<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 Coronary artery disease and explain in detail? [/INST] Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat.Risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, and excessive alcohol consumption. A number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, coronary computed tomographic angiography, and coronary angiogram, among others.Ways to reduce CAD risk include eating a healthy diet, regularly exercising, maintaining a healthy weight, and not smoking. Medications for diabetes, high cholesterol, or high blood pressure are sometimes used. There is limited evidence for screening people who are at low risk and do not have symptoms. Treatment involves the same measures as prevention. Additional medications such as antiplatelets (including aspirin), beta blockers, or nitroglycerin may be recommended. Procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be used in severe disease. In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improves life expectancy or decreases heart attack risk.In 2015, CAD affected 110 million people and resulted in 8.9 million deaths. It makes up 15.6% of all deaths, making it the most common cause of death globally. The risk of death from CAD for a given age decreased between 1980 and 2010, especially in developed countries. The number of cases of CAD for a given age also decreased between 1990 and 2010. In the United States in 2010, about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45; rates were higher among men than women of a given age.

Signs and symptoms
The narrowing of coronary arteries reduces the supply of oxygen-rich blood flowing to the heart, which becomes more pronounced during strenuous activities during which the heart beats faster. For some, this causes severe symptoms, while others experience no symptoms at all.The most common symptom is chest pain or discomfort that occurs regularly with activity, after eating, or at other predictable times; this phenomenon is termed stable angina and is associated with narrowing of the arteries of the heart. Angina also includes chest tightness, heaviness, pressure, numbness, fullness, or squeezing. Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction. In adults who go to the emergency department with an unclear cause of pain, about 30% have pain due to coronary artery disease. Angina, shortness of breath, sweating, nausea or vomiting, and lightheadedness are signs of a heart attack, or myocardial infarction, and immediate emergency medical services are crucial.

Symptoms in women
Symptoms in women can differ from those in men, and the most common symptom reported by women of all races is shortness of breath. Other symptoms more commonly reported by women than men are extreme fatigue, sleep disturbances, indigestion, and anxiety. However, some women do experience irregular heartbeat, dizziness, sweating, and nausea. Burning, pain, or pressure in the chest or upper abdomen that can travel to the arm or jaw can also be experienced in women, but it is less commonly reported by women than men. On average, women experience symptoms 10 years later than men. Women are less likely to recognize symptoms and seek treatment.

Risk factors
Coronary artery disease has a number of well determined risk factors. Some of these include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, family history, psychological stress and excessive alcohol. About half of cases are linked to genetics. Smoking and obesity are associated with about 36% and 20% of cases, respectively. Smoking just one cigarette per day about doubles the risk of CAD. Lack of exercise has been linked to 7–12% of cases. Exposure to the herbicide Agent Orange may increase risk. Rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and psoriatic arthritis are independent risk factors as well.Job stress appears to play a minor role accounting for about 3% of cases. In one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. In contrast, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. Having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience, is linked to an increased risk of coronary disease.

Blood fats
High blood cholesterol (specifically, serum LDL concentrations; also referred to as LDL-C to denote low-density lipoprotien cholesterol). HDL (high density lipoprotein) has a protective effect over development of coronary artery disease.
High blood triglycerides may play a role.
High levels of lipoprotein(a), a compound formed when LDL cholesterol combines with a protein known as apolipoprotein(a).Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed. Saturated fat is still a concern.

Genetics
The heritability of coronary artery disease has been estimated between 40% and 60%. Genome-wide association studies have identified over 160 genetic susceptibility loci for coronary artery disease.

Other
Endometriosis in women under the age of 40.
Depression and hostility appear to be risks.
The number of categories of adverse childhood experiences (psychological, physical, or sexual abuse; violence against mother; or living with household members who used substances, mentally ill, suicidal, or incarcerated) showed a graded correlation with the presence of adult diseases including coronary artery (ischemic heart) disease.
Hemostatic factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD.
Low hemoglobin.
In the Asian population, the b fibrinogen gene G-455A polymorphism was associated with the risk of CAD.

Pathophysiology
Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the hearts muscle cells. The hearts muscle cells may die from lack of oxygen and this is called a myocardial infarction (commonly referred to as a heart attack). It leads to damage, death, and eventual scarring of the heart muscle without regrowth of heart muscle cells. Chronic high-grade narrowing of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into a dangerous heart rhythm known as ventricular fibrillation, which often leads to death.Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis, the arterys lining becomes hardened, stiffened, and accumulates deposits of calcium, fatty lipids, and abnormal inflammatory cells – to form a plaque. Calcium phosphate (hydroxyapatite) deposits in the muscular layer of the blood vessels appear to play a significant role in stiffening the arteries and inducing the early phase of coronary arteriosclerosis. This can be seen in a so-called metastatic mechanism of calciphylaxis as it occurs in chronic kidney disease and hemodialysis. Although these people have kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing partial obstruction to blood flow. People with coronary artery disease might have just one or two plaques, or might have dozens distributed throughout their coronary arteries. A more severe form is chronic total occlusion (CTO) when a coronary artery is completely obstructed for more than 3 months.Cardiac syndrome X is chest pain (angina pectoris) and chest discomfort in people who do not show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary angiogram) is being performed. The exact cause of cardiac syndrome X is unknown. Explanations include microvascular dysfunction or epicardial atherosclerosis. For reasons that are not well understood, women are more likely than men to have it; however, hormones and other risk factors unique to women may play a role.

Diagnosis
For symptomatic people, stress echocardiography can be used to make a diagnosis for obstructive coronary artery disease. The use of echocardiography, stress cardiac imaging, and/or advanced non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.The diagnosis of "Cardiac Syndrome X" – the rare coronary artery disease that is more common in women, as mentioned, is a diagnosis of exclusion. Therefore, usually, the same tests are used as in any person with the suspected of having coronary artery disease:
Baseline electrocardiography (ECG)
Exercise ECG – Stress test
Exercise radioisotope test (nuclear stress test, myocardial scintigraphy)
Echocardiography (including stress echocardiography)
Coronary angiography
Intravascular ultrasound
Magnetic resonance imaging (MRI)The diagnosis of coronary disease underlying particular symptoms depends largely on the nature of the symptoms. The first investigation is an electrocardiogram (ECG/EKG), both for "stable" angina and acute coronary syndrome. An X-ray of the chest and blood tests may be performed.

Stable angina
In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various forms of cardiac stress tests may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery.Stable coronary artery disease (SCAD) is also often called stable ischemic heart disease (SIHD). A 2015 monograph explains that "Regardless of the nomenclature, stable angina is the chief manifestation of SIHD or SCAD." There are U.S. and European clinical practice guidelines for SIHD/SCAD.

Acute coronary syndrome
Diagnosis of acute coronary syndrome generally takes place in the emergency department, where ECGs may be performed sequentially to identify "evolving changes" (indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show elevation of the "ST segment", which in the context of severe typical chest pain is strongly indicative of an acute myocardial infarction (MI); this is termed a STEMI (ST-elevation MI) and is treated as an emergency with either urgent coronary angiography and percutaneous coronary intervention (angioplasty with or without stent insertion) or with thrombolysis ("clot buster" medication), whichever is available. In the absence of ST-segment elevation, heart damage is detected by cardiac markers (blood tests that identify heart muscle damage). If there is evidence of damage (infarction), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI). If there is no evidence of damage, the term "unstable angina" is used. This process usually necessitates hospital admission and close observation on a coronary care unit for possible complications (such as cardiac arrhythmias – irregularities in the heart rate). Depending on the risk assessment, stress testing or angiography may be used to identify and treat coronary artery disease in patients who have had an NSTEMI or unstable angina.

