<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Harlequin-type ichthyosis and explain in detail? [/INST] Harlequin-type ichthyosis is a genetic disorder that results in thickened skin over nearly the entire body at birth. The skin forms large, diamond/trapezoid/rectangle-shaped plates that are separated by deep cracks. These affect the shape of the eyelids, nose, mouth, and ears and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties. These plates fall off over several weeks. Other complications can include premature birth, infection, problems with body temperature, and dehydration. The condition is the most severe form of ichthyosis, a group of genetic disorders characterised by scaly skin.Harlequin-type ichthyosis is caused by mutations in the ABCA12 gene. This gene codes for a protein necessary for transporting lipids out of cells in the outermost layer of skin. The disorder is autosomal recessive and inherited from parents who are carriers. Diagnosis is often based on appearance at birth and confirmed by genetic testing. Before birth, amniocentesis or ultrasound may support the diagnosis.There is no cure for the condition. Early in life, constant supportive care is typically required. Treatments may include moisturizing cream, antibiotics, etretinate or retinoids. Around half of those affected die within the first few months; however, retinoid treatment can increase chances of survival. Children who survive the first year of life often have long-term problems such as red skin, joint contractures and delayed growth. The condition affects around 1 in 300,000 births. It was first documented in a diary entry by Reverend Oliver Hart in America in 1750.

Signs and symptoms
Newborns with harlequin-type ichthyosis present with thick, fissured armor-plate hyperkeratosis. Sufferers feature severe cranial and facial deformities. The ears may be very poorly developed or absent entirely, as may the nose. The eyelids may be everted (ectropion), which leaves the eyes and the area around them very susceptible to infection. Babies with this condition often bleed during birth. The lips are pulled back by the dry skin (eclabium).Joints are sometimes lacking in movement, and may be below the normal size. Hypoplasia is sometimes found in the fingers. Polydactyly has also been found on occasion. In addition, the fish mouth appearance, mouth breathing, and xerostomia place affected individuals at extremely high risk for developing rampant dental decay.Patients with this condition are extremely sensitive to changes in temperature due to their hard, cracked skin, which prevents normal heat loss. The skin also restricts respiration, which impedes the chest wall from expanding and drawing in enough air. This can lead to hypoventilation and respiratory failure. Patients are often dehydrated, as their plated skin is not well suited to retaining water.

Cause
Harlequin-type ichthyosis is caused by a loss-of-function mutation in the ABCA12 gene. This gene is important in the regulation of protein synthesis for the development of the skin layer. Mutations in the gene cause impaired transport of lipids in the skin layer and may also lead to shrunken versions of the proteins responsible for skin development. Less severe mutations result in a collodion membrane and congenital ichthyosiform erythroderma-like presentation.ABCA12 is an ATP-binding cassette transporter (ABC transporter), which are members of a large family of proteins that hydrolyze ATP to transport cargo across cell membranes. ABCA12 is thought to be a lipid transporter in keratinocytes necessary for lipid transport into lamellar granules during the formation of the lipid barrier in the skin.

Diagnosis
The diagnosis of harlequin-type ichthyosis relies on both physical examination and laboratory tests. Physical assessment at birth is vital for the initial diagnosis of harlequin ichthyosis. Physical examination reveals characteristic symptoms of the condition especially the abnormalities in the skin surface of newborns. Abnormal findings in physical assessments usually result in employing other diagnostic tests to ascertain the diagnosis.Genetic testing is the most specific diagnostic test for harlequin ichthyosis. This test reveals a loss of function mutation on the ABCA12 gene. Biopsy of skin may be done to assess the histologic characteristics of the cells. Histological findings usually reveal hyperkeratotic skin cells, which leads to a thick, white and hard skin layer.

Treatment
Constant care is required to moisturize and protect the skin. The hard outer layer eventually peels off, leaving the vulnerable inner layers of the dermis exposed. Early complications result from infection due to fissuring of the hyperkeratotic plates and respiratory distress due to physical restriction of chest wall expansion.Management includes supportive care and treatment of hyperkeratosis and skin barrier dysfunction. A humidified incubator is generally used. Intubation is often required until nares are present. Nutritional support with tube feeds is essential until eclabium resolves and infants can begin nursing. Ophthalmology consultation is useful for the early management of ectropion, which is initially pronounced and resolves as scales are shed. Liberal application of petrolatum is needed multiple times a day. In addition, careful debridement of constrictive bands of hyperkeratosis should be performed to avoid digital ischemia.Cases of digital autoamputation or necrosis have been reported due to cutaneous constriction bands. Relaxation incisions have been used to prevent this morbid complication.

Prognosis
In the past, the disorder was nearly always fatal, whether due to dehydration, infection (sepsis), restricted breathing due to the plating, or other related causes. The most common cause of death was systemic infection, and sufferers rarely survived for more than a few days. However, improved neonatal intensive care and early treatment with oral retinoids, such as the drug Isotretinoin, may improve survival. Early oral retinoid therapy has been shown to soften scales and encourage desquamation. After as little as two weeks of daily oral isotretinoin, fissures in the skin can heal, and plate-like scales can nearly resolve. Improvement in the eclabium and ectropion can also be seen in a matter of weeks.
Children who survive the neonatal period usually evolve to a less severe phenotype, resembling a severe congenital ichthyosiform erythroderma. Patients continue to suffer from temperature dysregulation and may have heat and cold intolerance. Patients can also have generalized poor hair growth, scarring alopecia, contractures of digits, arthralgias, failure to thrive, hypothyroidism, and short stature. Some patients develop a rheumatoid factor-positive polyarthritis. Survivors can also develop fish-like scales and retention of a waxy, yellowish material in seborrheic areas, with ear adhered to the scalp.The oldest known survivor is Nusrit "Nelly" Shaheen, who was born in 1984 and is in relatively good health as of June 2021. The maximum lifespan of patients with this disease has not yet been determined with the new treatments.A study published in 2011 in the Archives of Dermatology concluded: "Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing."

Epidemiology
The condition occurs in roughly 1 in 300,000 people. As an autosomal recessive condition, rates are higher among certain ethnic populations with a higher likelihood of consanguinity.

History
The disease has been known since 1750, and was first described in the diary of Rev. Oliver Hart from Charleston, South Carolina:

"On Thursday, April the 5th, 1750, I went to see a most deplorable object of a child, born the night before of one Mary Evans in Chastown. It was surprising to all who beheld it, and I scarcely know how to describe it. The skin was dry and hard and seemed to be cracked in many places, somewhat resembling the scales of a fish. The mouth was large and round and open. It had no external nose, but two holes where the nose should have been. The eyes appeared to be lumps of coagulated blood, turned out, about the bigness of a plum, ghastly to behold. It had no external ears, but holes where the ears should be. The hands and feet appeared to be swollen, were cramped up and felt quite hard </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Klismaphilia and explain in detail? [/INST] Klismaphilia (or klysmaphilia), from the Greek words κλύσμα ("enema", from κατακλυσμός, "deluge, flood") and φιλία ("love"), is a paraphilia involving enjoyment of, and sexual arousal from, enemas.

History
The term klismaphilia was coined in 1973 by Dr. Joanne Denko, an early investigator in this field, in her article "Klismaphilia: Enema as a Sexual Preference[:] Report of Two Cases," to describe the activities of some of her patients, whom she referred to as klismaphiliacs. Klismaphile has come into use as a synonym for klismaphiliac.

Manifestation
Klismaphiles might gain pleasure from a large, water distended belly or the feeling of internal pressure. An enema fetish may include the sexual attraction to the equipment, processes, environments, situations, or scenarios, and some may be sexually aroused by the preparations, such as by the feel and smell of a latex rubber or plastic syringe, by the smell of soapsuds enema solution, or by preparing the recipient. Often, klismaphiles report discovering these desires after a chance administration of an enema sometime in their childhood, but some do report discovering these feelings later on. Klismaphiles can gain satisfaction of enemas through fantasies, by actually receiving or giving one, or through the process of eliminating steps to being administered one (e.g., under the pretense of being constipated). Usually, klismaphiles carry out normal lives and successfully engage in this behavior secretly.
An enema can be an auxiliary to, or a substitute for, genital sexual activity.That some women use enemas while masturbating was documented by Alfred Kinsey in "Sexual Behavior in the Human Female." He stated, "There still other masturbatory techniques which were regularly or occasionally employed by some 11 percent of the females in the sample ... enemas, and other anal insertions, ... were employed.Sadomasochistic activities may incorporate enemas for erotic humiliation or for physical discomfort. BDSM punishment scenes can involve administering an enema in a manner that is humiliating and painful and for producing pain and cramps an extra-large volumes or highly irritating substances can be injected. Among the attractions to enema play in BDSM are erotic humiliation, dominance and submission, discipline, psychodrama, power exchange, and so on. An erotic enema allows acting out vulnerability in a primal form.

