<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Xerostomia and can you explain it in depth? [/INST] Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause.
This symptom is very common and is often seen as a side effect of many types of medication. It is more common in older people (mostly because this group tend to take several medications) and in persons who breathe through their mouths. Dehydration, radiotherapy involving the salivary glands, chemotherapy and several diseases can cause reduced salivation (hyposalivation), or a change in saliva consistency and hence a complaint of xerostomia. Sometimes there is no identifiable cause, and there may sometimes be a psychogenic reason for the complaint.

Definition
Xerostomia is the subjective sensation of dry mouth, which is often (but not always) associated with hypofunction of the salivary glands. The term is derived from the Greek words ξηρός (xeros) meaning "dry" and στόμα (stoma) meaning "mouth". A drug or substance that increases the rate of salivary flow is termed a sialogogue.
Hyposalivation is a clinical diagnosis that is made based on the history and examination, but reduced salivary flow rates have been given objective definitions. Salivary gland hypofunction has been defined as any objectively demonstrable reduction in whole and/or individual gland flow rates. An unstimulated whole saliva flow rate in a normal person is 0.3–0.4 ml per minute, and below 0.1 ml per minute is significantly abnormal. A stimulated saliva flow rate less than 0.5 ml per gland in 5 minutes or less than 1 ml per gland in 10 minutes is decreased. The term subjective xerostomia is sometimes used to describe the symptom in the absence of any clinical evidence of dryness. Xerostomia may also result from a change in composition of saliva (from serous to mucous). Salivary gland dysfunction is an umbrella term for the presence of xerostomia, salivary gland hyposalivation, and hypersalivation.

Signs and symptoms
Hyposalivation may give the following signs and symptoms:

Dental caries (xerostomia related caries) – Without the buffering effects of saliva, tooth decay becomes a common feature and may progress much more aggressively than it would otherwise ("rampant caries"). It may affect tooth surfaces that are normally spared, e.g., cervical caries and root surface caries. This is often seen in patients who have had radiotherapy involving the major salivary glands, termed radiation-induced caries. Therefore, it is important that any products used in managing dry mouth symptoms are sugar-free, as the presence of sugars in the mouth support the growth of oral bacteria, resulting in acid production and development of dental caries.
Acid erosion. Saliva acts as a buffer and helps to prevent demineralization of teeth.
Oral candidiasis – A loss of the antimicrobial actions of saliva may also lead to opportunistic infection with Candida species.
Ascending (suppurative) sialadenitis – an infection of the major salivary glands (usually the parotid gland) that may be recurrent. It is associated with hyposalivation, as bacteria are able to enter the ductal system against the diminished flow of saliva. There may be swollen salivary glands even without acute infection, possibly caused by autoimmune involvement.
Dysgeusia – altered taste sensation (e.g., a metallic taste) and dysosmia, altered sense of smell.
Intraoral halitosis –  possibly due to increased activity of halitogenic biofilm on the posterior dorsal tongue (although dysgeusia may cause a complaint of nongenuine halitosis in the absence of hyposalivation).
Burning mouth syndrome – a burning or tingling sensation in the mouth.
Saliva that appears thick or ropey.
Mucosa that appears dry.
A lack of saliva pooling in the floor of the mouth during examination.
Dysphagia – difficulty swallowing and chewing, especially when eating dry foods. Food may stick to the tissues during eating.
The tongue may stick to the palate, causing a clicking noise during speech, or the lips may stick together.
Gloves or a dental mirror may stick to the tissues.
Fissured tongue with atrophy of the filiform papillae and a lobulated, erythematous appearance of the tongue.
Saliva cannot be "milked" (expressed) from the parotid duct.
Difficulty wearing dentures, e.g., when swallowing or speaking. There may be generalized mucosal soreness and ulceration of the areas covered by the denture.
Mouth soreness and oral mucositis.
Lipstick or food may stick to the teeth.
A need to sip drinks frequently while talking or eating.
Dry, sore, and cracked lips and angles of mouth.
Thirst.However, sometimes the clinical findings do not correlate with the symptoms experienced. For example, a person with signs of hyposalivation may not complain of xerostomia. Conversely a person who reports experiencing xerostomia may not show signs of reduced salivary secretions (subjective xerostomia). In the latter scenario, there are often other oral symptoms suggestive of oral dysesthesia ("burning mouth syndrome"). Some symptoms outside the mouth may occur together with xerostomia.
These include:

Xerophthalmia (dry eyes).
Inability to cry.
Blurred vision.
Photophobia (light intolerance).
Dryness of other mucosae, e.g., nasal, laryngeal, and/or genital.
Burning sensation.
Itching or grittiness.
Dysphonia (voice changes).There may also be other systemic signs and symptoms if there is an underlying cause such as Sjögrens syndrome, for example, joint pain due to associated rheumatoid arthritis.

Cause
The differential of hyposalivation significantly overlaps with that of xerostomia. A reduction in saliva production to about 50% of the normal unstimulated level will usually result in the sensation of dry mouth. Altered saliva composition may also be responsible for xerostomia.

Physiologic
Salivary flow rate is decreased during sleep, which may lead to a transient sensation of dry mouth upon waking. This disappears with eating or drinking or with oral hygiene. When associated with halitosis, this is sometimes termed "morning breath". Dry mouth is also a common sensation during periods of anxiety, probably owing to enhanced sympathetic drive. Dehydration is known to cause hyposalivation, the result of the body trying to conserve fluid. Physiologic age-related changes in salivary gland tissues may lead to a modest reduction in salivary output and partially explain the increased prevalence of xerostomia in older people. However, polypharmacy is thought to be the major cause in this group, with no significant decreases in salivary flow rate being likely to occur through aging alone.

Drug induced
Aside from physiologic causes of xerostomia, iatrogenic effects of medications are the most common cause. A medication which is known to cause xerostomia may be termed xerogenic. Over 400 medications are associated with xerostomia. Although drug induced xerostomia is commonly reversible, the conditions for which these medications are prescribed are frequently chronic. The likelihood of xerostomia increases in relation to the total number of medications taken, whether the individual medications are xerogenic or not. The sensation of dryness usually starts shortly after starting the offending medication or after increasing the dose. Anticholinergic, sympathomimetic, or diuretic drugs are usually responsible.

Sjögrens syndrome
Xerostomia may be caused by autoimmune conditions which damage saliva-producing cells. Sjögrens syndrome is one such disease, and it is associated with symptoms including fatigue, myalgia and arthralgia. The disease is characterised by inflammatory changes in the moisture-producing glands throughout the body, leading to reduced secretions from glands that produce saliva, tears and other secretions throughout the body. Primary Sjögrens syndrome is the combination of dry eyes and xerostomia. Secondary Sjögrens syndrome is identical to primary form but with the addition of a combination of other connective tissue disorders such as systemic lupus erythematosus or rheumatoid arthritis.

Celiac disease
Xerostomia may be the only symptom of celiac disease, especially in adults, who often have no obvious digestive symptoms.

Radiation therapy
Radiation therapy for cancers of the head and neck (including brachytherapy for thyroid cancers) where the salivary glands are close to or within the field irradiated is another major cause of xerostomia. A radiation dose of 52 Gy is sufficient to cause severe salivary dysfunction. Radiotherapy for oral cancers usually involves up to 70 Gy of radiation, often given along with chemotherapy which may also have a damaging effect on saliva production. This side effect is a result of radiation damage of the parasympathetic nerves. Formation of salivary gland ducts depends on the secretion of a neuropeptide from the parasympathetic nerves, while development of the end buds of the salivary gland depends on acetylcholine from the parasympathetic nerves.

Sicca syndrome
"Sicca" simply means dryness. Sicca syndrome is not a specific condition, and there are varying definitions, but the term can describe oral and eye dryness that is not caused by autoimmune diseases (e.g., Sjögren syndrome).

Other causes
Oral dryness may also be caused by mouth breathing, usually caused by partial obstruction of the upper respiratory tract. Examples include hemorrhage, vomiting, diarrhea, and fever.Alcohol may be involved in the cause of salivary gland disease, liver disease, or dehydration.Smoking is another possible cause. Other recreational drugs such as methamphetamine, cannabis, hallucinogens, or heroin, may be implicated.
Hormonal disorders, such as poorly controlled diabetes, chronic graft versus host disease or low fluid intake in people undergoing hemodialysis for renal impairment may also result in xerostomia, due to dehydration.Nerve damage can be a cause of oral dryness. An injury to the face or surgery can cause nerve damage to your head and neck area which can effect the nerves that are associated with the salivary flow.Xerostomia may be a consequence of infection with hepatitis C virus (HCV) and a rare cause of salivary gland dysfunction may be sarcoidosis.Infection with Human Immunodeficiency Virus/Acquired immunodeficiency Syndrome (AIDS) can cause a related salivary gland disease known as Diffuse Infiltrative Lymphocytosis Syndrome (DILS).Similar to taste dysfunction, xerostomia is one of the most prevalent and persistent oral symptoms associated with COVID-19. Despite a close association with COVID-19, xerostomia, dry mouth and hyposalivation tend to be overlooked in COVID-19 patients and survivors, unlike ageusia, dysgeusia and hypogeusia.

