<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 Splenogonadal fusion and can you explain it in depth? [/INST] Splenogonadal fusion is a rare congenital malformation that results from an abnormal connection between the primitive spleen and gonad during gestation. A portion of the splenic tissue then descends with the gonad.  Splenogonadal fusion has been classified into two types: continuous, where there remains a connection between the main spleen and gonad; and discontinuous, where ectopic splenic tissue is attached to the gonad, but there is no connection to the orthotopic spleen. Patients can also be have an accessory spleen. Patients with continuous splenogonadal fusion frequently have additional congenital abnormalities including limb defects, micrognathia, skull anomalies, Spina bifida, cardiac defects, anorectal abnormalities, and most commonly cryptorchidism.  Terminal limb defects have been documented in at least 25 cases which makes up a separate diagnosis of splenogonadal fusion limb defect (SGFLD) syndrome.
The anomaly was first described in 1883 by Bostroem.  Since then more than 150 cases of splenogonadal fusion have been documented, predominantly in males.  The condition is considered benign.  A few cases of testicular neoplasm have been reported in association with splenogonadal fusion.  The reported cases have occurred in patients with a history of cryptorchidism, which is associated with an elevated risk of neoplasm.Splenogonadal fusion occurs with a male-to-female ratio of 16:1, and is seen nearly exclusively on the left side. The condition remains a diagnostic challenge, but preoperative consideration of the diagnosis and use of ultrasound may help avoid unnecessary orchiectomy. The presence of splenic tissue may be confirmed with a technetium-99m sulfur colloid scan.

Classification
Splenogonadal fusion is separated into two types:

Continuous (55%): The native spleen is connected to the gonad. The connection occurs through a cord of splenic tissue or fibrous band.
Discontinuous (45%): Ectopic splenic tissue is present and attached to the gonad. An accessory spleen is present and the native spleen lacks the direct attachment to the gonad.

Pathogenesis
The cause of splenogonadal fusion is still unclear, and there are several proposed mechanisms. A developmental field defect that occurs during blastogenesis is the current explanation of pathogenesis. The spleen derives from mesenchymal tissue and an inappropriate fusion can happen between the gonadal ridge during gut rotation, which occurs between weeks 5 and 8 of fetal life. Splenogonadal fusion may result from an unknown teratogenic insult. The timing of this insult may correlate to the severity of associated defects. There is also postulation that fusion may occur due to adhesion after an inflammatory response or a lack of apoptosis between the structures. Siblings documented to have splenogonadal fusion and an accessory spleen provides additional evidence of a possible genetic component.

Associated Conditions
Additional congenital abnormalities are most often found associated with the continuous type of splenogonadal fusion. These abnormalities include micrognathia, macroglossia, anal atresia, and pulmonary hypoplasia. The most commonly associated malformation is cryptorchidism. When limb abnormalities occur, Splenogonadal Fusion with Limb Defects is made as a separate diagnosis. Splenogonadal Fusion with Limb Defects is also of unknown cause but some literature suggests that the condition may be related to Hanhart syndrome and facial femoral syndrome. Splenogonadal fusion has also been identified in infants with Möbius syndrome and Poland syndrome.

Diagnosis
Diagnosis can be challenging pre-operatively, as patients are commonly asymptomatic. Physical examination can aid in diagnosis if the mass is palpated, but further confirmatory tests are necessary. Females are reportedly less affected by splenogonadal fusion, though it is possible that the condition is underdiagnosed due to the difficulty of internal gonad examination in females. On scrotal ultrasound, ectopic splenic tissue may appear as an encapsulated homogeneous extratesticular mass, isoechoic with the normal testis. Subtle hypoechoic nodules may be present in the mass. Limitations of doppler ultrasonography include visualizing the nonspecific paratesticular masses which can mimic malignancies such as rhabdomyosarcoma or embryonal sarcoma. Technetium-99m sulfur colloid scan is sensitive to target the liver, spleen, and bone marrow, therefore the scans can be used to identify ectopic splenic tissue when clinical suspicion is high. When technetium-99m sulfur colloid scans are not included in a patients diagnostic workup, the diagnosis is often not made until the surgeon performs an abdominal exploration using laparoscopy which can visualize the splenic tissue grossly. Evaluation by biopsy including frozen section procedure is confirmatory for splenogonadal fusion </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 Olecranon bursitis and can you explain it in depth? [/INST] Olecranon bursitis is a condition characterized by swelling, redness, and pain at the tip of the elbow. If the underlying cause is due to an infection, fever may be present. The condition is relatively common and is one of the most frequent types of bursitis.It usually occurs as a result of trauma or pressure to the elbow, infection, or certain medical conditions such as rheumatoid arthritis or gout. Olecranon bursitis is associated with certain types of work including plumbing, mining, gardening, and mechanics. The underlying mechanism is inflammation of the fluid filled sac between the olecranon and skin. Diagnosis is usually based on symptoms.Treatment involves avoiding further trauma, a compression bandage, and NSAIDs. If there is concern of infection the fluid should be drained and tested and antibiotics are typically recommended. The use of steroid injections is controversial. Surgery may be done if other measures are not effective.

