<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 Alcohol withdrawal syndrome and can you explain it in depth? [/INST] Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. More severe symptoms may include seizures, hallucinations, and delirium tremens (DTs). Symptoms typically begin around six hours following the last drink, are worst at 24 to 72 hours, and improve by seven days.Alcohol withdrawal may occur in those who are alcohol dependent. This may occur following a planned or unplanned decrease in alcohol intake. The underlying mechanism involves a decreased responsiveness of GABA receptors in the brain. The withdrawal process is typically followed using the Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar).The typical treatment of alcohol withdrawal is with benzodiazepines such as chlordiazepoxide or diazepam. Often the amounts given are based on a persons symptoms. Thiamine is recommended routinely. Electrolyte problems and low blood sugar should also be treated. Early treatment improves outcomes.In the Western world about 15% of people have problems with alcoholism at some point in time. Alcohol depresses the central nervous system, slowing cerebral messaging and altering the way signals are sent and received. Progressively larger amounts of alcohol are needed to achieve the same physical and emotional results. The drinker eventually must consume alcohol just to avoid the physical cravings and withdrawal symptoms. About half of people with alcoholism will develop withdrawal symptoms upon reducing their use, with four percent developing severe symptoms. Among those with severe symptoms up to 15% die. Symptoms of alcohol withdrawal have been described at least as early as 400 BC by Hippocrates. It is not believed to have become a widespread problem until the 1700s.

Signs and symptoms
Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as insomnia, trembling, and anxiety to severe and life-threatening symptoms such as alcoholic hallucinosis, delirium tremens, and autonomic instability.Withdrawal usually begins 6 to 24 hours after the last drink. It can last for up to one week. To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, generalized tonic–clonic seizures, and autonomic instability.The severity of symptoms is dictated by a number of factors, the most important of which are degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal. Symptoms are also grouped together and classified:

Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear.
Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures.
Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations.

Progression
Six to 12 hours after the ingestion of the last drink, withdrawal symptoms such as shaking, headache, sweating, anxiety, nausea or vomiting may occur. Twelve to 24 hours after cessation, the condition may progress to such major symptoms as confusion, hallucinations (with awareness of reality), while less severe symptoms may persist and develop including tremor, agitation, hyperactivity and insomnia.At 12 to 48 hours following the last ethanol ingestion, the possibility of generalized tonic–clonic seizures should be anticipated, occurring in 3-5% of cases. Meanwhile, none of the earlier withdrawal symptoms will typically have abated. Seizures carry the risk of major complications and death for the alcoholic.Although the persons condition usually begins to improve after 48 hours, withdrawal symptoms sometimes continue to increase in severity and advance to the most severe stage of withdrawal, delirium tremens. This occurs in 5 to 20% of patients experiencing detoxification and one third of untreated cases, which is characterized by hallucinations that are indistinguishable from reality, severe confusion, seizures, high blood pressure, and fever that can persist anywhere from 4 to 12 days.

Protracted withdrawal
A protracted alcohol withdrawal syndrome occurs in many alcoholics when withdrawal symptoms continue beyond the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with severity over time. This syndrome is sometimes referred to as the post-acute-withdrawal syndrome. Some withdrawal symptoms can linger for at least a year after discontinuation of alcohol. Symptoms can include a craving for alcohol, inability to feel pleasure from normally pleasurable things (known as anhedonia), clouding of sensorium, disorientation, nausea and vomiting or headache.Insomnia is a common protracted withdrawal symptom that persists after the acute withdrawal phase of alcohol. Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat the persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in these individuals because many of the traditional sleep aids (e.g., benzodiazepine receptor agonists and barbiturate receptor agonists) work via a GABAA receptor mechanism and are cross-tolerant with alcohol. However, trazodone is not cross-tolerant with alcohol. The acute phase of the alcohol withdrawal syndrome can occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal.

Pathophysiology
Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression and down regulation of GABAA receptors. During acute alcohol withdrawal, changes also occur such as upregulation of alpha4 containing GABAA receptors and downregulation of alpha1 and alpha3 containing GABAA receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross-tolerant drugs these changes in neurochemistry may gradually return towards normal. Adaptations to the NMDA system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels, which are elevated during chronic drinking, increase even further during the withdrawal state, and may result in excitotoxicity. Alterations in ECG (in particular an increase in QT interval) and EEG abnormalities (including abnormal quantified EEG) may occur during early withdrawal. Dysfunction of the hypothalamic–pituitary–adrenal axis and increased release of corticotropin-releasing hormone occur during both acute as well as protracted abstinence from alcohol and contribute to both acute and protracted withdrawal symptoms. Anhedonia/dysphoria symptoms, which can persist as part of a protracted withdrawal, may be due to dopamine underactivity.

Kindling
Kindling is a phenomenon where repeated alcohol detoxifications leads to an increased severity of the withdrawal syndrome. For example, binge drinkers may initially experience no withdrawal symptoms, but with each period of alcohol use followed by cessation, their withdrawal symptoms intensify in severity and may eventually result in full-blown delirium tremens with convulsive seizures. Alcoholics who experience seizures during detoxification are more likely to have had previous episodes of alcohol detoxification than patients who did not have seizures during withdrawal. In addition, people with previous withdrawal syndromes are more likely to have more medically complicated alcohol withdrawal symptoms.Kindling can cause complications and may increase the risk of relapse, alcohol-related brain damage and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alterations in the GABAA receptors. The mechanism behind kindling is sensitization of some neuronal systems and desensitization of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning. These adverse effects are believed to be due to the neurotoxic effects of repeated withdrawal from alcohol on aberrant neuronal plasticity and cortical damage. Repeated periods of acute intoxication followed by acute detoxification has profound effects on the brain and is associated with an increased risk of seizures as well as cognitive deficits. The effects on the brain are similar to those seen in alcoholics who have detoxified repeatedly but not as severe as in alcoholics who have no history of prior detox. Thus, the acute withdrawal syndrome appears to be the most important factor in causing damage or impairment to brain function. The brain regions most sensitive to harm from binge drinking are the amygdala and prefrontal cortex.People in adolescence who experience repeated withdrawals from binge drinking show impairments of long-term nonverbal memory. Alcoholics who have had two or more alcohol withdrawals show more frontal lobe cognitive dysfunction than those who have experienced one or no prior withdrawals. Kindling of neurons is the proposed cause of withdrawal-related cognitive damage. Kindling from repeated withdrawals leads to accumulating neuroadaptive changes. Kindling may also be the reason for cognitive damage seen in binge drinkers.

Diagnosis
Many hospitals use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol in order to assess the level of withdrawal present and therefore the amount of medication needed. When overuse of alcohol is suspected but drinking history is unclear, testing for elevated values of carbohydrate-deficient transferrin or gammaglutamyl transferase can help make the diagnosis of alcohol overuse and dependence more clear. The CIWA has also been shortened (now called the CIWA-Ar), while retaining its validity and reliability, to help assess patients more efficiently due to the life-threatening nature of alcohol withdrawal.Other conditions that may present similarly include benzodiazepine withdrawal syndrome (a condition also mainly caused by GABAA receptor adaptation).

Treatment
Benzodiazepines  are effective for the management of symptoms as well as the prevention of seizures. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome. In those with severe symptoms inpatient care is often required. In those with lesser symptoms treatment at home may be possible with daily visits with a health care provider.

