<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hypercapnia and explain in detail? [/INST] Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the bodys metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation".
Acute hypercapnia is called acute hypercapnic respiratory failure (AHRF) and is a medical emergency as it generally occurs in the context of acute illness. Chronic hypercapnia, where metabolic compensation is usually present, may cause symptoms but is not generally an emergency. Depending on the scenario both forms of hypercapnia may be treated with medication, with mask-based non-invasive ventilation or with mechanical ventilation.
Hypercapnia is a hazard of underwater diving associated with breath-hold diving, scuba diving, particularly on rebreathers, and deep diving where it is associated with increased breathing gas density due to the high ambient pressure.

Signs and symptoms
Hypercapnia may happen in the context of an underlying health condition, and symptoms may relate to this condition or directly to the hypercapnia. Specific symptoms attributable to early hypercapnia are dyspnea (breathlessness), headache, confusion and lethargy. Clinical signs include flushed skin, full pulse (bounding pulse), rapid breathing, premature heart beats, muscle twitches, and hand flaps (asterixis). The risk of dangerous irregularities of the heart beat is increased. Hypercapnia also occurs when the breathing gas is contaminated with carbon dioxide, or respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide, which can occur when gas density limits ventilation at high ambient pressures.In severe hypercapnia (generally

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    {\displaystyle {P_{a_{CO_{2}}}}}
   greater than 10 kPa or 75 mmHg), symptomatology progresses to disorientation, panic, hyperventilation, convulsions, unconsciousness, and eventually death.

Causes
Carbon dioxide is a normal metabolic product but it accumulates in the body if it is produced faster than it is cleared. During strenuous exercise the production rate of carbon dioxide can increase more than tenfold over the production rate during rest. Carbon dioxide is dissolved in the blood and elimination is by gas exchange in the lungs during breathing. Hypercapnia is generally caused by hypoventilation, lung disease, or diminished consciousness. It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, such as from volcanic or geothermal activity, or by rebreathing exhaled carbon dioxide. In this situation the hypercapnia can also be accompanied by respiratory acidosis.Acute hypercapnic respiratory failure may occur in acute illness caused by chronic obstructive pulmonary disease (COPD), chest wall deformity, some forms of neuromuscular disease (such as myasthenia gravis, and obesity hypoventilation syndrome. AHRF may also develop in any form of respiratory failure where the breathing muscles become exhausted, such as severe pneumonia and acute severe asthma. It can also be a consequence of profound suppression of consciousness such as opioid overdose.

During diving
Normal respiration in divers results in alveolar hypoventilation resulting in inadequate CO2 elimination or hypercapnia. Lanphiers work at the US Navy Experimental Diving Unit answered the question, "Why dont divers breathe enough?":
Higher inspired oxygen (

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    {\displaystyle {P_{i_{O_{2}}}}}
  ) at 4 atm (400 kPa) accounted for not more than 25% of the elevation in end tidal CO2 (ETCO2) above values found at the same work rate when breathing air just below the surface.
Increased work of breathing accounted for most of the elevation of

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   (alveolar gas equation) in exposures above 1 atm (100 kPa), as indicated by the results when helium was substituted for nitrogen at 4 atm (400 kPa).
Inadequate ventilatory response to exertion was indicated by the fact that, despite resting values in the normal range,

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    {\displaystyle {P_{et_{CO_{2}}}}}
   rose markedly with exertion even when the divers breathed air at a depth of only a few feet.A variety of reasons exists for carbon dioxide not being expelled completely when the diver exhales:

The diver is exhaling into a vessel that does not allow all the CO2 to escape to the environment, such as a long snorkel, full-face diving mask, or diving helmet, and the diver then reinhales from that vessel, causing increased dead space.
The carbon dioxide scrubber in the divers rebreather is failing to remove sufficient carbon dioxide from the loop (higher inspired CO2), or the breathing gas is contaminated with CO2.
The diver is overexercising, producing excess carbon dioxide due to elevated metabolic activity and respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide.
Gas density limits ventilation at high ambient pressures. The density of the breathing gas is higher at depth, so the effort required to fully inhale and exhale increases, making breathing more difficult and less efficient (high work of breathing). Higher gas density also causes gas mixing within the lung to be less efficient, thus increasing the effective dead space.
The diver is deliberately hypoventilating, known as "skip breathing".

Skip breathing
Skip breathing is a controversial technique to conserve breathing gas when using open-circuit scuba, which consists of briefly holding ones breath between inhalation and exhalation (i.e., "skipping" a breath). It can lead to CO2 not being exhaled efficiently. The risk of burst lung (pulmonary barotrauma of ascent) is increased if the breath is held while ascending.  It is particularly counterproductive with a rebreather, where the act of breathing pumps the gas around the "loop", pushing carbon dioxide through the scrubber and mixing freshly injected oxygen.In closed-circuit rebreather diving, exhaled carbon dioxide must be removed from the breathing system, usually by a scrubber containing a solid chemical compound with a high affinity for CO2, such as soda lime. If not removed from the system, it may be reinhaled, causing an increase in the inhaled concentration.Under hyperbaric conditions, hypercapnia contributes to nitrogen narcosis and oxygen toxicity by causing cerebral vasodilation which increases the dosage of oxygen to the brain.

Mechanism
Hypercapnia normally triggers a reflex which increases breathing and access to oxygen (O2), such as arousal and turning the head during sleep. A failure of this reflex can be fatal, for example as a contributory factor in sudden infant death syndrome.Hypercapnia can induce increased cardiac output, an elevation in arterial blood pressure (higher levels of carbon dioxide stimulate aortic and carotid chemoreceptors with afferents -CN IX and X- to medulla oblongata with following chrono- and ino-tropic effects), and a propensity toward cardiac arrhythmias. Hypercapnia may increase pulmonary capillary resistance.

Physiological effects
A high arterial partial pressure of carbon dioxide (

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    {\displaystyle {P_{a_{CO_{2}}}}}
  ) causes changes in brain activity that adversely affect both fine muscular control and reasoning. EEG changes denoting minor narcotic effects can be detected for expired gas end tidal partial pressure of carbon dioxide (

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    {\displaystyle {P_{ET_{CO_{2}}}}}
  ) increase from 40 torrs (0.053 atm) to approximately 50 torrs (0.066 atm). The diver does not necessarily notice these effects.Higher levels of

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   have a stronger narcotic effect: Confusion and irrational behaviour may occur around 72 torrs (0.095 atm), and loss of consciousness around 90 torrs (0.12 atm). High

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   triggers the fight or flight response, affects hormone levels and can cause anxiety, irritability and inappropriate or panic responses, which can be beyond the control of the subject, sometimes with little or no warning. Vasodilation is another effect, notably in the skin, where feelings of unpleasant heat are reported, and in the brain, where blood flow can increase by 50% at a

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    {\displaystyle {P_{ET_{CO_{2}}}}}
   of 50 torrs (0.066 atm), Intracranial pressure may rise, with a throbbing headache. If associated with a high

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   the high delivery of oxygen to the brain may increase the risk of CNS oxygen toxicity at partial pressures usually considered acceptable.In many people a high

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   causes a feeling of shortness of breath, but the lack of this symptom is no guarantee that the other effects are not occurring. A significant percentage of rebreather deaths have been associated with CO2 retention. The effects of high

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   can take several minutes to hours to resolve once the cause has been removed.

Diagnosis
Blood gas tests may be performed, typically by radial artery puncture, in the setting of acute breathing problems or other acute medical illness. Hypercapnia is generally defined as an arterial blood carbon dioxide level over 45 mmHg (6 kPa). Since carbon dioxide is in equilibrium with carbonic acid in the blood, hypercapnia drives serum pH down, resulting in respiratory acidosis. Clinically, the effect of hypercapnia on pH is estimated using the ratio of the arterial pressure of carbon dioxide to the concentration of bicarbonate ion,

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    {\displaystyle {P_{a_{CO_{2}/HCO_{3}^{-}}}}}
  .

