<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ashermans syndrome and can you explain it in depth? [/INST] Ashermans syndrome (AS) is an acquired uterine condition that occurs when scar tissue (adhesions) form inside the uterus and/or the cervix. It is characterized by variable scarring inside the uterine cavity, where in many cases the front and back walls of the uterus stick to one another. AS can be the cause of menstrual disturbances, infertility, and placental abnormalities. Although the first case of intrauterine adhesion was published in 1894 by Heinrich Fritsch, it was only after 54 years that a full description of Asherman syndrome was carried out by Joseph Asherman. A number of other terms have been used to describe the condition and related conditions including:  uterine/cervical atresia, traumatic uterine atrophy, sclerotic endometrium, and endometrial sclerosis.There is not any one cause of AS. Risk factors can include myomectomy, cesarean section, infections, age, genital tuberculosis, and obesity. Genetic predisposition to AS is being investigated. There are also studies that show that a severe pelvic infection, independent of surgery may cause AS. AS can develop even if the woman has not had any uterine surgeries, trauma, or pregnancies. While rare in North America and European countries, genital tuberculosis is a cause of Ashermans in other countries such as India.

History
The condition was first described in 1894 by Heinrich Fritsch (Fritsch, 1894) and further characterized by the Israeli gynecologist Joseph Asherman (1889–1968) in 1948.It is also known as Fritsch syndrome, or Fritsch-Asherman syndrome.

Signs and symptoms
It is often characterized by a decrease in flow and duration of bleeding (absence of menstrual bleeding, little menstrual bleeding, or infrequent menstrual bleeding) and infertility. Menstrual anomalies are often but not always correlated with severity: adhesions restricted to only the cervix or lower uterus may block menstruation. Pain during menstruation and ovulation is sometimes experienced and can be attributed to blockages.
It has been reported that 88% of AS cases occur after a D&C is performed on a recently pregnant uterus, following a missed or incomplete miscarriage, birth, or during an elective termination (abortion) to remove retained products of conception.

Causes
The cavity of the uterus is lined by the endometrium. This lining is composed of two layers, the functional layer (adjacent to the uterine cavity) which is shed during menstruation and an underlying basal layer (adjacent to the myometrium), which is necessary for regenerating the functional layer. Trauma to the basal layer, typically after a dilation and curettage (D&C) performed after a miscarriage, or delivery, or abortion, can lead to the development of intrauterine scars resulting in adhesions that can obliterate the cavity to varying degrees. In the extreme, the whole cavity can be scarred and occluded. Even with relatively few scars, the endometrium may fail to respond to estrogen.Ashermans syndrome affects women of all races and ages equally, suggesting no underlying genetic predisposition for its development. AS can result from other pelvic surgeries including cesarean sections, removal of fibroid tumours (myomectomy) and from other causes such as IUDs, pelvic irradiation, schistosomiasis and genital tuberculosis. Chronic endometritis from genital tuberculosis is a significant cause of severe intrauterine adhesions (IUA) in the developing world, often resulting in total obliteration of the uterine cavity which is difficult to treat.An artificial form of AS can be surgically induced by endometrial ablation in women with excessive uterine bleeding, in lieu of hysterectomy.

Diagnosis
The history of a pregnancy event followed by a D&C leading to secondary amenorrhea or hypomenorrhea is typical. Hysteroscopy is the gold standard for diagnosis. Imaging by sonohysterography or hysterosalpingography will reveal the extent of the scar formation. Ultrasound is not a reliable method of diagnosing Ashermans Syndrome. Hormone studies show normal levels consistent with reproductive function.

Classification
Various classification systems were developed to describe Ashermans syndrome (citations to be added), some taking into account the amount of functioning residual endometrium, menstrual pattern, obstetric history and other factors which are thought to play a role in determining the prognoses. With the advent of techniques which allow visualization of the uterus, classification systems were developed to take into account the location and severity of adhesions inside the uterus. This is useful as mild cases with adhesions restricted to the cervix may present with amenorrhea and infertility, showing that symptoms alone do not necessarily reflect severity. Other patients may have no adhesions but amenorrhea and infertility due to a sclerotic atrophic endometrium. The latter form has the worst prognosis.

Prevention
A 2013 review concluded that there were no studies reporting on the link between intrauterine adhesions and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to surgical management (e.g. D&C), medical management or conservative management (that is, watchful waiting). There is an association between surgical intervention in the uterus and the development of intrauterine adhesions, and between intrauterine adhesions and pregnancy outcomes, but there is still no clear evidence of any method of prevention of adverse pregnancy outcomes.In theory, the recently pregnant uterus is particularly soft under the influence of hormones and hence, easily injured. D&C (including dilation and curettage, dilation and evacuation/suction curettage and manual vacuum aspiration) is a blind, invasive procedure, making it difficult to avoid endometrial trauma. Medical alternatives to D&C for evacuation of retained placenta/products of conception exist including misoprostol and mifepristone. Studies show this less invasive and cheaper method to be an efficacious, safe and an acceptable alternative to surgical management for most women. It was suggested as early as in 1993 that the incidence of IUA might be lower following medical evacuation (e.g. Misoprostol) of the uterus, thus avoiding any intrauterine instrumentation. So far, one study supports this proposal, showing that women who were treated for missed miscarriage with misoprostol did not develop IUA, while 7.7% of those undergoing D&C did. The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging.Alternatively, D&C could be performed under ultrasound guidance rather than as a blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury.Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the recurrence of AS, as the longer the period after fetal death following D&C, the more likely adhesions may be to occur. Therefore, immediate evacuation following fetal death may prevent IUA.The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative that could theoretically improve future pregnancy outcomes, although it could be less effective if tissue is abundant. Also, hysteroscopy is not a widely or routinely used technique and requires expertise.There is no data to indicate that suction D&C is less likely than sharp curette to result in Ashermans. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration.Intrauterine adhesions also form after hysteroscopic surgery such as myomectomy, polypectomy or septum removal. Mechanical barriers such as Womed Leaf or hyaluronic acid gels can be used to prevent formation of IUA after such adhesiogenic procedures or after D&C.

Treatment
Fertility may sometimes be restored by removal of adhesions, depending on the severity of the initial trauma and other individual patient factors. Operative hysteroscopy is used for visual inspection of the uterine cavity during adhesion dissection (adhesiolysis). However, hysteroscopy is yet to become a routine gynaecological procedure and only 15% of US gynecologists perform office hysteroscopy. Adhesion dissection can be technically difficult and must be performed with care in order to not create new scars and further exacerbate the condition. In more severe cases, adjunctive measures such as laparoscopy are used in conjunction with hysteroscopy as a protective measure against uterine perforation. Microscissors are usually used to cut adhesions. Electrocauterization is not recommended.As IUA frequently reform after surgery, techniques have been developed to prevent recurrence of adhesions. Methods to prevent adhesion reformation include the use of mechanical barriers (Foley catheter, saline-filled balloon uterine stents, gel barriers (Seprafilm, Spraygel, autocrosslinked hyaluronic acid gel Hyalobarrier) and mechanical barrier film (Womed Leaf) to maintain opposing walls apart during healing, thereby preventing the reformation of adhesions. Antibiotic prophylaxis is necessary in the presence of mechanical barriers to reduce the risk of possible infections. A common pharmacological method for preventing reformation of adhesions is sequential hormonal therapy with estrogen followed by a progestin to stimulate endometrial growth and prevent opposing walls from fusing together. However, there have been no randomized controlled trials (RCTs) comparing post-surgical adhesion reformation with and without hormonal treatment and the ideal dosing regimen or length of estrogen therapy is not known. A recent meta analysis compared different post surgical prevention barrier strategies and concluded that there was no single clearly superior treatment. Furthermore, diagnostic severity and outcomes are assessed according to different criteria (e.g. menstrual pattern, adhesion reformation rate, conception rate, live birth rate). Clearly, more comparable studies are needed in which reproductive outcome can be analysed systematically.Follow-up tests (HSG, hysteroscopy or SHG) are necessary to ensure that adhesions have not reformed. Further surgery may be necessary to restore a normal uterine cavity. According to a recent study among 61 patients, the overall rate of adhesion recurrence was 27.9% and in severe cases this was 41.9%. Another study found that postoperative adhesions reoccur in close to 50% of severe AS and in 21.6% of moderate cases. Mild IUA, unlike moderate to severe synechiae, do not appear to reform.