Signs and symptoms
Symptoms include swelling in the elbow, which can sometimes be large enough to restrict motion. There is pain originating in the elbow joint from mild to severe which can spread to the rest of the arm.
If the bursa is infected, there also will be prominent redness and the skin will feel very warm. Another symptom would include the infected bursa possibly opening spontaneously and draining pus.

Causes
Bursitis normally develops as a result either of a single injury to the elbow (for example, a hard blow to the tip of the elbow), or perhaps more commonly due to repeated minor injuries, such as repeated leaning on the point of the elbow on a hard surface. The chance of developing bursitis is higher if ones job or hobby involves a repetitive movement (for example, tennis, golf, or even repetitive computer work involving leaning on ones elbow). The likelihood of developing the condition is increased as one gets older.As a reaction to injury, the lining of the bursa becomes inflamed. It then secretes a much greater than normal amount of fluid into the closed cavity of the bursa, from where it has nowhere to go. The bursa therefore inflates, producing a swelling over the proximal end of the ulna which is usually inflamed and tender.Another possible cause of inflammation of the bursa is infection, which can usually (but not always) be traced to a crack or other lesion in the skin which allowed for bacteria of the normal skin flora to invade deeper layers of tissue.This bursa is located just over the extensor aspect of the extreme proximal end of the ulna </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 Lymphangitis and can you explain it in depth? [/INST] Lymphangitis is an inflammation or an infection of the lymphatic channels that occurs as a result of infection at a site distal to the channel. The most common cause of lymphangitis in humans is Streptococcus pyogenes (Group A strep), hemolytic streptococci, and in some cases, mononucleosis, cytomegalovirus, tuberculosis, syphilis, and the fungus Sporothrix schenckii.  Lymphangitis is sometimes mistakenly called "blood poisoning". In reality, "blood poisoning" is synonymous with sepsis.
Lymphatic vessels are smaller than capillaries and tiny venules and are ubiquitous in the body. These vessels are fitted with valves to direct flow in only one direction. Fluid diffusing through the thin-walled small capillaries should be collected and the lymphatic system does just that: a fluid rich in protein, minerals, nutrients, and other substances useful for tissue growth. As well as essential nutrients, the lymphatic system can also transport or carry cancer cells, defective or damaged cells, and pathogens such as bacteria and viruses, as well as foreign bodies and organisms. The lymph nodes are found in close proximity to unique white blood cells that engulf or metabolize pathogens (bacteria and viruses) and defective or cancerous cells, preventing infections and malignant cancer cells from spreading.
 Infection spreads out of the wound site to enter the lymphatic system. The wound may be small or it may be an abscess constantly feeding bacteria into the lymphatic system. After infection, lymph nodes enlarge. Ear, skin, nose, and eye infections can spread into the lymphatic system. Red streaks in the skin along the direction of regional lymph nodes indicate lymphatic involvement. Infection may spread within hours and can cause sepsis and death.

Symptoms and signs
Warm skin over site of infection. The person may also have chills and a high fever - between 38 and 40 degrees Celsius - along with moderate throbbing pain and swelling. The red streaks can be clearly outlined and demarcated or just barely visible, particularly in dark-skinned patients. Malaise, tenderness at the site of infection, skin ulcers (a rare symptom of lymphangitis), rapid pulse, and enlarged, swollen, and tender lymph nodes are also seen. Appetite loss has been documented with the presence of inflammation (inflammation-associated anorexia), but it is unclear whether appetite loss seen in patients with lymphangitis leads to weight loss; in cases that develop after lymphedema—which can be upwards of 8.14% of the time—weight gain has actually been documented.If these symptoms are absent, it is suggestive of other underlying disorders such as tuberculosis, lymphoma, or Hodgkin’s disease. A person with lymphangitis should be hospitalized and closely monitored by medical professionals </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 Cholesterol embolism and can you explain it in depth? [/INST] Cholesterol embolism occurs when cholesterol is released, usually from an atherosclerotic plaque, and travels as an embolus in the bloodstream to lodge (as an embolism) causing an obstruction in blood vessels further away. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene of the extremities and sometimes kidney failure; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. When the kidneys are involved, the disease is referred to as atheroembolic renal disease. The diagnosis usually involves biopsy (removing a tissue sample) from an affected organ. Cholesterol embolism is treated by removing the cause and giving supportive therapy; statin drugs have been found to improve the prognosis.

