<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 Anorexia nervosa and explain in detail? [/INST] Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Anorexia is a term of Greek origin: an- (ἀν-, prefix denoting negation) and orexis (ὄρεξις, "appetite"), translating literally to "a loss of appetite"; the adjective nervosa indicating the functional and non-organic nature of the disorder. Anorexia nervosa  was coined by Gull in 1873 but, despite literal translation, the symptom of hunger is frequently present and the pathological control of this instinct is a source of satisfaction for the patients.
Individuals with anorexia nervosa commonly see themselves as overweight, although they are in fact underweight. The DSM-5 describes this perceptual symptom as "disturbance in the way in which ones body weight or shape is experienced". In research and clinical settings, this symptom is called "body image disturbance". Individuals with anorexia nervosa also often deny that they have a problem with low weight. They may weigh themselves frequently, eat small amounts, and only eat certain foods. Some exercise excessively, force themselves to vomit (in the "anorexia purging" subtype), or use laxatives to lose weight and control body shapes, and/or binge eat. Medical complications may include osteoporosis, infertility, and heart damage, among others. Women will often stop having menstrual periods. In extreme cases, patients with anorexia nervosa who continually refuse significant dietary intake and weight restoration interventions, and are declared incompetent to make decisions by a psychiatrist, may be fed by force under restraint via nasogastric tube after asking their parents or proxies to make the decision for them.The cause of anorexia is currently unknown. There appear to be some genetic components with identical twins more often affected than fraternal twins. Cultural factors also appear to play a role, with societies that value thinness having higher rates of the disease. Additionally, it occurs more commonly among those involved in activities that value thinness, such as high-level athletics, modeling, and dancing. Anorexia often begins following a major life-change or stress-inducing event. The diagnosis requires a significantly low weight and the severity of disease is based on body mass index (BMI) in adults with mild disease having a BMI of greater than 17, moderate a BMI of 16 to 17, severe a BMI of 15 to 16, and extreme a BMI less than 15. In children, a BMI for age percentile of less than the 5th percentile is often used.Treatment of anorexia involves restoring the patient back to a healthy weight, treating their underlying psychological problems, and addressing behaviors that promote the problem. While medications do not help with weight gain, they may be used to help with associated anxiety or depression. Different therapy methods may be useful, such as cognitive behavioral therapy or an approach where parents assume responsibility for feeding their child, known as Maudsley family therapy. Sometimes people require admission to a hospital to restore weight. Evidence for benefit from nasogastric tube feeding is unclear; such an intervention may be highly distressing for both anorexia patients and healthcare staff when administered against the patients will under restraint. Some people with anorexia will have a single episode and recover while others may have recurring episodes over years. Many complications improve or resolve with the regaining of weight.Globally, anorexia is estimated to affect 2.9 million people as of 2015. It is estimated to occur in 0.3% to 4.3% of women and 0.2% to 0.3% of men in Western countries at some point in their life. About 0.4% of young women are affected in a given year and it is estimated to occur ten times more commonly among women than men. Rates in most of the developing world are unclear. Often it begins during the teen years or young adulthood. While anorexia became more commonly diagnosed during the 20th century it is unclear if this was due to an increase in its frequency or simply better diagnosis. In 2013, it directly resulted in about 600 deaths globally, up from 400 deaths in 1990. Eating disorders also increase a persons risk of death from a wide range of other causes, including suicide. About 5% of people with anorexia die from complications over a ten-year period, a nearly six times increased risk. The term "anorexia nervosa" was first used in 1873 by William Gull to describe this condition.
In recent years, evolutionary psychiatry as an emerging scientific discipline has been studying mental disorders from an evolutionary perspective. It is still debated whether eating disorders such as anorexia have evolutionary functions or if they are problems resulting from a modern lifestyle.

Signs and symptoms
Anorexia nervosa is an eating disorder characterized by attempts to lose weight to the point of starvation. A person with anorexia nervosa may exhibit a number of signs and symptoms, the type and severity of which may vary and be present but not readily apparent.Anorexia nervosa, and the associated malnutrition that results from self-imposed starvation, can cause complications in every major organ system in the body. Hypokalaemia, a drop in the level of potassium in the blood, is a sign of anorexia nervosa. A significant drop in potassium can cause abnormal heart rhythms, constipation, fatigue, muscle damage, and paralysis.Signs and symptoms may be classified in physical, cognitive, affective, behavioral and perceptual:

Physical symptoms
A low body mass index for ones age and height
Amenorrhea, a symptom that occurs after prolonged weight loss, causing menstruation to stop
Dry hair and skin, as well as hair thinning
Fear of even the slightest weight gain; taking all precautionary measures to avoid weight gain or becoming "overweight"
Rapid, continuous weight loss
Lanugo: soft, fine hair growing over the face and body
Bradycardia or tachycardia.
Chronic fatigue
Orange discoloration of the skin, particularly the feet (Carotenosis)
Infertility
Halitosis (from vomiting or starvation-induced ketosis)
Hypotension or orthostatic hypotension
Having severe muscle tension, aches and pains
Insomnia
Abdominal distension

Cognitive symptoms
An obsession with counting calories and monitoring fat contents of food.
Preoccupation with food, recipes, or cooking; may cook elaborate dinners for others, but not eat the food themselves or consume a very small portion.
Admiration of thinner people.
Thoughts of being fat or not thin enough
An altered mental representation of ones body
Impaired theory of mind, exacerbated by lower BMI and depression
Difficulty in abstract thinking and problem solving
Rigid and inflexible thinking
Poor self-esteem
Hypercriticism and perfectionism

Affective symptoms
Depression
Ashamed of oneself or ones body
Anxiety disorders
Rapid mood swings
Emotional dysregulation
Alexithymia

Behavioral symptoms
Food restrictions despite being underweight or at a healthy weight.
Food rituals, such as cutting food into tiny pieces, refusing to eat around others, and hiding or discarding of food.
Purging (only in the anorexia purging subtype) with laxatives, diet pills, ipecac syrup, or diuretics to flush food out of their system after eating or engage in self-induced vomiting.
Excessive exercise, including micro-exercising, for example making small persistent movements of fingers or toes.
Self harming or self-loathing.
Solitude: may avoid friends and family and become more withdrawn and secretive.

Perceptual symptoms
Perception of self as overweight, in contradiction to an underweight reality (namely "body image disturbance")
Intolerance to cold and frequent complaints of being cold; body temperature may lower (hypothermia) in an effort to conserve energy due to malnutrition.
Altered body schema (i.e. an implicit representation of the body evoked by acting)
Altered interoception

Interoception
Interoception involves the conscious and unconscious sense of the internal state of the body, and it has an important role in homeostasis and regulation of emotions. Aside from noticeable physiological dysfunction, interoceptive deficits also prompt individuals with anorexia to concentrate on distorted perceptions of multiple elements of their body image. This exists in both people with anorexia and in healthy individuals due to impairment in interoceptive sensitivity and interoceptive awareness.Aside from weight gain and outer appearance, people with anorexia also report abnormal bodily functions such as indistinct feelings of fullness. This provides an example of miscommunication between internal signals of the body and the brain. Due to impaired interoceptive sensitivity, powerful cues of fullness may be detected prematurely in highly sensitive individuals, which can result in decreased calorie consumption and generate anxiety surrounding food intake in anorexia patients. People with anorexia also report difficulty identifying and describing their emotional feelings and the inability to distinguish emotions from bodily sensations in general, called alexithymia.Interoceptive awareness and emotion are deeply intertwined, and could mutually impact each other in abnormalities. Anorexia patients also exhibit emotional regulation difficulties that ignite emotionally-cued eating behaviors, such as restricting food or excessive exercising. Impaired interoceptive sensitivity and interoceptive awareness can lead anorexia patients to adapt distorted interpretations of weight gain that are cued by physical sensations related to digestion (e.g., fullness). Combined, these interoceptive and emotional elements could together trigger maladaptive and negatively reinforced behavioral responses that assist in the maintenance of anorexia. In addition to metacognition, people with anorexia also have difficulty with social cognition including interpreting others emotions, and demonstrating empathy. Abnormal interoceptive awareness and interoceptive sensitivity shown through all of these examples have been observed so frequently in anorexia that they have become key characteristics of the illness.

Comorbidity
Other psychological issues may factor into anorexia nervosa. Some people have a previous disorder which may increase their vulnerability to developing an eating disorder and some develop them afterwards. The presence of psychiatric comorbidity has been shown to affect the severity and type of anorexia nervosa symptoms in both adolescents and adults.Obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD) are highly comorbid with AN. OCD is linked with more severe symptomatology and worse prognosis. The causality between personality disorders and eating disorders has yet to be fully established. Other comorbid conditions include depression, alcoholism, borderline and other personality disorders, anxiety disorders, attention deficit hyperactivity disorder, and body dysmorphic disorder (BDD). Depression and anxiety are the most common comorbidities, and depression is associated with a worse outcome. Autism spectrum disorders occur more commonly among people with eating disorders than in the general population. Zucker et al. (2007) proposed that conditions on the autism spectrum make up the cognitive endophenotype underlying anorexia nervosa and appealed for increased interdisciplinary collaboration.

Causes
There is evidence for biological, psychological, developmental, and sociocultural risk factors, but the exact cause of eating disorders is unknown.

