<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 Proctalgia fugax and can you explain it in depth? [/INST] Proctalgia fugax, a variant of levator ani syndrome, is a severe, episodic pain in the regions of the rectum and anus. It can be caused by cramping of the levator ani muscle, particularly in the pubococcygeal part.

Signs and symptoms
It most often occurs in the middle of the night and lasts from seconds to minutes; pain and aching lasting twenty minutes or longer would likely be diagnosed instead as levator ani syndrome. In a study published in 2007 involving 1809 patients, the attacks occurred in the daytime (33 percent) as well as at night (33 percent) and the average number of attacks was 13. Onset can be in childhood; however, in multiple studies the average age of onset was 45. Many studies showed that women are affected more commonly than men, but this can be at least partly explained by mens reluctance to seek medical advice concerning rectal pain. Data on the number of people affected vary, but prevalence may be as high as 8–18%. It is thought that only 17–20% of patients consult a physician, so obtaining accurate data on occurrence presents a challenge.During an episode, the patient feels spasm-like, sometimes excruciating, pain in the rectum or anus, often misinterpreted as a need to defecate. To be diagnosed as proctalgia fugax, the pain must arise de novo (meaning the absence of clear cause). As such, pain associated with constipation (either chronic, or acute), penetrative anal intercourse, trauma (such as tears or fissures of the rectal sphincter or anal canal), side-effects of some medications (particularly opiates), or rectal foreign body insertion preclude this diagnosis.  The pain episode subsides by itself as the spasm disappears on its own, but may reoccur.Because of the high incidence of internal anal sphincter thickening with the disorder, it is thought to be a disorder of that muscle or that it is a neuralgia of pudendal nerves. It is not known to be linked to any disease process.

Prevention
High-voltage pulsed galvanic stimulation (HGVS) has been shown to be of prophylactic benefit, to reduce the incidence of attacks </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 Pilar sheath acanthoma 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 Membranous glomerulonephritis and can you explain it in depth? [/INST] Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (i.e., those of European, Middle Eastern, or North African ancestry.).

It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) recently becoming the most common.

Signs and symptoms
Most people will present as nephrotic syndrome, with the triad of albuminuria, edema and low serum albumin (with or without kidney failure).  High blood pressure and high cholesterol are often also present. Others may not have symptoms and may be picked up on screening, with urinalysis finding high amounts of protein loss in the urine. A definitive diagnosis of membranous nephropathy requires a kidney biopsy, though given the very high specificity of anti-PLA2R antibody positivity this can sometimes be avoided in patients with nephrotic syndrome and preserved kidney function

Causes
Primary/idiopathic
85% of MGN cases are classified as primary membranous glomerulonephritis—that is to say, the cause of the disease is idiopathic (of unknown origin or cause). This can also be referred to as idiopathic membranous nephropathy.One study has identified antibodies to an M-type phospholipase A2 receptor in 70% (26 of 37) cases evaluated. Testing for these anti-PLA2R has revolutionised diagnosis and treatment of this disease in antibody positive patients, and tracking titre level over time allows you to predict risk of disease progression and chance of spontaneous remissionIn 2014, a second autoantigen was discovered, the thrombospondin type 1 domain-containing 7A (THSD7A) system that might account for an additional 5-10% of membranous nephropathy cases, and appears to be associated with malignancies. New studies are identifying novel auto-antigens responsible for causing a membranous nephropathy pattern of injury continue to be published, with antibodies against NELL-1 and EXT1/EXT2 in 2019, Semaphorin3B and Protocadherin 7 (PCDH7) in 2020, and serine protease HTRA1 in 2021.

Secondary
The remainder is secondary due to:

autoimmune conditions (e.g., systemic lupus erythematosus).
infections (e.g., syphilis, malaria, hepatitis B, hepatitis C, HIV).
drugs (e.g., captopril, NSAIDs, penicillamine, probenecid, Bucillamine, Anti-TNF therapy, Tiopronin).
inorganic salts (e.g. gold, mercury).
tumors, frequently solid tumors of the lung and colon; hematological malignancies such as chronic lymphocytic leukemia are less common.

Pathogenesis
MGN is caused by immune complex formation in the glomerulus. The immune complexes are formed by binding of antibodies to antigens in the glomerular basement membrane. The antigens may be part of the basement membrane, or deposited from elsewhere by the systemic circulation.The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack complex (MAC) on the glomerular epithelial cells. This, in turn, stimulates release of proteases and oxidants by the mesangial and epithelial cells, damaging the capillary walls and causing them to become "leaky". In addition, the epithelial cells also seem to secrete an unknown mediator that reduces nephrin synthesis and distribution.Within membranous glomerulonephritis, especially in cases caused by viral hepatitis, serum C3 levels are low.Similar to other causes of nephrotic syndrome (e.g., focal segmental glomerulosclerosis or minimal change disease), membranous nephropathy is known to predispose affected individuals to develop blood clots such as pulmonary emboli. Membranous nephropathy in particular is known to increase this risk more than other causes of nephrotic syndrome though the reason for this is not yet clear.

Morphology
The defining point of MGN is the presence of subepithelial immunoglobulin-containing deposits along the glomerular basement membrane (GBM).
By light microscopy, the basement membrane is observed to be diffusely thickened. Using Jones stain, the GBM appears to have a "spiked" or "holey" appearance.
On electron microscopy, subepithelial deposits that nestle against the glomerular basement membrane seems to be the cause of the thickening. Also, the podocytes lose their foot processes. As the disease progresses, the deposits will eventually be cleared, leaving cavities in the basement membrane. These cavities will later be filled with basement membrane-like material, and if the disease continues even further, the glomeruli will become sclerosed and finally hyalinized.
Immunofluorescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement membrane.Although it usually affects the entire glomerulus, it can affect parts of the glomerulus in some cases.

Treatment
Treatment of secondary membranous nephropathy is guided by the treatment of the original disease. For treatment of idiopathic membranous nephropathy, the treatment options include immunosuppressive drugs and non-specific anti-proteinuric measures such as ACE inhibitors or angiotensin II receptor blockers.  Given spontaneous remission is common, international guidelines recommend a period of watchful waiting before considering immunosuppressive treatment </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 Genitopatellar syndrome and can you explain it in depth? [/INST] Genitopatellar syndrome is a rare disorder consisting of  congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies. Additional symptoms include microcephaly, severe psychomotor disability.
In 2012, it was shown that mutations in the gene KAT6B cause the syndrome. Genitopatellar syndrome (GTPTS) can be caused by heterozygous mutation in the KAT6B gene on chromosome 10q22. The Say-Barber-Biesecker variant of Ohdo syndrome, which has many overlapping features with GTPTS, can also be caused by heterozygous mutation in the KAT6B gene.

Signs and symptoms
Genitopatellar syndrome is characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability and abnormalities affecting other parts of the body. It is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an unusually small head (microcephaly) and structural brain abnormalities, including agenesis of the corpus callosum.Major features include:
Patellar hypoplasia/agenesis
Flexion contractures at the hips and knees
Agenesis of the corpus callosum with microcephaly
Hydronephrosis and/or multiple kidney cysts
Atrial septal defect
Intestinal malrotation
Talipes equinovarus (including club feet)
Feeding difficultiesOther features may include:
Dental anomalies (delayed eruption of teeth)
Hearing loss
Thyroid anomalies
Anal anomalies
Hypotonia
Global developmental delay/intellectual disability

Cause
Genitopatellar syndrome is inherited in an autosomal dominant fashion. The mutation responsible for the syndrome occurs in the KAT6B gene. This gene is located on the long arm of chromosome 10 (10q22.2).The KAT6B gene gene product is an enzyme called histone acetyltransferase which functions in regulating and making of histone which are proteins that attach to DNA and give the chromosomes their shape. The function of histone acetyltransferase produced from KAT6B is unknown but it is considered as a regulator of early development. There is little known about how the mutation in the KAT6B causes the syndrome but researchers suspects that the mutations occur near the end of the KAT6B gene and causes it to produce shortened acetyltransferase enzyme. The shortened enzyme alters the regulation of other genes. On the other hand, the mutation of KAT6B leading to the specific features of genitopatellar syndrome is still not surely proven.

Diagnosis
Even though clinical diagnostic criteria have not been 100 percent defined for genitopatellar syndrome, the researchers stated that the certain physical features could relate to KAT6B mutation and result in the molecular genetic testing. The researchers stated that the Individuals with two major features or one major feature and two minor features are likely to have a KAT6B mutation.
To diagnose the Genitopatellar Syndrome, there are multiple ways to evaluate </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 Diplegia and can you explain it in depth? [/INST] Diplegia, when used singularly, refers to paralysis affecting symmetrical parts of the body. This is different from hemiplegia which refers to spasticity restricted to one side of the body, paraplegia which refers to paralysis restricted to the legs and hip, and quadriplegia which requires the involvement of all four limbs but not necessarily symmetrical. Diplegia is the most common cause of crippling in children, specifically in children with cerebral palsy. Other causes may be due to injury of the spinal cord. There is no set course of progression for people with diplegia. Symptoms may get worse but the neurological part does not change. The primary parts of the brain that are affected by diplegia are the ventricles, fluid filled compartments in the brain, and the wiring from the center of the brain to the cerebral cortex. There is also usually some degeneration of the cerebral neurons, as well as problems in the upper motor neuron system.
The term diplegia can refer to any bodily area, such as the face, arms, or legs.

Facial diplegia
Facial diplegia refers to people with paralysis of both sides of their face. Bilateral occurs when the onset of the second side occurs within one month of the onset of the first side.  Facial diplegia occurs in 50% of patients with Guillain–Barré syndrome. Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult-onset muscular dystrophy with facial weakness being a distinct feature of FSHD in over 90% of cases.

