<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 Iron overload and can you explain it in depth? [/INST] Iron overload or haemochromatosis (also spelled hemochromatosis in American English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosis (HH or HHC), a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions.

Signs and symptoms
Organs most commonly affected by haemochromatosis include the liver, heart, and endocrine glands.Haemochromatosis may present with the following clinical syndromes:

liver: chronic liver disease and cirrhosis of the liver.
heart: heart failure, cardiac arrhythmia.
hormones: diabetes (see below) and hypogonadism (insufficiency of the sex hormone producing glands) which leads to low sex drive and/or loss of fertility in men and loss of menstrual cycle in women.
metabolism: diabetes in people with iron overload occurs as a result of selective iron deposition in islet beta cells in the pancreas leading to functional failure and cell death.
skeletal: arthritis, from calcium pyrophosphate deposition in joints leading to joint pains. The most commonly affected joints are those of the hands, particularly the knuckles of the second and third fingers.
skin: melanoderma (darkening or bronzing of the skin).The skins deep tan color, in concert with insulin insufficiency due to pancreatic damage, is the source of a nickname for this condition: "bronze diabetes" (for more information, see the history of haemochromatosis).

Causes
The term haemochromatosis was initially used to refer to what is now more specifically called haemochromatosis type 1 (or HFE-related hereditary haemochromatosis). Currently, haemochromatosis (without further specification) is mostly defined as iron overload with a hereditary or primary cause, or originating from a metabolic disorder. However, the term is currently also used more broadly to refer to any form of iron overload, thus requiring specification of the cause, for example, hereditary haemochromatosis. Hereditary haemochromatosis is an autosomal recessive disorder with estimated prevalence in the population of 1 in 200 among patients with European ancestry, with lower incidence in other ethnic groups. The gene responsible for hereditary haemochromatosis (known as HFE gene) is located on chromosome 6; the majority of hereditary haemochromatosis patients have mutations in this HFE gene.Hereditary haemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues. This typically begins to be expressed in the third to fifth decades of life, but may occur in children. The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disorder if left untreated, and recognizing that treatment is relatively simple, early diagnosis before symptoms or signs appear is important.In general, the term haemosiderosis is used to indicate the pathological effect of iron accumulation in any given organ, which mainly occurs in the form of the iron-storage complex haemosiderin. Sometimes, the simpler term siderosis is used instead.
Other definitions distinguishing haemochromatosis or haemosiderosis that are occasionally used include:

Haemosiderosis is haemochromatosis caused by excessive blood transfusions, that is, haemosiderosis is a form of secondary haemochromatosis.
Haemosiderosis is haemosiderin deposition within cells, while haemochromatosis is haemosiderin within cells and interstitium.
Haemosiderosis is iron overload that does not cause tissue damage, while haemochromatosis does.
Haemosiderosis is arbitrarily differentiated from haemochromatosis by the reversible nature of the iron accumulation in the reticuloendothelial system.The causes of haemochromatosis broken down into two subcategories: primary cases (hereditary or genetically determined) and less frequent secondary cases (acquired during life). People of Celtic (Irish, Scottish, Welsh, Cornish, Breton etc.), English, and Scandinavian origin have a particularly high incidence, with about 10% being carriers of the principal genetic variant, the C282Y mutation on the HFE gene, and 1% having the condition. This has been recognised in several laymans alternative names such as Celtic curse, Irish illness, British gene, and Scottish sickness.
The overwhelming majority depend on mutations of the HFE gene discovered in 1996, but since then others have been discovered and sometimes are grouped together as "non-classical hereditary haemochromatosis", "non-HFE related hereditary haemochromatosis", or "non-HFE haemochromatosis".
Most types of hereditary haemochromatosis have autosomal recessive inheritance, while type 4 has autosomal dominant inheritance.

Secondary haemochromatosis
Severe chronic haemolysis of any cause, including intravascular haemolysis and ineffective erythropoiesis (haemolysis within the bone marrow)
Multiple frequent blood transfusions (either whole blood or just red blood cells), which are usually needed either by individuals with hereditary anaemias (such as beta-thalassaemia major, sickle cell anaemia, and Diamond–Blackfan anaemia) or by older patients with severe acquired anaemias such as in myelodysplastic syndromes.
Excess parenteral (non-ingested) iron supplements, such as what can acutely happen in iron poisoning
Excess dietary iron
Some disorders do not normally cause haemochromatosis on their own, but may do so in the presence of other predisposing factors. These include cirrhosis (especially related to alcohol use disorder), steatohepatitis of any cause, porphyria cutanea tarda, prolonged haemodialysis, and post-portacaval shunting

Diagnosis
There are several methods available for diagnosing and monitoring iron loading.

Blood test
Blood tests are usually the first test if there is a clinical suspicion of iron overload. Serum ferritin testing is a low-cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of iron overload is that it can be elevated in a variety of other medical conditions including infection, inflammation, fever, liver disease, kidney disease, and cancer. Also, total iron binding capacity may be low, but can also be normal. In males and postmenopausal females, normal range of serum ferritin is between 12 and 300 ng/mL (670 pmol/L) . In premenopausal females, normal range of serum ferritin is between 12 and 150 or 200 ng/mL (330 or 440 pmol/L). If the person is showing the symptoms, they may need to be tested more than once throughout their lives as a precaution, most commonly in women after menopause. Transferrin saturation is a more specific test.

Genetics
DNA/screening: the current standard of practice in diagnosis of haemochromatosis, places emphasis on genetic testing. Positive HFE analysis confirms the clinical diagnosis of haemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals with a family history of haemochromatosis. The alleles evaluated by HFE gene analysis are evident in ~80% of patients with haemochromatosis; a negative report for HFE gene does not rule out haemochromatosis. First degree relatives of those with primary haemochromatosis should be screened to determine if they are a carrier or if they could develop the disease. This can allow preventive measures to be taken. Screening the general population is not recommended.

Biopsy
Liver biopsy is the removal of small sample in order to be studied and can determine the cause of inflammation or cirrhosis. In someone with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated. In this case, diagnosis of haemochromatosis is based on biochemical analysis and histologic examination of a liver biopsy. Assessment of the hepatic iron index (HII) is considered the "gold standard" for diagnosis of haemochromatosis.Magnetic resonance imaging (MRI) is used as a noninvasive way to accurately estimate iron deposition levels in the liver as well as heart, joints, and pituitary gland.

Treatment
Phlebotomy
Phlebotomy/venesection: routine treatment consists of regularly scheduled phlebotomies (bloodletting or erythrocytapheresis). When first diagnosed, the phlebotomies may be performed every week or fortnight, until iron levels can be brought to within normal range. Once the serum ferritin and transferrin saturation are within the normal range, treatments may be scheduled every two to three months depending upon the rate of reabsorption of iron. A phlebotomy session typically draws between 450 and 500 mL of blood. The blood drawn is sometimes donated.

Diet
A diet low in iron is generally recommended, but has little effect compared to venesection. The human diet contains iron in two forms: heme iron and non-heme iron. Heme iron is the most easily absorbed form of iron. People with iron overload may be advised to avoid food that are high in heme iron. Highest in heme iron is red meat such as beef, venison, lamb, buffalo, and fish such as bluefin tuna. A strict low-iron diet is usually not necessary. Non-heme iron is not as easily absorbed in the human system and is found in plant-based foods such as grains, beans, vegetables, fruits, nuts, and seeds.

Medication
Medication: For those unable to tolerate routine blood draws, there are chelating agents available for use. The drug deferoxamine binds with iron in the bloodstream and enhances its elimination in urine and faeces. Typical treatment for chronic iron overload requires subcutaneous injection over a period of 8–12 hours daily. Two newer iron-chelating drugs that are licensed for use in patients receiving regular blood transfusions to treat thalassaemia (and, thus, who develop iron overload as a result) are deferasirox and deferiprone.

Chelating polymers
A minimally invasive approach to hereditary haemochromatosis treatment is the maintenance therapy with polymeric chelators. These polymers or particles have a negligible or null systemic biological availability and they are designed to form stable complexes with Fe2+ and Fe3+ in the GIT and thus limiting their uptake and long-term accumulation. Although this method has only a limited efficacy, unlike small-molecular chelators, the approach has virtually no side effects in sub-chronic studies. Interestingly, the simultaneous chelation of Fe2+ and Fe3+ increases the treatment efficacy.

Prognosis
In general, provided there has been no liver damage, patients should expect a normal life expectancy if adequately treated by venesection. If the serum ferritin is greater than 1000 ug/L at diagnosis there is a risk of liver damage and cirrhosis which may eventually shorten their life. The presence of cirrhosis increases the risk of hepatocellular carcinoma.

Epidemiology
HHC is most common in certain European populations (such as those of Irish or Scandinavian descent) and occurs in 0.6% of some unspecified population. Men have a 24-fold increased rate of iron-overload disease compared with women.

Stone Age
Diet and the environment are thought to have had large influence on the mutation of genes related to iron overload. Starting during the Mesolithic era, communities of people lived in an environment that was fairly sunny, warm and had the dry climates of the Middle East. Most humans who lived at that time were foragers and their diets consisted largely of game, fish and wild plants. Archaeologists studying dental plaque have found evidence of tubers, nuts, plantains, grasses and other foods rich in iron. Over many generations, the human body became well-adapted to a high level of iron content in the diet.