Genetic
Anorexia nervosa is highly heritable. Twin studies have shown a heritability rate of 28–58%. First-degree relatives of those with anorexia have roughly 12 times the risk of developing anorexia. Association studies have been performed, studying 128 different polymorphisms related to 43 genes including genes involved in regulation of eating behavior, motivation and reward mechanics, personality traits and emotion. Consistent associations have been identified for polymorphisms associated with agouti-related peptide, brain derived neurotrophic factor, catechol-o-methyl transferase, SK3 and opioid receptor delta-1. Epigenetic modifications, such as DNA methylation, may contribute to the development or maintenance of anorexia nervosa, though clinical research in this area is in its infancy.A 2019 study found a genetic relationship with mental disorders, such as schizophrenia, obsessive–compulsive disorder, anxiety disorder and depression; and metabolic functioning with a negative correlation with fat mass, type 2 diabetes and leptin.One gene that has been linked to anorexia might be of particular interest.  This gene codes for a protein called the estrogen related receptor alpha (ERRalpha).  In some tissues, this gene alters the ability of estrogen and estrogen receptors to interact with DNA and change the function of cells. Since estrogen has potent effects upon appetite and feeding, any genetic abnormality in the estrogen signaling pathway could contribute to the symptoms of anorexia and explain why anorexia typically appears in young women just after the onset of puberty.

Environmental
Obstetric complications: prenatal and perinatal complications may factor into the development of anorexia nervosa, such as preterm birth, maternal anemia, diabetes mellitus, preeclampsia, placental infarction, and neonatal heart abnormalities. Neonatal complications may also have an influence on harm avoidance, one of the personality traits associated with the development of AN.Neuroendocrine dysregulation: altered signalling of peptides that facilitate communication between the gut, brain and adipose tissue, such as ghrelin, leptin, neuropeptide Y and orexin, may contribute to the pathogenesis of anorexia nervosa by disrupting regulation of hunger and satiety.Gastrointestinal diseases: people with gastrointestinal disorders may be more at risk of developing disorders of eating practices than the general population, principally restrictive eating disturbances. An association of anorexia nervosa with celiac disease has been found. The role that gastrointestinal symptoms play in the development of eating disorders seems rather complex. Some authors report that unresolved symptoms prior to gastrointestinal disease diagnosis may create a food aversion in these persons, causing alterations to their eating patterns. Other authors report that greater symptoms throughout their diagnosis led to greater risk. It has been documented that some people with celiac disease, irritable bowel syndrome or inflammatory bowel disease who are not conscious about the importance of strictly following their diet, choose to consume their trigger foods to promote weight loss. On the other hand, individuals with good dietary management may develop anxiety, food aversion and eating disorders because of concerns around cross contamination of their foods. Some authors suggest that medical professionals should evaluate the presence of an unrecognized celiac disease in all people with eating disorder, especially if they present any gastrointestinal symptom (such as decreased appetite, abdominal pain, bloating, distension, vomiting, diarrhea or constipation), weight loss, or growth failure; and also routinely ask celiac patients about weight or body shape concerns, dieting or vomiting for weight control, to evaluate the possible presence of eating disorders, especially in women.Studies have hypothesized the continuance of disordered eating patterns may be epiphenomena of starvation. The results of the Minnesota Starvation Experiment showed normal controls exhibit many of the behavioral patterns of AN when subjected to starvation. This may be due to the numerous changes in the neuroendocrine system, which results in a self-perpetuating cycle.Anorexia nervosa is more likely to occur in a persons pubertal years. Some explanatory hypotheses for the rising prevalence of eating disorders in adolescence are "increase of adipose tissue in girls, hormonal changes of puberty, societal expectations of increased independence and autonomy that are particularly difficult for anorexic adolescents to meet; [and] increased influence of the peer group and its values."

Psychological
Early theories of the cause of anorexia linked it to childhood sexual abuse or dysfunctional families; evidence is conflicting, and well-designed research is needed. The fear of food is known as sitiophobia or cibophobia, and is part of the differential diagnosis. Other psychological causes of anorexia include low self-esteem, feeling like there is lack of control, depression, anxiety, and loneliness. People with anorexia are, in general, highly perfectionistic and most have obsessive compulsive personality traits which may facilitate sticking to a restricted diet. It has been suggested that patients with anorexia are rigid in their thought patterns, and place a high level of importance upon being thin.A risk factor for anorexia is trauma. Although the prevalence rates vary greatly, between 37% and 100%, there appears to be a link between traumatic events and eating disorder diagnosis. Approximately 72% of individuals with anorexia report experiencing a traumatic event prior to the onset of eating disorder symptoms, with binge-purge subtype reporting the highest rates. There are many traumatic events that may be risk factors for development of anorexia, the first identified traumatic event predicting anorexia was childhood sexual abuse. However, other traumatic events, such as physical and emotional abuse have also been found to be risk factors. Interpersonal, as opposed to non-interpersonal trauma, has been seen as the most common type of traumatic event, which can encompass sexual, physical, and emotional abuse. Individuals who experience repeated trauma, like those who experience trauma perpetrated by a caregiver or loved one, have increased symptom severity of anorexia and a greater prevalence of comorbid psychiatric diagnoses.In individuals with anorexia, the prevalence rates for those who also qualify for a PTSD diagnosis ranges from 4% to 52% in non-clinical samples to 10% to 47% in clinical samples. A complicated symptom profile develops when trauma and anorexia meld; the bodily experience of the individual is changed and intrusive thoughts and sensations may be experienced. Traumatic events can lead to intrusive and obsessive thoughts, and the symptom of anorexia that has been most closely linked to a PTSD diagnosis is increased obsessive thoughts pertaining to food. Similarly, impulsivity is linked to the purge and binge-purge subtypes of anorexia, trauma, and PTSD. Emotional trauma (e.g., invalidation, chaotic family environment in childhood) may lead to difficulty with emotions, particularly the identification of and how physical sensations contribute to the emotional response. Trauma and traumatic events can disturb an individuals sense of self and affect their ability to thrive, especially within their bodies.When trauma is perpetrated on an individual, it can lead to feelings of not being safe within their own body; that their body is for others to use and not theirs alone. Individuals may experience a feeling of disconnection from their body after a traumatic experience, leading to a desire to distance themselves from the body. Trauma overwhelms individuals emotionally, physically, and psychologically. Both physical and sexual abuse can lead to an individual seeing their body as belonging to an "other" and not to the "self". Individuals who feel as though they have no control over their bodies due to trauma may use food as a means of control because the choice to eat is an unmatched expression of control. By exerting control over food, individuals can choose when to eat and how much to eat. Individuals, particularly children experiencing abuse, may feel a loss of control over their life, circumstances, and their own bodies. Particularly sexual abuse, but also physical abuse, can make individuals feel that the body is not a safe place and an object over which another has control. Starvation, in the case of anorexia, may also lead to reduction in the body as a sexual object, making starvation a solution. Restriction may also be a means by which the pain an individual is experiencing can be communicated.

Sociological
Anorexia nervosa has been increasingly diagnosed since 1950; the increase has been linked to vulnerability and internalization of body ideals. People in professions where there is a particular social pressure to be thin (such as models and dancers) were more likely to develop anorexia, and those with anorexia have much higher contact with cultural sources that promote weight loss. This trend can also be observed for people who partake in certain sports, such as jockeys and wrestlers. There is a higher incidence and prevalence of anorexia nervosa in sports with an emphasis on aesthetics, where low body fat is advantageous, and sports in which one has to make weight for competition. Family group dynamics can play a role in the cause of anorexia including negative expressed emotion in overprotective families where blame is frequently experienced among its members. When there is a constant pressure from people to be thin, teasing and bullying can cause low self-esteem and other psychological symptoms.

Media effects
Persistent exposure to media that present body ideals may constitute a risk factor for body dissatisfaction and anorexia nervosa. The cultural ideal for body shape for men versus women continues to favor slender women and athletic, V-shaped muscular men. A 2002 review found that, of the magazines most popular among people aged 18 to 24 years, those read by men, unlike those read by women, were more likely to feature ads and articles on shape than on diet. Body dissatisfaction and internalization of body ideals are risk factors for anorexia nervosa that threaten the health of both male and female populations.Another online aspect contributing to higher rates of eating disorders such as anorexia nervosa are websites and communities on social media that stress the importance of attainment of body ideals extol and promote anorexia nervosa through the use of religious metaphors, lifestyle descriptions, "thinspiration" or "fitspiration" (inspirational photo galleries and quotes that aim to serve as motivators for attainment of body ideals). Pro-anorexia websites reinforce internalization of body ideals and the importance of their attainment.The media portray a false view of what people truly look like. In magazines and movies and even on billboards most of the actors/models are digitally altered in multiple ways. People then strive to look like these "perfect" role models when in reality they are not near perfection themselves.

