<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Rumination syndrome and explain in detail? [/INST] Rumination syndrome, or merycism, is a chronic motility disorder characterized by effortless regurgitation of most meals following consumption, due to the involuntary contraction of the muscles around the abdomen. There is no retching, nausea, heartburn, odour, or abdominal pain associated with the regurgitation, as there is with typical vomiting, and the regurgitated food is undigested. The disorder has been historically documented as affecting only infants, young children, and people with cognitive disabilities (the prevalence is as high as 10% in institutionalized patients with various mental disabilities).
It is increasingly being diagnosed in a greater number of otherwise healthy adolescents and adults, though there is a lack of awareness of the condition by doctors, patients and the general public.
Rumination syndrome presents itself in a variety of ways, with especially high contrast existing between the presentation of the typical adult patient without a mental disability and the presentation of an adult with a mental disability. Like related gastrointestinal disorders, rumination can adversely affect normal functioning and the social lives of individuals. It has been linked with depression.
Little comprehensive data regarding rumination syndrome in otherwise healthy individuals exists because most people are private about their illness and are often misdiagnosed due to the number of symptoms and the clinical similarities between rumination syndrome and other disorders of the stomach and esophagus, such as gastroparesis and bulimia nervosa. These symptoms include the acid-induced erosion of the esophagus and enamel, halitosis, malnutrition, severe weight loss and an unquenchable appetite. Individuals may begin regurgitating within a minute following ingestion, and the full cycle of ingestion and regurgitation can mimic the binging and purging of bulimia.
Diagnosis of rumination syndrome is non-invasive and based on a history of the individual. Treatment is promising, with upwards of 85% of individuals responding positively to treatment, including infants and mentally disabled people.

Signs and symptoms
While the number and severity of symptoms vary among individuals, repetitive regurgitation of undigested food (known as rumination) after the start of a meal is always present. In some individuals, the regurgitation is small, occurring over a long period of time following ingestion, and can be rechewed and swallowed. In others, the amount can be bilious and short-lasting, and must be expelled.
While some only experience symptoms following some meals, most experience episodes following any ingestion, from a single bite to a large meal. However, some long-term patients will find a select couple of food or drink items that do not trigger a response.
Unlike typical vomiting, regurgitation is typically described as effortless and unforced. There is seldom nausea preceding the expulsion, and the undigested food lacks the bitter taste and odour of stomach acid and bile.Symptoms can begin to manifest at any point from the ingestion of the meal to 120 minutes thereafter. However, the more common range is between 30 seconds to 1 hour after the completion of a meal. Symptoms tend to cease when the ruminated contents become acidic.Abdominal pain (38.1%), lack of fecal production or constipation (21.1%), nausea (17.0%), diarrhea (8.2%), bloating (4.1%), and dental decay (3.4%) are also described as common symptoms in day-to-day life. These symptoms are not necessarily prevalent during regurgitation episodes, and can happen at any time. Weight loss is often observed (42.2%) at an average loss of 9.6 kilograms, and is more common in cases where the disorder has gone undiagnosed for a longer period of time, though this may be expected of the nutrition deficiencies that often accompany the disorder as a consequence of its symptoms. Depression has also been linked with rumination syndrome, though its effects on rumination syndrome are unknown.Acid erosion of the teeth can be a feature of rumination, as can halitosis (bad breath).

Causes
The cause of rumination syndrome is unknown. However, studies have drawn a correlation between hypothesized causes and the history of patients with the disorder. In infants and the cognitively impaired, the disease has normally been attributed to overstimulation and under-stimulation from parents and caregivers, causing the individual to seek self-gratification and self-stimulus due to the lack or abundance of external stimuli. The disorder has also commonly been attributed to a bout of illness, a period of stress in the individuals recent past, and to changes in medication.In adults and adolescents, hypothesized causes generally fall into one of either category: habit-induced, and trauma-induced. Habit-induced individuals generally have a history of bulimia nervosa or of intentional regurgitation (magicians and professional regurgitators, for example), which though initially self-induced, forms a subconscious habit that can continue to manifest itself outside the control of the affected individual. Trauma-induced individuals describe an emotional or physical injury (such as recent surgery, psychological distress, concussions, deaths in the family, etc.), which preceded the onset of rumination, often by several months.

Pathophysiology
Rumination syndrome is a poorly understood disorder, and a number of theories have speculated the mechanisms that cause the regurgitation, which is a unique symptom to this disorder. While no theory has gained a consensus, some are more notable and widely published than others.The most widely documented mechanism is that the ingestion of food causes gastric distention, which is followed by abdominal compression and the simultaneous relaxation of the lower esophageal sphincter (LES). This creates a common cavity between the stomach and the oropharynx that allows the partially digested material to return to the mouth. There are several offered explanations for the sudden relaxation of the LES. Among these explanations is that it is a learned voluntary relaxation, which is common in those with or having had bulimia. While this relaxation may be voluntary, the overall process of rumination is still generally involuntary. Relaxation due to intra-abdominal pressure is another proposed explanation, which would make abdominal compression the primary mechanism. The third is an adaptation of the belch reflex, which is the most commonly described mechanism. The swallowing of air immediately prior to regurgitation causes the activation of the belching reflex that triggers the relaxation of the LES. Patients often describe a feeling similar to the onset of a belch preceding rumination.

Diagnosis
Rumination syndrome is diagnosed based on a complete history of the individual. Costly and invasive studies such as gastroduodenal manometry and esophageal pH testing are unnecessary and will often aid in misdiagnosis. Based on typical observed features, several criteria have been suggested for diagnosing rumination syndrome. The primary symptom, the regurgitation of recently ingested food, must be consistent, occurring for at least six weeks of the past twelve months. The regurgitation must begin within 30 minutes of the completion of a meal. Patients may either chew the regurgitated matter or expel it. The symptoms must stop within 90 minutes, or when the regurgitated matter becomes acidic. The symptoms must not be the result of a mechanical obstruction, and should not respond to the standard treatment for gastroesophageal reflux disease.In adults, the diagnosis is supported by the absence of classical or structural diseases of the gastrointestinal system. Supportive criteria include a regurgitant that does not taste sour or acidic, is generally odourless, is effortless, or at most preceded by a belching sensation, that there is no retching preceding the regurgitation, and that the act is not associated with nausea or heartburn.Patients visit an average of five physicians over 2.75 years before being correctly diagnosed with rumination syndrome.

Differential diagnosis
Rumination syndrome in adults is a complicated disorder whose symptoms can mimic those of several other gastroesophageal disorders and diseases. Bulimia nervosa and gastroparesis are especially prevalent among the misdiagnoses of rumination.Bulimia nervosa, among adults and especially adolescents, is by far the most common misdiagnosis patients will hear during their experiences with rumination syndrome. This is due to the similarities in symptoms to an outside observer—"vomiting" following food intake—which, in long-term patients, may include ingesting copious amounts to offset malnutrition, and a lack of willingness to expose their condition and its symptoms. While it has been suggested that there is a connection between rumination and bulimia, unlike bulimia, rumination is not self-inflicted. Adults and adolescents with rumination syndrome are generally well aware of their gradually increasing malnutrition, but are unable to control the reflex. In contrast, those with bulimia intentionally induce vomiting, and seldom re-swallow food.Gastroparesis is another common misdiagnosis. Like rumination syndrome, patients with gastroparesis often bring up food following the ingestion of a meal. Unlike rumination, gastroparesis causes vomiting (in contrast to regurgitation) of food, which is not being digested further, from the stomach. This vomiting occurs several hours after a meal is ingested, preceded by nausea and retching, and has the bitter or sour taste typical of vomit.

Classification
Rumination syndrome is a condition which affects the functioning of the stomach and esophagus, also known as a functional gastroduodenal disorder. In patients that have a history of eating disorders, Rumination syndrome is grouped alongside eating disorders such as bulimia and pica, which are themselves grouped under non-psychotic mental disorder. In most healthy adolescents and adults who have no mental disability, Rumination syndrome is considered a motility disorder instead of an eating disorder, because the patients tend to have had no control over its occurrence and have had no history of eating disorders.

Treatment and prognosis
There is presently no known cure for rumination. Proton pump inhibitors and other medications have been used to little or no effect.
Treatment is different for infants and mentally disabled adults than for adults and adolescents of typical intelligence. Among infants and mentally disabled adults, behavioral and mild aversion training has been shown to cause improvement in most cases. Aversion training involves associating the ruminating behavior with negative results, and rewarding good behavior and eating. Placing a sour or bitter taste on the tongue when the individual begins the movements or breathing patterns typical of his or her ruminating behavior is the generally accepted method for aversion training,
although some older studies advocate the use of pinching.
In patients of normal intelligence, rumination is not an intentional behavior and is habitually reversed using diaphragmatic breathing to counter the urge to regurgitate. Alongside reassurance, explanation and habit reversal, patients are shown how to breathe using their diaphragms prior to and during the normal rumination period. A similar breathing pattern can be used to prevent normal vomiting. Breathing in this method works by physically preventing the abdominal contractions required to expel stomach contents.
Supportive therapy and diaphragmatic breathing has shown to cause improvement in 56% of cases, and total cessation of symptoms in an additional 30% in one study of 54 adolescent patients who were followed up 10 months after initial treatments. Patients who successfully use the technique often notice an immediate change in health for the better. Individuals who have had bulimia or who intentionally induced vomiting in the past have a reduced chance for improvement due to the reinforced behavior. The technique is not used with infants or young children due to the complex timing and concentration required for it to be successful. Most infants grow out of the disorder within a year or with aversive training.

