R-flox mice, we selectively deleted AT2R from mPFC neurons using a Cre-expressing adeno-associated virus. Mice then underwent Pavlovian auditory fear conditioning, elevated plus maze, and open field testing.</AbstractText Immunohistochemistry results revealed that AT2R was densely expressed throughout the mPFC and primarily expressed in somatostatin interneurons in a sex-dependent manner. Following fear conditioning, mPFC-AT2R Cre-lox deletion impaired extinction and increased exploratory behavior in female but not male mice, while locomotion was unaltered by mPFC-AT2R deletion in both sexes.</AbstractText These results identify mPFC-AT2R+ neurons as a novel subgroup of somatostatin interneurons and reveal their role in regulating fear learning in a sex-dependent manner, potentially offering insights into novel therapeutic targets for posttraumatic stress disorder.</AbstractText Posttraumatic stress disorder (PTSD) is a significant predictor of cardiovascular disease (CVD), although the underlying mechanisms are poorly understood. The brain renin-angiotensin system (RAS) is important for cardiovascular and emotional stress regulation and may better help understand the link between PTSD and CVD risk. Our research reveals that the brain angiotensin II type 2 receptor (AT2R) subtype is located on specific somatostatin (SOM+) interneurons in the medial prefrontal cortex (mPFC) and plays a role in fear memory extinction, particularly in females. These findings reveal a role for the mPFC-AT2R in fear-based learning and memory, offering potential insights into the mechanisms underlying the PTSD-CVD association and therapeutic strategies.</AbstractText
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Fear-based disorders such as post-traumatic stress disorder (PTSD) steepen age-related cognitive decline and double the risk for developing Alzheimer's disease (AD). Because of the seemingly hyperactive properties of fear memories, PTSD symptoms can worsen with age. Perturbations in the synaptic circuitry supporting fear memory extinction are key neural substrates of PTSD. The basolateral amygdala (BLA) is a medial temporal lobe structure that is critical in the encoding, consolidation, and retrieval of fear memories. As little is known about fear extinction memory and BLA synaptic dysfunction within the context of aging and AD, the goal of this study was to investigate how fear extinction memory deficits and basal amygdaloid nucleus (BA) synaptic dysfunction differentially associate in nonpathologic aging and AD in the TgF344AD (TgAD) rat model of AD. Young, middle-aged, and older-aged WT and TgAD rats were trained on a delay fear conditioning and extinction procedure before <i
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To investigate the impact of multidisciplinary team (MDT) intervention for early mobilization (EM) of patients with aneurysmal subarachnoid hemorrhage (aSAH) in the intensive care unit (ICU).</AbstractText A retrospective uncontrolled before-after observational study was conducted to assess patient outcomes before and after introducing MDT in the stroke care unit (SCU). Participants admitted to the SCU from April 2017 to September 2023 were categorized into conventional (April 2017 to June 2020) and MDT (July 2020 to September 2023) groups. The measured primary outcome was the days until sitting, standing, and walking commenced.</AbstractText A total of 131 patients were screened, with 115 included in the analysis. The MDT group comprised 56 individuals (48.7%), whereas the conventional group consisted of 59 patients (51.3%). The MDT group exhibited a significantly shorter duration until sitting (4 [3-7] vs. 7 [5-17], p <0.001), standing (5 [3-7] vs. 10 [5-17], p <0.001), and walking (7 [5-10] vs. 16 [7-23], p <0.001) commenced. Furthermore, the MDT group showed a significantly higher ICU mobility scale (IMS) (8 [5-8] vs. 5 [3-8], p <0.001) at SCU discharge, shorter length of SCU stay (16 [15-17] vs. 17 [15-24], p = 0.048), and hospital stay (34 [25-48] vs. 48 [33-80], p = 0.006).</AbstractText This study suggests that MDT played a facilitative role in promoting the EM of patients with aSAH. Their involvement streamlined the mobilization process, shortening the days until the initiation of mobilization.</AbstractText
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Sex-Dependent Effects of Angiotensin Type 2 Receptor-Expressing Medial Prefrontal Cortex Interneurons in Fear Extinction Learning. The renin-angiotensin system has been identified as a potential therapeutic target for posttraumatic stress disorder, although its mechanisms are not well understood. Brain angiotensin type 2 receptors (AT2Rs) are a subtype of angiotensin II receptors located in stress and anxiety-related regions, including the medial prefrontal cortex (mPFC), but their function and mechanism in the mPFC remain unexplored. Therefore, we used a combination of imaging, cre/lox, and behavioral methods to investigate mPFC-AT2R-expressing neurons in fear and stess related behavior.</AbstractText To characterize mPFC-AT2R-expressing neurons in the mPFC, AT2R-Cre/tdTomato male and female mice were used for immunohistochemistry. mPFC brain sections were stained with glutamatergic or interneuron markers, and density of AT2R+ cells and colocalization with each marker were quantified. To assess fear-related behaviors in AT2R-flox mice, we selectively deleted AT2R from mPFC neurons using a Cre-expressing adeno-associated virus. Mice then underwent Pavlovian auditory fear conditioning, elevated plus maze, and open field testing.</AbstractText Immunohistochemistry results revealed that AT2R was densely expressed throughout the mPFC and primarily expressed in somatostatin interneurons in a sex-dependent manner. Following fear conditioning, mPFC-AT2R Cre-lox deletion impaired extinction and increased exploratory behavior in female but not male mice, while locomotion was unaltered by mPFC-AT2R deletion in both sexes.</AbstractText These results identify mPFC-AT2R+ neurons as a novel subgroup of somatostatin interneurons and reveal their role in regulating fear learning in a sex-dependent manner, potentially offering insights into novel therapeutic targets for posttraumatic stress disorder.</AbstractText Posttraumatic stress disorder (PTSD) is a significant predictor of cardiovascular disease (CVD), although the underlying mechanisms are poorly understood. The brain renin-angiotensin system (RAS) is important for cardiovascular and emotional stress regulation and may better help understand the link between PTSD and CVD risk. Our research reveals that the brain angiotensin II type 2 receptor (AT2R) subtype is located on specific somatostatin (SOM+) interneurons in the medial prefrontal cortex (mPFC) and plays a role in fear memory extinction, particularly in females. These findings reveal a role for the mPFC-AT2R in fear-based learning and memory, offering potential insights into the mechanisms underlying the PTSD-CVD association and therapeutic strategies.</AbstractText
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Impairments in Fear Extinction Memory and Basolateral Amygdala Plasticity in the TgF344-AD Rat Model of Alzheimer's Disease Are Distinct from Nonpathological Aging. Fear-based disorders such as post-traumatic stress disorder (PTSD) steepen age-related cognitive decline and double the risk for developing Alzheimer's disease (AD). Because of the seemingly hyperactive properties of fear memories, PTSD symptoms can worsen with age. Perturbations in the synaptic circuitry supporting fear memory extinction are key neural substrates of PTSD. The basolateral amygdala (BLA) is a medial temporal lobe structure that is critical in the encoding, consolidation, and retrieval of fear memories. As little is known about fear extinction memory and BLA synaptic dysfunction within the context of aging and AD, the goal of this study was to investigate how fear extinction memory deficits and basal amygdaloid nucleus (BA) synaptic dysfunction differentially associate in nonpathologic aging and AD in the TgF344AD (TgAD) rat model of AD. Young, middle-aged, and older-aged WT and TgAD rats were trained on a delay fear conditioning and extinction procedure before <i
|
The Impact of Multidisciplinary Team Intervention for Early Mobilization of Patients with Aneurysmal Subarachnoid Hemorrhage in Stroke Care Unit: A Retrospective Cohort Study. To investigate the impact of multidisciplinary team (MDT) intervention for early mobilization (EM) of patients with aneurysmal subarachnoid hemorrhage (aSAH) in the intensive care unit (ICU).</AbstractText A retrospective uncontrolled before-after observational study was conducted to assess patient outcomes before and after introducing MDT in the stroke care unit (SCU). Participants admitted to the SCU from April 2017 to September 2023 were categorized into conventional (April 2017 to June 2020) and MDT (July 2020 to September 2023) groups. The measured primary outcome was the days until sitting, standing, and walking commenced.</AbstractText A total of 131 patients were screened, with 115 included in the analysis. The MDT group comprised 56 individuals (48.7%), whereas the conventional group consisted of 59 patients (51.3%). The MDT group exhibited a significantly shorter duration until sitting (4 [3-7] vs. 7 [5-17], p <0.001), standing (5 [3-7] vs. 10 [5-17], p <0.001), and walking (7 [5-10] vs. 16 [7-23], p <0.001) commenced. Furthermore, the MDT group showed a significantly higher ICU mobility scale (IMS) (8 [5-8] vs. 5 [3-8], p <0.001) at SCU discharge, shorter length of SCU stay (16 [15-17] vs. 17 [15-24], p = 0.048), and hospital stay (34 [25-48] vs. 48 [33-80], p = 0.006).</AbstractText This study suggests that MDT played a facilitative role in promoting the EM of patients with aSAH. Their involvement streamlined the mobilization process, shortening the days until the initiation of mobilization.</AbstractText
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40206816
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37020858
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40175553
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Mechanical Thrombectomy for Large Vessel Occlusion Strokes Involving a Cerebral Aneurysm in the Target Vessel: Case Series.
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The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia.
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Psilocybin's lasting action requires pyramidal cell types and 5-HT(2A) receptors.
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<b
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Transient receptor potential (TRP) proteins are part of a superfamily of polymodal cation channels that can be activated by mechanical, physical, and chemical stimuli. In the vascular endothelium, TRP channels regulate two fundamental parameters: the membrane potential and the intracellular Ca<sup
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Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses<sup
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Mechanical Thrombectomy for Large Vessel Occlusion Strokes Involving a Cerebral Aneurysm in the Target Vessel: Case Series. <b
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The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia. Transient receptor potential (TRP) proteins are part of a superfamily of polymodal cation channels that can be activated by mechanical, physical, and chemical stimuli. In the vascular endothelium, TRP channels regulate two fundamental parameters: the membrane potential and the intracellular Ca<sup
|
Psilocybin's lasting action requires pyramidal cell types and 5-HT(2A) receptors. Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses<sup
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40168711
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36660177
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40242463
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Ascl1-mediated enhancement of GABAergic neuronal function in differentiated F11 cells under high glucose conditions.
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Gabapentinoid Prescribing Practices at a Large Academic Medical Center.
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Impact of rapid temperature fluctuations on acute stroke risk: a nationwide case-crossover study from 2001 to 2020.
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Gamma-aminobutyric acid (GABA)ergic neurons play a key role in pain modulation within the dorsal root ganglion (DRG), making them critical targets for therapeutic studies. This study utilized F11 cells as an in vitro model to examine GABAergic function under high-glucose conditions mimicking diabetic neuropathy. Differentiated F11 cells exhibited increased sensory neuronal marker expression and functional action potentials. Overexpression of the transcription factor Achaete-scute homolog 1 (Ascl1) via lentiviral vectors enhanced GABAergic characteristics, including upregulation of GAD65, GAD67, VGAT, and GABA release. Under high-glucose conditions, Ascl1 modulated pro-inflammatory cytokines (TNF-α, NF-κB, IL-1β), anti-inflammatory cytokines (IL-4, IL-10), and pain-related channels (TRPV1, TRPA1, Nav1.8), reversing pathological changes. Temporal control of Ascl1 during differentiation reduced hypersensitivity and improved cell viability, mediated by parvalbumin in a specific GABAergic subtype. These findings highlight the therapeutic potential of Ascl1 in neuropathic pain and the scalability of F11 cells for high-throughput screening of GABAergic therapeutics.</AbstractText
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To evaluate indications for gabapentinoid prescription at an academic medical center.</AbstractText We retrospectively reviewed patients aged 18 years or older who were prescribed gabapentinoids (gabapentin or pregabalin) during the 2019 calendar year at an academic medical center in the US Midwest. Patient demographic characteristics, indications for gabapentinoid prescription, and prescribing clinician specialities were abstracted from a random sample, and the findings were extrapolated to the overall cohort.</AbstractText A total of 6205 prescriptions for gabapentinoids were initially identified. In the random sample of prescriptions (n=721), 89.5% were for gabapentin and 10.5% were for pregabalin. More women than men were prescribed gabapentinoids, and the mean ± SD patient age was 58.6±16.9 years. The top 5 indications for gabapentinoid prescriptions were neuropathic pain, musculoskeletal pain, restless legs syndrome, anxiety, and headache. A majority (66.7%) of prescriptions had substantial-to-modest evidence, but 29.0% of prescriptions had conflicting or insufficient evidence.</AbstractText To our knowledge, this study is one of the first to manually review clinical notes from multiple clinical specialities to ascertain indications for gabapentinoid prescriptions. Although most prescriptions had modest evidence to support their use, a high percentage of gabapentinoid prescriptions were issued for indications not supported by robust evidence. This suggests that prescribers are gravitating toward gabapentinoid use for reasons that are currently not fully understood. Clinician intent for off-label gabapentinoid prescriptions at the point of care should be further studied to understand the factors that lead to these clinical decisions.</AbstractText
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Climate factors greatly affect cardiovascular health, with stroke ranking among serious global concerns. However, the impact of rapid temperature fluctuations on stroke risk remains underexplored. Given Taiwan's aging population and the intensifying effects of climate change, understanding influence of ambient temperatures on stroke risk is crucial for public health protection. This study aimed to explore the link between ambient temperature, sudden day-to-day temperature changes, and stroke onset in Taiwan, taking air pollutants into consideration.</AbstractText We conducted a time-stratified case-crossover study from 2001 to 2020 using Distributed Lag Nonlinear Models (DLNM) within conditional logistic regression to examine lagged associations between temperature parameters and stroke risk. We analyzed associations separately for total stroke, ischemic stroke, and hemorrhagic stroke to identify potential differences in risk patterns, using odds ratios (ORs) relative to the temperature associated with the lowest stroke risk. Data from the National Health Insurance Research Database (NHIRD) identified the study population, including 1,100,074 first-time stroke emergency events and self-matched with 2,200,148 non-stroke onset dates as controls. The primary exposure assessments included daily temperatures (mean, maximum, and minimum) and temperature fluctuations (diurnal temperature range (DTR), sudden day-to-day temperature increases (TDI), and sudden day-to-day temperature decrease (TDD)), adjusted for air pollutants (PM<sub Through DLNM exposure-lag-response effect analysis after adjustment for PM<sub Our findings indicate that sudden day-to-day temperature increases and decreases are significant predictors of stroke onset. These results emphasize a noteworthy relationship between temperature and stroke risk over consecutive days, supporting interventions aimed at reducing stroke incidence.</AbstractText This research was supported by the National Science and Technology Council (NSTC), Executive Yuan, Taiwan, grant No. NSTC-111-2119-M-865-002.</AbstractText
|
Ascl1-mediated enhancement of GABAergic neuronal function in differentiated F11 cells under high glucose conditions. Gamma-aminobutyric acid (GABA)ergic neurons play a key role in pain modulation within the dorsal root ganglion (DRG), making them critical targets for therapeutic studies. This study utilized F11 cells as an in vitro model to examine GABAergic function under high-glucose conditions mimicking diabetic neuropathy. Differentiated F11 cells exhibited increased sensory neuronal marker expression and functional action potentials. Overexpression of the transcription factor Achaete-scute homolog 1 (Ascl1) via lentiviral vectors enhanced GABAergic characteristics, including upregulation of GAD65, GAD67, VGAT, and GABA release. Under high-glucose conditions, Ascl1 modulated pro-inflammatory cytokines (TNF-α, NF-κB, IL-1β), anti-inflammatory cytokines (IL-4, IL-10), and pain-related channels (TRPV1, TRPA1, Nav1.8), reversing pathological changes. Temporal control of Ascl1 during differentiation reduced hypersensitivity and improved cell viability, mediated by parvalbumin in a specific GABAergic subtype. These findings highlight the therapeutic potential of Ascl1 in neuropathic pain and the scalability of F11 cells for high-throughput screening of GABAergic therapeutics.</AbstractText
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Gabapentinoid Prescribing Practices at a Large Academic Medical Center. To evaluate indications for gabapentinoid prescription at an academic medical center.</AbstractText We retrospectively reviewed patients aged 18 years or older who were prescribed gabapentinoids (gabapentin or pregabalin) during the 2019 calendar year at an academic medical center in the US Midwest. Patient demographic characteristics, indications for gabapentinoid prescription, and prescribing clinician specialities were abstracted from a random sample, and the findings were extrapolated to the overall cohort.</AbstractText A total of 6205 prescriptions for gabapentinoids were initially identified. In the random sample of prescriptions (n=721), 89.5% were for gabapentin and 10.5% were for pregabalin. More women than men were prescribed gabapentinoids, and the mean ± SD patient age was 58.6±16.9 years. The top 5 indications for gabapentinoid prescriptions were neuropathic pain, musculoskeletal pain, restless legs syndrome, anxiety, and headache. A majority (66.7%) of prescriptions had substantial-to-modest evidence, but 29.0% of prescriptions had conflicting or insufficient evidence.</AbstractText To our knowledge, this study is one of the first to manually review clinical notes from multiple clinical specialities to ascertain indications for gabapentinoid prescriptions. Although most prescriptions had modest evidence to support their use, a high percentage of gabapentinoid prescriptions were issued for indications not supported by robust evidence. This suggests that prescribers are gravitating toward gabapentinoid use for reasons that are currently not fully understood. Clinician intent for off-label gabapentinoid prescriptions at the point of care should be further studied to understand the factors that lead to these clinical decisions.</AbstractText
|
Impact of rapid temperature fluctuations on acute stroke risk: a nationwide case-crossover study from 2001 to 2020. Climate factors greatly affect cardiovascular health, with stroke ranking among serious global concerns. However, the impact of rapid temperature fluctuations on stroke risk remains underexplored. Given Taiwan's aging population and the intensifying effects of climate change, understanding influence of ambient temperatures on stroke risk is crucial for public health protection. This study aimed to explore the link between ambient temperature, sudden day-to-day temperature changes, and stroke onset in Taiwan, taking air pollutants into consideration.</AbstractText We conducted a time-stratified case-crossover study from 2001 to 2020 using Distributed Lag Nonlinear Models (DLNM) within conditional logistic regression to examine lagged associations between temperature parameters and stroke risk. We analyzed associations separately for total stroke, ischemic stroke, and hemorrhagic stroke to identify potential differences in risk patterns, using odds ratios (ORs) relative to the temperature associated with the lowest stroke risk. Data from the National Health Insurance Research Database (NHIRD) identified the study population, including 1,100,074 first-time stroke emergency events and self-matched with 2,200,148 non-stroke onset dates as controls. The primary exposure assessments included daily temperatures (mean, maximum, and minimum) and temperature fluctuations (diurnal temperature range (DTR), sudden day-to-day temperature increases (TDI), and sudden day-to-day temperature decrease (TDD)), adjusted for air pollutants (PM<sub Through DLNM exposure-lag-response effect analysis after adjustment for PM<sub Our findings indicate that sudden day-to-day temperature increases and decreases are significant predictors of stroke onset. These results emphasize a noteworthy relationship between temperature and stroke risk over consecutive days, supporting interventions aimed at reducing stroke incidence.</AbstractText This research was supported by the National Science and Technology Council (NSTC), Executive Yuan, Taiwan, grant No. NSTC-111-2119-M-865-002.</AbstractText
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40081341
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22114292
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40781123
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Sex Differences in Progression of Neurodegeneration: The Age, Gene/Environment Susceptibility-Reykjavik Study.
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Increased functional selectivity over development in rostrolateral prefrontal cortex.
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A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity.
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Advancing age is associated with global brain atrophy. Cross-sectional studies have found sex differences in neuroanatomy; however, longitudinal studies assessing sex differences in neurodegeneration are currently scarce. The effects of age and sex on brain atrophy may not be uniform across the whole brain and may partially explain the sex differences observed in dementia. The current study aimed to examine sex differences in longitudinal atrophy patterns in gray and white matter regions in older adults.</AbstractText The study sample included 1,480 individuals from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, a population-based cohort study, that underwent two magnetic resonance imaging scans within an average of 5 years between assessments. Individuals were also followed-up for incident dementia diagnosis. Linear regression models were used to assess sex differences between mean differences in gray and white matter regions, correcting for age, education, baseline intracranial volume, baseline regional volumes, hypertension, body mass index, and apolipoprotein (APOE) e4 allele status.</AbstractText Men showed increased longitudinal atrophy in the total gray matter, as well as in the parietal cortex, cingulate cortex, caudate nucleus, brainstem, left cerebellum, precentral gyrus, putamen, globus pallidus, and orbitofrontal cortex. Whereas women exhibited greater atrophy over time in total white matter, but not in specific regions. No moderation was found between sex differences in incident dementia regarding atrophy patterns.</AbstractText While men show larger gray matter volumes cross-sectionally, their rates of atrophy over time are steeper compared to women. Sex differences in brain atrophy seem to be specifically detrimental in men in regions related to executive functioning, motor control, and emotion processing.</AbstractText
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Relational reasoning, or the ability to identify and consider relationships between multiple mental representations, is a fundamental component of high-level cognition (Robin and Holyoak, 1995). The capacity to reason with relations enables abstract thought and may be at the core of what makes human cognition unique (Penn et al., 2008). This capacity improves throughout childhood and adolescence (Ferrer et al., 2009). Here, we sought to better understand the neural mechanisms that support its emergence. We have hypothesized previously, based on fMRI research in adults, that (1) inferior parietal lobe (IPL) plays a central role in representing relationships between mental representations (first-order relations) and (2) rostrolateral prefrontal cortex (RLPFC) integrates inputs from IPL to build second-order relational structures (i.e., relations between relations). In the present study, we examined fMRI and cortical thickness data from 85 children and adolescents (ages 6-18 years). Participants performed a relational matching task in which they viewed arrays of four visual stimuli and determined whether two stimuli shared a particular feature (a first-order relational judgment) or whether two pairs of stimuli matched according to the same feature (a second-order relational judgment). fMRI results provide evidence for increased functional selectivity across ages 6-18 years in RLPFC and IPL. Specifically, young children engaged RLPFC and IPL indiscriminately for first-order and second-order relational judgments, and activation for first-order relations diminished with age whereas activation for second-order relations stayed elevated. Examination of cortical thickness revealed that increased functional selectivity in RLPFC could be partly accounted for by cortical thinning in IPL.</AbstractText
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Optogenetics is a method to regulate cells, tissues and organisms using light. It is applied to study neurons and to develop diagnostic and therapeutic tools for neuron-related diseases. The cation-conducting channelrhodopsin ChR2 triggers photoinduced depolarization of neuronal cells but generates lower ion currents due to the syn-pathway of its branched photocycle. In contrast, the homologous anion-conducting ACR1 from Guillardia theta (GtACR1), exhibits high photocurrents. Here, we investigate the mechanistic cause for the observed high photocurrents in GtACR1 using FTIR spectroscopy. Unexpectedly, we discovered that the O intermediate of GtACR1 is photoactivable, allowing for fast and efficient channel reopening. Our vibrational spectra show a photocyclic reaction sequence after O excitation similar to the ground state photocycle but with slightly altered channel conformation and protonation states. Our results provide deeper insights into the gating mechanism of channelrhodopsins and pave the way to advance the development of optimized optogenetic tools in future.</AbstractText
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Sex Differences in Progression of Neurodegeneration: The Age, Gene/Environment Susceptibility-Reykjavik Study. Advancing age is associated with global brain atrophy. Cross-sectional studies have found sex differences in neuroanatomy; however, longitudinal studies assessing sex differences in neurodegeneration are currently scarce. The effects of age and sex on brain atrophy may not be uniform across the whole brain and may partially explain the sex differences observed in dementia. The current study aimed to examine sex differences in longitudinal atrophy patterns in gray and white matter regions in older adults.</AbstractText The study sample included 1,480 individuals from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, a population-based cohort study, that underwent two magnetic resonance imaging scans within an average of 5 years between assessments. Individuals were also followed-up for incident dementia diagnosis. Linear regression models were used to assess sex differences between mean differences in gray and white matter regions, correcting for age, education, baseline intracranial volume, baseline regional volumes, hypertension, body mass index, and apolipoprotein (APOE) e4 allele status.</AbstractText Men showed increased longitudinal atrophy in the total gray matter, as well as in the parietal cortex, cingulate cortex, caudate nucleus, brainstem, left cerebellum, precentral gyrus, putamen, globus pallidus, and orbitofrontal cortex. Whereas women exhibited greater atrophy over time in total white matter, but not in specific regions. No moderation was found between sex differences in incident dementia regarding atrophy patterns.</AbstractText While men show larger gray matter volumes cross-sectionally, their rates of atrophy over time are steeper compared to women. Sex differences in brain atrophy seem to be specifically detrimental in men in regions related to executive functioning, motor control, and emotion processing.</AbstractText
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Increased functional selectivity over development in rostrolateral prefrontal cortex. Relational reasoning, or the ability to identify and consider relationships between multiple mental representations, is a fundamental component of high-level cognition (Robin and Holyoak, 1995). The capacity to reason with relations enables abstract thought and may be at the core of what makes human cognition unique (Penn et al., 2008). This capacity improves throughout childhood and adolescence (Ferrer et al., 2009). Here, we sought to better understand the neural mechanisms that support its emergence. We have hypothesized previously, based on fMRI research in adults, that (1) inferior parietal lobe (IPL) plays a central role in representing relationships between mental representations (first-order relations) and (2) rostrolateral prefrontal cortex (RLPFC) integrates inputs from IPL to build second-order relational structures (i.e., relations between relations). In the present study, we examined fMRI and cortical thickness data from 85 children and adolescents (ages 6-18 years). Participants performed a relational matching task in which they viewed arrays of four visual stimuli and determined whether two stimuli shared a particular feature (a first-order relational judgment) or whether two pairs of stimuli matched according to the same feature (a second-order relational judgment). fMRI results provide evidence for increased functional selectivity across ages 6-18 years in RLPFC and IPL. Specifically, young children engaged RLPFC and IPL indiscriminately for first-order and second-order relational judgments, and activation for first-order relations diminished with age whereas activation for second-order relations stayed elevated. Examination of cortical thickness revealed that increased functional selectivity in RLPFC could be partly accounted for by cortical thinning in IPL.</AbstractText
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A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity. Optogenetics is a method to regulate cells, tissues and organisms using light. It is applied to study neurons and to develop diagnostic and therapeutic tools for neuron-related diseases. The cation-conducting channelrhodopsin ChR2 triggers photoinduced depolarization of neuronal cells but generates lower ion currents due to the syn-pathway of its branched photocycle. In contrast, the homologous anion-conducting ACR1 from Guillardia theta (GtACR1), exhibits high photocurrents. Here, we investigate the mechanistic cause for the observed high photocurrents in GtACR1 using FTIR spectroscopy. Unexpectedly, we discovered that the O intermediate of GtACR1 is photoactivable, allowing for fast and efficient channel reopening. Our vibrational spectra show a photocyclic reaction sequence after O excitation similar to the ground state photocycle but with slightly altered channel conformation and protonation states. Our results provide deeper insights into the gating mechanism of channelrhodopsins and pave the way to advance the development of optimized optogenetic tools in future.</AbstractText
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19726751
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16635578
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19286384
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Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls.
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Divide and conquer: a defense of functional localizers.
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The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy.
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In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationship with dementia severity are unclear. We investigated the brain uptake of the amyloid ligand (11)C-labeled Pittsburgh compound B ([(11)C]PIB) and volumetric brain changes over a 2-year follow-up in patients with AD and in aged healthy controls.</AbstractText Fourteen patients with AD (mean age 72 years, SD 6.6) and 13 healthy controls (mean age 68 years, SD 5.4) were examined at baseline and after 2 years (patients with AD: mean 2.0 years, SD 0.2; controls: mean 2.1 years, SD 0.6) with [(11)C]PIB PET, MRI, and neuropsychological assessments. [(11)C]PIB uptake was analyzed with a voxel-based statistical method (SPM), and quantitative data were obtained with automated region-of-interest analysis. MRI data were analyzed with voxel-wise tensor-based morphometry.</AbstractText The [(11)C]PIB uptake of the patients with AD did not increase significantly during follow-up when compared with that of the controls. MRI showed progressive brain volume change in the patients with AD, e.g., in the hippocampal region, temporal cortex, and precuneus (p < 0.05). The mean Mini-Mental State Examination score of the patients with AD declined from 24.3 (SD 3.1) at baseline to 21.6 (SD 3.9) at follow-up (p = 0.009). Cognitive decline was also evident in other neuropsychological test results. Baseline neocortical [(11)C]PIB uptake ratios predicted subsequent volumetric brain changes in the controls (r = 0.725, p = 0.005).</AbstractText The results suggest no (or only little) increase in (11)C-labeled Pittsburgh compound B ([(11)C]PIB) uptake during 2 years of Alzheimer disease progression, despite advancing brain atrophy and declining cognitive performance. Nevertheless, changes in [(11)C]PIB uptake during a longer follow-up cannot be excluded. High cortical [(11)C]PIB uptake may predict ongoing brain atrophy in cognitively normal individuals.</AbstractText
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Numerous functionally distinct regions of cortex (e.g., V1, MT, the fusiform face area) can be easily identified in any normal human subject in just a few minutes of fMRI scanning. However, the locations of these regions vary across subjects. Investigations of these regions have therefore often used a functional region of interest (fROI) approach in which the region is first identified functionally in each subject individually, before subsequent scans in the same subjects test specific hypotheses concerning that region. This fROI method, which resembled long-established practice in visual neurophysiology, has methodological, statistical, and theoretical advantages over standard alternatives (such as whole-brain analyses of group data): (i) because functional properties are more consistently and robustly associated with fROIs than with locations in stereotaxic space, functional hypotheses concerning fROIs are often the most straightforward to frame, motivate, and test, (ii) because hypotheses are tested in only a handful of fROIs (instead of in tens of thousands of voxels), advance specification of fROIs provides a massive increase in statistical power over whole-brain analyses, and (iii) some fROIs may serve as candidate distinct components of the mind/brain worth investigation as such. Of course fROIs can be productively used in conjunction with other complementary methods. Here, we explain the motivation for and advantages of the fROI approach, and we rebut the criticism of this method offered by Friston et al. (Friston, K., Rotshtein, P., Geng, J., Sterzer, P., Henson, R., in press. A critique of functional localizers. NeuroImage).</AbstractText
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We report the detailed clinical, electrophysiological and molecular analysis of a patient with Charcot-Marie-Tooth (CMT) disease. DNA sequencing of the coding sequences of the neurofilament light chain polypeptide (NEFL) gene revealed a c.64C>T heterozygous, missense mutation resulting in a Pro22Ser amino acid substitution. Clinical and electrophysiological studies revealed a mixed axonal and demyelinating neuropathy, with widespread demyelination involving both proximal and distal nerve segments. Mutations at this site in the NEFL gene have been previously linked to an axonal neuropathy or distal nerve demyelination. Our results emphasize the complexity of genotype-phenotype correlations in CMT and underline the possible importance of host factors and gene interactions in the development of clinical phenotypes.</AbstractText
|
Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. In Alzheimer disease (AD), the accumulation pattern of beta-amyloid over time and its relationship with dementia severity are unclear. We investigated the brain uptake of the amyloid ligand (11)C-labeled Pittsburgh compound B ([(11)C]PIB) and volumetric brain changes over a 2-year follow-up in patients with AD and in aged healthy controls.</AbstractText Fourteen patients with AD (mean age 72 years, SD 6.6) and 13 healthy controls (mean age 68 years, SD 5.4) were examined at baseline and after 2 years (patients with AD: mean 2.0 years, SD 0.2; controls: mean 2.1 years, SD 0.6) with [(11)C]PIB PET, MRI, and neuropsychological assessments. [(11)C]PIB uptake was analyzed with a voxel-based statistical method (SPM), and quantitative data were obtained with automated region-of-interest analysis. MRI data were analyzed with voxel-wise tensor-based morphometry.</AbstractText The [(11)C]PIB uptake of the patients with AD did not increase significantly during follow-up when compared with that of the controls. MRI showed progressive brain volume change in the patients with AD, e.g., in the hippocampal region, temporal cortex, and precuneus (p < 0.05). The mean Mini-Mental State Examination score of the patients with AD declined from 24.3 (SD 3.1) at baseline to 21.6 (SD 3.9) at follow-up (p = 0.009). Cognitive decline was also evident in other neuropsychological test results. Baseline neocortical [(11)C]PIB uptake ratios predicted subsequent volumetric brain changes in the controls (r = 0.725, p = 0.005).</AbstractText The results suggest no (or only little) increase in (11)C-labeled Pittsburgh compound B ([(11)C]PIB) uptake during 2 years of Alzheimer disease progression, despite advancing brain atrophy and declining cognitive performance. Nevertheless, changes in [(11)C]PIB uptake during a longer follow-up cannot be excluded. High cortical [(11)C]PIB uptake may predict ongoing brain atrophy in cognitively normal individuals.</AbstractText
|
Divide and conquer: a defense of functional localizers. Numerous functionally distinct regions of cortex (e.g., V1, MT, the fusiform face area) can be easily identified in any normal human subject in just a few minutes of fMRI scanning. However, the locations of these regions vary across subjects. Investigations of these regions have therefore often used a functional region of interest (fROI) approach in which the region is first identified functionally in each subject individually, before subsequent scans in the same subjects test specific hypotheses concerning that region. This fROI method, which resembled long-established practice in visual neurophysiology, has methodological, statistical, and theoretical advantages over standard alternatives (such as whole-brain analyses of group data): (i) because functional properties are more consistently and robustly associated with fROIs than with locations in stereotaxic space, functional hypotheses concerning fROIs are often the most straightforward to frame, motivate, and test, (ii) because hypotheses are tested in only a handful of fROIs (instead of in tens of thousands of voxels), advance specification of fROIs provides a massive increase in statistical power over whole-brain analyses, and (iii) some fROIs may serve as candidate distinct components of the mind/brain worth investigation as such. Of course fROIs can be productively used in conjunction with other complementary methods. Here, we explain the motivation for and advantages of the fROI approach, and we rebut the criticism of this method offered by Friston et al. (Friston, K., Rotshtein, P., Geng, J., Sterzer, P., Henson, R., in press. A critique of functional localizers. NeuroImage).</AbstractText
|
The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy. We report the detailed clinical, electrophysiological and molecular analysis of a patient with Charcot-Marie-Tooth (CMT) disease. DNA sequencing of the coding sequences of the neurofilament light chain polypeptide (NEFL) gene revealed a c.64C>T heterozygous, missense mutation resulting in a Pro22Ser amino acid substitution. Clinical and electrophysiological studies revealed a mixed axonal and demyelinating neuropathy, with widespread demyelination involving both proximal and distal nerve segments. Mutations at this site in the NEFL gene have been previously linked to an axonal neuropathy or distal nerve demyelination. Our results emphasize the complexity of genotype-phenotype correlations in CMT and underline the possible importance of host factors and gene interactions in the development of clinical phenotypes.</AbstractText
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32770510
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31539583
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34873258
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Biophysical Analysis of Lipid Domains by Fluorescence Microscopy.
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Limited positive predictive value of diffusion tensor tractography in determining clinically relevant white matter damage in brain stem cavernous malformations: A retrospective study in a single center surgical cohort.
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Phasic pupillary responses reveal differential engagement of attentional control in bilingual spoken language processing.
|
The study of the structure and dynamics of membrane domains in vivo is a challenging task. However, major advances could be achieved through the application of microscopic and spectroscopic techniques coupled with the use of model membranes, where the relations between lipid composition and the type, amount and properties of the domains present can be quantitatively studied.This chapter provides protocols to study membrane organization and visualize membrane domains by fluorescence microscopy both in artificial membrane and living cell models of Gaucher Disease (GD ). We describe a bottom-up multiprobe methodology, which enables understanding how the specific lipid interactions established by glucosylceramide, the lipid that accumulates in GD , affect the biophysical properties of model and cell membranes, focusing on its ability to influence the formation, properties and organization of lipid raft domains. In this context, we address the preparation of (1) raft-mimicking giant unilamellar vesicles labeled with a combination of fluorophores that allow for the visualization and comprehensive characterization of those membrane domains and (2) human fibroblasts exhibiting GD phenotype to assess the biophysical properties of biological membrane in living cells using fluorescence microscopy.</AbstractText
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Diffusion tensor tractography (DTT) might reflect the postoperative clinical outcome of the patients with brain stem (BS) tumors correlating well with the neurological symptoms, but cavernous malformation (CM) is a hemorrhagic tumor prone to artifacts that may limit DTT. We set out to determine the correlation of DTT findings with the neurological examination before and after surgical resection in patients with BSCMs.</AbstractText DTT findings were evaluated bilaterally for fiber tract displacement or deviation, deformation and interruption in every patient before and after the surgery. Neurological examination was performed at admission, discharge and outpatient follow-up visit. The sensitivity, specificity, positive and negative predictive values of DTT were calculated both pre- and post-operatively.</AbstractText There were 25 patients (9 men 16 women) with a mean age of 39.5±13.9 years. The mean size of the CMs was 6909±8374mm<sup Positive findings on DTT such as fiber tract deviation, deformation, disruption or interruption should be taken cautiously before drawing conclusions of a clinically relevant damage of white matter tracts.</AbstractText
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Language processing is cognitively demanding, requiring attentional resources to efficiently select and extract linguistic information as utterances unfold. Previous research has associated changes in pupil size with increased attentional effort. However, it is unknown whether the behavioral ecology of speakers may differentially affect engagement of attentional resources involved in conversation. For bilinguals, such an act potentially involves competing signals in more than one language and how this competition arises may differ across communicative contexts. We examined changes in pupil size during the comprehension of unilingual and codeswitched speech in a richly-characterized bilingual sample. In a visual-world task, participants saw pairs of objects as they heard instructions to select a target image. Instructions were either unilingual or codeswitched from one language to the other. We found that only bilinguals who use each of their languages in separate communicative contexts and who have high attention ability, show differential attention to unilingual and codeswitched speech. Bilinguals for whom codeswitching is common practice process unilingual and codeswitched speech similarly, regardless of attentional skill. Taken together, these results suggest that bilinguals recruit different language control strategies for distinct communicative purposes. The interactional context of language use critically determines attentional control engagement during language processing.</AbstractText
|
Biophysical Analysis of Lipid Domains by Fluorescence Microscopy. The study of the structure and dynamics of membrane domains in vivo is a challenging task. However, major advances could be achieved through the application of microscopic and spectroscopic techniques coupled with the use of model membranes, where the relations between lipid composition and the type, amount and properties of the domains present can be quantitatively studied.This chapter provides protocols to study membrane organization and visualize membrane domains by fluorescence microscopy both in artificial membrane and living cell models of Gaucher Disease (GD ). We describe a bottom-up multiprobe methodology, which enables understanding how the specific lipid interactions established by glucosylceramide, the lipid that accumulates in GD , affect the biophysical properties of model and cell membranes, focusing on its ability to influence the formation, properties and organization of lipid raft domains. In this context, we address the preparation of (1) raft-mimicking giant unilamellar vesicles labeled with a combination of fluorophores that allow for the visualization and comprehensive characterization of those membrane domains and (2) human fibroblasts exhibiting GD phenotype to assess the biophysical properties of biological membrane in living cells using fluorescence microscopy.</AbstractText
|
Limited positive predictive value of diffusion tensor tractography in determining clinically relevant white matter damage in brain stem cavernous malformations: A retrospective study in a single center surgical cohort. Diffusion tensor tractography (DTT) might reflect the postoperative clinical outcome of the patients with brain stem (BS) tumors correlating well with the neurological symptoms, but cavernous malformation (CM) is a hemorrhagic tumor prone to artifacts that may limit DTT. We set out to determine the correlation of DTT findings with the neurological examination before and after surgical resection in patients with BSCMs.</AbstractText DTT findings were evaluated bilaterally for fiber tract displacement or deviation, deformation and interruption in every patient before and after the surgery. Neurological examination was performed at admission, discharge and outpatient follow-up visit. The sensitivity, specificity, positive and negative predictive values of DTT were calculated both pre- and post-operatively.</AbstractText There were 25 patients (9 men 16 women) with a mean age of 39.5±13.9 years. The mean size of the CMs was 6909±8374mm<sup Positive findings on DTT such as fiber tract deviation, deformation, disruption or interruption should be taken cautiously before drawing conclusions of a clinically relevant damage of white matter tracts.</AbstractText
|
Phasic pupillary responses reveal differential engagement of attentional control in bilingual spoken language processing. Language processing is cognitively demanding, requiring attentional resources to efficiently select and extract linguistic information as utterances unfold. Previous research has associated changes in pupil size with increased attentional effort. However, it is unknown whether the behavioral ecology of speakers may differentially affect engagement of attentional resources involved in conversation. For bilinguals, such an act potentially involves competing signals in more than one language and how this competition arises may differ across communicative contexts. We examined changes in pupil size during the comprehension of unilingual and codeswitched speech in a richly-characterized bilingual sample. In a visual-world task, participants saw pairs of objects as they heard instructions to select a target image. Instructions were either unilingual or codeswitched from one language to the other. We found that only bilinguals who use each of their languages in separate communicative contexts and who have high attention ability, show differential attention to unilingual and codeswitched speech. Bilinguals for whom codeswitching is common practice process unilingual and codeswitched speech similarly, regardless of attentional skill. Taken together, these results suggest that bilinguals recruit different language control strategies for distinct communicative purposes. The interactional context of language use critically determines attentional control engagement during language processing.</AbstractText
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38731254
|
32977890
|
39208462
|
Neural Adaptation at Stimulus Onset and Speed of Neural Processing as Critical Contributors to Speech Comprehension Independent of Hearing Threshold or Age.
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Cross-modal plasticity and central deficiencies: the case of deafness and the use of cochlear implants.
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A new hybrid learning control system for robots based on spiking neural networks.
|
<b
|
The primary objective of this chapter is to describe the consequences of central deficiencies on the neurodevelopment of children. We approach this topic from the standpoint of congenital deafness. Thus we first present the current state of knowledge on cortical reorganization following congenital deafness. The allocation of auditory cortices to other sensory systems can enhance sensory processing and therefore the cognitive functions related to them. Second, we explore the linguistic development of deaf children. Given that the English written system is speech-based, its acquisition is complex and atypical for deaf children, usually leading to poorer achievements. Next, we explore the impact of a neural prosthesis named the cochlear implant on the neurocognitive and linguistic development of deaf children. In some cases, it allows the individuals to, at least partially, regain access to the lost sense. We also comment on the specific needs of the deaf population when it comes to neuropsychological assessment. Finally, we touch on the specific context of deaf children born of deaf parents, and therefore naturally exposed to sign language as the only means of communication.</AbstractText
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This paper presents a new hybrid learning and control method that can tune their parameters based on reinforcement learning. In the new proposed method, nonlinear controllers are considered multi-input multi-output functions and then the functions are replaced with SNNs with reinforcement learning algorithms. Dopamine-modulated spike-timing-dependent plasticity (STDP) is used for reinforcement learning and manipulating the synaptic weights between the input and output of neuronal groups (for parameter adjustment). Details of the method are presented and some case studies are done on nonlinear controllers such as Fractional Order PID (FOPID) and Feedback Linearization. The structure and the dynamic equations for learning are presented, and the proposed algorithm is tested on robots and results are compared with other works. Moreover, to demonstrate the effectiveness of SNNFOPID, we conducted rigorous testing on a variety of systems including a two-wheel mobile robot, a double inverted pendulum, and a four-link manipulator robot. The results revealed impressively low errors of 0.01 m, 0.03 rad, and 0.03 rad for each system, respectively. The method is tested on another controller named Feedback Linearization, which provides acceptable results. Results show that the new method has better performance in terms of Integral Absolute Error (IAE) and is highly useful in hardware implementation due to its low energy consumption, high speed, and accuracy. The duration necessary for achieving full and stable proficiency in the control of various robotic systems using SNNFOPD, and SNNFL on an Asus Core i5 system within Simulink's Simscape environment is as follows: - Two-link robot manipulator with SNNFOPID: 19.85656 hours - Two-link robot manipulator with SNNFL: 0.45828 hours - Double inverted pendulum with SNNFOPID: 3.455 hours - Mobile robot with SNNFOPID: 3.71948 hours - Four-link robot manipulator with SNNFOPID: 16.6789 hours. This method can be generalized to other controllers and systems like robots.</AbstractText
|
Neural Adaptation at Stimulus Onset and Speed of Neural Processing as Critical Contributors to Speech Comprehension Independent of Hearing Threshold or Age. <b
|
Cross-modal plasticity and central deficiencies: the case of deafness and the use of cochlear implants. The primary objective of this chapter is to describe the consequences of central deficiencies on the neurodevelopment of children. We approach this topic from the standpoint of congenital deafness. Thus we first present the current state of knowledge on cortical reorganization following congenital deafness. The allocation of auditory cortices to other sensory systems can enhance sensory processing and therefore the cognitive functions related to them. Second, we explore the linguistic development of deaf children. Given that the English written system is speech-based, its acquisition is complex and atypical for deaf children, usually leading to poorer achievements. Next, we explore the impact of a neural prosthesis named the cochlear implant on the neurocognitive and linguistic development of deaf children. In some cases, it allows the individuals to, at least partially, regain access to the lost sense. We also comment on the specific needs of the deaf population when it comes to neuropsychological assessment. Finally, we touch on the specific context of deaf children born of deaf parents, and therefore naturally exposed to sign language as the only means of communication.</AbstractText
|
A new hybrid learning control system for robots based on spiking neural networks. This paper presents a new hybrid learning and control method that can tune their parameters based on reinforcement learning. In the new proposed method, nonlinear controllers are considered multi-input multi-output functions and then the functions are replaced with SNNs with reinforcement learning algorithms. Dopamine-modulated spike-timing-dependent plasticity (STDP) is used for reinforcement learning and manipulating the synaptic weights between the input and output of neuronal groups (for parameter adjustment). Details of the method are presented and some case studies are done on nonlinear controllers such as Fractional Order PID (FOPID) and Feedback Linearization. The structure and the dynamic equations for learning are presented, and the proposed algorithm is tested on robots and results are compared with other works. Moreover, to demonstrate the effectiveness of SNNFOPID, we conducted rigorous testing on a variety of systems including a two-wheel mobile robot, a double inverted pendulum, and a four-link manipulator robot. The results revealed impressively low errors of 0.01 m, 0.03 rad, and 0.03 rad for each system, respectively. The method is tested on another controller named Feedback Linearization, which provides acceptable results. Results show that the new method has better performance in terms of Integral Absolute Error (IAE) and is highly useful in hardware implementation due to its low energy consumption, high speed, and accuracy. The duration necessary for achieving full and stable proficiency in the control of various robotic systems using SNNFOPD, and SNNFL on an Asus Core i5 system within Simulink's Simscape environment is as follows: - Two-link robot manipulator with SNNFOPID: 19.85656 hours - Two-link robot manipulator with SNNFL: 0.45828 hours - Double inverted pendulum with SNNFOPID: 3.455 hours - Mobile robot with SNNFOPID: 3.71948 hours - Four-link robot manipulator with SNNFOPID: 16.6789 hours. This method can be generalized to other controllers and systems like robots.</AbstractText
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12069095
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12069095
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12057903
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A model to assess SAR for surface coil magnetic resonance spectroscopy measurements.
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A model to assess SAR for surface coil magnetic resonance spectroscopy measurements.
