<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pruritic folliculitis of pregnancy and can you explain it in depth? [/INST] Pruritic folliculitis of pregnancy is a skin condition that occurs in one in 3000 people, about 0.2% of cases, who are in their second to third trimester of pregnancy where the hair follicle becomes inflamed or infected, resulting in a pus filled bump. Some dermatologic conditions aside from pruritic folliculitis during pregnancy include "pruritic urticarial papules and plaques of pregnancy, atopic eruption of pregnancy, pemphigoid gestationis, intrahepatic cholestasis of pregnancy, and pustular psoriasis of pregnancy". This pruritic folliculitis of pregnancy differs from typical pruritic folliculitis; in pregnancy, it is characterized by sterile hair follicles becoming inflamed mainly involving the trunk, contrasting how typical pruritic folliculitis is mainly localized on "the upper back, shoulders, and chest." This condition was first observed after some pregnant individuals showed signs of folliculitis that were different than seen before.  The inflammation was thought to be caused by hormonal imbalance, infection from bacteria, fungi, viruses or even an ingrown hair. However, there is no known definitive cause as of yet. These bumps usually begin on the belly and then spread to upper regions of the body as well as the thighs. This condition does not harm the fetus or the mother and usually resolves after delivery of the baby. The rate of incidence could possibly be higher but due to the unknown etiology of the condition, misdiagnosis, and varying levels of severity, it is difficult to differentiate. Pruritic folliculitis of pregnancy is currently classified as atopic eruption of pregnancy (AEP) in a retrospective study done in 2006 that compared this condition to eczema and prurigo of pregnancy, which occurred in 49.7% and 0.8% of cases respectively, with eczema clearly being more frequent. Unlike typical pruritic folliculitis which does not resolve on its own, pruritic folliculitis of pregnancy clears spontaneously on delivery or in postpartum period. Fortunately, pruritic folliculitis of pregnancy has no mortality effects or significant adverse effects on the mother or on the fetus.Currently, there are no treatment guidelines for this condition due to the nature of its unknown etiology but symptom relief is strongly emphasized using non-pharmacological interventions such as warm baths or wearing loose clothing. If itchiness and discomfort persists, benzoyl peroxide, low to mid potency topical steroids, or antihistamines can be tried. Novel treatments have also shown potential in treating case studies of pruritic folliculitis of pregnancy, such as using ultraviolet phototherapy. However, further investigation is still required to study its efficacy and safety in second to third trimester pregnant patients.

History
This condition was first observed in six people in 1981 with many different speculations but no real evidence as to a specific cause. These people had papules starting at various times throughout the second to third trimester with varying severity. Biopsies were taken from these people over a 15 month period in order to examine the composition of these papules. After using H&E, hematoxylin and eosin, to stain the samples, the researchers only found some inflammatory cells like neutrophils, monocytes, lymphocytes, and eosinophils. In four of the samples, immunofluorescence microscopy, where fluorescent antibodies bind to a protein of interest and the expression levels are observed through microscopy, was used but there were no signs of immunoglobulins such as IgG, IgM, IgA or C3 found. Since the first description of this condition, there were very few case reports after, indicating the infrequency of pruritic folliculitis. This was also shown by a prospective study that was conducted in 1994 by Roger et al. that concluded with one individual out of 3,192 pregnant mothers (0.03%) had symptoms which were consistent with the diagnosis of pruritic folliculitis.

Pathophysiology
Folliculitis, by itself, is a common inflammation process of hair follicles in response to infection or damage to the hair follicles. This inflammatory response can be caused by bacteria, fungi, viruses, or simply ingrown hair. However, pruritic folliculitis of pregnancy is different in that it only occurs in pregnant individuals and during the second or third trimester of pregnancy. There is no clear mechanism in how pruritic folliculitis of pregnancy develops. Because this is a rare condition, there is still currently not enough research to study the cause of it. Some research suggest that this condition may be due to hormone level imbalance during pregnancy . Other research indicate that this condition could be due to immunological changes, such as the reduction of T helper 1 immune cells and the increase in T helper 2 immune cells that occur specifically when pregnant. However, there is not enough evidence to clearly support these claims. Although the pathophysiology of pruritic folliculitis of pregnancy is currently unknown, it has not been significantly linked to harm to either mother or baby. Moreover, this condition resolves after pregnancy and does not affect the development of the baby or recovery of the mother after delivery.

Suspected risk factors
There are currently no studies into the etiology behind pruritic folliculitis specifically in pregnancy; however, suspected risk factors include:

Dry skin
Genetics affecting hormone production
Poor personal hygiene
Family history of pruritus in pregnancy
Family history of eczema, hay fever, or asthma
Pruritus while taking contraceptive pill prior to pregnancy

Signs and Symptoms
The signs and symptoms of pruritic folliculitis of pregnancy include: redness of the skin, small red bumps that surrounds a hair follicle, and red bumps that are filled with pus "that usually appear first on the abdomen and may spread to the chest, upper portion of the back, shoulders, arms, and thighs" and it occurs during the second or third trimester of pregnancy.  These symptoms are typically "mildly pruritic or asymptomatic" lasting between one week to several months. However, symptoms usually self-relieves spontaneously within one month after birth.

Diagnosis
The diagnosis of pruritic folliculitis of pregnancy is established based on clinical features such as redness of the skin consisting of small red bumps that surrounds a hair follicle and histopathologic features such as immune cells within the pus along with microscopic testing that shows there is no bacteria, microorganism, or other conditions that could cause itchy skin. Diagnosis for pruritic folliculitis of pregnancy requires patients to go through a biopsy, which consists of taking samples from the tissue to evaluate whether their lesions match the physical factors of pruritic folliculitis. Other pregnancy associated skin diseases must be ruled out along side obstetric cholestasis, which is a disorder that affects the liver during pregnancy.There is a great deal of overlap between the following conditions in pregnancy: eczema, prurigo, and pruritic folliculitis. Because of this, they are grouped in a class called atopic eruption of pregnancy.  Compared to other pregnancy associated skin conditions, conditions in the class of atopic eruption of pregnancy occurs much earlier.

Management/Treatment
There is currently no official treatment guidelines for pruritic folliculitis of pregnancy as its etiology and clinical presentations still require further investigation; however, the goal of treatment is to relieve symptoms without causing harm to the mother or fetus. Non-pharmacological intervention is recommended first before using pharmacological agents to treat symptoms.
Since pruritic folliculitis of pregnancy appears in later stages of pregnancy and self-resolves post-partum, non-pharmacological interventions are recommended first to relieve itching symptoms. These interventions focuses on incorporating lifestyle changes which include: switching to loose-fitting clothes, using emollients, taking warm baths, avoiding harsh soaps, and maintaining good personal hygiene.If itching symptoms still persist, low to mid potency topical corticosteroids and first-generation antihistamines can be considered and may improve appearance of skin lesions. However, they may also not provide complete relief. Commonly used agents to treat pruritic folliculitis of pregnancy include: 10% topical benzoyl peroxide, 1% topical hydrocortisone, first generation H1 receptor blockers such as diphenhydramine or chlorpheniramine, and a short course of systemic corticosteroids such as prednisone.Narrowband ultraviolet B phototherapy has also been explored as a novel treatment option for pruritic folliculitis of pregnancy in one case study. Further investigation that leads to clinical trials is still required to understand the efficacy and safety of this unconventional treatment option.A comprehensive literature review using Medline and Cochrane Database relating to skin disease in pregnancy from 1990-2005 found that pruritic folliculitis of pregnancy has no associated morbidity for the mother or fetus and the condition will go away after pregnancy.An article from American Family Physician in 2007 states pruritic folliculitis of pregnancy has "no identified adverse effects" on pregnancy risks and that pruritic folliculitis of pregnancy can be treated using topical corticosteroids, topical benzoyl peroxide, or ultraviolet B light therapy.