Tolerance
CO2 toxicity in animal models
Tests performed on mongrel dogs showed the physiological effect of carbon dioxide on the body of the animal: after inhalation of a 50% CO2 and 50% air mixture, respiratory movement increased for about 2 minutes, and then, it decreased for 30 to 90 minutes </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Caroli disease and explain in detail? [/INST] Caroli disease (communicating cavernous ectasia, or congenital cystic dilatation of the intrahepatic biliary tree) is a rare inherited disorder characterized by cystic dilatation (or ectasia) of the bile ducts within the liver. There are two patterns of Caroli disease: focal or simple Caroli disease consists of abnormally widened bile ducts affecting an isolated portion of liver. The second form is more diffuse, and when associated with portal hypertension and congenital hepatic fibrosis, is often referred to as "Caroli syndrome". The underlying differences between the two types are not well understood. Caroli disease is also associated with liver failure and polycystic kidney disease. The disease affects about one in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease.Caroli disease is distinct from other diseases that cause ductal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives.

Signs and symptoms
The first symptoms typically include fever, intermittent abdominal pain, and an enlarged liver. Occasionally, yellow discoloration of the skin occurs. Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, biliary abscess, sepsis, liver cirrhosis, kidney failure, and cholangiocarcinoma (7% affected). People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population. After recognizing symptoms of related diseases, Caroli disease can be diagnosed.Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma. These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including enlarged spleen, hematemesis, and melena. These problems can severely affect the patients quality of life. In a 10-year period between 1995 and 2005, only 10 patients were surgically treated for Caroli disease, with an average patient age of 45.8 years.After reviewing 46 cases of Caroli disease before 1990,  21.7% of the cases were the result of an intrahepatic cyst or nonobstructive biliary tree dilation, 34.7% were linked with congenital hepatic fibrosis, 13% were isolated choledochal cystic dilation, and the remaining 24.6% had a combination of all three.

Causes
The cause appears to be genetic; the simple form is an autosomal dominant trait, while the complex form is an autosomal recessive trait. Females are more prone to Caroli disease than males. Family history may include kidney and liver disease due to the link between Caroli disease and ARPKD. PKHD1, the gene linked to ARPKD, has been found mutated in patients with Caroli syndrome. PKHD1 is expressed primarily in the kidneys with lower levels in the liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys. The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined.

Diagnosis
Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree.  Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI  show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Treatment
The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases.Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis. Ursodiol is given to treat cholelithiasis </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Metabolic syndrome and explain in detail? [/INST] Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic syndrome is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.Insulin resistance, metabolic syndrome, and prediabetes are closely related to one another and have overlapping aspects. The syndrome is thought to be caused by an underlying disorder of energy utilization and storage. The cause of the syndrome is an area of ongoing medical research.

Signs and symptoms
The key sign of metabolic syndrome is central obesity, also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by adipose tissue accumulation predominantly around the waist and trunk. Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level, impaired fasting glucose, insulin resistance, or prediabetes. Associated conditions include hyperuricemia; fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease; polycystic ovarian syndrome in women and erectile dysfunction in men; and acanthosis nigricans.

Complication
Metabolic syndrome can lead to several serious and chronic complications, including type-2 diabetes, cardiovascular diseases, stroke, kidney disease and nonalcoholic fatty liver disease.

Causes
The mechanisms of the complex pathways of metabolic syndrome are under investigation. The pathophysiology is very complex and has been only partially elucidated. Most people affected by the condition are older, obese, sedentary, and have a degree of insulin resistance. Stress can also be a contributing factor. The most important risk factors are diet (particularly sugar-sweetened beverage consumption), genetics, aging, sedentary behavior or low physical activity, disrupted chronobiology/sleep, mood disorders/psychotropic medication use, and excessive alcohol use. The pathogenic role played in the syndrome by the excessive expansion of adipose tissue occurring under sustained overeating, and its resulting lipotoxicity was reviewed by Vidal-Puig.There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. Markers of systemic inflammation, including C-reactive protein, are often increased, as are fibrinogen, interleukin 6, tumor necrosis factor-alpha (TNF-α), and others. Some have pointed to a variety of causes, including increased uric acid levels caused by dietary fructose.Research shows that Western diet habits are a factor in development of metabolic syndrome, with high consumption of food that is not biochemically suited to humans. Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance. The continuous provision of energy via dietary carbohydrate, lipid, and protein fuels, unmatched by physical activity/energy demand, creates a backlog of the products of mitochondrial oxidation, a process associated with progressive mitochondrial dysfunction and insulin resistance.

Stress
Recent research indicates prolonged chronic stress can contribute to metabolic syndrome by disrupting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis). A dysfunctional HPA-axis causes high cortisol levels to circulate, which results in raising glucose and insulin levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" osteoporosis. HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to cardiovascular disease (CVD), type 2 diabetes and stroke. Psychosocial stress is also linked to heart disease.

Obesity
Central obesity is a key feature of the syndrome, being both a sign and a cause, in that the increasing adiposity often reflected in high waist circumference may both result from and contribute to insulin resistance. However, despite the importance of obesity, affected people who are of normal weight may also be insulin-resistant and have the syndrome.

Sedentary lifestyle
Physical inactivity is a predictor of CVD events and related mortality. Many components of metabolic syndrome are associated with a sedentary lifestyle, including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome.

Aging
Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndromes prevalence is seen in most populations around the world.

Diabetes mellitus type 2
The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a complication of metabolic syndrome. In people with impaired glucose tolerance or impaired fasting glucose, presence of metabolic syndrome doubles the risk of developing type 2 diabetes. It is likely that prediabetes and metabolic syndrome denote the same disorder, defining it by the different sets of biological markers.The presence of metabolic syndrome is associated with a higher prevalence of CVD than found in people with type 2 diabetes or impaired glucose tolerance without the syndrome. Hypoadiponectinemia has been shown to increase insulin resistance and is considered to be a risk factor for developing metabolic syndrome.

Coronary heart disease
The approximate prevalence of the metabolic syndrome in people with coronary artery disease (CAD) is 50%, with a prevalence of 37% in people with premature coronary artery disease (age 45), particularly in women. With appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced.

Lipodystrophy
Lipodystrophic disorders in general are associated with metabolic syndrome. Both genetic (e.g., Berardinelli-Seip congenital lipodystrophy, Dunnigan familial partial lipodystrophy) and acquired (e.g., HIV-related lipodystrophy in people treated with highly active antiretroviral therapy) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndromes components.

Rheumatic diseases
There is research that associates comorbidity with rheumatic diseases. Both psoriasis and psoriatic arthritis have been found to be associated with metabolic syndrome.

Chronic obstructive pulmonary disease
Metabolic syndrome is seen to be a comorbidity in up to 50 percent of those with chronic obstructive pulmonary disease (COPD). It may pre-exist or may be a consequence of the lung pathology of COPD.

Pathophysiology
It is common for there to be a development of visceral fat, after which the adipocytes (fat cells) of the visceral fat increase plasma levels of TNF-α and alter levels of other substances (e.g., adiponectin, resistin, and PAI-1). TNF-α has been shown to cause the production of inflammatory cytokines and also possibly trigger cell signaling by interaction with a TNF-α receptor that may lead to insulin resistance. An experiment with rats fed a diet with 33% sucrose has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. The progression from visceral fat to increased TNF-α to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells, which play a role in inflammation. Chronic inflammation contributes to an increased risk of hypertension, atherosclerosis and diabetes.The involvement of the endocannabinoid system in the development of metabolic syndrome is indisputable. Endocannabinoid overproduction may induce reward system dysfunction and cause executive dysfunctions (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors. The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet. The resulting oversupply of omega-6 fatty acids, particularly arachidonic acid (AA), is an important factor in the pathogenesis of metabolic syndrome. Arachidonic acid (with its precursor – linoleic acid) serves as a substrate to the production of inflammatory mediators known as eicosanoids, whereas the arachidonic acid-containing compound diacylglycerol (DAG) is a precursor to the endocannabinoid 2-arachidonoylglycerol (2-AG) while fatty acid amide hydrolase (FAAH) mediates the metabolism of anandamide into arachidonic acid. Anandamide can also be produced from N-acylphosphatidylethanolamine via several pathways. Anandamide and 2-AG can also be hydrolized into arachidonic acid, potentially leading to increased eicosanoid synthesis.