Mechanisms
Evidence from physiological, pharmacological and neuroimaging studies suggest serotonin (also called 5-HT) may play a role in anorexia. While acutely ill, metabolic changes may produce a number of biological findings in people with anorexia that are not necessarily causative of the anorexic behavior. For example, abnormal hormonal responses to challenges with serotonergic agents have been observed during acute illness, but not recovery. Nevertheless, increased cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid (a metabolite of serotonin), and changes in anorectic behavior in response to acute tryptophan depletion (tryptophan is a metabolic precursor to serotonin) support a role in anorexia. The activity of the 5-HT2A receptors has been reported to be lower in patients with anorexia in a number of cortical regions, evidenced by lower binding potential of this receptor as measured by PET or SPECT, independent of the state of illness. While these findings may be confounded by comorbid psychiatric disorders, taken as a whole they indicate serotonin in anorexia. These alterations in serotonin have been linked to traits characteristic of anorexia such as obsessiveness, anxiety, and appetite dysregulation.Neuroimaging studies investigating the functional connectivity between brain regions have observed a number of alterations in networks related to cognitive control, introspection, and sensory function. Alterations in networks related to the dorsal anterior cingulate cortex may be related to excessive cognitive control of eating related behaviors. Similarly, altered somatosensory integration and introspection may relate to abnormal body image. A review of functional neuroimaging studies reported reduced activations in "bottom up" limbic region and increased activations in "top down" cortical regions which may play a role in restrictive eating.Compared to controls, people who have recovered from anorexia show reduced activation in the reward system in response to food, and reduced correlation between self reported liking of a sugary drink and activity in the striatum and anterior cingulate cortex. Increased binding potential of 11C radiolabelled raclopride in the striatum, interpreted as reflecting decreased endogenous dopamine due to competitive displacement, has also been observed.Structural neuroimaging studies have found global reductions in both gray matter and white matter, as well as increased cerebrospinal fluid volumes. Regional decreases in the left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate have also been reported in acutely ill patients. However, these alterations seem to be associated with acute malnutrition and largely reversible with weight restoration, at least in nonchronic cases in younger people. In contrast, some studies have reported increased orbitofrontal cortex volume in currently ill and  in recovered patients, although findings are inconsistent. Reduced white matter integrity in the fornix has also been reported.

Diagnosis
A diagnostic assessment includes the persons current circumstances, biographical history, current symptoms, and family history. The assessment also includes a mental state examination, which is an assessment of the persons current mood and thought content, focusing on views on weight and patterns of eating.

DSM-5
Anorexia nervosa is classified under the Feeding and Eating Disorders in the latest revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM 5). There is no specific BMI cut-off that defines low weight required for the diagnosis of anorexia nervosa.The diagnostic criteria for anorexia nervosa (all of which needing to be met for diagnosis) are:
Restriction of energy intake relative to requirements leading to a low body weight. (Criterion A)
Intense fear of gaining weight or persistent behaviors that interfere with gaining weight. (Criterion B)
Disturbance in the way a persons weight or body shape is experienced or a lack of recognition about the risks of the low body weight. (Criterion C)Relative to the previous version of the DSM (DSM-IV-TR), the 2013 revision (DSM5) reflects changes in the criteria for anorexia nervosa. Most notably, the amenorrhea (absent period) criterion was removed. Amenorrhea was removed for several reasons: it does not apply to males, it is not applicable for females before or after the age of menstruation or taking birth control pills, and some women who meet the other criteria for AN still report some menstrual activity.

Subtypes
There are two subtypes of AN:
Binge-eating/purging type: patients with anorexia could show binge eating and purging behavior. It is different from bulimia nervosa in terms of the individuals weight. An individual with binge-eating/purging type anorexia is usually significantly underweight. People with bulimia nervosa on the other hand can sometimes be normal-weight or overweight.
Restricting type: the individual uses restricting food intake, fasting, diet pills, or exercise as a means for losing weight; they may exercise excessively to keep off weight or prevent weight gain, and some individuals eat only enough to stay alive. In the restrictive type, there are no recurrent episodes of binge-eating or purging present.

Levels of severity
Body mass index (BMI) is used by the DSM-5 as an indicator of the level of severity of anorexia nervosa. The DSM-5 states these as follows:
Mild: BMI of greater than 17
Moderate: BMI of 16–16.99
Severe: BMI of 15–15.99
Extreme: BMI of less than 15

Investigations
Medical tests to check for signs of physical deterioration in anorexia nervosa may be performed by a general physician or psychiatrist, including:

Complete blood count (CBC): a test of the white blood cells, red blood cells and platelets used to assess the presence of various disorders such as leukocytosis, leukopenia, thrombocytosis and anemia which may result from malnutrition.
Urinalysis: a variety of tests performed on the urine used in the diagnosis of medical disorders, to test for substance abuse, and as an indicator of overall health
Chem-20: Chem-20 also known as SMA-20 a group of twenty separate chemical tests performed on blood serum. Tests include protein and electrolytes such as potassium, chlorine and sodium and tests specific to liver and kidney function.
Glucose tolerance test: Oral glucose tolerance test (OGTT) used to assess the bodys ability to metabolize glucose. Can be useful in detecting various disorders such as diabetes, an insulinoma, Cushings Syndrome, hypoglycemia and polycystic ovary syndrome.
Lipid profile: includes cholesterol (including total cholesterol, HDL and LDL) and triglycerides.
Serum cholinesterase test: a test of liver enzymes (acetylcholinesterase and pseudocholinesterase) useful as a test of liver function and to assess the effects of malnutrition.
Liver Function Test: A series of tests used to assess liver function some of the tests are also used in the assessment of malnutrition, protein deficiency, kidney function, bleeding disorders, and Crohns Disease.
Luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH): Tests the pituitary glands response to GnRh, a hormone produced in the hypothalamus. Hypogonadism is often seen in anorexia nervosa cases.
Creatine kinase (CK) test: measures the circulating blood levels of creatine kinase an enzyme found in the heart (CK-MB), brain (CK-BB) and skeletal muscle (CK-MM).
Blood urea nitrogen (BUN) test: urea nitrogen is the byproduct of protein metabolism first formed in the liver then removed from the body by the kidneys. The BUN test is primarily used to test kidney function. A low BUN level may indicate the effects of malnutrition.
BUN-to-creatinine ratio: A BUN to creatinine ratio is used to predict various conditions. A high BUN/creatinine ratio can occur in severe hydration, acute kidney failure, congestive heart failure, and intestinal bleeding. A low BUN/creatinine ratio can indicate a low protein diet, celiac disease, rhabdomyolysis, or cirrhosis of the liver.
Electrocardiogram (EKG or ECG): measures electrical activity of the heart. It can be used to detect various disorders such as hyperkalemia.
Electroencephalogram (EEG): measures the electrical activity of the brain. It can be used to detect abnormalities such as those associated with pituitary tumors.
Thyroid function tests: tests used to assess thyroid functioning by checking levels of thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3).

Differential diagnoses
A variety of medical and psychological conditions have been misdiagnosed as anorexia nervosa; in some cases the correct diagnosis was not made for more than ten years.
The distinction between binge purging anorexia, bulimia nervosa and Other Specified Feeding or Eating Disorders (OSFED) is often difficult for non-specialist clinicians. A main factor differentiating binge-purge anorexia from bulimia is the gap in physical weight. Patients with bulimia nervosa are ordinarily at a healthy weight, or slightly overweight. Patients with binge-purge anorexia are commonly underweight. Moreover, patients with the binge-purging subtype may be significantly underweight and typically do not binge-eat large amounts of food. In contrast, those with bulimia nervosa tend to binge large amounts of food. It is not unusual for patients with an eating disorder to "move through" various diagnoses as their behavior and beliefs change over time.

Treatment
There is no conclusive evidence that any particular treatment for anorexia nervosa works better than others.Treatment for anorexia nervosa tries to address three main areas.

Restoring the person to a healthy weight;
Treating the psychological disorders related to the illness;
Reducing or eliminating behaviors or thoughts that originally led to the disordered eating.In some clinical settings a specific body image intervention is performed to reduce body dissatisfaction and body image disturbance. Although restoring the persons weight is the primary task at hand, optimal treatment also includes and monitors behavioral change in the individual as well. There is some evidence that hospitalization might adversely affect long term outcome, but sometimes is necessary. Psychotherapy for individuals with AN is challenging as they may value being thin and may seek to maintain control and resist change. Initially, developing a desire to change is fundamental. Despite no evidence for better treatment in adults patients, research stated that family based therapy is the primary choice for adolescents with AN.

Therapy
Family-based treatment (FBT) has been shown to be more successful than individual therapy for adolescents with AN. Various forms of family-based treatment have been proven to work in the treatment of adolescent AN including conjoint family therapy (CFT), in which the parents and child are seen together by the same therapist, and separated family therapy (SFT) in which the parents and child attend therapy separately with different therapists. Proponents of family therapy for adolescents with AN assert that it is important to include parents in the adolescents treatment.A four- to five-year follow up study of the Maudsley family therapy, an evidence-based manualized model, showed full recovery at rates up to 90%. Although this model is recommended by the NIMH, critics claim that it has the potential to create power struggles in an intimate relationship and may disrupt equal partnerships. Cognitive behavioral therapy (CBT) is useful in adolescents and adults with anorexia nervosa. One of the most known psychotherapy in the field is CBT-E, an enhanced cognitive-behavior therapy specifically focus to eating disorder psychopathology. Acceptance and commitment therapy is a third-wave cognitive-behavioral therapy which has shown promise in the treatment of AN. Cognitive remediation therapy (CRT) is also used in treating anorexia nervosa.  Schema-Focused Therapy (a form of CBT) was developed by Dr. Jeffrey Young and is effective in helping patients identify origins and triggers for disordered eating.

Diet
Diet is the most essential factor to work on in people with anorexia nervosa, and must be tailored to each persons needs. Food variety is important when establishing meal plans as well as foods that are higher in energy density. People must consume adequate calories, starting slowly, and increasing at a measured pace. Evidence of a role for zinc supplementation during refeeding is unclear.

Medication
Pharmaceuticals have limited benefit for anorexia itself. There is a lack of good information from which to make recommendations concerning the effectiveness of antidepressants in treating anorexia. Administration of olanzapine has been shown to result in a modest but statistically significant increase in body weight of anorexia nervosa patients.

Admission to hospital
Patients with AN may be deemed to have a lack of insight regarding the necessity of treatment, and thus may be involuntarily treated without their consent.: 1038  AN has a high mortality and patients admitted in a severely ill state to medical units are at particularly high risk. Diagnosis can be challenging, risk assessment may not be performed accurately, consent and the need for compulsion may not be assessed appropriately, refeeding syndrome may be missed or poorly treated and the behavioural and family problems in AN may be missed or poorly managed. Guidelines published by the Royal College of Psychiatrists recommend that medical and psychiatric experts work together in managing severely ill people with AN.

