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32707081
|
Pregnancy-induced adaptation of central sensitivity to leptin and insulin.
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Pregnancy is a time of increased food intake and fat deposition in the mother, and adaptations of glucose homeostasis to meet the energy demands of the growing fetus. As part of these adaptations, leptin and insulin concentrations increase in the maternal circulation during pregnancy. Central effects of leptin and insulin, however, are counterproductive to pregnancy, as increased action of these hormones in the brain lead to suppression of food intake. To prevent this, it is well documented that pregnancy induces a state of leptin- and insulin-insensitivity in the brain, particularly the hypothalamus, in a range of species. While the mechanisms underlying leptin- or insulin-insensitivity during pregnancy vary between species, there is evidence of reduced transport into the brain, impaired activation of intracellular signalling pathways, including reduced leptin receptor expression, and attenuated activation of downstream neuronal pathways, especially for leptin insensitivity. Pregnancy-induced changes in prolactin, growth hormone and leptin are discussed in terms of their role in mediating this reduced response to leptin and insulin. Copyright © 2020 Elsevier B. V. All rights reserved.
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10.1016/j.mce.2020.110933
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6829994
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Improved emergency department patient flow: five years of experience with a scribe system.
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Alternative methods for rapidly producing accurate medical records, usually dictation-transcription systems or nurse-scribe methods, have been used in emergency departments. We now have more than five years of experience with a non-nurse scribe system. This system has proven effective in generating accurate and complete medical records while enhancing patient flow. We describe the system and its implementation.
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10.1016/s0196-0644(83)80559-9
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10501459
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Dopamine D1/D2 agonists injected into nucleus accumbens and ventral pallidum differentially affect locomotor activity depending on site.
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Ventral pallidal dopamine has been recently shown to play an important role in psychostimulant reward and locomotor activation. The aim of the present study was to compare the roles of ventral pallidal D1 and D2 receptors in evoking locomotor activity with those in the nucleus accumbens. The D1 agonist SKF 38393 and the D2 agonist quinpirole hydrochloride (0.3-3 microg/ 0.5 microl) were bilaterally injected into ventral pallidum or nucleus accumbens through pre-implanted cannulae. In the ventral pallidum, 0.3-1 microg SKF 38393 increased locomotor activity while 3 microg had no effect; 3 microg quinpirole suppressed locomotion while 0.3-1 microg had no effect. Locomotor activity induced by an equigram (0.3 microg) mixture of SKF 38393 and quinpirole, while significantly higher than that induced by 0.3 microg quinpirole was not significantly higher than that induced by 0.3 microg SKF 38393 alone. At the 3 microg dose, SKF 38393 injections into anterior ventral pallidum increased activity; injections into posterior ventral pallidum decreased activity. In the nucleus accumbens, 0.3-3 microg SKF 38393 dramatically increased locomotor activity while quinpirole moderately increased locomotion. In the group that had previously received the full quinpirole dose range, injection of the equigram (0.3 microg) mixture of SKF 38393 and quinpirole induced locomotor activation which was higher than that induced by either drug alone or by the addition of the effect of each drug alone, i. e. synergy occurred. Moreover, rats that had previously received SKF 38393 developed a sensitized locomotor response to subsequent SKF 38393, quinpirole or the mixture of these two drugs. The difference in locomotor response to dopamine agonists between the ventral pallidum and nucleus accumbens is consistent with electrophysiological evidence collected at these two sites. These findings suggest that, unlike the nucleus accumbens, where D1 and D2 receptor activation may facilitate each other to induce a synergistic effect on locomotor activity, ventral pallidal D1 and D2 receptors may be located on different neurons and coupled with different, if not opposite, behavioral output.
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10.1016/s0306-4522(99)00235-3
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26398249
|
Q Fever Outbreak among Workers at a Waste-Sorting Plant.
|
An outbreak of Q fever occurred in February-April 2014 among workers at a waste-sorting plant in Bilbao (Spain). The outbreak affected 58.5% of investigated employees, 47.2% as confirmed cases (PCR and/or serology) and 11.3% as probable cases (symptoms without laboratory confirmation). Only employees who had no-access to the waste processing areas of the plant were not affected and incidence of infection was significantly higher among workers not using respiratory protection masks. Detection by qPCR of Coxiella burnetii in dust collected from surfaces of the plant facilities confirmed exposure of workers inside the plant. Animal remains sporadically detected among the residues received for waste-sorting were the most probable source of infection. After cleaning and disinfection, all environmental samples tested negative. Personal protection measures were reinforced and made compulsory for the staff and actions were taken to raise farmers' awareness of the biological risk of discharging animal carcasses as urban waste.
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10.1371/journal.pone.0138817
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12629158
|
Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice.
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necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome. necdin is upregulated during neuronal differentiation and is thought to play a role in cell cycle arrest in terminally differentiated neurons. Most necdin-deficient Ndn(tm2Stw) mutant pups carrying a targeted replacement of Ndn with a lacZ reporter gene die in the neonatal period of apparent respiratory insufficiency. We now demonstrate that the defect can be explained by abnormal neuronal activity within the putative respiratory rhythm-generating center, the pre-Bötzinger complex. Specifically, the rhythm is unstable with prolonged periods of depression of respiratory rhythmogenesis. These observations suggest that the developing respiratory center is particularly sensitive to loss of necdin activity and may reflect abnormalities of respiratory rhythm-generating neurons or conditioning neuromodulatory drive. We propose that necdin deficiency may contribute to observed respiratory abnormalities in individuals with Prader-Willi syndrome through a similar suppression of central respiratory drive.
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33756012
|
Factors related to the uncontrolled fasting blood sugar among type 2 diabetic patients attending primary health care center, Abha city, Saudi Arabia.
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To identify risk factors related to uncontrolled fasting blood sugar among type 2 diabetic patients. A systematic random sampling technique was followed to include 450 diabetic patients attending Al-Qabil Primary Health Care Center in Abha City, Saudi Arabia. Collected data comprised sociodemographic characteristics (age, gender, height, weight, education, employment, body mass index, and smoking), while disease-related characteristics included duration of diabetes, fasting blood sugar control, hypertension, and regularity of follow up visits. Fasting blood sugar was uncontrolled among 76.9% of selected patients with type 2 diabetes mellitus. Overweight and obesity were present among 81.6%. Significant risk factors for uncontrolled blood sugar included older age, male gender (P =.037), illiteracy (P =.020), being employed (P =.003), longer duration of disease (P =.023), hypertension (P =.010), and smoking (P =.001). Prevalence of uncontrolled fasting blood sugar is high among patients with type 2 diabetes mellitus. Risk factors associated with uncontrolled fasting blood sugar include older age, male gender, illiteracy, being employed, longer duration of disease, hypertension, smoking, and obesity. Therefore, for better control of blood sugar among diabetics, it is recommended to control the blood pressure and body weight of diabetics and avoid smoking. © 2021 John Wiley & Sons Ltd.
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10.1111/ijcp.14168
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32739455
|
Caffeic acid phenethyl ester reversed cadmium-induced cell death in hippocampus and cortex and subsequent cognitive disorders in mice: Involvements of AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.
|
Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl 2 (1.5 mg/kg/day body weight). For the CdCl 2 -treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl 2 -initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis. Copyright © 2020 Elsevier Ltd. All rights reserved.
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10.1016/j.fct.2020.111636
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10188633
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Stress induces Fos expression in neurons of the thalamic paraventricular nucleus that innervate limbic forebrain sites.
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The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus that responds strongly to exposure to various stressors. Many of the projection targets of PVT neurons, including the medial prefrontal cortex, nucleus accumbens, and central/basolateral nuclei of the amygdala, are also activated by stress. We sought to determine if PVT neurons that respond to stress are those that project to one or more of these forebrain sites. Retrograde tract tracing combined with immunohistochemical detection of Fos protein-like immunoreactivity was used to assess the activation of target-specific populations of PVT projection neurons by mild footshock stress in the rat. Stress markedly increased Fos protein-like immunoreactivity in PVT neurons, but without regard to the projection target of the thalamic neurons. Thus, the percentage of PVT cells that were retrogradely labeled from either the prefrontal cortex, nucleus accumbens, or amygdala, and that expressed Fos-like immunoreactivity did not differ substantially across the three forebrain sites. These data suggest that the PVT may have a role as a generalized relay for information relating to stress, and may serve an important role in the stress-induced activation of limbic forebrain areas.
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10.1002/(SICI)1098-2396(199904)32:1<13::AID-SYN2>3.0.CO;2-R
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16906494
|
Fourier transform near-infrared vibrational circular dichroism used for on-line monitoring the epimerization of 2,2-dimethyl-1,3-dioxolane-4-methanol: A pseudo racemization reaction.
|
Near-infrared (near-IR) Fourier transform vibrational circular dichroism (FT-VCD) spectroscopy has been used to monitor the epimerization of (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol (S-DDM). The near-IR-VCD spectra display clear isolated VCD bands at the range of 4700-5050 cm(-1) resulting from the OH stretch-bend combination bands of S-DDM, which were found to decrease in intensity with increasing reaction time. The near-IR-VCD spectra of 10 reference samples obtained were subjected to partial least-squares (PLS) regression analysis, and the results were used to build predictive models for enantiomeric excess (EE) determination. Multivariate regression was carried out on three different sets of spectra, corresponding to the epimerization of S-DDM in three different solvents: methylcyclohexane, carbon tetrachloride and tetrahydrofuran. The effects of solvent in DDM epimerization are discussed in terms of the relative stabilization of the reaction intermediate of the DDM epimerization reaction. The results of these near-IR-VCD studies for the determination of EE highlights the potential of VCD for in situ real-time process monitoring of the reaction kinetics of chiral molecules in solution. (c) 2006 Wiley-Liss, Inc.
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10.1002/chir.20263
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21299903
|
Molecular identification and transmission studies of X-cell parasites from Atlantic cod Gadus morhua (Gadiformes: Gadidae) and the northern black flounder Pseudopleuronectes obscurus (Pleuronectiformes: Pleuronectidae).
|
Epidermal pseudotumours from Hippoglossoides dubius and Acanthogobius flavimanus in Japan and gill lesions in Limanda limanda from the UK have been shown to be caused by phylogenetically related protozoan parasites, known collectively as X-cells. However, the phylogenetic position of the X-cell group is not well supported within any of the existing protozoan phyla and they are currently thought to be members of the Alveolata. Ultrastructural features of X-cells in fish pseudotumours are somewhat limited and no typical environmental stages, such as spores or flagellated cells, have been observed. The life cycles for these parasites have not been demonstrated and it remains unknown how transmission to a new host occurs. In the present study, pseudobranchial pseudotumours from Atlantic cod, Gadus morhua, in Iceland and epidermal pseudotumours from the northern black flounder, Pseudopleuronectes obscurus, in Japan were used in experimental transmission studies to establish whether direct transmission of the parasite is achievable. In addition, X-cells from Atlantic cod were sequenced to confirm whether they are phylogenetically related to other X-cells and epidermal pseudotumours from the northern black flounder were analysed to establish whether the same parasite is responsible for infecting different flatfish species in Japan. Phylogenetic analyses of small subunit ribosomal DNA (SSU rDNA) sequence data from Atlantic cod X-cells show that they are a related parasite that occupies a basal position to the clade containing other X-cell parasites. The X-cell parasite causing epidermal pseudotumours in P. obscurus is the same parasite that causes pseudotumours in H. dubius. Direct, fish to fish, transmission of the X-cell parasites used in this study, via oral feeding or injection, was not achieved. Non-amoeboid X-cells are contained within discrete sac-like structures that are loosely attached to epidermal pseudotumours in flatfish; these X-cells are able to tolerate exposure to seawater. A sensitive nested PCR assay was developed for the sub clinical detection of both parasites and to assist in future life cycle studies. PCR revealed that the parasite in P. obscurus was detectable in non-pseudotumourous areas of fish that had pseudotumours present in other areas of the body. The inability to successfully transmit both parasites in this study suggests that either host detachment combined with a period of independent development or an alternate host is required to complete the life cycle for X-cell parasites. Phylogenetic analyses of SSU rDNA confirm a monophyletic grouping for all sequenced X-cell parasites, but do not robustly support their placement within any established protist phylum. Analysis of SSU rDNA from X-cells in Japanese flatfish reveals that the same parasite can infect more than one species of fish.
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10.1186/1756-3305-4-15
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11606548
|
DNA dinucleotide evolution in humans: fitting theory to facts.
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We examine length distributions of approximately 6000 human dinucleotide microsatellite loci, representing chromosomes 1-22, from the GDB database. Under the stepwise mutation model, results from theory and simulation are compared with the empirical data. In both constant and expanding population scenarios, a simple single-step model with parameters chosen to account for the observed variance of microsatellite lengths produces results inconsistent with the observed heterozygosity and the dispersion of length skewness. Complicating the model by allowing a variable mutation rate accounts for the homozygosity, and introducing a small probability of a large mutation step accounts for the dispersion in skewnesses. We discuss these results in light of the long-term evolution of microsatellites.
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10.1093/genetics/159.2.737
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38878375
|
Composite superplastic aerogel scaffolds containing dopamine and bioactive glass-based fibers for skin and bone tissue regeneration.
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Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e. g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines. Copyright © 2024 Elsevier Inc. All rights reserved.
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10.1016/j.jcis.2024.06.098
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8389935
|
Characterization of the regulatory functions of varicella-zoster virus open reading frame 4 gene product.
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Varicella-zoster virus (VZV) open reading frame 4 (ORF4) encodes a protein with a predicted molecular weight of 51,540 presenting amino acid sequence homology with the immediate-early regulatory protein ICP27 of herpes simplex virus type 1. To investigate the regulatory properties of the ORF4 gene product, we performed a series of transient expression assays in Vero cells, using a plasmid expressing ORF4 as effector and several VZV genes and heterologous genes as targets. The VZV target plasmids contained promoter/regulatory regions from genes belonging to the three putative VZV kinetic classes fused to the chloramphenicol acetyltransferase (CAT) gene. The heterologous target plasmids consisted of promoter/regulatory regions of human cytomegalovirus, Rous sarcoma virus, and human immunodeficiency virus type 1 fused to the reporter gene. These experiments demonstrated that the ORF4 gene product activated expression of ORF62 in a dose-dependent fashion but had no effect on the expression of the three other putative immediate-early genes (ORF4, ORF61, and ORF63). When various amounts of ORF4 were transfected in the presence of early gene promoters, dose-dependent transactivation was evidenced with the thymidine kinase gene (ORF36) and the major DNA-binding protein gene (ORF29) promoters; interestingly, little activity was detected with the promoter of the DNA polymerase gene (ORF28). No activation of late gene expression, represented by the glycoprotein I and glycoprotein II genes, was seen even over a wide range of concentrations of input ORF4 plasmid. Expression of pCMVCAT, pRSVCAT, and pHIVCAT was also stimulated by the ORF4 gene product. CAT mRNA analysis showed that activation of VZV target promoters occurs at the transcriptional and/or posttranscriptional level.
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10.1128/JVI.67.7.4379-4385.1993
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39513442
|
A computer simulation study of a chiral active ring polymer.
