<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mesangial proliferative glomerulonephritis and can you explain it in depth? [/INST] Mesangial proliferative glomerulonephritis (MesPGN) is a morphological pattern characterized by a numerical increase in mesangial cells and expansion of the extracellular matrix within the mesangium of the glomerulus. The increase in the number of mesangial cells can be diffuse or local and immunoglobulin and/or complement deposition can also occur. MesPGN is associated with a variety of disease processes affecting the glomerulus, though can be idiopathic. The clinical presentation of MesPGN usually consists of hematuria or nephrotic syndrome. Treatment is often consistent with the histologic pattern of and/or disease process contributing to mesangial proliferative glomerulonephritis, and usually involves some form of immunosuppressant.

Mechanism
MesPGN often occurs as a result of glomerular injury, though can be idiopathic. MesPGN has been associated with disease processes such as: IgA nephropathy, IgM nephropathy, systemic lupus erythematous, Alports syndrome, resolving post-infectious glomerulonephritis, and complement nephropathy, such as C1Q nephropathy.IgA nephropathy is the most common cause of MesPGN. It is thought abnormally glycosylated IgA form polymers and deposit in the mesangium. Subsequently, IgA immune complexes bind to IgA receptors on mesangial cells and induce injury to mesangial cells through release of cytokines and growth factors that promote infiltration of leukocytes, mesangial cell proliferation, and mesangial matrix expansion.In the context of resolving post-infectious glomerulonephritis, MesPGN can be seen after an infection with a nephritogenic strain of group A streptococci. Pathogenesis of post-streptococcal glomerulonephritis includes injury to the glomerulus by immune complexes (IgG) passively trapped in the glomerulus, which leads to an inflammatory response from recruited immune cells, cytokines, chemical mediators, and complement and coagulation cascade activation. The inflammatory response includes endothelial and mesangial cell proliferation.Mesangial proliferative glomerulonephritis of Lupus nephritis, Class II is also noted by mesangial hypercellularity and matrix expansion. Microscopic haematuria with or without proteinuria may be seen in Class II Lupus nephritis. Hypertension, nephrotic syndrome, and acute kidney injury are very rare at this stage.Idiopathic mesangial proliferative glomerulonephritis is less established in the literature. Idiopathic mesangial proliferative glomerulonephritis does not involve the deposition of either IgA or IgG immune complexes, though there can be focal or diffuse IgM deposits in the mesangium. The relationship of IgM and mesangial proliferative glomerulonephritis is hypothesized to involve either formed or deposited IgM complexes in the mesangium leading to T-cell mediated inflammatory response, mesangial proliferation, and glomerular injury or, as a result of mesangial proliferation, decreased clearance of monocytic IgM complexes.

Diagnosis
Most glomerulonephritis classification and prognosis are aided by histological evaluation by renal biopsy. The renal biopsy is classically evaluated with light microscopy, electron microscopy, and immunohistology to diagnose a histological pattern, which is then compared to clinical evaluation through history, physical, and laboratory evaluation. The laboratory evaluation usually follows that of a standard nephrology work up and will likely be targeted to a differential diagnosis. Studies focusing on mesangial proliferative glomerulonephritis often use defined clinical criteria and histological criteria to select patients for research. For example, one study used the following histological criteria: "Glomeruli with mesangial hypercellularity (four or more cells/mesangium with or without mesangial matrix expansion and immune complex deposits)". The histologic pattern of injury can also provide insight into the prognosis of the glomerular disorder. Mesangial proliferation indicates a mild, though active, lesion </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Rhinoscleroma and can you explain it in depth? [/INST] Rhinoscleroma, is a chronic granulomatous bacterial disease of the nose that can sometimes infect the upper respiratory tract. It most commonly affects the nasal cavity—the nose is involved in 95–100 per cent of cases—however, it can also affect the nasopharynx, larynx, trachea, and bronchi. Slightly more females than males are affected and patients are usually 10 to 30 years of age. Rhinoscleroma is considered a tropical disease and is mostly endemic to North Africa, South Asia and Central America, less common in the United States.

Signs and symptoms
Rhinoscleroma has been divided into 3 stages: catarrhal/atrophic, granulomatous, and sclerotic stages. The catarrhal stage begins with a nonspecific rhinitis, which progresses into purulent, fetid rhinorrhea, and crusting, which can last for weeks or even months. The granulomatous stage results in the development of a bluish red nasal mucosa and the development of intranasal rubbery nodules or polyps. Nose bleeds, nasal deformity, and destruction of the nasal cartilage are also noted (Hebra nose). The damage may result in anesthesia of the soft palate, enlargement of the uvula, dysphonia, and various degrees of airway obstruction. The fibrotic stage is characterized by sclerosis and fibrosis. Lymphadenitis is absent.

Causes
It is caused by Klebsiella rhinoscleromatis—subspecies of
Klebsiella pneumoniae— a gram-negative, encapsulated, nonmotile, rod-shaped bacillus (diplobacillus), member of the family Enterobacteriaceae. It is sometimes referred to as the "Frisch bacillus," named for Anton von Frisch who identified the organism in 1882. It is contracted directly by droplets or by contamination of material that is subsequently inhaled.

Diagnosis
A positive culture in MacConkey agar is diagnostic, but cultures are only positive in 50–60% of cases. Diagnostic characteristics are most commonly found in the granulomatous stage and are described as being plasma cells with birefringent inclusions, Russell bodies, pseudoepitheliomatous hyperplasia, and groups of large vacuolated histiocytes containing Klebsiella rhinoscleromatis (Mikulicz cells).

Treatment
It is not lethal in nature and is responsive to tetracycline or ciprofloxacin. Surgical treatment include rhinoplasty. However, if left untreated the disease can lead to sepsis, bleeding, or other chronic conditions that can be fatal.

History
Hans von Hebra (1847–1902) wrote the classical description of the disease in a paper published in the January 1870 issue of the Wiener Medizinische Wochenschrift. Hans von Hebra was the son of Czech born dermatologist Ferdinand Ritter von Hebra (1816–1880), founder of the New Vienna School of Dermatology. He was assisted by M. Kohn who provided much of the histology for the paper. M. Kohn is the birth name of Moritz Kaposi (1837–1902). In 1876, Mikulicz contributed to the microscopic histology. In 1882, Anton Von Frisch (1849–1917) discovered the gram-negative bacillus which causes the disease.

Terminology
Hebra nose. Scleroma. Fr: Sclérome. Sp: Rinoscleroma. Ger: Sklerom. Nasen-Rachenrauminduration.Archaic terms include: Syphilis of the nose. Nasal leprosy. Scleroma neonatorum. Scleroma respiratorum. Scrofulous lupus.

See also
Erythrasma
List of cutaneous conditions
List of inclusion bodies that aid in diagnosis of cutaneous conditions

Notes
References
DiBartolomeo, Joseph R. (1976), Scleroma of the nose and pharynx. Journal: West. J. Med., vol. 124., pp. 13–17.
Frisch, Anton von (1882), Zur Aetiologie des Rhinoskleroms. Journal: Wiener Medizinische Wochenschrift; vol. 32, pp. 969–972.
Hebra, Hans von (1870), Ueber ein eigenthümliches Neugebilde an der Nase; Rhinosclerom; nebst histologischem Befunde vom Dr. M. Kohn. Journal: Wiener Medizinische Wochenschrift; vol. 20, pp. 1–5.
Morton, Leslie T. (1970), A medical bibliography (Garrison and Morton). Philadelphia & Toronto: J </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Chronic sclerosing sialadenitis and can you explain it in depth? [/INST] Chronic sclerosing sialadenitis is a chronic (long-lasting) inflammatory condition affecting the salivary gland. Relatively rare in occurrence, this condition is benign, but presents as hard, indurated and enlarged masses that are clinically indistinguishable from salivary gland neoplasms or tumors. It is now regarded as a manifestation of IgG4-related disease.Involvement of the submandibular glands is also known as Küttners tumor, named after Hermann Küttner (1870–1932), a German Oral and Maxillofacial Surgeon, who reported four cases of submandibular gland lesions for the first time in 1896.

Presentation
The inflammatory lesions in Küttners tumor may occur on one side (unilateral) or both sides (bilateral), predominantly involving the submandibular gland, but is also known to occur in other major and minor salivary glands, including the parotid gland.
Overall, salivary gland tumors are relatively rare, with approximately 2.5–3 cases per 100,000 people per year seen in the Western world; however, salivary gland malignancies account for 3–5% of all head and neck cancers. However, salivary tumors show a great deal of morphological diversity, as well as variations in the nature of the lesion (malignant vs. benign):  approximately 20% to 25% of parotid tumors, 35% to 40% of submandibular tumors, and more than 90% of sublingual gland tumors are malignant. This situation underscores the diagnostic challenges in respect of Küttners tumor; despite being benign, this condition mimics the clinical appearance of malignancy in the salivary gland.
The swollen masses of Küttners tumor are generally painful, and patients are advised surgical resection (known as sialadenectomy) of a part or whole of the glandular tissue upon suspicion of possible malignancy. It is only upon post-surgical histopathology of the excised mass that the diagnosis of Küttners tumor is definitively made.

Histological features
The histopathological features that characterize Küttners tumor include:

Heavy infiltration of the glandular tissue by lymphocytes (predominantly activated B-cells and helper T-cells) as well as plasma cells (collectively known as Lymphoplasmacytic Infiltrate).
Presence of reactive lymphoid follicles in the infiltrate, marked by a lack of atypical lymphoid cells (this is in sharp contrast to the presentations in lymphoma).
Atrophy and loss of acini (groups of secretory cells found in the salivary glands).
Encasement of the glandular ducts in thick fibrous tissues, as a result of chronic presence of inflammatory infiltrate in that area - a condition known as periductal fibrosis.
Eventual periductal and interlobular (inside the gland) sclerosis (replacement of regular tissue with hard connective tissue).

