<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 Molar pregnancy and explain in detail? [/INST] A molar pregnancy also known as a hydatidiform mole, is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus. A molar pregnancy is a type of gestational trophoblastic disease that used to be known as a hydatidiform mole. A molar pregnancy grows into a mass in the uterus that has swollen chorionic villi that grow in clusters resembling grapes. A molar pregnancy can develop when a fertilized egg does not contain an original maternal nucleus. The products of conception may or may not contain fetal tissue. Molar pregnancies are categorized as partial moles or complete moles, with the word mole being used to denote simply a clump of growing tissue, or a growth.
A complete mole is caused by a single sperm (90% of the time) or two (10% of the time) sperm combining with an egg which has lost its DNA. In the first case, the sperm then reduplicates, forming a "complete" 46 chromosome set. The genotype is typically 46,XX (diploid) due to the subsequent mitosis of the fertilizing sperm but can also be 46,XY (diploid). 46,YY (diploid) is not observed. In contrast, a partial mole occurs when a normal egg is fertilized by one or two sperm which then reduplicates itself, yielding the genotypes of 69,XXY (triploid) or 92,XXXY (tetraploid).Complete moles have a 2–4% risk of developing into choriocarcinoma in Western countries and 10–15% in Eastern countries and a 15% risk of becoming an invasive mole. Incomplete moles can become invasive (<5% risk) but are not associated with choriocarcinoma. Complete hydatidiform moles account for 50% of all cases of choriocarcinoma.
Molar pregnancies are a relatively rare complication of pregnancy, making up 1 in 1,000 pregnancies in the US, with much higher rates in Asia (e.g. up to 1 in 100 pregnancies in Indonesia).

Signs and symptoms
Molar pregnancies usually present with painless vaginal bleeding in the fourth to fifth months of pregnancy. The uterus may be larger than expected, or the ovaries may be enlarged. There may also be more vomiting than would be expected (hyperemesis). Sometimes there is an increase in blood pressure along with protein in the urine. Blood tests will show very high levels of human chorionic gonadotropin (hCG).

Cause
The cause of this condition is not completely understood. Potential risk factors may include defects in the egg, abnormalities within the uterus, or nutritional deficiencies. Women under 20 or over 40 years of age have a higher risk. Other risk factors include diets low in protein, folic acid, and carotene. The diploid set of sperm-only DNA means that all chromosomes have sperm-patterned methylation suppression of genes. This leads to overgrowth of the syncytiotrophoblast whereas dual egg-patterned methylation leads to a devotion of resources to the embryo, with an underdeveloped syncytiotrophoblast. This is considered to be the result of evolutionary competition, with male genes driving for high investment into the fetus versus female genes driving for resource restriction to maximise the number of children.

Pathophysiology
A hydatidiform mole is a pregnancy/conceptus in which the placenta contains grapelike vesicles (small sacs) that are usually visible to the naked eye. The vesicles arise by distention of the chorionic villi by fluid. When inspected under the microscope, hyperplasia of the trophoblastic tissue is noted. If left untreated, a hydatidiform mole will almost always end as a spontaneous abortion (miscarriage).

Based on morphology, hydatidiform moles can be divided into two types: in complete moles, all the chorionic villi are vesicular, and no sign of embryonic or fetal development is present. In partial moles some villi are vesicular, whereas others appear more normal, and embryonic/fetal development may be seen but the fetus is always malformed and is never viable.
In rare cases a hydatidiform mole co-exists in the uterus with a normal, viable fetus. These cases are due to twinning. The uterus contains the products of two conceptions: one with an abnormal placenta and no viable fetus (the mole), and one with a normal placenta and a viable fetus. Under careful surveillance it is often possible for the woman to give birth to the normal child and to be cured of the mole.

Parental origin
In most complete moles, all nuclear genes are inherited from the father only (androgenesis). In approximately 80% of these androgenetic moles, the most probable mechanism is that an empty egg is fertilized by a single sperm, followed by a duplication of all chromosomes/genes (a process called endoreduplication). In approximately 20% of complete moles, the most probable mechanism is that an empty egg is fertilized by two sperm. In both cases, the moles are diploid (i.e. there are two copies of every chromosome). In all these cases, the mitochondrial genes are inherited from the mother, as usual.
Most partial moles are triploid (three chromosome sets). The nucleus contains one maternal set of genes and two paternal sets. The mechanism is usually the reduplication of the paternal haploid set from a single sperm, but may also be the consequence of dispermic (two sperm) fertilization of the egg.In rare cases, hydatidiform moles are tetraploid (four chromosome sets) or have other chromosome abnormalities.
A small percentage of hydatidiform moles have biparental diploid genomes, as in normal living persons; they have two sets of chromosomes, one inherited from each biological parent. Some of these moles occur in women who carry mutations in the gene NLRP7, predisposing them towards molar pregnancy. These rare variants of hydatidiform mole may be complete or partial.

Diagnosis
The diagnosis is strongly suggested by ultrasound (sonogram), but definitive diagnosis requires histopathological examination. On ultrasound, the mole resembles a bunch of grapes ("cluster of grapes" or "honeycombed uterus" or "snow-storm"). There is increased trophoblast proliferation and enlarging of the chorionic villi, and angiogenesis in the trophoblasts is impaired.Sometimes symptoms of hyperthyroidism are seen, due to the extremely high levels of hCG, which can mimic the effects of thyroid-stimulating hormone.

Treatment
Hydatidiform moles should be treated by evacuating the uterus by uterine suction or by surgical curettage as soon as possible after diagnosis, in order to avoid the risks of choriocarcinoma. Patients are followed up until their serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level. Invasive or metastatic moles (cancer) may require chemotherapy and often respond well to methotrexate. As they contain paternal antigens, the response to treatment is nearly 100%. Patients are advised not to conceive for half a year after hCG levels have normalized. The chances of having another molar pregnancy are approximately 1%.
Management is more complicated when the mole occurs together with one or more normal fetuses.
In some women, the growth can develop into gestational trophoblastic neoplasia. For women who have complete hydatidiform mole and are at high risk of this progression, evidence suggests giving prophylactic chemotherapy (known as P-chem) may reduce the risk of this happening. However P-chem may also increase toxic side effects, so more research is needed to explore its effects.

Anesthesia
The uterine curettage is generally done under the effect of anesthesia, preferably spinal anesthesia in hemodynamically stable patients. The advantages of spinal anesthesia over general anesthesia include ease of technique, favorable effects on the pulmonary system, safety in patients with hyperthyroidism and non-tocolytic pharmacological properties.  Additionally, by maintaining patients consciousness one can diagnose the complications like uterine perforation, cardiopulmonary distress and thyroid storm at an earlier stage than when the patient is sedated or is under general anesthesia.

Prognosis
More than 80% of hydatidiform moles are benign. The outcome after treatment is usually excellent. Close follow-up is essential to ensure that treatment has been successful </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 Hyperaldosteronism and explain in detail? [/INST] Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis).
This cause of mineralocorticoid excess is primary hyperaldosteronism reflecting excess production of aldosterone by adrenal zona glomerulosa. Bilateral micronodular hyperplasia is more common than unilateral adrenal adenoma.

Signs and symptoms
It can be asymptomatic, but these symptoms may be present:
Fatigue
Headache
High blood pressure
Hypokalemia
Hypernatraemia
Hypomagnesemia
Intermittent or temporary paralysis
Muscle spasms
Muscle weakness
Numbness
Polyuria
Polydipsia
Tingling
Metabolic alkalosis
Nocturia
Blurry Vision
Dizziness/Vertigo

Cause
The causes of primary hyperaldosteronism are adrenal hyperplasia and adrenal adenoma (Conns syndrome).
These cause hyperplasia of aldosterone-producing cells of the adrenal cortex resulting in primary hyperaldosteronism.
The causes of secondary hyperaldosteronism are accessory renal veins, fibromuscular dysplasia, reninoma, renal tubular acidosis, nutcracker syndrome, ectopic tumors, massive  ascites, left ventricular failure, and cor pulmonale.
These act either by decreasing circulating fluid volume or by decreasing cardiac output, with resulting increase in renin release leading to secondary hyperaldosteronism. Secondary hyperaldosteronism can also be caused by proximal renal tubular acidosis
Secondary hyperaldosteronism can also be a symptom of genetic conditions Bartters Syndrome and Gitelmans Syndrome.

Diagnosis
When taking a blood test, the aldosterone-to-renin ratio is abnormally increased in primary hyperaldosteronism, and decreased or normal but with high renin in secondary hyperaldosteronism.

Types
In endocrinology, the terms primary and secondary are used to describe the abnormality (e.g., elevated aldosterone) in relation to the defect, i.e., the tumors location. It also refers to causes that are genetic (primary) or due to another condition or influence (secondary).