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We investigate a ring polymer under the influence of chiral active Brownian forces in two dimensions using coarse-grained computer simulations. We observe a non-monotonic behavior of the radius of gyration of an active Brownian ring as a function of active force. However, the shrinkage of the ring in the intermediate strength of active forces becomes more pronounced in the presence of chiral active forces, and the shrinkage is monotonic at a given activity level as a function of the angular frequency controlling the direction of the active force. The distribution of radius of gyration, inter-monomer distance, and radial distribution suggest that the monomers come close to each other, eventually leading to the shrinkage of the ring. Moreover, the bond-correlation suggests that the chirality introduces a local folding of the monomers. Furthermore, using the diameter correlation function, we show that the ring performs tank-treading motion with a frequency following power-law relation with active force with exponent 3/2. The mean squared displacement of the monomers further assists the tank-treading dynamics by exhibiting oscillatory behavior. © 2024 Author(s). Published under an exclusive license by AIP Publishing.
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10.1063/5.0232538
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28720239
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Effect of diet and exercise intervention in Chinese pregnant women on gestational weight gain and perinatal outcomes: A quasi-experimental study.
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Aim To determine the effect of a diet and exercise intervention in pregnant women on total gestational weight gain, weekly weight gain, 42-days postpartum weight retention, mode of delivery, and infant birth weight. One hundred and one eligible Chinese pregnant women whose pre-pregnancy body mass index ranged from 18.5 to 24.9 were recruited between June 2013 and June 2014 from a tertiary hospital. Ninety participants, 45 in each group, completed the study. Intervention women received three face-to-face interventions and three follow-up phone calls which were developed based on the Transtheoretical Model. Gestational weight was measured at each prenatal check. Mode of delivery and infant birth weight were collected from the medical record. The 42-days postpartum weight was measured during the postpartum visits. (1) The total gestational weight gain and mean weight gain per week in the intervention group were significantly less than the control group (P=0.045 and P=0.008 respectively). (2) Infant birth weight was significantly lower in the intervention group (P=0.012). (3) Postpartum weight retention was significantly less in the intervention group (P=0.001). 4) There were not significant differences in mode of delivery. 5) Infant birth weight was significantly less than the control group (P=0.012). The lifestyle intervention significantly reduced gestational weight gain, optimized infant weight and lowered postpartum weight retention. Promotion of gestational weight management is needed and cultural health beliefs about pregnancy and postpartum practices should be considered when developing the intervention plan. Copyright © 2017 Elsevier Inc. All rights reserved.
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10.1016/j.apnr.2017.05.001
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27073040
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The Risk of Hospital Admission Due to Traumatic Brain Injury Is Increased in Older Persons With Severe Functional Limitations.
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Hospital admissions due to traumatic brain injuries (TBIs) in older persons are increasing. Falls are the leading mechanism of injury in this age group. TBIs are associated with unfavorable outcomes such as mortality and institutionalization. To estimate rates of TBIs in older persons with severe functional limitations, expressed as "care need," living in the community, and in older persons with care need living in nursing homes compared with older persons without care need. More than 1.2 million persons aged 65 years and older living in Bavaria, Germany, and insured with one of the largest German health insurances (health care and long-term care insurance). Age-standardized rates were calculated based on hospital claims data and claims data of the long-term care insurance and were compared between groups. The 3 groups were defined by claims data of the long-term care insurance. TBI in older persons account for 4.8 hospital admissions per 1000 person-years. Overall TBI rates do not differ significantly between men and women. TBI rates are lowest in persons without care need and are highest for older persons living in nursing homes. Their contribution to the overall burden of TBI is lower than their contribution to the burden of fragility fractures. TBIs in older persons are common. Those with severe functional limitations are at increased risk for TBI. Nursing home residents have the highest rates of TBI. Fall prevention programs should seek to prevent not only fragility fractures but also head impact. Copyright © 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
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10.1016/j.jamda.2016.02.032
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512694
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Central conduction time as an index of ischaemia in subarachnoid haemorrhage.
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Central conduction time (CCT) has been measured in 12 healthy volunteers, and in 16 patients admitted to a neurosurgical unit following subarachnoid haemorrhage. Twelve of the patients were subsequently operated upon for the obliteration of an intracranial aneurysm. CCT has been found to have low standard deviation in control cases, and in the normal side following subarachnoid haemorrhage from aneurysms in the Circle of Willis, and to be prolonged during the development of ischaemic complications, either of the haemorrhage or following surgery. Evidence so far suggests that CCT may be useful as a monitor of developing ischaemia in association with surgery for subarachnoid haemorrhage.
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10.1016/0022-510x(79)90227-2
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17638927
|
Residential exposure to traffic is associated with coronary atherosclerosis.
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Long-term exposure to fine-particulate-matter (PM2.5) air pollution may accelerate the development and progression of atherosclerosis. We investigated the associations of long-term residential exposure to traffic and fine particulate matter with the degree of coronary atherosclerosis. We used baseline data on 4494 participants (age 45 to 74 years) from the German Heinz Nixdorf Recall Study, a population-based, prospective cohort study that started in 2000. To assess exposure differences, distances between residences and major roads were calculated, and annual fine particulate matter concentrations, derived from a small-scale dispersion model, were assigned to each address. The main outcome was coronary artery calcification (CAC) assessed by electron-beam computed tomography. We evaluated the association between air pollution and CAC with logistic and linear regression analyses, controlling for individual level risk factors of coronary atherosclerosis. Compared with participants living >200 m away from a major road, participants living within 50, 51 to 100, and 101 to 200 m had odds ratios of 1.63 (95% CI, 1.14 to 2.33), 1.34 (95% CI, 1.00 to 1.79), and 1.08 (95% CI, 0.85 to 1.39), respectively, for a high CAC (CAC above the age- and gender-specific 75th percentile). A reduction in the distance between the residence and a major road by half was associated with a 7.0% (95% CI, 0.1 to 14.4) higher CAC. Fine particulate matter exposure was associated with CAC only in subjects who had not been working full-time for at least 5 years. Long-term residential exposure to high traffic is associated with the degree of coronary atherosclerosis.
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10.1161/CIRCULATIONAHA.107.693622
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16437896
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[Intrahepatic cholangiocarcinoma: case report].
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The primitive tumors of the liver are relatively rare in the Western countries (around the 0.7% of all the neoplasms) while they present more elevated incidence in Africa and in the South Asian East. While the hepatocellular carcinoma rises up in the 50-70% of the cases in livers cirrosis, this correlation is not valid for the form of carcinoma to departure from the learned intra and extra biliar. The etiology of the intrahepatic colangiocarcinoma (CC) stays unknown. They have stayed observe, on the other hand, of the conditions sometimes correlated to the development of the CC (Carolí morbs, ulcerative colitis, asbestosis). The CC usually rises up from the epithelial cells of surface that delimit the biliary ducts, although different studies suggest that these tumors can also originate from the learned smaller biliary ducts, from the hepatic cysts of the policistic illness and from the complexes of von Meyenburg. The low incidence of the CC, the clinical atypical debut, the not facility of a precise diagnosis have aroused our interest so that the present job wants to be a modest scientific contribution to this type of pathology.
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10551409
|
Cutaneous involvement in lymphoblastic lymphoma.
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Lymphoblastic leukemia/lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes of B- or T-cell phenotype. Involvement of the skin is relatively uncommon. We examined retrospectively the clinicopathologic, immunophenotypic, and molecular genetic features of six patients with cutaneous involvement of LBL (B-LBL=5; T-LBL=1). Patients presented clinically with solitary, large tumors located on the head (3 cases) or the back (1 case), or with generalized tumors (2 cases). Ulceration was uncommon. In two patients the onset of skin lesions was concomitant to the diagnosis of lymphoblastic leukemia. Histopathologic examination showed in all cases a dense, diffuse, monomorphous infiltrate located in the entire dennis and subcutaneous fat. A typical "starry sky" pattern was observed in the majority of the lesions. In some areas neoplastic cells were aligned in a "mosaic-like" fashion. Cytomorphologically, medium sized lymphoid cells with round or convoluted nuclei, inconspicuous nucleoli and scant cytoplasm predominated. There were no significant differences in the histopathologic features of skin lesions in T- and B-LBL. In B-LBL, CD79a was more useful than CD20 in determining the phenotype of neoplastic cells (4/5 cases positive for CD79a as compared to 2/5 cases positive for CD20). TdT, CD10 and CD43 were positive in 4 cases, CD34 in 2. The case of T-LBL revealed positivity for CD1a, CD3, CD43 and TdT, and negativity for CD34 and for B-cell markers. All neoplasms were positive for CD99 and bcl-2, and showed a high proliferation rate. Molecular genetic analysis of J(H) and T-cell receptor (TCR) genes performed using a polymerase chain reaction technique revealed a monoclonal rearrangement of J(H) genes in all five B-LBLs. One of these cases showed also a concomitant TCR-gamma gene rearrangement. A monoclonal rearrangement of the TCR-gamma gene was detected in the case of T-LBL. Our study shows that skin lesions of LBL present characteristic clinicopathologic and molecular features allowing the differentiation from other cutaneous lymphomas, even in cases without clinical history of previous precursor lymphoblastic leukemia/lymphoma.
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10.1111/j.1600-0560.1999.tb01861.x
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17216731
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[The significance of Bernard Brouwer's contribution to Dutch neurology and neurosurgery. On the 125th anniversary of the year of his birth].
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Following his training under Winkler and carrying out research at the Central Institute for Brain Research in Amsterdam, in 1923 Bernard Brouwer (1881-1949) became the firstprofessor ofneurologyindependent from psychiatry, in the Netherlands. His most important scientific work included comparative anatomical studies of the cerebellum and the projection of retinal fibres on the geniculate body and occipital cortex. He gained international fame and in 1926, during one of his American lecture tours, he was invited to fill the new chair of experimental neurology at Johns Hopkins University. He refused this offer and instead started a new university clinic for neurology in Amsterdam, which included neurosurgery. He did however send a surgeon--Dr. Oljenick--to America to be trained by Cushing. The Amsterdam neurology clinic became an international exchange centre for students of neuroscience. The difficult decisions he had to make during his rectorate in the Second World War, were criticised in 1945. During the last years of his life, he was director of the Central Institute for Brain Research.
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22465140
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[Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts].
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High-frequency deep brain stimulation (HF-DBS) has become a widely used therapeutic method in the field of movement disorders for the treatment of Parkinson's disease, essential tremor or dystonia. New targets and indications are under evaluation in several other conditions such as cluster headache, obesity, epilepsy or psychiatric diseases (depression, OCD). However, the mechanisms of action of HF-DBS remain poorly understood. Herein we present a review of the literature and our current view of the question. The first part deals with the effects of stimulation itself on the different parts of the neuron and tries to answer the question of what is actually stimulated by DBS (cell bodies, dendrites or axons). The second part is devoted to the ortho- and antidromic effects of the stimulation. The third part more specifically focuses on the case of subthalamic nucleus stimulation. The target axons in the subthalamic area are discussed in the light of recent optogenetic studies. In conclusion, HF-DBS leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity (both ortho and antidromically). Which effects are relevant to the therapeutic effects of DBS is still unclear. Further investigations are required especially regarding the corticosubthalamic pathways. Copyright © 2012. Published by Elsevier Masson SAS.
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10.1016/j.neuchi.2012.02.006
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33113247
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Comparative analyses of transgene expression patterns after intra-striatal injections of rAAV2-retro in rats and rhesus monkeys: A light and electron microscopic study.
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Retrogradely-transducing viral vectors are versatile tools for anatomical and functional interrogations of neural circuits. These vectors can be applied in nonhuman primates (NHPs), powerful model species for neuroscientific studies with limited genetic tractability, but limited data are available regarding the tropism and transgene expression patterns of such viruses after injections in NHP brains. Consequently, NHP researchers must often rely on related data available from other species for experimental planning. To evaluate the suitability of rAAV2-retro in the NHP basal ganglia, we studied the transgene expression patterns at the light and electron microscope level after injections of rAAV2-retro vector encoding the opsin Jaws conjugated to a green fluorescent protein (GFP) in the putamen of rhesus macaques. For inter-species comparison, we injected the same vector in the rat dorsal striatum. In both species, GFP expression was observed in numerous cortical and subcortical regions with known striatal projections. However, important inter-species differences in pathway transduction were seen, including labeling of the intralaminar thalamostriatal projection in rats, but not monkeys. Electron microscopic ultrastructural observations within the basal ganglia revealed GFP labeling in both postsynaptic dendrites and presynaptic axonal terminals; the latter likely derived from anterograde transgene transport in neurons that project to the striatum, and from collaterals of these neurons. Our results suggest that certain neural pathways may be refractory to transduction by retrograde vectors in a species-specific manner, highlighting the need for caution when determining the suitability of a retrograde vector for NHP studies based solely on rodent data. © 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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10.1111/ejn.15027
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24250429
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The Incidence of Amikacin Ototoxicity in Multidrug-ResistantTuberculosis Patients.
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Amikacin has been shown to irreversibly suppressCochlear activity. The aim of this study is to assess the incidence of amikacinototoxicity in multidrug-resistant tuberculosis patients and riskfactors associated withthis ototoxicity. In this cross-sectional study, 41 patientswith multidrug-resistant tuberculosis (MDR-TB) were included. All patients received fixed dose of intravenous amikacin(500 mg/day) and anti-TB medications for six months. Baseline Pure-Tone Audiometry (PTA) was performed on all patients,before and during the drug treatment with the frequency range between 250 Hz and 8000 Hz. Patients were closely observed for the occurrence of symptomatic ototoxicity using a questionnaire. To find an association between the incidence of cochlear damage and patients' demographics, all patients' data were recorded. A total of 29 patients suffered from hearing loss (70.1%) (Male: n = 18; Female: n = 20). Using logistic regression, the incidence ofamikacinototoxicity was higher in men than in women. There was a negative correlation between the duration of the amikacin treatment and the difference in hearing thresholds(r = -0.34, p = 0.03). The mean of hearing threshold was significantly increased before and after the amikacin treatment((23.68 ± 19.26 vs. 38.93 ± 22.80) (p < 0.0001)). The incidence of hearing loss was remarkable in MDR-TB patients treating with amikacin. However, risk factors' determination and monitoring of audiometric result variations could haveinfluenced the incidence of the amikacin ototoxicity.
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36013731
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Isothermal Quenching of As-Cast Medium Carbon, High-Silicon AR Steel.
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Medium carbon high-silicon abrasion resistant (AR) steel was examined by performing dilatometry, light optical microscopy (LOM), scanning electron microscopy (SEM), and hardness measurements after isothermal bainitization and modified martempering and compared to direct quenching technology. A commercial thermodynamic tool was used for hardness prediction and compared to the measured one and revealed a rather good agreement for direct quenching, as was the case for isothermal holdings near to the martensite start (Ms). The predicted martensite start temperatures were in good agreement with the experimental data, the experimental value was 321 °C, while the predicted values were 324 and 296 °C. However, a higher discrepancy appeared for isothermal holding much above the martensite transition in the bainite region resulting in lower measured hardness compared to the predictions related to the actual kinetics and complexity of the formed final volume percentages of phase constituents such as bainite, martensite, and rest austenite, later as a part of unfinished bainite transformation at studied temperature. The predicted hardness values for quenching, isothermal holding at 280, 300 and 350 °C were 50.6, 50.6, 49.4 and 49.4 HRC, while the measured values were 53.3, 48.3, 48 and 43 HRC, respectively. A very good agreement between the thermodynamic prediction was achieved by comparing the measured Ms concerning prior austenite grain size as one of the crucial parameters for setting a proper heat treatment strategy of various isothermal quenchings making thermodynamic predictions for low alloyed steels a powerful tool for optimizing the heat-treating operations.