Signs and symptoms
The symptoms experienced in cholesterol embolism depend largely on the organ involved. Non-specific symptoms often described are fever, muscle ache and weight loss. Embolism to the legs causes a mottled appearance and purple discoloration of the toes, small infarcts and areas of gangrene due to tissue death that usually appear black, and areas of the skin that assume a marbled pattern known as livedo reticularis. The pain is usually severe and requires opiates. If the ulcerated plaque is below the renal arteries the manifestations appear in both lower extremities. Very rarely the ulcerated plaque is below the aortic bifurcation and those cases the changes occur only in one lower extremity.Kidney involvement leads to the symptoms of kidney failure, which are non-specific but usually cause nausea, reduced appetite (anorexia), raised blood pressure (hypertension), and occasionally the various symptoms of electrolyte disturbance such as an irregular heartbeat. Some patients report hematuria (bloody urine) but this may only be detectable on microscopic examination of the urine. Increased amounts of protein in the urine may cause edema (swelling) of the skin (a combination of symptoms known as nephrotic syndrome).If emboli have spread to the digestive tract, reduced appetite, nausea and vomiting may occur, as well as nonspecific abdominal pain, gastrointestinal hemorrhage (vomiting blood, or admixture of blood in the stool), and occasionally acute pancreatitis (inflammation of the pancreas).Both the central nervous system (brain and spinal cord) and the peripheral nervous system may be involved. Emboli to the brain may cause stroke-like episodes, headache and episodes of loss of vision in one eye (known as amaurosis fugax). Emboli to the eye can be seen by ophthalmoscopy and are known as plaques of Hollenhorst. Emboli to the spinal cord may cause paraparesis (decreased power in the legs) or cauda equina syndrome, a group of symptoms due to loss of function of the distal part of the spinal cord – loss of control over the bladder, rectum and skin sensation around the anus. If the blood supply to a single nerve is interrupted by an embolus, the result is loss of function in the muscles supplied by that nerve; this phenomenon is called a mononeuropathy.

Causes
It is relatively unusual (25% of the total number of cases) for cholesterol emboli to occur spontaneously; this usually happens in people with severe atherosclerosis of the large arteries such as the aorta. In the other 75% it is a complication of medical procedures involving the blood vessels, such as vascular surgery or angiography. In coronary catheterization, for instance, the incidence is 1.4%. Furthermore, cholesterol embolism may develop after the commencement of anticoagulants or thrombolytic medication that decrease blood clotting or dissolve blood clots, respectively. They probably lead to cholesterol emboli by removing blood clots that cover up a damaged atherosclerotic plaque; cholesterol-rich debris can then enter the bloodstream.

Diagnosis
Differential diagnosis
Findings on general investigations (such as blood tests) are not specific for cholesterol embolism, which makes diagnosis difficult. The main problem is the distinction between cholesterol embolism and vasculitis (inflammation of the small blood vessels), which may cause very similar symptoms - especially the skin findings and the kidney dysfunction. Worsening kidney function after an angiogram may also be attributed to kidney damage by substances used during the procedure (contrast nephropathy). Other causes that may lead to similar symptoms include ischemic kidney failure (kidney dysfunction due to an interrupted blood supply), a group of diseases known as thrombotic microangiopathies and endocarditis (infection of the heart valves with small clumps of infected tissue embolizing through the body).

Blood and urine
Tests for inflammation (C-reactive protein and the erythrocyte sedimentation rate) are typically elevated, and abnormal liver enzymes may be seen. If the kidneys are involved, tests of kidney function (such as urea and creatinine) are elevated. The complete blood count may show particularly high numbers of a type of white blood cell known as eosinophils (more than 0.5 billion per liter); this occurs in only 60-80% of cases, so normal eosinophil counts do not rule out the diagnosis. Examination of the urine may show red blood cells (occasionally in casts as seen under the microscope) and increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. If vasculitis is suspected, complement levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system. Complement levels are frequently reduced in cholesterol embolism, limiting the use of this test in the distinction between vasculitis and cholesterol embolism.