Prognosis
The extent of adhesion formation is critical. Mild to moderate adhesions can usually be treated with success. Extensive obliteration of the uterine cavity or fallopian tube openings (ostia) and deep endometrial or myometrial trauma may require several surgical interventions and/or hormone therapy or even be uncorrectable. If the uterine cavity is adhesion free but the ostia remain obliterated, IVF remains an option. If the uterus has been irreparably damaged, surrogacy or adoption may be the only options.Depending on the degree of severity, AS may result in infertility, repeated miscarriages, pain from trapped blood, and future obstetric complications If left untreated, the obstruction of menstrual flow resulting from adhesions can lead to endometriosis in some cases.Patients who carry a pregnancy even after treatment of IUA may have an increased risk of having abnormal placentation including placenta accreta where the placenta invades the uterus more deeply, leading to complications in placental separation after delivery. Premature delivery, second-trimester pregnancy loss, and uterine rupture are other reported complications. They may also develop incompetent cervix where the cervix can no longer support the growing weight of the fetus, the pressure causes the placenta to rupture and the mother goes into premature labour. Cerclage is a surgical stitch which helps support the cervix if needed.Pregnancy and live birth rate has been reported to be related to the initial severity of the adhesions with 93, 78, and 57% pregnancies achieved after treatment of mild, moderate and severe adhesions, respectively and resulting in 81, 66, and 32% live birth rates, respectively. The overall pregnancy rate after adhesiolysis was 60% and the live birth rate was 38.9% according to one study.Age is another factor contributing to fertility outcomes after treatment of AS. For women under 35 years of age treated for severe adhesions, pregnancy rates were 66.6% compared to 23.5% in women older than 35.

Epidemiology
AS has a reported incidence of 25% of D&Cs performed 1–4 weeks post-partum, up to 30.9% of D&Cs performed for missed miscarriages and 6.4% of D&Cs performed for incomplete miscarriages. In another study, 40% of patients who underwent repeated D&C for retained products of conception after missed miscarriage or retained placenta developed AS.In the case of missed miscarriages, the time period between fetal demise and curettage may increase the likelihood of adhesion formation due to fibroblastic activity of the remaining tissue.The risk of AS also increases with the number of procedures: one study estimated the risk to be 16% after one D&C and 32% after three or more D&Cs. However, a single curettage often underlies the condition.
In an attempts to estimate the prevalence of AS in the general population, it was found in 1.5% of women undergoing hysterosalpingography HSG, and between 5 and 39% of women with recurrent miscarriage.After miscarriage, a review estimated the prevalence of AS to be approximately 20% (95% confidence interval: 13% to 28%).

References
External links

"The secret syndrome leaving women infertile". Daily Mirror. UK. 29 April 2010. Sophie Blake talks about being diagnosed with Ashermans syndrome.
Bruton C (10 December 2007). "The hidden threat to fertility" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Okamoto syndrome and can you explain it in depth? [/INST] Okamoto syndrome (OS), also known as Au–Kline syndrome (AKS), is a very rare autosomal dominant genetic condition characterised by congenital hydronephrosis, low muscle tone, heart defects, intellectual disability and characteristic facial features. Those affected often have neurological and skeletal abnormalities, as well as frequent urinary tract infections. Language and walking are usually delayed. Facial features include prominent, downturned ears, an open, downturned mouth and drooping eyelids (ptosis).The syndrome is caused by mutations in the HNRNPK gene, which codes for heterogeneous nuclear ribonucleoprotein K. This protein is involved in the process of DNA transcription and translation into proteins. A mutation in this gene impairs DNA transcription, disrupting some developmental processes. As an autosomal dominant disorder, only one faulty copy of the gene is required for the condition to occur. The syndrome is typically diagnosed based on the physical symptoms and then confirmed by genetic testing.Treatment has centred around the symptoms. Sign language and assistive language technology can aid communication. The prognosis is not yet fully known, due to the lack of patients in literature, however most of the patients have at least lived through childhood. The urinary system defects have been the most significant contributors to mortality. As of May 2019, 26 individuals worldwide were known to be affected. The syndrome was first described in 1997 by Nobuhiko Okamoto et al., and the gene responsible was first identified in 2015 by Ping-Yee Billie Au, Antonie D. Kline et al. In 2019, Okamoto proposed that Au–Kline syndrome and Okamoto syndrome were synonymous.

Signs and symptoms
Kidneys
Individuals with Okamoto syndrome are usually born with hydronephrosis, or dilation of the internal structures of the kidneys, due to narrowing (stenosis) of the passage between the kidneys and the ureters (the ureteropelvic junction), leading to a build-up of urine. There is also often vesicoureteral reflux, in which urine passes backwards from the bladder to the ureters, and frequent urinary tract infections.

Heart
Individuals with Okamoto syndrome are typically born with heart defects, which can include aortic valve stenosis, atrial or ventricular septal defect, bicuspid aortic valve or patent ductus arteriosus.

Physical features
The syndrome has a characteristic facial appearance which is similar to that of Kabuki syndrome, including prominent, downward-displaced ears that are underdeveloped, long eyelids, epicanthic folds, a short, broad nose, an open, downturned mouth and a deep groove in the midline of the tongue. Cleft palate occurs in about half of those affected. There is sometimes webbing of the neck or bulging eyes, and less commonly there is excessive hair on the forehead or other parts of the body or a unibrow. Individuals with the syndrome may also have a broad first toe and crowding of the toes, and at least two affected individuals have had polydactyly of the fifth digit (postaxial polydactyly). Some of those affected have had undescended testicles (cryptorchidism). A small minority of those affected have had congenital joint contractures such as club foot.

Neurological
Those with Okamoto syndrome typically have severe mental disability and are usually born with microcephaly. There are typically language and walking delays, and those affected have very low muscle tone and decreased reflexes. They may have neural tube defects such as lipomyelomeningocele (a form of spina bifida) or may have syringomyelia (a cyst in the spinal cord). Those with the syndrome may also have symptoms of dysautonomia (impairments in the autonomic nervous system), including gastrointestinal dysmotility, contributing to gastroesophageal reflux disease, or neurogenic bladder dysfunction, in which bladder control is limited. Dysautonomia has also led to high pain tolerance and reduced sweating in some patients. Some of those with the syndrome have been found to have an underdeveloped corpus callosum, the main band of white matter that connects the two cerebral hemispheres.

Skeletal
Okamoto syndrome patients often have skeletal problems such as scoliosis or hip dysplasia, which can lead to hip dislocation. They may be born with congenital vertebral anomalies; parts of the spine may be fused and fail to segment. There may also be extra vertebrae in the lower back. Some of those affected have been reported to have premature fusion of the skull bones (craniosynostosis), particularly those across the midline and at the front of the skull. This has led to an elongated skull shape known as scaphocephaly as well as a ridge on the forehead known as a metopic ridge.

Growth
Those affected may be born with low weight and size and may display stunted growth in childhood, although this symptom has been variable and not in every individual with Okamoto syndrome.

Hearing and eyesight
A minority of those with Okamoto syndrome have had hearing loss of both sensorineural and conductive types, and a smaller minority have had optic nerve abnormalities.

Cause
Okamoto syndrome is caused by a mutation in the HNRNPK gene, located on chromosome 9 at position q21.32. HNRNPK codes for heterogeneous nuclear ribonucleoprotein K. Ribonucleoproteins are proteins that form complexes with RNA, and they are involved in the transcription of DNA into RNA in the nucleus. They usually bind with precursor messenger RNA (pre-mRNA), which is messenger RNA that has not yet had its introns removed during splicing to be ready for translation. A mutation in one of the two copies of HNRNPK results in defects in DNA transcription, and therefore some developmental processes are disrupted or not completed.Mutations in HNRNPK that have been reported include nonsense mutations, in which the protein is truncated and usually non-functional as a result, frameshift mutations, splice-site mutations and microdeletions encompassing the gene. Rarely, missense mutations, in which one amino acid in the protein is replaced by another, have also been reported.Deletions in the region encompassing HNRNPK have been found in the cells of acute myeloid leukemia in approximately 2% of cases. Acute myeloid leukemia cells are immature white blood cells (myeloblasts) that remain in the stem-cell stage, dividing continually. Additionally, a 2015 study found that a majority of mice who had one of their HNRNPK genes artificially knocked out developed myeloid cancers, with a third developing lymphoid cancers and 4% developing hepatocellular carcinomas. The mice were also smaller, had less developed organs and had higher postnatal mortality (30%). The median lifespan of the mice that survived was less than 50% that of wild-type mice. However, blood cancers had not yet been detected in any of the Okamoto syndrome patients as of 2018.Mutations in both copies of HNRNPK are embryonic lethal in mice. Mice with both copies of the gene knocked out die before the 14th day of embryonic development.

Diagnosis
The condition has usually been diagnosed based on the physical symptoms and confirmed by genetic testing. Methods have included whole exome sequencing and comparative genomic hybridization (for microdeletions). Sanger sequencing can confirm the nature of the mutation.

Treatment
Treatment is focussed on the symptoms. Atrial or ventricular septal defects are usually treated with observation but can be surgically corrected in severe cases. Some patients have been able to use sign language or assistive language devices to facilitate communication.