Primary
Primary aldosteronism (hyporeninemic hyperaldosteronism) was previously thought to be most commonly caused by an adrenal adenoma, termed Conns syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases. Differentiating between the two is important, as this determines treatment. Also, see congenital adrenal hyperplasia.
Adrenal carcinoma is an extremely rare cause of primary hyperaldosteronism.Two familial forms have been identified: type I (dexamethasone suppressible), and type II, which has been linked to the 7p22 gene.Features

Hypertension
Hypokalemia (e.g., may cause muscle weakness)
AlkalosisInvestigations

High serum aldosterone
Low serum renin
High-resolution CT abdomenManagement

Adrenal adenoma: surgery
Bilateral adrenocortical hyperplasia: aldosterone antagonist, e.g., spironolactone

Secondary
Secondary hyperaldosteronism (also hyperreninism, or hyperreninemic hyperaldosteronism) is due to overactivity of the renin–angiotensin–aldosterone system (RAAS).Secondary refers to an abnormality that indirectly results in pathology through a predictable physiologic pathway, i.e., a renin-producing tumor leads to increased aldosterone, as the bodys aldosterone production is normally regulated by renin levels. One cause is a juxtaglomerular cell tumor. Another is renal artery stenosis, in which the reduced blood supply across the juxtaglomerular apparatus stimulates the production of renin. Likewise, fibromuscular dysplasia may cause stenosis of the renal artery, and therefore secondary hyperaldosteronism. Other causes can come from the tubules: low reabsorption of sodium (as seen in Bartter and Gitelman syndromes) will lead to hypovolemia/hypotension, which will activate the renin–angiotensin system (RAAS).Secondary hyperaldosteronism can also be caused by excessive ingestion of licorice or other members of the Glycyrrhiza genus of plants that contain the triterpenoid saponin glycoside known as glycyrrhizin. Licorice and closely related plants are perennial shrubs, the roots of which are used in medicine as well as making candies and in cooking other desserts because of the sweet taste. Through inhibition of 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), glycyrrhizin allows cortisol to activate mineralocorticoid receptors in the kidney </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 Hyperkeratosis and explain in detail? [/INST] Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin, and also usually accompanied by an increase in the granular layer. As the corneum layer normally varies greatly in thickness in different sites, some experience is needed to assess minor degrees of hyperkeratosis.
It can be caused by vitamin A deficiency or chronic exposure to arsenic.
Hyperkeratosis can also be caused by B-Raf inhibitor drugs such as Vemurafenib and Dabrafenib.It can be treated with urea-containing creams, which dissolve the intercellular matrix of the cells of the stratum corneum, promoting desquamation of scaly skin, eventually resulting in softening of hyperkeratotic areas.

Types
Follicular
Follicular hyperkeratosis, also known as keratosis pilaris (KP), is a skin condition characterized by excessive development of keratin in hair follicles, resulting in rough, cone-shaped, elevated papules. The openings are often closed with a white plug of encrusted sebum. When called phrynoderma the condition is associated with nutritional deficiency or malnourishment.
This condition has been shown in several small-scale studies to respond well to supplementation with vitamins and fats rich in essential fatty acids. Deficiencies of vitamin E, vitamin A, and B-complex vitamins have been implicated in causing the condition.

By other specific site
Plantar hyperkeratosis is hyperkeratosis of the sole of the foot. It is recommended to surgically remove the dead skin, to provide symptomatic relief.
Hyperkeratosis of the nipple and areola is an uncommon benign, asymptomatic, acquired condition of unknown pathogenesis.: 636

Hereditary
Epidermolytic hyperkeratosis (also known as "Bullous congenital ichthyosiform erythroderma," "Bullous ichthyosiform erythroderma,": 482  or "bullous congenital ichthyosiform erythroderma of Brocq") is a rare skin disease in the ichthyosis family affecting around 1 in 250,000 people </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 Hypoestrogenism and explain in detail? [/INST] Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.
In women, low levels of estrogen may cause symptoms such as  hot flashes, sleeping disturbances, decreased bone health, and changes in the genitourinary system. Hypoestrogenism is most commonly found in women who are postmenopausal, have primary ovarian insufficiency (POI), or are presenting with amenorrhea (absence of menstrual periods). Hypoestrogenism includes primarily genitourinary effects, including thinning of the vaginal tissue layers and an increase in vaginal pH. With normal levels of estrogen, the environment of the vagina is protected against inflammation, infections, and sexually transmitted infections. Hypoestrogenism can also occur in men, for instance due to hypogonadism.
There are both hormonal and non-hormonal treatments to prevent the negative effects of low estrogen levels and improve quality of life.

Signs and symptoms
Vasomotor
Presentations of low estrogen levels include hot flashes, which are sudden, intense feelings of heat predominantly in the upper body, causing the skin to redden as if blushing. They are believed to occur due to the narrowing of the thermonuclear zone in the hypothalamus, making the body more sensitive to body temperature changes. Night disturbances are also common symptoms associated with hypoestrogenism. People may experience difficulty falling asleep, waking up several times a night, and early awakening with different variability between races and ethnic groups.

Genitourinary
Other classic symptoms include both physical and chemical changes of the vulva, vagina, and lower urinary tract. Genitals go through atrophic changes such as losing elasticity, losing vaginal rugae, and increasing of vaginal pH, which can lead to changes in the vaginal flora and increase the risk of tissue fragility and fissure. Other genital signs include dryness or lack of lubrication, burning, irritation, discomfort or pain, as well as impaired function. Low levels of estrogen can lead to limited genital arousal and cause dyspareunia, or painful sexual intercourse because of changes in the four layers of the vaginal wall. People with low estrogen will also experience higher urgency to urinate and dysuria, or painful urination. Hypoestrogenism is also considered one of the major risk factors for developing uncomplicated urinary tract infection in postmenopausal women who do not take hormone replacement therapy.

Bone health
Estrogen contributes to bone health in several ways; low estrogen levels increase bone resorption via osteoclasts and osteocytes, cells that help with bone remodeling, making bones more likely to deteriorate and increase risk of fracture. The decline in estrogen levels can ultimately lead to more serious illnesses, such as scoliosis or type I osteoporosis, a disease that thins and weakens bones, resulting in low bone density and fractures. Estrogen deficiency plays an important role in osteoporosis development for both genders, and it is more pronounced for women and at younger (menopausal) ages by five to ten years compared with men. Females are also at higher risk for osteopenia and osteoporosis.

Causes
A variety of conditions can lead to hypoestrogenism: menopause is the most common. Primary ovarian insufficiency (premature menopause) due to varying causes, such as radiation therapy, chemotherapy, or a spontaneous manifestation, can also lead to low estrogen and infertility.Hypogonadism (a condition where the gonads – testes for men and ovaries for women – have diminished activity) can decrease estrogen. In primary hypogonadism, elevated serum gonadotropins are detected on at least two occasions several weeks apart, indicating gonadal failure. In secondary hypogonadism (where the cause is hypothalamic or pituitary dysfunction) serum levels of gonadotropins may be low.Other causes include certain medications, gonadotropin insensitivity, inborn errors of steroid metabolism (for example, aromatase deficiency, 17α-hydroxylase deficiency, 17,20-lyase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, and cholesterol side-chain cleavage enzyme or steroidogenic acute regulatory protein deficiency) and functional amenorrhea.

Risks
Low endogenous estrogen levels can elevate the risk of cardiovascular disease in women who reach early menopause. Estrogen is needed to relax arteries using endothelial-derived nitric oxide resulting in better heart health by decreasing adverse atherogenic effects. Women with POI may have an increased risk of cardiovascular disease due to low estrogen production.

Pathophysiology
Estrogen deficiency has both vaginal and urologic effects; the female genitalia and lower urinary tract share common estrogen receptor function due to their embryological development. Estrogen is a vasoactive hormone (one that affects blood pressure) which stimulates blood flow and increases vaginal secretions and lubrication. Activated estrogen receptors also stimulate tissue proliferation in the vaginal walls, which contribute to the formation of rugae. This rugae aids in sexual stimulation by becoming lubricated, distended, and expanded.Genitourinary effects of low estrogen include thinning of the vaginal epithelium, loss of vaginal barrier function, decrease of vaginal folding, decrease of the elasticity of the tissues, and decrease of the secretory activity of the Bartholin glands, which leads to traumatization of the vaginal mucosa and painful sensations. This thinning of the vaginal epithelium layers can increase the risk of developing inflammation and infection, such as urinary tract infection.The vagina is largely dominated by bacteria from the genus Lactobacillus, which typically comprise more than 70% of the vaginal bacteria in women. These lactobacilli process glycogen and its breakdown products, which result in a maintained low vaginal pH. Estrogen levels are closely linked to lactobacilli abundance and vaginal pH, as higher levels of estrogen promote thickening of the vaginal epithelium and intracellular production of glycogen. This large presence of lactobacilli and subsequent low pH levels are hypothesized to benefit women by protecting against sexually transmitted pathogens and opportunistic infections, and therefore reducing disease risk.

Diagnosis
Hypoestrogenism is typically found in menopause and aids in diagnosis of other conditions such as POI and functional amenorrhea. Estrogen levels can be tested through several laboratory tests: vaginal maturation index, progestogen challenge test, and vaginal swabs for small parabasal cells.

Menopause
Menopause is usually diagnosed through symptoms of vaginal atrophy, pelvic exams, and taking a comprehensive medical history consisting of last menstruation cycle. There is no definitive testing available for determining menopause as the symptom complex is the primary indicator and because the lower levels of estradiol are harder to accurately detect after menopause. However, there can be laboratory tests done to differentiate between menopause and other diagnoses.