Tissue diagnosis
The microscopic examination of tissue (histology) gives the definitive diagnosis.  The diagnostic histopathologic finding is intravascular cholesterol crystals, which are seen as cholesterol clefts in routinely processed tissue (embedded in paraffin wax). The cholesterol crystals may be associated with macrophages, including giant cells, and eosinophils.The sensitivity of small core biopsies is modest, due to sampling error, as the process is often patchy </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 Band keratopathy 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 Splenosis and can you explain it in depth? [/INST] Splenosis is the result of spleen tissue breaking off the main organ and implanting at another site inside the body.  This is called heterotopic autotransplantation of the spleen.  It most commonly occurs as a result of traumatic splenic rupture or abdominal surgery. Depending on the location of the spleen, the new piece usually implants in another part of the abdominal cavity (including the pelvic cavity).  Single case reports also describe splenosis in the thoracic cavity, in subcutaneous tissue, in the liver or in the cranial cavity. Splenosis must be distinguished from the presence of additional spleens, which are innate and are the result of differences in embryological development. Additionally, splenosis must be differentiated from malignant tumors which may look similar when imaged.

History
Ectopic splenic tissue was first described in 1896 by Albrecht in Germany, whereas the term “splenosis” was first used by Buchbinder and Lipkoffin to describe their findings in 1939

Cause
A necessary requirement for splenosis is the rupture of the spleen, through a traumatic injury (such as a car wreck) or abdominal surgery, especially splenectomy. Splenosis in the abdominal category may occur in up to 65% of traumatic ruptures of the spleen. Splenosis in the thoracic cavity is rarer, because it requires the simultaneous rupture of the diaphragm. The implantation of spleen tissue under the skin may result from abdominal surgery or gunshot wounds.  Splenosis of the brain or liver is hypothesized to be the result of tiny pieces of spleen tissue traveling through the bloodstream.

Pathology
Macroscopically, splenosis manifests as individual pieces of reddish-blue tissue with variable shape, which can be as few as one and as many as 300, mostly in the abdominal cavity, and varying in size from a few millimeters to as large as 12 cm.  Due to the limited blood supply to these nodules, the typical size of splenic implants is usually less than 3 cm </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 Mismatch repair cancer syndrome and can you explain it in depth? [/INST] Mismatch repair cancer syndrome (MMRCS) is a cancer syndrome associated with biallelic DNA mismatch repair mutations. It is also known as Turcot syndrome (after Jacques Turcot, who described the condition in 1959) and by several other names.In MMRCS, neoplasia typically occurs in both the gut and the central nervous system (CNS) </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 Actinic granuloma 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 Human serum albumin and can you explain it in depth? [/INST] Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains oncotic pressure, among other functions.
Albumin is synthesized in the liver as preproalbumin, which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi apparatus to produce the secreted albumin.
The reference range for albumin concentrations in serum is approximately 35–50 g/L (3.5–5.0 g/dL).  It has a serum half-life of approximately 21 days. It has a molecular mass of 66.5 kDa.
The gene for albumin is located on chromosome 4 in locus 4q13.3 and mutations in this gene can result in anomalous proteins. The human albumin gene is 16,961 nucleotides long from the putative cap site to the first poly(A) addition site. It is split into 15 exons that are symmetrically placed within the 3 domains thought to have arisen by triplication of a single primordial domain.
Human serum albumin (HSA) is a highly water-soluble globular monomeric plasma protein with a relative molecular weight of 67 KDa, consisting of 585 amino acid residues, one sulfhydryl group and 17 disulfide bridges. Among nanoparticulate carriers, HSA nanoparticles have long been the center of attention in the pharmaceutical industry due to their ability to bind to various drug molecules, great stability during storage and in vivo usage, no toxicity and antigenicity, biodegradability, reproducibility, scale up of the production process and a better control over release properties. In addition, significant amounts of drug can be incorporated into the particle matrix because of the large number of drug binding sites on the albumin molecule.

Function
Maintains oncotic pressure
Transports thyroid hormones
Transports other hormones, in particular, ones that are fat-soluble
Transports fatty acids ("free" fatty acids) to the liver and to myocytes for utilization of energy
Transports unconjugated bilirubin
Transports many drugs; serum albumin levels can affect the half-life of drugs.  Competition between drugs for albumin binding sites may cause drug interaction by increasing the free fraction of one of the drugs, thereby affecting potency.
Competitively binds calcium ions (Ca2+)
Serum albumin, as a negative acute-phase protein, is down-regulated in inflammatory states. As such, it is not a valid marker of nutritional status; rather, it is a marker of an inflammatory state
Prevents photodegradation of folic acid
Prevent pathogenic effects of Clostridioides difficile toxins

Measurement
Serum albumin is commonly measured by recording the change in absorbance upon binding to a dye such as bromocresol green or bromocresol purple.