Diagnostic approach
A diagnosis of hyposalivation is based predominantly on the clinical signs and symptoms. The Challacombe scale maybe used to classify the extent of dryness. The rate of the salivary flow in an individuals mouth can also be measured. There is little correlation between symptoms and objective tests of salivary flow, such as sialometry. This test is simple and noninvasive, and involves measurement of all the saliva a patient can produce during a certain time, achieved by dribbling into a container. Sialometery can yield measures of stimulated salivary flow or unstimulated salivary flow. Stimulated salivary flow rate is calculated using a stimulant such as 10% citric acid dropped onto the tongue, and collection of all the saliva that flows from one of the parotid papillae over five or ten minutes. Unstimulated whole saliva flow rate more closely correlates with symptoms of xerostomia than stimulated salivary flow rate. Sialography involves introduction of radio-opaque dye such as iodine into the duct of a salivary gland. It may show blockage of a duct due to a calculus. Salivary scintiscanning using technetium is rarely used. Other medical imaging that may be involved in the investigation include chest x-ray (to exclude sarcoidosis), ultrasonography and magnetic resonance imaging (to exclude Sjögrens syndrome or neoplasia). A minor salivary gland biopsy, usually taken from the lip, may be carried out if there is a suspicion of organic disease of the salivary glands. Blood tests and urinalysis may be involved to exclude a number of possible causes. To investigate xerophthalmia, the Schirmer test of lacrimal flow may be indicated. Slit-lamp examination may also be carried out.

Treatment
The successful treatment of xerostomia is difficult to achieve and often unsatisfactory. This involves finding any correctable cause and removing it if possible, but in many cases it is not possible to correct the xerostomia itself, and treatment is symptomatic, and also focuses on  preventing tooth decay through improving oral hygiene. Where the symptom is caused by hyposalivation secondary to underlying chronic disease, xerostomia can be considered permanent or even progressive. The management of salivary gland dysfunction may involve the use of saliva substitutes and/or saliva stimulants:

Saliva substitutes – These are viscous products which are applied to the oral mucosa, which can be found in the form of sprays, gels, oils, mouthwashes, mouth rinses, pastilles or viscous liquids. This includes water, artificial salivas (mucin-based, carboxymethylcellulose-based), and other substances (milk, vegetable oil):
Mucin Spray: 4 Trials have been completed on the effects of Mucin Spray on Xerostomia, overall there is no strong evidence showing that Mucin Spray is more effective than  a placebo in reducing the symptoms of dry mouth.
Mucin Lozenge: Only 1 trial (Gravenmade 1993) has been completed regarding the effectiveness of Mucin Lozenges. Whilst it was assessed as being at high risk of bias, it showed that Mucin Lozenges were ineffective when compared to a placebo.
Mucoadhesive Disk: These disks are stuck to the palate and they contain lubricating agents, flavouring agents and some antimicrobial agents. One trial (Kerr 2010) assessed their effectiveness against a placebo disk. Strangely, patients from both groups (placebo and the real disk) reported an increase in subjective oral moistness. No adverse effects were reported. More research is needed in this area before conclusions are drawn.
Biotene oral Balance Gel & toothpaste: One trial has been completed (Epstein 1999) regarding the effectiveness of Biotene Oral Balance gel & toothpaste. The results showed that Biotene products were "more effective than control and reduced dry mouth on waking".
Saliva stimulants – organic acids (ascorbic acid, malic acid), chewing gum, parasympathomimetic drugs (choline esters, e.g. pilocarpine hydrochloride, cholinesterase inhibitors), and other substances (sugar-free mints, nicotinamide). Medications which stimulate saliva production traditionally have been administered through oral tablets, which the patient goes on to swallow, although some saliva stimulants can also be found in the form of toothpastes. Lozenges, which are retained in the mouth and then swallowed are becoming more and more popular. Lozenges are soft and gentle on the mouth and there is a belief that prolonged contact with the oral mucosa mechanically stimulates saliva production.Pilocarpine: A study by Taweechaisupapong in 2006 showed no statistical significant improvement in oral dryness and saliva production compared to placebo when administering pilocarpine lozenges.
Physostigmine Gel: A study by Knosravini in 2009 showed a reduction in the oral dryness and a 5 times increase in saliva following physostigmine treatment.
Chewing gum increases saliva production but there is no strong evidence that it improves dry mouth symptoms.
The Cochrane oral health group concluded there is insufficient evidence to determine whether pilocarpine or physostigmine are effective treatments for Xerostomia. More research is needed.
Dentirol chewing gum (xylitol): A study by Risheim in 1993 showed that when subjects had 2 sticks of gum up to 5 x daily, the gum gave subjective dry mouth symptom relief in approximately 1/3 of participants but no change in SWS (stimulated whole saliva).
Profylin lozenge (xylitol/sorbitol):A study by Risheim in 1993 showed that when subjects had 1 lozenge 4 to 8 x daily, Profylin lozenges gave subjective dry mouth symptom relief in approximately 1/3 of participants but no change in SWS (stimulated whole saliva).Saliva substitutes can improve xerostomia, but tend not to improve the other problems associated with salivary gland dysfunction. Parasympathomimetic drugs (saliva stimulants) such as pilocarpine may improve xerostomia symptoms and other problems associated with salivary gland dysfunction, but the evidence for treatment of radiation-induced xerostomia is limited. Both stimulants and substitutes relieve symptoms to some extent.  Salivary stimulants are probably only useful in people with some remaining detectable salivary function. A systematic review compromising of 36 randomised controlled trials for the treatment of dry mouth found that there was no strong evidence to suggest that a specific topical therapy is effective. This review also states that topical therapies can be expected to provide only short-term effects, which are reversible. The review reported limited evidence that oxygenated glycerol triester spray was more effective than electrolyte sprays. Sugar free chewing gum increases saliva production but there is no strong evidence that it improves symptoms.  Plus, there is no clear evidence to suggest whether chewing gum is more or less effective as a treatment </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Yersiniosis and can you explain it in depth? [/INST] Yersiniosis is an infectious disease caused by a bacterium of the genus Yersinia.  In the United States, most yersiniosis infections among humans are caused by Yersinia enterocolitica.
Infection with  Y. enterocolitica occurs most often in young children </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Zinc deficiency and can you explain it in depth? [/INST] Zinc deficiency  is defined either as insufficient zinc to meet the needs of the body, or as a serum zinc level below the normal range. However, since a decrease in the serum concentration is only detectable after long-term or severe depletion, serum zinc is not a reliable biomarker for zinc status. Common symptoms include increased rates of diarrhea. Zinc deficiency affects the skin and gastrointestinal tract; brain and central nervous system, immune, skeletal, and reproductive systems.
Zinc deficiency in humans is caused by reduced dietary intake, inadequate absorption, increased loss, or increased body system use. The most common cause is reduced dietary intake. In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men.The highest concentration of dietary zinc is found in oysters, meat, beans, and nuts. Increasing the amount of zinc in the soil and thus in crops and animals is an effective preventive measure. Zinc deficiency may affect up to 2 billion people worldwide.

Signs and symptoms
Skin, nails and hair
Zinc deficiency may manifest as acne, eczema, xerosis (dry, scaling skin), seborrheic dermatitis, or alopecia (thin and sparse hair). It may also impair or possibly prevent wound healing.

Mouth
Zinc deficiency can manifest as non-specific oral ulceration, stomatitis, or white tongue coating. Rarely it can cause angular cheilitis (sores at the corners of the mouth).

Vision, smell and taste
Severe zinc deficiency may disturb the sense of smell and taste. Night blindness may be a feature of severe zinc deficiency, although most reports of night blindness and abnormal dark adaptation in humans with zinc deficiency have occurred in combination with other nutritional deficiencies (e.g. vitamin A).

Immune system
Impaired immune function in people with zinc deficiency can lead to the development of respiratory, gastrointestinal, or other infections, e.g., pneumonia. The levels of inflammatory cytokines (e.g., IL-1β, IL-2, IL-6, and TNF-α) in blood plasma are affected by zinc deficiency and zinc supplementation produces a dose-dependent response in the level of these cytokines. During inflammation, there is an increased cellular demand for zinc and impaired zinc homeostasis from zinc deficiency is associated with chronic inflammation.

Diarrhea
Zinc deficiency contributes to an increased incidence and severity of diarrhea.

Appetite
Zinc deficiency may lead to loss of appetite. The use of zinc in the treatment of anorexia has been advocated since 1979 by Bakan. At least 15 clinical trials have shown that zinc improved weight gain in anorexia. A 1994 trial showed that zinc doubled the rate of body mass increase in the treatment of anorexia nervosa. Deficiency of other nutrients such as tyrosine, tryptophan and thiamine could contribute to this phenomenon of "malnutrition-induced malnutrition".

Cognitive function and hedonic tone
Cognitive functions, such as learning and hedonic tone, are impaired with zinc deficiency. Moderate and more severe zinc deficiencies are associated with behavioral abnormalities, such as irritability, lethargy, and depression (e.g., involving anhedonia). Zinc supplementation produces a rapid and dramatic improvement in hedonic tone (i.e., general level of happiness or pleasure) under these circumstances. Zinc supplementation has been reported to improve symptoms of ADHD and depression.

Psychological disorders
Low plasma zinc levels have been alleged to be associated with many psychological disorders.  Schizophrenia has been linked to decreased brain zinc levels. Evidence suggests that zinc deficiency could play a role in depression. Zinc supplementation may be an effective treatment in major depression.

Growth
Zinc deficiency in children can cause delayed growth and has been claimed to be the cause of stunted growth in one third of the worlds population.