Functional hypothalamic amenorrhea
Functional hypothalamic amenorrhea (FHA) is diagnosed based on findings of amenorrhea lasting three months or more, low serum hormone of gonadotropins and estradiol. Since common causes of FHA include exercising too much, eating too little, or being under too much stress, diagnosis of FHA includes assessing for any changes in exercise, weight, and stress. In addition, evaluation of amenorrhea includes a history and physical examination, biochemical testing,  imaging, and measuring estrogen level. Examination of menstrual problems and clinical tests to measure hormones such as serum prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH) can help rule out other potential causes of amenorrhea. These potential conditions include hyperprolactinemia, POI, and polycystic ovary syndrome.

Primary ovarian insufficiency
Primary ovarian insufficiency, also known as premature ovarian failure, can develop in women before the age of forty as a consequence of hypergonadotropic hypogonadism. POI can present as amenorrhea and has similar symptoms to menopause, but measuring FSH levels is used for diagnosis.

Treatment
Hormone replacement therapy (HRT) can be used to treat hypoestrogenism and menopause related symptoms, and low estrogen levels in both premenopausal and postmenopausal women. Low-dose estrogen medications are approved by the U.S. Food and Drug Administration for treatment of menopause-related symptoms </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 Hypophosphatasia and explain in detail? [/INST] Hypophosphatasia (; also called deficiency of alkaline phosphatase, phosphoethanolaminuria, or Rathbuns syndrome; sometimes abbreviated HPP) is a rare, and sometimes fatal, inherited metabolic bone disease. Clinical symptoms are heterogeneous, ranging from the rapidly fatal, perinatal variant, with profound skeletal hypomineralization, respiratory compromise or vitamin B6 dependent seizures to a milder, progressive osteomalacia later in life. Tissue non-specific alkaline phosphatase (TNSALP) deficiency in osteoblasts and chondrocytes impairs bone mineralization, leading to rickets or osteomalacia. The pathognomonic finding is subnormal serum activity of the TNSALP enzyme, which is caused by one of 388 genetic mutations identified to date, in the gene encoding TNSALP. Genetic inheritance is autosomal recessive for the perinatal and infantile forms but either autosomal recessive or autosomal dominant in the milder forms.
The prevalence of hypophosphatasia is not known; one study estimated the live birth incidence of severe forms to be 1:100,000. and some studies report a higher prevalence of milder disease.

Symptoms and signs
There is a remarkable variety of symptoms that depends, largely, on the age of the patient at initial presentation, ranging from death in utero to relatively mild bone problems with or without dentition symptoms in adult life although neurological and extra-skeletal symptoms are also reported. The stages of this disease are generally included in the following categories: perinatal, infantile, childhood, adult, benign prenatal and odontohypophosphatasia. Although several clinical sub-types of the disease have been characterized, based on the age at which skeletal lesions are discovered, the disease is best understood as a single continuous spectrum of severity.As the presentation of adult disease is highly variable, incorrect or missed diagnosis may occur. In one study, 19% of patients diagnosed with fibromyalgia had laboratory findings suggestive of possible hypophosphatasia.One case report details a 35-year old female with low serum ALP and mild pains but no history of rickets, fractures or dental problems. Subsequent evaluation showed osteopenia and renal microcalcifications and an elevation of PEA. The genetic mutations found in this case were previously reported in perinatal, infantile and childhood hypophosphatasia, but not adult hypophosphatasia.

Perinatal hypophosphatasia
Perinatal hypophosphatasia is the most lethal form. Profound hypomineralization results in caput membranaceum (a soft calvarium), deformed or shortened limbs during gestation and at birth, and rapid death due to respiratory failure. Stillbirth is not uncommon and long-term survival is rare. Neonates who manage to survive suffer increasing respiratory compromise due to softening of the bones (osteomalacia) and underdeveloped lungs (hypoplastic). Ultimately, this leads to respiratory failure. Epilepsy (seizures) can occur and can prove lethal. Regions of developing, unmineralized bone (osteoid) may expand and encroach on the marrow space, resulting in myelophthisic anemia.In radiographic examinations, perinatal hypophosphatasia can be distinguished from even the most severe forms of osteogenesis imperfecta and congenital dwarfism. Some stillborn skeletons show almost no mineralization; others have marked undermineralization and severe osteomalacia. Occasionally, there can be a complete absence of ossification in one or more vertebrae. In the skull, individual bones may calcify only at their centers. Another unusual radiographic feature is bony spurs that protrude laterally from the shafts of the ulnae and fibulae. Despite the considerable patient-to-patient variability and the diversity of radiographic findings, the X-ray can be considered diagnostic.

Infantile hypophosphatasia
Infantile hypophosphatasia presents in the first 6 months of life, with the onset of poor feeding and inadequate weight gain. Clinical manifestations of rickets often appear at this time. Although cranial sutures appear to be wide, this reflects hypomineralization of the skull, and there is often “functional” craniosynostosis. If the patient survives infancy, these sutures can permanently fuse. Defects in the chest, such as flail chest resulting from rib fractures, lead to respiratory compromise and pneumonia. Elevated calcium in the blood (hypercalcemia) and urine (hypercalcenuria) are also common, and may explain the renal problems and recurrent vomiting seen is this disease.Radiographic features in infants are generally less severe than those seen in perinatal hypophosphatasia. In the long bones, there is an abrupt change from a normal appearance in the shaft (diaphysis) to uncalcified regions near the ends (metaphysis), which suggests the occurrence of an abrupt metabolic change. In addition, serial radiography studies suggest that defects in skeletal mineralization (i.e. rickets) persist and become more generalized. Mortality is estimated to be 50% in the first year of life.

Childhood hypophosphatasia
Hypophosphatasia in childhood has variable clinical expression. As a result of defects in the development of the dental cementum, the deciduous teeth (baby teeth) are often lost before the age of 5. Frequently, the incisors are lost first; occasionally all of the teeth are lost prematurely. Dental radiographs can show the enlarged pulp chambers and root canals that are characteristic of rickets.Patients may experience delayed walking, a characteristic waddling gait, stiffness and pain, and muscle weakness (especially in the thighs) consistent with nonprogressive myopathy. Typically, radiographs show defects in calcification and characteristic bony defects near the ends of major long bones. Growth retardation, frequent fractures, and low bone density (osteopenia) are common. In severely-affected infants and young children, cranial bones can fuse prematurely, despite the appearance of open fontanels on radiographic studies. The illusion of open fontanels results from hypomineralization of large areas of the calvarium. Premature bony fusion of the cranial sutures may elevate intracranial pressure.

Adult hypophosphatasia
Adult hypophosphatasia can be associated with rickets, premature loss of deciduous teeth, or early loss of adult dentation followed by relatively good health. Osteomalacia results in painful feet due to poor healing of metatarsal stress fractures. Discomfort in the thighs or hips due to femoral pseudofractures can be distinguished from other types of osteomalacia by their location in the lateral cortices of the femora. The symptoms of this disease usually begin during middle age of an adult patient and can include bone pain, and hypomineralization.Some patients suffer from calcium pyrophosphate dihydrate crystal depositions with occasional attacks of arthritis (pseudogout), which appears to be the result of elevated endogenous inorganic pyrophosphate (PPi) levels. These patients may also suffer articular cartilage degeneration and pyrophosphate arthropathy. Radiographs reveal pseudofractures in the lateral cortices of the proximal femora and stress fractures, and patients may experience osteopenia, chondrocalcinosis, features of pyrophosphate arthropathy, and calcific periarthritis.

Odontohypophosphatasia
Odontohypophosphatasia is present when dental disease is the only clinical abnormality, and radiographic and/or histologic studies reveal no evidence of rickets or osteomalacia. Although hereditary leukocyte abnormalities and other disorders usually account for this condition, odontohypophosphatasia may explain some “early-onset periodontitis” cases.

Causes
Hypophosphatasia is associated with a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP is an enzyme that is tethered to the outer surface of osteoblasts and chondrocytes. TNSALP hydrolyzes several substances, including mineralization-inhibiting inorganic pyrophosphate (PPi) and pyridoxal 5’-phosphate (PLP), a major form of vitamin B.  A relationship describing physiologic regulation of mineralization has been termed the Stenciling Principle of mineralization, whereby enzyme-substrate pairs imprint mineralization patterns locally into the extracellular matrix (most notably described for bone) by degrading mineralization inhibitors (e.g. TNAP/TNSALP/ALPL enzyme degrading the pyrophosphate inhibition of mineralization, and PHEX enzyme degrading the osteopontin inhibition of mineralization). The Stenciling Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH).6.
When TSNALP enzymatic activity is low, inorganic pyrophosphate (PPi) accumulates outside of cells in the extracellular matrix of bones and teeth, and inhibits formation of hydroxyapatite mineral, the main hardening component of bone, causing rickets in infants and children and osteomalacia (soft bones) and odontomalacia (soft teeth) in children and adults. PLP is the principal form of vitamin B6 and must be dephosphorylated by TNSALP before it can cross the cell membrane. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters, which can cause seizures. In some cases, a build-up of calcium pyrophosphate dihydrate (CPPD) crystals in the joint can cause pseudogout.