Reference ranges
The normal range of human serum albumin in adults (> 3 y.o.) is 3.5–5.0  g/dL (35–50 g/L). For children less than three years of age, the normal range is broader, 2.9–5.5 g/dL.Low albumin (hypoalbuminemia) may be caused by liver disease, nephrotic syndrome, burns, protein-losing enteropathy, malabsorption, malnutrition, late pregnancy, artefact, genetic variations and malignancy.High albumin (hyperalbuminemia) is almost always caused by dehydration. In some cases of retinol (Vitamin A) deficiency, the albumin level can be elevated to high-normal values (e.g., 4.9 g/dL) because retinol causes cells to swell with water. (This is also the reason too much Vitamin A is toxic.)
This swelling also likely occurs during treatment with 13-cis retinoic acid (isotretnoin), a pharmaceutical for treating severe acne, amongst other conditions. In lab experiments it has been shown that all-trans retinoic acid down regulates human albumin production.

Pathology
Hypoalbuminemia
Hypoalbuminemia means low blood albumin levels. This can be caused by:

Liver disease; cirrhosis of the liver is most common
Excess excretion by the kidneys (as in nephrotic syndrome)
Excess loss in bowel (protein-losing enteropathy, e.g., Ménétriers disease)
Burns (plasma loss in the absence of skin barrier)
Redistribution (hemodilution [as in pregnancy], increased vascular permeability or decreased lymphatic clearance)
Acute disease states (referred to as a negative acute-phase protein)
Malnutrition and wasting
Mutation causing analbuminemia (very rare)
Anorexia nervosa (most common cause in adolescents)In clinical medicine, hypoalbuminemia significantly correlates with a higher mortality rates in several conditions such as heart failure, post-surgery, COVID-19.

Hyperalbuminemia
Hyperalbuminemia is an increased concentration of albumin in the blood. Typically, this condition is due to dehydration.  Hyperalbuminemia has also been associated with high protein diets.

Medical use
Human albumin solution (HSA) is available for medical use, usually at concentrations of 5–25%.
Human albumin is often used to replace lost fluid and help restore blood volume in trauma, burns and surgery patients. There is no strong medical evidence that albumin administration (compared to saline) saves lives for people who have hypovolaemia or for those who are critically ill due to burns or hypoalbuminaemia. It is also not known if there are people who are critically ill that may benefit from albumin. Therefore, the Cochrane Collaboration recommends that it should not be used, except in clinical trials.In acoustic droplet vaporization (ADV), albumin is sometimes used as a surfactant.  ADV has been proposed as a cancer treatment by means of occlusion therapy.Human serum albumin may be used to potentially reverse drug/chemical toxicity by binding to free drug/agent.Human albumin may also be used in treatment of decompensated cirrhosis.Human serum albumin has been used as a component of a frailty index.

Glycation
It has been known for a long time that human blood proteins like hemoglobin  and serum albumin may undergo a slow non-enzymatic glycation, mainly by formation of a Schiff base between ε-amino groups of lysine (and sometimes arginine) residues and glucose molecules in blood (Maillard reaction). This reaction can be inhibited in the presence of antioxidant agents. Although this reaction may happen normally, elevated glycoalbumin is observed in diabetes mellitus.Glycation has the potential to alter the biological structure and function of the serum albumin protein.Moreover, the glycation can result in the formation of Advanced Glycation End-Products (AGE), which result in abnormal biological effects. Accumulation of AGEs leads to tissue damage via alteration of the structures and functions of tissue proteins, stimulation of cellular responses, through receptors specific for AGE-proteins, and generation of reactive oxygen intermediates. AGEs also react with DNA, thus causing mutations and DNA transposition. Thermal processing of proteins and carbohydrates brings major changes in allergenicity </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 Gastrointestinal perforation and can you explain it in depth? [/INST] Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe abdominal pain and tenderness. When the hole is in the stomach or early part of the small intestine, the onset of pain is typically sudden while with a hole in the large intestine onset may be more gradual. The pain is usually constant in nature. Sepsis, with an increased heart rate, increased breathing rate, fever, and confusion may occur.The cause can include trauma such as from a knife wound, eating a sharp object, or a medical procedure such as colonoscopy, bowel obstruction such as from a volvulus, colon cancer, or diverticulitis, stomach ulcers, ischemic bowel, and a number of infections including C. difficile. A hole allows intestinal contents to enter the abdominal cavity. The entry of bacteria results in a condition known as peritonitis or in the formation of an abscess. A hole in the stomach can also lead to a chemical peritonitis due to gastric acid. A CT scan is typically the preferred method of diagnosis; however, free air from a perforation can often be seen on plain X-ray.Perforation anywhere along the gastrointestinal tract typically requires emergency surgery in the form of an exploratory laparotomy. This is usually carried out along with intravenous fluids and antibiotics. A number of different antibiotics may be used such as piperacillin/tazobactam or the combination of ciprofloxacin and metronidazole. Occasionally the hole can be sewn closed while other times a bowel resection is required. Even with maximum treatment the risk of death can be as high as 50%. A hole from a stomach ulcer occurs in about 1 per 10,000 people per year, while one from diverticulitis occurs in about 0.4 per 10,000 people per year.