Classification
The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) classifies klismaphilia under the diagnosis of "Paraphilias, Not Otherwise Specified". The diagnostic code is 302.9. Proactive treatment for klismaphilics is not generally recommended, due to the lack of any significant desire to be "cured". Health treatment for klismaphilia thus is typically only focused on ensuring the techniques employed and chemicals used are not harmful to the practitioner </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Radiation retinopathy and explain in detail? [/INST] Radiation retinopathy is damage to retina due to exposure to ionizing radiation. Radiation retinopathy has a delayed onset, typically after months or years of radiation, and is slowly progressive. In general, radiation retinopathy is seen around 18 months after treatment with external-beam radiation and with brachytherapy </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is African histoplasmosis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Carcinosis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Clear cell papillary renal cell carcinoma and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Gender dysphoria in children and explain in detail? [/INST] Gender dysphoria in children (GD), also known as gender incongruence of childhood,  is a formal diagnosis for children who experience significant discontent (gender dysphoria) due to a mismatch between their assigned sex and gender identity. The diagnostic label gender identity disorder in children (GIDC) was used by the Diagnostic and Statistical Manual of Mental Disorders (DSM) until it was renamed gender dysphoria in children in 2013 with the release of the DSM-5. The diagnosis was renamed to remove the stigma associated with the term disorder.Controversy surrounding the pathologization and treatment of a transgender identity and associated behaviors, particularly in children, has been evident in the literature since the 1980s. The majority of major medical associations such as the American Psychological Association, Substance Abuse and Mental Health Services Administration, and the World Professional Association for Transgender Health consider attempts to change a persons gender identity to be conversion therapy. The practice is considered unethical, pathologizing, and seriously harmful to transgender youth. Researchers also argue that therapeutic interventions that aim to alter a childs gender identity rely on the assumption that an adult transgender identity is undesirable, challenging this assumption along with the lack of clinical data to support outcomes and efficacy.Proponents of the older therapeutic approach to intervention argue that therapeutic intervention helps children be more comfortable in their bodies, have better peer relations and therefore better self-esteem, that research indicates there exist forms of distress associated directly with childrens gender variance, and that treatment can prevent adult GD. More modern therapeutic interventions do not seek to change a childs gender identity, but are instead focused on creating a supportive and safe environment for the child to explore their gender identity and gender expression.

Classification
Children with persistent gender dysphoria are characterized by more extreme gender dysphoria in childhood than children with desisting gender dysphoria. Some (but not all) gender variant youth will want or need to transition, which may involve social transition (changing dress, name, pronoun), and, for older youth and adolescents, medical transition (hormone therapy or surgery).

DSM-5 (2013)
In May 2013, the American Psychiatric Association published the DSM-5 update to the Diagnostic and Statistical Manual of Mental Disorders, in which the GIDC diagnosis was removed and replaced with gender dysphoria, for the first time in its own distinct chapter.  Subtyping by sexual orientation was deleted. The diagnosis for children was separated from that for adults. The creation of a specific diagnosis for children reflects the lesser ability of children to have insight into what they are experiencing, or ability to express it in the event that they have insight.Signs and symptoms, as outlined by the DSM-5, include a marked incongruence between experienced/expressed gender and assigned gender, of at least six months duration, as manifested by at least six of the following (one of which must be criterion A1):
A strong desire to be of the other gender or an insistence that one is the other gender
A strong preference for wearing clothes typical of the opposite gender
A strong preference for cross-gender roles in make-believe play or fantasy play
A strong preference for the toys, games or activities stereotypically used or engaged in by the other gender
A strong preference for playmates of the other gender
A strong rejection of toys, games and activities typical of ones assigned gender
A strong dislike of ones sexual anatomy
A strong desire for the physical sex characteristics that match ones experienced genderB. The condition is associated with clinically significant distress or impairment in social, school, or other important areas of functioning.

International Classification of Diseases (ICD)
The International Classification of Diseases (ICD-10) lists several disorders related to gender identity, including gender identity disorder of childhood (F64.2): Persistent and intense distress about ones assigned gender, manifested prior to puberty. The current edition has five different diagnoses for gender identity disorder, including one for when it manifests during childhood. The diagnoses of gender identity disorder is not given to intersex individuals (those born with "ambiguous" genitalia). Additionally, as with all psychological disorders, these symptoms must cause direct distress and an impairment of functioning of the individual exhibiting the symptoms.
F64.2 Gender identity disorder of childhood: A disorder, usually first manifest during early childhood (and always well before puberty), characterized by a persistent and intense distress about assigned sex, together with a desire to be (or insistence that one is) of the other sex. There is a persistent preoccupation with the dress and activities of the opposite sex and repudiation of the individuals own sex. The diagnosis requires a profound disturbance of the normal gender identity; mere tomboyishness in girls or girlish behavior in boys is not sufficient. Gender identity disorders in individuals who have reached or are entering puberty should not be classified here but in F66.0.
The ICD-11 significantly revises classification of gender identity-related conditions. Under "conditions related to sexual health", the ICD-11 lists "gender incongruence", which is coded into three conditions:
Gender incongruence of adolescence or adulthood (HA60): replaces F64.0
Gender incongruence of childhood (HA61): replaces F64.2
Gender incongruence, unspecified (HA6Z): replaces F64.9

Persistence
According to the American Academy of Pediatrics, "by age four most children have a stable sense of their gender identity" and "research substantiates that children who are prepubertal and assert [a transgender or gender diverse identity] know their gender as clearly and as consistently as their developmentally equivalent peers who identify as cisgender and benefit from the same level of social acceptance".If gender dysphoria persists during puberty, it is very likely permanent. For children with gender dysphoria, the period between 10 and 13 years is crucial with regard to long-term gender identity. Factors that are associated with gender dysphoria persisting through puberty include intensity of gender dysphoria, amount of cross-gendered behavior, and verbal identification with the desired/experienced gender (i.e. stating that they are a different gender rather than wish to be a different gender).Prospective studies have reported that gender dysphoria in children is more heavily linked to adult homosexuality than to an adult transgender identity, especially with regard to boys. The studies state that the majority of children diagnosed with gender dysphoria did not desire to be the other sex by puberty, with most growing up to identify as gay, lesbian, or bisexual, with or without therapeutic intervention.The prospective studies have been criticized  on the basis that they counted as desistance cases where the child was simply gender-nonconforming rather than dysphoric. While they met the criteria for gender identity disorder as defined in the DSM-III or DSM-IV, many would not have met the updated criteria for gender dysphoria in the DSM-5, established in 2013. In addition, prior to the DSM-III in 1980, there was no diagnostic criteria for gender dysphoria, so research on desistance rates published prior to 2000 reported inflated numbers of desistance.Additionally, the evidence offered has been criticized for citing studies which have been labelled conversion therapy for discouraging social transition and trying to prevent a transgender outcome. The studies have been used to argue for more caution in socially or medically transitioning transgender youth; however, they have been criticized as irrelevant due to tracking diagnoses rather than tracking evolution of gender identity or desire to transition. In addition, Bonifacio et al. state that "there is research to suggest" that some desistance of GD "may be caused, in part, by an internalizing pressure to conform rather than a natural progression to non–gender variance."According to a review published in 2022 considering more recent studies, the majority of pre-pubertal children who socially transition persist in their identity in 5 to 7 year follow ups.

Prevalence
According to a review published in 2020 relying on recent statistical surveys, 1.2% to 2.7% of children and adolescents identify as transgender. The data was drawn more from studies of adolescents than pre-pubertal youth and noted a difference in methodological quality between studies published before and after 2010. The review notes rising numbers of youth are self-identifying as trans and calls for more systematic studies and reviews in future.