Genetics
Perinatal and infantile hypophosphatasia are inherited as autosomal recessive traits with homozygosity or compound heterozygosity for two defective TNSALP alleles. The mode of inheritance for childhood, adult, and odonto forms of hypophosphatasia can be either autosomal dominant or recessive. Autosomal transmission accounts for the fact that the disease affects males and females with equal frequency. Genetic counseling is complicated by the disease’s variable inheritance pattern, and by incomplete penetration of the trait.Hypophosphatasia is a rare disease that has been reported worldwide and appears to affect individuals of all ethnicities. The prevalence of severe hypophosphatasia is estimated to be 1:100,000 in a population of largely Anglo-Saxon origin. The frequency of mild hypophosphatasia is more challenging to assess because the symptoms may escape notice or be misdiagnosed. The highest incidence of hypophosphatasia has been reported in the Mennonite population in Manitoba, Canada where one in every 25 individuals are considered carriers and one in every 2,500 newborns exhibits severe disease. Hypophosphatasia is considered particularly rare in people of African ancestry in the U.S.

Diagnosis
Dental findings
Hypophosphatasia is often discovered because of an early loss of deciduous (baby or primary) teeth with the root intact. Researchers have recently documented a positive correlation between dental abnormalities and clinical phenotype. Poor dentition is also noted in adults.

Laboratory testing
The symptom that best characterizes hypophosphatasia is low serum activity of alkaline phosphatase enzyme (ALP). In general, lower levels of enzyme activity correlate with more severe symptoms. The decrease in ALP activity leads to an increase in pyridoxal 5’-phosphate (PLP), which is the major form of Vitamin B6, in the blood, although tissue levels of Vitamin B6 may be unremarkable and correlates with disease severity. Urinary inorganic pyrophosphate (PPi) levels are elevated in most hypophosphatasia patients and, although it remains only a research technique, this increase has been reported to accurately detect carriers of the disease. In addition, most patients have an increased level of urinary phosphoethanolamine (PEA) although some may not. PLP screening is preferred over PEA due to cost and sensitivity.Tests for serum tissue-non-specific ALP (sometimes referred to as TNSALP) levels are part of the standard comprehensive metabolic panel (CMP) that is used in routine exams, although bone-specific ALP testing may be indicative of disease severity.

Radiography
Despite patient-to-patient variability and the diversity of radiographic findings, the X-ray is diagnostic in infantile hypophosphatasia. Skeletal defects are found in nearly all patients and include hypomineralization, rachitic changes, incomplete vertebrate ossification and, occasionally, lateral bony spurs on the ulnae and fibulae.In newborns, X-rays readily distinguish hypophosphatasia from osteogenesis imperfecta and congenital dwarfism. Some stillborn skeletons show almost no mineralization; others have marked undermineralization and severe rachitic changes. Occasionally there can be peculiar complete or partial absence of ossification in one or more vertebrae. In the skull, individual membranous bones may calcify only at their centers, making it appear that areas of the unossified calvarium have cranial sutures that are widely separated when, in fact, they are functionally closed. Small protrusions (or "tongues") of radiolucency often extend from the metaphyses into the bone shaft.
In infants, radiographic features of hypophosphatasia are striking, though generally less severe than those found in perinatal hypophosphatasia. In some newly diagnosed patients, there is an abrupt transition from relatively normal-appearing diaphyses to uncalcified metaphases, suggesting an abrupt metabolic change has occurred. Serial radiography studies can reveal the persistence of impaired skeletal mineralization (i.e. rickets), instances of sclerosis, and gradual generalized demineralization.
In adults, X-rays may reveal bilateral femoral pseudofractures in the lateral subtrochanteric diaphysis. These pseudofractures may remain for years, but they may not heal until they break completely or the patient receives intramedullary fixation. These patients may also experience recurrent metatarsal fractures. DXA may show abnormal bone mineral density which may correlate with disease severity, although bone mineral density in HPP patients may not be systemically reduced.

Genetic analysis
All clinical sub-types of hypophosphatasia have been traced to genetic mutations in the gene encoding TNSALP, which is localized on chromosome 1p36.1-34 in humans (ALPL; OMIM#171760). Approximately 388 distinct mutations have been described in the TNSALP gene.  "The Tissue Nonspecific Alkaline Phosphatase Gene Mutations Database". About 80% of the mutations are missense mutations. The number and diversity of mutations results in highly variable phenotypic expression, and there appears to be a correlation between genotype and phenotype in hypophosphatasia” </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 Hypoprothrombinemia and explain in detail? [/INST] Hypoprothrombinemia is a rare blood disorder in which a deficiency in immunoreactive prothrombin (Factor II), produced in the liver, results in an impaired blood clotting reaction, leading to an increased physiological risk for spontaneous bleeding. This condition can be observed in the gastrointestinal system, cranial vault, and superficial integumentary system, affecting both the male and female population. Prothrombin is a critical protein that is involved in the process of hemostasis, as well as illustrating procoagulant activities. This condition is characterized as an autosomal recessive inheritance congenital coagulation disorder affecting 1 per 2,000,000 of the population, worldwide, but is also attributed as acquired.

Signs and symptoms
There are various symptoms that are presented and are typically associated to a specific site that they appear at. Hypoprothrombinemia is characterized by a poor blood clotting function of prothrombin. Some symptoms are presented as severe, while others are mild, meaning that blood clotting is slower than normal. Areas that are usually affected are muscles, joints, and the brain, however, these sites are more uncommon.The most common symptoms include:

Easy bruising
Oral mucosal bleeding - Bleeding of the membrane mucus lining inside of the mouth.
Soft tissue bleeding.
Hemarthrosis - Bleeding in joint spaces.
Epistaxis - Acute hemorrhages from areas of the nasal cavity, nostrils, or nasopharynx.
Women with this deficiency experience menorrhagia: prolonged, abnormal heavy menstrual bleeding. This is typically a symptom of the disorder when severe blood loss occurs.Other reported symptoms that are related to the condition:

Prolonged periods of bleeding due to surgery, injury, or post birth.
Melena - Associated with acute gastrointestinal bleeding, dark black, tarry feces.
Hematochezia - Lower gastrointestinal bleeding, passage of fresh, bright red blood through the anus secreted in or with stools. If associated with upper gastrointestinal bleeding, suggestive of a more life-threatening issue.Type I: Severe hemorrhages are indicators of a more severe prothrombin deficiency that account for muscle hematomas, intracranial bleeding, postoperative bleeding, and umbilical cord hemorrhage, which may also occur depending on the severity, respectively.
Type II: Symptoms are usually more capricious, but can include a variety of the symptoms described previously. Less severe cases of the disorder typically do not involve spontaneous bleeding.

Causes
Hypoprothrombinemia can be the result of a genetic defect, may be acquired as the result of another disease process, or may be an adverse effect of medication. For example, 5-10% of patients with systemic lupus erythematosus exhibit acquired hypoprothrombinemia due to the presence of autoantibodies which bind to prothrombin and remove it from the bloodstream (lupus anticoagulant-hypoprothrombinemia syndrome). The most common viral pathogen that is involved is Adenovirus, with a prevalence of 50% in postviral cases.

Inheritance
Autosomal recessive condition in which both parents must carry the recessive gene in order to pass the disease on to offspring. If both parents have the autosomal recessive condition, the chance of mutation in offspring increases to 100%. An individual will be considered a carrier if one mutant copy of the gene is inherited, and will not illustrate any symptoms. The disease affects both men and women equally, and overall, is a very uncommon inherited or acquired disorder.

Non-inheritance and other factors
There are two types of prothrombin deficiencies that occur depending on the mutation:Type I (true deficiency), includes a missense or nonsense mutation, essentially decreasing prothrombin production. This is associated with bleeding from birth. Here, plasma levels of prothrombin are typically less than 10% of normal levels.Type II, known as dysprothrombinemia, includes a missense mutation at specific Xa factor cleavage sites and serine protease prothrombin regions. Type II deficiency creates a dysfunctional protein with decreased activity and usually normal or low-normal antigen levels. A vitamin K-dependent clotting factor is seldom seen as a contributor to inherited prothrombin deficiencies, but lack of Vitamin K decreases the synthesis of prothrombin in liver cells.Acquired underlying causes of this condition include severe liver disease, warfarin overdose, platelet disorders, and disseminated intravascular coagulation (DIC).
It may also be a rare adverse effect to ceftriaxone.

Mechanism
Hypoprothrombinemia is found to present itself as either inherited or acquired, and is a decrease in the synthesis of prothrombin. In the process of inheritance, it marks itself as an autosomal recessive disorder, meaning that both parents must be carriers of the defective gene in order for the disorder to be present in a child. Prothrombin is a glycoprotein that occurs in blood plasma and functions as a precursor to the enzyme, thrombin, which acts to convert fibrinogen into fibrin, therefore, fortifying clots. This clotting process is known as coagulation.The mechanism specific to prothrombin (factor II) includes the proteolytically cleaving, breakdown of proteins into smaller polypeptides or amino acids, of this coagulation factor in order to form thrombin at the beginning of the cascade, leading to stemming of blood loss. A mutation in factor II would essentially lead to hypoprothrombinemia. The mutation is presented on chromosome 11.Areas where the disease has been shown to present itself at include the liver, since the glycoprotein is stored in this area.
Acquired cases are results from an isolated factor II deficiency. Specific cases include:

Vitamin K deficiency: In the liver, vitamin K plays an important role in the synthesis of coagulation factor II. Bodys capacity in the storage of vitamin K is typically very low. Vitamin K-dependent coagulation factors have a very short half-life, sometimes leading to a deficiency when a depletion of vitamin K occurs. The liver synthesizes inactive precursor proteins in the absence of vitamin K (liver disease). Vitamin K deficiency leads to impaired clotting of the blood and in some cases, causes internal bleeding without an associated injury.
Disseminated intravascular coagulation (DIC): Involving abnormal, excessive generation of thrombin and fibrin within the blood. Relative to hypoprothrombinemia, due to increased platelet aggregation and coagulation factor consumption involved in the process.
Anticoagulants: warfarin overdose: Used as a treatment for prevention of blood clots, however, like most drugs, side effects have been shown to increase risk of excessive bleeding by functioning in the disruption of hepatic synthesis of coagulation factors II, VII, IX, and X. Vitamin K is an antagonist to warfarin drug, reversing its activity, causing it to be less effective in the process of blood clotting. Warfarin intake has been shown to interfere with Vitamin-K metabolism.