Clinical Studies and Case Reports
There was a case report about a 30 year old women who was in her tenth week of her second pregnancy. She had widespread papulopustular follicular eruption (rash involving hair follicles) mainly affecting her limbs.  She was first treated for a bacteria-associated folliculitis, to which she had some symptom relief. However, the continuation of the pruritic folliculitis still persisted. She was later diagnosised with pruritic folliculitis of pregnancy after a histopathologic test was done to confirm sterility and immune cells.  She then started "narrowband ultraviolet (UV) B phototherapy at 70% of the minimal erythemal dose with 20% increments using a three times per week treatment schedule" at 11 weeks of her pregnancy. With this treatment, her skin greatly improved after 10 treatments and completely resolved after 20 treatments.  She did not have pruritic folliculitis for the remainder of her pregnancy.Treatment, whether it is pharmacological or non-pharmacological, can vary in pregnant individuals with pruritic folliculitis. The patients choice to accept such treatment can vary as well. There have been case reports on resolution of pruritic folliculitis in patients who declined and accepted treatment </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Diffuse panbronchiolitis and can you explain it in depth? [/INST] Diffuse panbronchiolitis (DPB) is an inflammatory lung disease of unknown cause. It is a severe, progressive form of bronchiolitis, an inflammatory condition of the bronchioles (small air passages in the lungs). The term diffuse signifies that lesions appear throughout both lungs, while panbronchiolitis refers to inflammation found in all layers of the respiratory bronchioles (those involved in gas exchange). DPB causes severe inflammation and nodule-like lesions of terminal bronchioles, chronic sinusitis, and intense coughing with large amounts of sputum production.
The disease is believed to occur when there is susceptibility, or a lack of immune system resistance, to DPB-causing bacteria or viruses, caused by several genes that are found predominantly in individuals of East Asian descent. The highest incidence occurs among Japanese people, followed by Koreans. DPB occurs more often in males and usually begins around age 40. It was recognized as a distinct new disease in the early 1960s and was formally named diffuse panbronchiolitis in 1969.
If left untreated, DPB progresses to bronchiectasis, an irreversible lung condition that involves enlargement of the bronchioles, and pooling of mucus in the bronchiolar passages. Daily treatment of DPB with macrolide antibiotics such as erythromycin eases symptoms and increases survival time, but the disease currently has no known cure. The eventual result of DPB can be respiratory failure and heart problems.

Classification
The term "bronchiolitis" generally refers to inflammation of the bronchioles. DPB is classified as a form of "primary bronchiolitis", which means that the underlying cause of bronchiolitis is originating from or is confined to the bronchioles. Along with DPB, additional forms of primary bronchiolitis include bronchiolitis obliterans, follicular bronchiolitis, respiratory bronchiolitis, mineral dust airway disease, and a number of others. Unlike DPB, bronchiolitis that is not considered "primary" would be associated with diseases of the larger airways, such as chronic bronchitis.

Signs and symptoms
Symptoms of DPB include chronic sinusitis (inflamed paranasal sinuses), wheezing, crackles (respiratory sounds made by obstructions such as phlegm and secretions in the lungs), dyspnea (shortness of breath), and a severe cough that yields large amounts of sputum (coughed-up phlegm). There may be pus in the sputum, and affected individuals may have fever. Typical signs of DPB progression include dilation (enlargement) of the bronchiolar passages and hypoxemia (low levels of oxygen in the blood). If DPB is left untreated, bronchiectasis will occur; it is characterized by dilation and thickening of the walls of the bronchioles, inflammatory damage to respiratory and terminal bronchioles, and pooling of mucus in the lungs. DPB is associated with progressive respiratory failure, hypercapnia (increased levels of carbon dioxide in the blood), and can eventually lead to pulmonary hypertension (high blood pressure in the pulmonary vein and artery) and cor pulmonale (dilation of the right ventricle of the heart, or "right heart failure").

Cause
DPB is idiopathic, which means an exact physiological, environmental, or pathogenic cause of the disease is unknown. However, several factors are suspected to be involved with its pathogenesis (the way in which the disease works).The major histocompatibility complex (MHC) is a large genomic region found in most vertebrates that is associated with the immune system. It is located on chromosome 6 in humans. A subset of MHC in humans is human leukocyte antigen (HLA), which controls the antigen-presenting system, as part of adaptive immunity against pathogens such as bacteria and viruses. When human cells are infected by a pathogen, some of them can present parts of the pathogens proteins on their surfaces; this is called "antigen presentation". The infected cells then become targets for types of cytotoxic T-cells, which kill the infected cells so they can be removed from the body.Genetic predisposition for DPB susceptibility has been localized to two HLA haplotypes (a nucleotide or gene sequence difference between paired chromosomes, that is more likely to occur among a common ethnicity or trait) common to people of East Asian descent. HLA-B54 is associated with DPB in the Japanese, while HLA-A11 is associated with the disease in Koreans. Several genes within this region of class I HLA are believed to be responsible for DPB, by allowing increased susceptibility to the disease. The common genetic background and similarities in the HLA profile of affected Japanese and Korean individuals were considered in the search for a DPB gene. It was suggested that a mutation of a suspected disease-susceptibility gene located somewhere between HLA-B and HLA-A had occurred on an ancestral chromosome carrying both HLA-B54 and HLA-A11. Further, it is possible that a number of genetic recombination events around the disease locus (location on a chromosome) could have resulted in the disease being associated with HLA-B54 in the Japanese and HLA-A11 in Koreans. After further study, it was concluded that a DPB susceptibility gene is located near the HLA-B locus at chromosome 6p21.3. Within this area, the search for a genetic cause of the disease has continued.Because many genes belonging to HLA remain unidentified, positional cloning (a method used to identify a specific gene, when only its location on a chromosome is known) has been used to determine that a mucin-like gene is associated with DPB. In addition, diseases caused by identified HLA genes in the DPB-susceptibility region have been investigated. One of these, bare lymphocyte syndrome I (BLS I), exhibits a number of similarities with DPB in those affected, including chronic sinusitis, bronchiolar inflammation and nodules, and the presence of H. influenzae. Also like DPB, BLS I responds favorably to erythromycin therapy by showing a resolution of symptoms. The similarities between these two diseases, the corresponding success with the same mode of treatment, and the fact that the gene responsible for BLS I is located within the DPB-causing area of HLA narrows the establishment of a gene responsible for DPB. Environmental factors such as inhaling toxic fumes and cigarette smoking are not believed to play a role in DPB, and unknown environmental and other non-genetic causes—such as unidentified bacteria or viruses—have not been ruled out.Cystic fibrosis (CF), a progressive multi-system lung disease, has been considered in the search for a genetic cause of DPB. This is for a number of reasons. CF, like DPB, causes severe lung inflammation, abundant mucus production, infection, and shows a genetic predominance among Caucasians of one geographic group to the rarity of others; whereas DPB dominates among East Asians, CF mainly affects individuals of European descent. While no gene has been implicated as the cause of DPB, mutation in a specific gene—much more likely to occur in Europeans—causes CF. This mutation in the CF-causing gene is not a factor in DPB, but a unique polymorphism (variation) in this gene is known to occur in many Asians not necessarily affected by either disease. It is being investigated whether this gene in any state of mutation could contribute to DPB.

Pathophysiology
Inflammation is a normal part of the human immune response, whereby leukocytes (white blood cells), including neutrophils (white blood cells that specialize in causing inflammation), gather, and chemokines (proteins released from certain cells, which activate or elicit a response from other cells) accumulate at any location in the body where bacterial or viral infections occur. Inflammation interferes with the activity of bacteria and viruses, and serves to clear them from the body. In DPB, bacteria such as Haemophilus influenzae and Pseudomonas aeruginosa can cause the proliferation of inflammatory cells into the bronchiolar tissues. However, when neither bacteria are present with DPB, the inflammation continues for an as yet unknown reason. In either circumstance, inflammation in DPB can be so severe that nodules containing inflammatory cells form in the walls of the bronchioles. The presence of inflammation and infection in the airways also results in the production of excess mucus, which must be coughed up as sputum. The combination of inflammation, nodule development, infection, mucus, and frequent cough contributes to the breathing difficulties in DPB.The fact that inflammation in DPB persists with or without the presence of P. aeruginosa and H. influenzae provides a means to determine several mechanisms of DPB pathogenesis. Leukotrienes are eicosanoids, signaling molecules made from essential fatty acids, which play a role in many lung diseases by causing the proliferation of inflammatory cells and excess mucus production in the airways. In DPB and other lung diseases, the predominant mediator of neutrophil-related inflammation is leukotriene B4, which specializes in neutrophil proliferation via chemotaxis (the movement of some types of cells toward or away from certain molecules).Inflammation in DPB is also caused by the chemokine MIP-1alpha and its involvement with CD8+ T cells. Beta defensins, a family of antimicrobial peptides found in the respiratory tract, are responsible for further inflammation in DPB when a pathogen such as P. aeruginosa is present. If present with DPB, the human T-lymphotropic virus, type I, a retrovirus, modifies DPB pathogenesis by infecting T helper cells and altering their effectiveness in recognizing the presence of known or unknown pathogens involved with DPB.

Diagnosis
The diagnosis of DPB requires analysis of the lungs and bronchiolar tissues, which can require a lung biopsy, or the more preferred high resolution computed tomography (HRCT) scan of the lungs. The diagnostic criteria include severe inflammation in all layers of the respiratory bronchioles and lung tissue lesions that appear as nodules within the terminal and respiratory bronchioles in both lungs. The nodules in DPB appear as opaque lumps when viewed on X-rays of the lung, and can cause airway obstruction, which is evaluated by a pulmonary function test, or PFT.   Lung X-rays can also reveal dilation of the bronchiolar passages, another sign of DPB. HRCT scans often show blockages of some bronchiolar passages with mucus, which is referred to as the "tree-in-bud" pattern.  Hypoxemia, another sign of breathing difficulty, is revealed by measuring the oxygen and carbon dioxide content of the blood, using a blood test called arterial blood gas. Other findings observed with DPB include the proliferation of lymphocytes (white blood cells that fight infection), neutrophils, and foamy histiocytes (tissue macrophages) in the lung lining. Bacteria such as H. influenzae and P. aeruginosa are also detectable, with the latter becoming more prominent as the disease progresses. The white blood, bacterial and other cellular content of the blood can be measured by taking a complete blood count (CBC). Elevated levels of IgG and IgA (classes of immunoglobulins) may be seen, as well as the presence of rheumatoid factor (an indicator of autoimmunity). Hemagglutination, a clumping of red blood cells in response to the presence of antibodies in the blood, may also occur. Neutrophils, beta-defensins, leukotrienes, and chemokines can also be detected in bronchoalveolar lavage fluid injected then removed from the bronchiolar airways of individuals with DPB, for evaluation.