Risk assessment
There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking, and systolic blood pressure. When it comes to predicting risk in younger adults (18–39 years old), Framingham Risk Score remains below 10-12% for all deciles of baseline-predicted risk.Polygenic score is another way of risk assessment. In one study the relative risk of incident coronary events was 91% higher among participants at high genetic risk than among those at low genetic risk.

Prevention
Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Prevention involves adequate physical exercise, decreasing obesity, treating high blood pressure, eating a healthy diet, decreasing cholesterol levels, and stopping smoking. Medications and exercise are roughly equally effective. High levels of physical activity reduce the risk of coronary artery disease by about 25%. Life’s Essential 8 are the key measures for improving and maintaining cardiovascular health, as defined by the American Heart Association. AHA added sleep as a factor influencing heart health in 2022.Most guidelines recommend combining these preventive strategies. A 2015 Cochrane Review found some evidence that counseling and education to bring about behavioral change might help in high-risk groups. However, there was insufficient evidence to show an effect on mortality or actual cardiovascular events.In diabetes mellitus, there is little evidence that very tight blood sugar control improves cardiac risk although improved sugar control appears to decrease other problems such as kidney failure and blindness. The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease while high intake increases the risk.

Diet
A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. Vegetarians have a lower risk of heart disease, possibly due to their greater consumption of fruits and vegetables. Evidence also suggests that the Mediterranean diet and a high fiber diet lower the risk.The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause a precursor to atherosclerosis and increase the risk of coronary artery disease.Evidence does not support a beneficial role for omega-3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death). There is tentative evidence that intake of menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), may reduce the risk of CAD mortality.

Secondary prevention
Secondary prevention is preventing further sequelae of already established disease. Effective lifestyle changes include:

Weight control
Smoking cessation
Avoiding the consumption of trans fats (in partially hydrogenated oils)
Decreasing psychosocial stress
ExerciseAerobic exercise, like walking, jogging, or swimming, can reduce the risk of mortality from coronary artery disease. Aerobic exercise can help decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also increases HDL cholesterol.Although exercise is beneficial, it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force found "insufficient evidence" to recommend that doctors counsel patients on exercise but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity, and mortality", only the effectiveness of counseling itself. The American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise.Psychological symptoms are common in people with CHD, and while many psychological treatments may be offered following cardiac events, there is no evidence that they change mortality, the risk of revascularization procedures, or the rate of non-fatal myocardial infarction.Antibiotics for secondary prevention of coronary heart disease
Antibiotics may help patients with coronary disease to reduce the risk of heart attacks and strokes. However, the latest evidence suggests that antibiotics for secondary prevention of coronary heart disease are harmful with increased mortality and occurrence of stroke. So, the use of antibiotics is not currently supported for preventing secondary coronary heart disease.

Neuropsychological Assessment
A thorough systematic review found that indeed there is a link between a CHD condition and brain dysfunction in females/women. Consequently, since research is showing that cardiovascular diseases, like CHD, can play a role as a precursor for dementia, like Alzheimers disease, individuals with CHD should have a neuropsychological assessment.

Treatment
There are a number of treatment options for coronary artery disease:
Lifestyle changes
Medical treatment – commonly prescribed drugs (e.g., cholesterol lowering medications, beta-blockers, nitroglycerin, calcium channel blockers, etc.);
Coronary interventions as angioplasty and coronary stent;
Coronary artery bypass grafting (CABG)

Medications
Statins, which reduce cholesterol, reduce the risk of coronary artery disease
Nitroglycerin
Calcium channel blockers and/or beta-blockers
Antiplatelet drugs such as aspirinIt is recommended that blood pressure typically be reduced to less than 140/90 mmHg. The diastolic blood pressure however should not be lower than 60 mmHg. Beta blockers are recommended first line for this use.

Aspirin
In those with no previous history of heart disease, aspirin decreases the risk of a myocardial infarction but does not change the overall risk of death. It is thus recommended only in adults who are at increased risk for coronary artery disease where increased risk is defined as "men older than 90 years of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for example, hypertension, diabetes, or smoking) who are at increased risk for heart disease and may wish to consider aspirin therapy". More specifically, high-risk persons are "those with a 5-year risk ≥ 3%".

Anti-platelet therapy
Clopidogrel plus aspirin (dual anti-platelet therapy) reduces cardiovascular events more than aspirin alone in those with a STEMI. In others at high risk but not having an acute event, the evidence is weak. Specifically, its use does not change the risk of death in this group. In those who have had a stent, more than 12 months of clopidogrel plus aspirin does not affect the risk of death.

Surgery
Revascularization for acute coronary syndrome has a mortality benefit. Percutaneous revascularization for stable ischaemic heart disease does not appear to have benefits over medical therapy alone. In those with disease in more than one artery, coronary artery bypass grafts appear better than percutaneous coronary interventions. Newer "anaortic" or no-touch off-pump coronary artery revascularization techniques have shown reduced postoperative stroke rates comparable to percutaneous coronary intervention. Hybrid coronary revascularization has also been shown to be a safe and feasible procedure that may offer some advantages over conventional CABG though it is more expensive.

Epidemiology
As of 2010, CAD was the leading cause of death globally resulting in over 7 million deaths. This increased from 5.2 million deaths from CAD worldwide in 1990. It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life. Males are affected more often than females.It is estimated that 60% of the worlds cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the worlds population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the Indian Heart Association are working with the World Heart Federation to raise awareness about this issue.Coronary artery disease is the leading cause of death for both men and women and accounts for approximately 600,000 deaths in the United States every year. According to present trends in the United States, half of healthy 40-year-old men will develop CAD in the future, and one in three healthy 40-year-old women. It is the most common reason for death of men and women over 20 years of age in the United States.

Society and culture
Names
Other terms sometimes used for this condition are "hardening of the arteries" and "narrowing of the arteries". In Latin it is known as morbus ischaemicus cordis (MIC).

Support groups
The Infarct Combat Project (ICP) is an international nonprofit organization founded in 1998 which tries to decrease ischemic heart diseases through education and research.

Industry influence on research
In 2016 research into the archives of theSugar Association, the trade association for the sugar industry in the US, had sponsored an influential literature review published in 1965 in the New England Journal of Medicine that downplayed early findings about the role of a diet heavy in sugar in the development of CAD and emphasized the role of fat; that review influenced decades of research funding and guidance on healthy eating.

Research
Research efforts are focused on new angiogenic treatment modalities and various (adult) stem-cell therapies </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 Multiple endocrine neoplasia type 2 and explain in detail? [/INST] Multiple endocrine neoplasia type 2 (also known as "Pheochromocytoma and amyloid producing medullary thyroid carcinoma", "PTC syndrome," and "Sipple syndrome") is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer).  They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine.MEN2 is a sub-type of MEN (multiple endocrine neoplasia) and itself has sub-types, as discussed below.

Signs and symptoms
MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings. Medullary thyroid carcinoma (MTC) represents the most frequent initial diagnosis. Occasionally pheochromocytoma or primary hyperparathyroidism may be the initial diagnosis.Pheochromocytoma occurs in 33-50% of MEN2 cases. In MEN2A, primary hyperparathyroidism occurs in 10–50% of cases and is usually diagnosed after the third decade of life. Rarely, it may present in childhood or be the sole clinical manifestation of this syndrome.MEN2A associates medullary thyroid carcinoma with pheochromocytoma in about 20–50% of cases and with primary hyperparathyroidism in 5–20% of cases. MEN2B associates medullary thyroid carcinoma with pheochromocytoma in 50% of cases, with marfanoid habitus and with mucosal and digestive neurofibromatosis.In familial isolated medullary thyroid carcinoma the other components of the disease are absent.
In a review of 85 patients 70 had MEN2A and 15 had MEN2B. The initial manifestation of MEN2 was medullary thyroid carcinoma in 60% of patients, medullary thyroid carcinoma synchronous with pheochromocytoma in 34% and pheochromocytoma alone in 6%. 72% had bilateral pheochromocytomas.