Epidemiology
Rumination disorder was initially documented
as affecting newborns,
infants, children
and individuals with mental and functional disabilities (cognitively disabled).
It has since been recognized to occur in both males and females of all ages and cognitive abilities.Among cognitively disabled people, it is described with almost equal prevalence among infants (6–10% of the population) and institutionalized adults (8–10%).
In infants, it typically occurs within the first 3–12 months of age.The occurrence of rumination syndrome within the general population has not been defined. Rumination is sometimes described as rare, but has also been described as not rare, but rather rarely recognized.
The disorder has a female predominance. The typical age of adolescent onset is 12.9, give or take 0.4 years (±), with males affected sooner than females (11.0 ± 0.8 for males versus 13.8 ± 0.5 for females).There is little evidence concerning the impact of hereditary influence in rumination syndrome. However, case reports involving entire families with rumination exist.

History
The term rumination is derived from the Latin word ruminare, which means to chew the cud. First described in ancient times, and mentioned in the writings of Aristotle, rumination syndrome was clinically documented in 1618 by Italian anatomist Fabricus ab Aquapendente, who wrote of the symptoms in a patient of his.Among the earliest cases of rumination was that of a physician in the nineteenth century, Charles-Édouard Brown-Séquard, who acquired the condition as the result of experiments upon himself. As a way of evaluating and testing the acid response of the stomach to various foods, the doctor would swallow sponges tied to a string, then intentionally regurgitate them to analyze the contents. As a result of these experiments, the doctor eventually regurgitated his meals habitually by reflex.Numerous case reports exist from before the twentieth century, but were influenced greatly by the methods and thinking used in that time. By the early twentieth century, it was becoming increasingly evident that rumination presented itself in a variety of ways in response to a variety of conditions </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Glioma and explain in detail? [/INST] A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.

Signs and symptoms
Symptoms of gliomas depend on which part of the central nervous system is affected.  A brain glioma can cause headaches, vomiting, seizures, and cranial nerve disorders as a result of increased intracranial pressure. A glioma of the optic nerve can cause visual loss.  Spinal cord gliomas can cause pain, weakness, or numbness in the extremities.  Gliomas do not usually metastasize by the bloodstream, but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord. Complex visual hallucinations have been described as a symptom of low-grade glioma.A child who has a subacute disorder of the central nervous system that produces cranial nerve abnormalities (especially of cranial nerve VII and the lower bulbar nerves), long-tract signs, unsteady gait secondary to spasticity, and some behavioral changes is most likely to have a pontine glioma.

Causes
Hereditary disorders
The exact causes of gliomas are not known. Hereditary disorders such as neurofibromatoses (type 1 and type 2) and tuberous sclerosis complex are known to predispose to their development. Different oncogenes can cooperate in the development of gliomas.

Diet
Some studies of diet and vitamin supplementation appear to point out that dietary N-nitroso compounds may affect the risk of both childhood and adult brain tumors. Researchers have observed in some studies that brain tumor patients (or their mothers) have generally consumed more cured foods (also known as Curing) than control groups.  Recently, Drs. Lee, Wrensch and others found that adults with glioma were more likely to consume diets high in cured foods and low in vitamin C-rich fruits and vegetables, and to consume diets high in nitrites and low in vitamin C. The effect was more pronounced in men than women. However, the pattern of increased risk with increased consumption of cured foods, and decreased risk with greater consumption of fruits, vegetables, and antioxidant vitamins is compatible with other cancer studies that show increased consumption of vegetables and possibly of fruits is associated with decreased cancer risk.

Radiation
A link between gliomas and electromagnetic radiation from cell phones has not been conclusively proven. It was considered possible, though several large studies have found no conclusive evidence, as summarized by the NIHs National Cancer Institute review of the topic and its numerous citations, and the FCC. However, further research is still being pursued to obtain more robust evidence and verify that there is no relationship (the NIHs National Institute of Environmental Health Sciences most recent press release discussed an ongoing study showing mildly positive results, although it appears there may have been issues with the control group dying prematurely).

Infection with cytomegalovirus
Some studies have reported that glioblastomas are infected with cytomegalovirus, with suggestions that this may speed the development of tumors. However, this is a controversial opinion, with recent in-depth studies failing to find an association between viral infection and glioma growth. There is also evidence that previous studies may have been impacted by false-positive antibody staining artifacts.

Other causes
Though some studies have shown that farmers have higher rates of gliomas compared to the general population, exposure to farm animals or manure is not associated with glioma. Later studies have not found an association between farming and gliomas; similar conflicting data concerns teachers and glioma. More consistent data show that architects, surveyors, retail workers, butchers, and engineers have higher rates of gliomas. Most studies have found that pesticide exposure is probably not a cause of glioma, though a minority of studies have found an association.

Inherited polymorphisms of the DNA repair genes
Germ-line (inherited) polymorphisms of the DNA repair genes ERCC1, ERCC2 (XPD) and XRCC1 increase the risk of glioma. This indicates that altered or deficient repair of DNA damage contributes to the formation of gliomas.  DNA damages are a likely major primary cause of progression to cancer in general.  Excess DNA damages can give rise to mutations through translesion synthesis. Furthermore, incomplete DNA repair can give rise to epigenetic alterations or epimutations.  Such mutations and epimutations may provide a cell with a proliferative advantage which can then, by a process of natural selection, lead to progression to cancer.Epigenetic repression of DNA repair genes is often found in progression to sporadic glioblastoma.  For instance, methylation of the DNA repair gene MGMT promoter was observed in 51% to 66% of glioblastoma specimens.  In addition, in some glioblastomas, the MGMT protein is deficient due to another type of epigenetic alteration.  MGMT protein expression may also be reduced due to increased levels of a microRNA that inhibits the ability of the MGMT messenger RNA to produce the MGMT protein.  Zhang et al. found, in the glioblastomas without methylated MGMT promoters, that the level of microRNA miR-181d is inversely correlated with protein expression of MGMT and that the direct target of miR-181d is the MGMT mRNA 3UTR (the three prime untranslated region of MGMT messenger RNA).Epigenetic reductions in expression of another DNA repair protein, ERCC1, were found in an assortment of 32 gliomas.  For 17 of the 32 (53%) of the gliomas tested, ERCC1 protein expression was reduced or absent.  In the case of 12 gliomas (37.5%) this reduction was due to methylation of the ERCC1 promoter.  For the other 5 gliomas with reduced ERCC1 protein expression, the reduction could have been due to epigenetic alterations in microRNAs that affect ERCC1 expression.When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and such excess damages cause increased frequencies of mutation.  Mutations in gliomas frequently occur in either isocitrate dehydrogenase (IDH) 1 or 2 genes.  One of these mutations (mostly in IDH1) occurs in about 80% of low grade gliomas and secondary high-grade gliomas.  Wang et al. pointed out that IDH1 and IDH2 mutant cells produce an excess metabolic intermediate, 2-hydroxyglutarate, which binds to catalytic sites in key enzymes that are important in altering histone and DNA promoter methylation. Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP" that causes promoter hypermethylation and concomitant silencing of tumor suppressor genes such as DNA repair genes MGMT and ERCC1.  On the other hand, Cohen et al. and Molenaar et al. pointed out that mutations in IDH1 or IDH2 can cause increased oxidative stress.  Increased oxidative damage to DNA could be mutagenic. This is supported by an increased number of DNA double-strand breaks in IDH1-mutated glioma cells. Thus, IDH1 or IDH2 mutations act as driver mutations in glioma carcinogenesis, though it is not clear by which role they are primarily acting.  A study, involving 51 patients with brain gliomas who had two or more biopsies over time, showed that mutation in the IDH1 gene occurred prior to the occurrence of a p53 mutation or a 1p/19q loss of heterozygosity, indicating that an IDH1 mutation is an early driver mutation.

Pathophysiology
High-grade gliomas are highly vascular tumors and have a tendency to infiltrate diffusely.  They have extensive areas of necrosis and hypoxia.  Often, tumor growth causes a breakdown of the blood–brain barrier in the vicinity of the tumor.  As a rule, high-grade gliomas almost always grow back even after complete surgical excision, so are commonly called recurrent cancer of the brain.Conversely, low-grade gliomas grow slowly, often over many years, and can be followed without treatment unless they grow and cause symptoms.Several acquired (not inherited) genetic mutations have been found in gliomas. Tumor suppressor protein 53 (p53) is mutated early in the disease. p53 is the "guardian of the genome", which, during DNA and cell duplication, makes sure the DNA is copied correctly and destroys the cell (apoptosis) if the DNA is mutated and cannot be fixed. When p53 itself is mutated, other mutations can survive. Phosphatase and tensin homolog (PTEN), another tumor suppressor gene, is itself lost or mutated. Epidermal growth factor receptor, a growth factor that normally stimulates cells to divide, is amplified and stimulates cells to divide too much. Together, these mutations lead to cells dividing uncontrollably, a hallmark of cancer. In 2009, mutations in IDH1 and IDH2 were found to be part of the mechanism and associated with a less favorable prognosis.