Neolithic
In the Neolithic era, significant changes are thought to have occurred in both the environment and diet. Some communities of foragers migrated north, leading to changes in lifestyle and environment, with a decrease in temperatures and a change in the landscape which the foragers then needed to adapt to. As people began to develop and advance their tools, they learned new ways of producing food, and farming also slowly developed. These changes would have led to serious stress on the body and a decrease in the consumption of iron-rich foods. This transition is a key factor in the mutation of genes, especially those that regulated dietary iron absorption. Iron, which makes up 70% of red blood cell composition, is a critical micronutrient for effective thermoregulation in the body. Iron deficiency will lead to a drop in the core temperature. In the chilly and damp environments of Northern Europe, supplementary iron from food was necessary to keep temperatures regulated, however, without sufficient iron intake the human body would have started to store iron at higher rates than normal. In theory, the pressures caused by migrating north would have selected for a gene mutation that promoted greater absorption and storage of iron.

Viking hypothesis
Studies and surveys conducted to determine the frequencies of haemochromatosis help explain how the mutation migrated around the globe. In theory, the disease initially evolved from travelers migrating from the north </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 Catamenial pneumothorax and can you explain it in depth? [/INST] Catamenial pneumothorax is a spontaneous pneumothorax that recurs during menstruation, within 72 hours before or after the onset of a cycle. It usually involves the right side of the chest and right lung, and is associated with thoracic endometriosis. A third to a half of patients have pelvic endometriosis as well. Despite this association, CP is still considered to be misunderstood as is endometriosis considered to be underdiagnosed. The lack of a clear cause means that diagnosis and treatment is difficult. The disease is believed to be largely undiagnosed or misdiagnosed, leaving the true frequency unknown in the general population.
Catamenial pneumothorax is defined as at least two episodes of recurrent pneumothorax corresponding with menstruation. It was first described in 1958 when a woman presented with 12 episodes of right-sided pneumothorax over 1 year, recurring monthly with menstruation. Thoracotomy revealed thoracic endometriosis.Many patients present with chest pain close to their menstrual periods. Surgical exploration can be used in an attempt to visualize the problem; mechanical pleurodesis or hormonal suppressive therapy can also be used. Sometimes, a second surgical look can show fenestrations in the diaphragm. Due to the fact that endometriosis has been attributed to retrograde menstruation, upwards of 90% of women may have an immune deficiency. This prevents clearance of endometrial cells from the peritoneum.
Endometriosis is defined as tissue similar to the endometrial tissue that has implanted outside of the uterus. Mechanisms include retrograde menstruation resulting in abdomino-pelvic spread, blood-borne or lymphatic spread and deposition, and metaplasia.Thoracic endometriosis is the most common non-abdominal site of involvement and is also the primary risk factor for catamenial pneumothorax. Catamenial pneumothorax is the primary clinical presentation of thoracic endometriosis, and is defined as recurrent episodes of lung collapse within 72 hours before or after menstruation.

Signs and symptoms
Symptoms include chest or shoulder pain, cough, dyspnea, and shortness of breath. Chest and shoulder pain can be radiating out to the shoulder blades. A dry cough can also present and come with a "crackling" sound upon inhaling. Typically, it occurs in women aged 30 to 40 years, but it has been diagnosed in young girls as early as 10 years of age and post menopausal women (exclusively in women of menstrual age), most with a history of pelvic endometriosis.Chest pain requires immediate medical attention.

Pathophysiology
Although the exact cause is not known, a few theories come from metastatic, hormonal, and anatomical possibilities. The metastatic model proposes that endometrial tissue has migrated from the endometrium to the diaphragm or the pleural space, causing small holes in the diaphragm, allowing air into the pleural space. In the hormonal model, it is believed that prostaglandin F2 causes a narrowing of the bronchioles, the small tubes within the lungs. Narrowing of these can cause the alveoli to rupture which may trap air in the pleural space. In the anatomical model, researchers believe that the absence of the cervical mucous plug, which is normally there during the menstrual cycle, allows air to pass from the genital tract to the pleural space through fenestrations in the diaphragm. Another theory is that hormonal changes that come with the menstrual cycle can cause blebs to spontaneously rupture. Blebs are small blisters/pustules filled with air or fluid and can develop on the lungs.Endometrial tissue attaches within the thoracic cavity, forming chocolate-like cysts. Generally the parietal pleura is involved, but the lung itself, the visceral layer, the diaphragm, and more rarely the tracheobronchial tree may also be afflicted. The mechanism through which endometrial tissue reaches the thorax remains unclear.
Nearly 90% of cases occur on the right hemithorax, a phenomenon thought to potentially be due to the direction of flow of retroperitoneal fluid. Peritoneal flow occurs in a clockwise pattern, which could likely explain the tendency for catamenial pneumothoraces to be right-sided. Defects in the diaphragm, which are found often in affected individuals, could provide an entry path, as could microembolization through pelvic veins. Such diaphragmatic defects may be either congenital or acquired.
The cysts can release blood; the endometrial cyst "menstruates" in the lung. Endometrial cells undergo structural changes during the secretory phase of the menstrual cycle, in a process called decidualization. Decidualized pleural endometrial implants can disrupt the pleura and lead to pneumothorax (and hemothorax).

Diagnosis
Diagnosis can be hinted by high recurrence rates of lung collapse in a woman of reproductive age with endometriosis.  CA-125 is elevated.
Clinical diagnosis can be made based on history and imaging, while the gold standard for definitive diagnosis remains Video-assisted thoracoscopic surgery, or VATS, which allows not only the visualization of the lesion, but also surgical treatment via cauterization of the ectopic endometrial tissue. Special staining under a microscope or utilizing a cell marker, such as PAX8, can be used to positively identify endometrial stroma.

Classification
Catamenial pneumothorax is the most common form of thoracic endometriosis syndrome, which also includes
catamenial hemothorax, catamenial hemoptysis, catamenial hemothorax and endometriosis lung nodules, as well as some exceptional presentations.

Treatment
Pneumothorax can be a medical emergency, as it can become associated with decreased lung function, and if progressed to tension pneumothorax, potentially fatal. In many cases, catamenial pneumothorax will resolve spontaneously and not require immediate intervention.  In more severe cases, a chest tube may be required to release air and/or blood and to allow the lung to re-expand.Surgery, hormonal treatments and combined approaches have all been proposed, with variable results in terms of short and long term outcome. These have both been effective, separately and together. Both have been used to treat women with this condition, and specifics depend on each patient and each situation. Surgery may be used to excise endometrial tissue from the lungs and pleural space as well as repair damage and holes in the diaphragm. Surgery may also be used to remove blisters (blebs) </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 Acrocallosal syndrome and can you explain it in depth? [/INST] Acrocallosal syndrome (also known as ACLS) is an extremely rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and intellectual disabilities, and other symptoms. The syndrome was first described by Albert Schinzel in 1979. Mutations in KIF7 are causative for ACLS, and mutations in GLI3 are associated with a similar syndrome.

Signs and symptoms
Acrocallosal syndrome (ACLS, ACS, Schinzel-type, Hallux-duplication) is a rare, heterogeneous autosomal recessive disorder first discovered by Albert Schinzel (1979) in a 3-year-old boy. Characteristics of this syndrome include agenesis of the corpus callosum, macrocephaly, hypertelorism, poor motor skills, intellectual disability, extra fingers and toes (particularly hallux duplication), and cleft palate. Seizures may also occur.

Mechanism
Mutations in the KIF7 gene are causative for ACLS. KIF7 is a 1343 amino acid protein with a kinesin motor, coiled coil, and Gli-binding domains. It is associated with ciliary motor function and is a key factor in the ciliary Hedgehog signaling pathway that is crucial during embryogenesis. Mutations in Hedgehog signaling components such as KIF7 and GLI3 may lead to ciliopathies and defects in the brain and other areas associated with ACLS and related disorders.Mutations in the GLI3 gene may cause ACLS or similar syndromes such as Greig cephalopolysyndactyly syndrome, Pallister–Hall syndrome, or certain types of polydactyly. KIF7 interacts with Gli transcription factors, so mutations in the KIF7 gene may be upstream effectors of GLI3, resulting in similar symptoms.

Diagnosis
ACLS is typically diagnosed on the basis of physical examination </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 Myelokathexis 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 Pinta 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 Aortic stenosis and can you explain it in depth? [/INST] Aortic stenosis (AS or AoS) is the narrowing  of the exit of the left ventricle of the heart (where the aorta begins), such that problems result. It may occur at the aortic valve as well as above and below this level. It typically gets worse over time. Symptoms often come on gradually with a decreased ability to exercise often occurring first. If heart failure, loss of consciousness, or heart related chest pain occur due to AS the outcomes are worse. Loss of consciousness typically occurs with standing or exercising. Signs of heart failure include shortness of breath especially when lying down, at night, or with exercise, and swelling of the legs. Thickening of the valve without narrowing is known as aortic sclerosis.Causes include being born with a bicuspid aortic valve, and rheumatic fever; a normal valve may also harden over the decades. A bicuspid aortic valve affects about one to two percent of the population. As of 2014 rheumatic heart disease mostly occurs in the developing world. Risk factors are similar to those of coronary artery disease and include smoking, high blood pressure, high cholesterol, diabetes, and being male. The aortic valve usually has three leaflets and is located between the left ventricle of the heart, and the aorta. AS typically results in a heart murmur. Its severity can be divided into mild, moderate, severe, and very severe, distinguishable by ultrasound scan of the heart.Aortic stenosis is typically followed using repeated ultrasound scans. Once it has become severe, treatment primarily involves valve replacement surgery, with transcatheter aortic valve replacement (TAVR) being an option in some who are at high risk from surgery. Valves may either be mechanical or bioprosthetic, with each having risks and benefits. Another less invasive procedure, balloon aortic valvuloplasty (BAV), may result in benefit, but for only a few months. Complications such as heart failure may be treated in the same way as in those with mild to moderate AS. In those with severe disease a number of medications should be avoided, including ACE inhibitors, nitroglycerin, and some beta blockers. Nitroprusside or phenylephrine may be used in those with decompensated heart failure depending on the blood pressure.Aortic stenosis is the most common valvular heart disease in the developed world. It affects about 2% of people who are over 65 years of age. Estimated rates were not known in most of the developing world as of 2014. In those who have symptoms, without repair the chance of death at five years is about 50% and at 10 years is about 90%. Aortic stenosis was first described by French physician Lazare Rivière in 1663.