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10.3390/ma15165595
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2489050
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Preferential usage of JH2 in D-J joinings with DQ52 in murine lymphocytes.
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Southern blot analysis of genomic DNA of normal mouse thymocytes with a JH4 probe, a probe for JH4 of Igh genes, consistently showed a second band in addition to a germline band. The same band was also observed in analysis with a 5' DQ probe, a 5'-flanking sequence of DQ52, thus suggesting the use of DQ52. By analyzing EcoRI- and PvuII-digested genomic DNA, the above-observed band was demonstrated to be the result of DQ52-JH2 joining. This was further confirmed utilizing a T cell leukemia line with known DQ52-JH joinings. We then quantitatively estimated the frequencies of JH segment usages in joining with DQ52, through plaque hybridization assays. Three hundred and fifty JH4-positive clones were obtained from 7 x 10(5) plaques by plaque hybridization. Forty-eight randomly selected non-germline clones were purified and the use of JH segments was determined through Southern blot analysis. Nine clones used JH1, 29 used JH2, 9 used JH3, and 1 used JH4, thus indicating an apparent preferential usage of JH2 segment. Southern blot analysis of genomic DNA of progenitor B cells in culture showed a dominant band of DQ52-JH2 joining 1 week after initiation of culture. This may indicate that the dominant DQ52-JH2 joining in thymocytes is representative of early D-J joinings in progenitor B cells.
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10.1093/intimm/1.6.643
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35260608
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HIDTI: integration of heterogeneous information to predict drug-target interactions.
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Identification of drug-target interactions (DTIs) plays a crucial role in drug development. Traditional laboratory-based DTI discovery is generally costly and time-consuming. Therefore, computational approaches have been developed to predict interactions between drug candidates and disease-causing proteins. We designed a novel method, termed heterogeneous information integration for DTI prediction (HIDTI), based on the concept of predicting vectors for all of unknown/unavailable heterogeneous drug- and protein-related information. We applied a residual network in HIDTI to extract features of such heterogeneous information for predicting DTIs, and tested the model using drug-based ten-fold cross-validation to examine the prediction performance for unseen drugs. As a result, HIDTI outperformed existing models using heterogeneous information, and was demonstrating that our method predicted heterogeneous information on unseen data better than other models. In conclusion, our study suggests that HIDTI has the potential to advance the field of drug development by accurately predicting the targets of new drugs. © 2022. The Author(s).
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10.1038/s41598-022-07608-3
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28264154
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Deep-Learning-Based Drug-Target Interaction Prediction.
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Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.
|
10.1021/acs.jproteome.6b00618
|
18207708
|
Mechanistic model for the acute effect of fluvoxamine on 5-HT and 5-HIAA concentrations in rat frontal cortex.
|
A mechanistic model is proposed to predict the time course of the concentrations of 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) in rat frontal cortex following acute administration of SSRIs. In the model, SSRIs increase synaptic 5-HT concentrations by reversible blockade of the SERT in a direct concentration-dependent manner, while the 5-HT response is attenuated by negative feedback via 5-HT autoreceptors. In principle, the model allows for the description of oscillatory patterns in the time course of 5-HT and 5-HIAA concentrations in brain extracellular fluid. The model was applied in a pharmacokinetic-pharmacodynamic (PK/PD) investigation on the time course of the microdialysate 5-HT and 5-HIAA response in rat frontal cortex following a 30-min intravenous infusion of 3.7 and 7.3mg/kg fluvoxamine. Directly after administration of fluvoxamine, concentrations of 5-HT were increased to approximately 450-600% of baseline values while 5-HIAA concentrations were decreased. Thereafter 5-HT and 5-HIAA concentrations gradually returned to baseline values in 6-10h, respectively. The PK/PD analysis revealed that inhibition of 5-HT reuptake was directly related to the fluvoxamine concentration in plasma, with 50% inhibition of 5-HT reuptake occurring at a plasma concentration of 1.1ng/ml (EC50). The levels of 5-HT at which 50% of the inhibition of the 5-HT response was reached (IC50) amounted to 272% of baseline. The model was unable to capture the oscillatory patterns in the individual concentration time curves, which appeared to occur randomly. The proposed mechanistic model is the first step in modeling of complex neurotransmission processes. The model constitutes a useful basis for prediction of the time course of median 5-HT and 5-HIAA concentrations in the frontal cortex in behavioral pharmacology studies in vivo.
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10.1016/j.ejps.2007.12.001
|
19114019
|
The effect of time-to-surgery on outcome in elderly patients with proximal femoral fractures.
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Whether reducing time-to-surgery for elderly patients suffering from hip fracture results in better outcomes remains subject to controversial debates. As part of a prospective observational study conducted between January 2002 and September 2003 on hip-fracture patients from 268 acute-care hospitals all over Germany, we investigated the relationship of time-to-surgery with frequency of post-operative complications and one-year mortality in elderly patients (age > or =65) with isolated proximal femoral fracture (femoral neck fracture or pertrochanteric femoral fracture). Patients with short ( 12 h to 36 h) times-to-surgery, counting from the time of the fracture event, were compared for patient characteristics, operative procedures, post-operative complications and one-year mortality. Hospital data were available for 2916 hip-fracture patients (mean age (SD) in years: 82.1 (7.4), median age: 82; 79.7% women). Comparison of groups with short (n = 802), medium (n = 1191) and long (n = 923) time-to-surgery revealed statistically significant differences in a few patient characteristics (age, American Society of Anesthesiologists ratings classification and type of admission) and in operative procedures (total hip endoprosthesis, hemi-endoprosthetic implants, other osteosynthetic procedures). However, comparison of these same groups for frequency of postoperative complications revealed only some non-significant associations with certain complications such as post-operative bleeding requiring treatment (early surgery patients) and urinary tract infections (delayed surgery patients). Both unadjusted rates of one-year all-cause mortality (between 18.1% and 20.5%), and the multivariate-adjusted hazard ratios (HR for time-to-surgery: 1.04; p = 0.55) showed no association between mortality and time-to-surgery. Although this study found a trend toward more frequent post-operative complications in the longest time-to-surgery group, there was no effect of time-to-surgery on mortality. Shorter time-to-surgery may be associated with somewhat lower rates of post-operative complications such as decubitus ulcers, urinary tract infections, thromboses, pneumonia and cardiovascular events, and with somewhat higher rates of others such as post-operative bleeding or implant complications.
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10.1186/1471-2474-9-171
|
9506965
|
Enhancement of estrogen receptor transcriptional activity by the coactivator GRIP-1 highlights the role of activation function 2 in determining estrogen receptor pharmacology.
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The human estrogen receptor (ER) contains two major activation functions (AFs) responsible for its transcriptional activity. One of these, activation function 2 (AF-2), located within the hormone-binding domain (HBD), has been shown to mediate the ligand-dependent transcriptional activity of ER as well as other members of the nuclear receptor superfamily. Recently, proteins interacting with the HBD of several nuclear receptors have been cloned. One of these proteins, glucocorticoid receptor interacting protein (GRIP-1), has been shown to interact with ER and was originally hypothesized to mediate its transcriptional activity through AF-2. However, we find in this study that the transcriptional activity of ER, containing mutations in the AF-2 core sequence, can be enhanced by coexpression of the coactivator GRIP-1, suggesting that this protein may not rely solely on the AF-2 domain for interaction. We propose, therefore, that the HBD of ER either contains multiple binding sites that are necessary for association with GRIP-1 or, alternatively, that this coactivator contacts the receptor in an undetermined region within the HBD. Importantly, these studies demonstrate also that mutations or deletion of AF-2 alter the ligand pharmacology of the receptor such that ER loses the ability to discriminate between agonists and antagonists. Interestingly, on these mutant receptors GRIP-1 still functions as a coactivator independent of the nature of the bound ligand. It is likely, therefore, that the C-terminal AF-2 domain may function as a molecular switch allowing the wild-type receptor to discriminate between agonists and antagonists as well as providing a surface with which associated proteins can interact.
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10.1074/jbc.273.12.6679
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21740203
|
Nursing home admissions and long-stay conversions among persons with and without serious mental illness.
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The appropriateness of nursing homes for individuals with serious mental illness remains a controversial issue in long-term care policy more than a decade since the landmark U. S. Supreme Court Olmstead decision in 1999, which affirmed the rights of persons with disabilities to live in their communities. Using national nursing home Minimum Data Set assessments from 2005, the authors compared the demographic, clinical, and functional characteristics of persons with and without serious mental illness newly admitted to nursing homes. They found that newly admitted people with serious mental illness were younger and more likely to become long-stay residents than those admitted with other conditions, despite a higher proportion of residents with serious mental illness, including the elderly, classified as low-care status. The most substantial and clinically significant difference for rates of low-care status 90 days after initial admission are for persons younger than 65 with serious mental illness versus those younger than 65 without serious mental illness (33% vs. 8.5%, or 3.9 times greater). There is a notable difference in low-care status between persons aged 65 and older with serious mental illness and those aged 65 and older without serious mental illness (14% vs. 6.6%, or 2.1 times greater). These results suggest that a substantial number of adults with serious mental illness residing in nursing homes may have the functional capacity to live in less restrictive environments.
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10.1080/08959420.2011.579511
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19633988
|
Aromatic plants in nests of the blue tit Cyanistes caeruleus protect chicks from bacteria.
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Several bird species add fresh fragments of plants which are rich in volatile secondary compounds to their nests. It has been suggested, although never tested, that birds use fresh plants to limit the growth of nest microorganisms. On Corsica, blue tits (Cyanistes caeruleus) incorporate fresh fragments of aromatic plants into their nests. These plants do not reduce infestation by nest ectoparasites, but have been shown to improve growth and condition of chicks at fledging. To understand the mechanisms underlying such benefits, we experimentally tested the effects of these plants on the bacteria living on blue tits. Aromatic plants significantly affected the structure of bacterial communities, in particular reducing bacterial richness on nestlings. In addition, in this population where there is a strong association between bacterial density and infestation by blood-sucking Protocalliphora blow fly larvae, these plants reduced bacterial density on the most infested chicks. Aromatic plants had no significant effect on the bacteria living on adult blue tits. This study provides the first evidence that fresh plants brought to the nests by adult birds limit bacterial richness and density on their chicks.
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10.1007/s00442-009-1418-6
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31442552
|
Bulbine frutescens phytochemical inhibits notch signaling pathway and induces apoptosis in triple negative and luminal breast cancer cells.
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Breast cancer (BCa) is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to BCa recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Bulbine frutescens (Asphodelaceae), a traditional medicinal plant in South Africa possess bioactive flavonoids and terpenoids. Polar (methanol) and non-polar (hexane) B. frutescens plant extracts were prepared. GC-MS analysis revealed the differential presence of secondary metabolites in both methanolic and hexane extracts. We hereby first time evaluated the anticancer potential of B. frutescens methanolic and hexane extract in triple-negative and luminal BCa cells. B. frutescens extracts significantly decreased cell viability (IC 50 4.8-28.4 μg/ml) and induced cell cycle arrest at G 1 phase in MDA-MB-231 and T47D cells as confirmed by spectrophotometry and flow cytometry technique. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in extract-treated BCa cells. Fluorescence spectrophotometry and confocal microscopy showed B. frutescens induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells. Flow cytometric apoptosis analysis of B. frutescens extracts treated MDA-MB-231 cells showed ≈13% increase in early apoptotic population in comparison to non-treated cells. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens extracts. Moreover, RTPCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract-treated BCa cells. Western Blot analysis showed increased procaspase 3 protein expression in extract-treated BCa cells. In all the assays methanolic extract showed better anti-cancer properties. Literature-based identification of methanol soluble phytochemicals in B. frutescens and in silico docking study revealed Bulbineloneside D as a potent ϒ-secretase enzyme inhibitor. In comparison to standard notch inhibitor, lead phytochemical showed two additional hydrophobic interactions with Ala80 and Leu81 amino acids. In conclusion, B. frutescens phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. B. frutescens phytochemicals have the ability to downregulate the notch signaling pathway in triple-negative and luminal breast cancer cells. Copyright © 2019. Published by Elsevier Inc.
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10.1016/j.lfs.2019.116783
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35922553
|
Integrative phosphatidylcholine metabolism through phospholipase A 2 in rats with chronic kidney disease.
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Dysregulation in lipid metabolism is the leading cause of chronic kidney disease (CKD) and also the important risk factors for high morbidity and mortality. Although lipid abnormalities were identified in CKD, integral metabolic pathways for specific individual lipid species remain to be clarified. We conducted ultra-high-performance liquid chromatography-high-definition mass spectrometry-based lipidomics and identified plasma lipid species and therapeutic effects of Rheum officinale in CKD rats. Adenine-induced CKD rats were administered Rheum officinale. Urine, blood and kidney tissues were collected for analyses. We showed that exogenous adenine consumption led to declining kidney function in rats. Compared with control rats, a panel of differential plasma lipid species in CKD rats was identified in both positive and negative ion modes. Among the 50 lipid species, phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC) and lysophosphatidic acid (LysoPA) accounted for the largest number of identified metabolites. We revealed that six PCs had integral metabolic pathways, in which PC was hydrolysed into LysoPC, and then converted to LysoPA, which was associated with increased cytosolic phospholipase A 2 protein expression in CKD rats. The lower levels of six PCs and their corresponding metabolites could discriminate CKD rats from control rats. Receiver operating characteristic curves showed that each individual lipid species had high values of area under curve, sensitivity and specificity. Administration of Rheum officinale significantly improved impaired kidney function and aberrant PC metabolism in CKD rats. Taken together, this study demonstrates that CKD leads to PC metabolism disorders and that the dysregulation of PC metabolism is involved in CKD pathology. © 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
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10.1038/s41401-022-00947-x
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33289263
|
Three questions about the eco-physiology of overwintering underground.
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In cold environments ectotherms can be dormant underground for long periods. In 1941 Cowles proposed an ecological trade-off involving the depth at which ectotherms overwintered: on warm days, only shallow reptiles could detect warming soils and become active; but on cold days, they risked freezing. Cowles discovered that most reptiles at a desert site overwintered at shallow depths. To extend his study, we compiled hourly soil temperatures (5 depths, 90 sites, continental USA) and physiological data, and simulated consequences of overwintering at fixed depths. In warm localities shallow ectotherms have lowest energy costs and largest reserves in spring, but in cold localities, they risk freezing. Ectotherms shifting hourly to the coldest depth potentially reduce energy expenses, but paradoxically sometimes have higher expenses than those at fixed depths. Biophysical simulations for a desert site predict that shallow ectotherms have increased opportunities for mid-winter activity but need to move deep to digest captured food. Our simulations generate testable predictions to eco-physiological questions but rely on physiological responses to acute cold rather than to natural cooling profiles. Furthermore, natural-history data to test most predictions do not exist. Thus, our simulation approach uncovers knowledge gaps and suggests research agendas for studying ectotherms overwintering underground. © 2020 John Wiley & Sons Ltd.