Refeeding syndrome
The rate of refeeding can be difficult to establish, because the fear of refeeding syndrome (RFS) can lead to underfeeding.  It is thought that RFS, with falling phosphate and potassium levels,  is more likely to occur when BMI is very low, and when medical comorbidities such as infection or cardiac failure, are present.  In those circumstances, it is recommended to start refeeding slowly but to build up rapidly as long as RFS does not occur.  Recommendations on energy requirements vary, from 5–10 kcal/kg/day in the most medically compromised patients, who appear to have the highest risk of RFS, to 1900 kcal/day.

Experience of treatment
Patients involved in treatment sometimes felt that treatment focused on biological aspects of body weight and eating behaviour change rather than their perceptions or emotional state.: 8  Patients felt that a therapists trust in them shown by being treated as a complete person with their own capacities was significant.: 9  Some patients defined recovery from AN in terms of reclaiming a lost identity.: 10 Healthcare workers involved in the treatment of anorexia reported frustration and anger to set backs in treatment and noncompliance and were afraid of patients dying. Some healthcare workers felt that they did not understand the treatment and that medical doctors were making decisions.: 11  They may feel powerless to improve a patients situation and deskilled as a result.: 12  Healthcare workers involved in monitoring patients consumption of food felt watched themselves.: 12  Healthcare workers often feel a degree of moral dissonance of not being in control of outcomes which they may protect against by focusing on individual tasks, avoiding identifying with patients (for example by making their eating behavior very different and not sharing personal information with patients), and blaming patients for their distress.: 13,14  Healthcare workers would inflexibly follow process to avoid responsibility.: 13  Healthcare workers attempted to reach balance by gradually giving patients back control avoiding feeling sole responsibility for outcomes, being mindful of their emotional state, and trying to view eating disorders as external from patients.: 13

Prognosis
AN has the highest mortality rate of any psychological disorder. The mortality rate is 11 to 12 times greater than in the general population, and the suicide risk is 56 times higher. Half of women with AN achieve a full recovery, while an additional 20–30% may partially recover. Not all people with anorexia recover completely: about 20% develop anorexia nervosa as a chronic disorder. If anorexia nervosa is not treated, serious complications such as heart conditions and kidney failure can arise and eventually lead to death.  The average number of years from onset to remission of AN is seven for women and three for men. After ten to fifteen years, 70% of people no longer meet the diagnostic criteria, but many still continue to have eating-related problems.Alexithymia (inability to identify and describe ones own emotions) influences treatment outcome. Recovery is also viewed on a spectrum rather than black and white. According to the Morgan-Russell criteria, individuals can have a good, intermediate, or poor outcome. Even when a person is classified as having a "good" outcome, weight only has to be within 15% of average, and normal menstruation must be present in females. The good outcome also excludes psychological health. Recovery for people with anorexia nervosa is undeniably positive, but recovery does not mean a return to normal.

Complications
Anorexia nervosa can have serious implications if its duration and severity are significant and if onset occurs before the completion of growth, pubertal maturation, or the attainment of peak bone mass. Complications specific to adolescents and children with anorexia nervosa can include the following:
Growth retardation may occur, as height gain may slow and can stop completely with severe weight loss or chronic malnutrition. In such cases, provided that growth potential is preserved, height increase can resume and reach full potential after normal intake is resumed. Height potential is normally preserved if the duration and severity of illness are not significant or if the illness is accompanied by delayed bone age (especially prior to a bone age of approximately 15 years), as hypogonadism may partially counteract the effects of undernutrition on height by allowing for a longer duration of growth compared to controls. Appropriate early treatment can preserve height potential, and may even help to increase it in some post-anorexic subjects, due to factors such as long-term reduced estrogen-producing adipose tissue levels compared to premorbid levels. In some cases, especially where onset is before puberty, complications such as stunted growth and pubertal delay are usually reversible.Anorexia nervosa causes alterations in the female reproductive system; significant weight loss, as well as psychological stress and intense exercise, typically results in a cessation of menstruation in women who are past puberty. In patients with anorexia nervosa, there is a reduction of the secretion of gonadotropin releasing hormone in the central nervous system, preventing ovulation. Anorexia nervosa can also result in pubertal delay or arrest. Both height gain and pubertal development are dependent on the release of growth hormone and gonadotropins (LH and FSH) from the pituitary gland. Suppression of gonadotropins in people with anorexia nervosa has been documented. Typically, growth hormone (GH) levels are high, but levels of IGF-1, the downstream hormone that should be released in response to GH are low; this indicates a state of "resistance" to GH due to chronic starvation. IGF-1 is necessary for bone formation, and decreased levels in anorexia nervosa contribute to a loss of bone density and potentially contribute to osteopenia or osteoporosis. Anorexia nervosa can also result in reduction of peak bone mass. Buildup of bone is greatest during adolescence, and if onset of anorexia nervosa occurs during this time and stalls puberty, low bone mass may be permanent.Hepatic steatosis, or fatty infiltration of the liver, can also occur, and is an indicator of malnutrition in children. Neurological disorders that may occur as complications include seizures and tremors. Wernicke encephalopathy, which results from vitamin B1 deficiency, has been reported in patients who are extremely malnourished; symptoms include confusion, problems with the muscles responsible for eye movements and abnormalities in walking gait.
The most common gastrointestinal complications of anorexia nervosa are delayed stomach emptying and constipation, but also include elevated liver function tests, diarrhea, acute pancreatitis, heartburn, difficulty swallowing, and, rarely, superior mesenteric artery syndrome. Delayed stomach emptying, or gastroparesis, often develops following food restriction and weight loss; the most common symptom is bloating with gas and abdominal distension, and often occurs after eating. Other symptoms of gastroparesis include early satiety, fullness, nausea, and vomiting. The symptoms may inhibit efforts at eating and recovery, but can be managed by limiting high-fiber foods, using liquid nutritional supplements, or using metoclopramide to increase emptying of food from the stomach. Gastroparesis generally resolves when weight is regained.

Cardiac complications
Anorexia nervosa increases the risk of sudden cardiac death, though the precise cause is unknown. Cardiac complications include structural and functional changes to the heart. Some of these cardiovascular changes are mild and are reversible with treatment, while others may be life-threatening. Cardiac complications can include arrhythmias, abnormally slow heart beat, low blood pressure, decreased size of the heart muscle, reduced heart volume, mitral valve prolapse, myocardial fibrosis, and pericardial effusion.Abnormalities in conduction and repolarization of the heart that can result from anorexia nervosa include QT prolongation, increased QT dispersion, conduction delays,  and junctional escape rhythms. Electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, can cause anomalies in the electrical activity of the heart, and result in life-threatening arrhythmias. Hypokalemia most commonly results in patients with anorexia when restricting is accompanied by purging (induced vomiting or laxative use). Hypotension (low blood pressure) is common, and symptoms include fatigue and weakness. Orthostatic hypotension, a marked decrease in blood pressure when standing from a supine position, may also occur. Symptoms include lightheadedness upon standing, weakness, and cognitive impairment, and may result in fainting or near-fainting. Orthostasis in anorexia nervosa indicates worsening cardiac function and may indicate a need for hospitalization.  Hypotension and orthostasis generally resolve upon recovery to a normal weight. The weight loss in anorexia nervosa also causes atrophy of cardiac muscle. This leads to decreased ability to pump blood, a reduction in the ability to sustain exercise, a diminished ability to increase blood pressure in response to exercise, and a subjective feeling of fatigue.Some individuals may also have a decrease in cardiac contractility. Cardiac complications can be life-threatening, but the heart muscle generally improves with weight gain, and the heart normalizes in size over weeks to months, with recovery. Atrophy of the heart muscle is a marker of the severity of the disease, and while it is reversible with treatment and refeeding, it is possible that it may cause permanent, microscopic changes to the heart muscle that increase the risk of sudden cardiac death. Individuals with anorexia nervosa may experience chest pain or palpitations; these can be a result of mitral valve prolapse. Mitral valve prolapse occurs because the size of the heart muscle decreases while the tissue of the mitral valve remains the same size. Studies have shown rates of mitral valve prolapse of around 20 percent in those with anorexia nervosa, while the rate in the general population is estimated at 2–4 percent. It has been suggested that there is an association between mitral valve prolapse and sudden cardiac death, but it has not been proven to be causative, either in patients with anorexia nervosa or in the general population.

Relapse
Rates of relapse after treatment range from 9–52% with many studies reporting a relapse rate of at least 25%. Relapse occurs in approximately a third of people in hospital, and is greatest in the first six to eighteen months after release from an institution.

Epidemiology
Anorexia is estimated to occur in 0.9% to 4.3% of women and 0.2% to 0.3% of men in Western countries at some point in their life. About 0.4% of young females are affected in a given year and it is estimated to occur three to ten times less commonly in males. Rates in most of the developing world are unclear. Often it begins during the teen years or young adulthood. Medical students are a high risk group, with an overall estimated prevalence of 10.4% globally.The lifetime rate of atypical anorexia nervosa, a form of ED-NOS in which the person loses a significant amount of weight and is at risk for serious medical complications despite having a higher body-mass index, is much higher, at 5–12%.While anorexia became more commonly diagnosed during the 20th century it is unclear if this was due to an increase in its frequency or simply better diagnosis. Most studies show that since at least 1970 the incidence of AN in adult women is fairly constant, while there is some indication that the incidence may have been increasing for girls aged between 14 and 20.