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Altered calcium-mediated cell signaling in keratinocytes cultured from patients with neurofibromatosis type 1.
|
Surface coils are widely used in magnetic resonance (MR) studies due to their superior signal to noise properties. Application of excessive power levels to transmit surface coils may result in local tissue damage. A homogeneous muscle tissue model for the conservative prediction of surface coil specific absorption rate (SAR) is introduced. Based on this model, sequence parameters can be limited to provide operational levels within safety guidelines. It is demonstrated that this model provides worst-case SAR estimates at MR frequencies of 25.75 MHz and 63.6 MHz. The dependence of SAR on model structure and geometry is analysed and conclusions on the relationship between SAR levels and local anatomy are drawn. By making a worst-case assumption for the tissue parameters the model provides safe operational levels for all tissue types. Power-demanding proton-decoupled 31P magnetic resonance spectroscopy experiments are possible based on the SAR estimates provided. To date SAR values are calculated for 1 g of tissue. Changes in regulations to calculate SAR values for 10 g tissue masses, and the according averaging of local SAR over a larger volume, have been proposed by the International Electrotechnical Commission. A comparative study shows that up to 100% more energy may be applied to surface coils if SAR values are determined for 10 g tissue masses rather than 1 g tissue masses.</AbstractText
|
Surface coils are widely used in magnetic resonance (MR) studies due to their superior signal to noise properties. Application of excessive power levels to transmit surface coils may result in local tissue damage. A homogeneous muscle tissue model for the conservative prediction of surface coil specific absorption rate (SAR) is introduced. Based on this model, sequence parameters can be limited to provide operational levels within safety guidelines. It is demonstrated that this model provides worst-case SAR estimates at MR frequencies of 25.75 MHz and 63.6 MHz. The dependence of SAR on model structure and geometry is analysed and conclusions on the relationship between SAR levels and local anatomy are drawn. By making a worst-case assumption for the tissue parameters the model provides safe operational levels for all tissue types. Power-demanding proton-decoupled 31P magnetic resonance spectroscopy experiments are possible based on the SAR estimates provided. To date SAR values are calculated for 1 g of tissue. Changes in regulations to calculate SAR values for 10 g tissue masses, and the according averaging of local SAR over a larger volume, have been proposed by the International Electrotechnical Commission. A comparative study shows that up to 100% more energy may be applied to surface coils if SAR values are determined for 10 g tissue masses rather than 1 g tissue masses.</AbstractText
|
Capacitative calcium entry and calcium wave propagation were studied in keratinocytes cultured from control persons and patients with type 1 neurofibromatosis. The cells were stimulated mechanically in the presence of inhibitors of gap-junctional or ATP-mediated communication to determine which pathways are operative in Ca(2+) signaling between these cells. Keratinocytes cultured from patients with type 1 neurofibromatosis (NF1) had a tendency to form cultures with markedly altered calcium-related signaling characteristics. Specifically, the resting Ca(2+) levels, intracellular Ca(2+) stores, capacitative calcium influx, and gap-junctional signal transduction were defective in NF1 keratinocytes. Western transfer analysis revealed apparently equal connexin 43 protein levels in normal control and in NF1 keratinocytes. Indirect immunofluorescence, however, demonstrated that connexin 43 was relatively evenly distributed in NF1 cells and did not form typical gap-junctional plaques between keratinocytes. Furthermore, the speed of the calcium wave was reduced in NF1 cells compared to normal keratinocytes. The results demonstrate that keratinocytes cultured from patients with NF1 display altered calcium-mediated signaling between cells.</AbstractText
|
A model to assess SAR for surface coil magnetic resonance spectroscopy measurements. Surface coils are widely used in magnetic resonance (MR) studies due to their superior signal to noise properties. Application of excessive power levels to transmit surface coils may result in local tissue damage. A homogeneous muscle tissue model for the conservative prediction of surface coil specific absorption rate (SAR) is introduced. Based on this model, sequence parameters can be limited to provide operational levels within safety guidelines. It is demonstrated that this model provides worst-case SAR estimates at MR frequencies of 25.75 MHz and 63.6 MHz. The dependence of SAR on model structure and geometry is analysed and conclusions on the relationship between SAR levels and local anatomy are drawn. By making a worst-case assumption for the tissue parameters the model provides safe operational levels for all tissue types. Power-demanding proton-decoupled 31P magnetic resonance spectroscopy experiments are possible based on the SAR estimates provided. To date SAR values are calculated for 1 g of tissue. Changes in regulations to calculate SAR values for 10 g tissue masses, and the according averaging of local SAR over a larger volume, have been proposed by the International Electrotechnical Commission. A comparative study shows that up to 100% more energy may be applied to surface coils if SAR values are determined for 10 g tissue masses rather than 1 g tissue masses.</AbstractText
|
A model to assess SAR for surface coil magnetic resonance spectroscopy measurements. Surface coils are widely used in magnetic resonance (MR) studies due to their superior signal to noise properties. Application of excessive power levels to transmit surface coils may result in local tissue damage. A homogeneous muscle tissue model for the conservative prediction of surface coil specific absorption rate (SAR) is introduced. Based on this model, sequence parameters can be limited to provide operational levels within safety guidelines. It is demonstrated that this model provides worst-case SAR estimates at MR frequencies of 25.75 MHz and 63.6 MHz. The dependence of SAR on model structure and geometry is analysed and conclusions on the relationship between SAR levels and local anatomy are drawn. By making a worst-case assumption for the tissue parameters the model provides safe operational levels for all tissue types. Power-demanding proton-decoupled 31P magnetic resonance spectroscopy experiments are possible based on the SAR estimates provided. To date SAR values are calculated for 1 g of tissue. Changes in regulations to calculate SAR values for 10 g tissue masses, and the according averaging of local SAR over a larger volume, have been proposed by the International Electrotechnical Commission. A comparative study shows that up to 100% more energy may be applied to surface coils if SAR values are determined for 10 g tissue masses rather than 1 g tissue masses.</AbstractText
|
Altered calcium-mediated cell signaling in keratinocytes cultured from patients with neurofibromatosis type 1. Capacitative calcium entry and calcium wave propagation were studied in keratinocytes cultured from control persons and patients with type 1 neurofibromatosis. The cells were stimulated mechanically in the presence of inhibitors of gap-junctional or ATP-mediated communication to determine which pathways are operative in Ca(2+) signaling between these cells. Keratinocytes cultured from patients with type 1 neurofibromatosis (NF1) had a tendency to form cultures with markedly altered calcium-related signaling characteristics. Specifically, the resting Ca(2+) levels, intracellular Ca(2+) stores, capacitative calcium influx, and gap-junctional signal transduction were defective in NF1 keratinocytes. Western transfer analysis revealed apparently equal connexin 43 protein levels in normal control and in NF1 keratinocytes. Indirect immunofluorescence, however, demonstrated that connexin 43 was relatively evenly distributed in NF1 cells and did not form typical gap-junctional plaques between keratinocytes. Furthermore, the speed of the calcium wave was reduced in NF1 cells compared to normal keratinocytes. The results demonstrate that keratinocytes cultured from patients with NF1 display altered calcium-mediated signaling between cells.</AbstractText
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26759479
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15858403
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28707202
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Facial Expressions Evoke Differential Neural Coupling in Macaques.
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Neural correlates of frustration.
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Executive functioning impairment in women treated with chemotherapy for breast cancer: a systematic review.
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In humans and monkeys, face perception activates a distributed cortical network that includes extrastriate, limbic, and prefrontal regions. Within face-responsive regions, emotional faces evoke stronger responses than neutral faces ("valence effect"). We used fMRI and Dynamic Causal Modeling (DCM) to test the hypothesis that emotional faces differentially alter the functional coupling among face-responsive regions. Three monkeys viewed conspecific faces with neutral, threatening, fearful, and appeasing expressions. Using Bayesian model selection, various models of neural interactions between the posterior (TEO) and anterior (TE) portions of inferior temporal (IT) cortex, the amygdala, the orbitofrontal (OFC), and ventrolateral prefrontal cortex (VLPFC) were tested. The valence effect was mediated by feedback connections from the amygdala to TE and TEO, and feedback connections from VLPFC to the amygdala and TE. Emotional faces were associated with differential effective connectivity: Fearful faces evoked stronger modulations in the connections from the amygdala to TE and TEO; threatening faces evoked weaker modulations in the connections from the amygdala and VLPFC to TE; and appeasing faces evoked weaker modulations in the connection from VLPFC to the amygdala. Our results suggest dynamic alterations in neural coupling during the perception of behaviorally relevant facial expressions that are vital for social communication.</AbstractText
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Psychological considerations suggest that the omission of rewards in humans comprises two effects: first, an allocentric effect triggering learning and behavioural changes potentially processed by dopaminergic neurons according to the prediction error theory; second, an egocentric effect representing the individual's emotional reaction, commonly called frustration. We investigated this second effect in the context of omission of monetary reward with functional magnetic resonance imaging. As expected, the contrast omission relative to receipt of reward led to a decrease in ventral striatal activation consistent with prediction error theory. Increased activation for this contrast was found in areas previously related to emotional pain: the right anterior insula and the right ventral prefrontal cortex. We interpreted this as a neural correlate of the egocentric effect.</AbstractText
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Women with breast cancer have reported adverse cognitive effects following chemotherapy. Evidence is mixed on whether executive functioning is particularly impaired in women treated with chemotherapy, in part due to the wide range of tasks used to measure executive processes. We performed a systematic review of the published literature to evaluate whether some subcomponents of executive functioning are more vulnerable to impairment than others among breast cancer survivors who had been treated with chemotherapy.</AbstractText Studies published as of April 2017 were identified using three electronic databases (MEDLINE, PsycINFO, and Web of Science) and a manual search of relevant reference lists. The methodological quality of included studies was assessed using a checklist of predefined criteria.</AbstractText Of 1280 identified articles, a total of 41 were included for review. Study findings were categorized into three primary subdomains of executive functioning: inhibition, shifting, and updating. Although there was heterogeneity in the neuropsychological measures used to assess executive functioning, tests could be grouped into the subcomponents they assessed. Inhibition appears relatively spared from the effects of chemotherapy, whereas impairments in shifting and updating are more commonly found following chemotherapy.</AbstractText Examination of subcomponents of executive functioning is recommended to better characterize the nature of executive dysfunction in women treated with chemotherapy. Future studies should include executive functioning tasks of varying complexity, use of multiple tasks to increase reliability, and alternative indices to capture performance, such as within-person variability.</AbstractText
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Facial Expressions Evoke Differential Neural Coupling in Macaques. In humans and monkeys, face perception activates a distributed cortical network that includes extrastriate, limbic, and prefrontal regions. Within face-responsive regions, emotional faces evoke stronger responses than neutral faces ("valence effect"). We used fMRI and Dynamic Causal Modeling (DCM) to test the hypothesis that emotional faces differentially alter the functional coupling among face-responsive regions. Three monkeys viewed conspecific faces with neutral, threatening, fearful, and appeasing expressions. Using Bayesian model selection, various models of neural interactions between the posterior (TEO) and anterior (TE) portions of inferior temporal (IT) cortex, the amygdala, the orbitofrontal (OFC), and ventrolateral prefrontal cortex (VLPFC) were tested. The valence effect was mediated by feedback connections from the amygdala to TE and TEO, and feedback connections from VLPFC to the amygdala and TE. Emotional faces were associated with differential effective connectivity: Fearful faces evoked stronger modulations in the connections from the amygdala to TE and TEO; threatening faces evoked weaker modulations in the connections from the amygdala and VLPFC to TE; and appeasing faces evoked weaker modulations in the connection from VLPFC to the amygdala. Our results suggest dynamic alterations in neural coupling during the perception of behaviorally relevant facial expressions that are vital for social communication.</AbstractText
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Neural correlates of frustration. Psychological considerations suggest that the omission of rewards in humans comprises two effects: first, an allocentric effect triggering learning and behavioural changes potentially processed by dopaminergic neurons according to the prediction error theory; second, an egocentric effect representing the individual's emotional reaction, commonly called frustration. We investigated this second effect in the context of omission of monetary reward with functional magnetic resonance imaging. As expected, the contrast omission relative to receipt of reward led to a decrease in ventral striatal activation consistent with prediction error theory. Increased activation for this contrast was found in areas previously related to emotional pain: the right anterior insula and the right ventral prefrontal cortex. We interpreted this as a neural correlate of the egocentric effect.</AbstractText
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Executive functioning impairment in women treated with chemotherapy for breast cancer: a systematic review. Women with breast cancer have reported adverse cognitive effects following chemotherapy. Evidence is mixed on whether executive functioning is particularly impaired in women treated with chemotherapy, in part due to the wide range of tasks used to measure executive processes. We performed a systematic review of the published literature to evaluate whether some subcomponents of executive functioning are more vulnerable to impairment than others among breast cancer survivors who had been treated with chemotherapy.</AbstractText Studies published as of April 2017 were identified using three electronic databases (MEDLINE, PsycINFO, and Web of Science) and a manual search of relevant reference lists. The methodological quality of included studies was assessed using a checklist of predefined criteria.</AbstractText Of 1280 identified articles, a total of 41 were included for review. Study findings were categorized into three primary subdomains of executive functioning: inhibition, shifting, and updating. Although there was heterogeneity in the neuropsychological measures used to assess executive functioning, tests could be grouped into the subcomponents they assessed. Inhibition appears relatively spared from the effects of chemotherapy, whereas impairments in shifting and updating are more commonly found following chemotherapy.</AbstractText Examination of subcomponents of executive functioning is recommended to better characterize the nature of executive dysfunction in women treated with chemotherapy. Future studies should include executive functioning tasks of varying complexity, use of multiple tasks to increase reliability, and alternative indices to capture performance, such as within-person variability.</AbstractText
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38913442
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34166620
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37528503
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Sleep Disorders and Dementia Risk in Older Patients with Kidney Failure: A Retrospective Cohort Study.
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Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort.
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Benefits of a targeted rehabilitation of number transcoding in secondary acalculia: A single-case experimental design.
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Older patients with kidney failure who are newly diagnosed with sleep disorders are at higher risk of developing any type of dementia, vascular dementia, and other/mixed types of dementia. For older patients with kidney failure who are diagnosed with obstructive sleep apnea, positive airway pressure therapy is an intervention that is associated with lower dementia risk.</AbstractText Community-dwelling older adults with sleep disorders are at higher risk of developing dementia. Greater than 50% of older patients with kidney failure experience sleep disorders, which may explain their high burden of dementia.</AbstractText Among 216,158 patients (aged 66 years and older) with kidney failure (United States Renal Data System; 2008–2019), we estimated the risk of dementia (including subtypes) associated with sleep disorders using Cox proportional hazards models with propensity score weighting. We tested whether positive airway pressure (PAP) therapy was associated with reduced dementia risk among patients with obstructive sleep apnea (OSA).</AbstractText 26.3% of patients were diagnosed with sleep disorders; these patients had a higher 5-year unadjusted cumulative incidence for any type of dementia (36.2% versus 32.3%; <i Older patients with kidney failure and sleep disorders are at a higher risk of dementia. Sleep is an important modifiable factor that should be considered for targeted interventions to mitigate dementia risk in patients with kidney failure. For patients with OSA, PAP therapy is associated with lower dementia risk.</AbstractText
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Infections have been hypothesised to increase the risk of dementia. Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. We aimed to compare the risk of Alzheimer's disease and other dementias across a wide range of hospital-treated bacterial and viral infections in two large cohorts with long follow-up periods.</AbstractText In this large, multicohort, observational study, the analysis was based on a primary cohort consisting of pooled individual-level data from three prospective cohort studies in Finland (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study) and an independent replication cohort from the UK Biobank. Community-dwelling adults (≥18 years) with no dementia at study entry were included. Follow-up was until Dec 31, 2012, in the Health and Social Support study, Dec 31, 2016, in the public sector study and the Still Working study, and Feb 7, 2018, in the replication cohort. Through record linkage to national hospital inpatient registers, we ascertained exposure to 925 infectious diseases (using the International Classification of Diseases 10th Revision codes) before dementia onset, and identified incident dementia from hospital records, medication reimbursement entitlements, and death certificates. Hazard ratios (HRs) for the associations of each infectious disease or disease group (index infection) with incident dementia were assessed by use of Cox proportional hazards models. We then repeated the analysis after excluding incident dementia cases that occurred during the first 10 years after initial hospitalisation due to the index infection.</AbstractText From March 1, 1986, to Jan 1, 2005, 260 490 people were included in the primary cohort, and from Dec 19, 2006, to Oct 1, 2010, 485 708 people were included in the replication cohort. In the primary cohort analysis based on 3 947 046 person-years at risk (median follow-up 15·4 years [IQR 9·8-21·0]), 77 108 participants had at least one hospital-treated infection before dementia onset and 2768 developed dementia. Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR [aHR] 1·48 [95% CI 1·37-1·60]) and replication cohort (2·60 [2·38-2·83]). The association remained when analyses were restricted to new dementia cases that occurred more than 10 years after infection (aHR 1·22 [95% CI 1·09-1·36] in the primary cohort, the replication cohort had insufficient follow-up data for this analysis), and when comorbidities and other dementia risk factors were considered. There was evidence of a dose-response association between the number of episodes of hospital-treated infections and dementia risk in both cohorts (p<sub Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease. This association is not limited to CNS infections, suggesting that systemic effects are sufficient to affect the brain. The absence of infection specificity combined with evidence of dose-response relationships between infectious disease burden and dementia risk support the hypothesis that increased dementia risk is driven by general inflammation rather than specific microbes.</AbstractText UK Medical Research Council, US National Institute on Aging, Wellcome Trust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science.</AbstractText
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Despite its potentially significant functional and emotional impact, acalculia is still too rarely assessed and managed by speech and language therapists. Research on the rehabilitation of numerical transcoding remains scarce in the literature and, despite positive results, presents a low level of evidence.</AbstractText The present study aims to evaluate the effectiveness of a targeted rehabilitation of numerical transcoding in two patients suffering from a chronic secondary acalculia.</AbstractText Two post-brain injury females with secondary acalculia took part in a single-case experimental design with multiple baseline across subjects according to a three-phase experimental protocol: baseline involving global cognitive rehabilitation (5-7 measurements with randomized sequential introduction); targeted intervention (10 measurements); follow-up (2 immediate measurements and 1 month after the end of the intervention). Repeated outcome measures consisted of six lists composed of numbers of equivalent difficulty that were used alternately to assess numerical transcoding. We used a reverse digit span as a control measure to assess the specificity of the intervention. Rehabilitation lasted 5 weeks and consisted of errorless learning with colour cues, tables and number-words cards.</AbstractText During baseline period involving global cognitive rehabilitation, transcoding scores remained unchanged. In contrast, there was a significant improvement in scores for both patients during the intervention phase targeting transcoding and maintenance of benefits 1-month post-intervention.</AbstractText This study demonstrates that a specific rehabilitation targeting numerical transcoding following chronic secondary acalculia can be effective in improving transcoding skills.</AbstractText What is already known on the subject Transcoding difficulties in patients with acalculia can cause a significant disability in everyday life activities. In secondary acalculia, rehabilitation of cognitive functions associated with number processing (attention, working memory, language) is not sufficient for improvement of transcoding. What this paper adds to existing knowledge An intervention specifically targeting numerical transcoding significantly and durably improves the skills of patients with chronic secondary acalculia. What are the potential or actual clinical implications of this work? Procedural error-free intervention using colour cueing, tables, cards with number-words, copy and repetition seems effective to improve transcoding skills in chronic acalculia.</AbstractText
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Sleep Disorders and Dementia Risk in Older Patients with Kidney Failure: A Retrospective Cohort Study. Older patients with kidney failure who are newly diagnosed with sleep disorders are at higher risk of developing any type of dementia, vascular dementia, and other/mixed types of dementia. For older patients with kidney failure who are diagnosed with obstructive sleep apnea, positive airway pressure therapy is an intervention that is associated with lower dementia risk.</AbstractText Community-dwelling older adults with sleep disorders are at higher risk of developing dementia. Greater than 50% of older patients with kidney failure experience sleep disorders, which may explain their high burden of dementia.</AbstractText Among 216,158 patients (aged 66 years and older) with kidney failure (United States Renal Data System; 2008–2019), we estimated the risk of dementia (including subtypes) associated with sleep disorders using Cox proportional hazards models with propensity score weighting. We tested whether positive airway pressure (PAP) therapy was associated with reduced dementia risk among patients with obstructive sleep apnea (OSA).</AbstractText 26.3% of patients were diagnosed with sleep disorders; these patients had a higher 5-year unadjusted cumulative incidence for any type of dementia (36.2% versus 32.3%; <i Older patients with kidney failure and sleep disorders are at a higher risk of dementia. Sleep is an important modifiable factor that should be considered for targeted interventions to mitigate dementia risk in patients with kidney failure. For patients with OSA, PAP therapy is associated with lower dementia risk.</AbstractText
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Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort. Infections have been hypothesised to increase the risk of dementia. Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. We aimed to compare the risk of Alzheimer's disease and other dementias across a wide range of hospital-treated bacterial and viral infections in two large cohorts with long follow-up periods.</AbstractText In this large, multicohort, observational study, the analysis was based on a primary cohort consisting of pooled individual-level data from three prospective cohort studies in Finland (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study) and an independent replication cohort from the UK Biobank. Community-dwelling adults (≥18 years) with no dementia at study entry were included. Follow-up was until Dec 31, 2012, in the Health and Social Support study, Dec 31, 2016, in the public sector study and the Still Working study, and Feb 7, 2018, in the replication cohort. Through record linkage to national hospital inpatient registers, we ascertained exposure to 925 infectious diseases (using the International Classification of Diseases 10th Revision codes) before dementia onset, and identified incident dementia from hospital records, medication reimbursement entitlements, and death certificates. Hazard ratios (HRs) for the associations of each infectious disease or disease group (index infection) with incident dementia were assessed by use of Cox proportional hazards models. We then repeated the analysis after excluding incident dementia cases that occurred during the first 10 years after initial hospitalisation due to the index infection.</AbstractText From March 1, 1986, to Jan 1, 2005, 260 490 people were included in the primary cohort, and from Dec 19, 2006, to Oct 1, 2010, 485 708 people were included in the replication cohort. In the primary cohort analysis based on 3 947 046 person-years at risk (median follow-up 15·4 years [IQR 9·8-21·0]), 77 108 participants had at least one hospital-treated infection before dementia onset and 2768 developed dementia. Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR [aHR] 1·48 [95% CI 1·37-1·60]) and replication cohort (2·60 [2·38-2·83]). The association remained when analyses were restricted to new dementia cases that occurred more than 10 years after infection (aHR 1·22 [95% CI 1·09-1·36] in the primary cohort, the replication cohort had insufficient follow-up data for this analysis), and when comorbidities and other dementia risk factors were considered. There was evidence of a dose-response association between the number of episodes of hospital-treated infections and dementia risk in both cohorts (p<sub Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease. This association is not limited to CNS infections, suggesting that systemic effects are sufficient to affect the brain. The absence of infection specificity combined with evidence of dose-response relationships between infectious disease burden and dementia risk support the hypothesis that increased dementia risk is driven by general inflammation rather than specific microbes.</AbstractText UK Medical Research Council, US National Institute on Aging, Wellcome Trust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science.</AbstractText
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Benefits of a targeted rehabilitation of number transcoding in secondary acalculia: A single-case experimental design. Despite its potentially significant functional and emotional impact, acalculia is still too rarely assessed and managed by speech and language therapists. Research on the rehabilitation of numerical transcoding remains scarce in the literature and, despite positive results, presents a low level of evidence.</AbstractText The present study aims to evaluate the effectiveness of a targeted rehabilitation of numerical transcoding in two patients suffering from a chronic secondary acalculia.</AbstractText Two post-brain injury females with secondary acalculia took part in a single-case experimental design with multiple baseline across subjects according to a three-phase experimental protocol: baseline involving global cognitive rehabilitation (5-7 measurements with randomized sequential introduction); targeted intervention (10 measurements); follow-up (2 immediate measurements and 1 month after the end of the intervention). Repeated outcome measures consisted of six lists composed of numbers of equivalent difficulty that were used alternately to assess numerical transcoding. We used a reverse digit span as a control measure to assess the specificity of the intervention. Rehabilitation lasted 5 weeks and consisted of errorless learning with colour cues, tables and number-words cards.</AbstractText During baseline period involving global cognitive rehabilitation, transcoding scores remained unchanged. In contrast, there was a significant improvement in scores for both patients during the intervention phase targeting transcoding and maintenance of benefits 1-month post-intervention.</AbstractText This study demonstrates that a specific rehabilitation targeting numerical transcoding following chronic secondary acalculia can be effective in improving transcoding skills.</AbstractText What is already known on the subject Transcoding difficulties in patients with acalculia can cause a significant disability in everyday life activities. In secondary acalculia, rehabilitation of cognitive functions associated with number processing (attention, working memory, language) is not sufficient for improvement of transcoding. What this paper adds to existing knowledge An intervention specifically targeting numerical transcoding significantly and durably improves the skills of patients with chronic secondary acalculia. What are the potential or actual clinical implications of this work? Procedural error-free intervention using colour cueing, tables, cards with number-words, copy and repetition seems effective to improve transcoding skills in chronic acalculia.</AbstractText
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33483296
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34305580
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34382767
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High-density surface electromyography to assess motor unit firing rate in Charcot-Marie-Tooth disease type 1A patients.
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Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats.
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Fluorescence Probe for Imaging N-Methyl-d-aspartate Receptors and Monitoring GSH Selectively Using Two-Photon Microscopy.
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The aim of this study was to elucidate the characteristics of the motor unit (MU) firing rate in Charcot-Marie-Tooth disease type 1A (CMT1A) patients and its longitudinal change using high-density surface-electromyography (surface-EMG) and MU decomposition analysis.</AbstractText Nineteen patients with CMT1A and 21 force-matched healthy controls prospectively underwent surface-EMG recording of the vastus lateralis muscle during ramp-up and sustained contractions on performing isometric knee extension. After decomposition analysis, instantaneous firing rates (IFRs) of individually identified MUs were calculated. In CMT1A patients, follow-up measurements were performed one year after the baseline. Comparison of IFRs and clinical variables between CMT1A patients and controls at the baseline and between the baseline and after one year in CMT1A patients was performed.</AbstractText Mean IFRs of MUs were lower in CMT1A patients than in controls. This was true at various force levels in ramp-up contractions (p < 0.01. e.g., 10.3 (CMT1A patients) vs. 12.2 (controls) pulses-per-second (pps) at 22.5-27.5% of maximal voluntary contraction (MVC) in MUs recruited at <7.5% of MVC) and at any time-point during sustained contractions (p < 0.001. e.g., 8.0 vs. 9.3 pps, respectively, at 10-20 seconds). In CMT1A patients, mean IFRs at 0-10 seconds of sustained contraction were significantly decreased over one year (from 8.06 to 7.52 pps; p = 0.027), whereas the disease severity score and MVC of knee extension did not change over time.</AbstractText CMT1A patients had a lower individual MU firing rate.</AbstractText The MU firing rate is a potential short-term biomarker of axonal damage in CMT1A patients.</AbstractText
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We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1β, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters.</AbstractText
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<i
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High-density surface electromyography to assess motor unit firing rate in Charcot-Marie-Tooth disease type 1A patients. The aim of this study was to elucidate the characteristics of the motor unit (MU) firing rate in Charcot-Marie-Tooth disease type 1A (CMT1A) patients and its longitudinal change using high-density surface-electromyography (surface-EMG) and MU decomposition analysis.</AbstractText Nineteen patients with CMT1A and 21 force-matched healthy controls prospectively underwent surface-EMG recording of the vastus lateralis muscle during ramp-up and sustained contractions on performing isometric knee extension. After decomposition analysis, instantaneous firing rates (IFRs) of individually identified MUs were calculated. In CMT1A patients, follow-up measurements were performed one year after the baseline. Comparison of IFRs and clinical variables between CMT1A patients and controls at the baseline and between the baseline and after one year in CMT1A patients was performed.</AbstractText Mean IFRs of MUs were lower in CMT1A patients than in controls. This was true at various force levels in ramp-up contractions (p < 0.01. e.g., 10.3 (CMT1A patients) vs. 12.2 (controls) pulses-per-second (pps) at 22.5-27.5% of maximal voluntary contraction (MVC) in MUs recruited at <7.5% of MVC) and at any time-point during sustained contractions (p < 0.001. e.g., 8.0 vs. 9.3 pps, respectively, at 10-20 seconds). In CMT1A patients, mean IFRs at 0-10 seconds of sustained contraction were significantly decreased over one year (from 8.06 to 7.52 pps; p = 0.027), whereas the disease severity score and MVC of knee extension did not change over time.</AbstractText CMT1A patients had a lower individual MU firing rate.</AbstractText The MU firing rate is a potential short-term biomarker of axonal damage in CMT1A patients.</AbstractText
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Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats. We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1β, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters.</AbstractText
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Fluorescence Probe for Imaging N-Methyl-d-aspartate Receptors and Monitoring GSH Selectively Using Two-Photon Microscopy. <i
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38993021
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27802274
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39297260
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Ultrashort echo time magnetic resonance elastography for quantification of the mechanical properties of short T2 tissues via optimal control-based radiofrequency pulses.
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Topology, Cross-Frequency, and Same-Frequency Band Interactions Shape the Generation of Phase-Amplitude Coupling in a Neural Mass Model of a Cortical Column.
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THE THEORY OF MIND AND PSYCHOTIC SYMPTOMS PHENOMENOLOGY IN SUBSTANCE-INDUCED PSYCHOTIC DISORDER AND SCHIZOPHRENIA.
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The aim of the current study is to demonstrate the feasibility of radiofrequency (RF) pulses generated via an optimal control (OC) algorithm to perform magnetic resonance elastography (MRE) and quantify the mechanical properties of materials with very short transverse relaxation times (T2 < 5 ms) for the first time. OC theory applied to MRE provides RF pulses that bring isochromats from the equilibrium state to a fixed target state, which corresponds to the phase pattern of a conventional MRE acquisition. Such RF pulses applied with a constant gradient allow to simultaneously perform slice selection and motion encoding in the slice direction. Unlike conventional MRE, no additional motion-encoding gradients (MEGs) are needed, enabling shorter echo times. OC pulses were implemented both in turbo spin echo (OC rapid acquisition with refocused echoes [RARE]) and ultrashort echo time (OC UTE) sequences to compare their motion-encoding efficiency with the conventional MEG encoding (classical MEG MRE). MRE experiments were carried out on agar phantoms with very short T2 values and on an ex vivo bovine tendon. Magnitude images, wave field images, phase-to-noise ratio (PNR), and shear storage modulus maps were compared between OC RARE, OC UTE, and classical MEG MRE in samples with different T2 values. Shear storage modulus values of the agar phantoms were in agreement with values found in the literature, and that of the bovine tendon was corroborated with rheometry measurements. Only the OC sequences could encode motion in very short T2 samples, and only OC UTE sequences yielded magnitude images enabling proper visualization of short T2 samples and tissues. The OC UTE sequence produced the best PNRs, demonstrating its ability to perform anatomical and mechanical characterization. Its success warrants in vivo confirmation in further studies.</AbstractText
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Phase-amplitude coupling (PAC), a type of cross-frequency coupling (CFC) where the phase of a low-frequency rhythm modulates the amplitude of a higher frequency, is becoming an important indicator of information transmission in the brain. However, the neurobiological mechanisms underlying its generation remain undetermined. A realistic, yet tractable computational model of the phenomenon is thus needed. Here we analyze a neural mass model of a cortical column, comprising fourteen neuronal populations distributed across four layers (L2/3, L4, L5 and L6). A control analysis showed that the conditional transfer entropy (cTE) measure is able to correctly estimate the flow of information between neuronal populations. Then, we computed cTE from the phases to the amplitudes of the oscillations generated in the cortical column. This approach provides information regarding directionality by distinguishing PAC from APC (amplitude-phase coupling), i.e. the information transfer from amplitudes to phases, and can be used to estimate other types of CFC such as amplitude-amplitude coupling (AAC) and phase-phase coupling (PPC). While experiments often only focus on one or two PAC combinations (e.g., theta-gamma or alpha-gamma), we found that a cortical column can simultaneously generate almost all possible PAC combinations, depending on connectivity parameters, time constants, and external inputs. PAC interactions with and without an anatomical equivalent (direct and indirect interactions, respectively) were analyzed. We found that the strength of PAC between two populations was strongly correlated with the strength of the effective connections between the populations and, on average, did not depend on whether the PAC connection was direct or indirect. When considering a cortical column circuit as a complex network, we found that neuronal populations making indirect PAC connections had, on average, higher local clustering coefficient, efficiency, and betweenness centrality than populations making direct connections and populations not involved in PAC connections. This suggests that their interactions were more effective when transmitting information. Since approximately 60% of the obtained interactions represented indirect connections, our results highlight the importance of the topology of cortical circuits for the generation of the PAC phenomenon. Finally, our results demonstrated that indirect PAC interactions can be explained by a cascade of direct CFC and same-frequency band interactions, suggesting that PAC analysis of experimental data should be accompanied by the estimation of other types of frequency interactions for an integrative understanding of the phenomenon.</AbstractText
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The study aimed to determine clinical indicators that could be used to differentiate between patients diagnosed with substance-induced psychotic disorder (SIPD) and patients diagnosed with schizophrenia by comparing their psychotic symptoms and theory of mind (ToM).</AbstractText The study included 43 male patients diagnosed with schizophrenia according to DSM-5 criteria and 43 male patients diagnosed with SIPD. The patients were administered the Sociodemographic and Clinical Data Form, Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Psychotic Symptom Evaluation Scale (PSYRATS), and Reading the Mind in the Eyes Test (RMET).</AbstractText In patients diagnosed with schizophrenia, the scores on SAPS subscales for structural thought disorder and bizarre behavior, as well as SANS total scores, were significantly higher compared to patients diagnosed with SIPD (z=2.679, p=0.007; z=2.984, p=0.003; z=6.916, p<0.001). The scores for recognizing negative and neutral expressions on the RMET were significantly higher in patients with SIPD than in patients with schizophrenia (z=3.540; p<0.001; z=4.404, p<0.001). It was found that as the scores on the SANS total and Affect Blunting or Flattening subscale, as well as the scores on the SAPS Bizarre Behavior subscale decrease, the probability of having SIPD increases.</AbstractText In patients diagnosed with SIPD, there are fewer disorganized and negative symptoms compared to patients diagnosed with schizophrenia. Patients with SIPD can recognize negative and neutral expressions better than patients with schizophrenia. When making a differential diagnosis between SIPD and schizophrenia, as blunting in affect, total negative symptoms, and severity of bizarre behavior decrease, the probability of being diagnosed with SIPD increases relative to the probability of being diagnosed with schizophrenia.</AbstractText
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Ultrashort echo time magnetic resonance elastography for quantification of the mechanical properties of short T2 tissues via optimal control-based radiofrequency pulses. The aim of the current study is to demonstrate the feasibility of radiofrequency (RF) pulses generated via an optimal control (OC) algorithm to perform magnetic resonance elastography (MRE) and quantify the mechanical properties of materials with very short transverse relaxation times (T2 < 5 ms) for the first time. OC theory applied to MRE provides RF pulses that bring isochromats from the equilibrium state to a fixed target state, which corresponds to the phase pattern of a conventional MRE acquisition. Such RF pulses applied with a constant gradient allow to simultaneously perform slice selection and motion encoding in the slice direction. Unlike conventional MRE, no additional motion-encoding gradients (MEGs) are needed, enabling shorter echo times. OC pulses were implemented both in turbo spin echo (OC rapid acquisition with refocused echoes [RARE]) and ultrashort echo time (OC UTE) sequences to compare their motion-encoding efficiency with the conventional MEG encoding (classical MEG MRE). MRE experiments were carried out on agar phantoms with very short T2 values and on an ex vivo bovine tendon. Magnitude images, wave field images, phase-to-noise ratio (PNR), and shear storage modulus maps were compared between OC RARE, OC UTE, and classical MEG MRE in samples with different T2 values. Shear storage modulus values of the agar phantoms were in agreement with values found in the literature, and that of the bovine tendon was corroborated with rheometry measurements. Only the OC sequences could encode motion in very short T2 samples, and only OC UTE sequences yielded magnitude images enabling proper visualization of short T2 samples and tissues. The OC UTE sequence produced the best PNRs, demonstrating its ability to perform anatomical and mechanical characterization. Its success warrants in vivo confirmation in further studies.</AbstractText
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Topology, Cross-Frequency, and Same-Frequency Band Interactions Shape the Generation of Phase-Amplitude Coupling in a Neural Mass Model of a Cortical Column. Phase-amplitude coupling (PAC), a type of cross-frequency coupling (CFC) where the phase of a low-frequency rhythm modulates the amplitude of a higher frequency, is becoming an important indicator of information transmission in the brain. However, the neurobiological mechanisms underlying its generation remain undetermined. A realistic, yet tractable computational model of the phenomenon is thus needed. Here we analyze a neural mass model of a cortical column, comprising fourteen neuronal populations distributed across four layers (L2/3, L4, L5 and L6). A control analysis showed that the conditional transfer entropy (cTE) measure is able to correctly estimate the flow of information between neuronal populations. Then, we computed cTE from the phases to the amplitudes of the oscillations generated in the cortical column. This approach provides information regarding directionality by distinguishing PAC from APC (amplitude-phase coupling), i.e. the information transfer from amplitudes to phases, and can be used to estimate other types of CFC such as amplitude-amplitude coupling (AAC) and phase-phase coupling (PPC). While experiments often only focus on one or two PAC combinations (e.g., theta-gamma or alpha-gamma), we found that a cortical column can simultaneously generate almost all possible PAC combinations, depending on connectivity parameters, time constants, and external inputs. PAC interactions with and without an anatomical equivalent (direct and indirect interactions, respectively) were analyzed. We found that the strength of PAC between two populations was strongly correlated with the strength of the effective connections between the populations and, on average, did not depend on whether the PAC connection was direct or indirect. When considering a cortical column circuit as a complex network, we found that neuronal populations making indirect PAC connections had, on average, higher local clustering coefficient, efficiency, and betweenness centrality than populations making direct connections and populations not involved in PAC connections. This suggests that their interactions were more effective when transmitting information. Since approximately 60% of the obtained interactions represented indirect connections, our results highlight the importance of the topology of cortical circuits for the generation of the PAC phenomenon. Finally, our results demonstrated that indirect PAC interactions can be explained by a cascade of direct CFC and same-frequency band interactions, suggesting that PAC analysis of experimental data should be accompanied by the estimation of other types of frequency interactions for an integrative understanding of the phenomenon.</AbstractText
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THE THEORY OF MIND AND PSYCHOTIC SYMPTOMS PHENOMENOLOGY IN SUBSTANCE-INDUCED PSYCHOTIC DISORDER AND SCHIZOPHRENIA. The study aimed to determine clinical indicators that could be used to differentiate between patients diagnosed with substance-induced psychotic disorder (SIPD) and patients diagnosed with schizophrenia by comparing their psychotic symptoms and theory of mind (ToM).</AbstractText The study included 43 male patients diagnosed with schizophrenia according to DSM-5 criteria and 43 male patients diagnosed with SIPD. The patients were administered the Sociodemographic and Clinical Data Form, Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Psychotic Symptom Evaluation Scale (PSYRATS), and Reading the Mind in the Eyes Test (RMET).</AbstractText In patients diagnosed with schizophrenia, the scores on SAPS subscales for structural thought disorder and bizarre behavior, as well as SANS total scores, were significantly higher compared to patients diagnosed with SIPD (z=2.679, p=0.007; z=2.984, p=0.003; z=6.916, p<0.001). The scores for recognizing negative and neutral expressions on the RMET were significantly higher in patients with SIPD than in patients with schizophrenia (z=3.540; p<0.001; z=4.404, p<0.001). It was found that as the scores on the SANS total and Affect Blunting or Flattening subscale, as well as the scores on the SAPS Bizarre Behavior subscale decrease, the probability of having SIPD increases.</AbstractText In patients diagnosed with SIPD, there are fewer disorganized and negative symptoms compared to patients diagnosed with schizophrenia. Patients with SIPD can recognize negative and neutral expressions better than patients with schizophrenia. When making a differential diagnosis between SIPD and schizophrenia, as blunting in affect, total negative symptoms, and severity of bizarre behavior decrease, the probability of being diagnosed with SIPD increases relative to the probability of being diagnosed with schizophrenia.</AbstractText
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40045805
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34920435
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40733816
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Instrumental assessment of INPH: structural and functional neuroimaging.
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Complete posterior cranial vault distraction osteogenesis to correct Chiari malformation type I associated with craniosynostosis.
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Rational design of freeze-crosslinked polysaccharide sponges for efficient non-compressible hemostasis and liver repair.
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For the accurate diagnosis of idiopathic normal pressure hydrocephalus (iNPH) an accurate neuroimaging is essential. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key neuroradiological feature and novel imaging techniques, including voxel-based morphometry and AI-assisted analyses are emerging as powerful tools to investigate iNPH pathophysiology. Converging evidence also suggests a role for dopaminergic dysfunction in iNPH. Molecular imaging of the dopamine transporter (DaT) enables the investigation of dopaminergic function and holds potential for advancing differential diagnosis and guiding treatment decisions in iNPH.</AbstractText A comprehensive literature search was conducted using MeSH key words. Studies assessing the role of structural and functional neuroimaging in iNPH. The evidence was summarized, and key results were provided.</AbstractText DESH is crucial for accurate diagnosis and treatment planning. Advanced structural and functional imaging techniques are expanding our understanding of iNPH pathophysiology. Only few functional imaging studies have directly examined the dopaminergic dysfunction in iNPH and severe methodological limitations exist in both clinical classification and imaging processing. Nonetheless, evidence supports the presence of dopaminergic dysfunction in iNPH, which may be linked to specific clinical symptoms, aid in differential diagnosis, and be reversed with shunt surgery treatment.</AbstractText This review covers the structural and functional imaging data in iNPH, providing a comprehensive outlook of the current knowledge, highlighting the limitations and possible future perspectives.</AbstractText
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Posterior vault distraction osteogenesis (PVDO) is an effective tool to increase intracranial volume and expand the posterior cranial fossa. During PVDO, the authors extended osteotomy posterior to the foramen magnum to fully expand the posterior cranial fossa. The aim of this study was to investigate the efficacy of complete PVDO in posterior fossa expansion and treatment of Chiari malformation type I (CM-I) in patients with craniosynostosis.</AbstractText Patients with craniosynostosis who had undergone complete PVDO between January 2012 and May 2020 were reviewed retrospectively. A coronal osteotomy extending to the foramen magnum was performed and the foramen magnum was decompressed by removing its posterior rim with a 1-mm Kerrison rongeur. Four distractor devices were placed and the vector of distraction was controlled from the posterior to the inferior-posterior direction, depending on the deformity. Changes in the intracranial volume, posterior cranial fossa area, and cerebellar tonsillar descent were measured after complete PVDO by using CT and MRI.</AbstractText A total of 11 patients with craniosynostosis and concurrent CM-I were included in the study. The mean age was 34.6 ± 24.0 months (continuous variables are expressed as the mean ± SD throughout). One patient had sleep apnea, which was consistent with CM-I, and another patient had a headache, which was nonspecific. The intracranial volume increased from 1179.6 ± 180.2 cm3 to 1440.6 ± 251.5 cm3 (p = 0.003; 24.5% increase compared to the preoperative volume). The posterior skull base area increased from 44.9 ± 19.3 cm2 to 72.7 ± 18.1 cm2 (p = 0.004). Cerebellar tonsillar descent decreased in all 11 patients after complete PVDO (preoperative: 10.8 ± 3.7 mm, postoperative: 2.7 ± 3.0 mm; p = 0.003). Among the 11 patients, 5 showed complete resolution of cerebellar tonsillar herniation.</AbstractText Complete PVDO can more efficiently expand the posterior cranial fossa, unlike conventional methods. Moreover, it helps to relieve cerebellar tonsillar herniation. Complete PVDO is a powerful tool to increase the intracranial and posterior fossa volumes in patients with craniosynostosis and concurrent CM-I.</AbstractText
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Non-compressible hemorrhage is a life-threatening challenge, and shape-memory hemostatic sponges that require no removal are ideal for inaccessible hemorrhage wounds. In this study, we freeze-crosslinked two polysaccharides by tuning their ratios to fully utilize their inherent physiochemical properties. The obtained shape memory sponges exhibit tunable mechanical properties, high absorbent capacities, and compression resilience. The effect of Oxidizing bacteria cellulose (OBC)/Carboxymethyl chitosan (CMCS) ratios on their hemostatic behaviors and liver repair was also systemically studied. In particular, both in vitro coagulation and in vivo hemostasis experiments suggest that the sponges of high OBC/CMCS ratio perform better in terms of compression resilience and hemostasis. The in vitro culture of primary hepatocytes and histological analysis of livers implanted with OBC/CMCS sponges suggest those of high OBC/CMCS ratios are conducive for hepatocytes adhesion and promote liver repair by microvessel formation and cell infiltration with reduced inflammatory effects or foreign body reactions. These easily manufactured hemostatic sponges are suitable for uncontrollable hemorrhage and in situ tissue repair, providing guidance for the rational design of next-generation hemostatic materials.</AbstractText
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Instrumental assessment of INPH: structural and functional neuroimaging. For the accurate diagnosis of idiopathic normal pressure hydrocephalus (iNPH) an accurate neuroimaging is essential. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key neuroradiological feature and novel imaging techniques, including voxel-based morphometry and AI-assisted analyses are emerging as powerful tools to investigate iNPH pathophysiology. Converging evidence also suggests a role for dopaminergic dysfunction in iNPH. Molecular imaging of the dopamine transporter (DaT) enables the investigation of dopaminergic function and holds potential for advancing differential diagnosis and guiding treatment decisions in iNPH.</AbstractText A comprehensive literature search was conducted using MeSH key words. Studies assessing the role of structural and functional neuroimaging in iNPH. The evidence was summarized, and key results were provided.</AbstractText DESH is crucial for accurate diagnosis and treatment planning. Advanced structural and functional imaging techniques are expanding our understanding of iNPH pathophysiology. Only few functional imaging studies have directly examined the dopaminergic dysfunction in iNPH and severe methodological limitations exist in both clinical classification and imaging processing. Nonetheless, evidence supports the presence of dopaminergic dysfunction in iNPH, which may be linked to specific clinical symptoms, aid in differential diagnosis, and be reversed with shunt surgery treatment.</AbstractText This review covers the structural and functional imaging data in iNPH, providing a comprehensive outlook of the current knowledge, highlighting the limitations and possible future perspectives.</AbstractText
|
Complete posterior cranial vault distraction osteogenesis to correct Chiari malformation type I associated with craniosynostosis. Posterior vault distraction osteogenesis (PVDO) is an effective tool to increase intracranial volume and expand the posterior cranial fossa. During PVDO, the authors extended osteotomy posterior to the foramen magnum to fully expand the posterior cranial fossa. The aim of this study was to investigate the efficacy of complete PVDO in posterior fossa expansion and treatment of Chiari malformation type I (CM-I) in patients with craniosynostosis.</AbstractText Patients with craniosynostosis who had undergone complete PVDO between January 2012 and May 2020 were reviewed retrospectively. A coronal osteotomy extending to the foramen magnum was performed and the foramen magnum was decompressed by removing its posterior rim with a 1-mm Kerrison rongeur. Four distractor devices were placed and the vector of distraction was controlled from the posterior to the inferior-posterior direction, depending on the deformity. Changes in the intracranial volume, posterior cranial fossa area, and cerebellar tonsillar descent were measured after complete PVDO by using CT and MRI.</AbstractText A total of 11 patients with craniosynostosis and concurrent CM-I were included in the study. The mean age was 34.6 ± 24.0 months (continuous variables are expressed as the mean ± SD throughout). One patient had sleep apnea, which was consistent with CM-I, and another patient had a headache, which was nonspecific. The intracranial volume increased from 1179.6 ± 180.2 cm3 to 1440.6 ± 251.5 cm3 (p = 0.003; 24.5% increase compared to the preoperative volume). The posterior skull base area increased from 44.9 ± 19.3 cm2 to 72.7 ± 18.1 cm2 (p = 0.004). Cerebellar tonsillar descent decreased in all 11 patients after complete PVDO (preoperative: 10.8 ± 3.7 mm, postoperative: 2.7 ± 3.0 mm; p = 0.003). Among the 11 patients, 5 showed complete resolution of cerebellar tonsillar herniation.</AbstractText Complete PVDO can more efficiently expand the posterior cranial fossa, unlike conventional methods. Moreover, it helps to relieve cerebellar tonsillar herniation. Complete PVDO is a powerful tool to increase the intracranial and posterior fossa volumes in patients with craniosynostosis and concurrent CM-I.</AbstractText
|
Rational design of freeze-crosslinked polysaccharide sponges for efficient non-compressible hemostasis and liver repair. Non-compressible hemorrhage is a life-threatening challenge, and shape-memory hemostatic sponges that require no removal are ideal for inaccessible hemorrhage wounds. In this study, we freeze-crosslinked two polysaccharides by tuning their ratios to fully utilize their inherent physiochemical properties. The obtained shape memory sponges exhibit tunable mechanical properties, high absorbent capacities, and compression resilience. The effect of Oxidizing bacteria cellulose (OBC)/Carboxymethyl chitosan (CMCS) ratios on their hemostatic behaviors and liver repair was also systemically studied. In particular, both in vitro coagulation and in vivo hemostasis experiments suggest that the sponges of high OBC/CMCS ratio perform better in terms of compression resilience and hemostasis. The in vitro culture of primary hepatocytes and histological analysis of livers implanted with OBC/CMCS sponges suggest those of high OBC/CMCS ratios are conducive for hepatocytes adhesion and promote liver repair by microvessel formation and cell infiltration with reduced inflammatory effects or foreign body reactions. These easily manufactured hemostatic sponges are suitable for uncontrollable hemorrhage and in situ tissue repair, providing guidance for the rational design of next-generation hemostatic materials.</AbstractText
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34677355
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34706221
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33998311
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Investigating the Regulation of Neural Differentiation and Injury in PC12 Cells Using Microstructure Topographic Cues.
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An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury.
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Who Returns? Understanding Varieties of Longitudinal Participation in MIDUS.