Management
The WPATH Standards of Care and other therapeutic interventions do not seek to change a childs gender identity. Instead, clinicians advise children and their parents to avoid goals based on gender identity and to instead cope with the childs distress by embracing psychoeducation and to be supportive of their gender variant identity and behavior as it develops. A clinician may suggest that the parent be attentive, listen, and encourage an environment for the child to explore and express their identified gender identity, which may be termed the true gender. This can remove the stigma associated with their dysphoria, as well as the pressure to conform to a gender identity or role they do not identify with, which may be termed the false gender self. WPATH Standards of Care also recommend assessing and treating any co-existing mental health issues. By contrast, the majority of major medical associations define attempts to change an individuals gender identity or gender expression as conversion therapy.Treatment may also take the form of puberty blockers (such as leuprorelin), cross-sex hormones (i.e., administering estrogen to a child assigned male at birth or testosterone to a child assigned female at birth), or sex reassignment surgery with the aim of bringing ones physical body in line with their identified gender. Delaying puberty allows for the child to mentally mature while preventing them from developing a body they may not want, so that they may hopefully make a more informed decision about their gender identity once they are an adolescent. It can also help reduce anxiety and depression.According to the American Psychiatric Association, "Due to the dynamic nature of puberty development, lack of gender-affirming interventions (i.e. social, psychological,
and medical) is not a neutral decision; youth often experience worsening dysphoria and negative impact on mental health as the incongruent and unwanted puberty progresses. Trans-affirming treatment, such as the use of puberty suppression, is associated with the relief of emotional distress, and notable gains in psychosocial and emotional development, in trans and gender diverse youth".In its position statement published December 2020, the Endocrine Society stated that there is durable evidence for a biological underpinning to gender identity and that pubertal suppression, hormone therapy, and medically indicated surgery are effective and relatively safe when monitored appropriately and have been established as the standard of care. They noted a decrease in suicidal ideation among youth who have access to gender-affirming care and comparable levels of depression to cisgender peers among socially transitioned pre-pubertal youth. In its 2017 guideline on treating those with gender dysphoria, it recommends puberty blockers be started when the child has started puberty ( Tanner Stage 2 for breast or genital development) and cross-sex hormones be started at 16, though they note "there may be compelling reasons to initiate sex hormone treatment prior to the age of 16 years in some adolescents with GD/gender incongruence". They recommend a multidisciplinary team of medical and mental health professionals manage the treatment for those under 18. They also recommend "monitoring clinical pubertal development every 3 to 6 months and laboratory parameters every 6 to 12 months during sex hormone treatment".For adolescents, WPATH says that physical interventions such as puberty blockers, hormone therapy, or surgery may be appropriate. Before any physical interventions are initiated, however, a psychiatric assessment exploring the psychological, family, and social issues around the adolescents gender dysphoria should be undertaken. Some medical professionals disagree that adolescents are cognitively mature enough to make a decision with regard to hormone therapy or surgery, and advise that irreversible genital procedures should not be performed on individuals under the age of legal consent in their respective country.A review published in Child and Adolescent Mental Health found that puberty blockers are fully reversible, and that they are associated with such positive outcomes as decreased suicidality in adulthood, improved affect and psychological functioning, and improved social life.In 2020, a review article commissioned by NHS England was published by the National Institute for Health and Care Excellence, concluding that the quality of evidence for puberty blocker outcomes (for mental health, quality of life and impact on gender dysphoria) was of very low certainty based on the GRADE scale. In the UK, Bell v Tavistock considered the case of a patient who had changed her mind, now believing she was too young to have made such a decision, and concluded "Where the decision is significant and life changing then there is a greater onus to ensure that the child understands and is able to weigh the information". Following the ruling, NHS England announced that children under 16 would no longer be given puberty blockers without court authorization. This ruling was overturned on appeal in 2021, once again allowing children under 16 to consent to puberty blockers.Data from the Tavistock clinic found that children who were given puberty blockers were very likely to transition, with 43/44 (98%) of children who were given puberty blockers ultimately going on to take cross-sex hormones.

History
Past attempts at therapeutic intervention often included conversion therapy, viewing gender non-conformity as a problem to be fixed rather than natural variation. In addition, gender identity, gender expression, and sexual orientation were often conflated as problems to be corrected and replaced with the "correct" gendered behavior. Noting that many transgender and homosexual adults reported gender-nonconformity in childhood, clinicians at the time viewed early childhood intervention as a way to prevent a later LGBT identification. Notable proponents of the view that a trans "outcome" should be discouraged have included Richard Green, John Money, George Rekers, Ole Ivar Lovaas, Kenneth Zucker and Susan Bradley.The introduction of the GIDC diagnosis into the DSM-III in 1980 was preceded by numerous US studies and treatments on feminine boys beginning as early as the 1950s and 1960s, most prominently by John Money and Richard Green at the Johns Hopkins Hospital and the University of California, Los Angeles (UCLA). The prevention of transsexuality and / or homosexuality was explicitly stated as the goal of many of these studies: "My focus will be what we might consider the prevention of transsexualism." Bryant states that feminine boys were not a new phenomenon at this time; however, the public emergence of adult transsexual women (male to female) in the 1950s was new and created a number of problems for psychologists, motivating some to undertake efforts at preventing their further emergence. Meyerowitz chronicles the deep disagreements which erupted between psychologists and physicians after Christine Jorgensens public gender transition, namely over whether transsexuals should be permitted to align their bodies with their inner identities or whether their inner identities must be brought in line with their bodies. At the time, transsexual women were beginning to publish first-person narratives which highlighted their awareness of their femininity at a young age and Bryant states that some clinicians and researchers thus turned their attention to feminine boys, constructing sissies as a new "medicalized patient and research population."In 1960, Green and Money published a paper titled "Incongruous Gender Role: Nongenital Manifestations in Prepubertal Boys," detailing their observations of 5 children assigned male at birth(AMAB) who "showed incongruities in gender role", ranging from preferring to play with girls to praying God would change them into a girl. Citing that adult gay men and transgender women recollect gender incongruity in childhood, they later concluded
early intervention is best in cases of gender incongruity and that "part of the successful rearing of a child is orienting him, from birth, to his biologically and culturally acceptable gender role. This, as far as we know, is best achieved by providing a relationship between husband and wife exemplifying these respective roles."In 1968, Green published "Childhood Cross-Gender Identification", a paper reviewing the therapy of nine AMAB children who were younger than 8 and "clearly prepubertal". The first six were from the collaborative papers between Green and Money, the last 3 were from Robert Stoller. Citing the failure of attempts to "cure" adult trans women, he reported early diagnosis and treatment may be effective in preventing manifestations of adulthood cross-gender identification. The stated goals of family therapy are for "for the husband and wife to gain some perspective on the second class citizen of the husband and of the significance of their unbalanced roles in shaping their sons personality. Additional focus is on the masculinity-inhibiting of mothers anxiety over her sons healthy aggression and her greater comfort with what to her is his less threatening behavior."Another early researcher was George Alan Rekers, who later became an administrator at NARTH, who focused his 1972 doctoral research on the treatment of feminine boys. In this work, Rekers describes a litany of feminine behaviours which he catalogues including: feminine posture, gait, arm and hand gestures, feminine inflection in speech, as well as interest in feminine clothing, games and conversation topics. Using classical behaviour modification techniques he and a team of research assistants set about extinguishing problem feminine behaviours in three boys in particular, enlisting the help of parents and occasionally teachers to provide rewards and punishments corresponding to behaviours identified as wanted or unwanted. Rekers dissertation describes in detail, the case of Kraig (a pseudonym for Kirk Andrew Murphy) whose mother was instructed over earphones to alternately praise or ignore him depending on whether he played with a table of toys deemed to be feminine (typically dolls) or masculine (typically weapons). She was also trained to monitor his behaviour at home, with research assistants visiting weekly to ensure she was correctly completing her four times daily observations of Kraigs gendered behaviour. Physical punishment from Kraigs father is named as one of the primary consequences for feminine behaviour at home. Throughout Rekerss future work, he cites his treatments with Kraig as a success, claiming that "Kraigs feminine behaviours have apparently ceased entirely […]."In 1974, Rekers and Ole Ivar Lovaas published the article "Behavioral Treatment of Deviant Sex-Role Behaviors in a Male Child." The article cited Green and Money as a source of the "growing evidence that childhood cross-gender manifestations are indicative of later adult sexual abnormalities; e.g., transvestism, transsexualism, or some forms of homosexuality." It noted that many transgender women and gay men reported their "cross-gender behaviors began in early childhood" and the research showed it was difficult or impossible to shift in adults; the authors felt the best way to prevent "future sexual deviance", or at least make it unlikely as possible, was to correct gender noncomforming behavior at a young age. The method the paper detailed was a token based reinforcement system administered by the parents which rewarded gender conformity and punished deviancy. Blue chips were a sign of good behavior and could be swapped for chocolate bars, red chips were a sign of bad behavior and resulted in isolation and beatings.In contrast to this, a number of facts about Kraig have become public information, including: that he was a gay man; that according to his family, he never recovered from these treatments; and that in 2003, at the age of 38, he committed suicide. Even without confirmed knowledge of such outcomes, by the mid-1970s Rekerss publications on his treatment modality were already attracting harsh criticism from scholarly and popular media sources, and Bryant speculates that this is one possible explanation for why many clinicians do not publish on their treatment techniques, focusing instead on less controversial aspects of GD, such as diagnostic criteria.Therapeutic approaches for GD differ from those used on adults and have included behavior therapy, psychodynamic therapy, group therapy, and parent counseling. This includes aiming to reduce gender dysphoria, making children more comfortable with their bodies, lessening ostracism, and reducing the childs psychiatric comorbidity.Therapeutic intervention seeks to identify and resolve underlying factors (including familial factors), encourage the child to identify with their assigned sex, and encourage same-sex friendships. Parent counseling involves setting limits on the childs cross-gender behavior, encouraging gender-neutral or sex-typical activities, examining familial factors, and examining parental factors such as psychopathology. Researchers Zucker and Susan Bradley state that it has been found that boys with GD often have mothers who, to an extent, reinforced behavior more stereotypical of young girls. They also state that children with GD tend to come from families where cross-gender role behavior was not explicitly discouraged. However, they also acknowledge that one could view these findings as merely indicative of the fact that parents who were more accepting of their childs cross-gender role behavior are also more likely to bring their children to a clinical psychiatrist as opposed to parents who are less accepting of cross-gender role behavior in their children.In 2002, Zucker acknowledged limited data on gender dysphoria in children, stating that "apart from a series of intrasubject behaviour therapy case reports from the 1970s, one will find not a single randomized controlled treatment trial in the literature". He has stated that "the therapist must rely on the clinical wisdom that has accumulated and to utilize largely untested case formulation conceptual models to inform treatment approaches and decisions." In 2018, in a narrative systemic review titled "Conversion therapies and access to transition-related healthcare in transgender people", Zuckers work was provided as a case study in conversion therapy including open-ended play psychotherapy, parent counselling, and parent-guided interventions to prevent "transsexualism". The study was criticized by the reviewers for relying on flawed estimates of desistance as well as actively trying to reduce cross-gender identification.In 2015, the American Psychological Association and the Substance Abuse and Mental Health Services Administration collaborated on a report stating "conversion therapy—efforts to change an individuals sexual orientation, gender identity, or gender expression—is a practice that is not supported by credible evidence and has been disavowed by behavioral health experts and associations. Conversion therapy perpetuates outdated views of gender roles and identities as well as the negative stereotype that being a sexual or gender minority or identifying as LGBTQ is an abnormal aspect of human development. Most importantly, it may put young people at risk of serious harm." Already by 2017, the majority of major medical associations had defined attempts to change an individuals gender identity or gender expression as conversion therapy.In 2021, the World Professional Association for Transgender Health concluded that treatment aimed at trying to change a persons gender identity and expression to become more congruent with sex assigned at birth "is no longer considered ethical." Edgardo Menvielle, a child-adolescent psychiatrist at the Childrens National Medical Center in Washington advised that "Therapists who advocate changing gender variant behaviours should be avoided." Developmental and clinical psychologist Diane Ehrensaft told the Psychiatric Times, "The mental health profession has been consistently doing harm to children who are not gender normal, and they need to retrain."