Causes
Facial paralysis is usually caused by traumatic, infectious, neurological, metabolic, toxic, vascular, and idiopathic conditions. While over 50% of the cases of unilateral facial paralysis are caused by idiopathic conditions, less than 20% of bilateral cases are idiopathic. The most common infectious cause of facial diplegia is Lyme disease.

Treatment
The treatment for facial diplegia depends on the underlying cause. Some causes are usually treatable such as infectious, toxic, and vascular by treating the main problem first. After the underlying problem is cured, the facial paralysis usually will go away.

Diplegia of the arms
People with diplegia in their arms experience difficulties in reaching, pointing, grasping, releasing, manipulating objects and many other motor functions performed by the hands and arms.

Causes
There are several ways of getting diplegia in the arms. It is very common for people with cerebral palsy to have diplegia of the arms. Although most people with cerebral palsy have diplegia in their legs, some people have diplegia in their arms. Other ways of getting paralysis of both arms is through a traumatic event or injury.

Treatment
There are several different modes of treatment for people with paralysis in their upper limbs. For example, behavioral and environmental treatments may include physiotherapy, occupational therapy, motor learning, strength training, and neurodevelopment treatment. Another treatment may be through the use of splints and casts. Electrophysical agents may be used such as neuromuscular electrical stimulation (NMES). Sometimes pharmacological treatments are necessary such as Botulinum toxin type A. On more severe cases surgery of the upper limbs may be required.

Diplegia in the legs
Diplegia of the legs consists of paralysis of both legs. There are 3 levels of severity. Mild diplegia means the person can usually walk but might walk a little differently, can usually play and run to a limited extent. Moderate diplegia means the person can usually walk but with a slight bend in the knees. They usually cant run and have to use the handrails to go up and down steps. People with severe diplegia usually need crutches, a walker, or a wheelchair to be able to get around.Children with diplegia in the legs have a delayed growth in their leg muscles which causes the muscles to be short. This then causes the joints to become stiff and the range of motion to decrease as the child grows. “For the majority of children with diplegia, growth and development are not a problem. Children with diplegia are eventually able to walk, just normally later; they generally attend regular schools and become independently functioning adults.”

Causes
The most common cause of diplegia in the legs is cerebral palsy. Paralysis of the legs may also be caused by trauma, injury, or genetics, but this is very rare.

Age of onset
Usually occurs within 2 periods:
With premature babies
full diagnosis usually between ages 2–5 yearsDiplegia is usually not diagnosed before the age of 2 years yet the symptoms and signs of the earlier stages are typical and should enable the diagnosis to be made before the contractures have occurred. Parents suspecting diplegia should take their child to the doctor to potentially get an earlier diagnosis.

Treatment and care
This is broken up by age categories. Different ages require different forms of treatment which may include: therapy, bracing, walkers, wheelchairs, and surgery. Currently the treatments for children are concentrated primarily on independent walking but instead a more independence-oriented therapeutic approach would be more beneficial. This way the child can still focus on walking but at the same time be taught to do things for themselves while using the best method of walking for them. This could include using a walker or wheelchair to get around and do things easier than focusing all the attention on walking so early.
For people requiring surgery, distal hamstring lengthening is the most common operation performed because it reduces knee flexion and improves knee motion.

Birth to 1 year
“This first year sees the development of many milestones, such as head control, reaching out for a toy, sitting, starting to vocalize sounds, and finger feeding.”  Most parents want their children to excel very fast, but there is a wide upper and lower range of development time for premature babies so its very hard to diagnose cerebral palsy or diplegia this early. The most common symptom of a child with diplegia is stiff lower extremities. This should become apparent by the six month mark which means he or she does not have severe diplegia. During this age if a child is not moving his legs on his own then it is recommended to do some exercise, especially gentle stretching with the child.

1 to 3 years
“This is the age at which the characteristics of diplegia become more noticeable, mainly because, unlike other children at this age, the child with diplegia is not walking.”  By the age of three, it is important for the child to be in a specialized school environment so the child can participate in physical therapy and learn social skills. Parents should not force the child to sit, crawl, or walk a certain way during this age period. Let the child do whats comfortable for them and allow the therapist to correct this problem. If you want to help your child walk more, then push toys are recommended for walking aids. Regular exams should be done to make sure the childs legs are growing normally and he or she is not having any problems with the hip.

4 to 6 years
“This is the age range at which the child with diplegia makes the most significant physical improvement in motor function.”  During this time period the child makes major improvements in motor function. He or she should be in a regular school and focus on cognitive issues not therapy. A child using a walking aid for mobility to move around with the other children is not a bad thing. If a child is not walking yet, then this is usually caused by a problem in balance, muscle coordination, spasticity, or leg alignment. Each of these reasons should be looked into closely so the problem can be addressed and fixed.

7 to 12 years
“By the time a child reaches this age  the rate of physical improvement has leveled off in areas such as balance and coordination, and its a good idea to refocus the child’s attention away from additional physical improvement and toward intellectual learning.”  During this time period a child should lean away from physical therapy and do more outdoor or social exercises such as sports and adaptive P.E. Usually by age 8-10 a child has reached maximum walking ability. This will usually decrease a little when a child hits puberty and gains height and weight because walking becomes harder during this changing period. Any significant problems in walking should be addressed with surgery at this stage.

13 to 18 years
“During this time period of a child’s development, a major issue is separating from the family.”  Parents should learn how to cope with their child growing up and give them more freedom and independence </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 pulmonary aspergillosis and can you explain it in depth? [/INST] Chronic pulmonary aspergillosis is a long-term fungal infection caused by members of the genus Aspergillus—most commonly Aspergillus fumigatus. The term describes several disease presentations with considerable overlap, ranging from an aspergilloma—a clump of Aspergillus mold in the lungs—through to a subacute, invasive form known as chronic necrotizing pulmonary aspergillosis which affects people whose immune system is weakened. Many people affected by chronic pulmonary aspergillosis have an underlying lung disease, most commonly tuberculosis, allergic bronchopulmonary aspergillosis, asthma, or lung cancer.

Classification
Chronic pulmonary aspergillosis as a term encompasses a number of different presentations of varying severity. There is considerable overlap between disease forms which adds to confusion during diagnosis. The primary differentiation comes from radiological findings and serology.

Aspergilloma
An aspergilloma is a fungus ball composed of Aspergillus hypha - the long filamentous strands which extend from the fungus to enable growth and reproduction. They can arise within any bodily cavity, though in chronic pulmonary aspergillosis they form within pulmonary cavities that have been colonized by Aspergillus spp. If there is a single, stable cavity that provides minimal symptoms, the term simple aspergilloma is commonly used to distinguish it from more severe forms of chronic pulmonary aspergillosis.

Aspergillus nodule
Aspergillus can form single or multiple nodules which may or may not form a cavity. Whilst usually benign in nature, they can sometimes cause symptoms such as cough or an exacerbation of existing disease such as asthma. Histologically, there is necrosis surrounded by granulomatous inflammation with some multinucleated giant cells present.

Chronic cavitary pulmonary aspergillosis
When people without immunocompromise undergo formation of one or more pulmonary cavities, this is called chronic cavitary pulmonary aspergillosis. Historically it was also known as "complex aspergilloma" in contrast to a "simple aspergilloma"; this is now considered inaccurate as many cases do not have a visible aspergilloma on imaging. In contrast to aspergilloma and Aspergillus nodules, the vast majority of people with chronic cavitary pulmonary aspergillosis have positive tests for IgG antibodies.

Chronic fibrosing pulmonary aspergillosis
When chronic cavitary pulmonary aspergillosis is left untreated, it can progress to a form of aspergillosis known as chronic fibrosing pulmonary aspergillosis). As a result of the ongoing inflammation over an extended period of time, extensive fibrosis of the lung parenchyma occurs. This leads to a state known colloquially as "destroyed lung", and has features resembling treated pulmonary tuberculosis.

Chronic necrotizing pulmonary aspergillosis
Also known as subacute invasive pulmonary aspergillosis, this form of chronic pulmonary aspergillosis leads to progressive features over the course of one to three months—usually in people with some degree of immunocompromise. It is more common in people who are elderly or dependent on alcohol, or with diseases such as diabetes, malnutrition, chronic obstructive pulmonary disease or HIV/AIDS. In contrast to chronic cavitary pulmonary aspergillosis, for example, IgG antibodies for Aspergillus or an antigen called galactomannan may be found in the blood as well as in sputum samples.

Signs and symptoms
People with chronic pulmonary aspergillosis typically present with a prolonged, several month history of unintentional weight loss, chronic cough which is normally productive of sputum, shortness of breath and haemoptysis. One small case series of 18 people found these to be the most common presenting symptoms. Less common symptoms include severe fatigue or malaise, chest pain, sputum production without cough, and fever. Fever would not typically be expected unless they had the subacute invasive subtype. Furthermore, it is possible for less severe subtypes to be asymptomatic. Beyond the direct symptoms, it is possible to have general signs of underlying lung pathology such as digital clubbing—especially when there has been an underlying disease such as tuberculosis or where disease has caused heart failure (known as cor pulmonale).

Complications
Chronic pulmonary aspergillosis can cause bleeding into the lung parenchyma which can range from mild to life-threatening. If left untreated, as the disease progresses the fungus can spread into the bloodstream causing a state known as fungemia. This widespread infection can distribute fungal spores to other parts of the body, and lead to areas of infarction, and cause haemorrhages.