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10.1111/ele.13636
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10584001
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The hemolytic enterotoxin HBL is broadly distributed among species of the Bacillus cereus group.
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The prevalence of the hemolytic enterotoxin complex HBL was determined in all species of the Bacillus cereus group with the exception of Bacillus anthracis. hblA, encoding the binding subunit B, was detected by PCR and Southern analysis and was confirmed by partial sequencing of 18 strains. The sequences formed two clusters, one including B. cereus and Bacillus thuringiensis strains and the other one consisting of Bacillus mycoides, Bacillus pseudomycoides, and Bacillus weihenstephanensis strains. From eight B. thuringiensis strains, the enterotoxin gene hblA could be amplified. Seven of them also expressed the complete HBL complex as determined with specific antibodies against the L(1), L(2), and B components. Eleven of 16 B. mycoides strains, all 3 B. pseudomyoides strains, 9 of 15 B. weihenstephanensis strains, and 10 of 23 B. cereus strains carried hblA. While HBL was not expressed in the B. pseudomycoides strains, the molecular assays were in accordance with the immunological assays for the majority of the remaining strains. In summary, the hemolytic enterotoxin HBL seems to be broadly distributed among strains of the B. cereus group and relates neither to a certain species nor to a specific environment. The consequences of this finding for food safety considerations need to be evaluated.
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10.1128/AEM.65.12.5436-5442.1999
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12553306
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Human immunodeficiency virus type 1 RNA polymerase chain reaction reasonably excludes infection in exposed infants.
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A nucleic acid sequence-based amplification (NASBA) assay that detects HIV RNA may be helpful in excluding perinatal HIV infection. We reviewed the records of 190 infants born to HIV-infected mothers. The sensitivity and specificity of the NASBA assay were 100% when measured at two time periods in the first 9 months of life. The HIV RNA NASBA assay should be considered a valid diagnostic test in this population.
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10.1097/00006454-200301000-00027
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20108443
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[Expression of DC-SIGNR in the primary trophoblast cells and its significance].
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To study the expression of DC-SIGNR in human placenta and trophoblast cells cultured in vitro, and provided a basis for experiment in vitro aiming to investigate the mechanism of receptor-mediated intrauterine transmission. Primary culture system of human chorionic trophoblast cells were established. The expression of DC-SIGN and DC-SIGNR was determined by Immunohistochemistry (IHC) stain. DC-SIGNR was mainly expressed in the membrane and plasm in placental trophoblast cells, Hofbauer cells and placental vascular endothelial cells. The expression of DC-SIGNR in human placenta and trophoblast cells cultured in vitro is determined by IHC; The study provides a cellular basis for experiment in vitro aiming to investigate the mechanism of receptor-mediated intrauterine transmission.
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408220
|
Hepatic infarction and diabetic ketoacidosis.
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A 36-year-old man with brittle diabetes mellitus developed hepatic infarction immediately after an episode of ketoacidosis. The infarction was documented by angiogram 99mTc sulfur colloid scan, and biopsy. Except for the association with ketoacidosis, no other possible cause of hepatic infarction was found.
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27288074
|
Impulsivity, Stimulant Abuse, and Dopamine Receptor Signaling.
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The nonmedical use of amphetamine-type stimulants is a worldwide problem, with substantial medical and social consequences. Nonetheless, the identification of a pharmacological treatment for amphetamine use disorder remains elusive. Stimulant users exhibit neurochemical evidence of dopamine-system dysfunction as well as impulsive behaviors that may interfere with the success of treatments for their addiction. This review focuses on the potential role of dopaminergic neurotransmission in impulsivity, both in healthy individuals and chronic stimulant users who meet criteria for methamphetamine dependence. Presented are findings related to the potential contributions of signaling through dopamine D1- and D2-type receptors to self-control impulsivity in methamphetamine- dependent users. The information available points to signaling through striatal D2-type dopamine receptors as a potential therapeutic target for stimulant use disorders, but medications that target D2-type dopamine receptors have not been successful in treating stimulant-use disorders, possibly because D2-type receptors are downregulated. Other means to augment D2-type receptor signaling are therefore under consideration, and one promising approach is the addition of exercise training as an adjunct to behavioral treatment for addiction. © 2016 Elsevier Inc. All rights reserved.
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10.1016/bs.apha.2016.01.002
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9130747
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Evaluation of intrauterine abnormalities in infertile patients by sonohysterography.
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The purpose of this study was to assess the usefulness of sonohysterography in the detection of abnormalities of the uterine cavity in infertile patients, compared with other diagnostic methods. Transvaginal ultrasonography, sonohysterography, hysterosalpingography and finally hysteroscopy were performed in 37 patients with primary and 25 patients with secondary infertility. Suspected uterine anomalies were also confirmed by laparoscopy. Transvaginal ultrasonography and hysterosalpingography were able to detect 36.3 and 72.7% of uterine pathologies respectively. Sonohysterography was able to detect all the anomalies except for a single endometrial polyp (90.3%). However, there was no significant difference between the diagnostic capabilities of these methods. We recommend the use of sonohysterography as an easy, cheap and noninvasive method for the diagnosis of intrauterine pathologies in infertile patients.
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10.1093/humrep/12.3.487
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12112285
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Effects of Melilotus officinalis on acute inflammation.
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Our study investigated the effects of Melilotus officinalis L. extract, containing 0.25% coumarin, on acute inflammation induced with oil of turpentine in male rabbits. The results were compared with those from a group treated with hydrocortisone sodium hemisuccinate and one injected with coumarin before inflammation was induced. The effects were evaluated by measuring serum citrulline, a test of in vitro phagocytosis, total leukocyte count and differential leukocyte count expressed as a percentage. M. officinalis had antiinflammatory effects because it reduced the activation of circulating phagocytes and lowered citrulline production. These properties were similar to those of hydrocortisone sodium hemisuccinate and coumarin. In the bone marrow acute phase response, M. officinalis had an inhibitory action that was lower than that of hydrocortisone sodium hemisuccinate and similar to coumarin. Copyright 2002 John Wiley & Sons, Ltd.
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10.1002/ptr.875
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37394075
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Comparative study of the toxicity mechanisms of quinolone antibiotics on soybean seedlings: Insights from molecular docking and transcriptomic analysis.
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The ecological effects of quinolone antibiotics (QNs) on non-target organisms have received widespread attention. The toxicological mechanisms of three common QNs, that is, enrofloxacin, levofloxacin, and ciprofloxacin, on soybean seedlings were investigated in this study. Enrofloxacin and levofloxacin caused significant growth inhibition, ultrastructural alterations, photosynthetic suppression, and stimulation of the antioxidant system, with levofloxacin exhibiting the strongest toxic effects. Ciprofloxacin (<1 mg·L -1 ) did not have a significant effect on the soybean seedlings. As the concentrations of enrofloxacin and levofloxacin increased, antioxidant enzyme activities, malondialdehyde content, and hydrogen peroxide levels also increased. Meanwhile, the chlorophyll content and chlorophyll fluorescence parameters decreased, indicating that the plants underwent oxidative stress and photosynthesis was suppressed. The cellular ultrastructure was also disrupted, which was manifested by swollen chloroplasts, increased starch granules, disintegration of plastoglobules, and mitochondrial degradation. The molecular docking results suggested that the QNs have an affinity for soybean target protein receptors (4TOP, 2IUJ, and 1FHF), with levofloxacin having the highest binding energy (-4.97, -3.08, -3.8, respectively). Transcriptomic analysis has shown that genes were upregulated under the enrofloxacin and levofloxacin treatments were mainly involved in ribosome metabolism and processes to synthesize oxidative stress-related proteins. Downregulated genes in the levofloxacin treatment were primarily enriched in photosynthesis-related pathways, indicating that levofloxacin significantly inhibited gene expression for photosynthesis. Genes expression level by quantitative real-time PCR analysis was consistent with the transcriptomic results. This study confirmed the toxic effect of QNs on soybean seedlings, and provided new insights into the environmental risks of antibiotics. Copyright © 2023 Elsevier B. V. All rights reserved.
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10.1016/j.scitotenv.2023.165254
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38227697
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Coronary Sinus Narrowing Improves Coronary Microcirculation Function in Patients With Refractory Angina: A Multicenter Prospective INROAD Study.
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The underlying mechanisms responsible for the clinical benefits following coronary sinus narrowing and pressure elevation remain unclear. The present study aims to investigate whether coronary sinus narrowing improves the indexes of coronary microcirculatory function. Patients with refractory angina who had a clinical indication for reducer implantation underwent invasive physiological assessments before and 4 months after the procedure. The primary outcome was the change in the values of the index of microcirculatory resistance. Secondary end points included changes in coronary flow reserve and the resistive resistance ratio values. Angina status was assessed with the Canadian Cardiology Society class and the Seattle Angina Questionnaire. Twenty-four patients with a history of obstructive coronary artery disease and prior coronary revascularization (surgical and percutaneous) treated with reducer implantation were enrolled, and 21 of them (87%) underwent repeated invasive coronary physiological assessment after 4 months. The index of microcirculatory resistance values decreased from 33.35±19.88 at baseline to 15.42±11.36 at 4-month follow-up ( P <0.001; mean difference, -17.90 [95% CI, -26.16 to -9.64]). A significant (≥20% from baseline) reduction of the index of microcirculatory resistance was observed in 15 (71.4% [95% CI, 47.8%-88.7%]) patients. The number of patients with abnormal index of microcirculatory resistance (≥25) decreased from 12 (57%) to 4 (19%; P =0.016). Coronary flow reserve increased from 2.46±1.52 to 4.20±2.52 (mean difference, 1.73 [95% CI, 0.51-2.96]). Similar findings were observed for resistive resistance ratio values. Overall, 16 patients (76.1%) had an improvement of 1 Canadian Cardiology Society class. Seattle Angina Questionnaire summary score increase of around 3 points (3.01 [95% CI, 1.39-4.61]). Coronary sinus reduction implantation is associated with a significant improvement in the parameters of coronary microcirculatory function. These findings provide insights into the improvement of angina symptoms and may have implications for the treatment of coronary microvascular dysfunction. URL: https://www. clinicaltrials. gov; Unique identifier: NCT05174572.
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10.1161/CIRCINTERVENTIONS.123.013481
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15470229
|
The structure of cell wall alpha-glucan from fission yeast.
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Morphology and structural integrity of fungal cells depend on cell wall polysaccharides. The chemical structure and biosynthesis of two types of these polysaccharides, chitin and (1-->3)-beta-glucan, have been studied extensively, whereas little is known about alpha-glucan. Here we describe the chemical structure of alpha-glucan isolated from wild-type and mutant cell walls of the fission yeast Schizosaccharomyces pombe. Wild-type alpha-glucan was found to consist of a single population of linear glucose polymers, approximately 260 residues in length. These glucose polymers were composed of two interconnected linear chains, each consisting of approximately 120 (1-->3)-linked alpha-d-glucose residues and some (1-->4)-linked alpha-D-glucose residues at the reducing end. By contrast, alpha-glucan of an alpha-glucan synthase mutant with an aberrant cell morphology and reduced alpha-glucan levels consisted of a single chain only. We propose that alpha-glucan biosynthesis involves an ordered series of events, whereby two alpha-glucan chains are coupled to create mature cell wall alpha-glucan. This mature form of cell wall alpha-glucan is essential for fission-yeast morphogenesis.
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10.1093/glycob/cwi002
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29695107
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Microstructure and Deformation Response of TRIP-Steel Syntactic Foams to Quasi-Static and Dynamic Compressive Loads.
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The implementation of hollow S60HS glass microspheres and Fillite 106 cenospheres in a martensitically transformable AISI 304L stainless steel matrix was realized by means of metal injection molding of feedstock with varying fractions of the filler material. The so-called TRIP-steel syntactic foams were studied with respect to their behavior under quasi-static compression and dynamic impact loading. The interplay between matrix material behavior and foam structure was discussed in relation to the findings of micro-structural investigations, electron back scatter diffraction EBSD phase analyses and magnetic measurements. During processing, the cenospheres remained relatively stable retaining their shape while the glass microspheres underwent disintegration associated with the formation of pre-cracked irregular inclusions. Consequently, the AISI 304L/Fillite 106 syntactic foams exhibited a higher compression stress level and energy absorption capability as compared to the S60HS-containing variants. The -martensite kinetic of the steel matrix was significantly influenced by material composition, strain rate and arising deformation temperature. The highest ferromagnetic -martensite phase fraction was detected for the AISI 304L/S60HS batches and the lowest for the TRIP-steel bulk material. Quasi-adiabatic sample heating, a gradual decrease in strain rate and an enhanced degree of damage controlled the mechanical deformation response of the studied syntactic foams under dynamic impact loading.
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10.3390/ma11050656
|
32318693
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Factor, Concurrent and Predictive Validity of the Readiness to Change Questionnaire [Treatment Version] Among Non-Treatment-Seeking Individuals.
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This study assessed the factor, concurrent and predictive validity of the revised Readiness to Change Questionnaire [Treatment Version] (RCQ[TV]) among non-treatment-seeking individuals. Non-treatment-seeking patients (Mage = 34.8, SD = 12.4) who screened positive for alcohol misuse were recruited from three urban Level I Trauma Centers and completed the RCQ[TV] (Heather et al. [(1999) Development of a treatment version of the Readiness to Change Questionnaire. Addict Res7, 63-83]). A confirmatory factor analysis supported the three-factor structure of the RCQ[TV]. Observed scores for precontemplation, contemplation and action demonstrated concurrent validity, as they were correlated with drinking and alcohol-related problems prior to baseline assessment. Finally, RCQ[TV] scores at baseline added to the predictability of an alcohol consumption composite score at a 3-month follow-up after controlling for baseline alcohol consumption and randomization to treatment arm. The results of the present study suggest that the RCQ[TV] has desirable psychometric properties and supports the use of the RCQ[TV] among non-treatment-seeking patients with alcohol misuse. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.
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10.1093/alcalc/agaa021
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22045518
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Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases.