Diagnosis
Diagnosis of inherited hypoprothrombinemia, relies heavily on a patients medical history, family history of bleeding issues, and lab exams performed by a hematologist </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 Hair loss and explain in detail? [/INST] Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body.  Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring is not usually present. Hair loss in some people causes psychological distress.Common types include male- or female-pattern hair loss, alopecia areata, and a thinning of hair known as telogen effluvium. The cause of male-pattern hair loss is a combination of genetics and male hormones; the cause of female pattern hair loss is unclear; the cause of alopecia areata is autoimmune; and the cause of telogen effluvium is typically a physically or psychologically stressful event. Telogen effluvium is very common following pregnancy.Less common causes of hair loss without inflammation or scarring include the pulling out of hair, certain medications including chemotherapy, HIV/AIDS, hypothyroidism, and malnutrition including iron deficiency. Causes of hair loss that occurs with scarring or inflammation include fungal infection, lupus erythematosus, radiation therapy, and sarcoidosis. Diagnosis of hair loss is partly based on the areas affected.Treatment of pattern hair loss may simply involve accepting the condition, which can also include shaving ones head. Interventions that can be tried include the medications minoxidil (or finasteride) and hair transplant surgery. Alopecia areata may be treated by steroid injections in the affected area, but these need to be frequently repeated to be effective. Hair loss is a common problem. Pattern hair loss by age 50 affects about half of men and a quarter of women. About 2% of people develop alopecia areata at some point in time.

Terminology
Baldness is the partial or complete lack of hair growth, and part of the wider topic of "hair thinning". The degree and pattern of baldness varies, but its most common cause is androgenic hair loss, alopecia androgenetica, or alopecia seborrheica, with the last term primarily used in Europe.

Hypotrichosis
Hypotrichosis is a condition of abnormal hair patterns, predominantly loss or reduction. It occurs, most frequently, by the growth of vellus hair in areas of the body that normally produce terminal hair. Typically, the individuals hair growth is normal after birth, but shortly thereafter the hair is shed and replaced with sparse, abnormal hair growth. The new hair is typically fine, short and brittle, and may lack pigmentation. Baldness may be present by the time the subject is 25 years old.

Signs and symptoms
Symptoms of hair loss include hair loss in patches usually in circular patterns, dandruff, skin lesions, and scarring. Alopecia areata (mild – medium level) usually shows in unusual hair loss areas, e.g., eyebrows, backside of the head or above the ears, areas the male pattern baldness usually does not affect. In male-pattern hair loss, loss and thinning begin at the temples and the crown and hair either thins out or falls out. Female-pattern hair loss occurs at the frontal and parietal.
People have between 100,000 and 150,000 hairs on their head. The number of strands normally lost in a day varies but on average is 100. In order to maintain a normal volume, hair must be replaced at the same rate at which it is lost. The first signs of hair thinning that people will often notice are more hairs than usual left in the hairbrush after brushing or in the basin after shampooing. Styling can also reveal areas of thinning, such as a wider parting or a thinning crown.

Skin conditions
A substantially blemished face, back and limbs could point to cystic acne. The most severe form of the condition, cystic acne, arises from the same hormonal imbalances that cause hair loss and is associated with dihydrotestosterone production.

Psychological
The psychology of hair thinning is a complex issue. Hair is considered an essential part of overall identity: especially for women, for whom it often represents femininity and attractiveness. Men typically associate a full head of hair with youth and vigor. People experiencing hair thinning often find themselves in a situation where their physical appearance is at odds with their own self-image and commonly worry that they appear older than they are or less attractive to others. Psychological problems due to baldness, if present, are typically most severe at the onset of symptoms.Hair loss induced by cancer chemotherapy has been reported to cause changes in self-concept and body image. Body image does not return to the previous state after regrowth of hair for a majority of patients. In such cases, patients have difficulties expressing their feelings (alexithymia) and may be more prone to avoiding family conflicts. Family therapy can help families to cope with these psychological problems if they arise.

Causes
Although not completely understood, hair loss can have many causes:

Pattern hair loss
Male pattern hair loss is believed to be due to a combination of genetics and the male hormone dihydrotestosterone. The cause in female pattern hair loss remains unclear.

Infection
Dissecting cellulitis of the scalp
Fungal infections (such as tinea capitis)
Folliculitis from various causes
Demodex folliculitis, caused by Demodex folliculorum, a microscopic mite that feeds on the sebum produced by the sebaceous glands, denies hair essential nutrients and can cause thinning. Demodex folliculorum is not present on every scalp and is more likely to live in an excessively oily scalp environment.
Secondary syphilis

Drugs
Temporary or permanent hair loss can be caused by several medications, including those for blood pressure problems, diabetes, heart disease and cholesterol. Any that affect the bodys hormone balance can have a pronounced effect: these include the contraceptive pill, hormone replacement therapy, steroids and acne medications.
Some treatments used to cure mycotic infections can cause massive hair loss.
Medications (side effects from drugs, including chemotherapy, anabolic steroids, and birth control pills)

Trauma
Traction alopecia is most commonly found in people with ponytails or cornrows who pull on their hair with excessive force. In addition, rigorous brushing and heat styling, rough scalp massage can damage the cuticle, the hard outer casing of the hair. This causes individual strands to become weak and break off, reducing overall hair volume.
Frictional alopecia is hair loss caused by rubbing of the hair or follicles, most infamously around the ankles of men from socks, where even if socks are no longer worn, the hair often will not grow back.
Trichotillomania is the loss of hair caused by compulsive pulling and bending of the hairs. Onset of this disorder tends to begin around the onset of puberty and usually continues through adulthood.  Due to the constant extraction of the hair roots, permanent hair loss can occur.
Traumas such as childbirth, major surgery, poisoning, and severe stress may cause a hair loss condition known as telogen effluvium, in which a large number of hairs enter the resting phase at the same time, causing shedding and subsequent thinning. The condition also presents as a side effect of chemotherapy – while targeting dividing cancer cells, this treatment also affects hairs growth phase with the result that almost 90% of hairs fall out soon after chemotherapy starts.
Radiation to the scalp, as when radiotherapy is applied to the head for the treatment of certain cancers there, can cause baldness of the irradiated areas.

Pregnancy
Hair loss often follows childbirth in the postpartum period without causing baldness. In this situation, the hair is actually thicker during pregnancy owing to increased circulating oestrogens. Approximately three months after giving birth (typically between 2 and 5 months), oestrogen levels drop and hair loss occurs, often particularly noticeably around the hairline and temple area. Hair typically grows back normally and treatment is not indicated. A similar situation occurs in women taking the fertility-stimulating drug clomiphene.

Other causes
Autoimmune disease. Alopecia areata is an autoimmune disorder also known as "spot baldness" that can result in hair loss ranging from just one location (Alopecia areata monolocularis) to every hair on the entire body (Alopecia areata universalis). Although thought to be caused by hair follicles becoming dormant, what triggers alopecia areata is not known. In most cases the condition corrects itself, but it can also spread to the entire scalp (alopecia totalis) or to the entire body (alopecia universalis).
Skin diseases and cancer. Localized or diffuse hair loss may also occur in cicatricial alopecia (lupus erythematosus, lichen plano pilaris, folliculitis decalvans, central centrifugal cicatricial alopecia, postmenopausal frontal fibrosing alopecia, etc.). Tumours and skin outgrowths also induce localized baldness (sebaceous nevus, basal cell carcinoma, squamous cell carcinoma).
Hypothyroidism (an under-active thyroid) and the side effects of its related medications can cause hair loss, typically frontal, which is particularly associated with thinning of the outer third of the eyebrows (also seen with syphilis). Hyperthyroidism (an over-active thyroid) can also cause hair loss, which is parietal rather than frontal.
Sebaceous cysts. Temporary loss of hair can occur in areas where sebaceous cysts are present for considerable duration (normally one to several weeks).
Congenital triangular alopecia – It is a triangular, or oval in some cases, shaped patch of hair loss in the temple area of the scalp that occurs mostly in young children. The affected area mainly contains vellus hair follicles or no hair follicles at all, but it does not expand. Its causes are unknown, and although it is a permanent condition, it does not have any other effect on the affected individuals.
Hair growth conditions. Gradual thinning of hair with age is a natural condition known as involutional alopecia. This is caused by an increasing number of hair follicles switching from the growth, or anagen, phase into a resting phase, or telogen phase, so that remaining hairs become shorter and fewer in number. An unhealthy scalp environment can play a significant role in hair thinning by contributing to miniaturization or causing damage.
Obesity. Obesity-induced stress, such as that induced by a high-fat diet (HFD), targets hair follicle stem cells (HFSCs) to accelerate hair thinning in mice. It is likely that similar molecular mechanism play a role in human hair loss.Other causes of hair loss include:

Alopecia mucinosa
Biotinidase deficiency
Chronic inflammation
Diabetes
Pseudopelade of Brocq
Telogen effluvium
Tufted folliculitis

Genetics
Genetic forms of localized autosomal recessive hypotrichosis include:

Pathophysiology
Hair follicle growth occurs in cycles. Each cycle consists of a long growing phase (anagen), a short transitional phase (catagen) and a short resting phase (telogen). At the end of the resting phase, the hair falls out (exogen) and a new hair starts growing in the follicle, beginning the cycle again.
Normally, about 40 (0–78 in men) hairs reach the end of their resting phase each day and fall out.  When more than 100 hairs fall out per day, clinical hair loss (telogen effluvium) may occur. A disruption of the growing phase causes abnormal loss of anagen hairs (anagen effluvium).