Signs and symptoms
Signs and symptoms may include a sudden pain in the epigastrium to the right of the midline indicating the perforation of a duodenal ulcer, while a gastric ulcer perforation reveals itself by burning pain in epigastrium, with flatulence and dyspepsia.In intestinal perforation, pain starts from the site of perforation and spreads across the abdomen.Gastrointestinal perforation results in severe abdominal pain intensified by movement, nausea, vomiting and hematemesis </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 Ceruminous adenoma and can you explain it in depth? [/INST] A ceruminous adenoma  is a benign glandular neoplasm which arises from the ceruminous glands located within the external auditory canal. These glands are found within the outer one third to one half of the external auditory canal, more common along the posterior surface; therefore, the tumor develops within a very specific location.

Signs and symptoms
Ceruminous adenoma are rare tumors, accounting for less than 1% of all external ear tumors. The patients will present with a mass, perhaps associated pain, and may have changes in hearing (usually a sensorineural or a conductive hearing loss). Some patients have tinnitus. Nerve paralysis is very uncommon.

Pathology findings
The tumors are usually small, with a mean size of about 1.2 cm.
The tumors are separated into three histologic types based on the dominant findings:

Ceruminous adenoma
Ceruminous pleomorphic adenoma
Ceruminous syringocystadenoma papilliferumAll of the tumors are unencapsulated, but are usually well defined or circumscribed. The overlying surface epithelium is not involved. The tumor shows a dual or biphasic appearance, with glandular or cystic spaces showing inner luminal secretory cells with abundant granular, eosinophilic cytoplasm subtended by basal, myoepithelial cells at the periphery, adjacent to the basement membrane. The luminal cells will often have decapitation (apocrine) secretions and will also have yellow-brown, ceroid, lipofuscin-like (cerumen) pigment granules. There is no pleomorphic, limited mitoses, and no necrosis.Immunohistochemistry can be performed to confirm the biphasic nature of the tumor. All cells are positive with pancytokeratin and epithelial membrane antigen; only the luminal cells are positive with CK7; only the basal  cells are positive with CK5/6, p63, S100 protein. CD117 can be positive in either population. The cells are negative with chromogranin, synaptophysin and CK20.

Diagnosis
The major diagnosis from which to separate ceruminous adenoma is ceruminous adenocarcinoma, which shows an infiltrative growth, pleomorphism, mitoses, necrosis, and lacks ceroid pigment granules. Other tumors which need to be excluded include a neuroendocrine adenoma of the middle ear (middle ear adenoma), paraganglioma, and endolymphatic sac tumor.

Management
The tumors are usually removed in small pieces due to the anatomic confines of the area.

Prognosis
Patients treated with complete surgical excision can expect an excellent long term outcome without any problems </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 Schizencephaly and can you explain it in depth? [/INST] Schizencephaly (from Greek  skhizein to split, and  enkephalos brain) is a rare birth defect characterized by abnormal clefts lined with grey matter that form the ependyma of the cerebral ventricles to the pia mater. These clefts can occur bilaterally or unilaterally. Common clinical features of this malformation include epilepsy, motor deficits, and psychomotor retardation.