Differential diagnosis
In the differential diagnosis (finding the correct diagnosis between diseases that have overlapping features) of some obstructive lung diseases, DPB is often considered. A number of DPB symptoms resemble those found with other obstructive lung diseases such as asthma, chronic bronchitis, and emphysema. Wheezing, coughing with sputum production, and shortness of breath are common symptoms in such diseases, and obstructive respiratory functional impairment is found on pulmonary function testing. Cystic fibrosis, like DPB, causes severe lung inflammation, excess mucus production, and infection; but DPB does not cause disturbances of the pancreas nor the electrolytes, as does CF, so the two diseases are different and probably unrelated.  DPB is distinguished by the presence of lesions that appear on X-rays as nodules in the bronchioles of both lungs; inflammation in all tissue layers of the respiratory bronchioles; and its higher prevalence among individuals with East Asian lineage.DPB and bronchiolitis obliterans are two forms of primary bronchiolitis. Specific overlapping features of both diseases include strong cough with large amounts of often pus-filled sputum; nodules viewable on lung X-rays in the lower bronchi and bronchiolar area; and chronic sinusitis. In DPB, the nodules are more restricted to the respiratory bronchioles, while in OB they are often found in the membranous bronchioles (the initial non-cartilaginous section of the bronchiole, that divides from the tertiary bronchus) up to the secondary bronchus. OB is a bronchiolar disease with worldwide prevalence, while DPB has more localized prevalence, predominantly in Japan. Prior to clinical recognition of DPB in recent years, it was often misdiagnosed as bronchiectasia, COPD, IPF, phthisis miliaris, sarcoidosis or alveolar cell carcinoma.

Treatment
Macrolide antibiotics, such as erythromycin, are an effective treatment for DPB when taken regularly over an extended period of time. Clarithromycin or roxithromycin are also commonly used. The successful results of macrolides in DPB and similar lung diseases stems from managing certain symptoms through immunomodulation (adjusting the immune response), which can be achieved by taking the antibiotics in low doses. Treatment consists of daily oral administration of erythromycin for two to three years, an extended period that has been shown to dramatically improve the effects of DPB. This is apparent when an individual undergoing treatment for DPB, among a number of disease-related remission criteria, has a normal neutrophil count detected in BAL fluid, and blood gas (an arterial blood test that measures the amount of oxygen and carbon dioxide in the blood) readings show that free oxygen in the blood is within the normal range. Allowing a temporary break from erythromycin therapy in these instances has been suggested, to reduce the formation of macrolide-resistant P. aeruginosa. However, DPB symptoms usually return, and treatment would need to be resumed. Although highly effective, erythromycin may not prove successful in all individuals with the disease, particularly if macrolide-resistant P. aeruginosa is present or previously untreated DPB has progressed to the point where respiratory failure is occurring.With erythromycin therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil proliferation, but also lymphocyte activity and obstructive mucus and water secretions in airways. The antibiotic effects of macrolides are not involved in their beneficial effects toward reducing inflammation in DPB. This is evident because the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of macrolide-resistant P. aeruginosa, erythromycin therapy still reduces inflammation.A number of factors are involved in suppression of inflammation by erythromycin and other macrolides. They are especially effective at inhibiting the proliferation of neutrophils, by diminishing the ability of interleukin 8 and leukotriene B4 to attract them. Macrolides also reduce the efficiency of adhesion molecules that allow neutrophils to stick to bronchiolar tissue linings. Mucus production in the airways is a major culprit in the morbidity and mortality of DPB and other respiratory diseases. The significant reduction of inflammation in DPB attributed to erythromycin therapy also helps to inhibit the production of excess mucus.

Prognosis
Untreated DPB leads to bronchiectasis, respiratory failure, and death. A journal report from 1983 indicated that untreated DPB had a five-year survival rate of 62.1%, while the 10-year survival rate was 33.2%. With erythromycin treatment, individuals with DPB now have a much longer life expectancy due to better management of symptoms, delay of progression, and prevention of associated infections like P. aeruginosa. The 10-year survival rate for treated DPB is about 90%. In DPB cases where treatment has resulted in significant improvement, which sometimes happens after about two years, treatment has been allowed to end for a while. However, individuals allowed to stop treatment during this time are closely monitored. As DPB has been proven to recur, erythromycin therapy must be promptly resumed once disease symptoms begin to reappear. In spite of the improved prognosis when treated, DPB currently has no known cure.

Epidemiology
DPB has its highest prevalence among the Japanese, at 11 per 100,000 population. Korean, Chinese, and Thai individuals with the disease have been reported as well. A genetic predisposition among East Asians is suggested. The disease is more common in males, with the male to female ratio at 1.4–2:1 (or about 5 men to 3 women). The average onset of the disease is around age 40, and two-thirds of those affected are non-smokers, although smoking is not believed to be a cause. The presence of HLA-Bw54 increases the risk of diffuse panbronchiolitis 13.3-fold.In Europe and the Americas, a relatively small number of DPB cases have been reported in Asian immigrants and residents, as well as in individuals of non-Asian ancestry </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Graft-versus-host disease and can you explain it in depth? [/INST] Graft-versus-host disease (GvHD)  is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donors immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipients bodys cells, which leads to GvHD. This should not be confused with a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donors immune systems white blood cells reject the recipient. The underlying principle (alloimmunity) is the same, but the details and course may differ. GvHD can also occur after a blood transfusion if the blood products used have not been irradiated or treated with an approved pathogen reduction system.

Types
In the clinical setting, graft-versus-host disease is divided into acute and chronic forms, and scored or graded on the basis of the tissue affected and the severity of the reaction.In the classical sense, acute graft-versus-host disease is characterized by selective damage to the liver, skin (rash), mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host disease target organs include the immune system (the hematopoietic system, e.g., the bone marrow and the thymus) itself, and the lungs in the form of immune-mediated pneumonitis. Biomarkers can be used to identify specific causes of GvHD, such as elafin in the skin. Chronic graft-versus-host disease also attacks the above organs, but over its long-term course can also cause damage to the connective tissue and exocrine glands.Mucosal damage to the vagina can result in severe pain and scarring, and appears in both acute and chronic GvHD. This can result in an inability to have sexual intercourse.

Acute
The acute or fulminant form of the disease (aGvHD) is normally observed within the first 10 to 100 days post-transplant, and is a major challenge to transplants owing to associated morbidity and mortality. About one-third to one-half of allogeneic transplant recipients will develop acute GvHD. Its less common in younger patients and in those with closer human leukocyte antigens (HLA) matches between donor and the patient.The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms can include Nausea, vomiting, stomach cramps, diarrhea (watery and sometimes bloody), loss of appetite, jaundice, abdominal pain, and weight loss.Acute GvHD of the GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting. This is typically diagnosed via intestinal biopsy. Liver GvHD is measured by the bilirubin level in acute patients. Skin GvHD results in a diffuse red maculopapular rash, sometimes in a lacy pattern.
Acute GvHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GvHD usually have a poor prognosis. If the GvHD is severe and requires intense immunosuppression involving steroids and additional agents to get under control, the patient may develop severe infections as a result of the immunosuppression and may die of infection.  However, a 2016 study found that the prognosis for patients with grade IV GvHD has improved in recent years.

Chronic
The chronic form of graft-versus-host disease (cGvHD) normally begins 90 to 600 days post-transplant. The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.The first symptom of cGvHD is commonly a rash on the palms of the hands or the soles of the feet, and the rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:
Decreased appetite
Diarrhea
Abdominal (belly) cramps
Weight loss
Yellowing of the skin and eyes (jaundice)
Enlarged liver
Bloated abdomen (belly)
Pain in the upper right part of the abdomen (belly)
Increased levels of liver enzymes in the blood (seen on blood tests)
Skin that feels tight
Dry, burning eyes
Dryness or painful sores in the mouth
Burning sensations when eating acidic foods
Bacterial infections
Blockages in the smaller airways of the lungsIn the oral cavity, chronic graft-versus-host disease manifests as lichen planus with a higher risk of malignant transformation to oral squamous cell carcinoma in comparison to the classical oral lichen planus. Oral cancer associated with graft-versus-host disease may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-hematopoietic stem cell transplantation patients.