Underrepresentation
Eating disorders are less reported in preindustrial, non-westernized countries than in Western countries. In Africa, not including South Africa, the only data presenting information about eating disorders occurs in case reports and isolated studies, not studies investigating prevalence. Western countries experience slightly higher rates of eating disorders than non-western countries. Theories to explain these lower rates of eating disorders, lower reporting and lower research rates in include the effects of westernisation, and culture change.Men (and women) who might otherwise be diagnosed with anorexia may not meet the DSM-IV criteria for BMI since they have muscle weight, but have very little fat. In many cases a subclinical "not otherwise specified" diagnosis is made instead; ED-NOS in the DSM-IV, and other specified feeding or eating disorder or unspecified feeding or eating disorder in the DSM-5. ED-NOS was the most diagnosed eating disorder in 2009, and it was also shown that AN did not differ significantly in eating pathology or general psychopathology from EDNOS involving restrictive eating.The elderly population is increasingly experiencing anorexia nervosa, which has been termed the "Anorexia of Aging". The eating disorder is similar to that of typical anorexia nervosa but is more often accompanied by the overuse of laxatives in order to purge the individual of ingested food. Most geriatric anorexia patients limit their food intake to dairy or grains, whereas an adolescent anorexic has a more general limitation.This eating disorder that affects older adults has two types - early onset and late onset. Early onset refers to a recurrence of anorexia in late life in an individual who experienced the disease during their youth. Late onset describes instances where the eating disorder begins for the first time late in life.
The stimulus for anorexia in elderly patients is typically a loss of control over their lives, which can be brought on by many events, including moving into an assisted living facility. This is also a time when most older individuals experience a rise in conflict with family members, such as limitations on driving or limitations on personal freedom, which increases the likelihood of an issue with anorexia. There can be physical issues in the elderly that leads to anorexia of aging, including a decline in chewing ability, a decline in taste and smell, and a decrease in appetite. Psychological reasons for the elderly to develop anorexia can include depression and bereavement, and even an indirect attempt at suicide. There are also common comorbid psychiatric conditions with aging anorexics, including major depression, anxiety disorder, obsessive compulsive disorder, bipolar disorder, schizophrenia, and dementia.The signs and symptoms that go along with anorexia of aging are similar to what is observed in adolescent anorexia, including sudden weight loss, unexplained hair loss or dental problems, and a desire to eat alone.There are also several medical conditions that can result from anorexia in the elderly. An increased risk of illness and death can be a result of anorexia. There is also a decline in muscle and bone mass as a result of a reduction in protein intake during anorexia. Another result of anorexia in the aging population is irreparable damage to kidneys, heart or colon and an imbalance of electrolytes.Many assessments are available to diagnose anorexia in the aging community. These assessments include the Simplified Nutritional Assessment Questionnaire (SNAQ) and Functional Assessment of Anorexia/Cachexia Therapy (FAACT). Specific to the geriatric populace, the interRAI system identifies detrimental conditions in assisted living facilities and nursing homes. Even a simple screening for nutritional insufficiencies such as low levels of important vitamins, can help to identify someone who has anorexia of aging.Anorexia in the elderly should be identified by the retirement communities but is often overlooked, especially in patients with dementia. Some studies report that malnutrition is prevalent in nursing homes, with up to 58% of residents suffering from it, which can lead to the difficulty of identifying anorexia. One of the challenges with assisted living facilities is that they often serve bland, monotonous food, which lessens residents desire to eat.The treatment for anorexia of aging is undifferentiated as anorexia for any other age group. Some of the treatment options include outpatient and inpatient facilities, antidepressant medication and behavioral therapy such as meal observation and discussing eating habits.Male and female athletes are often overlooked as anorexic. Research emphasizes the importance to take athletes diet, weight and symptoms into account when diagnosing anorexia, instead of just looking at weight and BMI. For athletes, ritualized activities such as weigh-ins place emphasis on gaining and losing large amounts of weight, which may promote the development of eating disorders among them. While women use diet pills, which is an indicator of unhealthy behavior and an eating disorder, men use steroids, which contextualizes the beauty ideals for genders </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 Anthrax and explain in detail? [/INST] Anthrax is an infection caused by the bacterium Bacillus anthracis. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The skin form presents with a small blister with surrounding swelling that often turns into a painless ulcer with a black center. The inhalation form presents with fever, chest pain and shortness of breath. The intestinal form presents with diarrhea (which may contain blood), abdominal pains, nausea and vomiting. The injection form presents with fever and an abscess at the site of drug injection.According to the Centers for Disease Control the first clinical descriptions of cutaneous anthrax were given by Maret in 1752 and Fournier in 1769. Before that anthrax had been described only through historical accounts. The Prussian scientist Robert Koch (1843–1910) was the first to identify Bacillus anthracis as the bacterium that causes anthrax.
Anthrax is spread by contact with the bacteriums spores, which often appear in infectious animal products. Contact is by breathing or eating or through an area of broken skin. It does not typically spread directly between people. Risk factors include people who work with animals or animal products, travelers, and military personnel. Diagnosis can be confirmed by finding antibodies or the toxin in the blood or by culture of a sample from the infected site.Anthrax vaccination is recommended for people at high risk of infection. Immunizing animals against anthrax is recommended in areas where previous infections have occurred. A two-month course of antibiotics such as ciprofloxacin, levofloxacin and doxycycline after exposure can also prevent infection. If infection occurs, treatment is with antibiotics and possibly antitoxin. The type and number of antibiotics used depend on the type of infection. Antitoxin is recommended for those with widespread infection.A rare disease, human anthrax is most common in Africa and central and southern Asia. It also occurs more regularly in Southern Europe than elsewhere on the continent and is uncommon in Northern Europe and North America. Globally, at least 2,000 cases occur a year, with about two cases a year in the United States. Skin infections represent more than 95% of cases. Without treatment the risk of death from skin anthrax is 23.7%. For intestinal infection the risk of death is 25 to 75%, while respiratory anthrax has a mortality of 50 to 80%, even with treatment. Until the 20th century anthrax infections killed hundreds of thousands of people and animals each year. Anthrax has been developed as a weapon by a number of countries. In herbivorous animals infection occurs when they eat or breathe in the spores while grazing. Animals may become infected by killing and/or eating infected animals.

Etymology
The English name comes from anthrax (ἄνθραξ), the Greek word for coal, possibly having Egyptian etymology, because of the characteristic black skin lesions developed by people with a cutaneous anthrax infection. The central black eschar surrounded by vivid red skin has long been recognised as typical of the disease. The first recorded use of the word "anthrax" in English is in a 1398 translation of Bartholomaeus Anglicus work De proprietatibus rerum (On the Properties of Things, 1240).Anthrax was historically known by a wide variety of names indicating its symptoms, location and groups considered most vulnerable to infection. They included Siberian plague, Cumberland disease, charbon, splenic fever, malignant edema, woolsorters disease and la maladie de Bradford.

Signs and symptoms
Skin
Cutaneous anthrax, also known as hide-porters disease, is when anthrax occurs on the skin. It is the most common form (>90% of anthrax cases). It is the least dangerous form (low mortality with treatment, 23.7% mortality without). Cutaneous anthrax presents as a boil-like skin lesion that eventually forms an ulcer with a black center (eschar). The black eschar often shows up as a large, painless, necrotic ulcer (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. In general, cutaneous infections form within the site of spore penetration between two and five days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally do not cause pain. Nearby lymph nodes may become infected, reddened, swollen, and painful. A scab forms over the lesion soon, and falls off in a few weeks. Complete recovery may take longer.
Cutaneous anthrax is typically caused when B. anthracis spores enter through cuts on the skin. This form is found most commonly when humans handle infected animals and/or animal products.

Injection
In December 2009, an outbreak of anthrax occurred among injecting heroin users in the Glasgow and Stirling areas of Scotland, resulting in 14 deaths. The source of the anthrax is believed to have been dilution of the heroin with bone meal in Afghanistan. Injected anthrax may have symptoms similar to cutaneous anthrax, and may also cause infection deep into the muscle and spread faster.

Lungs
Inhalation anthrax usually develops within a week after exposure, but may take up to 2 months. During the first few days of illness, most people have fever, chills, and fatigue. These symptoms may be accompanied by cough, shortness of breath, chest pain, and nausea or vomiting, making inhalation anthrax difficult to distinguish from influenza and community-acquired pneumonia. This is often described as the prodromal period.Over the next day or so, shortness of breath, cough, and chest pain become more common, and complaints not involving the chest such as nausea, vomiting, altered mental status, sweats, and headache develop in one-third or more of people. Upper respiratory tract symptoms occur in only a quarter of people, and muscle pains are rare. Altered mental status or shortness of breath generally brings people to healthcare and marks the fulminant phase of illness.It infects the lymph nodes in the chest first, rather than the lungs themselves, a condition called hemorrhagic mediastinitis, causing bloody fluid to accumulate in the chest cavity, thereby causing shortness of breath. The second (pneumonia) stage occurs when the infection spreads from the lymph nodes to the lungs. Symptoms of the second stage develop suddenly within hours or days after the first stage. Symptoms include high fever, extreme shortness of breath, shock, and rapid death within 48 hours in fatal cases.

Gastrointestinal
Gastrointestinal (GI) infection is most often caused by consuming anthrax-infected meat and is characterized by diarrhea, potentially with blood, abdominal pains, acute inflammation of the intestinal tract, and loss of appetite. Occasional vomiting of blood can occur. Lesions have been found in the intestines and in the mouth and throat. After the bacterium invades the gastrointestinal system, it spreads to the bloodstream and throughout the body, while continuing to make toxins.