Benzodiazepines
Benzodiazepines are the most commonly used medication for the treatment of alcohol withdrawal and are generally safe and effective in suppressing symptoms of alcohol withdrawal. This class of medication is generally effective in symptoms control, but need to be used carefully. Although benzodiazepines have a long history of successfully treating and preventing withdrawal, there is no consensus on the ideal one to use. The most commonly used agents are long-acting benzodiazepines, such as chlordiazepoxide and diazepam. These are believed to be superior to other benzodiazepines for treatment of delirium and allow for longer periods between doses. However, benzodiazepines with intermediate half-lives like lorazepam may be safer in people with liver problems. Benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizure, compared to other common methods of treatment.The primary debate between use of long-acting benzodiazepines and short-acting is that of ease of use. Longer-acting drugs, such as diazepam, can be administered less frequently. However, evidence does exist that "symptom-triggered regimens" such as those used when treating with lorazepam, are as safe and effective, but have decreased treatment duration and medication quantity used.Although benzodiazepines are very effective at treating alcohol withdrawal, they should be carefully used. Benzodiazepines should only be used for brief periods in alcoholics who are not already dependent on them, as they share cross tolerance with alcohol. There is a risk of replacing an alcohol addiction with benzodiazepine dependence or adding another addiction. Furthermore, disrupted GABA benzodiazepine receptor function is part of alcohol dependence and chronic benzodiazepines may prevent full recovery from alcohol induced mental effects. The combination of benzodiazepines and alcohol can amplify the adverse psychological effects of each other causing enhanced depressive effects on mood and increase suicidal actions and are generally contraindicated except for alcohol withdrawal.

Vitamins
Alcoholics are often deficient in various nutrients, which can cause severe complications during alcohol withdrawal, such as the development of Wernicke syndrome. To help to prevent Wernicke syndrome, these individuals should be administered a multivitamin preparation with sufficient quantities of thiamine and folic acid. During alcohol withdrawal, the prophylactic administration of thiamine, folic acid, and pyridoxine intravenously is recommended before starting any carbohydrate-containing fluids or food. These vitamins are often combined into a banana bag for intravenous administration.

Anticonvulsants
Very limited evidence indicates that topiramate or pregabalin may be useful in the treatment of alcohol withdrawal syndrome </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 Alopecia areata and can you explain it in depth? [/INST] Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. Often, it results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are possible factors in bringing on alopecia areata in individuals at risk, but in most cases there is no obvious trigger. People are generally otherwise healthy. In a few cases, all the hair on the scalp is lost (alopecia totalis), or all body hair is lost (alopecia universalis). Hair loss can be permanent, or temporary. It is distinctive from pattern hair loss, which is common among males.
Alopecia areata is believed to be an autoimmune disease resulting from a breach in the immune privilege of the hair follicles. Risk factors include a family history of the condition. Among identical twins, if one is affected, the other has about a 50% chance of also being affected. The underlying mechanism involves failure by the body to recognize its own cells, with subsequent immune-mediated destruction of the hair follicle.No cure for the condition is known. Efforts may be used to try to speed hair regrowth, such as cortisone injections. Sunscreen, head coverings to protect from cold and sun, and glasses, if the eyelashes are missing, are recommended. In some cases, the hair regrows, and the condition does not reoccur. In others, hair loss and regrowth occurs over years. Among those in whom all body hair is lost, fewer than 10% recover.About 0.15% of people are affected at any one time, and 2% of people are affected at some point in time. Onset is usually in childhood. Females are affected at higher rates than males.

Signs and symptoms
Typical first symptoms of alopecia areata are small bald patches. The underlying skin is unscarred and looks superficially normal. Although these patches can take many shapes, they are usually round or oval. Alopecia areata most often affects the scalp and beard, but may occur on any part of the body with hair. Different areas of the skin may exhibit hair loss and regrowth at the same time. The disease may also go into remission for a time, or may be permanent. It is common in children.The area of hair loss may tingle or be mildly painful. The hair tends to fall out over a short period of time, with the loss commonly occurring more on one side of the scalp than the other.Exclamation point hairs, narrower along the length of the strand closer to the base, producing a characteristic "exclamation point" appearance, are often present. These hairs are very short (3–4 mm), and can be seen surrounding the bald patches.When healthy hair is pulled out, at most a few should come out, and ripped hair should not be distributed evenly across the tugged portion of the scalp. In cases of alopecia areata, hair  tends to pull out more easily along the edge of the patch where the follicles are already being attacked by the bodys immune system than away from the patch where they are still healthy.Nails may have pitting or trachyonychia.

Causes
Alopecia areata is thought to be a systemic autoimmune disorder in which the body attacks its own anagen hair follicles and suppresses or stops hair growth. For example, T cell lymphocytes cluster around affected follicles, causing inflammation and subsequent hair loss. Hair follicles in a normal state are thought to be kept secure from the immune system, a phenomenon called immune privilege. A breach in this immune privilege state is considered as the cause of alopecia areata. A few cases of babies being born with congenital alopecia areata have been reported.Alopecia areata is not contagious. It occurs more frequently in people who have affected family members, suggesting heredity may be a factor. Strong evidence of genetic association with increased risk for alopecia areata was found by studying families with two or more affected members. This study identified at least four regions in the genome that are likely to contain these genes. In addition, alopecia areata shares genetic risk factors with other autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, and celiac disease. It may be the only manifestation of celiac disease.Endogenous retinoids metabolic defect is a key part of the pathogenesis of the alopecia areata.In 2010, a genome-wide association study was completed that identified 129 single nucleotide polymorphisms that were associated with alopecia areata. The genes that were identified include those involved in
controlling the activation and proliferation of regulatory T cells, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, interleukin-2 receptor A, and Eos (also known as Ikaros family zinc finger 4), as well as the human leukocyte antigen. The study also identified two genes, PRDX5 and STX17, that are expressed in the hair follicle.

Diagnosis
Alopecia areata is usually diagnosed based on clinical features.
Trichoscopy may aid in establishing the diagnosis. In alopecia areata, trichoscopy shows regularly distributed "yellow dots" (hyperkeratotic plugs), small exclamation-mark hairs, and  "black dots" (destroyed hairs in the hair follicle opening).Oftentimes, however, discrete areas of hair loss surrounded by exclamation mark hairs is sufficient for clinical diagnosis of alopecia areata. Sometimes, reddening of the skin, erythema, may also be present in the balding area.A biopsy is rarely needed to make the diagnosis or aid in the management of alopecia areata. Histologic findings may include peribulbar lymphocytic infiltration resembling a "swarm of bees", a shift in the anagen-to-telogen ratio towards telogen, and dilated follicular infundibulae. Other helpful findings can include pigment incontinence in the hair bulb and follicular stelae. Occasionally, in inactive alopecia areata, no inflammatory infiltrates are found.

Classification
Commonly, alopecia areata involves hair loss in one or more round spots on the scalp.
Hair may also be lost more diffusely over the whole scalp, in which case the condition is called diffuse alopecia areata.
Alopecia areata monolocularis describes baldness in only one spot. It may occur anywhere on the head.
Alopecia areata multilocularis refers to multiple areas of hair loss.
Ophiasis refers to hair loss in the shape of a wave at the circumference of the head.
The disease may be limited only to the beard, in which case it is called alopecia areata barbae.
If the person loses all the hair on the scalp, the disease is then called alopecia areata totalis.
If all body hair, including pubic hair, is lost, the diagnosis then becomes alopecia areata universalis.Alopecia areata totalis and universalis are rare.