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In this study, we designed and manufactured a series of different microstructure topographical cues for inducing neuronal differentiation of cells in vitro, with different topography, sizes, and structural complexities. We cultured PC12 cells in these microstructure cues and then induced neural differentiation using nerve growth factor (NGF). The pheochromocytoma cell line PC12 is a validated neuronal cell model that is widely used to study neuronal differentiation. Relevant markers of neural differentiation and cytoskeletal F-actin were characterized. Cellular immunofluorescence detection and axon length analysis showed that the differentiation of PC12 cells was significantly different under different isotropic and anisotropic topographic cues. The expression differences of the growth cone marker growth-associated protein 43 (GAP-43) and sympathetic nerve marker tyrosine hydroxylase (TH) genes were also studied in different topographic cues. Our results revealed that the physical environment has an important influence on the differentiation of neuronal cells, and 3D constraints could be used to guide axon extension. In addition, the neurotoxin 6-hydroxydopamine (6-OHDA) was used to detect the differentiation and injury of PC12 cells under different topographic cues. Finally, we discussed the feasibility of combining the topographic cues and the microfluidic chip for neural differentiation research.</AbstractText
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Axons in the adult mammalian central nervous system fail to regenerate after spinal cord injury. Neurons lose their capacity to regenerate during development, but the intracellular processes underlying this loss are unclear. We found that critical components of the presynaptic active zone prevent axon regeneration in adult mice. Transcriptomic analysis combined with live-cell imaging revealed that adult primary sensory neurons downregulate molecular constituents of the synapse as they acquire the ability to rapidly grow their axons. Pharmacogenetic reduction of neuronal excitability stimulated axon regeneration after adult spinal cord injury. Genetic gain- and loss-of-function experiments uncovered that essential synaptic vesicle priming proteins of the presynaptic active zone, but not clostridial-toxin-sensitive VAMP-family SNARE proteins, inhibit axon regeneration. Systemic administration of Baclofen reduced voltage-dependent Ca<sup
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<b
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Investigating the Regulation of Neural Differentiation and Injury in PC12 Cells Using Microstructure Topographic Cues. In this study, we designed and manufactured a series of different microstructure topographical cues for inducing neuronal differentiation of cells in vitro, with different topography, sizes, and structural complexities. We cultured PC12 cells in these microstructure cues and then induced neural differentiation using nerve growth factor (NGF). The pheochromocytoma cell line PC12 is a validated neuronal cell model that is widely used to study neuronal differentiation. Relevant markers of neural differentiation and cytoskeletal F-actin were characterized. Cellular immunofluorescence detection and axon length analysis showed that the differentiation of PC12 cells was significantly different under different isotropic and anisotropic topographic cues. The expression differences of the growth cone marker growth-associated protein 43 (GAP-43) and sympathetic nerve marker tyrosine hydroxylase (TH) genes were also studied in different topographic cues. Our results revealed that the physical environment has an important influence on the differentiation of neuronal cells, and 3D constraints could be used to guide axon extension. In addition, the neurotoxin 6-hydroxydopamine (6-OHDA) was used to detect the differentiation and injury of PC12 cells under different topographic cues. Finally, we discussed the feasibility of combining the topographic cues and the microfluidic chip for neural differentiation research.</AbstractText
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An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury. Axons in the adult mammalian central nervous system fail to regenerate after spinal cord injury. Neurons lose their capacity to regenerate during development, but the intracellular processes underlying this loss are unclear. We found that critical components of the presynaptic active zone prevent axon regeneration in adult mice. Transcriptomic analysis combined with live-cell imaging revealed that adult primary sensory neurons downregulate molecular constituents of the synapse as they acquire the ability to rapidly grow their axons. Pharmacogenetic reduction of neuronal excitability stimulated axon regeneration after adult spinal cord injury. Genetic gain- and loss-of-function experiments uncovered that essential synaptic vesicle priming proteins of the presynaptic active zone, but not clostridial-toxin-sensitive VAMP-family SNARE proteins, inhibit axon regeneration. Systemic administration of Baclofen reduced voltage-dependent Ca<sup
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Who Returns? Understanding Varieties of Longitudinal Participation in MIDUS. <b
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28665957
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23486868
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29616149
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Post-dengue acute disseminated encephalomyelitis: A case report and meta-analysis.
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Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution.
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Immersive Virtual Reality Therapy with Myoelectric Control for Treatment-resistant Phantom Limb Pain: Case Report.
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Dengue is one of the most common infectious diseases. The aim of this study was to systematically review acute disseminated encephalomyelitis (ADEM) and to represent a new case.</AbstractText We searched for articles in nine databases for case reports, series or previous reviews reporting ADEM cases in human. We used Fisher's exact and Mann-Whitney U tests. Classification trees were used to find the predictors of the disease outcomes. We combined findings using fixed- and random-effects models. A 13-year-old girl was admitted to the hospital due to fever. She has a urinary retention. The neurological examinations revealed that she became lethargic and quadriplegic. She had upper limbs weakness and lower limbs complete paraplegia. Her status gradually improved after the treatment. She was nearly intact with the proximal part of her legs had a mild weakness in discharge. The prevalence of ADEM among dengue patients was 0.4% [95% confidence intervals (95% CI) 0.1-2.5%], all neurological disorders among dengue was 2.6% [95% CI 1.8-3.8%], and ADEM among neurological disorders was 6.8% [95% CI 3.4-13%]. The most frequent manifestation of ADEM was altered sensorium/consciousness (58%), seizures and urination problems (35%), vision problems (31%), slurred speech (23%), walk problems (15%) then ataxia (12%). There was a significant difference between cases having complete recovery or bad outcomes in the onset day of neurological manifestations being earlier and in temperature being higher in cases having bad outcomes (p-value < 0.05). This was confirmed by classification trees which included these two variables.</AbstractText The prevalence of ADEM among dengue and other dengue-related neurological disorders is not too rare. The high fever of ADEM cases at admission and earlier onset day of neurological manifestations are associated with the bad outcomes.</AbstractText
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Neuromyelitis optica and its spectrum disorder (NMOSD) can present similarly to relapsing-remitting multiple sclerosis (RRMS). Using a quantitative lesion mapping approach, this research aimed to identify differences in MRI brain lesion distribution between aquaporin-4 antibody-positive NMOSD and RRMS, and to test their diagnostic potential.</AbstractText Clinical brain MRI sequences for 44 patients with aquaporin-4 antibody-positive NMOSD and 50 patients with RRMS were examined for the distribution and morphology of brain lesions. T2 lesion maps were created for each subject allowing the quantitative comparison of the 2 conditions with lesion probability and voxel-wise analysis.</AbstractText Sixty-three percent of patients with NMOSD had brain lesions and of these 27% were diagnostic of multiple sclerosis. Patients with RRMS were significantly more likely to have lesions adjacent to the body of the lateral ventricle than patients with NMOSD. Direct comparison of the probability distributions and the morphologic attributes of the lesions in each group identified criteria of "at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion; or a Dawson's finger-type lesion," which could distinguish patients with multiple sclerosis from those with NMOSD with 92% sensitivity, 96% specificity, 98% positive predictive value, and 86% negative predictive value.</AbstractText Careful inspection of the distribution and morphology of MRI brain lesions can distinguish RRMS and NMOSD.</AbstractText
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<b
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Post-dengue acute disseminated encephalomyelitis: A case report and meta-analysis. Dengue is one of the most common infectious diseases. The aim of this study was to systematically review acute disseminated encephalomyelitis (ADEM) and to represent a new case.</AbstractText We searched for articles in nine databases for case reports, series or previous reviews reporting ADEM cases in human. We used Fisher's exact and Mann-Whitney U tests. Classification trees were used to find the predictors of the disease outcomes. We combined findings using fixed- and random-effects models. A 13-year-old girl was admitted to the hospital due to fever. She has a urinary retention. The neurological examinations revealed that she became lethargic and quadriplegic. She had upper limbs weakness and lower limbs complete paraplegia. Her status gradually improved after the treatment. She was nearly intact with the proximal part of her legs had a mild weakness in discharge. The prevalence of ADEM among dengue patients was 0.4% [95% confidence intervals (95% CI) 0.1-2.5%], all neurological disorders among dengue was 2.6% [95% CI 1.8-3.8%], and ADEM among neurological disorders was 6.8% [95% CI 3.4-13%]. The most frequent manifestation of ADEM was altered sensorium/consciousness (58%), seizures and urination problems (35%), vision problems (31%), slurred speech (23%), walk problems (15%) then ataxia (12%). There was a significant difference between cases having complete recovery or bad outcomes in the onset day of neurological manifestations being earlier and in temperature being higher in cases having bad outcomes (p-value < 0.05). This was confirmed by classification trees which included these two variables.</AbstractText The prevalence of ADEM among dengue and other dengue-related neurological disorders is not too rare. The high fever of ADEM cases at admission and earlier onset day of neurological manifestations are associated with the bad outcomes.</AbstractText
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Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution. Neuromyelitis optica and its spectrum disorder (NMOSD) can present similarly to relapsing-remitting multiple sclerosis (RRMS). Using a quantitative lesion mapping approach, this research aimed to identify differences in MRI brain lesion distribution between aquaporin-4 antibody-positive NMOSD and RRMS, and to test their diagnostic potential.</AbstractText Clinical brain MRI sequences for 44 patients with aquaporin-4 antibody-positive NMOSD and 50 patients with RRMS were examined for the distribution and morphology of brain lesions. T2 lesion maps were created for each subject allowing the quantitative comparison of the 2 conditions with lesion probability and voxel-wise analysis.</AbstractText Sixty-three percent of patients with NMOSD had brain lesions and of these 27% were diagnostic of multiple sclerosis. Patients with RRMS were significantly more likely to have lesions adjacent to the body of the lateral ventricle than patients with NMOSD. Direct comparison of the probability distributions and the morphologic attributes of the lesions in each group identified criteria of "at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion; or a Dawson's finger-type lesion," which could distinguish patients with multiple sclerosis from those with NMOSD with 92% sensitivity, 96% specificity, 98% positive predictive value, and 86% negative predictive value.</AbstractText Careful inspection of the distribution and morphology of MRI brain lesions can distinguish RRMS and NMOSD.</AbstractText
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Immersive Virtual Reality Therapy with Myoelectric Control for Treatment-resistant Phantom Limb Pain: Case Report. <b
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39202391
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23219967
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38687457
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A Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker-Warburg-like Features.
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Increased gait variability in mice with small cerebellar cortex lesions and normal rotarod performance.
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Assessment of the deep learning-based gamma passing rate prediction system for 1.5 T magnetic resonance-guided linear accelerator.
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Tubulinopathies are associated with malformations of cortical development but not Walker-Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker-Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker-Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the <i
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The physiological and pathophysiological role of the cerebellum in neuromotor performance and gait is a prominent research topic in contemporary brain research. However, it has proven difficult to measure subtle neuromotor changes and cerebellar dysfunction in laboratory rodents with some of the common behavioural assays. Rotarod assays and gait analyses have been used extensively as indicators of neuromotor performance, and more specifically, cerebellar function. Standard rotarod procedures fail to reveal subtle motor alterations, whereas automated gait analysis could be more sensitive in this respect. In the present study, we compared detailed treadmill gait analysis to the standard accelerating rotarod assay in its ability to reveal neuromotor alterations in mice with small bilateral lesions in the cerebellar cortex. This small lesion model showed no readily observable signs of ataxia or abnormal activity. In the rotarod test, cerebellar-lesioned mice performed at the level of control animals, and basic gait parameters were not altered. However, cerebellar-lesioned mice did show increased front base-width and hind stride length variability, as well as increased stride length incongruity between different paws. We conclude that small cerebellar lesions lead to increased gait variability as it does in humans with cerebellar dysfunction. Treadmill gait analysis is better suited than accelerating rotarod assays to measure such subtle neuromotor defects.</AbstractText
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Measurement-based verification is impossible for the patient-specific quality assurance (QA) of online adaptive magnetic resonance imaging-guided radiotherapy (oMRgRT) because the patient remains on the couch throughout the session. We assessed a deep learning (DL) system for oMRgRT to predict the gamma passing rate (GPR). This study collected 125 verification plans [reference plan (RP), 100; adapted plan (AP), 25] from patients with prostate cancer treated using Elekta Unity. Based on our previous study, we employed a convolutional neural network that predicted the GPRs of nine pairs of gamma criteria from 1%/1 mm to 3%/3 mm. First, we trained and tested the DL model using RPs (n = 75 and n = 25 for training and testing, respectively) for its optimization. Second, we tested the GPR prediction accuracy using APs to determine whether the DL model could be applied to APs. The mean absolute error (MAE) and correlation coefficient (r) of the RPs were 1.22 ± 0.27% and 0.29 ± 0.10 in 3%/2 mm, 1.35 ± 0.16% and 0.37 ± 0.15 in 2%/2 mm, and 3.62 ± 0.55% and 0.32 ± 0.14 in 1%/1 mm, respectively. The MAE and r of the APs were 1.13 ± 0.33% and 0.35 ± 0.22 in 3%/2 mm, 1.68 ± 0.47% and 0.30 ± 0.11 in 2%/2 mm, and 5.08 ± 0.29% and 0.15 ± 0.10 in 1%/1 mm, respectively. The time cost was within 3 s for the prediction. The results suggest the DL-based model has the potential for rapid GPR prediction in Elekta Unity.</AbstractText
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A Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker-Warburg-like Features. Tubulinopathies are associated with malformations of cortical development but not Walker-Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker-Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker-Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the <i
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Increased gait variability in mice with small cerebellar cortex lesions and normal rotarod performance. The physiological and pathophysiological role of the cerebellum in neuromotor performance and gait is a prominent research topic in contemporary brain research. However, it has proven difficult to measure subtle neuromotor changes and cerebellar dysfunction in laboratory rodents with some of the common behavioural assays. Rotarod assays and gait analyses have been used extensively as indicators of neuromotor performance, and more specifically, cerebellar function. Standard rotarod procedures fail to reveal subtle motor alterations, whereas automated gait analysis could be more sensitive in this respect. In the present study, we compared detailed treadmill gait analysis to the standard accelerating rotarod assay in its ability to reveal neuromotor alterations in mice with small bilateral lesions in the cerebellar cortex. This small lesion model showed no readily observable signs of ataxia or abnormal activity. In the rotarod test, cerebellar-lesioned mice performed at the level of control animals, and basic gait parameters were not altered. However, cerebellar-lesioned mice did show increased front base-width and hind stride length variability, as well as increased stride length incongruity between different paws. We conclude that small cerebellar lesions lead to increased gait variability as it does in humans with cerebellar dysfunction. Treadmill gait analysis is better suited than accelerating rotarod assays to measure such subtle neuromotor defects.</AbstractText
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Assessment of the deep learning-based gamma passing rate prediction system for 1.5 T magnetic resonance-guided linear accelerator. Measurement-based verification is impossible for the patient-specific quality assurance (QA) of online adaptive magnetic resonance imaging-guided radiotherapy (oMRgRT) because the patient remains on the couch throughout the session. We assessed a deep learning (DL) system for oMRgRT to predict the gamma passing rate (GPR). This study collected 125 verification plans [reference plan (RP), 100; adapted plan (AP), 25] from patients with prostate cancer treated using Elekta Unity. Based on our previous study, we employed a convolutional neural network that predicted the GPRs of nine pairs of gamma criteria from 1%/1 mm to 3%/3 mm. First, we trained and tested the DL model using RPs (n = 75 and n = 25 for training and testing, respectively) for its optimization. Second, we tested the GPR prediction accuracy using APs to determine whether the DL model could be applied to APs. The mean absolute error (MAE) and correlation coefficient (r) of the RPs were 1.22 ± 0.27% and 0.29 ± 0.10 in 3%/2 mm, 1.35 ± 0.16% and 0.37 ± 0.15 in 2%/2 mm, and 3.62 ± 0.55% and 0.32 ± 0.14 in 1%/1 mm, respectively. The MAE and r of the APs were 1.13 ± 0.33% and 0.35 ± 0.22 in 3%/2 mm, 1.68 ± 0.47% and 0.30 ± 0.11 in 2%/2 mm, and 5.08 ± 0.29% and 0.15 ± 0.10 in 1%/1 mm, respectively. The time cost was within 3 s for the prediction. The results suggest the DL-based model has the potential for rapid GPR prediction in Elekta Unity.</AbstractText
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37323312
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24687457
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36892941
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Metabolic Syndrome in Type 2 Diabetes Mellitus Patients: Prevalence, Risk Factors, and Associated Microvascular Complications.
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Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy.
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Evaluating the Usability of an Emergency Department After Visit Summary: Staged Heuristic Evaluation.
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Background The chronic macro and microvascular complications of diabetes mellitus pose serious health challenges. Metabolic syndrome (MetSy) is characterized by central obesity, glucose intolerance, hyperinsulinemia, low high-density lipoproteins (HDLs), high triglycerides (TGs), and hypertension. MetSy precedes or accompanies diabetes, and it has been linked to an increased risk of cardiovascular disease and premature death. This study aimed to estimate prevalence, identify risk factors, and evaluate associated microvascular complications among MetSy patients with type 2 diabetes mellitus (T2DM). Methodology Over the period of March 20, 2022, to March 31, 2023, a prospective cohort study was conducted at the Outdoor Clinic and Medicine Department of Sheikh Zayed Hospital, Rahim Yar Khan. Based on the International Diabetes Federation MetSy criteria, a total of 160 patients fulfilling the inclusion criteria were selected. A special proforma was used to obtain sociodemographic, clinical, and laboratory variables of MetSy in diabetic participants. Blood pressure and anthropometric measurements such as waist circumference (WC) and body mass index (BMI) were measured. Fasting venous blood was collected to analyze biochemical variables such as fasting blood sugar (FBS), TG, and high-density lipoprotein-cholesterol (HDL-C). The microvascular complications of T2DM were established using fundus ophthalmoscopy and neurological and kidney function assessments with the help of laboratory tests. These variables were matched between MetSy and no MetSy groups along with the presence or absence of diabetes microvascular complications. This information was analyzed based on these assessments and patient interviews. Results Of the 160 T2DM patients, the mean age was 52 years with a predominance of females (51.8%) in the 50-59-year age group (56.8%). The average BMI for females was 29.38 ± 0.54 kg/m², and 32 (20%) had obesity. Females exhibited a large WC of 93.52 ± 1.58 cm, and 48 of 83 females had reported diabetes microvascular complications. A significant p-value was observed for hypertension, high TG, low HDL-C, large WC, obesity, BMI, age, and female gender on comparing diabetics with metabolic syndrome (MetSy+) and those without metabolic syndrome (MetSy-). The prevalence of microvascular complications in T2DM patients with MetSy+ was 52.5% compared with 47.5% in MetSy-. The prevalence of diabetic retinopathy was 24.9% (95% confidence interval (CI) = 20.3%-29.6%), nephropathy was 16.8% (95% CI = 12.8%-20.7%), and neuropathy was 10.8% (95% CI = 7.4%-13.3%). Conclusions The prevalence of MetSy observed among T2DM patients was 65%, with married obese females in the 50-59-year age group being more likely to be affected than males. Hypertension, poor glycemic control, high TG, low HDL-C, and greater anthropometric waist measurements and BMI were additional risk factors that tended to increase the MetSy burden in T2DM. Diabetic retinopathy, nephropathy, and neuropathy were the most prevalent microvascular complications of diabetes, and immediate attention is needed to stop their detrimental effects. Longer uncontrolled diabetes, increasing age, and hypertension were independent predictors of microvascular complications. To further reduce the risks of complications that threaten healthy aging and prognosis for these patients, MetSy screening, health education, and better diabetic management are crucial.</AbstractText
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Peroxynitrite, a product of the reaction of superoxide with nitric oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP-ribosylation), mitochondrial dysfunction and impaired stress signalling, as well as protein nitration. In this study, we sought to determine the effect of preventing protein nitration or increasing peroxynitrite decomposition on diabetic neuropathy in mice after an extended period of untreated diabetes.</AbstractText C57Bl6/J male control and diabetic mice were treated with the peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS, 10 mg/kg/day) or protein nitration inhibitor (-)-epicatechin gallate (20 mg/kg/day) for 4 weeks, after an initial 28 weeks of hyperglycaemia.</AbstractText Untreated diabetic mice developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia and loss of intraepidermal nerve fibres. Both FeTMPS and epicatechin gallate partially corrected sensory nerve conduction slowing and small sensory nerve fibre dysfunction without alleviation of hyperglycaemia. Correction of motor nerve conduction deficit and increase in intraepidermal nerve fibre density were found with FeTMPS treatment only.</AbstractText Peroxynitrite injury and protein nitration are implicated in the development of diabetic peripheral neuropathy. The findings indicate that both structural and functional changes of chronic diabetic peripheral neuropathy can be reversed and provide rationale for the development of a new generation of antioxidants and peroxynitrite decomposition catalysts for treatment of diabetic peripheral neuropathy.</AbstractText
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Heuristic evaluations, while commonly used, may inadequately capture the severity of identified usability issues. In the domain of health care, usability issues can pose different levels of risk to patients. Incorporating diverse expertise (eg, clinical and patient) in the heuristic evaluation process can help assess and address potential negative impacts on patient safety that may otherwise go unnoticed. One document that should be highly usable for patients-with the potential to prevent adverse outcomes-is the after visit summary (AVS). The AVS is the document given to a patient upon discharge from the emergency department (ED), which contains instructions on how to manage symptoms, medications, and follow-up care.</AbstractText This study aims to assess a multistage method for integrating diverse expertise (ie, clinical, an older adult care partner, and health IT) with human factors engineering (HFE) expertise in the usability evaluation of the patient-facing ED AVS.</AbstractText We conducted a three-staged heuristic evaluation of an ED AVS using heuristics developed for use in evaluating patient-facing documentation. In stage 1, HFE experts reviewed the AVS to identify usability issues. In stage 2, 6 experts of varying expertise (ie, emergency medicine physicians, ED nurses, geriatricians, transitional care nurses, and an older adult care partner) rated each previously identified usability issue on its potential impact on patient comprehension and patient safety. Finally, in stage 3, an IT expert reviewed each usability issue to identify the likelihood of successfully addressing the issue.</AbstractText In stage 1, we identified 60 usability issues that violated a total of 108 heuristics. In stage 2, 18 additional usability issues that violated 27 heuristics were identified by the study experts. Impact ratings ranged from all experts rating the issue as "no impact" to 5 out of 6 experts rating the issue as having a "large negative impact." On average, the older adult care partner representative rated usability issues as being more significant more of the time. In stage 3, 31 usability issues were rated by an IT professional as "impossible to address," 21 as "maybe," and 24 as "can be addressed."</AbstractText Integrating diverse expertise when evaluating usability is important when patient safety is at stake. The non-HFE experts, included in stage 2 of our evaluation, identified 23% (18/78) of all the usability issues and, depending on their expertise, rated those issues as having differing impacts on patient comprehension and safety. Our findings suggest that, to conduct a comprehensive heuristic evaluation, expertise from all the contexts in which the AVS is used must be considered. Combining those findings with ratings from an IT expert, usability issues can be strategically addressed through redesign. Thus, a 3-staged heuristic evaluation method offers a framework for integrating context-specific expertise efficiently, while providing practical insights to guide human-centered design.</AbstractText
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Metabolic Syndrome in Type 2 Diabetes Mellitus Patients: Prevalence, Risk Factors, and Associated Microvascular Complications. Background The chronic macro and microvascular complications of diabetes mellitus pose serious health challenges. Metabolic syndrome (MetSy) is characterized by central obesity, glucose intolerance, hyperinsulinemia, low high-density lipoproteins (HDLs), high triglycerides (TGs), and hypertension. MetSy precedes or accompanies diabetes, and it has been linked to an increased risk of cardiovascular disease and premature death. This study aimed to estimate prevalence, identify risk factors, and evaluate associated microvascular complications among MetSy patients with type 2 diabetes mellitus (T2DM). Methodology Over the period of March 20, 2022, to March 31, 2023, a prospective cohort study was conducted at the Outdoor Clinic and Medicine Department of Sheikh Zayed Hospital, Rahim Yar Khan. Based on the International Diabetes Federation MetSy criteria, a total of 160 patients fulfilling the inclusion criteria were selected. A special proforma was used to obtain sociodemographic, clinical, and laboratory variables of MetSy in diabetic participants. Blood pressure and anthropometric measurements such as waist circumference (WC) and body mass index (BMI) were measured. Fasting venous blood was collected to analyze biochemical variables such as fasting blood sugar (FBS), TG, and high-density lipoprotein-cholesterol (HDL-C). The microvascular complications of T2DM were established using fundus ophthalmoscopy and neurological and kidney function assessments with the help of laboratory tests. These variables were matched between MetSy and no MetSy groups along with the presence or absence of diabetes microvascular complications. This information was analyzed based on these assessments and patient interviews. Results Of the 160 T2DM patients, the mean age was 52 years with a predominance of females (51.8%) in the 50-59-year age group (56.8%). The average BMI for females was 29.38 ± 0.54 kg/m², and 32 (20%) had obesity. Females exhibited a large WC of 93.52 ± 1.58 cm, and 48 of 83 females had reported diabetes microvascular complications. A significant p-value was observed for hypertension, high TG, low HDL-C, large WC, obesity, BMI, age, and female gender on comparing diabetics with metabolic syndrome (MetSy+) and those without metabolic syndrome (MetSy-). The prevalence of microvascular complications in T2DM patients with MetSy+ was 52.5% compared with 47.5% in MetSy-. The prevalence of diabetic retinopathy was 24.9% (95% confidence interval (CI) = 20.3%-29.6%), nephropathy was 16.8% (95% CI = 12.8%-20.7%), and neuropathy was 10.8% (95% CI = 7.4%-13.3%). Conclusions The prevalence of MetSy observed among T2DM patients was 65%, with married obese females in the 50-59-year age group being more likely to be affected than males. Hypertension, poor glycemic control, high TG, low HDL-C, and greater anthropometric waist measurements and BMI were additional risk factors that tended to increase the MetSy burden in T2DM. Diabetic retinopathy, nephropathy, and neuropathy were the most prevalent microvascular complications of diabetes, and immediate attention is needed to stop their detrimental effects. Longer uncontrolled diabetes, increasing age, and hypertension were independent predictors of microvascular complications. To further reduce the risks of complications that threaten healthy aging and prognosis for these patients, MetSy screening, health education, and better diabetic management are crucial.</AbstractText
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Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy. Peroxynitrite, a product of the reaction of superoxide with nitric oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP-ribosylation), mitochondrial dysfunction and impaired stress signalling, as well as protein nitration. In this study, we sought to determine the effect of preventing protein nitration or increasing peroxynitrite decomposition on diabetic neuropathy in mice after an extended period of untreated diabetes.</AbstractText C57Bl6/J male control and diabetic mice were treated with the peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS, 10 mg/kg/day) or protein nitration inhibitor (-)-epicatechin gallate (20 mg/kg/day) for 4 weeks, after an initial 28 weeks of hyperglycaemia.</AbstractText Untreated diabetic mice developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia and loss of intraepidermal nerve fibres. Both FeTMPS and epicatechin gallate partially corrected sensory nerve conduction slowing and small sensory nerve fibre dysfunction without alleviation of hyperglycaemia. Correction of motor nerve conduction deficit and increase in intraepidermal nerve fibre density were found with FeTMPS treatment only.</AbstractText Peroxynitrite injury and protein nitration are implicated in the development of diabetic peripheral neuropathy. The findings indicate that both structural and functional changes of chronic diabetic peripheral neuropathy can be reversed and provide rationale for the development of a new generation of antioxidants and peroxynitrite decomposition catalysts for treatment of diabetic peripheral neuropathy.</AbstractText
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Evaluating the Usability of an Emergency Department After Visit Summary: Staged Heuristic Evaluation. Heuristic evaluations, while commonly used, may inadequately capture the severity of identified usability issues. In the domain of health care, usability issues can pose different levels of risk to patients. Incorporating diverse expertise (eg, clinical and patient) in the heuristic evaluation process can help assess and address potential negative impacts on patient safety that may otherwise go unnoticed. One document that should be highly usable for patients-with the potential to prevent adverse outcomes-is the after visit summary (AVS). The AVS is the document given to a patient upon discharge from the emergency department (ED), which contains instructions on how to manage symptoms, medications, and follow-up care.</AbstractText This study aims to assess a multistage method for integrating diverse expertise (ie, clinical, an older adult care partner, and health IT) with human factors engineering (HFE) expertise in the usability evaluation of the patient-facing ED AVS.</AbstractText We conducted a three-staged heuristic evaluation of an ED AVS using heuristics developed for use in evaluating patient-facing documentation. In stage 1, HFE experts reviewed the AVS to identify usability issues. In stage 2, 6 experts of varying expertise (ie, emergency medicine physicians, ED nurses, geriatricians, transitional care nurses, and an older adult care partner) rated each previously identified usability issue on its potential impact on patient comprehension and patient safety. Finally, in stage 3, an IT expert reviewed each usability issue to identify the likelihood of successfully addressing the issue.</AbstractText In stage 1, we identified 60 usability issues that violated a total of 108 heuristics. In stage 2, 18 additional usability issues that violated 27 heuristics were identified by the study experts. Impact ratings ranged from all experts rating the issue as "no impact" to 5 out of 6 experts rating the issue as having a "large negative impact." On average, the older adult care partner representative rated usability issues as being more significant more of the time. In stage 3, 31 usability issues were rated by an IT professional as "impossible to address," 21 as "maybe," and 24 as "can be addressed."</AbstractText Integrating diverse expertise when evaluating usability is important when patient safety is at stake. The non-HFE experts, included in stage 2 of our evaluation, identified 23% (18/78) of all the usability issues and, depending on their expertise, rated those issues as having differing impacts on patient comprehension and safety. Our findings suggest that, to conduct a comprehensive heuristic evaluation, expertise from all the contexts in which the AVS is used must be considered. Combining those findings with ratings from an IT expert, usability issues can be strategically addressed through redesign. Thus, a 3-staged heuristic evaluation method offers a framework for integrating context-specific expertise efficiently, while providing practical insights to guide human-centered design.</AbstractText
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39630175
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34575707
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38758800
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Personality disorders and schizophrenia spectrum disorders in the Italian forensic psychiatric population: clinical features, pattern of violence and treatment.
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Dialectical Behaviour Therapy Improves Emotion Dysregulation Mainly in Binge Eating Disorder and Bulimia Nervosa: A Systematic Review and Meta-Analysis.
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TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease.
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Starting in 2015, the Residencies for Execution of Security Measures (REMS) became the place of treatment and care for dangerous offenders who were acquitted due to a mental disorder in Italy. Schizophrenia spectrum disorders (SSD) and personality disorders (PD) are the most common psychiatric disorders among REMS patients. This study aimed to identify and describe potential clinical, therapeutic, and criminal-related differences in REMS patients with SSD and PD. A sample of 528 REMS patients extracted from a previous observational retrospective study underwent secondary analysis. The group of PD patients (n = 150) comprised more females (<i
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Emotion dysregulation is a transdiagnostic phenomenon in Eating Disorders (ED), and Dialectical Behaviour Therapy (DBT) (which was developed for reducing dysregulated emotions in personality disorders) has been employed in patients with ED. This systematic review and meta-analysis investigated whether the effect of DBT was stronger on emotion dysregulation, general psychopathology, and Body Mass Index (BMI) in participants with ED, when compared to a control group (active therapy and waitlist). Eleven studies were identified in a systematic search in accordance with PRISMA guidelines. Most studies included participants with Binge Eating Disorder (BED) (<i
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Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (<i
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Personality disorders and schizophrenia spectrum disorders in the Italian forensic psychiatric population: clinical features, pattern of violence and treatment. Starting in 2015, the Residencies for Execution of Security Measures (REMS) became the place of treatment and care for dangerous offenders who were acquitted due to a mental disorder in Italy. Schizophrenia spectrum disorders (SSD) and personality disorders (PD) are the most common psychiatric disorders among REMS patients. This study aimed to identify and describe potential clinical, therapeutic, and criminal-related differences in REMS patients with SSD and PD. A sample of 528 REMS patients extracted from a previous observational retrospective study underwent secondary analysis. The group of PD patients (n = 150) comprised more females (<i
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Dialectical Behaviour Therapy Improves Emotion Dysregulation Mainly in Binge Eating Disorder and Bulimia Nervosa: A Systematic Review and Meta-Analysis. Emotion dysregulation is a transdiagnostic phenomenon in Eating Disorders (ED), and Dialectical Behaviour Therapy (DBT) (which was developed for reducing dysregulated emotions in personality disorders) has been employed in patients with ED. This systematic review and meta-analysis investigated whether the effect of DBT was stronger on emotion dysregulation, general psychopathology, and Body Mass Index (BMI) in participants with ED, when compared to a control group (active therapy and waitlist). Eleven studies were identified in a systematic search in accordance with PRISMA guidelines. Most studies included participants with Binge Eating Disorder (BED) (<i
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TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease. Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (<i
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39641210
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10756415
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40581727
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Dynamics of magnetic cortico-cortical responses evoked by single-pulse electrical stimulation.
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Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy.
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Atypical chronic clinical manifestations of spotted fever rickettsial infections in Sri Lanka: a case series of 246 patients.
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Intracranial single-pulse electrical stimulation (SPES) can elicit cortico-cortical evoked potentials. Their investigation with intracranial EEG is biased by the limited number and selected location of electrodes, which could be circumvented by simultaneous non-invasive whole-scalp recording. This study aimed at investigating the ability of magnetoencephalography (MEG) to characterize cortico-cortical evoked fields (CCEFs) and effective connectivity between the epileptogenic zone (EZ) and non-epileptogenic zone (i.e., non-involved [NIZ]).</AbstractText A total of 301 SPES trains (at 0.9 Hz during 120 s) were performed in 10 patients with refractory focal epilepsy. MEG signals were denoised, epoched, averaged, and decomposed using independent component analysis. Significant response deflections and significant source generators were detected. Peak latency/amplitude were compared between each different cortical/subcortical structure of the NIZ containing more than five SPES, and then between the EZ and corresponding brain structures in the NIZ.</AbstractText MEG detected and localized polymorphic/polyphasic CCEFs, including one to eight significant consecutive deflections. The latency and amplitude of CCEFs within the NIZ differed significantly depending on the stimulated brain structure. Compared with the corresponding NIZ, SPES within the extratemporal EZ demonstrated delayed CCEF latency, whereas SPES within the temporal EZ showed decreased CCEF amplitude. SPES within the EZ elicited a significantly higher rate of CCEFs within the stimulated lobe compared with those within the NIZ.</AbstractText This study reveals polymorphic CCEFs with complex spatiotemporal dynamics both within the NIZ and EZ. It highlights significant differences in effective connectivity of the epileptogenic network. These cortico-cortical evoked responses could thus contribute to increasing the yield of intracranial recordings.</AbstractText
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Electrocorticograms of 32 patients with medically intractable seizures, recorded through intracranial electrodes, were retrospectively analyzed. The objective was to assess whether quantitative analysis of interictal spikes may be used for delineation of the epileptogenic zone.</AbstractText We used a newly developed computer program for automatic detection of interictal spikes and averaging procedures. This allowed determination of the earliest spike of each spike cluster, the maximal averaged spike amplitude, the highest spike frequency, and the shortest averaged spike duration at each recording site.</AbstractText The following results were obtained: (a) Within a zone </=2 cm from the site of seizure origin, we localized the averaged earliest spike of a spike cluster in 27 (84%) of 32 patients, the highest averaged spike amplitude in 24 (75%) of 32, the shortest averaged spike duration in 22 (69%) of 32, and the maximal spike frequency in 17 (53%) of 32; (b) No correlation was found between spike occurrence and histopathology; (c) No evidence was found for decreased postoperative seizure control in patients with several multilobar or bihemispheric occurrence of spike clusters.</AbstractText The zones of the earliest spike and seizure origin demonstrate a high correlation that favors a common epileptic generator. Removal of all brain areas demonstrating spike clusters is unnecessary to achieve seizure control. Quantification of interictal spike activity is a valuable tool for localization of the seizure generator.</AbstractText
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Atypical chronic rheumatological and neurological problems are often encountered in clinical practice and contribute to significant morbidity. They are typically treated symptomatically, while the etiology remains obscure. The contribution of rickettsioses as a treatable etiology in this broad array of conditions is worth testing.</AbstractText We analyzed 246 patients diagnosed with chronic rickettsial infection between October 2016 and April 2024 in the Central Province of Sri Lanka, where spotted fever is endemic. The diagnosis was confirmed by positive rickettsia-specific Immunoglobulin G (IgG) titers through indirect immunofluorescence assay and clinical improvement with anti-rickettsial antibiotics. Clinical manifestations and serological profiles were documented.</AbstractText Of the 246 patients (mean age 56.7 years; SD = 17.7), 63.3% were female. The most common presentations included arthritis (22%), parkinsonism (15%), apathy (15%), excessive sleepiness (11%), enthesopathy (18%), frozen shoulder (3%), and hearing impairment (9%). Neurological impairments, such as brachial neuritis and sciatica, were present in 10%. Mucocutaneous manifestations occurred in 8%, and non-specific body pain in 13%. Nearly 80% of patients had IgG titers of 1/512 or higher, with 13.4% having titers of 1/2048. Treatment with doxycycline, chloramphenicol, or combination of both resulted in significant recovery in all patients.</AbstractText Chronic conditions like arthritis, enthesopathy, and neurological impairments may stem from rickettsial infection, as indicated by their prevalence, especially in endemic areas. The positive response to antibiotics highlights the importance of raising awareness and considering rickettsial infection in patients with unexplained chronic symptoms. Further research is needed to better understand these manifestations and optimize management.</AbstractText
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Dynamics of magnetic cortico-cortical responses evoked by single-pulse electrical stimulation. Intracranial single-pulse electrical stimulation (SPES) can elicit cortico-cortical evoked potentials. Their investigation with intracranial EEG is biased by the limited number and selected location of electrodes, which could be circumvented by simultaneous non-invasive whole-scalp recording. This study aimed at investigating the ability of magnetoencephalography (MEG) to characterize cortico-cortical evoked fields (CCEFs) and effective connectivity between the epileptogenic zone (EZ) and non-epileptogenic zone (i.e., non-involved [NIZ]).</AbstractText A total of 301 SPES trains (at 0.9 Hz during 120 s) were performed in 10 patients with refractory focal epilepsy. MEG signals were denoised, epoched, averaged, and decomposed using independent component analysis. Significant response deflections and significant source generators were detected. Peak latency/amplitude were compared between each different cortical/subcortical structure of the NIZ containing more than five SPES, and then between the EZ and corresponding brain structures in the NIZ.</AbstractText MEG detected and localized polymorphic/polyphasic CCEFs, including one to eight significant consecutive deflections. The latency and amplitude of CCEFs within the NIZ differed significantly depending on the stimulated brain structure. Compared with the corresponding NIZ, SPES within the extratemporal EZ demonstrated delayed CCEF latency, whereas SPES within the temporal EZ showed decreased CCEF amplitude. SPES within the EZ elicited a significantly higher rate of CCEFs within the stimulated lobe compared with those within the NIZ.</AbstractText This study reveals polymorphic CCEFs with complex spatiotemporal dynamics both within the NIZ and EZ. It highlights significant differences in effective connectivity of the epileptogenic network. These cortico-cortical evoked responses could thus contribute to increasing the yield of intracranial recordings.</AbstractText
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Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy. Electrocorticograms of 32 patients with medically intractable seizures, recorded through intracranial electrodes, were retrospectively analyzed. The objective was to assess whether quantitative analysis of interictal spikes may be used for delineation of the epileptogenic zone.</AbstractText We used a newly developed computer program for automatic detection of interictal spikes and averaging procedures. This allowed determination of the earliest spike of each spike cluster, the maximal averaged spike amplitude, the highest spike frequency, and the shortest averaged spike duration at each recording site.</AbstractText The following results were obtained: (a) Within a zone </=2 cm from the site of seizure origin, we localized the averaged earliest spike of a spike cluster in 27 (84%) of 32 patients, the highest averaged spike amplitude in 24 (75%) of 32, the shortest averaged spike duration in 22 (69%) of 32, and the maximal spike frequency in 17 (53%) of 32; (b) No correlation was found between spike occurrence and histopathology; (c) No evidence was found for decreased postoperative seizure control in patients with several multilobar or bihemispheric occurrence of spike clusters.</AbstractText The zones of the earliest spike and seizure origin demonstrate a high correlation that favors a common epileptic generator. Removal of all brain areas demonstrating spike clusters is unnecessary to achieve seizure control. Quantification of interictal spike activity is a valuable tool for localization of the seizure generator.</AbstractText
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Atypical chronic clinical manifestations of spotted fever rickettsial infections in Sri Lanka: a case series of 246 patients. Atypical chronic rheumatological and neurological problems are often encountered in clinical practice and contribute to significant morbidity. They are typically treated symptomatically, while the etiology remains obscure. The contribution of rickettsioses as a treatable etiology in this broad array of conditions is worth testing.</AbstractText We analyzed 246 patients diagnosed with chronic rickettsial infection between October 2016 and April 2024 in the Central Province of Sri Lanka, where spotted fever is endemic. The diagnosis was confirmed by positive rickettsia-specific Immunoglobulin G (IgG) titers through indirect immunofluorescence assay and clinical improvement with anti-rickettsial antibiotics. Clinical manifestations and serological profiles were documented.</AbstractText Of the 246 patients (mean age 56.7 years; SD = 17.7), 63.3% were female. The most common presentations included arthritis (22%), parkinsonism (15%), apathy (15%), excessive sleepiness (11%), enthesopathy (18%), frozen shoulder (3%), and hearing impairment (9%). Neurological impairments, such as brachial neuritis and sciatica, were present in 10%. Mucocutaneous manifestations occurred in 8%, and non-specific body pain in 13%. Nearly 80% of patients had IgG titers of 1/512 or higher, with 13.4% having titers of 1/2048. Treatment with doxycycline, chloramphenicol, or combination of both resulted in significant recovery in all patients.</AbstractText Chronic conditions like arthritis, enthesopathy, and neurological impairments may stem from rickettsial infection, as indicated by their prevalence, especially in endemic areas. The positive response to antibiotics highlights the importance of raising awareness and considering rickettsial infection in patients with unexplained chronic symptoms. Further research is needed to better understand these manifestations and optimize management.</AbstractText
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36477592
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25740521
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36592964
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Subjective age of acquisition norms for 1604 English words by Spanish L2 speakers of English and their relationship with lexico-semantic, affective, sociolinguistic and proficiency variables.
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Cortical activity predicts which older adults recognize speech in noise and when.
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Characterization of Electrospun Polysuccinimide-Dopamine Conjugates and Effect on Cell Viability and Uptake.
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Psycholinguistic studies have shown that there are many variables implicated in language comprehension and production. At the lexical level, subjective age of acquisition (AoA), the estimate of the age at which a word is acquired, is key for stimuli selection in psycholinguistic studies. AoA databases in English are often used when testing a variety of phenomena in second language (L2) speakers of English. However, these have limitations, as the norms are not provided by the target population (L2 speakers of English) but by native English speakers. In this study, we asked native Spanish L2 speakers of English to provide subjective AoA ratings for 1604 English words, and investigated whether factors related to 14 lexico-semantic and affective variables, both in Spanish and English, and to the speakers' profile (i.e., sociolinguistic variables and L2 proficiency), were related to the L2 AoA ratings. We used boosted regression trees, an advanced form of regression analysis based on machine learning and boosting algorithms, to analyse the data. Our results showed that the model accounted for a relevant proportion of deviance (58.56%), with the English AoA provided by native English speakers being the strongest predictor for L2 AoA. Additionally, L2 AoA correlated with L2 reaction times. Our database is a useful tool for the research community running psycholinguistic studies in L2 speakers of English. It adds knowledge about which factors-linked to the characteristics of both the linguistic stimuli and the speakers-affect L2 subjective AoA. The database and the data can be downloaded from: https://osf.io/gr8xd/?view_only=73b01dccbedb4d7897c8d104d3d68c46 .</AbstractText
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Speech recognition in noise can be challenging for older adults and elicits elevated activity throughout a cingulo-opercular network that is hypothesized to monitor and modify behaviors to optimize performance. A word recognition in noise experiment was used to test the hypothesis that cingulo-opercular engagement provides performance benefit for older adults. Healthy older adults (N = 31; 50-81 years of age; mean pure tone thresholds <32 dB HL from 0.25 to 8 kHz, best ear; species: human) performed word recognition in multitalker babble at 2 signal-to-noise ratios (SNR = +3 or +10 dB) during a sparse sampling fMRI experiment. Elevated cingulo-opercular activity was associated with an increased likelihood of correct recognition on the following trial independently of SNR and performance on the preceding trial. The cingulo-opercular effect increased for participants with the best overall performance. These effects were lower for older adults compared with a younger, normal-hearing adult sample (N = 18). Visual cortex activity also predicted trial-level recognition for the older adults, which resulted from discrete decreases in activity before errors and occurred for the oldest adults with the poorest recognition. Participants demonstrating larger visual cortex effects also had reduced fractional anisotropy in an anterior portion of the left inferior frontal-occipital fasciculus, which projects between frontal and occipital regions where activity predicted word recognition. Together, the results indicate that older adults experience performance benefit from elevated cingulo-opercular activity, but not to the same extent as younger adults, and that declines in attentional control can limit word recognition.</AbstractText
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Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer-drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.</AbstractText
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Subjective age of acquisition norms for 1604 English words by Spanish L2 speakers of English and their relationship with lexico-semantic, affective, sociolinguistic and proficiency variables. Psycholinguistic studies have shown that there are many variables implicated in language comprehension and production. At the lexical level, subjective age of acquisition (AoA), the estimate of the age at which a word is acquired, is key for stimuli selection in psycholinguistic studies. AoA databases in English are often used when testing a variety of phenomena in second language (L2) speakers of English. However, these have limitations, as the norms are not provided by the target population (L2 speakers of English) but by native English speakers. In this study, we asked native Spanish L2 speakers of English to provide subjective AoA ratings for 1604 English words, and investigated whether factors related to 14 lexico-semantic and affective variables, both in Spanish and English, and to the speakers' profile (i.e., sociolinguistic variables and L2 proficiency), were related to the L2 AoA ratings. We used boosted regression trees, an advanced form of regression analysis based on machine learning and boosting algorithms, to analyse the data. Our results showed that the model accounted for a relevant proportion of deviance (58.56%), with the English AoA provided by native English speakers being the strongest predictor for L2 AoA. Additionally, L2 AoA correlated with L2 reaction times. Our database is a useful tool for the research community running psycholinguistic studies in L2 speakers of English. It adds knowledge about which factors-linked to the characteristics of both the linguistic stimuli and the speakers-affect L2 subjective AoA. The database and the data can be downloaded from: https://osf.io/gr8xd/?view_only=73b01dccbedb4d7897c8d104d3d68c46 .</AbstractText
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Cortical activity predicts which older adults recognize speech in noise and when. Speech recognition in noise can be challenging for older adults and elicits elevated activity throughout a cingulo-opercular network that is hypothesized to monitor and modify behaviors to optimize performance. A word recognition in noise experiment was used to test the hypothesis that cingulo-opercular engagement provides performance benefit for older adults. Healthy older adults (N = 31; 50-81 years of age; mean pure tone thresholds <32 dB HL from 0.25 to 8 kHz, best ear; species: human) performed word recognition in multitalker babble at 2 signal-to-noise ratios (SNR = +3 or +10 dB) during a sparse sampling fMRI experiment. Elevated cingulo-opercular activity was associated with an increased likelihood of correct recognition on the following trial independently of SNR and performance on the preceding trial. The cingulo-opercular effect increased for participants with the best overall performance. These effects were lower for older adults compared with a younger, normal-hearing adult sample (N = 18). Visual cortex activity also predicted trial-level recognition for the older adults, which resulted from discrete decreases in activity before errors and occurred for the oldest adults with the poorest recognition. Participants demonstrating larger visual cortex effects also had reduced fractional anisotropy in an anterior portion of the left inferior frontal-occipital fasciculus, which projects between frontal and occipital regions where activity predicted word recognition. Together, the results indicate that older adults experience performance benefit from elevated cingulo-opercular activity, but not to the same extent as younger adults, and that declines in attentional control can limit word recognition.</AbstractText
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Characterization of Electrospun Polysuccinimide-Dopamine Conjugates and Effect on Cell Viability and Uptake. Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer-drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.</AbstractText
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38107313
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39310214
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37195902
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A three-dimensional deep learning model for inter-site harmonization of structural MR images of the brain: Extensive validation with a multicenter dataset.
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Predicting Age from White Matter Diffusivity with Residual Learning.
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On aging and age-specific effects of spontaneous mutations.