Diagnosis
Because they are not usually associated with an increased loss rate, male-pattern and female-pattern hair loss do not generally require testing. If hair loss occurs in a young man with no family history, drug use could be the cause.

The pull test helps to evaluate diffuse scalp hair loss. Gentle traction is exerted on a group of hairs (about 40–60) on three different areas of the scalp. The number of extracted hairs is counted and examined under a microscope. Normally, fewer than three hairs per area should come out with each pull. If more than ten hairs are obtained, the pull test is considered positive.
The pluck test is conducted by pulling hair out "by the roots". The root of the plucked hair is examined under a microscope to determine the phase of growth, and is used to diagnose a defect of telogen, anagen, or systemic disease. Telogen hairs have tiny bulbs without sheaths at their roots. Telogen effluvium shows an increased percentage of hairs upon examination. Anagen hairs have sheaths attached to their roots. Anagen effluvium shows a decrease in telogen-phase hairs and an increased number of broken hairs.
Scalp biopsy is used when the diagnosis is unsure; a biopsy allows for differing between scarring and nonscarring forms. Hair samples are taken from areas of inflammation, usually around the border of the bald patch.
Daily hair counts are normally done when the pull test is negative. It is done by counting the number of hairs lost. The hair from the first morning combing or during washing should be counted. The hair is collected in a clear plastic bag for 14 days. The strands are recorded. If the hair count is >100/day, it is considered abnormal except after shampooing, where hair counts will be up to 250 and be normal.
Trichoscopy is a noninvasive method of examining hair and scalp. The test may be performed with the use of a handheld dermoscope or a video dermoscope. It allows differential diagnosis of hair loss in most cases.There are two types of identification tests for female pattern baldness: the Ludwig Scale and the Savin Scale. Both track the progress of diffused thinning, which typically begins on the crown of the head behind the hairline, and becomes gradually more pronounced. For male pattern baldness, the Hamilton–Norwood scale tracks the progress of a receding hairline and/or a thinning crown, through to a horseshoe-shaped ring of hair around the head and on to total baldness.In almost all cases of thinning, and especially in cases of severe hair loss, it is recommended to seek advice from a doctor or dermatologist. Many types of thinning have an underlying genetic or health-related cause, which a qualified professional will be able to diagnose.

Management
Hiding hair loss
Head
One method of hiding hair loss is the comb over, which involves restyling the remaining hair to cover the balding area. It is usually a temporary solution, useful only while the area of hair loss is small. As the hair loss increases, a comb over becomes less effective.
Another method is to wear a hat or a hairpiece such as a wig or toupee. The wig is a layer of artificial or natural hair made to resemble a typical hair style. In most cases the hair is artificial. Wigs vary widely in quality and cost. In the United States, the best wigs – those that look like real hair – cost up to tens of thousands of dollars. Organizations also collect individuals donations of their own natural hair to be made into wigs for young cancer patients who have lost their hair due to chemotherapy or other cancer treatment in addition to any type of hair loss.

Eyebrows
Though not as common as the loss of hair on the head, chemotherapy, hormone imbalance, forms of hair loss, and other factors can also cause loss of hair in the eyebrows. Loss of growth in the outer one third of the eyebrow is often associated with hypothyroidism. Artificial eyebrows are available to replace missing eyebrows or to cover patchy eyebrows. Eyebrow embroidery is another option which involves the use of a blade to add pigment to the eyebrows. This gives a natural 3D look for those who are worried about an artificial look and it lasts for two years. Micropigmentation (permanent makeup tattooing) is also available for those who want the look to be permanent.

Medications
Treatments for the various forms of hair loss have limited success. Three medications have evidence to support their use in male pattern hair loss: minoxidil, finasteride, and dutasteride. They typically work better to prevent further hair loss, than to regrow lost hair. On June 13, 2022, the U.S. Food and Drug Administration (FDA) approved Olumiant (baricitinib) for adults with severe alopecia areatal. It is the first FDA approved drug for systemic treatment, or treatment for any area of the body.
Minoxidil (Rogaine) is a nonprescription medication approved for male pattern baldness and alopecia areata. In a liquid or foam, it is rubbed into the scalp twice a day. Some people have an allergic reaction to the propylene glycol in the minoxidil solution and a minoxidil foam was developed without propylene glycol. Not all users will regrow hair. Minoxidil is also prescribed tablets to be taken orally to encourage hair regrowth although is not FDA approved to treat hair loss. The longer the hair has stopped growing, the less likely minoxidil will regrow hair. Minoxidil is not effective for other causes of hair loss. Hair regrowth can take 1 to 6 months to begin. Treatment must be continued indefinitely. If the treatment is stopped, hair loss resumes. Any regrown hair and any hair susceptible to being lost, while Minoxidil was used, will be lost. Most frequent side effects are mild scalp irritation, allergic contact dermatitis, and unwanted hair in other parts of the body.
Finasteride (Propecia) is used in male-pattern hair loss in a pill form, taken 1 milligram per day. It is not indicated for women and is not recommended in pregnant women (as it is known to cause birth defects in fetuses). Treatment is effective starting within 6 weeks of treatment. Finasteride causes an increase in hair retention, the weight of hair, and some increase in regrowth. Side effects in about 2% of males include decreased sex drive, erectile dysfunction, and ejaculatory dysfunction. Treatment should be continued as long as positive results occur. Once treatment is stopped, hair loss resumes.
Corticosteroids injections into the scalp can be used to treat alopecia areata. This type of treatment is repeated on a monthly basis. Oral pills for extensive hair loss may be used for alopecia areata. Results may take up to a month to be seen.
Immunosuppressants applied to the scalp have been shown to temporarily reverse alopecia areata, though the side effects of some of these drugs make such therapy questionable.
There is some tentative evidence that anthralin may be useful for treating alopecia areata.
Hormonal modulators (oral contraceptives or antiandrogens such as  spironolactone and flutamide) can be used for female-pattern hair loss associated with hyperandrogenemia.

Surgery
Hair transplantation is usually carried out under local anaesthetic. A surgeon will move healthy hair from the back and sides of the head to areas of thinning. The procedure can take between four and eight hours, and additional sessions can be carried out to make hair even thicker. Transplanted hair falls out within a few weeks, but regrows permanently within months. Hair transplants, takes tiny plugs of skin, each which contains a few hairs, and implants the plugs into bald sections. The plugs are generally taken from the back or sides of the scalp. Several transplant sessions may be necessary.
Surgical options, such as follicle transplants, scalp flaps, and hair loss reduction, are available. These procedures are generally chosen by those who are self-conscious about their hair loss, but they are expensive and painful, with a risk of infection and scarring. Once surgery has occurred, six to eight months are needed before the quality of new hair can be assessed.
Scalp reduction is the process is the decreasing of the area of bald skin on the head. In time, the skin on the head becomes flexible and stretched enough that some of it can be surgically removed. After the hairless scalp is removed, the space is closed with hair-covered scalp. Scalp reduction is generally done in combination with hair transplantation to provide a natural-looking hairline, especially those with extensive hair loss.
Hairline lowering can sometimes be used to lower a high hairline secondary to hair loss, although there may be a visible scar after further hair loss.
Wigs are an alternative to medical and surgical treatment; some patients wear a wig or hairpiece. They can be used permanently or temporarily to cover the hair loss. High-quality,  natural-looking wigs and hairpieces are available.

Chemotherapy
Hypothermia caps may be used to prevent hair loss during some kinds of chemotherapy, specifically, when taxanes or anthracyclines are administered. It is not recommended to be used when cancer is present in the skin of the scalp or for lymphoma or leukemia. There are generally only minor side effects from scalp cooling given during chemotherapy.

Embracing baldness
Instead of attempting to conceal their hair loss, some people embrace it by either doing nothing about it or sporting a shaved head. The general public became more accepting of men with shaved heads in the early 1950s, when Russian-American actor Yul Brynner began sporting the look; the resulting phenomenon inspired many of his male fans to shave their heads. Male celebrities then continued to bring mainstream popularity to shaved heads, including athletes such as Michael Jordan and Zinedine Zidane and actors such as Dwayne Johnson, Ben Kingsley, and Jason Statham. Baldness in females, however, is still viewed as less "normal" in various parts of the world.