Causes
Three criteria, known as the Billingham criteria, must be met in order for GvHD to occur.
An immuno-competent graft is administered, with viable and functional immune cells.
The recipient is immunologically different from the donor – histo-incompatible.
The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells.After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient after perceiving host tissues as antigenically foreign. The T cells produce an excess of cytokines, including TNF-α and interferon-gamma (IFNγ). A wide range of host antigens can initiate graft-versus-host disease, among them the human leukocyte antigens (HLA). However, graft-versus-host disease can occur even when HLA-identical siblings are the donors. HLA-identical siblings or HLA-identical unrelated donors often have genetically different proteins (called minor histocompatibility antigens) that can be presented by major histocompatibility complex (MHC) molecules to the donors T-cells, which see these antigens as foreign and so mount an immune response.Antigens most responsible for graft loss are HLA-DR (first six months), HLA-B (first two years), and HLA-A (long-term survival).While donor T-cells are undesirable as effector cells of graft-versus-host disease, they are valuable for engraftment by preventing the recipients residual immune system from rejecting the bone marrow graft (host-versus-graft). In addition, as bone marrow transplantation is frequently used to treat cancer, mainly leukemias, donor T-cells have proven to have a valuable graft-versus-tumor effect. A great deal of current research on allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host disease aspects of T-cell physiology from the desirable graft-versus-tumor effect.

Transfusion-associated GvHD
This type of GvHD is associated with transfusion of un-irradiated blood to immunocompromised recipients. It can also occur in situations in which the blood donor is homozygous and the recipient is heterozygous for an HLA haplotype. It is associated with higher mortality (80–90%) due to involvement of bone marrow lymphoid tissue, however the clinical manifestations are similar to GVHD resulting from bone marrow transplantation. Transfusion-associated GvHD is rare in modern medicine. It is almost entirely preventable by controlled irradiation of blood products to inactivate the white blood cells (including lymphocytes) within.

Thymus transplantation
Thymus transplantation may be said to be able to cause a special type of GvHD because the recipients thymocytes would use the donor thymus cells as models when going through the negative selection to recognize self-antigens, and could therefore still mistake own structures in the rest of the body for being non-self. This is a rather indirect GvHD because it is not directly cells in the graft itself that causes it but cells in the graft that make the recipients T cells act like donor T cells. It can be seen as a multiple-organ autoimmunity in xenotransplantation experiments of the thymus between different species. Autoimmune disease is a frequent complication after human allogeneic thymus transplantation, found in 42% of subjects over 1 year post transplantation. However, this is partially explained by the fact that the indication itself, that is, complete DiGeorge syndrome, increases the risk of autoimmune disease.

Thymoma-associated multiorgan autoimmunity (TAMA)
A GvHD-like disease called thymoma-associated multiorgan autoimmunity (TAMA) can occur in patients with thymoma. In these patients rather than a donor being a source of pathogenic T cells, the patients own malignant thymus produces self-directed T cells. This is because the malignant thymus is incapable of appropriately educating developing thymocytes to eliminate self-reactive T cells. The result is a disease virtually indistinguishable from GvHD.

Mechanism
The pathophysiology of GvHD includes three phases:
The afferent phase: activation of APC (antigen presenting cells)
The efferent phase: activation, proliferation, differentiation and migration of effector cells
The effector phase: target tissue destructionActivation of APC occurs in the first stage of GvHD. Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, especially intestinal mucosa. This allows the microbial products to enter and stimulate pro-inflammatory cytokines such as IL-1 and TNF-α. These proinflammatory cytokines increase the expression of MHC and adhesion molecules on APCs, thereby increasing the ability of APC to present antigen.
The second phase is characterized by the activation of effector cells. Activation of donor T-cells further enhances the expression of MHC and adhesion molecules, chemokines and the expansion of CD8 + and CD4 + T-cells and guest B-cells. In the final phase, these effector cells migrate to target organs and mediate tissue damage, resulting in multiorgan failure.

Prevention
DNA-based tissue typing allows for more precise HLA matching between donors and transplant patients, which has been proven to reduce the incidence and severity of GvHD and to increase long-term survival.
The T-cells of umbilical cord blood (UCB) have an inherent immunological immaturity, and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GvHD.
Methotrexate, cyclosporin and tacrolimus are common drugs used for GvHD prophylaxis. Further research is necessary to evaluate whether mesenchymal stromal cells can also be used for the prophylaxis.
Graft-versus-host disease can largely be avoided by performing a T-cell-depleted bone marrow transplant. However, these types of transplants come at a cost of diminished graft-versus-tumor effect, greater risk of engraftment failure, or cancer relapse, and general immunodeficiency, resulting in a patient more susceptible to viral, bacterial, and fungal infection. In a multi-center study, disease-free survival at 3 years was not different between T cell-depleted and T cell-replete transplants.

Treatment
Intravenously administered glucocorticoids, such as prednisone, are the standard of care in acute GvHD and chronic GVHD. The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse. Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect.. Cyclosporine and tacrolimus are calcineurin inhibitors </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Familial episodic pain syndrome and can you explain it in depth? [/INST] Familial episodic pain syndrome, also known simply as FEPS, is a group of rare genetic peripheral neuropathies which are characterized by recurrent random episodes of intense pain which occur most often in the upper or lower parts of the body occurring in several members of the same family. They are often triggered by cold temperatures, physical exercise, fatigue, etc. It may or may not get better with age.

Types
This disorder is distributed into three types:

FEPS Type 1
This type of familial episodic pain syndrome is characterized by infancy-onset intense and debilitating upper-body episodic pain </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gastric volvulus and can you explain it in depth? [/INST] Gastric volvulus or volvulus of stomach is a twisting of all or part of the stomach by more than 180 degrees with obstruction of the flow of material through the stomach, variable loss of blood supply and possible tissue death. The twisting can occur around the long axis of the stomach: this is called organoaxial or around the axis perpendicular to this, called mesenteroaxial. Obstruction is more likely in organoaxial twisting than with mesenteroaxial while the latter is more associated with ischemia. About one third of the cases are associated with a hiatus hernia. Treatment is surgical.
The classic triad (Borchardts Triad) of gastric volvulus, described by Borchardt in 1904, consists of severe epigastric pain, retching (due to sour taste in mouth) without vomiting, inability to pass a nasogastric tube and reportedly occurs in 70% of cases. Sometimes severe pain at the top of left shoulder, this may be due to internal bleeding irritating the diaphragm upon respiration.

Classification
Organoaxial type
In an organoaxial gastric volvulus, the stomach rotates around an axis that connects the gastroesophageal junction and the pylorus. The antrum rotates in opposite direction to the fundus of the stomach. This is the most common type of gastric volvulus, occurring in approximately 59% of cases, and it is usually associated with diaphragmatic defects. Strangulation and necrosis commonly occur with organoaxial gastric volvulus and have been reported in 5–28% of cases. The key imaging feature of organoaxial volvulus is that the greater curvature is located above the lesser curvature of the stomach.

Mesenteroaxial type
The mesenteroaxial axis bisects the lesser and greater curvatures. The antrum rotates anteriorly and superiorly so that the posterior surface of the stomach lies anteriorly. The rotation is usually incomplete and occurs intermittently. Vascular compromise is uncommon. This cause comprises approximately 29% of cases of gastric volvulus. The key imaging feature of mesenteroaxial volvulus is that the antrum is above the gastroesophageal junction.

Combined type
The combined type of gastric volvulus is a rare form in which the stomach twists mesentericoaxially and organoaxially. This type of gastric volvulus makes up the remainder of cases and is usually observed in patients with chronic volvulus.

Cause
Type 1
Gastric volvulus of unknown cause comprises two thirds of cases and is presumably due to abnormal laxity of the gastrosplenic, gastroduodenal, gastrophrenic, and gastrohepatic ligaments. Type 1 gastric volvulus is more common in adults but has been reported in children.

Type 2
Type 2 gastric volvulus is found in one third of patients and is usually associated with congenital or acquired abnormalities that result in abnormal mobility of the stomach.

Diagnosis
On chest radiography, a retrocardiac, gas-filled viscus may be seen in cases of intrathoracic stomach, which confirms the diagnosis. Plain abdominal radiography reveals a massively distended viscus in the upper abdomen. In organoaxial volvulus, plain films may show a horizontally oriented stomach with a single air-fluid level and a paucity of distal gas. In mesenteroaxial volvulus, plain abdominal radiographic findings include a spherical stomach on supine images and 2 air-fluid levels on erect images, with the antrum positioned superior to the fundus.

Upper GI studies
The diagnosis of gastric volvulus is usually based on barium studies; however, some authors recommend computed tomography (CT) scanning as the imaging modality of choice.
Upper gastrointestinal (GI) contrast radiographic studies (using barium or Gastrografin) are sensitive and specific if performed with the stomach in the "twisted" state and may show an upside-down stomach </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Arterial tortuosity syndrome and can you explain it in depth? [/INST] Arterial tortuosity syndrome is a rare congenital connective tissue condition disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. It is associated with hyperextensible skin and hypermobility of joints, however symptoms vary depending on the person. Because ATS is so rare, not much is known about the disease.