Cause
Bacteria
Bacillus anthracis is a rod-shaped, Gram-positive, facultative anaerobic bacterium about 1 by 9 μm in size. It was shown to cause disease by Robert Koch in 1876 when he took a blood sample from an infected cow, isolated the bacteria, and put them into a mouse. The bacterium normally rests in spore form in the soil, and can survive for decades in this state. Herbivores are often infected while grazing, especially when eating rough, irritant, or spiky vegetation; the vegetation has been hypothesized to cause wounds within the GI tract, permitting entry of the bacterial spores into the tissues. Once ingested or placed in an open wound, the bacteria begin multiplying inside the animal or human and typically kill the host within a few days or weeks. The spores germinate at the site of entry into the tissues and then spread by the circulation to the lymphatics, where the bacteria multiply.The production of two powerful exotoxins and lethal toxin by the bacteria causes death. Veterinarians can often tell a possible anthrax-induced death by its sudden occurrence, and by the dark, nonclotting blood that oozes from the body orifices. Most anthrax bacteria inside the body after death are outcompeted and destroyed by anaerobic bacteria within minutes to hours post mortem. However, anthrax vegetative bacteria that escape the body via oozing blood or through the opening of the carcass may form hardy spores. These vegetative bacteria are not contagious. One spore forms per one vegetative bacterium. The triggers for spore formation are not yet known, though oxygen tension and lack of nutrients may play roles. Once formed, these spores are very hard to eradicate.The infection of herbivores (and occasionally humans) by the inhalational route normally begins with inhaled spores being transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the lymph nodes in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity can cause chest pain and difficulty breathing. Once in the lymph nodes, the spores germinate into active bacilli that multiply and eventually burst the macrophages, releasing many more bacilli into the bloodstream to be transferred to the entire body. Once in the bloodstream, these bacilli release three proteins named lethal factor, edema factor, and protective antigen. The three are not toxic by themselves, but their combination is incredibly lethal to humans. Protective antigen combines with these other two factors to form lethal toxin and edema toxin, respectively. These toxins are the primary agents of tissue destruction, bleeding, and death of the host. If antibiotics are administered too late, even if the antibiotics eradicate the bacteria, some hosts still die of toxemia because the toxins produced by the bacilli remain in their systems at lethal dose levels.

Exposure
The spores of anthrax are able to survive in harsh conditions for decades or even centuries. Such spores can be found on all continents, including Antarctica. Disturbed grave sites of infected animals have been known to cause infection after 70 years.Historically, inhalational anthrax was called woolsorters disease because it was an occupational hazard for people who sorted wool. Today, this form of infection is extremely rare in advanced nations, as almost no infected animals remain.Occupational exposure to infected animals or their products (such as skin, wool, and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. Anthrax in livestock grazing on open range where they mix with wild animals still occasionally occurs in the United States and elsewhere.Many workers who deal with wool and animal hides are routinely exposed to low levels of anthrax spores, but most exposure levels are not sufficient to develop anthrax infections. A lethal infection is reported to result from inhalation of about 10,000–20,000 spores, though this dose varies among host species. Little documented evidence is available to verify the exact or average number of spores needed for infection.

Mode of infection
Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous) and causes distinct clinical symptoms based on its site of entry. In general, an infected human is quarantined. However, anthrax does not usually spread from an infected human to an uninfected human. If the disease is fatal to the persons body, though, its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent further contamination. Inhalational anthrax, if left untreated until obvious symptoms occur, is usually fatal.Anthrax can be contracted in laboratory accidents or by handling infected animals, their wool, or their hides. It has also been used in biological warfare agents and by terrorists to intentionally infect as exemplified by the 2001 anthrax attacks.

Mechanism
The lethality of the anthrax disease is due to the bacteriums two principal virulence factors: the poly-D-glutamic acid capsule, which protects the bacterium from phagocytosis by host neutrophils, and the tripartite protein toxin, called anthrax toxin. Anthrax components: protective antigen (PA), edema factor (EF), and lethal factor (LF). PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling (edema), respectively.
To enter the cells, the edema and lethal factors use another protein produced by B. anthracis called protective antigen, which binds to two surface receptors on the host cell. A cell protease then cleaves PA into two fragments: PA20 and PA63. PA20 dissociates into the extracellular medium, playing no further role in the toxic cycle. PA63 then oligomerizes with six other PA63 fragments forming a heptameric ring-shaped structure named a prepore. Once in this shape, the complex can competitively bind up to three EFs or LFs, forming a resistant complex. Receptor-mediated endocytosis occurs next, providing the newly formed toxic complex access to the interior of the host cell. The acidified environment within the endosome triggers the heptamer to release the LF and/or EF into the cytosol. It is unknown how exactly the complex results in the death of the cell.
Edema factor is a calmodulin-dependent adenylate cyclase. Adenylate cyclase catalyzes the conversion of ATP into cyclic AMP (cAMP) and pyrophosphate. The complexation of adenylate cyclase with calmodulin removes calmodulin from stimulating calcium-triggered signaling, thus inhibiting the immune response. To be specific, LF inactivates neutrophils (a type of phagocytic cell) by the process just described so they cannot phagocytose bacteria. Throughout history, lethal factor was presumed to cause macrophages to make TNF-alpha and interleukin 1, beta (IL1B). TNF-alpha is a cytokine whose primary role is to regulate immune cells, as well as to induce inflammation and apoptosis or programmed cell death. Interleukin 1, beta is another cytokine that also regulates inflammation and apoptosis. The overproduction of TNF-alpha and IL1B ultimately leads to septic shock and death. However, recent evidence indicates anthrax also targets endothelial cells that line serous cavities such as the pericardial cavity, pleural cavity, and peritoneal cavity, lymph vessels, and blood vessels, causing vascular leakage of fluid and cells, and ultimately hypovolemic shock and septic shock.

Diagnosis
Various techniques may be used for the direct identification of B. anthracis in clinical material. Firstly, specimens may be Gram stained. Bacillus spp. are quite large in size (3 to 4 μm long), they may grow in long chains, and they stain Gram-positive. To confirm the organism is B. anthracis, rapid diagnostic techniques such as polymerase chain reaction-based assays and immunofluorescence microscopy may be used.All Bacillus species grow well on 5% sheep blood agar and other routine culture media. Polymyxin-lysozyme-EDTA-thallous acetate can be used to isolate B. anthracis from contaminated specimens, and bicarbonate agar is used as an identification method to induce capsule formation. Bacillus spp. usually grow within 24 hours of incubation at 35 °C, in ambient air (room temperature) or in 5% CO2. If bicarbonate agar is used for identification, then the medium must be incubated in 5% CO2. B. anthracis colonies are medium-large, gray, flat, and irregular with swirling projections, often referred to as having a "medusa head" appearance, and are not hemolytic on 5% sheep blood agar. The bacteria are not motile, susceptible to penicillin, and produce a wide zone of lecithinase on egg yolk agar. Confirmatory testing to identify B. anthracis includes gamma bacteriophage testing, indirect hemagglutination, and enzyme-linked immunosorbent assay to detect antibodies. The best confirmatory precipitation test for anthrax is the Ascoli test.

Prevention
Precautions are taken to avoid contact with the skin and any fluids exuded through natural body openings of a deceased body that is suspected of harboring anthrax. The body should be put in strict quarantine. A blood sample is collected and sealed in a container and analyzed in an approved laboratory to ascertain if anthrax is the cause of death. The body should be sealed in an airtight body bag and incinerated to prevent the transmission of anthrax spores. Microscopic visualization of the encapsulated bacilli, usually in very large numbers, in a blood smear stained with polychrome methylene blue (McFadyean stain) is fully diagnostic, though the culture of the organism is still the gold standard for diagnosis. Full isolation of the body is important to prevent possible contamination of others.Protective, impermeable clothing and equipment such as rubber gloves, rubber apron, and rubber boots with no perforations are used when handling the body. No skin, especially if it has any wounds or scratches, should be exposed. Disposable personal protective equipment is preferable, but if not available, decontamination can be achieved by autoclaving. Used disposable equipment is burned and/or buried after use. All contaminated bedding or clothing is isolated in double plastic bags and treated as biohazard waste. Respiratory equipment capable of filtering small particles, such the US National Institute for Occupational Safety and Health- and Mine Safety and Health Administration-approved high-efficiency respirator, is worn.

Vaccines
Vaccines against anthrax for use in livestock and humans have had a prominent place in the history of medicine. The French scientist Louis Pasteur developed the first effective vaccine in 1881. Human anthrax vaccines were developed by the Soviet Union in the late 1930s and in the US and UK in the 1950s. The current FDA-approved US vaccine was formulated in the 1960s.Currently administered human anthrax vaccines include acellular (United States) and live vaccine (Russia) varieties. All currently used anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever) and serious adverse reactions occur in about 1% of recipients. The American product, BioThrax, is licensed by the FDA and was formerly administered in a six-dose primary series at 0, 2, 4 weeks and 6, 12, 18 months, with annual boosters to maintain immunity. In 2008, the FDA approved omitting the week-2 dose, resulting in the currently recommended five-dose series. New second-generation vaccines currently being researched include recombinant live vaccines and recombinant subunit vaccines. In the 20th century the use of a modern product (BioThrax) to protect American troops against the use of anthrax in biological warfare was controversial.