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Recent reports suggest a role of hypovitaminosis D in the pathogenesis of inflammatory autoimmune diseases (ARD); we investigated 25(OH)vitamin D plasma level before and after supplementation in ARD and NARD (non-ARD: osteoporosis and/or OA) patients. We retrospectively evaluated 572 consecutive clinical records of adult patients at immuno-rheumatology and rehabilitative units of our institution from January 2006 to October 2009. We excluded patients with vitamin D supplementation or renal failure, primary hyperparathyroidism, liver failure. We recorded 25(OH)vitamin D plasma concentration of 245 patients together with other clinical data. We then evaluated 25(OH)vitamin D plasma concentration of 100 (43 ARD and 57 NARD) patients previously included who underwent 750-1,000 UI/die 25(OH)vitamin D supplementation for at least 6 months. Appropriate statistical analysis was performed. The median 25(OH)vitamin D concentration was not significantly different between 119 ARD [33.4 (IQR 22.5-54.9) nmol/l] and 126 NARD patients 32.9 (IQR 18.7-50.2). In stepwise logistic regression, female sex (F:13.7), winter-spring season (F:5.6) and older age (F:5.3), but not ARD, predicted plasma 25(OH)vitamin D <75 nmol/l. Cholecalciferol supplementation increased 25(OH)vitamin D plasma concentration equally in both ARD and NARD; however, only 29/100 patients reached a plasma level ≥75 nmol/l without differences between ARD and NARD (χ(2) = n. s.). Hypovitaminosis D is common in rheumatic patients. Sex and age but not ARD are risk factors for this condition. 750-1,000 UI/die of cholecalciferol is not sufficient to normalize plasma level in these patients. Increase of plasma 25(OH)vitamin D after treatment is not influenced by the presence of an inflammatory autoimmune disease.
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10.1007/s00296-011-2170-x
|
33618124
|
Low working memory load facilitates attention bias modification training.
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Implementations of attention bias modification training (ABMT) attempt to retrain attention away from rather than towards threat, thereby disrupting the anxiety-related attentional bias (AB). Yet, results of ABMT studies have been mixed due to limitations in knowledge of mechanisms underlying ABMT efficacy. Dual-process models of anxiety posit that ABMT works primarily through strengthening of the top-down cognitive control of attention to threat. If this is the case, introducing a working memory load (WML) during ABMT should reduce training efficacy. However, prior studies employing this method show mixed results (Booth, Mackintosh, Mobini, Oztop, & Nunn, 2014; Clarke et al., 2017) and fail to directly compare low and high WML with no WML or to account for individual differences in anxiety and working memory capacity (WMC). The present study (N = 306) assessed trait anxiety and WMC in neurotypical adults who were then randomly assigned to ABMT that trained attention toward or away from threat, with either no, low, or high WML, for a total of six training groups. Attentional bias was assessed before and after training. Results showed ABMT successfully trained attention under low WML, but not under high or no WML, suggesting that ABMT is facilitated by engaging but not overtaxing WML. Copyright © 2021 Elsevier Ltd. All rights reserved.
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10.1016/j.brat.2021.103828
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9869998
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Inferior vena cava-tricuspid annulus isthmus is a critical site of unidirectional block during the induction of common atrial flutter.
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Until recently no clinical studies had reported precise right atrium (RA) mapping when performing induction of atrial flutter (AFl). We studied the mode of tachycardia initiation in 16 patients (pts) referred for radiofrequency (RF) AFl ablation. AFl induction was performed at the beginning of the procedure (n = 10), or after previous AFl termination during RF delivery (n = 6). Detailed analysis of AFl initiation was provided by duodecapolar (Halo) and multipolar catheters positioned in the peritricuspidian region at the lateral right atrial wall (LRA), the inferior vena cavatricuspid annulus (IVC-TA) isthmus and the interatrial septum. Induction was obtained during incremental pacing (IAP) (15 pts) or programmed stimulation (1 pt) from the proximal coronary sinus (PCS). Atrial flutter with counterclockwise (CCW) RA rotation was induced in all pts by PCS pacing. During PCS IAP, at long pacing cycle lengths, impulse propagated in a clockwise (CW) direction through the IVC-TA isthmus and then upward at low (L) LRA. This led to a collision at the mid LRA with another wave front propagating in a CCW direction at the septum. IAP from PCS induced a progressive delay of propagation at the IVC-TA isthmus resulting in a prolongation of the PCS-Mid Isthmus interval from 85 +/- 29 to 151 +/- 42 msec. At same pacing cycle lengths (CL), the PCS-HLRA interval was comparatively less prolonged, from 75 +/- 12 to 105 +/- 18 msec, p = 0.0007. This preferential slowing of conduction between PCS and mid isthmus, during IAP from PCS, was associated with a displacement of the zone of collision to the Low LRA. Finally a CW functional block occurred at the IVC-TA isthmus and CCW AFl was induced through a period of transient concealed entrainment. The paced CL required to initiate flutter ranged from 290 to 180 msec and the mean CL of induced atrial flutter was 254 +/- 27 msec. The IVC-TA isthmus has decremental properties and exhibits wenckebach phenomenon during incremental PCS pacing. Initiation of a counterclockwise flutter by PCS pacing is associated with appearance of a functional unidirectional block at the IVC-TA isthmus.
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10.1023/a:1009768924691
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18643778
|
Mutations linked to interstitial lung disease can abrogate anti-amyloid function of prosurfactant protein C.
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The newly synthesized proSP-C (surfactant protein C precursor) is an integral ER (endoplasmic reticulum) membrane protein with a single metastable polyvaline alpha-helical transmembrane domain that comprises two-thirds of the mature peptide. More than 20 mutations in the ER-lumenal CTC (C-terminal domain of proSP-C), are associated with ILD (interstitial lung disease), and some of the mutations cause intracellular accumulation of cytotoxic protein aggregates and a corresponding decrease in mature SP-C. In the present study, we showed that: (i) human embryonic kidney cells expressing the ILD-associated mutants proSP-C(L188Q) and proSP-C(DeltaExon4) accumulate Congo Red-positive amyloid-like inclusions, whereas cells transfected with the mutant proSP-C(I73T) do not; (ii) transfection of CTC into cells expressing proSP-C(L188Q) results in a stable CTC-proSP-C(L188Q) complex, increased proSP-C(L188Q) half-life and reduced formation of Congo Red-positive deposits; (iii) replacement of the metastable polyvaline transmembrane segment with a stable polyleucine transmembrane segment likewise prevents formation of amyloid-like proSP-C(L188Q) aggregates; and (iv) binding of recombinant CTC to non-helical SP-C blocks SP-C amyloid fibril formation. These results suggest that CTC can prevent the polyvaline segment of proSP-C from promoting formation of amyloid-like deposits during biosynthesis, by binding to non-helical conformations. Mutations in the Brichos domain of proSP-C may lead to ILD via loss of CTC chaperone function.
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10.1042/BJ20080981
|
32399066
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Wild Leporinus friderici induced spawning with different dose of mGnRHa and metoclopramide or carp pituitary extract.
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Breeding technology is of utmost importance for reproduction of wild fish in captivity for the reintroduction and selective breeding programs purposes. The main challenge is that when applied to wild undomesticated specimens, conventional protocols often cause breeders and/or embryo mortality and spawning failure. In this study, we evaluated the reproductive performance of wild Leporinus friderici, a great importance fish for subsistence fishing in South American rivers, applying conventional and lower-dose hormonal therapies by means of two consecutive experiments. In the first, a conventional (0.5 and 5.5 mg/kg) and a lower carp pituitary extract (CPE) dose (0.5 and 1.0 mg/kg) were applied. In the second, a conventional mammalian GnRH analogue associated with metoclopramide (mGnRHa + MET) (40 µg mGnRHa + 20 mg MET/kg) and a lower dose (4 μg mGnRHa + 2 mg MET/kg and 8 µg + 4 mg of mGnRHa + MET/kg) were applied. Ovulation was observed in all treatments, however, only lower CPE protocol provided viable embryos. High levels of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and 17β estradiol ( E 2 ) detected in conventional, but not in lower CPE dose, at ovulation, might be associated to the mortality of the embryos. The use of lower CPE dose applied here was the best way to obtain L. friderici viable embryos. These results directly contribute to the knowledge about poorly explored effects of reproductive management and hormonal therapies in wild-type breeders, showing that the use of reduced doses may be an alternative to reproductive success.
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10.21451/1984-3143-AR2019-0078
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26990689
|
Estrogen and ERα enhanced β-catenin degradation and suppressed its downstream target genes to block the metastatic function of HA22T hepatocellular carcinoma cells via modulating GSK-3β and β-TrCP expression.
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In our previous experiments, we found β-catenin was highly expressed in the tumor area with high invasive ability and poor prognosis. In this study, we have examined the mechanism by which ERα regulates β-catenin expression as well as the metastasis ability of hepatocellular cancer HA22T cells. To identify whether the anticancer effect of estrogen and ERα is mediated through suppression of β-catenin expression, we co-transfected pCMV-β-catenin and ERα into HA22T cells, and determined the cell motility by wound healing, invasion, and migration assays. Results showed that estrogen and/or ERα inhibited β-catenin gene expression and repressed HA22T cell motility demonstrated that similar data was observed in cells expressing the ERα stable clone. Moreover, we examined the protein-protein interaction between ERα and β-catenin by immunostain, co-immunoprecipitation, and Western blotting. E2 enhanced the binding of ERα with β-catenin and then triggered β-catenin to bind with E3 ligase (βTrCP) to promote β-catenin degradation. Finally by employing systematic ChIP studies, we showed ERα can interact directly with the β-catenin promoter region following E2 treatment. All our results reveal that estrogen and ERα blocked metastatic function of HA22T cells by modulating GSK3β and βTrCP expression and further enhanced β-catenin degradation and suppressed its downstream target genes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 519-529, 2017. © 2016 Wiley Periodicals, Inc.
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10.1002/tox.22256
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39409213
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Impedance Spectroscopy Study of Charge Transfer in the Bulk and Across the Interface in Networked SnO 2 /Ga 2 O 3 Core-Shell Nanobelts in Ambient Air.
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Metal oxide core-shell fibrous nanostructures are promising gas-sensitive materials for the detection of a wide variety of both reducing and oxidizing gases. In these structures, two dissimilar materials with different work functions are brought into contact to form a coaxial heterojunction. The influence of the shell material on the transportation of the electric charge carriers along these structures is still not very well understood. This is due to homo-, hetero- and metal/semiconductor junctions, which make it difficult to investigate the electric charge transfer using direct current methods. However, in order to improve the gas-sensing properties of these complex structures, it is necessary to first establish a good understanding of the electric charge transfer in ambient air. In this article, we present an impedance spectroscopy study of networked SnO 2 /Ga 2 O 3 core-shell nanobelts in ambient air. Tin dioxide nanobelts were grown directly on interdigitated gold electrodes, using the thermal sublimation method, via the vapor-liquid-solid (VLS) mechanism. Two forms of a gallium oxide shell of varying thickness were prepared via halide vapor-phase epitaxy (HVPE), and the impedance spectra were measured at 189-768 °C. The bulk resistance of the core-shell nanobelts was found to be reduced due to the formation of an electron accumulation layer in the SnO 2 core. At temperatures above 530 °C, the thermal reduction of SnO 2 and the associated decrease in its work function caused electrons to flow from the accumulation layer into the Ga 2 O 3 shell, which resulted in an increase in bulk resistance. The junction resistance of said core-shell nanostructures was comparable to that of SnO 2 nanobelts, as both structures are likely connected through existing SnO 2 /SnO 2 homojunctions comprising thin amorphous layers.
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10.3390/s24196173
|
1823040
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Superficial bladder cancer: survival and prognostic factors.
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Two hundred and seventeen consecutive patients with superficial bladder cancer stages Ta-T1 were analyzed for survival and prognostic factors. The overall 5-year survival was 88 +/- 5.3%. Factors that impacted significantly on survival were: grade of anaplasia (GI 92 +/- 5.9% vs. GII 87 +/- 7.5% vs. GIII 68 +/- 20.7%; p = 0.01); increasing grade of anaplasia (98 +/- 1.9% vs. 55 +/- 15.6%; p less than 0.0001); progression in tumor stage (100% vs. 58 +/- 12.5%; p less than 0.0001); index of recurrences greater than 0.7 (100% vs. 71 +/- 10%; p less than 0.0001); the presence of urothelial dysplasia (98 +/- 1.7% vs. 77 +/- 9.8%; p less than 0.05); inflammatory infiltrate (90 +/- 7% vs. 83 +/- 7.3%; p less than 0.01), and residual tumor post-TUR (89 +/- 5.5% vs. 68 +/- 18.6%; p less than 0.001). Tumor stage did not impact on survival (p greater than 0.05). Using multivariate statistical analysis only the grade of anaplasia (p less than 0.0001) and increasing grade of anaplasia (p = 0.001) demonstrated significant prognostic value. Eight percent of patients died because of tumor progression. Of these patients, 87% were T1 and had concomitant urothelial dysplasia. Twenty-five percent had carcinoma in situ and the mean index of recurrence was 1.59. Seventy-five percent of patients dying because of tumor progression developed muscle-infiltrating cancer (greater than or equal to T2GIII) and 25% developed previously metastatic spread without evidence of local progression (T1GIII).(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1159/000471697
|
23642244
|
Functional attachment of soft tissues to bone: development, healing, and tissue engineering.
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Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue-to-bone interface, and concludes with a summary of challenges and future directions.
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10.1146/annurev-bioeng-071910-124656
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30915094
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Induced Systemic Resistance (ISR) and Fe Deficiency Responses in Dicot Plants.
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Plants develop responses to abiotic stresses, like Fe deficiency. Similarly, plants also develop responses to cope with biotic stresses provoked by biological agents, like pathogens and insects. Some of these responses are limited to the infested damaged organ, but other responses systemically spread far from the infested organ and affect the whole plant. These latter responses include the Systemic Acquired Resistance (SAR) and the Induced Systemic Resistance (ISR). SAR is induced by pathogens and insects while ISR is mediated by beneficial microbes living in the rhizosphere, like bacteria and fungi. These root-associated mutualistic microbes, besides impacting on plant nutrition and growth, can further boost plant defenses, rendering the entire plant more resistant to pathogens and pests. In the last years, it has been found that ISR-eliciting microbes can induce both physiological and morphological responses to Fe deficiency in dicot plants. These results suggest that the regulation of both ISR and Fe deficiency responses overlap, at least partially. Indeed, several hormones and signaling molecules, like ethylene (ET), auxin, and nitric oxide (NO), and the transcription factor MYB72, emerged as key regulators of both processes. This convergence between ISR and Fe deficiency responses opens the way to the use of ISR-eliciting microbes as Fe biofertilizers as well as biopesticides. This review summarizes the progress in the understanding of the molecular overlap in the regulation of ISR and Fe deficiency responses in dicot plants. Root-associated mutualistic microbes, rhizobacteria and rhizofungi species, known for their ability to induce morphological and/or physiological responses to Fe deficiency in dicot plant species are also reviewed herein.
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10.3389/fpls.2019.00287
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16334703
|
Off-axis effects on the multipulse structure of sperm whale usual clicks with implications for sound production.
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Sperm whales (Physeter macrocephalus) produce multipulsed clicks with their hypertrophied nasal complex. The currently accepted view of the sound generation process is based on the click structure measured directly in front of, or behind, the whale where regular interpulse intervals (IPIs) are found between successive pulses in the click. Most sperm whales, however, are recorded with the whale in an unknown orientation with respect to the hydrophone where the multipulse structure and the IPI do not conform to a regular pulse pattern. By combining far-field recordings of usual clicks with acoustic and orientation information measured by a tag on the clicking whale, we analyzed clicks from known aspects to the whale. We show that a geometric model based on the bent horn theory for sound production can explain the varying off-axis multipulse structure. Some of the sound energy that is reflected off the frontal sac radiates directly into the water creating an intermediate pulse p1/2 seen in off-axis recordings. The powerful p1 sonar pulse exits the front of the junk as predicted by the bent-horn model, showing that the junk of the sperm whale nasal complex is both anatomically and functionally homologous to the melon of smaller toothed whales.