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In multicenter MRI studies, pooling the imaging data can introduce site-related variabilities and can therefore bias the subsequent analyses. To harmonize the intensity distributions of brain MR images in a multicenter dataset, unsupervised deep learning methods can be employed. Here, we developed a model based on cycle-consistent adversarial networks for the harmonization of T1-weighted brain MR images. In contrast to previous works, it was designed to process three-dimensional whole-brain images in a stable manner while optimizing computation resources. Using six different MRI datasets for healthy adults (n=1525 in total) with different acquisition parameters, we tested the model in (i) three pairwise harmonizations with site effects of various sizes, (ii) an overall harmonization of the six datasets with different age distributions, and (iii) a traveling-subject dataset. Our results for intensity distributions, brain volumes, image quality metrics and radiomic features indicated that the MRI characteristics at the various sites had been effectively homogenized. Next, brain age prediction experiments and the observed correlation between the gray-matter volume and age showed that thanks to an appropriate training strategy and despite biological differences between the dataset populations, the model reinforced biological patterns. Furthermore, radiologic analyses of the harmonized images attested to the conservation of the radiologic information in the original images. The robustness of the harmonization model (as judged with various datasets and metrics) demonstrates its potential for application in retrospective multicenter studies.</AbstractText
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Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural magnetic resonance imaging (MRI) data has become an important proxy task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest (ROIs). The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 ± 0.19 years for cognitively normal participants and MAE of 6.62 ± 0.30 years for cognitively impaired participants, while the second method achieves MAE of 4.69 ± 0.23 years for cognitively normal participants and MAE of 4.96 ± 0.28 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.</AbstractText
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Evolutionary theory assumes that mutations that cause aging either have beneficial early-life effects that gradually become deleterious with advancing age (antagonistic pleiotropy [AP]) or that they only have deleterious effects at old age (mutation accumulation [MA]). Mechanistically, aging is predicted to result from damage accumulating in the soma. While this scenario is compatible with AP, it is not immediately obvious how damage would accumulate under MA. In a modified version of the MA theory, it has been suggested that mutations with weakly deleterious effects at young age can also contribute to aging, if they generate damage that gradually accumulates with age. Mutations with increasing deleterious effects have recently gained support from theoretical work and studies of large-effect mutations. Here we address if spontaneous mutations also have negative effects that increase with age. We accumulate mutations with early-life effects in Drosophila melanogaster across 27 generations and compare their relative effects on fecundity early and late in life. Our mutation accumulation lines on average have substantially lower early-life fecundity compared to controls. These effects were further maintained throughout life, but they did not increase with age. Our results suggest that most spontaneous mutations do not contribute to damage accumulation and aging.</AbstractText
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A three-dimensional deep learning model for inter-site harmonization of structural MR images of the brain: Extensive validation with a multicenter dataset. In multicenter MRI studies, pooling the imaging data can introduce site-related variabilities and can therefore bias the subsequent analyses. To harmonize the intensity distributions of brain MR images in a multicenter dataset, unsupervised deep learning methods can be employed. Here, we developed a model based on cycle-consistent adversarial networks for the harmonization of T1-weighted brain MR images. In contrast to previous works, it was designed to process three-dimensional whole-brain images in a stable manner while optimizing computation resources. Using six different MRI datasets for healthy adults (n=1525 in total) with different acquisition parameters, we tested the model in (i) three pairwise harmonizations with site effects of various sizes, (ii) an overall harmonization of the six datasets with different age distributions, and (iii) a traveling-subject dataset. Our results for intensity distributions, brain volumes, image quality metrics and radiomic features indicated that the MRI characteristics at the various sites had been effectively homogenized. Next, brain age prediction experiments and the observed correlation between the gray-matter volume and age showed that thanks to an appropriate training strategy and despite biological differences between the dataset populations, the model reinforced biological patterns. Furthermore, radiologic analyses of the harmonized images attested to the conservation of the radiologic information in the original images. The robustness of the harmonization model (as judged with various datasets and metrics) demonstrates its potential for application in retrospective multicenter studies.</AbstractText
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Predicting Age from White Matter Diffusivity with Residual Learning. Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural magnetic resonance imaging (MRI) data has become an important proxy task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest (ROIs). The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 ± 0.19 years for cognitively normal participants and MAE of 6.62 ± 0.30 years for cognitively impaired participants, while the second method achieves MAE of 4.69 ± 0.23 years for cognitively normal participants and MAE of 4.96 ± 0.28 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.</AbstractText
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On aging and age-specific effects of spontaneous mutations. Evolutionary theory assumes that mutations that cause aging either have beneficial early-life effects that gradually become deleterious with advancing age (antagonistic pleiotropy [AP]) or that they only have deleterious effects at old age (mutation accumulation [MA]). Mechanistically, aging is predicted to result from damage accumulating in the soma. While this scenario is compatible with AP, it is not immediately obvious how damage would accumulate under MA. In a modified version of the MA theory, it has been suggested that mutations with weakly deleterious effects at young age can also contribute to aging, if they generate damage that gradually accumulates with age. Mutations with increasing deleterious effects have recently gained support from theoretical work and studies of large-effect mutations. Here we address if spontaneous mutations also have negative effects that increase with age. We accumulate mutations with early-life effects in Drosophila melanogaster across 27 generations and compare their relative effects on fecundity early and late in life. Our mutation accumulation lines on average have substantially lower early-life fecundity compared to controls. These effects were further maintained throughout life, but they did not increase with age. Our results suggest that most spontaneous mutations do not contribute to damage accumulation and aging.</AbstractText
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39954128
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32931076
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40524113
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Brain tissue metal concentrations and Alzheimer's disease neuropathology in total joint arthroplasty patients versus controls.
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Standard-space atlas of the viscoelastic properties of the human brain.
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Paragastric Neural Blockade Effectively Controls Visceral Pain After Primary Laparoscopic Sleeve Gastrectomy.
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We examined whether total joint arthroplasty (TJA) is associated with increased metal accumulation in the brain and histopathologic changes of Alzheimer's disease. We measured ultra-trace metal concentrations (aluminum, chromium, cobalt, manganese, molybdenum, nickel, titanium, and vanadium) on postmortem frozen tissues of the occipital lobe of 177 subjects (89 non-TJA and 88 TJA) using a triple-quadrupole inductively coupled plasma mass spectrometry and correlated elemental concentrations to the degree of Alzheimer's disease neuropathic change (ADNC). To effectively assess the relationship between TJA and brain metal concentrations, subjects with and without TJA were matched for baseline clinical characteristics and showed no difference in postmortem Alzheimer's disease neuropathic change. TJA subjects had increased concentrations of cobalt and titanium and both metals were associated with increased amyloid plaques. In both the TJA and non-TJA subjects, increased concentrations of cobalt, titanium, manganese, and molybdenum were associated with increased odds of neuritic and diffuse plaques. Lastly, the brain's inter-metal correlations were altered in the presence of increased neuritic plaques and/or implantable artificial joints. These findings suggest that metal concentrations and homeostasis vary in presence of TJA.</AbstractText
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Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast-based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18-35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, μ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM-152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross-center comparisons.</AbstractText
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Surgical advancements and the implementation of Enhanced Recovery After Surgery (ERAS) protocols have contributed to reduced postoperative pain and faster recovery. Despite these improvements in perioperative care, pain remains one of the most distressing symptoms, particularly during the early postoperative period. Visceral pain (VP), rather than somatic pain, is the predominant source of discomfort and is often difficult to manage with standard pain control methods. This study aims to replicate the findings of previous randomized controlled trials (RCTs) on the effectiveness of paragastric neural blockade (PGNB) in controlling VP, addressing the ongoing clinical challenge of inadequate pain control despite standard multimodal analgesia (MMA).</AbstractText A retrospective study was conducted from January to September 2024, comparing a control group (standard MMA including transversus abdominis plane [TAP] block, n=50) with a PGNB group (same protocol plus PGNB, n=50). The primary outcome was pain intensity (Numeric rating scale [NRS] score 0-10) within 48 hours post-surgery. Secondary outcomes included time to first analgesic use, cumulative analgesic doses, nausea/vomiting incidence, and hemodynamic changes.</AbstractText NRS scores were significantly lower in the PGNB group within 8 hours postoperatively (p<0.001). The time to first rescue analgesic use was prolonged (1084.08±902.78 minutes vs. 260.60±482.25 minutes; p<0.001) and the cumulative frequency of analgesic use on the day of surgery was also lower in the PGNB group (0.46 times vs. 1.34 times; p<0.001). No significant differences in the incidence of postoperative nausea and vomiting (PONV) were observed on postoperative days (PODs) 0 and 2, although POD 1 showed higher nausea in the PGNB group (p=0.002). The operative time was significantly longer in the PGNB group (113.90±14.54 minutes vs. 97.86±20.78 minutes; p<0.001). There was one case of localized hematoma at the injection site, which was controlled with local compression and resolved within a few minutes. No other complications were observed.</AbstractText PGNB effectively reduces VP and the need for rescue analgesics during the early postoperative period following LSG, without any major complications.</AbstractText
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Brain tissue metal concentrations and Alzheimer's disease neuropathology in total joint arthroplasty patients versus controls. We examined whether total joint arthroplasty (TJA) is associated with increased metal accumulation in the brain and histopathologic changes of Alzheimer's disease. We measured ultra-trace metal concentrations (aluminum, chromium, cobalt, manganese, molybdenum, nickel, titanium, and vanadium) on postmortem frozen tissues of the occipital lobe of 177 subjects (89 non-TJA and 88 TJA) using a triple-quadrupole inductively coupled plasma mass spectrometry and correlated elemental concentrations to the degree of Alzheimer's disease neuropathic change (ADNC). To effectively assess the relationship between TJA and brain metal concentrations, subjects with and without TJA were matched for baseline clinical characteristics and showed no difference in postmortem Alzheimer's disease neuropathic change. TJA subjects had increased concentrations of cobalt and titanium and both metals were associated with increased amyloid plaques. In both the TJA and non-TJA subjects, increased concentrations of cobalt, titanium, manganese, and molybdenum were associated with increased odds of neuritic and diffuse plaques. Lastly, the brain's inter-metal correlations were altered in the presence of increased neuritic plaques and/or implantable artificial joints. These findings suggest that metal concentrations and homeostasis vary in presence of TJA.</AbstractText
|
Standard-space atlas of the viscoelastic properties of the human brain. Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast-based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18-35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, μ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM-152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross-center comparisons.</AbstractText
|
Paragastric Neural Blockade Effectively Controls Visceral Pain After Primary Laparoscopic Sleeve Gastrectomy. Surgical advancements and the implementation of Enhanced Recovery After Surgery (ERAS) protocols have contributed to reduced postoperative pain and faster recovery. Despite these improvements in perioperative care, pain remains one of the most distressing symptoms, particularly during the early postoperative period. Visceral pain (VP), rather than somatic pain, is the predominant source of discomfort and is often difficult to manage with standard pain control methods. This study aims to replicate the findings of previous randomized controlled trials (RCTs) on the effectiveness of paragastric neural blockade (PGNB) in controlling VP, addressing the ongoing clinical challenge of inadequate pain control despite standard multimodal analgesia (MMA).</AbstractText A retrospective study was conducted from January to September 2024, comparing a control group (standard MMA including transversus abdominis plane [TAP] block, n=50) with a PGNB group (same protocol plus PGNB, n=50). The primary outcome was pain intensity (Numeric rating scale [NRS] score 0-10) within 48 hours post-surgery. Secondary outcomes included time to first analgesic use, cumulative analgesic doses, nausea/vomiting incidence, and hemodynamic changes.</AbstractText NRS scores were significantly lower in the PGNB group within 8 hours postoperatively (p<0.001). The time to first rescue analgesic use was prolonged (1084.08±902.78 minutes vs. 260.60±482.25 minutes; p<0.001) and the cumulative frequency of analgesic use on the day of surgery was also lower in the PGNB group (0.46 times vs. 1.34 times; p<0.001). No significant differences in the incidence of postoperative nausea and vomiting (PONV) were observed on postoperative days (PODs) 0 and 2, although POD 1 showed higher nausea in the PGNB group (p=0.002). The operative time was significantly longer in the PGNB group (113.90±14.54 minutes vs. 97.86±20.78 minutes; p<0.001). There was one case of localized hematoma at the injection site, which was controlled with local compression and resolved within a few minutes. No other complications were observed.</AbstractText PGNB effectively reduces VP and the need for rescue analgesics during the early postoperative period following LSG, without any major complications.</AbstractText
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26400940
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29176580
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26966636
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Enhanced Neural Responses to Imagined Primary Rewards Predict Reduced Monetary Temporal Discounting.
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Reduced loss aversion in pathological gambling and alcohol dependence is associated with differential alterations in amygdala and prefrontal functioning.
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Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver.
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The pervasive tendency to discount the value of future rewards varies considerably across individuals and has important implications for health and well-being. Here, we used fMRI with human participants to examine whether an individual's neural representation of an imagined primary reward predicts the degree to which the value of delayed monetary payments is discounted. Because future rewards can never be experienced at the time of choice, imagining or simulating the benefits of a future reward may play a critical role in decisions between alternatives with either immediate or delayed benefits. We found that enhanced ventromedial prefrontal cortex response during imagined primary reward receipt was correlated with reduced discounting in a separate monetary intertemporal choice task. Furthermore, activity in enhanced ventromedial prefrontal cortex during reward imagination predicted temporal discounting behavior both between- and within-individual decision makers with 62% and 73% mean balanced accuracy, respectively. These results suggest that the quality of reward imagination may impact the degree to which future outcomes are discounted. Significance statement: We report a novel test of the hypothesis that an important factor influencing the discount rate for future rewards is the quality with which they are imagined or estimated in the present. Previous work has shown that temporal discounting is linked to individual characteristics ranging from general intelligence to the propensity for addiction. We demonstrate that individual differences in a neurobiological measure of primary reward imagination are significantly correlated with discounting rates for future monetary payments. Moreover, our neurobiological measure of imagination can be used to accurately predict choice behavior both between and within individuals. These results suggest that improving reward imagination may be a useful therapeutic target for individuals whose high discount rates promote detrimental behaviors.</AbstractText
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Diagnostic criteria for pathological gambling and alcohol dependence (AD) include repeated addictive behavior despite severe negative consequences. However, the concept of loss aversion (LA) as a facet of value-based decision making has not yet been used to directly compare these disorders. We hypothesized reduced LA in pathological gamblers (PG) and AD patients, correlation of LA with disorder severity, and reduced loss-related modulation of brain activity. 19 PG subjects, 15 AD patients and 17 healthy controls (HC) engaged in a LA task in a functional magnetic resonance imaging setting. Imaging analyses focused on neural gain and loss sensitivity in the meso-cortico-limbic network of the brain. Both PG and AD subjects showed reduced LA. AD subjects showed altered loss-related modulation of activity in lateral prefrontal regions. PG subjects showed indication of altered amygdala-prefrontal functional connectivity. Although we observed reduced LA in both a behavioral addiction and a substance-related disorder our neural findings might challenge the notion of complete neuro-behavioral congruence of substance-use disorders and behavioral addictions.</AbstractText
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Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano-scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been reported to date. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of carbon-based nanomaterials. We hypothesized pulmonary exposure to Ag core AgNP induces a measureable increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and is associated with depressed coronary constrictor and relaxation responses. Secondarily, we addressed the potential contribution of silver ion release on AgNP toxicity.</AbstractText Male Sprague-Dawley rats were exposed to 200 μl of 1 mg/ml of 20 nm citrate-capped Ag core AgNP, 0.01, 0.1, 1 mg/ml Silver Acetate (AgAc), or a citrate vehicle by intratracheal (IT) instillation. One and 7 days following IT instillation the lungs were evaluated for inflammation and the presence of silver; serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and coronary artery reactivity were assessed.</AbstractText AgNP instillation resulted in modest pulmonary inflammation with detection of silver in lung tissue and alveolar macrophages, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17α, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Silver within lung tissue was persistent at 7 days post IT instillation and was associated with an elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. AgAc resulted in a concentration dependent infarct expansion and depressed vascular reactivity without marked pulmonary inflammation or serum cytokine response.</AbstractText Based on these data, IT instillation of AgNP increases circulating levels of several key cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.</AbstractText
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Enhanced Neural Responses to Imagined Primary Rewards Predict Reduced Monetary Temporal Discounting. The pervasive tendency to discount the value of future rewards varies considerably across individuals and has important implications for health and well-being. Here, we used fMRI with human participants to examine whether an individual's neural representation of an imagined primary reward predicts the degree to which the value of delayed monetary payments is discounted. Because future rewards can never be experienced at the time of choice, imagining or simulating the benefits of a future reward may play a critical role in decisions between alternatives with either immediate or delayed benefits. We found that enhanced ventromedial prefrontal cortex response during imagined primary reward receipt was correlated with reduced discounting in a separate monetary intertemporal choice task. Furthermore, activity in enhanced ventromedial prefrontal cortex during reward imagination predicted temporal discounting behavior both between- and within-individual decision makers with 62% and 73% mean balanced accuracy, respectively. These results suggest that the quality of reward imagination may impact the degree to which future outcomes are discounted. Significance statement: We report a novel test of the hypothesis that an important factor influencing the discount rate for future rewards is the quality with which they are imagined or estimated in the present. Previous work has shown that temporal discounting is linked to individual characteristics ranging from general intelligence to the propensity for addiction. We demonstrate that individual differences in a neurobiological measure of primary reward imagination are significantly correlated with discounting rates for future monetary payments. Moreover, our neurobiological measure of imagination can be used to accurately predict choice behavior both between and within individuals. These results suggest that improving reward imagination may be a useful therapeutic target for individuals whose high discount rates promote detrimental behaviors.</AbstractText
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Reduced loss aversion in pathological gambling and alcohol dependence is associated with differential alterations in amygdala and prefrontal functioning. Diagnostic criteria for pathological gambling and alcohol dependence (AD) include repeated addictive behavior despite severe negative consequences. However, the concept of loss aversion (LA) as a facet of value-based decision making has not yet been used to directly compare these disorders. We hypothesized reduced LA in pathological gamblers (PG) and AD patients, correlation of LA with disorder severity, and reduced loss-related modulation of brain activity. 19 PG subjects, 15 AD patients and 17 healthy controls (HC) engaged in a LA task in a functional magnetic resonance imaging setting. Imaging analyses focused on neural gain and loss sensitivity in the meso-cortico-limbic network of the brain. Both PG and AD subjects showed reduced LA. AD subjects showed altered loss-related modulation of activity in lateral prefrontal regions. PG subjects showed indication of altered amygdala-prefrontal functional connectivity. Although we observed reduced LA in both a behavioral addiction and a substance-related disorder our neural findings might challenge the notion of complete neuro-behavioral congruence of substance-use disorders and behavioral addictions.</AbstractText
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Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver. Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano-scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been reported to date. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of carbon-based nanomaterials. We hypothesized pulmonary exposure to Ag core AgNP induces a measureable increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and is associated with depressed coronary constrictor and relaxation responses. Secondarily, we addressed the potential contribution of silver ion release on AgNP toxicity.</AbstractText Male Sprague-Dawley rats were exposed to 200 μl of 1 mg/ml of 20 nm citrate-capped Ag core AgNP, 0.01, 0.1, 1 mg/ml Silver Acetate (AgAc), or a citrate vehicle by intratracheal (IT) instillation. One and 7 days following IT instillation the lungs were evaluated for inflammation and the presence of silver; serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and coronary artery reactivity were assessed.</AbstractText AgNP instillation resulted in modest pulmonary inflammation with detection of silver in lung tissue and alveolar macrophages, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17α, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Silver within lung tissue was persistent at 7 days post IT instillation and was associated with an elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. AgAc resulted in a concentration dependent infarct expansion and depressed vascular reactivity without marked pulmonary inflammation or serum cytokine response.</AbstractText Based on these data, IT instillation of AgNP increases circulating levels of several key cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.</AbstractText
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36324991
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26803755
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34067008
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Distinct Brain-Oscillatory Neuroanatomical Architecture of Perception-Action Integration in Adolescents With Tourette Syndrome.
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The system neurophysiological basis of backward inhibition.
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MRI-Based Quantitation of Hepatic Steatosis Does Not Predict Hypertrophy Rate after Portal Vein Embolization in Patients with Colorectal Liver Metastasis and Normal to Moderately Elevated Fat Fraction.
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Gilles de la Tourette Syndrome (GTS) is a neurodevelopmental disorder with a peak of symptom severity around late childhood and early adolescence. Previous findings in adult GTS suggest that changes in perception-action integration, as conceptualized in the theory of event coding framework, are central for the understanding of GTS. However, the neural mechanisms underlying these processes in adolescence are elusive.</AbstractText A total of 59 children/adolescents aged 9 to 18 years (<i Behavioral data showed robust event file binding effects in both groups without group differences. Neurophysiological data showed that theta and beta band activity were involved in event file integration in both groups. However, the functional neuroanatomical organization was markedly different for theta band activity between the groups. The typically developing group mainly relied on superior frontal regions, whereas the GTS group engaged parietal and inferior frontal regions. A more consistent functional neuroanatomical activation pattern was observed for the beta band, engaging inferior parietal and temporal regions in both groups.</AbstractText Perception-action integration processes lag behind in persisting GTS but not in the GTS population as a whole, underscoring differences in developmental trajectories and the importance of longitudinal investigations for the understanding of GTS. The findings corroborate known differences in the functional/structural brain organization in GTS and suggest an important role of theta band activity in these patients.</AbstractText
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Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as 'backward inhibition' (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm.</AbstractText
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The aim of this study was to correlate the pre-procedural magnetic-resonance-imaging-based hepatic fat fraction (hFF) with the degree of hypertrophy after portal vein embolization (PVE) in patients with colorectal cancer liver metastases (CRCLM). Between 2011 November and 2020 February, 68 patients with CRCLM underwent magnetic resonance imaging (MRI; 1.5 Tesla) of the liver before PVE. Using T1w chemical shift imaging (DUAL FFE), the patients were categorized as having a normal (<5%) or an elevated (>5%) hFF. The correlation of hFF, age, gender, initial tumor mass, history of chemotherapy, degree of liver hypertrophy, and kinetic growth rate after PVE was investigated using multiple regression analysis and Spearman's test. A normal hFF was found in 43/68 patients (63%), whereas 25/68 (37%) patients had an elevated hFF. The mean hypertrophy and kinetic growth rates in patients with normal vs. elevated hFF were 24 ± 31% vs. 28 ± 36% and 9 ± 9 % vs. 8 ± 10% (<i
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Distinct Brain-Oscillatory Neuroanatomical Architecture of Perception-Action Integration in Adolescents With Tourette Syndrome. Gilles de la Tourette Syndrome (GTS) is a neurodevelopmental disorder with a peak of symptom severity around late childhood and early adolescence. Previous findings in adult GTS suggest that changes in perception-action integration, as conceptualized in the theory of event coding framework, are central for the understanding of GTS. However, the neural mechanisms underlying these processes in adolescence are elusive.</AbstractText A total of 59 children/adolescents aged 9 to 18 years (<i Behavioral data showed robust event file binding effects in both groups without group differences. Neurophysiological data showed that theta and beta band activity were involved in event file integration in both groups. However, the functional neuroanatomical organization was markedly different for theta band activity between the groups. The typically developing group mainly relied on superior frontal regions, whereas the GTS group engaged parietal and inferior frontal regions. A more consistent functional neuroanatomical activation pattern was observed for the beta band, engaging inferior parietal and temporal regions in both groups.</AbstractText Perception-action integration processes lag behind in persisting GTS but not in the GTS population as a whole, underscoring differences in developmental trajectories and the importance of longitudinal investigations for the understanding of GTS. The findings corroborate known differences in the functional/structural brain organization in GTS and suggest an important role of theta band activity in these patients.</AbstractText
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The system neurophysiological basis of backward inhibition. Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as 'backward inhibition' (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm.</AbstractText
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MRI-Based Quantitation of Hepatic Steatosis Does Not Predict Hypertrophy Rate after Portal Vein Embolization in Patients with Colorectal Liver Metastasis and Normal to Moderately Elevated Fat Fraction. The aim of this study was to correlate the pre-procedural magnetic-resonance-imaging-based hepatic fat fraction (hFF) with the degree of hypertrophy after portal vein embolization (PVE) in patients with colorectal cancer liver metastases (CRCLM). Between 2011 November and 2020 February, 68 patients with CRCLM underwent magnetic resonance imaging (MRI; 1.5 Tesla) of the liver before PVE. Using T1w chemical shift imaging (DUAL FFE), the patients were categorized as having a normal (<5%) or an elevated (>5%) hFF. The correlation of hFF, age, gender, initial tumor mass, history of chemotherapy, degree of liver hypertrophy, and kinetic growth rate after PVE was investigated using multiple regression analysis and Spearman's test. A normal hFF was found in 43/68 patients (63%), whereas 25/68 (37%) patients had an elevated hFF. The mean hypertrophy and kinetic growth rates in patients with normal vs. elevated hFF were 24 ± 31% vs. 28 ± 36% and 9 ± 9 % vs. 8 ± 10% (<i
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30322874
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21315282
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29707427
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Involvement of 5-HT(1A) and 5-HT(2A) Receptors but Not α (2)-Adrenoceptors in the Acute Electrophysiological Effects of Cariprazine in the Rat Brain In Vivo.
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Development of a PET radioligand for the central 5-HT1B receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds.
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Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study.
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Cariprazine, an orally active and potent dopamine D<sub
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The serotonin 1B (5-HT(1B)) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT(1B) receptor in the primate brain in vivo.</AbstractText Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [(11)C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography.</AbstractText In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/μmol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [(11)C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT(1B) receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics.</AbstractText Candidate [(11)C]6, i.e., [(11)C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT(1B) receptors and was nominated for further preclinical characterization and PET examination in human subjects.</AbstractText
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One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.</AbstractText We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).</AbstractText ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.</AbstractText Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.</AbstractText
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Involvement of 5-HT(1A) and 5-HT(2A) Receptors but Not α (2)-Adrenoceptors in the Acute Electrophysiological Effects of Cariprazine in the Rat Brain In Vivo. Cariprazine, an orally active and potent dopamine D<sub
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Development of a PET radioligand for the central 5-HT1B receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds. The serotonin 1B (5-HT(1B)) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT(1B) receptor in the primate brain in vivo.</AbstractText Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [(11)C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography.</AbstractText In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/μmol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [(11)C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT(1B) receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics.</AbstractText Candidate [(11)C]6, i.e., [(11)C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT(1B) receptors and was nominated for further preclinical characterization and PET examination in human subjects.</AbstractText
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Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study. One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.</AbstractText We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).</AbstractText ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.</AbstractText Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.</AbstractText
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23294475
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17729007
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22522975
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Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
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Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis.
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fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations.
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It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited.</AbstractText We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease.</AbstractText In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34-11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0-498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL.</AbstractText We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.</AbstractText
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Borrelia infections, especially chronic neuroborreliosis (NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive.</AbstractText To evaluate brain magnetic resonance imaging (MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration.</AbstractText Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- (with and without gadolinium), T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery (FLAIR) imaging were used.</AbstractText White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls (no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients (rho = 0.83, P<0.01) and in controls (rho = 0.61, P<0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2-weighted imaging.</AbstractText A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.</AbstractText
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Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes.</AbstractText
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Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection. It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited.</AbstractText We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease.</AbstractText In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34-11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0-498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL.</AbstractText We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.</AbstractText
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Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis. Borrelia infections, especially chronic neuroborreliosis (NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive.</AbstractText To evaluate brain magnetic resonance imaging (MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration.</AbstractText Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- (with and without gadolinium), T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery (FLAIR) imaging were used.</AbstractText White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls (no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients (rho = 0.83, P<0.01) and in controls (rho = 0.61, P<0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2-weighted imaging.</AbstractText A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.</AbstractText
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fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations. Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes.</AbstractText
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36273869
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37700036
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36077913
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Quality of life in a 61-year-old paraplegic patient with myelomeningocele: illustrative case.
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A novel method to quantify perivascular space enlargement near the syrinx in a rodent model of post-traumatic syringomyelia.
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The Future of Biomarkers in Veterinary Medicine: Emerging Approaches and Associated Challenges.
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Limited data exist on survival of patients with myelomeningocele (MM) into late adulthood. Patients born prior to 1975 received less surgical treatment and demonstrated poorer survival. Patients born after 1975 show lower mortality rates because of advancements in prenatal care, diagnostics, technology, and treatment. The increasing number of adult patients with MM demonstrates these successes but also highlights the need for a better understanding of both medical management and quality-of-life issues in this population.</AbstractText A 61-year-old woman presented to the hospital with a functional level T12, vertebral level low lumbar MM that had developed a tissue defect with a cerebrospinal fluid leak. The patient had her MM closed at birth and since then had received no additional surgical treatment or repair of her MM defect. After successful treatment, the patient continues to follow up for additional decompression procedures and admits to a good quality of life.</AbstractText This case adds to the limited literature describing management of patients with MM over the age of 60. The patient's self-described good quality of life and longevity align with reports of importance of independence, level of education, bowel management, ability to provide self-care, strong interpersonal relationships, and absence of shunted hydrocephalus.</AbstractText
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Posttraumatic syringomyelia (PTS) is an enigmatic condition characterized by the development of fluid-filled cysts (syrinxes) within the spinal cord. Perivascular spaces (PVS) are a critical component of fluid transport within the central nervous system (CNS), with dilated PVSs variably implicated in the pathogenesis of syringomyelia. The extent and spatial distribution of dilated PVSs in syringomyelia, however, remains unclear. This study aims to develop a method to assess PVS dimensions across multiple spinal cord segments in rats with PTS. Syrinxes were induced in two Sprague-Dawley rats at C6/7 with computer-controlled motorized spinal cord impaction; two control rats underwent sham laminectomies. Spinal cord segments were obtained at C4, C6 and C8, cleared via tissue clearing protocols, stained with immunofluorescent antibodies and imaged under confocal microscopy. Qualitative and quantitative analyses of PVS size were performed. Arteriolar PVSs were enlarged in the perisyringeal region of the spinal cord, compared to the control cord. No PVS enlargement was observed above or below the syrinx. These results confirm previous incidental findings of enlarged PVSs in the perisyringeal region, providing new insights into PVS dimensions across multiple spinal segments, and providing a novel method for quantifying spinal cord perivascular space size distributions.</AbstractText
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New biomarkers promise to transform veterinary practice through rapid diagnosis of diseases, effective monitoring of animal health and improved welfare and production efficiency. However, the road from biomarker discovery to translation is not always straightforward. This review focuses on molecular biomarkers under development in the veterinary field, introduces the emerging technological approaches transforming this space and the role of 'omics platforms in novel biomarker discovery. The vast majority of veterinary biomarkers are at preliminary stages of development and not yet ready to be deployed into clinical translation. Hence, we examine the major challenges encountered in the process of biomarker development from discovery, through validation and translation to clinical practice, including the hurdles specific to veterinary practice and to each of the 'omics platforms-transcriptomics, proteomics, lipidomics and metabolomics. Finally, recommendations are made for the planning and execution of biomarker studies with a view to assisting the success of novel biomarkers in reaching their full potential.</AbstractText
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Quality of life in a 61-year-old paraplegic patient with myelomeningocele: illustrative case. Limited data exist on survival of patients with myelomeningocele (MM) into late adulthood. Patients born prior to 1975 received less surgical treatment and demonstrated poorer survival. Patients born after 1975 show lower mortality rates because of advancements in prenatal care, diagnostics, technology, and treatment. The increasing number of adult patients with MM demonstrates these successes but also highlights the need for a better understanding of both medical management and quality-of-life issues in this population.</AbstractText A 61-year-old woman presented to the hospital with a functional level T12, vertebral level low lumbar MM that had developed a tissue defect with a cerebrospinal fluid leak. The patient had her MM closed at birth and since then had received no additional surgical treatment or repair of her MM defect. After successful treatment, the patient continues to follow up for additional decompression procedures and admits to a good quality of life.</AbstractText This case adds to the limited literature describing management of patients with MM over the age of 60. The patient's self-described good quality of life and longevity align with reports of importance of independence, level of education, bowel management, ability to provide self-care, strong interpersonal relationships, and absence of shunted hydrocephalus.</AbstractText
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A novel method to quantify perivascular space enlargement near the syrinx in a rodent model of post-traumatic syringomyelia. Posttraumatic syringomyelia (PTS) is an enigmatic condition characterized by the development of fluid-filled cysts (syrinxes) within the spinal cord. Perivascular spaces (PVS) are a critical component of fluid transport within the central nervous system (CNS), with dilated PVSs variably implicated in the pathogenesis of syringomyelia. The extent and spatial distribution of dilated PVSs in syringomyelia, however, remains unclear. This study aims to develop a method to assess PVS dimensions across multiple spinal cord segments in rats with PTS. Syrinxes were induced in two Sprague-Dawley rats at C6/7 with computer-controlled motorized spinal cord impaction; two control rats underwent sham laminectomies. Spinal cord segments were obtained at C4, C6 and C8, cleared via tissue clearing protocols, stained with immunofluorescent antibodies and imaged under confocal microscopy. Qualitative and quantitative analyses of PVS size were performed. Arteriolar PVSs were enlarged in the perisyringeal region of the spinal cord, compared to the control cord. No PVS enlargement was observed above or below the syrinx. These results confirm previous incidental findings of enlarged PVSs in the perisyringeal region, providing new insights into PVS dimensions across multiple spinal segments, and providing a novel method for quantifying spinal cord perivascular space size distributions.</AbstractText
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The Future of Biomarkers in Veterinary Medicine: Emerging Approaches and Associated Challenges. New biomarkers promise to transform veterinary practice through rapid diagnosis of diseases, effective monitoring of animal health and improved welfare and production efficiency. However, the road from biomarker discovery to translation is not always straightforward. This review focuses on molecular biomarkers under development in the veterinary field, introduces the emerging technological approaches transforming this space and the role of 'omics platforms in novel biomarker discovery. The vast majority of veterinary biomarkers are at preliminary stages of development and not yet ready to be deployed into clinical translation. Hence, we examine the major challenges encountered in the process of biomarker development from discovery, through validation and translation to clinical practice, including the hurdles specific to veterinary practice and to each of the 'omics platforms-transcriptomics, proteomics, lipidomics and metabolomics. Finally, recommendations are made for the planning and execution of biomarker studies with a view to assisting the success of novel biomarkers in reaching their full potential.</AbstractText
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29691954
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34385508
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30469728
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Children's neural processing of moral scenarios provides insight into the formation and reduction of in-group biases.
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Peer victimization and the association with hippocampal development and working memory in children with ADHD and typically-developing children.
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Broadband lower-IF RF receiver based on microwave photonic mixer and Kramers-Kronig detection.
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Survival is dependent on sociality within groups which ensure sustenance and protection. From an early age, children show a natural tendency to sort people into groups and discriminate among them. The computations guiding evaluation of third-party behaviors are complex, requiring integration of intent, consequences, and knowledge of group affiliation. This study examined how perceiving third-party morally laden behavior influences children's likelihood to exhibit or reduce group bias. Following a minimal group paradigm assignment, young children (4-7 years) performed a moral evaluation task where group affiliations and moral actions were systematically juxtaposed, so that they were exposed to disproportionately antisocial in-group and prosocial out-group scenarios. Electroencephalography was recorded, and group preference was assessed with a resource allocation game before and after the EEG session. Across all children, evaluations of others' moral actions arose from early and automatic processing (~150 ms), followed by later interactive processing of affiliation and moral valence (~500 ms). Importantly, individual differences in bias manifestation and attitude change were predicted by children's neural responses. Children with high baseline bias selectively exhibited a rapid detection (~200 ms) of scenarios inconsistent with their bias (in-group harm and out-group help). Changes in bias corresponded to distinct patterns in longer latency neural processing. These new developmental neuroscience findings elucidate the multifaceted processing involved in moral evaluation of others' actions, their group affiliations, the nature of the integration of both into full judgments, and the relation of individual differences in neural responses to social decision-making in childhood.</AbstractText
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The symptoms of hyperactivity-impulsivity and inattention displayed by children with ADHD put them at risk of experiencing peer victimization. Hippocampal maturation, may reduce a child's vulnerability to the experience of peer victimization, as it has been associated with decreased ADHD symptomatology. Working memory is an important executive function in the formation and maintenance of social relationships, which is often impaired in ADHD. We aimed to evaluate the relationship between problem behaviours, peer victimization, hippocampal morphology, and working memory in children with and without ADHD. 218 typically-developing participants (50.5% male) and 232 participants diagnosed with ADHD (77.6% male) were recruited. The ADHD group was subdivided into inattentive (ADHD-I) or combined (ADHD-C) types. The Child Behavior Checklist measured problem behaviours and peer victimization. Children underwent Magnetic Resonance Imaging (MRI). Hippocampal subfield volumes were obtained using FreeSurfer. The Wechsler Intelligence Scale for Children-fifth edition measured working memory (WM). The ADHD-C group displayed significantly higher levels of problem behaviours and peer victimization (all, p < 0.001), compared to the other groups. Left Cornu Ammonis 3 (CA3) volume was a positive predictor of peer victimization (all, p < 0.013). Left CA3 volume was a positive predictor of WM and left Cornu Ammonis 4 (CA4) volume negatively predicted WM (all, p < 0.025). A cluster analysis revealed that children displaying symptoms of hyperactivity-impulsivity are the most at risk for peer victimization. Interventions focusing on minimizing peer victimization may aid in mitigating adverse downstream effects, and assist in promoting brain health and cognitive function.</AbstractText
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A broadband lower- intermediate-frequency (IF) radio frequency (RF) receiver with low cost and complexity based on a microwave photonic mixer and Kramers-Kronig (KK) detection is proposed and experimentally demonstrated. The feasibility of the proposed RF receiver is verified by comparing the error vector magnitude (EVM) performance of a down-converted IF signal with and without KK detection. EVM is measured as a function of IF carrier frequency, input local oscillator (LO) power, input RF power, and the coupling ratio between RF and LO paths. With KK detection, EVM can be improved by more than 9.5% when the IF carrier frequency is close to half of the signal bandwidth. This implies that a lower IF frequency can be down-converted with good EVM and that a low-speed photodetector and a low sampling rate analog to digital converter can be used for wideband RF signal reception.</AbstractText
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Children's neural processing of moral scenarios provides insight into the formation and reduction of in-group biases. Survival is dependent on sociality within groups which ensure sustenance and protection. From an early age, children show a natural tendency to sort people into groups and discriminate among them. The computations guiding evaluation of third-party behaviors are complex, requiring integration of intent, consequences, and knowledge of group affiliation. This study examined how perceiving third-party morally laden behavior influences children's likelihood to exhibit or reduce group bias. Following a minimal group paradigm assignment, young children (4-7 years) performed a moral evaluation task where group affiliations and moral actions were systematically juxtaposed, so that they were exposed to disproportionately antisocial in-group and prosocial out-group scenarios. Electroencephalography was recorded, and group preference was assessed with a resource allocation game before and after the EEG session. Across all children, evaluations of others' moral actions arose from early and automatic processing (~150 ms), followed by later interactive processing of affiliation and moral valence (~500 ms). Importantly, individual differences in bias manifestation and attitude change were predicted by children's neural responses. Children with high baseline bias selectively exhibited a rapid detection (~200 ms) of scenarios inconsistent with their bias (in-group harm and out-group help). Changes in bias corresponded to distinct patterns in longer latency neural processing. These new developmental neuroscience findings elucidate the multifaceted processing involved in moral evaluation of others' actions, their group affiliations, the nature of the integration of both into full judgments, and the relation of individual differences in neural responses to social decision-making in childhood.</AbstractText
|
Peer victimization and the association with hippocampal development and working memory in children with ADHD and typically-developing children. The symptoms of hyperactivity-impulsivity and inattention displayed by children with ADHD put them at risk of experiencing peer victimization. Hippocampal maturation, may reduce a child's vulnerability to the experience of peer victimization, as it has been associated with decreased ADHD symptomatology. Working memory is an important executive function in the formation and maintenance of social relationships, which is often impaired in ADHD. We aimed to evaluate the relationship between problem behaviours, peer victimization, hippocampal morphology, and working memory in children with and without ADHD. 218 typically-developing participants (50.5% male) and 232 participants diagnosed with ADHD (77.6% male) were recruited. The ADHD group was subdivided into inattentive (ADHD-I) or combined (ADHD-C) types. The Child Behavior Checklist measured problem behaviours and peer victimization. Children underwent Magnetic Resonance Imaging (MRI). Hippocampal subfield volumes were obtained using FreeSurfer. The Wechsler Intelligence Scale for Children-fifth edition measured working memory (WM). The ADHD-C group displayed significantly higher levels of problem behaviours and peer victimization (all, p < 0.001), compared to the other groups. Left Cornu Ammonis 3 (CA3) volume was a positive predictor of peer victimization (all, p < 0.013). Left CA3 volume was a positive predictor of WM and left Cornu Ammonis 4 (CA4) volume negatively predicted WM (all, p < 0.025). A cluster analysis revealed that children displaying symptoms of hyperactivity-impulsivity are the most at risk for peer victimization. Interventions focusing on minimizing peer victimization may aid in mitigating adverse downstream effects, and assist in promoting brain health and cognitive function.</AbstractText
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Broadband lower-IF RF receiver based on microwave photonic mixer and Kramers-Kronig detection. A broadband lower- intermediate-frequency (IF) radio frequency (RF) receiver with low cost and complexity based on a microwave photonic mixer and Kramers-Kronig (KK) detection is proposed and experimentally demonstrated. The feasibility of the proposed RF receiver is verified by comparing the error vector magnitude (EVM) performance of a down-converted IF signal with and without KK detection. EVM is measured as a function of IF carrier frequency, input local oscillator (LO) power, input RF power, and the coupling ratio between RF and LO paths. With KK detection, EVM can be improved by more than 9.5% when the IF carrier frequency is close to half of the signal bandwidth. This implies that a lower IF frequency can be down-converted with good EVM and that a low-speed photodetector and a low sampling rate analog to digital converter can be used for wideband RF signal reception.</AbstractText
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31611771
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15937014
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30236710
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Previous Musical Experience and Cortical Thickness Relate to the Beneficial Effect of Motor Synchronization on Auditory Function.
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A theory of cortical responses.
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ABA-dependent salt and drought stress improve strawberry fruit quality.
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Auditory processing can be enhanced by motor system activity. During auditory-motor synchronization, motor activity guides auditory attention and thus facilitates auditory processing through active sensing. Previous research on enhanced auditory processing through motor synchronization has been limited to easy tasks with simple stimulus material. Further, the mechanisms and brain regions underlying this synchronization are unclear. We investigated the effect of motor synchronization on auditory processing with naturalistic, musical auditory material in a discrimination task. We further assessed how previous musical training and cortical thickness of specific brain regions relate to different aspects of auditory-motor synchronization. We conducted an auditory-motor experiment in 139 adults. The task involved melody discrimination and beat tapping synchronization. Additionally, 68 participants underwent structural MRI. We found that individuals with better auditory-motor synchronization accuracy showed improved melody discrimination, and that melody discrimination was better in trials with higher tapping accuracy. However, melody discrimination was worse in the tapping than in the listening only condition. Longer previous musical training and thicker Heschl's gyri were associated with better melody discrimination and better tapping synchrony. <i
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This article concerns the nature of evoked brain responses and the principles underlying their generation. We start with the premise that the sensory brain has evolved to represent or infer the causes of changes in its sensory inputs. The problem of inference is well formulated in statistical terms. The statistical fundaments of inference may therefore afford important constraints on neuronal implementation. By formulating the original ideas of Helmholtz on perception, in terms of modern-day statistical theories, one arrives at a model of perceptual inference and learning that can explain a remarkable range of neurobiological facts.It turns out that the problems of inferring the causes of sensory input (perceptual inference) and learning the relationship between input and cause (perceptual learning) can be resolved using exactly the same principle. Specifically, both inference and learning rest on minimizing the brain's free energy, as defined in statistical physics. Furthermore, inference and learning can proceed in a biologically plausible fashion. Cortical responses can be seen as the brain's attempt to minimize the free energy induced by a stimulus and thereby encode the most likely cause of that stimulus. Similarly, learning emerges from changes in synaptic efficacy that minimize the free energy, averaged over all stimuli encountered. The underlying scheme rests on empirical Bayes and hierarchical models of how sensory input is caused. The use of hierarchical models enables the brain to construct prior expectations in a dynamic and context-sensitive fashion. This scheme provides a principled way to understand many aspects of cortical organization and responses. The aim of this article is to encompass many apparently unrelated anatomical, physiological and psychophysical attributes of the brain within a single theoretical perspective. In terms of cortical architectures, the theoretical treatment predicts that sensory cortex should be arranged hierarchically, that connections should be reciprocal and that forward and backward connections should show a functional asymmetry (forward connections are driving, whereas backward connections are both driving and modulatory). In terms of synaptic physiology, it predicts associative plasticity and, for dynamic models, spike-timing-dependent plasticity. In terms of electrophysiology, it accounts for classical and extra classical receptive field effects and long-latency or endogenous components of evoked cortical responses. It predicts the attenuation of responses encoding prediction error with perceptual learning and explains many phenomena such as repetition suppression, mismatch negativity (MMN) and the P300 in electroencephalography. In psychophysical terms, it accounts for the behavioural correlates of these physiological phenomena, for example, priming and global precedence. The final focus of this article is on perceptual learning as measured with the MMN and the implications for empirical studies of coupling among cortical areas using evoked sensory responses.</AbstractText
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Strawberry crop is very sensitive to osmotic stress conditions. We investigated the effect of the stress induced by mild drought (DS) and salt (SS) stresses, on molecular, physiological, and metabolic processes in the strawberry crop (Fragaria ananassa), cv. Camarosa. The results showed that the fruit yield was not affected. Mild DS and SS also resulted in an increased content of phenolics, anthocyanins, and l-ascorbic acid, and an increased antioxidant activity. These effects were accompanied by increased levels of ABA and its derivatives (phaseic and dehydrophasic acids), alongside the upregulation of several genes involved on their synthesis. Therefore, the results obtained in this study suggest that mild DS and SS improve the functional quality of strawberry fruits through and ABA-dependent mechanism.</AbstractText
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Previous Musical Experience and Cortical Thickness Relate to the Beneficial Effect of Motor Synchronization on Auditory Function. Auditory processing can be enhanced by motor system activity. During auditory-motor synchronization, motor activity guides auditory attention and thus facilitates auditory processing through active sensing. Previous research on enhanced auditory processing through motor synchronization has been limited to easy tasks with simple stimulus material. Further, the mechanisms and brain regions underlying this synchronization are unclear. We investigated the effect of motor synchronization on auditory processing with naturalistic, musical auditory material in a discrimination task. We further assessed how previous musical training and cortical thickness of specific brain regions relate to different aspects of auditory-motor synchronization. We conducted an auditory-motor experiment in 139 adults. The task involved melody discrimination and beat tapping synchronization. Additionally, 68 participants underwent structural MRI. We found that individuals with better auditory-motor synchronization accuracy showed improved melody discrimination, and that melody discrimination was better in trials with higher tapping accuracy. However, melody discrimination was worse in the tapping than in the listening only condition. Longer previous musical training and thicker Heschl's gyri were associated with better melody discrimination and better tapping synchrony. <i
|
A theory of cortical responses. This article concerns the nature of evoked brain responses and the principles underlying their generation. We start with the premise that the sensory brain has evolved to represent or infer the causes of changes in its sensory inputs. The problem of inference is well formulated in statistical terms. The statistical fundaments of inference may therefore afford important constraints on neuronal implementation. By formulating the original ideas of Helmholtz on perception, in terms of modern-day statistical theories, one arrives at a model of perceptual inference and learning that can explain a remarkable range of neurobiological facts.It turns out that the problems of inferring the causes of sensory input (perceptual inference) and learning the relationship between input and cause (perceptual learning) can be resolved using exactly the same principle. Specifically, both inference and learning rest on minimizing the brain's free energy, as defined in statistical physics. Furthermore, inference and learning can proceed in a biologically plausible fashion. Cortical responses can be seen as the brain's attempt to minimize the free energy induced by a stimulus and thereby encode the most likely cause of that stimulus. Similarly, learning emerges from changes in synaptic efficacy that minimize the free energy, averaged over all stimuli encountered. The underlying scheme rests on empirical Bayes and hierarchical models of how sensory input is caused. The use of hierarchical models enables the brain to construct prior expectations in a dynamic and context-sensitive fashion. This scheme provides a principled way to understand many aspects of cortical organization and responses. The aim of this article is to encompass many apparently unrelated anatomical, physiological and psychophysical attributes of the brain within a single theoretical perspective. In terms of cortical architectures, the theoretical treatment predicts that sensory cortex should be arranged hierarchically, that connections should be reciprocal and that forward and backward connections should show a functional asymmetry (forward connections are driving, whereas backward connections are both driving and modulatory). In terms of synaptic physiology, it predicts associative plasticity and, for dynamic models, spike-timing-dependent plasticity. In terms of electrophysiology, it accounts for classical and extra classical receptive field effects and long-latency or endogenous components of evoked cortical responses. It predicts the attenuation of responses encoding prediction error with perceptual learning and explains many phenomena such as repetition suppression, mismatch negativity (MMN) and the P300 in electroencephalography. In psychophysical terms, it accounts for the behavioural correlates of these physiological phenomena, for example, priming and global precedence. The final focus of this article is on perceptual learning as measured with the MMN and the implications for empirical studies of coupling among cortical areas using evoked sensory responses.</AbstractText
|
ABA-dependent salt and drought stress improve strawberry fruit quality. Strawberry crop is very sensitive to osmotic stress conditions. We investigated the effect of the stress induced by mild drought (DS) and salt (SS) stresses, on molecular, physiological, and metabolic processes in the strawberry crop (Fragaria ananassa), cv. Camarosa. The results showed that the fruit yield was not affected. Mild DS and SS also resulted in an increased content of phenolics, anthocyanins, and l-ascorbic acid, and an increased antioxidant activity. These effects were accompanied by increased levels of ABA and its derivatives (phaseic and dehydrophasic acids), alongside the upregulation of several genes involved on their synthesis. Therefore, the results obtained in this study suggest that mild DS and SS improve the functional quality of strawberry fruits through and ABA-dependent mechanism.</AbstractText
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33196376
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26527846
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34057088
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Hard but so valuable to define hard criteria for empirical theories of consciousness.