Causes
The table in the multiple endocrine neoplasia article lists the genes involved in the various MEN syndromes.  Most cases of MEN2 derive from a variation in the RET proto-oncogene, and are specific for cells of neural crest origin.  A database of MEN-implicated RET mutations is maintained by the University of Utah Department of Physiology.The protein produced by the RET gene plays an important role in the TGF-beta (transforming growth factor beta) signaling system.  Because the TGF-beta system operates in nervous tissues throughout the body, variations in the RET gene can have effects in nervous tissues throughout the body. MEN2 generally results from a gain-of-function variant of a RET gene.  Other diseases, such as Hirschsprung disease, result from loss-of-function variants.  OMIM # 164761 lists the syndromes associated with the RET gene.

Genetics
When inherited, multiple endocrine neoplasia type 2 is transmitted in an autosomal dominant pattern, which means affected people have one affected parent, and possibly affected siblings and children </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 Dependent personality disorder and explain in detail? [/INST] Dependent personality disorder (DPD) is characterized by a pervasive psychological dependence on other people. This personality disorder is a long-term condition in which people depend on others to meet their emotional and physical needs, with only a minority achieving normal levels of independence. Dependent personality disorder is a cluster C personality disorder, which is characterized by excessive fear and anxiety. It begins prior to early adulthood, and it is present in a variety of contexts and is associated with inadequate functioning. Symptoms can include anything from extreme passivity, devastation or helplessness when relationships end, avoidance of responsibilities and severe submission.

Signs and symptoms
People who have dependent personality disorder are overdependent on other people when it comes to making decisions. They cannot make a decision on their own as they need constant approval from other people. Consequently, individuals diagnosed with DPD tend to place needs and opinions of others above their own as they do not have the confidence to trust their decisions. This kind of behaviour can explain why people with DPD tend to show passive and clingy behaviour. These individuals display a fear of separation and cannot stand being alone. When alone, they experience feelings of isolation and loneliness due to their overwhelming dependence on other people. Generally people with DPD are also pessimistic: they expect the worst out of situations or believe that the worst will happen. They tend to be more introverted and are more sensitive to criticism and fear rejection.

Risk factors
People with a history of neglect and an abusive upbringing are more susceptible to develop DPD, specifically those involved in long-term abusive relationships. Those with overprotective or authoritarian parents are also more at risk to develop DPD. Having a family history of anxiety disorder can play a role in the development of DPD as a 2004 twin study found a 0.81 heritability for personality disorders collectively.

Causes
The exact cause of dependent personality disorder is unknown. A study in 2012 estimated that between 55% and 72% of the risk of the condition is inherited from ones parents. The difference between a "dependent personality" and a "dependent personality disorder" is somewhat subjective, which makes diagnosis sensitive to cultural influences such as gender role expectations.
Dependent traits in children tended to increase with parenting behaviours and attitudes characterized by overprotectiveness and authoritarianism. Thus the likelihood of developing dependent personality disorder increased, since these parenting traits can limit them from developing a sense of autonomy, rather teaching them that others are powerful and competent.Traumatic or adverse experiences early in an individuals life, such as neglect and abuse or serious illness, can increase the likelihood of developing personality disorders, including dependent personality disorder, later on in life. This is especially prevalent for those individuals who also experience high interpersonal stress and poor social support.There is a higher frequency of the disorder seen in women than men, hence expectations relating to gender role may contribute to some extent.

Diagnosis
Clinicians and clinical researchers conceptualize dependent personality disorder in terms of four related components:

Cognitive: a perception of oneself as powerless and ineffectual, coupled with the belief that other people are comparatively powerful and potent.
Motivational: a desire to obtain and maintain relationships with protectors and caregivers.
Behavioral: a pattern of relationship-facilitating behavior designed to strengthen interpersonal ties and minimize the possibility of abandonment and rejection.
Emotional: fear of abandonment, fear of rejection, and anxiety regarding evaluation by figures of authority.

American Psychiatric Association and DSM
The Diagnostic and Statistical Manual of Mental Disorders (DSM) contains a dependent personality disorder diagnosis. It refers to a pervasive and excessive need to be taken care of which leads to submissive and clinging behavior and fears of separation. This begins prior to early adulthood and can be present in a variety of contexts.In the DSM Fifth Edition (DSM-5), there is one criterion by which there are eight features of dependent personality disorder. The disorder is indicated by at least five of the following factors:
Has difficulty making everyday decisions without an excessive amount of advice and reassurance from others.
Needs others to assume responsibility for most major areas of their life.
Has difficulty expressing disagreement with others because of fear of loss of support or approval.
Has difficulty initiating projects or doing things on their own (because of a lack of self confidence in judgment or abilities rather than a lack of motivation or energy).
Goes to excessive lengths to obtain nurturance and support from others, to the point of volunteering to do things that are unpleasant.
Feels uncomfortable or helpless when alone because of exaggerated fears of being unable to care for themselves.
Urgently seeks another relationship as a source of care and support when a close relationship ends.
Is unrealistically preoccupied with fears of being left to take care of themselves.The diagnosis of personality disorders in the fourth edition Diagnostic and Statistical Manual of Mental Disorders, including dependent personality disorder, was found to be problematic due to reasons such as excessive diagnostic comorbidity, inadequate coverage, arbitrary boundaries with normal psychological functioning, and heterogeneity among individuals within the same categorial diagnosis.

World Health Organization
The World Health Organizations ICD-10 lists dependent personality disorder as F60.7 Dependent personality disorder:
It is characterized by at least 4 of the following:
Encouraging or allowing others to make most of ones important life decisions;
Subordination of ones own needs to those of others on whom one is dependent, and undue compliance with their wishes;
Unwillingness to make even reasonable demands on the people one depends on;
Feeling uncomfortable or helpless when alone, because of exaggerated fears of inability to care for oneself;
Preoccupation with fears of being abandoned by a person with whom one has a close relationship, and of being left to care for oneself;
Limited capacity to make everyday decisions without an excessive amount of advice and reassurance from others.Associated features may include perceiving oneself as helpless, incompetent, and lacking stamina.
Includes:

Asthenic, inadequate, passive, and self-defeating personality (disorder)
It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.

SWAP-200
The SWAP-200 is a diagnostic tool that was proposed with the goal of overcoming limitations, such as limited external validity for the diagnostic criteria for dependent personality disorder, to the DSM. It serves as a possible alternative nosological system that emerged from the efforts to create an empirically based approach to personality disorders – while also preserving the complexity of clinical reality. Dependent personality disorder is considered a clinical prototype in the context of the SWAP-200. Rather than discrete symptoms, it provides composite description characteristic criteria – such as personality tendencies.Based on the Q-Sort method and prototype matching, the SWAP-200 is a personality assessment procedure relying on an external observers judgment. It provides:

A personality diagnosis expressed as the matching with ten prototypical descriptions of DSM-IV personality disorders.
A personality diagnosis based on the matching of the patient with 11 Q-factors of personality derived empirically.
A dimensional profile of healthy and adaptive functioning.The traits that define dependent personality disorder according to SWAP-200 are:

They tend to become attached quickly and/or intensely, developing feelings and expectations that are not warranted by the history or context of the relationship.
Since they tend to be ingratiating and submissive, people with DPD tend to be in relationships in which they are emotionally or physically abused.
They tend to feel ashamed, inadequate, and depressed.
They also feel powerless and tend to be suggestible.
They are often anxious and tend to feel guilty.
These people have difficulty acknowledging and expressing anger and struggle to get their own needs and goals met.
Unable to soothe or comfort themselves when distressed, they require involvement of another person to help regulate their emotions.