Causes
Aspergillosis is an infection caused by fungi from the genus Aspergillus. The vast majority of cases are caused by Aspergillus fumigatus—a filamentous fungus found ubiquitously on every continent including Antarctica. Other species of Aspergillus include A. flavus and A. terreus.The major risk factors for chronic pulmonary aspergillosis are previous cavity formation from other respiratory conditions. Examples include collapsed lungs which have formed bullae, chronic obstructive lung disease, lung cancer, and fibrocavitary sarcoidosis. Another risk factor is immunosuppression; most commonly, this includes allogeneic stem cell transplantation, prolonged neutropaenia, immunosuppressive drug therapy, chronic granulomatous disease and haematological malignancies. Certain demographics are also at higher risk, including the elderly, male gender and those with a low body mass index.There appears to be increasing evidence for complex genetic factors increasing the risk of developing chronic pulmonary aspergillosis, such as defects to toll-like receptor (TLR) 4, IL1 and IL15, TLR3, TLR10, TREM1, VEGFA, DENND1B, and PLAT.

Mechanism
The full underlying pathogenesis is not completely understood. Most people with chronic pulmonary aspergillosis have functional immune status, but usually have underlying structural damage to the lungs from an underlying process or disease. Most commonly, pre-existing pulmonary cavities from other diseases such as tuberculosis become colonised with Aspergillus conidia which have been inhaled—humans inhale between 1,000 and 10 billion spores per day, of which A. fumigatus is the most common.Aspergillomas themselves usually form in existing cavities but the cavities may form directly from chronic pulmonary aspergillosis. People with pulmonary tuberculosis with a cavity larger than 2 cm appear to have a 20% increased risk of developing chronic pulmonary aspergillosis.It is postulated that conidia, once inhaled, are attacked by the host immune defences—specifically phagocytes and alveolar macrophage resident in the small airways. It is unknown whether these defences are sufficient to clear conidia or whether they are directly responsible for the inflammation leading to chronic pulmonary aspergillosis. Some Aspergillus have the ability to inhibit phagocyte nicotinamide adenine dinucleotide phosphate oxidase activation which is one of the core defence systems against filamentous fungi, which may increase susceptibility of the host to chronic pulmonary aspergillosis.

Diagnosis
The diagnosis of chronic pulmonary aspergillosis is often initially considered when patients present with a history of unintentional weight loss and fatigue. Confirmation of this suspicion is normally achieved with a combination of radiological imaging and serological testing, with the goal of excluding other diagnoses like tuberculosis and finding evidence of fungus present. Whilst cavities seen on chest X-rays can raise suspicion, positive IgG testing for Aspergillus is required for confirmation.Sputum samples can be sent for culture, but where these return negative patients should undergo bronchoscopy and bronchoalveolar lavage for further culture samples. Concurrent infections with non-tuberculous mycobacteria, or atypical infections such as MRSA or Pseudomonas aeruginosa are common and these can also form cavities.To confirm the presence of an aspergilloma, there needs to be radiological evidence of a round mass in the lungs with confirmatory evidence either from culture or IgG testing. The distinction between simple aspergilloma, and more advanced chronic cavitary pulmonary aspergillosis, will depend on the severity of inflammation, radiological evidence, and changes over time. To confirm chronic pulmonary aspergillosis, the current criteria is one large cavity or more than two small cavities, either with or without aspergilloma. This must be accompanied by at least one symptom of fever, weight loss, fatigue, cough, sputum production, haemoptysis or shortness of breath for at least 3 months. Furthermore, as with aspergilloma, there must be positive IgG testing but this can be with or without culture </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 45,X/46,XY mosaicism and can you explain it in depth? [/INST] 45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis, is a mutation of sex development in humans associated with sex chromosome aneuploidy and mosaicism of the Y chromosome.  This is called a mosaic karyotype because, like tiles in mosaic floors or walls, there is more than one type of cell. It is a fairly rare chromosomal disorder at birth, with an estimated incidence rate of about 1 in 15,000 live births.  Mosaic loss of the Y chromosome in previously non-mosaic men grows increasingly common with age.The clinical manifestations are highly variable, ranging from partial virilisation and ambiguous genitalia at birth, to patients with completely male or female gonads. Most individuals with this karyotype have apparently normal male genitalia, and a minority have female genitalia, with a significant number of individuals showing genital abnormalities or intersex characteristics. A significantly higher than normal number of other developmental abnormalities are also found in individuals with X0/XY mosaicism. Psychomotor development is normal.

Signs and symptoms
Although similar in some ways to true hermaphroditism, the conditions can be distinguished histologically and by karyotyping.  The observable characteristics (phenotype) of this condition are highly variable, ranging from gonadal dysgenesis in males, to Turner-like females and phenotypically normal males.  The phenotypical expression may be ambiguous, male or female depending on the extent of the mosaicism. The most common presentation of 45,X/46,XY karyotype is phenotypically normal male, next being genital ambiguity.There is a range of chromosomal anomalies within 45,X/46,XY where the variations are very complex, and the actual result in living individuals is often not a simple picture. Most patients with this karyotype are known to have abnormal gonadal histology and heights considerably below their genetic potential. High gonadotropin levels have been described in both male and female patients, as well as low levels of testosterone in male patients. Dosage loss of SHOX gene is commonly associated with short stature. Psychomotor development is normal.
As the gonads may not be symmetrical, the development of the Müllerian duct and Wolffian duct may be asymmetrical, too.  Because of the presence of dysgenetic gonadal tissue and Y chromosome material, there is a high risk of the development of a gonadoblastoma.

Causes
In a normal situation, all the cells in an individual will have 46 chromosomes with one being an X and one a Y or with two Xs. However, sometimes during this complicated early copying process (DNA replication and cell division), one chromosome can be lost </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 Acne conglobata and can you explain it in depth? [/INST] Acne conglobata is a highly inflammatory disease presenting with comedones, nodules, abscesses, and draining sinus tracts.This condition generally begins between the ages of 18 and 30. It usually persists for a very long time, and often until the patient is around 40 years old.  Although it often occurs where there is already an active acne problem, it can also happen to people whose acne has subsided.  Although the cause of this type of acne is unknown, it is associated with testosterone and thus appears mainly in males.  It can be caused by anabolic steroid abuse and sometimes appears in males after stopping testosterone therapy.  It can also happen to someone who has a tumor that is releasing large amounts of androgens, or to people in remission from diseases, such as leukemia </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 Tetra-amelia syndrome and can you explain it in depth? [/INST] Tetra-amelia syndrome (tetra- + amelia), also called autosomal recessive tetraamelia, is an extremely rare autosomal recessive congenital disorder characterized by the absence of all four limbs. Other areas of the body are also affected by malformations, such as the face, skull, reproductive organs, anus, lungs and pelvis. The disorder can be caused by recessive mutations in the WNT3 or RSPO2 genes.

Presentation
Tetra-amelia syndrome is characterized by the complete absence of all four limbs. The syndrome causes severe malformations of various parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia. In many cases, the lungs are underdeveloped, which makes breathing difficult or impossible </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 Rasmussen syndrome and can you explain it in depth? [/INST]  </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Meralgia paraesthetica and can you explain it in depth? [/INST] Meralgia paresthetica or meralgia paraesthetica  is numbness or pain in the outer thigh not caused by injury to the thigh, but by injury to a nerve that extends from the spinal column to the thigh.
This chronic neurological disorder involves a single nerve—the  lateral cutaneous nerve of the thigh, which is also called the lateral femoral cutaneous nerve (and hence the syndrome lateral femoral cutaneous neuropathy).  The term "meralgia paraesthetica" combines four Greek roots to mean "thigh pain with anomalous perception".  The disorder has also been nicknamed bikini brief syndrome and skinny pants syndrome, because it can be caused by wearing tight clothing.

Signs and symptoms
Pain on the outer side of the thigh, occasionally extending to the outer side of the knee, usually constant.
A burning sensation, tingling, or numbness in the same area
Multiple bee-sting like pains in the affected area
Occasionally, aching in the groin area or pain spreading across the buttocks
Usually more sensitive to light touch than to firm pressure
Hypersensitivity to heat (warm water from shower feels like it is burning the area)
Occasionally, patients may complain of itching or a bothersome sensation rather than pain in the affected area.The entire distribution of the nerve is rarely affected. Usually, the unpleasant sensation(s) affect only part of the skin supplied by the nerve.

Cause
The lateral femoral cutaneous nerve most often becomes injured by entrapment or compression where it passes between the upper front hip bone (ilium) and the inguinal ligament near the attachment at the anterior superior iliac spine (the upper point of the hip bone).  Less commonly, the nerve may be entrapped by other anatomical or abnormal structures, or damaged by diabetic or other neuropathy or trauma such as from seat belt injury in an accident.The nerve may become painful over a period of time as weight gain makes underwear, belting or the waistband of pants gradually exert higher levels of pressure. Pain may be acute and radiate into the rib cage, and into the groin, thigh, and knee. Alternately, weight loss or aging may remove protective fat layers under the skin, so the nerve can compress against underwear, outer clothing, and—most commonly— by belting. Long periods of standing or leg exercise that increases tension on the inguinal ligament may also cause pressure.The lateral cutaneous nerve of the thigh can occasionally be damaged during laparoscopic hernia repair, or scarring from the operation can lead to meralgia paraesthetica.