Diagnosis
A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity published a guideline to harmonize the definition of the metabolic syndrome. This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. Whether it is better at this time to set the level at which risk starts to increase or at which there is already substantially increased risk will be up to local decision-making groups. However, for international comparisons and to facilitate the etiology, it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.The previous definitions of the metabolic syndrome by the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program (NCEP) are very similar, and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if body mass index (BMI) is greater than 30 kg/m2, central obesity can be assumed, and waist circumference does not need to be measured.  However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography.

IDF
The International Diabetes Federation consensus worldwide definition of metabolic syndrome (2006) is:
Central obesity (defined as waist circumference# with ethnicity-specific values) AND any two of the following:

Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality
Reduced HDL cholesterol:  < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality
Raised blood pressure (BP): systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension
Raised fasting plasma glucose (FPG): >100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetesIf FPG is >5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome.
# If BMI is >30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured

WHO
The World Health Organization (1999)  requires the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following:

Blood pressure ≥ 140/90 mmHg
Dyslipidemia: triglycerides (TG) ≥ 1.695 mmol/L  and HDL cholesterol ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female)
Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or BMI > 30 kg/m2
Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g

EGIR
The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following:
Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female)
Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia
Blood pressure ≥ 140/90 mmHg or antihypertensive medication
Fasting plasma glucose ≥ 6.1 mmol/L

NCEP
The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following:
Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female)
Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl)
Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

American Heart Association
There is confusion as to whether, in 2004, the American Heart Association and National Heart, Lung, and Blood Institute intended to create another set of guidelines or simply update the National Cholesterol Education Program definition.
Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female)
Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dL)
Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure ≥ 130/85 mmHg (or treated for hypertension)
Fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), or use of medication for hyperglycemia

Other
High-sensitivity C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism. Fatty liver disease and steatohepatitis can be considered manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution.
Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome.

Prevention
Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day), and a healthy, reduced calorie diet.  Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily because of a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of an Imperial pint (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors findings, while others dispute them. A systematic review of four randomized controlled trials said that, in the short term, a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.

Management
Medications
Generally, the individual disorders that compose the metabolic syndrome are treated separately </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anomic aphasia and explain in detail? [/INST] Anomic aphasia  (also known as dysnomia, nominal aphasia, and amnesic aphasia) is a mild, fluent type of aphasia where individuals have word retrieval failures and cannot express the words they want to say (particularly nouns and verbs). Anomia is a deficit of expressive language. Anomia is a symptom of all forms of aphasia, but patients whose primary deficit is word retrieval are diagnosed with anomic aphasia. Individuals with aphasia who display anomia can often describe an object in detail and maybe even use hand gestures to demonstrate how the object is used, but cannot find the appropriate word to name the object. Patients with anomic aphasia have relatively preserved speech fluency, repetition, comprehension, and grammatical speech.

Types
Word selection anomia is caused by damage to the posterior inferior temporal area. This type of anomia occurs when the patient knows how to use an object and can correctly select the target object from a group of objects, and yet cannot name the object. Some patients with word selection anomia may exhibit selective impairment in naming particular types of objects, such as animals or colors.  In the subtype known as color anomia, the patient can distinguish between colors but cannot identify them by name or name the color of an object. The patients can separate colors into categories, but they cannot name them.
Semantic anomia is caused by damage to the angular gyrus. This is a disorder in which the meaning of words becomes lost. In patients with semantic anomia, a naming deficit is accompanied by a recognition deficit. Thus, unlike patients with word selection anomia, patients with semantic anomia are unable to select the correct object from a group of objects, even when provided with the name of the target object.
Disconnection anomia results from the severing of connections between sensory and language cortices. Patients with disconnection anomia may exhibit modality-specific anomia, where the anomia is limited to a specific sensory modality, such as hearing. For example, a patient who is perfectly capable of naming a target object when it is presented via certain sensory modalities like audition or touch, may be unable to name the same object when the object is presented visually. Thus, in such a case, the patients anomia arises as a consequence of a disconnect between their visual cortex and language cortices.Patients with disconnection anomia may also exhibit callosal anomia, in which damage to the corpus callosum prevents sensory information from being transmitted between the two hemispheres of the brain. Therefore, when sensory information is unable to reach the hemisphere that is language-dominant (typically the left hemisphere in most individuals), the result is anomia. For instance, if patients with this type of disconnection anomia hold an object in their left hand, this somatosensory information about the object would be sent to the right hemisphere of the brain, but then would be unable to reach the left hemisphere due to callosal damage. Thus, this somatosensory information would fail to be transmitted to language areas in the left hemisphere, in turn resulting in the inability to name the object in the left hand. In this example, the patient would have no problem with naming, if the test object were to be held in the right hand. This type of anomia may also arise as a consequence of a disconnect between sensory and language cortices.
Articulatory initiation anomia results from damage to the frontal area. Characteristics of this anomia are non-fluent output, word-finding pauses, deficient word lists. Patients perform better at confrontation naming tasks, the selection of a label for a corresponding picture, than word list tasks. Patients are aided in word selection by prompting, unlike those with word selection anomia.
Phonemic substitution anomia results from damage to the inferior parietal area. Patients maintain fluent output but exhibit literal and neologistic paraphasia. Literal paraphasia is the incorrect substitution of phonemes, and neologistic paraphasia is the use of non-real words in the place of real words. Patients naming ability is contaminated by paraphasia.
Modality-specific anomia is caused by damage to the sensory cortex, pathways to the dominant angular gyrus, or both. In these patients, word-finding is worst in one sensory modality, for example visual or tactile.

Causes
Anomic aphasia occurring by itself may be caused by damage to almost anywhere in the left hemisphere and in some cases can be seen in instances of right hemisphere damage. Anomia can be genetic or caused by damage to various parts of the parietal lobe or the temporal lobe of the brain due to traumatic injury, stroke, or a brain tumor. While anomic aphasia is primarily caused by structural lesions, they may also originate in Alzheimers disease (anomia may be the earliest language deficit in posterior cortical atrophy variant of Alzheimers) or other neurodegenerative diseases.Although the main causes are not specifically known, many researchers have found factors contributing to anomic aphasia. People with damage to the left hemisphere of the brain are more likely to have anomic aphasia. Brocas area, the speech production center in the brain, was linked to being the source for speech execution problems, with the use of functional magnetic resonance imaging (fMRI), now commonly used to study anomic patients. Other experts believe that damage to Wernickes area, which is the speech comprehension area of the brain, is connected to anomia because the patients cannot comprehend the words that they are hearing.Although many experts have believed that damage to Brocas area or Wernickes area are the main causes of anomia, current studies have shown that damage in the left parietal lobe is the cause of anomic aphasia. One study was conducted using a word repetition test as well as fMRI in order to see the highest level of activity as well as where the lesions are in the brain tissue. Fridrikkson, et al. saw that damage to neither Brocas area nor Wernickes area were the sole sources of anomia in the subjects. Therefore, the original anomia model, which theorized that damage occurred on the surface of the brain in the grey matter was debunked, and it was found that the damage was in the white matter deeper in the brain, on the left hemisphere. More specifically, the damage was in a part of the nerve tract called the arcuate fasciculus, for which the mechanism of action is unknown, though it is known to connect the posterior (back) of the brain to the anterior (front) and vice versa.While anomic aphasia is associated with lesions throughout the left hemisphere, severe and isolated anomia has been considered a sign of deep temporal lobe or lateral temporo-occipital damage. Damage to these areas is seen in patients showing infarction limited to regions supplied by the dominant posterior cerebral artery (PCA) and is referred to as posterior cerebral artery syndrome.