Psychodynamic Diagnostic Manual
The Psychodynamic Diagnostic Manual (PDM) approaches dependent personality disorder in a descriptive, rather than prescriptive sense and has received empirical support. The Psychodynamic Diagnostic Manual includes two different types of dependent personality disorder:
Passive-aggressive
Counter-dependent The PDM-2 adopts and applies a prototypic approach, using empirical measures like the SWAP-200. It was influenced by a developmental and empirically grounded perspective, as proposed by Sidney Blatt. This model is of particular interest when focusing on dependent personality disorder, claiming that psychopathology comes from distortions of two main coordinates of psychological development:

The anaclitic/introjective dimension.
The relatedness/self-definition dimension.The anaclitic personality organization in individuals exhibits difficulties in interpersonal relatedness, exhibiting the following behaviours:

Preoccupation with relationships
Fear of abandonment and of rejection
Seeking closeness and intimacy
Difficulty managing interpersonal boundaries
Tend to have an anxious-preoccupied attachment style.Introjective personality style is associated with problems in self-definition.

Differential diagnosis
There are similarities between individuals with dependent personality disorder and individuals with borderline personality disorder, in that they both have a fear of abandonment. Those with dependent personality disorder do not exhibit impulsive behaviour, unstable affect, and poor self-image experienced by those with borderline personality disorder, differentiating the two disorders.

Treatment
People who have DPD are generally treated with psychotherapy. The main goal of this therapy is to make the individual more independent and help them form healthy relationships with the people around them. This is done by improving their self-esteem and confidence.Medication can be used to treat patients with depression or anxiety because of their DPD, but this does not treat the core problems caused by DPD.

Epidemiology
Based on a recent survey of 43,093 Americans, 0.49% of adults meet diagnostic criteria for DPD (National Epidemiologic Survey on Alcohol and Related Conditions; NESARC; Grant et al., 2004).
Traits related to DPD, like most personality disorders, emerge in childhood or early adulthood. Findings from the NESArC study found that 18 to 29 year olds have a greater chance of developing DPD. DPD is more common among women compared to men as 0.6% of women have DPD compared to 0.4% of men.A 2004 twin study suggests a heritability of 0.81 for developing dependent personality disorder. Because of this, there is significant evidence that this disorder runs in families.Children and adolescents with a history of anxiety disorders and physical illnesses are more susceptible to acquiring this disorder.

Millons subtypes
Psychologist Theodore Millon identified five adult subtypes of dependent personality disorder. Any individual dependent may exhibit none or one of the following:

History
The conceptualization of dependency, within classical psychoanalytic theory, is directly related to Freuds oral psychosexual stage of development. Frustration or over-gratification was said to result in an oral fixation and in an oral type of character, characterized by feeling dependent on others for nurturance and by behaviours representative of the oral stage. Later psychoanalytic theories shifted the focus from a drive-based approach of dependency to the recognition of the importance of early relationships and establishing separation from these early caregivers, in which the exchanges between the caregiver and the child become internalized, and the nature of these interactions becomes part of the concepts of the self and of others.

References
Sources
Beck, Aaron T; Freeman, Arthur (1990). Cognitive Therapy of Personality Disorders. New York: Guilford Press. ISBN 978-0-89862-434-2.
Millon, Theodore; Davis, Roger Dale (1996). Disorders of Personality: DSM-IV and Beyond. New York: Wiley. ISBN 978-0-471-01186-6.
Millon, Theodore (1981). Disorders of Personality: DSM-III, Axis II. New York: Wiley. ISBN 978-0-471-06403-9.
Perry, J. C. (1996). "Dependent personality disorder".  In Gabbard, Glen O.; Atkinson, Sarah D. (eds.). Synopsis of Treatments of Psychiatric Disorders. American Psychiatric Press. pp. 995–998. ISBN 978-0-88048-859-4.
Gjerde, L. C.; Czajkowski, N.; Røysamb, E.; Ørstavik, R. E.; Knudsen, G. P.; Østby, K.; Torgersen, S.; Myers, J.; Kendler, K. S.; Reichborn-Kjennerud, T. (2012). "The heritability of avoidant and dependent personality disorder assessed by personal interview and questionnaire". Acta Psychiatrica Scandinavica. 126 (6): 448–457. doi:10.1111/j.1600-0447.2012.01862.x. PMC 3493848. PMID 22486635.
Millon, Theodore; Millon, Carrie M.; Meagher, Sarah; Grossman, Seth; Ramnath, Rowena (2004). Personality Disorders in Modern Life. Wiley. ISBN 978-0-471-66850-3.
Millon, Theodore (2006). "Personality Subtypes".
Kantor, Martin (1992). Diagnosis and Treatment of the Personality Disorders. Ishiyaku EuroAmerica. ISBN 978-0-912791-89-0.
Ellison, J. M.; Adler, D. A. (1990). "A strategy for the pharmacotherapy of personality disorders".  In Adler, David A. (ed.). Treating Personality Disorders. San Francisco: Jossey-Bass. pp. 43–63. ISBN 978-1-55542-811-2.
Adler, David A., ed. (1990). Treating Personality Disorders. San Francisco: Jossey-Bass. ISBN 978-1-55542-811-2.
Richards, Henry Jay (1993). Therapy of the Substance Abuse Syndromes. New York: Jason Aronson. ISBN 978-0-87668-539-6.
Zimmerman, Mark (1994). Diagnosing DSM-IV-R Psychiatric Disorders in Primary Care Settings: An Interview Guide for the Nonpsychiatrist Physician. Psych Products. ISBN 978-0-9633821-3-9.
Ekleberry, Sharon (2014). "Dependent Personality Disorder (DPD)". Treating Co-Occurring Disorders. pp. 63–64. ISBN 978-1-317-82549-4.
Oldham, John M.; Morris, Lois B. (1990). The Personality Self-portrait: Why You Think, Work, Love, and Act the Way You Do. Bantam. ISBN 978-0-553-05757-7.
Sperry, Len (1995). Psychopharmacology and Psychotherapy: Strategies for Maximizing Treatment Outcomes. Psychology Press. ISBN 978-0-87630-787-8.
Stone, Michael H. (1993). Abnormalities of Personality: Within and Beyond the Realm of Treatment. Norton. ISBN 978-0-393-70127-2.
Benjamin, Lorna Smith (1993) </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 Nasal septum perforation and explain in detail? [/INST] A nasal septum perforation is a medical condition in which the nasal septum, the bony/cartilaginous wall dividing the nasal cavities, develops a hole or fissure.
This may be brought on directly, as in the case of nasal piercings, or indirectly, as by long-term topical drug application, including intranasal ethylphenidate, methamphetamine, cocaine, crushed prescription pills, or decongestant nasal sprays, chronic epistaxis, excessive nose picking and as a complication of nasal surgery like septoplasty or rhinoplasty. Much less common causes for perforated nasal septums include rare granulomatous inflammatory conditions like granulomatosis with polyangiitis. It has been reported as a side effect of anti-angiogenesis drugs like bevacizumab.