Signs and symptoms
Symptoms related to aortic stenosis depend on the degree of stenosis. Most people with mild to moderate aortic stenosis do not have symptoms. Symptoms usually present in individuals with severe aortic stenosis, though they may also occur in those with mild to moderate aortic stenosis. The three main symptoms of aortic stenosis are loss of consciousness, anginal chest pain and shortness of breath with activity or other symptoms of heart failure such as shortness of breath while lying flat, episodes of shortness of breath at night, or swollen legs and feet. It may also be accompanied by the characteristic "Dresden china" appearance of pallor with a light flush.

Angina
Angina in setting of heart failure also increases the risk of death. In people with angina, the 5-year mortality rate is 50% if the aortic valve is not replaced.Angina in the setting of AS occurs due to left ventricular hypertrophy (LVH) that is caused by the constant production of increased pressure required to overcome the pressure gradient caused by the AS. While the muscular layer of the left ventricle thickens, the arteries that supply the muscle do not get significantly longer or bigger, so the muscle may not receive enough blood supply to meet its oxygen requirement. This ischemia may first be evident during exercise when the heart muscle requires increased blood supply to compensate for the increased workload.  The individual may complain of anginal chest pain with exertion. Exercise stress testing with or without imaging is strictly contraindicated in symptomatic patients with severe aortic stenosis. Exercise stress test is now recommended by current guidelines in asymptomatic patients and may provide incremental prognostic value.Eventually, however, the heart muscle will require more blood supply at rest than can be supplied by the coronary artery branches. At this point there may be signs of ventricular strain pattern (ST segment depression and T wave inversion) on the EKG, suggesting subendocardial ischemia.  The subendocardium is the region that is most susceptible to ischemia because it is the most distant from the epicardial coronary arteries.

Syncope
Syncope (fainting spells) from aortic valve stenosis is usually exertional. In the setting of heart failure it increases the risk of death. In people with syncope, the three-year mortality rate is 50% if the aortic valve is not replaced.It is unclear why aortic stenosis causes syncope. One theory is that severe AS produces a nearly fixed cardiac output. When a person with aortic stenosis exercises, their peripheral vascular resistance will decrease as the blood vessels of the skeletal muscles dilate to allow the muscles to receive more blood to allow them to do more work. This decrease in peripheral vascular resistance is normally compensated for by an increase in the cardiac output.  Since people with severe AS cannot increase their cardiac output, the blood pressure falls and the person will faint due to decreased blood perfusion to the brain.A second theory is that during exercise the high pressures generated in the hypertrophied left ventricle cause a vasodepressor response, which causes a secondary peripheral vasodilation that, in turn, causes decreased blood flow to the brain resulting in loss of consciousness. Indeed, in aortic stenosis, because of the fixed obstruction to blood flow out from the heart, it may be impossible for the heart to increase its output to offset peripheral vasodilation.A third mechanism may sometimes be operative. Due to the hypertrophy of the left ventricle in aortic stenosis, including the consequent inability of the coronary arteries to adequately supply blood to the myocardium (see "Angina" below), abnormal heart rhythms may develop. These can lead to syncope.Finally, in calcific aortic stenosis at least, the calcification in and around the aortic valve can progress and extend to involve the electrical conduction system of the heart. If that occurs, the result may be heart block, a potentially lethal condition of which syncope may be a symptom.

Congestive heart failure
Congestive heart failure (CHF) carries a grave prognosis in people with AS. People with CHF attributable to AS have a 2-year mortality rate of 50% if the aortic valve is not replaced. CHF in the setting of AS is due to a combination of left ventricular hypertrophy with fibrosis, systolic dysfunction (a decrease in the ejection fraction) and diastolic dysfunction (elevated filling pressure of the LV).

Associated symptoms
In Heydes syndrome, aortic stenosis is associated with gastrointestinal bleeding due to angiodysplasia of the colon. Recent research has shown that the stenosis causes a form of von Willebrand disease by breaking down its associated coagulation factor (factor VIII-associated antigen, also called von Willebrand factor), due to increased turbulence around the stenotic valve.

Complications
Notwithstanding the foregoing, the American Heart Association changed its recommendations regarding antibiotic prophylaxis for endocarditis. Specifically, as of 2007 it is recommended that such prophylaxis should be limited only to those with prosthetic heart valves, those with previous episode(s) of endocarditis, and those with certain types of congenital heart disease.Since the stenosed aortic valve may limit the hearts output, people with aortic stenosis are at risk of syncope and dangerously low blood pressure should they use any of a number of medications for cardiovascular diseases that often coexist with aortic stenosis. Examples include nitroglycerin, nitrates, ACE inhibitors, terazosin (Hytrin), and hydralazine. Note that all of these substances lead to peripheral vasodilation. Under normal circumstances, in the absence of aortic stenosis, the heart is able to increase its output and thereby offset the effect of the dilated blood vessels. In some cases of aortic stenosis, however, due to the obstruction of blood flow out of the heart caused by the stenosed aortic valve, cardiac output cannot be increased. Low blood pressure or syncope may ensue.

Causes
Aortic stenosis is most commonly caused by age-related progressive calcification (>50% of cases), with a mean age of 65 to 70 years. Another major cause of aortic stenosis is the calcification of a congenital bicuspid aortic valve or, more rarely, a congenital unicuspid aortic valve. Those with unicuspid aortic valves typically need intervention when very young, often as a newborn. While those with congenital bicuspid aortic valve make up 30-40% of those presenting during adulthood and typically presenting earlier (ages 40+ to 50+) than those with tricuspid aortic valves (65+).Acute rheumatic fever post-inflammatory is the cause of less than 10% of cases. Rare causes of aortic stenosis include Fabry disease, systemic lupus erythematosus, Paget disease, high blood uric acid levels, and infection.

Pathophysiology
The human aortic valve normally consists of three cusps or leaflets and has an opening of 3.0-4.0 square centimeters. When the left ventricle contracts, it forces blood through the valve into the aorta and subsequently to the rest of the body. When the left ventricle expands again, the aortic valve closes and prevents the blood in the aorta from flowing backward (regurgitation) into the left ventricle. In aortic stenosis, the opening of the aortic valve becomes narrowed or constricted (stenotic) (e.g., due to calcification). Degenerative (the most common variety), and bicuspid aortic stenosis both begin with damage to endothelial cells from increased mechanical stress. Inflammation is thought to be involved in the earlier stages of the pathogenesis of AS and its associated risk factors are known to promote the deposition of LDL cholesterol and lipoprotein(a), a highly damaging substance, into the aortic valve, causing significant damage and stenosis over time. Infiltration of inflammatory cells (macrophages, T lymphocytes), followed by the release of inflammatory mediators such as interleukin-1-beta and transforming growth factor beta-1 occurs.
Subsequently, fibroblasts differentiate into osteoblast-like cells, which results in abnormal bone matrix deposition leading to progressive valvular calcification and stenosis.As a consequence of this stenosis, the left ventricle must generate a higher pressure with each contraction to effectively move blood forward into the aorta. Initially, the LV generates this increased pressure by thickening its muscular walls (myocardial hypertrophy). The type of hypertrophy most commonly seen in AS is known as concentric hypertrophy, in which the walls of the LV are (approximately) equally thickened.
In the later stages, the left ventricle dilates, the wall thins, and the systolic function deteriorates (resulting in impaired ability to pump blood forward). Morris and Innasimuthu et al. showed that different coronary anatomy is associated with different valve diseases. Research was in progress in 2010 to see if different coronary anatomy might lead to turbulent flow at the level of valves leading to inflammation and degeneration.

Diagnosis
Palpation
Aortic stenosis is most often diagnosed when it is asymptomatic and can sometimes be detected during routine examination of the heart and circulatory system. Good evidence exists to demonstrate that certain characteristics of the peripheral pulse can rule in the diagnosis. In particular, there may be a slow and/or sustained upstroke of the arterial pulse, and the pulse may be of low volume. This is sometimes referred to as pulsus parvus et tardus. There may also be a noticeable delay between the first heart sound (on auscultation) and the corresponding pulse in the carotid artery (apical-carotid delay). In a similar manner, there may be a delay between the appearance of each pulse in the brachial artery (in the arm) and the radial artery (in the wrist).