During pregnancy
Zinc deficiency during pregnancy can negatively affect both the mother and fetus. Animal studies indicate that maternal zinc deficiency can upset both the sequencing and efficiency of the birth process. An increased incidence of difficult and prolonged labor, hemorrhage, uterine dystocia and placental abruption has been documented in zinc deficient animals. These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger protein. A review of pregnancy outcomes in women with acrodermatitis enteropathica, reported that out of every seven pregnancies, there was one abortion and two malfunctions, suggesting the human fetus is also susceptible to the teratogenic effects of severe zinc deficiency. However, a review on zinc supplementation trials during pregnancy did not report a significant effect of zinc supplementation on neonatal survival.Zinc deficiency can interfere with many metabolic processes when it occurs during infancy and childhood, a time of rapid growth and development when nutritional needs are high. Low maternal zinc status has been associated with less attention during the neonatal period and worse motor functioning. In some studies, supplementation has been associated with motor development in very low birth weight infants and more vigorous and functional activity in infants and toddlers.

Testosterone production
Zinc is required to produce testosterone. Thus, zinc deficiency can lead to reduced circulating testosterone, which could lead to sexual immaturity (Ananda Parsad, et al.) hypogonadism, and delayed puberty.

Causes
Dietary deficiency
Zinc deficiency can be caused by a diet high in phytate-containing whole grains, foods grown in zinc deficient soil, or processed foods containing little or no zinc. Conservative estimates suggest that 25% of the worlds population is at risk of zinc deficiency.In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men. RDA for pregnancy is 11 mg/day. RDA for lactation is 12 mg/day. For infants up to 12 months the RDA is 3 mg/day. For children ages 1–13 years the RDA increases with age from 3 to 8 mg/day. The following table summarizes most of the foods with significant quantities of zinc, listed in order of quantity per serving, unfortified. Note that all of the top 10 entries are meat, beans, or nuts.

Recent research findings suggest that increasing atmospheric carbon dioxide concentrations will exacerbate zinc deficiency problems in populations that consume grains and legumes as staple foods. A meta-analysis of data from 143 studies comparing the nutrient content of grasses and legumes grown in ambient and elevated CO2 environments found that the edible portions of wheat, rice, peas and soybeans grown in elevated CO2 contained less zinc and iron. Global atmospheric CO2 concentration is expected to reach 550 p.p.m. in the late 21st century. At this CO2 level the zinc content of these crops was 3.3 to 9.3% lower than that of crops grown in the present atmosphere. A model of the nutritional impact of these lower zinc quantities on the populations of 151 countries predicts that an additional 175 million people could face dietary zinc deficiency as the result of increasing atmospheric CO2.

Inadequate absorption
Acrodermatitis enteropathica is an inherited deficiency of the zinc carrier protein ZIP4 resulting in inadequate zinc absorption. It presents as growth retardation, severe diarrhea, hair loss, skin rash (most often around the genitalia and mouth) and opportunistic candidiasis and bacterial infections.Numerous small bowel diseases which cause destruction or malfunction of the gut mucosa enterocytes and generalized malabsorption are associated with zinc deficiency.

Increased loss
Exercising, high alcohol intake, and diarrhea all increase loss of zinc from the body. Changes in intestinal tract absorbability and permeability due, in part, to viral, protozoal, or bacteria pathogens may also encourage fecal losses of zinc.

Chronic disease
The mechanism of zinc deficiency in some diseases has not been well defined; it may be multifactorial.Wilsons disease, sickle cell disease, chronic kidney disease, chronic liver disease have all been associated with zinc deficiency. It can also occur after bariatric surgery, mercury exposure and tartrazine.Although marginal zinc deficiency is often found in depression, low zinc levels could either be a cause or a consequence of mental disorders and their symptoms.

Mechanism
As biosystems are unable to store zinc, regular intake is necessary. Excessively low zinc intake can lead to zinc deficiency, which can negatively impact an individuals health. The mechanisms for the clinical manifestations of zinc deficiency are best appreciated by recognizing that zinc functions in the body in three areas: catalytic, structural, and regulatory. Zinc (Zn) is only common in its +2 oxidative state, where it typically coordinates with tetrahedral geometry. It is important in maintaining basic cellular functions such as DNA replication, RNA transcription, cell division and cell activations. However, having too much or too little zinc can cause these functions to be compromised.
Zinc is a critical component of the catalytic site of hundreds of kinds of different metalloenzymes in each human being. In its structural role, zinc coordinates with certain protein domains, facilitating protein folding and producing structures such as zinc fingers. In its regulatory role, zinc is involved in the regulation of nucleoproteins and the activity of various inflammatory cells. For example, zinc regulates the expression of metallothionein, which has multiple functions, such as intracellular zinc compartmentalization and antioxidant function. Thus zinc deficiency results in disruption of hundreds of metabolic pathways, causing numerous clinical manifestations, including impaired growth and development, and disruption of reproductive and immune function.Pra1 (pH regulated antigen 1) is a candida albicans protein that scavenges host zinc.

Diagnosis
Diagnosis is typically made based on clinical suspicion and a low level of zinc in the blood. Any level below 70 mcg/dl (normal 70-120 mcg/dl)is considered as zinc deficiency. Zinc deficiency could be also associated with low alkaline phosphatase since it acts a cofactor for this enzyme.There is a paucity of adequate zinc biomarkers, and the most widely used indicator, plasma zinc, has poor sensitivity and specificity.

Classification
Zinc deficiency can be classified as acute, as may occur during prolonged inappropriate zinc-free total parenteral nutrition; or chronic, as may occur in dietary deficiency or inadequate absorption.

Prevention
Five interventional strategies can be used:

Adding zinc to soil, called agronomic biofortification, which both increases crop yields and provides more dietary zinc.
Adding zinc to food, called food fortification. The Republic of China, India, Mexico and about 20 other countries, mostly on the east coast of sub-Saharan Africa, fortify wheat flour and/or maize flour with zinc.
Adding zinc rich foods to diet. The foods with the highest concentration of zinc are proteins, especially animal meats, the highest being oysters. Per ounce, beef, pork, and lamb contain more zinc than fish. The dark meat of a chicken has more zinc than the light meat. Other good sources of zinc are nuts, whole grains, legumes, and yeast. Although whole grains and cereals are high in zinc, they also contain chelating phytates which bind zinc and reduce its bioavailability.
Oral repletion via tablets (e.g. zinc gluconate) or liquid (e.g. zinc acetate). Oral zinc supplementation in healthy infants more than six months old has been shown to reduce the duration of any subsequent diarrheal episodes by about 11 hours.
Oral repletion via multivitamin/mineral supplements containing zinc gluconate, sulfate, or acetate. It is not clear whether one form is better than another.

Epidemiology
Zinc deficiency affects about 2.2 billion people around the world. Severe zinc deficiency is rare, and is mainly seen in persons with acrodermatitis enteropathica, a severe defect in zinc absorption due to a congenital deficiency in the zinc carrier protein ZIP4 in the enterocyte. Mild zinc deficiency due to reduced dietary intake is common. Conservative estimates suggest that 25% of the worlds population is at risk of zinc deficiency. Zinc deficiency is thought to be a leading cause of infant mortality.Providing micronutrients, including zinc, to humans is one of the four solutions to major global problems identified in the Copenhagen Consensus from an international panel of economists.

History
Significant historical events related to zinc deficiency began in 1869 when zinc was first discovered to be essential to the growth of an organism Aspergillus niger. In 1929 Lutz measured zinc in numerous human tissues using the dithizone technique and estimated total body zinc in a 70 kg man to be 2.2 grams. Zinc was found to be essential to the growth of rats in 1933. In 1939 beriberi patients in China were noted to have decreased zinc levels in skin and nails. In 1940 zinc levels in a series of autopsies found it to be present in all tissues examined. In 1942 a study showed most zinc excretion was via the feces. In 1950 a normal serum zinc level was first defined, and found to be 17.3–22.1 micromoles/liter. In 1956 cirrhotic patients were found to have low serum zinc levels. In 1963 zinc was determined to be essential to human growth, three enzymes requiring zinc as a cofactor were described, and a report was published of a 21-year-old Iranian man with stunted growth, infantile genitalia, and anemia which were all reversed by zinc supplementation. In 1972 fifteen Iranian rejected army inductees with symptoms of zinc deficiency were reported: all responded to zinc. In 1973 the first case of acrodermatitis enteropathica due to severe zinc deficiency was described. In 1974 the National Academy of Sciences declared zinc to be an essential element for humans and established a recommended daily allowance. In 1978 the Food and Drug Administration required zinc to be in total parenteral nutrition fluids. In the 1990s there was increasing attention on the role of zinc deficiency in childhood morbidity and mortality in developing countries. In 2002 the zinc transporter protein ZIP4 was first identified as the mechanism for absorption of zinc in the gut across the basolateral membrane of the enterocyte. By 2014 over 300 zinc containing enzymes have been identified, as well as over 1000 zinc containing transcription factors.Phytate was recognized as removing zinc from nutrients given to chicken and swine in 1960. That it can cause human zinc deficiency however was not recognized until Reinholds work in Iran in the 1970s. This phenomenon is central to the high risk of zinc deficiency worldwide.

Soils and crops
Soil zinc is an essential micronutrient for crops. Almost half of the worlds cereal crops are deficient in zinc, leading to poor crop yields. Many agricultural countries around the world are affected by zinc deficiency. In China, zinc deficiency occurs on around half of the agricultural soils, affecting mainly rice and maize. Areas with zinc deficient soils are often regions with widespread zinc deficiency in humans. A basic knowledge of the dynamics of zinc in soils, understanding of the uptake and transport of zinc in crops and characterizing the response of crops to zinc deficiency are essential steps in achieving sustainable solutions to the problem of zinc deficiency in crops and humans.