Signs and symptoms
Among the signs and symptoms demonstrated, by this condition are the following:
Arachnodactyly
Congenital diaphragmatic hernia
Mental dysfunction
Keratoconus
Aortic regurgitation
Blepharophimosis

Genetics
Arterial tortuosity syndrome exhibits autosomal recessive inheritance, and the responsible gene is located at chromosome 20q13. The gene associated with arterial tortuosity syndrome is SLC2A10 and has no less than 23 mutations in those individuals found to have the aforementioned condition.

Pathophysiology
The mechanism of this condition is apparently controlled by(or due to) the SLC2A10 gene. The molecular genetic pathogenesis finds that SLC2A10 encodes GLUT10(in nuclear membrane, or the endoplasmic reticulum, the later of which GLUT10 transports DHA into).Clinically speaking, according to one review, the condition of tortuosity is seen more with the advance of age.

Diagnosis
In terms of the diagnosis of arterial tortuosity syndrome can be done via genetic testing, as well as the following listed below:
CT
MRI
Echocardiogram
Physical exam(for specific characteristics)

Treatment
The treatment of arterial tortuosity syndrome entails possible surgery for aortic aneurysms, as well as, follow ups which should consist of EGC. The prognosis of this condition has it at about 12% mortality

References
Further reading
Segade, Fernando (16 July 2010). "Glucose transporter 10 and arterial tortuosity syndrome: the vitamin C connection". FEBS Letters. 584 (14): 2990–2994. doi:10.1016/j.febslet.2010.06.011. ISSN 1873-3468. PMID 20547159. S2CID 33856792.Review
Wetzel-Strong, Sarah E; Detter, Matthew R; Marchuk, Douglas A (2017-01-01). "The pathobiology of vascular malformations: insights from human and model organism genetics". The Journal of Pathology. 241 (2): 281–293. doi:10.1002/path.4844 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Placenta accreta spectrum and can you explain it in depth? [/INST] Placenta accreta occurs when all or part of the placenta attaches abnormally to the myometrium (the muscular layer of the uterine wall). Three grades of abnormal placental attachment are defined according to the depth of attachment and invasion into the muscular layers of the uterus:

Accreta – chorionic villi attached to the myometrium, rather than being restricted within the decidua basalis.
Increta – chorionic villi invaded into the myometrium.
Percreta – chorionic villi invaded through the perimetrium (uterine serosa).Because of abnormal attachment to the myometrium, placenta accreta is associated with an increased risk of heavy bleeding at the time of attempted vaginal delivery. The need for transfusion of blood products is frequent, and surgical removal of the uterus (hysterectomy) is sometimes required to control life-threatening bleeding.Rates of placenta accreta are increasing. As of 2016, placenta accreta affects an estimated 1 in 272 pregnancies.

Risk factors
An important risk factor for placenta accreta is placenta previa in the presence of a uterine scar. Placenta previa is an independent risk factor for placenta accreta. Additional reported risk factors for placenta accreta include maternal age and multiparity, other prior uterine surgery, prior uterine curettage, uterine irradiation, endometrial ablation, Asherman syndrome, uterine leiomyomata, uterine anomalies, and smoking.
The condition is increased in incidence by the presence of scar tissue i.e. Ashermans syndrome usually from past uterine surgery, especially from a past dilation and curettage, (which is used for many indications including miscarriage, termination, and postpartum hemorrhage), myomectomy, or caesarean section. A thin decidua can also be a contributing factor to such trophoblastic invasion. Some studies suggest that the rate of incidence is higher when the fetus is female. Other risk factors include low-lying placenta, anterior placenta, congenital or acquired uterine defects (such as uterine septa), leiomyoma, ectopic implantation of placenta (including cornual pregnancy).Pregnant women above 35 years of age who have had a caesarian section and now have a placenta previa overlying the uterine scar have a 40% chance of placenta accreta.

Pathogenesis
The placenta forms an abnormally firm and deep attachment to the uterine wall. There is absence of the decidua basalis and incomplete development of the Nitabuchs layer. There are three forms of placenta accreta, distinguishable by the depth of penetration.

Diagnosis
When the antepartum diagnosis of placenta accreta is made, it is usually based on ultrasound findings in the second or third trimester. Sonographic findings that may be suggestive of placenta accreta include:

Loss of normal hypoechoic retroplacental zone
Multiple vascular lacunae (irregular vascular spaces) within placenta, giving "Swiss cheese" appearance
Blood vessels or placental tissue bridging uterine-placental margin, myometrial-bladder interface, or crossing the uterine serosa
Retroplacental myometrial thickness of <1 mm
Numerous coherent vessels visualized with 3-dimensional power Doppler in basal viewUnfortunately, the diagnosis is not easy and is affected by a significant interobserver variability. In doubtful cases it is possible to perform a nuclear magnetic resonance (MRI) of the pelvis, which has a very good sensitivity and specificity for this disorder.  MRI findings associated with placenta accreta include dark T2 bands, bulging of the uterus, and loss of the dark T2 interface.Although there are isolated case reports of placenta accreta being diagnosed in the first trimester or at the time of abortion <20 weeks gestational age, the predictive value of first-trimester ultrasound for this diagnosis remains unknown. Women with a placenta previa or "low-lying placenta" overlying a uterine scar early in pregnancy should undergo follow-up imaging in the third trimester with attention to the potential presence of placenta accreta.

Complications
Damage to local organs (e.g., bowel, bladder, uterus and neurovascular structures in the retroperitoneum and lateral pelvic sidewalls from placental implantation and its removal;
Postoperative bleeding requiring repeated surgery;
Amniotic fluid embolism;
Complications (such as dilutional coagulopathy, consumptive coagulopathy, acute transfusion reactions, transfusion-associated lung injury, acute respiratory distress syndrome, and electrolyte abnormalities) caused by transfusion of large volumes of blood products, crystalloids, and other volume expanders;
Postoperative thromboembolism, infection, multisystem organ failure, and maternal death.The exact incidence of maternal mortality related to placenta accreta and its complications is unknown, but it is significant, especially if the urinary bladder is involved

Treatment
Treatment may be delivery by caesarean section and abdominal hysterectomy if placenta accreta is diagnosed before birth </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Entoptic phenomenon and can you explain it in depth? [/INST] Entoptic phenomena (from Ancient Greek  ἐντός (entós) within, and  ὀπτικός (optikós) visual) are visual effects whose source is within the human eye itself. (Occasionally, these are called entopic phenomena, which is probably a typographical mistake.)
In Helmholtzs words: "Under suitable conditions light falling on the eye may render visible certain objects within the eye itself. These perceptions are called entoptical."

Overview
Entoptic images have a physical basis in the image cast upon the retina. Hence, they are different from optical illusions, which are caused by the visual system and characterized by a visual percept that (loosely said) appears to differ from reality. Because entoptic images are caused by phenomena within the observers own eye, they share one feature with optical illusions and hallucinations: the observer cannot share a direct and specific view of the phenomenon with others.
Helmholtz[1] commented on entoptic phenomena which could be seen easily by some observers, but could not be seen at all by others. This variance is not surprising because the specific aspects of the eye that produce these images are unique to each individual. Because of the variation between individuals, and the inability for two observers to share a nearly identical stimulus, these phenomena are unlike most visual sensations. They are also unlike most optical illusions which are produced by viewing a common stimulus. Yet, there is enough commonality between the main entoptic phenomena that their physical origin is now well understood.

Examples
Some examples of entoptical effects include:

Floaters or muscae volitantes are slowly drifting blobs of varying size, shape, and transparency, which are particularly noticeable when viewing a bright, featureless background (such as the sky) or a point source of diffuse light very close to the eye. They are shadow images of objects floating in liquid between the retina and the jelly inside the eye (the vitreous) or in the vitreous humor itself. They are visible because they move; if they were pinned to retina by the vitreous or fixed within the vitreous they would be as invisible as ordinary viewing of any stationary object, such as the retinal blood vessels (see Purkinje tree below). Some may be individual red blood cells swollen due to osmotic pressure. Others may be chains of red blood cells stuck together; diffraction patterns can be seen around these.[2] Others may be "coagula of the proteins of the vitreous gel, to embryonic remnants, or the condensation round the walls of Cloquets canal" that exist in pockets of liquid within the vitreous.[3]  The first two sort of floaters may collect over the fovea (the center of vision), and therefore be more visible, when a person is lying on his or her back looking upwards.
Blue field entoptic phenomenon has the appearance of tiny bright dots moving rapidly along squiggly lines in the visual field. It is much more noticeable when viewed against a field of pure blue light and is caused by white blood cells moving in the capillaries in front of the retina.  White cells are larger than red blood cells and can be larger than the diameter of a capillary, so must deform to fit.  As a large, deformed white blood cell goes through a capillary, a space opens up in front of it and red blood cells pile up behind. This makes the dots of light appear slightly elongated with dark tails.[4][5]
Haidingers brush is a very subtle bowtie or hourglass shaped pattern that is seen when viewing a field with a component of blue light that is plane or circularly polarized. Its easier to see if the polarisation is rotating with respect to the observers eye, although some observers can see it in the natural polarisation of sky light. If the light is all blue, it will appear as a dark shadow; if the light is full spectrum, it will appear yellow. It is due to the preferential absorption of blue polarized light by pigment molecules in the fovea.[6][7]
Purkinje images are the reflections from the anterior and posterior surfaces of the cornea and the anterior and posterior surfaces of the lens. Although these first four reflections are not entoptic—they are seen by others who are looking at someone’s eye— Becker[8] described how light can reflect from the posterior surface of the lens and then again from the anterior surface of the cornea to focus a second image on the retina, this one much fainter and inverted. Tscherning[9] referred to this as the sixth image (the fifth image is formed by reflections from the anterior surfaces of the lens and cornea to form an image too far in front of the retina to be visible) and noted it was much fainter and best seen with a relaxed emmetropic eye. To see it, one must be in a dark room, with one eye closed; one must look straight ahead while moving a light back and forth in the field of the open eye. Then one should see the sixth Purkinje as a dimmer image moving in the opposite direction.
The Purkinje tree is an image of the retinal blood vessels in ones own eye, first described by Purkyně in 1823.[10]  It can be seen by shining the beam of a small bright light through the pupil from the periphery of a subjects vision.  This results in an image of the light being focused on the periphery of the retina. Light from this spot then casts shadows of the blood vessels (which lie on top of the retina) onto unadapted portions of the retina. Normally the image of the retinal blood vessels is invisible because of adaptation. Unless the light moves, the image disappears within a second or so. If the light is moved at about 1 Hz, adaptation is defeated, and a clear image can be seen indefinitely. The vascular figure is often seen by patients during an ophthalmic examination when the examiner is using an ophthalmoscope. Another way in which the shadows of blood vessels may be seen is by holding a bright light against the eyelid at the corner of the eye. The light penetrates the eye and casts a shadow on the blood vessels as described previously. The light must be jiggled to defeat adaptation. Viewing in both cases is improved in a dark room while looking at a featureless background. This topic is discussed in more detail by Helmholtz.
Purkinjes blue arcs are associated with the activity of the nerves sending signals from where a spot of light is focussed on the retina near the fovea to the optic disk. To see it, one needs to look at the right edge of a small red light in a dark room with the right eye (left eye closed) after dark-adapting for about 30 seconds; one should see two faint blue arcs starting at the light and heading towards the blind spot. When one looks at the left edge, one will see a faint blue spike going from the light to the right.[11]
A phosphene is the perception of light without light actually entering the eye, for instance caused by pressure applied to the closed eyes.A phenomenon that could be entoptical if the eyelashes are considered to be part of the eye is seeing light diffracted through the eyelashes. The phenomenon appears as one or more light disks crossed by dark blurry lines (the shadows of the lashes), each having fringes of spectral colour. The disk shape is given by the circular aperture of the pupil.

See also
References
Sources
Jan E. Purkyně, 1823: Beiträge zur Kenntniss des Sehens in subjectiver Hinsicht in Beobachtungen und Versuche zur Physiologie der Sinne, In Commission der J.G. Calveschen Buchhandlung, Prag.
H. von Helmholtz, Handbuch der Physiologischen Optik, published as "Helmholtzs Treatise on Physiological Optics, Translated from the Third German Edition," ed. James P. C. Southall; 1925; The Optical Society of America.
Leonard Zusne, 1990: Anomalistic Psychology: A Study of Magical Thinking; Lea; ISBN 0-8058-0508-7 [12]
Becker, O., 1860, “Über Wahrnehmung eines Reflexbildes im eigenen Auge [About perception of a reflected image in your own eye],” Wiener Medizinische Wochenschrift, pp. 670 672 & 684 688.
M. Tscherning, 1920, Physiologic Optics; Third Edition, (English translation by C. Weiland). Philadelphia: Keystone Publishing Co. pp. 55–56.
White, Harvey E., and Levatin, Paul, 1962, "Floaters in the eye," Scientific American, Vol. 206, No. 6, June, 1962, pp. 199 127.
Duke Elder, W. S. (ed.), 1962, System of Ophthalmology, Volume 7, The Foundations of Ophthalmology: heredity pathology diagnosis and therapeutics, St. Louis, The C.V. Mosby Company. p450.
Snodderly, D.M., Weinhaus, R.S., & Choi, J.C. (1992). Neural-vascular relationships in central retina of Macaque monkeys (Macaca fascicularis). Journal of Neuroscience, 12(4), 1169-1193. Available online at: http://www.jneurosci.org/cgi/reprint/12/4/1169.pdf.
Sinclair, S.H., Azar-Cavanagh, M., Soper, K.A., Tuma, R.F., & Mayrovitz, H.N. (1989). Investigation of the source of the blue field entoptic phenomenon </s>


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


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


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Early childhood caries and can you explain it in depth? [/INST] Early childhood caries (ECC), formerly known as nursing bottle caries, baby bottle tooth decay, night bottle mouth and night bottle caries, is a disease that affects teeth in children aged between birth and 71 months. ECC is characterized by the presence of 1 or more decayed (noncavitated or cavitated lesions), missing (due to caries), or filled tooth surfaces in any primary tooth. ECC has been shown to be a very common, transmissible bacterial infection, usually passed from the primary caregiver to the child. The main bacteria responsible for dental caries are Streptococcus mutans (S. mutans) and Lactobacillus. There is also evidence that supports that those who are in lower socioeconomic populations are at greater risk of developing ECC.

Aetiology
Early childhood caries (ECC) is a multi-factorial disease, referring to various risk factors that inter-relate to increase risk of developing the disease. These risk factors include but not limits to, cariogenic bacteria, diet practices and socioeconomic factors. Normally after 6 months, deciduous teeth begin to erupt means, they are susceptible to tooth decay or dental caries. In some unfortunate cases, infants and young children have experienced severe tooth decay called ECC. This can result in the child experiencing severe pain, extensive dental restorations or extractions. The good news is that ECC is preventable, however, still remains a large burden particularly towards health care expenditure.

Microbial factors
The primary cariogenic bacteria involved in ECC are S. mutans and Lactobacillus. The oral flora in an infant oral cavity is not colonised with normal oral flora until the eruption of the primary dentition at approximately 6 to 30 months of age. The colonisation of S. Mutans from mother to infant is well documented. Over time this combination of food debris and bacteria form a biofilm on the tooth surface called plaque. In plaque, the cariogenic microorganisms are those that produce lactic acid as a by-product from fermentable carbohydrates. Examples of these fermentable carbohydrates include fructose, sucrose and glucose. Cariogenic bacteria thrive on these sugars and help them to weaken the adjacent tooth surface. A poor oral care routine and a diet that is high in fermentable carbohydrates favour acidic attack in the oral cavity. This prolonged acidic exposure allows the net loss of minerals from the tooth. This diminishes the strength of the tooth and is called demineralisation. For the outer layer of the tooth (enamel) to reach cavitation, there is a breakdown of the enamel matrix that allows the influx of the cariogenic bacteria. As cavitation progresses into dentine, the dental caries is classified severe, this causes ECC.

Dietary factors
Diet plays a key role in the process of dental caries. The type of foods along with the frequency at which they are consumed can determine the risk it puts for also developing carious lesions. With new products being put on supermarket shelves with irresistible prices, this can largely influence what people buy. It is common for infants and young children to frequently consume fermentable carbohydrates, in the form of liquids. The consumption of liquids containing fermentable carbohydrate, include drinks such as: juice, breast milk, formula, soda. These consumables all have the potential to increase the risk of dental caries due to prolonged contact between sugars in the liquid and cariogenic bacteria on the tooth surface.
Recent research has shown that breastfeeding does not increase caries risk up to 12 months of age. Poor feeding practices without appropriate preventive measures can lead to a distinctive pattern of caries in susceptible infants and toddlers commonly known as baby bottle tooth decay or ECC. Frequent and long duration bottle feeding, especially at night, is associated with ECC. This finding can be attributed to the fact that there is less salivary flow at night and hence less capacity for buffering and remineralisation. Each time a child drinks these liquids, acids attack for 20 minutes or longer. A parents education and health awareness has a major influence on the caries experience of their child - feeding practices, dietary habits and food choices.