Auscultation
The first heart sound may be followed by a sharp ejection sound ("ejection click") best heard at the lower left sternal border and the apex, and, thus, appear to be "split". The ejection sound, caused by the impact of left ventricular outflow against the partially fused aortic valve leaflets, is more commonly associated with a mobile bicuspid aortic valve than an immobile calcified aortic valve. The intensity of this sound does not vary with respiration, which helps distinguish it from the ejection click produced by a stenotic pulmonary valve, which will diminish slightly in intensity during inspiration.An easily heard systolic, crescendo-decrescendo (i.e., ejection) murmur is heard loudest at the upper right sternal border, at the 2nd right intercostal space, and radiates to the carotid arteries bilaterally. The murmur increases with squatting and decreases with standing and isometric muscular contraction such as the Valsalva maneuver, which helps distinguish it from hypertrophic obstructive cardiomyopathy (HOCM). The murmur is louder during expiration but is also easily heard during inspiration. The more severe the degree of the stenosis, the later the peak occurs in the crescendo-decrescendo of the murmur.The second heart sound (A2) tends to become decreased and softer as the aortic stenosis becomes more severe. This is a result of the increasing calcification of the valve preventing it from "snapping" shut and producing a sharp, loud sound. Due to increases in left ventricular pressure from the stenotic aortic valve, over time the ventricle may hypertrophy, resulting in diastolic dysfunction. As a result, there may be a fourth heart sound due to the stiff ventricle. With continued increases in ventricular pressure, dilatation of the ventricle will occur, and a third heart sound may be manifest.Finally, aortic stenosis often co-exists with some degree of aortic insufficiency (aortic regurgitation). Hence, the physical exam in aortic stenosis may also reveal signs of the latter, for example, an early diastolic decrescendo murmur. Indeed, when both valve abnormalities are present, the expected findings of either may be modified or may not even be present. Rather, new signs that reflect the presence of simultaneous aortic stenosis and insufficiency, e.g., pulsus bisferiens, emerge.According to a meta-analysis, the most useful findings for ruling in aortic stenosis in the clinical setting were slow rate of rise of the carotid pulse (positive likelihood ratio ranged 2.8–130 across studies), mid to late peak intensity of the murmur (positive likelihood ratio, 8.0–101), and decreased intensity of the second heart sound (positive likelihood ratio, 3.1–50).Other peripheral signs include:
sustained, heaving apex beat, which is not displaced unless systolic dysfunction of the left ventricle has developed
A precordial thrill
narrowed pulse pressure

Electrocardiogram
Although aortic stenosis does not lead to any specific findings on the electrocardiogram (ECG), it still often leads to a number of electrocardiographic abnormalities. ECG manifestations of left ventricular hypertrophy (LVH) are common in aortic stenosis and arise as a result of the stenosis having placed a chronically high-pressure load on the left ventricle (with LVH being the expected response to chronic pressure loads on the left ventricle no matter what the cause).As noted above, the calcification process that occurs in aortic stenosis can progress to extend beyond the aortic valve and into the electrical conduction system of the heart. Evidence of this phenomenon may rarely include ECG patterns characteristic of certain types of heart block such as Left bundle branch block.

Heart catheterization
Cardiac chamber catheterization provides a definitive diagnosis, indicating severe stenosis in valve area of <1.0 cm2 (normally about 3 cm2). It can directly measure the pressure on both sides of the aortic valve. The pressure gradient may be used as a decision point for treatment. It is useful in symptomatic people before surgery. The standard for diagnosis of aortic stenosis is non-invasive testing with echocardiography. Cardiac catheterization is reserved for cases in which there is a discrepancy between the clinical picture and non-invasive testing, due to risks inherent to crossing the aortic valve, such as stroke.

Echocardiogram
Echocardiogram (heart ultrasound) is the best non-invasive way to evaluate the aortic valve anatomy and function.
The aortic valve area can be calculated non-invasively using echocardiographic flow velocities. Using the velocity of the blood through the valve, the pressure gradient across the valve can be calculated by the continuity equation or using the modified Bernoullis equation: Gradient = 4(velocity)² mmHg A normal aortic valve has a gradient of only a few mmHg. A decreased valvular area causes increased pressure gradient, and these parameters are used to classify and grade the aortic stenosis as mild, moderate or severe. The pressure gradient can be abnormally low in the presence of mitral stenosis, heart failure, co-existent aortic regurgitation and also ischaemic heart disease (disease related to the decreased blood supply and oxygen causing ischemia).Echocardiogram may also show left ventricular hypertrophy, thickened and immobile aortic valve, and dilated aortic root. However, it may appear deceptively normal in acute cases.

Chest X-ray
A chest X-ray can also assist in the diagnosis and provide clues as to the severity of the disease, showing the degree of calcification of the valve, and in a chronic condition, an enlarged left ventricle and atrium.

Computer tomography
The use of CT calcium scoring is gaining spread as a diagnostic tool to complement echo in the assessment of patients with aortic stenosis. Aortic valve calcium scoring by multidetector computed tomography (CT-AVC) is used to quantify the degree of calcification of the aortic valve. According to the 2021 ESC/EACTS Guidelines for the management of valvular heart disease the recommended thresholds indicating severe aortic stenosis are > 1200 AU in women and > 2000 AU in men.

Management
Treatment is generally not necessary in people without symptoms. In moderate cases echocardiography is performed every 1–2 years to monitor the progression, possibly complemented with a cardiac stress test. In severe cases, echocardiography is performed every 3–6 months. In both moderate and mild cases, the person should immediately make a revisit or be admitted for inpatient care if any new related symptoms appear. There are no therapeutic options currently available to treat people with aortic valve stenosis; however, studies in 2014 indicated that the disease occurs as a result of active cellular processes, suggesting that targeting these processes may lead to viable therapeutic approaches.

Medication
Observational studies demonstrated an association between lowered cholesterol with statins and decreased progression, but a randomized clinical trial published in 2005 failed to find any effect on calcific aortic stenosis. The effect of statins on the progression of AS is unclear. A 2007 study found a slowing of aortic stenosis with rosuvastatin. In 2013 it was reported that trials did not show any benefit in slowing AS progression, but did demonstrate a decrease in ischemic cardiovascular events.In general, medical therapy has relatively poor efficacy in treating aortic stenosis.  However, it may be useful to manage commonly coexisting conditions that correlate with aortic stenosis:
Any angina is generally treated with beta-blockers and/or calcium blockers. Nitrates are contraindicated due to their potential to cause profound hypotension in aortic stenosis.
Any hypertension is treated aggressively, but caution must be taken in administering beta-blockers.
Any heart failure is generally treated with digoxin and diuretics, and, if not contraindicated, cautious administration of ACE inhibitors.

Aortic valve repair
Aortic valve repair or aortic valve reconstruction describes the reconstruction of both form and function of the native and dysfunctioning aortic valve. Most frequently it is applied for the treatment of aortic regurgitation. It can also become necessary for the treatment of an aortic aneurysm, less frequently for congenital aortic stenosis.

Aortic valve replacement
In adults, symptomatic severe aortic stenosis usually requires aortic valve replacement (AVR). While Surgical AVR has remained the most effective treatment for this disease process and is currently recommended for patients after the onset of symptoms, as of 2016 aortic valve replacement approaches included open-heart surgery, minimally invasive cardiac surgery (MICS), and minimally invasive catheter-based (percutaneous) aortic valve replacement.  However, surgical aortic valve replacement is well-studied, and generally has a good and well-established longer-term prognosis.A diseased aortic valve is most commonly replaced using a surgical procedure with either a mechanical or a tissue valve. The procedure is done either in an open-heart surgical procedure or, in a smaller but growing number of cases, a minimally invasive cardiac surgery (MICS) procedure. Minimally invasive approach via right minithoracotomy is most beneficial in the high risk patient such as the elderly, the obese, those with chronic obstructive pulmonary, chronic kidney disease and those requiring re-operative surgery.

Transcatheter aortic valve replacement
Globally more than 250,000 people have received transcatheter aortic valve intervention (TAVI). For people who are not candidates for surgical valve replacement and most patients who are older than 75, TAVI may be a suitable alternative. Conduction abnormalities requiring permanent pacemaker (PPM) implantation remain a common finding after TAVI due to the close proximity of the atrioventricular conduction system to the aortic root.

Balloon valvuloplasty
For infants and children, balloon valvuloplasty, where a balloon is inflated to stretch the valve and allow greater flow, may also be effective. In adults, however, it is generally ineffective, as the valve tends to return to a stenosed state. The surgeon will make a small incision at the top of the persons leg and proceed to insert the balloon into the artery. The balloon is then advanced up to the valve and is inflated to stretch the valve open.

Heart failure
Acute decompensated heart failure due to AS may be temporarily managed by an intra-aortic balloon pump while pending surgery. In those with high blood pressure nitroprusside may be carefully used. Phenylephrine may be used in those with very low blood pressure.