Diagnosis
Diagnosis is largely based on patient  description and relevant details about recent surgeries, hip injuries, or repetitive activities that could irritate the nerve </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 Perlman syndrome and can you explain it in depth? [/INST] Perlman syndrome (PS) (also called renal hamartomas, nephroblastomatosis and fetal gigantism) is a rare overgrowth disorder present at birth. It is characterized by polyhydramnios and fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms tumor at an early age. The prognosis for Perlman syndrome is poor and it is associated with a high neonatal mortality.
Perlman syndrome is an uncommon genetic disorder grouped with overgrowth syndrome in which an abnormal increase is often noted at birth in the size of the body or a body part of the infant. The disorder, also called renal hamartomas, nephroblastomatosis and fetal gigantism, has also been grouped with Renal cell carcinoma. The characteristic features include polyhydramnios, fetal overgrowth, including macrocephaly, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms tumor at an early age.

Signs and symptoms
Genetics
The gene thought to cause some of the cases of Perlman syndrome is DIS3L2 found on chromosome 2 at 2q37.2 and is thought to have an important role in the mitotic cell cycle. Although both sexes are affected, the sex ratio of male to female is 2:1 </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 Starvation and can you explain it in depth? [/INST] Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organisms life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death. The term inanition refers to the symptoms and effects of starvation. Starvation may also be used as a means of torture or execution.
According to the World Health Organization (WHO), hunger is the single gravest threat to the worlds public health. The WHO also states that malnutrition is by far the biggest contributor to child mortality, present in half of all cases. Undernutrition is a contributory factor in the death of 3.1 million children under five every year. Figures on actual starvation are difficult to come by, but according to the Food and Agriculture Organization, the less severe condition of undernourishment currently affects about 842 million people, or about one in eight (12.5%) people in the world population.The bloated stomach represents a form of malnutrition called kwashiorkor. The exact pathogenesis of kwashiorkor is not clear, as initially it was thought to relate to diets high in carbohydrates (e.g. maize) but low in protein. While many patients have low albumin, this is thought to be a consequence of the condition. Possible causes such as aflatoxin poisoning, oxidative stress, immune dysregulation, and altered gut microbiota have been suggested. Treatment can help mitigate symptoms such as the pictured weight loss and muscle wasting, however prevention is of utmost importance.Without any food, humans usually die in around 2 months. There was a surprising case when someone survived 382 days. Lean people can usually survive with a loss of up to 18% of their body mass. Obese people can tolerate more, possibly over 20%. Females survive longer than males.

Signs and symptoms
The following are some of the symptoms of starvation:

Changes in behaviour or mental status
The beginning stages of starvation impact mental status and behaviours. These symptoms show up as irritable mood, fatigue, trouble concentrating, and preoccupation with food thoughts. People with those symptoms tend to be easily distracted and have no energy.

Physical signs
As starvation progresses, the physical symptoms set in. The timing of these symptoms depends on age, size, and overall health. It usually takes days to weeks, and includes weakness, fast heart rate, shallow breaths that are slowed, thirst, and constipation. There may also be diarrhea in some cases. The eyes begin to sink in and glass over. The muscles begin to become smaller and muscle wasting sets in. One prominent sign in children is a swollen belly. Skin loosens and turns pale in color, and there may be swelling of the feet and ankles.

Weakened immune system
Symptoms of starvation may also appear as a weakened immune system, slow wound healing, and poor response to infection. Rashes may develop on the skin. The body directs any nutrients available to keeping organs functioning.

Other symptoms
Other effects of starvation may include:

Anemia
Gallstones
Hypotension
Stomach disease
Cardiovascular and respiratory diseases
Irregular or absent menstrual periods in women
Kidney disease or failure
Electrolyte imbalance
Emaciation
Oliguria

Stages of starvation
The symptoms of starvation show up in three stages. Phase one and two can show up in anyone that skips meals, diets, and goes through fasting. Phase three is more severe, can be fatal, and results from long-term starvation.
Phase one: When meals are skipped, the body begins to maintain blood sugar levels by producing glycogen in the liver and breaking down stored fat and protein. The liver can provide glycogen for the first few hours. After that, the body begins to break down fat and protein. The body uses Fatty acids as an energy source for muscles but lowers the amount of glucose sent to the brain. Another chemical that comes from fatty acids is glycerol. It can be used as glucose for energy but eventually runs out.
Phase two: Phase two can last for weeks at a time. In this phase, the body mainly uses stored fat for energy. The breakdown occurs in the liver and turns fat into ketones. After fasting for one week, the brain will use these ketones and any available glucose. Using ketones lowers the need for glucose, and the body slows the breakdown of proteins.
Phase three: By this point, the fat stores are gone, and the body begins to turn to stored protein for energy. This means it needs to break down muscle tissues full of protein; the muscles break down very quickly. Protein is essential for cells to work correctly, and when it runs out, the cells can no longer function.
The cause of death due to starvation is usually an infection or the result of tissue breakdown. This is due to the body becoming unable to produce enough energy to fight off bacteria and viruses. The final stage of starvation includes signals like hair color loss, skin flaking, swelling in the extremities, and a bloated belly. Even though they may feel hunger, people in the final stage of starvation usually cannot eat enough food to recover.

Causes
The body expends more energy than it takes in. This imbalance can arise from one or more medical conditions or circumstantial situations, which can include:
Medical reasons

Anorexia nervosa
Bulimia nervosa
Eating disorder, not otherwise specified
Celiac disease
Coma
Major depressive disorder
Diabetes mellitus
Digestive disease
Constant vomitingCircumstantial causes

Child, elder, or dependant abuse
Famine for any reason, such as political strife and war
Hunger striking
Excessive fasting
Poverty
Torture

Biochemistry
With a typical high-carbohydrate diet, the human body relies on free blood glucose as its primary energy source. Glucose can be obtained directly from dietary sugars and by the breakdown of other carbohydrates. In the absence of dietary sugars and carbohydrates, glucose is obtained from the breakdown of stored glycogen. Glycogen is a readily-accessible storage form of glucose, stored in notable quantities in the liver and skeletal muscle.
After the exhaustion of the glycogen reserve, and for the next two to three days, fatty acids become the principal metabolic fuel. At first, the brain continues to use glucose. If a non-brain tissue is using fatty acids as its metabolic fuel, the use of glucose in the same tissue is switched off.  Thus, when fatty acids are being broken down for energy, all of the remaining glucose is made available for use by the brain.After two or three days of fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement for glucose. After fasting for three days, the brain gets 30% of its energy from ketone bodies. After four days, this may increase to 70% or more. Thus, the production of ketone bodies cuts the brains glucose requirement from 80 g per day to 30 g per day, about 35% of normal, with 65% derived from ketone bodies. But of the brains remaining 30 g requirement, 20 g per day can be produced by the liver from glycerol (itself a product of fat breakdown). This still leaves a deficit of about 10 g of glucose per day that must be supplied from another source; this other source will be the bodys own proteins.
After exhaustion of fat stores, the cells in the body begin to break down protein. This releases alanine and lactate produced from pyruvate, which can be converted into glucose by the liver. Since much of human muscle mass is protein, this phenomenon is responsible for the wasting away of muscle mass seen in starvation. However, the body is able to choose which cells will break down protein and which will not. About 2–3 g of protein has to be broken down to synthesize 1 g of glucose; about 20–30 g of protein is broken down each day to make 10 g of glucose to keep the brain alive. However, this number may decrease the longer the fasting period is continued, in order to conserve protein.
Starvation ensues when the fat reserves are completely exhausted and protein is the only fuel source available to the body. Thus, after periods of starvation, the loss of body protein affects the function of important organs, and death results, even if there are still fat reserves left. In a leaner person, the fat reserves are depleted faster, and the protein, sooner, therefore death occurs sooner.) Ultimately, the cause of death is in general cardiac arrhythmia or cardiac arrest, brought on by tissue degradation and electrolyte imbalances. Conditions like metabolic acidosis may also kill starving people.

Prevention
Starvation can be caused by factors beyond the control of the individual. The Rome Declaration on World Food Security outlines several policies aimed at increasing food security and, consequently, preventing starvation. These include:

Poverty reduction
Prevention of wars and political instability
Food aid
Agricultural sustainability
Reduction of economic inequalitySupporting farmers in areas of food insecurity through such measures as free or subsidized fertilizers and seeds increases food harvest and reduces food prices.

Treatment
Patients that suffer from starvation can be treated, but this must be done cautiously to avoid refeeding syndrome. Rest and warmth must be provided and maintained. Food can be given gradually in small quantities. The quantity of food can be increased over time. Proteins may be administered intravenously to raise the level of serum proteins.  For worse situations, hospice care and opioid medications can be used.

Organizations
Many organizations have been highly effective at reducing starvation in different regions. Aid agencies give direct assistance to individuals, while political organizations pressure political leaders to enact more macro-scale policies that will reduce famine and provide aid.

Statistics
According to estimates by the Food and Agriculture Organization, between 720 and 811 million people were affected by hunger globally in 2020.  This was a decrease from estimated 925 million in 2010 and roughly 1 billion in 2009. In 2007, 923 million people were reported as being undernourished, an increase of 80 million since 1990–92.
An estimated 820 million people did not have enough to eat in 2018, up from 811 million in the previous year, which is the third year of increase in a row.As the definitions of starving and malnourished people are different, the number of starving people is different from that of malnourished. Generally, far fewer people are starving than are malnourished.
The proportion of malnourished and starving people in the world has been more or less continually decreasing for at least several centuries. This is due to an increasing supply of food and to overall gains in economic efficiency. In 40 years, the proportion of malnourished people in the developing world has been more than halved. The proportion of starving people has decreased even faster.