Prognosis
The prognosis of the disorder is not yet fully known. A minority of patients have died in infancy due to complications from their urinary system defects, including infections in Okamotos first two patients, however most have lived through childhood and into adolescence </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Psychogenic amnesia and can you explain it in depth? [/INST] Psychogenic amnesia or dissociative amnesia is a  memory disorder characterized by sudden retrograde episodic memory loss, said to occur for a period of time ranging from hours to years to decades. More recently, "dissociative amnesia" has been defined as a dissociative disorder "characterized by retrospectively reported memory gaps. These gaps involve an inability to recall personal information, usually of a traumatic or stressful nature." In a change from the DSM-IV to the DSM-5, dissociative fugue is now  subsumed under dissociative amnesia.The atypical clinical syndrome of the memory disorder (as opposed to organic amnesia) is that a person with psychogenic amnesia is profoundly unable to remember personal information about themselves; there is a lack of conscious self-knowledge which affects even simple self-knowledge, such as who they are. Psychogenic amnesia is distinguished from organic amnesia in that it is supposed to result from a nonorganic cause: no structural brain damage or brain lesion should be evident but some form of psychological stress should precipitate the amnesia, however psychogenic amnesia as a memory disorder is controversial.

Definition
Psychogenic amnesia is the presence of retrograde amnesia (the inability to retrieve stored memories leading up to the onset of amnesia), and an absence of anterograde amnesia (the inability to form new long term memories). Access to episodic memory can be impeded, while the degree of impairment to short term memory, semantic memory and procedural memory is thought to vary among cases. If other memory processes are affected, they are usually much less severely affected than retrograde autobiographical memory, which is taken as the hallmark of psychogenic amnesia. However the wide variability of memory impairment among cases of psychogenic amnesia raises questions as to its true neuropsychological criteria, as despite intense study of a wide range of cases there is little consensus of which memory deficits are specific to psychogenic amnesia.Past literature has suggested psychogenic amnesia can be situation-specific or global-transient, the former referring to memory loss for a particular incident, and the latter relating to large retrograde amnesic gaps of up to many years in personal identity. The most commonly cited examples of global-transient psychogenic amnesia are fugue states, of which there is a sudden retrograde loss of autobiographical memory resulting in impairment of personal identity and usually accompanied by a period of wandering. Suspected cases of psychogenic amnesia have been heavily reported throughout the literature since 1935 where it was reported by Abeles and Schilder. There are many clinical anecdotes of psychogenic or dissociative amnesia attributed to stressors ranging from cases of child sexual abuse to soldiers returning from combat.

Cause
Neurological cause of psychogenic amnesia is controversial. Even in cases of organic amnesia, where there is lesion or structural damage to the brain, caution must still be taken in defining causation, as only damage to areas of the brain crucial to memory processing is possible to result in memory impairment. Organic causes of amnesia can be difficult to detect, and often both organic cause and psychological triggers can be entangled. Failure to find an organic cause may result in the diagnosis that the amnesia is psychological, however it is possible that some organic causes may fall below a threshold of detection, while other neurological ails are thought to be unequivocally organic (such as a migraine) even though no functional damage is evident. Possible malingering must also be taken into account. Some researchers have cautioned against psychogenic amnesia becoming a "wastebasket" diagnosis when organic amnesia is not apparent. Other researchers have hastened to defend the notion of psychogenic amnesia and its right not to be dismissed as a clinical disorder.  Diagnoses of psychogenic amnesia have dropped since agreement in the field of transient global amnesia, suggesting some over diagnosis at least. Speculation also exists about psychogenic amnesia due to its similarities with pure retrograde amnesia, as both share similar retrograde loss of memory. Also, although no functional damage or brain lesions are evident in the case of pure retrograde amnesia, unlike psychogenic amnesia it is not thought that purely psychological or psychogenic triggers are relevant to pure retrograde amnesia. Psychological triggers such as emotional stress are common in everyday life, yet pure retrograde amnesia is considered very rare. Also the potential for organic damage to fall below threshold of being identified does not necessarily mean it is not present, and it is highly likely that both psychological factors and organic cause exist in pure retrograde amnesia.

Comparison with organic amnesia
Psychogenic amnesia is supposed to differ from organic amnesia in a number of ways; one being that unlike organic amnesia, psychogenic amnesia is thought to occur when no structural damage to the brain or brain lesion is evident. Psychological triggers are instead considered as preceding psychogenic amnesia, and indeed many anecdotal case studies which are cited as evidence of psychogenic amnesia hail from traumatic experiences such as World War II. As aforementioned however, an etiology of psychogenic amnesia is controversial as causation is not always clear (see above paragraph), and both elements of psychological stress and organic amnesia may be present among cases. Often, but not necessarily, a premorbid history of psychiatric illness such as depression is thought to be present in conjunction to triggers of psychological stress. Lack of psychological evidence precipitating amnesia doesnt mean there isnt any, for example trauma during childhood has even been cited as triggering amnesia later in life, but such an argument runs the risk of psychogenic amnesia becoming an umbrella term for any amnesia of which there is no apparent organic cause. Due to organic amnesia often being difficult to detect, defining between organic and psychogenic amnesia is not easy and often context of precipitating experiences are considered (for example, if there has been drug abuse) as well as the symptomology the patient presents with. Psychogenic amnesia is supposed to differ from organic amnesia qualitatively in that retrograde loss of autobiographical memory while semantic memory remains intact is said to be specific of psychogenic amnesia. Another difference that has been cited between organic and psychogenic amnesia is the temporal gradient of retrograde loss of autobiographical memory. The temporal gradient of loss in most cases of organic amnesia is said to be steepest at its most recent premorbid period, whereas for psychogenic amnesia the temporal gradient of retrograde autobiographical memory loss is said to be quite consistently flat. Although there is much literature on psychogenic amnesia as dissimilar to organic amnesia, the distinction between neurological and psychological features is often difficult to discern and remains controversial.

Diagnosis
Functional assessment of brain activity can be assessed for psychogenic amnesia using imaging techniques such as fMRI, PET and EEG, in accordance with clinical data. Some research has suggested that organic and psychogenic amnesia to some extent share the involvement of the same structures of the temporo-frontal region in the brain.  It has been suggested that deficits in episodic memory may be attributable to dysfunction in the limbic system, while self-identity deficits have been suggested as attributable to functional changes related to the posterior parietal cortex.  To reiterate however, care must be taken when attempting to define causation as only ad hoc reasoning about the aetiology of psychogenic amnesia is possible, which means cause and consequence can be infeasible to untangle.

Treatments
Because psychogenic amnesia is defined by its lack of physical damage to the brain, treatment by physical methods is difficult. Nonetheless, distinguishing between organic and dissociative memory loss has been described as an essential first-step in effective treatments </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Persistent tunica vasculosa lentis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sotos syndrome and can you explain it in depth? [/INST] Sotos syndrome is a rare genetic disorder characterized by excessive physical growth during the first years of life. Excessive growth often starts in infancy and continues into the early teen years. The disorder may be accompanied by autism, mild intellectual disability, delayed motor, cognitive, and social development, hypotonia (low muscle tone), and speech impairments. Children with Sotos syndrome tend to be large at birth and are often taller, heavier, and have relatively large skulls (macrocephaly) than is normal for their age. Signs of the disorder, which vary among individuals, include a disproportionately large skull with a slightly protrusive forehead, large hands and feet, large mandible, hypertelorism (an abnormally increased distance between the eyes), and downslanting eyes. Clumsiness, an awkward gait, and unusual aggressiveness or irritability may also occur.
Although most cases of Sotos syndrome occur sporadically, familial cases have also been reported. It is similar to Weaver syndrome.

Signs and symptoms
This syndrome is characterized by overgrowth and advanced bone age. Affected individuals have dysmorphic features, with macrodolichocephaly, downslanting palpebral fissures and a pointed chin. The facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers, and have an unusually large skull and large head. Adult height is usually in the normal range, although Broc Brown has the condition and was named the worlds tallest teenager.  As of late 2016, he was 78" and still growing.Individuals with Sotos syndrome often have intellectual impairment, and most also display autistic traits. Frequent behavioral impairments include attention deficit hyperactivity disorder (ADHD), phobias, obsessive compulsive disorder, tantrums, and impulsive behaviors (impulse control disorder). Problems with speech and language are also common. Affected individuals may often have stuttering, difficulty with sound production, or a monotone voice. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs include scoliosis, seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience jaundice and poor feeding. A small number of patients with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer has been associated with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If persons with this disorder have any increased cancer risk, their risk is only slightly greater than that of the general population.

Genetics
Mutations in the NSD1 gene cause Sotos syndrome. The NSD1 gene provides instructions for making a protein (histone methyltransferase) that is involved in normal growth and development. The function of this protein is unknown, however </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Degloving and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ectropion and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Degos disease and can you explain it in depth? [/INST] Degos disease, also known as Köhlmeier-Degos disease or malignant atrophic papulosis, is an extremely rare condition caused by blockage of arteries and veins. Individuals with this condition will develop papules. Those diagnosed with this disease may also develop complications due to impairment of internal organs. The exact underlying mechanism is still unknown, and an effective treatment is still being developed. There are fewer than 50 living patients presently known worldwide, and fewer than 200 reported in medical literature. However, many individuals may go undiagnosed due to rarity of the disease. Most individuals develop symptoms between the ages of 20–50; however, cases outside of this age range have been reported as well.