Prognosis
If untreated, severe symptomatic aortic stenosis carries a poor prognosis, with a 2-year mortality rate of 50-60% and a 3-year survival rate of less than 30% </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 Lichen scrofulosorum 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 7p22.1 microduplication syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Dyslexia and can you explain it in depth? [/INST] Dyslexia, also known as reading disorder, is a disorder characterized by reading below the expected level for ones age. Different people are affected to different degrees. Problems may include difficulties in spelling words, reading quickly, writing words, "sounding out" words in the head, pronouncing words when reading aloud and understanding what one reads. Often these difficulties are first noticed at school. The difficulties are involuntary, and people with this disorder have a normal desire to learn. People with dyslexia have higher rates of attention deficit hyperactivity disorder (ADHD), developmental language disorders, and difficulties with numbers.Dyslexia is believed to be caused by the interaction of genetic and environmental factors. Some cases run in families. Dyslexia that develops due to a traumatic brain injury, stroke, or dementia is sometimes called "acquired dyslexia" or alexia. The underlying mechanisms of dyslexia result from differences within the brains language processing. Dyslexia is diagnosed through a series of tests of memory, vision, spelling, and reading skills. Dyslexia is separate from reading difficulties caused by hearing or vision problems or by insufficient teaching or opportunity to learn.Treatment involves adjusting teaching methods to meet the persons needs. While not curing the underlying problem, it may decrease the degree or impact of symptoms. Treatments targeting vision are not effective. Dyslexia is the most common learning disability and occurs in all areas of the world. It affects 3–7% of the population; however, up to 20% of the general population may have some degree of symptoms.  While dyslexia is more often diagnosed in boys, this is partly explained by a self-fulfilling referral bias among teachers and professionals. It has even been suggested that the condition affects men and women equally. Some believe that dyslexia is best considered as a different way of learning, with both benefits and downsides.

Classification
Dyslexia is divided into developmental and acquired forms. Acquired dyslexia occurs subsequent to neurological insult, such as traumatic brain injury or stroke. People with acquired dyslexia exhibit some of the signs or symptoms of the developmental disorder, but require different assessment strategies and treatment approaches. Pure alexia, also known as agnosic alexia or pure word blindness, is one form of alexia which makes up "the peripheral dyslexia" group.

Signs and symptoms
In early childhood, symptoms that correlate with a later diagnosis of dyslexia include delayed onset of speech and a lack of phonological awareness. A common myth closely associates dyslexia with mirror writing and reading letters or words backwards. These behaviors are seen in many children as they learn to read and write, and are not considered to be defining characteristics of dyslexia.School-age children with dyslexia may exhibit signs of difficulty in identifying or generating rhyming words, or counting the number of syllables in words–both of which depend on phonological awareness. They may also show difficulty in segmenting words into individual sounds (such as sounding out the three sounds of k, a, and t in cat) or may struggle to blend sounds, indicating reduced phonemic awareness.Difficulties with word retrieval or naming things is also associated with dyslexia.: 647  People with dyslexia are commonly poor spellers, a feature sometimes called dysorthographia or dysgraphia, which depends on the skill of orthographic coding.Problems persist into adolescence and adulthood and may include difficulties with summarizing stories, memorization, reading aloud, or learning foreign languages. Adults with dyslexia can often read with good comprehension, though they tend to read more slowly than others without a learning difficulty and perform worse in spelling tests or when reading nonsense words–a measure of phonological awareness.

Associated conditions
Dyslexia often co-occurs with other learning disorders, but the reasons for this comorbidity have not been clearly identified. These associated disabilities include:

Dysgraphia
A disorder involving difficulties with writing or typing, sometimes due to problems with eye–hand coordination; it also can impede direction- or sequence-oriented processes, such as tying knots or carrying out repetitive tasks. In dyslexia, dysgraphia is often multifactorial, due to impaired letter-writing automaticity, organizational and elaborative difficulties, and impaired visual word forming, which makes it more difficult to retrieve the visual picture of words required for spelling.
Attention deficit hyperactivity disorder (ADHD)
A disorder characterized by problems sustaining attention, hyperactivity, or acting impulsively. Dyslexia and ADHD commonly occur together. Approximately 15% or 12–24% of people with dyslexia have ADHD; and up to 35% of people with ADHD have dyslexia.
Auditory processing disorder
A listening disorder that affects the ability to process auditory information. This can lead to problems with auditory memory and auditory sequencing. Many people with dyslexia have auditory processing problems, and may develop their own logographic cues to compensate for this type of deficit. Some research suggests that auditory processing skills could be the primary shortfall in dyslexia.
Developmental coordination disorder
A neurological condition characterized by difficulty in carrying out routine tasks involving balance, fine-motor control and kinesthetic coordination; difficulty in the use of speech sounds; and problems with short-term memory and organization.

Causes
Researchers have been trying to find the neurobiological basis of dyslexia since the condition was first identified in 1881. For example, some have tried to associate the common problem among people with dyslexia of not being able to see letters clearly to abnormal development of their visual nerve cells.

Neuroanatomy
Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), have shown a correlation between both functional and structural differences in the brains of children with reading difficulties. Some people with dyslexia show less electrical activation in parts of the left hemisphere of the brain involved with reading, such as the inferior frontal gyrus, inferior parietal lobule, and the middle and ventral temporal cortex. Over the past decade, brain activation studies using PET to study language have produced a breakthrough in the understanding of the neural basis of language. Neural bases for the visual lexicon and for auditory verbal short-term memory components have been proposed, with some implication that the observed neural manifestation of developmental dyslexia is task-specific (i.e., functional rather than structural). fMRIs of people with dyslexia indicate an interactive role of the cerebellum and cerebral cortex as well as other brain structures in reading.The cerebellar theory of dyslexia proposes that impairment of cerebellum-controlled muscle movement affects the formation of words by the tongue and facial muscles, resulting in the fluency problems that some people with dyslexia experience. The cerebellum is also involved in the automatization of some tasks, such as reading. The fact that some children with dyslexia have motor task and balance impairments could be consistent with a cerebellar role in their reading difficulties. However, the cerebellar theory has not been supported by controlled research studies.

Genetics
Research into potential genetic causes of dyslexia has its roots in post-autopsy examination of the brains of people with dyslexia. Observed anatomical differences in the language centers of such brains include microscopic cortical malformations known as ectopias, and more rarely, vascular micro-malformations, and microgyrus—a smaller than usual size for the gyrus. The previously cited studies and others suggest that abnormal cortical development, presumed to occur before or during the sixth month of fetal brain development, may have caused the abnormalities. Abnormal cell formations in people with dyslexia have also been reported in non-language cerebral and subcortical brain structures. Several genes have been associated with dyslexia, including DCDC2 and KIAA0319 on chromosome 6, and DYX1C1 on chromosome 15.

Gene–environment interaction
The contribution of gene–environment interaction to reading disability has been intensely studied using twin studies, which estimate the proportion of variance associated with a persons environment and the proportion associated with their genes. Both environmental and genetic factors appear to contribute to reading development. Studies examining the influence of environmental factors such as parental education and teaching quality have determined that genetics have greater influence in supportive, rather than less optimal, environments. However, more optimal conditions may just allow those genetic risk factors to account for more of the variance in outcome because the environmental risk factors have been minimized.As environment plays a large role in learning and memory, it is likely that epigenetic modifications play an important role in reading ability. Measures of gene expression, histone modifications, and methylation in the human periphery are used to study epigenetic processes; however, all of these have limitations in the extrapolation of results for application to the human brain.

Language
The orthographic complexity of a language directly affects how difficult it is to learn to read it.: 266  English and French have comparatively "deep" phonemic orthographies within the Latin alphabet writing system, with complex structures employing spelling patterns on several levels: letter-sound correspondence, syllables, and morphemes.: 421  Languages such as Spanish, Italian and Finnish primarily employ letter-sound correspondence—so-called "shallow" orthographies—which makes them easier to learn for people with dyslexia.: 266  Logographic writing systems, such as Chinese characters, have extensive symbol use; and these also pose problems for dyslexic learners.

Pathophysiology
For most people who are right-hand dominant, the left hemisphere of their brain is more specialized for language processing. With regard to the mechanism of dyslexia, fMRI studies suggest that this specialization is less pronounced or absent in people with dyslexia. In other studies, dyslexia is correlated with anatomical differences in the corpus callosum, the bundle of nerve fibers that connects the left and right hemispheres.Data via diffusion tensor MRI indicate changes in connectivity or in gray matter density in areas related to reading and language. Finally, the left inferior frontal gyrus has shown differences in phonological processing in people with dyslexia. Neurophysiological and imaging procedures are being used to ascertain phenotypic characteristics in people with dyslexia, thus identifying the effects of dyslexia-related genes.

Dual route theory
The dual-route theory of reading aloud was first described in the early 1970s. This theory suggests that two separate mental mechanisms, or cognitive routes, are involved in reading aloud. One mechanism is the lexical route, which is the process whereby skilled readers can recognize known words by sight alone, through a "dictionary" lookup procedure. The other mechanism is the nonlexical or sublexical route, which is the process whereby the reader can "sound out" a written word. This is done by identifying the words constituent parts (letters, phonemes, graphemes) and applying knowledge of how these parts are associated with each other, for example, how a string of neighboring letters sound together. The dual-route system could explain the different rates of dyslexia occurrence between different languages (e.g., the consistency of phonological rules in the Spanish language could account for the fact that Spanish-speaking children show a higher level of performance in non-word reading, when compared to English-speakers).

Diagnosis
Dyslexia is a heterogeneous, dimensional learning disorder that impairs accurate and fluent word reading and spelling. Typical—but not universal—features include difficulties with phonological awareness; inefficient and often inaccurate processing of sounds in oral language (phonological processing); and verbal working memory deficits.Dyslexia is a neurodevelopmental disorder, subcategorized in diagnostic guides as a learning disorder with impairment in reading (ICD-11 prefixes "developmental" to "learning disorder"; DSM-5 uses "specific"). Dyslexia is not a problem with intelligence. Emotional problems often arise secondary to learning difficulties. The National Institute of Neurological Disorders and Stroke describes dyslexia as "difficulty with phonological processing (the manipulation of sounds), spelling, and/or rapid visual-verbal responding".The British Dyslexia Association defines dyslexia as "a learning difficulty that primarily affects the skills involved in accurate and fluent word reading and spelling" and is characterized by "difficulties in phonological awareness, verbal memory and verbal processing speed". Phonological awareness enables one to identify, discriminate, remember (working memory), and mentally manipulate the sound structures of language—phonemes, onsite-rime segments, syllables, and words.