Society and culture
Diagnostic dispute
Pickstone-Taylor has called Zucker and Bradleys therapeutic intervention "something disturbingly close to reparative therapy for homosexuals." Other academics, such as Maddux et al., have also compared it to such therapy. They argue that the goal is preventing a transgender identity because reparative therapy is believed to reduce the chances of adult GD, "which Zucker and Bradley characterize as undesirable."Author Phyllis Burke wrote, "The diagnosis of GID in children, as supported by Zucker and Bradley, is simply child abuse." Zucker dismisses Burkes book as "simplistic" and "not particularly illuminating;" and journalist Stephanie Wilkinson said Zucker characterized Burkes book as "the work of a journalist whose views shouldnt be put into the same camp as those of scientists like Richard Green or himself."Critics argue that the GIDC diagnosis was a backdoor maneuver to replace homosexuality in the DSM; Zucker and Robert Spitzer counter that the GIDC inclusion was based on "expert consensus," which is "the same mechanism that led to the introduction of many new psychiatric diagnoses, including those for which systematic field trials were not available when the DSM-III was published." Katherine Wilson of GID Reform Advocates stated:
In the case of gender non-conforming children and adolescents, the GID criteria are significantly broader in scope in the DSM-IV (APA, 1994, p. 537) than in earlier revisions, to the concern of many civil libertarians. A child may be diagnosed with Gender Identity Disorder without ever having stated any desire to be, or insistence of being, the other sex. Boys are inexplicably held to a much stricter standard of conformity than girls. Most psychologists who specialize in gender identity disorder in children note a higher level of male patients brought to them, rather than female patients. A possible explanation would be that cross-sex behavior is less acceptable and therefore more noticeable and more likely to be viewed as problematic by the childs parents (Bradley, Zucker, 1997). Preference for cross-dressing or simulating female attire meets the diagnostic criterion for boys but not for girls, who must insist on wearing only male clothing to merit diagnosis. References to "stereotypical" clothing, toys and activities of the other sex are imprecise in an American culture where much childrens clothing is unisex and appropriate sex role is the subject of political debate. Equally puzzling is a criterion which lists a "strong preference for playmates of the other sex" as symptomatic, and seems to equate mental health with sexual discrimination and segregation.
Some clinicians, such as Wilson et al., argue that GIDC "has served to pressurize boys to conform to traditional gender and heterosexual roles." Feder states that the diagnosis is based on the reactions of others to the child, not the behavior itself. Langer et al. state "Gender atypicality is a social construction that varies over time according to culture and social class and therefore should not be pathologized." Zucker refuted their claims in a response.  Psychiatrist Domenico Di Ceglie opined that for therapeutic intervention, "efficacy is unclear," and psychologist Bernadette Wren says, "There is little evidence, however, that any psychological treatments have much effect in changing gender identity although some treatment centres continue to promote this as an aim (e.g. Zucker, & Bradley, 1995)."Therapeutic intervention for GIDC came under renewed scrutiny in May 2008, when Kenneth Zucker was appointed to the DSM-5 committee on GIDC.  According to MSNBC, "The petition accuses Zucker of having engaged in junk science and promoting hurtful theories during his career." Zucker is accused by LGBT activists of promoting "gender-conforming therapies in children" and "treating children with GID with an eye toward preventing adult homosexuality or transsexuality." Zucker "rejects the junk-science charge, saying that there has to be an empirical basis to modify anything in the DSM </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Temporal lobe epilepsy and explain in detail? [/INST] Temporal lobe epilepsy (TLE) is a chronic disorder of the nervous system which is characterized by recurrent, unprovoked focal seizures that originate in the temporal lobe of the brain and last about one or two minutes. TLE is the most common form of epilepsy with focal seizures. A focal seizure in the temporal lobe may spread to other areas in the brain when it may become a focal to bilateral seizure.
TLE is diagnosed by taking a medical history, blood tests, and brain imaging. It can have a number of causes such as head injury, stroke, brain infections, structural lesions in the brain, or brain tumors, or it can be of unknown onset. The first line of treatment is through anticonvulsants. Surgery may be an option, especially when there is an observable abnormality in the brain. Another treatment option is electrical stimulation of the brain through an implanted device called the vagus nerve stimulator (VNS).

Types
Over forty types of epilepsy are recognized and these are divided into two main groups: focal seizures and generalized seizures. Focal seizures account for approximately sixty percent of all adult cases. Temporal lobe epilepsy (TLE) is the single most common form of focal seizure.The International League Against Epilepsy (ILAE) recognizes two main types of temporal lobe epilepsy: mesial temporal lobe epilepsy (MTLE), arising in the hippocampus, the parahippocampal gyrus and the amygdala which are located in the inner (medial) aspect of the temporal lobe, and lateral temporal lobe epilepsy (LTLE), the rarer type, arising in the neocortex at the outer (lateral) surface of the temporal lobe. The seizures of LTLE are characterized by auditory or visual features. Autosomal dominant lateral temporal lobe epilepsy (ADLTLE) is a rare hereditary condition, often associated with mutations in the LGI1 gene.

Signs and symptoms
When a seizure begins in the temporal lobe, its effects depend on the precise location of its point of origin, its locus. In 1981, the ILAE recognized three types of seizures occurring in temporal lobe epilepsy. The classification was based on EEG findings. However, as of 2017 the general classification of seizures has been revised. The newer classification uses three key features: where the seizures begin, the level of awareness during a seizure, and other features.

Focal seizures
Focal seizures in the temporal lobe involve small areas of the lobe such as the amygdala and hippocampus.The newer classification gives two types of focal onset seizures, as focal aware and  focal impaired awareness.

Focal aware seizures
Focal aware means that the level of consciousness is not altered during the seizure. In temporal lobe epilepsy, a focal seizure usually causes abnormal sensations only. Often, the patient cannot describe the sensations.These may be:

Sensations such as déjà vu (a feeling of familiarity), jamais vu (a feeling of unfamiliarity)
Amnesia of a single memory or set of memories
A sudden sense of unprovoked fear and anxiety
Nausea
Auditory, visual, olfactory, gustatory, or tactile hallucinations; olfactory hallucinations often seem indescribable to patients beyond "pleasant" or "unpleasant"
Visual distortions such as macropsia and micropsia
Dissociation or derealisation
Synesthesia (stimulation of one sense experienced in a second sense)
Dysphoric or euphoric feelings, fear, anger, and other emotionsFocal aware seizures are often called "auras" when they serve as a warning sign of a subsequent seizure. Regardless, an aura is actually a seizure itself, and such a focal seizure may or may not progress to a focal impaired awareness seizure. People who experience only focal aware seizures may not recognize what they are, nor seek medical care.

Focal impaired awareness seizures
Focal impaired awareness seizures are seizures which impair consciousness to some extent: they alter the persons ability to interact normally with their environment. They usually begin with a focal aware seizure, then spread to a larger portion of the temporal lobe, resulting in impaired consciousness. They may include autonomic and psychic features present in focal aware seizures.Signs may include:
Motionless staring
Automatic movements of the hands or mouth
Confusion and disorientation
Altered ability to respond to others, unusual speech
Transient aphasia (losing ability to speak, read, or comprehend spoken word)These seizures tend to have a warning or aura before they occur, and when they occur they generally tend to last only 1–2 minutes. It is not uncommon for an individual to be tired or confused for up to 15 minutes after a seizure has occurred, although postictal confusion can last for hours or even days. Though they may not seem harmful, due to the fact that the individual does not normally seize, they can be extremely harmful if the individual is left alone around dangerous objects. For example, if a person with complex partial seizures is driving alone, this can cause them to run into the ditch, or worse, cause an accident involving multiple people. With this type, some people do not even realize they are having a seizure and most of the time their memory from right before to after the seizure is wiped. First-aid is only required if there has been an injury or if this is the first time a person has had a seizure.