Symptoms and signs
The characteristic symptom of Degos disease is the development of papules. Initially, individuals may have skin lesions or rashes, but they will proceed to develop distinct bumps, or papules. Papules are circular in shape, have a porcelain-white center and red border. As papules age, the white centers will skin in and only the border will remain raised. Typically, papules range from 0.5 to 1 cm in width. Papules appear on the trunk and upper extremities and are not found on the individuals palms, soles, scalp, or face.Symptoms vary, depending on whether an individual has the benign variant or malignant variant of the disease. Both the benign and malignant forms have development of the characteristic papules. Individuals with the benign form will have the typical papules persisting anywhere from a few years to throughout their whole lives. In the benign form, no inner organs are affected. If an individual develops the malignant form, it means that not only are the papules present, but inner organs are involved. Most malignant cases involve problems of the gastrointestinal tract leading to small intestine lesions, abdominal pain, diarrhea, and bowel perforation. If the central nervous system is involved, symptoms can include headaches, dizziness, seizures, paralysis of cranial nerves, weakness, stroke, damage to small areas of the brain due to artery blockage (cerebral infarcts, and cerebral hemorrhage). Additional organs commonly impacted include the heart, lungs, and kidneys. Symptoms that may develop from damage to these organs include double vision (diplopia), clouding of lenses of eyes, swelling of the optic disc (papilledema), partial loss of vision, shortness of breath, chest pain, epilepsy, and thickening of pericardium.Someone with the benign form may suddenly develop symptoms of the malignant form. Symptoms can last anywhere from a few weeks to several years. Onset of symptoms typically begins to manifest between the ages of 20–50. A few cases of this condition in newborns have also been described.

Causes
The papules characteristic for this disease develop due to infarctions, or blockages in small-medium arteries and veins. The underlying cause is unknown for this disease. Though not confirmed, some cases have shown signs of inheritance between first-degree relatives. It has been suggested that the disease has a familial inheritance pattern; it is thought to be an autosomal dominant disorder. In most cases of familial inheritance, the benign variant of the disease has been present.Due to the lack of knowledge of the pathomechanism for this condition prevention strategies are not known. However, in order to prevent worsening of symptoms, consistent evaluations should be conducted by a physician.

Mechanism
Although this disease has been known for around 70 years, the pathomechanism underlying it is still unknown. Several hypotheses have been developed regarding the underlying mechanism for Degos disease. One theory suggests that inflammation of blood vessels may trigger the condition. Another theory has to do with Degos disease as a coagulopathy. Development of a thrombus and resulting reduction of blood flow is common in this condition. A reduction in blood flow throughout the body can lead to damaged endothelial cells and may perhaps lead to the formation of the characteristic papules. Another hypothesis suggests that abnormal swelling and proliferation of the vascular endothelium can lead to intestinal and central nervous system thrombosis, and ultimately lead to development of symptoms associated with Degos disease. Overall, individuals with Degos disease have abnormal blockages in their arteries and veins; however, the cause of these blockages is unknown.

Diagnosis
Clinical evaluation and identification of characteristics papules may allow a dermatologist to diagnose Degos disease. The papules have a white center and are bordered with a red ring. After lesions begin to appear, the diagnosis for Degos disease can be supported by histological findings. Most cases will show a wedge-shaped connective tissue necrosis in the deep corium. This shape is due to the blockage/occlusion of small arteries.Individuals may be diagnosed with the benign form if only the papules are present. However, an individual may be diagnosed with the malignant form if involvement of other organs like the lungs, intestine and/or central nervous system occurs. The malignant, or systematic form of this condition may suddenly develop even after having papules present for several years. In order to quickly diagnose this shift to the malignant variant of the disease, it is important for individuals to have consistent follow-up evaluations. In these evaluations, depending on which organs are suspected to be involved, the following procedures and tests may be conducted: skin inspection, brain magnetic resonance tomography, colonoscopy, chest X-ray, and/or abdominal ultrasound.

Treatment
Due to the lack of knowledge around the underlying mechanism of malignant atrophic papulosis, an effective treatment method has not been developed. Treatment for this condition is symptomatic. However, several treatment methods have been tested and are still being developed as more information regarding the condition is found. Fibrinolytic and immunosuppressive therapeutic regimens were tested and found to be mostly unsuccessful as treatment methods.After treating conditions comorbid with Degos disease, physicians have recently found improvement in symptoms with the use of eculizumab and treprostinil. Discovered by dermatopathologist, Cynthia Magro, response to eculizumab is often immediate and dramatic, but has been of limited duration and is expensive, needing to be infused every 14 days. Treprostinil use has been reported to result in clearing of gastrointestinal and central nervous system findings as well as clearing of cutaneous lesions, but reports are limited. Treprostinil may be more effective than other vasodilators because it may also increase the population of circulating endothelial cells, allowing angiogenesis.

Recent research
A 46-year-old male patient was diagnosed with the malignant, systemic form of the disease and was severely ill. The diagnosing dermatopathologist, Cynthia Magro MD, identified the presence of C5b-9 complexes in the involved vessels of the skin biopsy </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Shingles and can you explain it in depth? [/INST] Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Otherwise, there are typically few symptoms though some people may have fever or headache, or feel tired. The rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.Shingles and chickenpox are distinct human diseases but are closely related in their life cycles. Both originate from infection of an individual with the varicella zoster virus (VZV). Chickenpox, also called varicella, results from the initial infection with the virus, typically occurring during childhood or adolescence. Once the chickenpox has resolved, the virus can remain inactive (dormant) in human nerve cells (dorsal root ganglia or cranial nerves) for years or decades, after which it may reactivate. Shingles results when the dormant varicella virus is reactivated. The virus then travels along nerve bodies to nerve endings in the skin, producing blisters. During an outbreak of shingles, exposure to the varicella virus found in shingles blisters can cause chickenpox in someone who has not yet had chickenpox; this initial infection will not trigger shingles, however. How the virus remains dormant in the body or subsequently re-activates is not well understood.Risk factors for reactivation of the dormant virus include old age, poor immune function, and having contracted chickenpox before 18 months of age. Diagnosis is typically based on the signs and symptoms presented. Varicella zoster virus is not the same as herpes simplex virus, although they belong to the same family of herpesviruses.Shingles vaccines reduce the risk of shingles by 50% to 90%, depending on the vaccine used. Vaccination also decreases rates of postherpetic neuralgia, and, if shingles occurs, its severity. If shingles develops, antiviral medications such as aciclovir can reduce the severity and duration of disease if started within 72 hours of the appearance of the rash. Evidence does not show a significant effect of antivirals or steroids on rates of postherpetic neuralgia. Paracetamol, NSAIDs, or opioids may be used to help with acute pain.It is estimated that about a third of people develop shingles at some point in their lives. While shingles is more common among older people, children may also get the disease. According to the US National Institutes of Health, the number of new cases per year ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals to 3.9 to 11.8 per 1,000 person-years among those older than 65 years of age. About half of those living to age 85 will have at least one attack, and fewer than 5% will have more than one attack. Although symptoms can be severe, risk of death is very low: 0.28 to 0.69 deaths per million.The disease has been recognized since ancient times.

Signs and symptoms
The earliest symptoms of shingles, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia (oversensitivity), or paresthesia ("pins and needles": tingling, pricking, or numbness). Pain can be mild to severe in the affected dermatome, with sensations that are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.Shingles in children is often painless, but people are more likely to get shingles as they age, and the disease tends to be more severe.In most cases, after one to two days – but sometimes as long as three weeks – the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occur on the torso but can appear on the face, eyes, or other parts of the body. At first, the rash appears similar to the first appearance of hives; however, unlike hives, shingles causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline.  Zoster sine herpete ("zoster without herpes") describes a person who has all of the symptoms of shingles except this characteristic rash.Later the rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise continue. The painful vesicles eventually become cloudy or darkened as they fill with blood, and crust over within seven to ten days; usually the crusts fall off and the skin heals, but sometimes, after severe blistering, scarring and discolored skin remain.