Assessment
The following can be done to assess for dyslexia:
Apply a multidisciplinary team approach involving the childs parent(s) and teacher(s), school psychologist, pediatrician, and, as appropriate, speech and language pathologist (speech therapist), and occupational therapist.Gain familiarity with typical ages children reach various general developmental milestones, and domain-specific milestones, such as phonological awareness (recognizing rhyming words; identifying the initial sounds in words).Do not rely on tests exclusively. Careful observation of the child in the school and home environments, and sensitive, comprehensive parental interviews are just as important as tests.Look at the empirically supported response to intervention (RTI) approach, which "... involves monitoring the progress of a group of children through a programme of intervention rather than undertaking a static assessment of their current skills. Children with the most need are those who fail to respond to effective teaching, and they are readily identified using this approach."

Assessment tests
There is a wide range of tests that are used in clinical and educational settings to evaluate the possibility of dyslexia. If initial testing suggests that a person might have dyslexia, such tests are often followed up with a full diagnostic assessment to determine the extent and nature of the disorder. Some tests can be administered by a teacher or computer; others require specialized training and are given by psychologists. Some test results indicate how to carry out teaching strategies. Because a variety of different cognitive, behavioral, emotional, and environmental factors all could contribute to difficultly learning to read, a comprehensive evaluation should consider these different possibilities. These tests and observations can include:
General measures of cognitive ability, such as the Wechsler Intelligence Scale for Children, Woodcock-Johnson Tests of Cognitive Abilities, or Stanford-Binet Intelligence Scales. Low general cognitive ability would make reading more difficult. Cognitive ability measures also often try to measure different cognitive processes, such as verbal ability, nonverbal and spatial reasoning, working memory, and processing speed. There are different versions of these tests for different age groups. Almost all of these require additional training to give and score correctly, and are done by psychologists. According to Mather and Schneider (2015), a confirmatory profile and/or pattern of scores on cognitive tests confirming or ruling-out reading disorder has not yet been identified.
Screening or evaluation for mental health conditions: Parents and teachers can complete rating scales or behavior checklists to gather information about emotional and behavioral functioning for younger people. Many checklists have similar versions for parents, teachers, and younger people old enough to read reasonably well (often 11 years and older) to complete. Examples include the Behavioral Assessment System for Children, and the Strengths and Difficulties Questionnaire. All of these have nationally representative norms, making it possible to compare the level of symptoms to what would be typical for the younger persons age and biological sex. Other checklists link more specifically to psychiatric diagnoses, such as the Vanderbilt ADHD Rating Scales or the Screen for Child Anxiety Related Emotional Disorders (SCARED). Screening uses brief tools that are designed to catch cases with a disorder, but they often get false positive scores for people who do not have the disorder. Screeners should be followed up by a more accurate test or diagnostic interview as a result. Depressive disorders and anxiety disorders are two-three times higher in people with dyslexia, and attention-deficit/hyperactivity disorder is more common, as well.
Review of academic achievement and skills: Average spelling/reading ability for a dyslexic is a percentage ranking <16, well below normal. In addition to reviewing grades and teacher notes, standardized test results are helpful in evaluating progress. These include group administered tests, such as the Iowa Tests of Educational Development, that a teacher may give to a group or whole classroom of younger people at the same time. They also could include individually administered tests of achievement, such as the Wide Range Achievement Test, or the Woodcock-Johnson (which also includes a set of achievement tests). The individually administered tests again require more specialized training.

Screening
Screening procedures seek to identify children who show signs of possible dyslexia. In the preschool years, a family history of dyslexia, particularly in biological parents and siblings, predicts an eventual dyslexia diagnosis better than any test. In primary school (ages 5–7), the ideal screening procedure consists of training primary school teachers to carefully observe and record their pupils progress through the phonics curriculum, and thereby identify children progressing slowly. When teachers identify such students they can supplement their observations with screening tests such as the Phonics screening check used by United Kingdom schools during Year one.
In the medical setting, child and adolescent psychiatrist M. S. Thambirajah emphasizes that "[g]iven the high prevalence of developmental disorders in school-aged children, all children seen in clinics should be systematically screened for developmental disorders irrespective of the presenting problem/s." Thambirajah recommends screening for developmental disorders, including dyslexia, by conducting a brief developmental history, a preliminary psychosocial developmental examination, and obtaining a school report regarding academic and social functioning.

Management
Through the use of compensation strategies, therapy and educational support, individuals with dyslexia can learn to read and write. There are techniques and technical aids that help to manage or conceal symptoms of the disorder. Reducing stress and anxiety can sometimes improve written comprehension. For dyslexia intervention with alphabet-writing systems, the fundamental aim is to increase a childs awareness of correspondences between graphemes (letters) and phonemes (sounds), and to relate these to reading and spelling by teaching how sounds blend into words. Reinforced collateral training focused on reading and spelling may yield longer-lasting gains than oral phonological training alone. Early intervention can be successful in reducing reading failure.Research does not suggest that specially-tailored fonts (such as Dyslexie and OpenDyslexic) help with reading. Children with dyslexia read text set in a regular font such as Times New Roman and Arial just as quickly, and they show a preference for regular fonts over specially-tailored fonts. Some research has pointed to increased letter-spacing being beneficial.There is currently no evidence showing that music education significantly improves the reading skills of adolescents with dyslexia.

Prognosis
Dyslexic children require special instruction for word analysis and spelling from an early age. The prognosis, generally speaking, is positive for individuals who are identified in childhood and receive support from friends and family. The New York educational system (NYED) indicates "a daily uninterrupted 90-minute block of instruction in reading" and "instruction in phonemic awareness, phonics, vocabulary development, reading fluency" so as to improve the individuals reading ability.

Epidemiology
The prevalence of dyslexia is unknown, but it has been estimated to be as low as 5% and as high as 17% of the population. Dyslexia is diagnosed more often in males.There are different definitions of dyslexia used throughout the world. Further, differences in writing systems may affect development of written language ability due to the interplay between auditory and written representations of phonemes. Dyslexia is not limited to difficulty in converting letters to sounds, and Chinese people with dyslexia may have difficulty converting Chinese characters into their meanings. The Chinese vocabulary uses logographic, monographic, non-alphabet writing where one character can represent an individual phoneme.The phonological-processing hypothesis attempts to explain why dyslexia occurs in a wide variety of languages. Furthermore, the relationship between phonological capacity and reading appears to be influenced by orthography.

History
Dyslexia was clinically described by Oswald Berkhan in 1881, but the term dyslexia was coined in 1883 by Rudolf Berlin, an ophthalmologist in Stuttgart. He used the term to refer to the case of a young boy who had severe difficulty learning to read and write, despite showing typical intelligence and physical abilities in all other respects. In 1896, W. Pringle Morgan, a British physician from Seaford, East Sussex, published a description of a reading-specific learning disorder in a report to the British Medical Journal titled "Congenital Word Blindness". The distinction between phonological versus surface types of dyslexia is only descriptive, and without any etiological assumption as to the underlying brain mechanisms. However, studies have alluded to potential differences due to variation in performance. Over time, we have changed from the intelligence-based model to the age-based model, in terms of those with Dyslexia.

Society and culture
As is the case with any disorder, society often makes an assessment based on incomplete information. Before the 1980s, dyslexia was thought to be a consequence of education, rather than a neurological disability. As a result, society often misjudges those with the disorder. There is also sometimes a workplace stigma and negative attitude towards those with dyslexia. If the instructors of a person with dyslexia lack the necessary training to support a child with the condition, there is often a negative effect on the students learning participation.Since at least the 1960s in the UK, the children diagnosed with developmental dyslexia have consistently been from privileged families. Although half of prisoners in the UK have significant reading difficulties, very few have ever been evaluated for dyslexia. Access to some special educational resources and funding is contingent upon having a diagnosis of dyslexia.  As a result, when Staffordshire and Warwickshire proposed in 2018 to teach reading to all children with reading difficulties, using techniques proven to be successful for most children with a diagnosis of dyslexia, without first requiring the families to obtain an official diagnosis, dyslexia advocates and parents of children with dyslexia were fearful that they were losing a privileged status.

Stigma and Success
The stigma surrounding dyslexia is just beginning to be understood.As awareness increases, it is informative to observe the long list of notable people who struggled with dyslexia but ended up with successful careers, among them Whoopi Goldberg, who said:

When I was a kid they didn’t call it dyslexia. They called it you know, you were slow, or you were retarded, or whatever. What you can never change is the effect that the words ‘dumb’ and ‘stupid’ have on young people. I knew I wasn’t stupid, and I knew I wasn’t dumb.
Their success was not without struggle. Henry Winker said:

You want so badly to be able to do it and you cant. And no matter how hard you try, its not working...I would study my words. I would know them cold. I would know them backwards and forwards. I would go to class. I would pray that I had retained them. Then I would get the test and spend a lot of time thinking about where the hell those words went. I knew them. They must have fallen out of my head...I didnt have the slightest idea of how to spell the words that I knew a block and a half away in my apartment the night before.