Treatment
The objective assessment of treatment efficacy is very difficult and spontaneous remission is unpredictable, but if the affected area is patched, the hair may regrow spontaneously in many cases. None of the existing therapeutic options are curative or preventive.In cases of severe hair loss, limited success has been achieved by using the corticosteroid medications clobetasol or fluocinonide, corticosteroid injections, or cream. Application of corticosteroid creams to the affected skin is less effective and takes longer to produce results. Steroid injections are commonly used in sites where the areas of hair loss on the head are small or especially where eyebrow hair has been lost. Whether they are effective is uncertain. Some other medications that have been used are minoxidil, Elocon (mometasone) ointment (steroid cream), irritants (anthralin or topical coal tar), and topical immunotherapy ciclosporin, sometimes in different combinations. Topical corticosteroids frequently fail to enter the skin deeply enough to affect the hair bulbs, which are the treatment target, and small lesions typically also regrow spontaneously. Oral corticosteroids may decrease the hair loss, but only for the period during which they are taken, and these medications can cause serious side effects. No one treatment is effective in all cases, and some individuals may show no response to any treatment. Few treatments have been well evaluated. A 2008 meta-analysis of oral and topical corticosteroids, topical ciclosporin, photodynamic therapy, and topical minoxidil showed no benefit of hair growth compared with placebo, especially with regard to long-term benefits. For more severe cases, recent studies have shown promising results with the individual use of the immunosuppressant Methotrexate or adjunct use with corticosteroids. However, as relapse of the condition may occur long-term treatment is recommended.When alopecia areata is associated with celiac disease, treatment with a gluten-free diet allows for complete and permanent regrowth of scalp and other body hair in many people, but in others, remissions and recurrences are seen. This improvement is probably due to the normalization of the immune response as a result of gluten withdrawal from the diet.In June 2022, the U.S. Food and Drug Administration (FDA) authorized baricitinib for the treatment of severe alopecia areata.

Prognosis
In most cases that begin with a small number of patches of hair loss, hair grows back after a few months to a year. In cases with a greater number of patches, hair can either grow back or progress to alopecia areata totalis or, in rare cases, alopecia areata universalis.No loss of body function occurs, and the effects of alopecia areata are psychological (loss of self-image due to hair loss), although these can be severe </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 Altitude sickness and can you explain it in depth? [/INST] Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptoms may include headaches, vomiting, tiredness, confusion, trouble sleeping, and dizziness. Acute mountain sickness can progress to high-altitude pulmonary edema (HAPE) with associated shortness of breath or high-altitude cerebral edema (HACE) with associated confusion. Chronic mountain sickness may occur after long-term exposure to high altitude.Altitude sickness typically occurs only above 2,500 metres (8,000 ft), though some are affected at lower altitudes. Risk factors include a prior episode of altitude sickness, a high degree of activity, and a rapid increase in elevation. Diagnosis is based on symptoms and is supported in those who have more than a minor reduction in activities. It is recommended that at high altitude any symptoms of headache, nausea, shortness of breath, or vomiting be assumed to be altitude sickness.Prevention is by gradually increasing elevation by no more than 300 metres (1,000 ft) per day. Being physically fit does not decrease the risk. Treatment is generally by descending and sufficient fluids. Mild cases may be helped by ibuprofen, acetazolamide, or dexamethasone. Severe cases may benefit from oxygen therapy and a portable hyperbaric bag may be used if descent is not possible. Treatment efforts, however, have not been well studied.AMS occurs in about 20% of people after rapidly going to 2,500 metres (8,000 ft) and 40% of people going to 3,000 metres (10,000 ft). While AMS and HACE occurs equally frequently in males and females, HAPE occurs more often in males. The earliest description of altitude sickness is attributed to a Chinese text from around 30 BCE which describes "Big Headache Mountains", possibly referring to the Karakoram Mountains around Kilik Pass.

Signs and symptoms
People have different susceptibilities to altitude sickness; for some otherwise healthy people, acute altitude sickness can begin to appear at around 2,000 metres (6,600 ft) above sea level, such as at many mountain ski resorts, equivalent to a pressure of 80 kilopascals (0.79 atm). This is the most frequent type of altitude sickness encountered. Symptoms often manifest within ten hours of ascent and generally subside within two days, though they occasionally develop into the more serious conditions. Symptoms include headache, confusion, fatigue, stomach illness, dizziness, and sleep disturbance. Exertion may aggravate the symptoms.Those individuals with the lowest initial partial pressure of end-tidal pCO2 (the lowest concentration of carbon dioxide at the end of the respiratory cycle, a measure of a higher alveolar ventilation) and corresponding high oxygen saturation levels tend to have a lower incidence of acute mountain sickness than those with high end-tidal pCO2 and low oxygen saturation levels.

Primary symptoms
Headaches are the primary symptom used to diagnose altitude sickness, although a headache is also a symptom of dehydration. A headache occurring at an altitude above 2,400 metres (7,900 ft) – a pressure of 76 kilopascals (0.75 atm) – combined with any one or more of the following symptoms, may indicate altitude sickness:

Severe symptoms
Symptoms that may indicate life-threatening altitude sickness include:

Pulmonary edema (fluid in the lungs)
Symptoms similar to bronchitis
Persistent dry cough
Fever
Shortness of breath even when restingCerebral edema (swelling of the brain)
Headache that does not respond to analgesics
Unsteady gait
Gradual loss of consciousness
Increased nausea and vomiting
Retinal hemorrhageThe most serious symptoms of altitude sickness arise from edema (fluid accumulation in the tissues of the body). At very high altitude, humans can get either high-altitude pulmonary edema (HAPE), or high-altitude cerebral edema (HACE). The physiological cause of altitude-induced edema is not conclusively established. It is currently believed, however, that HACE is caused by local vasodilation of cerebral blood vessels in response to hypoxia, resulting in greater blood flow and, consequently, greater capillary pressures. On the other hand, HAPE may be due to general vasoconstriction in the pulmonary circulation (normally a response to regional ventilation-perfusion mismatches) which, with constant or increased cardiac output, also leads to increases in capillary pressures. For those with HACE, dexamethasone may provide temporary relief from symptoms in order to keep descending under their own power.HAPE can progress rapidly and is often fatal. Symptoms include fatigue, severe dyspnea at rest, and cough that is initially dry but may progress to produce pink, frothy sputum. Descent to lower altitudes alleviates the symptoms of HAPE.
HACE is a life-threatening condition that can lead to coma or death. Symptoms include headache, fatigue, visual impairment, bladder dysfunction, bowel dysfunction, loss of coordination, paralysis on one side of the body, and confusion. Descent to lower altitudes may save those affected by HACE.

Cause
Altitude sickness can first occur at 1,500 metres (4,900 ft), with the effects becoming severe at extreme altitudes (greater than 5,500 metres (18,000 ft)). Only brief trips above 6,000 metres (20,000 ft) are possible and supplemental oxygen is needed to avert sickness.
As altitude increases, the available amount of oxygen to sustain mental and physical alertness decreases with the overall air pressure, though the relative percentage of oxygen in air, at about 21%, remains practically unchanged up to 21,000 metres (69,000 ft). The RMS velocities of diatomic nitrogen and oxygen are very similar and thus no change occurs in the ratio of oxygen to nitrogen until stratospheric heights.
Dehydration due to the higher rate of water vapor lost from the lungs at higher altitudes may contribute to the symptoms of altitude sickness.The rate of ascent, altitude attained, amount of physical activity at high altitude, as well as individual susceptibility, are contributing factors to the onset and severity of high-altitude illness.
Altitude sickness usually occurs following a rapid ascent and can usually be prevented by ascending slowly. In most of these cases, the symptoms are temporary and usually abate as altitude acclimatization occurs. However, in extreme cases, altitude sickness can be fatal.
High altitude illness can be classified according to the altitude: high (1,500–3,500 metres (4,900–11,500 ft)), very high (3,500–5,500 metres (11,500–18,000 ft)) and extreme (above 5,500 metres (18,000 ft)).