Face
Shingles may have additional symptoms, depending on the dermatome involved. The trigeminal nerve is the most commonly involved nerve, of which the ophthalmic division is the most commonly involved branch. When the virus is reactivated in this nerve branch it is termed zoster ophthalmicus. The skin of the forehead, upper eyelid and orbit of the eye may be involved. Zoster ophthalmicus occurs in approximately 10% to 25% of cases. In some people, symptoms may include conjunctivitis, keratitis, uveitis, and optic nerve palsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain.Shingles oticus, also known as Ramsay Hunt syndrome type II, involves the ear. It is thought to result from the virus spreading from the facial nerve to the vestibulocochlear nerve. Symptoms include hearing loss and vertigo (rotational dizziness).Shingles may occur in the mouth if the maxillary or mandibular division of the trigeminal nerve is affected, in which the rash may appear on the mucous membrane of the upper jaw (usually the palate, sometimes the gums of the upper teeth) or the lower jaw (tongue or gums of the lower teeth) respectively. Oral involvement may occur alone or in combination with a rash on the skin over the cutaneous distribution of the same trigeminal branch. As with shingles of the skin, the lesions tend to only involve one side, distinguishing it from other oral blistering conditions. In the mouth, shingles appears initially as 1–4 mm opaque blisters (vesicles), which break down quickly to leave ulcers that heal within 10–14 days. The prodromal pain (before the rash) may be confused with toothache. Sometimes this leads to unnecessary dental treatment. Post-herpetic neuralgia uncommonly is associated with shingles in the mouth. Unusual complications may occur with intra-oral shingles that are not seen elsewhere. Due to the close relationship of blood vessels to nerves, the virus can spread to involve the blood vessels and compromise the blood supply, sometimes causing ischemic necrosis. Therefore, oral involvement rarely causes complications, such as osteonecrosis, tooth loss, periodontitis (gum disease), pulp calcification, pulp necrosis, periapical lesions and tooth developmental anomalies.

Disseminated shingles
In those with poor immune function, disseminated shingles may occur (wide rash).
It is defined as more than twenty skin lesions appearing outside either the primarily affected dermatome or dermatomes directly adjacent to it. Besides the skin, other organs, such as the liver or brain, may also be affected (causing hepatitis or encephalitis, respectively), making the condition potentially lethal.: 380

Pathophysiology
The causative agent for shingles is the varicella zoster virus (VZV) – a double-stranded DNA virus related to the herpes simplex virus. Most individuals are infected with this virus as children which causes an episode of chickenpox. The immune system eventually eliminates the virus from most locations, but it remains dormant (or latent) in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the trigeminal ganglion in the base of the skull.Shingles occurs only in people who have been previously infected with VZV; although it can occur at any age, approximately half of the cases in the United States occur in those aged 50 years or older. Shingles can recur. In contrast to the frequent recurrence of herpes simplex symptoms, repeated attacks of shingles are unusual. It is extremely rare for a person to have more than three recurrences.The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase. Due to difficulties in studying VZV reactivation directly in humans (leading to reliance on small-animal models), its latency is less well understood than that of the herpes simplex virus.  Virus-specific proteins continue to be made by the infected cells during the latent period, so true latency, as opposed to chronic, low-level, active infection, has not been proven to occur in VZV infections. Although VZV has been detected in autopsies of nervous tissue, there are no methods to find dormant virus in the ganglia of living people.
Unless the immune system is compromised, it suppresses reactivation of the virus and prevents shingles outbreaks. Why this suppression sometimes fails is poorly understood, but shingles is more likely to occur in people whose immune systems are impaired due to aging, immunosuppressive therapy, psychological stress, or other factors. Upon reactivation, the virus replicates in neuronal cell bodies, and virions are shed from the cells and carried down the axons to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.As with chickenpox and other forms of alpha-herpesvirus infection, direct contact with an active rash can spread the virus to a person who lacks immunity to it. This newly infected individual may then develop chickenpox, but will not immediately develop shingles.The complete sequence of the viral genome was published in 1986.

Diagnosis
If the rash has appeared, identifying this disease (making a differential diagnosis) requires only a visual examination, since very few diseases produce a rash in a dermatomal pattern (sometimes called, by doctors on TV "a dermatonal map"). However, herpes simplex virus (HSV) can occasionally produce a rash in such a pattern (zosteriform herpes simplex).When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), shingles can be difficult to diagnose. Apart from the rash, most symptoms can occur also in other conditions.
Laboratory tests are available to diagnose shingles. The most popular test detects VZV-specific IgM antibody in blood; this appears only during chickenpox or shingles and not while the virus is dormant. In larger laboratories, lymph collected from a blister is tested by polymerase chain reaction (PCR) for VZV DNA, or examined with an electron microscope for virus particles. Molecular biology tests based on in vitro nucleic acid amplification (PCR tests) are currently considered the most reliable. Nested PCR test has high sensitivity, but is susceptible to contamination leading to false positive results. The latest real-time PCR tests are rapid, easy to perform, and as sensitive as nested PCR, and have a lower risk of contamination. They also have more sensitivity than viral cultures.

Differential diagnosis
Shingles can be confused with herpes simplex, dermatitis herpetiformis and impetigo, and skin reactions caused by contact dermatitis, candidiasis, certain drugs and insect bites.

Prevention
Shingles can be prevented by the chickenpox vaccine if the vaccine is administered before the individual gets chickenpox. If primary infection has already occurred, there are shingles vaccines that reduce the risk of developing shingles or developing severe shingles if the disease occurs. They include a live attenuated virus vaccine, Zostavax, and an adjuvanted subunit vaccine, Shingrix.A review by Cochrane concluded that Zostavax was useful for preventing shingles for at least three years. This equates to about 50% relative risk reduction. The vaccine reduced rates of persistent, severe pain after shingles by 66% in people who contracted shingles despite vaccination. Vaccine efficacy was maintained through four years of follow up. It has been recommended that people with primary or acquired immunodeficiency should not receive the live vaccine.Two doses of Shingrix are recommended, which provide about 90% protection at 3.5 years. As of 2016, it had been studied only in people with an intact immune system. It appears to also be effective in the very old.In the UK, shingles vaccination is offered by the National Health Service (NHS) to all people in their 70s. As of 2021 Zostavax is the usual vaccine, but Shingrix vaccine is recommended if Zostavax is unsuitable, for example for those with immune system issues. Vaccination is not available to people over 80 as "it seems to be less effective in this age group". By August 2017, just under half of eligible 70–78 year olds had been vaccinated. About 3% of those eligible by age have conditions that suppress their immune system, and should not receive Zostavax. There had been 1,104 adverse reaction reports by April 2018. In the US, it is recommended that healthy adults 50 years and older receive two doses of Shingrix, two to six months apart.

Treatment
The aims of treatment are to limit the severity and duration of pain, shorten the duration of a shingles episode, and reduce complications. Symptomatic treatment is often needed for the complication of postherpetic neuralgia.
However, a study on untreated shingles shows that, once the rash has cleared, postherpetic neuralgia is very rare in people under 50 and wears off in time; in older people, the pain wore off more slowly, but even in people over 70, 85% were free from pain a year after their shingles outbreak.

Analgesics
People with mild to moderate pain can be treated with over-the-counter pain medications. Topical lotions containing calamine can be used on the rash or blisters and may be soothing. Occasionally, severe pain may require an opioid medication, such as morphine. Once the lesions have crusted over, capsaicin cream (Zostrix) can be used. Topical lidocaine and nerve blocks may also reduce pain. Administering gabapentin along with antivirals may offer relief of postherpetic neuralgia.

Antivirals
Antiviral drugs may reduce the severity and duration of shingles; however, they do not prevent postherpetic neuralgia. Of these drugs, aciclovir has been the standard treatment, but the newer drugs valaciclovir and famciclovir demonstrate similar or superior efficacy and good safety and tolerability. The drugs are used both for prevention (for example in people with HIV/AIDS) and as therapy during the acute phase. Complications in immunocompromised individuals with shingles may be reduced with intravenous aciclovir. In people who are at a high risk for repeated attacks of shingles, five daily oral doses of aciclovir are usually effective.

Steroids
Corticosteroids do not appear to decrease the risk of long-term pain. Side effects however appear to be minimal. Their use in Ramsay Hunt syndrome had not been properly studied as of 2008.

Zoster ophthalmicus
Treatment for zoster ophthalmicus is similar to standard treatment for shingles at other sites. A trial comparing acyclovir with its prodrug, valacyclovir, demonstrated similar efficacies in treating this form of the disease. The significant advantage of valacyclovir over acyclovir is its dosing of only three times/day (compared with acyclovirs five times/day dosing), which could make it more convenient for people and improve adherence with therapy.

Prognosis
The rash and pain usually subside within three to five weeks, but about one in five people develops a painful condition called postherpetic neuralgia, which is often difficult to manage. In some people, shingles can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve (a dermatomal distribution), but without an accompanying rash. This condition may involve complications that affect several levels of the nervous system and cause many cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary), ear damage, or encephalitis. Although initial infections with VZV during pregnancy, causing chickenpox, may lead to infection of the fetus and complications in the newborn, chronic infection or reactivation in shingles are not associated with fetal infection.There is a slightly increased risk of developing cancer after a shingles episode. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus. Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.Although shingles typically resolves within 3–5 weeks, certain complications may arise:

Secondary bacterial infection.
Motor involvement, including weakness especially in "motor herpes zoster".
Eye involvement: trigeminal nerve involvement (as seen in herpes ophthalmicus) should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus.
Postherpetic neuralgia, a condition of chronic pain following shingles.