Signs and symptoms
A perforated septum can vary in size and location, and is usually found deep inside the nose. It may be asymptomatic, or cause a variety of signs and symptoms. Small perforations can cause a whistling noise when breathing. Larger perforations usually have more severe symptoms. These can be a combination of crusting, blood discharge, difficulty breathing, nasal pressure and discomfort. The closer the perforation is to the nostrils, the more likely it is to cause symptoms.

Cause
Infective causes include syphilis, leprosy, and rhinoscleroma. Non-infective causes include cocaine abuse, an in situ foreign body, chronic use of topical nasal decongestants, methamphetamine, facial trauma, or may develop as a consequence of nasal surgery.

Treatment
Septal perforations are managed with a multitude of options. The treatment often depends on the severity of symptoms and the size of the perforations. Generally speaking anterior septal perforations are more bothersome and symptomatic. Posterior septal perforations, which mainly occur iatrogenically, are often managed with simple observation and are at times intended portions of skull base surgery. Septal perforations that are not bothersome can be managed with simple observation. While no septal perforation will spontaneously close, for the majority of septal perforations that are unlikely to get larger observation is an appropriate form of management. For perforations that bleed or are painful, initial management should include humidification and application of salves to the perforation edges to promote healing. Mucosalization of the perforation edges will help prevent pain and recurrent epistaxis and majority of septal perforations can be managed without surgery.
For perforations in which anosmia, or the loss of smell, and a persistent whistling are a concern, the use of a silicone septal button is a treatment option. These can be placed while the patient is awake and usually in the clinic setting. While complications of button insertion are minimal, the presence of the button can be bothersome to most patients.
For patients who desire definitive close, surgery is the only option. Prior to determining candidacy for surgical closure, the etiology of the perforation must be determined. Often this requires a biopsy of the perforation to rule out autoimmune causes. If a known cause such as cocaine is the offending agent, it must be ensured that the patient is not still using the irritant.
For those that are determined to be medically cleared for surgery, the anatomical location and size of the perforation must be determined. This is often done with a combination of a CT scan of the sinuses without contrast and an endoscopic evaluation by an Ear Nose and Throat doctor. Once dimensions are obtained the surgeon will decide if it is possible to close the perforation. Multiple approaches to access the septum have been described in the literature. While sublabial and midfacial degloving approaches have been described, the most popular today is the rhinoplasty approach. This can include both open and closed methods </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 Robinow syndrome and explain in detail? [/INST] Robinow syndrome is an extremely rare genetic disorder characterized by short-limbed dwarfism, abnormalities in the head, face, and external genitalia, as well as vertebral segmentation. The disorder was first described in 1969 by human geneticist Meinhard Robinow, along with physicians Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.Two forms of the disorder exist, dominant and recessive, of which the former is more common. Patients with the dominant version often suffer moderately from the aforementioned symptoms. Recessive cases, on the other hand, are usually more physically marked, and individuals may exhibit more skeletal abnormalities. The recessive form is particularly frequent in Turkey. However, this can likely be explained by a common ancestor, as these patients families can be traced to a single town in Eastern Turkey. Clusters of the autosomal recessive form have also been documented in Oman and Czechoslovakia.The syndrome is also known as Robinow-Silverman-Smith syndrome, Robinow dwarfism, fetal face, fetal face syndrome, fetal facies syndrome, acral dysostosis with facial and genital abnormalities, or mesomelic dwarfism-small genitalia syndrome.  The recessive form was previously known as Covesdem syndrome.

Signs and symptoms
Robinow noted the resemblance of affected patients faces to that of a fetus, using the term "fetal facies" to describe the appearance of a small face and widely spaced eyes. Clinical features also may include a short, upturned nose, a prominent forehead, and a flat nasal bridge. The upper lip may be "tented", exposing dental crowding, "tongue tie", or gum hypertrophy.
Though the eyes do not protrude, abnormalities in the lower eyelid may give that impression. Surgery may be necessary if the eyes cannot close fully. In addition, the ears may be set low on the head or have a deformed pinna.Patients suffer from dwarfism, short lower arms, small feet, and small hands. Fingers and toes may also be abnormally short and laterally or medially bent. The thumb may be displaced and some patients, notably in Turkey, experience ectrodactyly. All patients often suffer from vertebral segmentation abnormalities. Those with the dominant variant have, at most, a single butterfly vertebra. Those with the recessive form, however, may suffer from hemivertebrae, vertebral fusion, and rib anomalies. Some cases resemble Jarcho-Levin syndrome or spondylocostal dysostosis.Genital defects characteristically seen in males include a micropenis with a normally developed scrotum and testes. Sometimes, testicles may be undescended, or the patient may suffer from hypospadias. Female genital defects may include a reduced size clitoris and underdeveloped labia minora. Infrequently, the labia majora may also be underdeveloped. Some research has shown that females may experience vaginal atresia or haematocolpos.The autosomal recessive form of the disorder tends to be much more severe. Examples of differences are summarized in the following table:

Associated conditions
Medical conditions include frequent ear infection, hearing loss, hypotonia, developmental problems, respiratory problems, eating difficulties, light sensitivity, and esophageal reflux.Data on fertility and the development of secondary sex characteristics is relatively sparse. It has been reported that both male and female patients have had children. Males who have reproduced have all had the autosomal dominant form of the disorder; the fertility of those with the recessive variant is unknown.Researchers have also reported abnormalities in the renal tract of affected patients. Hydronephrosis is a relatively common condition, and researchers have theorized that this may lead to urinary tract infections. In addition, a number of patients have suffered from cystic dysplasia of the kidney.A number of other conditions are often associated with Robinow syndrome. About 15% of reported patients suffer from congenital heart defects. Though there is no clear pattern, the most common conditions include pulmonary stenosis and atresia. In addition, though intelligence is generally normal, around 15% of patients show developmental delays.

Genetics
Genetic studies have linked the autosomal recessive form of the disorder to the ROR2 gene on position 9 of the long arm of chromosome 9. The gene is responsible for aspects of bone and cartilage growth. This same gene is involved in causing autosomal dominant brachydactyly B.

The autosomal dominant form has been linked to three genes - WNT5A, Segment polarity protein dishevelled homolog DVL-1 (DVL1) and Segment polarity protein dishevelled homolog DVL-3 (DVL3). This form is often caused by new mutations and is generally less severe than the recessive form. Two further genes have been linked to this disorder - Frizzled-2 (FZD2) and Nucleoredoxin (NXN gene). All of these genes belong to the same metabolic pathway - the WNT system. This system is involved in secretion for various compounds both in the fetus and in the adult.
A fetal ultrasound can offer prenatal diagnosis 19 weeks into pregnancy. However, the characteristics of a fetus suffering from the milder dominant form may not always be easy to differentiate from a more serious recessive case. Genetic counseling is an option given the availability of a family history.

Diagnosis
Robinow syndrome is suspected by clinical findings and family history and confirmed by typical ROR-2 biallelic pathogenic variants identified by molecular genetic testing.

Treatment
Treatment of the various manifestations will usually be addressed by a multidisciplinary team.

History
The disorder was first described in 1969 by the German-American Human Geneticist Meinhard Robinow (1909–1997), along with physicians Frederic N </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 Metageria and explain in detail? [/INST]  </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 Hashimotos encephalopathy and explain in detail? [/INST] Hashimotos encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological condition characterized by encephalopathy, thyroid autoimmunity, and good clinical response to corticosteroids. It is associated with Hashimotos thyroiditis, and was first described in 1966. It is sometimes referred to as a neuroendocrine disorder, although the conditions relationship to the endocrine system is widely disputed.  It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.Up to 2005, almost 200 case reports of this disease were published. Between 1990 and 2000, 43 cases were published. Since that time, research has expanded and numerous cases are being reported by scientists around the world, suggesting that this rare condition is likely to have been significantly undiagnosed in the past. Over 100 scientific articles on Hashimotos encephalopathy were published between 2000 and 2013.