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Sociology of Low Expectations: Recalibration as Innovation Work in Biomedicine.
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Systolic Blood Pressure and Cognition in the Elderly: The Northern Manhattan Study.
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I congratulate Doerig, Schurger, and Herzog for their stimulating contribution for an empirical approach to theories of consciousness. I must also admit that the excellent way Global Neuronal Workspace Theory (GNWT) I've contributed to since 2001 passes the test they designed may contribute to my enthusiasm (see Table 1 of their article). In this Comment, I focus on two points: highlighting a potential epistemological weakness of their approach, and proposing how GNWT can solve the 'small network argument.'</AbstractText
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Social scientists have drawn attention to the role of hype and optimistic visions of the future in providing momentum to biomedical innovation projects by encouraging innovation alliances. In this article, we show how less optimistic, uncertain, and modest visions of the future can also provide innovation projects with momentum. Scholars have highlighted the need for clinicians to carefully manage the expectations of their prospective patients. Using the example of a pioneering clinical team providing deep brain stimulation to children and young people with movement disorders, we show how clinicians confront this requirement by drawing on their professional knowledge and clinical expertise to construct visions of the future with their prospective patients; visions which are personalized, modest, and tainted with uncertainty. We refer to this vision-constructing work as recalibration, and we argue that recalibration enables clinicians to manage the tension between the highly optimistic and hyped visions of the future that surround novel biomedical interventions, and the exigencies of delivering those interventions in a clinical setting. Drawing on work from science and technology studies, we suggest that recalibration enrolls patients in an innovation alliance by creating a shared understanding of how the "effectiveness" of an innovation shall be judged.</AbstractText
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Increasing evidence suggests that hypertension is a risk factor for cognitive impairment and dementia. The relationship between blood pressure and cognition in a racially and ethnically diverse population remains unclear.</AbstractText To study association of blood pressure with cognition cross-sectionally and longitudinally in the elderly.</AbstractText Participants are stroke-free individuals from the racially and ethnically diverse Northern Manhattan Study (NOMAS) (n = 1215). General linear models are constructed to examine blood pressure in relation to cognition cross-sectionally and longitudinally at a five-year follow-up.</AbstractText We found a cross-sectional association of systolic blood pressure (SBP) with word fluency/semantic memory, executive function, and processing speed/visual motor integration (VMI) function. This association was independent of demographics, vascular risk factors, white matter hyperintensity volume (WMHV), and carotid intima-media thickness (cIMT). The cross-sectional association of SBP with processing speed/VMI and executive function was attenuated after adjusting anti-hypertension medications in the models. Baseline SBP was associated with the change of processing speed/VMI function after adjusting vascular risk factors, WMHV, and cIMT at a 5-year follow-up. This longitudinal association was not found after adjusting anti-hypertension medications in the models. Further analyses revealed that individuals with category SBP from < 120 mmHg to≥140 mmHg had a linear decline in processing speed/VMI function at a 5-year follow-up.</AbstractText We show that SBP is negatively associated with cognition cross-sectionally and longitudinally in the elderly. Anti-hypertension treatment eliminates the negative association of SBP with processing speed/VMI function longitudinally. Our findings support the treatment of stage 1 systolic hypertension in the elderly.</AbstractText
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Hard but so valuable to define hard criteria for empirical theories of consciousness. I congratulate Doerig, Schurger, and Herzog for their stimulating contribution for an empirical approach to theories of consciousness. I must also admit that the excellent way Global Neuronal Workspace Theory (GNWT) I've contributed to since 2001 passes the test they designed may contribute to my enthusiasm (see Table 1 of their article). In this Comment, I focus on two points: highlighting a potential epistemological weakness of their approach, and proposing how GNWT can solve the 'small network argument.'</AbstractText
|
Sociology of Low Expectations: Recalibration as Innovation Work in Biomedicine. Social scientists have drawn attention to the role of hype and optimistic visions of the future in providing momentum to biomedical innovation projects by encouraging innovation alliances. In this article, we show how less optimistic, uncertain, and modest visions of the future can also provide innovation projects with momentum. Scholars have highlighted the need for clinicians to carefully manage the expectations of their prospective patients. Using the example of a pioneering clinical team providing deep brain stimulation to children and young people with movement disorders, we show how clinicians confront this requirement by drawing on their professional knowledge and clinical expertise to construct visions of the future with their prospective patients; visions which are personalized, modest, and tainted with uncertainty. We refer to this vision-constructing work as recalibration, and we argue that recalibration enables clinicians to manage the tension between the highly optimistic and hyped visions of the future that surround novel biomedical interventions, and the exigencies of delivering those interventions in a clinical setting. Drawing on work from science and technology studies, we suggest that recalibration enrolls patients in an innovation alliance by creating a shared understanding of how the "effectiveness" of an innovation shall be judged.</AbstractText
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Systolic Blood Pressure and Cognition in the Elderly: The Northern Manhattan Study. Increasing evidence suggests that hypertension is a risk factor for cognitive impairment and dementia. The relationship between blood pressure and cognition in a racially and ethnically diverse population remains unclear.</AbstractText To study association of blood pressure with cognition cross-sectionally and longitudinally in the elderly.</AbstractText Participants are stroke-free individuals from the racially and ethnically diverse Northern Manhattan Study (NOMAS) (n = 1215). General linear models are constructed to examine blood pressure in relation to cognition cross-sectionally and longitudinally at a five-year follow-up.</AbstractText We found a cross-sectional association of systolic blood pressure (SBP) with word fluency/semantic memory, executive function, and processing speed/visual motor integration (VMI) function. This association was independent of demographics, vascular risk factors, white matter hyperintensity volume (WMHV), and carotid intima-media thickness (cIMT). The cross-sectional association of SBP with processing speed/VMI and executive function was attenuated after adjusting anti-hypertension medications in the models. Baseline SBP was associated with the change of processing speed/VMI function after adjusting vascular risk factors, WMHV, and cIMT at a 5-year follow-up. This longitudinal association was not found after adjusting anti-hypertension medications in the models. Further analyses revealed that individuals with category SBP from < 120 mmHg to≥140 mmHg had a linear decline in processing speed/VMI function at a 5-year follow-up.</AbstractText We show that SBP is negatively associated with cognition cross-sectionally and longitudinally in the elderly. Anti-hypertension treatment eliminates the negative association of SBP with processing speed/VMI function longitudinally. Our findings support the treatment of stage 1 systolic hypertension in the elderly.</AbstractText
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40743111
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21153487
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40523512
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Water, sanitation, and hygiene (WASH) factors and the incidence of communicable diseases in Urban Bangladesh: Evidence from municipal areas.
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Breast cancer health promotion in Qatar: a survey of community pharmacists' interests and needs.
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Locomotor activity depends on β-arrestin recruitment by the dopamine D(1) receptor in the striatal D(1)-D(3) receptor heteromer.
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Safe drinking water, sanitation, and hygiene (WASH) are crucial for health and development, especially in low- and middle-income countries (LMICs) where WASH-related diseases are prevalent. Bangladesh, with high poverty rates and a large population, faces significant WASH challenges. This study examines the association between hygiene-related factors and communicable diseases in two Bangladeshi municipalities.</AbstractText A descriptive cross-sectional study was conducted from June 1 to July 30, 2021, in Savar and Satkhira municipalities, chosen for their diverse socioeconomic and geographic characteristics. A stratified random sampling method targeted poor, marginalised, and socially excluded populations. A total of 607 interviews were conducted using a structured questionnaire, collecting data on socio-demographics, hygiene practices, and disease history. Participants were included if they were adults (aged 18 or older), had resided in the municipality for at least one year, and provided informed consent to participate. Data were analysed using SPSS, employing chi-square tests and logistic regression to assess associations between variables.</AbstractText The study revealed that 24.1% of participants had a communicable disease, with diarrhoea being the most common. Significant predictors of communicable diseases included gender, with females being more likely affected (OR: 3.21, 95% CI: 1.19 to 8.66, p = 0.003), and the source of drinking water, with tube well users at higher risk (OR: 2.81, 95% CI: 1.13 to 7.02, p = 0.015). Poor hand hygiene significantly increased disease risk (OR: 12.31, 95% CI: 2.86 to 53.03, p < 0.001).</AbstractText Communicable diseases are prevalent in Bangladeshi municipalities, primarily driven by poor WASH conditions. Enhancing access to safe drinking water and implementing community-based WASH interventions, such as hygiene education campaigns, improved sanitation infrastructure, and school-based awareness programs, are vital for reducing the disease burden. Further research should explore the effectiveness and scalability of these targeted strategies.</AbstractText
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Breast cancer is the most common cancer in women in Qatar. Despite the sustained efforts to increase breast cancer public awareness via campaigns and public screening programmes, breast cancer screening rate remains low. The involvement of community pharmacists in the communication and distribution of breast cancer screening information should have a significant positive impact. The objectives of this study were to determine the degree of community pharmacists' involvement in breast cancer health promotion activities in Qatar, to explore their attitudes towards the involvement in breast cancer health promotion, to assess their breast cancer knowledge, to gauge their interest in receiving breast cancer continuous education and to list their perceived barriers for including breast cancer health promotion activities into their daily practice.</AbstractText Community pharmacies in Qatar.</AbstractText The study objectives were addressed in a cross-sectional survey of all community pharmacists in Qatar.</AbstractText The extent of community pharmacists' involvement in breast cancer health promotion activities, the community pharmacists' interest and comfort in providing breast cancer health promotion, their breast cancer knowledge, their interest in receiving breast cancer continuous education, their attitudes and beliefs towards breast cancer health promotion and their perceived barriers for integrating breast cancer heath promotion activities into their daily practice.</AbstractText Over a 12-week period, we collected 195 surveys (60% response rate). Eighty-eight percent indicated that they never invited healthcare professionals to provide breast cancer education in the pharmacy, 78% said that they never distributed breast cancer educational materials, and 58% reported that they never counseled patients about breast cancer. Nevertheless, more than 60% were highly interested in being engaged in breast cancer health promotion activities. In addition, 87% believed that discussing breast cancer awareness with female patients in the pharmacy was beneficial to patients. Yet pharmacists perceived many barriers for integrating breast cancer health promotion into their daily practice including lack of educational materials (79%) and lack of public recognition (61%). Moreover, their breast cancer knowledge mean score was 63% with 77% expressing a high interest in receiving breast cancer continuous education.</AbstractText Despite their low involvement in breast cancer health promotion, the majority of pharmacists were interested in educating patients about breast cancer. However, low breast cancer knowledge and other barriers can prevent actualizing this role. Further work should focus on providing these pharmacists with breast cancer continuous education and overcoming all stated barriers.</AbstractText
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Several dopaminergic compounds, including the clinically used pramipexole, are labelled as preferential dopamine D<sub
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Water, sanitation, and hygiene (WASH) factors and the incidence of communicable diseases in Urban Bangladesh: Evidence from municipal areas. Safe drinking water, sanitation, and hygiene (WASH) are crucial for health and development, especially in low- and middle-income countries (LMICs) where WASH-related diseases are prevalent. Bangladesh, with high poverty rates and a large population, faces significant WASH challenges. This study examines the association between hygiene-related factors and communicable diseases in two Bangladeshi municipalities.</AbstractText A descriptive cross-sectional study was conducted from June 1 to July 30, 2021, in Savar and Satkhira municipalities, chosen for their diverse socioeconomic and geographic characteristics. A stratified random sampling method targeted poor, marginalised, and socially excluded populations. A total of 607 interviews were conducted using a structured questionnaire, collecting data on socio-demographics, hygiene practices, and disease history. Participants were included if they were adults (aged 18 or older), had resided in the municipality for at least one year, and provided informed consent to participate. Data were analysed using SPSS, employing chi-square tests and logistic regression to assess associations between variables.</AbstractText The study revealed that 24.1% of participants had a communicable disease, with diarrhoea being the most common. Significant predictors of communicable diseases included gender, with females being more likely affected (OR: 3.21, 95% CI: 1.19 to 8.66, p = 0.003), and the source of drinking water, with tube well users at higher risk (OR: 2.81, 95% CI: 1.13 to 7.02, p = 0.015). Poor hand hygiene significantly increased disease risk (OR: 12.31, 95% CI: 2.86 to 53.03, p < 0.001).</AbstractText Communicable diseases are prevalent in Bangladeshi municipalities, primarily driven by poor WASH conditions. Enhancing access to safe drinking water and implementing community-based WASH interventions, such as hygiene education campaigns, improved sanitation infrastructure, and school-based awareness programs, are vital for reducing the disease burden. Further research should explore the effectiveness and scalability of these targeted strategies.</AbstractText
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Breast cancer health promotion in Qatar: a survey of community pharmacists' interests and needs. Breast cancer is the most common cancer in women in Qatar. Despite the sustained efforts to increase breast cancer public awareness via campaigns and public screening programmes, breast cancer screening rate remains low. The involvement of community pharmacists in the communication and distribution of breast cancer screening information should have a significant positive impact. The objectives of this study were to determine the degree of community pharmacists' involvement in breast cancer health promotion activities in Qatar, to explore their attitudes towards the involvement in breast cancer health promotion, to assess their breast cancer knowledge, to gauge their interest in receiving breast cancer continuous education and to list their perceived barriers for including breast cancer health promotion activities into their daily practice.</AbstractText Community pharmacies in Qatar.</AbstractText The study objectives were addressed in a cross-sectional survey of all community pharmacists in Qatar.</AbstractText The extent of community pharmacists' involvement in breast cancer health promotion activities, the community pharmacists' interest and comfort in providing breast cancer health promotion, their breast cancer knowledge, their interest in receiving breast cancer continuous education, their attitudes and beliefs towards breast cancer health promotion and their perceived barriers for integrating breast cancer heath promotion activities into their daily practice.</AbstractText Over a 12-week period, we collected 195 surveys (60% response rate). Eighty-eight percent indicated that they never invited healthcare professionals to provide breast cancer education in the pharmacy, 78% said that they never distributed breast cancer educational materials, and 58% reported that they never counseled patients about breast cancer. Nevertheless, more than 60% were highly interested in being engaged in breast cancer health promotion activities. In addition, 87% believed that discussing breast cancer awareness with female patients in the pharmacy was beneficial to patients. Yet pharmacists perceived many barriers for integrating breast cancer health promotion into their daily practice including lack of educational materials (79%) and lack of public recognition (61%). Moreover, their breast cancer knowledge mean score was 63% with 77% expressing a high interest in receiving breast cancer continuous education.</AbstractText Despite their low involvement in breast cancer health promotion, the majority of pharmacists were interested in educating patients about breast cancer. However, low breast cancer knowledge and other barriers can prevent actualizing this role. Further work should focus on providing these pharmacists with breast cancer continuous education and overcoming all stated barriers.</AbstractText
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Locomotor activity depends on β-arrestin recruitment by the dopamine D(1) receptor in the striatal D(1)-D(3) receptor heteromer. Several dopaminergic compounds, including the clinically used pramipexole, are labelled as preferential dopamine D<sub
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40657727
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30585333
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40740735
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Self-other generalisation shapes social interaction and is disrupted in borderline personality disorder.
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Are everyday sadists specifically attracted to violent video games and do they emotionally benefit from playing those games?
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The Iris File Extension.
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Generalising information from ourselves to others, and others to ourselves allows for both a dependable source of navigation and adaptability in interpersonal exchange. Disturbances to social development in sensitive periods can cause enduring and distressing damage to lasting healthy relationships. However, identifying the mechanisms of healthy exchange has been difficult. We introduce a theory of self-other generalisation tested with data from a three-phase social value orientation task - the Intentions Game. We involved humans with (<i
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The present research tested the hypothesis that everyday sadists show a distinct preference for violent video games and examined the relationship between everyday sadism and participant's mood after violent video game play. In Study 1, participants watched three trailers for video games that differed in their level of violent content. Whereas everyday sadists were attracted to a violent video game, there was no significant positive association between everyday sadism and attraction to the nonviolent video games. Study 2 showed that after playing a violent video game, there was a significant positive relationship between everyday sadism and participant's positive mood and a negative relationship between everyday sadism and participant's negative mood. In contrast, after playing a nonviolent video game, the relationship between everyday sadism and participant's negative mood was less pronounced. Overall, these studies show that everyday sadists specifically like to play violent video games and suggest that this tendency is adaptive in that they emotionally benefit from playing violent video games.</AbstractText
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A modern digital pathology vendor-agnostic binary slide format specifically targeting the unmet need of efficient real-time transfer and display has not yet been established. The growing adoption of digital pathology only intensifies the need for an intermediary digital slide format that emphasizes performance for use between slide servers and image management software. The DICOM standard is a well-established format widely used for the long-term storage of both images and associated critical metadata. However, it was inherently designed for radiology rather than digital pathology, a discipline that imposes a unique set of performance requirements due to high-speed multi-pyramidal rendering within whole slide viewer applications. Here, we introduce the Iris file extension, a binary container specification explicitly designed for performance-oriented whole slide image (WSI) viewer systems. The Iris file extension specification is explicit and straightforward, adding modern compression support, a dynamic structure with fully optional metadata features, computationally trivial deep file validation, corruption recovery capabilities, and slide annotations. In addition to the file specification document, we provide source code to allow for (de)serialization and validation of a binary stream against the standard. We also provide corresponding binary builds with C++, Python, and JavaScript language support. Finally, we provide full encoder and decoder implementation source code, as well as binary builds (part of the separate Iris Codec Community module), with language bindings for C++ and Python, allowing for easy integration with existing WSI solutions. We provide the Iris File Extension specification openly to the community in the form of a Creative Commons Attribution-No Derivative 4.0 International license.</AbstractText
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Self-other generalisation shapes social interaction and is disrupted in borderline personality disorder. Generalising information from ourselves to others, and others to ourselves allows for both a dependable source of navigation and adaptability in interpersonal exchange. Disturbances to social development in sensitive periods can cause enduring and distressing damage to lasting healthy relationships. However, identifying the mechanisms of healthy exchange has been difficult. We introduce a theory of self-other generalisation tested with data from a three-phase social value orientation task - the Intentions Game. We involved humans with (<i
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Are everyday sadists specifically attracted to violent video games and do they emotionally benefit from playing those games? The present research tested the hypothesis that everyday sadists show a distinct preference for violent video games and examined the relationship between everyday sadism and participant's mood after violent video game play. In Study 1, participants watched three trailers for video games that differed in their level of violent content. Whereas everyday sadists were attracted to a violent video game, there was no significant positive association between everyday sadism and attraction to the nonviolent video games. Study 2 showed that after playing a violent video game, there was a significant positive relationship between everyday sadism and participant's positive mood and a negative relationship between everyday sadism and participant's negative mood. In contrast, after playing a nonviolent video game, the relationship between everyday sadism and participant's negative mood was less pronounced. Overall, these studies show that everyday sadists specifically like to play violent video games and suggest that this tendency is adaptive in that they emotionally benefit from playing violent video games.</AbstractText
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The Iris File Extension. A modern digital pathology vendor-agnostic binary slide format specifically targeting the unmet need of efficient real-time transfer and display has not yet been established. The growing adoption of digital pathology only intensifies the need for an intermediary digital slide format that emphasizes performance for use between slide servers and image management software. The DICOM standard is a well-established format widely used for the long-term storage of both images and associated critical metadata. However, it was inherently designed for radiology rather than digital pathology, a discipline that imposes a unique set of performance requirements due to high-speed multi-pyramidal rendering within whole slide viewer applications. Here, we introduce the Iris file extension, a binary container specification explicitly designed for performance-oriented whole slide image (WSI) viewer systems. The Iris file extension specification is explicit and straightforward, adding modern compression support, a dynamic structure with fully optional metadata features, computationally trivial deep file validation, corruption recovery capabilities, and slide annotations. In addition to the file specification document, we provide source code to allow for (de)serialization and validation of a binary stream against the standard. We also provide corresponding binary builds with C++, Python, and JavaScript language support. Finally, we provide full encoder and decoder implementation source code, as well as binary builds (part of the separate Iris Codec Community module), with language bindings for C++ and Python, allowing for easy integration with existing WSI solutions. We provide the Iris File Extension specification openly to the community in the form of a Creative Commons Attribution-No Derivative 4.0 International license.</AbstractText
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29267344
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30547282
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40601669
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Perceptual training to improve hip fracture identification in conventional radiographs.
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Statistical learning of anomalous regions in complex faux X-ray images does not transfer between detection and discrimination.
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DMSU-Net++: A dual multiscale retinal vessel segmentation method based on improved U-Net+.
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Diagnosing certain fractures in conventional radiographs can be a difficult task, usually taking years to master. Typically, students are trained ad-hoc, in a primarily-rule based fashion. Our study investigated whether students can more rapidly learn to diagnose proximal neck of femur fractures via perceptual training, without having to learn an explicit set of rules. One hundred and thirty-nine students with no prior medical or radiology training were shown a sequence of plain film X-ray images of the right hip and for each image were asked to indicate whether a fracture was present. Students were told if they were correct and the location of any fracture, if present. No other feedback was given. The more able students achieved the same level of accuracy as board certified radiologists at identifying hip fractures in less than an hour of training. Surprisingly, perceptual learning was reduced when the training set was constructed to over-represent the types of images participants found more difficult to categorise. Conversely, repeating training images did not reduce post-training performance relative to showing an equivalent number of unique images. Perceptual training is an effective way of helping novices learn to identify hip fractures in X-ray images and should supplement the current education programme for students.</AbstractText
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The visual environment contains predictable information - "statistical regularities" - that can be used to aid perception and attentional allocation. Here we investigate the role of statistical learning in facilitating search tasks that resemble medical-image perception. Using faux X-ray images, we employed two tasks that mimicked two problems in medical-image perception: detecting a target signal that is poorly segmented from the background; and discriminating a candidate anomaly from benign signals. In the first, participants searched a heavily camouflaged target embedded in cloud-like noise. In the second, the noise opacity was reduced, but the target appeared among visually similar distractors. We tested the hypothesis that learning may be task-specific. To this end, we introduced statistical regularities by presenting the target disproportionately more frequently in one region of the space. This manipulation successfully induced incidental learning of the target's location probability, producing faster search when the target appeared in the high-probability region. The learned attentional preference persisted through a testing phase in which the target's location was random. Supporting the task-specificity hypothesis, when the task changed between training and testing, the learned priority did not transfer. Eye tracking showed fewer, but longer, fixations in the detection than in the discrimination task. The observation of task-specificity of statistical learning has implications for theories of spatial attention and sheds light on the design of effective training tasks.</AbstractText
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Retinal blood vessels are of different sizes and shapes, and even contain very fine capillaries with complex structural morphology, making accurate segmentation a difficult task. To address the above problems, we propose an improved retinal segmentation method DMSU-Net++ (Double Multiscale U-Net++) based on U-Net++. The method innovatively introduces a multiscale feature extraction module WTSAFM, which realises multiscale feature extraction via wavelet transform, and can capture image information of different frequencies more effectively while enhancing global context understanding. In addition, a dual multi-scale feature extraction module is constructed by cascading MFE modules to compensate for the spatial lack of information in WTSAFM, which further improves the accuracy of the model in dealing with different scale information. This method is experimented on the proposed method on two publicly available retinal vessel segmentation datasets, DRIVE and CHASE-DB1, and the experiments show that the F1-score of this method on the two datasets is 82.75 and 82.81, the Sensitivity is 83.74 and 85, and the AUC is 97.86 and 98.36, respectively. Compared with other methods, the method shows better segmentation performance with better accurate recognition.</AbstractText
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Perceptual training to improve hip fracture identification in conventional radiographs. Diagnosing certain fractures in conventional radiographs can be a difficult task, usually taking years to master. Typically, students are trained ad-hoc, in a primarily-rule based fashion. Our study investigated whether students can more rapidly learn to diagnose proximal neck of femur fractures via perceptual training, without having to learn an explicit set of rules. One hundred and thirty-nine students with no prior medical or radiology training were shown a sequence of plain film X-ray images of the right hip and for each image were asked to indicate whether a fracture was present. Students were told if they were correct and the location of any fracture, if present. No other feedback was given. The more able students achieved the same level of accuracy as board certified radiologists at identifying hip fractures in less than an hour of training. Surprisingly, perceptual learning was reduced when the training set was constructed to over-represent the types of images participants found more difficult to categorise. Conversely, repeating training images did not reduce post-training performance relative to showing an equivalent number of unique images. Perceptual training is an effective way of helping novices learn to identify hip fractures in X-ray images and should supplement the current education programme for students.</AbstractText
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Statistical learning of anomalous regions in complex faux X-ray images does not transfer between detection and discrimination. The visual environment contains predictable information - "statistical regularities" - that can be used to aid perception and attentional allocation. Here we investigate the role of statistical learning in facilitating search tasks that resemble medical-image perception. Using faux X-ray images, we employed two tasks that mimicked two problems in medical-image perception: detecting a target signal that is poorly segmented from the background; and discriminating a candidate anomaly from benign signals. In the first, participants searched a heavily camouflaged target embedded in cloud-like noise. In the second, the noise opacity was reduced, but the target appeared among visually similar distractors. We tested the hypothesis that learning may be task-specific. To this end, we introduced statistical regularities by presenting the target disproportionately more frequently in one region of the space. This manipulation successfully induced incidental learning of the target's location probability, producing faster search when the target appeared in the high-probability region. The learned attentional preference persisted through a testing phase in which the target's location was random. Supporting the task-specificity hypothesis, when the task changed between training and testing, the learned priority did not transfer. Eye tracking showed fewer, but longer, fixations in the detection than in the discrimination task. The observation of task-specificity of statistical learning has implications for theories of spatial attention and sheds light on the design of effective training tasks.</AbstractText
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DMSU-Net++: A dual multiscale retinal vessel segmentation method based on improved U-Net+. Retinal blood vessels are of different sizes and shapes, and even contain very fine capillaries with complex structural morphology, making accurate segmentation a difficult task. To address the above problems, we propose an improved retinal segmentation method DMSU-Net++ (Double Multiscale U-Net++) based on U-Net++. The method innovatively introduces a multiscale feature extraction module WTSAFM, which realises multiscale feature extraction via wavelet transform, and can capture image information of different frequencies more effectively while enhancing global context understanding. In addition, a dual multi-scale feature extraction module is constructed by cascading MFE modules to compensate for the spatial lack of information in WTSAFM, which further improves the accuracy of the model in dealing with different scale information. This method is experimented on the proposed method on two publicly available retinal vessel segmentation datasets, DRIVE and CHASE-DB1, and the experiments show that the F1-score of this method on the two datasets is 82.75 and 82.81, the Sensitivity is 83.74 and 85, and the AUC is 97.86 and 98.36, respectively. Compared with other methods, the method shows better segmentation performance with better accurate recognition.</AbstractText
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31035952
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30707275
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30475984
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Is MRCP necessary to diagnose pancreas divisum?
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Native T1 mapping of autoimmune pancreatitis as a quantitative outcome surrogate.
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A plugin for the Ensembl Variant Effect Predictor that uses MaxEntScan to predict variant spliceogenicity.
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The purpose of this study is to compare the performance of three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) with non-MRCP T2-weighted magnetic resonance imaging (MRI) sequences for diagnosis of pancreas divisum (PD).</AbstractText This is a retrospective study of 342 consecutive patients with abdominal MRI including 3D-MRCP. 3D-MRCP was a coronal respiration-navigated T2-weighted sequence with 1.5 mm slice thickness. Non-MRCP T2-weighted sequences were (1) a coronal inversion recovery sequence (TIRM) with 6 mm slice thickness and (2) a transverse single shot turbo spin echo sequence (HASTE) with 4 mm slice thickness. For 3D-MRCP, TIRM, and HASTE, presence of PD and assessment of evaluability were determined in a randomized manner. A consensus read by two radiologists using 3D-MRCP, non-MRCP T2-weighted sequences, and other available imaging sequences served as reference standard for diagnosis of PD. Statistical analysis included performance analysis of 3D-MRCP, TIRM, and HASTE and testing for noninferiority of non-MRCP T2-weighted sequences compared with 3D-MRCP.</AbstractText Thirty-three of 342 patients (9.7%) were diagnosed with PD using the reference standard. Sensitivity/specificity of 3D-MRCP for detecting PD were 81.2%/69.7% (p < 0.001). Sensitivity/specificity of TIRM and HASTE were 92.5%/93.9 and 98.1%/97.0%, respectively (p < 0.001 each). Grouped sensitivity/specificity of non-MRCP T2-weighted sequences were 99.8%/91.0%. Non-MRCP T2-weighted sequences were non-inferior to 3D-MRCP alone for diagnosis of PD. 20.2, 7.3%, and 2.3% of 3D-MRCP, TIRM, and HASTE, respectively, were not evaluable due to motion artifacts or insufficient duct depiction.</AbstractText Non-MRCP T2-weighted MRI sequences offer high performance for diagnosis of PD and are noninferior to 3D-MRCP alone.</AbstractText Not applicable.</AbstractText
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To investigate the ability of T1 mapping to visualize and quantify the short-term and mid-term response of autoimmune pancreatitis (AIP) to corticosteroid treatment (CST) and to correlate T1 relaxation time of the pancreas with clinical status and serum IgG4 level.</AbstractText The institutional review board approved this prospective study, and all patients provided written informed consent. Pancreatic MRI including native T1 mapping was performed in 39 AIP patients before and during CST, and 40 patients without pancreatic diseases served as control. T1 relaxation time of the pancreatic head, body, and tail was measured in each patient. Clinical symptoms and serum IgG4 level of the patients were recorded.</AbstractText The native T1 relaxation time of AIP was significantly elongated compared to normal pancreatic tissue (1124.5 ms ± 95.7 ms vs 784.3 ms ± 41.8 ms, p < 0.001). After short-term CST (4 weeks), T1 relaxation time of AIP already shortened significantly (957.2 ms ± 97.3 ms, p < 0.001). After mid-term CST (12 weeks), the T1 relaxation time further shortened towards normalization (844.2 ms ± 71.6 ms, p < 0.001). In 33 AIP patients with elevated serum IgG4 at baseline, T1 relaxation time demonstrated a significant positive correlation with serum IgG4 level (r = 0.329, p = 0.011). In six AIP patients with normal serum IgG4 level at baseline, T1 relaxation time shortening preceded or was in accordance with symptom relief.</AbstractText Native T1 mapping can be used to assess parenchymal inflammation of AIP and to quantify response to treatment. It provides a quantitative outcome surrogate for AIP.</AbstractText • Parenchymal inflammation in autoimmune pancreatitis results in T1 relaxation time elongation, which shortens after effective treatment. • T1 relaxation time of the pancreas correlates with serum IgG4 level, and in serum IgG4-negative AIP patients, T1 relaxation time shortening predicts clinical improvement. • T1 mapping provides a quantitative outcome surrogate for AIP.</AbstractText
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Assessing the pathogenicity of genetic variants can be a complex and challenging task. Spliceogenic variants, which alter mRNA splicing, may yield mature transcripts that encode non-functional protein products, an important predictor of Mendelian disease risk. However, most variant annotation tools do not adequately assess spliceogenicity outside the native splice site and thus the disease-causing potential of variants in other intronic and exonic regions is often overlooked. Here, we present a plugin for the Ensembl Variant Effect Predictor that packages MaxEntScan and extends its functionality to provide splice site predictions using a maximum entropy model. The plugin incorporates a sliding window algorithm to predict splice site loss or gain for any variant that overlaps a transcript feature. We also demonstrate the utility of the plugin by comparing our predictions to two mRNA splicing datasets containing several cancer-susceptibility genes.</AbstractText Source code is freely available under the Apache License, Version 2.0: https://github.com/Ensembl/VEP_plugins.</AbstractText Supplementary data are available at Bioinformatics online.</AbstractText
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Is MRCP necessary to diagnose pancreas divisum? The purpose of this study is to compare the performance of three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) with non-MRCP T2-weighted magnetic resonance imaging (MRI) sequences for diagnosis of pancreas divisum (PD).</AbstractText This is a retrospective study of 342 consecutive patients with abdominal MRI including 3D-MRCP. 3D-MRCP was a coronal respiration-navigated T2-weighted sequence with 1.5 mm slice thickness. Non-MRCP T2-weighted sequences were (1) a coronal inversion recovery sequence (TIRM) with 6 mm slice thickness and (2) a transverse single shot turbo spin echo sequence (HASTE) with 4 mm slice thickness. For 3D-MRCP, TIRM, and HASTE, presence of PD and assessment of evaluability were determined in a randomized manner. A consensus read by two radiologists using 3D-MRCP, non-MRCP T2-weighted sequences, and other available imaging sequences served as reference standard for diagnosis of PD. Statistical analysis included performance analysis of 3D-MRCP, TIRM, and HASTE and testing for noninferiority of non-MRCP T2-weighted sequences compared with 3D-MRCP.</AbstractText Thirty-three of 342 patients (9.7%) were diagnosed with PD using the reference standard. Sensitivity/specificity of 3D-MRCP for detecting PD were 81.2%/69.7% (p < 0.001). Sensitivity/specificity of TIRM and HASTE were 92.5%/93.9 and 98.1%/97.0%, respectively (p < 0.001 each). Grouped sensitivity/specificity of non-MRCP T2-weighted sequences were 99.8%/91.0%. Non-MRCP T2-weighted sequences were non-inferior to 3D-MRCP alone for diagnosis of PD. 20.2, 7.3%, and 2.3% of 3D-MRCP, TIRM, and HASTE, respectively, were not evaluable due to motion artifacts or insufficient duct depiction.</AbstractText Non-MRCP T2-weighted MRI sequences offer high performance for diagnosis of PD and are noninferior to 3D-MRCP alone.</AbstractText Not applicable.</AbstractText
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Native T1 mapping of autoimmune pancreatitis as a quantitative outcome surrogate. To investigate the ability of T1 mapping to visualize and quantify the short-term and mid-term response of autoimmune pancreatitis (AIP) to corticosteroid treatment (CST) and to correlate T1 relaxation time of the pancreas with clinical status and serum IgG4 level.</AbstractText The institutional review board approved this prospective study, and all patients provided written informed consent. Pancreatic MRI including native T1 mapping was performed in 39 AIP patients before and during CST, and 40 patients without pancreatic diseases served as control. T1 relaxation time of the pancreatic head, body, and tail was measured in each patient. Clinical symptoms and serum IgG4 level of the patients were recorded.</AbstractText The native T1 relaxation time of AIP was significantly elongated compared to normal pancreatic tissue (1124.5 ms ± 95.7 ms vs 784.3 ms ± 41.8 ms, p < 0.001). After short-term CST (4 weeks), T1 relaxation time of AIP already shortened significantly (957.2 ms ± 97.3 ms, p < 0.001). After mid-term CST (12 weeks), the T1 relaxation time further shortened towards normalization (844.2 ms ± 71.6 ms, p < 0.001). In 33 AIP patients with elevated serum IgG4 at baseline, T1 relaxation time demonstrated a significant positive correlation with serum IgG4 level (r = 0.329, p = 0.011). In six AIP patients with normal serum IgG4 level at baseline, T1 relaxation time shortening preceded or was in accordance with symptom relief.</AbstractText Native T1 mapping can be used to assess parenchymal inflammation of AIP and to quantify response to treatment. It provides a quantitative outcome surrogate for AIP.</AbstractText • Parenchymal inflammation in autoimmune pancreatitis results in T1 relaxation time elongation, which shortens after effective treatment. • T1 relaxation time of the pancreas correlates with serum IgG4 level, and in serum IgG4-negative AIP patients, T1 relaxation time shortening predicts clinical improvement. • T1 mapping provides a quantitative outcome surrogate for AIP.</AbstractText
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A plugin for the Ensembl Variant Effect Predictor that uses MaxEntScan to predict variant spliceogenicity. Assessing the pathogenicity of genetic variants can be a complex and challenging task. Spliceogenic variants, which alter mRNA splicing, may yield mature transcripts that encode non-functional protein products, an important predictor of Mendelian disease risk. However, most variant annotation tools do not adequately assess spliceogenicity outside the native splice site and thus the disease-causing potential of variants in other intronic and exonic regions is often overlooked. Here, we present a plugin for the Ensembl Variant Effect Predictor that packages MaxEntScan and extends its functionality to provide splice site predictions using a maximum entropy model. The plugin incorporates a sliding window algorithm to predict splice site loss or gain for any variant that overlaps a transcript feature. We also demonstrate the utility of the plugin by comparing our predictions to two mRNA splicing datasets containing several cancer-susceptibility genes.</AbstractText Source code is freely available under the Apache License, Version 2.0: https://github.com/Ensembl/VEP_plugins.</AbstractText Supplementary data are available at Bioinformatics online.</AbstractText
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35792417
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38761445
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35196138
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Sensitivity of portable low-field magnetic resonance imaging for multiple sclerosis lesions.
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Assessment of first-time and repeated acute adverse reactions to gadolinium-based contrast agents in MRI: A retrospective study.
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Cluttering in the Speech of Young Men With Fragile X Syndrome.
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Magnetic resonance imaging (MRI) is a fundamental tool in the diagnosis and management of neurological diseases such as multiple sclerosis (MS). New portable, low-field strength, MRI scanners could potentially lower financial and technical barriers to neuroimaging and reach underserved or disabled populations, but the sensitivity of these devices for MS lesions is unknown. We sought to determine if white matter lesions can be detected on a portable 64mT scanner, compare automated lesion segmentations and total lesion volume between paired 3T and 64mT scans, identify features that contribute to lesion detection accuracy, and explore super-resolution imaging at low-field. In this prospective, cross-sectional study, same-day brain MRI (FLAIR, T1w, and T2w) scans were collected from 36 adults (32 women; mean age, 50 ± 14 years) with known or suspected MS using Siemens 3T (FLAIR: 1 mm isotropic, T1w: 1 mm isotropic, and T2w: 0.34-0.5 × 0.34-0.5 × 3-5 mm) and Hyperfine 64mT (FLAIR: 1.6 × 1.6 × 5 mm, T1w: 1.5 × 1.5 × 5 mm, and T2w: 1.5 × 1.5 × 5 mm) scanners at two centers. Images were reviewed by neuroradiologists. MS lesions were measured manually and segmented using an automated algorithm. Statistical analyses assessed accuracy and variability of segmentations across scanners and systematic scanner biases in automated volumetric measurements. Lesions were identified on 64mT scans in 94% (31/33) of patients with confirmed MS. The average smallest lesions manually detected were 5.7 ± 1.3 mm in maximum diameter at 64mT vs 2.1 ± 0.6 mm at 3T, approaching the spatial resolution of the respective scanner sequences (3T: 1 mm, 64mT: 5 mm slice thickness). Automated lesion volume estimates were highly correlated between 3T and 64mT scans (r = 0.89, p < 0.001). Bland-Altman analysis identified bias in 64mT segmentations (mean = 1.6 ml, standard error = 5.2 ml, limits of agreement = -19.0-15.9 ml), which over-estimated low lesion volume and under-estimated high volume (r = 0.74, p < 0.001). Visual inspection revealed over-segmentation was driven venous hyperintensities on 64mT T2-FLAIR. Lesion size drove segmentation accuracy, with 93% of lesions > 1.0 ml and all lesions > 1.5 ml being detected. Using multi-acquisition volume averaging, we were able to generate 1.6 mm isotropic images on the 64mT device. Overall, our results demonstrate that in established MS, a portable 64mT MRI scanner can identify white matter lesions, and that automated estimates of total lesion volume correlate with measurements from 3T scans.</AbstractText
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To identify gadolinium-based contrast agents (GBCAs)-related and patient-related risk factors for acute adverse reactions (AARs), and to examine the incidence and severity of repeated AARs.</AbstractText This study retrospectively evaluated all intravenous GBCA injections in MRI studies at a single institution from January 2012 to September 2019. First-time AARs in patients without a past history of AARs and risk factors were assessed using multivariable regression models with generalized estimating equations. For patients with a past history of AAR(s), we evaluated the incidence of repeated AARs using the Fisher's exact test, as well as the severity of these repeated AARs.</AbstractText First-time AARs occurred in 129 of 41,827 GBCA injections (0.31 %; 0.70 % of 18,431 patients). With gadoterate meglumine as the reference, the odds ratio (OR) for allergic-like reactions to three GBCAs ranged from 3.27 to 8.03 (p = 0.012 to <0.001). For chemotoxic reactions, the OR was 3.75 (p = 0.001) for gadoteridol. Outpatients had a lower OR for chemotoxic reactions, while higher ORs were observed in head/neck and breast MRI (p < 0.05). The OR for age was 0.99 (p < 0.05). Patients with a past history of AAR(s) had a 3.6 % incidence of mild repeated AARs for all GBCA, significantly higher than the 0.31 % in first-time AARs (p < 0.001). No effectiveness was found for steroid premedication.</AbstractText The occurrence of first-time AARs was related to the GBCA used and other factors. The incidence of repeated AARs was higher than first-time AARs, though all were mild in severity.</AbstractText
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Cluttering is a fluency disorder that has been noted clinically in individuals with fragile X syndrome (FXS). Yet, cluttering has not been systematically characterized in this population, hindering identification and intervention efforts. This study examined the rates of cluttering in male young adults with FXS using expert clinical opinion, the alignment between expert clinical opinion and objectively quantified features of cluttering from language transcripts, and the association between cluttering and aspects of the FXS phenotype.</AbstractText Thirty-six men with FXS (aged 18-26 years; <i Clinical experts determined that 50% of participants met the criteria for a cluttering diagnosis. Phrase repetitions were the most salient feature that distinguished individuals who cluttered. Although the presence of cluttering was not associated with autism symptoms or mean length of utterance, cluttering was more likely to occur when nonverbal cognitive ability was higher, ADHD symptoms were elevated, and anxiety symptoms were low.</AbstractText Half of the male young adults with FXS exhibited cluttering, which supports FXS as a genetic diagnosis that is highly enriched for risk of cluttering. Cluttering was associated with increased ADHD symptoms and cognitive ability and reduced anxiety symptoms. This study contributes a new description of the clinical presentation of cluttering in men with FXS and may lead to improved understanding of the potential underlying mechanisms of cluttering and eventual refinements to treatment and diagnosis.</AbstractText
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Sensitivity of portable low-field magnetic resonance imaging for multiple sclerosis lesions. Magnetic resonance imaging (MRI) is a fundamental tool in the diagnosis and management of neurological diseases such as multiple sclerosis (MS). New portable, low-field strength, MRI scanners could potentially lower financial and technical barriers to neuroimaging and reach underserved or disabled populations, but the sensitivity of these devices for MS lesions is unknown. We sought to determine if white matter lesions can be detected on a portable 64mT scanner, compare automated lesion segmentations and total lesion volume between paired 3T and 64mT scans, identify features that contribute to lesion detection accuracy, and explore super-resolution imaging at low-field. In this prospective, cross-sectional study, same-day brain MRI (FLAIR, T1w, and T2w) scans were collected from 36 adults (32 women; mean age, 50 ± 14 years) with known or suspected MS using Siemens 3T (FLAIR: 1 mm isotropic, T1w: 1 mm isotropic, and T2w: 0.34-0.5 × 0.34-0.5 × 3-5 mm) and Hyperfine 64mT (FLAIR: 1.6 × 1.6 × 5 mm, T1w: 1.5 × 1.5 × 5 mm, and T2w: 1.5 × 1.5 × 5 mm) scanners at two centers. Images were reviewed by neuroradiologists. MS lesions were measured manually and segmented using an automated algorithm. Statistical analyses assessed accuracy and variability of segmentations across scanners and systematic scanner biases in automated volumetric measurements. Lesions were identified on 64mT scans in 94% (31/33) of patients with confirmed MS. The average smallest lesions manually detected were 5.7 ± 1.3 mm in maximum diameter at 64mT vs 2.1 ± 0.6 mm at 3T, approaching the spatial resolution of the respective scanner sequences (3T: 1 mm, 64mT: 5 mm slice thickness). Automated lesion volume estimates were highly correlated between 3T and 64mT scans (r = 0.89, p < 0.001). Bland-Altman analysis identified bias in 64mT segmentations (mean = 1.6 ml, standard error = 5.2 ml, limits of agreement = -19.0-15.9 ml), which over-estimated low lesion volume and under-estimated high volume (r = 0.74, p < 0.001). Visual inspection revealed over-segmentation was driven venous hyperintensities on 64mT T2-FLAIR. Lesion size drove segmentation accuracy, with 93% of lesions > 1.0 ml and all lesions > 1.5 ml being detected. Using multi-acquisition volume averaging, we were able to generate 1.6 mm isotropic images on the 64mT device. Overall, our results demonstrate that in established MS, a portable 64mT MRI scanner can identify white matter lesions, and that automated estimates of total lesion volume correlate with measurements from 3T scans.</AbstractText
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Assessment of first-time and repeated acute adverse reactions to gadolinium-based contrast agents in MRI: A retrospective study. To identify gadolinium-based contrast agents (GBCAs)-related and patient-related risk factors for acute adverse reactions (AARs), and to examine the incidence and severity of repeated AARs.</AbstractText This study retrospectively evaluated all intravenous GBCA injections in MRI studies at a single institution from January 2012 to September 2019. First-time AARs in patients without a past history of AARs and risk factors were assessed using multivariable regression models with generalized estimating equations. For patients with a past history of AAR(s), we evaluated the incidence of repeated AARs using the Fisher's exact test, as well as the severity of these repeated AARs.</AbstractText First-time AARs occurred in 129 of 41,827 GBCA injections (0.31 %; 0.70 % of 18,431 patients). With gadoterate meglumine as the reference, the odds ratio (OR) for allergic-like reactions to three GBCAs ranged from 3.27 to 8.03 (p = 0.012 to <0.001). For chemotoxic reactions, the OR was 3.75 (p = 0.001) for gadoteridol. Outpatients had a lower OR for chemotoxic reactions, while higher ORs were observed in head/neck and breast MRI (p < 0.05). The OR for age was 0.99 (p < 0.05). Patients with a past history of AAR(s) had a 3.6 % incidence of mild repeated AARs for all GBCA, significantly higher than the 0.31 % in first-time AARs (p < 0.001). No effectiveness was found for steroid premedication.</AbstractText The occurrence of first-time AARs was related to the GBCA used and other factors. The incidence of repeated AARs was higher than first-time AARs, though all were mild in severity.</AbstractText
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Cluttering in the Speech of Young Men With Fragile X Syndrome. Cluttering is a fluency disorder that has been noted clinically in individuals with fragile X syndrome (FXS). Yet, cluttering has not been systematically characterized in this population, hindering identification and intervention efforts. This study examined the rates of cluttering in male young adults with FXS using expert clinical opinion, the alignment between expert clinical opinion and objectively quantified features of cluttering from language transcripts, and the association between cluttering and aspects of the FXS phenotype.</AbstractText Thirty-six men with FXS (aged 18-26 years; <i Clinical experts determined that 50% of participants met the criteria for a cluttering diagnosis. Phrase repetitions were the most salient feature that distinguished individuals who cluttered. Although the presence of cluttering was not associated with autism symptoms or mean length of utterance, cluttering was more likely to occur when nonverbal cognitive ability was higher, ADHD symptoms were elevated, and anxiety symptoms were low.</AbstractText Half of the male young adults with FXS exhibited cluttering, which supports FXS as a genetic diagnosis that is highly enriched for risk of cluttering. Cluttering was associated with increased ADHD symptoms and cognitive ability and reduced anxiety symptoms. This study contributes a new description of the clinical presentation of cluttering in men with FXS and may lead to improved understanding of the potential underlying mechanisms of cluttering and eventual refinements to treatment and diagnosis.</AbstractText
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29130867
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20346985
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29364068
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Using the experience-sampling method to examine the psychological mechanisms by which participatory art improves wellbeing.
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Exercise as a countermeasure to psycho-physiological deconditioning during long-term confinement.
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Methods for chair restraint and training of the common marmoset on oculomotor tasks.