Diagnosis
Classification
Gliomas are classified by cell type, by grade, and by location.

By type of cell
Gliomas are named according to the specific type of cell with which they share histological features, but not necessarily from which they originate. The main types of glioma are:
Ependymomas: ependymal cells
Astrocytomas: astrocytes (glioblastoma multiforme is a malignant astrocytoma and the most common primary brain tumor among adults).
Oligodendrogliomas: oligodendrocytes
Brainstem glioma: develop in the brain stem
Optic nerve glioma: develop in or around the optic nerve
Mixed gliomas, such as oligoastrocytomas, contain cells from different types of glia

By grade
Gliomas are further categorized according to their grade, which is determined by pathologic evaluation of the tumor. The neuropathological evaluation and diagnostics of brain tumor specimens is performed according to WHO Classification of Tumours of the Central Nervous System.

Biologically benign gliomas [WHO grade I] are comparatively low risk and can be removed surgically depending on their location
Low-grade gliomas [WHO grade II] are well-differentiated (not anaplastic);  these tend to exhibit  benign tendencies and portend a better prognosis for the patient. However, they have a uniform rate of recurrence and increase in grade over time so should be classified as malignant.
High-grade [WHO grades III–IV] gliomas are undifferentiated or anaplastic; these are malignant and carry a worse prognosis.Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma, under which tumors are graded from I (least advanced disease—best prognosis) to IV (most advanced disease—worst prognosis).

By location
Gliomas can be classified according to whether they are above or below a membrane in the brain called the tentorium. The tentorium separates the cerebrum (above) from the cerebellum (below).

The supratentorial is above the tentorium, in the cerebrum, and mostly found in adults (70%).
The infratentorial is below the tentorium, in the cerebellum, and mostly found in children (70%).
The pontine tumors are located in the pons of the brainstem. The brainstem has three parts (pons, midbrain, and medulla); the pons controls critical functions such as breathing, making surgery on these extremely dangerous.

Treatment
Treatment for brain gliomas depends on the location, the cell type, and the grade of malignancy. Often, treatment is a combined approach, using surgery, radiation therapy, and chemotherapy. A prolonged survival was observed when treating with radiotherapy and concomitant temozolomide. Radiotherapy was given for 5 days a week for 6 week, with a total of 60 Gy. Temozolomide was given daily during the treatment of radiotherapy, at a dose of 75 mg per square meter of body surface area per day. When radiotherapy ended additionally six cycles of temozolomide were given, for five days during each cycle of 28 days. The radiation therapy is in the form of external beam radiation or the stereotactic approach using radiosurgery. Spinal cord tumors can be treated by surgery and radiation. Temozolomide is a chemotherapy drug which can be administered easily in an outpatient setting and is able to cross the blood–brain barrier effectively. Treatment via immunotherapy may help some gliomas. Experimental therapies like oncolytic viruses have shown potential therapeutic benefits in clinical trials but has not been approved for use in clinic.

Refractory disease
For recurrent high-grade glioblastoma, recent studies have taken advantage of angiogenic blockers such as bevacizumab in combination with conventional chemotherapy, with encouraging results.

Relative effectiveness
A 2017 meta-analysis compared surgical resection versus biopsy as the initial surgical management option for a person with a low-grade glioma.  Results show the evidence is insufficient to make a reliable decision. The relative effectiveness of surgical resection compared to biopsy for people with malignant glioma (high-grade) is unknown.For high-grade gliomas, a 2003 meta-analysis compared radiotherapy with radiotherapy and chemotherapy.  It showed a small but clear improvement from using chemotherapy with radiotherapy. A 2019 meta-analysis suggested that for people with less aggressive gliomas, radiotherapy may increase the risk of long term neurocognitive side effects. Whilst, evidence is uncertain on whether there are long term neurocognitive side effects associated with chemoradiotherapy.Temozolomide is effective for treating Glioblastoma Multiforme (GBM) compared to radiotherapy alone. A 2013 meta-analysis showed that Temozolomide prolongs survival and delays progression, but is associated with an increase in side effects such as blood complications, fatigue, and  infection.  For people with recurrent GBM, when comparing temozolomide with chemotherapy, there may be an improvement in the time-to-progression and the persons quality of life, but no improvement in overall survival, with temozolomide treatment. Evidence suggests that for people with recurrent high-grade gliomas who have not had chemotherapy before, there are similar survival and time-to-progression outcomes between treatment with temozolomide or the chemotherapy multidrug known as PCV (procarvazine, lomustine and vincristine).A mutational analysis of 23 initial low-grade gliomas and recurrent tumors from the same patients has challenged the benefits and usage of Temozolomide. The study showed that when lower-grade brain tumors of patients are removed and patients are further treated with Temozolomide, 6 out of 10 times the recurrent tumors were more aggressive and acquired alternative and more mutations. As one of the last authors, Costello, stated "They had a 20- to 50-fold increase in the number of mutations. A patient who received surgery alone who might have had 50 mutations in the initial tumor and 60 in the recurrence. But patients who received TMZ might have 2,000 mutations in the recurrence." Further, new mutations were verified to carry known signatures of Temozolomide induced mutations. The research suggests that Temozolomide for the treatment of certain brain tumors should be thoroughly thought. Unjudicious usage of Temozolomide might lower the prognosis of the patients further, or increase their burden. Further understanding of the mechanisms of Temozolomide induced mutations and novel combination approaches could be promising.

Prognosis
Prognosis of gliomas is given in relation to what grade (as scored by the World Health Organization system) of tumour the patient presents with. Typically, any tumour presenting as above WHO grade I (i.e. a malignant tumour as opposed to a benign tumour) will have a prognosis resulting in eventual death, varying from years (WHO grade II/III) to months (WHO grade IV). Prognosis can also be given based on cellular subtype, which may also impact prognosis.

Low grade
For low-grade tumors, the prognosis is somewhat more optimistic. Patients diagnosed with a low-grade glioma are 17 times as likely to die as matched patients in the general population.
The age-standardized 10-year relative survival rate was 47%. One study reported that low-grade oligodendroglioma patients have a median survival of 11.6 years; another reported a median survival of 16.7 years. Unfortunately, approximately 70% of low-grade (WHO grade-II) will progress to high-grade tumours within 5–10 years

High grade
This group comprises anaplastic astrocytomas and glioblastoma multiforme. Whereas the median overall survival of anaplastic (WHO grade III) gliomas is approximately 3 years, glioblastoma multiforme has a poor median overall survival of c. 15 months.Postoperative conventional daily radiotherapy improves survival for adults with good functional well‐being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.

Diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma primarily affects children, usually between the ages of 5 and 7 </s>


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cracked nipple and explain in detail? [/INST] Cracked nipple (nipple trauma or nipple fissure) is a condition that can occur in breastfeeding women as a result of a number of possible causes. Developing a cracked nipple can result in soreness, dryness or irritation to, or bleeding of, one or both nipples during breastfeeding. The mother with a cracked nipple can have severe nipple pain when the baby is nursing. This severe pain is a disincentive for continued breastfeeding. The crack can appear as a cut across the tip of the nipple and may extend to its base. Cracked nipple develop after the birth of the infant and is managed with pharmacological and nonpharmacological treatment.

Signs and symptoms
Cracked nipples are classified as a breast disorder. The nipple is not only the structure to deliver milk to the infant, it also contains small, sebaceous glands or Montgomery glands to lubricate the skin of the areola. Cracked nipples are most often associated with breastfeeding and appear as cracks or small lacerations or breaks in the skin of the nipple. In some instances an ulcer will form. The nipple in a nursing mother is in regular contact with a nursing infant. Cracked nipples are trauma to the nipple and can be quite painful. Cracked nipples typically appear three to seven days after the birth.If the nipples appears to be wedge-shaped, white and flattened, this may indicate that the latch is not good and there is a potential of developing cracked nipples.

Complications
Bacteria can enter the breast through cracked nipples, which increase the risk of mastitis. Candida infection (thrush) of the nipple can also occur, resulting in deep-pink, cracked, and sore nipples.

Contraindications for breastfeeding
Because cracked nipples can result in the infant being exposed to blood, women with certain blood-borne diseases may be advised to stop breastfeeding if they have a cracked nipple. It has been found safe for breastfeeding mothers with hepatitis B and cracked nipples to breastfeed. In the event that a nursing woman experiences cracked and bleeding nipples or breast inflammation within one to two weeks immediately following an acute Toxoplasmosis infection (when the organism is still circulating in her bloodstream), it is theoretically possible that she could transmit Toxoplasma gondii to the infant through her breast milk. Immune suppressed women could have circulating Toxoplasma for even longer periods of time. However, the likelihood of human milk transmission is very small. Transmission risk of HIV increases if the mother has cracked and bleeding nipples An uncommon infection in the mother, Chagas disease, can be transmitted to the nursing infant via cracked nipples. Women with hepatitis C are advised to abstain from breastfeeding if their nipples are cracked or bleeding.