Pathogenesis
The cause and pathogenesis of this chronic condition are not very well understood. Several factors have been postulated:

Formation of a hard salivary calculus or sialolith by accumulation of calcium salts in the duct of the salivary gland (a process known as Sialolithiasis) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Q fever and can you explain it in depth? [/INST] Q fever or query fever is a disease caused by infection with Coxiella burnetii, a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including cats and dogs. The infection results from inhalation of a spore-like small-cell variant, and from contact with the milk, urine, feces, vaginal mucus, or semen of infected animals. Rarely, the disease is tick-borne. The incubation period is 9–40 days. Humans are vulnerable to Q fever, and infection can result from even a few organisms. The bacterium is an obligate intracellular pathogenic parasite.

Signs and symptoms
Incubation period is usually two to three weeks. The most common manifestation is flu-like symptoms: abrupt onset of fever, malaise, profuse perspiration, severe headache, muscle pain, joint pain, loss of appetite, upper respiratory problems, dry cough, pleuritic pain, chills, confusion, and gastrointestinal symptoms, such as nausea, vomiting, and diarrhea. About half of infected individuals exhibit no symptoms.During its course, the disease can progress to an atypical pneumonia, which can result in a life-threatening acute respiratory distress syndrome, whereby such symptoms usually occur during the first four to five days of infection.Less often, Q fever causes (granulomatous) hepatitis, which may be asymptomatic or become symptomatic with malaise, fever, liver enlargement, and pain in the right upper quadrant of the abdomen. Whereas transaminase values are often elevated, jaundice is uncommon. Retinal vasculitis is a rare manifestation of Q fever.The chronic form of Q fever is virtually identical to endocarditis (i.e. inflammation of the inner lining of the heart), which can occur months or decades following the infection. It is usually fatal if untreated. However, with appropriate treatment, the mortality falls to around 10%.

Diagnosis
Diagnosis is usually based on serology (looking for an antibody response) rather than looking for the organism itself. Serology allows the detection of chronic infection by the appearance of high levels of the antibody against the virulent form of the bacterium. Molecular detection of bacterial DNA is increasingly used. Contrary to most obligate intracellular parasites, Coxiella burnetii can be grown in an axenic culture, but its culture is technically difficult and not routinely available in most microbiology laboratories.Q fever can cause endocarditis (infection of the heart valves) which may require transoesophageal echocardiography to diagnose.  Q fever hepatitis manifests as an elevation of alanine transaminase and aspartate transaminase, but a definitive diagnosis is only possible on liver biopsy, which shows the characteristic fibrin ring granulomas.

Prevention
Research done in the 1960s–1970s by French Canadian-American microbiologist and virologist Paul Fiset was instrumental in the development of the first successful Q fever vaccine.Protection is offered by Q-Vax, a whole-cell, inactivated vaccine developed by an Australian vaccine manufacturing company, CSL Limited. The intradermal vaccination is composed of killed C. burnetii organisms. Skin and blood tests should be done before vaccination to identify pre-existing immunity, because vaccinating people who already have  immunity can result in a severe local reaction. After a single dose of vaccine, protective immunity lasts for many years. Revaccination is not generally required. Annual screening is typically recommended.In 2001, Australia introduced a national Q fever vaccination program for people working in "at risk" occupations. Vaccinated or previously exposed people may have their status recorded on the Australian Q Fever Register, which may be a condition of employment in the meat processing industry or in veterinary research. An earlier killed vaccine had been developed in the Soviet Union, but its side effects prevented its licensing abroad.Preliminary results suggest vaccination of animals may be a method of control. Published trials proved that use of a registered phase vaccine (Coxevac) on infected farms is a tool of major interest to manage or prevent early or late abortion, repeat breeding, anoestrus, silent oestrus, metritis, and decreases in milk yield when C. burnetii is the major cause of these problems.

Treatment
Treatment of acute Q fever with antibiotics is very effective and should be given in consultation with an infectious diseases specialist. Commonly used antibiotics include doxycycline, tetracycline, chloramphenicol, ciprofloxacin, ofloxacin, and hydroxychloroquine. Chronic Q fever is more difficult to treat and can require up to four years of treatment with doxycycline and quinolones or doxycycline with hydroxychloroquine. If a person has Chronic Q fever, doxycycline and hydroxychloroquine will be prescribed for at least eighteen months. Q fever in pregnancy is especially difficult to treat because doxycycline and ciprofloxacin are contraindicated in pregnancy. The preferred treatment for pregnancy and children under the age of eight is co-trimoxazole.

Epidemiology
The pathogenic agent is found worldwide, with the exception of New Zealand. The bacterium is extremely sustainable and virulent: a single organism is able to cause an infection. The common source of infection is the inhalation of contaminated dust, contact with contaminated milk, meat, or wool, and particularly birthing products. Ticks can transfer the pathogenic agent to other animals. Transfer between humans seems extremely rare and has so far been described in very few cases.Some studies have shown more men to be affected than women, which may be attributed to different employment rates in typical professions.
"At risk" occupations include:
Veterinary personnel;
Stockyard workers;
Farmers;
Sheep shearers;
Animal transporters;
Laboratory workers handling potentially infected veterinary samples or visiting abattoirs;
People who cull and process kangaroos; and
Hide (tannery) workers.

History
Q fever was first described in 1935 by Edward Holbrook Derrick in slaughterhouse workers in Brisbane, Queensland. The "Q" stands for "query" and was applied at a time when the causative agent was unknown; it was chosen over suggestions of abattoir fever and Queensland rickettsial fever, to avoid directing negative connotations at either the cattle industry or the state of Queensland.The pathogen of Q fever was discovered in 1937, when Frank Macfarlane Burnet and Mavis Freeman isolated the bacterium from one of Derricks patients. It was originally identified as a species of Rickettsia. H.R. Cox and Gordon Davis elucidated the transmission when they isolated it from ticks found in the US state of Montana in 1938.  It is a zoonotic disease whose most common animal reservoirs are cattle, sheep, and goats. Coxiella burnetii – named for Cox and Burnet – is no longer regarded as closely related to the Rickettsiae, but as similar to Legionella and Francisella, and is a Gammaproteobacterium.

Society and culture
An early mention of Q fever was important in one of the early Dr. Kildare films (1939, Calling Dr. Kildare). Kildares mentor Dr. Gillespie (Lionel Barrymore) tires of his protégé working fruitlessly on "exotic diagnoses" ("I think its Q fever!") and sends him to work in a neighborhood clinic, instead.Q fever was also highlighted in an episode of the U.S. television medical drama House ("The Dig", season seven, episode 18).

Biological warfare
C. burnetii has been used to develop biological weapons.The United States investigated it as a potential biological warfare agent in the 1950s, with eventual standardization as agent OU. At Fort Detrick and Dugway Proving Ground, human trials were conducted on Whitecoat volunteers to determine the median infective dose (18 MICLD50/person i.h.) and course of infection. The Deseret Test Center dispensed biological Agent OU with ships and aircraft, during Project 112 and Project SHAD.  As a standardized biological, it was manufactured in large quantities at Pine Bluff Arsenal, with 5,098 gallons in the arsenal in bulk at the time of demilitarization in 1970.
C. burnetii is currently ranked as a "category B" bioterrorism agent by the CDC. It can be contagious, and is very stable in aerosols in a wide range of temperatures. Q fever microorganisms may survive on surfaces up to 60 days. It is considered a good agent in part because its ID50 (number of bacilli needed to infect 50% of individuals) is considered to be one, making it the lowest known.

In animals
Q fever can affect many species of domestic and wild animals, including ruminants (cattle, sheep, goats, bison, deers...), carnivores (dogs, cats, seals...), rodents, reptiles and birds.
However, ruminants (cattle, goats and sheep) are the most frequently affected animals, and can serve as a reservoir for the bacteria.

Clinical signs
In contrast to humans, even though a respiratory and cardiac infection could be experimentally reproduced in cattle, the clinical signs mainly affect the reproductive system. Q fever in ruminants is therefore mainly responsible for abortions, metritis, retained placenta and infertility.
The clinical signs vary between species </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Psychosis and can you explain it in depth? [/INST] Psychosis is an abnormal condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior that is inappropriate for a given situation. There may also be sleep problems, social withdrawal, lack of motivation, and difficulties carrying out daily activities. Psychosis can have serious adverse outcomes.As with many psychiatric phenomena, psychosis has several different causes. These include mental illness, such as schizophrenia or schizoaffective disorder, bipolar disorder, sensory deprivation and in rare cases, major depression (psychotic depression). Other causes include: trauma, sleep deprivation, some medical conditions, certain medications, and drugs such as cannabis, hallucinogens, and stimulants. One type, known as postpartum psychosis, can occur after giving birth. The neurotransmitter dopamine is believed to play an important role. Acute psychosis is considered primary if it results from a psychiatric condition and secondary if it is caused by a medical condition or drugs. The diagnosis of a mental health condition requires excluding other potential causes. Testing may be done to check for central nervous system diseases, toxins, or other health problems as a cause.Treatment may include antipsychotic medication, psychotherapy, and social support. Early treatment appears to improve outcomes. Medications appear to have a moderate effect. Outcomes depend on the underlying cause. In the United States about 3% of people develop psychosis at some point in their lives. The condition has been described since at least the 4th century BCE by Hippocrates and possibly as early as 1500 BCE in the Egyptian Ebers Papyrus.