Focal to bilateral seizures or generalized seizures
Seizures which begin in the temporal lobe, and then spread to involve both sides of the brain are termed focal to bilateral. Where both sides of the brain or the whole brain are involved from the onset, these seizures are known as generalized seizures and may be tonic clonic. The arms, trunk, and legs stiffen (the tonic phase), in either a flexed or extended position, and then jerk (the clonic phase). These were previously known as grand mal seizures. The word grand mal comes from the French term, meaning major affliction.

Postictal period
There is some period of recovery in which neurological function is altered after each of these seizure types. This is the postictal state. The degree and length of postictal impairment directly correlates with the severity of the seizure type. Focal aware seizures often last less than sixty seconds; focal with impaired awareness seizures may last up to two minutes; and generalized tonic clonic seizures may last up to three minutes. The postictal state in seizures other than focal aware may last much longer than the seizure itself.
Because a major function of the temporal lobe is short-term memory, a focal with impaired awareness seizure, and a focal to bilateral seizure can cause amnesia for the period of the seizure, meaning that the seizure may not be remembered.

Complications
Depression
Individuals with temporal lobe epilepsy have a higher prevalence of depression than the general population. Although the psychosocial impacts of epilepsy may be causative, there are also links in the phenomenology and neurobiology of TLE and depression.

Memory
The temporal lobe and particularly the hippocampus play an important role in memory processing. Declarative memory (memories which can be consciously recalled) is formed in the area of the hippocampus called the dentate gyrus.Temporal lobe epilepsy is associated with memory disorders and loss of memory. Animal models and clinical studies show that memory loss correlates with temporal lobe neuronal loss in temporal lobe epilepsy. Verbal memory deficit correlates with pyramidal cell loss in TLE. This is more so on the left in verbal memory loss. Neuronal loss on the right is more prominent in non-verbal (visuospatial memory loss).

Childhood onset
After childhood onset, one third will "grow out" of TLE, finding a lasting remission up to an average of 20 years. The finding of a lesion such as hippocampal sclerosis (a scar in the hippocampus), tumour, or dysplasia, on magnetic resonance imaging (MRI) predicts the intractability of seizures.

Personality
The effect of temporal lobe epilepsy on personality is a historical observation dating to the 1800s. Personality and behavioural change in temporal lobe epilepsy is seen as a chronic condition when it persists for more than three months.Geschwind syndrome is a set of behavioural phenomena seen in some people with TLE. Documented by Norman Geschwind, signs include: hypergraphia (compulsion to write (or draw) excessively), hyperreligiosity (intense religious or philosophical experiences or interests), hyposexuality (reduced sexual interest or drive), circumstantiality (result of a non-linear thought pattern, talks at length about irrelevant and trivial details). The personality changes generally vary by hemisphere.The existence of a "temporal lobe epileptic personality" and of Geschwind syndrome have been disputed and research is inconclusive.

Causes
The causes of TLE include mesial temporal sclerosis, traumatic brain injury, brain infections, such as encephalitis and meningitis, hypoxic brain injury, stroke, cerebral tumours, and genetic syndromes. Temporal lobe epilepsy is not the result of psychiatric illness or fragility of the personality.

Febrile seizures
Although the theory is controversial, there is a link between febrile seizures (seizures coinciding with episodes of fever in young children) and subsequent temporal lobe epilepsy, at least epidemiologically.

Human herpes virus 6
In the mid-1980s, human herpesvirus 6 (HHV-6) was suggested as a possible causal link between febrile convulsions and mesial temporal lobe epilepsy. However, although the virus is found in temporal lobe tissue at surgery for TLE, it has not been recognised as a major factor in febrile seizures or TLE.

Reelin
Dispersion of the granule cell layer in the hippocampal dentate gyrus is occasionally seen in temporal lobe epilepsy and has been linked to the downregulation of reelin, a protein that normally keeps the layer compact by containing neuronal migration. It is unknown whether changes in reelin expression play a role in epilepsy.

Pathophysiology
Neuronal loss
In TLE, there is loss of neurons in region CA1 and CA3 of the hippocampus. There is also damage to mossy cells and inhibitory interneurons in the hilar region of the hippocampus (region IV) and to the granule cells of the dentate gyrus. In animal models, neuronal loss occurs during seizures but in humans, neuronal loss predates the first seizure and does not necessarily continue with seizure activity. The loss of the GABA-mediated inhibitory interneurons may increase the hyperexcitability of neurons of the hippocampus leading to recurrent seizures. According to the "dormant basket cell" hypothesis, mossy cells normally excite basket cells which in turn, inhibit granule cells. Loss of mossy cells lowers the threshold of action potentials of the granule cells.

GABA reversal
In certain patients with temporal lobe epilepsy it has been found that the subiculum could generate epileptic activity. It has been found that GABA reversal potential is depolarising in the subpopulation of the pyramidal cells due to the lack of KCC2 co-transporter. It has been shown that it is theoretically possible to generate seizures in the neural networks due to down-regulation of KCC2, consistent with the chloride measurements during the transition to seizure and KCC2 blockade experiments.

Granule cell dispersion in the dentate gyrus
Granule cell dispersion is a type of developmental migration and a pathological change found in the TLE brain which was first described in 1990. The granule cells of the dentate gyrus are tightly packed forming a uniform, laminated layer with no monosynaptic connections. This structure provides a filter for the excitability of neurons.In TLE, granule cells are lost, the structure is no longer closely packed and there are changes in the orientation of dendrites. These changes may or may not be epileptogenic. For instance, if the dendrites of granule cells reconnect, it may be in a way (through the laminar planes) that allows hyperexcitability. However, not all patients have granule cell dispersion.: 387–389

Aberrant mossy fiber sprouting
Mossy fibers are the axons of granule cells. They project into the hilus of the dentate gyrus and stratum lucidum in the CA3 region giving inputs to both excitatory and inhibitory neurons.In the TLE brain, where granule cells are damaged or lost, axons, the mossy fibres, sprout in order to reconnect to other granule cell dendrites. This is an example of synaptic reorganization. This was noted in human tissue in 1974 and in animal models in 1985. In TLE, the sprouting mossy fibres are larger than in the normal brain and their connections may be aberrant. Mossy fibre sprouting continues from one week to two months after injury.: 416–431 Aberrant mossy fibre sprouting may create excitatory feedback circuits that lead to temporal lobe seizures. This is evident in intracellular recordings. Stimulation of aberrant mossy fibre areas increases the excitatory postsynaptic potential response.However, aberrant mossy fiber sprouting may inhibit excitatory transmission by synapsing with basket cells which are inhibitory neurons and by releasing GABA and neuropeptide Y which are inhibitory neurotransmitters. Also, in animal models, granule cell hyper-excitability is recorded before aberrant mossy fibre sprouting has occurred.

Diagnosis
The diagnosis of temporal lobe epilepsy can include the following methods: Magnetic resonance imaging (MRI), CT scans, positron emission tomography (PET), EEG, and magnetoencephalography.

Imaging
CT scan is useful as the emergency situations when the suspected cause of epilepsy is due to conditions such as intracerebral haemorrhage, or brain abscesses, or when MRI imaging is not readily available or there is any contraindications to MRI such as the presence of cardiac pacemakers or cochlear implants in the subjects body. CT scan also detect some abnormal calcifications in the brain that is characteristic of diseases such as tuberous sclerosis and Sturge-Weber syndrome. However, CT scan is not sensitive or specific enough when compared in MRI in detecting the common causes of epilepsy such as small tumours, vascular malformations, abnormalities of cerebral cortex development, or abnormalities in the medial part of the temporal lobe.MRI is the imaging choice when assessing those with epilepsy. In newly diagnosed epilepsy, MRI can detect brain lesion in up to 12 to 14% of the cases. However, for those with chronic epilepsy, MRI can detect brain lesion in 80% of the cases. However, in cases where there is definite clinical and EEG diagnosis of idiopathic generalized epilepsy, or Rolandic epilepsy, MRI scan is not needed.

Differential diagnosis
Other medical conditions with similar symptoms include panic attacks, psychosis spectrum disorders, tardive dyskinesia, and occipital lobe epilepsy.

Treatments
Anticonvulsants
Many anticonvulsant oral medications are available for the management of temporal lobe seizures. Most anticonvulsants function by decreasing the excitation of neurons, for example, by blocking fast or slow sodium channels or by modulating calcium channels; or by enhancing the inhibition of neurons, for example by potentiating the effects of inhibitory neurotransmitters like GABA.In TLE, the most commonly used older medications are phenytoin, carbamazepine, primidone, valproate, and phenobarbital. Newer drugs, such as gabapentin, topiramate, levetiracetam, lamotrigine, pregabalin, tiagabine, lacosamide, and zonisamide promise similar effectiveness, with possibly fewer side-effects. Felbamate and vigabatrin are newer, but can have serious adverse effects so they are not considered as first-line treatments.Up to one third of patients with medial temporal lobe epilepsy will not have adequate seizure control with medication alone. For patients with medial TLE whose seizures remain uncontrolled after trials of several types of anticonvulsants (that is, the epilepsy is intractable), surgical excision of the affected temporal lobe may be considered.