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To measure the immediate impact of art-making in everyday life on diverse indices of wellbeing ('in the moment' and longer term) in order to improve understanding of the psychological mechanisms by which art may improve mental health.</AbstractText Using the experience-sampling method, 41 artists were prompted (with a 'beep' on a handheld computer) at random intervals (10 times a day, for one week) to answer a short questionnaire. The questionnaire tracked art-making and enquired about mood, cognition and state of consciousness. This resulted in 2,495 sampled experiences, with a high response rate in which 89% of questionnaires were completed.</AbstractText Multi-level modelling was used to evaluate the impact of art-making on experience, with 2,495 'experiences' (experiential-level) nested within 41 participants (person-level). Recent art-making was significantly associated with experiential shifts: improvement in hedonic tone, vivid internal imagery and the flow state. Furthermore, the frequency of art-making across the week was associated with person-level measures of wellbeing: eudemonic happiness and self-regulation. Cross-level interactions, between experiential and person-level variables, suggested that hedonic tone improved more for those scoring low on eudemonic happiness, and further that, those high in eudemonic happiness were more likely to experience phenomenological features of the flow state and to experience inner dialogue while art-making.</AbstractText Art-making has both immediate and long-term associations with wellbeing. At the experiential level, art-making affects multiple dimensions of conscious experience: affective, cognitive and state factors. This suggests that there are multiple routes to wellbeing (improving hedonic tone, making meaning through inner dialogue and experiencing the flow state). Recommendations are made to consider these factors when both developing and evaluating public health interventions that involve participatory art.</AbstractText
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Confinement studies are performed to simulate the psychological effects that may be experienced on a long-term space flight. A general psycho-physiological model assumes that mood and cognitive functioning are impaired during confinement as a result of an absence of physical activity. The aim of the MARS500 study initiated by the Institute of Biomedical Problems (IBMP) and the European Space Agency (ESA) is to gather data, knowledge and experience to help prepare for a real mission to Mars. A test run with 105 days of isolation was performed prior to 520 days of isolation. Psycho-physiological data of this study are presented here. We hypothesized that exercise, as it has been shown in laboratory settings, would be able to prevent and counteract mood changes during isolation. Electrocortical data (EEG) and a self report on current psychological and physical state were recorded several times prior to and after exercise during the isolation period. Data revealed a clear effect of exercise on mood and electrocortical activity. Moreover, it was shown that mood and brain cortical activity decreased during the first 11 weeks of isolation and reached baseline again in the last week of isolation. A correlation analysis revealed a significant relation between mood data and electrocortical activity. We conclude (1) that confinement is accompanied by psycho-physiological changes and (2) that exercise is a suitable method to counteract psycho-physiological deconditioning during confinement.</AbstractText
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The oculomotor system is the most thoroughly understood sensorimotor system in the brain, due in large part to electrophysiological studies carried out in macaque monkeys trained to perform oculomotor tasks. A disadvantage of the macaque model is that many cortical oculomotor areas of interest lie within sulci, making high-density array and laminar recordings impractical. Many techniques of molecular biology developed in rodents, such as optogenetic manipulation of neuronal subtypes, are also limited in this species. The common marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to frontoparietal oculomotor areas, and may bridge the gap between systems neuroscience in macaques and molecular techniques. Techniques for restraint, training, and neural recording in these animals have been well developed in auditory neuroscience. Those for oculomotor neuroscience, however, remain at a relatively early stage. In this article we provide details of a custom-designed restraint chair for marmosets, a combination head restraint/recording chamber allowing access to cortical oculomotor areas and providing stability suitable for eye movement and neural recordings, as well as a training protocol for oculomotor tasks. We additionally report the results of a psychophysical study in marmosets trained to perform a saccade task using these methods, showing that, as in rhesus and humans, marmosets exhibit a "gap effect," a decrease in reaction time when the fixation stimulus is removed before the onset of a visual saccade target. These results are the first evidence of this effect in marmosets and support the common marmoset model for neurophysiological investigations of oculomotor control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in behaving primates has provided a wealth of information regarding the neural circuits underlying the control of eye movements. Such studies require restraint of the animal within a primate chair, head fixation, methods of acclimating the animals to this restraint, and the use of operant conditioning methods for training on oculomotor tasks. In contrast to the macaque model, relatively few studies have reported in detail methods for use in the common marmoset. In this report we detail custom-designed equipment and methods by which we have used to successfully train head-restrained marmosets to perform basic oculomotor tasks.</AbstractText
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Using the experience-sampling method to examine the psychological mechanisms by which participatory art improves wellbeing. To measure the immediate impact of art-making in everyday life on diverse indices of wellbeing ('in the moment' and longer term) in order to improve understanding of the psychological mechanisms by which art may improve mental health.</AbstractText Using the experience-sampling method, 41 artists were prompted (with a 'beep' on a handheld computer) at random intervals (10 times a day, for one week) to answer a short questionnaire. The questionnaire tracked art-making and enquired about mood, cognition and state of consciousness. This resulted in 2,495 sampled experiences, with a high response rate in which 89% of questionnaires were completed.</AbstractText Multi-level modelling was used to evaluate the impact of art-making on experience, with 2,495 'experiences' (experiential-level) nested within 41 participants (person-level). Recent art-making was significantly associated with experiential shifts: improvement in hedonic tone, vivid internal imagery and the flow state. Furthermore, the frequency of art-making across the week was associated with person-level measures of wellbeing: eudemonic happiness and self-regulation. Cross-level interactions, between experiential and person-level variables, suggested that hedonic tone improved more for those scoring low on eudemonic happiness, and further that, those high in eudemonic happiness were more likely to experience phenomenological features of the flow state and to experience inner dialogue while art-making.</AbstractText Art-making has both immediate and long-term associations with wellbeing. At the experiential level, art-making affects multiple dimensions of conscious experience: affective, cognitive and state factors. This suggests that there are multiple routes to wellbeing (improving hedonic tone, making meaning through inner dialogue and experiencing the flow state). Recommendations are made to consider these factors when both developing and evaluating public health interventions that involve participatory art.</AbstractText
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Exercise as a countermeasure to psycho-physiological deconditioning during long-term confinement. Confinement studies are performed to simulate the psychological effects that may be experienced on a long-term space flight. A general psycho-physiological model assumes that mood and cognitive functioning are impaired during confinement as a result of an absence of physical activity. The aim of the MARS500 study initiated by the Institute of Biomedical Problems (IBMP) and the European Space Agency (ESA) is to gather data, knowledge and experience to help prepare for a real mission to Mars. A test run with 105 days of isolation was performed prior to 520 days of isolation. Psycho-physiological data of this study are presented here. We hypothesized that exercise, as it has been shown in laboratory settings, would be able to prevent and counteract mood changes during isolation. Electrocortical data (EEG) and a self report on current psychological and physical state were recorded several times prior to and after exercise during the isolation period. Data revealed a clear effect of exercise on mood and electrocortical activity. Moreover, it was shown that mood and brain cortical activity decreased during the first 11 weeks of isolation and reached baseline again in the last week of isolation. A correlation analysis revealed a significant relation between mood data and electrocortical activity. We conclude (1) that confinement is accompanied by psycho-physiological changes and (2) that exercise is a suitable method to counteract psycho-physiological deconditioning during confinement.</AbstractText
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Methods for chair restraint and training of the common marmoset on oculomotor tasks. The oculomotor system is the most thoroughly understood sensorimotor system in the brain, due in large part to electrophysiological studies carried out in macaque monkeys trained to perform oculomotor tasks. A disadvantage of the macaque model is that many cortical oculomotor areas of interest lie within sulci, making high-density array and laminar recordings impractical. Many techniques of molecular biology developed in rodents, such as optogenetic manipulation of neuronal subtypes, are also limited in this species. The common marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to frontoparietal oculomotor areas, and may bridge the gap between systems neuroscience in macaques and molecular techniques. Techniques for restraint, training, and neural recording in these animals have been well developed in auditory neuroscience. Those for oculomotor neuroscience, however, remain at a relatively early stage. In this article we provide details of a custom-designed restraint chair for marmosets, a combination head restraint/recording chamber allowing access to cortical oculomotor areas and providing stability suitable for eye movement and neural recordings, as well as a training protocol for oculomotor tasks. We additionally report the results of a psychophysical study in marmosets trained to perform a saccade task using these methods, showing that, as in rhesus and humans, marmosets exhibit a "gap effect," a decrease in reaction time when the fixation stimulus is removed before the onset of a visual saccade target. These results are the first evidence of this effect in marmosets and support the common marmoset model for neurophysiological investigations of oculomotor control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in behaving primates has provided a wealth of information regarding the neural circuits underlying the control of eye movements. Such studies require restraint of the animal within a primate chair, head fixation, methods of acclimating the animals to this restraint, and the use of operant conditioning methods for training on oculomotor tasks. In contrast to the macaque model, relatively few studies have reported in detail methods for use in the common marmoset. In this report we detail custom-designed equipment and methods by which we have used to successfully train head-restrained marmosets to perform basic oculomotor tasks.</AbstractText
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32863021
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26441373
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32143546
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Experience sampling of the degree of mind wandering distinguishes hidden attentional states.
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A systematic review of the neurophysiology of mindfulness on EEG oscillations.
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Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery.
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Experience sampling of attentional states has consistently demonstrated that mind wandering is a frequent and disruptive obstacle when one must sustain attention during continuous task performance. Yet, methods commonly used to assess the subjective experience of mind wandering may conflate several potential sources of meaningful variation in individuals' degree of task engagement. In the present study, we examined evidence for distinct and identifiable patterns in subjective reports of the degree of task-related attentional focus during a sustained attention task in a large sample of adults (N = 537). Experience sampling probes embedded in the task assessed task-related focus using a continuum of response ratings ranging from 1 (on-task) to 6 (off-task). Participants used a range of probe response options in categorizing their current attentional state, and the continuum of probe ratings differentiated patterns of behavioral performance in the moments preceding probes. Markov-chain modeling of the categorical time series sequence of probe ratings further revealed distinct and behaviorally relevant hidden states underlying probe rating behavior. We replicated these findings in two additional independent data sets. Collectively, these findings suggest that three or more hidden attentional states best account for subjective ratings of task-related focus. The implications of these findings for models of sustained attention and mind wandering are discussed.</AbstractText
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Mindfulness meditation has been purported to be a beneficial practice for wellbeing. It would therefore be expected that the neurophysiology of mindfulness would reflect this impact on wellbeing. However, investigations of the effects of mindfulness have generated mixed reports of increases, decreases, as well as no differences in EEG oscillations in comparison with a resting state and a variety of tasks. We have performed a systematic review of EEG studies of mindfulness meditation in order to determine any common effects and to identify factors which may impact on the effects. Databases were reviewed from 1966 to August 2015. Eligibility criteria included empirical quantitative analyses of mindfulness meditation practice and EEG measurements acquired in relation to practice. A total of 56 papers met the eligibility criteria and were included in the systematic review, consisting of a total 1715 subjects: 1358 healthy individuals and 357 individuals with psychiatric diagnoses. Studies were principally examined for power outcomes in each bandwidth, in particular the power differentials between mindfulness and a control state, as well as outcomes relating to hemispheric asymmetry and event-related potentials. The systematic review revealed that mindfulness was most commonly associated with enhanced alpha and theta power as compared to an eyes closed resting state, although such outcomes were not uniformly reported. No consistent patterns were observed with respect to beta, delta and gamma bandwidths. In summary, mindfulness is associated with increased alpha and theta power in both healthy individuals and in patient groups. This co-presence of elevated alpha and theta may signify a state of relaxed alertness which is conducive to mental health.</AbstractText
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<b
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Experience sampling of the degree of mind wandering distinguishes hidden attentional states. Experience sampling of attentional states has consistently demonstrated that mind wandering is a frequent and disruptive obstacle when one must sustain attention during continuous task performance. Yet, methods commonly used to assess the subjective experience of mind wandering may conflate several potential sources of meaningful variation in individuals' degree of task engagement. In the present study, we examined evidence for distinct and identifiable patterns in subjective reports of the degree of task-related attentional focus during a sustained attention task in a large sample of adults (N = 537). Experience sampling probes embedded in the task assessed task-related focus using a continuum of response ratings ranging from 1 (on-task) to 6 (off-task). Participants used a range of probe response options in categorizing their current attentional state, and the continuum of probe ratings differentiated patterns of behavioral performance in the moments preceding probes. Markov-chain modeling of the categorical time series sequence of probe ratings further revealed distinct and behaviorally relevant hidden states underlying probe rating behavior. We replicated these findings in two additional independent data sets. Collectively, these findings suggest that three or more hidden attentional states best account for subjective ratings of task-related focus. The implications of these findings for models of sustained attention and mind wandering are discussed.</AbstractText
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A systematic review of the neurophysiology of mindfulness on EEG oscillations. Mindfulness meditation has been purported to be a beneficial practice for wellbeing. It would therefore be expected that the neurophysiology of mindfulness would reflect this impact on wellbeing. However, investigations of the effects of mindfulness have generated mixed reports of increases, decreases, as well as no differences in EEG oscillations in comparison with a resting state and a variety of tasks. We have performed a systematic review of EEG studies of mindfulness meditation in order to determine any common effects and to identify factors which may impact on the effects. Databases were reviewed from 1966 to August 2015. Eligibility criteria included empirical quantitative analyses of mindfulness meditation practice and EEG measurements acquired in relation to practice. A total of 56 papers met the eligibility criteria and were included in the systematic review, consisting of a total 1715 subjects: 1358 healthy individuals and 357 individuals with psychiatric diagnoses. Studies were principally examined for power outcomes in each bandwidth, in particular the power differentials between mindfulness and a control state, as well as outcomes relating to hemispheric asymmetry and event-related potentials. The systematic review revealed that mindfulness was most commonly associated with enhanced alpha and theta power as compared to an eyes closed resting state, although such outcomes were not uniformly reported. No consistent patterns were observed with respect to beta, delta and gamma bandwidths. In summary, mindfulness is associated with increased alpha and theta power in both healthy individuals and in patient groups. This co-presence of elevated alpha and theta may signify a state of relaxed alertness which is conducive to mental health.</AbstractText
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Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery. <b
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37151137
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29216391
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37016005
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Improved automatic identification of isolated rapid eye movement sleep behavior disorder with a 3D time-of-flight camera.
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Prevalence and determinants of rapid eye movement sleep behavior disorder in the general population.
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Self-forgiveness is associated with increased volumes of fusiform gyrus in healthy individuals.
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Automatic 3D video analysis of the lower body during rapid eye movement (REM) sleep has been recently proposed as a novel tool for identifying people with isolated REM sleep behavior disorder (iRBD), but, so far, it has not been validated on unseen subjects. This study aims at validating this technology in a large cohort and at improving its performances by also including an analysis of movements in the head, hands and upper body.</AbstractText Fifty-three people with iRBD and 128 people without RBD (of whom 89 had sleep disorders considered RBD differential diagnoses) were included in the study. An automatic algorithm identified movements from 3D videos during REM sleep in four regions of interest (ROIs): head, hands, upper body and lower body. The movements were divided into categories according to duration: short (0.1-2 s), medium (2-15 s) and long (15-300 s). For each ROI and duration range, features were obtained from the identified movements. Logistic regression models using as predictors the features from one single ROI or a combination of ROIs were trained and tested in a 10-runs 10-fold cross-validation scheme on the task of differentiating people with iRBD from people without RBD.</AbstractText The best differentiation was achieved using short movements in all four ROIs (test accuracy 0.866 ± 0.007, test F1 score = 0.783 ± 0.010). Single group analyses showed that people with iRBD were distinguished successfully from subjects with RBD differential diagnoses.</AbstractText Automatic 3D video analysis might be implemented in clinical routine as a supportive screening tool for identifying people with RBD.</AbstractText
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Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with neurodegenerative synucleinopathies. Its prevalence is largely unknown. This study determined the prevalence and characteristics of RBD in the general population using gold-standard polysomnography.</AbstractText Full polysomnographic data from 1,997 participants (age = 59 ± 11.1 years, 53.6% women) participating in a population-based study (HypnoLaus, Lausanne, Switzerland) were collected. Sleep-related complaints and habits were investigated using various sleep measures including the Munich Parasomnia Screening (MUPS) questionnaire, which includes two questions evaluating complex motor behaviors suggestive of RBD. Full polysomnography was performed at home. For participants screening positive for RBD, muscle activity during REM sleep was quantified to diagnose RBD.</AbstractText Three hundred sixty-eight participants endorsed dream-enactment behavior on either of the two MUPS questions, and 21 fulfilled polysomnographic criteria for RBD, resulting in an estimated prevalence of 1.06% (95% CI = 0.61-1.50), with no difference between men and women. Compared with RBD- participants, RBD+ took more frequently antidepressants and antipsychotics (23.8% vs. 5.4%, p = .005; 14.3% vs. 1.5%, p = .004, respectively) and were more frequently smokers or ex-smokers (85% vs. 56.6%, p = .011). On polysomnography, RBD+ had more stage N2 sleep (52 ± 11.5% vs. 46.3 ± 10.2%, p = .024) and less REM sleep (18 ± 6.4% vs. 21.9 ± 6.2%, p = .007), lower apnea-hypopnea index in REM sleep (3.8 ± 5.2 vs. 8.9 ± 13/hour, p = .035), and lower autonomic arousal index (31 ± 14.9 vs. 42.6 ± 19.5/hour, p = .002).</AbstractText In our middle-to-older age population-based sample, the prevalence of RBD was 1.06%, with no difference between men and women. RBD was associated with antidepressant and antipsychotic use and with minor differences in sleep structure.</AbstractText
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Self-forgiveness (SF) involves a process through which negative moral emotions directed at the self are replaced by benevolence and acceptance. Lower SF scores can be associated with less self-compassion, higher psychological distress, and lower life dissatisfaction. However, neural correlates of SF have not been investigated yet. We enrolled a total of 79 healthy individuals. The Self-Forgiveness Scale (SFS), Self-Compassion Scale (SCS), Connor-Davidson Resilience Scale (CD-RISC), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) were evaluated. Voxel-wise correlational analyses showed a significant positive correlation between the total SFS scores and gray matter volumes (GMVs) in the fusiform gyrus (FG). In addition, the GMVs in the FG were significantly positively associated with the total SCS and CD-RISC scores and negatively correlated with the total BDI-II and BAI scores. These findings suggest that the FG related to the mirror neuron system might be a neural correlate of SF. Furthermore, its increased volumes of FG in healthy individuals can be associated with the capacity to overcome stressful life events.</AbstractText
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Improved automatic identification of isolated rapid eye movement sleep behavior disorder with a 3D time-of-flight camera. Automatic 3D video analysis of the lower body during rapid eye movement (REM) sleep has been recently proposed as a novel tool for identifying people with isolated REM sleep behavior disorder (iRBD), but, so far, it has not been validated on unseen subjects. This study aims at validating this technology in a large cohort and at improving its performances by also including an analysis of movements in the head, hands and upper body.</AbstractText Fifty-three people with iRBD and 128 people without RBD (of whom 89 had sleep disorders considered RBD differential diagnoses) were included in the study. An automatic algorithm identified movements from 3D videos during REM sleep in four regions of interest (ROIs): head, hands, upper body and lower body. The movements were divided into categories according to duration: short (0.1-2 s), medium (2-15 s) and long (15-300 s). For each ROI and duration range, features were obtained from the identified movements. Logistic regression models using as predictors the features from one single ROI or a combination of ROIs were trained and tested in a 10-runs 10-fold cross-validation scheme on the task of differentiating people with iRBD from people without RBD.</AbstractText The best differentiation was achieved using short movements in all four ROIs (test accuracy 0.866 ± 0.007, test F1 score = 0.783 ± 0.010). Single group analyses showed that people with iRBD were distinguished successfully from subjects with RBD differential diagnoses.</AbstractText Automatic 3D video analysis might be implemented in clinical routine as a supportive screening tool for identifying people with RBD.</AbstractText
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Prevalence and determinants of rapid eye movement sleep behavior disorder in the general population. Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with neurodegenerative synucleinopathies. Its prevalence is largely unknown. This study determined the prevalence and characteristics of RBD in the general population using gold-standard polysomnography.</AbstractText Full polysomnographic data from 1,997 participants (age = 59 ± 11.1 years, 53.6% women) participating in a population-based study (HypnoLaus, Lausanne, Switzerland) were collected. Sleep-related complaints and habits were investigated using various sleep measures including the Munich Parasomnia Screening (MUPS) questionnaire, which includes two questions evaluating complex motor behaviors suggestive of RBD. Full polysomnography was performed at home. For participants screening positive for RBD, muscle activity during REM sleep was quantified to diagnose RBD.</AbstractText Three hundred sixty-eight participants endorsed dream-enactment behavior on either of the two MUPS questions, and 21 fulfilled polysomnographic criteria for RBD, resulting in an estimated prevalence of 1.06% (95% CI = 0.61-1.50), with no difference between men and women. Compared with RBD- participants, RBD+ took more frequently antidepressants and antipsychotics (23.8% vs. 5.4%, p = .005; 14.3% vs. 1.5%, p = .004, respectively) and were more frequently smokers or ex-smokers (85% vs. 56.6%, p = .011). On polysomnography, RBD+ had more stage N2 sleep (52 ± 11.5% vs. 46.3 ± 10.2%, p = .024) and less REM sleep (18 ± 6.4% vs. 21.9 ± 6.2%, p = .007), lower apnea-hypopnea index in REM sleep (3.8 ± 5.2 vs. 8.9 ± 13/hour, p = .035), and lower autonomic arousal index (31 ± 14.9 vs. 42.6 ± 19.5/hour, p = .002).</AbstractText In our middle-to-older age population-based sample, the prevalence of RBD was 1.06%, with no difference between men and women. RBD was associated with antidepressant and antipsychotic use and with minor differences in sleep structure.</AbstractText
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Self-forgiveness is associated with increased volumes of fusiform gyrus in healthy individuals. Self-forgiveness (SF) involves a process through which negative moral emotions directed at the self are replaced by benevolence and acceptance. Lower SF scores can be associated with less self-compassion, higher psychological distress, and lower life dissatisfaction. However, neural correlates of SF have not been investigated yet. We enrolled a total of 79 healthy individuals. The Self-Forgiveness Scale (SFS), Self-Compassion Scale (SCS), Connor-Davidson Resilience Scale (CD-RISC), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) were evaluated. Voxel-wise correlational analyses showed a significant positive correlation between the total SFS scores and gray matter volumes (GMVs) in the fusiform gyrus (FG). In addition, the GMVs in the FG were significantly positively associated with the total SCS and CD-RISC scores and negatively correlated with the total BDI-II and BAI scores. These findings suggest that the FG related to the mirror neuron system might be a neural correlate of SF. Furthermore, its increased volumes of FG in healthy individuals can be associated with the capacity to overcome stressful life events.</AbstractText
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36102173
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38159060
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34980287
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Serotonin Transporter Imaging in Multiple System Atrophy and Parkinson's Disease.
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Significance of a positive tau PET scan with a negative amyloid PET scan.
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Olivetolic acid, a cannabinoid precursor in Cannabis sativa, but not CBGA methyl ester exhibits a modest anticonvulsant effect in a mouse model of Dravet syndrome.
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Both Parkinson's disease (PD) and multiple system atrophy (MSA) exhibit degeneration of brainstem serotoninergic nuclei, affecting multiple subcortical and cortical serotoninergic projections. In MSA, medullary serotoninergic neuron pathology is well documented, but serotonin system changes throughout the rest of the brain are less well characterized.</AbstractText To use serotonin transporter [<sup We performed serotonin transporter PET imaging in 18 patients with MSA, 23 patients with PD, and 16 healthy controls to explore differences in brainstem, subcortical, and cortical regions of interest.</AbstractText Patients with MSA showed lower serotonin transporter distribution volume ratios compared with patients with PD in the medulla, raphe pontis, ventral striatum, limbic cortex, and thalamic regions, but no differences in the dorsal striatal, ventral anterior cingulate, or total cortical regions. Controls showed greater cortical serotonin transporter binding compared with PD or MSA groups but lower serotonin transporter binding in the striatum and other relevant basal ganglia regions. There were no regional differences in binding between patients with MSA-parkinsonian subtype (n = 8) and patients with MSA-cerebellar subtype (n = 10). Serotonin transporter distribution volume ratios in multiple different regions of interest showed an inverse correlation with the severity of Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score in patients with MSA but not patients with PD.</AbstractText Brainstem and some forebrain subcortical region serotoninergic deficits are more severe in MSA compared with PD and show an MSA-specific correlation with the severity of motor impairments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</AbstractText
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The implications of positive tau positron emission tomography (T) with negative beta amyloid positron emission tomography (A) are not well understood. We investigated cognitive performance in participants who were T+ but A-.</AbstractText We evaluated 98 participants from the Mayo Clinic who were T+ and A-. Participants were matched 2:1 to A- and T- cognitively unimpaired (CU) controls. Cognitive test scores were compared between different groups.</AbstractText The A-T+ group demonstrated lower performance than the A-T- group on the Mini-Mental Status Exam (MMSE) (p < 0.001), Wechsler Memory Scale-Revised Logical Memory I (p < 0.001) and Logical Memory II (p < 0.001), Auditory Verbal Learning Test (AVLT) delayed recall (p = 0.004), category fluency (animals p = 0.005; vegetables p = 0.021), Trail Making Test A and B (p < 0.001), and others. There were no significant differences in demographic features or apolipoprotein E (APOE) e4 genotype between CU A-T+ and CI A-T+.</AbstractText A-T+ participants show an association with lower cognitive performance.</AbstractText
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Cannabigerolic acid (CBGA), a precursor cannabinoid in Cannabis sativa, has recently been found to have anticonvulsant properties in the Scn1a<sup The brain and plasma pharmacokinetic profiles of CBGA methyl ester and olivetolic acid were examined following 10 mg/kg intraperitoneal (i.p.) administration in mice (n = 4). The anticonvulsant potential of each was examined in male and female Scn1a<sup CBGA methyl ester exhibited relatively limited brain penetration (13%), although somewhat superior to that of 2% for CBGA. No anticonvulsant effects were observed against thermally induced seizures in Scn1a<sup Olivetolic acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a<sup
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Serotonin Transporter Imaging in Multiple System Atrophy and Parkinson's Disease. Both Parkinson's disease (PD) and multiple system atrophy (MSA) exhibit degeneration of brainstem serotoninergic nuclei, affecting multiple subcortical and cortical serotoninergic projections. In MSA, medullary serotoninergic neuron pathology is well documented, but serotonin system changes throughout the rest of the brain are less well characterized.</AbstractText To use serotonin transporter [<sup We performed serotonin transporter PET imaging in 18 patients with MSA, 23 patients with PD, and 16 healthy controls to explore differences in brainstem, subcortical, and cortical regions of interest.</AbstractText Patients with MSA showed lower serotonin transporter distribution volume ratios compared with patients with PD in the medulla, raphe pontis, ventral striatum, limbic cortex, and thalamic regions, but no differences in the dorsal striatal, ventral anterior cingulate, or total cortical regions. Controls showed greater cortical serotonin transporter binding compared with PD or MSA groups but lower serotonin transporter binding in the striatum and other relevant basal ganglia regions. There were no regional differences in binding between patients with MSA-parkinsonian subtype (n = 8) and patients with MSA-cerebellar subtype (n = 10). Serotonin transporter distribution volume ratios in multiple different regions of interest showed an inverse correlation with the severity of Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score in patients with MSA but not patients with PD.</AbstractText Brainstem and some forebrain subcortical region serotoninergic deficits are more severe in MSA compared with PD and show an MSA-specific correlation with the severity of motor impairments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</AbstractText
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Significance of a positive tau PET scan with a negative amyloid PET scan. The implications of positive tau positron emission tomography (T) with negative beta amyloid positron emission tomography (A) are not well understood. We investigated cognitive performance in participants who were T+ but A-.</AbstractText We evaluated 98 participants from the Mayo Clinic who were T+ and A-. Participants were matched 2:1 to A- and T- cognitively unimpaired (CU) controls. Cognitive test scores were compared between different groups.</AbstractText The A-T+ group demonstrated lower performance than the A-T- group on the Mini-Mental Status Exam (MMSE) (p < 0.001), Wechsler Memory Scale-Revised Logical Memory I (p < 0.001) and Logical Memory II (p < 0.001), Auditory Verbal Learning Test (AVLT) delayed recall (p = 0.004), category fluency (animals p = 0.005; vegetables p = 0.021), Trail Making Test A and B (p < 0.001), and others. There were no significant differences in demographic features or apolipoprotein E (APOE) e4 genotype between CU A-T+ and CI A-T+.</AbstractText A-T+ participants show an association with lower cognitive performance.</AbstractText
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Olivetolic acid, a cannabinoid precursor in Cannabis sativa, but not CBGA methyl ester exhibits a modest anticonvulsant effect in a mouse model of Dravet syndrome. Cannabigerolic acid (CBGA), a precursor cannabinoid in Cannabis sativa, has recently been found to have anticonvulsant properties in the Scn1a<sup The brain and plasma pharmacokinetic profiles of CBGA methyl ester and olivetolic acid were examined following 10 mg/kg intraperitoneal (i.p.) administration in mice (n = 4). The anticonvulsant potential of each was examined in male and female Scn1a<sup CBGA methyl ester exhibited relatively limited brain penetration (13%), although somewhat superior to that of 2% for CBGA. No anticonvulsant effects were observed against thermally induced seizures in Scn1a<sup Olivetolic acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a<sup
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37698782
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20018709
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38987277
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Dorsal and ventral fronto-amygdala networks underlie risky decision-making in age-related cognitive decline.
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Performance level modulates adult age differences in brain activation during spatial working memory.
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Body part categorical matching in chimpanzees (Pan troglodytes).
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Older adults often have difficulty in making decisions under uncertainty, increasing the risk of financial exploitation. However, it is still under investigation about the extent to which cognitive decline influences risky decision-making and the underlying neural correlates. We hypothesized that the individual differences of risk-taking behavior depend on cognitive integrity, in which the dorsal and ventral fronto-amygdala connectivity would play dissociable roles. In the current study, thirty-six young and 51 older adults were tested with the Iowa gambling task combing resting-state and task-related functional magnetic resonance imaging. The results showed significant changes in behaviors and the fronto-amygdala network in older adults relative to young adults. More importantly, age-effect on risk-taking behaviors was remarkably different in cognitively normal and impaired older adults. In resting-state analysis, task performance was positively correlated with the ventral fronto-amygdala connectivity and negatively correlated with the dorsal fronto-amygdala connectivity in cognitively impaired older adults, compared with cognitively normal individuals. Furthermore, task-related analysis confirmed the relationships between dorsal/ventral fronto-amygdala network and risk-taking behaviors depending on cognitive integrity. These findings indicate that the fronto-amygdala network is crucial for understanding altered risky decision-making in aging, suggesting dissociable contributions of the dorsal and ventral pathways in the context of cognitive decline.</AbstractText
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Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20-30 years) and 30 older (60-70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more "youth-like" load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.</AbstractText
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Humans categorize body parts, reflecting our knowledge about bodies, and this could be useful in higher-level activities involving bodies. We tested whether humans' closest living relatives-chimpanzees-have the same ability using touchscreen tasks, focusing on the major parts: heads, torsos, arms, and legs. Six chimpanzees were trained to perform a body part matching-to-sample task using sets of pictures of chimpanzee bodies, where in each trial, the sample and choice pictures were the same. Five passed the training and received the test sessions, where three trial types were mixed: trained same-individual picture pairs; novel same-individual picture pairs; and novel different-individual picture pairs. All participants performed better than the chance level in all conditions and for all body parts. Further analyses showed differences in performance when the samples were different body parts. For example, the results revealed better performances for heads and torsos than arms and legs in "novel different-individual pairs". The study showed that chimpanzees can visually match and categorize body parts in this experiment setting, even across different chimpanzees' bodies, suggesting potential biological understanding. Different performances for body parts suggested a deviated categorization from humans. We hope this study will inspire future research on the evolution of body perception.</AbstractText
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Dorsal and ventral fronto-amygdala networks underlie risky decision-making in age-related cognitive decline. Older adults often have difficulty in making decisions under uncertainty, increasing the risk of financial exploitation. However, it is still under investigation about the extent to which cognitive decline influences risky decision-making and the underlying neural correlates. We hypothesized that the individual differences of risk-taking behavior depend on cognitive integrity, in which the dorsal and ventral fronto-amygdala connectivity would play dissociable roles. In the current study, thirty-six young and 51 older adults were tested with the Iowa gambling task combing resting-state and task-related functional magnetic resonance imaging. The results showed significant changes in behaviors and the fronto-amygdala network in older adults relative to young adults. More importantly, age-effect on risk-taking behaviors was remarkably different in cognitively normal and impaired older adults. In resting-state analysis, task performance was positively correlated with the ventral fronto-amygdala connectivity and negatively correlated with the dorsal fronto-amygdala connectivity in cognitively impaired older adults, compared with cognitively normal individuals. Furthermore, task-related analysis confirmed the relationships between dorsal/ventral fronto-amygdala network and risk-taking behaviors depending on cognitive integrity. These findings indicate that the fronto-amygdala network is crucial for understanding altered risky decision-making in aging, suggesting dissociable contributions of the dorsal and ventral pathways in the context of cognitive decline.</AbstractText
|
Performance level modulates adult age differences in brain activation during spatial working memory. Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20-30 years) and 30 older (60-70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more "youth-like" load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.</AbstractText
|
Body part categorical matching in chimpanzees (Pan troglodytes). Humans categorize body parts, reflecting our knowledge about bodies, and this could be useful in higher-level activities involving bodies. We tested whether humans' closest living relatives-chimpanzees-have the same ability using touchscreen tasks, focusing on the major parts: heads, torsos, arms, and legs. Six chimpanzees were trained to perform a body part matching-to-sample task using sets of pictures of chimpanzee bodies, where in each trial, the sample and choice pictures were the same. Five passed the training and received the test sessions, where three trial types were mixed: trained same-individual picture pairs; novel same-individual picture pairs; and novel different-individual picture pairs. All participants performed better than the chance level in all conditions and for all body parts. Further analyses showed differences in performance when the samples were different body parts. For example, the results revealed better performances for heads and torsos than arms and legs in "novel different-individual pairs". The study showed that chimpanzees can visually match and categorize body parts in this experiment setting, even across different chimpanzees' bodies, suggesting potential biological understanding. Different performances for body parts suggested a deviated categorization from humans. We hope this study will inspire future research on the evolution of body perception.</AbstractText
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35549711
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38040329
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37304527
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[Physical restraints in acute hospitals: A quantitative observational study as a starting point for the further development of quality management].
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A Systematic Review of the State of Neurosurgical Disparities Research: Past, Present, and Future.
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Image quality and radiation dose in spinal surgery: a comparison of three imaging systems in phantom.
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Physical restraints in acute hospitals: A quantitative observational study as a starting point for the further development of quality management <b <b
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The social determinants of health, which influence healthcare access, patient outcomes, and population-level burden of disease, contribute to health disparities experienced by marginalized patient populations. In the present study, we sought to evaluate the landscape of health disparities research within neurosurgery.</AbstractText Embase, Ovid-MEDLINE, Scopus, Web of Science, Cochrane Library, and ProQuest Dissertations databases were queried for original research on health disparities regarding access to, outcomes of, and/or postoperative management after neurosurgical procedures in the United States.</AbstractText Of 883 studies screened, 196 were included, of which 144 had a neurosurgery-affiliated author. We found a significant increase in the number of neurosurgical disparities reports beginning in 2010, with only 10 studies reported before 2010. Of the included studies, 3.1% used prospective methods and 63.8% used data from national registries. The disparities analyzed were racial/ethnic (79.6%), economic/socioeconomic (53.6%), gender (18.9%), and disabled populations (0.5%), with 40.1% analyzing multiple or intersecting disparities. Of the included reports, 96.9% were in phase 1 (detecting phase of disparities research), with a few studies in phase 2 (understanding phase), and none in phase 3 (reducing phase). The spine was the most prevalent subspecialty evaluated (34.2%), followed by neuro-oncology (19.9%), cerebrovascular (16.3%), pediatrics (10.7%), functional (9.2%), general neurosurgery (5.1%), and trauma (4.1%). Senior authors with a neurosurgical affiliation accounted for 79.2% of the reports, 93% of whom were academically affiliated.</AbstractText Although a recent increase has occurred in neurosurgical disparities research within the past decade, most studies were limited to the detection of disparities without understanding or evaluating any interventions for a reduction in disparities. Future research in neurosurgical disparities should incorporate the latter 2 factors to reduce disparities and improve outcomes for all patients.</AbstractText
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Using optimal settings for x-ray scans is crucial for obtaining three-dimensional images of high quality while keeping the patient dose low. Our work compares dose and image quality (IQ) of three intraoperative imaging systems [O-arm cone-beam computed tomography (CBCT), ClarifEye C-arm CBCT, and Airo computed tomography] used for spinal surgery.</AbstractText Patients of 70, 90, and 110 kg were simulated with an anthropomorphic phantom by adding tissue-equivalent material. Titanium inserts were placed in the phantom spine for reproducing metal artifacts in the images. Organ dose was measured with thermo-luminescent dosimeters for effective dose (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" The ClarifEye protocols resulted in the lowest <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" Both CBCT systems provided better IQ compared with Airo for navigation of lumbar spinal surgery for the original phantom. Metal artifacts particularly affect O-arm images decreasing the subjective IQ. The high spatial resolution of CBCT systems resulted in a relevant parameter for the visibility of anatomical features important for spine navigation. Low dose protocols were enough to obtain a clinically acceptable contrast-to-noise ratio in the bones.</AbstractText
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[Physical restraints in acute hospitals: A quantitative observational study as a starting point for the further development of quality management]. Physical restraints in acute hospitals: A quantitative observational study as a starting point for the further development of quality management <b <b
|
A Systematic Review of the State of Neurosurgical Disparities Research: Past, Present, and Future. The social determinants of health, which influence healthcare access, patient outcomes, and population-level burden of disease, contribute to health disparities experienced by marginalized patient populations. In the present study, we sought to evaluate the landscape of health disparities research within neurosurgery.</AbstractText Embase, Ovid-MEDLINE, Scopus, Web of Science, Cochrane Library, and ProQuest Dissertations databases were queried for original research on health disparities regarding access to, outcomes of, and/or postoperative management after neurosurgical procedures in the United States.</AbstractText Of 883 studies screened, 196 were included, of which 144 had a neurosurgery-affiliated author. We found a significant increase in the number of neurosurgical disparities reports beginning in 2010, with only 10 studies reported before 2010. Of the included studies, 3.1% used prospective methods and 63.8% used data from national registries. The disparities analyzed were racial/ethnic (79.6%), economic/socioeconomic (53.6%), gender (18.9%), and disabled populations (0.5%), with 40.1% analyzing multiple or intersecting disparities. Of the included reports, 96.9% were in phase 1 (detecting phase of disparities research), with a few studies in phase 2 (understanding phase), and none in phase 3 (reducing phase). The spine was the most prevalent subspecialty evaluated (34.2%), followed by neuro-oncology (19.9%), cerebrovascular (16.3%), pediatrics (10.7%), functional (9.2%), general neurosurgery (5.1%), and trauma (4.1%). Senior authors with a neurosurgical affiliation accounted for 79.2% of the reports, 93% of whom were academically affiliated.</AbstractText Although a recent increase has occurred in neurosurgical disparities research within the past decade, most studies were limited to the detection of disparities without understanding or evaluating any interventions for a reduction in disparities. Future research in neurosurgical disparities should incorporate the latter 2 factors to reduce disparities and improve outcomes for all patients.</AbstractText
|
Image quality and radiation dose in spinal surgery: a comparison of three imaging systems in phantom. Using optimal settings for x-ray scans is crucial for obtaining three-dimensional images of high quality while keeping the patient dose low. Our work compares dose and image quality (IQ) of three intraoperative imaging systems [O-arm cone-beam computed tomography (CBCT), ClarifEye C-arm CBCT, and Airo computed tomography] used for spinal surgery.</AbstractText Patients of 70, 90, and 110 kg were simulated with an anthropomorphic phantom by adding tissue-equivalent material. Titanium inserts were placed in the phantom spine for reproducing metal artifacts in the images. Organ dose was measured with thermo-luminescent dosimeters for effective dose (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" The ClarifEye protocols resulted in the lowest <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" Both CBCT systems provided better IQ compared with Airo for navigation of lumbar spinal surgery for the original phantom. Metal artifacts particularly affect O-arm images decreasing the subjective IQ. The high spatial resolution of CBCT systems resulted in a relevant parameter for the visibility of anatomical features important for spine navigation. Low dose protocols were enough to obtain a clinically acceptable contrast-to-noise ratio in the bones.</AbstractText
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40620472
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29408539
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40064234
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Decreased diffusion tensor image analysis along the perivascular space index is related with clinical classification in essential tremor.
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Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort.
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Inhibiting NCX delays the early onset of Ca(2+) alternans in myocytes from spontaneously hypertensive rats (SHR).
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The glymphatic dysfunction involved in various neurodegenerative diseases. However, the relationship between glymphatic activity and essential tremor (ET) has not been fully elucidated. Our study explored the impact of glymphatic function on ET and its clinical classification. Participants comprised 37 pure ET, 38 ET-plus and 50 normal controls. Glymphatic function was evaluated via the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Statistical comparisons of DTI-ALPS index among patients with pure ET, those with ET-plus and normal controls were conducted using general linear model analysis. Age, gender and disease duration were included as confounding variable. To confirm the relation between the DTI-ALPS index and the clinical characteristics of pure ET and ET-plus, we conducted partial Spearman rank correlation analyses while controlling for age and disease duration. The DTI-ALPS index in ET-plus patients was significantly lower than that in normal controls (<i
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Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).</AbstractText
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Spontaneously hypertensive rats (SHR) are more susceptible to cardiac alternans, a precursor to arrhythmias. Ca<sup
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Decreased diffusion tensor image analysis along the perivascular space index is related with clinical classification in essential tremor. The glymphatic dysfunction involved in various neurodegenerative diseases. However, the relationship between glymphatic activity and essential tremor (ET) has not been fully elucidated. Our study explored the impact of glymphatic function on ET and its clinical classification. Participants comprised 37 pure ET, 38 ET-plus and 50 normal controls. Glymphatic function was evaluated via the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Statistical comparisons of DTI-ALPS index among patients with pure ET, those with ET-plus and normal controls were conducted using general linear model analysis. Age, gender and disease duration were included as confounding variable. To confirm the relation between the DTI-ALPS index and the clinical characteristics of pure ET and ET-plus, we conducted partial Spearman rank correlation analyses while controlling for age and disease duration. The DTI-ALPS index in ET-plus patients was significantly lower than that in normal controls (<i
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Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort. Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).</AbstractText
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Inhibiting NCX delays the early onset of Ca(2+) alternans in myocytes from spontaneously hypertensive rats (SHR). Spontaneously hypertensive rats (SHR) are more susceptible to cardiac alternans, a precursor to arrhythmias. Ca<sup
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28843214
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29058410
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27709512
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Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder.
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Spin System Modeling of Nuclear Magnetic Resonance Spectra for Applications in Metabolomics and Small Molecule Screening.
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Neural correlates of immediate and prolonged effects of cognitive reappraisal and distraction on emotional experience.
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State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with fine granularities, based on fMRI data.</AbstractText
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The exceptionally rich information content of nuclear magnetic resonance (NMR) spectra is routinely used to identify and characterize molecules and molecular interactions in a wide range of applications, including clinical biomarker discovery, drug discovery, environmental chemistry, and metabolomics. The set of peak positions and intensities from a reference NMR spectrum generally serves as the identifying signature for a compound. Reference spectra normally are collected under specific conditions of pH, temperature, and magnetic field strength, because changes in conditions can distort the identifying signatures of compounds. A spin system matrix that parametrizes chemical shifts and coupling constants among spins provides a much richer feature set for a compound than a spectral signature based on peak positions and intensities. Spin system matrices expand the applicability of NMR spectral libraries beyond the specific conditions under which data were collected. In addition to being able to simulate spectra at any field strength, spin parameters can be adjusted to systematically explore alterations in chemical shift patterns due to variations in other experimental conditions, such as compound concentration, pH, or temperature. We present methodology and software for efficient interactive optimization of spin parameters against experimental 1D-<sup
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Cognitive emotion regulation strategies are important components of cognitive-behavioral therapy (CBT). Additionally, up-regulation and difficulties in the down-regulation of negative feelings are associated with mental disorders. However, little is known about the lasting effects of cognitive emotion regulation strategies on emotional experience and associated neural activation. Therefore, this study investigated immediate and prolonged effects of emotion regulation using cognitive reappraisal and distraction on subjective report and its neural correlates. Twenty-seven healthy females took part in a 2-day functional magnetic resonance imaging study. They were instructed to either up-regulate or down-regulate their negative feelings using a situation-focused cognitive reappraisal strategy, to distract themselves by imagining a specific neutral situation, or to passively look at repeatedly presented aversive and neutral pictures. Re-exposure to the same stimuli without a regulation instruction was conducted one day later. Self-reported negative feelings and blood-oxygen-level-dependent responses served as main outcome variables. As expected, the results show successful immediate up- or down-regulation of negative feelings by cognitive reappraisal and down-regulation of negative feelings by distraction. Furthermore, these changes in negative feelings were correlated with amygdala activation. A lasting effect on emotional experience associated with stronger ventromedial prefrontal cortex activation was found for down-regulation of negative feelings via cognitive reappraisal. Compared to distraction, down-regulation via cognitive reappraisal led to reduced negative feelings and stronger dorso- and ventrolateral prefrontal cortex responses one day later. While cognitive reappraisal and distraction are both effective strategies during active regulation, only cognitive reappraisal had a lasting effect. These findings might have implications for CBT.</AbstractText
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Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder. State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with fine granularities, based on fMRI data.</AbstractText
|
Spin System Modeling of Nuclear Magnetic Resonance Spectra for Applications in Metabolomics and Small Molecule Screening. The exceptionally rich information content of nuclear magnetic resonance (NMR) spectra is routinely used to identify and characterize molecules and molecular interactions in a wide range of applications, including clinical biomarker discovery, drug discovery, environmental chemistry, and metabolomics. The set of peak positions and intensities from a reference NMR spectrum generally serves as the identifying signature for a compound. Reference spectra normally are collected under specific conditions of pH, temperature, and magnetic field strength, because changes in conditions can distort the identifying signatures of compounds. A spin system matrix that parametrizes chemical shifts and coupling constants among spins provides a much richer feature set for a compound than a spectral signature based on peak positions and intensities. Spin system matrices expand the applicability of NMR spectral libraries beyond the specific conditions under which data were collected. In addition to being able to simulate spectra at any field strength, spin parameters can be adjusted to systematically explore alterations in chemical shift patterns due to variations in other experimental conditions, such as compound concentration, pH, or temperature. We present methodology and software for efficient interactive optimization of spin parameters against experimental 1D-<sup
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Neural correlates of immediate and prolonged effects of cognitive reappraisal and distraction on emotional experience. Cognitive emotion regulation strategies are important components of cognitive-behavioral therapy (CBT). Additionally, up-regulation and difficulties in the down-regulation of negative feelings are associated with mental disorders. However, little is known about the lasting effects of cognitive emotion regulation strategies on emotional experience and associated neural activation. Therefore, this study investigated immediate and prolonged effects of emotion regulation using cognitive reappraisal and distraction on subjective report and its neural correlates. Twenty-seven healthy females took part in a 2-day functional magnetic resonance imaging study. They were instructed to either up-regulate or down-regulate their negative feelings using a situation-focused cognitive reappraisal strategy, to distract themselves by imagining a specific neutral situation, or to passively look at repeatedly presented aversive and neutral pictures. Re-exposure to the same stimuli without a regulation instruction was conducted one day later. Self-reported negative feelings and blood-oxygen-level-dependent responses served as main outcome variables. As expected, the results show successful immediate up- or down-regulation of negative feelings by cognitive reappraisal and down-regulation of negative feelings by distraction. Furthermore, these changes in negative feelings were correlated with amygdala activation. A lasting effect on emotional experience associated with stronger ventromedial prefrontal cortex activation was found for down-regulation of negative feelings via cognitive reappraisal. Compared to distraction, down-regulation via cognitive reappraisal led to reduced negative feelings and stronger dorso- and ventrolateral prefrontal cortex responses one day later. While cognitive reappraisal and distraction are both effective strategies during active regulation, only cognitive reappraisal had a lasting effect. These findings might have implications for CBT.</AbstractText
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21598866
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10091618
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22254584
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Drug therapies for tardive dyskinesia: Part 1.
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Reduction of Parkinsonian signs in patients with Parkinson's disease by dopaminergic versus anticholinergic single-dose challenges.
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Graphic patterns of cortical functional connectivity of depressed patients on the basis of EEG measurements.