Signs and symptoms
Hallucinations
A hallucination is defined as sensory perception in the absence of external stimuli. Hallucinations are different from illusions and perceptual distortions, which are the misperception of external stimuli. Hallucinations may occur in any of the senses and take on almost any form. They may consist of simple sensations (such as lights, colors, sounds, tastes, or smells) or more detailed experiences (such as seeing and interacting with animals and people, hearing voices, and having complex tactile sensations). Hallucinations are generally characterized as being vivid and uncontrollable. Auditory hallucinations, particularly experiences of hearing voices, are the most common and often prominent feature of psychosis.
Up to 15% of the general population may experience auditory hallucinations (though not all are due to psychosis). The prevalence of auditory hallucinations in patients with schizophrenia is generally put around 70%, but may go as high as 98%. Reported prevalence in bipolar disorder ranges between 11% and 68%. During the early 20th century, auditory hallucinations were second to visual hallucinations in frequency, but they are now the most common manifestation of schizophrenia, although rates vary between cultures and regions. Auditory hallucinations are most commonly intelligible voices. When voices are present, the average number has been estimated at three. Content, like frequency, differs significantly, especially across cultures and demographics. People who experience auditory hallucinations can frequently identify the loudness, location of origin, and may settle on identities for voices. Western cultures are associated with auditory experiences concerning religious content, frequently related to sin. Hallucinations may command a person to do something potentially dangerous when combined with delusions.So-called "minor hallucinations", such as extracampine hallucinations, or false perceptions of people or movement occurring outside of ones visual field, frequently occur in neurocognitive disorders, such as Parkinsons disease.Visual hallucinations occur in roughly a third of people with schizophrenia, although rates as high as 55% are reported. The prevalence in bipolar disorder is around 15%. Content commonly involves animate objects, although perceptual abnormalities such as changes in lighting, shading, streaks, or lines may be seen. Visual abnormalities may conflict with proprioceptive information, and visions may include experiences such as the ground tilting. Lilliputian hallucinations are less common in schizophrenia, and are more common in various types of encephalopathy, such as peduncular hallucinosis.A visceral hallucination, also called a cenesthetic hallucination, is characterized by visceral sensations in the absence of stimuli. Cenesthetic hallucinations may include sensations of burning, or re-arrangement of internal organs.

Delusions
Psychosis may involve delusional beliefs. A delusion is a fixed, false idiosyncratic belief, which does not change even when presented with incontrovertible evidence to the contrary. Delusions are context- and culture-dependent: a belief which inhibits critical functioning and is widely considered delusional in one population may be common (and even adaptive) in another, or in the same population at a later time. Since normative views may contradict available evidence, a belief need not contravene cultural standards in order to be considered delusional.
Prevalence in schizophrenia is generally considered at least 90%, and around 50% in bipolar disorder.
The DSM-5 characterizes certain delusions as "bizarre" if they are clearly implausible, or are incompatible with the surrounding cultural context. The concept of bizarre delusions has many criticisms, the most prominent being judging its presence is not highly reliable even among trained individuals.A delusion may involve diverse thematic content. The most common type is a persecutory delusion, in which a person believes that an entity seeks to harm them. Others include delusions of reference (the belief that some element of ones experience represents a deliberate and specific act by or message from some other entity), delusions of grandeur (the belief that one possesses special power or influence beyond ones actual limits), thought broadcasting (the belief that ones thoughts are audible) and thought insertion (the belief that ones thoughts are not ones own). A delusion may also involve misidentification of objects, persons, or environs that the afflicted should reasonably be able to recognize; such examples include Cotards syndrome (the belief that oneself is partly or wholly dead) and clinical lycanthropy (the belief that oneself is or has transformed into an animal).
The subject matter of delusions seems to reflect the current culture in a particular time and location. For example, in the US, during the early 1900s syphilis was a common topic, during the second world war Germany, during the cold war communists, and in recent years technology has been a focus. Some psychologists, such as those who practice the Open Dialogue method, believe that the content of psychosis represents an underlying thought process that may, in part, be responsible for psychosis, though the accepted medical position is that psychosis is due to a brain disorder.
Historically, Karl Jaspers classified psychotic delusions into primary and secondary types. Primary delusions are defined as arising suddenly and not being comprehensible in terms of normal mental processes, whereas secondary delusions are typically understood as being influenced by the persons background or current situation (e.g., ethnicity; also religious, superstitious, or political beliefs).

Disorganization of speech/thought or behavior
Disorganization is split into disorganized speech (or thought), and grossly disorganized motor behavior. Disorganized speech or thought, also called formal thought disorder, is disorganization of thinking that is inferred from speech. Characteristics of disorganized speech include rapidly switching topics, called derailment or loose association; switching to topics that are unrelated, called tangential thinking; incomprehensible speech, called word salad or incoherence. Disorganized motor behavior includes repetitive, odd, or sometimes purposeless movement. Disorganized motor behavior rarely includes catatonia, and although it was a historically prominent symptom, it is rarely seen today. Whether this is due to historically used treatments or the lack thereof is unknown.Catatonia describes a profoundly agitated state in which the experience of reality is generally considered impaired. There are two primary manifestations of catatonic behavior. The classic presentation is a person who does not move or interact with the world in any way while awake. This type of catatonia presents with waxy flexibility. Waxy flexibility is when someone physically moves part of a catatonic persons body and the person stays in the position even if it is bizarre and otherwise nonfunctional (such as moving a persons arm straight up in the air and the arm staying there).
The other type of catatonia is more of an outward presentation of the profoundly agitated state described above. It involves excessive and purposeless motor behaviour, as well as an extreme mental preoccupation that prevents an intact experience of reality. An example is someone walking very fast in circles to the exclusion of anything else with a level of mental preoccupation (meaning not focused on anything relevant to the situation) that was not typical of the person prior to the symptom onset. In both types of catatonia, there is generally no reaction to anything that happens outside of them. It is important to distinguish catatonic agitation from severe bipolar mania, although someone could have both.

Negative symptoms
Negative symptoms include reduced emotional expression (flat affect), decreased motivation (avolition), and reduced spontaneous speech (poverty of speech, alogia). Individuals with this condition lack interest and spontaneity, and have the inability to feel pleasure (anhedonia).

Psychosis in adolescents
Psychosis is rare in adolescents.  Young people who have psychosis may have trouble connecting with the world around them and may experience hallucinations and/or delusions. Adolescents with psychosis may also have cognitive deficits that may make it harder for the youth to socialize and work. Potential impairments include the speed of mental processing, ability to focus without getting distracted (limited attention span), and deficits in verbal memory. If an adolescent is experiencing psychosis, they most likely have comorbidity meaning they could have multiple mental illnesses. Because of this, it can be difficult to determine if it is psychosis or autism spectrum disorder, social or generalized anxiety disorder, or obsessive-compulsive disorder.

History
Etymology
The word psychosis was introduced to the psychiatric literature in 1841 by Karl Friedrich Canstatt in his work Handbuch der Medizinischen Klinik. He used it as a shorthand for psychic neurosis. At that time neurosis meant any disease of the nervous system, and Canstatt was thus referring to what was considered a psychological manifestation of brain disease. Ernst von Feuchtersleben is also widely credited as introducing the term in 1845, as an alternative to insanity and mania.
The term stems from Modern Latin psychosis, "a giving soul or life to, animating, quickening" and that from Ancient Greek ψυχή (psyche), "soul" and the suffix -ωσις (-osis), in this case  "abnormal condition".In its adjective form "psychotic", references to psychosis can be found in both clinical and non-clinical discussions. However, in a non-clinical context, "psychotic" is a nonspecific colloquialism used to mean "insane".

Classification
The word was also used to distinguish a condition considered a disorder of the mind, as opposed to neurosis, which was considered a disorder of the nervous system. The psychoses thus became the modern equivalent of the old notion of madness, and hence there was much debate on whether there was only one (unitary) or many forms of the new disease. One type of broad usage would later be narrowed down by Koch in 1891 to the psychopathic inferiorities—later renamed abnormal personalities by Schneider.The division of the major psychoses into manic depressive illness (now called bipolar disorder) and dementia praecox (now called schizophrenia) was made by Emil Kraepelin, who attempted to create a synthesis of the various mental disorders identified by 19th-century psychiatrists, by grouping diseases together based on classification of common symptoms. Kraepelin used the term manic depressive insanity to describe the whole spectrum of mood disorders, in a far wider sense than it is usually used today.
In Kraepelins classification this would include unipolar clinical depression, as well as bipolar disorder and other mood disorders such as cyclothymia. These are characterised by problems with mood control and the psychotic episodes appear associated with disturbances in mood, and patients often have periods of normal functioning between psychotic episodes even without medication. Schizophrenia is characterized by psychotic episodes that appear unrelated to disturbances in mood, and most non-medicated patients show signs of disturbance between psychotic episodes.

Treatment
Early civilizations considered madness a supernaturally inflicted phenomenon. Archaeologists have unearthed skulls with clearly visible drillings, some datable back to 5000 BC suggesting that trepanning was a common treatment for psychosis in ancient times.  Written record of supernatural causes and resultant treatments can be traced back to the New Testament. Mark 5:8–13 describes a man displaying what would today be described as psychotic symptoms. Christ cured this "demonic madness" by casting out the demons and hurling them into a herd of swine. Exorcism is still utilized in some religious circles as a treatment for psychosis presumed to be demonic possession. A research study of out-patients in psychiatric clinics found that 30 percent of religious patients attributed the cause of their psychotic symptoms to evil spirits. Many of these patients underwent exorcistic healing rituals that, though largely regarded as positive experiences by the patients, had no effect on symptomology. Results did, however, show a significant worsening of psychotic symptoms associated with exclusion of medical treatment for coercive forms of exorcism.