Biofortification
Soil and foliar application of zinc fertilizer can effectively increase grain zinc and reduce the phytate:zinc ratio in grain. People who eat bread prepared from zinc enriched wheat have a significant increase in serum zinc.Zinc fertilization not only increases zinc content in zinc deficient crops, it also increases crop yields. Balanced crop nutrition supplying all essential nutrients, including zinc, is a cost effective management strategy. Even with zinc-efficient varieties, zinc fertilizers are needed when the available zinc in the topsoil becomes depleted.
Plant breeding can improve zinc uptake capacity of plants under soil conditions with low chemical availability of zinc. Breeding can also improve zinc translocation which elevates zinc content in edible crop parts as opposed to the rest of the plant.
Central Anatolia, in Turkey, was a region with zinc-deficient soils and widespread zinc deficiency in humans. In 1993, a research project found that yields could be increased by 6 to 8-fold and child nutrition dramatically increased through zinc fertilization. Zinc was added to fertilizers. While the product was initially made available at the same cost, the results were so convincing that Turkish farmers significantly increased the use of the zinc-fortified fertilizer (1 percent of zinc) within a few years, despite the repricing of the products to reflect the added value of the content. Nearly ten years after the identification of the zinc deficiency problem, the total amount of zinc-containing compound fertilizers produced and applied in Turkey reached a record level of 300,000 tonnes per annum. It is estimated that the economic benefits associated with the application of zinc fertilizers on zinc deficient soils in Turkey is around US$100 million per year. Zinc deficiency in children has been dramatically reduced.

References
Further reading
Maret W (2013). "Chapter 14 Zinc and the Zinc Proteome".  In Banci L (ed.). Metallomics and the Cell </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Zollinger–Ellison syndrome and can you explain it in depth? [/INST] Zollinger–Ellison syndrome (Z-E syndrome) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea.
The syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin. Too much gastrin in the blood (hypergastrinemia) results in the overproduction of gastric acid by parietal cells in the stomach. Gastrinomas most commonly arise in the duodenum, pancreas or stomach.In 75% of cases Zollinger–Ellison syndrome occurs sporadically, while in 25% of cases it occurs as part of an autosomal dominant syndrome called multiple endocrine neoplasia type 1 (MEN 1).

Signs and symptoms
Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment.
Chronic diarrhea, including steatorrhea (fatty stools)
Pain in the esophagus, especially between and after meals at night
Nausea
Wheezing
Vomiting blood
Malnourishment
Loss of appetite
MalabsorptionGastrinomas may occur as single tumors or as multiple small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and to lymph nodes near the pancreas and small bowel.
Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type 1 (MEN 1). MEN I patients have tumors in their pituitary gland and parathyroid glands, in addition to tumors of the pancreas.

Pathophysiology
Gastrin works on the parietal cells of the gastric glands, causing them to secrete more hydrogen ions into the stomach lumen. In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Normally, hydrogen ion secretion is controlled by a negative feedback loop by gastric cells to maintain a suitable pH, however, the neuroendocrine tumor that is present in individuals with Zollinger–Ellison Syndrome has no regulation, resulting in excessively large amounts of secretion. Thus, there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The increase in acidity contributes to the development of peptic ulcers in the stomach, duodenum (first portion of the small bowel) and occasionally the jejunum (second portion of the small bowel), the last of which is an atypical ulcer.

Diagnosis
Zollinger–Ellison syndrome may be suspected when the above symptoms prove resistant to treatment when the symptoms are especially suggestive of the syndrome, or when endoscopy is suggestive. The diagnosis is made through several laboratory tests and imaging studies:
Secretin stimulation test, which measures evoked gastrin levels </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Skeletal fluorosis and can you explain it in depth? [/INST] Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride leading to weakened bones. In advanced cases, skeletal fluorosis causes painful damage to bones and joints.

Symptoms
Symptoms are mainly promoted in the bone structure. Due to a high fluoride concentration in the body, the bone is hardened and thus less elastic, resulting in an increased frequency of fractures. Other symptoms include thickening of the bone structure and accumulation of bone tissue, which both contribute to impaired joint mobility. Ligaments and cartilage can become ossified. Most patients with skeletal fluorosis show side effects from the high fluoride dose such as ruptures of the stomach lining and nausea.
Fluoride can also damage the parathyroid glands, leading to hyperparathyroidism, the uncontrolled secretion of parathyroid hormones. These hormones regulate calcium concentration in the body. An elevated parathyroid hormone concentration results in a depletion of calcium in bone structures and thus a higher calcium concentration in the blood. As a result, bone flexibility decreases making the bone more susceptible to fractures.

Causes
Common causes of fluorosis include inhalation of fluoride dusts or fumes by workers in industry and consumption of fluoride from drinking water (levels of fluoride in excess of levels that are considered safe.)
In India, especially the Nalgonda region (Telangana), a common cause of fluorosis is fluoride-rich drinking water that is sourced from deep-bore wells. Over half of groundwater sources in India have fluoride above recommended levels.Fluorosis can also occur as a result of volcanic activity. The 1783 eruption of the Laki volcano in Iceland is estimated to have killed about 22% of the Icelandic population, and 60% of livestock, as a result of fluorosis and sulfur dioxide gases.  The 1693 eruption of Hekla also led to fatalities of livestock under similar conditions.

Skeletal fluorosis phases
Treatment
As of now, there are no established treatments for skeletal fluorosis patients. However, it is reversible in some cases, depending on the progression of the disease. If fluorine intake is stopped, the amount in bone will decrease and be excreted via urine.  However, it is a very slow process to eliminate the fluorine from the body completely. Minimal results are seen in patients.
Treatment of side effects is also very difficult. For example, a patient with a bone fracture cannot be treated according to standard procedures, because the bone is very brittle. In this case, recovery will take a very long time and a pristine healing cannot be guaranteed. However, further fluorosis can be prevented by drinking defluoridated water. It is recently suggested that drinking of defluoridated water from the "calcium amended-hydroxyapatite" defluoridation method may help in the fluorosis reversal.  Defluoridated water from this suggested method provides calcium-enriched alkaline drinking water as generally fluoride contaminated water has a low amount of calcium mineral and drinking alkaline water helps in eliminating the toxic fluoride from the body.

Epidemiology
In some areas, skeletal fluorosis is endemic </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Amylase and can you explain it in depth? [/INST] An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin amylum) into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of starch but little sugar, such as rice and potatoes, may acquire a slightly sweet taste as they are chewed because amylase degrades some of their starch into sugar. The pancreas and salivary gland make amylase (alpha amylase) to hydrolyse dietary starch into disaccharides and trisaccharides which are converted by other enzymes to glucose to supply the body with energy. Plants and some bacteria also produce amylase. Specific amylase proteins are designated by different Greek letters. All amylases are glycoside hydrolases and act on α-1,4-glycosidic bonds.

Classification
α-Amylase
The α-amylases (EC 3.2.1.1 ) (CAS 9014-71-5) (alternative names: 1,4-α-D-glucan glucanohydrolase; glycogenase) are calcium metalloenzymes.  By acting at random locations along the starch chain, α-amylase breaks down long-chain saccharides, ultimately yielding either maltotriose and maltose from amylose, or maltose, glucose and "limit dextrin" from amylopectin. They belong to glycoside hydrolase family 13.
Because it can act anywhere on the substrate, α-amylase tends to be faster-acting than β-amylase.  In animals, it is a major digestive enzyme, and its optimum pH is 6.7–7.0.In human physiology, both the salivary and pancreatic amylases are α-amylases.
The α-amylase form is also found in plants, fungi (ascomycetes and basidiomycetes) and bacteria (Bacillus).

β-Amylase
Another form of amylase, β-amylase (EC 3.2.1.2 ) (alternative names: 1,4-α-D-glucan maltohydrolase; glycogenase; saccharogen amylase) is also synthesized by bacteria, fungi, and plants.  Working from the non-reducing end, β-amylase catalyzes the hydrolysis of the second α-1,4 glycosidic bond, cleaving off two glucose units (maltose) at a time.  During the ripening of fruit, β-amylase breaks starch into maltose, resulting in the sweet flavor of ripe fruit. They belong to glycoside hydrolase family 14.
Both α-amylase and β-amylase are present in seeds; β-amylase is present in an inactive form prior to germination, whereas α-amylase and proteases appear once germination has begun. Many microbes also produce amylase to degrade extracellular starches.  Animal tissues do not contain β-amylase, although it may be present in microorganisms contained within the digestive tract. The optimum pH for β-amylase is 4.0–5.0.

γ-Amylase
γ-Amylase (EC 3.2.1.3 ) (alternative names: Glucan 1,4-a-glucosidase; amyloglucosidase; exo-1,4-α-glucosidase; glucoamylase; lysosomal α-glucosidase; 1,4-α-D-glucan glucohydrolase) will cleave α(1–6) glycosidic linkages, as well as the last α-1,4 glycosidic bond at the nonreducing end of amylose and amylopectin, yielding glucose. The γ-amylase has the most acidic optimum pH of all amylases because it is most active around pH 3. They belong to a variety of different GH families, such as glycoside hydrolase family 15 in fungi, glycoside hydrolase family 31 of human MGAM, and glycoside hydrolase family 97 of bacterial forms.