Surgical interventions
Epilepsy surgery has been performed since the 1860s and doctors have observed that it is highly effective in producing freedom from seizures. However, it was not until 2001 that a scientifically sound study was carried out to examine the effectiveness of temporal lobectomy.Temporal lobe surgery can be complicated by decreased cognitive function. However, after temporal lobectomy, memory function is supported by the opposite temporal lobe; and recruitment of the frontal lobe. Cognitive rehabilitation may also help.

Other treatments
Where surgery is not recommended, further management options include new (including experimental) anticonvulsants, and vagus nerve stimulation. The ketogenic diet is also recommended for children, and some adults. Other options include brain cortex responsive neural stimulators, deep brain stimulation, stereotactic radiosurgery, such as the gamma knife, and laser ablation.

Effects on society
The first to record and catalog the abnormal symptoms and signs of TLE was Norman Geschwind. He found a constellation of symptoms that included hypergraphia, hyperreligiosity, collapse, and pedantism, now called Geschwind syndrome.
Vilayanur S. Ramachandran explored the neural basis of the hyperreligiosity seen in TLE using the galvanic skin response (GSR), which correlates with emotional arousal, to determine whether the hyperreligiosity seen in TLE was due to an overall heightened emotional state or was specific to religious stimuli </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sinusitis and explain in detail? [/INST] Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, headaches, a poor sense of smell, sore throat, and  cough. It is defined as acute sinusitis if it lasts less than 4 weeks, and as chronic sinusitis if it lasts for more than 12 weeks.Sinusitis can be caused by infection, allergies, air pollution, or structural problems in the nose. Most cases are caused by a viral infection. Recurrent episodes are more likely in persons with asthma, cystic fibrosis, and poor immune function. Diagnostic imaging is not usually needed unless complications are suspected. In chronic cases, confirmatory testing is recommended by either direct visualization or computed tomography.Some cases may be prevented by hand washing, avoiding smoking, and immunization. Pain killers such as naproxen, nasal steroids, and nasal irrigation may be used to help with symptoms. Recommended initial treatment for acute sinusitis is watchful waiting. If symptoms do not improve in 7–10 days or get worse, then an antibiotic may be used or changed. In those in whom antibiotics are used, either amoxicillin or amoxicillin/clavulanate is recommended first line. Surgery may occasionally be used in people with chronic disease.Sinusitis is a common condition. It affects between about 10 and 30 percent of people each year in the United States and Europe. Chronic sinusitis affects about 12.5% of people. Treatment of sinusitis in the United States results in more than US$11 billion in costs. The unnecessary and ineffective treatment of viral sinusitis with antibiotics is common.

Signs and symptoms
Headache, facial pain, or pressure of a dull, constant, or aching sort over the affected sinuses is common with both acute and chronic stages of sinusitis.  This pain is usually localized to the involved sinus and may worsen when the affected person bends over or lies down.  Pain often starts on one side of the head and progresses to both sides.
Acute sinusitis may be accompanied by a thick nasal discharge that is usually green in color, and may contain pus or blood. Often, a localized headache or toothache is present, and these symptoms distinguish a sinus-related headache from other types of headaches, such as tension and migraine headaches. Another way to distinguish between toothache and sinusitis is that the pain in sinusitis is usually worsened by tilting the head forward and with the Valsalva maneuver.Other symptoms associated with acute rhinosinusitis include cough, fatigue, hyposmia, anosmia and ear fullness or pressure.Sinus infections can also cause middle-ear problems due to the congestion of the nasal passages. This can be demonstrated by dizziness, "a pressurized or heavy head", or vibrating sensations in the head. Postnasal drip is also a symptom of chronic rhinosinusitis.Halitosis (bad breath) is often stated to be a symptom of chronic rhinosinusitis; however, gold-standard breath analysis techniques have not been applied. Theoretically,  several possible mechanisms of both objective and subjective halitosis may be involved.A 2005 review suggested that most "sinus headaches" are migraines. The confusion occurs in part because migraine involves activation of the trigeminal nerves, which innervate both the sinus region and the meninges surrounding the brain. As a result, accurately determining the site from which the pain originates is difficult. People with migraines do not typically have the thick nasal discharge that is a common symptom of a sinus infection.Symptoms of chronic sinusitis may include nasal congestion, facial pain, headache, night-time coughing, an increase in previously minor or controlled asthma symptoms, general malaise, thick green or yellow discharge, feeling of facial fullness or tightness that may worsen when bending over, dizziness, aching teeth, and bad breath. Often, chronic sinusitis can lead to anosmia, the loss of the sense of smell.

By location
The four paired paranasal sinuses are the frontal, ethmoidal, maxillary, and sphenoidal sinuses. The ethmoidal sinuses are further subdivided into anterior and posterior ethmoid sinuses, the division of which is defined as the basal lamella of the middle nasal concha. In addition to the severity of disease, discussed below, sinusitis can be classified by the sinus cavity it affects:

Maxillary – can cause pain or pressure in the maxillary (cheek) area (e.g., toothache, or headache) (J01.0/J32.0)
Frontal – can cause pain or pressure in the frontal sinus cavity (located above the eyes), headache, particularly in the forehead (J01.1/J32.1)
Ethmoidal – can cause pain or pressure pain between/behind the eyes, the sides of the upper part of the nose (the medial canthi), and headaches (J01.2/J32.2)
Sphenoidal – can cause pain or pressure behind the eyes, but is often felt in the top of the head, over the mastoid processes, or the back of the head.

Complications
Complications are thought to be rare (1 case per 10,000).The proximity of the brain to the sinuses makes the most dangerous complication of sinusitis, particularly involving the frontal and sphenoid sinuses, infection of the brain by the invasion of anaerobic bacteria through the bones or blood vessels. Abscesses, meningitis, and other life-threatening conditions may result. In extreme cases, the patient may experience mild personality changes, headache, altered consciousness, visual problems, seizures, coma, and possibly death.Sinus infection can spread through anastomosing veins or by direct extension to close structures. Orbital complications were categorized by Chandler et al. into five stages according to their severity (see table). Contiguous spread to the orbit may result in periorbital cellulitis, subperiosteal abscess, orbital cellulitis, and abscess. Orbital cellulitis can complicate acute ethmoiditis if anterior and posterior ethmoidal veins thrombophlebitis enables the spread of the infection to the lateral or orbital side of the ethmoid labyrinth. Sinusitis may extend to the central nervous system, where it may cause cavernous sinus thrombosis, retrograde meningitis, and epidural, subdural, and brain abscesses. Orbital symptoms frequently precede intracranial spread of the infection . Other complications include sinobronchitis, maxillary osteomyelitis, and frontal bone osteomyelitis. Osteomyelitis of the frontal bone often originates from a spreading thrombophlebitis. A periostitis of the frontal sinus causes an osteitis and a periostitis of the outer membrane, which produces a tender, puffy swelling of the forehead.The diagnosis of these complications can be assisted by noting local tenderness and dull pain, and can be confirmed by CT and nuclear isotope scanning. The most common microbial causes are anaerobic bacteria and S. aureus. Treatment includes performing surgical drainage and administration of antimicrobial therapy. Surgical debridement is rarely required after an extended course of parenteral antimicrobial therapy. Chronic sinus infections may lead to mouth breathing, which can result in mouth dryness and an increased risk of gingivitis. Decongestants may also cause mouth dryness.If an odontogenic infection involves the maxillary sinus, odontogenic sinusitis (ODS) may ensue. Odontogenic sinusitis can often spread to other sinuses such as the ethmoid, frontal and (less frequently) sphenoid sinus, and even to the contralateral nasal cavity. In rare instances, these infections may involve the orbit, causing orbital cellulitis, which may in turn result in blindness, or determine central nervous system complications such as meningitis, subdural empyema, brain abscess and life-threatening cavernous sinus thrombosis.Infection of the eye socket is a rare complication of ethmoid sinusitis, which may result in the loss of sight and is accompanied by fever and severe illness.  Another possible complication is the infection of the bones (osteomyelitis) of the forehead and other facial bones – Potts puffy tumor.

Causes
Maxillary sinusitis may also develop from problems with the teeth, and these cases were calculated to be about 40% in one study and 50% in another. The cause of this situation is usually a periapical or periodontal infection of a maxillary posterior tooth, where the inflammatory exudate has eroded through the bone superiorly to drain into the maxillary sinus.An estimated 0.5 to 2.0% of viral rhinosinusitis (VRS) will develop into bacterial infections in adults and 5 to 10% in children.

Acute
Acute sinusitis is usually precipitated by an earlier upper respiratory tract infection, generally of viral origin, mostly caused by rhinoviruses (with RVA and RVC giving more severe infection than RVB), coronaviruses, and influenza viruses, others caused by adenoviruses, human parainfluenza viruses, human respiratory syncytial virus, enteroviruses other than rhinoviruses, and metapneumovirus. If the infection is of bacterial origin, the most common three causative agents are Streptococcus pneumoniae (38%), Haemophilus influenzae (36%), and Moraxella catarrhalis (16%). Until recently, H. influenzae was the most common bacterial agent to cause sinus infections. However, introduction of the H. influenzae type B (Hib) vaccine has dramatically decreased these infections and now non-typable H. influenzae (NTHI) is predominantly seen in clinics. Other sinusitis-causing bacterial pathogens include S. aureus and other streptococci species, anaerobic bacteria and, less commonly, Gram-negative bacteria. Viral sinusitis typically lasts for 7 to 10 days.Acute episodes of sinusitis can also result from fungal invasion. These infections are typically seen in people with diabetes or other immune deficiencies (such as AIDS or transplant on immunosuppressive antirejection medications) and can be life-threatening. In type I diabetics, ketoacidosis can be associated with sinusitis due to mucormycosis.