The medical teachings of the fourth-century philosopher and physician Hippocrates of Cos proposed a natural, rather than supernatural, cause of human illness. In Hippocrates work, the Hippocratic corpus, a holistic explanation for health and disease was developed to include madness and other "diseases of the mind."  Hippocrates writes:

Men ought to know that from the brain, and from the brain only, arise our pleasures, joys, laughter, and jests, as well as our sorrows, pains, griefs and tears. Through it, in particular, we think, see, hear, and distinguish the ugly from the beautiful, the bad from the good, the pleasant from the unpleasant…. It is the same thing which makes us mad or delirious, inspires us with dread and fear, whether by night or by day, brings sleeplessness, inopportune mistakes, aimless anxieties, absentmindedness, and acts that are contrary to habit.
Hippocrates espoused a theory of humoralism wherein disease is resultant of a shifting balance in bodily fluids including blood, phlegm, black bile, and yellow bile. According to humoralism, each fluid or "humour" has temperamental or behavioral correlates. In the case of psychosis, symptoms are thought to be caused by an excess of both blood and yellow bile. Thus, the proposed surgical intervention for psychotic or manic behavior was bloodletting.18th-century physician, educator, and widely considered "founder of American psychiatry", Benjamin Rush, also prescribed bloodletting as a first-line treatment for psychosis. Although not a proponent of humoralism, Rush believed that active purging and bloodletting were efficacious corrections for disruptions in the circulatory system, a complication he believed was the primary cause of "insanity". Although Rushs treatment modalities are now considered antiquated and brutish, his contributions to psychiatry, namely the biological underpinnings of psychiatric phenomenon including psychosis, have been invaluable to the field. In honor of such contributions, Benjamin Rushs image is in the official seal of the American Psychiatric Association.
Early 20th-century treatments for severe and persisting psychosis were characterized by an emphasis on shocking the nervous system. Such therapies include insulin shock therapy, cardiazol shock therapy, and electroconvulsive therapy. Despite considerable risk, shock therapy was considered highly efficacious in the treatment of psychosis including schizophrenia. The acceptance of high-risk treatments led to more invasive medical interventions including psychosurgery.

In 1888, Swiss psychiatrist Gottlieb Burckhardt performed the first medically sanctioned psychosurgery in which the cerebral cortex was excised. Although some patients showed improvement of symptoms and became more subdued, one patient died and several developed aphasia or seizure disorders. Burckhardt would go on to publish his clinical outcomes in a scholarly paper. This procedure was met with criticism from the medical community and his academic and surgical endeavors were largely ignored. In the late 1930s, Egas Moniz conceived the leucotomy (AKA prefrontal lobotomy) in which the fibers connecting the frontal lobes to the rest of the brain were severed. Monizs primary inspiration stemmed from a demonstration by neuroscientists John Fulton and Carlyles 1935 experiment in which two chimpanzees were given leucotomies and pre- and post-surgical behavior was compared. Prior to the leucotomy, the chimps engaged in typical behavior including throwing feces and fighting. After the procedure, both chimps were pacified and less violent. During the Q&A, Moniz asked if such a procedure could be extended to human subjects, a question that Fulton admitted was quite startling. Moniz would go on to extend the controversial practice to humans with various psychotic disorders, an endeavor for which he received a Nobel Prize in 1949. Between the late 1930s and early 1970s, the leucotomy was a widely accepted practice, often performed in non-sterile environments such as small outpatient clinics and patient homes. Psychosurgery remained standard practice until the discovery of antipsychotic pharmacology in the 1950s.The first clinical trial of antipsychotics (also commonly known as neuroleptics) for the treatment of psychosis took place in 1952. Chlorpromazine (brand name: Thorazine) passed clinical trials and became the first antipsychotic medication approved for the treatment of both acute and chronic psychosis. Although the mechanism of action was not discovered until 1963, the administration of chlorpromazine marked the advent of the dopamine antagonist, or first generation antipsychotic. While clinical trials showed a high response rate for both acute psychosis and disorders with psychotic features, the side effects were particularly harsh, which included high rates of often irreversible Parkinsonian symptoms such as tardive dyskinesia. With the advent of atypical antipsychotics (also known as second generation antipsychotics) came a dopamine antagonist with a comparable response rate but a far different, though still extensive, side-effect profile that included a lower risk of Parkinsonian symptoms but a higher risk of cardiovascular disease.  Atypical antipsychotics remain the first-line treatment for psychosis associated with various psychiatric and neurological disorders including schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia, and some autism spectrum disorders.Dopamine is now one of the primary neurotransmitters implicated in psychotic symptomology. Blocking dopamine receptors (namely, the dopamine D2 receptors) and decreasing dopaminergic activity continues to be an effective but highly unrefined effect of antipsychotics, which are commonly used to treat psychosis. Recent pharmacological research suggests that the decrease in dopaminergic activity does not eradicate psychotic delusions or hallucinations, but rather attenuates the reward mechanisms involved in the development of delusional thinking; that is, connecting or finding meaningful relationships between unrelated stimuli or ideas. The author of this research paper acknowledges the importance of future investigation:

The model presented here is based on incomplete knowledge related to dopamine, schizophrenia, and antipsychotics—and as such will need to evolve as more is known about these.
Freuds former student Wilhelm Reich explored independent insights into the physical effects of neurotic and traumatic upbringing, and published his holistic psychoanalytic treatment with a schizophrenic. With his incorporation of breathwork and insight with the patient, a young woman, she achieved sufficient self-management skills to end the therapy.Lacan extended Freuds ideas to create a psychoanalytic model of psychosis based upon the concept of "foreclosure", the rejection of the symbolic concept of the father.

Society
Psychiatrist David Healy has criticised pharmaceutical companies for promoting simplified biological theories of mental illness that seem to imply the primacy of pharmaceutical treatments while ignoring social and developmental factors that are known important influences in the etiology of psychosis.

Disability
The classification of psychosis as a social disability is a common occurrence.
Psychosis is considered to be among the top 10 causes of social disability among adult men and women in developed countries. And the traditional, negative narrative around disability has been shown to strongly and adversely influence the pathways through employment and education for people experiencing psychosis.Social disability by way of social disconnection is a significant public health concern and is associated with a broad range of negative outcomes, including premature mortality. Social disconnection refers to the ongoing absence of family or social relationships with marginal participation in social activities.
N. Myers (2019), N. A. L. Myers (2012) and Brown (2011) found that reduced participation in social networks, not only negatively effects the individual on a physical and mental level, it has been shown that failure to be included in social networks influences the individuals ability to participate in the wider community through employment and education opportunities.
N. Myers (2019) discuss how equal opportunity to participate in meaningful relationships with friends, family and partners, as well as engaging in social constructs such as employment, can provide significant physical and mental value to peoples lives. And how breaking the disability mindset around people experiencing psychosis is imperative for their overall, long-term health and wellbeing as well as the contributions they are able to make to their immediate social connections and the wider community.

Causes
The symptoms of psychosis may be caused by serious psychiatric disorders such as schizophrenia, a number of medical illnesses, and trauma. Psychosis may also be temporary or transient, and be caused by medications or substance use disorder (substance-induced psychosis).

Normal states
Brief hallucinations are not uncommon in those without any psychiatric disease, including healthy children. Causes or triggers include:
Falling asleep and waking: hypnagogic and hypnopompic hallucinations
Bereavement, in which hallucinations of a deceased loved one are common
Severe sleep deprivation
Extreme stress (see below)

Trauma and Stress
Traumatic life events have been linked with an elevated risk of developing psychotic symptoms. Childhood trauma has specifically been shown to be a predictor of adolescent and adult psychosis. Individuals with psychotic symptoms are three times more likely to have experienced childhood trauma (e.g., physical or sexual abuse, physical or emotional neglect) than those in the general population. Increased individual vulnerability toward psychosis may interact with traumatic experiences promoting an onset of future psychotic symptoms, particularly during sensitive developmental periods. Importantly, the relationship between traumatic life events and psychotic symptoms appears to be dose-dependent in which multiple traumatic life events accumulate, compounding symptom expression and severity. However, acute, stressful events can also trigger brief psychotic episodes. Trauma prevention and early intervention may be an important target for decreasing the incidence of psychotic disorders and ameliorating its effects.A healthy person could become psychotic if he is placed in an empty room with no light and sound after 15 minutes a  phenomenon known as sensory deprivation.Neuroticism, a personality trait associated with vulnerability to stressors, is an independent predictor of the development of psychosis.

Psychiatric disorders
From a diagnostic standpoint, organic disorders were believed to be caused by physical illness affecting the brain (that is, psychiatric disorders secondary to other conditions) while functional disorders were considered disorders of the functioning of the mind in the absence of physical disorders (that is, primary psychological or psychiatric disorders). Subtle physical abnormalities have been found in illnesses traditionally considered functional, such as schizophrenia. The DSM-IV-TR avoids the functional/organic distinction, and instead lists traditional psychotic illnesses, psychosis due to general medical conditions, and substance-induced psychosis.
Primary psychiatric causes of psychosis include the following:
schizophrenia
affective (mood) disorders, including major depression, and severe depression or mania in bipolar disorder (manic depression). People experiencing a psychotic episode in the context of depression may experience persecutory or self-blaming delusions or hallucinations, while people experiencing a psychotic episode in the context of mania may form grandiose delusions.
schizoaffective disorder, involving symptoms of both schizophrenia and mood disorders
delusional disorder (persistent delusional disorder)Psychotic symptoms may also be seen in:
Schizotypal personality disorder
Certain personality disorders in times of stress (including paranoid personality disorder, schizoid personality disorder, and borderline personality disorder)
Major depressive disorder in its severe form, although it is possible and more likely to have severe depression without psychosis
Bipolar disorder in the manic and mixed episodes of bipolar I disorder and depressive episodes of both bipolar I and bipolar II; however, it is possible to experience such states without psychotic symptoms.
Post-traumatic stress disorder
Chronic hallucinatory psychosis
Shared delusional disorder
Sometimes in obsessive–compulsive disorder (OCD)
Dissociative disorders, due to many overlapping symptoms, careful differential diagnosis includes especially dissociative identity disorder.