Antibiotics
Preventive antibiotics are recommended in those who have been exposed. Early detection of sources of anthrax infection can allow preventive measures to be taken. In response to the anthrax attacks of October 2001, the United States Postal Service (USPS) installed biodetection systems (BDSs) in their large-scale mail processing facilities. BDS response plans were formulated by the USPS in conjunction with local responders including fire, police, hospitals, and public health. Employees of these facilities have been educated about anthrax, response actions, and prophylactic medication. Because of the time delay inherent in getting final verification that anthrax has been used, prophylactic antibiotic treatment of possibly exposed personnel must be started as soon as possible.

Treatment
Anthrax cannot be spread from person to person, except in the rare case of skin exudates from cutaneous anthrax. However, a persons clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash-down with antimicrobial soap and water. Wastewater is treated with bleach or another antimicrobial agent. Effective decontamination of articles can be accomplished by boiling them in water for 30 minutes or longer. Chlorine bleach is ineffective in destroying spores and vegetative cells on surfaces, though formaldehyde is effective. Burning clothing is very effective in destroying spores. After decontamination, there is no need to immunize, treat, or isolate contacts of persons ill with anthrax unless they were also exposed to the same source of infection.

Antibiotics
Early antibiotic treatment of anthrax is essential; delay significantly lessens chances for survival. Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones (ciprofloxacin), doxycycline, erythromycin, vancomycin, or penicillin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin. In possible cases of pulmonary anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death. Many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough.

Monoclonal antibodies
In May 2009, Human Genome Sciences submitted a biologic license application (BLA, permission to market) for its new drug, raxibacumab (brand name ABthrax) intended for emergency treatment of inhaled anthrax. On 14 December 2012, the US Food and Drug Administration approved raxibacumab injection to treat inhalational anthrax. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. anthracis. In March 2016, FDA approved a second anthrax treatment using a monoclonal antibody which neutralizes the toxins produced by B. anthracis. Obiltoxaximab is approved to treat inhalational anthrax in conjunction with appropriate antibacterial drugs, and for prevention when alternative therapies are not available or appropriate.

Prognosis
Cutaneous anthrax is rarely fatal if treated, because the infection area is limited to the skin, preventing the lethal factor, edema factor, and protective antigen from entering and destroying a vital organ. Without treatment, about 20% of cutaneous skin infection cases progress to toxemia and death.Before 2001, fatality rates for inhalation anthrax were 90%; since then, they have fallen to 45%. People that progress to the fulminant phase of inhalational anthrax nearly always die, with one case study showing a death rate of 97%. Anthrax meningoencephalitis is also nearly always fatal.GI infections can be treated, but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences. This form of anthrax is the rarest.

Epidemiology
Globally, at least 2,000 cases occur a year.

United States
The last fatal case of natural inhalational anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. To minimize the chance of spreading the disease, the body was transported to UCLA in a sealed plastic body bag within a sealed metal container for autopsy.Gastrointestinal anthrax is exceedingly rare in the United States, with only two cases on record. The first case was reported in 1942, according to the Centers for Disease Control and Prevention. During December 2009, the New Hampshire Department of Health and Human Services confirmed a case of gastrointestinal anthrax in an adult female.
In 2007 two cases of cutaneous anthrax were reported in Danbury, Connecticut. The case involved the maker of traditional African-style drums who was working with a goat hide purchased from a dealer in New York City which had been previously cleared by Customs. While the hide was being scraped, a spider bite led to the spores entering the bloodstream. His son also became infected.The CDC investigated the source of the December 2009 infection and the possibility that it was contracted from an African drum recently used by the woman taking part in a drum circle. The woman apparently inhaled anthrax, in spore form, from the hide of the drum. She became critically ill, but with gastrointestinal anthrax rather than inhaled anthrax, which made her unique in American medical history. The building where the infection took place was cleaned and reopened to the public and the woman recovered. The New Hampshire state epidemiologist, Jodie Dionne-Odom, stated "It is a mystery. We really dont know why it happened."

Croatia
In July 2022, dozens of cattle in a nature park in Lonjsko Polje, a flood plain by the Sava river, died of anthrax and 6 people have been hospitalized with light, skin-related symptoms.

United Kingdom
In November 2008, a drum maker in the United Kingdom who worked with untreated animal skins died from anthrax. In December 2009, an outbreak of anthrax occurred among heroin addicts in the Glasgow and Stirling areas of Scotland, resulting in 14 deaths. The source of the anthrax is believed to have been dilution of the heroin with bone meal in Afghanistan.

History
Discovery
Robert Koch, a German physician and scientist, first identified the bacterium that caused the anthrax disease in 1875 in Wollstein (now Wolsztyn - a town in Poland). His pioneering work in the late 19th century was one of the first demonstrations that diseases could be caused by microbes. In a groundbreaking series of experiments, he uncovered the lifecycle and means of transmission of anthrax. His experiments not only helped create an understanding of anthrax but also helped elucidate the role of microbes in causing illness at a time when debates still took place over spontaneous generation versus cell theory. Koch went on to study the mechanisms of other diseases and won the 1905 Nobel Prize in Physiology or Medicine for his discovery of the bacterium causing tuberculosis.Although Koch arguably made the greatest theoretical contribution to understanding anthrax, other researchers were more concerned with the practical questions of how to prevent the disease. In Britain, where anthrax affected workers in the wool, worsted, hides, and tanning industries, it was viewed with fear. John Henry Bell, a doctor born & based in Bradford, first made the link between the mysterious and deadly "woolsorters disease" and anthrax, showing in 1878 that they were one and the same. In the early 20th century, Friederich Wilhelm Eurich, the German bacteriologist who settled in Bradford with his family as a child, carried out important research for the local Anthrax Investigation Board. Eurich also made valuable contributions to a Home Office Departmental Committee of Inquiry, established in 1913 to address the continuing problem of industrial anthrax. His work in this capacity, much of it collaboration with the factory inspector G. Elmhirst Duckering, led directly to the Anthrax Prevention Act (1919).

First vaccination
Anthrax posed a major economic challenge in France and elsewhere during the 19th century. Horses, cattle, and sheep were particularly vulnerable, and national funds were set aside to investigate the production of a vaccine. French scientist Louis Pasteur was charged with the production of a vaccine, following his successful work in developing methods that helped to protect the important wine and silk industries.In May 1881, Pasteur – in collaboration with his assistants Jean-Joseph Henri Toussaint, Émile Roux and others – performed a public experiment at Pouilly-le-Fort to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat, and several cattle. The animals of one group were injected with an anthrax vaccine prepared by Pasteur twice, at an interval of 15 days; the control group was left unvaccinated. Thirty days after the first injection, both groups were injected with a culture of live anthrax bacteria. All the animals in the unvaccinated group died, while all of the animals in the vaccinated group survived.After this apparent triumph, which was widely reported in the local, national, and international press, Pasteur made strenuous efforts to export the vaccine beyond France. He used his celebrity status to establish Pasteur Institutes across Europe and Asia, and his nephew, Adrien Loir, travelled to Australia in 1888 to try to introduce the vaccine to combat anthrax in New South Wales. Ultimately, the vaccine was unsuccessful in the challenging climate of rural Australia, and it was soon superseded by a more robust version developed by local researchers John Gunn and John McGarvie Smith.The human vaccine for anthrax became available in 1954. This was a cell-free vaccine instead of the live-cell Pasteur-style vaccine used for veterinary purposes. An improved cell-free vaccine became available in 1970.

Engineered strains
The Sterne strain of anthrax, named after the Trieste-born immunologist Max Sterne, is an attenuated strain used as a vaccine, which contains only the anthrax toxin virulence plasmid and not the polyglutamic acid capsule expressing plasmid.
Strain 836, created by the Soviet bioweapons program in the 1980s, was later called by the Los Angeles Times "the most virulent and vicious strain of anthrax known to man".
The virulent Ames strain, which was used in the 2001 anthrax attacks in the United States, has received the most news coverage of any anthrax outbreak. The Ames strain contains two virulence plasmids, which separately encode for a three-protein toxin, called anthrax toxin, and a polyglutamic acid capsule.
Nonetheless, the Vollum strain, developed but never used as a biological weapon during the Second World War, is much more dangerous. The Vollum (also incorrectly referred to as Vellum) strain was isolated in 1935 from a cow in Oxfordshire. This same strain was used during the Gruinard bioweapons trials. A variation of Vollum, known as "Vollum 1B", was used during the 1960s in the US and UK bioweapon programs. Vollum 1B is widely believed to have been isolated from William A. Boyles, a 46-year-old scientist at the US Army Biological Warfare Laboratories at Camp (later Fort) Detrick, Maryland, who died in 1951 after being accidentally infected with the Vollum strain.
US Air Force researchers have developed a vaccine strain to produce an improved anthrax vaccine which requires a minimal number of injections to achieve and maintain long-term immunity. It is designated as the Alls/Gifford (Curlicue) strain.