Alternative medicine
Dietary supplements are not typically recommended. There is only one small trial of saw palmetto which shows tentative benefit in those with  mild to moderate androgenetic alopecia. There is no evidence for biotin. Evidence for most other alternative medicine remedies is also insufficient. There was no good evidence for ginkgo, aloe vera, ginseng, bergamot, hibiscus, or sophora as of 2011.Many people use unproven treatments to treat hair loss. Egg oil, in Indian, Japanese, Unani (Roghan Baiza Murgh) and Chinese traditional medicine, was traditionally used as a treatment for hair loss.

Research
Research is looking into connections between hair loss and other health issues. While there has been speculation about a connection between early-onset male pattern hair loss and heart disease, a review of articles from 1954 to 1999 found no conclusive connection between baldness and coronary artery disease </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 Ichthyosis vulgaris and explain in detail? [/INST] Ichthyosis vulgaris (also known as "autosomal dominant ichthyosis" and "Ichthyosis simplex") is a skin disorder causing dry, scaly skin. It is the most common form of ichthyosis,: 486  affecting around 1 in 250 people. For this reason it is known as common ichthyosis. It is usually an autosomal dominant inherited disease (often associated with filaggrin), although a rare non-heritable version called acquired ichthyosis exists.: 560

Presentation
The symptoms of the inherited form of ichthyosis vulgaris are not usually present at birth but generally develop between three months and five years of age. The symptoms will often improve with age, although they may grow more severe again in old age.The condition is not life-threatening; the impact on the patient, if it is a mild case, is generally restricted to mild itching and the social impact of having skin with an unusual appearance. People with mild cases have symptoms that include scaly patches on the shins, fine white scales on the forearms and upper arms, and rough palms. People with the mildest cases have no symptoms other than faint, tell-tale "mosaic lines" between the Achilles tendons and the calf muscles.

Severe cases, although rare, do exist. Severe cases entail the buildup of scales everywhere, with areas of the body that have a concentration of sweat glands being least affected. Areas where the skin rubs against together, such as the armpits, the groin, and the "folded" areas of the elbow and knees, are less affected. Various topical treatments are available to "exfoliate" the scales. These include lotions that contain alpha-hydroxy acids.

Associated conditions
Many people with severe ichthyosis have problems sweating due to the buildup of scales on the skin. This may lead to problems such as "prickly itch", which results from the afflicted skin being unable to sweat due to the buildup of scales, or problems associated with overheating. The majority of people with vulgaris can sweat at least a little </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 Immune thrombocytopenic purpura and explain in detail? [/INST] Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of other causes of low platelets. It causes a characteristic red or purple bruise-like rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. The acute form often follows an infection and spontaneously resolves within two months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown.
ITP is an autoimmune disease with antibodies detectable against several platelet surface structures.
ITP is diagnosed by identifying a low platelet count on a complete blood count (a common blood test). However, since the diagnosis depends on the exclusion of other causes of a low platelet count, additional investigations (such as a bone marrow biopsy) may be necessary in some cases.
In mild cases, only careful observation may be required but very low counts or significant bleeding may prompt treatment with corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, or immunosuppressive medications. Refractory ITP (not responsive to conventional treatment or constant relapsing after splenectomy) requires treatment to reduce the risk of clinically significant bleeding. Platelet transfusions may be used in severe cases with very low platelet counts in people who are bleeding. Sometimes the body may compensate by making abnormally large platelets.

Signs and symptoms
Signs include the spontaneous formation of bruises (purpura) and petechiae (tiny bruises), especially on the extremities, bleeding from the nostrils and/or gums, and menorrhagia (excessive menstrual bleeding), any of which may occur if the platelet count is below 20,000 per μl. A very low count (<10,000 per μl) may result in the spontaneous formation of hematomas (blood masses) in the mouth or on other mucous membranes. Bleeding time from minor lacerations or abrasions is usually prolonged.Serious and possibly fatal complications due to extremely low counts (<5,000 per μl) include subarachnoid or intracerebral hemorrhage (bleeding inside the skull or brain), lower gastrointestinal bleeding or other internal bleeding. An ITP patient with an extremely low count is vulnerable to internal bleeding caused by blunt abdominal trauma, as might be experienced in a motor vehicle crash. These complications are not likely when the platelet count is above 20,000 per μl.

Pathogenesis
In approximately 60 percent of cases, antibodies against platelets can be detected. Most often these antibodies are against platelet membrane glycoproteins IIb-IIIa or Ib-IX, and are of the immunoglobulin G (IgG) type. The Harrington–Hollingsworth experiment established the immune pathogenesis of ITP.The coating of platelets with IgG renders them susceptible to opsonization and phagocytosis by splenic macrophages, as well by Kupffer cells in the liver. The IgG autoantibodies are also thought to damage megakaryocytes, the precursor cells to platelets, although this is believed to contribute only slightly to the decrease in platelet numbers. Recent research now indicates that impaired production of the glycoprotein hormone, thrombopoietin, which is the stimulant for platelet production, may be a contributing factor to the reduction in circulating platelets. This observation has led to the development of a class of ITP-targeted medications referred to as thrombopoietin receptor agonists.The stimulus for auto-antibody production in ITP is probably abnormal T cell activity. Preliminary findings suggest that these T cells can be influenced by medications that target B cells, such as rituximab.

Diagnosis
The diagnosis of ITP is a process of exclusion. First, it has to be determined that there are no blood abnormalities other than a low platelet count, and no physical signs other than bleeding. Then, secondary causes (5–10 percent of suspected ITP cases) should be excluded. Such secondary causes include leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others. All patients with presumed ITP should be tested for HIV and hepatitis C virus, as platelet counts may be corrected by treating the underlying disease. In approximately 2.7 to 5 percent of cases, autoimmune hemolytic anemia and ITP coexist, a condition referred to as Evans syndrome.Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder.Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed  and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinicians preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.

Treatment
With rare exceptions, there is usually no need to treat based on platelet counts. Many older recommendations suggested a certain platelet count threshold (usually somewhere below 20.0/µl) as an indication for hospitalization or treatment. Current guidelines recommend treatment only in cases of significant bleeding.
Treatment recommendations sometimes differ for adult and pediatric ITP.

Steroids
Initial treatment usually consists of the administration of corticosteroids, a group of medications that suppress the immune system. The dose and mode of administration is determined by platelet count and whether there is active bleeding: in urgent situations, infusions of dexamethasone or methylprednisolone may be used, while oral prednisone or prednisolone may suffice in less severe cases. Once the platelet count has improved, the dose of steroid is gradually reduced while the possibility of relapse is monitored. 60–90 percent will experience a relapse during dose reduction or cessation. Long-term steroids are avoided if possible because of potential side-effects that include osteoporosis, diabetes and cataracts.

Anti-D
Another option, suitable for Rh-positive patients with functional spleens is intravenous administration of Rho(D) immune globulin [Human; Anti-D]. The mechanism of action of anti-D is not fully understood. However, following administration, anti-D-coated red blood cell complexes saturate Fcγ receptor sites on macrophages, resulting in preferential destruction of red blood cells (RBCs), therefore sparing antibody-coated platelets. There are two anti-D products indicated for use in patients with ITP: WinRho SDF and Rhophylac. The most common adverse reactions are headache (15%), nausea/vomiting (12%) chills (<2%) and fever (1%).

Steroid-sparing agents
There is increasing use of immunosuppressants such as mycophenolate mofetil and azathioprine because of their effectiveness. In chronic refractory cases, where immune pathogenesis has been confirmed, the off-label use of the vinca alkaloid and chemotherapy agent vincristine may be attempted. However, vincristine has significant side effects and its use in treating ITP must be approached with caution, especially in children.

Intravenous immunoglobulin
Intravenous immunoglobulin (IVIg) may be infused in some cases in order to decrease the rate at which macrophages consume antibody-tagged platelets. However, while sometimes effective, it is costly and produces improvement that generally lasts less than a month. Nevertheless, in the case of an ITP patient already scheduled for surgery who has a dangerously low platelet count and has experienced a poor response to other treatments, IVIg can rapidly increase platelet counts, and can also help reduce the risk of major bleeding by transiently increasing platelet counts.

Thrombopoietin receptor agonists
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow.  In this, they differ from the previously discussed agents that act by attempting to curtail platelet destruction. Two such products are currently available:

Romiplostim (trade name Nplate) is a thrombopoiesis stimulating Fc-peptide fusion protein (peptibody) that is administered by subcutaneous injection. Designated an orphan drug in 2003 under United States law, clinical trials demonstrated romiplostim to be effective in treating chronic ITP, especially in relapsed post-splenectomy patients. Romiplostim was approved by the United States Food and Drug Administration (FDA) for long-term treatment of adult chronic ITP on August 22, 2008.
Eltrombopag (trade name Promacta in the US, Revolade in the EU) is an orally-administered agent with an effect similar to that of romiplostim. It too has been demonstrated to increase platelet counts and decrease bleeding in a dose-dependent manner. Developed by GlaxoSmithKline and also designated an orphan drug by the FDA, Promacta was approved by the FDA on November 20, 2008.Thrombopoietin receptor agonists exhibited the greatest success so far in treating patients with refractory ITP.Side effects of thrombopoietin receptor agonists include headache, joint or muscle pain, dizziness, nausea or vomiting, and an increased risk of blood clots.