Cause
Some studies indicate that cracked nipples are caused by poor latch. Yet other causes could be poor positioning, use of a feeding bottle, breast engorgement, inexperience, semi-protruding nipples, use of breast pumps and light pigmentation of the nipples. Breast engorgement is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and curvature of the nipple region by making the breast inflexible, flat, hard, and swollen. The nipples on an engorged breast are flat.When the baby is latched on correctly, the nipple is located against the soft palate in the back of the babys mouth. When the nipple is near the front of the mouth and being pinched against the hard palate, this will cause pain and development of cracked nipples. One cause of painful, cracked nipples is the incorrect positioning and incorrect latching on to the breast by the infant. The baby can create cracked nipples due to the strong sucking pressure, stretching and pulling the nipple, the friction and rubbing of skin to skin. The cause of sore, cracked nipples can also be from a yeast or Candida infection in the baby or the mother or both. Thrush can develop after the use of antibiotics. For first-time breastfeeding mothers, it normally takes a few tries before the latch is right, which can make the nipples tender and sore the first few days. If the nipples become cracked or bleed, the latch may need to be corrected. Women are advised to keep on breastfeeding, as it will actually help the nipples heal. A little breast milk or purified lanolin cream or ointment helps the healing process.If a feeding bottle is used in addition to breastfeeding, cracked nipples may result because the different sucking techniques required for the bottle and the breast vary. Bottle-feeding babies uses his or her tongue to regulate the flow of milk. This same technique will cause friction on the nipple while breastfeeding. This, in turn, encourages the continued use of the bottle with less time breastfeeding.Pain caused by cracked nipples can sometimes lead to the cessation of breast-feeding. In addition to cracks, blisters or ulcers can form.

Prevention
The nipples of nursing mothers naturally make a lubricant to prevent drying, cracking, or infections. Cracked nipples may be able to be prevented by:

Avoid soaps and harsh washing or drying of the breasts and nipples. This can cause dryness and cracking.
Rubbing a little breast milk on the nipple after feeding to protect it.
Keeping the nipples dry to prevent cracking and infection.
Using seashells to keep nipples healthy through continuous contact with breast milkRoman chamomile is sometimes used as a remedy in alternative medicine to treat cracked nipples by a topical application. However, there is no scientific evidence for its efficacy, and is in fact considered unsafe for use during pregnancy.

Treatment
Cracked nipples can be treated with 100% lanolin. Glycerin nipple pads can be chilled and placed over the nipples to help soothe and heal cracked or painful nipples. If the cause of cracked nipples is from thrush, treatment is usually begun with nystatin. If the mother is symptomatic then the mother and the baby can be treated. Continuing to breastfeed will actually help the nipples heal. A little breast milk or purified lanolin cream or ointment helps the healing process. Breastfeeding professionals that include nurses, midwives and lactation consultants are able to assist in the treatment of cracked nipples.Advice from others is abundant but there have been some treatments that have been identified as not being effective in healing or preventing cracked nipples. These ineffective treatments are keeping the breastfeeding short and using a nipple guard. Keeping the feedings short so that the nipples can rest is not effective in relieving the pain of cracked nipples and it could have a negative effect on the milk supply. Nipple shields do not improve latching on.

Epidemiology
In a survey in New York City, 35% of nursing mothers stopped breastfeeding after one week due to the pain of cracked nipples. Thirty percent stopped breastfeeding between weeks one and three </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Twin and explain in detail? [/INST] Twins are two offspring produced by the same pregnancy. Twins can be either monozygotic (identical), meaning that they develop from one zygote, which splits and forms two embryos, or dizygotic (non-identical or fraternal), meaning that each twin develops from a separate egg and each egg is fertilized by its own sperm cell. Since identical twins develop from one zygote, they will share the same sex, while fraternal twins may or may not.  In rare cases twins can have the same mother and different fathers (heteropaternal superfecundation).
In contrast, a fetus that develops alone in the womb (the much more common case, in humans) is called a singleton, and the general term for one offspring of a multiple birth is a multiple. Unrelated look-alikes whose resemblance parallels that of twins are referred to as doppelgängers.

Statistics
The human twin birth rate in the United States rose 76% from 1980 through 2009, from 9.4 to 16.7 twin sets (18.8 to 33.3 twins) per 1,000 births. The Yoruba people have the highest rate of twinning in the world, at 45–50 twin sets (90–100 twins) per 1,000 live births, possibly because of high consumption of a specific type of yam containing a natural phytoestrogen which may stimulate the ovaries to release an egg from each side. In Central Africa, there are 18–30 twin sets (or 36–60 twins) per 1,000 live births. In North America, South Asia (India, Pakistan, Bangladesh, Nepal), and Southeast Asia, the lowest rates are found; only 6 to 9 twin sets per 1,000 live births. North America and Europe have intermediate rates of 9 to 16 twin sets per 1,000 live births.Multiple pregnancies are much less likely to carry to full term than single births, with twin pregnancies lasting on average 37 weeks, three weeks less than full term. Women who have a family history of fraternal twins have a higher chance of producing fraternal twins themselves, as there is a genetically linked tendency to hyper-ovulate. There is no known genetic link for identical twinning. Other factors that increase the odds of having fraternal twins include maternal age, fertility drugs and other fertility treatments, nutrition, and prior births. Some women intentionally turn to fertility drugs in order to conceive twins.

Types and zygosity
The vast majority of twins are either dizygotic (fraternal) or monozygotic (identical). Less common variants are discussed further down the article.
Fraternal twins can be any of the following:

Female–female twins: Sometimes called sororal twins (25%).
Male–male twins: Sometimes called fraternal twins (25%).
Female-male twins: This is the most common pairing (50%), simply by virtue of it encompassing both "female-male" (25%) and "male-female" (25%) twins.Among non-twin births, male singletons are slightly (about five percent) more common than female singletons. The rates for singletons vary slightly by country. For example, the sex ratio of birth in the US is 1.05 males/female, while it is 1.07 males/female in Italy. However, males are also more susceptible than females to die in utero, and since the death rate in utero is higher for twins, it leads to female twins being more common than male twins.Zygosity is the degree of identity in the genome of twins.

Dizygotic (fraternal) twins
Dizygotic (DZ) or fraternal twins (also referred to as "non-identical twins", "dissimilar twins", "biovular twins", and, informally in the case of females, "sororal twins") usually occur when two fertilized eggs are implanted in the uterus wall at the same time. When two eggs are independently fertilized by two different sperm cells, fraternal twins result. The two eggs, or ova, form two zygotes, hence the terms dizygotic and biovular. Fraternal twins are, essentially, two ordinary siblings who happen to develop in the womb together and who are born at the same time, since they arise from two separate eggs fertilized by two separate sperm, just like ordinary siblings. This is the most common type of twin.Dizygotic twins, like any other siblings, will practically always have different sequences on each chromosome, due to chromosomal crossover during meiosis. Dizygotic twins share only 50 percent of each others genes, which resemble amongst siblings that are conceived and born at different times. Like any other siblings, dizygotic twins may look similar, particularly as they are the same age. However, dizygotic twins may also look very different from each other (for example, be of opposite sexes).
Studies show that there is a genetic proclivity for dizygotic twinning. However, it is only the mother who has any effect on the chances of having such twins; there is no known mechanism for a father to cause the release of more than one ovum. Dizygotic twinning ranges from six per thousand births in Japan (similar to the rate of monozygotic twins) to 14 and more per thousand in some African countries.Dizygotic twins are also more common for older mothers, with twinning rates doubling in mothers over the age of 35. With the advent of technologies and techniques to assist women in getting pregnant, the rate of fraternals has increased markedly.

Monozygotic (identical) twins
Monozygotic (MZ) or identical twins occur when a single egg is fertilized to form one zygote (hence, "monozygotic") which then divides into two separate embryos. The chances of having identical twins is relatively rare — around 3 or 4 in every 1,000 births.

Mechanism
Regarding spontaneous or natural monozygotic twinning, a recent theory proposes that monozygotic twins are probably formed when a blastocyst contains two inner cell masses (ICM), each of which will lead to a separate fetus, rather than by the embryo splitting while hatching from the zona pellucida (the gelatinous protective coating around the blastocyst).Monozygotic twins may also be created artificially by embryo splitting. It can be used as an expansion of in vitro fertilization (IVF) to increase the number of available embryos for embryo transfer.

Incidence
Monozygotic twinning occurs in birthing at a rate of about 3 in every 1000 deliveries worldwide (about 0.3% of the world population).The likelihood of a single fertilization resulting in monozygotic twins is uniformly distributed in all populations around the world. This is in marked contrast to dizygotic twinning, which ranges from about six per thousand births in Japan (almost similar to the rate of identical twins, which is around 4–5) to 15 and more per thousand in some parts of India and up to over 20 in some Central African countries. The exact cause for the splitting of a zygote or embryo is unknown.
IVF techniques are more likely to create dizygotic twins. For IVF deliveries, there are nearly 21 pairs of twins for every 1,000.