Socioeconomic factors
Dental caries still today, remains the most prevalent disease worldwide. This means the disease is highly preventable, yet it is still burdening millions of children and into adulthood with pain and potentially lower quality of life. There are several studies by Locker and Mota-Veloso reporting that there is a two-way relationship that exists between dental caries and levels of education, household income that effect quality of life and social positioning. Locker suggested that the relationship between oral disease and health-related quality of life outcomes can be mediated by personal and environmental variables. Previous studies have also mentioned that the rate of ECC has decreased. However, these results can tend to dis-include communities where equity still exists. More health promotion initiatives and policy-making that collaborate directly with the community to increase meeting their needs, should be implemented.While the primary aetiology is due to microbial factors, it is also largely influenced by the social, behavioral and economic determinants in which children are surrounded by. such factors include living in a low income earning family that may not have the budget to afford visiting a dental clinic. Secondly, having limited access to healthcare and education where important messages about the consumption of carcinogenic foods are not being transferred to children or their parents. Distribution of budget should be made to reach rural and remote communities to implement health promotion strategies to increase awareness about diet and oral hygiene.
The education, occupation and income of families also greatly affects the quality of life. Children greatly rely on their parents or guardians for help concerning their health and well-being. Studies have shown that families of lower socioeconomic status are less likely to regularly attend the dentist and access preventive dental resources. ECC also has an accumulative effect for those that live in rural areas.

Prevention
Early childhood caries can be prevented through the combination of the following: adhering to a healthy nutritional diet, optimal plaque removal, use of fluoridation on the tooth surface once erupted, care taken by the mother during the pre-natal and peri-natal period and regular dental visits. The following are recommendations to help prevent ECC.

Adequate diet
Dietary habits and the presence of cariogenic bacteria within the oral cavity are an important factor in the risk of ECC. ECC is commonly caused by bottle feeding, frequent snacking and a high sugar diet
In regards to preventing ECC through bottle feeding, it is fundamental not to allow the child to sleep using ‘sippy cups’ or bottles as this is a large factor contributing to baby bottle decay/caries. This is highly encouraged as it prevents continuous exposure to non-milk extrinsic sugars and therefore the potential progression of caries – this means the oral cavity can return to a neutral pH and therefore decreased acidity. These researches also suggest trying to introduce cups to children as they approach their first birthday and to reduce the use of a bottle.
A low-sugar and high nutritional diet is recommended for both the mother and the child especially during breastfeeding, and it is also recommended to avoid frequent snackingA 2019 Cochrane review concluded that there is a 15% drop in risk of developing ECC, when mother with infants or pregnant women were given advice on a healthy child diet and feeding practices. Consequently, resulting in less decay for the child.

Optimal plaque removal
On eruption of the first primary tooth in a child, tooth brushing and cleaning should be performed by an adult. This is important as the plaque that attaches to the surface of the tooth has bacteria that have the ability to cause caries (decay) on the tooth surface.
It is recommended to brush childrens teeth using a soft bristled, age and size appropriate toothbrush and age appropriate toothpaste twice daily, however children below the age of two usually dont require toothpaste. These researches also suggest that it is suitable to brush childrens teeth until they reach the approximate age of 6; where they will begin to learn adequate dexterity and cognition needed for adequate brushing by themselves. It is encouraged to watch children brushing their teeth until they are competently able to brush appropriately alone.

Fluoride
Fluoride is a natural mineral that naturally occurs throughout the world – it is also the active ingredient of many toothpastes specifically for its remineralizing effects on enamel, often repairing the tooth surface and reducing the risk of caries.
The use of fluoridated toothpaste is highly recommended by dental professionals; whereby studies suggest that the correct daily use of fluoride on the dentition of children has a high caries-preventive effect and therefore prevents has potential to prevent ECC. However, it is important to use fluoridated toothpastes correctly; children below the age of two do not usually require toothpaste unless they are already at a high risk of ECC as diagnosed by a dental professional, and therefore it is recommended to use a small sized ‘smear’ of toothpaste to incorporate fluoride, with caution removing the toothpaste from within the mouth and not allowing the child to swallow the substances.

Pre-natal and peri-natal period
Prevention of early childhood caries begins before the baby is born; women are advised to maintain a well-balanced diet of high nutritional value, especially during the third trimester and within the infants first year of life. This is since enamel undergoes maturation; if the diet is not sufficient, a common condition that may occur is enamel hypoplasia.
Enamel hypoplasia is a developmental defect of enamel that occurs during tooth development, mainly pre-natally or during early childhood. Teeth affected by enamel hypoplasia are commonly at a higher risk of caries since there is an increased loss of minerals and therefore the tooth surface is able to breakdown more easily than in comparison to a non-hypoplastic tooth. It is therefore suggested to the mother to maintain a healthy diet since evidence suggests malnourishment during the perinatal period increases the risk of hypoplastic teeth in an infant.

Dental visits
It is recommended to parents and caregivers to take their children to a dental professional for examination as soon as the first few teeth start to erupt into the oral cavity. The dental professional will assess all the present dentition for early carious demineralization and may provide recommendations to the parents or caregivers the best way to prevent ECC and what actions to take.
Studies suggest that children who have attended visits within the first few years of life (an early preventive dental visit) potentially experience less dental related issues and incur lower dental related costs throughout their lives.

Treatment
The current standard of care for Severe Early Childhood Caries includes restoration and extraction of carious teeth and, where possible, includes early intervention which includes application of topical fluoride, oral hygiene instructions and education.
The initial visit is important as it allows dental professionals to flag unfavourable behaviour or eating habits. This will also allow dental clinician, working in a collaborative team, to perform diagnostic testing to determine the rate and progression of the disease. This is done by performing risk assessment based on the childs age, as well as the social, behavioural, and medical history of the child. Children at low risk may not need any restorative therapy, and frequent visits should be made to detect possible early lesions. Children at moderate risk may require restoration of progressing and cavitated lesions, while white spot and enamel proximal lesions should be treated by preventive techniques and monitored for progression. Children at high risk, however, may require earlier restorative intervention of enamel proximal lesions, as well as intervention of progressing and cavitated lesions to minimize continual caries development. As Early Childhood Caries occurs in children under the age of 5, restorative treatment is conventionally performed under general anesthetic to prevent a traumatic experience for the child. Still, the literature shows a high rate of caries relapse after treatment under general anesthesia, sometimes as early as 6 months after treatment was rendered.Dental professionals now have a safe, inexpensive, and less invasive option to manage Early Childhood Caries: Silver Diamine Fluoride (SDF) is a liquid containing silver and fluoride that can be brushed on teeth to stop decay, relieve sensitivity, and prevent cavities from getting worse. Silver kills the bacteria that cause tooth decay and fluoride helps strengthen the tooth. SDF is applied directly to the area of decay without first having to drill the tooth. SDF is an inexpensive option that is simple to apply; however, although it stops the decay from progressing, it does not fill the cavity, and the tooth may still need to be restored with a filling or crown. After treatment with SDF, arrested decay will become black, but a dental provider can cover the treated area with a white filling material if needed. This may be less of a problem in baby teeth, which will be lost as the child ages, than for permanent teeth. Even so, because applying SDF is quick, it may be especially helpful for young children and other patients who have trouble sitting still during dental treatments, avoiding the need for sedation or general anesthesia. However, the use of SDF remains controversial and more good quality research is needed to be conclusive on its effectiveness, its need and its adverse effects on early caries and childrens health especially for those in developed countries. This is particularly important in light of the FDA warnings about using general anesthetics and sedation in young children.  The American Dental Association recognizes SDF as an effective approach to conservatively manage dental decay.Depending on the level of cavitation of the teeth, different types of restorations may be employed. Stainless steel (preformed) crowns are pre-fabricated crown forms which can be adapted to individual primary molars and cemented in place to provide a definitive restoration or can be fitted using the Hall Technique </s>


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


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hypereosinophilic syndrome and can you explain it in depth? [/INST] Hypereosinophilic syndrome  is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.HES is a diagnosis of exclusion, after clonal eosinophilia (such as FIP1L1-PDGFRA-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out.There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects.
If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone. The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.

Signs and symptoms
As HES affects many organs at the same time, symptoms may be numerous. Some possible symptoms a patient may present with include:

Cardiomyopathy
Skin lesions
Thromboembolic disease
Pulmonary disease
Neuropathy
Hepatosplenomegaly
Reduced ventricular size
Atopic eczema

Diagnosis
Numerous techniques are used to diagnose hypereosinophilic syndrome, of which the most important is blood testing. In HES, the eosinophil count is greater than 1.5 × 109/L. On some smears the eosinophils may appear normal in appearance, but morphologic abnormalities, such as a lowering of granule numbers and size, can be observed </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Brachymetatarsia and can you explain it in depth? [/INST] Brachymetatarsia is a condition in which there is one or more abnormally short or overlapping toe bones (metatarsals). This condition may result due to a congenital defect or it may be an acquired condition </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Angelman syndrome and can you explain it in depth? [/INST] Angelman syndrome or Angelmans syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.Angelman syndrome is due to a lack of function of part of chromosome 15, typically due to a new mutation rather than one inherited from a persons parents. Most of the time, it is due to a deletion or mutation of the UBE3A gene on that chromosome. Occasionally, it is due to inheriting two copies of chromosome 15 from a persons father and none from their mother (paternal uniparental disomy). As the fathers versions are inactivated by a process known as genomic imprinting, no functional version of the gene remains. Diagnosis is based on symptoms and possibly genetic testing.No cure is available. Treatment is generally supportive in nature. Anti-seizure medications are used in those with seizures. Physical therapy and bracing may help with walking. Those affected have a nearly normal life expectancy.AS affects 1 in 12,000 to 20,000 people. Males and females are affected with equal frequency. It is named after British pediatrician Harry Angelman, who first described the syndrome in 1965. An older term, happy puppet syndrome, is generally considered pejorative. Prader–Willi syndrome is a separate condition, caused by a similar loss of the fathers chromosome 15.