Society and culture
Site cleanup
Anthrax spores can survive for very long periods of time in the environment after release. Chemical methods for cleaning anthrax-contaminated sites or materials may use oxidizing agents such as peroxides, ethylene oxide, Sandia Foam, chlorine dioxide (used in the Hart Senate Office Building), peracetic acid, ozone gas, hypochlorous acid, sodium persulfate, and liquid bleach products containing sodium hypochlorite. Nonoxidizing agents shown to be effective for anthrax decontamination include methyl bromide, formaldehyde, and metam sodium. These agents destroy bacterial spores. All of the aforementioned anthrax decontamination technologies have been demonstrated to be effective in laboratory tests conducted by the US EPA or others.Decontamination techniques for Bacillus anthracis spores are affected by the material with which the spores are associated, environmental factors such as temperature and humidity, and microbiological factors such as the spore species, anthracis strain, and test methods used.A bleach solution for treating hard surfaces has been approved by the EPA. Chlorine dioxide has emerged as the preferred biocide against anthrax-contaminated sites, having been employed in the treatment of numerous government buildings over the past decade. Its chief drawback is the need for in situ processes to have the reactant on demand.
To speed the process, trace amounts of a nontoxic catalyst composed of iron and tetroamido macrocyclic ligands are combined with sodium carbonate and bicarbonate and converted into a spray. The spray formula is applied to an infested area and is followed by another spray containing tert-butyl hydroperoxide.Using the catalyst method, complete destruction of all anthrax spores can be achieved in under 30 minutes. A standard catalyst-free spray destroys fewer than half the spores in the same amount of time.
Cleanups at a Senate Office Building, several contaminated postal facilities, and other US government and private office buildings, a collaborative effort headed by the Environmental Protection Agency showed decontamination to be possible, but time-consuming and costly. Clearing the Senate Office Building of anthrax spores cost $27 million, according to the Government Accountability Office. Cleaning the Brentwood postal facility in Washington cost $130 million and took 26 months. Since then, newer and less costly methods have been developed.Cleanup of anthrax-contaminated areas on ranches and in the wild is much more problematic. Carcasses may be burned, though often 3 days are needed to burn a large carcass and this is not feasible in areas with little wood. Carcasses may also be buried, though the burying of large animals deeply enough to prevent resurfacing of spores requires much manpower and expensive tools. Carcasses have been soaked in formaldehyde to kill spores, though this has environmental contamination issues. Block burning of vegetation in large areas enclosing an anthrax outbreak has been tried; this, while environmentally destructive, causes healthy animals to move away from an area with carcasses in search of fresh grass. Some wildlife workers have experimented with covering fresh anthrax carcasses with shadecloth and heavy objects. This prevents some scavengers from opening the carcasses, thus allowing the putrefactive bacteria within the carcass to kill the vegetative B. anthracis cells and preventing sporulation. This method also has drawbacks, as scavengers such as hyenas are capable of infiltrating almost any exclosure.The experimental site at Gruinard Island is said to have been decontaminated with a mixture of formaldehyde and seawater by the Ministry of Defence. It is not clear whether similar treatments had been applied to US test sites.

Biological warfare
Anthrax spores have been used as a biological warfare weapon. Its first modern incidence occurred when Nordic rebels, supplied by the German General Staff, used anthrax with unknown results against the Imperial Russian Army in Finland in 1916. Anthrax was first tested as a biological warfare agent by Unit 731 of the Japanese Kwantung Army in Manchuria during the 1930s; some of this testing involved intentional infection of prisoners of war, thousands of whom died. Anthrax, designated at the time as Agent N, was also investigated by the Allies in the 1940s.A long history of practical bioweapons research exists in this area. For example, in 1942, British bioweapons trials severely contaminated Gruinard Island in Scotland with anthrax spores of the Vollum-14578 strain, making it a no-go area until it was decontaminated in 1990. The Gruinard trials involved testing the effectiveness of a submunition of an "N-bomb" –  a biological weapon containing dried anthrax spores. Additionally, five million "cattle cakes" (animal feed pellets impregnated with anthrax spores) were prepared and stored at Porton Down for "Operation Vegetarian" –  anti livestock attacks against Germany to be made by the Royal Air Force. The plan was for anthrax-based biological weapons to be dropped on Germany in 1944. However, the edible cattle cakes and the bomb were not used; the cattle cakes were incinerated in late 1945.
Weaponized anthrax was part of the US stockpile prior to 1972, when the United States signed the Biological Weapons Convention. President Nixon ordered the dismantling of US biowarfare programs in 1969 and the destruction of all existing stockpiles of bioweapons. In 1978–79, the Rhodesian government used anthrax against cattle and humans during its campaign against rebels. The Soviet Union created and stored 100 to 200 tons of anthrax spores at Kantubek on Vozrozhdeniya Island; they were abandoned in 1992 and destroyed in 2002.American military and British Army personnel are no longer routinely vaccinated against anthrax prior to active service in places where biological attacks are considered a threat.

Sverdlovsk incident (2 April 1979)
Despite signing the 1972 agreement to end bioweapon production, the government of the Soviet Union had an active bioweapons program that included the production of hundreds of tons of anthrax after this period. On 2 April 1979, some of the over one million people living in Sverdlovsk (now called Ekaterinburg, Russia), about 1,370 kilometres (850 mi) east of Moscow, were exposed to an accidental release of anthrax from a biological weapons complex located near there. At least 94 people were infected, of whom at least 68 died. One victim died four days after the release, 10 over an eight-day period at the peak of the deaths, and the last six weeks later. Extensive cleanup, vaccinations, and medical interventions managed to save about 30 of the victims. Extensive cover-ups and destruction of records by the KGB continued from 1979 until Russian President Boris Yeltsin admitted this anthrax accident in 1992. Jeanne Guillemin reported in 1999 that a combined Russian and United States team investigated the accident in 1992.Nearly all of the night-shift workers of a ceramics plant directly across the street from the biological facility (compound 19) became infected, and most died. Since most were men, some NATO governments suspected the Soviet Union had developed a sex-specific weapon. The government blamed the outbreak on the consumption of anthrax-tainted meat, and ordered the confiscation of all uninspected meat that entered the city. They also ordered all stray dogs to be shot and people not have contact with sick animals. Also, a voluntary evacuation and anthrax vaccination program was established for people from 18 to 55.To support the cover-up story, Soviet medical and legal journals published articles about an outbreak in livestock that caused GI anthrax in people having consumed infected meat, and cutaneous anthrax in people having come into contact with the animals. All medical and public health records were confiscated by the KGB. In addition to the medical problems the outbreak caused, it also prompted Western countries to be more suspicious of a covert Soviet bioweapons program and to increase their surveillance of suspected sites. In 1986, the US government was allowed to investigate the incident, and concluded the exposure was from aerosol anthrax from a military weapons facility. In 1992, President Yeltsin admitted he was "absolutely certain" that "rumors" about the Soviet Union violating the 1972 Bioweapons Treaty were true. The Soviet Union, like the US and UK, had agreed to submit information to the UN about their bioweapons programs, but omitted known facilities and never acknowledged their weapons program.

Anthrax bioterrorism
In theory, anthrax spores can be cultivated with minimal special equipment and a first-year collegiate microbiological education.
To make large amounts of an aerosol form of anthrax suitable for biological warfare requires extensive practical knowledge, training, and highly advanced equipment.Concentrated anthrax spores were used for bioterrorism in the 2001 anthrax attacks in the United States, delivered by mailing postal letters containing the spores. The letters were sent to several news media offices and two Democratic senators: Tom Daschle of South Dakota and Patrick Leahy of Vermont. As a result, 22 were infected and five died </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 Anticholinergic and explain in detail? [/INST] Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.These agents inhibit the parasympathetic nervous system by selectively blocking the binding of ACh to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, sweat glands, and many other parts of the body.In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central and peripheral nervous system and at the neuromuscular junction: antimuscarinic agents, and antinicotinic agents (ganglionic blockers, neuromuscular blockers).The term "anticholinergic" is typically used to refer to antimuscarinics which competitively inhibit the binding of ACh to muscarinic acetylcholine receptors; such agents do not antagonize the binding at nicotinic acetylcholine receptors at the neuromuscular junction, although the term is sometimes used to refer to agents which do so.

Medical uses
Anticholinergic drugs are used to treat a variety of conditions:

Dizziness (including vertigo and motion sickness-related symptoms)
Extrapyramidal symptoms, a potential side-effect of antipsychotic medications
Gastrointestinal disorders (e.g., peptic ulcers, diarrhea, pylorospasm, diverticulitis, ulcerative colitis, nausea, and vomiting)
Genitourinary disorders (e.g., cystitis, urethritis, and prostatitis)
Insomnia, although usually only on a short-term basis
Respiratory disorders (e.g., asthma, chronic bronchitis, and chronic obstructive pulmonary disease [COPD])
Sinus bradycardia due to a hypersensitive vagus nerve
Organophosphate based nerve agent poisoning, such as VX, sarin, tabun, and soman (atropine is favoured in conjunction with an oxime, usually pralidoxime)Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures.Until the beginning of the 20th century anticholinergic drugs were widely used to treat psychiatric disorders.

Physiological effects
Delirium (often with hallucinations and delusions indistinguishable from reality)
Ocular symptoms (from eye drops): mydriasis, pupil dilation, and acute angle-closure glaucoma in those with shallow anterior chamber
Anhidrosis, dry mouth, dry skin
Fever
Constipation
Tachycardia
Urinary retention
Cutaneous vasodilationClinically the most significant feature is delirium, particularly in the elderly, who are most likely to be affected by the toxidrome.

Side effects
Long-term use may increase the risk of both cognitive and physical decline. It is unclear whether they affect the risk of death generally. However, in older adults they do appear to increase the risk of death.Possible effects of anticholinergics include:

Possible effects in the central nervous system resemble those associated with delirium, and may include:

Older patients are at a higher risk of experiencing CNS side effects.

Toxicity
An acute anticholinergic syndrome is reversible and subsides once all of the causative agents have been excreted. Reversible acetylcholinesterase inhibitor agents such as physostigmine can be used as an antidote in life-threatening cases. Wider use is discouraged due to the significant side effects related to cholinergic excess including seizures, muscle weakness, bradycardia, bronchoconstriction, lacrimation, salivation, bronchorrhea, vomiting, and diarrhea. Even in documented cases of anticholinergic toxicity, seizures have been reported after the rapid administration of physostigmine </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 Antisialagogue and explain in detail? [/INST]  </s>