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Blocking dopamine (DA) receptors in the basal ganglia can cause parkinsonian symptoms, acute dystonia, akathisia, tardive dyskinesia (TD), and neuroleptic malignant syndrome. TD is characterized by abnormal, involuntary, irregular motor movements involving muscles of the head, limbs, or trunk. Many drug therapies have been tried for TD, but none are approved by the U.S. Food and Drug Administration. The second-generation antipsychotic drugs should be considered as a treatment of first choice for clinically significant TD, because they will also be potentially effective as a primary treatment for the underlying disorder. Dopamine-depleting drugs are effective for TD, but their practical use is severely limited because of tolerability and safety concerns. Various DA-modulating drugs have been tried; clinical evidence of efficacy suggests that amantadine (Symmetrel®) and naloxone (Narcan®) are worthwhile to try. Although efficacy evidence for buspirone (Buspar®) in TD is limited, this drug is safe and well tolerated and would be reasonable to try. Bromocriptine (Parlodel®), selegiline (Deprenyl®), and cholinergic-modulating drugs are not considered effective for TD.</AbstractText
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We investigated the effect of an anticholinergic (biperiden) and a dopamine agonist (apomorphine) on tremor, rigidity, and akinesia in patients with idiopathic Parkinson's disease. In a standardized, crossover study design 17 patients received single-dose challenges of 5 mg biperiden intravenously and a previously determined dose of apomorphine subcutaneously on 2 consecutive days. Resting (RT), postural (PT), and action tremor (AT) were assessed using spectral analysis of accelerometer data, and Unified Parkinson's Disease Rating Scale (UPDRS) scores for rigidity and akinesia were determined before and after administration of the study drug. Both single-dose challenges significantly reduced the amplitude of RT, PT, and AT, but only apomorphine significantly reduced UPDRS scores for rigidity and akinesia. In only one patient was tremor reduced by the dopamine agonist but not by the anticholinergic. We found that anticholinergic and dopaminergic agents are both effective in reducing tremor in IPD, and there was no evidence for a selective anticholinergic responsiveness of parkinsonian tremor. Akinesia and rigidity, on the other hand, were not improved by biperiden. We therefore conclude that dopaminergic substances are as effective as anticholinergics in patients with parkinsonian tremor and additionally improve other parkinsonian signs.</AbstractText
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Considerable evidences have shown a decrease of neuronal activity in the left frontal lobe of depressed patients, but the underlying cortical network is still unclear. The present study intends to investigate the conscious-state brain network patterns in depressed patients compared with control individuals. Cortical functional connectivity is quantified by the partial directed coherence (PDC) analysis of multichannel EEG signals from 12 depressed patients and 12 healthy volunteers. The corresponding PDC matrices are first converted into unweighted graphs by applying a threshold to obtain the topographic property in-degree (K(in)). A significantly larger K(in) in the left hemisphere is identified in depressed patients, while a symmetric pattern is found in the control group. Another two topographic measures, i.e., clustering coefficients (C) and characteristic path length (L), are obtained from the original weighted PDC digraphs. Compared with control individuals, significantly smaller C and L are revealed in the depression group, indicating a random network-like architecture due to affective disorder. This study thereby provides further support for the presence of a hemispheric asymmetry syndrome in the depressed patients. More importantly, we present evidence that depression is characterized by a loss of optimal small-world network characteristics in conscious state.</AbstractText
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Drug therapies for tardive dyskinesia: Part 1. Blocking dopamine (DA) receptors in the basal ganglia can cause parkinsonian symptoms, acute dystonia, akathisia, tardive dyskinesia (TD), and neuroleptic malignant syndrome. TD is characterized by abnormal, involuntary, irregular motor movements involving muscles of the head, limbs, or trunk. Many drug therapies have been tried for TD, but none are approved by the U.S. Food and Drug Administration. The second-generation antipsychotic drugs should be considered as a treatment of first choice for clinically significant TD, because they will also be potentially effective as a primary treatment for the underlying disorder. Dopamine-depleting drugs are effective for TD, but their practical use is severely limited because of tolerability and safety concerns. Various DA-modulating drugs have been tried; clinical evidence of efficacy suggests that amantadine (Symmetrel®) and naloxone (Narcan®) are worthwhile to try. Although efficacy evidence for buspirone (Buspar®) in TD is limited, this drug is safe and well tolerated and would be reasonable to try. Bromocriptine (Parlodel®), selegiline (Deprenyl®), and cholinergic-modulating drugs are not considered effective for TD.</AbstractText
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Reduction of Parkinsonian signs in patients with Parkinson's disease by dopaminergic versus anticholinergic single-dose challenges. We investigated the effect of an anticholinergic (biperiden) and a dopamine agonist (apomorphine) on tremor, rigidity, and akinesia in patients with idiopathic Parkinson's disease. In a standardized, crossover study design 17 patients received single-dose challenges of 5 mg biperiden intravenously and a previously determined dose of apomorphine subcutaneously on 2 consecutive days. Resting (RT), postural (PT), and action tremor (AT) were assessed using spectral analysis of accelerometer data, and Unified Parkinson's Disease Rating Scale (UPDRS) scores for rigidity and akinesia were determined before and after administration of the study drug. Both single-dose challenges significantly reduced the amplitude of RT, PT, and AT, but only apomorphine significantly reduced UPDRS scores for rigidity and akinesia. In only one patient was tremor reduced by the dopamine agonist but not by the anticholinergic. We found that anticholinergic and dopaminergic agents are both effective in reducing tremor in IPD, and there was no evidence for a selective anticholinergic responsiveness of parkinsonian tremor. Akinesia and rigidity, on the other hand, were not improved by biperiden. We therefore conclude that dopaminergic substances are as effective as anticholinergics in patients with parkinsonian tremor and additionally improve other parkinsonian signs.</AbstractText
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Graphic patterns of cortical functional connectivity of depressed patients on the basis of EEG measurements. Considerable evidences have shown a decrease of neuronal activity in the left frontal lobe of depressed patients, but the underlying cortical network is still unclear. The present study intends to investigate the conscious-state brain network patterns in depressed patients compared with control individuals. Cortical functional connectivity is quantified by the partial directed coherence (PDC) analysis of multichannel EEG signals from 12 depressed patients and 12 healthy volunteers. The corresponding PDC matrices are first converted into unweighted graphs by applying a threshold to obtain the topographic property in-degree (K(in)). A significantly larger K(in) in the left hemisphere is identified in depressed patients, while a symmetric pattern is found in the control group. Another two topographic measures, i.e., clustering coefficients (C) and characteristic path length (L), are obtained from the original weighted PDC digraphs. Compared with control individuals, significantly smaller C and L are revealed in the depression group, indicating a random network-like architecture due to affective disorder. This study thereby provides further support for the presence of a hemispheric asymmetry syndrome in the depressed patients. More importantly, we present evidence that depression is characterized by a loss of optimal small-world network characteristics in conscious state.</AbstractText
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34497490
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23831171
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33706854
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The Corticospinal Excitability Can Be Predicted by Spontaneous Electroencephalography Oscillations.
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Graph theory analysis of cortical-subcortical networks in late-life depression.
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Quantitative MRI Analysis of the Talocrural and Talonavicular Joints in Ballet Dancers.
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Transcranial magnetic stimulation (TMS) has a wide range of clinical applications, and there is growing interest in neural oscillations and corticospinal excitability determined by TMS. Previous studies have shown that corticospinal excitability is influenced by fluctuations of brain oscillations in the sensorimotor region, but it is unclear whether brain network activity modulates corticospinal excitability. Here, we addressed this question by recording electroencephalography (EEG) and TMS measurements in 32 healthy individuals. The resting motor threshold (RMT) and active motor threshold (AMT) were determined as markers of corticospinal excitability. The least absolute shrinkage and selection operator (LASSO) was used to identify significant EEG metrics and then correlation analysis was performed. The analysis revealed that alpha2 power in the sensorimotor region was inversely correlated with RMT and AMT. Innovatively, graph theory was used to construct a brain network, and the relationship between the brain network and corticospinal excitability was explored. It was found that the global efficiency in the theta band was positively correlated with RMT. Additionally, the global efficiency in the alpha2 band was negatively correlated with RMT and AMT. These findings indicated that corticospinal excitability can be modulated by the power spectrum in sensorimotor regions and the global efficiency of functional networks. EEG network analysis can provide a useful supplement for studying the association between EEG oscillations and corticospinal excitability.</AbstractText
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Late-life major depression (LLD) is characterized by distinct epidemiologic and psychosocial factors, as well as medical comorbidities that are associated with specific neuroanatomical differences. The purpose of this study was to use interregional correlations of cortical and subcortical volumes to examine cortical-subcortical structural network properties in subjects with LLD compared with healthy comparison subjects.</AbstractText This was a cross-sectional neuroimaging study conducted in the general community. We recruited 73 healthy elderly comparison subjects and 53 subjects with LLD who volunteered in response to advertisements. Brain network connectivity measures were generated by correlating regional volumes after controlling for age, gender, and intracranial volume by using the Brain Connectivity Toolbox.</AbstractText Results for overall network strength revealed that LLD networks showed a greater magnitude of associations for both positive and negative correlation weights compared with healthy elderly networks. LLD networks also demonstrated alterations in brain network structure compared with healthy comparison subjects. LLD networks were also more vulnerable to targeted attacks compared with healthy elderly comparison subjects, and this vulnerability was attenuated when controlling for white matter alterations.</AbstractText Overall, this study demonstrates that cortical-subcortical network properties are altered in LLD and may reflect the underlying neuroanatomical vulnerabilities of the disorder.</AbstractText
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The ankles of ballet dancers are routinely under heavy loading that may lead to osteoarthritic changes. It would be clinically useful to identify such pathology as early as possible in a dancer's career. Therefore, the purpose of this study was to compare quantitative measurements in magnetic resonance (MR) images of the talocrural and talonavicular joints in ballet dancers and healthy non-dancers for use in formulating prediction of chronic injury and degenerative joint disease in these locations. Quantitative measurements in MR images of the talocrural and talonavicular joints were compared in 10 female ballet dancers, 10 healthy female non-dancers, and nine male ballet dancers. Fat-suppressed density-weighted proton, T1rho, and T2 mapping images were acquired with a 3.0 T MR scanner. Medial and lateral subchondral bone distance between the tibia and talus (MSBD and LSBD), axial navicular-talus axis angle (ANT angle), sagittal talar neck angle against the posterior talocalcaneal joint (TN angle), and curvature of navicular surface at the talonavicular joint were measured on sagittal images. The medial subchondral bone distance was found to be significantly larger in female dancers than female non-dancers (4.05 mm vs. 2.75 mm, p < 0.05), whereas there were no significant differences in LSBD (2.63 mm vs. 2.63 mm, p = 0.87). Axial navicular talus angles in female dancers were significantly larger than those in female non-dancers (38.9° vs. 24.3°, p < 0.05). There was a tendency for the TN angle to be smaller and navicular curvature (NC) to be larger in female dancers compared to female non-dancers, though the differences were not significant (TN angle: 16.6° vs. 22.3°, p = 0.09, and NC: 0.186 vs. 0.165, p = 0.28). There were no significant differences in T1rho or T2 values of talonavicular joint cartilage. These results show that the bony anatomy of dancers' ankles may adapt to the stresses placed on them by ballet.</AbstractText
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The Corticospinal Excitability Can Be Predicted by Spontaneous Electroencephalography Oscillations. Transcranial magnetic stimulation (TMS) has a wide range of clinical applications, and there is growing interest in neural oscillations and corticospinal excitability determined by TMS. Previous studies have shown that corticospinal excitability is influenced by fluctuations of brain oscillations in the sensorimotor region, but it is unclear whether brain network activity modulates corticospinal excitability. Here, we addressed this question by recording electroencephalography (EEG) and TMS measurements in 32 healthy individuals. The resting motor threshold (RMT) and active motor threshold (AMT) were determined as markers of corticospinal excitability. The least absolute shrinkage and selection operator (LASSO) was used to identify significant EEG metrics and then correlation analysis was performed. The analysis revealed that alpha2 power in the sensorimotor region was inversely correlated with RMT and AMT. Innovatively, graph theory was used to construct a brain network, and the relationship between the brain network and corticospinal excitability was explored. It was found that the global efficiency in the theta band was positively correlated with RMT. Additionally, the global efficiency in the alpha2 band was negatively correlated with RMT and AMT. These findings indicated that corticospinal excitability can be modulated by the power spectrum in sensorimotor regions and the global efficiency of functional networks. EEG network analysis can provide a useful supplement for studying the association between EEG oscillations and corticospinal excitability.</AbstractText
|
Graph theory analysis of cortical-subcortical networks in late-life depression. Late-life major depression (LLD) is characterized by distinct epidemiologic and psychosocial factors, as well as medical comorbidities that are associated with specific neuroanatomical differences. The purpose of this study was to use interregional correlations of cortical and subcortical volumes to examine cortical-subcortical structural network properties in subjects with LLD compared with healthy comparison subjects.</AbstractText This was a cross-sectional neuroimaging study conducted in the general community. We recruited 73 healthy elderly comparison subjects and 53 subjects with LLD who volunteered in response to advertisements. Brain network connectivity measures were generated by correlating regional volumes after controlling for age, gender, and intracranial volume by using the Brain Connectivity Toolbox.</AbstractText Results for overall network strength revealed that LLD networks showed a greater magnitude of associations for both positive and negative correlation weights compared with healthy elderly networks. LLD networks also demonstrated alterations in brain network structure compared with healthy comparison subjects. LLD networks were also more vulnerable to targeted attacks compared with healthy elderly comparison subjects, and this vulnerability was attenuated when controlling for white matter alterations.</AbstractText Overall, this study demonstrates that cortical-subcortical network properties are altered in LLD and may reflect the underlying neuroanatomical vulnerabilities of the disorder.</AbstractText
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Quantitative MRI Analysis of the Talocrural and Talonavicular Joints in Ballet Dancers. The ankles of ballet dancers are routinely under heavy loading that may lead to osteoarthritic changes. It would be clinically useful to identify such pathology as early as possible in a dancer's career. Therefore, the purpose of this study was to compare quantitative measurements in magnetic resonance (MR) images of the talocrural and talonavicular joints in ballet dancers and healthy non-dancers for use in formulating prediction of chronic injury and degenerative joint disease in these locations. Quantitative measurements in MR images of the talocrural and talonavicular joints were compared in 10 female ballet dancers, 10 healthy female non-dancers, and nine male ballet dancers. Fat-suppressed density-weighted proton, T1rho, and T2 mapping images were acquired with a 3.0 T MR scanner. Medial and lateral subchondral bone distance between the tibia and talus (MSBD and LSBD), axial navicular-talus axis angle (ANT angle), sagittal talar neck angle against the posterior talocalcaneal joint (TN angle), and curvature of navicular surface at the talonavicular joint were measured on sagittal images. The medial subchondral bone distance was found to be significantly larger in female dancers than female non-dancers (4.05 mm vs. 2.75 mm, p < 0.05), whereas there were no significant differences in LSBD (2.63 mm vs. 2.63 mm, p = 0.87). Axial navicular talus angles in female dancers were significantly larger than those in female non-dancers (38.9° vs. 24.3°, p < 0.05). There was a tendency for the TN angle to be smaller and navicular curvature (NC) to be larger in female dancers compared to female non-dancers, though the differences were not significant (TN angle: 16.6° vs. 22.3°, p = 0.09, and NC: 0.186 vs. 0.165, p = 0.28). There were no significant differences in T1rho or T2 values of talonavicular joint cartilage. These results show that the bony anatomy of dancers' ankles may adapt to the stresses placed on them by ballet.</AbstractText
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38897333
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29962010
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39296910
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Fatigued or bored? Investigating the effect of different types of mental fatigue on 3 km running performance.
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Compassion fatigue in nursing: A concept analysis.
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Refractory Epilepsy in Adult Patient With COQ8A Variant Improves With CoQ10 Supplementation: A Case for Exome Sequencing in the ICU.
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Mental fatigue has been highly cited as having a negative impact on endurance performance. Few, however, have investigated whether different types of mental fatigue, namely active and passive fatigue, might affect endurance performance differently. This study used a repeated-measures design where 11 participants completed a 3 km run after three 32-min conditions: an actively fatiguing task (Task-load Dual-back; TloadDback); a passively fatiguing task (Mackworth Clock); and a control task (Documentary). Subjective ratings and performance on a second task (Flanker task) were taken before and after the 32-min tasks, while ratings of perceived effort, motivation and workload were taken during the 3 km run. Results showed that both fatigue conditions were mentally fatiguing, with the TloadDback rated as more demanding and the Mackworth Clock more boring and less motivating. Performance on subsequent tasks showed different effects: the TloadDback condition had the slowest responses on the post-test Flanker task, while the Mackworth Clock condition had the slowest completion time on the 3 km run, though this difference in completion times was non-significant. These results suggest that different cognitive tasks lead to different types of mental fatigue, which can lead to different outcomes on subsequent cognitive tasks but non-significant differences on subsequent physical tasks. This study highlights that to understand the influence of mental fatigue on physical performance, it is important to understand the cognitive tasks used and how different cognitive and physical tasks interact. Future work should examine whether performance outcomes in other areas commonly affected by mental fatigue, like technical and tactical sporting skills, are affected differently by active and passive fatigue.</AbstractText
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The aim of this article is to clarify the concept of compassion fatigue to develop methods for prevention and mitigation of compassion fatigue in the nursing profession.</AbstractText Compassion fatigue occurs when nurses develop declining empathetic ability from repeated exposure to others' suffering. Conceptual clarity is vital to curtail compassion fatigue via preventative and restorative measures at the individual and organizational level.</AbstractText Concept analysis.</AbstractText Databases searched were OVID, CINAHL Complete, Science Direct, Academic One File, Criminal Justice Abstracts, Education Full Text (H.W. Wilson), PsycARTICLES, PsycINFO, Social Work Abstracts, and Teacher Reference Center. Keywords included concept analysis, compassion fatigue, secondary traumatic stress, burnout, vicarious traumatization, compassion satisfaction, nursing, psychology, and social work. The timeline for data collection was from 1990 to 2017.</AbstractText Walker and Avant's method of concept analysis.</AbstractText Compassion fatigue occurred across disciplines. Nurses were predisposed to compassion fatigue by repeated exposure of others' suffering, high stress environments, and the continuous giving of self. The consequences of compassion fatigue negatively impacted the nurse, patient, organization, and healthcare system.</AbstractText All nurses are at risk for compassion fatigue. Prevention of compassion fatigue is achieved through professional boundaries, self-care measures, self-awareness, and education on the concept at the individual and organizational level.</AbstractText
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Describe a case of stroke-like episodes and refractory status epilepticus diagnosed with primary CoQ10 deficiency-4 (COQ10D4) using whole-exome sequencing in the intensive care unit (ICU), with treatment implications.</AbstractText A patient presented to the emergency department with 1 month of progressively worsening focal motor status epilepticus and stroke-like imaging abnormalities. Multiple seizure medications, ketogenic diet, and elective intubation for anesthetic drips failed to achieve sustained seizure freedom. Genetic testing was pursued for prognostic information and identified potential treatment.</AbstractText Whole-exome sequencing revealed compound heterozygous variants of <i Whole-exome sequencing is a fast and cost-effective means to diagnose rare neurologic disease in critically ill patients and can uncover treatment options. While primarily used in the neonatal ICU, appropriately selected adult patients may also benefit.</AbstractText
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Fatigued or bored? Investigating the effect of different types of mental fatigue on 3 km running performance. Mental fatigue has been highly cited as having a negative impact on endurance performance. Few, however, have investigated whether different types of mental fatigue, namely active and passive fatigue, might affect endurance performance differently. This study used a repeated-measures design where 11 participants completed a 3 km run after three 32-min conditions: an actively fatiguing task (Task-load Dual-back; TloadDback); a passively fatiguing task (Mackworth Clock); and a control task (Documentary). Subjective ratings and performance on a second task (Flanker task) were taken before and after the 32-min tasks, while ratings of perceived effort, motivation and workload were taken during the 3 km run. Results showed that both fatigue conditions were mentally fatiguing, with the TloadDback rated as more demanding and the Mackworth Clock more boring and less motivating. Performance on subsequent tasks showed different effects: the TloadDback condition had the slowest responses on the post-test Flanker task, while the Mackworth Clock condition had the slowest completion time on the 3 km run, though this difference in completion times was non-significant. These results suggest that different cognitive tasks lead to different types of mental fatigue, which can lead to different outcomes on subsequent cognitive tasks but non-significant differences on subsequent physical tasks. This study highlights that to understand the influence of mental fatigue on physical performance, it is important to understand the cognitive tasks used and how different cognitive and physical tasks interact. Future work should examine whether performance outcomes in other areas commonly affected by mental fatigue, like technical and tactical sporting skills, are affected differently by active and passive fatigue.</AbstractText
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Compassion fatigue in nursing: A concept analysis. The aim of this article is to clarify the concept of compassion fatigue to develop methods for prevention and mitigation of compassion fatigue in the nursing profession.</AbstractText Compassion fatigue occurs when nurses develop declining empathetic ability from repeated exposure to others' suffering. Conceptual clarity is vital to curtail compassion fatigue via preventative and restorative measures at the individual and organizational level.</AbstractText Concept analysis.</AbstractText Databases searched were OVID, CINAHL Complete, Science Direct, Academic One File, Criminal Justice Abstracts, Education Full Text (H.W. Wilson), PsycARTICLES, PsycINFO, Social Work Abstracts, and Teacher Reference Center. Keywords included concept analysis, compassion fatigue, secondary traumatic stress, burnout, vicarious traumatization, compassion satisfaction, nursing, psychology, and social work. The timeline for data collection was from 1990 to 2017.</AbstractText Walker and Avant's method of concept analysis.</AbstractText Compassion fatigue occurred across disciplines. Nurses were predisposed to compassion fatigue by repeated exposure of others' suffering, high stress environments, and the continuous giving of self. The consequences of compassion fatigue negatively impacted the nurse, patient, organization, and healthcare system.</AbstractText All nurses are at risk for compassion fatigue. Prevention of compassion fatigue is achieved through professional boundaries, self-care measures, self-awareness, and education on the concept at the individual and organizational level.</AbstractText
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Refractory Epilepsy in Adult Patient With COQ8A Variant Improves With CoQ10 Supplementation: A Case for Exome Sequencing in the ICU. Describe a case of stroke-like episodes and refractory status epilepticus diagnosed with primary CoQ10 deficiency-4 (COQ10D4) using whole-exome sequencing in the intensive care unit (ICU), with treatment implications.</AbstractText A patient presented to the emergency department with 1 month of progressively worsening focal motor status epilepticus and stroke-like imaging abnormalities. Multiple seizure medications, ketogenic diet, and elective intubation for anesthetic drips failed to achieve sustained seizure freedom. Genetic testing was pursued for prognostic information and identified potential treatment.</AbstractText Whole-exome sequencing revealed compound heterozygous variants of <i Whole-exome sequencing is a fast and cost-effective means to diagnose rare neurologic disease in critically ill patients and can uncover treatment options. While primarily used in the neonatal ICU, appropriately selected adult patients may also benefit.</AbstractText
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40517266
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33766256
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40354811
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Determinants of myocardial fibrosis in patients with immune-mediated inflammatory diseases.
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Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.
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Feasibility of phase-locked transcranial magnetic stimulation of cerebellum for the treatment of essential tremor.
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Myocardial fibrosis is an important adverse prognostic marker, however; determinants of myocardial fibrosis in immune-mediated inflammatory diseases (IMIDs) remain poorly defined. We aimed to identify determinants of myocardial fibrosis in patients with IMIDs, as measured by cardiovascular magnetic resonance (CMR) extracellular volume (ECV).</AbstractText Cross-sectional study of 116 patients with IMIDs undergoing clinical CMR at Manchester University NHS Foundation Trust. IMIDs included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), ankylosing spondylitis, psoriatic arthritis and vasculitis. CMR included pre- and post-contrast T1 mapping to measure myocardial ECV, with same day blood sampling. Determinants of ECV were investigated with univariable and multivariable linear regression.</AbstractText ECV varied significantly according to IMID diagnosis (ANOVA F statistic 2.80, P = 0.015); ECV was higher in patients with SSc compared to other IMIDs. Major determinants of ECV as a continuous variable were SSc, smoking and body mass index (BMI); regression coefficients 3.33 (95% confidence interval 0.82-5.84), 3.08 (0.73-5.43), and - 0.19 (-0.29 - -0.09) respectively, P < 0.01 (SSc, smoking and lower BMI were associated with increased ECV). Approximately a quarter of the variability in ECV could be explained by these predictors (optimism adjusted R<sup SSc is associated with a higher burden of myocardial fibrosis compared to other IMIDs. In patients with IMIDs, independent determinants of myocardial fibrosis were presence of SSc, smoking and BMI. Importantly, participants underwent CMR for clinical indications and may not be representative of IMID populations in the community.</AbstractText
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Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.</AbstractText This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.</AbstractText In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.</AbstractText Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.</AbstractText The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.</AbstractText
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<i
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Determinants of myocardial fibrosis in patients with immune-mediated inflammatory diseases. Myocardial fibrosis is an important adverse prognostic marker, however; determinants of myocardial fibrosis in immune-mediated inflammatory diseases (IMIDs) remain poorly defined. We aimed to identify determinants of myocardial fibrosis in patients with IMIDs, as measured by cardiovascular magnetic resonance (CMR) extracellular volume (ECV).</AbstractText Cross-sectional study of 116 patients with IMIDs undergoing clinical CMR at Manchester University NHS Foundation Trust. IMIDs included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), ankylosing spondylitis, psoriatic arthritis and vasculitis. CMR included pre- and post-contrast T1 mapping to measure myocardial ECV, with same day blood sampling. Determinants of ECV were investigated with univariable and multivariable linear regression.</AbstractText ECV varied significantly according to IMID diagnosis (ANOVA F statistic 2.80, P = 0.015); ECV was higher in patients with SSc compared to other IMIDs. Major determinants of ECV as a continuous variable were SSc, smoking and body mass index (BMI); regression coefficients 3.33 (95% confidence interval 0.82-5.84), 3.08 (0.73-5.43), and - 0.19 (-0.29 - -0.09) respectively, P < 0.01 (SSc, smoking and lower BMI were associated with increased ECV). Approximately a quarter of the variability in ECV could be explained by these predictors (optimism adjusted R<sup SSc is associated with a higher burden of myocardial fibrosis compared to other IMIDs. In patients with IMIDs, independent determinants of myocardial fibrosis were presence of SSc, smoking and BMI. Importantly, participants underwent CMR for clinical indications and may not be representative of IMID populations in the community.</AbstractText
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Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis. Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.</AbstractText This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.</AbstractText In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.</AbstractText Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.</AbstractText The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.</AbstractText
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Feasibility of phase-locked transcranial magnetic stimulation of cerebellum for the treatment of essential tremor. <i
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27037829
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21118669
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26475058
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Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic effects on rod photoreceptor synapses via matrix-associated proteins.
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Ca(2+) sources for the exocytotic release of glutamate from astrocytes.
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Projecting future temperature-related mortality in three largest Australian cities.
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Heterotrimeric G-proteins couple metabotropic receptors to downstream effectors. In retinal ON bipolar cells, Go couples the metabotropic receptor mGluR6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell. Light, via GTPase-activating proteins, deactivates Go , opens TRPM1 and depolarizes the cell. Go comprises Gαo1 , Gβ3 and Gγ13; all are necessary for efficient coupling. In addition, Gβ3 contributes to trafficking of certain cascade proteins and to maintaining the synaptic structure. The goal of this study was to determine the role of Gαo1 in maintaining the cascade and synaptic integrity. Using mice lacking Gαo1 , we quantified the immunostaining of certain mGluR6-related components. Deleting Gαo1 greatly reduced staining for Gβ3, Gγ13, Gβ5, RGS11, RGS7 and R9AP. Deletion of Gαo1 did not affect mGluR6, TRPM1 or PCP2. In addition, deleting Gαo1 reduced the number of rod bipolar dendrites that invaginate the rod terminal, similar to the effect seen in the absence of mGluR6, Gβ3 or the matrix-associated proteins, pikachurin, dystroglycan and dystrophin, which are localized presynaptically to the rod bipolar cell. We therefore tested mice lacking mGluR6, Gαo1 and Gβ3 for expression of these matrix-associated proteins. In all three genotypes, staining intensity for these proteins was lower than in wild type, suggesting a retrograde trans-synaptic effect. We propose that the mGluR6 macromolecular complex is connected to the presynaptic rod terminal via a protein chain that includes the matrix-associated proteins. When a component of the macromolecular chain is missing, the chain may fall apart and loosen the dendritic tip adherence within the invagination.</AbstractText
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Astrocytes can exocytotically release the gliotransmitter glutamate from vesicular compartments. Increased cytosolic Ca(2+) concentration is necessary and sufficient for this process. The predominant source of Ca(2+) for exocytosis in astrocytes resides within the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate and ryanodine receptors of the ER provide a conduit for the release of Ca(2+) to the cytosol. The ER store is (re)filled by the store-specific Ca(2+)-ATPase. Ultimately, the depleted ER is replenished by Ca(2+) which enters from the extracellular space to the cytosol via store-operated Ca(2+) entry; the TRPC1 protein has been implicated in this part of the astrocytic exocytotic process. Voltage-gated Ca(2+) channels and plasma membrane Na(+)/Ca(2+) exchangers are additional means for cytosolic Ca(2+) entry. Cytosolic Ca(2+) levels can be modulated by mitochondria, which can take up cytosolic Ca(2+) via the Ca(2+) uniporter and release Ca(2+) into cytosol via the mitochondrial Na(+)/Ca(2+) exchanger, as well as by the formation of the mitochondrial permeability transition pore. The interplay between various Ca(2+) sources generates cytosolic Ca(2+) dynamics that can drive Ca(2+)-dependent exocytotic release of glutamate from astrocytes. An understanding of this process in vivo will reveal some of the astrocytic functions in health and disease of the brain. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.</AbstractText
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We estimated net annual temperature-related mortality in Brisbane, Sydney and Melbourne in Australia using 62 global climate model projections under three IPPC SRES CO2 emission scenarios (A2, A1B and B1). In all cities, all scenarios resulted in increases in summer temperature-related deaths for future decades, and decreases in winter temperature-related deaths. However, Brisbane and Sydney will increase the net annual temperature-related deaths in the future, while a slight decrease will happen in Melbourne. Additionally, temperature-related mortality will largely increase beyond the summer (including January, February, March, November and December) in Brisbane and Sydney, while temperature-related mortality will largely decrease beyond the winter in Melbourne. In conclusion, temperature increases for Australia are expected to result in a decreased burden of cold-related mortality and an increased burden of heat-related mortality, but the balance of these differences varied by city. In particular, the seasonal patterns in temperature-related deaths will be shifted.</AbstractText
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Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic effects on rod photoreceptor synapses via matrix-associated proteins. Heterotrimeric G-proteins couple metabotropic receptors to downstream effectors. In retinal ON bipolar cells, Go couples the metabotropic receptor mGluR6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell. Light, via GTPase-activating proteins, deactivates Go , opens TRPM1 and depolarizes the cell. Go comprises Gαo1 , Gβ3 and Gγ13; all are necessary for efficient coupling. In addition, Gβ3 contributes to trafficking of certain cascade proteins and to maintaining the synaptic structure. The goal of this study was to determine the role of Gαo1 in maintaining the cascade and synaptic integrity. Using mice lacking Gαo1 , we quantified the immunostaining of certain mGluR6-related components. Deleting Gαo1 greatly reduced staining for Gβ3, Gγ13, Gβ5, RGS11, RGS7 and R9AP. Deletion of Gαo1 did not affect mGluR6, TRPM1 or PCP2. In addition, deleting Gαo1 reduced the number of rod bipolar dendrites that invaginate the rod terminal, similar to the effect seen in the absence of mGluR6, Gβ3 or the matrix-associated proteins, pikachurin, dystroglycan and dystrophin, which are localized presynaptically to the rod bipolar cell. We therefore tested mice lacking mGluR6, Gαo1 and Gβ3 for expression of these matrix-associated proteins. In all three genotypes, staining intensity for these proteins was lower than in wild type, suggesting a retrograde trans-synaptic effect. We propose that the mGluR6 macromolecular complex is connected to the presynaptic rod terminal via a protein chain that includes the matrix-associated proteins. When a component of the macromolecular chain is missing, the chain may fall apart and loosen the dendritic tip adherence within the invagination.</AbstractText
|
Ca(2+) sources for the exocytotic release of glutamate from astrocytes. Astrocytes can exocytotically release the gliotransmitter glutamate from vesicular compartments. Increased cytosolic Ca(2+) concentration is necessary and sufficient for this process. The predominant source of Ca(2+) for exocytosis in astrocytes resides within the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate and ryanodine receptors of the ER provide a conduit for the release of Ca(2+) to the cytosol. The ER store is (re)filled by the store-specific Ca(2+)-ATPase. Ultimately, the depleted ER is replenished by Ca(2+) which enters from the extracellular space to the cytosol via store-operated Ca(2+) entry; the TRPC1 protein has been implicated in this part of the astrocytic exocytotic process. Voltage-gated Ca(2+) channels and plasma membrane Na(+)/Ca(2+) exchangers are additional means for cytosolic Ca(2+) entry. Cytosolic Ca(2+) levels can be modulated by mitochondria, which can take up cytosolic Ca(2+) via the Ca(2+) uniporter and release Ca(2+) into cytosol via the mitochondrial Na(+)/Ca(2+) exchanger, as well as by the formation of the mitochondrial permeability transition pore. The interplay between various Ca(2+) sources generates cytosolic Ca(2+) dynamics that can drive Ca(2+)-dependent exocytotic release of glutamate from astrocytes. An understanding of this process in vivo will reveal some of the astrocytic functions in health and disease of the brain. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.</AbstractText
|
Projecting future temperature-related mortality in three largest Australian cities. We estimated net annual temperature-related mortality in Brisbane, Sydney and Melbourne in Australia using 62 global climate model projections under three IPPC SRES CO2 emission scenarios (A2, A1B and B1). In all cities, all scenarios resulted in increases in summer temperature-related deaths for future decades, and decreases in winter temperature-related deaths. However, Brisbane and Sydney will increase the net annual temperature-related deaths in the future, while a slight decrease will happen in Melbourne. Additionally, temperature-related mortality will largely increase beyond the summer (including January, February, March, November and December) in Brisbane and Sydney, while temperature-related mortality will largely decrease beyond the winter in Melbourne. In conclusion, temperature increases for Australia are expected to result in a decreased burden of cold-related mortality and an increased burden of heat-related mortality, but the balance of these differences varied by city. In particular, the seasonal patterns in temperature-related deaths will be shifted.</AbstractText
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39418458
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20141252
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39547861
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Emotions observed during sessions of dialectical behavior therapy predict outcome for borderline personality disorder.
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Externalizing psychopathology and marital adjustment in long-term marriages: results from a large combined sample of married couples.
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Representational spaces in orbitofrontal and ventromedial prefrontal cortex: task states, values, and beyond.
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We examined whether the emotions that clients experience within session are associated with treatment outcome in dialectical behavior therapy (DBT) for borderline personality disorder (BPD).</AbstractText Participants were 52 adults who met criteria for BPD and were enrolled in a 12-month DBT treatment. The Classification of Affective-Meaning States, an observer-rated measure of discrete emotions, was used to code videos of individual DBT sessions. Raters coded three psychotherapy sessions for each participant: one session from each of the early, working, and late phases of psychotherapy. Self-report measures of BPD symptoms were used to assess treatment outcome.</AbstractText More emotional experience overall during the early phase predicted fewer BPD symptoms at 12-month treatment outcome, explaining 19% of the variance in symptoms. However, increases across treatment in global distress predicted higher levels of BPD (24% of the variance explained) and depression symptoms (15% explained) at termination. Increases in emotional flexibility (i.e., variation between states) from the early to working phase predicted fewer depressive symptoms at termination (14% explained). Self-compassion coded during the working phase also predicted a better treatment outcome (explaining 19%-34%).</AbstractText Clients' in-session emotional experiences predict treatment outcome 8-10 months later. Clients with BPD may benefit from more overall exploration of their emotional experiences early in DBT, as well as expression of self-compassion. Increases in nonspecific, intense negative affect anticipates poor prognosis, whereas increases in emotional flexibility during early treatment anticipates better prognosis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).</AbstractText
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The current study evaluated the associations between externalizing psychopathology and marital adjustment in a combined sample of 1,805 married couples. We further considered the role of personality in these associations, as personality has been found to predict both the development of externalizing psychopathology as well as marital distress and instability. Diagnostic interviews assessed conduct disorder, adult symptoms of antisocial personality disorder, and alcohol dependence. Personality was assessed using the Multidimensional Personality Questionnaire. The Dyadic Adjustment Scale was used to measure marital adjustment. Results indicate that more externalizing psychopathology, greater negative emotionality, and lower communal positive emotionality were associated with reduced marital adjustment in both individuals and their spouses. Low constraint was associated with reduced marital adjustment for individuals but not for their spouses. Multivariate analyses indicated externalizing psychopathology continued to predict marital adjustment even when accounting for overlap with personality. These results highlight the importance of examining the presence of externalizing psychopathology and the personality attributes of both members of a dyad when considering psychological predictors of marital adjustment.</AbstractText
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The orbitofrontal cortex (OFC) and ventromedial-prefrontal cortex (vmPFC) play a key role in decision-making and encode task states in addition to expected value. We review evidence suggesting a connection between value and state representations and argue that OFC / vmPFC integrate stimulus, context, and outcome information. Comparable encoding principles emerge in late layers of deep reinforcement learning (RL) models, where single nodes exhibit similar forms of mixed-selectivity, which enables flexible readout of relevant variables by downstream neurons. Based on these lines of evidence, we suggest that outcome-maximization leads to complex representational spaces that are insufficiently characterized by linear value signals that have been the focus of most prior research on the topic. Major outstanding questions concern the role of OFC/ vmPFC in learning across tasks, in encoding of task-irrelevant aspects, and the role of hippocampus-PFC interactions.</AbstractText
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Emotions observed during sessions of dialectical behavior therapy predict outcome for borderline personality disorder. We examined whether the emotions that clients experience within session are associated with treatment outcome in dialectical behavior therapy (DBT) for borderline personality disorder (BPD).</AbstractText Participants were 52 adults who met criteria for BPD and were enrolled in a 12-month DBT treatment. The Classification of Affective-Meaning States, an observer-rated measure of discrete emotions, was used to code videos of individual DBT sessions. Raters coded three psychotherapy sessions for each participant: one session from each of the early, working, and late phases of psychotherapy. Self-report measures of BPD symptoms were used to assess treatment outcome.</AbstractText More emotional experience overall during the early phase predicted fewer BPD symptoms at 12-month treatment outcome, explaining 19% of the variance in symptoms. However, increases across treatment in global distress predicted higher levels of BPD (24% of the variance explained) and depression symptoms (15% explained) at termination. Increases in emotional flexibility (i.e., variation between states) from the early to working phase predicted fewer depressive symptoms at termination (14% explained). Self-compassion coded during the working phase also predicted a better treatment outcome (explaining 19%-34%).</AbstractText Clients' in-session emotional experiences predict treatment outcome 8-10 months later. Clients with BPD may benefit from more overall exploration of their emotional experiences early in DBT, as well as expression of self-compassion. Increases in nonspecific, intense negative affect anticipates poor prognosis, whereas increases in emotional flexibility during early treatment anticipates better prognosis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).</AbstractText
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Externalizing psychopathology and marital adjustment in long-term marriages: results from a large combined sample of married couples. The current study evaluated the associations between externalizing psychopathology and marital adjustment in a combined sample of 1,805 married couples. We further considered the role of personality in these associations, as personality has been found to predict both the development of externalizing psychopathology as well as marital distress and instability. Diagnostic interviews assessed conduct disorder, adult symptoms of antisocial personality disorder, and alcohol dependence. Personality was assessed using the Multidimensional Personality Questionnaire. The Dyadic Adjustment Scale was used to measure marital adjustment. Results indicate that more externalizing psychopathology, greater negative emotionality, and lower communal positive emotionality were associated with reduced marital adjustment in both individuals and their spouses. Low constraint was associated with reduced marital adjustment for individuals but not for their spouses. Multivariate analyses indicated externalizing psychopathology continued to predict marital adjustment even when accounting for overlap with personality. These results highlight the importance of examining the presence of externalizing psychopathology and the personality attributes of both members of a dyad when considering psychological predictors of marital adjustment.</AbstractText
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Representational spaces in orbitofrontal and ventromedial prefrontal cortex: task states, values, and beyond. The orbitofrontal cortex (OFC) and ventromedial-prefrontal cortex (vmPFC) play a key role in decision-making and encode task states in addition to expected value. We review evidence suggesting a connection between value and state representations and argue that OFC / vmPFC integrate stimulus, context, and outcome information. Comparable encoding principles emerge in late layers of deep reinforcement learning (RL) models, where single nodes exhibit similar forms of mixed-selectivity, which enables flexible readout of relevant variables by downstream neurons. Based on these lines of evidence, we suggest that outcome-maximization leads to complex representational spaces that are insufficiently characterized by linear value signals that have been the focus of most prior research on the topic. Major outstanding questions concern the role of OFC/ vmPFC in learning across tasks, in encoding of task-irrelevant aspects, and the role of hippocampus-PFC interactions.</AbstractText
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36386331
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30776697
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35835481
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Association of the P441L KCNQ1 variant with severity of long QT syndrome and risk of cardiac events.
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Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome.
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New-onset Bell's palsy after neuroinvasive West Nile virus.
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Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.</AbstractText
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This study aimed to investigate the genetic etiology of epilepsy in a cohort of Chinese children.</AbstractText Targeted next-generation sequencing (NGS) was performed for 120 patients with unexplained epilepsy, including 71 patients with early-onset epileptic encephalopathies, and 16 patients with Dravet syndrome (including three patients with a Dravet-like phenotype) but without SCN1A pathogenic variants.</AbstractText Pathogenic variants of 14 genes were discovered in 22 patients (18%). A de novo KCND3 pathogenic variant (c.1174G > A, p.Val392Ile) was identified in a boy with refractory epilepsy, psychomotor regression, attention deficit, and visual decline. Pathogenic variants in other coding genes were excluded via whole exome sequencing. This KCND3 variant was previously confirmed to be pathogenic by Giudicessi, et al. However, the clinical profile was different: sudden death at 20 years old without any medical history of neurological disorders, nor with any diseases typically caused by KCND3 pathogenic variants such as Brugada syndrome, spinocerebellar ataxia type 19/22 or ataxia accompanied by epilepsy. This indicates that we have identified a new KCND3 phenotype. In addition, we also uncovered a GRIN1 pathogenic variant and a novel HCN1 pathogenic variant in the Dravet cohort.</AbstractText Our study highlights the significant utility of NGS panels in the genetic diagnosis of pediatric epilepsy. Our findings indicate that KCND3 pathogenic variants may be responsible for a wider phenotypic spectrum than previously thought, by including childhood epileptic encephalopathy. Furthermore, this study provides evidence that GRIN1 and HCN1 are candidate genes for Dravet and Dravet-like phenotypes.</AbstractText
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In this case report, a patient was diagnosed with new-onset Bell's palsy 3 weeks after the onset of neuroinvasive West Nile virus. This was the second case report of West Nile virus-associated Bell's palsy, highlighting the need to monitor these patients for peripheral neuropathies. This case report is also intended to raise awareness about the prevalence of West Nile virus in the USA.</AbstractText
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Association of the P441L KCNQ1 variant with severity of long QT syndrome and risk of cardiac events. Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.</AbstractText
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Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome. This study aimed to investigate the genetic etiology of epilepsy in a cohort of Chinese children.</AbstractText Targeted next-generation sequencing (NGS) was performed for 120 patients with unexplained epilepsy, including 71 patients with early-onset epileptic encephalopathies, and 16 patients with Dravet syndrome (including three patients with a Dravet-like phenotype) but without SCN1A pathogenic variants.</AbstractText Pathogenic variants of 14 genes were discovered in 22 patients (18%). A de novo KCND3 pathogenic variant (c.1174G > A, p.Val392Ile) was identified in a boy with refractory epilepsy, psychomotor regression, attention deficit, and visual decline. Pathogenic variants in other coding genes were excluded via whole exome sequencing. This KCND3 variant was previously confirmed to be pathogenic by Giudicessi, et al. However, the clinical profile was different: sudden death at 20 years old without any medical history of neurological disorders, nor with any diseases typically caused by KCND3 pathogenic variants such as Brugada syndrome, spinocerebellar ataxia type 19/22 or ataxia accompanied by epilepsy. This indicates that we have identified a new KCND3 phenotype. In addition, we also uncovered a GRIN1 pathogenic variant and a novel HCN1 pathogenic variant in the Dravet cohort.</AbstractText Our study highlights the significant utility of NGS panels in the genetic diagnosis of pediatric epilepsy. Our findings indicate that KCND3 pathogenic variants may be responsible for a wider phenotypic spectrum than previously thought, by including childhood epileptic encephalopathy. Furthermore, this study provides evidence that GRIN1 and HCN1 are candidate genes for Dravet and Dravet-like phenotypes.</AbstractText
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New-onset Bell's palsy after neuroinvasive West Nile virus. In this case report, a patient was diagnosed with new-onset Bell's palsy 3 weeks after the onset of neuroinvasive West Nile virus. This was the second case report of West Nile virus-associated Bell's palsy, highlighting the need to monitor these patients for peripheral neuropathies. This case report is also intended to raise awareness about the prevalence of West Nile virus in the USA.</AbstractText
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40722872
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19837031
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40742796
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Chronic Ammonia Stress in Chinese Perch (Siniperca chuatsi): Oxidative Response, Nitrogen Metabolism, and Multi-Enzyme-Mediated Molecular Detoxification Defense Mechanisms.
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Cellular and molecular mechanisms of pain.
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Communication and end-of-life care in dementia: insights from a close family member working in healthcare.
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Chinese perch (<i
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The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.</AbstractText
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There is very little documented evidence on the experiences of healthcare professionals caring for their own family outside of their role. This article explores the differences in the care received as the author shares her perspectives of caring for her mother, who was diagnosed with dementia. The author reflects on the care received and the impact of communication, as well as the ethical limitations of caring for a member of her own family. Significant references to communication barriers already exist within the literature, relating to end-of-life conversations. The presence of a relative who has a healthcare background may further impact the communication approach of healthcare professionals. Communication barriers also influence conversations about future care needs and preferences, including access to advance care planning, specialist palliative care and anticipatory medications, which may be difficult to access for patients with a non-cancer diagnosis such as dementia. While they may be challenging, effective and empathic end-of-life conversations open up patient choices, prevent inappropriate palliative care and may even impact the bereavement process.</AbstractText
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Chronic Ammonia Stress in Chinese Perch (Siniperca chuatsi): Oxidative Response, Nitrogen Metabolism, and Multi-Enzyme-Mediated Molecular Detoxification Defense Mechanisms. Chinese perch (<i
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Cellular and molecular mechanisms of pain. The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.</AbstractText
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Communication and end-of-life care in dementia: insights from a close family member working in healthcare. There is very little documented evidence on the experiences of healthcare professionals caring for their own family outside of their role. This article explores the differences in the care received as the author shares her perspectives of caring for her mother, who was diagnosed with dementia. The author reflects on the care received and the impact of communication, as well as the ethical limitations of caring for a member of her own family. Significant references to communication barriers already exist within the literature, relating to end-of-life conversations. The presence of a relative who has a healthcare background may further impact the communication approach of healthcare professionals. Communication barriers also influence conversations about future care needs and preferences, including access to advance care planning, specialist palliative care and anticipatory medications, which may be difficult to access for patients with a non-cancer diagnosis such as dementia. While they may be challenging, effective and empathic end-of-life conversations open up patient choices, prevent inappropriate palliative care and may even impact the bereavement process.</AbstractText
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29516549
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25885265
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29742139
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CEST-MRI studies of cells loaded with lanthanide shift reagents.
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MPnRAGE: A technique to simultaneously acquire hundreds of differently contrasted MPRAGE images with applications to quantitative T1 mapping.
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A novel soft tissue prediction methodology for orthognathic surgery based on probabilistic finite element modelling.