Epidemiology
Varicella zoster virus (VZV) has a high level of infectivity and has a worldwide prevalence. Shingles is a re-activation of latent VZV infection: zoster can only occur in someone who has previously had chickenpox (varicella).
Shingles has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age. The incidence rate of shingles ranges from 1.2 to 3.4 per 1,000 person‐years among younger healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years, and incidence rates worldwide are similar.
This relationship with age has been demonstrated in many countries, and is attributed to the fact that cellular immunity declines as people grow older.
Another important risk factor is immunosuppression. Other risk factors include psychological stress. According to a study in North Carolina, "black subjects were significantly less likely to develop zoster than were white subjects." It is unclear whether the risk is different by sex. Other potential risk factors include mechanical trauma and exposure to immunotoxins.There is no strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who had shingles were twice as likely to develop it themselves, but a 2010 study found no such link.Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost. This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the United States, there was concern that, because older adults would no longer receive this natural periodic boost, there would be an increase in the incidence of shingles.
Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995. However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community. A later study by Patel et al. concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles increased by more than $700 million annually for those over age 60. Another study by Yih et al. reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased, and the occurrence of shingles among adults increased by 90%. The results of a further study by Yawn et al. showed a 28% increase in shingles incidence from 1996 to 2001. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.In one study, it was estimated that 26% of those who contract shingles eventually present complications. Postherpetic neuralgia arises in approximately 20% of people with shingles. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV in the earlier study, or to the introduction of antivirals in California before 1994.

History
Shingles has a long recorded history, although historical accounts fail to distinguish the blistering caused by VZV and those caused by smallpox, ergotism, and erysipelas. In the late 18th century William Heberden established a way to differentiate shingles and smallpox, and in the late 19th century, shingles was differentiated from erysipelas. In 1831 Richard Bright hypothesized that the disease arose from the dorsal root ganglion, and an 1861 paper by Felix von Bärensprung confirmed this.Recognition that chickenpox and shingles were caused by the same virus came at the beginning of the 20th century. Physicians began to report that cases of shingles were often followed by chickenpox in younger people who lived with the person with shingles. The idea of an association between the two diseases gained strength when it was shown that lymph from a person with shingles could induce chickenpox in young volunteers. This was finally proved by the first isolation of the virus in cell cultures, by the Nobel laureate Thomas Huckle Weller, in 1953. Some sources also attribute the first isolation of the herpes zoster virus to Evelyn Nicol.Until the 1940s the disease was considered benign, and serious complications were thought to be very rare. However, by 1942, it was recognized that shingles was a more serious disease in adults than in children and that it increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed individuals showed that the disease was not as benign as once thought, and the search for various therapeutic and preventive measures began. By the mid-1960s, several studies identified the gradual reduction in cellular immunity in old age, observing that in a cohort of 1,000 people who lived to the age of 85, approximately 500 (i.e., 50%) would have at least one attack of shingles, and 10 (i.e., 1%) would have at least two attacks.In historical shingles studies, shingles incidence generally increased with age. However, in his 1965 paper, Hope-Simpson suggested that the "peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed".
Lending support to this hypothesis that contact with children with chickenpox boosts adult cell-mediated immunity to help postpone or suppress shingles, a study by Thomas et al. reported that adults in households with children had lower rates of shingles than households without children. Also, the study by Terada et al. indicated that pediatricians reflected incidence rates from 1/2 to 1/8 that of the general population their age.

Etymology
The family name of all the herpesviruses derives from the Greek word herpēs, from herpein ("to creep"), referring to the latent, recurring infections typical of this group of viruses. Zoster comes from Greek zōstēr, meaning "belt" or "girdle", after the characteristic belt-like dermatomal rash. The common name for the disease, shingles, derives from the Latin cingulus, a variant of Latin cingulum, meaning "girdle".

Research
Until the mid-1990s, infectious complications of the central nervous system (CNS) caused by VZV reactivation were regarded as rare. The presence of rash, as well as specific neurological symptoms, were required to diagnose a CNS infection caused by VZV. Since 2000, PCR testing has become more widely used, and the number of diagnosed cases of CNS infection has increased.Classic textbook descriptions state that VZV reactivation in the CNS is restricted to immunocompromised individuals and the elderly; however, studies have found that most participants are immunocompetent, and less than 60 years old. Historically, vesicular rash was considered a characteristic finding, but studies have found that rash is only present in 45% of cases.
In addition, systemic inflammation is not as reliable an indicator as previously thought: the mean level of C-reactive protein and mean white blood cell count are within the normal range in participants with VZV meningitis.
MRI and CT scans are usually normal in cases of VZV reactivation in the CNS. CSF pleocytosis, previously thought to be a strong indicator of VZV encephalitis, was absent in half of a group of people diagnosed with VZV encephalitis by PCR.The frequency of CNS infections presented at the emergency room of a community hospital is not negligible, so a means of diagnosing cases is needed. PCR is not a foolproof method of diagnosis, but because so many other indicators have turned out to not be reliable in diagnosing VZV infections in the CNS, screening for VZV by PCR is recommended. Negative PCR does not rule out VZV involvement, but a positive PCR can be used for diagnosis, and appropriate treatment started (for example, antivirals can be prescribed rather than antibiotics).The introduction of DNA analysis techniques has shown some complications of varicella-zoster to be more common than previously thought. For example, sporadic meningoencephalitis (ME) caused by varicella-zoster was regarded as rare disease, mostly related to childhood chickenpox. However, meningoencephalitis caused by varicella-zoster is increasingly recognized as a predominant cause of ME among immunocompetent adults in non-epidemic circumstances.Diagnosis of complications of varicella-zoster, particularly in cases where the disease reactivates after years or decades of latency, is difficult. A rash (shingles) can be present or absent. Symptoms vary, and there is a significant overlap in symptoms with herpes-simplex symptoms.Although DNA analysis techniques such as polymerase chain reaction (PCR) can be used to look for DNA of herpesviruses in spinal fluid or blood, the results may be negative, even in cases where other definitive symptoms exist. Notwithstanding these limitations, the use of PCR has resulted in an advance in the state of the art in our understanding of herpesviruses, including VZV, during the 1990s and 2000s </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is X-linked recessive chondrodysplasia punctata and can you explain it in depth? [/INST] X-linked recessive chondrodysplasia punctata is a type of chondrodysplasia punctata that can involve the skin, hair, and cause short stature with skeletal abnormalities, cataracts, and deafness.: 500 This condition is also known as arylsulfatase E deficiency, CDPX1, and X-linked recessive chondrodysplasia punctata 1. The syndrome rarely affects females, but they can be carriers of the recessive allele.  Although the exact number of people diagnosed with CDPX1 is unknown, it was estimated that 1 in 500,000 have CDPX1 in varying severity. This condition is not linked to a specific ethnicity. The mutation that leads to a deficiency in arylsulfatase E. (ARSE) occurs in the coding region of the gene. Absence of stippling, deposits of calcium, of bones and cartilage, shown on x-ray, does not rule out chondrodysplasia punctata or a normal chondrodysplasia punctata 1 (CDPX1) gene without mutation. Stippling of the bones and cartilage is rarely seen after childhood. Phalangeal abnormalities are important clinical features to look for once the stippling is no longer visible. Other, more severe, clinical features include respiratory abnormalities, hearing loss, cervical spine abnormalities, delayed cognitive development, ophthalmologic abnormalities, cardiac abnormalities, gastroesophageal reflux, and feeding difficulties. CDPX1 actually has a spectrum of severity; different mutations within the CDPX1 gene have different effects on the catalytic activity of the ARSE protein. The mutations vary between missense, nonsense, insertions, and deletions.

Cause
The only known cause of this condition is a mutation in the X-linked chondrodysplasia punctata 1 (CDPX1) gene. Mutations in this gene result in a deficiency of arylsulfatase E </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cutis marmorata telangiectatica congenita and can you explain it in depth? [/INST] Cutis marmorata telangiectatica congenita is a rare congenital vascular disorder that usually manifests in affecting the blood vessels of the skin. The condition was first recognised and described in 1922 by Cato van Lohuizen, a Dutch pediatrician whose name was later adopted in the other common name used to describe the condition – Van Lohuizen Syndrome. CMTC is also used synonymously with congenital generalized phlebectasia, nevus vascularis reticularis, congenital phlebectasia, livedo telangiectatica, congenital livedo reticularis and Van Lohuizen syndrome.It should not be confused with the more general term "cutis marmorata", which refers to livedo reticularis caused by cold.