Genetic and epigenetic similarity
Monozygotic twins are genetically nearly identical and they are always the same sex unless there has been a mutation during development. The children of monozygotic twins test genetically as half-siblings (or full siblings, if a pair of monozygotic twins reproduces with another pair or with the same person), rather than first cousins. Identical twins do not have the same fingerprints however, because even within the confines of the womb, the fetuses touch different parts of their environment, giving rise to small variations in their corresponding prints and thus making them unique.Monozygotic twins always have the same genotype. Normally due to an environmental factor or the deactivation of different X chromosomes in female monozygotic twins, and in some extremely rare cases, due to aneuploidy, twins may express different sexual phenotypes, normally from an XXY Klinefelter syndrome zygote splitting unevenly.Monozygotic twins, although genetically very similar, are not genetically exactly the same. The DNA in white blood cells of 66 pairs of monozygotic twins was analyzed for 506,786 single-nucleotide polymorphisms known to occur in human populations. Polymorphisms appeared in 2 of the 33 million comparisons, leading the researchers to extrapolate that the blood cells of monozygotic twins may have on the order of one DNA-sequence difference for every 12 million nucleotides, which would imply hundreds of differences across the entire genome. The mutations producing the differences detected in this study would have occurred during embryonic cell-division (after the point of fertilization). If they occur early in fetal development, they will be present in a very large proportion of body cells.
Another cause of difference between monozygotic twins is epigenetic modification, caused by differing environmental influences throughout their lives. Epigenetics refers to the level of activity of any particular gene. A gene may become switched on, switched off, or could become partially switched on or off in an individual. This epigenetic modification is triggered by environmental events. Monozygotic twins can have markedly different epigenetic profiles. A study of 80 pairs of monozygotic twins ranging in age from three to 74 showed that the youngest twins have relatively few epigenetic differences. The number of epigenetic differences increases with age. Fifty-year-old twins had over three times the epigenetic difference of three-year-old twins. Twins who had spent their lives apart (such as those adopted by two different sets of parents at birth) had the greatest difference. However, certain characteristics become more alike as twins age, such as IQ and personality.In January 2021, new research from a team of researchers in Iceland was published in the journal Nature Genetics suggesting that identical twins may not be quite as identical as previously thought. The four-year study of monozygotic (identical) twins and their extended families revealed that these twins have genetic differences that begin in the early stages of embryonic development.

Polar body and semi-identical twins
A 1981 study of a deceased triploid XXX twin fetus without a heart showed that although its fetal development suggested that it was an identical twin, as it shared a placenta with its healthy twin, tests revealed that it was probably a polar body twin. The authors were unable to predict whether a healthy fetus could result from a polar body twinning. However, a study in 2012 found that it is possible for a polar body to result in a healthy fetus.In 2003, a study argued that many cases of triploidy arise from sesquizygotic (semi-identical) twinning.

Sesquizygotic twin type
See Semi-identical (sesquizygotic) twins below, under Unusual twinnings.

Degree of separation
The degree of separation of the twins in utero depends on if and when they split into two zygotes.  Dizygotic twins were always two zygotes.  Monozygotic twins split into two zygotes at some time very early in the pregnancy.  The timing of this separation determines the chorionicity (the number of placentae) and amniocity (the number of sacs) of the pregnancy.  Dichorionic twins either never divided (i.e.: were dizygotic) or they divided within the first 4 days. Monoamnionic twins divide after the first week.
In very rare cases, twins become conjoined twins. Non-conjoined monozygotic twins form up to day 14 of embryonic development, but when twinning occurs after 14 days, the twins will likely be conjoined. Furthermore, there can be various degrees of shared environment of twins in the womb, potentially leading to pregnancy complications.
It is a common misconception that two placentas automatically implies dizygotic twins, but if monozygotic twins separate early enough, the arrangement of sacs and placentas in utero is in fact indistinguishable from that of dizygotic twins.

Demographics
A 2006 study has found that insulin-like growth factor present in dairy products may increase the chance of dizygotic twinning. Specifically, the study found that vegan mothers (who exclude dairy from their diets) are one-fifth as likely to have twins as vegetarian or omnivore mothers, and concluded that "Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation."From 1980 to 1997, the number of twin births in the United States rose 52%. This rise can at least partly be attributed to the increasing popularity of fertility drugs and procedures such as IVF, which result in multiple births more frequently than unassisted fertilizations do. It may also be linked to the increase of growth hormones in food.

Ethnicity
About 1 in 90 human births (1.1%) results from a twin pregnancy. The rate of dizygotic twinning varies greatly among ethnic groups, ranging as high as about 45 per 1000 births (4.5%) for the Yoruba to 10% for Linha São Pedro, a tiny Brazilian settlement which belongs to the city of Cândido Godói. In Cândido Godói, one in five pregnancies has resulted in twins. The Argentine historian Jorge Camarasa has put forward the theory that experiments of the Nazi doctor Josef Mengele could be responsible for the high ratio of twins in the area. His theory was rejected by Brazilian scientists who had studied twins living in Linha São Pedro; they suggested genetic factors within that community as a more likely explanation. A high twinning rate has also been observed in other places of the world, including:

Igbo-Ora in Nigeria
Kodinhi, located in Kerala, India
Mohammadpur Umri, located in Uttar Pradesh, IndiaThe widespread use of fertility drugs causing hyperovulation (stimulated release of multiple eggs by the mother) has caused what some call an "epidemic of multiple births". In 2001, for the first time ever in the US, the twinning rate exceeded 3% of all births. Nevertheless, the rate of monozygotic twins remains at about 1 in 333 across the globe.
In a study on the maternity records of 5750 Hausa women living in the Savannah zone of Nigeria, there were 40 twins and 2 triplets per 1000 births. Twenty-six percent of twins were monozygotic. The incidence of multiple births, which was about five times higher than that observed in any western population, was significantly lower than that of other ethnic groups, who live in the hot and humid climate of the southern part of the country. The incidence of multiple births was related to maternal age but did not bear any association to the climate or prevalence of malaria.Twins are more common in people of African descent.

Predisposing factors
The predisposing factors of monozygotic twinning are unknown.
Dizygotic twin pregnancies are slightly more likely when the following factors are present in the woman:

She is of West African descent (especially Yoruba)
She is between the age of 30 and 40 years
She is greater than average height and weight
She has had several previous pregnancies.Women undergoing certain fertility treatments may have a greater chance of dizygotic multiple births. In the United States it has been estimated that by 2011 36% of twin births resulted from conception by assisted reproductive technology.The risk of twin birth can vary depending on what types of fertility treatments are used. With in vitro fertilisation (IVF), this is primarily due to the insertion of multiple embryos into the uterus. Ovarian hyperstimulation without IVF has a very high risk of multiple birth. Reversal of anovulation with clomifene (trade names including Clomid) has a relatively less but yet significant risk of multiple pregnancy.

Delivery interval
A 15-year German study of 8,220 vaginally delivered twins (that is, 4,110 pregnancies) in Hesse yielded a mean delivery time interval of 13.5 minutes. The delivery interval between the twins was measured as follows:

Within 15 minutes: 75.8%
16–30 minutes: 16.4%
31–45 minutes: 4.3%
46–60 minutes: 1.7%
Over 60 minutes: 1.8% (72 instances)The study stated that the occurrence of complications "was found to be more likely with increasing twin-to-twin delivery time interval" and suggested that the interval be kept short, though it noted that the study did not examine causes of complications and did not control for factors such as the level of experience of the obstetrician, the wish of the women giving birth, or the "management strategies" of the procedure of delivering the second twin.
There have also been cases in which twins are born a number of days apart. Possibly the worldwide record for the duration of the time gap between the first and the second delivery was the birth of twins 97 days apart in Cologne, Germany, the first of which was born on November 17, 2018.

Complications during pregnancy
Vanishing twins
Researchers suspect that as many as 1 in 8 pregnancies start out as multiples, but only a single fetus is brought to full term, because the other fetus has died very early in the pregnancy and has not been detected or recorded. Early obstetric ultrasonography exams sometimes reveal an "extra" fetus, which fails to develop and instead disintegrates and vanishes in the uterus. There are several reasons for the "vanishing" fetus, including it being embodied or absorbed by the other fetus, placenta or the mother. This is known as vanishing twin syndrome. Also, in an unknown proportion of cases, two zygotes may fuse soon after fertilization, resulting in a single chimeric embryo, and, later, fetus.

Conjoined twins
Conjoined twins (or the once-commonly used term "siamese") are monozygotic twins whose bodies are joined together during pregnancy. This occurs when the zygote starts to split after day 12 following fertilization and fails to separate completely. This condition occurs in about 1 in 50,000 human pregnancies.
Most conjoined twins are now evaluated for surgery to attempt to separate them into separate functional bodies. The degree of difficulty rises if a vital organ or structure is shared between twins, such as the brain, heart, liver or lungs.