Subtypes
Subtypes of psychosis include:

Postpartum psychosis, occurring shortly after giving birth, primarily associated with maternal bipolar disorder
Monothematic delusions
Myxedematous psychosis
Stimulant psychosis
Tardive psychosis
Shared psychosis (folie à deux)

Cycloid psychosis
Cycloid psychosis is typically an acute, self-limiting form of psychosis with psychotic and mood symptoms that progress from normal to full-blown, usually between a few hours to days, and not related to drug intake or brain injury. While proposed as a distinct entity, clinically separate from schizophrenia and affective disorders, cycloid psychosis is not formally acknowledged by current ICD or DSM criteria. Its unclear place in psychiatric nosology has likely contributed to the limited scientific investigation and literature on the topic.

Postpartum psychosis
Postpartum psychosis is a rare yet serious and debilitating form of psychosis. Symptoms range from fluctuating moods and insomnia to mood-incongruent delusions related to the individual or the infant. Women experiencing postpartum psychosis are at increased risk for suicide or infanticide. Many women who experience first-time psychosis from postpartum often have bipolar disorder, meaning they could experience an increase of psychotic episodes even after postpartum.

Medical conditions
A very large number of medical conditions can cause psychosis, sometimes called secondary psychosis. Examples include:

disorders causing delirium (toxic psychosis), in which consciousness is disturbed
neurodevelopmental disorders and chromosomal abnormalities, including velocardiofacial syndrome
neurodegenerative disorders, such as Alzheimers disease, dementia with Lewy bodies, and Parkinsons disease
focal neurological disease, such as stroke, brain tumors, multiple sclerosis, and some forms of epilepsy
malignancy (typically via masses in the brain, paraneoplastic syndromes)
infectious and postinfectious syndromes, including infections causing delirium, viral encephalitis, HIV/AIDS, malaria, syphilis
endocrine disease, such as hypothyroidism, hyperthyroidism, Cushings syndrome, hypoparathyroidism and hyperparathyroidism; sex hormones also affect psychotic symptoms and sometimes giving birth can provoke psychosis, termed postpartum psychosis
inborn errors of metabolism, such as Wilsons disease, porphyria, and homocysteinemia.
nutritional deficiency, such as vitamin B12 deficiency
other acquired metabolic disorders, including electrolyte disturbances such as hypocalcemia, hypernatremia, hyponatremia, hypokalemia, hypomagnesemia, hypermagnesemia, hypercalcemia, and hypophosphatemia, but also hypoglycemia, hypoxia, and failure of the liver or kidneys
autoimmune and related disorders, such as systemic lupus erythematosus (lupus, SLE), sarcoidosis, Hashimotos encephalopathy, anti-NMDA-receptor encephalitis, and non-celiac gluten sensitivity
poisoning, by therapeutic drugs (see below), recreational drugs (see below), and a range of plants, fungi, metals, organic compounds, and a few animal toxins
sleep disorders, such as in narcolepsy (in which REM sleep intrudes into wakefulness)
parasitic diseases, such as neurocysticercosis
huntington disease

Psychoactive drugs
Various psychoactive substances (both legal and illegal) have been implicated in causing, exacerbating, or precipitating psychotic states or disorders in users, with varying levels of evidence. This may be upon intoxication for a more prolonged period after use, or upon withdrawal. Individuals who experience substance-induced psychosis tend to have a greater awareness of their psychosis and tend to have higher levels of suicidal thinking compared to those who have a primary psychotic illness. Drugs commonly alleged to induce psychotic symptoms include alcohol, cannabis, cocaine, amphetamines, cathinones, psychedelic drugs (such as LSD and psilocybin), κ-opioid receptor agonists (such as enadoline and salvinorin A) and NMDA receptor antagonists (such as phencyclidine and ketamine). Caffeine may worsen symptoms in those with schizophrenia and cause psychosis at very high doses in people without the condition. Cannabis and other illicit recreational drugs are often associated with psychosis in adolescents and cannabis use before 15 years old may increase the risk of psychosis in adulthood.

Alcohol
Approximately three percent of people with alcoholism experience psychosis during acute intoxication or withdrawal. Alcohol related psychosis may manifest itself through a kindling mechanism. The mechanism of alcohol-related psychosis is due to the long-term effects of alcohol consumption resulting in distortions to neuronal membranes, gene expression, as well as thiamin deficiency. It is possible that hazardous alcohol use via a kindling mechanism can cause the development of a chronic substance-induced psychotic disorder, i.e. schizophrenia. The effects of an alcohol-related psychosis include an increased risk of depression and suicide as well as causing psychosocial impairments. Delirium Tremens, a symptom of chronic alcoholism which can appear in the acute withdraw phase, shares many symptoms with alcohol-related psychosis suggesting a common mechanism.

Cannabis
According to current studies, cannabis use is associated with increased risk of psychotic disorders, and the more often cannabis is used the more likely a person is to develop a psychotic illness. Furthermore, people with a history of cannabis use develop psychotic symptoms earlier than those who have never used cannabis. Some debate exists regarding the causal relationship between cannabis use and psychosis with some studies suggesting that cannabis use hastens the onset of psychosis primarily in those with pre-existing vulnerability. Indeed, cannabis use plays an important role in the development of psychosis in vulnerable individuals, and cannabis use in adolescence should be discouraged. Some studies indicate that the effects of two active compounds in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), have opposite effects with respect to psychosis. While THC can induce psychotic symptoms in healthy individuals, limited evidence suggests that CBD may have antipsychotic effects.

Methamphetamine
Methamphetamine induces a psychosis in 26–46 percent of heavy users. Some of these people develop a long-lasting psychosis that can persist for longer than six months. Those who have had a short-lived psychosis from methamphetamine can have a relapse of the methamphetamine psychosis years later after a stressful event such as severe insomnia or a period of hazardous alcohol use despite not relapsing back to methamphetamine. Individuals who have a long history of methamphetamine use and who have experienced psychosis in the past from methamphetamine use are highly likely to re-experience methamphetamine psychosis if drug use is recommenced. Methamphetamine-induced psychosis is likely gated by genetic vulnerability, which can produce long-term changes in brain neurochemistry following repetitive use.

Medication
Administration, or sometimes withdrawal, of a large number of medications may provoke psychotic symptoms. Drugs that can induce psychosis experimentally or in a significant proportion of people include stimulants, such as amphetamine and other sympathomimetics, dopamine agonists, ketamine, corticosteroids (often with mood changes in addition), and some anticonvulsants such as vigabatrin.

Pathophysiology
Neuroimaging
The first brain image of an individual with psychosis was completed as far back as 1935 using a technique called pneumoencephalography (a painful and now obsolete procedure where cerebrospinal fluid is drained from around the brain and replaced with air to allow the structure of the brain to show up more clearly on an X-ray picture).
Both first episode psychosis, and high risk status is associated with reductions in grey matter volume (GMV). First episode psychotic and high risk populations are associated with similar but distinct abnormalities in GMV. Reductions in the right middle temporal gyrus, right superior temporal gyrus (STG), right parahippocampus, right hippocampus, right middle frontal gyrus, and left anterior cingulate cortex (ACC) are observed in high risk populations. Reductions in first episode psychosis span a region from the right STG to the right insula, left insula, and cerebellum, and are more severe in the right ACC, right STG, insula and cerebellum.Another meta analysis reported bilateral reductions in insula, operculum, STG, medial frontal cortex, and ACC, but also reported increased GMV in the right lingual gyrus and left precentral gyrus.  The Kraepelinian dichotomy is made questionable by grey matter abnormalities in bipolar and schizophrenia; schizophrenia is distinguishable from bipolar in that regions of grey matter reduction are generally larger in magnitude, although adjusting for gender differences reduces the difference to the left dorsomedial prefrontal cortex, and right dorsolateral prefrontal cortex.During attentional tasks, first episode psychosis is associated with hypoactivation in the right middle frontal gyrus, a region generally described as encompassing the dorsolateral prefrontal cortex (dlPFC). In congruence with studies on grey matter volume, hypoactivity in the right insula, and right inferior parietal lobe is also reported. During cognitive tasks, hypoactivities in the right insula, dACC, and the left precuneus, as well as reduced deactivations in the right basal ganglia, right thalamus, right inferior frontal and left precentral gyri are observed. These results are highly consistent and replicable possibly except the abnormalities of the right inferior frontal gyrus. Decreased grey matter volume in conjunction with bilateral hypoactivity is observed in anterior insula, dorsal medial frontal cortex, and dorsal ACC. Decreased grey matter volume and bilateral hyperactivity is reported in posterior insula, ventral medial frontal cortex, and ventral ACC.

Hallucinations
Studies during acute experiences of hallucinations demonstrate increased activity in primary or secondary sensory cortices. As auditory hallucinations are most common in psychosis, most robust evidence exists for increased activity in the left middle temporal gyrus, left superior temporal gyrus, and left inferior frontal gyrus (i.e. Brocas area). Activity in the ventral striatum, hippocampus, and ACC are related to the lucidity of hallucinations, and indicate that activation or involvement of emotional circuitry are key to the impact of abnormal activity in sensory cortices. Together, these findings indicate abnormal processing of internally generated sensory experiences, coupled with abnormal emotional processing, results in hallucinations. One proposed model involves a failure of feedforward networks from sensory cortices to the inferior frontal cortex, which normally cancel out sensory cortex activity during internally generated speech. The resulting disruption in expected and perceived speech is thought to produce lucid hallucinatory experiences.