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10.1121/1.2082707
|
38899488
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Bioluminescent aptamer-based microassay for detection of melanoma inhibitory activity protein (MIA).
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Melanoma inhibitory activity protein (MIA) does obviously offer the potential to reveal clinical manifestations of melanoma. Despite a pressing need for effective diagnosis of this highly fatal disease, there are no clinically approved MIA detection ELISA kits available. A recommended MIA threshold has not yet been defined, mostly by reason of variability in immunoglobulins' affinity and stability, the difference in sample preparation and assay conditions. Here we present a pair of high-affinity DNA aptamers developed as an alternative recognition and binding element for MIA detection. Their stability and reproducible synthesis are expected to ensure this analysis under standard conditions. The devised aptamer-based solid-phase microassay of model standard and control human sera involves luciferase NLuc as a highly sensitive reporter. Bioluminescence dependence on MIA concentration ranges in a linear manner from 2.5 to 250 ng mL -1, providing a MIA detection limit of 1.67 ± 0.57 ng mL -1.
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10.1039/d4ay00706a
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1379093
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Effects of chronic amitriptyline administration on saliva from the parotid and submandibular glands of the rat.
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The effect of prolonged treatment with amitriptyline on the secretory activity of rat salivary glands evoked by parasympathetic nerve stimulation and isoprenaline administration has been studied. Low doses of amitriptyline (10 mg/kg per day for 2 or 4 weeks), did not significantly affect salivary flow evoked by either parasympathetic nerve or isoprenaline stimulation. Higher doses of amitriptyline (50 mg/kg/day for 2 or 4 weeks) however, markedly decreased parasympathetic-evoked salivary secretion (flow and volume) from both parotid and submandibular glands, while isoprenaline-evoked secretions were unaffected. Sodium, potassium, and calcium concentrations of nerve-elicited or isoprenaline-evoked saliva were not significantly altered by amitriptyline treatment. Protein concentration and amylase activity of nerve-elicited parotid saliva were, however, greatly increased by chronic amitriptyline administration. Possible mechanisms for drug-induced increase in nerve-elicited salivary protein concentration include changes in cholinergic receptor binding, release of neuropeptides and variations in phosphatidylinositol turnover, which need further study.
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10.1007/BF01824205
|
1523400
|
The impact of the banning of tributyltin-based antifouling paints on the Sydney rock oyster, Saccostrea commercialis.
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Two years after the banning in New South Wales (Australia) of tributyltin (TBT)-based antifouling paints for vessels under 25 metres in length, the impact on the Sydney rock oyster, Saccostrea commercialis, has been assessed. Reduced growth and shell deformities present before banning were found to be absent and healthy oysters contained TBT at concentrations close to the detection limit of 0.2 micrograms Sn kg-1. High tissue concentrations of both copper and zinc, prior to banning were also significantly reduced. This behaviour was predicted by field experiments which showed that TBT had a synergistic effect on the uptake of copper. The distribution of both TBT and copper in the various organs of the oyster were examined in an attempt to explain this synergism.
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10.1016/0048-9697(92)90048-w
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10221285
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Treatment of restless legs syndrome with tramadol: an open study.
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Tramadol is a central analgesic that seems to have fewer side effects and a lower abuse potential than classical opioids. Since the treatment of restless legs syndrome (RLS) with levodopa or classical opioids is problematic, new treatment possibilities would be valuable. We treated 12 patients who fulfilled at least the minimal diagnostic criteria proposed by the International Restless Legs Syndrome Study Group as well as the criteria proposed by Gibb and Lees, some of them treatment resistant or prone to side effects of previous medications, with 50 to 150 mg of tramadol per day in an open study. The follow-up lasted from 15 to 24 months. Ten patients reported clear amelioration and 1 reported slight amelioration of their symptoms, while 1 reported no effect. Tramadol was described to be the most effective treatment and free of side effects when compared with several other treatments. No major tolerance against treatment effect emerged among those who needed only a single evening dose. Compared with other treatments for RLS, tramadol seems to be superior in some cases, possibly because of its unique pharmacodynamic profile. Controlled studies are needed. Meanwhile, we believe that tramadol should be considered before other opioids are prescribed. We recommend intermittent treatment and careful monitoring.
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10.4088/jcp.v60n0407
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15503711
|
Overview of adult outcomes in pediatric-onset spinal cord injuries: implications for transition to adulthood.
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To provide an overview of the adult outcomes of individuals with pediatric-onset spinal cord injuries (SCIs) and the implications of those findings for transition to adulthood. Structured interview including standardized measures. Individuals who sustained SCI at or = 24 years of age at interview; matched community controls. A structured interview including demographics and medical complications. Standardized measures include the Functional Independence Measure, Craig Handicap Assessment and Reporting Technique (CHART), Short Form-12 (SF-12), and Satisfaction with Life Scale (SWLS). Of 265 individuals interviewed (mean age at injury, 13.9 years; mean age at follow-up, 27.8 years), 67% were males, 87% were white, and 59% had tetraplegia. Results showed that 32% had a college degree, 57% were employed, 65% were living independently, and 20% were married; the median income was 12,000 dollars. Compared with controls, subjects were less likely to live independently, be married, have children, or be employed. They showed significantly less community participation, significantly lower life satisfaction, and significantly lower perceived physical health. Multiple regression analyses were conducted for 5 outcomes (independent living, employment, income, CHART total, and SWLS), using demographic factors, impairment, medical complications, use of street drugs, and functional independence as independent variables. Functional independence and education were significantly associated with all five outcomes. Illegal drug use was associated with independent living, employment, and SWLS. Race was associated with employment and CHART. Medical complications were associated with CHART and SWLS. Gender was only associated with living independently, and age at injury was only associated with SWLS. Level of injury was not associated with any of the outcomes. Adults with pediatric-onset SCI have adult outcomes that are below the level of their peers. These results have implications for improving the transition to adulthood for future patients with pediatric-onset SCI.
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10.1080/10790268.2004.11753545
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31220173
|
Vital signs and impaired cognition in older emergency department patients: The APOP study.
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Cognitive impairment is a frequent problem among older patients attending the Emergency Department (ED) and can be the result of pre-existing cognitive impairment, delirium, or neurologic disorders. Another cause can also be acute disturbance of brain perfusion and oxygenation, which may be reversed by optimal resuscitation. This study aimed to assess the relationship between vital signs, as a measure of acute hemodynamic changes, and cognitive impairment in older ED patients. Prospective cohort study. ED's of two tertiary care and two secondary care hospitals in the Netherlands. 2629 patients aged 70-years and older. Vital signs were measured at the moment of ED arrival as part of routine clinical care. Cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT). The median age of patients was 78 years (IQR 74-84). Cognitive impairment was present in 738 patients (28.1%). When comparing lowest with highest quartiles, a systolic blood pressure of 21/min) was associated with increased risk of impaired cognition (OR 2.16, 95% CI 1.58-2.95) as well as oxygen saturation of <95% (OR 1.64, 95%CI 1.24-2.19). Abnormal vital signs associated with decreased brain perfusion and oxygenation are also associated with cognitive impairment in older ED patients. This may partially be explained by the association between disease severity and delirium, but also by acute disturbance of brain perfusion and oxygenation. Future studies should establish whether normalization of vital signs will also acutely improve cognition.
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10.1371/journal.pone.0218596
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10391948
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A cytoskeletal localizing domain in the cyclase-associated protein, CAP/Srv2p, regulates access to a distant SH3-binding site.
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In the yeast, Saccharomyces cerevisiae, adenylyl cyclase consists of a 200-kDa catalytic subunit (CYR1) and a 70-kDa subunit (CAP/SRV2). CAP/Srv2p assists the small G protein Ras to activate adenylyl cyclase. CAP also regulates the cytoskeleton through an actin sequestering activity and is directed to cortical actin patches by a proline-rich SH3-binding site (P2). In this report we analyze the role of the actin cytoskeleton in Ras/cAMP signaling. Two alleles of CAP, L16P(Srv2) and R19T (SupC), first isolated in genetic screens for mutants that attenuate cAMP levels, reduced adenylyl cyclase binding, and cortical actin patch localization. A third mutation, L27F, also failed to localize but showed no loss of either cAMP signaling or adenylyl cyclase binding. However, all three N-terminal mutations reduced CAP-CAP multimer formation and SH3 domain binding, although the SH3-binding site is about 350 amino acids away. Finally, disruption of the actin cytoskeleton with latrunculin-A did not affect the cAMP phenotypes of the hyperactive Ras2(Val19) allele. These data identify a novel region of CAP that controls access to the SH3-binding site and demonstrate that cytoskeletal localization of CAP or an intact cytoskeleton per se is not necessary for cAMP signaling.
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10.1074/jbc.274.28.19985
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18756747
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[The risk factors and clinical forms of diabetic foot infections in dependence on the type of diabetes mellitus].
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The aim of the work--the study of risk factors and detection of prevailing clinical form of diabetic foot infections (DFI) in dependence on type diabetes mellitus (DM). 157 patients with DM and DFI (25 type 1 DM cases and 132 type 2 DM cases) and 689 DM patients without DFI (282 type 1 DM cases and 407 type 2 DM cases) were examined. DFI cases differed from both type DM without DFI in greater number of complications. Associated with decompensated DM amputations and developing ulcerations were been mentioned in history in about a quarter of both type DM patients. DFI risk factors in type 1 DM appeared to be a combination of sensor and autonomic neuropathy (OR: 6.58; 95% CI: 2.74-14.9; a < 0.05), preprpoliferative retinopathy (RP) (OR: 4.62; 95% CI: 1.98-10.7; a < 0.05), in type 2 DM: macroangiopathy of lower extremities (OR: 4.59; 95% CI 2.98-7.1; a < 0.05), obesity (OR: 4.65; 95% CI 2.42-8.9; a < 0.05), concomitant exertional angina (OR 3.3; 95% CI 2.2-5.1; a < 0.05), a proteinuric stage of nephropathy (OR: 2.6; 95% CI: 1.74-3.9; a < 0.05), prominent sensor neuropathy (OR: 2.3; 95% CI 1.3-4.2; a < 0.05), preprpoliferative RP (OR: 2.1; 95% CI 1.41-3.13; a < 0.05). In type 1 DM and DFI neuropathic form of DFI prevailed (88%), in type 2 DM--neuroischemic form of DFI (66%). Ischemic form of DFI was determined in type 2 DM only (6%). In type 2 DM cases with DFI there was revealed a high rate of risk factors of atherosclerosis.
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6952287
|
Reye's syndrome and aspirin use: a possible immunological relationship.
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Reye's syndrome is a serious childhood disease usually associated with an antecedent viral illness such as influenza or chicken pox. Recent reports indicate a relationship between moderate aspirin use during the viral infection and the development of Reye's disease. The blastogenic response of cultured lymphocytes to lectins mimics their in vivo response to viral antigens. We report here that physiological doses of the cyclooxygenase inhibitor aspirin, induce marked hyperactivity in this response. Mouse spleen lymphocyte cultures were treated with phytohemagglutinin (PHA) and mitogenesis was assayed after 72 hours by measuring incorporation of 3H thymidine. Addition of aspirin produced up to 3-fold increases in the PHA response. The effect was specific for T-lymphocytes and response to the B lymphocyte mitogen LPS was not significantly affected. The hyperproliferative effect was dose-dependent being maximum at aspirin levels of 300-400 microM and was reversed by addition of prostaglandin E2 (10-9M). Maximum effects were observed when aspirin was added to cells within 8-10 hours of exposure to antigen. The observations suggest that Reye's syndrome may result from an aspirin-induced aberration in the immune response to a viral infection.
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10.1016/0262-1746(82)90044-0
|
31430248
|
Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017-2018.
|
We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1-October 31, 2017, and June 1-September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.
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10.3201/eid2511.190726
|
23499537
|
Spatial distribution and historical input of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in sediments from a subtropical estuary (Guaratuba Bay, SW Atlantic).
|
This study evaluated the occurrence and distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in 22 surface sediment samples and one core collected in Guaratuba Bay, a large and well-preserved estuary in Southern Atlantic, Brazil. The concentration of PCBs in the superficial sediment samples ranged from <LQ (below the limit of quantification) to 5.62 ng g⁻¹, while the concentration of OCPs ranged from <LQ to 0.74 ng g⁻¹. The spatial distribution of the organochlorine compounds (OCs) suggested that the sources of these contaminants are located outside the bay and are related to human activities on the margins of the two main rivers that discharge in the region. The OCs in the sediment core ranged from <LQ to 0.52 ng g⁻¹ and from <LQ to 1.52 ng g⁻¹ for PCBs and OCPs, respectively. Despite their usage worldwide, the low concentrations of OCs in Guaratuba Bay suggest low input levels, which may represent the background levels for this region. Copyright © 2013 Elsevier Ltd. All rights reserved.
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10.1016/j.marpolbul.2013.02.022
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1325724
|
Field trials of an inactivated virus vaccine against porcine parvovirus.
|
Serological response and reproductive performance were estimated in field trials of an inactivated virus vaccine against porcine parvovirus. Experiments were carried out in 10 selected pig breeding herds. A total of 277 seronegative gilts were used. Two hundred and twenty animals were vaccinated twice before mating, fourteen days apart and revaccinated after farrowing. Blood samples were obtained from both vaccinated and non-vaccinated (57 animal) control gilts, one week after the 2nd dose of vaccination, at farrowing time and one week after revaccination. Although there were considerable variations among the herds, the number of returns to oestrus in all herds was higher in vaccinated gilts (11.81%) than in the controls (10.52%). This difference, however, was not statistically significant. The reproductive performance results revealed the absence of an increase in the total born, as pooled values, in vaccinated gilts compared to controls. However, when these results are interpreted in relation to serological data, many control gilts were already seropositive before mating, or remained seronegative at farrowing. According to our results, the duration of immunity with this vaccine is apparently short, as there is a clear decrease in the titres between the 1st and the 2nd sampling times (2.35 +/- 0.14 and 1.97 +/- 0.08, respectively).
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10.1111/j.1439-0450.1992.tb01178.x
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19411558
|
Dose-response models: how might we think about linearity and nonlinearity?
|
We add to the issues raised by Dr David Ropeik's article Risk Communication and Non-Linearity (forthcoming, BELLE Newsletter, 2008) regarding the thinking about the acceptance of linear and nonlinear (hormetic) dose-response models. We summarize some of the perceptual aspects discussed by Ropeik (2008) and comment on decision-making by the single decision-maker. It seems that the heuristics discussed by Ropeik (2008) are related to those private decision-makers who may not benefit from extensive technical, scientific, and legal advice sufficiently to make well-informed decisions and, perhaps more importantly, may not have the funds for that advice. Dose-response models are intangible, abstract quantities: unlike private goods and services, they are not priced by the market. We suggest a duality between the private and the public decision-maker that in the end may loose its crispness, because it can occur in the same person. Nonetheless, this duality is evident at the analysis phase of decision-making, relative to the decision phase, and thus, provides a convenient way to address the issues addressed by Ropeik (2008). In particular, for at least legal and common sense reasons, the public decision-maker must follow a scientific-analytical causal process - as represented by models of dose-response - to select and justify her choice of one over the other. Whether the final decision as to which model is to be used in regulatory law is a matter that goes beyond the analytical aspects of the choice and is governed by political and other aspects of governance.