Chronic
By definition, chronic sinusitis lasts longer than 12 weeks and can be caused by many different diseases that share chronic inflammation of the sinuses as a common symptom. It is subdivided into cases with and without polyps. When polyps are present, the condition is called chronic hyperplastic sinusitis; however, the causes are poorly understood. It may develop with anatomic derangements, including deviation of the nasal septum and the presence of concha bullosa (pneumatization of the middle concha) that inhibit the outflow of mucus, or with allergic rhinitis, asthma, cystic fibrosis, and dental infections.Chronic rhinosinusitis represents a multifactorial inflammatory disorder, rather than simply a persistent bacterial infection. The medical management of chronic rhinosinusitis is now focused upon controlling the inflammation that predisposes people to obstruction, reducing the incidence of infections. Surgery may be needed if medications are not working.Attempts have been made to provide a more consistent nomenclature for subtypes of chronic sinusitis. The presence of eosinophils in the mucous lining of the nose and paranasal sinuses has been demonstrated for many people, and this has been termed eosinophilic mucin rhinosinusitis (EMRS). Cases of EMRS may be related to an allergic response, but allergy is not often documented, resulting in further subcategorization into allergic and nonallergic EMRS.A more recent, and still debated, development in chronic sinusitis is the role that fungi play in this disease. Whether fungi are a definite factor in the development of chronic sinusitis remains unclear, and if they are, what is the difference between those who develop the disease and those who remain free of symptoms. Trials of antifungal treatments have had mixed results.Recent theories of sinusitis indicate that it often occurs as part of a spectrum of diseases that affect the respiratory tract (i.e., the "one airway" theory) and is often linked to asthma.Both smoking and secondhand smoke are associated with chronic rhinosinusitis.Other diseases such as cystic fibrosis and granulomatosis with polyangiitis can also cause chronic sinusitis.

Pathophysiology
Biofilm bacterial infections may account for many cases of antibiotic-refractory chronic sinusitis. Biofilms are complex aggregates of extracellular matrix and interdependent microorganisms from multiple species, many of which may be difficult or impossible to isolate using standard clinical laboratory techniques. Bacteria found in biofilms have their antibiotic resistance increased up to 1000 times when compared to free-living bacteria of the same species.  A recent study found that biofilms were present on the mucosa of 75% of people undergoing surgery for chronic sinusitis.

Diagnosis
Classification
Sinusitis (or rhinosinusitis) is defined as an inflammation of the mucous membrane that lines the paranasal sinuses and is classified chronologically into several categories:
Acute sinusitis – A new infection that may last up to four weeks and can be subdivided symptomatically into severe and nonsevere. Some use definitions up to 12 weeks.
Recurrent acute sinusitis – Four or more full episodes of acute sinusitis that occur within one year
Subacute sinusitis – An infection that lasts between four and 12 weeks, and represents a transition between acute and chronic infection.
Chronic sinusitis – When the signs and symptoms last for more than 12 weeks.
Acute exacerbation of chronic sinusitis – When the signs and symptoms of chronic sinusitis exacerbate, but return to baseline after treatment.Roughly 90% of adults have had sinusitis at some point in their lives.

Acute
Health care providers distinguish bacterial and viral sinusitis by watchful waiting. If a person has had sinusitis for fewer than 10 days without the symptoms becoming worse, then the infection is presumed to be viral. When symptoms last more than 10 days or get worse in that time, then the infection is considered bacterial sinusitis. Pain in the teeth and bad breath are also more indicative of bacterial disease.Imaging by either X-ray, CT or MRI is generally not recommended unless complications develop. Pain caused by sinusitis is sometimes confused for pain caused by pulpitis (toothache) of the maxillary teeth, and vice versa. Classically, the increased pain when tilting the head forwards separates sinusitis from pulpitis.For cases of maxillary sinusitis, limited field CBCT imaging, as compared to periapical radiographs, improves the ability to detect the teeth as the sources for sinusitis. A coronal CT picture may also be useful.

Chronic
For sinusitis lasting more than 12 weeks, a CT scan is recommended. On a CT scan, acute sinus secretions have a radiodensity of 10 to 25 Hounsfield units (HU), but in a more chronic state they become more viscous, with a radiodensity of 30 to 60 HU.Nasal endoscopy and clinical symptoms are also used to make a positive diagnosis. A tissue sample for histology and cultures can also be collected and tested. Nasal endoscopy involves inserting a flexible fiber-optic tube with a light and camera at its tip into the nose to examine the nasal passages and sinuses.
Sinus infections, if they result in tooth pain, usually present with pain involving more than one of the upper teeth, whereas a toothache usually involves a single tooth. Dental examination and appropriate radiography aid in ruling out pain arises from a tooth.

Treatment
Recommended treatments for most cases of sinusitis include rest and drinking enough water to thin the mucus. Antibiotics are not recommended for most cases.Breathing low-temperature steam such as from a hot shower or gargling can relieve symptoms. There is tentative evidence for nasal irrigation in acute sinusitis, for example during upper respiratory infections. Decongestant nasal sprays containing oxymetazoline may provide relief, but these medications should not be used for more than the recommended period. Longer use may cause rebound sinusitis. It is unclear if nasal irrigation, antihistamines, or decongestants work in children with acute sinusitis. There is no clear evidence that plant extracts such as Cyclamen europaeum are effective as an intranasal wash to treat acute sinusitis. Evidence is inconclusive on whether anti-fungal treatments improve symptoms or quality of life.

Antibiotics
Most sinusitis cases are caused by viruses and resolve without antibiotics. However, if symptoms do not resolve within 10 days, amoxicillin/clavulanate is a reasonable antibiotic association for first treatment. A 2018 Cochrane review, however, found no evidence that people with symptoms lasting seven days or more before consulting their physician are more likely to have bacterial sinusitis as one study found that about 80% of patients have symptoms lasting more than 7 days and another about 70%. Antibiotics are specifically not recommended in those with mild / moderate disease during the first week of infection due to risk of adverse effects, antibiotic resistance, and cost.Fluoroquinolones, and a newer macrolide antibiotic such as clarithromycin or a tetracycline like doxycycline, are used in those who have severe allergies to penicillins. Because of increasing resistance to amoxicillin the 2012 guideline of the Infectious Diseases Society of America recommends amoxicillin-clavulanate as the initial treatment of choice for bacterial sinusitis. The guidelines also recommend against other commonly used antibiotics, including azithromycin, clarithromycin, and trimethoprim/sulfamethoxazole, because of growing antibiotic resistance. The FDA recommends against the use of fluoroquinolones when other options are available due to higher risks of serious side effects.A short-course (3–7 days) of antibiotics seems to be just as effective as the typical longer-course (10–14 days) of antibiotics for those with clinically diagnosed acute bacterial sinusitis without any other severe disease or complicating factors. The IDSA guideline suggest five to seven days of antibiotics is long enough to treat a bacterial infection without encouraging resistance. The guidelines still recommend children receive antibiotic treatment for ten days to two weeks.

Corticosteroids
For unconfirmed acute sinusitis, nasal sprays using corticosteroids have not been found to be better than a placebo either alone or in combination with antibiotics. For cases confirmed by radiology or nasal endoscopy, treatment with intranasal corticosteroids alone or in combination with antibiotics is supported. The benefit, however, is small.For confirmed chronic rhinosinusitis, there is limited evidence that intranasal steroids improve symptoms and insufficient evidence that one type of steroid is more effective.There is only limited evidence to support short treatment with corticosteroids by mouth for chronic rhinosinusitis with nasal polyps. There is limited evidence to support corticosteroids by mouth in combination with antibiotics for acute sinusitis; it has only short-term effect improving the symptoms.

Surgery
For sinusitis of dental origin, treatment focuses on removing the infection and preventing reinfection, by removal of the microorganisms, their byproducts, and pulpal debris from the infected root canal. Systemic antibiotics are ineffective as a definitive solution, but may afford temporary relief of symptoms by improving sinus clearing, and may be appropriate for rapidly spreading infections, but debridement and disinfection of the root canal system at the same time is necessary. Treatment options include non-surgical root canal treatment, periradicular surgery, tooth replantation, or extraction of the infected tooth.For chronic or recurring sinusitis, referral to an otolaryngologist may be indicated, and treatment options may include nasal surgery. Surgery should only be considered for those people who do not benefit with medication </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Papular purpuric gloves and socks syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Monochromacy and explain in detail? [/INST] Monochromacy (from Greek mono, meaning "one" and chromo, meaning "color") is the ability of organisms or machines to perceive only light intensity, without respect to spectral composition (color).  Organisms with monochromacy are called monochromats.
Many mammals, such as cetaceans, the owl monkey and the Australian sea lion (pictured at right) are monochromats.
In humans, absence of color vision is one among several other symptoms of severe inherited or acquired diseases, including achromatopsia or blue cone monochromacy, together affecting about 1 in 30,000 people. The affected can distinguish light, dark, and shades of gray but not color.