High altitude
At high altitude, 1,500 to 3,500 metres (4,900 to 11,500 ft), the onset of physiological effects of diminished inspiratory oxygen pressure (PiO2) includes decreased exercise performance and increased ventilation (lower arterial partial pressure of carbon dioxide: PCO2). While arterial oxygen transport may be only slightly impaired the arterial oxygen saturation (SaO2) generally stays above 90%. Altitude sickness is common between 2,400 and 4,000 metres (7,900 and 13,100 ft) because of the large number of people who ascend rapidly to these altitudes.

Very high altitude
At very high altitude, 3,500 to 5,500 metres (11,500 to 18,000 ft), maximum SaO2 falls below 90% as the arterial PO2 falls below 60mmHg. Extreme hypoxemia may occur during exercise, during sleep, and in the presence of high altitude pulmonary edema or other acute lung conditions. Severe altitude illness occurs most commonly in this range.

Extreme altitude
Above 5,500 metres (18,000 ft), marked hypoxemia, hypocapnia, and alkalosis are characteristic of extreme altitudes. Progressive deterioration of physiologic function eventually outstrips acclimatization. As a result, no permanent human habitation occurs above 6,000 metres (20,000 ft). A period of acclimatization is necessary when ascending to extreme altitude; abrupt ascent without supplemental oxygen for other than brief exposures invites severe altitude sickness.

Mechanism
The physiology of altitude sickness centres around the alveolar gas equation; the atmospheric pressure is low, but there is still 20.9% oxygen. Water vapour still occupies the same pressure too—this means that there is less oxygen pressure available in the lungs and blood. Compare these two equations comparing the amount of oxygen in blood at altitude:
The hypoxia leads to an increase in minute ventilation (hence both low CO2, and subsequently bicarbonate), Hb increases through haemoconcentration and erythrogenesis. Alkalosis shifts the haemoglobin dissociation constant to the left, 2,3-BPG increases to counter this. Cardiac output increases through an increase in heart rate.The bodys response to high altitude includes the following:
↑ Erythropoietin → ↑ hematocrit and haemoglobin
↑ 2,3-BPG (allows ↑ release of O2 and a right shift on the Hb-O2 disassociation curve)
↑ kidney excretion of bicarbonate (use of acetazolamide can augment for treatment)
Chronic hypoxic pulmonary vasoconstriction (can cause right ventricular hypertrophy)People with high-altitude sickness generally have reduced hyperventilator response, impaired gas exchange, fluid retention or increased sympathetic drive. There is thought to be an increase in cerebral venous volume because of an increase in cerebral blood flow and hypocapnic cerebral vasoconstriction causing oedema.

Diagnosis
Altitude sickness is typically self-diagnosed since symptoms are consistent: nausea, vomiting, headache, and can generally be deduced from a rapid change in altitude or oxygen levels. However, some symptoms may be confused with dehydration. Some severe cases may require professional diagnosis which can be assisted with multiple different methods such as using an MRI or CT scan to check for abnormal buildup of fluids in the lung or brain.

Prevention
Ascending slowly is the best way to avoid altitude sickness. Avoiding strenuous activity such as skiing, hiking, etc. in the first 24 hours at high altitude may reduce the symptoms of AMS. Alcohol and sleeping pills are respiratory depressants, and thus slow down the acclimatization process and should be avoided. Alcohol also tends to cause dehydration and exacerbates AMS. Thus, avoiding alcohol consumption in the first 24–48 hours at a higher altitude is optimal.

Pre-acclimatization
Pre-acclimatization is when the body develops tolerance to low oxygen concentrations before ascending to an altitude. It significantly reduces risk because less time has to be spent at altitude to acclimatize in the traditional way. Additionally, because less time has to be spent on the mountain, less food and supplies have to be taken up. Several commercial systems exist that use altitude tents, so called because they mimic altitude by reducing the percentage of oxygen in the air while keeping air pressure constant to the surroundings. Examples of pre-acclimation measures include remote ischaemic preconditioning, using hypobaric air breathing in order to simulate altitude, and positive end-expiratory pressure.

Altitude acclimatization
Altitude acclimatization is the process of adjusting to decreasing oxygen levels at higher elevations, in order to avoid altitude sickness. Once above approximately 3,000 metres (10,000 ft) – a pressure of 70 kilopascals (0.69 atm) – most climbers and high-altitude trekkers take the "climb-high, sleep-low" approach. For high-altitude climbers, a typical acclimatization regimen might be to stay a few days at a base camp, climb up to a higher camp (slowly), and then return to base camp. A subsequent climb to the higher camp then includes an overnight stay. This process is then repeated a few times, each time extending the time spent at higher altitudes to let the body adjust to the oxygen level there, a process that involves the production of additional red blood cells. Once the climber has acclimatized to a given altitude, the process is repeated with camps placed at progressively higher elevations. The rule of thumb is to ascend no more than 300 m (1,000 ft) per day to sleep. That is, one can climb from 3,000 m (9,800 ft) (70 kPa or 0.69 atm) to 4,500 m (15,000 ft) (58 kPa or 0.57 atm) in one day, but one should then descend back to 3,300 m (10,800 ft) (67.5 kPa or 0.666 atm) to sleep. This process cannot safely be rushed, and this is why climbers need to spend days (or even weeks at times) acclimatizing before attempting to climb a high peak. Simulated altitude equipment such as altitude tents provide hypoxic (reduced oxygen) air, and are designed to allow partial pre-acclimation to high altitude, reducing the total time required on the mountain itself.
Altitude acclimatization is necessary for some people who move rapidly from lower altitudes to higher altitudes .

Medications
The drug acetazolamide (trade name Diamox) may help some people making a rapid ascent to sleeping altitude above 2,700 metres (9,000 ft), and it may also be effective if started early in the course of AMS. Acetazolamide can be taken before symptoms appear as a preventive measure at a dose of 125 mg twice daily. The Everest Base Camp Medical Centre cautions against its routine use as a substitute for a reasonable ascent schedule, except where rapid ascent is forced by flying into high altitude locations or due to terrain considerations. The Centre suggests a dosage of 125 mg twice daily for prophylaxis, starting from 24 hours before ascending until a few days at the highest altitude or on descending; with 250 mg twice daily recommended for treatment of AMS. The Centers for Disease Control and Prevention (CDC) suggest the same dose for prevention of 125 mg acetazolamide every 12 hours. Acetazolamide, a mild diuretic, works by stimulating the kidneys to secrete more bicarbonate in the urine, thereby acidifying the blood. This change in pH stimulates the respiratory center to increase the depth and frequency of respiration, thus speeding the natural acclimatization process. An undesirable side-effect of acetazolamide is a reduction in aerobic endurance performance. Other minor side effects include a tingle-sensation in hands and feet. Although a sulfonamide; acetazolamide is a non-antibiotic and has not been shown to cause life-threatening allergic cross-reactivity in those with a self-reported sulfonamide allergy. Dosage of 1000 mg/day will produce a 25% decrease in performance, on top of the reduction due to high-altitude exposure. The CDC advises that Dexamethasone be reserved for treatment of severe AMS and HACE during descents, and notes that Nifedipine may prevent HAPE.There is insufficient evidence to determine the safety of sumatriptan and if it may help prevent altitude sickness. Despite their popularity, antioxidant treatments have not been found to be effective medications for prevention of AMS. Interest in phosphodiesterase inhibitors such as sildenafil has been limited by the possibility that these drugs might worsen the headache of mountain sickness. A promising possible preventive for altitude sickness is myo-inositol trispyrophosphate (ITPP), which increases the amount of oxygen released by hemoglobin.
Prior to the onset of altitude sickness, ibuprofen is a suggested non-steroidal anti-inflammatory and painkiller that can help alleviate both the headache and nausea associated with AMS. It has not been studied for the prevention of cerebral edema (swelling of the brain) associated with extreme symptoms of AMS.