Chimerism
A chimera is an ordinary person or animal except that some of their parts actually came from their twin or from the mother. A chimera may arise either from monozygotic twin fetuses (where it would be impossible to detect), or from dizygotic fetuses, which can be identified by chromosomal comparisons from various parts of the body. The number of cells derived from each fetus can vary from one part of the body to another, and often leads to characteristic mosaicism skin coloration in human chimeras. A chimera may be intersex, composed of cells from a male twin and a female twin. In one case DNA tests determined that a woman, Lydia Fairchild, mystifyingly, was not the mother of two of her three children; she was found to be a chimera, and the two children were conceived from eggs derived from cells of their mothers twin.

Parasitic twins
Sometimes one twin fetus will fail to develop completely and continue to cause problems for its surviving twin. One fetus acts as a parasite towards the other.
Sometimes the parasitic twin becomes an almost indistinguishable part of the other, and sometimes this needs to be treated medically.

Partial molar twins
A very rare type of parasitic twinning is one where a single viable twin is endangered when the other zygote becomes cancerous, or "molar". This means that the molar zygotes cellular division continues unchecked, resulting in a cancerous growth that overtakes the viable fetus. Typically, this results when one twin has either triploidy or complete paternal uniparental disomy, resulting in little or no fetus and a cancerous, overgrown placenta, resembling a bunch of grapes.

Miscarried twin
Occasionally, a woman will suffer a miscarriage early in pregnancy, yet the pregnancy will continue; one twin was miscarried but the other was able to be carried to term. This occurrence is similar to the vanishing twin syndrome, but typically occurs later, as the twin is not reabsorbed.

Low birth weight
It is very common for twins to be born at a low birth weight. More than half of twins are born weighing less than 5.5 pounds (2.5 kg), while the average birth weight of a healthy baby should be around 6–8 pounds (3–4 kg). This is largely due to the fact that twins are typically born premature. Premature birth and low birth weights, especially when under 3.5 pounds (1.6 kg), can increase the risk of several health-related issues, such as vision and hearing loss, mental disabilities, and cerebral palsy. There is an increased possibility of potential complications as the birth weight of the baby decreases.

Twin-to-twin transfusion syndrome
Monozygotic twins who share a placenta can develop twin-to-twin transfusion syndrome. This condition means that blood from one twin is being diverted into the other twin. One twin, the donor twin, is small and anemic, the other, the recipient twin, is large and polycythemic. The lives of both twins are endangered by this condition.

Stillbirths
Stillbirths occurs when a fetus dies after 20 weeks of gestation. There are two types of stillbirth, including intrauterine death and intrapartum death. Intrauterine death occurs when a baby dies during late pregnancy. Intrapartum death, which is more common, occurs when a baby dies while the mother is giving birth. The cause of stillbirth is often unknown, but the rate of babies who are stillborn is higher in twins and multiple births. Caesareans or inductions are advised after 38 weeks of pregnancy for twins, because the risk of stillbirth increases after this time.

Heterotopic pregnancy
Heterotopic pregnancy is an exceedingly rare type of dizygotic twinning in which one twin implants in the uterus as normal and the other remains in the fallopian tube as an ectopic pregnancy. Ectopic pregnancies must be resolved because they can be life-threatening to the mother. However, in most cases, the intrauterine pregnancy can be salvaged.

Management of birth
For otherwise healthy twin pregnancies where both twins are head down a trial of vaginal delivery is recommended at between 37 and 38 weeks. Vaginal delivery in this case does not worsen the outcome for the infant as compared with Caesarean section.  There is controversy on the best method of delivery where the first twin is head first and the second is not. When the first twin is not head down a caesarean section is often recommended.  It is estimated that 75% of twin pregnancies in the United States were delivered by caesarean section in 2008. In comparison, the rate of caesarean section for all pregnancies in the general population varies between 14% and 40%. In twins that share the same placenta, delivery may be considered at 36 weeks. For twins who are born early, there is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding).

Human twin studies
Twin studies are utilized in an attempt to determine how much of a particular trait is attributable to either genetics or environmental influence. These studies compare monozygotic and dizygotic twins for medical, genetic, or psychological characteristics to try to isolate genetic influence from epigenetic and environmental influence. Twins that have been separated early in life and raised in separate households are especially sought-after for these studies, which have been used widely in the exploration of human nature.  Classical twin studies are now being supplemented with molecular genetic studies which identify individual genes.

Unusual twinnings
Bi-paternal twins
This phenomenon is known as heteropaternal superfecundation. One 1992 study estimates that the frequency of heteropaternal superfecundation among dizygotic twins, whose parents were involved in paternity suits, was approximately 2.4%; see the references section, below, for more details.Dizygotic twins from biracial couples can sometimes be mixed twins, which exhibit differing ethnic and racial features. One such pairing was born in London in 1993 to a white mother and Caribbean father.

Monozygotic twins of different sexes
Among monozygotic twins, in extremely rare cases, twins have been born with different sexes (one male, one female). When monozygotic twins are born with different sexes it is because of chromosomal defects.  The probability of this is so small that multiples having different sexes is universally accepted as a sound basis for in utero clinical determination that the multiples are not monozygotic.
Another abnormality that can result in monozygotic twins of different sexes is if the egg is fertilized by a male sperm but during cell division only the X chromosome is duplicated. This results in one normal male (XY) and one female with Turner syndrome (45,X).  In these cases, although the twins did form from the same fertilized egg, it is incorrect to refer to them as genetically identical, since they have different karyotypes.

Semi-identical (sesquizygotic) twins
Monozygotic twins can develop differently, due to their genes being differently activated. More unusual are "semi-identical twins", also known as "sesquizygotic". As of 2019, only two cases have been reported. These "half-identical twins" are hypothesized to occur when an unfertilized egg cleaves into two identical attached ova, both of which are viable for fertilization. Both ova are then fertilized, each by a different sperm, and the coalesced zygotes undergo further cell duplications developing as a chimeric blastomere. If this blastomere then undergoes a twinning event, two embryos will be formed, with different paternal genetic information and identical maternal genetic information.
This results in a set of twins with identical gene sequence from the mothers side, but different sequences from the fathers side. Cells in each fetus carry chromosomes from either sperm, resulting in chimeras. This form had been speculated until only recently being recorded.

In 2007, a study reported a case of a pair of living twins, which shared an identical set of maternal chromosomes, while each having a distinct set of paternal chromosomes, albeit from the same man, and thus they most likely share half of their fathers genetic makeup. The twins were both found to be chimeras. One was an intersex XX, and one a XY male. The exact mechanism of fertilization could not be determined but the study stated that it was unlikely to be a case of polar body twinning.In 2019, a second case of sesquizygotic twins was reported and molecular evidence of the phenomenon was documented by Gabbett and Fisk. In this case, the twins shared 100% of their maternal chromosomes and 78% of their paternal genomic information. The authors postulate two sperm from the same man fertilized an ovum simultaneously. The chromosomes assorted themselves through heterogonesis to form three cell lines. The purely paternal cell line died out due to genomic imprinting lethality, while the other two cell lines, each conisiting of the same maternal DNA but only 50% identical paternal DNA, formed a morula which subsequently split into twins

Mirror image twins
Mirror image twins result when a fertilized egg splits later in the embryonic stage than normal timing, around day 9–12. This type of twinning could exhibit characteristics with reversed asymmetry, such as opposite dominant handedness, dental structure, or even organs (situs inversus). If the split occurs later than this time period, the twins risk being conjoined. There is no DNA-based zygosity test that can determine if twins are indeed mirror image. The term "mirror image" is used because the twins, when facing each other, appear as matching reflections.

Language development
There have been many studies highlighting the development of language in twins compared to single-born children. These studies have converged on the notion that there is a greater rate of delay in language development in twins compared to their single-born counterparts.  The reasons for this phenomenon are still in question; however, cryptophasia was thought to be the major cause.  Idioglossia is defined as a private language that is usually invented by young children, specifically twins. Another term to describe what some people call "twin talk" is cryptophasia where a language is developed by twins that only they can understand.  The increased focused communication between two twins may isolate them from the social environment surrounding them.  Idioglossia has been found to be a rare occurrence and the attention of scientists has shifted away from this idea.  However, there are researchers and scientists that say cryptophasia or idioglossia is not a rare phenomenon. Current research is looking into the impacts of a richer social environment for these twins to stimulate their development of language.

Animals
Twins are common in many mammal species, including cats, sheep, ferrets, giant pandas,Cow,dolphins, dogs, deer, marmosets, tamarins, and elephants. The incidence of twinning among cattle is about 1–4%, and research is underway to improve the odds of twinning, which can be more profitable for the breeder if complications can be sidestepped or managed. A female calf that is the twin of a bull becomes partially masculinized and is known as a freemartin.