Signs and symptoms
The onset of symptoms tends to be fairly gradual and to occur over 1-12 years.Symptoms of Hashimotos encephalopathy may include:
Personality changes
Aggression
Delusional behavior
Concentration and memory problems
Coma
Disorientation
Headaches
Jerks in the muscles (myoclonus – 65% of cases)
Lack of coordination (ataxia – 65% of cases)
Partial paralysis on the right side
Psychosis
Seizures (60% of cases)
Sleep abnormalities (55% of cases)
Speech problems (transient aphasia – 80% of cases)
Status epilepticus (20% of  cases)
Tremors (80% of cases)

Pathogenesis
The mechanism of pathogenesis is not known, but is thought to be an autoimmune disorder, similar to Hashimotos thyroiditis, as its name suggests.Consistent with this hypothesis, autoantibodies to alpha-enolase have been found to be associated with Hashimotos encephalopathy. Since enolase is the penultimate step in glycolysis, if it were inhibited (for example by being bound by autoantibodies), one would expect decreased energy production by each cell, leading to resulting atrophy of the affected organ.This would occur most likely through each cell shrinking in size in response to the energy deficit (and/or in extreme situations from some cells dying via either apoptosis or necrosis, depending on location). This may occur as a result of enough ATP not being available to maintain cellular functions - notably, failure of the Na/K ATPase, resulting in a loss of the gradient to drive the Na/Ca antiporter, which normally keeps Ca+2 out of cells so it does not build to toxic levels that will rupture cell lysosomes leading to apoptosis. An additional feature of a low-energy state is failure to maintain axonal transport via dynein/kinesin ATPases, which in many diseases results in neuronal injury to both the brain and/or periphery.

Pathology
Very little is known about the pathology of Hashimotos encephalopathy. Post mortem studies of some individuals have shown lymphocytic vasculitis of venules and veins in the brain stem and a diffuse gliosis involving gray matter more than white matter.As mentioned above, autoantibodies to alpha-enolase associated with Hashimotos encephalopathy have thus far been the most hypothesized mechanism of injury.

Diagnosis
Laboratory and radiological findings
Increased liver enzyme levels (55% cases)
Increased thyroid-stimulating hormone (55% cases)
Increased erythrocyte sedimentation rate (25% cases)Cerebrospinal fluid findings:
Raised protein (25% cases)
Negative for 14–3–3 protein
May contain antithyroid antibodies
Magnetic resonance imaging abnormalities consistent with encephalopathy (26% f cases)
Single photon emission computed tomography shows focal and global hypoperfusion (75% of cases)
Cerebral angiography is normalThyroid hormone abnormalities are common (>80% of cases):
Subclinical hypothyroidism (35% of cases)
Overt hypothyroidism (20% of cases)
Hyperthyroidism (5% of cases)
Euthyroid on levothyroxine (10%  of cases)
Euthyroid not on levothyroxine (20% of cases)Thyroid antibodies – both antithyroid peroxidase antibodies (anti-TPO, antithyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) – in the disease are elevated, but their levels do not correlate with the severity.Electroencephalogram studies, while almost always abnormal (98% of cases), are usually not diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, and photoparoxysmal and photomyogenic responses may be seen.A study from 2006 suggested the following diagnostic criteria:
Encephalopathy with cognitive impairment and at least one of the following features:
neuropsychiatric symptoms (e.g. hallucination, delusion or paranoia)
Myoclonus, generalised tonic-clonic or partial seizures
focal-neurological deficits
Elevated titres of thyroid tissue antibodies (TPO-ab or microsomal)
Euthyroidism (potentially achieved by treatment with L-T4 or L-T3) or mild hypothyroidism with TSH concentration below 20 mIU/L
No evidence for infectious, toxic, metabolic or neoplastic processes in blood, urine or CSF analyses
No serological evidence for neuronal antibodies (e.g. voltage-gated calcium channel, voltage-gated potassium channel, or other currently recognized paraneoplastic antibodies) to support another diagnosis
In imaging studies no evidence for vascular, neoplastic or structural lesions that might explain the symptoms
Complete or nearly complete remission after initiation of glucocorticoid therapy.

Definition
A relapsing encephalopathy occurs in association with autoimmune (Hashimotos or Ords thyroiditis), with high titers of antithyroid antibodies. Clinically, the condition may present one or more symptoms.  Onset is often gradual and may go unnoticed by the patient and close associates to the patients. Symptoms sometimes resolve themselves within days to weeks, leaving a patient undiagnosed. For many other patients, the condition may result in ongoing problems with a variety of manifestations, often confusing clinicians due to the diffuse nature of symptoms.

Differential diagnosis
Alzheimers disease
Cerebrovascular accidents (stroke)
Creutzfeldt–Jakob disease
Epilepsy
Migraine (including basilar, hemiplegic, and retinal types)
Other forms of autoimmune encephalitis, including forms of limbic encephalitis such as anti-NMDA receptor encephalitis
Schizophrenia
Spontaneous cerebrospinal fluid leak
Viral encephalitis
Transient ischemic attack

Treatment
Because most patients respond to corticosteroids or immunosuppressant treatment, this condition is now also referred to as steroid-responsive encephalopathy.Initial treatment is usually with oral prednisone (50–150 mg/day) or high-dose intravenous methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required.Failure of some patients to respond to this first-line treatment has produced a variety of alternative treatments, including azathioprine, cyclophosphamide, chloroquine, methotrexate, periodic intravenous immunoglobulin, and plasma exchange. No controlled trials have been conducted, so the optimal treatment is not known.Seizures, if present, are controlled with typical antiepileptic agents.

Prognosis
Duration of treatment is usually between 2 and 25 years. Earlier reports suggested that 90% of cases stay in remission after discontinuation of treatment, but this is at odds with more recent studies, which suggest that relapse commonly occurs after initial high-dose steroid treatment. Left untreated, this condition can result in coma and death.

Epidemiology
The prevalence has been estimated to be 2.1/100,000 with a male-to-female ratio of 1:4. The mean age of onset is 44 with 20% of cases presenting before the age of 18 years. Most reported cases occur during the patients fifth decade of life.

History
The first case of HE was described by Brain et al. in 1966. The patient was a 48-year-old man with hypothyroidism, multiple episodes of encephalopathy, stroke-like symptoms, and Hashimotos thyroiditis confirmed by elevated antithyroid antibodies.