Signs and symptoms
Signs and symptoms of Angelman syndrome and their relative frequency in affected individuals are:

Consistent (100%)
Developmental delay, functionally severe
Speech impairment, no or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
Behavioral characteristics of the following types: any combination of atypical frequent laughter/smiling; atypically happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span

Frequent (more than 80%)
Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
Seizures, onset usually less than 3 years of age
Abnormal EEG, characteristic pattern with large amplitude slow-spike waves

Associated (20–80%)
Cause
Angelman syndrome is caused by the lack of expression of a gene known as UBE3A during development. This gene is located within a region of chromosome 15 known as 15q11-q13 and is part of the ubiquitin pathway. In fact, UBE3A codes for a very selective E6-AP ubiquitin ligase for which MAPK1, PRMT5, CDK1, CDK4, β-catenin, and UBXD8 have been identified as ubiquitination targetsTypically, a fetus inherits a maternal copy of UBE3A and a paternal copy of UBE3A. In certain areas of the developing brain, the paternal copy of UBE3A is inactivated through a process known as imprinting and the fetus relies on the functioning maternal copy of UBE3A in order to develop normally. In an individual with AS, however, the maternal UBE3A gene is absent or not functioning normally. This can be due to genetic errors such as the deletion or mutation of a segment of chromosome 15, uniparental disomy, or translocation. While Angelman syndrome can be caused by a single mutation in the UBE3A gene, the most common genetic defect leading to Angelman syndrome is a 5- to 7-Mb (megabase) maternal deletion in chromosomal region 15q11.2-q13.Specifically, the paternal copy of UBE3A is known to be imprinted within the hippocampus, cortex, thalamus, olfactory bulb, and cerebellum. Therefore, in these areas of the brain, a functioning maternal copy of UBE3A is essential for proper development.Region 15q11-13 is implicated in both Angelman syndrome and Prader–Willi syndrome (PWS). While AS results from mutation, loss or abnormal imprinting involving the UBE3A gene within this region on the maternal chromosome, loss of a different cluster of genes within the same region on the paternal chromosome causes PWS.The methylation test that is performed for Angelman syndrome looks for methylation on the genes neighbor SNRPN, which is silenced by methylation on the maternal copy of the gene.

Neurophysiology
The electroencephalogram (EEG) in AS is usually abnormal, more so than clinically expected. This EEG facilitates the differential diagnosis of AS, but is not pathognomonic. Three distinct interictal patterns are seen in these patients. The most common pattern is a very large amplitude 2–3 Hz rhythm most prominent in prefrontal leads. Next most common is a symmetrical 4–6 Hz high voltage rhythm. The third pattern, 3–6 Hz activity punctuated by spikes and sharp waves in occipital leads, is associated with eye closure. Paroxysms of laughter have no relation to the EEG, ruling out this feature as a gelastic phenomenon.EEG anomalies may be used as a quantitative biomarkers to "chart progression of AS and as clinical outcome measures". Slow delta activity (~3 Hz) is greatly increased in AS relative to typically developing children, yet more pronounced in children with partial 15q deletions as opposed to those with etiologies principally affecting UBE3A. Theta activity (~5 Hz) is much greater in children with partial 15q deletions. Thus, delta activity appears to be chiefly reflective of UBE3A dysfunction with some modulation from other 15q genes, whereas theta activity may be an electrophysiological readout of genes beyond UBE3A such as GABRA5, GABRB3, and GABRG3. Future clinical trials in AS might exploit the foregoing by using EEG as a readout of drug target engagement.It appears that the neurons of people with Angelman syndrome are formed correctly, but they cannot function properly.

Diagnosis
The diagnosis of Angelman syndrome is based on:
A history of delayed motor milestones and then later a delay in general development, especially of speech
Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait.
Characteristic facial appearance (but not in all cases).
A history of epilepsy and an abnormal EEG tracing.
A happy disposition with frequent laughter
A deletion or inactivity on chromosome 15 by array comparative genomic hybridization (aCGH) or by BACs-on-Beads technology.Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (US); these criteria underwent revision in 2005.Seizures are a consequence, but so is excessive laughter, which is a major hindrance to early diagnosis.

Differential diagnosis
Other conditions that can appear similar include:
Autism spectrum
Cerebral palsy
Rett syndrome
Mowat–Wilson syndrome
Adenylosuccinate lyase deficiency
Pitt–Hopkins syndrome
Phelan–McDermid syndrome
Prader–Willi syndrome

Treatment
There is currently no cure available. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because people with AS often have multiple types of seizures. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Many individuals with Angelman syndrome sleep for a maximum of five hours at any one time. Mild laxatives are also used frequently to encourage regular bowel movements. Early intervention with physiotherapy is sometimes used to encourage joint mobility and prevent stiffening of the joints. Speech and Language Therapy is commonly employed to assist individuals with Angelman syndrome and their communication issues.Occupational therapists can contribute to the development and augmentation of non-verbal communication skills by addressing the foundational skills such as finger isolation, motor planning, hand-eye coordination, spatial awareness, and refining gestures. This is important because individuals with Angelman Syndrome who already possess some form of non-verbal communication have a much harder time adapting to changes in a new or existing AAC device because they can communicate their needs much faster nonverbally.Occupational therapists can assist individuals with Angelman syndrome with many other skills as well. Many individuals with Angelman syndrome also have difficulty processing sensory information and responding appropriately to sensory stimuli. Occupational therapists can work together with these individuals to improve their visual perceptual skills and increase their sensory awareness.Those with the syndrome are generally happy and contented people who like human contact and play. People with AS exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as a child with AS develops, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for their limited use of speech. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most affected people will not develop more than 5–10 words, if any at all.

Prognosis
The severity of the symptoms associated with Angelman syndrome varies significantly across the population of those affected. Some speech and a greater degree of self-care are possible among the least profoundly affected. Walking and the use of simple sign language may be beyond the reach of the more profoundly affected. Early and continued participation in physical, occupational (related to the development of fine-motor control skills), and communication (speech) therapies are believed to significantly improve the prognosis (in the areas of cognition and communication) of individuals affected by AS. Further, the specific genetic mechanism underlying the condition is thought to correlate to the general prognosis of the affected person. On one end of the spectrum, a mutation to the UBE3A gene is thought to correlate to the least affected, whereas larger deletions on chromosome 15 are thought to correspond to the most affected.The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The seizures decrease in frequency and often cease altogether and the EEG abnormalities are less obvious. Medication is typically advisable to those with seizure disorders. Often overlooked is the contribution of the poor sleep patterns to the frequency and/or severity of the seizures. Medication may be worthwhile to help deal with this issue and improve the prognosis with respect to seizures and sleep. Also noteworthy are the reports that the frequency and severity of seizures temporarily escalate in pubescent Angelman syndrome girls, but do not seem to affect long-term health.The facial features remain recognizable with age, but many adults with AS look remarkably youthful for their age.Puberty and menstruation begin at around the average age.  Sexual development is thought to be unaffected, as evidenced by a single reported case of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome.The majority of those with AS achieve continence by day and some by night. Angelman syndrome is not a degenerative syndrome, and thus people with AS may improve their living skills with support.Dressing skills are variable and usually limited to items of clothing without buttons or zippers. Most adults can eat with a knife or spoon and fork, and can learn to perform simple household tasks. Particular problems which have arisen in adults are a tendency to obesity (more in females), and worsening of scoliosis if it is present. The affectionate nature may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable. People with Angelman syndrome appear to have a reduced but near-normal life expectancy, dying on average 10 to 15 years earlier than the general population.

Epidemiology
Though the prevalence of Angelman syndrome is not precisely known, there are some estimates. The best data available are from studies of school age children, ages 6–13 years, living in Sweden and from Denmark where the diagnosis of AS children in medical clinics was compared to an 8-year period of about 45,000 births. The Swedish study showed an AS prevalence of about 1/20,000 and the Danish study showed a minimum AS prevalence of about 1/10,000.

History
Harry Angelman, a pediatrician working in Warrington, England, first reported three children with this condition in 1965. Angelman later described his choice of the title "Puppet Children" to describe these cases as being related to an oil painting he had seen while vacationing in Italy:

The history of medicine is full of interesting stories about the discovery of illnesses. The saga of Angelmans syndrome is one such story. It was purely by chance that nearly thirty years ago (e.g.  [sic], circa 1964) three handicapped children were admitted at various times to my childrens ward in England. They had a variety of disabilities and although at first sight they seemed to be suffering from different conditions I felt that there was a common cause for their illness </s>