Uses
Fermentation
α- and β-amylases are important in brewing beer and liquor made from sugars derived from starch.  In fermentation, yeast ingests sugars and excretes ethanol.  In beer and some liquors, the sugars present at the beginning of fermentation have been produced by "mashing" grains or other starch sources (such as potatoes). In traditional beer brewing, malted barley is mixed with hot water to create a "mash", which is held at a given temperature to allow the amylases in the malted grain to convert the barleys starch into sugars.  Different temperatures optimize the activity of alpha or beta amylase, resulting in different mixtures of fermentable and unfermentable sugars. In selecting mash temperature and grain-to-water ratio, a brewer can change the alcohol content, mouthfeel, aroma, and flavor of the finished beer.
In some historic methods of producing alcoholic beverages, the conversion of starch to sugar starts with the brewer chewing grain to mix it with saliva. This practice continues to be practiced in home production of some traditional drinks, such as chhaang in the Himalayas, chicha  in the Andes and kasiri in Brazil and Suriname.

Flour additive
Amylases are used in breadmaking and to break down complex sugars, such as starch (found in flour), into simple sugars. Yeast then feeds on these simple sugars and converts it into the waste products of ethanol and carbon dioxide. This imparts flavour and causes the bread to rise. While amylases are found naturally in yeast cells, it takes time for the yeast to produce enough of these enzymes to break down significant quantities of starch in the bread. This is the reason for long fermented doughs such as sourdough. Modern breadmaking techniques have included amylases (often in the form of malted barley) into bread improver, thereby making the process faster and more practical for commercial use.α-Amylase is often listed as an ingredient on commercially package-milled flour.  Bakers with long exposure to amylase-enriched flour are at risk of developing dermatitis or asthma.

Molecular biology
In molecular biology, the presence of amylase can serve as an additional method of selecting for successful integration of a reporter construct in addition to antibiotic resistance. As reporter genes are flanked by homologous regions of the structural gene for amylase, successful integration will disrupt the amylase gene and prevent starch degradation, which is easily detectable through iodine staining.

Medical uses
Amylase also has medical applications in the use of pancreatic enzyme replacement therapy (PERT). It is one of the components in Sollpura (liprotamase) to help in the breakdown of saccharides into simple sugars.

Other uses
An inhibitor of alpha-amylase, called phaseolamin, has been tested as a potential diet aid.When used as a food additive, amylase has E number E1100, and may be derived from pig pancreas or mold fungi.
Bacilliary amylase is also used in clothing and dishwasher detergents to dissolve starches from fabrics and dishes.
Factory workers who work with amylase for any of the above uses are at increased risk of occupational asthma. Five to nine percent of bakers have a positive skin test, and a fourth to a third of bakers with breathing problems are hypersensitive to amylase.

Hyperamylasemia
Blood serum amylase may be measured for purposes of medical diagnosis. A higher than normal concentration may reflect any of several medical conditions, including acute inflammation of the pancreas (it may be measured concurrently with the more specific lipase), perforated peptic ulcer, torsion of an ovarian cyst, strangulation, ileus, mesenteric ischemia, macroamylasemia and mumps.  Amylase may be measured in other body fluids, including urine and peritoneal fluid.
A January 2007 study from Washington University in St. Louis suggests that saliva tests of the enzyme could be used to indicate sleep deficits, as the enzyme increases its activity in correlation with the length of time a subject has been deprived of sleep.

History
In 1831, Erhard Friedrich Leuchs (1800–1837) described the hydrolysis of starch by saliva, due to the presence of an enzyme in saliva, "ptyalin", an amylase. it was named after the Ancient Greek name for saliva: πτύαλον - ptyalon.
The modern history of enzymes began in 1833, when French chemists Anselme Payen and Jean-François Persoz isolated an amylase complex from germinating barley and named it "diastase". It is from this term that all subsequent enzyme names tend to end in the suffix -ase.
In 1862, Alexander Jakulowitsch Danilewsky (1838–1923) separated pancreatic amylase from trypsin.

Evolution
Salivary amylase
Saccharides are a food source rich in energy. Large polymers such as starch are partially hydrolyzed in the mouth by the enzyme amylase before being cleaved further into sugars. Many mammals have seen great expansions in the copy number of the amylase gene. These duplications allow for the pancreatic amylase AMY2 to re-target to the salivary glands, allowing animals to detect starch by taste and to digest starch more efficiently and in higher quantities. This has happened independently in mice, rats, dogs, pigs, and most importantly, humans after the agricultural revolution.Following the agricultural revolution 12,000 years ago, human diet began to shift more to plant and animal domestication in place of hunting and gathering </s>


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


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


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


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Spontaneous coronary artery dissection and can you explain it in depth? [/INST] Spontaneous coronary artery dissection (SCAD) is an uncommon but dangerous condition in which one of the arteries that supply the heart spontaneously develops a blood collection, or hematoma, within the artery wall. This leads to a separation and weakening of the walls of the artery.
SCAD is a major cause of heart attacks in young, otherwise healthy women without known risk factors. While the exact cause is not yet known, SCAD is likely related to changes that occur during and after pregnancy, as well as other diseases. These changes lead to the dissection of the wall which restricts blood flow to the heart and causes symptoms. SCAD is often diagnosed in the cath lab with angiography, though more advanced confirmatory tests exist. While the risk of death due to SCAD is low, it has a relatively high rate of recurrence leading to further heart attack-like symptoms in the future. It was first described in 1931.

Signs and symptoms
SCAD often presents like a heart attack in young to middle-aged, healthy women. This pattern usually includes chest pain, rapid heartbeat, shortness of breath, sweating, extreme tiredness, nausea, and dizziness. A minority of people with SCAD may also present in cardiogenic shock (2-5%), ventricular arrhythmias (3-11%), or after sudden cardiac death. Pregnancy- and postpartum-associated SCAD generally have worse outcomes compared to other cases.

Causes
Risk factors include pregnancy and the postpartum period. Evidence suggests that estrogen- and progesterone-related vascular changes affect the coronary arteries during this period, contributing to SCAD. Some case reports and case series suggest associations with autoimmune inflammatory diseases, but there have not been larger studies to explore this relationship. Underlying heritable conditions such as fibromuscular dysplasia and connective-tissue disorders (e.g., Marfan syndrome, Ehlers–Danlos syndrome, and Loeys–Dietz syndrome) are associated with SCAD, but SCAD otherwise lacks a significant genetic component. SCAD triggers may include severe physical or emotional stress, but many cases have no obvious cause.

Pathophysiology
SCAD symptoms are the result of a restriction in the size of the affected coronary artery. The dissection leads to a collection of blood, or hematoma, between the layers of the artery wall. The hematoma does not carry oxygen to the heart muscle but instead forms a "false lumen" that restricts the flow of blood through the "true lumen" to the heart muscle. As yet, there is no consensus on why the hematoma develops in the first place.The restriction limits the availability of oxygen and nutrients to the heart muscle, or myocardium. As a result, the myocardium continues to demand oxygen but is not adequately supplied by the coronary artery. This imbalance leads to ischemia, damage, and eventually death of myocardium, causing a heart attack (myocardial infarction).

Diagnosis
Given the demographics of SCAD, it is important to maintain a high index of suspicion for the condition in otherwise low-risk women presenting with symptoms of acute coronary syndrome. Initial evaluation may show ECG changes of ST elevation, like heart attacks due to other causes. SCAD comprises 2-4% of all cases of acute coronary syndrome.With typically elevated cardiac biomarkers and ECG changes, people will often undergo coronary angiography evaluation. It is important to recognize SCAD through angiography as other confirmatory measures carry increased risks.

Angiography
There are 3 types of SCAD based on angiographic and anatomical criteria; with the designations based on the location and extent of the hematoma within the walls of the coronary arteries. Type 1 SCAD results from an intimal tear of the coronary artery (a tear of the innermost layer of the arterial wall) creating a false lumen as blood flows into the new space. A type 1 SCAD lesion is seen on angiography or intravascular imaging as a radiolucent flap separating the two flow channels; separating the false lumen from the true lumen of the coronary artery. Type 2 SCAD, the most common type of SCAD lesions, seen in 60-75% of patients, occurs due to an intramural hematoma or a collection of blood in the muscular layer of the coronary artery wall with the absence of intimal tearing. This is seen on coronary angiography as an abrupt change in coronary caliber with a long segment of a diffusely narrowed artery (typically longer than 20 mm). Type 2 SCAD is subdivided into type 2A where the narrowed segment of the coronary artery is flanked by normal caliber segments and type 2B where the stenosis continues to the terminus of a coronary artery. Type 3 SCAD, the least common type, is also due to an intramural hematoma causing coronary stenosis, but the lesions are shorter than as seen in type 2 SCAD, being less than 20 mm in length. Due to the short segment of coronary stenosis in type 3 SCAD, it is often difficult to differentiate type 3 SCAD lesions from coronary stenosis due to atherosclerotic plaques and intra-coronary imaging is often needed to distinguish between the two. Some authors have proposed a fourth designation of SCAD, type 4 SCAD, in which there is a complete intraluminal occlusion of the coronary artery due to any of the  previously mentioned types (Type 1–3).

Intracoronary imaging
Intracoronary imaging (ICI), consisting of intracoronary optical coherence tomography (OCT) and intravascular ultrasound (IVUS) can help distinguish SCAD from an atherosclerotic lesion when it is difficult to do so with angiography. ICI techniques provide a direct view of the walls of the coronary artery to confirm SCAD, but may actually worsen the dissection as the probes are inserted into the damaged area. ICI confers a 3.4% risk of iatrogenic dissection in people with SCAD compared to 0.2% risk in the general population. Between the two ICI methods, OCT - a newer technique - has superior spatial resolution than IVUS and is the preferred technique if ICI is required, but the need to inject extra contrast with OCT poses risk for worsening the dissection.