Humans
Human vision relies on a duplex retina, comprising two types of photoreceptor cells. Rods are primarily responsible for dim-light scotopic vision and cones are primarily responsible for day-light photopic vision. For all known vertebrates, scotopic vision is monochromatic, since there is typically only one class of rod cell. However, the presence of multiple cone classes contributing to photopic vision enables color vision during daytime conditions.
Most humans have three classes of cones, each with a different class of opsin. These three opsins have different spectral sensitivities, which is a prerequisite for trichromacy. An alteration of any of these three cone opsins can lead to colorblindness.

Anomalous Trichromacy, when all three cones are functional, but one or more is altered in its spectral sensitivity.
Dichromacy, when one of the cones is non-functional and one of the red-green or blue-yellow opponent channels are fully disabled.
Cone Monochromacy, when two of the cones are non-functional and both chromatic opponent channels are disabled. Vision is reduced to blacks, whites, and greys.
Rod Monochromacy (Achromatopsia), when all three of the cones are non-functional and therefore photopic vision (and therefore color vision) is disabled.Monochromacy of photopic vision is a symptom of both Cone Monochromacy and Rod Monochromacy, so these two conditions are typically referred to collectively as monochromacy.

Rod Monochromacy
Rod monochromacy (RM), also called congenital complete achromatopsia or total color blindness, is a rare and extremely severe form of an autosomal recessively inherited retinal disorder resulting in severe visual handicap. People with RM have a reduced visual acuity, (usually about 0.1 or 20/200), have total color blindness, photo-aversion and nystagmus. The nystagmus and photo-aversion usually are present during the first months of life, and the prevalence of the disease is estimated to be 1 in 30,000 worldwide. Since patients with RM have no cone function, they lack photopic vision, relying entirely on their rods and scotopic vision, which is necessarily monochromatic. They therefore cannot see any color but only shades of grey.

Cone Monochromacy
Cone monochromacy (CM) is a condition defined by the exhibition of only one class of cones. A cone monochromat can have good pattern vision at normal daylight levels, but will not be able to distinguish hues.
As humans typically exhibit three classes of cones, cone monochromats can hypothetically derive their photopic vision from any one of them, leading to three categories of cone monochromats:
Blue cone monochromacy (BCM), also known as S-cone monochromacy, is an X-linked cone disease. It is a rare congenital stationary cone dysfunction syndrome, affecting less than 1 in 100,000 individuals, and is characterized by the absence of L- and M-cone function. BCM results from mutations in a single red or red–green hybrid opsin gene, mutations in both the red and the green opsin genes or deletions within the adjacent LCR (locus control region) on the X chromosome.
Green cone monochromacy (GCM), also known as M-cone monochromacy, is a condition where the blue and red cones are absent in the fovea. The prevalence of this type of monochromacy is estimated to be less than 1 in 1 million.
Red cone monochromacy (RCM), also known as L-cone monochromacy, is a condition where the blue and green cones are absent in the fovea. Like GCM, the prevalence of RCM is also estimated at less than 1 in 1 million.Cone Monochromats with normal rod function can sometimes exhibit mild color vision due to conditional dichromacy. In mesopic conditions, both rods and cones are active and opponent interactions between the cones and rods can afford slight color vision.According to Jay Neitz, a color vision researcher at the University of Washington, each of the three standard color-detecting cones in the retina of trichromats can detect approximately 100 gradations of color. The brain can process the combinations of these three values so that the average human can distinguish about one million colors. Therefore, a monochromat would be able to distinguish about 100 colors.

Mammals
Until the 1960s popular belief held that most mammals outside of primates were monochromats. In the last half-century, however, a focus on behavioral and genetic testing of mammals has accumulated extensive evidence of at least dichromatic color vision in a number of mammalian orders. Mammals are now usually assumed to be dichromats (possessing S- and L-cones), with monochromats viewed as the exceptions.
Two mammalian orders containing marine mammals exhibit monochromatic vision:

Pinnipeds (including seals, sea lions and walruses)
Cetaceans (including dolphins and whales)Unlike the trichromacy exhibited in most primates, Owl monkeys (genus Aotus) are also monochromats. Several members of the family Procyonidae (raccoon, crab-eating raccoon and kinkajou) and a few rodents have been demonstrated as cone monochromats, having lost functionality of the S-cone (retaining the L-cone).The light available in an animals habitat is a significant determiner of a mammals color vision. Marine, Nocturnal or Burrowing mammals, which experience less light, have less evolutionary pressure to preserve dichromacy, so often evolve monochromacy.A recent study using through PCR analysis of genes OPN1SW, OPN1LW, and PDE6C determined that all mammals in the cohort Xenarthra (representing sloths, anteaters and armadillos) developed rod monochromacy through a stem ancestor.

See also
Achromatopsia
Blue cone monochromacy
Cone dystrophy
Dichromacy
Trichromacy
Tetrachromacy

References
External links
Rossi, Ethan (February 2013). "Visual Function and Cortical Organization in Carriers of Blue Cone Monochromacy". PLOS ONE. 8 (2): e57956 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Epidermolysis bullosa dystrophica and explain in detail? [/INST] Epidermolysis bullosa dystrophica or dystrophic EB (DEB) is an inherited disease affecting the skin and other organs."Butterfly child" is the colloquial name for a child born with the disease, as their skin is seen to be as delicate and fragile as the wings of a butterfly.

Signs and symptoms
The deficiency in anchoring fibrils impairs the adherence between the epidermis and the underlying dermis. The skin of DEB patients is thus highly susceptible to severe blistering. Collagen VII is also associated with the epithelium of the esophageal lining, and DEB patients may have chronic scarring, webbing, and obstruction of the esophagus. Affected individuals are often severely malnourished due to trauma to the oral and esophageal mucosa and require feeding tubes for nutrition. They also have iron-deficiency anemia of uncertain origin, which leads to chronic fatigue.Open wounds on the skin heal slowly or not at all, often scarring extensively, and are particularly susceptible to infection. Many individuals bathe in a bleach and water mixture to fight off these infections. The chronic inflammation leads to errors in the DNA of the affected skin cells, which in turn causes squamous cell carcinoma (SCC). The majority of these patients die before the age of 30, either of SCC or complications related to DEB.The chronic inflammatory state seen in recessive dystrophic epidermolysis bullosa (RDEB) may cause small fiber peripheral neuropathy (SFN); RDEB patients have reported the sensation of pain in line with neuropathic pain qualities.

Causes
DEB is caused by genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII collagen (collagen VII). DEB-causing mutations can be either dominant or recessive. Most families with family members with this condition have distinct mutations.Collagen VII is a very large molecule (300 kDa) that dimerizes to form a semicircular looping structure: the anchoring fibril. Anchoring fibrils are thought to form a structural link between the epidermal basement membrane and the fibrillar collagens in the upper dermis.

Pathophysiology
In the absence of mutations of the COL7A1 gene, an autoimmune response against type VII collagen can result in an acquired form of epidermolysis bullosa called epidermolysis bullosa acquisita.There exist other types of inherited epidermolysis bullosa, junctional epidermolysis bullosa and epidermolysis bullosa simplex, which are not related to type VII collagen deficiency. These arise from mutations in the genes encoding other proteins of the epidermis or the basement membrane at the junction between the epidermis and the dermis.

Diagnosis
Classification
See also
Epidermolysis bullosa

References
Sources
Freedberg, Irwin M.; Eisen, Arthur Z.; Wolff, Klauss; Austen, K. Frank; Goldsmith, Lowell A.; Katz, Stephen I., eds. (2003). Fitzpatricks Dermatology in General Medicine (6th ed.) </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Capsulitis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Uterine hyperstimulation and explain in detail? [/INST] Uterine hyperstimulation or hypertonic uterine dysfunction is a potential complication of labor induction.  This is displayed as Uterine tachysystole- the contraction frequency numbering more than five in a 10-minute time frame or as contractions exceeding more than two minutes in duration.  Uterine hyperstimulation may result in fetal heart rate abnormalities, uterine rupture, or placental abruption.  It is usually treated by administering terbutaline.

Causes
Mistoprostol is a drug treatment for peptic ulcers that can also cause abortion or induce labor. The use of this drug (inserted vaginally) to induce labor can cause uterine hyperstimulation.

Treatment
Treatments of uterine hyperstimulation are primarily experimental. Those that have shown to alleviate the conditions are:

Prostoglandin E2 is administered before labor to minimize risk of uterine hyperstimulation and to minimize the effects on Fetal Heart Rate.Administration of tocolytic treatment with β2-adrenergic drugs has shown to stabilize uterine contractions while also effectively lowering Fetal Heart Rate.
The usage of a balloon catheter to induce labor rather than Prostoglandin E2 lowers the risk of uterine hyperstimulation and its effect on fetal heart rate.

References

National Collaborating Centre for Womens and Childrens Health (UK). Induction of Labour. London: RCOG Press; 2008 Jul </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Dermatomycosis and explain in detail? [/INST]  </s>