Diagnosis
The best way to see if anomic aphasia has developed is by using verbal and imaging tests. The combination seems to be most effective, since either test done alone may give false positives or false negatives. For example, the verbal test is used to see if a speech disorder presents, and whether the problem is in speech production or comprehension.  Patients with Alzheimers disease have speech problems linked to dementia or progressive aphasias, which can include anomia. The imaging test, mostly done using MRI scans, is ideal for lesion mapping or viewing deterioration in the brain. However, imaging cannot diagnose anomia on its own because the lesions may not be located deep enough to damage the white matter or the arcuate fasciculus. However, anomic aphasia is very difficult to associate with a specific lesion location in the brain. Therefore, the combination of speech tests and imaging tests has the highest sensitivity and specificity.Picture-naming tests, such as the Philadelphia Naming Test (PNT), are also utilized in diagnosing aphasias. Analysis of picture-naming is compared with reading, picture categorizing, and word categorizing. There is a considerable similarity among aphasia syndromes in terms of picture-naming behavior, however anomic aphasiacs produced the fewest phonemic errors and the most multiword circumlocutions. These results suggest minimal word-production difficulty in anomic aphasia relative to other aphasia syndromes.Anomic aphasia has been diagnosed in some studies using the Aachen Aphasia Test (AAT), which tests language functioning after brain injury. This test aims to: identify the presence of aphasia; provide a profile of the speakers language functioning according to different language modalities (speaking, listening, reading, writing) and different levels of linguistic description (phonology, morphology, semantics, and syntax); give a measure of severity of any breakdown. This test was administered to patients participating in a study in 2012, and researchers found that on the naming subtest of the AAT patients showed relevant naming difficulties and tended to substitute the words they could not produce with circumlocutions.The Western Aphasia Battery is another test that is conducted with the goal of classifying aphasia subtypes and rating the severity of the aphasiac impairment. The test is composed of four language and three performance domains. Syndrome classification is determined by the pattern of performance on the four language subtests, which assess spontaneous speech, comprehension, repetition, and naming.Doing a hearing test first is important, in case the patient cannot clearly hear the words or sentences needed in the speech repetition test. In the speech tests, the person is asked to repeat a sentence with common words; if the person cannot identify the word, but he or she can describe it, then the person is highly likely to have anomic aphasia. However, to be completely sure, the test is given while a test subject is in an fMRI scanner, and the exact location of the lesions and areas activated by speech are pinpointed. Few simpler or cheaper options are available, so lesion mapping and speech repetition tests are the main ways of diagnosing anomic aphasia.

Definition
Anomic aphasia (anomia) is a type of aphasia characterized by problems recalling words, names, and numbers. Speech is fluent and receptive language is not impaired in someone with anomic aphasia. Subjects often use circumlocutions (speaking in a roundabout way) to avoid a name they cannot recall or to express a certain word they cannot remember. Sometimes, the subject can recall the name when given clues. Additionally, patients are able to speak with correct grammar; the main problem is finding the appropriate word to identify an object or person.Sometimes, subjects may know what to do with an object, but still not be able to give a name to the object. For example, if a subject is shown an orange and asked what it is called, the subject may be well aware that the object can be peeled and eaten, and may even be able to demonstrate this by actions or even verbal responses; however, they cannot recall that the object is called an "orange". Sometimes, when a person with this condition is multilingual, they might confuse the language they are speaking in trying to find the right word (inadvertent code-switching).

Management
No method is available to completely cure anomic aphasia. However, treatments can help improve word-finding skills.
Although a person with anomia may find recalling many types of words to be difficult, such as common nouns, proper nouns, verbs, etc., many studies have shown that treatment for object words, or nouns, has shown promise in rehabilitation research. The treatment includes visual aids, such as pictures, and the patient is asked to identify the object or activity. However, if that is not possible, then the patient is shown the same picture surrounded by words associated with the object or activity. Throughout the process, positive encouragement is provided. The treatment shows an increase in word finding during treatment; however, word identifying decreased two weeks after the rehabilitation period. Therefore, it shows that rehabilitation effort needs to be continuous for word-finding abilities to improve from the baseline. The studies show that verbs are harder to recall or repeat, even with rehabilitation.Other methods in treating anomic aphasia include circumlocution-induced naming therapy (CIN), wherein the patient uses circumlocution to assist with his or her naming rather than just being told to name the item pictured after given some sort of cue. Results suggest that the patient does better in properly naming objects when undergoing this therapy because CIN strengthens the weakened link between semantics and phonology for patients with anomia, since they often know what an object is used for, but cannot verbally name it.Anomia is often challenging for the families and friends of those affected by it. One way to overcome this is computer-based treatment models, effective especially when used with clinical therapy. Leemann et al. provided anomic patients with computerized-assisted therapy (CAT) sessions, along with traditional therapy sessions using treatment lists of words. Some of the patients received a drug known to help relieve symptoms of anomia (levodopa), while others received a placebo. The researchers found that the drug had no significant effects on improvement with the treatment lists, but almost all of the patients improved after the CAT sessions. They concluded that this form of computerized treatment is effective in increasing naming abilities in anomic patients.Additionally, one study researched the effects of using "excitatory (anodal) transcranial direct current stimulation" over the right temporoparietal cortex, a brain area that seems to correlate to language. The electrical stimulation seemed to enhance language training outcome in patients with chronic aphasia.Contextual repetition priming treatment is a technique which involves repeated repetition of names of pictures that are related semantically, phonologically, or are unrelated. Patients with impaired access to lexical-semantic representations show no long-term improvement in naming, but patients with good access to semantics show long-term benefits.Development of self-cueing strategies can also facilitate word retrieval. Patients identify core words that can be retrieved without struggle, and establish a relationship between cue words and words that begin with the same sound but cannot be retrieved. Patients then learn to use the cue word to facilitate word retrieval for the target object.

Epidemiology
Many different populations can and do have anomia. For instance, deaf patients who have had a stroke can demonstrate semantic and phonological errors, much like hearing anomic patients </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Navicular syndrome and explain in detail? [/INST] Navicular syndrome, often called navicular disease, is a syndrome of lameness problems in horses.  It most commonly describes an inflammation or degeneration of the navicular bone and its surrounding tissues, usually on the front feet. It can lead to significant and even disabling lameness.

Description of the navicular area
Knowledge of equine forelimb anatomy is especially useful for understanding navicular syndrome. The navicular bone lies behind the coffin bone and under the small pastern bone. The deep digital flexor (DDF) tendon runs down the back of the cannon and soft tissue in that area and under the navicular bone before attaching to the back of the coffin bone. The DDF tendon flexes the coffin joint, and the navicular bone acts as a fulcrum that the DDF tendon runs over.The navicular bone is supported by several ligaments above, below, and on the side. One of these ligaments is the impar ligament, which attaches the navicular bone to the coffin bone (distal phalanx). Cartilage lies between the navicular bone and the coffin joint, as well as between the navicular bone and the DDF tendon. The navicular bursa - a small sac that protects the DDF and navicular bone from abrasion as the tendon slides over the area - lies between the navicular bone and the DDF tendon.

Causes and contributing factors
There is no single known cause of navicular syndrome, although there are many theories, and several primary factors.
The first factor is compression of the navicular bone under the DDF tendon and the back of the small pastern bone. Repeated compression in this area can cause cartilage degeneration, with the cartilage flattening and gradually becoming less springy and shock-absorbing. It may also begin to erode. Cartilage degeneration is common in navicular horses, usually along the flexor surface. This finding, and the associated biochemical changes, have led some researchers to conclude that there are elements in navicular disease common to osteoarthritis, and to suggest similar therapeutic regimes.Cartilage erosion may progress to the point that the bone underneath will become exposed. With the cartilage no longer present to protect it, the navicular bursa and DDF tendon may become damaged by the constant rubbing against the navicular bone. Navicular bursitis (inflammation of the navicular bursa) may occur, even if cartilage damage is not severe. This is probably due to the friction between the navicular bone and the DDF tendon from compression.
Constant compression can also increase the bone density directly under the cartilage surfaces, especially on the flexor side. This tends to make the bone more brittle, and thus more likely to break.
Another main factor is the tension placed on the ligaments that support the navicular bone. Some experts believe that the degenerative process begins with excess tension placed on these ligaments, causing strain and inflammation. Inflammation from strain of the impar ligament can decrease blood flow to and from the navicular bone, as the major blood vessels supplying the bone run up and down this area. If the ligament continues to be strained, it can thicken and permanently reduce blood flow to the navicular bone.
Because veins are more easily compressed than arteries, blood flow to the bone would be less obstructed than blood flow from the bone. This would cause a buildup of pressure within the navicular bone. The navicular bone, in response to both the increased pressure and overall decreased blood supply, would absorb mineral from its center.
Excess tension can also cause exostoses where the ligaments attach to the navicular bone, giving the bone a "canoe" shape. If tension is extreme, the ligaments may actually tear.
Recent research has found correlations between "toe-first landing" of the hooves and navicular problems, due to excessive strain put on the deep digital flexor tendon, as a consequence of misalignment of the lower joints.
Toe-first landing, usually seen as a consequence of navicular disease, may actually be a cause or at least a contributing factor to the onset of tendon inflammation and bone modifications.
Toe-first landing is often caused by frog and heel overtrimming, long toes, and/or poor shoeing.