Delusions
The two-factor model of delusions posits that dysfunction in both belief formation systems and belief evaluation systems are necessary for delusions. Dysfunction in evaluations systems localized to the right lateral prefrontal cortex, regardless of delusion content, is supported by neuroimaging studies and is congruent with its role in conflict monitoring in healthy persons. Abnormal activation and reduced volume is seen in people with delusions, as well as in disorders associated with delusions such as frontotemporal dementia, psychosis and Lewy body dementia. Furthermore, lesions to this region are associated with "jumping to conclusions", damage to this region is associated with post-stroke delusions, and hypometabolism this region associated with caudate strokes presenting with delusions.
The aberrant salience model suggests that delusions are a result of people assigning excessive importance to irrelevant stimuli. In support of this hypothesis, regions normally associated with the salience network demonstrate reduced grey matter in people with delusions, and the neurotransmitter dopamine, which is widely implicated in salience processing, is also widely implicated in psychotic disorders.
Specific regions have been associated with specific types of delusions. The volume of the hippocampus and parahippocampus is related to paranoid delusions in Alzheimers disease, and has been reported to be abnormal post mortem in one person with delusions. Capgras delusions have been associated with occipito-temporal damage, and may be related to failure to elicit normal emotions or memories in response to faces.

Negative symptoms
Psychosis is associated with ventral striatal (VS) which is the part of the brain that is involved with the desire to naturally satisfy the bodys needs. When high reports of negative symptoms were recorded, there were significant irregularities in the left VS. Anhedonia, the inability to feel pleasure, is a commonly reported symptom in psychosis; experiences are present in most people with schizophrenia. The impairment that may present itself as anhedonia derives from the inability to not only identify goals, but to also identify and engage in the behaviors necessary to achieve goals. Studies support a deficiency in the neural representation of goals and goal directed behavior by demonstrating that when the reward is not anticipated, there is a strong correlation of high reaction in the ventral striatum; reinforcement learning is intact when contingencies about stimulus-reward are implicit, but not when they require explicit neural processing; reward prediction errors are what the actual reward is versus what the reward was predicted to be. In most cases positive prediction errors are considered an abnormal occurrence. A positive prediction error response occurs when there is an increased activation in a brain region, typically the striatum, in response to unexpected rewards. A negative prediction error response occurs when there is a decreased activation in a region when predicted rewards do not occur. Anterior Cingulate Cortex (ACC) response, taken as an indicator of effort allocation, does not increase with reward or reward probability increase, and is associated with negative symptoms; deficits in Dorsolateral Prefrontal Cortex (dlPFC) activity and failure to improve performance on cognitive tasks when offered monetary incentives are present; and dopamine mediated functions are abnormal.

Neurobiology
Psychosis has been traditionally linked to the overactivity of the neurotransmitter dopamine. In particular to its effect in the mesolimbic pathway. The two major sources of evidence given to support this theory are that dopamine receptor D2 blocking drugs (i.e., antipsychotics) tend to reduce the intensity of psychotic symptoms, and that drugs that accentuate dopamine release, or inhibit its reuptake (such as amphetamines and cocaine) can trigger psychosis in some people (see stimulant psychosis).NMDA receptor dysfunction has been proposed as a mechanism in psychosis.  This theory is reinforced by the fact that dissociative NMDA receptor antagonists such as ketamine, PCP and dextromethorphan (at large overdoses) induce a psychotic state. The symptoms of dissociative intoxication are also considered to mirror the symptoms of schizophrenia, including negative symptoms.  NMDA receptor antagonism, in addition to producing symptoms reminiscent of psychosis, mimics the neurophysiological aspects, such as reduction in the amplitude of P50, P300, and MMN evoked potentials. Hierarchical Bayesian neurocomputational models of sensory feedback, in agreement with neuroimaging literature, link NMDA receptor hypofunction to delusional or hallucinatory symptoms via proposing a failure of NMDA mediated top down predictions to adequately cancel out enhanced bottom up AMPA mediated predictions errors. Excessive prediction errors in response to stimuli that would normally not produce such a response is thought to root from conferring excessive salience to otherwise mundane events. Dysfunction higher up in the hierarchy, where representation is more abstract, could result in delusions. The common finding of reduced GAD67 expression in psychotic disorders may explain enhanced AMPA mediated signaling, caused by reduced GABAergic inhibition.The connection between dopamine and psychosis is generally believed to be complex. While dopamine receptor D2 suppresses adenylate cyclase activity, the D1 receptor increases it. If D2-blocking drugs are administered, the blocked dopamine spills over to the D1 receptors. The increased adenylate cyclase activity affects genetic expression in the nerve cell, which takes time. Hence antipsychotic drugs take a week or two to reduce the symptoms of psychosis. Moreover, newer and equally effective antipsychotic drugs actually block slightly less dopamine in the brain than older drugs whilst also blocking 5-HT2A receptors, suggesting the dopamine hypothesis may be oversimplified. Soyka and colleagues found no evidence of dopaminergic dysfunction in people with alcohol-induced psychosis and Zoldan et al. reported moderately successful use of ondansetron, a 5-HT3 receptor antagonist, in the treatment of levodopa psychosis in Parkinsons disease patients.A review found an association between a first-episode of psychosis and prediabetes.Prolonged or high dose use of psychostimulants can alter normal functioning, making it similar to the manic phase of bipolar disorder. NMDA antagonists replicate some of the so-called "negative" symptoms like thought disorder in subanesthetic doses (doses insufficient to induce anesthesia), and catatonia in high doses). Psychostimulants, especially in one already prone to psychotic thinking, can cause some "positive" symptoms, such as delusional beliefs, particularly those persecutory in nature.

Culture
Cross-cultural studies into schizophrenia have found that individual experiences of psychosis and ‘hearing voices’ vary across cultures. In countries such as the United States where there exists a predominantly biomedical understanding of the body, the mind and in turn, mental health, subjects were found to report their hallucinations as having ‘violent content’ and self-describing as ‘crazy’. This lived experience is at odds with the lived experience of subjects in Accra, Ghana, who describe the voices they hear as having ‘spiritual meaning’ and are often reported as positive in nature; or subjects in Chennai, India, who describe their hallucinations as kin, family members or close friends, and offering guidance.These differences are attributed to ‘social kindling’ or how ones social context shapes how an individual interprets and experiences sensations such as hallucinations. This concept aligns with pre-existing cognitive theory such as reality modelling and is supported by recent research that demonstrates that individuals with psychosis can be taught to attend to their hallucinations differently, which in turn alters the hallucinations themselves. Such research creates pathways for social or community-based treatment, such as reality monitoring, for individuals with schizophrenia and other psychotic disorders, providing alternatives to, or supplementing traditional pharmacologic management.
Cross-cultural studies explore the way in which psychosis varies in different cultures, countries and religions. The cultural differences are based on the individual or shared illness narratives surrounding cultural meanings of illness experience. In countries such as India, Cambodia and Muslim majority countries, they each share alternative epistemologies. These are known as knowledge systems that focus on the connections between mind, body, culture, nature, and society. Cultural perceptions of mental disorders such as psychosis or schizophrenia are believed to be caused by jinn (spirits) in Muslim majority countries. Furthermore, those in Arab-Muslim societies perceive those who act differently than the social norm as “crazy” or as abnormal behaviour. This differs from the lived experience of individuals in India and how they attain their perspectives on mental health issues through a variety of spiritual and healing traditions. In Cambodia, hallucinations are linked with spirit visitation, a term they call “cultural kindling”. These examples of differences are attributed to culture and the way it shapes conceptions of mental disorders. These cultural differences can be useful in bridging the gap of cultural understanding and psychiatric signs and symptoms.

Diagnosis
To make a diagnosis of a mental illness in someone with psychosis other potential causes must be excluded. An initial assessment includes a comprehensive history and physical examination by a health care provider. Tests may be done to exclude substance use, medication, toxins, surgical complications, or other medical illnesses. A person with psychosis is referred to as psychotic.
Delirium should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors, including medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure:

Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism,
Basic electrolytes and serum calcium to rule out a metabolic disturbance,
Full blood count including ESR to rule out a systemic infection or chronic disease, and
Serology to exclude syphilis or HIV infection.Other investigations include:

EEG to exclude epilepsy, and an
MRI or CT scan of the head to exclude brain lesions.Because psychosis may be precipitated or exacerbated by common classes of medications, medication-induced psychosis should be ruled out, particularly for first-episode psychosis. Both substance- and medication-induced psychosis can be excluded to a high level of certainty, using toxicology screening.
Because some dietary supplements may also induce psychosis or mania, but cannot be ruled out with laboratory tests, a psychotic individuals family, partner, or friends should be asked whether the patient is currently taking any dietary supplements.Common mistakes made when diagnosing people who are psychotic include:
Not properly excluding delirium,
Not appreciating medical abnormalities (e.g., vital signs),
Not obtaining a medical history and family history,
Indiscriminate screening without an organizing framework,
Missing a toxic psychosis by not screening for substances and medications,
Not asking their family or others about dietary supplements,
Premature diagnostic closure, and
Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder.Only after relevant and known causes of psychosis are excluded, a mental health clinician may make a psychiatric differential diagnosis using a persons family history, incorporating information from the person with psychosis, and information from family, friends, or significant others.
Types of psychosis in psychiatric disorders may be established by formal rating scales. The Brief Psychiatric Rating Scale (BPRS) assesses the level of 18 symptom constructs of psychosis such as hostility, suspicion, hallucination, and grandiosity. It is based on the clinicians interview with the patient and observations of the patients behavior over the previous 2–3 days. The patients family can also answer questions on the behavior report. During the initial assessment and the follow-up, both positive and negative symptoms of psychosis can be assessed using the 30 item Positive and Negative Symptom Scale (PANSS).The DSM-5 characterizes disorders as psychotic or on the schizophrenia spectrum if they involve hallucinations, delusions, disorganized thinking, grossly disorganized motor behavior, or negative symptoms. The DSM-5 does not include psychosis as a definition in the glossary, although it defines "psychotic features", as well as "psychoticism" with respect to personality disorder. The ICD-10 has no specific definition of psychosis.Factor analysis of symptoms generally regarded as psychosis frequently yields a five factor solution, albeit five factors that are distinct from the five domains defined by the DSM-5 to encompass psychotic or schizophrenia spectrum disorders. The five factors are frequently labeled as hallucinations, delusions, disorganization, excitement, and emotional distress. The DSM-5 emphasizes a psychotic spectrum, wherein the low end is characterized by schizoid personality disorder, and the high end is characterized by schizophrenia.