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Magnetic resonance imaging has been used extensively to track in vivo implanted cells that have been previously labeled with relaxation enhancers. However, this approach is not suitable to track multiple cell populations, as it may lead to confounding results in case the contrast agent is released from the labeled cells. This paper demonstrates how the use of CEST agents can overcome these issues. After encapsulating paramagnetic lanthanide shift reagents, we may shift the absorption frequency of the intracellular water resonance (δ<sup Eu-HPDO3A, Dy-HPDO3A, and Tm-HPDO3A were used as shift reagents for labeling murine breast cancer cells and murine macrophages by hypotonic swelling and pinocytosis. The CEST-MR images were acquired at 7 T, and the saturation transfer effect was measured. Samples at different dilution of cells were analyzed to quantify the detection threshold. In vitro experiments of cell proliferation were carried out. Finally, murine breast cancer cells were injected subcutaneously in mice, and MR images were acquired to assess the proliferation index in vivo.</AbstractText It was found that entrapment of the paramagnetic complexes into endosomes (i.e., using the pinocytosis route) leads to an enhanced shift of the intracellular water resonance. δ<sup Cells can be visualized by CEST MRI after loading with paramagnetic shift reagent, by exploiting the large ensemble of the properly shifted intracellular water molecules. A better performance is obtained when the complexes are entrapped inside the endosomes. The observed (δ<sup
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To introduce a new technique called MPnRAGE, which produces hundreds of images with different T1 contrasts and a B1 corrected T1 map.</AbstractText An interleaved three-dimensional radial k-space trajectory with a sliding window reconstruction is used in conjunction with magnetization preparation pulses. This work modifies the SNAPSHOT-FLASH T1 fitting equations for radial imaging with view-sharing and develops a new rapid B1 correction procedure. MPnRAGE is demonstrated in phantoms and volunteers, including two volunteers with eight scans each and eight volunteers with two scans each. T1 values from MPnRAGE were compared with those from fast spin echo inversion recovery (FSE-IR) in phantoms and a healthy human brain at 3 Tesla (T).</AbstractText The T1 fit for human white and gray matter was T1MPnRAGE = 1.00 · T1FSE-IR + 24 ms, r(2) = 0.990. Voxel-wise coefficient of variation in T1 measurements across eight time points was between 0.02 and 0.08. Region of interest-based T1 values were reproducible to within 2% and agree well with literature values.</AbstractText In the same amount of time as a traditional MPRAGE exam (7.5 min), MPnRAGE was shown to produce hundreds of images with alternate T1 contrasts as well as an accurate and reproducible T1 map that is robust to B1 errors.</AbstractText
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Repositioning of the maxilla in orthognathic surgery is carried out for functional and aesthetic purposes. Pre-surgical planning tools can predict 3D facial appearance by computing the response of the soft tissue to the changes to the underlying skeleton. The clinical use of commercial prediction software remains controversial, likely due to the deterministic nature of these computational predictions. A novel probabilistic finite element model (FEM) for the prediction of postoperative facial soft tissues is proposed in this paper. A probabilistic FEM was developed and validated on a cohort of eight patients who underwent maxillary repositioning and had pre- and postoperative cone beam computed tomography (CBCT) scans taken. Firstly, a variables correlation assessed various modelling parameters. Secondly, a design of experiments (DOE) provided a range of potential outcomes based on uniformly distributed input parameters, followed by an optimisation. Lastly, the second DOE iteration provided optimised predictions with a probability range. A range of 3D predictions was obtained using the probabilistic FEM and validated using reconstructed soft tissue surfaces from the postoperative CBCT data. The predictions in the nose and upper lip areas accurately include the true postoperative position, whereas the prediction under-estimates the position of the cheeks and lower lip. A probabilistic FEM has been developed and validated for the prediction of the facial appearance following orthognathic surgery. This method shows how inaccuracies in the modelling and uncertainties in executing surgical planning influence the soft tissue prediction and it provides a range of predictions including a minimum and maximum, which may be helpful for patients in understanding the impact of surgery on the face.</AbstractText
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CEST-MRI studies of cells loaded with lanthanide shift reagents. Magnetic resonance imaging has been used extensively to track in vivo implanted cells that have been previously labeled with relaxation enhancers. However, this approach is not suitable to track multiple cell populations, as it may lead to confounding results in case the contrast agent is released from the labeled cells. This paper demonstrates how the use of CEST agents can overcome these issues. After encapsulating paramagnetic lanthanide shift reagents, we may shift the absorption frequency of the intracellular water resonance (δ<sup Eu-HPDO3A, Dy-HPDO3A, and Tm-HPDO3A were used as shift reagents for labeling murine breast cancer cells and murine macrophages by hypotonic swelling and pinocytosis. The CEST-MR images were acquired at 7 T, and the saturation transfer effect was measured. Samples at different dilution of cells were analyzed to quantify the detection threshold. In vitro experiments of cell proliferation were carried out. Finally, murine breast cancer cells were injected subcutaneously in mice, and MR images were acquired to assess the proliferation index in vivo.</AbstractText It was found that entrapment of the paramagnetic complexes into endosomes (i.e., using the pinocytosis route) leads to an enhanced shift of the intracellular water resonance. δ<sup Cells can be visualized by CEST MRI after loading with paramagnetic shift reagent, by exploiting the large ensemble of the properly shifted intracellular water molecules. A better performance is obtained when the complexes are entrapped inside the endosomes. The observed (δ<sup
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MPnRAGE: A technique to simultaneously acquire hundreds of differently contrasted MPRAGE images with applications to quantitative T1 mapping. To introduce a new technique called MPnRAGE, which produces hundreds of images with different T1 contrasts and a B1 corrected T1 map.</AbstractText An interleaved three-dimensional radial k-space trajectory with a sliding window reconstruction is used in conjunction with magnetization preparation pulses. This work modifies the SNAPSHOT-FLASH T1 fitting equations for radial imaging with view-sharing and develops a new rapid B1 correction procedure. MPnRAGE is demonstrated in phantoms and volunteers, including two volunteers with eight scans each and eight volunteers with two scans each. T1 values from MPnRAGE were compared with those from fast spin echo inversion recovery (FSE-IR) in phantoms and a healthy human brain at 3 Tesla (T).</AbstractText The T1 fit for human white and gray matter was T1MPnRAGE = 1.00 · T1FSE-IR + 24 ms, r(2) = 0.990. Voxel-wise coefficient of variation in T1 measurements across eight time points was between 0.02 and 0.08. Region of interest-based T1 values were reproducible to within 2% and agree well with literature values.</AbstractText In the same amount of time as a traditional MPRAGE exam (7.5 min), MPnRAGE was shown to produce hundreds of images with alternate T1 contrasts as well as an accurate and reproducible T1 map that is robust to B1 errors.</AbstractText
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A novel soft tissue prediction methodology for orthognathic surgery based on probabilistic finite element modelling. Repositioning of the maxilla in orthognathic surgery is carried out for functional and aesthetic purposes. Pre-surgical planning tools can predict 3D facial appearance by computing the response of the soft tissue to the changes to the underlying skeleton. The clinical use of commercial prediction software remains controversial, likely due to the deterministic nature of these computational predictions. A novel probabilistic finite element model (FEM) for the prediction of postoperative facial soft tissues is proposed in this paper. A probabilistic FEM was developed and validated on a cohort of eight patients who underwent maxillary repositioning and had pre- and postoperative cone beam computed tomography (CBCT) scans taken. Firstly, a variables correlation assessed various modelling parameters. Secondly, a design of experiments (DOE) provided a range of potential outcomes based on uniformly distributed input parameters, followed by an optimisation. Lastly, the second DOE iteration provided optimised predictions with a probability range. A range of 3D predictions was obtained using the probabilistic FEM and validated using reconstructed soft tissue surfaces from the postoperative CBCT data. The predictions in the nose and upper lip areas accurately include the true postoperative position, whereas the prediction under-estimates the position of the cheeks and lower lip. A probabilistic FEM has been developed and validated for the prediction of the facial appearance following orthognathic surgery. This method shows how inaccuracies in the modelling and uncertainties in executing surgical planning influence the soft tissue prediction and it provides a range of predictions including a minimum and maximum, which may be helpful for patients in understanding the impact of surgery on the face.</AbstractText
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40782673
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36501116
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40446364
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Alzheimer's disease: Clinical trials to watch.
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The Effects of Dietary Interventions on Brain Aging and Neurological Diseases.
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Rumination as a within-person indirect pathway between daily negative life events and suicidal ideation in recently hospitalized adults.
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Second-generation anti-amyloid therapies (ATTs) offer new options for early Alzheimer's disease treatment, but with modest efficacy and documented adverse events. Here we highlight several ongoing clinical trials, aiming to develop therapeutic agents with higher efficacy and better safety profiles including third-generation ATTs, aggregation inhibitors, Sigma-1 receptor agonists, anti-tau antisense oligonucleotides, and GLP-1 receptor agonists.</AbstractText
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Dietary interventions can ameliorate age-related neurological decline. Decades of research of in vitro studies, animal models, and clinical trials support their ability and efficacy to improve behavioral outcomes by inducing biochemical and physiological changes that lead to a more resilient brain. Dietary interventions including calorie restriction, alternate day fasting, time restricted feeding, and fasting mimicking diets not only improve normal brain aging but also slow down, or even reverse, the progression of neurological diseases. In this review, we focus on the effects of intermittent and periodic fasting on improving phenotypic outcomes, such as cognitive and motor-coordination decline, in the normal aging brain through an increase in neurogenesis and synaptic plasticity, and decrease in neuroinflammation, mitochondrial dysfunction, and oxidative stress. We summarize the results of various dietary interventions in animal models of age-related neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and Multiple Sclerosis and discuss the results of clinical trials that explore the feasibility of dietary interventions in the prevention and treatment of these diseases.</AbstractText
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Negative life events are often implicated as a near-term risk factor for suicidal ideation (SI); however ruminative processes may play a critical role in amplifying the distress following experiences of negative life events, ultimately leading to greater suicide risk. In the present work, we examined whether rumination indirectly impacted the association between negative events and SI intensity in a day-level ecological momentary assessment (EMA) study. Participants (N = 107; M<sub
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Alzheimer's disease: Clinical trials to watch. Second-generation anti-amyloid therapies (ATTs) offer new options for early Alzheimer's disease treatment, but with modest efficacy and documented adverse events. Here we highlight several ongoing clinical trials, aiming to develop therapeutic agents with higher efficacy and better safety profiles including third-generation ATTs, aggregation inhibitors, Sigma-1 receptor agonists, anti-tau antisense oligonucleotides, and GLP-1 receptor agonists.</AbstractText
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The Effects of Dietary Interventions on Brain Aging and Neurological Diseases. Dietary interventions can ameliorate age-related neurological decline. Decades of research of in vitro studies, animal models, and clinical trials support their ability and efficacy to improve behavioral outcomes by inducing biochemical and physiological changes that lead to a more resilient brain. Dietary interventions including calorie restriction, alternate day fasting, time restricted feeding, and fasting mimicking diets not only improve normal brain aging but also slow down, or even reverse, the progression of neurological diseases. In this review, we focus on the effects of intermittent and periodic fasting on improving phenotypic outcomes, such as cognitive and motor-coordination decline, in the normal aging brain through an increase in neurogenesis and synaptic plasticity, and decrease in neuroinflammation, mitochondrial dysfunction, and oxidative stress. We summarize the results of various dietary interventions in animal models of age-related neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and Multiple Sclerosis and discuss the results of clinical trials that explore the feasibility of dietary interventions in the prevention and treatment of these diseases.</AbstractText
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Rumination as a within-person indirect pathway between daily negative life events and suicidal ideation in recently hospitalized adults. Negative life events are often implicated as a near-term risk factor for suicidal ideation (SI); however ruminative processes may play a critical role in amplifying the distress following experiences of negative life events, ultimately leading to greater suicide risk. In the present work, we examined whether rumination indirectly impacted the association between negative events and SI intensity in a day-level ecological momentary assessment (EMA) study. Participants (N = 107; M<sub
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18370602
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15488911
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18641892
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Mirror neuron system differentially activated by facial expressions and social hand gestures: a functional magnetic resonance imaging study.
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An fMRI study of imitation: action representation and body schema.
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Neurobiology of apathy in Alzheimer's disease.
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Facial expressions and hand gestures are utilized in nonverbal communication to convey socially relevant information. One key process that mediates nonverbal communication is simulation. The mirror neuron system (MNS), which maps observed actions onto the motor representations used when producing those actions, likely plays a role in simulation. Previous neuroimaging experiments have identified a putative human MNS that includes the inferior parietal lobule (IPL) and the frontal operculum. Although understanding nonverbal communication presumably involves the MNS, it is unknown whether these two forms of nonverbal social communication have distinct representations within that system. Here we report the results of a functional magnetic resonance imaging experiment in which participants viewed, imitated, and produced facial expressions and social hand gestures. The observation and execution of facial expressions and social hand gestures activated the MNS, but the magnitude of response differed. Activation in the IPL was greater for social hand gestures, whereas activation in the frontal operculum was greater for viewing facial expressions. The locations of neural activity evoked by viewing facial expressions and social hand gestures in the frontal operculum were significantly different. These data argue that there are distinct representations of different types of social nonverbal communication in the MNS.</AbstractText
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Recent neuropsychological investigations of apraxia have led to new hypotheses about the representational defects associated with imitation impairments in neurological patients. This fMRI experiment investigated the relation between imitation and the body schema in healthy subjects. Experimental conditions were derived from a factorial plan, and participants were asked to watch a human model performing bodily gestures and then to execute either an identical or a different action, with the same or different limbs. Brain areas activated when subjects imitated the model were traced to the representation of the action (main effect of performing an identical action regardless of limb), to the body schema (using the same limb regardless of action), or to both. The first set of analyses yielded a network associated with visual perception, indicating that action representation is primarily visuospatial not motor, while the second analysis highlighted regions involved in body schema including the inferior parietal cortex and the insula. It is suggested that imitation of simple body gestures requires both a visuospatial description of the observed model, sustained by visual perception areas in the right occipitotemporal and superior parietal cortices and a visuospatial description of one's own body, supported by the left inferior parietal lobule. These results favor a model of praxis proposing that imitation deficits in left inferior parietal lobe patients with apraxia reflect primarily an impairment of the body schema, while deficits of praxis in right parietal patients are limited to gestures demanding in terms of visuospatial analysis.</AbstractText
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Apathy is considered the most frequent neuropsychiatric disturbance in dementia and its outcome is generally deleterious. Apathy can be related to a dysfunction of the anatomical-system that supports the generation of voluntary actions, namely the prefrontal cortex and/or the prefrontal-subcortical circuits. In Alzheimer's disease, pathological and neuroimaging data indicate that apathy is likely due to a dysfunction of the medial prefrontal cortex. Accordingly, in this review article, we propose a pathophysiological model to explain apathetic behavior in Alzheimer's disease, combining data from neuroimaging, neuropathology and experimental research on the role of orbito-frontal cortex, anterior cingulate cortex, basal ganglia and dopamine in decision-making neurobiology.</AbstractText
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Mirror neuron system differentially activated by facial expressions and social hand gestures: a functional magnetic resonance imaging study. Facial expressions and hand gestures are utilized in nonverbal communication to convey socially relevant information. One key process that mediates nonverbal communication is simulation. The mirror neuron system (MNS), which maps observed actions onto the motor representations used when producing those actions, likely plays a role in simulation. Previous neuroimaging experiments have identified a putative human MNS that includes the inferior parietal lobule (IPL) and the frontal operculum. Although understanding nonverbal communication presumably involves the MNS, it is unknown whether these two forms of nonverbal social communication have distinct representations within that system. Here we report the results of a functional magnetic resonance imaging experiment in which participants viewed, imitated, and produced facial expressions and social hand gestures. The observation and execution of facial expressions and social hand gestures activated the MNS, but the magnitude of response differed. Activation in the IPL was greater for social hand gestures, whereas activation in the frontal operculum was greater for viewing facial expressions. The locations of neural activity evoked by viewing facial expressions and social hand gestures in the frontal operculum were significantly different. These data argue that there are distinct representations of different types of social nonverbal communication in the MNS.</AbstractText
|
An fMRI study of imitation: action representation and body schema. Recent neuropsychological investigations of apraxia have led to new hypotheses about the representational defects associated with imitation impairments in neurological patients. This fMRI experiment investigated the relation between imitation and the body schema in healthy subjects. Experimental conditions were derived from a factorial plan, and participants were asked to watch a human model performing bodily gestures and then to execute either an identical or a different action, with the same or different limbs. Brain areas activated when subjects imitated the model were traced to the representation of the action (main effect of performing an identical action regardless of limb), to the body schema (using the same limb regardless of action), or to both. The first set of analyses yielded a network associated with visual perception, indicating that action representation is primarily visuospatial not motor, while the second analysis highlighted regions involved in body schema including the inferior parietal cortex and the insula. It is suggested that imitation of simple body gestures requires both a visuospatial description of the observed model, sustained by visual perception areas in the right occipitotemporal and superior parietal cortices and a visuospatial description of one's own body, supported by the left inferior parietal lobule. These results favor a model of praxis proposing that imitation deficits in left inferior parietal lobe patients with apraxia reflect primarily an impairment of the body schema, while deficits of praxis in right parietal patients are limited to gestures demanding in terms of visuospatial analysis.</AbstractText
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Neurobiology of apathy in Alzheimer's disease. Apathy is considered the most frequent neuropsychiatric disturbance in dementia and its outcome is generally deleterious. Apathy can be related to a dysfunction of the anatomical-system that supports the generation of voluntary actions, namely the prefrontal cortex and/or the prefrontal-subcortical circuits. In Alzheimer's disease, pathological and neuroimaging data indicate that apathy is likely due to a dysfunction of the medial prefrontal cortex. Accordingly, in this review article, we propose a pathophysiological model to explain apathetic behavior in Alzheimer's disease, combining data from neuroimaging, neuropathology and experimental research on the role of orbito-frontal cortex, anterior cingulate cortex, basal ganglia and dopamine in decision-making neurobiology.</AbstractText
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37951144
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23264798
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37152034
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Estimating the prevalence and incidence of multiple system atrophy in the USA: Insights from a national claims database.
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Hummingbird sign in progressive supranuclear palsy disease.
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Intra-fraction motion of pelvic oligometastases and feasibility of PTV margin reduction using MRI guided adaptive radiotherapy.
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Published literature on the prevalence and incidence of multiple system atrophy (MSA) in the US are scarce or based on relatively older studies. The objective of this study was to estimate the prevalence and cumulative incidence of MSA in the US.</AbstractText This was a retrospective study of individuals aged 30 years or older in a large US claims database from 2016 to 2021. The primary endpoint was ≥1 MSA claim. Persons with ≥2 MSA claims were also examined. Incident cases aged ≥30 years with a minimum of one-year of continuous enrollment prior to and following cohort entry were identified. Prevalence and cumulative incidence of MSA were estimated for year 2021 and were also standardized to the 2021 US population.</AbstractText The crude prevalence of MSA was 7.2 per 100,000 persons in 2021 and increased with age. After standardization to the US population, the age-adjusted prevalence was 12.4 per 100,000 translating to 41,133 persons in the 2021 US population. In persons with ≥2 MSA claims, the crude and age-adjusted prevalence were 3.1 and 5.7 per 100,000 persons. The crude cumulative incidence of MSA for individuals aged 30 years and older was 9.8 per 100,000 persons in 2021. The estimated cumulative incidence of MSA in individuals 30 years or older, age-adjusted to the 2021 U S. population, was 14.2 per 100,000.</AbstractText This study provides real-world evidence on the prevalence and cumulative incidence of MSA in the US to better understand the medical care needs and treatment.</AbstractText
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Progressive supranuclear palsy (PSP) is characterized by slowness, rigidity, bradykinesia, repeated falls, downgaze limitation and dementia. Midbrain atrophy on magnetic resonance imaging is highly suggestive of PSP and is described as "hummingbird sign". This sign is very helpful in differentiating PSP patients from those with Parkinson's disease.We hereby report a 72-year-old female case of PSP primarily diagnosed with Parkinson's disease.</AbstractText
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This study assesses the impact of intra-fraction motion and PTV margin size on target coverage for patients undergoing radiation treatment of pelvic oligometastases. Dosimetric sparing of the bowel as a function of the PTV margin is also evaluated.</AbstractText Seven patients with pelvic oligometastases previously treated on our MR-linac (35 Gy in 5 fractions) were included in this study. Retrospective adaptive plans were created for each fraction on the daily MRI datasets using PTV margins of 5 mm, 3 mm, and 2 mm. Dosimetric constraint violations and GTV coverage were measured as a function of PTV margin size. The impact of intra-fraction motion on GTV coverage was assessed by tracking the GTV position on the cine MR images acquired during treatment delivery and creating an intra-fraction dose distribution for each IMRT beam. The intra-fraction dose was accumulated for each fraction to determine the total dose delivered to the target for each PTV size.</AbstractText All OAR constraints were achieved in 85.7%, 94.3%, and 100.0% of fractions when using 5 mm, 3 mm, and 2 mm PTV margins while scaling to 95% PTV coverage. Compared to plans with a 5 mm PTV margin, there was a 27.4 ± 12.3% (4.0 ± 2.2 Gy) and an 18.5 ± 7.3% (2.7 ± 1.4 Gy) reduction in the bowel D<sub A 2 mm PTV margin achieved a minimum of 95% GTV coverage while reducing the dose to the bowel for all patients.</AbstractText
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Estimating the prevalence and incidence of multiple system atrophy in the USA: Insights from a national claims database. Published literature on the prevalence and incidence of multiple system atrophy (MSA) in the US are scarce or based on relatively older studies. The objective of this study was to estimate the prevalence and cumulative incidence of MSA in the US.</AbstractText This was a retrospective study of individuals aged 30 years or older in a large US claims database from 2016 to 2021. The primary endpoint was ≥1 MSA claim. Persons with ≥2 MSA claims were also examined. Incident cases aged ≥30 years with a minimum of one-year of continuous enrollment prior to and following cohort entry were identified. Prevalence and cumulative incidence of MSA were estimated for year 2021 and were also standardized to the 2021 US population.</AbstractText The crude prevalence of MSA was 7.2 per 100,000 persons in 2021 and increased with age. After standardization to the US population, the age-adjusted prevalence was 12.4 per 100,000 translating to 41,133 persons in the 2021 US population. In persons with ≥2 MSA claims, the crude and age-adjusted prevalence were 3.1 and 5.7 per 100,000 persons. The crude cumulative incidence of MSA for individuals aged 30 years and older was 9.8 per 100,000 persons in 2021. The estimated cumulative incidence of MSA in individuals 30 years or older, age-adjusted to the 2021 U S. population, was 14.2 per 100,000.</AbstractText This study provides real-world evidence on the prevalence and cumulative incidence of MSA in the US to better understand the medical care needs and treatment.</AbstractText
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Hummingbird sign in progressive supranuclear palsy disease. Progressive supranuclear palsy (PSP) is characterized by slowness, rigidity, bradykinesia, repeated falls, downgaze limitation and dementia. Midbrain atrophy on magnetic resonance imaging is highly suggestive of PSP and is described as "hummingbird sign". This sign is very helpful in differentiating PSP patients from those with Parkinson's disease.We hereby report a 72-year-old female case of PSP primarily diagnosed with Parkinson's disease.</AbstractText
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Intra-fraction motion of pelvic oligometastases and feasibility of PTV margin reduction using MRI guided adaptive radiotherapy. This study assesses the impact of intra-fraction motion and PTV margin size on target coverage for patients undergoing radiation treatment of pelvic oligometastases. Dosimetric sparing of the bowel as a function of the PTV margin is also evaluated.</AbstractText Seven patients with pelvic oligometastases previously treated on our MR-linac (35 Gy in 5 fractions) were included in this study. Retrospective adaptive plans were created for each fraction on the daily MRI datasets using PTV margins of 5 mm, 3 mm, and 2 mm. Dosimetric constraint violations and GTV coverage were measured as a function of PTV margin size. The impact of intra-fraction motion on GTV coverage was assessed by tracking the GTV position on the cine MR images acquired during treatment delivery and creating an intra-fraction dose distribution for each IMRT beam. The intra-fraction dose was accumulated for each fraction to determine the total dose delivered to the target for each PTV size.</AbstractText All OAR constraints were achieved in 85.7%, 94.3%, and 100.0% of fractions when using 5 mm, 3 mm, and 2 mm PTV margins while scaling to 95% PTV coverage. Compared to plans with a 5 mm PTV margin, there was a 27.4 ± 12.3% (4.0 ± 2.2 Gy) and an 18.5 ± 7.3% (2.7 ± 1.4 Gy) reduction in the bowel D<sub A 2 mm PTV margin achieved a minimum of 95% GTV coverage while reducing the dose to the bowel for all patients.</AbstractText
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33187607
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29536502
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34272767
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Long-Term Neurocognitive, Mental Health Consequences of Contact Sports.
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Concussion: A History of Science and Medicine, 1870-2005.
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Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI.
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This article presents a brief history and literature review of chronic traumatic encephalopathy (CTE) in professional athletes that played contact sports. The hypothesis that CTE results from concussion or sub-concussive blows is based largely on several case series investigations with considerable bias. Evidence of CTE in its clinical presentation has not been generally noted in studies of living retired athletes. However, these studies also demonstrated limitation in research methodology. This paper aims to present a balanced perspective amidst a politically charged subject matter.</AbstractText
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To review the intellectual history of concussion from the mid-19th century to the opening decade of the 21st century.</AbstractText Head injuries (HI) and their acute and long-term effects have been investigated for centuries, with major reviews of the topic appearing by 1870. Thus, while it has long been acknowledged that chronic traumatic encephalopathy was first described by Harrison Martland in 1928, an examination of the history of concussion research up to Martland's seminal report places his studies in a deeper historical context. This history makes clear that Martland's findings were one among many such studies showcasing the lasting dangers of blows to the head. In the years after Martland published his study, his paper was frequently cited in other papers that made clear that blows to the head, of all ranges of severity, were dangerous injuries with potentially life-changing consequences.</AbstractText The author has engaged in an historical analysis of the development and elaboration of concussion research in clinical medicine, neurology, neurosurgery, and those scientific disciplines related to clinical medicine. The author has found numerous primary sources from the history of medicine and science that describe the acute and chronic effects of single and repeated sub-concussive and concussive blows to the head.</AbstractText This study makes clear that evidence-based methodologies inevitably short-change the knowledge of past clinicians and scientists by holding these figures to normative standards of recent invention. What criticism of this kind fails to recognize is that past investigators, many of them pioneers in their fields, published their work in ways that matched the highest normative standards of their day for the presentation of evidence.</AbstractText It has been recognized for a long time that concussions are dangerous injuries with potentially life-changing consequences, ranging from permanent symptoms to degenerative neurological states. The intellectual history of medicine and science from 1870 to the recent past shows both a continuity of clinical observations about HI and a steady, incremental accumulation of knowledge refining our understanding of those observations from a remarkably wide sphere of scientific disciplines.</AbstractText
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A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool. Therefore, better noninvasive tests are required to determine which livers will function following implantation and hence can be safely transplanted. This study assesses the temperature sensitivity of proton density fat fraction and relaxometry parameters and examines their potential for assessment of liver function ex vivo.</AbstractText Six ex vivo human livers were scanned during static cold storage following normothermic machine perfusion. Proton density fat fraction, T<sub Strong linear temperature sensitivities were observed for proton density fat fraction (R<sup Temperature correction is essential for robust measurement of proton density fat fraction and T<sub
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Long-Term Neurocognitive, Mental Health Consequences of Contact Sports. This article presents a brief history and literature review of chronic traumatic encephalopathy (CTE) in professional athletes that played contact sports. The hypothesis that CTE results from concussion or sub-concussive blows is based largely on several case series investigations with considerable bias. Evidence of CTE in its clinical presentation has not been generally noted in studies of living retired athletes. However, these studies also demonstrated limitation in research methodology. This paper aims to present a balanced perspective amidst a politically charged subject matter.</AbstractText
|
Concussion: A History of Science and Medicine, 1870-2005. To review the intellectual history of concussion from the mid-19th century to the opening decade of the 21st century.</AbstractText Head injuries (HI) and their acute and long-term effects have been investigated for centuries, with major reviews of the topic appearing by 1870. Thus, while it has long been acknowledged that chronic traumatic encephalopathy was first described by Harrison Martland in 1928, an examination of the history of concussion research up to Martland's seminal report places his studies in a deeper historical context. This history makes clear that Martland's findings were one among many such studies showcasing the lasting dangers of blows to the head. In the years after Martland published his study, his paper was frequently cited in other papers that made clear that blows to the head, of all ranges of severity, were dangerous injuries with potentially life-changing consequences.</AbstractText The author has engaged in an historical analysis of the development and elaboration of concussion research in clinical medicine, neurology, neurosurgery, and those scientific disciplines related to clinical medicine. The author has found numerous primary sources from the history of medicine and science that describe the acute and chronic effects of single and repeated sub-concussive and concussive blows to the head.</AbstractText This study makes clear that evidence-based methodologies inevitably short-change the knowledge of past clinicians and scientists by holding these figures to normative standards of recent invention. What criticism of this kind fails to recognize is that past investigators, many of them pioneers in their fields, published their work in ways that matched the highest normative standards of their day for the presentation of evidence.</AbstractText It has been recognized for a long time that concussions are dangerous injuries with potentially life-changing consequences, ranging from permanent symptoms to degenerative neurological states. The intellectual history of medicine and science from 1870 to the recent past shows both a continuity of clinical observations about HI and a steady, incremental accumulation of knowledge refining our understanding of those observations from a remarkably wide sphere of scientific disciplines.</AbstractText
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Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI. A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool. Therefore, better noninvasive tests are required to determine which livers will function following implantation and hence can be safely transplanted. This study assesses the temperature sensitivity of proton density fat fraction and relaxometry parameters and examines their potential for assessment of liver function ex vivo.</AbstractText Six ex vivo human livers were scanned during static cold storage following normothermic machine perfusion. Proton density fat fraction, T<sub Strong linear temperature sensitivities were observed for proton density fat fraction (R<sup Temperature correction is essential for robust measurement of proton density fat fraction and T<sub
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16634654
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36466607
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17016664
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Rhesus macaques (Macaca mulatta) monitor uncertainty during numerosity judgments.
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Advanced aging effects on implicit motor imagery and its links to motor performance: An investigation via mental rotation of letters, hands, and feet.
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Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma.
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Two rhesus macaques (Macaca mulatta) judged arrays of dots on a computer screen as having more or fewer dots than a center value that was never presented in trials. After learning a center value, monkeys were given an uncertainty response that let them decline to make the numerosity judgment on that trial. Across center values (3-7), errors occurred most often for sets adjacent in numerosity to the center value. The monkeys also used the uncertainty response most frequently on these difficult trials. A 2nd experiment showed that monkeys' responses reflected numerical magnitude and not the surface-area illumination of the displays. This research shows that monkeys' uncertainty-monitoring capacity extends to the domain of numerical cognition. It also shows monkeys' use of the purest uncertainty response possible, uncontaminated by any secondary motivator.</AbstractText
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This study focuses on changes in implicit motor imagery during advanced aging and these changes' co-occurrences with physical motor deficits. We administered a mental rotation (MR) task with letters, hands, and feet to 28 young adults (20-27 years) and to 71 older adults (60-87 years), and assessed motor skills (gait mobility and hand dexterity) and neuropsychological performance. Compared to young adults, older adults showed lower MR performance for all stimuli and stronger biomechanical constraint effects on both hand and foot rotation. Moreover, the foot biomechanical constraint effect continued to increase during late adulthood, and declines in hand and foot motor imagery emerged at earlier old ages than declines in visual imagery. These results first demonstrated distinct aging trajectories of hand motor imagery, foot motor imagery, and visual imagery. Exploratory partial correlation analysis for older adults showed positive associations of low-level perceptual-motor skills (Trail Making Test-A performance) with hand and foot MR performance and positive associations of mobility (Timed Up and Go test performance) with foot and letter MR performance. These associations exhibited somewhat different patterns from those of young adults and raised the possibility that age-related declines in motor (and visual) imagery co-occur with declines in motor functioning.</AbstractText
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Glucocorticoids (GCs) such as dexamethasone (DEX) have been widely used as co-medication in cancer therapy because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, GCs are used in a supportive-care role, even though no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that GCs induce treatment resistance in some solid tumours. Since it is unknown whether GC-induced resistance occurs only occasionally or is a more common phenomenon, we performed a screening study using several established cell lines from bone, brain, breast and cervix carcinoma as well as melanoma and neuroblastoma together with fresh surgical resections from patients with breast cancer. We found that DEX inhibits cisplatin and 5-fluorouracil-induced apoptosis and promotes the growth of the majority of examined malignant cells. In contrast, and as expected, DEX acted pro-apoptotically and promoted the cytotoxic effect of chemotherapy in established and primary lymphoid cells. Thus, these data demonstrate the need for detailed molecular studies to clarify the mechanism of differential glucocorticoid signaling as well as controlled, prospective clinical studies.</AbstractText
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Rhesus macaques (Macaca mulatta) monitor uncertainty during numerosity judgments. Two rhesus macaques (Macaca mulatta) judged arrays of dots on a computer screen as having more or fewer dots than a center value that was never presented in trials. After learning a center value, monkeys were given an uncertainty response that let them decline to make the numerosity judgment on that trial. Across center values (3-7), errors occurred most often for sets adjacent in numerosity to the center value. The monkeys also used the uncertainty response most frequently on these difficult trials. A 2nd experiment showed that monkeys' responses reflected numerical magnitude and not the surface-area illumination of the displays. This research shows that monkeys' uncertainty-monitoring capacity extends to the domain of numerical cognition. It also shows monkeys' use of the purest uncertainty response possible, uncontaminated by any secondary motivator.</AbstractText
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Advanced aging effects on implicit motor imagery and its links to motor performance: An investigation via mental rotation of letters, hands, and feet. This study focuses on changes in implicit motor imagery during advanced aging and these changes' co-occurrences with physical motor deficits. We administered a mental rotation (MR) task with letters, hands, and feet to 28 young adults (20-27 years) and to 71 older adults (60-87 years), and assessed motor skills (gait mobility and hand dexterity) and neuropsychological performance. Compared to young adults, older adults showed lower MR performance for all stimuli and stronger biomechanical constraint effects on both hand and foot rotation. Moreover, the foot biomechanical constraint effect continued to increase during late adulthood, and declines in hand and foot motor imagery emerged at earlier old ages than declines in visual imagery. These results first demonstrated distinct aging trajectories of hand motor imagery, foot motor imagery, and visual imagery. Exploratory partial correlation analysis for older adults showed positive associations of low-level perceptual-motor skills (Trail Making Test-A performance) with hand and foot MR performance and positive associations of mobility (Timed Up and Go test performance) with foot and letter MR performance. These associations exhibited somewhat different patterns from those of young adults and raised the possibility that age-related declines in motor (and visual) imagery co-occur with declines in motor functioning.</AbstractText
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Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma. Glucocorticoids (GCs) such as dexamethasone (DEX) have been widely used as co-medication in cancer therapy because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, GCs are used in a supportive-care role, even though no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that GCs induce treatment resistance in some solid tumours. Since it is unknown whether GC-induced resistance occurs only occasionally or is a more common phenomenon, we performed a screening study using several established cell lines from bone, brain, breast and cervix carcinoma as well as melanoma and neuroblastoma together with fresh surgical resections from patients with breast cancer. We found that DEX inhibits cisplatin and 5-fluorouracil-induced apoptosis and promotes the growth of the majority of examined malignant cells. In contrast, and as expected, DEX acted pro-apoptotically and promoted the cytotoxic effect of chemotherapy in established and primary lymphoid cells. Thus, these data demonstrate the need for detailed molecular studies to clarify the mechanism of differential glucocorticoid signaling as well as controlled, prospective clinical studies.</AbstractText
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18353686
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9417966
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18633346
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The perception of pain in others suppresses somatosensory oscillations: a magnetoencephalography study.
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Premotor cortex activation during observation and naming of familiar tools.
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Survival analysis: time-dependent effects and time-varying risk factors.
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Accumulating evidence demonstrates that similar neural circuits are activated during the first-hand experience of pain and the observation of pain in others. However, most functional MRI studies did not detect signal change in the primary somatosensory cortex during pain empathy. To test if the perception of pain in others involves the primary somatosensory cortex, neuromagnetic oscillatory activity was recorded from the primary somatosensory cortex in 16 participants while they observed static pictures depicting body parts in painful and non-painful situations. The left median nerve was stimulated at the wrist, and the poststimulus rebounds of the approximately 10-Hz somatosensory cortical oscillations were quantified. Compared to the baseline condition, the level of the approximately 10-Hz oscillations was suppressed during both of the observational situations, indicating the activation of the primary somatosensory cortex. Importantly, watching painful compared to non-painful situations suppressed somatosensory oscillations to a significant stronger degree. In addition, the suppression caused by perceiving others in the painful relative to the non-painful situations correlated with the perspective taking subscale of the interpersonal reaction index. These results, consistent with the mirror-neuron system, demonstrate that the perception of pain in others modulates neural activity in primary somatosensory cortex and supports the idea that the perception of pain in others elicits subtle somatosensory activity that may be difficult to detect by fMRI techniques.</AbstractText
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Positron emission tomography was used to investigate whether observation of real objects (tools of common use) activates premotor areas in the absence of any overt motor demand. Silent naming of the presented tools and silent naming of their use were also studied. Right-handed normal subjects were employed. Tool observation strongly activated the left dorsal premotor cortex. In contrast, silent tool naming activated Broca's area without additional activity in the dorsal premotor cortex. Silent tool-use naming, in addition to activating Broca's area, increased the activity in the left dorsal premotor cortex and recruited the left ventral premotor cortex and the left supplementary motor area. These data indicate that, even in the absence of any subsequent movement, the left premotor cortex processes objects that, like tools, have a motor valence. This dorsal premotor activation, which further augments when the subject names the tool use, should reflect the neural activity related to motor schemata for object use. The presence of an activation of both dorsal premotor cortex and ventral premotor cortex during tool-use naming suggests a role for these two areas in understanding object semantics.</AbstractText
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In traditional Kaplan-Meier or Cox regression analysis, usually a risk factor measured at baseline is related to mortality thereafter. During follow-up, however, things may change: either the effect of a fixed baseline risk factor may vary over time, resulting in a weakening or strengthening of associations over time, or the risk factor itself may vary over time. In this paper, short-term versus long-term effects (so-called time-dependent effects) of a fixed baseline risk factor are addressed. An example is presented showing that underweight is a strong risk factor for mortality in dialysis patients, especially in the short run. In contrast, overweight is a risk factor for mortality, which is stronger in the long run than in the short run. In addition, the analysis of how time-varying risk factors (so-called time-dependent risk factors) are related to mortality is demonstrated by paying attention to the pitfall of adjusting for sequelae. The proper analysis of effects over time should be driven by a clear research question. Both kinds of research questions, that is those of time-dependent effects as well those of time-dependent risk factors, can be analyzed with time-dependent Cox regression analysis. It will be shown that using time-dependent risk factors usually implies focusing on short-term effects only.</AbstractText
|
The perception of pain in others suppresses somatosensory oscillations: a magnetoencephalography study. Accumulating evidence demonstrates that similar neural circuits are activated during the first-hand experience of pain and the observation of pain in others. However, most functional MRI studies did not detect signal change in the primary somatosensory cortex during pain empathy. To test if the perception of pain in others involves the primary somatosensory cortex, neuromagnetic oscillatory activity was recorded from the primary somatosensory cortex in 16 participants while they observed static pictures depicting body parts in painful and non-painful situations. The left median nerve was stimulated at the wrist, and the poststimulus rebounds of the approximately 10-Hz somatosensory cortical oscillations were quantified. Compared to the baseline condition, the level of the approximately 10-Hz oscillations was suppressed during both of the observational situations, indicating the activation of the primary somatosensory cortex. Importantly, watching painful compared to non-painful situations suppressed somatosensory oscillations to a significant stronger degree. In addition, the suppression caused by perceiving others in the painful relative to the non-painful situations correlated with the perspective taking subscale of the interpersonal reaction index. These results, consistent with the mirror-neuron system, demonstrate that the perception of pain in others modulates neural activity in primary somatosensory cortex and supports the idea that the perception of pain in others elicits subtle somatosensory activity that may be difficult to detect by fMRI techniques.</AbstractText
|
Premotor cortex activation during observation and naming of familiar tools. Positron emission tomography was used to investigate whether observation of real objects (tools of common use) activates premotor areas in the absence of any overt motor demand. Silent naming of the presented tools and silent naming of their use were also studied. Right-handed normal subjects were employed. Tool observation strongly activated the left dorsal premotor cortex. In contrast, silent tool naming activated Broca's area without additional activity in the dorsal premotor cortex. Silent tool-use naming, in addition to activating Broca's area, increased the activity in the left dorsal premotor cortex and recruited the left ventral premotor cortex and the left supplementary motor area. These data indicate that, even in the absence of any subsequent movement, the left premotor cortex processes objects that, like tools, have a motor valence. This dorsal premotor activation, which further augments when the subject names the tool use, should reflect the neural activity related to motor schemata for object use. The presence of an activation of both dorsal premotor cortex and ventral premotor cortex during tool-use naming suggests a role for these two areas in understanding object semantics.</AbstractText
|
Survival analysis: time-dependent effects and time-varying risk factors. In traditional Kaplan-Meier or Cox regression analysis, usually a risk factor measured at baseline is related to mortality thereafter. During follow-up, however, things may change: either the effect of a fixed baseline risk factor may vary over time, resulting in a weakening or strengthening of associations over time, or the risk factor itself may vary over time. In this paper, short-term versus long-term effects (so-called time-dependent effects) of a fixed baseline risk factor are addressed. An example is presented showing that underweight is a strong risk factor for mortality in dialysis patients, especially in the short run. In contrast, overweight is a risk factor for mortality, which is stronger in the long run than in the short run. In addition, the analysis of how time-varying risk factors (so-called time-dependent risk factors) are related to mortality is demonstrated by paying attention to the pitfall of adjusting for sequelae. The proper analysis of effects over time should be driven by a clear research question. Both kinds of research questions, that is those of time-dependent effects as well those of time-dependent risk factors, can be analyzed with time-dependent Cox regression analysis. It will be shown that using time-dependent risk factors usually implies focusing on short-term effects only.</AbstractText
|
37264457
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24589176
|
37160454
|
Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration.
|
Verbal fluency in cerebral small vessel disease and Alzheimer's disease.
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Artificial intelligence tools in clinical neuroradiology: essential medico-legal aspects.
|
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan (<sup
|
Patterns of verbal fluency deficits have been explored across different neurodegenerative disorders. This study sought to investigate the specific pattern of verbal fluency performance in cerebral small vessel disease (SVD), which is the most common cause of vascular cognitive impairment, and compare this with Alzheimer's disease (AD). Participants with SVD (n = 45), AD (n = 24) and healthy controls (n = 80) completed assessments of semantic and phonemic fluency. Mixed-model analyses of covariance were used to compare performance on the different fluency tasks between the groups, and a discriminant function analysis was conducted to examine group differentiation. The SVD group was impaired in both fluency tasks when compared to the controls. In contrast, the AD group displayed impairment in semantic fluency only. Discriminant function analysis revealed that fluency scores correctly classified 80% of SVD patients and 92% of AD patients. The pattern of performance observed in the SVD group may reflect deficits in executive function and processing speed impacting equivalently on semantic and phonemic fluency. The differences between the SVD and AD groups highlighted in this study may be useful for distinguishing between these conditions.</AbstractText
|
Commercial software based on artificial intelligence (AI) is entering clinical practice in neuroradiology. Consequently, medico-legal aspects of using Software as a Medical Device (SaMD) become increasingly important. These medico-legal issues warrant an interdisciplinary approach and may affect the way we work in daily practice. In this article, we seek to address three major topics: medical malpractice liability, regulation of AI-based medical devices, and privacy protection in shared medical imaging data, thereby focusing on the legal frameworks of the European Union and the USA. As many of the presented concepts are very complex and, in part, remain yet unsolved, this article is not meant to be comprehensive but rather thought-provoking. The goal is to engage clinical neuroradiologists in the debate and equip them to actively shape these topics in the future.</AbstractText
|
Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration. Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan (<sup
|
Verbal fluency in cerebral small vessel disease and Alzheimer's disease. Patterns of verbal fluency deficits have been explored across different neurodegenerative disorders. This study sought to investigate the specific pattern of verbal fluency performance in cerebral small vessel disease (SVD), which is the most common cause of vascular cognitive impairment, and compare this with Alzheimer's disease (AD). Participants with SVD (n = 45), AD (n = 24) and healthy controls (n = 80) completed assessments of semantic and phonemic fluency. Mixed-model analyses of covariance were used to compare performance on the different fluency tasks between the groups, and a discriminant function analysis was conducted to examine group differentiation. The SVD group was impaired in both fluency tasks when compared to the controls. In contrast, the AD group displayed impairment in semantic fluency only. Discriminant function analysis revealed that fluency scores correctly classified 80% of SVD patients and 92% of AD patients. The pattern of performance observed in the SVD group may reflect deficits in executive function and processing speed impacting equivalently on semantic and phonemic fluency. The differences between the SVD and AD groups highlighted in this study may be useful for distinguishing between these conditions.</AbstractText
|
Artificial intelligence tools in clinical neuroradiology: essential medico-legal aspects. Commercial software based on artificial intelligence (AI) is entering clinical practice in neuroradiology. Consequently, medico-legal aspects of using Software as a Medical Device (SaMD) become increasingly important. These medico-legal issues warrant an interdisciplinary approach and may affect the way we work in daily practice. In this article, we seek to address three major topics: medical malpractice liability, regulation of AI-based medical devices, and privacy protection in shared medical imaging data, thereby focusing on the legal frameworks of the European Union and the USA. As many of the presented concepts are very complex and, in part, remain yet unsolved, this article is not meant to be comprehensive but rather thought-provoking. The goal is to engage clinical neuroradiologists in the debate and equip them to actively shape these topics in the future.</AbstractText
|
26656563
|
16909237
|
24916076
|
Getting to know you: general and specific neural computations for learning about people.
|
Technical intelligence in animals: the kea model.
|
Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line.
|
Learning about other peoples' attributes, e.g. whether an individual is generous or selfish, is central to human social cognition. It is well documented that a network of cortical regions is reliably activated when we engage social processes. However, little is known about the specific computations performed by these regions or whether such processing is specialized for the social domain. We investigated these questions using a task in which participants (N= 26) learned about four peoples' generosity by watching them choose to share money with third party partners, or not. In a non-social control condition, participants learned the win/loss rates of four lotteries. fMRI analysis revealed learning-related general (social + non-social) prediction error signals in the dorsomedial and dorsolateral prefrontal cortices (bilaterally), and in the right lateral parietal cortex. Socially specific (social > non-social) prediction error signals were found in the precuneus. Interestingly, the region that exhibited social prediction errors was a distinct subregion of the area in the precuneus and posterior cingulate cortex that exhibited a commonly reported main effect of higher overall activity for social vs non-social stimuli. These findings elucidate the domain--general and--specific computations underlying learning about other people and demonstrate the increased explanatory power of computational approaches to social cognition.</AbstractText
|
The ability to act on information flexibly is one of the cornerstones of intelligent behavior. As particularly informative example, tool-oriented behavior has been investigated to determine to which extent nonhuman animals understand means-end relations, object affordances, and have specific motor skills. Even planning with foresight, goal-directed problem solving and immediate causal inference have been a focus of research. However, these cognitive abilities may not be restricted to tool-using animals but may be found also in animals that show high levels of curiosity, object exploration and manipulation, and extractive foraging behavior. The kea, a New Zealand parrot, is a particularly good example. We here review findings from laboratory experiments and field observations of keas revealing surprising cognitive capacities in the physical domain. In an experiment with captive keas, the success rate of individuals that were allowed to observe a trained conspecific was significantly higher than that of naive control subjects due to their acquisition of some functional understanding of the task through observation. In a further experiment using the string-pulling task, a well-probed test for means-end comprehension, we found the keas finding an immediate solution that could not be improved upon in nine further trials. We interpreted their performance as insightful in the sense of being sensitive of the relevant functional properties of the task and thereby producing a new adaptive response without trial-and-error learning. Together, these findings contribute to the ongoing debate on the distribution of higher cognitive skills in the animal kingdom by showing high levels of sensorimotor intelligence in animals that do not use tools. In conclusion, we suggest that the 'Technical intelligence hypothesis' (Byrne, Machiavellian intelligence II: extensions and evaluations, pp 289-211, 1997), which has been proposed to explain the origin of the ape/monkey grade-shift in intelligence by a selection pressure upon an increased efficiency in foraging behavior, should be extended, that is, applied to some birds as well.</AbstractText
|
Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target.</AbstractText
|
Getting to know you: general and specific neural computations for learning about people. Learning about other peoples' attributes, e.g. whether an individual is generous or selfish, is central to human social cognition. It is well documented that a network of cortical regions is reliably activated when we engage social processes. However, little is known about the specific computations performed by these regions or whether such processing is specialized for the social domain. We investigated these questions using a task in which participants (N= 26) learned about four peoples' generosity by watching them choose to share money with third party partners, or not. In a non-social control condition, participants learned the win/loss rates of four lotteries. fMRI analysis revealed learning-related general (social + non-social) prediction error signals in the dorsomedial and dorsolateral prefrontal cortices (bilaterally), and in the right lateral parietal cortex. Socially specific (social > non-social) prediction error signals were found in the precuneus. Interestingly, the region that exhibited social prediction errors was a distinct subregion of the area in the precuneus and posterior cingulate cortex that exhibited a commonly reported main effect of higher overall activity for social vs non-social stimuli. These findings elucidate the domain--general and--specific computations underlying learning about other people and demonstrate the increased explanatory power of computational approaches to social cognition.</AbstractText
|
Technical intelligence in animals: the kea model. The ability to act on information flexibly is one of the cornerstones of intelligent behavior. As particularly informative example, tool-oriented behavior has been investigated to determine to which extent nonhuman animals understand means-end relations, object affordances, and have specific motor skills. Even planning with foresight, goal-directed problem solving and immediate causal inference have been a focus of research. However, these cognitive abilities may not be restricted to tool-using animals but may be found also in animals that show high levels of curiosity, object exploration and manipulation, and extractive foraging behavior. The kea, a New Zealand parrot, is a particularly good example. We here review findings from laboratory experiments and field observations of keas revealing surprising cognitive capacities in the physical domain. In an experiment with captive keas, the success rate of individuals that were allowed to observe a trained conspecific was significantly higher than that of naive control subjects due to their acquisition of some functional understanding of the task through observation. In a further experiment using the string-pulling task, a well-probed test for means-end comprehension, we found the keas finding an immediate solution that could not be improved upon in nine further trials. We interpreted their performance as insightful in the sense of being sensitive of the relevant functional properties of the task and thereby producing a new adaptive response without trial-and-error learning. Together, these findings contribute to the ongoing debate on the distribution of higher cognitive skills in the animal kingdom by showing high levels of sensorimotor intelligence in animals that do not use tools. In conclusion, we suggest that the 'Technical intelligence hypothesis' (Byrne, Machiavellian intelligence II: extensions and evaluations, pp 289-211, 1997), which has been proposed to explain the origin of the ape/monkey grade-shift in intelligence by a selection pressure upon an increased efficiency in foraging behavior, should be extended, that is, applied to some birds as well.</AbstractText
|
Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line. Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target.</AbstractText
|
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