Presentation
Schizencephaly can be distinguished from porencephaly by the fact that in schizencephaly, the fluid-filled component is entirely lined by heterotopic grey matter, while a porencephalic cyst is lined mostly by white matter. Individuals with clefts in both hemispheres, or bilateral clefts, are often developmentally delayed and have delayed speech and language skills and corticospinal dysfunction. Individuals with smaller, unilateral clefts (clefts in one hemisphere) may be weak or paralyzed on one side of the body and may have average or near-average intelligence. Patients with schizencephaly may also have varying degrees of microcephaly, Cognitive impairment, hemiparesis (weakness or paralysis affecting one side of the body), or quadriparesis (weakness or paralysis affecting all four extremities), and may have reduced muscle tone (hypotonia) </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 Masticatory muscle myositis and can you explain it in depth? [/INST] Masticatory muscle myositis (MMM) is an inflammatory disease in dogs affecting the muscles of mastication (chewing).  It is also known as atrophic myositis or eosinophilic myositis.  MMM is the most common inflammatory myopathy in dogs.  The disease mainly affects large breed dogs.  German Shepherd Dogs  and Cavalier King Charles Spaniels may be predisposed.  There is a similar disease of the eye muscles found in Golden Retrievers.  Symptoms of acute MMM include swelling of the jaw muscles, drooling, and pain on opening the mouth.  Ophthalmic signs may include third eyelid protrusion, red eyes, and exophthalmos (protruding eyeballs).  In chronic MMM there is atrophy of the jaw muscles, and scarring of the masticatory muscles due to fibrosis may result in inability to open the mouth (trismus).  The affected muscles include the temporalis, masseter, and pterygoid muscles </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 Progressive muscular atrophy and can you explain it in depth? [/INST] Progressive muscular atrophy (PMA), also called Duchenne–Aran disease and Duchenne–Aran muscular atrophy, is a disorder characterised by the degeneration of lower motor neurons, resulting in generalised, progressive loss of muscle function.
PMA is classified among motor neuron diseases (MND) where it is thought to account for around 4% of all MND cases.PMA affects only the lower motor neurons, in contrast to amyotrophic lateral sclerosis (ALS), the most common MND, which affects both the upper and lower motor neurons, or primary lateral sclerosis, another MND, which affects only the upper motor neurons. The distinction is important because PMA is associated with a better prognosis than ALS.

Signs and symptoms
As a result of lower motor neuron degeneration, the symptoms of PMA include:
muscle weakness
muscle atrophy
fasciculationsSome patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as flail limb (either flail arm or flail leg) and are associated with a better prognosis.

Diagnosis
PMA is a diagnosis of exclusion, there is no specific test which can conclusively establish whether a patient has the condition. Instead, a number of other possibilities have to be ruled out, such as multifocal motor neuropathy or spinal muscular atrophy. Tests used in the diagnostic process include MRI, clinical examination, and EMG. EMG tests in patients who do have PMA usually show denervation (neuron death) in most affected body parts, and in some unaffected parts too.It typically takes longer to be diagnosed with PMA than ALS, an average of 20 months for PMA vs 15 months in ALS.

Differential diagnosis
In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the absence of:
brisk reflexes
spasticity
Babinskis sign
emotional labilityThe importance of correctly recognizing progressive muscular atrophy as opposed to ALS is important for several reasons.

The prognosis is a little better. A recent study found the 5-year survival rate in PMA to be 33% (vs 20% in ALS) and the 10-year survival rate to be 12% (vs 6% in ALS).
Patients with PMA do not have the cognitive change identified in certain groups of patients with MND.
Because PMA patients do not have UMN signs, they usually do not meet the World Federation of Neurology El Escorial Research Criteria for "Definite" or "Probable" ALS and so are ineligible to participate in the majority of clinical trials conducted in ALS.
Because of its rarity (even compared to ALS) and confusion about the condition, some insurance policies or local healthcare policies may not recognize PMA as being the life-changing illness that it is. In cases where being classified as being PMA rather than ALS is likely to restrict access to services, it may be preferable to be diagnosed as "slowly progressive ALS" or "lower motor neuron predominant" ALS.An initial diagnosis of PMA could turn out to be slowly progressive ALS many years later, sometimes even decades after the initial diagnosis </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 Lipoatrophia semicircularis 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 Curlings ulcer 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 Encephalopathy and can you explain it in depth? [/INST] Encephalopathy (; from Ancient Greek: ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome has many possible organic and inorganic causes.