Contributing factors
Conformation
Certain conformational defects may contribute to navicular syndrome, especially defects that promote concussion. These include upright pasterns, small feet, narrow and upright feet, significant downhill build (commonly seen in American Quarter Horses), and long toes with low heels (commonly seen in Thoroughbreds).
The long toe, low heel conformation places constant stress on the navicular bone, even as the horse is standing.  Upright feet increase concussion, especially in the heel region of the hoof where the navicular bone is located. Excess concussion cannot be absorbed as well by the structures designed to do so (the frog, heels, and digital cushion), so more impact is transmitted to the structures within the foot.
Poor hoof shape is usually inherited, although poor shoeing and trimming can contribute to these shapes.
With the long toe, low heel conformation can come contracted heels (narrowing of the heel) which further compresses the navicular bone along with sheared heels adding more stress to the tendons and navicular bones.

Shoeing
Poor trimming, shoe selection, or inappropriate shoe attachment are well-known causes of lameness, and navicular disease is fairly common in the modern-day domesticated horse. However, it is also seen in wild horse populations. Those who advocate "barefoot trimming" of domestic horses propose that in nature, a horses hoof is designed to expand and contract as the horse moves. This expanding and contracting acts as an auxiliary blood pump, and aids the circulation of blood to the lower extremities. When an inflexible metal shoe is improperly attached to the hoof, the hoof can no longer work as designed, and blood flow is inhibited. However, evidence of navicular degeneration has been established in the fossil record of early horses. Mary Thompson, a vertebrate paleontologist at Idaho Museum of Natural History, has found evidence in many species of early horses and concludes, "The results of this study strongly suggest that man’s intervention (whether by increased usage or improper breeding practices) may not be the sole cause of the syndrome", although she cautions that her results are preliminary.

Work
Working on steep hills, galloping, and jumping all contribute to navicular syndrome, as they place greater stress on the DDF tendons, and may cause overextension of the pastern and coffin joints.
Regular exercise on hard or irregular ground increases concussion on the hoof, thus increasing the risk of navicular syndrome.
It is possible that standing can also increase the chance of navicular disease (such as a horse that spends most of the day in a stall with little turnout, as with some racehorses and show horses). Blood flow to the hoof decreases when the horse is not in motion. The horse is also constantly applying pressure to the navicular bones (which is intermittent as the horse moves).

Body weight
Horses with a high weight-to-foot-size ratio may have an increased chance of exhibiting symptoms of navicular syndrome, since the relative load on the foot increases. This might explain why the syndrome is seen more frequently in Thoroughbreds, American Quarter Horses, and Warmbloods as opposed to ponies and Arabians.

Signs
Heel pain is very common in horses with navicular syndrome. Lameness may begin as mild and intermittent, and progress to severe. This may be due to strain and inflammation of the ligaments supporting the navicular bone, reduced blood flow and increased pressure within the hoof, damage to the navicular bursa or DDF tendon, or from cartilage erosion.
Affected horses display a "tiptoe" gait - trying to walk on the toes due to heel pain. They may stumble frequently. The lameness may switch from one leg to another, and may not be consistent. Lameness usually occurs in both front feet, although one foot may be more sore than the other.
Lameness is usually mild (1–2 on a scale of 5). It can be made worse when the horse is worked on a hard surface or on a circle.
After several months of pain, the feet may begin to change shape, especially the foot that has been experiencing the most pain, which tends to become more upright and narrow.

Treatment and prognosis
No single treatment works for all cases, probably because there is no single cause for all cases. The degenerative changes are usually quite advanced by the time the horse is consistently lame, and these changes are believed to be non-reversible. At this time, it is best to manage the condition and focus on alleviating pain and slowing the degeneration.

Trimming
Putting the foot into proper neurological and biomechanical balance is crucial.  Often navicular horses have long toes and underrun heels with very little inner wall depth or strength.  Exposing the horse to proper stimulus to improve hoof form and structure is also vital.

Hoof care
The issue of hoof care is a subject of great debate. Corrective shoeing can be beneficial to horses suffering from navicular disease, although sometimes the effects are only temporary. Others believe that removing the shoes altogether is the best way to manage this disease, as it allows increased circulation to the hoof.  People on both sides agree that proper hoof shape and angle are an important long-term management plan for a horse with navicular disease.  As with laminitis, different horses may respond in different ways to a given technique, so the farrier, owner, and veterinarian should work as a team to formulate a plan and to adapt if the initial plan is not effective.
People who choose to treat navicular disease through shoeing may use a shoe designed to lift and support the heels.  This can sometimes be accomplished with a flat shoe and trimming alone. Wedge pads or wedged shoes are often used, but can amplify heel-related problems if present. Another strategy is to use a bar type shoe. Often, an egg-bar shoe, or straight bar shoe.  Some horses benefit from shoes that change the breakover of their foot (like a rolled toe). With or without shoes, the hoof must be trimmed in such a way as to restore the balance and angle that may have been lost. Horses with long toe-low heel conformation need careful trimming to counter this. Horses with upright feet may need their heels lowered and a shoe that will allow their heels to spread. Early intervention is key; in one study, shoeing was successful in 97% of horses treated within ten months of the onset of signs, while only 54% of horses lame for over a year responded.Advocates of barefoot trimming cite recent studies which show that removing the shoes can help alleviate the symptoms of navicular disease, and in some cases, reverse some of the damage done to the hoof. Because navicular disease can be caused, or at least exacerbated by shoeing, removing the cause is the first step in this strategy toward the management of pain in the animal. Successive carefully applied trims help to restore the natural angle and shape of the hoof, while walking helps to stimulate circulation to the hoof. It is not uncommon to find horses whose navicular disease is completely manageable through corrective barefoot trimming.  However, this may require a transition period lasting from weeks to years where the horse may remain lame, or may never become sound.If there is significant degeneration in the bone, a flexor cortex cyst, adhesions to the deep digital flexor tendon, or avulsion fractures, relief is typically incomplete no matter what foot care technique is used.

Exercise
Horses with navicular syndrome need a less intense work schedule. Their fitness can be maintained through slow long-distance work or swimming, as opposed to being worked at high speeds, up steep hills, or on hard surfaces, irregular terrain, or deep footing. Reducing the frequency of jumping is also important.  Some veterinarians and hoof care practitioners recommend exercising the horse on varied terrain to stimulate and strengthen the caudal hoof structures.

Medication
Vasodilators improve the blood flow into the vessels of the hoof. Examples include isoxsuprine (currently unavailable in the UK) and pentoxifylline.
Anticoagulants can also improve blood flow. The use of warfarin has been proposed, but the extensive monitoring required makes it unsuitable in most cases.
Anti-inflammatory drugs are used to treat the pain, and can help the lameness resolve sometimes if shoeing and training changes are made. Include Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other joint medications. The use of intramuscular glycosaminoglycans has been shown to decrease pain in horses with navicular disease, but this effect wanes after discontinuation of therapy.  Oral glycosaminoglycans may have a similar effect.Bisphosphonates can be useful in cases where bone remodeling is causing pain.Gallium nitrate (GaN) has been hypothesized as a possible treatment for navicular disease, but its benefits have not been confirmed by formal clinical studies. One pilot study examined horses given gallium nitrate in their feed rations. While it was absorbed slowly, it did stay in the animals system, providing a baseline dosage for future studies.