Over-the-counter herbal supplements and traditional medicines
Herbal supplements and traditional medicines are sometimes suggested to prevent high altitude sickness including ginkgo biloba, R crenulata, minerals such as iron, antacids, and hormonal-based supplements such as medroxyprogesterone and erythropoietin. Medical evidence to support the effectiveness and safety of these approaches is often contradictory or lacking. Indigenous peoples of the Americas, such as the Aymaras of the Altiplano, have for centuries chewed coca leaves to try to alleviate the symptoms of mild altitude sickness. This therapy has not yet been proven effective in a clinical study. In Chinese and Tibetan traditional medicine, an extract of the root tissue of Radix rhodiola is often taken in order to prevent the symptoms of high altitude sickness, however, no clear medical studies have confirmed the effectiveness or safety of this extract.

Oxygen enrichment
In high-altitude conditions, oxygen enrichment can counteract the hypoxia related effects of altitude sickness. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At 3,400 metres (11,200 ft) (67 kPa or 0.66 atm), raising the oxygen concentration level by 5% via an oxygen concentrator and an existing ventilation system provides an effective altitude of 3,000 m (10,000 ft) (70 kPa or 0.69 atm), which is more tolerable for those unaccustomed to high altitudes.Oxygen from gas bottles or liquid containers can be applied directly via a nasal cannula or mask. Oxygen concentrators based upon pressure swing adsorption (PSA), VSA, or vacuum-pressure swing adsorption (VPSA) can be used to generate the oxygen if electricity is available. Stationary oxygen concentrators typically use PSA technology, which has performance degradations at the lower barometric pressures at high altitudes </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 Amblyopia and can you explain it in depth? [/INST] Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to fully process input from one eye and over time favors the other eye. It results in decreased vision in an eye that typically appears normal in other respects. Amblyopia is the most common cause of decreased vision in a single eye among children and younger adults.The cause of amblyopia can be any condition that interferes with focusing during early childhood. This can occur from poor alignment of the eyes (strabismic), an eye being irregularly shaped such that focusing is difficult, one eye being more nearsighted or farsighted than the other (refractive), or clouding of the lens of an eye (deprivational). After the underlying cause is addressed, vision is not restored right away, as the mechanism also involves the brain. Amblyopia can be difficult to detect, so vision testing is recommended for all children around the ages of four to five.Early detection improves treatment success. Glasses may be all the treatment needed for some children. If this is not sufficient, treatments which encourage or force the child to use the weaker eye are used. This is done by either using a patch or putting atropine in the stronger eye. Without treatment, amblyopia typically persists. Treatment in adulthood is usually much less effective.Amblyopia begins by the age of five. In adults, the disorder is estimated to affect 1–5% of the population. While treatment improves vision, it does not typically restore it to normal in the affected eye. Amblyopia was first described in the 1600s. The condition may make people ineligible to be pilots or police officers. The word amblyopia is from Greek ἀμβλύς amblys, meaning "blunt", and ὤψ ōps, meaning "sight".

Signs and symptoms
Many people with amblyopia, especially those who only have a mild form, are not aware they have the condition until tested at older ages, since the vision in their stronger eye is normal. People with amblyopia typically have poor stereo vision, since it requires both eyes. They further may have, on the affected eye, poor pattern recognition, poor visual acuity, and low sensitivity to contrast and motion.Amblyopia is characterized by several functional abnormalities in spatial vision, including reductions in visual acuity, contrast sensitivity function, and vernier acuity, as well as spatial distortion, abnormal spatial interactions, and impaired contour detection. In addition, individuals with amblyopia have binocular abnormalities such as impaired stereoacuity (stereoscopic acuity) and abnormal binocular summation. Also, central vision in amblyopes is more crowded than central vision in normal observers.These deficits are usually specific to the amblyopic eye. Subclinical deficits of the "better" eye have also been demonstrated.People with amblyopia also have problems of binocular vision such as limited stereoscopic depth perception and usually have difficulty seeing the three-dimensional images in hidden stereoscopic displays such as autostereograms. Perception of depth, from monocular cues such as size, perspective, and motion parallax remains normal.

Cause
Amblyopia has three main causes:

Strabismic: by strabismus (misaligned eyes)
Refractive: by anisometropia (difference of a certain degree of nearsightedness, farsightedness, or astigmatism), or by significant amount of equal refractive error in both eyes
Deprivational: by deprivation of vision early in life by vision-obstructing disorders such as congenital cataract

Strabismus
Strabismus, sometimes also incorrectly called lazy eye, is a condition in which the eyes are misaligned. Strabismus usually results in normal vision in the preferred sighting (or "fellow") eye (the eye that the person prefers to use), but may cause abnormal vision in the deviating or strabismic eye due to the difference between the images projecting to the brain from the two eyes.
Adult-onset strabismus usually causes double vision (diplopia), since the two eyes are not fixed on the same object.
Childrens brains are more neuroplastic, so can more easily adapt by suppressing images from one of the eyes, eliminating the double vision. This plastic response of the brain, interrupts the brains normal development, resulting in the amblyopia. Recent evidence points to a cause of infantile strabismus lying with the input to the visual cortex.Those with strabismic amblyopia tend to show ocular motion deficits when reading, even when they use the nonamblyopic eye. In particular, they tend to make more saccades per line than persons with normal stereo vision, and to have a reduced reading speed, especially when reading a text with small font size.Strabismic amblyopia is treated by clarifying the visual image with glasses, or encouraging use of the amblyopic eye with an eyepatch over the dominant eye or pharmacologic penalization of the better eye. Penalization usually consists of applying atropine drops to temporarily paralyze the accommodation reflex, leading to the blurring of vision in the good eye. It also dilates the pupil. This helps to prevent the bullying and teasing associated with wearing a patch, although sometimes application of the eye drops is challenging. The ocular alignment itself may be treated with surgical or nonsurgical methods, depending on the type and severity of the strabismus.

Refractive
Refractive amblyopia may result from anisometropia (unequal refractive error between the two eyes). Anisometropia exists when there is a difference in the power between the two eyes. The eye which provides the brain with a clearer image typically becomes the dominant eye. The image in the other eye is blurred, which results in abnormal development of one half of the visual system. Refractive amblyopia is usually less severe than strabismic amblyopia and is commonly missed by primary care physicians because of its less dramatic appearance and lack of obvious physical manifestation, such as with strabismus. Given that the refractive correction of anisometropia by means of spectacles typically leads to different image magnification for the two eyes, which may in turn prevent binocular vision, a refractive correction using contact lenses is to be considered. Also pediatric refractive surgery is a treatment option, in particular if conventional approaches have failed due to aniseikonia or lack of compliance or both.Frequently, amblyopia is associated with a combination of anisometropia and strabismus. In some cases, the vision between the eyes can differ to the point where one eye has twice average vision while the other eye is completely blind.

Deprivation and occlusion
Deprivation amblyopia (amblyopia ex anopsia) results when the ocular media become opaque, such as is the case with congenital cataract or corneal haziness. These opacities prevent adequate visual input from reaching the eye, and disrupt development. If not treated in a timely fashion, amblyopia may persist even after the cause of the opacity is removed. Sometimes, drooping of the eyelid (ptosis) or some other problem causes the upper eyelid to physically occlude a childs vision, which may cause amblyopia quickly.  Occlusion amblyopia may be a complication of a hemangioma that blocks some or all of the eye. Other possible causes of deprivation and occlusion amblyopia include obstruction in the vitreous and aphakia. Deprivation amblyopia accounts for less than 3% of all individuals affected by amblyopia.