Research
Most dyslexia research relates to alphabetic writing systems, and especially to European languages. However, substantial research is also available regarding people with dyslexia who speak Arabic, Chinese, Hebrew, or other languages </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 Torticollis and can you explain it in depth? [/INST] Torticollis, also known as wry neck, is a dystonic condition defined by an abnormal, asymmetrical head or neck position, which may be due to a variety of causes. The term torticollis is derived from the Latin words tortus for twisted and collum for neck.The most common case has no obvious cause, and the pain and difficulty with turning the head usually goes away after a few days, even without treatment in adults.

Signs and symptoms
Torticollis is a fixed or dynamic tilt, rotation, with flexion or extension of the head and/or neck.
The type of torticollis can be described depending on the positions of the head and neck.
laterocollis: the head is tipped toward the shoulder
rotational torticollis: the head rotates along the longitudinal  axis
anterocollis: forward flexion of the head and neck
retrocollis: hyperextension of head and neck backwardA combination of these movements may often be observed. Torticollis can be a disorder in itself as well as a symptom in other conditions.
Other symptoms include:
Neck pain
Occasional formation of a mass
Thickened or tight sternocleidomastoid muscle
Tenderness on the cervical spine
Tremor in head
Unequal shoulder heights
Decreased neck movement

Causes
A multitude of conditions may lead to the development of torticollis including: muscular fibrosis, congenital spine abnormalities, or toxic or traumatic brain injury.
A rough categorization discerns between congenital torticollis and acquired torticollis.Other categories include:
Osseous
Traumatic
CNS/PNS
Ocular
Non-muscular soft tissue
Spasmodic
Drug induced
Oral ties (lip and tongue ties)

Congenital muscular torticollis
The congenital muscular torticollis is the most common torticollis which is present at birth. The cause of congenital muscular torticollis is unclear. Birth trauma or intrauterine malposition is considered to be the cause of damage to the sternocleidomastoid muscle in the neck. Other alterations to the muscle tissue arise from repetitive microtrauma within the womb or a sudden change in the calcium concentration in the body which causes a prolonged period of muscle contraction.Any of these mechanisms can result in a shortening or excessive contraction of the sternocleidomastoid muscle, which curtails its range of motion in both rotation and lateral bending. The head typically is tilted in lateral bending toward the affected muscle and rotated toward the opposite side. In other words,  the head itself is tilted in the direction towards the shortened muscle with the chin tilted in the opposite direction.Congenital Torticollis is presented at 1–4 weeks of age, and a hard mass usually develops. It is normally diagnosed using ultrasonography and a colour histogram or clinically through evaluating the infants passive cervical range of motion.Congenital torticollis constitutes the majority of cases seen in clinical practice. The reported incidence of congenital torticollis is 0.3-2.0%. Sometimes a mass, such as a sternocleidomastoid tumor, is noted in the affected muscle.  Torticollis does not resolve on its own and may result in plagiocephaly.

Acquired torticollis
Noncongenital muscular torticollis may result from scarring or disease of cervical vertebrae, adenitis, tonsillitis, rheumatism, enlarged cervical glands, retropharyngeal abscess, or cerebellar tumors. It may be spasmodic (clonic) or permanent (tonic). The latter type may be due to Potts Disease (tuberculosis of the spine).
A self-limiting spontaneously occurring form of torticollis with one or more painful neck muscles is by far the most common (stiff neck) and will pass spontaneously in 1–4 weeks. Usually the sternocleidomastoid muscle or the trapezius muscle is involved. Sometimes draughts, colds, or unusual postures are implicated; however, in many cases, no clear cause is found. These episodes are commonly seen by physicians.Most commonly this self-limiting form relates to an untreated dental occlusal dysfunction, which is brought on by clenching and grinding the teeth during sleep. Once the occlusion is treated it will completely resolve. Treatment is accomplished with an occlusal appliance, and equilibration of the dentition.

Tumors of the skull base (posterior fossa tumors) can compress the nerve supply to the neck and cause torticollis, and these problems must be treated surgically.
Infections in the posterior pharynx can irritate the nerves supplying the neck muscles and cause torticollis, and these infections may be treated with antibiotics if they are not too severe, but could require surgical debridement in intractable cases.
Ear infections and surgical removal of the adenoids can cause an entity known as Grisels syndrome, a subluxation of the upper cervical joints, mostly the atlantoaxial joint, due to inflammatory laxity of the ligaments caused by an infection.
The use of certain drugs, such as antipsychotics, can cause torticollis.
Antiemetics - Neuroleptic Class - Phenothiazines
There are many other rare causes of torticollis.  A very rare cause of acquired torticollis is fibrodysplasia ossificans progressiva (FOP), the hallmark of which is malformed great toes.

Spasmodic torticollis
Torticollis with recurrent, but transient contraction of the muscles of the neck and especially of the sternocleidomastoid, is called spasmodic torticollis. Synonyms are "intermittent torticollis", "cervical dystonia" or "idiopathic cervical dystonia", depending on cause.

Trochlear torticollis
Torticollis may be unrelated to the sternocleidomastoid muscle, instead caused by damage to the trochlear nerve (fourth cranial nerve), which supplies the superior oblique muscle of the eye. The superior oblique muscle is involved in depression, abduction, and intorsion of the eye. When the trochlear nerve is damaged, the eye is extorted because the superior oblique is not functioning. The affected person will have vision problems unless they turn their head away from the side that is affected, causing intorsion of the eye and balancing out the extorsion of the eye. This can be diagnosed by the Bielschowsky test, also called the head-tilt test, where the head is turned to the affected side. A positive test occurs when the affected eye elevates, seeming to float up.

Anatomy
The underlying anatomical distortion causing torticollis is a shortened sternocleidomastoid muscle. This is the muscle of the neck that originates at the sternum and clavicle and inserts on the mastoid process of the temporal bone on the same side. There are two sternocleidomastoid muscles in the human body and when they both contract, the neck is flexed. The main blood supply for these muscles come from the occipital artery, superior thyroid artery, transverse scapular artery and transverse cervical artery. The main innervation to these muscles is from cranial nerve XI (the accessory nerve) but the second, third and fourth cervical nerves are also involved. Pathologies in these blood and nerve supplies can lead to torticollis.

Diagnosis
Evaluation of a child with torticollis begins with history taking to determine circumstances surrounding birth and any possibility of trauma or associated symptoms. Physical examination reveals decreased rotation and bending to the side opposite from the affected muscle. Some say that congenital cases more often involve the right side, but there is not complete agreement about this in published studies. Evaluation should include a thorough neurologic examination, and the possibility of associated conditions such as developmental dysplasia of the hip and clubfoot should be examined.  Radiographs of the cervical spine should be obtained to rule out obvious bony abnormality, and MRI should be considered if there is concern about structural problems or other conditions.
Ultrasonography can be used to visualize muscle tissue, with a colour histogram generated to determine cross-sectional area and thickness of the muscle.Evaluation by an optometrist or an ophthalmologist should be considered in children to ensure that the torticollis is not caused by vision problems (IV cranial nerve palsy, nystagmus-associated "null position," etc.).
Differential diagnosis for torticollis includes
Cranial nerve IV palsy
Spasmus nutans
Sandifer syndrome
Myasthenia gravis
Cerebrospinal fluid leakCervical dystonia appearing in adulthood has been believed to be idiopathic in nature, as specific imaging techniques most often find no specific cause.

Treatment
Initially, the condition is treated with physical therapies, such as stretching to release tightness, strengthening exercises to improve muscular balance, and handling to stimulate symmetry. A TOT collar is sometimes applied. Early initiation of treatment is very important for full recovery and to decrease chance of relapse.

Physical therapy
Physical therapy is an option for treating torticollis in a non-invasive and cost-effective manner. In the children above 1 year of age, surgical release of the tight sternocleidomastoid muscle is indicated along with aggressive therapy and appropriate splinting. Occupational therapy rehabilitation in Congenital muscular torticollis concentrates on observation, orthosis, gentle stretching, myofascial release techniques, parents’ counseling-training, and home exercise program. While outpatient infant physiotherapy is effective, home therapy performed by a parent or guardian is just as effective in reversing the effects of congenital torticollis. It is important for physical therapists to educate parents on the importance of their role in the treatment and to create a home treatment plan together with them for the best results for their child. Five components have been recognized as the "first choice intervention" in PT for treatment of torticollis and include neck passive range of motion, neck and trunk active range of motion, development of symmetrical movement, environmental adaptations, and caregiver education. In therapy, parents or guardians should expect their child to be provided with these important components, explained in detail below. Lateral neck flexion and overall range of motion can be regained quicker in newborns when parents conduct physical therapy exercises several times a day.Physical therapists should teach parents and guardians to perform the following exercises:
Stretching the neck and trunk muscles actively. Parents can help promote this stretching at home with infant positioning. For example, prone positioning will encourage the child to lift their chin off the ground, thereby strengthening their bilateral neck and spine extensor muscles, and stretching their neck flexor muscles. Active rotation exercises in supine, sitting or prone position by using toys, lights and sounds to attract infants attention to turn neck and look toward the non-affected side.
Stretching the muscle in a prone position passively. Passive stretching is manual, and does not include infant involvement. Two people can be involved in these stretches, one person stabilizing the infant while the other holds the head and slowly brings it through the available range of motion. Passive stretching should not be painful to the child, and should be stopped if the child resists. Also, discontinue the stretch if changes in breathing or circulation are seen or felt.
Stretching the muscle in a lateral position supported by a pillow (have infant lie on the side with the neck supported by pillow). Affected side should be against the pillow to deviate the neck towards the non-affected side.
Environmental adaptations can control posture in strollers, car seats  and swings (using U-shaped neck pillow or blankets to hold neck in neutral position)
Passive cervical rotation (much like stretching when being supported by a pillow, have affected side down)
Position infant in the crib with affected side by the wall so they must turn to the non-affected side to face outPhysical therapists often encourage parents and caregivers of children with torticollis to modify the environment to improve neck movements and position. Modifications may include:

Adding neck supports to the car seat to attain optimal neck alignment
Reducing time spent in a single position
Using toys to encourage the child to look in the direction of limited neck movement
Alternating sides when bottle or breastfeeding
Encouraging prone playtime (tummy time). Although the Back to Sleep campaign promotes infants sleeping on their backs to avoid sudden infant death syndrome during sleep, parents should still ensure that their infants spend some waking hours on their stomachs.