Capital punishment
Historically, starvation has been used as a death sentence. From the beginning of civilization to the Middle Ages, people were immured, and died for want of food.
In ancient Greco-Roman societies, starvation was sometimes used to dispose of guilty upper-class citizens, especially erring female members of patrician families. In the year 31, Livilla, the niece and daughter-in-law of Tiberius, was discreetly starved to death by her mother for her adulterous relationship with Sejanus and for her complicity in the murder of her own husband, Drusus the Younger.
Another daughter-in-law of Tiberius, named Agrippina the Elder (a granddaughter of Augustus and the mother of Caligula), also died of starvation, in 33 AD; however, it is unclear if her starvation was self-inflicted.
A son and daughter of Agrippina were also executed by starvation for political reasons; Drusus Caesar, her second son, was put in prison in 33 AD, and starved to death by orders of Tiberius (he managed to stay alive for nine days by chewing the stuffing of his bed); Agrippinas youngest daughter, Julia Livilla, was exiled on an island in 41 by her uncle, Emperor Claudius, and her death by starvation was arranged by the empress Messalina.
It is also possible that Vestal Virgins were starved when found guilty of breaking their vows of celibacy.
Ugolino della Gherardesca, his sons, and other members of his family were immured in the Muda, a tower of Pisa, and starved to death in the thirteenth century. Dante, his contemporary, wrote about Gherardesca in his masterpiece The Divine Comedy.
In Sweden in 1317, King Birger of Sweden imprisoned his two brothers for a coup they had staged several years earlier (Nyköping Banquet). According to legend they died of starvation a few weeks later, since their brother had thrown the prison key in the castle moat.
In Cornwall in the UK in 1671, John Trehenban from St Columb Major was condemned to be starved to death in a cage at Castle An Dinas for the murder of two girls.
The Makah, a Native American tribe inhabiting the Pacific Northwest near the modern border of Canada and the United States, practiced death by starvation as a punishment for slaves.

Concentration camps and ghettos
Many of the prisoners in the Nazi concentration camps were murdered through deliberate maltreatment, disease, starvation, and overwork, or were executed as unfit for labor. Many occupants of ghettos in eastern Europe also starved to death, most notoriously in the Warsaw Ghetto in German-occupied Poland. Prisoners were transported in inhumane conditions by rail freight cars, in which many died before reaching their destination. The prisoners were confined to the cattle cars for days or even weeks, with little or no food or water. Many died of dehydration in the intense heat of summer or froze to death in winter. Nazi concentration camps in Europe from 1933 to 1945 deliberately underfed prisoners, who were at the same time forced to perform heavy labour. Their diet was restricted to watery vegetable soup and a little bread, with little to no dietary fats, proteins or other essential nutrients. Such treatment led to loss of body tissues, and when prisoners became skeletal, the so-called Muselmann were murdered by gas or bullets when examined by camp doctors.

Starvation was also used as a punishment where victims were locked into a small cell until dead, a process which could take many days.
Saint Maximilian Kolbe, a martyred Polish friar, underwent a sentence of starvation in Auschwitz concentration camp in 1941. Ten prisoners had been condemned to death by starvation in the wake of a successful escape from the camp. Kolbe volunteered to take the place of a man with a wife and children. After two weeks of starvation, Kolbe and three other inmates remained alive; they were then executed with injections of phenol.

See also
References
Further reading

Online books, and library resources in your library and in other libraries about Starvation
U.N. Chief: Hunger Kills 17,000 Kids Daily - by CNN
Wilson, DE; Zeikus, R; Chan, IF (Apr 1987) </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 Platinosis and can you explain it in depth? [/INST] Platinosis is an allergy-like reaction to exposure to soluble salts of platinum.
The symptoms of platinosis may include asthma, dermatitis, dyspnea, conjunctival vasodilatation, and rhinopharyngitis.
The symptoms are progressive, sometimes taking months to years to appear.  Platinosis is usually associated with workers in industries related to platinum production.
The effects are permanent.
Halogeno-platinum compounds are among the most potent respiratory and skin sensitisers known, therefore it is vital that exposure via the skin and by breathing contaminated air is carefully controlled.
In practice, the compounds mainly responsible for platinum sensitisation are typically the soluble, ionic, platinum-chloro compounds such as ammonium hexachloroplatinate and tetrachloroplatinate, and hexachloroplatinic acid. Other ionic halogeno compounds are also sensitisers, the order of allergenicity being Cl > Br > I.
Neutral compounds such as cis-platin and ammine and nitro complexes such as [Pt(NH3)4]Cl2, K2[Pt(NO2)4] and platinum nitrate are not considered to be allergenic; neither is the metal.

See also
Heavy metal poisoning

References
Parrot, Jl; Hébert, R; Saindelle, A; Ruff, F (Nov 1969). "Platinum and platinosis. Allergy and histamine release due to some platinum salts". Archives of Environmental Health. 19 (5): 685–91. doi:10.1080/00039896.1969.10666910. PMID 4187030.
Saindelle, A; Ruff, F; Hébert, R; Parrot, Jl (Oct 1968). "A new histamine liberator: chloroplatinate. An occupational allergy: platinosis" [A new histamine liberator: chloroplatinate. An occupational allergy: platinosis]. Revue Française dAllergologie (in French). 8 (4): 205–14. doi:10.1016/S0370-4688(68)80018-3. PMID 4180839.
Parrot, Jl; Saindelle, A; Ruff, F (Dec 1967). "Platinum and platinosis. Histamine release by some platinum salts and platinum allergy" [Platinum and platinosis. Histamine release by some platinum salts and platinum allergy]. La Presse Médicale (in French) </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 Pemphigus and can you explain it in depth? [/INST] Pemphigus ( or ) is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes. The name is derived from the Greek root pemphix, meaning "pustule".In pemphigus, autoantibodies form against desmoglein, which forms the "glue" that attaches adjacent epidermal cells via attachment points called desmosomes. When autoantibodies attack desmogleins, the cells become separated from each other and the epidermis becomes detached, a phenomenon called acantholysis. This causes blisters that slough off and turn into sores. In some cases, these blisters can cover a large area of the skin.Originally, the cause of this disease was unknown, and "pemphigus" was used to refer to any blistering disease of the skin and mucosa.  In 1964, researchers found that the blood of patients with pemphigus contained antibodies to the layers of skin that separate to form the blisters. In 1971, an article investigating the autoimmune nature of this disease was published.

Types
The several types of pemphigus (pemphigus vulgaris, pemphigus foliaceus, intraepidermal neutrophilic IgA dermatosis, and paraneoplastic pemphigus) vary in severity. Skin lesions caused by pemphigus can lead to fatal infections, so treatment is extremely important.

Pemphigus vulgaris (PV - ICD-10 L10.0) is the most common form of the disorder and occurs when antibodies attack desmoglein 3. Sores often originate in the mouth, making eating difficult and uncomfortable. Although PV may occur at any age, it is most common among people between 40 and 60. It is more frequent among Ashkenazi Jews. Rarely, it is associated with myasthenia gravis.  Nail disease may be the only finding and has prognostic value in management.
Pemphigus foliaceus (PF) is the least severe of the three varieties. Desmoglein 1, the protein that is targeted by the autoantibodies, is enriched in the upper skin layers. PF is characterized by crusty sores that often begin on the scalp, and may move to the chest, back, and face. Mouth sores do not occur. This form is also frequent among Ashkenazi Jews. It is not as painful as PV, and is often misdiagnosed as dermatitis or eczema
Intraepidermal neutrophilic IgA dermatosis is characterized histologically by intraepidermal bullae with neutrophils, some eosinophils, and acantholysis.
The least common and most severe type of pemphigus is paraneoplastic pemphigus (PNP). This disorder is a complication of cancer, usually lymphoma or Castlemans disease. It may precede the diagnosis of the tumor. Painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the disease process often involves the lungs, causing bronchiolitis obliterans (constrictive bronchiolitis). Though much less frequent, it is still found the most in the Ashkenazi Jewish population. Complete removal of and/or cure of the tumor may improve the skin disease, but lung damage is generally irreversible.
Endemic pemphigus foliaceus includes fogo selvagem, the new variant of endemic pemphigus foliaceus in El Bagre, Colombia, and the Tunisian endemic pemphigus in North Africa.Hailey-Hailey disease, also called familial benign pemphigus, is an inherited skin disease, not an autoimmune disease, so it is not considered part of the pemphigus group of diseases.

Diagnosis
Pemphigus defines a group of autoimmune intraepithelial blistering diseases that are characterized by loss of normal cell-cell adhesion (acantholysis), and by the presence of pathogenic (predominantly IgG) autoantibodies reacting against epithelial adhesion molecules. Pemphigus is further divided in two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). However, several other disorders such as IgA pemphigus, IgE pemphigus, pemphigus herpetiformis, drug-induced pemphigus, Senear Usher syndrome, and endemic pemphigus foliaceus exist, and are recognized by a dermatologist from the appearance and distribution of the skin lesions. It is also commonly diagnosed by specialists practicing otolaryngology- head and neck surgery, periodontists, oral and maxillofacial surgeons, and eye doctors, as lesions can affect the eyes and mucous membranes of the oral cavity. Intraorally, it resembles the more common diseases lichen planus and mucous membrane pemphigoid. Definitive diagnosis requires examination of a skin or mucous membrane biopsy by a dermatopathologist or oral pathologist. The skin biopsy is taken from the edge of a blister, prepared for histopathology and examined with a microscope. The pathologist looks for an intraepidermal vesicle caused by the breaking apart of epidermal cells (acantholysis). Thus, the superficial (upper) portion of the epidermis sloughs off, leaving the bottom layer of cells on the "floor" of the blister. This bottom layer of cells is said to have a "tombstone" appearance.
Definitive diagnosis also requires the demonstration of antidesmoglein autoantibodies by direct immunofluorescence on the skin biopsy. These antibodies appear as IgG deposits along the desmosomes between epidermal cells, a pattern reminiscent of chicken wire. Antidesmoglein antibodies can also be detected in a blood sample using the ELISA technique.