Signs and symptoms
People with visible marks generally feel fine (physically) and can act normally, but when it is mentioned, they may become withdrawn and self-conscious. Some children may have low self-esteem due to the condition.CMTC is an uncommon, sporadic congenital vascular malformation characterized by a generalized or localized reticulated cutaneous vascular network.Cutaneous lesions described in patients with CMTC include nevus flammeus, hemangioma, nevus anemicus, café-au-lait spots, melanocytic nevus, aplasia cutis and acral cyanosis.It has a marbled bluish to deep-purple appearance. The dark skin lesions often show a palpable loss of dermal substance. The reticulated mottling frequently appears more prominent in a cold environment (physiologic cutis marmorata), but tends not to disappear with warming. Hence, the erythema may be worsened by cooling, physical activity, or crying.CMTC frequently involves the extremities, with the lower extremities involved most commonly, followed by the upper extremities, and then the trunk and face. The lower extremities often show atrophy and seldom show hypertrophy resulting in limb circumference discrepancy.When located on the trunk, the lesions of CMTC tend to show mosaic distribution in streaks with a sharp midline demarcation seen across the abdomen. The lesions are primarily localized, but can be segmental or generalized, often unilateral in appearance. Diffuse involvement of the skin is usually not observed.
Although its course is variable, the majority of lesions in mild cases fade by adolescence. Ulceration and secondary infection are complications in severe cases and can be fatal if present in the neonatal period.

Causes
Fewer than 100 cases of CMTC have been published worldwide. Petrozzi reported the first case of CMTC in the United States in 1970. CMTC is believed to be more common than suspected, as studies have shown that milder forms of the disease are not being recognized as CMTC.The pathophysiology is still unclear, with most cases occurring sporadically, although rare cases were reported in families. Studies indicated the primary involvement of capillaries, venules and veins, and possibly also that of arterioles and lymphatics.
Hypotheses that have been proposed include: environmental/external factors; peripheral neural dysfunction; failure of the development of mesodermic vessels in an early embryonic stage; autosomal dominant inheritance with incomplete penetrance and, finally, the theory of Happle.

Diagnosis
Differential diagnosis
During the first few weeks after birth, when the lesions are not very reticulated, CMTC may look very similar to vascular lesions such as port-wine stains. However, during follow-up, CMTC lesions become characteristic in their appearance. They must be differentiated from other causes of persistent reticulated vascular lesions, such as those in the following table:

Histology
Some patients have a few or no histopathologic abnormalities. Histological examination of a biopsy may show an increase in the number and size of capillaries and veins (rarely lymphatics), dilated capillaries located in the deeper dermis, and hyperplasia and swollen endothelial cells with occasional dilated veins and venous lakes.

Associated abnormalities
Associated abnormalities include the following:

Body asymmetry (extremities; macrocephaly)
Glaucoma
Cutaneous atrophy
Neurological anomalies
Vascular anomalies (nevus flammeus /Sturge-Weber/Klippel-Trénauna Adams Oliver syndrome)
Psychomotor and/or mental retardation
Chronic ulceration that can complicate long-term CMTC
Chronic urticaria.

Treatment
In general, there is no treatment available for CMTC, although associated abnormalities can be treated </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cutaneous myxoma and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Amelia and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Urinary retention and can you explain it in depth? [/INST] Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladder control, mild lower abdominal pain, and a weak urine stream. Those with long-term problems are at risk of urinary tract infections.Causes include blockage of the urethra, nerve problems, certain medications, and weak bladder muscles. Blockage can be caused by benign prostatic hyperplasia (BPH), urethral strictures, bladder stones, a cystocele, constipation, or tumors. Nerve problems can occur from diabetes, trauma, spinal cord problems, stroke, or heavy metal poisoning. Medications that can cause problems include anticholinergics, antihistamines, tricyclic antidepressants, cyclobenzaprine, diazepam, nonsteroidal anti-inflammatory drugs (NSAID), amphetamines, and opioids. Diagnosis is typically based on measuring the amount of urine in the bladder after urinating.Treatment is typically with a catheter either through the urethra or lower abdomen. Other treatments may include medication to decrease the size of the prostate, urethral dilation, a urethral stent, or surgery. Males are more often affected than females. In males over the age of 40 about 6 per 1,000 are affected a year. Among males over 80 this increases 30%.

Signs and symptoms
Onset can be sudden or gradual. When the onset is sudden, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladder control, mild lower abdominal pain, and a weak urine stream. Those with long-term problems are at risk of urinary tract infections.

Causes
Bladder
Infection
Detrusor sphincter dyssynergia
Neurogenic bladder (commonly spinal cord damage, pelvic splanchic nerve damage, cauda equina syndrome,  pontine micturition or storage center lesions, demyelinating diseases or Parkinsons disease)
Iatrogenic (caused by medical treatment/procedure) scarring of the bladder neck (commonly from removal of indwelling catheters or cystoscopy operations)
Damage to the bladder

Prostate
Benign prostatic hyperplasia (BPH)
Prostate cancer and other pelvic malignancies
Prostatitis

Penile urethra
Congenital urethral valves
Phimosis or pinhole meatus
Circumcision
Obstruction in the urethra, for example a stricture (usually caused either by injury or STD), a metastasis or a precipitated pseudogout crystal in the urine
Pseudodyssynergia
STD lesions (gonorrhoea causes numerous strictures, leading to a "rosary bead" appearance, whereas chlamydia usually causes a single stricture)
Emasculation

Postoperative
Risk factors include

Age: Older people may have degeneration of neural pathways involved with bladder function and it can lead to an increased risk of postoperative urinary retention. The risk of postoperative urinary retention increases up to 2.11 fold for people older than 60 years.
Medications: Anticholinergics and medications with anticholinergic properties, alpha-adrenergic agonists, opiates, nonsteroidal anti-inflammatories (NSAIDs), calcium-channel blockers and beta-adrenergic agonists, may increase the risk.
Anesthesia: General anesthetics during surgery may cause bladder atony by acting as a smooth muscle relaxant. General anesthetics can directly interfere with autonomic regulation of detrusor tone and predispose people to bladder overdistention and subsequent retention. Spinal anesthesia results in a blockade of the micturition reflex. Spinal anesthesia shows a higher risk of postoperative urinary retention compared to general anesthesia.
Benign prostatic hyperplasia: Men with benign prostatic hyperplasia are at an increased risk of acute urinary retention.
Surgery related: Operative times longer than 2 hours may lead to an increased risk of postoperative urinary retention 3-fold.
Postoperative pain.

Chronic
Chronic urinary retention that is due to bladder blockage which can either be as a result of muscle damage or neurological damage. If the retention is due to neurological damage, there is a disconnect between the brain to muscle communication, which can make it impossible to completely empty the bladder. If the retention is due to muscle damage, it is likely that the muscles are not able to contract enough to completely empty the bladder.The most common cause of chronic urinary retention is BPH. BPH is a result of the ongoing process of testosterone being converted to dihydrotestosterone which stimulates prostate growth. Over a persons lifetime, the prostate experiences constant growth due to the conversion of testosterone to dihydrotestosterone. This can cause the prostate to push on the urethra and block it, which can lead to urinary retention.

Other
Tethered spinal cord syndrome.
Psychogenic causes – psychosocial stresses, fear associated with urination, paruresis ("shy bladder syndrome") – in extreme cases, urinary retention can result.
Consumption of some psychoactive substances, mainly stimulants, such as MDMA or amphetamine.
Use of NSAIDs, or drugs with anticholinergic properties.
Stones or metastases, which can theoretically appear anywhere along the urinary tract, but vary in frequency depending on anatomy.
Muscarinic antagonists such as atropine and scopolamine.
Malfunctioning artificial urinary sphincter.

Diagnosis
Analysis of urine flow may aid in establishing the type of micturition (urination) abnormality. Common findings, determined by ultrasound of the bladder, include a slow rate of flow, intermittent flow, and a large amount of urine retained in the bladder after urination. A normal test result should be 20-25 mL/s peak flow rate. A post-void residual urine greater than 50 ml is a significant amount of urine and increases the potential for recurring urinary tract infections. In adults older than 60 years, 50-100 ml of residual urine may remain after each voiding because of the decreased contractility of the detrusor muscle. In chronic retention, ultrasound of the bladder may show massive increase in bladder capacity (normal capacity is 400-600 ml).Non-neurogenic chronic urinary retention does not have a standardized definition; however, urine volumes >300mL can be used as an informal indicator. Diagnosis of urinary retention is conducted over a period of 6 months, with 2 separate measurements of urine volume 6 months apart. Measurements should have a PVR (post-void residual) volume of >300mL.Determining the serum prostate-specific antigen (PSA) may help diagnose or rule out prostate cancer, though this is also raised in BPH and prostatitis. A TRUS biopsy of the prostate (trans-rectal ultra-sound guided) can distinguish between these prostate conditions. Serum urea and creatinine determinations may be necessary to rule out backflow kidney damage. Cystoscopy may be needed to explore the urinary passage and rule out blockages.In acute cases of urinary retention where associated symptoms in the lumbar spine are present such as pain, numbness (saddle anesthesia), parasthesias, decreased anal sphincter tone, or altered deep tendon reflexes, an MRI of the lumbar spine should be considered to further assess cauda equina syndrome.