Pathophysiology
Amblyopia is a developmental problem in the brain, not any intrinsic, organic neurological problem in the eyeball (although organic problems can lead to amblyopia which can continue to exist after the organic problem has resolved by medical intervention).
The part of the brain receiving images from the affected eye is not stimulated properly and does not develop to its full visual potential. This has been confirmed by direct brain examination. David H. Hubel and Torsten Wiesel won the Nobel Prize in Physiology or Medicine in 1981 for their work in showing the extent of the damage to ocular dominance columns produced in kittens by sufficient visual deprivation during the so-called "critical period". The maximum "critical period" in humans is from birth to two years old.

Diagnosis
Amblyopia is diagnosed by identifying low visual acuity in one or both eyes, out of proportion to the structural abnormality of the eye and excluding other visual disorders as causes for the lowered visual acuity. It can be defined as an interocular difference of two lines or more in acuity (e.g. on Snellen chart) when the eye optics are maximally corrected. In young children, visual acuity is difficult to measure and can be estimated by observing the reactions of the patient when one eye is covered, including observing the patients ability to follow objects with one eye.
Stereotests like the Lang stereotest are not reliable exclusion tests for amblyopia. A person who passes the Lang stereotest test is unlikely to have strabismic amblyopia, but could nonetheless have refractive or deprivational amblyopia. Binocular retinal birefringence scanning may be able to identify, already in very young children, amblyopia that is associated with strabismus, microstrabismus, or reduced fixation accuracy. Diagnosis and treatment of amblyopia as early as possible is necessary to keep the vision loss to a minimum. Screening for amblyopia is recommended in all people between three and five years of age.

Treatment
Treatment of strabismic or anisometropic amblyopia consists of correcting the optical deficit (wearing the necessary spectacle prescription) and often forcing use of the amblyopic eye, by patching the good eye, or instilling topical atropine in the good eye, or both.: 130  Atropine appears to result in similar outcomes to patching. If there is overpatching or overpenalizing the good eye when treating amblyopia, "reverse amblyopia" can result. Eye patching is usually done on a part-time schedule of about 4–6 hours a day. Treatment is continued as long as vision improves. It is not worthwhile continuing to patch for more than 6 months if no improvement continues.Deprivation amblyopia is treated by removing the opacity as soon as possible followed by patching or penalizing the good eye to encourage the use of the amblyopic eye </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 Amoebiasis and can you explain it in depth? [/INST] Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba Entamoeba histolytica. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, colonic ulcerations, abdominal pain, diarrhea, or bloody diarrhea. Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis. Anemia may develop due to prolonged gastric bleeding.Cysts of Entamoeba can survive for up to a month in soil or for up to 45 minutes under fingernails. Invasion of the intestinal lining results in bloody diarrhea. If the parasite reaches the bloodstream it can spread through the body, most frequently ending up in the liver where it can cause amoebic liver abscesses. Liver abscesses can occur without previous diarrhea. Diagnosis is typically made by stool examination using microscopy, but it can be difficult to distinguish E. hystolitica from other harmless entamoeba species. An increased white blood cell count may be present in severe cases. The most accurate test is finding specific antibodies in the blood, but it may remain positive following treatment. Bacterial colitis can result in similar symptoms.Prevention of amoebiasis is by improved sanitation, including separating food and water from faeces. There is no vaccine. There are two treatment options depending on the location of the infection. Amoebiasis in tissues is treated with either metronidazole, tinidazole, nitazoxanide, dehydroemetine or chloroquine, while luminal infection is treated with diloxanide furoate or iodoquinoline. Effective treatment against all stages of the disease may require a combination of medications. Infections without symptoms may be treated with just one antibiotic, and infections with symptoms are treated with two antibiotics.Amoebiasis is present all over the world, though most cases occur in the developing world. About 480 million people are currently infected with about 40 million new cases per year with significant symptoms. This results in the death of between 40,000–100,000 people a year. The first case of amoebiasis was documented in 1875 and in 1891 the disease was described in detail, resulting in the terms amoebic dysentery and amoebic liver abscess. Further evidence from the Philippines in 1913 found that upon swallowing cysts of E. histolytica volunteers developed the disease.

Signs and symptoms
Most infected people, about 90%, are asymptomatic, but this disease has the potential to become serious. It is estimated that about 40,000 to 100,000 people worldwide die annually due to amoebiasis.Infections can sometimes last for years if there is no treatment. Symptoms take from a few days to a few weeks to develop and manifest themselves, but usually it is about two to four weeks. Symptoms can range from mild diarrhea to dysentery with blood, coupled with intense abdominal pains. Extra-intestinal complications might also arise as a result of invasive infection which includes colitis, liver, lung, or brain abscesses. The blood comes from bleeding lesions created by the amoebae invading the lining of the colon. In about 10% of invasive cases the amoebae enter the bloodstream and may travel to other organs in the body. Most commonly this means the liver, as this is where blood from the intestine reaches first, but they can end up almost anywhere in the body.Onset time is highly variable and the average asymptomatic infection persists for over a year. It is theorized that the absence of symptoms or their intensity may vary with such factors as strain of amoeba, immune response of the host, and perhaps associated bacteria and viruses.In asymptomatic infections, the amoeba lives by eating and digesting bacteria and food particles in the gut, a part of the gastrointestinal tract. It does not usually come in contact with the intestine itself due to the protective layer of mucus that lines the gut. Disease occurs when amoeba comes in contact with the cells lining the intestine. It then secretes the same substances it uses to digest bacteria, which include enzymes that destroy cell membranes and proteins. This process can lead to penetration and digestion of human tissues, resulting first in flask-shaped ulcerations in the intestine. Entamoeba histolytica ingests the destroyed cells by phagocytosis and is often seen with red blood cells (a process known as erythrophagocytosis) inside when viewed in stool samples.  Especially in Latin America, a granulomatous mass (known as an amoeboma) may form in the wall of the ascending colon or rectum due to long-lasting immunological cellular response, and is sometimes confused with cancer.The ingestion of one viable cyst may cause an infection.Steroid therapy can occasionally provoke severe amoebic colitis in people with any E. histolytica infection. This bears high mortality: on average more than 50% with severe colitis die.

Cause
Amoebiasis is an infection caused by the amoeba Entamoeba histolytica.

Transmission
Amoebiasis is usually transmitted by the fecal-oral route, but it can also be transmitted indirectly through contact with dirty hands or objects as well as by anal-oral contact. Infection is spread through ingestion of the cyst form of the parasite, a semi-dormant and hardy structure found in feces. Any non-encysted amoebae, or trophozoites, die quickly after leaving the body but may also be present in stool: these are rarely the source of new infections. Since amoebiasis is transmitted through contaminated food and water, it is often endemic in regions of the world with limited modern sanitation systems, including México, Central America, western South America, South Asia, and western and southern Africa.Amoebic dysentery is one form of travelers diarrhea, although most travelers diarrhea is bacterial or viral in origin.

Pathogenesis
Amoebiasis results from tissue destruction induced by the E. histolytica parasite.
E. histolytica causes tissue damage by three main events: direct host cell killing, inflammation, and parasite invasion.