Microcurrent therapy
A Korean study has recently introduced an additional treatment called microcurrent therapy that may be effective in treating congenital torticollis. For this therapy to be effective the children should be under three months of age and have torticollis involving the entire sternocleidomastoid muscle with a palpable mass and a muscle thickness over 10 mm. Microcurrent therapy sends minute electrical signals into tissue to restore the normal frequencies in cells. Microcurrent therapy is completely painless and children can only feel the probe from the machine on their skin.Microcurrent therapy is thought to increase ATP and protein synthesis as well as enhance blood flow, reduce muscle spasms and decrease pain along with inflammation. It should be used in addition to regular stretching exercises and ultrasound diathermy. Ultrasound diathermy generates heat deep within body tissues to help with contractures, pain and muscle spasms as well as decrease inflammation. This combination of treatments shows remarkable outcomes in the duration of time children are kept in rehabilitation programs: Micocurrent therapy can cut the length of a rehabilitation program almost in half with a full recovery seen after 2.6 months.About 5–10% of cases fail to respond to stretching and require surgical release of the muscle.

Surgery
Surgical release involves the two heads of the sternocleidomastoid muscle being dissected free. This surgery can be minimally invasive and done laparoscopically. Usually surgery is performed on those who are over 12 months old. The surgery is for those who do not respond to physical therapy or botulinum toxin injection or have a very fibrotic sternocleidomastoid muscle. After surgery the child will be required to wear a soft neck collar (also called a Callots cast). There will be an intense physiotherapy program for 3–4 months as well as strengthening exercises for the neck muscles.Other treatments include:
Rest and analgesics for acute cases
Diazepam or other muscle relaxants
Botulinum toxin
Encouraging active movements for children 6–8 months of age
Ultrasound diathermy

Prognosis
Studies and evidence from clinical practice show that 85–90% of cases of congenital torticollis are resolved with conservative treatment such as physical therapy </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 Aquarium granuloma and can you explain it in depth? [/INST] Aquarium granuloma (also known as fish tank granuloma and swimming pool granuloma) is a rare skin condition caused by a non-tubercular mycobacterium known as Mycobacterium marinum. Skin infections with M. marinum in humans are relatively uncommon, and are usually acquired from contact with contaminated swimming pools, aquariums or infected fish.

Signs and symptoms
Aquarium granuloma presents as a slow-growing, inflamed red bump (nodule or plaque) at the site of infection. It is characterized by a painful, itchy skin lesion,  and may become ulcerated or crusted. Skin changes usually appear roughly three weeks after the aquatic exposure.If this condition is acquired from an aquarium, then often the dominant hand is affected. If this condition is acquired from a swimming pool, then symptoms can also develop on trauma-prone body zones, such as the elbows, knees, feet and tip of the nose.

Cause
For the infection to develop in humans, the two main factors required are exposure to contaminated water, and abrasion or injury to the skin. Hence, this infection is commonly seen in individuals who clean fish tanks, handle ornamental fish and work in wet fields.Aquatic systems with a high density of fish and warm waters appear to be conditions particularly favorable to this infectious agent, and increase the changes to contract fish tank granuloma. Poor water quality and various nutritional deficiencies are also possible contributing factors.Swimming pool granuloma can occur when there is inadequate chlorination of swimming pools.

Diagnosis
Aquarium granuloma is relatively nonspecific in clinical presentation. Therefore, more common skin conditions, like cellulitis, foreign body reaction, skin cancer, and fungal or parasitic infections, are often explored first. Overall, diagnosis and treatment of this rare skin infection is often delayed because of a lack of suspicion.Lab tests for finding M. marinum include cultures where a swab or sample is taken and grown in the laboratory. Cultures of M. marinum are fairly difficult to grow, and results may take several weeks. The culture may be negative, even if there is an active infection. Treatment may still be considered even if the test results are negative, especially if the patients history supports past fish or fish-tank exposure.
In the absence of positive culture results, a skin or tissue biopsy may be a helpful test to render a microscopic diagnosis. Another technique that can be used to detect the bacteria is Polymerase Chain Reaction (PCR) </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 Hypocapnia and can you explain it in depth? [/INST] Hypocapnia (from the Greek words υπό meaning below normal and καπνός kapnós meaning smoke), also known as hypocarbia, sometimes incorrectly called acapnia, is a state of reduced carbon dioxide in the blood. Hypocapnia usually results from deep or rapid breathing, known as hyperventilation.
Hypocapnia is the opposite of hypercapnia.

Effects
Even when marked, hypocapnia is normally well tolerated. Symptoms include tingling sensation (usually in the limbs), abnormal heartbeat, painful muscle cramps, and seizures. Acute hypocapnia causes hypocapnic alkalosis, which causes cerebral vasoconstriction leading to cerebral hypoxia, and this can cause transient dizziness, fainting, and anxiety. A low partial pressure of carbon dioxide in the blood also causes alkalosis (because CO2 is acidic in solution), leading to lowered plasma calcium ions (Hypocalcaemia), causing increased nerve and muscle excitability. This explains the other common symptoms of hyperventilation—pins and needles, muscle cramps and tetany in the extremities, especially hands and feet.Because the brain stem regulates breathing by monitoring the level of blood CO2 instead of O2, hypocapnia can suppress breathing to the point of blackout from cerebral hypoxia, as exhibited in shallow water blackout.
Hypocapnia also results in bronchoconstriction in order to decrease ventilation. This mechanism is meant to counteract hyperventilation, and decrease the amount of oxygen coming into the lungs </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 Calcium pyrophosphate dihydrate crystal deposition disease and can you explain it in depth? [/INST] Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, also known as pseudogout and pyrophosphate arthropathy, is a rheumatologic disease which is thought to be secondary to abnormal accumulation of calcium pyrophosphate dihydrate crystals within joint soft tissues. The knee joint is most commonly affected.

Signs and symptoms
When symptomatic, the disease classically begins with symptoms that are similar to a gout attack (thus the moniker "pseudogout"). These include:
severe pain
warmth
swelling of one or more jointsThe symptoms can be monoarticular (involving a single joint) or polyarticular (involving several joints). Symptoms usually last for days to weeks, and often recur. Although any joint may be affected, the knees, wrists, and hips are most common.X-ray, CT, or other imaging usually shows accumulation of calcium within the joint cartilage, known as chondrocalcinosis. There can also be findings of osteoarthritis.  The white blood cell count is often raised.

Cause
The cause of CPPD disease is unknown. Increased breakdown of adenosine triphosphate (ATP; the molecule used as energy currency in all living things), which results in increased pyrophosphate levels in joints, is thought to be one reason why crystals may develop.Familial forms are rare. One genetic study found an association between CPPD and a region of chromosome 8q.The gene ANKH is involved in crystal-related inflammatory reactions and inorganic phosphate transport.

Diagnosis
The disease is defined by presence of joint inflammation and the presence of CPPD crystals within the joint. The crystals are usually detected by imaging and/or joint fluid analysis.

Medical imaging, consisting of x-ray, CT, MRI, or ultrasound may detect chondrocalcinosis within the affected joint, indicating a substantial amount of calcium crystal deposition within the cartilage or ligaments. Ultrasound is a reliable method to diagnose CPPD. Using ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage or fibrocartilage.  By x-ray, CPPD can appear similar to other diseases such as ankylosing spondylitis and gout.

Arthrocentesis, or removing synovial fluid from the affected joint, is performed to test the synovial fluid for the calcium pyrophosphate crystals that are present in CPPD. When stained with H&E stain, calcium pyrophosphate crystals appears deeply blue ("basophilic"). However, CPP crystals are much better known for their rhomboid shape and weak positive birefringence on polarized light microscopy, and this method remains the most reliable method of identifying the crystals under the microscope. However, even this method has poor sensitivity, specificity, and inter-operator agreement.These two modalities currently define CPPD disease, but lack diagnostic accuracy. Thus, the diagnosis of CPPD disease is potentially epiphenomenological.

Treatment
Because any medication that could reduce the inflammation of CPPD bears a risk of causing organ damage, treatment is not advised if the condition is not causing pain.
For acute pseudogout, treatments include intra-articular corticosteroid injection, systemic corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), or, on occasion, high-dose colchicine. In general, NSAIDs are administered in low doses to help prevent CPPD </s>