See also
References
Further reading
Bacon, Kate. Twins in Society: Parents, Bodies, Space, and Talk (Palgrave Macmillan; 2010) 221 pages; explores the experience of child twins, adult twins, and parents of twins, with a focus on Britain.
Nieuwint, Aggie; Van Zalen-Sprock, Rieteke; Hummel, Pieter; Pals, Gerard; Van Vugt, John;  et al. (1999). "Identical twins with discordant karyotypes". Prenatal Diagnosis. 19 (1): 72–6. doi:10.1002/(SICI)1097-0223(199901)19:1<72::AID-PD465>3.0.CO;2-V. PMID 10073913. S2CID 19112883.
Wenk RE, Houtz T, Brooks M, Chiafari FA (1992). "How frequent is heteropaternal superfecundation?". Acta Geneticae Medicae et Gemellologiae. 41 (1): 43–7. doi:10.1017/S000156600000249X. PMID 1488855. S2CID 23507167.
Girela, Eloy; Lorente, Jose A.; Alvarez, J. Carlos; Rodrigo, Maria D.; Lorente, Miguel;  et al. (1997). "Indisputable double paternity in dizygous twins". Fertility and Sterility. 67 (6): 1159–61. CiteSeerX 10.1.1.378.4082. doi:10.1016/S0015-0282(97)81456-2. PMID 9176461.
Shinwell ES, Reichman B, Lerner-Geva L, Boyko V, Blickstein I (September 2007). ""Masculinizing" effect on respiratory morbidity in girls from unlike-sex preterm twins: a possible transchorionic paracrine effect". Pediatrics. 120 (3): e447–53. doi:10.1542/peds.2006-3574. PMID 17766488. S2CID 20498737. Retrieved 2008-10-06.
Lummaa V, Pettay JE, Russell AF (June 2007). "Male twins reduce fitness of female co-twins in humans". Proceedings of the National Academy of Sciences of the United States of America. 104 (26): 10915–20. Bibcode:2007PNAS..10410915L. doi:10.1073/pnas.0605875104. PMC 1904168. PMID 17576931.
Schein, Elyse; Paula Bernstein (2007). Identical Strangers: A Memoir of Twins Separated and Reunited. New York: Random House. ISBN 978-1-4000-6496-0. OCLC 123390922.
Helle, Samuli; Virpi Lummaa; Jukka Jokela (2004). "Selection for Increased Brood Size in Historical Human Populations" (PDF). Evolution. 58 (2): 430–436. doi:10.1111/j.0014-3820.2004.tb01658.x. PMID 15068359. S2CID 9460009. Archived from the original (PDF) on 2008-10-02. Retrieved 2008-10-02.
"TWINS Guide to the First Year" (PDF). TWINS Magazine. Fort Collins, Colorado. 2008. Archived from the original (PDF) on 2008-10-30 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Primary juvenile glaucoma and explain in detail? [/INST] Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life. It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous outflow in the absence of systemic anomalies or other ocular malformation.

Presentation
The typical infant who has congenital glaucoma usually is initially referred to an ophthalmologist because of apparent corneal edema. The commonly described triad of epiphora (excessive tearing), blepharospasm and photophobia may be missed until the corneal edema becomes apparent.

Systemic associations
Two of the more commonly encountered disorders that may be associated with congenital glaucoma are Aniridia and Sturge-Weber syndrome.

Genetics
JOAG is an autosomal dominant condition. The primary cause is the myocilin protein dysfunction. Myocilin gene mutations are identified in approximately 10% of patients affected by juvenile glaucoma.

Diagnosis
The diagnosis is clinical. The intraocular pressure (IOP) can be measured in the office in a conscious swaddled infant using a Tonopen or hand-held Goldmann tonometer. Usually, the IOP in normal infants is in the range of 11-14 mmHg. Buphthalmos and Haabs striae can often be seen in case of congenital glaucoma.

Differential diagnosis
Corneal cloudiness may have myriad of causes. Corneal opacity that results from hereditary dystrophies is usually symmetric.
Corneal enlargement may result from megalocornea, a condition in which the diameter of the cornea is larger than usual and the eye is otherwise normal.

Treatment
The preferred treatment of congenital glaucoma is surgical, not medical. The initial procedures of choice are goniotomy or trabeculotomy if the cornea is clear, and trabeculectomy ab externo if the cornea is hazy. The success rates are similar for both procedures in patients with clear corneas </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Neutrophilic eccrine hidradenitis and explain in detail? [/INST] Neutrophilic eccrine hidradenitis (NEH) usually is a cutaneous complication of chemotherapy, but it can also occur for other reasons. It consists of fever and non specific skin lesions. It is rare, and self-limited.

Signs and symptoms
Fever and a non specific skin eruption – with reddening (erythema) and swelling (oedema) of the skin – are the most common symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis. Generalised lesions resembling erythema multiforme have been reported.

Cause
The overwhelming majority of neutrophilic eccrine hidradenitis (NEH) is seen in people with cancer, especially leukaemia, who receive chemotherapy with a cytotoxic drug. These include: Bleomycin, chlorambucil, cyclophosphamide, cytarabine, doxorubicin, lomustine, mitoxantrone, topotecan, and vincristine.NEH was first described in 1982 in a patient with acute myeloid leukaemia (AML) who had received cytarabine as chemotherapy.Cancer itself, infections, and other medicinal drugs also can lead to NEH. NEH has been reported in patients with cancer who have not received any form of chemotherapy (i.e., as a paraneoplastic syndrome), in patients with HIV and/or AIDS, and after the use of paracetamol (acetaminophen). Also the use of targeted agents can lead to NEH, e.g. imatinib, a tyrosine kinase inhibitor.NEH has also been described without any known reason (idiopathic cases), including idiopathic cases in children.The exact cause of NEH is unknown </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Spermatocele and explain in detail? [/INST] Spermatocele is a fluid-filled cyst that develops at the top of the testicle of the epididymis. The fluid is usually a clear or milky white color and may contain sperm. Spermatoceles are typically filled with spermatozoa and they can vary in size from several millimeters to many centimeters. Small spermatoceles are relatively common, occurring in an estimated 30 percent of males. They are generally not painful. However, some people may experience discomfort such as a dull pain in the scrotum from larger spermatoceles. They are not cancerous, nor do they cause an increased risk of testicular cancer. Additionally, unlike varicoceles, they do not reduce fertility.

History
"Spermatocele" is originally derived from the Greek term spermatos (sperm) and kele (cavity or mass). Oftentimes, "epididymal cyst" has been used interchangeably with "spermatocele." However, it is important to note their differences. Epididymal cysts may appear anywhere along or within the epididymis and do not contain sperm, whereas spermatoceles may contain sperm. Epididymal cysts have been shown to occur more frequently in children before reaching puberty.

Epidemiology
Spermatoceles usually affect men who are middle-aged and can, although rarely, affect children during puberty. The incidence rate is around 5-20% for children. It is estimated that approximately 30 percent of men have been diagnosed with small spermatoceles while less have larger spermatoceles. The incidence of spermatoceles increases as men age. Before puberty, children from the male sex may develop a similar benign mass called epididymis cyst. Although both epididymis cyst and spermatocele may be referred as the same, the epididymis cyst does not contain sperm and it can occur anywhere within the epididymis. It can be differentiated through an ultrasound imagining. Epididymis cysts larger than 10mm in diameter are recommended for surgery but if there is no problem then surgery is discouraged as it can affect fertility in the future.

Chronic infectious epididymitis
Chronic infectious epididymitis is rare. Some signs and symptoms include localized tenderness and swelling in the epididymis, which are different from any tenderness/abnormality present in the testis, these are usually not found in lower urinary tract. Chronic infectious epididymitis may be diagnosed in healthy adolescents as well as men. Some factors that predispose individuals to chronic infectious epididymitis include sexual activity, heavy physical exertion, and bicycle or motorcycle riding. Those diagnosed with chronic or recurrent epididymitis should receive a CT scan with contrast and a prostate ultrasonography to rule out structural abnormality of the urinary tract. If suspected to have chronic infectious epididymitis, consider getting a urinalysis, urine culture, and urine nucleic acid amplification tests for presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Management of chronic infectious epididymitis is similar to management of acute infectious epididymitis, rarely does treatment extend to surgical management.

Chronic noninfectious epididymitis
Chronic noninfectious epididymitis – Trauma, autoimmune disease, or vasculitis can cause chronic noninfectious epididymitis, but no clear cause or origin of the disease is found in most cases.  Noninfectious epididymitis that happen spontaneously might be caused by the reflux of urine through the ejaculatory ducts and vas deferens into the epididymis, producing inflammation that leads to swelling and ductal obstruction. Men with history of vasectomy are also predisposed to chronic nonifectious epididymitis. Typical inciting factors include prolonged periods of sitting (long plane or car travel, sedentary desk jobs) or vigorous exercise (heavy lifting). Acute infectious epididymitis are often associated with more tenderness and swelling, whereas chronic noninfectious epididymitis tend to have less tenderness and swelling upon examination. Thorough past medical history and physical examination can help with determining the diagnosis. It is often that individuals with chronic noninfectious epididymitis will present with a history of a lack of symptom improvement while on antibiotic therapy. Management of chronic noninfectious epididymitis includes scrotal elevation, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (unless unable to take for medical reasons), and it is recommended that individuals avoid physical activities that may cause said symptoms. Those with sedentary jobs or often experience prolonged periods of time sitting should practice physical mobility more frequently.