Alternative names
Steroid-responsive encephalopathy associated with autoimmune thyroiditis, SREAT
Nonvasculitic autoimmune meningoencephalitis, NAIM
Encephalopathy associated with autoimmune thyroid disease, EAATD

References
Further reading
Hashimotos Encephalopathy SREAT Alliance (2013). Understanding Hashimotos Encephalopathy: A Guide for Patients, Families, and Caregivers, Featuring Stories of HE Patients from Around the World. North Charleston, SC: CreateSpace Independent Publishing Platform. ISBN 9781484883099. OCLC 890816771.
Schiess N, Pardo CA (October 2008). "Hashimotos encephalopathy". Annals of the New York Academy of Sciences. 1142 (1): 254–65 </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 Aschers syndrome and explain in detail? [/INST]  </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 Triparesis and explain in detail? [/INST]  </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 Distal trisomy 10q and explain in detail? [/INST] Distal trisomy 10 is a rare chromosomal disorder that causes several physical defects and intellectual disability.Humans, like all sexually reproducing species, have somatic cells that are in diploid [2N] state, meaning that N represent the number of chromosomes, and 2 the number of their copies. In humans, there are 23 chromosomes, but there are two sets of them, one from mother and one from father, totaling in 46, that are arranged according to their size, function and genes they carry. Each cell is supposed to have two of each, but sometimes due to mutations or malfunctions during cell division, mistakes are made that cause serious health problems. One such error is the cause of Distal trisomy 10q disorder.Each chromosome has two arms, labeled p (for petite, or short) and q (for long) </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 Ventricular dyssynchrony and explain in detail? [/INST]  </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 Hemolytic jaundice and explain in detail? [/INST] Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.As one of the three categories of jaundice, the most obvious sign of hemolytic jaundice is the discolouration or yellowing of the sclera and the skin of the patient, but additional symptoms may be observed depending on the underlying causes of hemolysis. Hemolytic causes associated with bilirubin overproduction are diverse and include disorders such as sickle cell anemia, hereditary spherocytosis, thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hemolysis secondary to drug toxicity, thalassemia minor, and congenital dyserythropoietic anemias. Pathophysiology of hemolytic jaundice directly involves the metabolism of bilirubin, where overproduction of bilirubin due to hemolysis exceeds the livers ability to conjugate bilirubin to glucuronic acid.Diagnosis of hemolytic jaundice is based mainly on visual assessment of the yellowing of the patients skin and sclera, while the cause of hemolysis must be determined using laboratory tests. Treatment of the condition is specific to the cause of hemolysis, but intense phototherapy and exchange transfusion can be used to help the patient excrete accumulated bilirubin. Complications related to hemolytic jaundice include hyperbilirubinemia and chronic bilirubin encephalopathy, which may be deadly without proper treatment.

Signs and symptoms
The signs and symptoms additional to the development of a yellowish colour in the sclera and skin are specific to the causes of hemolysis.
For example, if the patient has hemolytic jaundice resulting from sickle cell disease, vaso-occlusive phenomena like acute vaso-occlusive pain and acute chest syndrome may be observed in the acute phases, while in anemia, neurologic deficits and various pulmonary conditions may manifest in the chronic phase.Regardless of the causes, laboratory-confirmed elevation is predominantly seen in unconjugated bilirubin. Serum bilirubin concentration rarely exceeds 4 mg/dL, unless the patient has concurrent liver disease.

Causes
The underlying causes of hemolytic jaundice, as its name suggests, are disorders associated with hemolysis. Such disorders are manifold and the common causes include:

Sickle cell disease, in which a mutation in the globin gene causes the formation of sickle hemoglobin. This disease is marked by the manifestation of chronic compensated hemolytic anemia, with laboratory findings not limited to unconjugated hyperbilirubinemia but also elevated serum lactate dehydrogenase and low serum haptoglobin.
Thrombotic thrombocytopenic purpura, in which the reduced activity of the von Willebrand factor-cleaving protease ADAMTS13 causes a thrombotic microangiopathy. This disease, acquired or hereditary, is marked by very severe microangiopathic hemolytic anemia, with laboratory findings including extremely high serum lactate dehydrogenase and negative anti-RBC antibodies and Coombs test. Clinically, dark urine from hemoglobinuria may be observed because the hemolysis is intravascular (see Pathophysiology below).
Autoimmune hemolytic anemia (AIHA), in which autoantibodies react with self red blood cells and cause their destruction. This disease is marked by increased extravascular hemolysis, with laboratory findings including increased lactate dehydrogenase and decreased or absent haptoglobin in both warm and cold AIHA, and positive Coombs test. Clinically, jaundice or dark urine present in approximately one-third of the cases, and most of the symptoms are related to anemia.Other less commonly observed causes of hemolysis include:

Hemolysis secondary to drug toxicity
Thalassemia minor
Congenital dyserythropoietic anemiaThe above list is not exhaustive, and rare causes of hemolysis such as Bartonella infection, hemolysis due to transfusion reactions, and microangiopathic hemolytic anemia should be suspected when symptoms specific to those causes manifest.

Pathophysiology
Bilirubin overproduction
The mechanisms by which bilirubin is overproduced in hemolytic jaundice can be understood in relation to the two major sites of hemolysis: intravascular and extravascular.During intravascular hemolysis, red blood cells are broken down within the vasculature, allowing hemoglobin from the ruptured red blood cells to form haptoglobin-hemoglobin complexes with haptoglobin, which will be internalized and degraded by hepatocytes and the spleen. If the degree of hemolysis is abnormally high, the unbound hemoglobin is converted to methemoglobin from which the heme moiety is bound to hemopexin or to albumin, and both heme-hemopexin and heme-bound albumin are internalized by hepatocytes and subsequently degraded to bilirubin.
During extravascular hemolysis, red blood cells are destroyed by phagocytosis by macrophages in the reticuloendothelial system and digested by phagosomes. Hemoglobin within red blood cells are then degraded to release heme, which will be converted by microsomal heme oxygenase to iron, carbon monoxide and biliverdin, and are immediately reduced to unconjugated bilirubin by biliverdin reductase and released into the plasma.

Affinity of unconjugated bilirubin to albumin
In both settings of hemolysis mentioned above, only low levels of conjugated bilirubin may accumulate in the serum, with the amount falling within the normal limits of 4 percent of total bilirubin as conjugated bilirubin can be efficiently excreted in bile through being secreted across canalicular membrane. Increased levels of conjugated bilirubin will only be observed with coexisting hepatobiliary abnormalities. Only when the canalicular excretion capacity is exceeded, conjugated bilirubin will accumulate in the plasma. As unconjugated bilirubin has a high affinity to albumin, at high level it is not efficiently cleared through glomerular filtration and it binds to the elastic tissue of the skin and sclera, where high albumin content can be found. This explains the yellow discolouration observed in these tissues in hemolytic jaundice.

Diagnosis
Symptoms of jaundice can be observed superficially, thus visual methods are used to identify the condition. However, underlying causes of jaundice must be diagnosed through laboratory testing.

Visual assessment
In both newborns and adults, yellowing of the skin is a marker for jaundice. As most cases of jaundice are observed in newborns, healthcare workers use visual methods to identify the presence of this condition. A clinical jaundice scale, an adapted version of the Kramers scale, is used to quantify the severity of jaundice through the spread of skin discoloration from zone 1, the head, to zone 5, the palms and soles of the neonates body. Cephalocaudal progression of jaundice to zone 4 and 5 of the Kramers scale shows a significant positive correlation with serum bilirubin concentration of at least 11.0 mg per 100 ml, indicating the need for treatment.

Jaundice Eye Colour Index (JECI)
Conjunctival icterus can be quantified by the Jaundice Eye Colour Index (JECI) through digital photography of the sclera, where a JECI of 0 indicates a white colour, and a JECI of 0.1 indicates an intense yellow colour, which is a sign of hemolytic jaundice.