Classification
Pemphigus is a group of autoimmune blistering diseases that may be classified into these types:
Pemphigus vulgaris
Pemphigus vegetans
Pemphigus vegetans of Hallopeau
Pemphigus vegetans of Neumann
Pemphigus foliaceus, of which there several forms:
Pemphigus erythematosus or Senear–Usher Syndrome
Endemic pemphigus foliaceus with its three variants, Fogo Selvagem, the new variant endemic pemphigus Foliaeus and Tunisian endemic pemphigus foliaceus
Paraneoplastic pemphigus
IgA pemphigus, of which there several forms:
Subcorneal pustular dermatosis
Intraepidermal neutrophilic IgA dermatosis
Drug induced pemphigus

Treatment
If not treated, pemphigus can be fatal, usually from overwhelming opportunistic infection of lesions. The most common treatment is the administration of oral steroids, especially prednisone, often in high doses. The side effects of corticosteroids may require the use of so-called steroid-sparing or adjuvant drugs. One of the most dangerous side effects of high-dosage steroid treatments is intestinal perforations, which may lead to sepsis. Steroids and other medications being taken to treat pemphigus may also mask the effects of the perforations. Patients on high dosages of oral steroids should closely monitor their gastrointestinal health. As lesions are usually terribly painful, pain medication likely complicate and exacerbate the gastrointestinal issues caused by steroids.

Treatment options
Topical steroids, such as clobetasol
Intralesional injection of steroids, such as dexamethasone
Immunosuppressant drugs, such as CellCept (mycophenolic acid): In recent years, adjuvant drugs, especially biologics, have shown great promise </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 Mohr–Tranebjærg syndrome and can you explain it in depth? [/INST] Mohr–Tranebjærg syndrome (MTS) is a rare X-linked recessive syndrome also known as deafness–dystonia syndrome and caused by mutation in the TIMM8A gene. It is characterized by clinical manifestations commencing with early childhood onset hearing loss, followed by adolescent onset progressive dystonia or ataxia, visual impairment from early adulthood onwards and dementia from the 4th decade onwards. The severity of the symptoms may vary, but they progress usually to severe deafness and dystonia and sometimes are accompanied by cortical deterioration of vision and mental deterioration.

Signs and Symptoms
Mohr-Tranebjærg is characterized by a variety of symptoms affecting hearing loss. In the span of a subject with Mohr-Tranebjærg, by the age of early childhood, around 18 months, the development of quickly progressive prelingual or postlingual sensorineural hearing loss. The presence of auditory symptoms is characterized by preserved oto-acoustic emissions, abnormal auditory brain stem response, poor speech, and worsening in auditory symptoms even with auditory devices. Also, neuropsychological manifestations, possibly consisting of personality changes, paranoia, and mild intellectual deficit could emerge. During adolescence, there is a possibility that a slowly progressive movement disorder, similar to gegenhalten, dystonia, or ataxia could develop. Patients with Mohr-Tranebjærg experience reduced visual acuity, photophobia, acquired color vision defect and central scotomas developing at around 20 years of age, and leading to more severe blindness by age 30 or 40.The first symptom of DDON syndrome is hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), which begins in early childhood. The hearing impairment worsens over time, and most affected individuals have profound hearing loss by age 10.Individuals with Mohr Tranebjærg syndrome have normal vision during childhood, but they may develop vision problems due to breakdown of the nerves that carry information from the eyes to the brain (optic atrophy). Affected individuals can develop an increased sensitivity to light (photophobia) or other vision problems beginning in adolescence. Their sharpness of vision (visual acuity) slowly worsens, often leading to legal blindness in mid-adulthood.

Genetics
This condition is caused by mutations in the TIMM8A gene. This gene is located on the long arm of X chromosome (Xq22).
The protein encoded by this gene localizes to the intermembrane space in mitochondria where it functions in the import of nuclear encoded proteins into the mitochondrial inner membrane. How this produces the clinical picture is not yet clear.
The pattern of inheritance is X-linked recessive. Where the female is a carrier, male offspring have a 50 percent chance of inheriting the disease and female offspring have a 50 percent chance of being a carrier. Where the male is affected, male offspring do not inherit the pathogenic mutation and females are obligate carriers.TIMM8A is also referred to as DDP. Koehler determined the function of the DDP gene and concluded that the Mohr-Tranebjaerg syndrome is a novel type of mitochondrial disease that is most likely caused by a defective mitochondrial protein-import system.

Diagnosis
A combination of hearing impairment and recurrent infections due to XLA in a male patient should elicit sequencing of the TIMM8A gene. Neuroimaging is employed to verify the presence of cerebral atrophy. In cases of suspected CGS; testing for XLA is possible.

Differential diagnosis
This is long and includes

Arts syndrome
Autosomal recessive nonsyndromic sensorineural deafness type DFNB
Friedreich ataxia
MELAS syndrome
Mitochondrial DNA depletion syndrome (encephalomyopathic form with methylmalonic aciduria)
McLeod neuroacanthocytosis syndrome
Pendred syndrome
Usher syndrome type 1 and 2
Wolfram syndrome
X-linked spinocerebellar ataxia type 3 and 4

Treatment
Symptomatic Treatment
The treatment for Mohr-Tranebjærg vary depending on the symptoms and the evolution of these symptoms over time </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 Pelvic fracture and can you explain it in depth? [/INST] A pelvic fracture is a break of the bony structure of the pelvis. This includes any break of the sacrum, hip bones (ischium, pubis, ilium), or tailbone. Symptoms include pain, particularly with movement. Complications may include internal bleeding, injury to the bladder, or vaginal trauma.Common causes include falls, motor vehicle collisions, a vehicle hitting a pedestrian, or a direct crush injury. In younger people significant trauma is typically required while in older people less significant trauma can result in a fracture. They are divided into two types: stable and unstable. Unstable fractures are further divided into anterior posterior compression, lateral compression, vertical shear, and combined mechanism fractures. Diagnosis is suspected based on symptoms and examination with confirmation by X-rays or CT scan. If a person is fully awake and has no pain of the pelvis medical imaging is not needed.Emergency treatment generally follows advanced trauma life support. This begins with efforts to stop bleeding and replace fluids. Bleeding control may be achieved by using a pelvic binder or bed-sheet to support the pelvis. Other efforts may include angiographic embolization or preperitoneal packing. After stabilization, the pelvis may require surgical reconstruction.Pelvic fractures make up around 3% of adult fractures. Stable fractures generally have a good outcome. The risk of death with an unstable fracture is about 15%, while those who also have low blood pressure have a risk of death approaching 50%. Unstable fractures are often associated with injuries to other parts of the body.

Signs and symptoms
Symptoms include pain, particularly with movement.

Complications
Complications are likely to result in cases of excess blood loss or puncture to certain organs, possibly leading to shock. Swelling and bruising may result, more so in high-impact injuries. Pain in the affected areas may differ where severity of impact increases its likelihood and may radiate if symptoms are aggravated when one moves around.

Causes
Common causes include falls, motor vehicle collisions, a vehicle hitting a pedestrian, or a direct crush injury. In younger people significant trauma is typically required while in older people less significant trauma can result in a fracture.

Pathophysiology
The bony pelvis consists of the ilium (i.e., iliac wings), ischium, and pubis, which form an anatomic ring with the sacrum. Disruption of this ring requires significant energy. When it comes to the stability and the structure of the pelvis, or pelvic girdle, understanding its function as support for the trunk and legs helps to recognize the effect a pelvic fracture has on someone. The pubic bone, the ischium and the ilium make up the pelvic girdle, fused together as one unit. They attach to both sides of the spine and circle around to create a ring and sockets to place hip joints. Attachment to the spine is important to direct force into the trunk from the legs as movement occurs, extending to ones back. This requires the pelvis to be strong enough to withstand pressure and energy. Various muscles play important roles in pelvic stability. Because of the forces involved, pelvic fractures frequently involve injury to organs contained within the bony pelvis. In addition, trauma to extra-pelvic organs is common. Pelvic fractures are often associated with severe hemorrhage due to the extensive blood supply to the region. The veins of the presacral pelvic plexus are particularly vulnerable. Greater than 85 percent of bleeding due to pelvic fractures is venous or from the open surfaces of the bone.

Diagnosis
If a person is fully awake and has no pain in the pelvis, medical imaging of the pelvis is not needed.

Classification
Pelvic fractures are most commonly described using one of two classification systems. The different forces on the pelvis result in different fractures. Sometimes they are determined based on stability or instability.

Tile classification
The Tile classification system is based on the integrity of the posterior sacroiliac complex.In type A injuries, the sacroiliac complex is intact. The pelvic ring has a stable fracture that can be managed nonoperatively.
Type B injuries are caused by either external or internal rotational forces resulting in partial disruption of the posterior sacroiliac complex. These are often unstable.
Type C injuries are characterized by complete disruption of the posterior sacroiliac complex and are both rotationally and vertically unstable. These injuries are the result of great force, usually from a motor vehicle crash, fall from a height or severe compression.

Young-Burgess classification
The Young-Burgess classification system is based on mechanism of injury: anteroposterior compression type I, II and III, lateral
compression types I, II and III, and vertical shear, or a combination of forces.
Lateral compression (LC) fractures involve transverse fractures of the pubic rami, either ipsilateral or contralateral to a posterior injury.