Prevention
The evidence for the effectiveness of early interventions to prevent psychosis appeared inconclusive. But psychosis caused by drugs can be prevented. Whilst early intervention in those with a psychotic episode might improve short-term outcomes, little benefit was seen from these measures after five years. However, there is evidence that cognitive behavioral therapy (CBT) may reduce the risk of  becoming psychotic in those at high risk, and in 2014 the UK National Institute for Health and Care Excellence (NICE) recommended preventive CBT for people at risk of psychosis.

Treatment
The treatment of psychosis depends on the specific diagnosis (such as schizophrenia, bipolar disorder or substance intoxication). The first-line treatment for many psychotic disorders is antipsychotic medication,
 which can reduce the positive symptoms of psychosis in about 7 to 14 days. For youth or adolescents, treatment options include medications, psychological interventions, and social interventions.

Medication
The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or atypical antipsychotics are better. Tentative evidence supports that amisulpride, olanzapine, risperidone and clozapine may be more effective for positive symptoms but result in more side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two or three different antipsychotics) in 20% of people. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.

Psychotherapy
Psychological treatments such as acceptance and commitment therapy (ACT) are possibly useful in the treatment of psychosis, helping people to focus more on what they can do in terms of valued life directions despite challenging symptomology. Metacognitive training (MCT) is associated with reduced delusions, hallucinations and negative symptoms as well as improved self-esteem and functioning in individuals with schizophrenia spectrum disorders.There are many psychosocial interventions that seek to treat the symptoms of psychosis:  need adapted treatment, open dialogue, psychoanalysis/psychodynamic psychotherapy, major role therapy, soteria, psychosocial outpatient and inpatient treatment, milieu therapy, and  cognitive behavioral therapy (CBT). When these are used without antipsychotic medications, they may be somewhat effective for some people, especially for CBT, need-adapted treatment, and soteria.

Early intervention
Early intervention in psychosis is based on the observation that identifying and treating someone in the early stages of a psychosis can improve their longer term outcome. This approach advocates the use of an intensive multi-disciplinary approach during what is known as the critical period, where intervention is the most effective, and prevents the long-term morbidity associated with chronic psychotic illness.

Systematic reform
Addressing systematic reform is essential to creating effective prevention as well as supporting treatments and recovery for those with psychosis.
Waghorn et al. suggest that education interventions can be a building block to support those with psychosis to successfully participate in society. In their study they analyse the relationship between successful education attainment and psychosis. Findings suggest proportionately more school aged persons with psychosis discontinued their education, compared to those without psychosis.Waghorn et al. finds that specialised supported education for those with psychotic disorders can help lead to successful education attainment. Additionally, future employment outcomes are relative to such education attainment. Established approaches to supported education in the US include three basic models, self-contained classrooms, onsite support model and the mobile support model. Each model includes the participation of mental health service staff or educational facility staff in the students education arrangements.Potential benefits of specialised supported education found from this study include coordination with other service providers (e.g. income support, housing, etc.) to prevent disrupting education, providing specialised career counselling, development of coping skills in the academic environment. These examples provide beneficial ways for people with psychosis to finish studies successfully as well as counter future experiences of psychosis.

Research
Further research in the form of randomized controlled trials is needed to determine the effectiveness of treatment approaches for helping adolescents with psychosis. Through 10 randomized clinical trials, studies showed that Early Intervention Services (EIS) for patients with early-phase schizophrenia spectrum disorders have generated promising outcomes. EIS are specifically intended to fulfill the needs of patients with early-phase psychosis. In addition, one meta-analysis that consisted of four randomized clinical trials has examined the efficacy of EIS to Therapy as Usual (TAU) for early-phase psychosis, revealing that EIS techniques are superior to TAU.A study suggests that combining cognitive behavioral therapy (CBT) with SlowMo, an app that helps notice their "unhelpful fast-thinking" might be more effective for treating paranoia in people with psychosis than CBT alone.

See also
Open Dialogue
Metacognitive training

References
Bibliography
Badcock JC, Paulik G, eds. (2019). A Clinical Introduction to Psychosis: Foundations for Clinical Psychologists and Neuropsychologists (1st ed.). Cambridge, Massachusetts: Academic Press, imprint of Elsevier. doi:10.1016/C2017-0-01829-3. ISBN 978-0-12-815012-2. S2CID 243510002.
Lewandowski KE, Moustafa A, eds. (2019). Social Cognition in Psychosis (1st ed.). Cambridge, Massachusetts: Academic Press, imprint of Elsevier. doi:10.1016/C2017-0-03061-6. ISBN 978-0-12-815315-4. S2CID 239126550.
Semple D, Smyth R (2019). "Schizophrenia and related psychoses".  In Semple D, Smyth R (eds.). Oxford Handbook of Psychiatry (4th ed.). Oxford: Oxford University Press. pp. 179–240. doi:10.1093/med/9780198795551.003.0005. ISBN 978-0-19-879555-1.
Tamminga CA, van Os J, Reininghaus U, Ivleva E, eds. (2020) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Arthrogryposis and can you explain it in depth? [/INST] Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning "curving of joints" (arthron, "joint"; grȳpōsis, late Latin form of late Greek grūpōsis, "hooking").Children born with one or more joint contractures have abnormal fibrosis of the muscle tissue causing muscle shortening, and therefore are unable to perform active extension and flexion in the affected joint or joints.AMC has been divided into three groups: amyoplasia, distal arthrogryposis, and syndromic. Amyoplasia is characterized by severe joint contractures and muscle weakness. Distal arthrogryposis mainly involves the hands and feet. Types of arthrogryposis with a primary neurological or muscle disease belong to the syndromic group.

Signs and symptoms
Often,  every joint in a patient with arthrogryposis is  affected; in 84% all limbs are involved, in 11% only the legs, and in 4% only the arms are involved. Every joint in the body, when affected, displays typical signs and symptoms:  for example, the shoulder (internal rotation); wrist (volar and ulnar); hand (fingers in fixed flexion and thumb in palm); hip (flexed, abducted and externally rotated, frequently dislocated); elbow (extension and pronation) and foot clubfoot and less commonly congenital vertical talus.Range of motion can be different between joints because of the different deviations. Some types of arthrogryposis like amyoplasia have a symmetrical joint/limb involvement, with normal sensations. The contractures in the joints can  result in delayed  walking development in the first five years, but severity of contractures do not necessarily predict eventual walking ability or inability.Intelligence is normal to above normal in children with amyoplasia, but it is not known how many of these children have an above normal intelligence, and there is no literature available about the cause of this syndrome. There are a few syndromes like the Freeman–Sheldon and Gordon syndrome, which have craniofacial involvement. The amyoplasia form of arthrogryposis is sometimes accompanied with a midline facial hemangioma.
Arthrogryposis is not a diagnosis but a clinical finding, so this disease is often accompanied with other syndromes or diseases. These other diagnoses could affect any organ in a patient. There are a few slightly more common diagnoses such as pulmonary hypoplasia, cryptorchidism, congenital heart defects, tracheoesophageal fistulas, inguinal hernias, cleft palate, and eye abnormalities.

Causes
Research of arthrogryposis has shown that anything that inhibits normal joint movement before birth can result in joint contractures.  Arthrogryposis could be caused by genetic and environmental factors. In principle: any factor that curtails fetal movement can result in congenital contractures. The exact causes of arthrogryposis are unknown.

Extrinsic factors
The malformations of arthrogryposis can be secondary to environmental factors such as: decreased intrauterine movement, oligohydramnios (low volume or abnormal distribution of intrauterine fluid), and defects in the fetal blood supply. Other causes could be: hyperthermia, limb immobilization and viral infections. A specific virus that may cause arthrogryposis is contraction of  the Zika virus during pregnancy. Congenital Zika syndrome (CZS), may occur when there is vertical transmission of the Zika virus to the fetus. Myasthenia gravis of the mother leads also in rare cases to arthrogryposis. The major cause in humans is fetal akinesia, however, this is disputed lately.

Intrinsic factors
Arthrogryposis could also be caused by intrinsic factors. This includes molecular, muscle- and connective tissue development disorders or neurological abnormalities.

Molecular basis
Research has shown that there are more than 35 specific genetic disorders associated with arthrogryposis. Most of those mutations are missense, which means the mutation results in a different amino acid. Other mutations that could cause arthrogryposis are: single gene defects (X-linked recessive, autosomal recessive and autosomal dominant), mitochondrial defects and chromosomal disorders (for example: trisomy 18). This is mostly seen in distal arthrogryposis. Mutations in at least five genes (TNN12, TNNT3, TPM2, MYH3 and MYH8) could cause distal arthrogryposis. There could be also connective tissue, neurological or muscle development disorders.