Risk Factors
It is not well known what may be causing the growth of a spermatocele. It has been observed that pregnant women who were prescribed diethylstilbestro (DES) to prevent pregnancy complications, such as miscarriage, and gave birth to a son most likely increased the risk of the son to develop a spermatocele in the future. However, doctors stopped prescribing this medication in 1971 since it increased the risk of women developing a rare vaginal cancer.

Causes
Spermatoceles can originate as diverticulum from the tubules found in the head of the epididymis. Sperm accumulation gradually causes the diverticulum to increase in size, causing a spermatocele. Since there are many tubules connecting the epididymis to the testis, a blockage in one of the tubules may lead to formation of a cyst. In many instances they appear to occur spontaneously without any preceding instances of injury.Scarring of any part of the epididymis due to trauma or inflammation can cause it to become obstructed and in turn form a spermatocele.

Diagnosis
Spermatoceles can be discovered as incidental scrotal masses found on physical examination by a physician or by self-inspection of the scrotum and testicles. The various types of diagnosis for spermatocele types include hydrocele, varicocele, hernia, simple epididymal cyst, and neoplasm.The primary care physician may diagnose and manage benign causes of scrotal masses such as hydrocele, varicocele and spermatocele. However, if a "must not miss" diagnoses related to testicular masses such as testicular torsion, epididymitis, acute orchitis, strangulated hernia and testicular cancer is suspected, the family physician must refer to a urologist.
Finding a painless, cystic mass at the head of the epididymis that is clearly separate from the testicle can indicate a spermatocele. Shining a light through the mass through a process known as transillumination can also help differentiate between a fluid-filled cyst and a tumor, which would not allow as much light to pass. If uncertainty exists, ultrasonography of the scrotum can confirm the presence of a spermatocele. The location and history of any scrotal masses are crucial in determining whether or not the mass is benign or malignant. Lab tests such as a complete blood count (CBC test) or urine test can also be conducted to check for any possible infection or signs of inflammation.Spermatoceles come in varying sizes and shapes. Some spermatoceles are very small and can only be detected through an ultrasound. More commonly seen are spermatoceles that are a pea-sized lump. They tend to form above or behind a testicle and have a shape and size that looks like a pea. Larger growths have been reported to look similar to a third testicle and can be very discomforting. For those who are affected with large spermatoceles, some have reported feeling pain, heaviness, and fullness in the affected testicle.

When to see a doctor
If a person is experiencing pain and/or swelling in the scrotum or if a person notices a physical difference such as a mass during a testicular self-exam then they must seek medical attention quickly to help rule out any other causes and begin treatment.

Special Populations
Spermatoceles in Children
Epididymal cysts may arise in children due to numerous different reasons. They may even originate from a disturbance in endocrine factors during the development of the embryo. The incidence of these cysts are possibly linked to boys who are exposed to diethylstilbestrol, an estrogen medication, while in the fetus.Although the evidence and information for incidence of spermatoceles in children is lacking, there are general management guidelines for caregivers who may encounter spermatoceles in their children. Epididymal cysts are typically benign in nature. However, caregivers should take note of any discomfort and symptoms in children, including but not limited to, erythema, scrotal edema or swelling. Epididymal cysts appear in approximately 70% of boys who present as asymptomatic. The diagnosis of epididymal cysts in children can be discovered upon physical examination and eventually confirmed via ultrasound.

Treatment
Small cysts as well as asymptomatic larger cysts are better left alone and carefully observed. However, treatment can be considered if the cysts are causing discomfort/pain, enlarging in size, or per patient request. There are a few different treatment options, ranging in levels of invasiveness.

Medications
Certain drugs such as oral analgesics or anti-inflammatory medications can be taken by mouth to decrease spermatocele-related symptoms such as pain and/or swelling. At the moment, there is no medication that can inhibit the production of a spermatocele or cure it. Common medications recommended by doctors are acetaminophen (Tylenol) that can treat pain. To treat the inflammation and pain, non-steroidal anti-inflammatory drugs (NSAIDs) are recommended such as ibuprofen (Motrin, Advil), naproxen (Aleve), and others. Antibiotics may also be prescribed in cases where risk of infection and discomfort is indicated.

Medical Procedures
Aspiration and sclerotherapy are treatments that remove fluid from the spermatocele and seal the spermatocele sac closed from further fluid build-up, respectively. Due to a higher risk of epididymis damage, fertility problems, and further recurrences, these procedures are not recommended and not commonly used.

Surgical Treatments
Surgical treatments must be thoroughly discussed with people prior to any final decisions. Different types of surgical procedures may be chosen based on the extent of risk.A short procedure called a spermatocelectomy can be performed for spermatoceles that cause irritating symptoms. This standard procedure can be performed in an outpatient setting with the use of local or general anesthesia. This procedure typically consists of removing the spermatocele and a portion of the epididymis. The risk of epididymal injury is 17.12%. This incident may happen when the spermatocele is being dissected from the head of the epididymis. Spermatocelectomy can cause complications such as hematoma, wound infection, scrotal abscess as well as recurrence. After surgery, the doctor may recommend to apply ice packs for several days to help reduce swelling. Oral pain medications can also be taken for a few days to reduce discomfort. In addition, the patient returns 2–6 weeks after to inspect any progress/complications. If received a vasectomy, then two semen samples must be collected and analyzed after 6–12 weeks post-operation and several ejaculations. The centrifuged semen samples are used to look for the absence of viable sperm in the semen.

Risk of Complications
After surgical removal, it is possible that the pain will persist and recurrence can occur. Fertility may be compromised with these surgical procedures, so people may consider postponing surgery until after having children </s>


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

Signs and symptoms
It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin can be either generalised or localised. Biopsies have shown reduction and degeneration of dermal elastic fibres in the affected areas of skin. The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints may be loose (hypermobile) because of lax ligaments and tendons. When cutis laxa is severe, it can also affect the internal organs. The lungs, heart (supravalvular pulmonary stenosis), intestines, or arteries may be affected with a variety of severe impairments. In some cases, hernias and outpouching of the bladder can be observed. Patients can also present with whites of the eyes that are blue.

Causes
In many cases, cutis laxa is inherited. Autosomal dominant, autosomal recessive, and X-linked recessive forms have been described, but acquired forms also occur.Cutis laxa is associated with deficient or absent elastin fibers in the extracellular matrix. This can be related to decreased elastin synthesis or structural defects in the extracellular matrix.Cutis laxa may be caused by mutations in the genes: ELN, ATP6V0A2,ATP7A, FBLN4, FBLN5, and PYCR1. A related neurocutaneous syndrome may be caused by mutations in the gene ALDH18A1 (P5CS). Cutis laxa may also be seen in association with inherited connective tissue disorders such as Ehlers–Danlos syndromes </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sonoda syndrome and explain in detail? [/INST] Sonoda syndrome is a rare genetic disorder characterized by cranio-facial dysmorphisms, fingerprint abnormalities, intellectual disability, and congenital cardiopathy. It has been described in a Japanese family.

History
This condition has only been described once in history in three siblings from Japan (1987).This trio of siblings was born in Miyazaki Prefecture, Japan to healthy, non-consanguineous Japanese parents who were in their mid-20s (25 years old, to be exact). The parents height (the father was 170 cm tall and the mother was 153 cm tall), skin color (light), and craniofacial appearance were normal and average for their Japanese background, the mother did not have any history of miscarriage or stillbirth. While the both of them denied parental consanguinity, both of their familial lineages had lived in the same small isolated village for various years.The proband was a 6-year-old toddler girl, she was born weighing 2664 grams. Measurements taken in March 1983 (nearly 2 years after her birth) showed a height of 73.1 cm, a weight of 7.1 kg, and a head circumference of 46 cm. Physical examination done in 87 detailed her dark skin tone and light brown hair (which the authors described as uncommon among the Japanese), a round face, flat nasal bridge, small nose, nostril anteversion, and the presence of whorls and loops in her fingerprints (3 and 7, respectively). Routine laboratory tests and a 550-band level karyotype gave normal results. She was noted to have a heart murmur which was then discovered to be caused by a ventricular septal defect (a type of congenital heart defect), but it disappeared on its own few years after the physical examination that discovered said defect (thought to be caused by a spontaneous closure of said defect).The second case was her younger, 4-year-old toddler brother. He was born weighing 3042 grams, and was noted to have cyanosis at birth, which was an indicator for a possible heart anomaly. He learned how to control his head at 3 months of age and learned how to walk when he was 20 months old, at the age of 2 he was found to have a speech delay and could only say a handful of words. Physical examination done on him in July 1984 showed a height of 72.7 cm, a weight of 7.7 km, and a head circumference of 44.5 cm. He had the same skin tone, hair color, and facial characteristics as his proband sister. A systolic ejection murmur (grade 4/6) could be heard at his second left intercostal face, this same murmur was later discovered to be caused by pulmonary valve stenosis. Like his sister, he also had whorls and loops in his fingerprints (4 and 6, respectively), and he had routine laboratory tests and a karyotype which turned back normal. Physical examination done in him again in May 1987 showed a height of 94.3 cm, a weight of 45.2 kg, and a head circumference of 49.7 cm. His bone age was appropriate for his age.The third and final case was the youngest brother of the three, a 2-year old infant boy </s>