Grade I – Associated sacral compression on side of impact
Grade II – Associated posterior iliac ("crescent") fracture on side of impact
Grade III – Associated contralateral sacroiliac joint injuryThe most common force type, lateral compression (LC) forces, from side-impact automobile accidents and pedestrian injuries, can result in an internal rotation. The superior and inferior pubic rami may fracture anteriorly, for example. Injuries from shear forces, like falls from above, can result in disruption of ligaments or bones. When multiple forces occur, it is called combined mechanical injury (CMI). The best imaging modality to use for this classification is probably a pelvic CT scan.

Open book fracture
One specific kind of pelvic fracture is known as an open book fracture. This is often the result of a heavy impact to the groin (pubis), a common motorcycling accident injury. In this kind of injury, the left and right halves of the pelvis are separated at front and rear, the front opening more than the rear, i.e. like an open book that falls to the ground and splits in the middle. Depending on the severity, this may require surgical reconstruction before rehabilitation.  Forces from an anterior or posterior direction, like head-on car accidents, usually cause external rotation of the hemipelvis, an “open-book” injury. Open fractures have an increased risk of infection and hemorrhaging from vessel injury, leading to higher mortality.

Prevention
As the human body ages, the bones become weaker and brittle and are therefore more susceptible to fractures. Certain precautions are crucial in order to lower the risk of getting pelvic fractures. The most damaging is one from a car accident, cycling accident, or falling from a high building which can result in a high energy injury.  This can be very dangerous because the pelvis supports many internal organs and can damage these organs. Falling is one of the most common causes of pelvic fracture. Therefore, proper precautions should be taken to prevent this from happening.

Treatment
A pelvic fracture is often complicated and treatment can be a long and painful process </s>


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<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 Acromion and can you explain it in depth? [/INST] In human anatomy, the acromion (from Greek: akros, "highest", ōmos, "shoulder", plural: acromia) is a bony process on the scapula (shoulder blade). Together with the coracoid process it extends laterally over the shoulder joint.  The acromion is a continuation of the scapular spine, and hooks over anteriorly.  It articulates with the clavicle (collar bone) to form the acromioclavicular joint.

Structure
The acromion forms the summit of the shoulder, and is a large, somewhat triangular or oblong process, flattened from behind forward, projecting at first lateralward, and then curving forward and upward, so as to overhang the glenoid fossa. It starts from the base of acromion which marks its projecting point emerging from the spine of scapula.

Surfaces
Its superior surface, directed upward, backward, and lateralward, is convex, rough, and gives attachment to some fibers of the deltoideus, and in the rest of its extent is subcutaneous.  Its inferior surface is smooth and concave.

Borders
Its lateral border is thick and irregular, and presents three or four tubercles for the tendinous origins of the deltoid.  Its medial border, shorter than the lateral, is concave, gives attachment to a portion of the trapezius, and presents about its center a small oval surface for articulation with the acromial end of the clavicle.

Variation
There are three morphologically distinct types of acromia and a correlation between these morphologies and rotator cuff tear:

Os acromiale
The acromion has four ossification centers called (from tip to base) pre-acromion, meso-acromion, meta-acromion, and basi-acromion.  In most cases, the first three fuse at 15–18 years, whereas the base part fuses to the scapular spine at 12 years.  However, in between 1% and 15% of cases, this osseous union fails and the acromion remains separate as an accessory bone. This condition is referred to as os acromiale, but rarely causes pain.  Earlier estimates of its prevalence were as low as 1.4%, and this higher estimate was made by Sammarco in the year 2000, based on radiographic and anatomical studies.Four types of os acromiale can be distinguished:
A non-union between the meso- and meta-acromia, the most common or typical os acromiale
A non-union between the pre- and meso-acromia
A non-union between the pre- and meso-acromia; and between the meso- and meta-acromia, atypical
A non-union between the pre- and meso-acromia; between the pre- and meso-acromia; and between the meta- and basi-acromiaThis feature was common in skeletons recovered from the Mary Rose shipwreck: it is thought that in those men, much archery practice from childhood on with the mediaeval war bow (which needs a pull three times as strong as the modern standard Olympic bow) pulled at the acromion so much that it prevented bony fusion of the acromion with the scapula.
Although historically regarded as an incidental finding, the os acromiale may occasionally produce symptoms from subacromial impingement or instability at the site of non-union.  In people with symptoms of  os acromiale, dynamic ultrasound sometimes shows hypermobility in the area during shoulder movement, or graded compression with the probe.

In other animals
The acromion process of bats (Mammalia: Chiroptera) is particularly elongated compared to that of  humans.
Turtles have an acromion that forms the anterior part of the triradiate pectoral girdle (together with the coracoid and scapula).  In this highly specialized endoskeletal structure, the scapula is a dorsal (directed upwards) process attached to the first rib; the coracoid is a posteroventral (directed backward and down) process; and the acromion is a medioventral (directed inwards and down) process (also known as the prescapular process) located at the base of the scapula.  This had led to some controversy regarding the evolutionary origin of turtles, because in both pareiasaurs and non-mammalian therapsids the acromion is located at the dorsal tip of the scapula.
In modern turtles, the acromion projects ventrally and articulates with the plastron (the flat lower part of the shell), but it evolved in a common ancestor of pareiasaurs and turtles long before the plastron.  In these primitive ancestors, the acromion projected forward to form a strong and flexible articulation between the shoulder girdle and the clavicle.  Notwithstanding these changes, the acromion of turtles retains its original function, to support the shoulder girdle and increase stride length.

Additional images
Notes
 This article incorporates text in the public domain from page 203 of the 20th edition of Grays Anatomy (1918)

Habermeyer, Peter; Magosch, Petra; Lichtenberg, Sven (2006). Classifications and Scores of the Shoulder. Heidelberg: Springer. ISBN 978-3-540-24350-2.
Lee, Michael S. Y. (January 22, 1996). "The Homologies and Early Evolution of the Shoulder Girdle in Turtles". Proc. R. Soc. Lond. B. 263 (1366): 111–117. doi:10.1098/rspb.1996.0018. S2CID 84529868.
Rieppel, Olivier; Reisz, Robert R. (1999). "The Origin and Early Evolution of Turtles" </s>


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<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 Sebaceoma 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 Riddoch syndrome and can you explain it in depth? [/INST] The Riddoch syndrome is a term coined by Zeki and Ffytche (1998) in a paper published in Brain. The term acknowledges the work of George Riddoch who was the first to describe a condition in which a form of visual impairment, caused by lesions in the occipital lobe, leaves the sufferer blind but able to distinguish visual stimuli with specific characteristics when these appear in the patients blind field. The most common stimuli that can be perceived consciously are the presence and direction of fast moving objects (moving at a speed in excess of 10 degrees per second); in his work these moving objects were described as "vague and shadowy" </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 Magnesium deficiency and can you explain it in depth? [/INST] Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus. Complications may include seizures or cardiac arrest such as from torsade de pointes. Those with low magnesium often have low potassium.Causes include low dietary intake, alcoholism, diarrhea, increased urinary loss, poor absorption from the intestines, and diabetes mellitus. A number of medications may also cause low magnesium, including proton pump inhibitors (PPIs) and furosemide. The diagnosis is typically based on finding low blood magnesium levels (hypomagnesemia). Normal magnesium levels are between 0.6 and 1.1 mmol/L (1.46–2.68 mg/dL) with levels less than 0.6 mmol/L (1.46 mg/dL) defining hypomagnesemia. Specific electrocardiogram (ECG) changes may be seen.Treatment is with magnesium either by mouth or intravenously. For those with severe symptoms, intravenous magnesium sulfate may be used. Associated low potassium or low calcium should also be treated. The condition is relatively common among people in hospitals.

Signs and symptoms
Deficiency of magnesium can cause tiredness, generalized weakness, muscle cramps, abnormal heart rhythms, increased irritability of the nervous system with tremors, paresthesias, palpitations, low potassium levels in the blood, hypoparathyroidism which might result in low calcium levels in the blood, chondrocalcinosis, spasticity and tetany, migraines, epileptic seizures, basal ganglia calcifications and in extreme and prolonged cases coma, intellectual disability or death. Magnesium plays an important role in carbohydrate metabolism and its deficiency may worsen insulin resistance, a condition that often precedes diabetes, or may be a consequence of insulin resistance.People being treated on an intensive care unit (ICU) who have a low magnesium level may have a higher risk of requiring mechanical ventilation, and death.