Screening laboratory tests
Multiple tests can be used to diagnose jaundice, but results of different parameters must be compared to determine its etiology.
When a patient shows signs of jaundice such as the yellowing of the skin and sclera, a urine test is performed to check the levels of urobilinogen present. The presence of urobilinogen and its increased levels indicate that there are more than normal amounts of bilirubin in the intestine, showing that jaundice observed is not due to the blockage of bile flow, and is of pre-hepatic or hepatic causes. Normal colour of the patients urine indicates the absence of unconjugated bilirubin.Results from the urine test should be confirmed by a complete blood count (CBC) and serum testing for total serum bilirubin and fractionated bilirubin. Increased reticulocytes and the presence of schistocytes in the blood smear of the patient observed during CBC indicates hemolysis. If the patient has hemolytic jaundice, serum testing will show that conjugated bilirubin will only account for less than 15% of the total serum bilirubin due to the increase of unconjugated bilirubin.Analysis of liver biopsies will show the levels of alkaline phosphatase, aspartate transaminase, and alanine transaminase in the patient, which has a negative correlation with liver function. Normal levels of these enzymes indicate that there is no significant hepatocellular damage.When an infant is suspected to have hemolytic jaundice, abnormal morphologies of erythrocytes can be analyzed to find out the causes of hemolysis. A Coombs test should be performed, and end-tidal carbon monoxide concentration should be monitored to understand the rate of hemolysis in the infants body </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 Histoplasmosis and explain in detail? [/INST] Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; called disseminated histoplasmosis, it can be fatal if left untreated.
Histoplasmosis is common among AIDS patients because of their suppressed immunity. In immunocompetent individuals, past infection results in partial protection against ill effects if reinfected.
Histoplasma capsulatum is found in soil, often associated with decaying bat guano or bird droppings.  Disruption of soil from excavation or construction can release infectious elements that are inhaled and settle into the lung.
From 1938 to 2013 in the US, 105 outbreaks were reported in a total of 26 states plus Puerto Rico. In 1978 to 1979 during a large urban outbreak in which 100,000 people were exposed to the fungus in Indianapolis, victims had pericarditis, rheumatological syndromes, esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. Histoplasmosis mimics colds, pneumonia, and the flu, and can be shed by bats in their feces.

Signs and symptoms
If symptoms of histoplasmosis infection occur, they start within 3 to 17 days after exposure; the typical time is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases. Chronic histoplasmosis cases can  resemble tuberculosis; disseminated histoplasmosis affects multiple organ systems and is fatal unless treated.While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement. Lesions often left calcification nodules as they are healed.Presumed ocular histoplasmosis syndrome  causes chorioretinitis, where  the choroid and retina of the eyes are scarred, resulting in a loss of vision not unlike macular degeneration. Despite its name, the relationship to Histoplasma is controversial. Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.

Complications
In absence of proper treatment and especially in immunocompromised individuals, complications can arise. These include recurrent pneumonia, respiratory failure, fibrosing mediastinitis, superior vena cava syndrome, pulmonary vessel obstruction, and progressive fibrosis of lymph nodes. Fibrosing mediastinitis is a serious complication and can be fatal. Smokers with structural lung disease have higher probability of developing chronic cavitary histoplasmosis.After healing of lesions, hard, calcified lymph nodes can erode the walls of the airway, causing hemoptysis.

Mechanisms
H. capsulatum grows in soil and material contaminated with bird or bat droppings (guano). The fungus has been found in poultry-house litter, caves, areas harboring bats, and bird roosts (particularly those of starlings). The fungus is thermally dimorphic; in the environment, it grows as a brownish mycelium, and at body temperature (37°C in humans), it morphs into a yeast. Histoplasmosis is not contagious but is contracted by inhalation of the spores from disturbed soil or guano. The inoculum is represented principally by microconidia. These are inhaled and reach the alveoli. In the alveoli, macrophages ingest these microconidia. They survive inside the phagosome. As the fungus is thermally dimorphic, these microconidia are transformed into yeast. They grow and multiply inside the phagosome. The macrophages travel in lymphatic circulation and can spread the disease to different organs.Within the phagosome, the fungus has an absolute requirement for thiamine. Cell-mediated immunity for histoplasmosis develops within 2 weeks. If the patient has strong cellular immunity, macrophages, epithelial cells, and lymphocytes surround the organisms and contain them, and eventually calcify. In immunocompromised individuals, the organisms disseminate to different organs such as bone, spleen, liver, adrenal glands, and mucocutaneous membranes, resulting in progressive disseminated histoplasmosis. Chronic lung disease can manifest.

Diagnosis
Clinically,  a wide spectrum of disease manifestations occurs, making diagnosis somewhat difficult. More severe forms include the chronic pulmonary form, often occurring in the presence of underlying pulmonary disease, and a disseminated form, which is characterized by the progressive spread of infection to extrapulmonary sites. Oral manifestations have been reported as the main complaint of the disseminated forms, leading the patient to seek treatment, whereas pulmonary symptoms in disseminated disease may be mild or even misinterpreted as flu. Histoplasmosis can be diagnosed by samples containing the fungus taken from sputum (via bronchoalveolar lavage), blood, or infected organs.  It can also be diagnosed by detection of antigens in blood or urine samples by ELISA or polymerase chain reaction. Antigens can cross-react with antigens of African histoplasmosis (caused by Histoplasma duboisii), blastomycosis, coccidioidomycosis, paracoccidioidomycosis, and talaromycosis infection. Histoplasmosis can also be diagnosed by a test for antibodies against Histoplasma in the blood.  Histoplasma skin tests indicate whether persons have been exposed, but do not indicate whether they have the disease. Formal histoplasmosis diagnoses are often confirmed only by culturing the fungus directly. Sabouraud agar is one agar growth medium on which the fungus can be cultured. Cutaneous manifestations of disseminated disease are diverse and often present as a nondescript rash with systemic complaints. Diagnosis is best established by urine antigen testing, as blood cultures may take up to 6 weeks for diagnostic growth to occur and serum antigen testing often comes back with a false negative before 4 weeks of disseminated infection.

Types
Histoplasmosis may be divided into these types:: 316–317
Primary pulmonary histoplasmosis
Progressive disseminated histoplasmosis
Primary cutaneous histoplasmosis
African histoplasmosis

Prevention
Testing or decontaminating most sites that may be contaminated with H. capsulatum is impractical, but the sources below list environments where histoplasmosis is common, and precautions to reduce a persons risk of exposure, in the three parts of the world where the disease is prevalent. Precautions common to all geographical locations would be to avoid accumulations of bird or bat droppings.The US National Institute for Occupational Safety and Health  provides information on work practices and personal protective equipment that may reduce the risk of infection.A review paper includes information on locations in which Histoplasma has been found in Africa (in chicken runs, on bats, in the caves bats inhabit, and in soil), and a thorough reference list including English, French, and Spanish language references.

Treatment
In the majority of immunocompetent individuals, histoplasmosis resolves without any treatment. Antifungal medications are used to treat severe cases of acute histoplasmosis and all cases of chronic and disseminated disease. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole.Liposomal preparations of amphotericin B are more effective than deoxycholate preparations. The liposomal preparation is preferred in patients who might be at risk of nephrotoxicity, although all preparations of amphotericin B have risk of nephrotoxicity. Individuals taking amphotericin B are monitored for renal function. Liposomal amphotericin B is better at treating people with progressive disseminated Histoplasmosis and underlying HIV when compared to deoxycholate amphotericin B. Meanwhile, fluconazole performs poorly when compared to other azoles.Treatment with itraconazole must continue for at least a year in severe cases, while in acute pulmonary Histoplasmosis, 6 to 12 weeks treatment is sufficient. Alternatives to itraconazole are posaconazole, voriconazole, and fluconazole. Individuals taking itraconazole are monitored for hepatic function.

Prognosis
About 90% of patients with normal immune systems regain health without any intervention. Less than 5% need serious treatments.

Epidemiology
H. capsulatum is found throughout the world. It is endemic in certain areas of the United States, particularly in states bordering the Ohio River valley and the lower Mississippi River. The humidity and acidity patterns of soil are associated with endemicity. Bird and bat droppings in soil promote the growth of Histoplasma. Contact with such soil aerosolizes the microconidia, which can infect humans. It is also common in caves in Southern and East Africa. Positive Histoplasmin skin tests occur in as many as 90% of the people living in areas where H </s>