Complications
Acute urinary retention is a medical emergency and requires prompt treatment. The pain can be excruciating when urine is not able to flow out. Moreover, one can develop severe sweating, chest pain, anxiety and high blood pressure. Other patients may develop a shock-like condition and may require admission to a hospital. Serious complications of untreated urinary retention include bladder damage and chronic kidney failure. Urinary retention is a disorder treated in a hospital, and the quicker one seeks treatment, the fewer the complications.In the longer term, obstruction of the urinary tract may cause:
Bladder stones
Atrophy of the detrusor muscle (atonic bladder is an extreme form)
Hydronephrosis (congestion of the kidneys)
Hypertrophy of the detrusor muscle (the muscle that squeezes the bladder to empty it during urination)
Diverticula (formation of pouches) in the bladder wall (which can lead to stones and infection)

Treatment
In acute urinary retention, urinary catheterization, placement of a prostatic stent, or suprapubic cystostomy relieves the retention. In the longer term, treatment depends on the cause. BPH may respond to alpha blocker and 5-alpha-reductase inhibitor therapy, or surgically with prostatectomy or transurethral resection of the prostate (TURP).Use of alpha-blockers can provide relief of urinary retention following de-catheterization for both men and women. In case, if catheter cant be negotiated, suprapubic puncture can be done with lumbar puncture needle.

Medication
Some people with BPH are treated with medications. These include tamsulosin to relax smooth muscles in the bladder neck, and finasteride and dutasteride to decrease prostate enlargement. The drugs only work for mild cases of BPH but also have mild side effects. Some of the medications decrease libido and may cause dizziness, fatigue and lightheadedness.

Catheter
Acute urinary retention is treated by placement of a urinary catheter (small thin flexible tube) into the bladder. This can be either an intermittent catheter or a Foley catheter that is placed with a small inflatable bulb that holds the catheter in place.Intermittent catheterization can be done by a health care professional or by the person themselves (clean intermittent self catheterization).  Intermittent catheterization performed at the hospital is a sterile technique. Patients can be taught to use a self catheterization technique in one simple demonstration, and that reduces the rate of infection from long-term Foley catheters. Self catheterization requires doing the procedure periodically during the day, the frequency depending on fluid intake and bladder capacity. If fluid intake/outflow is around 1.5 litres per day, this would typically be performed roughly three times per day, i.e. roughly every six to eight hours during the day, more frequently when fluid intake is higher and/or bladder capacity lower.
For acute urinary retention, treatment requires urgent placement of a urinary catheter. A permanent urinary catheter may cause discomfort and pain that can last several days.
Older people with ongoing problems may require continued intermittent self catheterization (CISC). CISC has a lower infection risk compared to catheterization techniques that stay within the body. Challenges with CISC include compliance issues as some people may not be able to place the catheter themselves.

Surgery
The chronic form of urinary retention may require some type of surgical procedure. While both procedures are relatively safe, complications can occur.
In most patients with benign prostate hyperplasia (BPH), a procedure known as transurethral resection of the prostate (TURP) may be performed to relieve bladder obstruction. Surgical complications from TURP include a bladder infection, bleeding from the prostate, scar formation, inability to hold urine, and inability to have an erection. The majority of these complications are short lived, and most individuals recover fully within 6–12 months.

Sitting voiding position
A meta-analysis on the influence of voiding position on urodynamics in males with lower urinary tract symptoms showed that in the sitting position, the residual urine in the bladder was significantly reduced, the maximum urinary flow was increased, and the voiding time was decreased. For healthy males, no influence was found on these parameters, meaning that they can urinate in either position.

Epidemiology
Urinary retention is a common disorder in elderly males. The most common cause of urinary retention is BPH. This disorder starts around age 50 and symptoms may appear after 10–15 years. BPH is a progressive disorder and narrows the neck of the bladder leading to urinary retention. By the age of 70, almost 10 percent of males have some degree of BPH and 33% have it by the eighth decade of life. While BPH rarely causes sudden urinary retention, the condition can become acute in the presence of certain medications including antihypertensives, antihistamines, and antiparkinson medications, and after spinal anaesthesia or stroke.In young males, the most common cause of urinary retention is infection of the prostate (acute prostatitis). The infection is acquired during sexual intercourse and presents with low back pain, penile discharge, low grade fever and an inability to pass urine </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cochlear hydrops and can you explain it in depth? [/INST] Cochlear hydrops (or cochlear Menieres or cochlear endolymphatic hydrops) is a condition of the inner ear involving a pathological increase of fluid affecting the cochlea. This results in swelling that can lead to hearing loss or changes in hearing perception. It is a form of endolymphatic hydrops and related to Menieres disease. Cochlear hydrops refers to a case of inner-ear hydrops that only involves auditory symptoms and does not cause vestibular issues.

Cause and behavior
Cochlear hydrops refers to an increase in endolymphatic fluid in the inner ear. This build-up is either due to an overproduction or insufficient drainage of endolymph in the constant regulation of fluid in the inner ear. Usually, only one ear is affected. The root cause of the process is unclear and may vary from patient to patient, but can have auto-immune, viral, and/or allergic triggers, among others.The build-up of endolymph creates pressure in the scala media. This causes its diameter to increase, and the vestibular membrane to curve outwards in the direction of the vestibule. The changes to the membrane can result in changes to either the hearing perception or hearing threshold of a patient.Episodes are usually cyclical and symptoms fluctuate through time. Patients may be symptom-free between episodes, which themselves may progressively worsen, improve, or remain constant in severity or duration. For some, permanent damage occurs, and they may be left with long-term hearing loss, hearing distortion, tinnitus, and/or a feeling of fullness in the affected ear(s).A study looking at spiral ganglion cell counts compared to hair cell counts in the inner ear of patients who had Menieres disease found that they maintained more hair cells than spinal ganglion cells. Thus, it could be possible that hydrops affects auditory nerves more than hair cells. In contrast, a 2021 article by Richard Gacek posits that the hearing loss is actually caused by toxic nucleic acids that are released to the outer hair cells: "Since the outer hair cells (OHC) are freely surrounded by perilymph, their walls and nerve terminals are also bathed in this fluid. The few type-II spiral ganglion cells in contact with the OHC are unlikely to play a significant role in hearing loss because of their low numbers and the lack of a known connection to the central auditory pathway."

Symptoms
Cochlear hydrops preferentially affects the apex of the cochlea where low-frequency sounds are interpreted. Due to the fluid imbalance in this area, parts of the cochlea are stretched or under more tension than usual, which can lead to distortions of sound, changes in pitch perception, or hearing loss, all usually in the low frequencies.
Common symptoms include:

Low-frequency sensorineural hearing loss.
A feeling of fullness in the ear.
Tinnitus (ringing in the ear).
Diplacusis (the perception of sound being a different pitch in one ear).
Hyperacusis (an intolerance to loud sounds).
Depression or anxiety that the condition will worsen or progress to Menieres disease.As with Menieres disease, atypical, early, or mild cases may only present some symptoms.

Diagnosis
Diagnosis is based on symptoms and a hearing test that documents a loss in the low and mid frequencies, usually only in one ear. For patients with mild or atypical hydrops, the hearing thresholds may be normal, but they may experience a subjective, unilateral distortion of sounds in lower frequencies, such as diplacusis or that voices are sounding "robotic". Patients may also mention a feeling of pressure or fullness in the ear.To objectively test for the presence of hydrops, an electrocochleography (or ECOG) procedure can be done to detect elevated inner ear pressure. It is also possible to reveal the presence of hydrops with an MRI.If vertigo is experienced, the diagnosis progresses to Menieres disease. This occurs if the fluid increase leads to a leak or rupture of the membranes in the inner ear, causing a mixture of perilymph and endolymph.

Treatment
Treatment for cochlear hydrops is the same as for Menieres disease. Currently, no cure exists for either.If a patient has undergone sudden sensorineural hearing loss, a course of steroids is often prescribed in an attempt to recover the hearing. Steroids may be injected directly through the eardrum.Like Menieres Disease, a low salt diet is recommended as a preventative measure. A diuretic may be prescribed to help lower salt content.Betahistine is the most widely prescribed medication for the treatment of Menieres disease. The drug is thought to increase blood flow to the inner ear and to prevent the frequency and intensity of episodes. While Betahistine is considered safe, there is insufficient evidence that it is an effective treatment </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Dysmorphic feature and can you explain it in depth? [/INST] A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysmorphic features, their origins and proper nomenclature. One of the key challenges in identifying and describing dysmorphic features is the use and understanding of specific terms between different individuals. Clinical geneticists and pediatricians
are usually those most closely involved with the identification and description of dysmorphic features, as most are apparent during childhood.
Dysmorphic features can vary from isolated, mild anomalies such as clinodactyly or synophrys to severe congenital anomalies, such as heart defects and holoprosencephaly </s>