Other methods
Some studies propose coronary CT angiography to evaluate SCAD in lower-risk people, with research into the approach ongoing.

Management
Management depends upon the presenting symptoms. In most people who are hemodynamically stable without high-risk coronary involvement, conservative medical management with blood pressure control is recommended. In these people, especially if angiography demonstrates adequate coronary flow, the most likely course usually leads to spontaneous healing, often within 30 days. Anti-coagulation should be discontinued upon diagnosis of SCAD on coronary angiography as continuation of anti-coagulation may lead to hematoma and dissection propagation.In cases involving high-risk coronaries, hemodynamic instability, or a lack of improvement or worsening after initial attempts at treatment, urgent treatment with coronary stents or coronary artery bypass surgery may be necessary. Stents carry the risk of worsening the dissection or have an increased risk of other complications as the vessel walls in SCAD are already weak due to the disease before introducing the stent. Large studies into coronary artery bypass surgery are lacking, but this approach is used to redirect blood to the heart around the affected area for cases involving the left main coronary artery or when other approaches fail.Angina, or chest pain due to coronary insufficiency may persist for months after SCAD, sometimes even when repeat angiography shows vessel healing. Anti-anginal agents such as nitrates, calcium channel blockers and ranolazine are indicated as anti-anginal pharmacologic agents after SCAD. Control of hypertension is also indicated after SCAD, with beta blockers especially showing a reduction in the recurrence of SCAD. Statins are not recommended in the treatment post-SCAD (in the absence of other indications for statins) as the myocardial infarctions in SCAD are not the result of atherosclerotic plaques. Cardiac rehabilitation is recommended for all patients after myocardial infarction due to SCAD and is associated with a reduction in anginal symptoms increased psychological well-being. Dual antiplatelet therapy should be started after percutaneous coronary intervention (stents) is used to treat SCAD and continued for at least 1 year afterwards. Dual antiplatelet therapy during the acute phase and for at least 1 year after medically treated SCAD may be also used, based on expert consensus.Physical stress is associated with SCAD recurrence but there are no heart rate, blood pressure or weight exercise parameters that are established in those with SCAD. In general, it is recommended that those with SCAD avoid isometric exercise, high intensity endurance training, exercising to the point of exhaustion and activities involving a prolonged Valsalva to reduce the risk of SCAD recurrence.After addressing the SCAD, people are often treated with typical post-heart attack care, though people who are pregnant may need altered therapy due to the possibility of some teratogenic cardiac medications affecting fetal development. Depending on the clinical situation, providers may screen for associated connective tissue diseases.

Prognosis
People with SCAD have a low in-hospital mortality after treatment </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Bleeding diathesis and can you explain it in depth? [/INST] In medicine (hematology), bleeding diathesis  is an unusual susceptibility to bleed (hemorrhage) mostly due to hypocoagulability (a condition of irregular and slow blood clotting), in turn caused by a coagulopathy (a defect in the system of coagulation). Therefore, this may result in the reduction of platelets being produced and leads to excessive bleeding. Several types of coagulopathy are distinguished, ranging from mild to lethal. Coagulopathy can be caused by thinning of the skin (Cushings syndrome), such that the skin is weakened and is bruised easily and frequently without any trauma or injury to the body. Also, coagulopathy can be contributed by impaired wound healing or impaired clot formation.

Signs and symptoms
Complications
Following are some complications of coagulopathies, some of them caused by their treatments:

Causes
While there are several possible causes, they generally result in excessive bleeding and a lack of clotting.

Acquired
Acquired causes of coagulopathy include anticoagulation with warfarin, liver failure, vitamin K deficiency and disseminated intravascular coagulation. Additionally, the hemotoxic venom from certain species of snakes can cause this condition, for example Bothrops, rattlesnakes and other species of viper. Viral hemorrhagic fevers include dengue hemorrhagic fever and dengue shock syndrome.
Leukemia may also cause coagulopathy. Furthermore, cystic fibrosis has been known to cause bleeding diathesis, especially in undiagnosed infants, due to malabsorption of fat soluble vitamins like vitamin K.

Autoimmune causes of acquired coagulation disorders
There are autoimmune causes of coagulation disorders. They include acquired antibodies to coagulation factors, termed inhibitors of coagulation. The main inhibitor is directed against clotting factor VIII. Another example is antiphospholipid syndrome, an autoimmune, hypercoagulable state.

Causes other than coagulation
Bleeding diathesis may also be caused by impaired wound healing (as in scurvy), or by thinning of the skin, such as in Cushings syndrome.

Genetic
Some people lack genes that typically produce the protein coagulation factors that allow normal clotting. Various types of hemophilia and von Willebrand disease are the major genetic disorders associated with coagulopathy </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Breast development and can you explain it in depth? [/INST] Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a females life.
It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breast development ceases and the breasts atrophy. Breast development results in prominent and developed structures on the chest known as breasts in primates, which serve primarily as mammary glands. The process is mediated by an assortment of hormones (and growth factors), the most important of which include estrogen, progesterone, prolactin, and growth hormone.

Biochemistry
Hormones
The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin. These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.At puberty, gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile manner from the hypothalamus. GnRH induces the secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland. The secreted gonadotropins travel through the bloodstream to the ovaries and trigger the secretion of estrogen and progesterone in fluctuating amounts during each menstrual cycle. Growth hormone (GH), which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response to GH, are growth-mediating hormones. During prenatal development, infancy, and childhood, GH and IGF-1 levels are low, but progressively increase and reach a peak at puberty, with a 1.5- to 3-fold increase in pulsatile GH secretion and a 3-fold or greater increase in serum IGF-1 levels being capable of occurring at this time. In late adolescence and early adulthood, GH and IGF-1 levels significantly decrease, and continue to decrease throughout the rest of life. It has been found that both estrogen and GH are essential for breast development at puberty – in the absence of either, no development will take place. Moreover, most of the role of GH in breast development has been found to be mediated by its induction of IGF-1 production and secretion, as IGF-1 administration rescues breast development in the absence of GH. GH induction of IGF-1 production and secretion occurs in almost all types of tissue in the body, but especially in the liver, which is the source of approximately 80% of circulating IGF-1, as well as locally in the breasts. Although IGF-1 is responsible for most of the role of GH in mediating breast development, GH itself has been found to play a direct, augmenting role as well, as it increases estrogen receptor (ER) expression in breast stromal (connective) tissue, while IGF-1, in contrast, has been found to not do this. In addition to estrogen and GH/IGF-1 both being essential for pubertal breast development, they are synergistic in bringing it about.Despite the apparent necessity of GH/IGF-1 signaling in pubertal breast development however, women with Laron syndrome, in whom the growth hormone receptor (GHR) is defective and insensitive to GH and serum IGF-1 levels are very low, puberty, including breast development, is delayed, although full sexual maturity is always eventually reached. Moreover, breast development and size are normal (albeit delayed) in spite of GH/IGF-1 axis insufficiency, and in some the breasts may actually be large in relation to body size. The relatively large breasts in women with Laron syndrome have been suggested to be due to increased secretion of prolactin (which is known to produce breast enlargement) caused by a drift phenomenon from somatomammotrophic cells in the pituitary gland with a high GH secretion. An animal model of Laron syndrome, the GHR knockout mouse, shows severely impaired ductal outgrowth at 11 weeks of age. However, by 15 weeks, ductal development has caught up with that of normal mice and the ducts have fully distributed throughout the mammary fat pad, although the ducts remain narrower than those of wild-type mice. In any case, female GHR knockout mice can lactate normally. As such, it has been said that the phenotypes of women with Laron syndrome and GHR knockout mice are identical, with diminished body size and delayed sexual maturation accompanied by normal lactation. These data indicate that very low circulating levels of IGF-1 can nonetheless allow for full pubertal breast development.