Surgery
Palmar digital neurectomy (or "nerving" or "denerving") is not without adverse side effects and should therefore be used as a last resort. In this procedure, the palmar digital nerves are severed, so the horse loses sensation in the back of the foot. This procedure should only be performed if it will eliminate the lameness associated with navicular syndrome, and only after all other options have been explored. The procedure is usually performed on both front feet. Complications can include infection of the wound, continuation of the lameness (if the nerves regrow or if small branches of the nerves are not removed), neuromas, and rupture of the deep digital flexor tendon. After the neurectomy, if the horse becomes injured in the area the injury may go undetected for a long period of time, which risks the animals health. Due to this, the feet should be cleaned and inspected regularly. Neurectomy tends to lower the market value of a horse, and may even make the horse ineligible for competition. Neurectomy is controversial.   The most common misconception about "nerving" a horse is that it will permanently solve the lameness/pain issue.  In fact, though the time periods vary based on the individual horse and surgical method utilized, these nerves often regenerate and return sensation to the afflicted region within two to three years.
In navicular suspensory desmotomy, the ligaments supporting the navicular bone are severed. This makes the navicular bone more mobile, and thus reduces the tension of the other ligaments. It is successful about half of the time.

Prognosis
The prognosis for a horse with navicular syndrome is guarded </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Glomerulonephritis and explain in detail? [/INST] Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys).  Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.
As it is not strictly a single disease, its presentation depends on the specific disease entity: it may present with isolated hematuria and/or proteinuria (blood or protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute kidney injury, or chronic kidney disease.
They are categorized into several different pathological patterns, which are broadly grouped into non-proliferative or proliferative types. Diagnosing the pattern of GN is important because the outcome and treatment differ in different types. Primary causes are intrinsic to the kidney. Secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis), or diabetes.

Signs and symptoms
Glomerulonephritis refers to an inflammation of the glomerulus, which is the unit involved in filtration in the kidney. This inflammation typically results in one or both of the nephrotic or nephritic syndromes.: 500

Nephrotic syndrome
The nephrotic syndrome is characterised by the finding of edema in a person with increased protein in the urine and decreased protein in the blood, with increased fat in the blood. Inflammation that affects the cells surrounding the glomerulus, podocytes, increases the permeability to proteins, resulting in an increase in excreted proteins. When the amount of proteins excreted in the urine exceeds the livers ability to compensate, fewer proteins are detected in the blood – in particular albumin, which makes up the majority of circulating proteins. With decreased proteins in the blood, there is a decrease in the oncotic pressure of the blood. This results in edema, as the oncotic pressure in tissue remains the same. Although decreased intravascular oncotic (i.e. osmotic) pressure partially explains the patients edema, more recent studies have shown that extensive sodium retention in the distal nephron (collecting duct) is the predominant cause of water retention and edema in the nephrotic syndrome. This is worsened by the secretion of the hormone aldosterone by the adrenal gland, which is secreted in response to the decrease in circulating blood and causes sodium and water retention. Hyperlipidemia is thought to be a result of the increased activity of the liver.: 549

Nephritic syndrome
The nephritic syndrome is characterised by blood in the urine (especially Red blood cell casts with dysmorphic red blood cells) and a decrease in the amount of urine in the presence of hypertension. In this syndrome, inflammatory damage to cells lining the glomerulus are thought to result in destruction of the epithelial barrier, leading to blood being found in the urine. At the same time, reactive changes, e.g. proliferation of mesangial cells, may result in a decrease in kidney blood flow, resulting in a decrease in the production of urine. The renin–angiotensin system may be subsequently activated, because of the decrease in perfusion of juxtaglomerular apparatus, which may result in hypertension.: 554

Nonproliferative
This is characterised by forms of glomerulonephritis in which the number of cells is not changed. These forms usually result in the nephrotic syndrome. Causes include:

Minimal change disease
Minimal change disease is characterised as a cause of nephrotic syndrome without visible changes in the glomerulus on microscopy. Minimal change disease typically presents with  edema, an increase in proteins passed from urine and decrease in blood protein levels, and an increase in circulating lipids (i.e., nephrotic syndrome) and is the most common cause of the nephrotic syndrome in children. Although no changes may be visible by light microscopy, changes on electron microscopy within the glomeruli may show a fusion of the foot processes of the podocytes (cells lining the basement membrane of the capillaries of glomerulus). It is typically managed with corticosteroids and does not progress to chronic kidney disease.: 500 : 550

Focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis is characterised by a sclerosis of segments of some glomeruli. It is likely to present as a nephrotic syndrome. This form of glomerulonephritis may be associated with conditions such as HIV and heroin abuse, or inherited as Alport syndrome. The cause of about 20–30% of focal-segmental glomerulosclerosis is unknown. On microscopy, affected glomeruli may show an increase in hyalin, a pink and homogenous material, fat cells, an increase in the mesangial matrix and collagen. Treatment may involve corticosteroids, but up to half of people with focal segmental glomerulonephritis continue to have progressive deterioration of kidney function, ending in kidney failure.: 550–551

Membranous glomerulonephritis
Membranous glomerulonephritis may cause either nephrotic or a nephritic picture. About two-thirds are associated with auto-antibodies to phospholipase A2 receptor, but other associations include cancers of the lung and bowel, infections such as hepatitis B and malaria, drugs including penicillamine, and connective tissue diseases such as systemic lupus erythematosus. Individuals with cerebral shunts are at risk of developing shunt nephritis, which frequently produces MGN.Microscopically, MGN is characterized by a thickened glomerular basement membrane without a hyperproliferation of the glomerular cells. Immunofluorescence demonstrates diffuse granular uptake of IgG. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to end-stage kidney failure. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with corticosteroids is attempted if the disease progresses.
In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world.

Thin basement membrane disease
Thin basement membrane disease is an autosomal dominant inherited disease characterized by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent microscopic hematuria. This also may cause proteinuria which is usually mild and overall prognosis is excellent.

Fibronectin glomerulopathy
Fibronectin glomerulopathy is a rare form of glomerulopathy characterised by enlarged glomeruli with deposits in the mesangium and subendothelial space. The deposits have been shown to be fibronectin. This condition is inherited in an autosomal dominant fashion. About 40% of cases are due to mutations in the fibronectin (FN1) gene located on chromosome 2 (2q34).

Proliferative
Proliferative glomerulonephritis is characterised by an increased number of cells in the glomerulus. These forms usually present with a triad of blood in the urine, decreased urine production, and hypertension, the nephritic syndrome. These forms usually progress to end-stage kidney failure (ESKF) over weeks to years (depending on type).

IgA nephropathy
IgA nephropathy, also known as Bergers disease, is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a nephritic syndrome characterised by proteinuria, and visible blood in the urine. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of IgA in the space between glomerular capillaries.: 501 : 554–555 Henoch–Schönlein purpura refers to a form of IgA nephropathy, typically affecting children, characterised by a rash of small bruises affecting the buttocks and lower legs, with abdominal pain.: 501

Post-infectious
Post-infectious glomerulonephritis can occur after essentially any infection, but classically occurs after infection with the bacteria Streptococcus pyogenes. It typically occurs 1–4 weeks after a pharyngeal infection with this bacterium, and is likely to present with malaise, a slight fever, nausea and a mild nephritic syndrome of moderately increased blood pressure, gross haematuria, and smoky-brown urine. Circulating immune complexes that deposit in the glomeruli may lead to an inflammatory reaction. : 554–555 Diagnosis may be made on clinical findings or through antistreptolysin O antibodies found in the blood. A biopsy is seldom done, and the disease is likely to self-resolve in children in 1–4 weeks, with a poorer prognosis if adults are affected or if the affected children are obese. : 501

Membranoproliferative
Membranoproliferative GN (MPGN), also known as mesangiocapillary glomerulonephritis,: 502  is characterised by an increase in the number of cells in the glomerulus, and alterations in the glomerular basement membrane. These forms present with the nephritic syndrome, hypocomplementemia, and have a poor prognosis. Three subtypes have been proposed:: 552–553
Type 1 MPGN is caused by immune complex deposition in the mesangium and subendothelial space, typically secondary to systemic lupus erythematosus, hepatitis B and C, or other chronic or recurring infections. Circulating immune complexes may activate the complement system, leading to inflammation and an influx of inflammatory cells.: 552–553
Type 2 MPGN, also known as Dense Deposit Disease, is characterised by an excessive activation of the complement system. The C3 Nephritic Factor autoantibody stabilizes C3-convertase, which may lead to an excessive activation of complement.: 553  Type 2 MPGN is a subgroup of C3 glomerulopathy, a newly proposed diagnosis which also encompasses C3 Glomerulonephritis (C3GN).
Type 3 MPGN, which is caused by immune complex deposition in the subepithelial space.

Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis, also known as crescentic GN, is characterised by a rapid, progressive deterioration in kidney function. People with rapidly progressive glomerulonephritis may present with a nephritic syndrome. In management, steroid therapy is sometimes used, although the prognosis remains poor. Three main subtypes are recognised:: 557–558
Type 1 is Goodpasture syndrome, an autoimmune disease also affecting the lung </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Thrombophlebitis and explain in detail? [/INST] Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot). When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans (migratory thrombophlebitis).

Signs and symptoms
The following symptoms or signs are often associated with thrombophlebitis, although thrombophlebitis is not restricted to the veins of the legs.
Pain (area affected)
Skin redness/inflammation
Edema
Veins hard and cord-like
Tenderness

Complications
In terms of complications, one of the most serious occurs when the superficial blood clot is associated with a deep vein thrombosis; this can then dislodge, traveling through the heart and occluding the dense capillary network of the lungs This is a pulmonary embolism which can be life-threatening.

Causes
Thrombophlebitis causes include disorders related to increased tendency for blood clotting and reduced speed of blood in the veins such as prolonged immobility; prolonged traveling (sitting) may promote a blood clot leading to thrombophlebitis but this occurs relatively less. High estrogen states such as pregnancy, estrogen replacement therapy, or oral contraceptives are associated with an increased risk of thrombophlebitis.Specific disorders associated with thrombophlebitis include superficial thrombophlebitis which affects veins near the skin surface, deep vein thrombosis which affects deeper veins, and pulmonary embolism.Those with familial clotting disorders such as protein S deficiency, protein C deficiency, or factor V Leiden are also at increased risk of thrombophlebitis. Thrombophlebitis can be found in people with vasculitis including Behçets disease. Thrombophlebitis migrans can be a sign of malignancy – Trousseau sign of malignancy.

Diagnosis
The diagnosis for thrombophlebitis is primarily based on the appearance of the affected area. Frequent checks of the pulse, blood pressure, and temperature may be required. If the cause is not readily identifiable, tests may be performed to determine the cause, including the following:
Doppler ultrasound
Extremity arteriography
Blood coagulation studies (Blood clotting tests)

Prevention
Prevention consists of walking, drinking fluids and if currently hospitalized, changing of IV lines. Walking is especially suggested after a long period seated, particularly when one travels.

Treatment
In terms of treatment for this condition the individual may be advised to do the following: raise the affected area to decrease swelling, and relieve  pressure off of the affected area so it will encounter less pain. In certain circumstances drainage of the clot might be an option. In general, treatment may include the following:

Epidemiology
Thrombophlebitis occurs almost equally between women and men, though males do have a slightly higher possibility </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Dysmenorrhea and explain in detail? [/INST] Dysmenorrhea, also known as painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the pelvis or lower abdomen. Other symptoms may include back pain, diarrhea or nausea.Dysmenorrhea can occur without an underlying problem. Underlying issues that can cause dysmenorrhea include uterine fibroids, adenomyosis, and most commonly, endometriosis. It is more common among those with heavy periods, irregular periods, those whose periods started before twelve years of age and those who have a low body weight. A pelvic exam and ultrasound in individuals who are sexually active may be useful for diagnosis. Conditions that should be ruled out include ectopic pregnancy, pelvic inflammatory disease, interstitial cystitis and chronic pelvic pain.Dysmenorrhea occurs less often in those who exercise regularly and those who have children early in life. Treatment may include the use of a heating pad. Medications that may help include NSAIDs such as ibuprofen, hormonal birth control and the IUD with progestogen. Taking vitamin B1 or magnesium may help. Evidence for yoga, acupuncture and massage is insufficient. Surgery may be useful if certain underlying problems are present.Estimates of the percentage of women of reproductive age affected vary from 20% to 90%. It is the most common menstrual disorder. Typically, it starts within a year of the first menstrual period. When there is no underlying cause, often the pain improves with age or following having a child.

Signs and symptoms
The main symptom of dysmenorrhea is pain concentrated in the lower abdomen or pelvis. It is also commonly felt in the right or left side of the abdomen. It may radiate to the thighs and lower back.Symptoms often co-occurring with menstrual pain include nausea and vomiting, diarrhea, headache, dizziness, disorientation, fainting and fatigue. Symptoms of dysmenorrhea often begin immediately after ovulation and can last until the end of menstruation. This is because dysmenorrhea is often associated with changes in hormonal levels in the body that occur with ovulation. In particular, prostaglandins induce abdominal contractions that can cause pain and gastrointestinal symptoms. The use of certain types of birth control pills can prevent the symptoms of dysmenorrhea because they stop ovulation from occurring.
Dysmenorrhea is associated with increased pain sensitivity and heavy menstrual bleeding.For many women, primary dysmenorrhea gradually subsides in late second generation. Pregnancy has also been demonstrated to lessen the severity of dysmenorrhea, when menstruation resumes. However, dysmenorrhea can continue until menopause. 5–15% of women with dysmenorrhea experience symptoms severe enough to interfere with daily activities.

Causes
Dysmenorrhea can be classified as either primary or secondary based on the absence or presence of an underlying cause. Primary dysmenorrhea occurs without an associated underlying condition, while secondary dysmenorrhea has a specific underlying cause, typically a condition that affects the uterus or other reproductive organs.Painful menstrual cramps that result from an excess of prostaglandin release are referred to as primary dysmenorrhea. Primary dysmenorrhea usually begins within a year or two of menarche, typically with the onset of ovulatory cycles. Perimenstrual pain is often included as a component of premenstrual syndrome (PMS).
Secondary dysmenorrhea is the diagnosis given when menstruation pain is a secondary cause to another disorder. Conditions causing secondary dysmenorrhea include endometriosis, uterine fibroids, uterine adenomyosis, and polycystic ovary syndrome. Rarely, congenital malformations, intrauterine devices, certain cancers, and pelvic infections cause secondary dysmenorrhea. If the pain occurs between menstrual periods, lasts longer than the first few days of the period, or is not adequately relieved by the use of non-steroidal anti-inflammatory drugs (NSAIDs) or hormonal contraceptives, this could be a sign for secondary causes of dysmenorrhea.When laparoscopy is used for diagnosis, the most common cause of dysmenorrhea is endometriosis, in approximately 70% of adolescents.Other causes of secondary dysmenorrhea include leiomyoma, adenomyosis, ovarian cysts, pelvic congestion, and cavitated and accessory uterine mass.