Causes
Magnesium deficiency may result from gastrointestinal or kidney causes. Gastrointestinal causes include low dietary intake of magnesium, reduced gastrointestinal absorption or increased gastrointestinal loss due to rapid gastrointestinal transits. Kidney causes involve increased excretion of magnesium. Poor dietary intake of magnesium has become an increasingly important factor – many people consume diets high in refined foods such as white bread and polished rice which have been stripped of magnesium-rich plant fiber.Magnesium deficiency is not uncommon in hospitalized patients. Up to 12% of all people admitted to hospital, and as high as 60–65% of people in an intensive care unit, have hypomagnesemia.About 57% of the US population does not meet the US RDA for dietary intake of magnesium. The kidneys are very efficient at maintaining body levels; however, if the diet is deficient, or certain medications such as diuretics or proton pump inhibitors are used, or in chronic alcoholism, levels may drop.
Low levels of magnesium in blood may be due to not enough magnesium in the diet, the intestines not absorbing enough magnesium, or the kidneys excreting too much magnesium. Deficiencies may be due to the following conditions:

Medications
Loop and thiazide diuretic use (the most common cause of hypomagnesemia)
Antibiotics (i.e. aminoglycoside, amphotericin, pentamidine, gentamicin, tobramycin, viomycin) block resorption in the loop of Henle. 30% of patients using these antibiotics have hypomagnesemia.
Long term, high dosage use of proton-pump inhibitors such as omeprazole
Other drugs
Digitalis, displaces magnesium into the cell. Digitalis causes an increased intracellular concentration of sodium, which in turn increases intracellular calcium by passively increasing the action of the sodium-calcium exchanger in the sarcolemma. The increased intracellular calcium gives a positive inotropic effect.
Adrenergics, displace magnesium into the cell
Cisplatin, stimulates kidney excretion
Ciclosporin, stimulates kidney excretion
Mycophenolate mofetil

Genetics
Gitelman-like diseases, which include the syndromes caused by genetic mutations in SLC12A3, CLNCKB, BSND, KCNJ10, FXYD2, HNF1B or PCBD1. In these diseases, the hypomagnesemia is accompanied by other defects in electrolyte handling such as hypocalciuria and hypokalemia. The genes involved in this group of diseases all encode proteins that are involved in reabsorbing electrolytes (including magnesium) in the distal convoluted tubule of the kidney.
Hypercalciuric hypomagnesemic syndromes, which encompass the syndromes caused by mutations in CLDN16, CLDN19, CASR or CLCNKB. In these diseases, reabsorption of divalent cations (such as magnesium and calcium) in the thick ascending limb of Henles loop of the kidney is impaired. This results in loss of magnesium and calcium in the urine.
Mitochondriopathies, such as caused by mutations in SARS2, MT-TI or as seen with Kearns-Sayre syndrome.
Other genetic causes of hypomagnesemia, such as mutations in TRPM6, CNNM2, EGF, EGFR, KCNA1 or FAM111A. Many of the proteins encoded by these genes play a role in the transcellular absorption of magnesium in the distal convoluted tubule.

Metabolic abnormalities
Insufficient selenium, vitamin D or sunlight exposure, or vitamin B6.
Gastrointestinal causes: the distal digestive tract secretes high levels of magnesium. Therefore, secretory diarrhea can cause hypomagnesemia. Thus, Crohns disease, ulcerative colitis, Whipples disease and celiac sprue can all cause hypomagnesemia.
Postobstructive diuresis, diuretic phase of acute tubular necrosis (ATN) and kidney transplant.

Other
Acute myocardial infarction: within the first 48 hours after a heart attack, 80% of patients have hypomagnesemia. This could be the result of an intracellular shift because of an increase in catecholamines.
Malabsorption
Acute pancreatitis
Fluoride poisoning
Massive transfusion (MT) is a lifesaving treatment of hemorrhagic shock, but can be associated with significant complications.

Pathophysiology
Magnesium is a co-factor in over 300 functions in the body regulating many kinds of  biochemical reactions. It is involved in protein synthesis, muscle and nerve functioning, bone development, energy production, the maintenance of normal heart rhythm, and the regulation of glucose and blood pressure, among other important roles. Low magnesium intake over time can increase the risk of illnesses, including high blood pressure and heart disease, diabetes mellitus type 2, osteoporosis, and migraines.There is a direct effect on sodium (Na), potassium (K), and calcium (Ca) channels. Magnesium has several effects:

Potassium
Potassium channel efflux is inhibited by magnesium. Thus hypomagnesemia results in an increased excretion of potassium in kidney, resulting in a hypokalaemia. This condition is believed to occur secondary to the decreased normal physiologic magnesium inhibition of the ROMK channels in the apical tubular membrane.In this light, hypomagnesemia is frequently the cause of hypokalaemic patients failing to respond to potassium supplementation. Thus, clinicians should ensure that both magnesium and potassium is replaced when deficient. Patients with diabetic ketoacidosis should have their magnesium levels monitored to ensure that the serum loss of potassium, which is driven intracellularly by insulin administration, is not exacerbated by additional urinary losses.

Calcium
Release of calcium from the sarcoplasmic reticulum is inhibited by magnesium. Thus hypomagnesemia results in an increased intracellular calcium level. This inhibits the release of  parathyroid hormone, which can result in hypoparathyroidism and hypocalcemia. Furthermore, it makes skeletal and muscle receptors less sensitive to parathyroid hormone.

Arrhythmia
Magnesium is needed for the adequate function of the Na+/K+-ATPase pumps in cardiac myocytes, the muscles cells of the heart. A lack of magnesium inhibits reuptake of potassium, causing a decrease in intracellular potassium. This decrease in intracellular potassium results in a tachycardia.

Pre-eclampsia
Magnesium has an indirect antithrombotic effect upon platelets and endothelial function. Magnesium increases prostaglandins, decreases thromboxane, and decreases angiotensin II, microvascular leakage, and vasospasm through its function similar to calcium channel blockers. Convulsions are the result of cerebral vasospasm. The vasodilatatory effect of magnesium seems to be the major mechanism.

Asthma
Magnesium exerts a bronchodilatatory effect, probably by antagonizing calcium-mediated bronchoconstriction.

Neurological effects
reducing electrical excitation
modulating release of acetylcholine
antagonising N-methyl-D-aspartate (NMDA) glutamate receptors, an excitatory neurotransmitter of the central nervous system and thus providing neuroprotection from excitoxicity.

Diabetes mellitus
Magnesium deficiency is frequently observed in people with type 2 diabetes mellitus, with an estimated prevalence ranging between 11.0 and 47.7%.
Magnesium deficiency is strongly associated with high glucose and insulin resistance, which indicate that it is common in poorly controlled diabetes. Patients with type 2 diabetes and a magnesium deficiency have a higher risk of heart failure, atrial fibrillation and microvascular complications. Oral magnesium supplements has been demonstrated to improve insulin sensitivity and lipid profile.  However, their effect on cardiovascular risk in diabetes are to be determined.

Homeostasis
Magnesium is abundant in nature. It can be found in green vegetables, chlorophyll (chloroplasts), cocoa derivatives, nuts, wheat, seafood, and meat. It is absorbed primarily in the duodenum of the small intestine. The rectum and sigmoid colon can absorb magnesium. Forty percent of dietary magnesium is absorbed. Hypomagnesemia stimulates and hypermagnesemia inhibits this absorption.The body contains 21–28 grams of magnesium (0.864–1.152 mol). Of this, 53% is located in bone, 19% in non-muscular tissue, and 1% in extracellular fluid. For this reason, blood levels of magnesium are not an adequate means of establishing the total amount of available magnesium.The majority of serum magnesium is bound to chelators, including proteins and citrate. Roughly 33% is bound to proteins, and 5–10% is not bound. This "free" magnesium is essential in regulating intracellular magnesium. Normal plasma Mg is 1.7–2.3 mg/dL (0.69–0.94 mmol/L).
The kidneys regulate the serum magnesium. About 2400 mg of magnesium passes through the kidneys daily, of which 5% (120 mg) is excreted through urine. The loop of Henle is the major site for magnesium homeostasis, and 60% is reabsorbed.
Magnesium homeostasis comprises three systems: kidney, small intestine, and bone. In the acute phase of magnesium deficiency there is an increase in absorption in the distal small intestine and tubular resorption in the kidneys. When this condition persists, serum magnesium drops and is corrected with magnesium from bone tissue. The level of intracellular magnesium is controlled through the reservoir in bone tissue.

Diagnosis
Magnesium deficiency is not easy to directly measure. Typically the diagnosis is based on finding low blood magnesium levels (hypomagnesemia). Specifically by finding a plasma magnesium concentration of less than 0.6 mmol/L (1.46 mg/dL). Severe disease generally has a level of less than 0.50 mmol/L (1.25 mg/dL).Magnesium deficiency (or depletion) refers to low total body levels of magnesium which is usually determined by finding low blood levels (hypomagnesemia). Hypomagnesemia refers only to blood levels of magnesium. Either of magnesium deficiency and hypomagnesemia can be present without the other.

Electrocardiogram
The electrocardiogram (ECG) change may show a tachycardia with a prolonged QT interval. Other changes may include prolonged PR interval, ST segment depression, flipped T waves, and long QRS duration.

Treatments
Treatment of hypomagnesemia depends on the degree of deficiency and the clinical effects. Replacement by mouth is appropriate for people with mild symptoms, while intravenous replacement is recommended for people with severe effects.Numerous oral magnesium preparations are available. In two trials of magnesium oxide, one of the most common forms in magnesium dietary supplements because of its high magnesium content per weight, was less bioavailable than magnesium citrate, chloride, lactate or aspartate. Magnesium citrate has been reported as more bioavailable than oxide or amino-acid chelate forms.Intravenous magnesium sulfate (MgSO4) can be given in response to heart arrhythmias to correct for hypokalemia, preventing pre-eclampsia, and has been suggested as having a potential use in asthma.

Food
Food sources of magnesium include leafy green vegetables, beans, nuts, and seeds.

Epidemiology
The condition is relatively common among people in hospital.

History
Magnesium deficiency in humans was first described in the medical literature in 1934.

Plants
Magnesium deficiency is a detrimental plant disorder that occurs most often in strongly acidic, light, sandy soils, where magnesium can be easily leached away. Magnesium is an essential macronutrient constituting 0.2-0.4% of plants dry matter and is necessary for normal plant growth. Excess potassium, generally due to fertilizers, further aggravates the stress from magnesium deficiency, as does aluminium toxicity.Magnesium has an important role in photosynthesis because it forms the central atom of chlorophyll. Therefore, without sufficient amounts of magnesium, plants begin to degrade the chlorophyll in the old leaves </s>