Development of the breasts during the prenatal stage of life is independent of biological sex and sex hormones. During embryonic development, the breast buds, in which networks of tubules are formed, are generated from the ectoderm. These rudimentary tubules will eventually become the matured lactiferous (milk) ducts, which connect the lobules (milk "containers") of the breast, grape-like clusters of alveoli, to the nipples. Until puberty, the tubule networks of the breast buds remain rudimentary and quiescent, and the male and female breast do not show any differences. During puberty in females, estrogen, in conjunction with GH/IGF-1, through activation of ERα specifically (and notably not ERβ or GPER), causes growth of and transformation of the tubules into the matured ductal system of the breasts. Under the influence of estrogen, the ducts sprout and elongate, and terminal end buds (TEBs), bulbous structures at the tips of the ducts, penetrate into the fat pad and branch as the ducts elongate. This continues until a tree-like network of branched ducts that is embedded into and fills the entire fat pad of the breast is formed. In addition to its role in mediating ductal development, estrogen causes stromal tissue to grow and adipose (fat) tissue to accumulate, as well as the nipple-areolar complex to increase in size.Progesterone, in conjunction with GH/IGF-1 similarly to estrogen, affects the development of the breasts during puberty and thereafter as well. To a lesser extent than estrogen, progesterone contributes to ductal development at this time, as evidenced by the findings that progesterone receptor (PR) knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen acting on its own) ductal growth during puberty and by the fact that progesterone has been found to induce ductal growth on its own in the mouse mammary gland mainly via the induction of the expression of amphiregulin, the same growth factor that estrogen primarily induces to mediate its actions on ductal development. In addition, progesterone produces modest lobuloalveolar development (alveolar bud formation or ductal sidebranching) starting at puberty, specifically through activation of PRB (and notably not PRA), with growth and regression of the alveoli occurring to some degree with each menstrual cycle. However, only rudimentary alveoli develop in response to pre-pregnancy levels of progesterone and estrogen, and lobuloalveolar development will remain at this stage until pregnancy occurs, if it does. In addition to GH/IGF-1, estrogen is required for progesterone to affect the breasts, as estrogen primes the breasts by inducing the expression of the progesterone receptor (PR) in breast epithelial tissue. In contrast to the case of the PR, ER expression in the breast is stable and differs relatively little in the contexts of reproductive status, stage of the menstrual cycle, or exogenous hormonal therapy.During pregnancy, pronounced breast growth and maturation occurs in preparation of lactation and breastfeeding. Estrogen and progesterone levels increase dramatically, reaching levels by late pregnancy that are several hundred-fold higher than usual menstrual cycle levels. Estrogen and progesterone cause the secretion of high levels of prolactin from the anterior pituitary, which reach levels as high as 20 times greater than normal menstrual cycle levels. IGF-1 and IGF-2 levels also increase dramatically during pregnancy, due to secretion of placental growth hormone (PGH). Further ductal development, by estrogen, again in conjunction with GH/IGF-1, occurs during pregnancy. In addition, the concert of estrogen, progesterone (again specifically through PRB), prolactin, and other lactogens such as human placental lactogen (hPL) and PGH, in conjunction with GH/IGF-1, as well as insulin-like growth factor 2 (IGF-2), acting together, mediate the completion of lobuloalveolar development of the breasts during pregnancy. Both PR and prolactin receptor (PRLR) knockout mice fail to show lobuloalveolar development, and progesterone and prolactin have been found to be synergistic in mediating growth of alveoli, demonstrating the essential role of both of these hormones in this aspect of breast development. Growth hormone receptor (GHR) knockout mice also show greatly impaired lobuloalveolar development. In addition to their role in lobuloalveolar growth, prolactin and hPL act to increase the size of the nipple-areolar complex during pregnancy. By the end of the fourth month of pregnancy, at which time lobuloalveolar maturation is complete, the breasts are fully prepared for lactation and breastfeeding.Insulin, glucocorticoids such as cortisol (and by extension adrenocorticotropic hormone (ACTH)), and thyroid hormones such as thyroxine (and by extension thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH)) also play permissive but less well-understood/poorly-characterized roles in breast development during both puberty and pregnancy, and are required for full functional development. Leptin has also been found to be an important factor in mammary gland development, and has been found to promote mammary epithelial cell proliferation.In contrast to the female-associated sex hormones, estrogen and progesterone, the male-associated sex hormones, the androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts. At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue. In the absence of androgenic activity, such as in women with complete androgen insensitivity syndrome (CAIS), modest levels of estrogen (50 pg/mL) are capable of mediating significant breast development, with CAIS women showing breast volumes that are even above-average. The combination of much higher levels of androgens (about 10-fold higher) and much lower levels of estrogen (about 10-fold less), due to the ovaries in females producing high amounts of estrogens but low amounts of androgens and the testes in males producing high amounts of androgens but low amounts of estrogens, are why males generally do not grow prominent or well-developed breasts relative to females.Calcitriol, the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR), has, like the androgens, been reported to be a negative regulator of mammary gland development in mice, for instance, during puberty. VDR knockout mice show more extensive ductal development relative to wild-type mice, as well as precocious mammary gland development. In addition, VDR knockout has also been shown to result in increased responsiveness of mouse mammary gland tissue to estrogen and progesterone, which was represented by increased cell growth in response to these hormones. Conversely however, it has been found that VDR knockout mice show reduced ductal differentiation, represented by an increased number of undifferentiated TEBs, and this finding has been interpreted as indicating that vitamin D may be essential for lobuloalveolar development. As such, calcitriol, via the VDR, may be a negative regulator of ductal development but a positive regulator of lobuloalveolar development in the mammary gland.A possible mechanism of the negative regulatory effects of the VDR on breast development may be indicated by a study of vitamin D3 supplementation in women which found that vitamin D3 suppresses cyclooxygenase-2 (COX-2) expression in the breast, and by doing so, reduces and increases, respectively, the levels of prostaglandin E2 (PGE2) and transforming growth factor β2 (TGF-β2), a known inhibitory factor in breast development. Moreover, suppression of PGE2 in breast tissue is relevant because, via activation of prostaglandin EP receptors, PGE2 potently induces amphiregulin expression in breast tissue, and activation of the EGFR by amphiregulin increases COX-2 expression in breast tissue, in turn resulting in more PGE2, and thus, a self-perpetuating, synergistic cycle of growth amplification due to COX-2 appears to potentially be present in normal breast tissue. Accordingly, overexpression of COX-2 in mammary gland tissue produces mammary gland hyperplasia as well as precocious mammary gland development in female mice, mirroring the phenotype of VDR knockout mice, and demonstrating a strong stimulatory effect of COX-2, which is downregulated by VDR activation, on the growth of the mammary glands. Also in accordance, COX-2 activity in the breasts has been found to be positively associated with breast volume in women.

Growth factors
Estrogen, progesterone, and prolactin, as well as GH/IGF-1, produce their effects on breast development by modulating the local expression in breast tissue of an assortment of autocrine and paracrine growth factors, including IGF-1, IGF-2, amphiregulin, EGF, FGF, hepatocyte growth factor (HGF), tumor necrosis factor α (TNF-α), tumor necrosis factor β (TNF-β), transforming growth factor α (TGF-α), transforming growth factor β (TGF-β), heregulin, Wnt, RANKL, and leukemia inhibitory factor (LIF). These factors regulate cellular growth, proliferation, and differentiation via activation of intracellular signaling cascades that control cell function, such as Erk, Akt, JNK, and Jak/Stat.Based on research with epidermal growth factor receptor (EGFR) knockout mice, the EGFR, which is the molecular target of EGF, TGF-α, amphiregulin, and heregulin, has, similarly to the insulin-like growth factor-1 receptor (IGF-1R), been found to be essential for mammary gland development. Estrogen and progesterone mediate ductal development mainly through induction of amphiregulin expression, and thus downstream EGFR activation. Accordingly, ERα, amphiregulin, and EGFR knockout mice copy each other phenotypically in regards to their effects on ductal development. Also in accordance, treatment of mice with amphiregulin or other EGFR ligands like TGF-α or heregulin induces ductal and lobuloalveolar development in the mouse mammary gland, actions that occur even in the absence of estrogen and progesterone. As both the IGF-1R and the EGFR are independently essential for mammary gland development, and as combined application of IGF-1 and EGF, through their respective receptors, has been found to synergistically stimulate the growth of human breast epithelial cells, these growth factor systems appear to work together in mediating breast development.Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in macromastia, a very rare condition of extremely and excessively large breast size. Exposure of macromastic breast stromal tissue to non-macromastic breast epithelial tissue was found to cause increased alveolar morphogenesis and epithelial proliferation in the latter. A neutralizing antibody for HGF, but not for IGF-1 or EGF, was found to attenuate the proliferation of breast epithelial tissue caused by exposure to macromastic breast stromal cells, potentially directly implicating HGF in the breast growth and enlargement seen in macromastia. Also, a genome-wide association study has highly implicated HGF and its receptor, c-Met, in breast cancer aggressiveness.

Lactation
Upon parturition (childbirth), estrogen and progesterone rapidly drop to very low levels, with progesterone levels being undetectable. Conversely, prolactin levels remain elevated. As estrogen and progesterone block prolactin-induced lactogenesis by suppressing prolactin receptor (PRLR) expression in breast tissue, their sudden absence results in the commencement of milk production and lactation by prolactin. Expression of the PRLR in breast tissue may increase by as much as 20-fold when estrogen and progesterone levels drop upon childbirth. With suckling from the infant, prolactin and oxytocin are secreted and mediate milk production and letdown, respectively. Prolactin suppresses the secretion of LH and FSH, which in turn results in continued low levels of estrogen and progesterone, and temporary amenorrhea (absence of menstrual cycles) occurs. In the absence of regular, episodic suckling, which keeps prolactin concentrations high, levels of prolactin will quickly drop, the menstrual cycle will resume and hence normal estrogen and progesterone levels will return, and lactation will cease (that is, until next parturition, or until induced lactation (i.e., with a galactogogue), occurs).

Breast size and cancer risk
Some factors of breast morphology, including their density, are clearly implicated in breast cancer. While breast size is moderately heritable, the relationship between breast size and cancer is uncertain. The genetic variants influencing breast size have not been identified.Through genome-wide association studies, a variety of genetic polymorphisms have been linked to breast size. Some of these include rs7816345 near ZNF703 (zinc finger protein 703); rs4849887 and rs17625845 flanking INHBB (inhibin βB); rs12173570 near ESR1 (ERα); rs7089814 in ZNF365 (zinc finger protein 365); rs12371778 near PTHLH (parathyroid hormone-like hormone); rs62314947 near AREG (amphiregulin); as well as rs10086016 at 8p11.23 (which is in complete linkage disequilibrium with rs7816345) and rs5995871 at 22q13 (contains the MKL1 gene, which has been found to modulate the transcriptional activity of ERα). Many of these polymorphisms are also associated with the risk of developing breast cancer, revealing a potential positive association between breast size and breast cancer risk. However, conversely, some polymorphisms show a negative association between breast size and breast cancer risk. In any case, a meta-analysis concluded that breast size and risk of breast cancer are indeed importantly related.Circulating IGF-1 levels are positively associated with breast volume in women. In addition, the absence of the common 19-repeat allele in the IGF1 gene is also positively associated with breast volume in women, as well as with high IGF-1 levels during oral contraceptive use and with lessening of the normal age-associated decline in circulating IGF-1 concentrations in women. There is great variation in the prevalence of the IGF1 19-repeat allele between ethnic groups, and its absence has been reported to be highest among African-American women.Genetic variations in the androgen receptor (AR) have been linked to both breast volume (as well as body mass index) and breast cancer aggressiveness.COX-2 expression has been positively associated with breast volume and inflammation in breast tissue, as well as with breast cancer risk and prognosis.