Risk factors
Genetic factors, stress and depression are risk factors for dysmenorrhea. Risk factors for primary dysmenorrhea include: early age at menarche, long or heavy menstrual periods, smoking, and a family history of dysmenorrhea.Dysmenorrhea is a highly polygenic and heritable condition. There is strong evidence of familial predisposition and genetic factors increasing susceptibility to dysmenorrhea. There have been multiple polymorphisms and genetic variants in both metabolic genes and genes responsible for immunity which have been associated with the disorder.Three distinct possible phenotypes have been identified for dysmenorrhea which include "multiple severe symptoms", "mild localized pain", and "severe localized pain". While there are likely differences in genotypes underlying each phenotype, the specific correlating genotypes have not yet been identified. These phenotypes are prevalent at different levels in different population demographics, suggesting different allelic frequencies across populations (in terms of race, ethnicity, and nationality).Polymorphisms in the ESR1 gene have been commonly associated with severe dysmenorrhea. Variant genotypes in the metabolic genes such as CYP2D6 and GSTM1 have been similarly been correlated with an increased risk of severe menstrual pain, but not with moderate or occasional phentoypes.The occurrence and frequency of secondary dysmenorrhea (SD) has been associated with different alleles and genotypes of those with underlying pathologies, which can affect the pelvic region or other areas of the body. Individuals with disorders may have genetic mutations related to their diagnoses which produce dysmenorrhea as a symptom of their primary diagnosis. It has been found that those with fibromyalgia who have the ESR1 gene variation Xbal and possess the Xbal AA genotype are more susceptible to experiencing mild to severe menstrual pain resulting from their primary pathology. Commonly, genetic mutations which are a hallmark of or associated with specific disorders can produce dysmenorrhea as a symptom which accompanies the primary disorder.
In contrast with secondary dysmenorrhea, primary dysmenorrhea (PD) has no underlying pathology. Genetic mutation and variations have therefore been thought to underlie this disorder and contribute to the pathogenesis of PD. There are multiple single-nucleotide polymorphisms (SNP) associated with PD. Two of the most well studied include an SNP in the promoter of MIF and an SNP in the tumor necrosis factor (TNF-α) gene. When a cytosine 173 base pairs upstream of macrophage migration inhibitory factor (MIF) promoter was replaced by a guanine there was an associated increase in the likelihood of the individual experiencing PD. While a CC/GG genotype led to an increase in likelihood of the individual experiencing severe menstrual pain, a CC/GC genotype led to a more significant likelihood of the disorder impacting the individual overall and increasing the likelihood of any of the three phenotypes. A second associated SNP was located 308 base pairs upstream from the start codon of the TNF-α gene, in which guanine was substituted for adenine. A GG genotype at the loci is associated with the disorder and has been proposed as a possible genetic marker to predict PD.There has also been an association with mutations in the MEFV gene and dysmenorrhea, which are considered to be causative. The phenotypes associated with these mutations in the MEFV genes have been better studied; individuals who are heterozygous for these mutations are more likely to be affected by PD which presents as a severe pain phenotype.Genes related to immunity have been identified as playing a significant role in PD as well. IL1A was found to be the gene most associated with primary dysmenorrhea in terms of its phenotypic impact. This gene encodes a protein essential for the regulation of immunity and inflammation.15 While the mechanism of how it influences PD has yet to be discovered, it is assumed that possible mutations in IL1A or genes which interact with it impact the regulation of inflammation during menstruation. These mutations may therefore affect pain responses during menstruation which lead to the differing phenotypes associated with dysmenorrhea.
Two additionally well studied SNPs which are suspected to contribute to PD were found in ZM1Z1 (the mutant allele called rs76518691) and NGF (the mutant allele called rs7523831). Both ZMIZ1 and NGF are associated with autoimmune responses and diseases, as well as pain response. The implication of these genes impacting Dysmenorrhea is significant as it suggests mutations which affect the immune system (specifically the inflammatory response) and pain response may also be a cause of primary dysmenorrhea.

Mechanism
The underlying mechanism of primary dysmenorrhea is the contractions of the muscles of the uterus which induce a local ischemia.During an individuals menstrual cycle, the endometrium thickens in preparation for potential pregnancy. After ovulation, if the ovum is not fertilized and there is no pregnancy, the built-up uterine tissue is not needed and thus shed.
Prostaglandins and leukotrienes are released during menstruation, due to the build up of omega-6 fatty acids. Release of prostaglandins and other inflammatory mediators in the uterus cause the uterus to contract and can result in systemic symptoms such as nausea, vomiting, bloating and headaches or migraines. Prostaglandins are thought to be a major factor in primary dysmenorrhea. When the uterine muscles contract, they constrict the blood supply to the tissue of the endometrium, which, in turn, breaks down and dies. These uterine contractions continue as they squeeze the old, dead endometrial tissue through the cervix and out of the body through the vagina. These contractions, and the resulting temporary oxygen deprivation to nearby tissues, are thought to be responsible for the pain or cramps experienced during menstruation.
Compared with non-dysmnenorrhic individuals, those with primary dysmenorrhea have increased activity of the uterine muscle with increased contractility and increased frequency of contractions.

Diagnosis
The diagnosis of dysmenorrhea is usually made simply on a medical history of menstrual pain that interferes with daily activities. However, there is no universally accepted standard technique for quantifying the severity of menstrual pains. There are various quantification models, called menstrual symptometrics, that can be used to estimate the severity of menstrual pains as well as correlate them with pain in other parts of the body, menstrual bleeding and degree of interference with daily activities.

Further work-up
Once a diagnosis of dysmenorrhea is made, further workup is required to search for any secondary underlying cause of it, in order to be able to treat it specifically and to avoid the aggravation of a perhaps serious underlying cause.
Further work-up includes a specific medical history of symptoms and menstrual cycles and a pelvic examination. Based on results from these, additional exams and tests may be motivated, such as:

Gynecologic ultrasonography
Laparoscopy

Management
Treatments that target the mechanism of pain include non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives. NSAIDs inhibit prostaglandin production. With long-term treatment, hormonal birth control reduces the amount of uterine fluid/tissue expelled from the uterus. Thus resulting in shorter, less painful menstruation. These drugs are typically more effective than treatments that do not target the source of the pain (e.g. acetaminophen). Regular physical activity may limit the severity of uterine cramps.

NSAIDs
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen are effective in relieving the pain of primary dysmenorrhea.
They can have side effects of nausea, dyspepsia, peptic ulcer, and diarrhea.

Hormonal birth control
Use of hormonal birth control may improve symptoms of primary dysmenorrhea. A 2009 systematic review found limited evidence that the low or medium doses of estrogen contained in the birth control pill reduces pain associated with dysmenorrhea. In addition, no differences between different birth control pill preparations were found.Norplant and Depo-provera are also effective, since these methods often induce amenorrhea. The intrauterine system (Mirena IUD) may be useful in reducing symptoms.

Other
A review indicated the effectiveness of transdermal nitroglycerin.
Reviews indicated magnesium supplementation seemed to be effective.
A review indicated the usefulness of using calcium channel blockers.
Heat is effective compared to NSAIDs and is a preferred option by many patients, as it is easy to access and has no known side effects.Tamoxifen has been used effectively to reduce uterine contractility and pain in dysmenorrhea patients.There is some evidence that exercises performed 3 times a week for about 45 to 60 minutes, without particular intensity, reduces menstrual pain.

Alternative medicine
There is insufficient evidence to recommend the use of many herbal or dietary supplements for treating dysmenorrhea, including melatonin, vitamin E, fennel, dill, chamomile, cinnamon, damask rose, rhubarb, guava, and uzara.  Further research is recommended to follow up on weak evidence of benefit for: fenugreek, ginger, valerian, zataria, zinc sulphate, fish oil, and vitamin B1. A 2016 review found that evidence of safety is insufficient for most dietary supplements. There is some evidence for the use of fenugreek.One review found thiamine and vitamin E to be likely effective. It found the effects of fish oil and vitamin B12 to be unknown. Reviews found tentative evidence that ginger powder may be effective for primary dysmenorrhea. Reviews have found promising evidence for Chinese herbal medicine for primary dysmenorrhea, but that the evidence was limited by its poor methodological quality.A 2016 Cochrane review of acupuncture for dysmenorrhea concluded that it is unknown if acupuncture or acupressure is effective. There were also concerns of bias in study design and in publication, insufficient reporting (few looked at adverse effects), and that they were inconsistent. There are conflicting reports in the literature, including one review which found that acupressure, topical heat, and behavioral interventions are likely effective. It found the effect of acupuncture and magnets to be unknown.A 2007 systematic review found some scientific evidence that behavioral interventions may be effective, but that the results should be viewed with caution due to poor quality of the data.Spinal manipulation does not appear to be helpful </s>