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10.1177/0960327109103524
|
27836886
|
Dietary acrylamide and the risk of pancreatic cancer in the International Pancreatic Cancer Case-Control Consortium (PanC4).
|
Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 µg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals. permissions@oup. com.
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10.1093/annonc/mdw618
|
15131475
|
Interferon-alpha and lamivudine combination therapy of children with chronic hepatitis b infection who were interferon-alpha nonresponders.
|
Greater than one-half of children with chronic hepatitis B infection are nonresponders to interferon-alpha (IFN-alpha). The aim of this study was to investigate the efficacy of lamivudine (LMV) and IFN-alpha combination therapy in these children. Nineteen children were given LMV alone for 3 months; then IFN-alpha was added to LMV for 6 months. Virologic response was achieved in seven (36.8%) patients. LMV and IFN-alpha combination therapy may represent an effective treatment option.
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10.1097/01.inf.0000122611.11236.42
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2900130
|
Effects of alpha-adrenoceptor blockers on renal function and blood pressure adjustment in human hypertension.
|
In this paper the different aspects of the role played by alpha-adrenoceptors in the control of renin secretion from the juxtaglomerular apparatus and renal sodium and water reabsorption, and the effects of alpha-adrenoceptor antagonists on systemic haemodynamics, will be investigated. Animal experiments suggest that the renal alpha-adrenoceptors exert a restraining action on renin secretion while increasing tubular reabsorption of sodium and water. A recent study in man has confirmed the alpha-adrenoceptor-mediated inhibition of renin secretion. Previously available ganglion blocking and antiadrenergic agents, while causing a significant supine blood pressure reduction, can cause at the same time clinically relevant side effects such as orthostatic hypotension, sedation, drowsiness etc. The advent of selective alpha 1-adrenoceptor blockers, such as prazosin and urapidil, allow a significant blood pressure reduction without significant interference on haemodynamic adjustments and only induce a limited incidence of side effects.
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10.2165/00003495-198800356-00007
|
8531026
|
Central venous catheter infection with Rhodotorula minuta in a patient with AIDS taking suppressive doses of fluconazole.
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A case of Rhodotorula minuta central venous catheter infection with fungaemia is described in a patient with advanced acquired immunodeficiency syndrome (AIDS), HIV nephropathy, end-stage renal disease requiring haemodialysis, and a permanent Quinton catheter in place for 6 months. At the time of fungaemia, the patient was taking 100 mg fluconazole per os daily for a previous episode of Candida oesophagitis. R. minuta central venous catheter infection with fungaemia was successfully treated with 455 mg total dose amphotericin B (0.6 mg kg-1 day-1) over 25 days without removal of the catheter. In vitro antifungal susceptibility testing for R. minuta revealed a minimum inhibitory concentration to fluconazole of > 100 micrograms ml-1 and to amphotericin B of 1.2 microgram ml-1. Clinically evident fungaemia, even with an unusual organism such as R. minuta, may occur in patients with intravenous catheters, and while the immunosuppressed patient is receiving azole therapy.
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10.1080/02681219580000531
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38675550
|
Investigating the Catalytic Influence of Boron on Ni-Co/Ca Catalysts for Improved Syngas Generation from Rice Straw Pyrolysis.
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A series of boron-promoted Ni-Co/Ca catalysts were synthesized by the sol-gel method to enhance syngas generation from biomass pyrolysis. The efficiency of these catalysts was evaluated during the pyrolysis of rice straw in a fixed-bed reactor, varying the Ni/Co ratio, boron addition, calcination temperature, and residence time. The catalysts underwent comprehensive characterization using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis, scanning electron microscopy (SEM), and hydrogen temperature-programmed reduction (H 2 -TPR). The results indicated that the Ni-Co/Ca catalysts yielded superior syngas compared to singular Ni or Co catalysts, suggesting a synergistic interplay between nickel and cobalt. The incorporation of 4% boron significantly decreased the particle size of the active metals, enhancing both the catalytic activity and stability. Optimal syngas production was achieved under the following conditions: a biomass-to-catalyst mass ratio of 2:1, a Ni-Co ratio of 1:1, a calcination temperature of 400 °C, a pyrolysis temperature of 800 °C, and a 20 min residence time. These conditions led to a syngas yield of 431.8 mL/g, a 131.28% increase over the non-catalytic pyrolysis yield of 188.6 mL/g. This study not only demonstrates the potential of Ni-Co/Ca catalysts in biomass pyrolysis for syngas production but also provides a foundation for future catalyst performance optimization.
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10.3390/molecules29081730
|
33610121
|
Two transcription factors PU.1a and PU.1b have different functions in the immune system of teleost ayu.
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Transcription factor PU.1 is a regulator of macrophage function, however, the specific function of PU.1 in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of two PU.1 genes from ayu (Plecoglossus altivelis; PaPU.1a and PaPU.1b). Sequence comparisons showed that PaPU.1 were most closely related to the PU.1 of rainbow smelt (Osmerus mordax). The PU.1 transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaPU.1a and PaPU.1b proteins were upregulated in MO/MФ, after infection. RNA interference was employed to knockdown PaPU.1a and PaPU.1b to investigate their function in MO/MФ. The expression of inflammatory cytokines was regulated by PaPU.1a, but not PaPU.1b, in ayu MO/MФ upon V. anguillarum infection. Both PaPU.1a and PaPU.1b knockdown lowered the phagocytic activity of MO/MФ. Furthermore, PaPU.1b knockdown attenuated MO/MФ bacterial killing capability. Our results indicate that two PaPU.1 genes differentially modulate the immune response in ayu MO/MФ against bacterial infection. Copyright © 2021 Elsevier Ltd. All rights reserved.
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10.1016/j.molimm.2021.02.004
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9340027
|
[The significance of endothelin for physiologic and pathophysiologic processes of the lung].
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The endothelins (ETs) are a family of three vasoactive peptides (ET-1, ET-2, ET-3) that were first described in 1988. ETs have a wide range of action including vasoconstriction, vasodilatation, bronchoconstriction, and mitogenesis. Two types of ET receptors, classified as ETA and ETB receptors, have been identified in gene technology. Endothelins are produced by endothelial cells, smooth muscle cells, and bronchial epithelial cells. Their vasoactive effects contribute not only to homoeostasis but ETs seem also to be involved in several pulmonary diseases. Elevated ET plasma levels have been found in patients suffering from asthma, pulmonary fibrosis, pulmonary hypertension, and acute lung injury. This review gives a short summary of the actual facts in endothelin research, focussing on the effects of ET-1 in pulmonary circulation.
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10.1055/s-2007-995080
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22345578
|
TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors.
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We addressed the hypothesis that allergic inflammation in guinea pig airways leads to a phenotypic switch in vagal tracheal cough-causing, low-threshold mechanosensitive Aδ neurons, such that they begin expressing functional transient receptor potential vanilloid (TRPV1) channels. Guinea pigs were actively sensitized to ovalbumin (OVA) and beginning 21 days later exposed via aerosol to OVA daily for 3 days. Tracheal-specific neurons were identified in the nodose ganglion using retrograde tracing techniques. Tracheal specific neurons were isolated, and mRNA expression was evaluated at the single-neuron level using RT-PCR analysis. Electrophysiological studies have revealed that the vast majority of vagal nodose afferent nerves innervating the trachea are capsaicin-insensitive Aδ-fibers. Consistent with this, we found <20% of these neurons express TRPV1 mRNA or respond to capsaicin in a calcium assay. Allergen exposure induced de novo TRPV1 mRNA in a majority of the tracheal-specific nodose neurons (P < 0.05). The allergen-induced TRPV1 induction was mimicked by applying either brain-derived neurotrophic factor (BDNF) or glial-derived neurotrophic factor (GDNF) to the tracheal lumen. The BDNF-induced phenotypic change observed at the level of mRNA expression was mimicked using a calcium assay to assess functional TRPV1 ion channels. Finally, OVA exposure induced BDNF and GDNF production in the tracheal epithelium, the immediate vicinity of the nodose Aδ -fibers terminations. The induction of TRPV1 in nodose tracheal Aδ -fibers would substantively expand the nature of stimuli capable of activating these cough-causing nerves.
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10.1152/ajplung.00366.2011
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31887304
|
Take a deep breath and wake up: The protean role of serotonin preventing sudden death in infancy.
|
Recordings from infants who died suddenly and unexpectedly demonstrate the occurrence of recurring apneas, ineffective gasping, and finally, failure to restore eupnea and arouse prior to death. Immunohistochemical and autoradiographic data demonstrate a constellation of serotonergic defects in the caudal raphe nuclei in infants who died of Sudden Infant Death Syndrome (SIDS). The purpose of this review is to synthesize what is known about adaptive responses of the infant to severely hypoxic conditions, which unleash a flood of neuromodulators that inhibit cardiorespiratory function, thermogenesis, and arousal and the emerging role of serotonin, which combats this cardiorespiratory inhibition to foster autoresuscitation, eupnea, and arousal to ensure survival following an hypoxic episode. The laryngeal and carotid body chemoreflexes are potent in newborns and infants, and both reflexes can induce apnea and bradycardia, which may be adaptive initially, but must be terminated if an infant is to survive. Serotonin has a unique ability to touch on each of the processes that may be required to recover from hypoxic reflex apnea: gasping, the restoration of heart rate and blood pressure, termination of apneas and, eventually, stimulation of eupnea and arousal. Recurrent apneic events, bradycardia, ineffective gasping and a failure to terminate apneas and restore eupnea are observed in animals harboring defects in the caudal serotonergic system models - all of these phenotypes are reminiscent of and compatible with the cardiorespiratory recordings made in infants who subsequently died of SIDS. The caudal serotonergic system provides an organized, multi-pronged defense against reflex cardiorespiratory inhibition and the hypoxia that accompanies prolonged apnea, bradycardia and hypotension, and any deficiency of caudal serotonergic function will increase the propensity for sudden unexplained infant death. Copyright © 2019 Elsevier Inc. All rights reserved.
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10.1016/j.expneurol.2019.113165
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33617250
|
Diagnosing the SEI Layer in a Potassium Ion Battery Using Distribution of Relaxation Time.
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Understanding the solid electrolyte interphase (SEI) formation process in novel battery systems is of primary importance. Alongside increasingly powerful in situ techniques, searching for readily accessible, noninvasive, and low-cost tools to probe battery chemistry is highly demanded. Here, we applied distribution of relaxation time analysis to interpret in situ electrochemical impedance spectroscopy results during cycling, which is able to distinguish various electrochemical processes based on their time constants. By building a direct link between the SEI layer and the cell performances, it allows us to track the formation and evolution process of the SEI layer, diagnose the failure of the cell, and unveil the reaction mechanisms. For instance, in a K-ion cell using a SnS 2 /N-doped reduced graphene oxide composite electrode, we found that the worsened mass transport in the electrolyte phase caused by the weak SEI layer is the main reason for cell deterioration. In the electrolyte with potassium bis(fluorosulfonyl)imide, the porous structure of the composite electrode was reinforced by rapid formation of a robust SEI layer at the SnS 2 /electrolyte interface, and thus, the cell delivers a high capacity and good cyclability. This method lowers the barrier of in situ EIS analysis and helps public researchers to explore high-performance electrode materials.
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10.1021/acs.jpclett.1c00118
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34623379
|
Thermodynamic and structural basis of temperature-dependent gating in TRP channels.
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Living organisms require detecting the environmental thermal clues for survival, allowing them to avoid noxious stimuli or find prey moving in the dark. In mammals, the Transient Receptor Potential ion channels superfamily is constituted by 27 polymodal receptors whose activity is controlled by small ligands, peptide toxins, protons and voltage. The thermoTRP channels subgroup exhibits unparalleled temperature dependence -behaving as heat and cold sensors. Functional studies have dissected their biophysical features in detail, and the advances of single-particle Cryogenic Electron microscopy provided the structural framework required to propose detailed channel gating mechanisms. However, merging structural and functional evidence for temperature-driven gating of thermoTRP channels has been a hard nut to crack, remaining an open question nowadays. Here we revisit the highlights on the study of heat and cold sensing in thermoTRP channels in the light of the structural data that has emerged during recent years. © 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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10.1042/BST20210301
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23314461
|
AEGD programs: why now, why more?
|
With an increased number of dental schools graduating more dentists, along with the opening of new dental schools throughout the United States, more graduating dental students are considering utilizing Advanced Education in General Dentistry (AEGD) programs as a means to increase their understanding of the complexity of modern dentistry and to gain additional training and experience before heading into practice. This position paper describes how these programs can aid in transforming the face of dental education to address the needs of graduates and best educate the next generation of dental professionals. Its purpose is to examine reasons why dental students are choosing to participate in AEGD programs and to support a call for additional programs. An online survey of current AEGD residents was conducted to investigate reasons why they chose to enter this specific postgraduate opportunity. This position paper will also discuss how AEGD programs can be an effective training mechanism to address problematic issues such as access to care and dental licensure. Interest in AEGD programs will continue to rise, and this paper provides support for the expansion of such programs.
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31334580
|
MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis.
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MicroRNAs are powerful regulators in hepatocellular carcinoma (HCC) tumorigenesis. MicoRNA-191 (miR-191) has been reported to play an important role in HCC, However, the regulatory mechanism is still unclear. In this study, we investigated the role of miR-191 in HCC and studied its underlying mechanisms of action. The expression of miR-191 in HCC tissues was determined by quantitative real-time PCR (qRT-PCR). The role of miR-191 in HCC cells was examined by using both in vitro and in vivo assays. Downstream targets of miR-191 were determined by qRT-PCR and Western blot analysis. Dual-luciferase assays were performed to validate the interaction between miR-191 and its targets. The expression of miR-191 was significantly higher in HCC patients and a higher miR-191 expression predicted poorer prognosis. Analysis of The Cancer Genome Atlas data sets suggested that miR-191 positively correlated with cell cycle progression. Gain and loss of function assays showed that miR-191 promoted cell cycle progression and proliferation. Luciferase reporter assay showed that miR-191 directly targeted the 3'-untranslated region of KLF6 mRNA. Furthermore, circular RNA has_circ_0000204 could sponge with miR-191, resulting in inactivation of miR-191. Our study sheds light on the novel underlying mechanism of miR-191 in HCC, which may accelerate the development of cancer therapy. © 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
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10.1111/cpr.12635
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1975690
|
Site- and stereospecific ocular drug delivery by sequential enzymatic bioactivation.