Rare mutations
Women with CAIS, who are completely insensitive to the AR-mediated actions of androgens, have, as a group, above-average sized breasts. This is true despite the fact that they simultaneously have relatively low levels of estrogen, which demonstrates the powerful suppressant effect of androgens on estrogen-mediated breast development.Aromatase excess syndrome, an extremely rare condition characterized by marked hyperestrogenism, is associated with precocious breast development and macromastia in females and similarly precocious gynecomastia (womens breasts) in males. In complete androgen insensitivity syndrome, a condition in which the AR is defective and insensitive to androgens, there is full breast development with breast volumes that are in fact above average in spite of relatively low levels of estrogen (50 pg/mL estradiol). In aromatase deficiency, a form of hypoestrogenism in which aromatase is defective and cannot synthesize estrogen, and in complete estrogen insensitivity syndrome, a condition in which ERα is defective and insensitive to estrogen, breast development is completely absent.

See also
Breast augmentation
Breast enlargement
Mammoplasia
Premenstrual water retention
Thelarche

References
Further reading
Hovey, Russell C.; Aimo, Lucila (2010). "Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function". Journal of Mammary Gland Biology and Neoplasia. 15 (3): 279–290. doi:10.1007/s10911-010-9187-8. ISSN 1083-3021 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Asterixis and can you explain it in depth? [/INST] Asterixis, more colloquially referred to as flapping tremor, is a tremor of the hand when the wrist is extended, sometimes said to resemble a bird flapping its wings.  This motor disorder is characterized by an inability to maintain a position, which is demonstrated by jerking movements of the outstretched hands when bent upward at the wrist.  The tremor is caused by abnormal function of the diencephalic motor centers in the brain, which regulate the muscles involved in maintaining position.  Asterixis is associated with various encephalopathies due especially to faulty metabolism. The term derives from the Greek a, "not" and stērixis, "fixed position".
Asterixis is the inability to maintain posture due to a metabolic encephalopathy.  This can be elicited on physical exam by having the patient extend their arms and bend their hands back.
With a metabolic encephalopathy, the patient is unable to hold their hands back resulting in a “flapping” motion consistent with asterixis.  It can be seen in any metabolic encephalopathy e.g. chronic kidney failure, severe congestive heart failure, acute respiratory failure and commonly in decompensated liver failure.

Associated conditions and presentation
Usually there are brief, arrhythmic interruptions of sustained voluntary muscle contraction causing brief lapses of posture, with a frequency of 3–5 Hz </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tetraplegia and can you explain it in depth? [/INST] Tetraplegia, also known as quadriplegia, is paralysis caused by illness or injury that results in the partial or total loss of use of all four limbs and torso; paraplegia is similar but does not affect the arms. The loss is usually sensory and motor, which means that both sensation and control are lost. The paralysis may be flaccid or spastic.

Signs and symptoms
Although the most obvious symptom is impairment of the limbs, functioning is also impaired in the torso. This can mean a loss or impairment in controlling bowel and bladder, sexual function, digestion, breathing and other autonomic functions. Furthermore, sensation is usually impaired in affected areas. This can manifest as numbness, reduced sensation or burning neuropathic pain. Secondarily, because of their depressed functioning and immobility, people with tetraplegia are often more vulnerable to pressure sores, osteoporosis and fractures, frozen joints, spasticity, respiratory complications and infections, autonomic dysreflexia, deep vein thrombosis, and cardiovascular disease.The severity of the condition depends on both the level at which the spinal cord is injured and the extent of the injury. An individual with an injury at C1 (the highest cervical vertebra, at the base of the skull) will probably lose function from the neck down and be ventilator-dependent. An individual with a C7 injury may lose function from the chest down but still retain use of the arms and much of the hands.
The extent of the injury is also important. A complete severing of the spinal cord will result in complete loss of function from that vertebra down. A partial severing or even bruising of the spinal cord results in varying degrees of mixed function and paralysis. A common misconception with tetraplegia is that the victim cannot move legs, arms or any of the major function; this is often not the case. Some individuals with tetraplegia can walk and use their hands, as though they did not have a spinal cord injury, while others may use wheelchairs and they can still have function of their arms and mild finger movement; again, that varies on the spinal cord damage.It is common to have movement in limbs, such as the ability to move the arms but not the hands, or to be able to use the fingers but not to the same extent as before the injury. Furthermore, the deficit in the limbs may not be the same on both sides of the body; either left or right side may be more affected, depending on the location of the lesion on the spinal cord.

Causes
Tetraplegia is caused by damage to the brain or the spinal cord at a high level. The injury, which is known as a lesion, causes the loss of partial or total function of all four limbs, meaning the arms and the legs. Typical causes of this damage are trauma (such as a traffic collision, diving into shallow water, a fall, a sports injury), disease (such as transverse myelitis, Guillain–Barré syndrome, multiple sclerosis, or polio), or congenital disorders (such as muscular dystrophy).Tetraplegia is defined in many ways; C1–C4 usually affects arm movement more so than a C5–C7 injury; however, all tetraplegics have or have had some kind of finger dysfunction. So, it is not uncommon to have a tetraplegic with fully functional arms but no nervous control of their fingers and thumbs. It is possible to have a broken neck without becoming tetraplegic if the vertebrae are fractured or dislocated but the spinal cord is not damaged. Conversely, it is possible to injure the spinal cord without breaking the spine, for example when a ruptured disc or bone spur on the vertebra protrudes into the spinal column.

Diagnosis
Classification
Spinal cord injuries are classified as complete and incomplete by the American Spinal Injury Association (ASIA) classification. The ASIA scale grades patients based on their functional impairment as a result of the injury, grading a patient from A to D. This has considerable consequences for surgical planning and therapy.

Complete spinal-cord lesions
Pathophysiologically, the spinal cord of a person with tetraplegia can be divided into three segments which can be useful for classifying the injury.
First, there is an injured functional medullary segment. This segment has unparalysed, functional muscles; the action of these muscles is voluntary, not permanent and hand strength can be evaluated by the Medical Research Council (MRC) Scale. This scale is used when upper limb surgery is planned, as referred to in the International Classification for hand surgery in tetraplegic patients.A lesional segment (or an injured metamere) consists of denervated corresponding muscles. The lower motor neuron (LMN) of these muscles is damaged. These muscles are hypotonic, atrophic and have no spontaneous contraction. The existence of joint contractures should be monitored.Below the level of the injured metamere, there is an injured sublesional segment with the intact lower motor neuron, which means that medullary reflexes are present, but the upper cortical control is lost. These muscles show some increase in tone when elongated and sometimes spasticity, the trophicity is good.

Incomplete spinal-cord lesions
Incomplete spinal cord injuries result in varied post injury presentations. There are three main syndromes described, depending on the exact site and extent of the lesion.

Central cord syndrome: most of the cord lesion is in the gray matter of the spinal cord, sometimes the lesion continues in the white matter.
Brown-Séquard syndrome: hemisection of the spinal cord.
Anterior cord syndrome: a lesion of the anterior horns and the anterolateral tracts, with a possible division of the anterior spinal artery.For most patients with ASIA A (complete) tetraplegia, ASIA B (incomplete) tetraplegia and ASIA C (incomplete) tetraplegia, the International Classification level of the patient can be established without great difficulty. The surgical procedures according to the International Classification level can be performed. In contrast, for patients with ASIA D (incomplete) tetraplegia it is difficult to assign an International Classification other than International Classification level X (others). Therefore, it is more difficult to decide which surgical procedures should be performed. A far more personalized approach is needed for these patients. Decisions must be based more on experience than on texts or journals.The results of tendon transfers for patients with complete injuries are predictable. On the other hand, it is well known that muscles lacking normal excitation perform unreliably after surgical tendon transfers. Despite the unpredictable aspect in incomplete lesions, tendon transfers may be useful. The surgeon should be confident that the muscle to be transferred has enough power and is under good voluntary control. Pre-operative assessment is more difficult to assess in incomplete lesions.Patients with an incomplete lesion also often need therapy or surgery before the procedure to restore function to correct the consequences of the injury. These consequences are hypertonicity/spasticity, contractures, painful hyperesthesias and paralyzed proximal upper limb muscles with distal muscle sparing.Spasticity is a frequent consequence of incomplete injuries. Spasticity often decreases function, but sometimes a patient can control the spasticity in a way that it is useful to their function. The location and the effect of the spasticity should be analyzed carefully before treatment is planned. An injection of Botulinum toxin (Botox) into spastic muscles is a treatment to reduce spasticity. This can be used to prevent muscle shortening and early contractures.Over the last ten years, an increase in traumatic incomplete lesions is seen, due to the better protection in traffic.

Treatment
Upper limb paralysis refers to the loss of function of the elbow and hand. When upper limb function is absent as a result of a spinal cord injury it is a major barrier to regain autonomy. People with tetraplegia should be examined and informed concerning the options for reconstructive surgery of the tetraplegic arms and hands.

Prognosis
Delayed diagnosis of cervical spine injury has grave consequences for the victim </s>