Diagnosis
With colonoscopy it is possible to detect small ulcers of between 3–5mm, but diagnosis may be difficult as the mucous membrane between these areas can look either healthy or inflamed.
Trophozoites may be identified at the ulcer edge or within the tissue, using immunohistochemical staining with specific anti-E. histolytica antibodies.Asymptomatic human infections are usually diagnosed by finding cysts shed in the stool. Various flotation or sedimentation procedures have been developed to recover the cysts from fecal matter and stains help to visualize the isolated cysts for microscopic examination. Since cysts are not shed constantly, a minimum of three stools are examined. In symptomatic infections, the motile form (the trophozoite) is often seen in fresh feces. Serological tests exist, and most infected individuals (with symptoms or not) test positive for the presence of antibodies. The levels of antibody are much higher in individuals with liver abscesses. Serology only becomes positive about two weeks after infection. More recent developments include a kit that detects the presence of amoeba proteins in the feces, and another that detects ameba DNA in feces. These tests are not in widespread use due to their expense.Microscopy is still by far the most widespread method of diagnosis around the world. However it is not as sensitive or accurate in diagnosis as the other tests available. It is important to distinguish the E. histolytica cyst from the cysts of nonpathogenic intestinal protozoa such as Entamoeba coli by its appearance.  E. histolytica cysts have a maximum of four nuclei, while the commensal Entamoeba coli cyst has up to 8 nuclei.  Additionally, in E. histolytica, the endosome is centrally located in the nucleus, while it is usually off-center in Entamoeba coli.  Finally, chromatoidal bodies in E. histolytica cysts are rounded, while they are jagged in Entamoeba coli. However, other species, Entamoeba dispar and E. moshkovskii, are also commensals and cannot be distinguished from E. histolytica under the microscope. As E. dispar is much more common than E. histolytica in most parts of the world this means that there is a lot of incorrect diagnosis of E. histolytica infection taking place. The WHO recommends that infections diagnosed by microscopy alone should not be treated if they are asymptomatic and there is no other reason to suspect that the infection is actually E. histolytica.  Detection of cysts or trophozoites stools under microscope may require examination of several samples over several days to determine if they are present, because cysts are shed intermittently and may not show up in every sample.Typically, the organism can no longer be found in the feces once the disease goes extra-intestinal. Serological tests are useful in detecting infection by E. histolytica if the organism goes extra-intestinal and in excluding the organism from the diagnosis of other disorders. An Ova & Parasite (O&P) test or an E. histolytica fecal antigen assay is the proper assay for intestinal infections. Since antibodies may persist for years after clinical cure, a positive serological result may not necessarily indicate an active infection. A negative serological result, however, can be equally important in excluding suspected tissue invasion by E. histolytica.Stool antigen detection tests have helped to overcome some of the limitations of stool microscopy. Antigen detection tests are easy to use, but they have variable sensitivity and specificity, especially in low-endemic areas.Polymerase chain reaction (PCR) is considered the gold standard for diagnosis but remains underutilized.

Prevention
To help prevent the spread of amoebiasis around the home :
Wash hands thoroughly with soap and hot running water for at least 10 seconds after using the toilet or changing a babys diaper, and before handling food.
Clean bathrooms and toilets often; pay particular attention to toilet seats and taps.
Avoid sharing towels or face washers.To help prevent infection:
Avoid raw vegetables when in endemic areas, as they may have been fertilized using human feces.
Boil water or treat with iodine tablets.
Avoid eating street foods especially in public places where others are sharing sauces in one containerGood sanitary practice, as well as responsible sewage disposal or treatment, are necessary for the prevention of E. histolytica infection on an endemic level.  E.histolytica cysts are usually resistant to chlorination, therefore sedimentation and filtration of water supplies are necessary to reduce the incidence of infection.E. histolytica cysts may be recovered from contaminated food by methods similar to those used for recovering Giardia lamblia cysts from feces. Filtration is probably the most practical method for recovery from drinking water and liquid foods. E. histolytica cysts must be distinguished from cysts of other parasitic (but nonpathogenic) protozoa and from cysts of free-living protozoa as discussed above. Recovery procedures are not very accurate; cysts are easily lost or damaged beyond recognition, which leads to many falsely negative results in recovery tests.

Treatment
E. histolytica infections occur in both the intestine and (in people with symptoms) in tissue of the intestine and/or liver. Those with symptoms require treatment with two medications, an amoebicidal tissue-active agent and a luminal cysticidal agent. Individuals that are asymptomatic only need a luminal cysticidal agent.

Prognosis
In the majority of cases, amoebas remain in the gastrointestinal tract of the hosts. Severe ulceration of the gastrointestinal mucosal surfaces occurs in less than 16% of cases. In fewer cases, the parasite invades the soft tissues, most commonly the liver. Only rarely are masses formed (amoebomas) that lead to intestinal obstruction.(Mistaken for Ca caecum and appendicular mass) Other local complications include bloody diarrhea, pericolic and pericaecal abscess.Complications of hepatic amoebiasis includes subdiaphragmatic abscess, perforation of diaphragm to pericardium and pleural cavity, perforation to abdominal cavital (amoebic peritonitis) and perforation of skin (amoebiasis cutis).Pulmonary amoebiasis can occur from liver lesions by spread through the blood or by perforation of pleural cavity and lung. It can cause lung abscess, pulmono pleural fistula, empyema lung and broncho pleural fistula. It can also reach the brain through blood vessels and cause amoebic brain abscess and amoebic meningoencephalitis. Cutaneous amoebiasis can also occur in skin around sites of colostomy wound, perianal region, region overlying visceral lesion and at the site of drainage of liver abscess.Urogenital tract amoebiasis derived from intestinal lesion can cause amoebic vulvovaginitis (Mays disease), rectovesicle fistula and rectovaginal fistula.Entamoeba histolytica infection is associated with malnutrition and stunting of growth in children.

Epidemiology
Amoebiasis caused about 55,000 deaths worldwide in 2010, down from 68,000 in 1990.
In older textbooks it is often stated that 10% of the worlds population is infected with Entamoeba histolytica.  Nevertheless, this means that there are up to 50 million true E. histolytica infections and approximately seventy thousand die each year, mostly from liver abscesses or other complications.  Although usually considered a tropical parasite, the first case reported (in 1875) was actually in St Petersburg in Russia, near the Arctic Circle. Infection is more common in warmer areas, but this is because of both poorer hygiene and the parasitic cysts surviving longer in warm moist conditions.

History
Amoebiasis was first described by Fedor A. Lösch in 1875, in northern Russia </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 Anaplasmosis and can you explain it in depth? [/INST] Anaplasmosis is a tick-borne disease affecting ruminants, dogs, and horses, and is caused by Anaplasma bacteria. Anaplasmosis is an infectious but not contagious disease. Anaplasmosis can be transmitted through mechanical and biological vector processes. Anaplasmosis can also be referred to as "yellow bag" or "yellow fever" because the infected animal can develop a jaundiced look. Other signs of infection include weight loss, diarrhea, paleness of the skin, aggressive behavior, and high fever.Many different tick species can carry the bacteria that cause anaplasmosis.  The two major bacterial pathogens are Anaplasma marginale and Anaplasma phagocytophilum. These microorganisms  are Gram-negative, and infect red blood cells. Once the host is infected with anaplasmosis, the immune system will try to fight off and kill the infected red blood cells, but will also kill healthy red blood cells. The Anaplasma sparouinense species is responsible for a rare zoonosis, the Sparouine anaplasmosis, detected only in French Guiana, South America. This disease was described from a clandestine gold miner working deep in rainforest. Infection of his red blood cells led to a severe deterioration of his health and required his hospitalization. Molecular typing showed that Anaplasma sparouinense is distinct to all known species and more genetically related to recently described Anaplasma species causing infections in rainforest wild fauna of Brazil.While there are no current live or inactivated vaccines effective for all strains of A. marginale approved by the USDA for anaplasmosis, there are other means of prevention. Tick and fly control for herds of ruminants can be effective but also labor intensive. Chemical methods can also be used, including sanitizing surgical equipment after each use. Tetracycline drugs are the most common treatment for anaplasmosis, and can provide the animal with immunity for a period of time. The disease is more common in the South and West parts of the United States, but is no longer considered a major problem since the use of tetracycline drugs.