Muscle and connective tissue development disorders
Loss of muscle mass with an imbalance of muscle power at the joint can lead to connective tissue abnormality. This leads to joint fixation and reduced fetal movement. Also muscle abnormalities could lead to a reduction of fetal movement.
Those could be: dystrophy, myopathy and mitochondrial disorders. This is mostly the result of abnormal function of the dystrophin-glycoprotein-associated complex in the sarcolemma of skeletal muscles.

Neurological abnormalities
Seventy to eighty percent of cases of the most severe forms of arthrogryposis are caused by neurological abnormalities, which can be either genetic or environmental.The underlying aetiology and pathogenesis of congenital contractures, particularly arthrogryposis and the mechanism of the mutations remains an active area of investigation, because identifying these factors could help to develop treatment and congenital finding of arthrogryposis.

Diagnosis
Research on prenatal diagnosis has shown that a diagnosis can be made prenatally in approximately 50% of fetuses presenting arthrogryposis. It could be found during routine ultrasound scanning showing a lack of mobility and abnormal position of the foetus. There are other options for visualization of details and structures using techniques such as 4D ultrasound. In clinic a child can be diagnosed with arthrogryposis with physical examination, confirmed by ultrasound, MRI, or muscle biopsy.

Classification
Some of the different types of AMC include:

Arthrogryposis multiplex due to muscular dystrophy.
Arthrogryposis ectodermal dysplasia other anomalies, also known as Cote Adamopoulos Pantelakis syndrome, Trichooculodermovertebral syndrome, TODV syndrome and Alves syndrome.
Arthrogryposis epileptic seizures migrational brain disorder.
Arthrogryposis IUGR thoracic dystrophy, also known as Van Bervliet syndrome.
Arthrogryposis-like disorder, also known as Kuskokwim disease.
Arthrogryposis-like hand anomaly and sensorineural deafness.
Arthrogryposis multiplex congenita CNS calcification.
Arthrogryposis multiplex congenita distal (AMCD), also known as X-linked spinal muscular atrophy type 2.
Gordon syndrome, also known as distal arthrogryposis type 3.
Arthrogryposis multiplex congenita, distal type 2A, also known as Freeman–Sheldon syndrome.
Arthrogryposis multiplex congenita, distal type 2B, also known as Sheldon–Hall syndrome.
Arthrogryposis multiplex congenita neurogenic type (AMCN). This particular type of AMC has been linked to the AMCN gene on locus 5q35.
Arthrogryposis multiplex congenita pulmonary hypoplasia, also with a large number of synonyms.
Arthrogryposis multiplex congenita whistling face, also known as Illum syndrome.
Arthrogryposis multiplex congenita, distal type 1 (AMCD1).
Arthrogryposis multiplex with deafness, inguinal hernias, and early death. This syndrome is suspected to be inherited in an X-linked or autosomal recessive fashion. There were only three reported cases with all three patients dead.
Arthrogryposis ophthalmoplegia retinopathy, also known as Oculomelic amyoplasia.
Arthrogryposis renal dysfunction cholestasis syndrome, also known as ARC Syndrome.Another form has been related to mutations in the leucine-rich glioma-inactivated 4 (LGI4) gene.

Treatment
The treatment of arthrogryposis includes occupational therapy, physical therapy, splinting and surgery. An approach that occupational therapists use is orthopedic management. Using casts in order to correct joint deformities can be very effective since the joints can be misaligned and present with deformities. Another vital intervention that occupational therapists use to treat arthrogryposis, is range of motion exercises. This is in order to increase joint mobility. The primary long-term goals of these treatments are increasing joint mobility and muscle strength and the development of adaptive use patterns that allow for walking and independence with activities of daily living. Since arthrogryposis has many different types, the treatment varies between patients depending on the symptoms.
Only a few good articles exist in which a surgical technique that is used to treat arthrogryposis is described. These surgeries are explained below.

Passive enhancement
There are a number of passive devices for enhancing limb movement, intended to be worn to aid movement and encourage muscular development. For example, the Wilmington Robotic Exoskeleton is a potential assistive device built on a back brace, shadowing the upper arm and forearm. It can be difficult to fit and heavy and awkward to wear.Researchers at the University of Delaware are developing a light and unobtrusive therapeutic garment, suitable for babies and children, called the Playskin Lift. The garment looks like normal clothing but contains bundled steel wires under the arms, which help to push the arms toward a lifted position while allowing the wearer to move freely from that position.

Wrist surgery
Children with the amyoplasia type of arthrogryposis usually have flexion and ulnar deviation of the wrists. Dorsal carpal wedge osteotomy is indicated for wrists with excessive flexion contracture deformity when non-surgical interventions such as occupational therapy and splinting have failed to improve function. On the dorsal side, at the level of the midcarpus, a wedge osteotomy is made. Sufficient bone is resected to at least be able to put the wrist in a neutral position. If the wrist also has ulnar deviation, more bone can be taken from the radial side to correct this abnormality. This position is held into place with two cross K-wires. In addition, a tendon transfer of the extensor carpi ulnaris to the extensor carpi radialis brevis may be performed to correct ulnar deviation or wrist extension weakness, or both. This tendon transfer is only used if the extensor carpi ulnaris appears to be functional enough.

Thumb surgery
The soft tissue envelope in congenital contractual conditions such as clasped or arthrogrypotic thumbs is often deficient in two planes, the thumb-index web and the flexor aspect of the thumb.  There is often an appearance of increased skin at the base of the index finger that is part of the deformity. This tissue can be used to resurface the thumb-index web after a comprehensive release of all the tight structures to allow for a larger range of motion of the thumb. This technique is called the index rotation flap.The flap is taken from the radial side of the index finger. It is proximally based at the distal edge of the thumb-index web. The flap is made as wide as possible, but still small enough to close with the excessive skin on the palmar side of the index finger. The flap is rotated around the tightest part of the thumb to the metacarpophalangeal joint of the thumb, allowing for a larger range of motion.

Foot surgeries
Generally, foot surgery is usually reserved for patients with a walking or ambulatory potential. Foot surgery may also be indicated to assist brace and orthosis fitting and hence promote supported standing. The most common foot deformity in arthrogryposis is club feet or talipes equinovarus. In the early years of life the serial casting according to the Ponseti method usually yields good results. The Ponseti method can also be used as a first line treatment in older and more resistant cases. In such severe and neglected cases bony surgery in the form of foot osteotomies and arthrodesis is usually indicated. It is usually accompanied by soft tissue surgery in the form of release of contracted tendon and capsular structures. In older patients near skeletal maturity joint fusion or arthrodesis may be indicated as well. Less frequent patients with arthrogryposis may develop congenital vertical talus also known as rocker bottom foot. Similarly, congenital vertical talus is classically managed by serial casting according to the reversed Ponseti method </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Heart-hand syndrome, Spanish type and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Craniomandibular osteopathy and can you explain it in depth? [/INST] Craniomandibular osteopathy, also known as lions jaw, is a developmental disease in dogs causing extensive bony changes in the mandible and skull.  In this disease, a cyclical resorption of normal bone and replacement by immature bone occurs along the inner and outer surfaces of the affected bones.  It usually occurs between the ages of 3 and 8 months.  Breeds most commonly affected include the West Highland White Terrier, Scottish Terrier, Cairn Terrier, and Boston Terrier.  It is rare in large-breed dogs, but it has been reported.  Symptoms include firm swelling of the jaw, drooling, pain, and difficulty eating.
It is an inherited disease, especially in Westies, in which it has been recognized as an autosomal recessive trait </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tracheobronchomalacia and can you explain it in depth? [/INST] Tracheobronchomalacia or TBM is a condition characterized by flaccidity of the tracheal support cartilage which leads to tracheal collapse. This condition can also affect the bronchi. There are two forms of this condition: primary TBM and secondary TBM. Primary TBM is congenital and starts as early as birth.  It is mainly linked to genetic causes. Secondary TBM is acquired and starts in adulthood. It is mainly developed after an accident or chronic inflammation.Tracheobronchomalacia may also occur in people who have normal cartliginous structure of the trachea, but significant atrophy of the posterior wall, causing significant invagination of the trachea on expiration. In these cases it is more commonly known as Excessive Dynamic Airway Collapse (EDAC).

Signs and symptoms
Initially TBM may be asymptomatic or some patients do not experience symptoms at all. In a progressive TBM case symptoms include:

shortness of breath
a cough
mucus build up
stridor (a wheeze-like sound on breathing out)
difficulty in breathing
bluish coloration to skin around the nose and mouth
Chronic coughSymptoms may become worse if the patient is stressed, sick, lying down, or forcing a cough.

Cause
Congenital TBM is present from birth. Acquired TBM often has no clear cause but is frequently found together with other pulmonary diseases like asthma and Chronic obstructive pulmonary disease, as well as Gastroesophageal reflux disease. TBM can be caused by damage to the support cartilage or membranous wall of the trachea, this can be the result of physical trauma (such as from prolonged Tracheal intubation) or pathological changes caused by inflammatory diseases like Relapsing polychondritis. In patients with TBM in one study, the number of longitudinal elastic fibers in the pars of membranacea was reduced throughout the whole trachea.People with heritable connective tissue disorders like Ehlers–Danlos syndrome seem to have at an increased risk of both congenital and acquired TBM, although the extent of that risk is unknown. There have been studies linking long-term use of inhaled Corticosteroids to Tracheobronchomalacia.

Diagnosis
Diagnosis is conducted according to the severity of the symptoms. Initially pulmonary function tests are administered. These tests include the lungs capability of air intake and outtake, and gas flow of oxygen and carbon dioxide between the body and environment. Following these function tests a special type of Chest CT scan or a bronchoscopy will be ordered. The results of the scan and bronchoscopy will display the status of the condition </s>