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Intraocular enzymes convert the ketoxime analogues of some beta-adrenergic blockers via a sequential bioactivation process involving hydrolysis to the corresponding ketones followed by reduction to the aryloxyaminoalcohols, which then exert known and predictable physiological and pharmacological effects only at the site of the action--i. e., in the eye--without any systemic side effects. The sequential nature of the process is highlighted by the observation that the administration of the ketone intermediate also leads to its conversion to the beta-adrenergic antagonist, the active compound. The reduction is stereospecific resulting in the formation of the more potent S-(-)-form of the drug, thus providing prospect to glaucoma treatment. The same activation process of the ketoximes does not take place systemically, thus administration of these ketoximes does not produce cardiovascular effects.
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10.1023/a:1015863521513
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37434456
|
Peroxiredoxin 3 Inhibits Cardiac Fibrosis in Mice via NOX4-P38 Signalling.
|
Peroxiredoxin-3 (Prx-3) is widely acknowledged as an antioxidant that protects against mitochondrial reactive oxygen species. Nonetheless, its role in cardiac fibrosis has not been elucidated. We aim to explore the role and mechanism of Prx-3 in cardiac fibrosis. In this experimental study, mice received subcutaneous injections of isoproterenol (ISO) for 14 consecutive days (10 mg/kg/d for three days, followed by 5 mg/kg/d for 11 days) to establish a cardiac fibrosis model. The mice were subsequently injected with adenovirus-Prx-3 (ad-Prx-3) to enable Prx-3 overexpression. Echocardiography was used to evaluate cardiac function. Mice heart fibroblasts were isolated and stimulated with transforming growth factor β1 (TGFβ1) to induce fibrosis in vitro. Cells were also transfected with ad-Prx-3 for overexpression of Prx-3. Echocardiographic diameters and fibrosis markers indicated that Prx-3 could inhibit ISO-induced cardiac dysfunction and fibrosis. Fibroblasts with Prx-3 overexpression exhibited reduced activation, proliferation, and collagen transcription. We found that Prx-3 reduced the expression of NADPH oxidase 4 (NOX4) and reduced P38 levels. After treatment with a P38 inhibitor, the Prx-3 overexpression-induced anti-fibrosis effect was mitigated. Prx-3 could protect against ISO-induced cardiac fibrosis by inhibiting the NOX4-P38 pathway.
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10.22074/cellj.2023.557603.1082
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25760790
|
A service dog in group.
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Service dogs are sanctioned by the Americans with Disabilities Act as having protected rights allowing them to assist owners with disabilities. These dogs are appearing with increasing frequency in healthcare settings, and it is important for healthcare providers to understand the rules and regulations given to service animals and owners. We discuss processes that transpired when a service dog was brought into a psychodynamic psychotherapy group. The purpose of this paper is to highlight the unintended consequences of the Americans with Disabilities Act of 2010 as it concerns service dogs and the impact on the group process. Problems resulting from the introduction of service dogs into therapy groups should be anticipated and explicitly discussed in the course of the group's transactions.
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10.1521/ijgp.2015.65.2.307
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3306498
|
Fetal biophysical profile and perinatal death.
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Antepartum assessment of 5034 high-risk pregnancies to predict perinatal death included five biophysical variables (nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume) which combined to form a biophysical profile score. We assessed 4148 fetuses within seven days of delivery. The ability of each variable to predict perinatal death was expressed as the likelihood ratio, which incorporates sensitivity and specificity into one number. The predictive ability was most accurate with fetal movement (likelihood ratio 48.1) and the combined biophysical profile score (likelihood ratio 51.0). The biophysical profile score was more likely to predict perinatal death due to asphyxia (seven of eight) than lethal anomaly (six of 19). The overall perinatal mortality was 7.6 per 1000 total births. The perinatal mortality rate was 1.0 for a normal biophysical profile score, 31.3 for an equivocal score, and 200.0 for an abnormal score. The false-negative rate for the biophysical profile score was 0.7 per 1000.
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24499505
|
Polycyclic Aromatic Hydrocarbons in drinking water of Tehran, Iran.
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Distribution and seasonal variation of sixteen priority polycyclic aromatic hydrocarbons (PAHs) were investigated in the drinking water of Tehran, the capital of Iran. Detected single and total PAHs concentrations were in the range of 2.01-38.96 and 32.45-733.10 ng/L, respectively, which were quite high compared to the values recorded in other areas of the world. The average occurrence of PAHs with high molecular weights was 79.55%; for example, chrysene occurred in 60.6% of the samples, with a maximum concentration of 438.96 ng/L. In addition, mean carcinogen to non-carcinogen PAHs ratio was 63.84. Although the concentration of benzo[a]pyrene, as an indicator of water pollution to PAHs, was lower than the guideline value proposed by World Health Organization (WHO) as well as that of Iranian National Drinking Water Standards for all of the samples, the obtained results indicated that carcinogen PAHs present in the drinking water of Tehran can cause threats to human health.
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10.1186/2052-336X-11-25
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31758690
|
In vitro antifungal activity of luliconazole against nondermatophytic moulds.
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In vitro antifungal activity of luliconazole against nondermatophytic moulds causing superficial infections was compared with that of five classes of 12 topical and systemic drugs. The minimum inhibitory concentration (MIC) of the drugs against the genera of Neoscytalidium, Fusarium, Aspergillus, Scedosporium, and Alternaria was measured via modified microdilution method. In results, the nondermatophytic moulds were found to be less susceptible to drugs to which Neoscytalidium spp. and Fusarium spp. were typically drug resistant. However, luliconazole was effective against all the genera tested, including afore-mentioned two species, and had the lowest MICs among the drugs tested. © The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
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10.1093/mmy/myz117
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15269390
|
Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice.
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In vitro inhibitors of the accumulation of abnormal (protease-resistant) prion protein (PrP-res) can sometimes prolong the lives of scrapie-infected rodents. Here, transgenic mice were used to test the in vivo anti-scrapie activities of new PrP-res inhibitors, which, because they are approved drugs or edible natural products, might be considered for clinical trials in humans or livestock with transmissible spongiform encephalopathies (TSEs). These inhibitors were amodiaquine, thioridazine, thiothixene, trifluoperazine, tetrandrine, tannic acid and polyphenolic extracts of tea, grape seed and pine bark. Test compounds were administered for several weeks beginning 1-2 weeks prior to, or 2 weeks after, intracerebral or intraperitoneal 263K scrapie challenge. Tannic acid was also tested by direct preincubation with inoculum. None of the compounds significantly prolonged the scrapie incubation periods. These results highlight the need to assess TSE inhibitors active in cell culture against TSE infections in vivo prior to testing these compounds in humans and livestock.
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10.1099/vir.0.80082-0
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33691411
|
An Immunochemical Approach to Quantify and Assess the Potential Value of the Pseudomonas Quinolone Signal as a Biomarker of Infection.
|
Quorum sensing (QS) is a bacterial cell density-based communication system using low molecular weight signals called autoinducers (AIs). Identification and quantification of these molecules could provide valuable information related to the stage of colonization or infection as well as the stage of the disease. With this scenario, we report here for the first time the development of antibodies against the PQS (pseudomonas quinolone signal), the main signaling molecule from the pqs QS system of Pseudomonas aeruginosa, and the development of a microplate-based enzyme-linked immunosorbent assay (ELISA) able of quantifying this molecule in complex biological media in the low nanometer range (LOD, 0.36 ± 0.14 nM in culture broth media). Moreover, the PQS ELISA here reported has been found to be robust and reliable, providing accurate results in culture media. The technique allowed us to follow up the PQS profile of the release of bacterial clinical isolates obtained from patients of different disease status. A clear correlation was found between the PQS immunoreactivity equivalents and the chronic or acute infection conditions, which supports the reported differences on virulence and behavior of these bacterial strains due to their adaptation capability to the host environment. The results obtained point to the potential of the PQS as a biomarker of infection and to the value of the antibodies and the technology developed for improving diagnosis and management of P. aeruginosa infections based on the precise identification of the pathogen, appropriate stratification of the patients according to their disease status, and knowledge of the disease progression.
|
10.1021/acs.analchem.0c04731
|
37455270
|
Quail Rearing Practices and Potential for Avian Influenza Virus Transmission, Bangladesh.
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In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission. © 2023. EcoHealth Alliance.
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10.1007/s10393-023-01643-w
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19279289
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Disengaging insulin from corticosterone: roles of each on energy intake and disposition.
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Corticosterone and insulin play complex roles in the amount and composition of calories ingested, and the utilization and deposition of this energy. Understanding the interplay of these two hormones is complicated because increasing concentrations of corticosterone dose-dependently increase circulating insulin levels. We addressed individual contributions of each hormone by controlling, at steady-state levels, corticosterone (by adrenalectomy and exogenous replacement) and insulin (by streptozotocin-induced destruction of pancreatic beta-cells and exogenous replacement) across a spectrum of concentrations in rats, creating 8 hormonal combinations. For 5 days after surgery, all rats received chow. At day 5, they were subdivided into those that continued to receive chow and those that had a choice between chow, lard, and 32% sucrose for a further 5 days. During the choice/chow period, total calories ingested were stimulated by corticosterone and choice diet, and subject to a corticosterone-insulin interaction. Sucrose, but not lard, intake was stimulated by insulin. Body weight was increased by insulin, decreased by high corticosterone, and unaffected by diet. White adipose tissue depot weights were stimulated by insulin, corticosterone, and diet. Plasma triglycerides, free fatty acids, total ketone bodies, glucose, and glycerol were all significantly increased by corticosterone and the choice diet but inhibited by insulin. In contrast, plasma leptin was only increased by insulin and diet, plasma glucagon and liver glycogen was only affected by insulin and liver triglycerides, and arcuate nucleus proopiomelanocortin mRNA was only influenced by diet. Collectively, these data show that corticosterone and insulin determine the intake, form, and compartmentalization of energy both independently and interactively.
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10.1152/ajpregu.91016.2008
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22028735
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Suicidal behavior in the older patient with schizophrenia.
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Little is known about treating elderly suicidal patients with schizophrenia. The purpose of this article is to review the literature dealing with this population and to discuss what is required to advance this field. Most available studies from middle-aged and older individuals suggest that risk factors include hopelessness, lower quality of life, past traumatic events, depressive symptoms, lifetime suicidal ideation and past attempts; it is not clear whether these findings are generalizable to geriatric populations. Although little treatment research has been performed in older suicidal patients with schizophrenia, an integrated psychosocial and pharmacologic approach is recommended. In addition, one recent study augmented antipsychotic treatment with an SSRI (i. e., citalopram) in a sample of middle-aged and older individuals with schizophrenia with subsyndromal depression; in that study, serotonin selective reuptake inhibitor augmentation reduced depressive symptoms and suicidal ideation. More research is required to better understand suicidal behavior in older patients with schizophrenia.
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10.2217/ahe.11.23
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33351111
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The evolution of factor XI and the kallikrein-kinin system.
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Factor XI (FXI) is the zymogen of a plasma protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). In the original cascade model of coagulation, FXI is converted to FXIa by factor XIIa (FXIIa), a component, along with prekallikrein and high-molecular-weight kininogen (HK), of the plasma kallikrein-kinin system (KKS). More recent coagulation models emphasize thrombin as a FXI activator, bypassing the need for FXIIa and the KKS. We took an evolutionary approach to better understand the relationship of FXI to the KKS and thrombin generation. BLAST searches were conducted for FXI, FXII, prekallikrein, and HK using genomes for multiple vertebrate species. The analysis shows the KKS appeared in lobe-finned fish, the ancestors of all land vertebrates. FXI arose later from a duplication of the prekallikrein gene early in mammalian evolution. Features of FXI that facilitate efficient FIX activation are present in all living mammals, including primitive egg-laying monotremes, and may represent enhancement of FIX-activating activity inherent in prekallikrein. FXI activation by thrombin is a more recent acquisition, appearing in placental mammals. These findings suggest FXI activation by FXIIa may be more important to hemostasis in primitive mammals than in placental mammals. FXI activation by thrombin places FXI partially under control of the vitamin K-dependent coagulation mechanism, reducing the importance of the KKS in blood coagulation. This would explain why humans with FXI deficiency have a bleeding abnormality, whereas those lacking components of the KKS do not. © 2020 by The American Society of Hematology.
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10.1182/bloodadvances.2020002456
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30151321
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Qip gene in Fusarium oxysporum is required for normal hyphae morphology and virulence.
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Ribonucleic acid (RNA)-silencing mechanisms exist in many eukaryotes to regulate a variety of biological processes. The known molecular components are related to Dicers, Argonautes and RNA-dependent RNA polymerases. Previous biochemical studies have also suggested that Qip, with an exonuclease domain, facilitates the conversion of duplex small interfering RNAs into single strands. In our study, the Qip gene in Fusarium oxysporum was disrupted using homologous recombination technology. The deletion of the Qip gene resulted in a decrease in colony growth rates but increased the number of branches. Additionally, the Δ Qip mutant had a reduced pathogenicity in cabbage. Our results show Qip gene in F. oxysporum is required for normal hyphae morphology and virulence. The mutant will be useful for elucidating the relationship between the RNA-silencing mechanism and hyphal growth and development in F. oxysporum.
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10.1080/21501203.2015.1027313
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2617992
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[The role of immunogenetic research in studying hypertension].
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The distribution of antigens of the main complex of histocompatibility was studied in 50 patients suffering of hypertensive disease complicated by cerebrovascular disfunction of the brain. A correlation was found between the development of hypertensive disease and several antigens. Results of the study confirm the role of the role of the genetic factor in the development of hypertensive disease and the significance of immunogenetic investigations.
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30526176
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Protective mechanism of Wnt4 gene on Parkinson's disease (PD) transgenic Drosophila.
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The main pathological change of Parkinson's disease (PD) is progressive degeneration and necrosis of dopaminergic neurons in the midbrain, forming a Lewy body in many of the remaining neurons. Studies have found that in transgenic Drosophila, mutations in the PTEN-inducible kinase 1 (PINK1) gene may cause indirect flight muscle defects in Drosophila, and mitochondrial structural dysfunction as well. In this study, Wnt4 gene overexpression and knockdown were performed in PINK1 mutant PD transgenic Drosophila, and the protective effect of Wnt4 gene on PD transgenic Drosophila and its possible mechanism were explored. The Wnt4 gene was screened in the previous experiment; And by using the PD transgenic Drosophila model of the MHC-Gal4/UAS system, the PINK1 gene could be specifically activated in the Drosophila muscle tissue. In PINK1 mutation transgenic fruit flies, the Wnt4 gene to study its implication on PD transgenic fruit flies' wing normality and flight ability. We found that overexpression of Wnt4 gene significantly reduced abnormality rate of PD transgenic Drosophila and improved its flight ability, and then, increased ATP concentration, enhanced mitochondrial membrane potential and normalized mitochondrial morphology were found. All of these findings suggested Wnt4 gene may have a protective effect on PD transgenic fruit flies. Furthermore, in Wnt4 gene overexpression PD transgenic Drosophila, down-regulation autophagy and apoptosis-related proteins Ref(2)P, Pro-Caspase3, and up-regulation of Beclin1, Atg8a, Bcl2 protein were confirmed by Western Blotting. The results imply that the restoring of mitochondrial function though Wnt4 gene overexpression in the PINK1 mutant transgenic Drosophila may be related to autophagy and/or apoptosis.
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10.1080/00207454.2018.1557168
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