Surgery
Splenectomy (removal of the spleen) may be considered in patients who are either unresponsive to steroid treatment, have frequent relapses, or cannot be tapered off steroids after a few months. Platelets which have been bound by antibodies are taken up by macrophages in the spleen (which have Fc receptors), and so removal of the spleen reduces platelet destruction. The procedure is potentially risky in ITP cases due to the increased possibility of significant bleeding during surgery. Durable remission following splenectomy is achieved in 60 - 80 percent of ITP cases. Even though there is a consensus regarding the short-term efficacy of splenectomy, findings on its long-term efficacy and side-effects are controversial. After splenectomy, 11.6 - 75 percent of ITP cases relapsed, and 8.7 - 40 percent of ITP cases had no response to splenectomy. The use of splenectomy to treat ITP has diminished since the development of steroid therapy and other pharmaceutical remedies.

Platelet transfusion
Platelet transfusion alone is normally not recommended except in an emergency and is usually unsuccessful in producing a long-term platelet count increase. This is because the underlying autoimmune mechanism that is destroying the patients platelets will also destroy donor platelets, and so platelet transfusions are not considered a long-term treatment option.

H. pylori eradication
In adults, particularly those living in areas with a high prevalence of Helicobacter pylori (which normally inhabits the stomach wall and has been associated with peptic ulcers), identification and treatment of this infection has been shown to improve platelet counts in a third of patients. In a fifth, the platelet count normalized completely; this response rate is similar to that found in treatment with rituximab, which is more expensive and less safe. In children, this approach is not supported by evidence, except in high prevalence areas. Urea breath testing and stool antigen testing perform better than serology-based tests; moreover, serology may be false-positive after treatment with IVIG.

Other agents
Dapsone (also called diphenylsulfone, DDS, or avlosulfon) is an anti-infective sulfone medication. Dapsone may also be helpful in treating lupus, rheumatoid arthritis, and as a second-line treatment for ITP. The mechanism by which dapsone assists in ITP is unclear but an increased platelet count is seen in 40–60 percent of recipients.
The off-label use of rituximab, a chimeric monoclonal antibody against the B cell surface antigen CD20, may sometimes be an effective alternative to splenectomy. However, significant side-effects can occur, and randomized controlled trials are inconclusive.

Prognosis
In general patients with acute ITP will only rarely have life-threatening bleeding. most of the patients ultimately have stable but lower platelet counts which is hemostatic for a person. Unlike in pediatric patients who can be cured; most of the adults will run a chronic course even after splenectomy

Epidemiology
A normal platelet count is considered to be in the range of 150,000–450,000 per microlitre (μl) of blood for most healthy individuals. Hence one may be considered thrombocytopenic below that range, although the threshold for a diagnosis of ITP is not tied to any specific number.The incidence of ITP is estimated at 50–100 new cases per million per year, with children accounting for half of that number. At least 70 percent of childhood cases will end up in remission within six months, even without treatment. Moreover, a third of the remaining chronic cases will usually remit during follow-up observation, and another third will end up with only mild thrombocytopenia (defined as a platelet count above 50,000). A number of immune related genes and polymorphisms have been identified as influencing predisposition to ITP, with FCGR3a-V158 allele and KIRDS2/DL2 increasing susceptibility and KIR2DS5 shown to be protective.ITP is usually chronic in adults and the probability of durable remission is 20–40 percent. The male to female ratio in the adult group varies from 1:1.2 to 1.7 in most age ranges (childhood cases are roughly equal for both sexes) and the median age of adults at the diagnosis is 56–60. The ratio between male and female adult cases tends to widen with age. In the United States, the adult chronic population is thought to be approximately 60,000—with women outnumbering men approximately 2 to 1, which has resulted in ITP being designated an orphan disease.The mortality rate due to chronic ITP varies but tends to be higher relative to the general population for any age range. In a study conducted in Great Britain, it was noted that ITP causes an approximately 60 percent higher rate of mortality compared to sex- and age-matched subjects without ITP. This increased risk of death with ITP is largely concentrated in the middle-aged and elderly. Ninety-six percent of reported ITP-related deaths were individuals 45 years or older. No significant difference was noted in the rate of survival between males and females.

Pregnancy
Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patients own platelets and will also cross the placenta and react against fetal platelets.  Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia.  Approximately 10% of newborns affected by ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).No lab test can reliably predict if neonatal thrombocytopenia will occur </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 Impetigo and explain in detail? [/INST] Impetigo is a bacterial infection that involves the superficial skin. The most common presentation is yellowish crusts on the face, arms, or legs. Less commonly there may be large blisters which affect the groin or armpits. The lesions may be painful or itchy. Fever is uncommon.It is typically due to either Staphylococcus aureus or Streptococcus pyogenes. Risk factors include attending day care, crowding, poor nutrition, diabetes mellitus, contact sports, and breaks in the skin such as from mosquito bites, eczema, scabies, or herpes. With contact it can spread around or between people. Diagnosis is typically based on the symptoms and appearance.Prevention is by hand washing, avoiding people who are infected, and cleaning injuries. Treatment is typically with antibiotic creams such as mupirocin or fusidic acid. Antibiotics by mouth, such as cefalexin, may be used if large areas are affected. Antibiotic-resistant forms have been found.Impetigo affected about 140 million people (2% of the world population) in 2010. It can occur at any age, but is most common in young children. In some places the condition is also known as "school sores". Without treatment people typically get better within three weeks. Recurring infections can occur due to colonization of the nose by the bacteria. Complications may include cellulitis or poststreptococcal glomerulonephritis. The name is from the Latin impetere meaning "attack".

Signs and symptoms
Contagious impetigo
This most common form of impetigo, also called nonbullous impetigo, most often begins as a red sore near the nose or mouth which soon breaks, leaking pus or fluid, and forms a honey-colored scab, followed by a red mark which often heals without leaving a scar. Sores are not painful, but they may be itchy. Lymph nodes in the affected area may be swollen, but fever is rare. Touching or scratching the sores may easily spread the infection to other parts of the body.Skin ulcers with redness and scarring also may result from scratching or abrading the skin.

Bullous impetigo
Bullous impetigo, mainly seen in children younger than 2 years, involves painless, fluid-filled blisters, mostly on the arms, legs, and trunk, surrounded by red and itchy (but not sore) skin. The blisters may be large or small. After they break, they form yellow scabs.

Ecthyma
Ecthyma, the nonbullous form of impetigo, produces painful fluid- or pus-filled sores with redness of skin, usually on the arms and legs, become ulcers that penetrate deeper into the dermis. After they break open, they form hard, thick, gray-yellow scabs, which sometimes leave scars. Ecthyma may be accompanied by swollen lymph nodes in the affected area.

Causes
Impetigo is primarily caused by Staphylococcus aureus, and sometimes by Streptococcus pyogenes. Both bullous and nonbullous are primarily caused by S. aureus, with Streptococcus also commonly being involved in the nonbullous form.

Predisposing factors
Impetigo is more likely to infect children ages 2–5, especially those that attend school or day care. 70% of cases are the nonbullous form and 30% are the bullous form. Other factors can increase the risk of contracting impetigo such as diabetes mellitus, dermatitis, immunodeficiency disorders, and other irritable skin disorders. Impetigo occurs more frequently among people who live in warm climates.

Transmission
The infection is spread by direct contact with lesions or with nasal carriers. The incubation period is 1–3 days after exposure to Streptococcus and 4–10 days for Staphylococcus. Dried streptococci in the air are not infectious to intact skin. Scratching may spread the lesions.

Diagnosis
Impetigo is usually diagnosed based on its appearance. It generally appears as honey-colored scabs formed from dried serum and is often found on the arms, legs, or face. If a visual diagnosis is unclear a culture may be done to test for resistant bacteria.

Differential diagnosis
Other conditions that can result in symptoms similar to the common form include contact dermatitis, herpes simplex virus, discoid lupus, and scabies.Other conditions that can result in symptoms similar to the blistering form include other bullous skin diseases, burns, and necrotizing fasciitis.

Prevention
To prevent the spread of impetigo the skin and any open wounds should be kept clean and covered. Care should be taken to keep fluids from an infected person away from the skin of a non-infected person. Washing hands, linens, and affected areas will lower the likelihood of contact with infected fluids. Scratching can spread the sores; keeping nails short will reduce the chances of spreading. Infected people should avoid contact with others and eliminate sharing of clothing or linens. Children with impetigo can return to school 24 hours after starting antibiotic therapy as long as their draining lesions are covered.

Treatment
Antibiotics, either as a cream or by mouth, are usually prescribed. Mild cases may be treated with mupirocin ointments. In 95% of cases, a single 7-day antibiotic course results in resolution in children. It has been advocated that topical antiseptics are inferior to topical antibiotics, and therefore should not be used as a replacement. However, the National Institute for Health and Care Excellence (NICE) as of February 2020 recommends a hydrogen peroxide 1% cream antiseptic rather than topical antibiotics for localised non-bullous impetigo in otherwise well individuals. This recommendation is part of an effort to reduce the overuse of antimicrobials that may contribute to the development of resistant organisms such as MRSA.
More severe cases require oral antibiotics, such as dicloxacillin, flucloxacillin, or erythromycin. Alternatively, amoxicillin combined with clavulanate potassium, cephalosporins (first-generation) and many others may also be used as an antibiotic treatment </s>