Transmission
Mechanical and biological vector transmission work in different ways but both lead to infection of the red blood cells. Mechanical transmission happens in two ways, one when red blood cells are inoculated with the blood parasite through surgical equipment including needles, dehorners, ear taggers, castrating knives, and tattoo instruments. Another mechanical transmission mode is through the mouthparts of biting flies who carry an Anaplasma species of blood parasite.Biological vector transmission is through ticks that carry a blood parasite able to cause anaplasmosis. The most common Anaplasmosis-causing tick is Ixodes scapularis, also known as the black-legged tick or the deer tick. Ticks who contain species of many different Anaplasma species can transmit this disease through a bite. The blood parasite survives and can multiply in the tick, and can sit dormant for months without being transmitted to an animal. When bitten by a tick carrying a blood parasite, the blood parasite can then enter the new host and cause infection.Once infected with a species of Anaplasma, the parasite multiplies in the blood stream and attaches to red blood cells. The immune system will attempt to kill the infected blood cells but will also kill uninfected red blood cells in the process. The number of red blood cells being destroyed becomes larger than new red blood cells being made, causing the host to become anemic and leading to many other symptoms. Once infected with anaplasmosis, the cattle will always be a carrier of the infectious disease, and calves born from carriers will also carry the disease.

Signs and symptoms
Classic signs and symptoms of anaplasmosis will not occur until 3–6 weeks after infection. The most common symptoms of anaplasmosis include fever, a decreased number of white blood cells, platelets in the bloodstream, and abnormally elevated levels of liver enzymes. The erythema chronicum migrans rash may be seen with anaplasmosis as it is co-transmitted in 10% of Lyme disease cases.
Anemia may be severe and result in cardiovascular changes such as an increase in heart rate. Blood in the urine may occur due to the lysis of red blood cells. General systemic signs include diarrhea, anorexia, and weight loss. Infected animals may develop a jaundiced look which then turns into paleness around the eyes, muzzle, lips, and teats of the cattle.All cattle are susceptible to infection by Anaplasma marginale, but the severity worsens with age increase. Older cattle tend to exhibit the most severe clinical symptoms; cattle aged 1–3 may also show severe symptoms but are able to recover easier.

Causes
The two major species that cause anaplasmosis in ruminants include Anaplasma marginale and Anaplasma phagocytophilum. Anaplasma marginale is found worldwide and is transmitted by Rhipicephalus ticks. Anaplasma phagocytophilum is also found worldwide, mainly transmitted by Ixodes ticks. Other species that cause anaplasmosis in specific species include:

Cattle:
Anaplasma centrale - found mainly in South America, Africa and the Middle East
Sheep and goats:
Anaplasma ovis - found worldwide. There is a prevalence of 82.9% in sheep, and 74.9% in goats. This species is the most prevalent for causing anaplasmosis in sheep and goats, although Anaplasma phagocytophilium can also cause the disease. Anaplasma phagocytophilium has a prevalence of 11.9% in sheep, and 15.2% in goats.

Morphology
There are many strains of Anaplasma marginale, all with differing morphology, antigenic properties, protein sequence, and ability to be transmitted by ticks. Major surface proteins (MSP) have been found to play a major role in the infection by Anaplasma marginale. Out of the six MSP found on this species, three of the major surface proteins do not seem to differ between all strains, those including MSP1a, MSP4, and MSP5. The msp1a gene, which codes for MSP1a, is used as a marker for the identification of Anaplasma marginale because it has shown to be conserved in the multiplication of rickettsia in cattle and ticks and has been shown to be involved in adhesion to bovine erythrocytes and tick cells.Anaplasma phagocytophilum is a gram-negative bacterium that does not have lipopolysaccharides or peptidoglycan. The outer membrane does not have a capsule, and is coarse with irregular periplasmic spaces. This species was originally included in the genus Ehrlichia (Ehrlichia phagocytophilium), but is now included in the genus Anaplasma (Anaplasma phagocytophilium).

Prevention
Currently, no live or inactivated vaccines have been approved by the USDA that are effective against all strains of A. marginale. Some vaccines that rely on erythrocyte-derived antigen sources provide immunity or prevent clinical disease, although these do not prevent cattle from being infected with A. marginale. Other means of prevention can include testing all ruminants in a herd and eliminating any individuals who test positive for anaplasmosis, leading to an anaplasmosis-free herd. Vector control measures can also be used. Tick control is widely used in some countries, including Africa, but rarely used in the United States due to the fact that this prevention method is labor-intensive and expensive. In contrast, the control of flies is effective and there are many ways to do this. Chemical agents can be used, sanitation methods (such as cleaning stalls/pens regularly, manure management, and protecting feed), as well as biological control by natural enemies of flies (including bees, mites, parasitoids). Ways to prevent iatrogenic transmission include avoiding re-using of needles and sanitizing medical equipment between uses. Antimicrobial treatment can also be used, although it is more commonly used in the case of active infection. This includes the drugs tetracycline and imidocarb, and is used in healthy ruminants to decrease the clinical effects of an active infection.

Treatment
The most common source of treatment is the use of tetracycline drugs (including tetracycline, chlortetracycline, oxytetracycline, rolitetracycline, doxycycline, and minocycline) and imidocarb. An injection of tetracycline drugs can give ruminants immunity to Anaplasma species for at least eight months. Imidocarb has been shown to be highly effective against Anaplasma marginale, but has been identified as a possible carcinogen and is not approved in the United States or Europe. Countries such as South Africa, Australia, Israel, and South America have used live vaccines containing infectious Anaplasma centrale to prevent infection of Anaplasma marginale. Live vaccines are prohibited in the United States, and there has been production of vaccines consisting of nonliving Anaplasma marginale pulled from infected bovine erythrocytes, which can provide some immunity but leaves cattle susceptible to other strains of Anaplasma marginale. Supportive therapy such as blood products and fluids may be necessary.

Epidemiology
In the United States, anaplasmosis is notably present in the South and West, where the tick hosts Ixodes spp. are found.  It is also a seemingly increasing antibody in humans in Europe </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 Anaplastic astrocytoma and can you explain it in depth? [/INST] Anaplastic astrocytoma is a rare WHO grade III type of astrocytoma, which is a type of cancer of the brain. In the United States, the annual incidence rate for anaplastic astrocytoma is 0.44 per 100,000 people.

Signs and symptoms
Initial presenting symptoms most commonly are headache, depressed mental status, focal neurological deficits, and/or seizures. The growth rate and mean interval between onset of symptoms and diagnosis is approximately 1.5–2 years but is highly variable, being intermediate between that of low-grade astrocytomas and glioblastomas. Seizures are less common among patients with anaplastic astrocytomas compared to low-grade lesions.

Causes
Most high-grade gliomas occur sporadically or without identifiable cause. However, a small proportion (less than 5%) of persons with malignant astrocytoma have a definite or suspected hereditary predisposition. The main hereditary predispositions are mainly neurofibromatosis type I, Li-Fraumeni syndrome, hereditary nonpolyposis colorectal cancer and tuberous sclerosis. Anaplastic astrocytomas have also been associated with previous exposure to vinyl chloride and to high doses of radiation therapy to the brain.

Pathology
Anaplastic astrocytomas fall under the category of high grade gliomas (WHO grade III-IV), which are pathologically undifferentiated gliomas that carry a poor clinical prognosis.  Unlike glioblastomas (WHO grade IV), anaplastic astrocytomas lack vascular proliferation and necrosis on pathologic evaluation.  Compared to grade II tumors, anaplastic astrocytomas are more cellular, demonstrate more atypia, and mitoses are seen.

Treatment
The standard initial treatment is to remove as much of the tumor as possible without worsening neurologic deficits </s>