Signs and symptoms
The hallmark of encephalopathy is an altered mental state or delirium. Characteristic of the altered mental state is impairment of the cognition, attention, orientation, sleep–wake cycle and consciousness. An altered state of consciousness may range from failure of selective attention to drowsiness. Hypervigilance may be present; with or without: cognitive deficits, headache, epileptic seizures, myoclonus (involuntary twitching of a muscle or group of muscles) or asterixis ("flapping tremor" of the hand when wrist is extended).Depending on the type and severity of encephalopathy, common neurological symptoms are loss of cognitive function, subtle personality changes, and an inability to concentrate. Other neurological signs may include dysarthria, hypomimia, problems with movements (they can be clumsy or slow), ataxia, tremor. Other neurological signs may include involuntary grasping and sucking motions, nystagmus (rapid, involuntary eye movement), jactitation (restlessness while in bed), and respiratory abnormalities such as Cheyne-Stokes respiration (cyclic waxing and waning of tidal volume), apneustic respirations and post-hypercapnic apnea. Focal neurological deficits are less common.Wernicke encephalopathy can co-occur with Korsakoff alcoholic syndrome, characterized by amnestic-confabulatory syndrome: retrograde amnesia, anterograde amnesia, confabulations (invented memories), poor recall and disorientation.Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. It can cause paranoid and grandiose delusions, agitation, hallucinations (visual and auditory), bizarre behavior, fear, short-term memory loss, and confusion.HIV encephalopathy can lead to dementia.

Types
There are many types of encephalopathy. Some examples include:

Mitochondrial encephalopathy: Metabolic disorder caused by dysfunction of mitochondrial DNA. Can affect many body systems, particularly the brain and nervous system.
Glycine encephalopathy: A genetic metabolic disorder involving excess production of glycine.
Hepatic encephalopathy: Arising from advanced cirrhosis of the liver.
Hypoxic ischemic encephalopathy: Permanent or transitory encephalopathy arising from severely reduced oxygen delivery to the brain.
Static encephalopathy: Unchanging, or permanent, brain damage, usually caused by prenatal exposure to ethanol.
Uremic encephalopathy: Arising from high levels of toxins normally cleared by the kidneys—rare where dialysis is readily available.
Wernickes encephalopathy: Arising from thiamine (B1) deficiency, usually in the setting of alcoholism.
Hashimotos encephalopathy: Arising from an auto-immune disorder.
Anti-NMDA receptor encephalitis: An auto-immune encephalitis.
Hyperammonemia: a condition caused by high levels of ammonia, which is due to inborn errors of metabolism (including urea cycle disorder or multiple carboxylase deficiency), a diet with excessive levels of protein, deficiencies of specific nutrients such as  arginine or biotin, or organ failure.
Hypertensive encephalopathy: Arising from acutely increased blood pressure.
Chronic traumatic encephalopathy: a progressive degenerative disease associated with multiple concussions and other forms of brain injury
Lyme encephalopathy: Arising from Lyme disease bacteria, including Borrelia burgdorferi.
Toxic encephalopathy: A form of encephalopathy caused by chemicals and prescription drugs, often resulting in permanent brain damage.
Toxic-metabolic encephalopathy: A catch-all for brain dysfunction caused by infection, organ failure, or intoxication.
Transmissible spongiform encephalopathy: A collection of diseases all caused by prions, and characterized by "spongy" brain tissue (riddled with holes), impaired locomotion or coordination, and a 100% mortality rate. Includes bovine spongiform encephalopathy (mad cow disease), scrapie, and kuru among others.
Neonatal encephalopathy (hypoxic-ischemic encephalopathy): An obstetric form, often occurring due to lack of oxygen in bloodflow to brain-tissue of the fetus during labour or delivery.
Salmonella encephalopathy: A form of encephalopathy caused by food poisoning (especially out of peanuts and rotten meat) often resulting in permanent brain damage and nervous system disorders.
Encephalomyopathy: A combination of encephalopathy and myopathy.  Causes may include mitochondrial disease (particularly MELAS) or chronic hypophosphatemia, as may occur in cystinosis.
Creutzfeldt–Jakob disease (CJD; transmissible spongiform encephalopathy).
HIV encephalopathy (encephalopathy associated with HIV infection and AIDS, characterized by atrophy and ill-defined white matter hyperintensity).
Sepsis-associated encephalopathy (this type can occur in the setting of apparent sepsis, trauma, severe burns, or trauma, even without clear identification of an infection).
Epileptic encephalopathies:
Early infantile epileptic encephalopathy (acquired or congenital abnormal cortical development).
Early myoclonic epileptic encephalopathy (possibly due to metabolic disorders).
Gluten encephalopathy: Focal abnormalities of the white matter (generally area of low perfusion) are appreciated through magnetic resonance. Migraine is the most common symptom reported.

Toxicity from chemotherapy
Chemotherapy medication, for example, fludarabine can cause a
permanent severe global encephalopathy. Ifosfamide can cause
a severe encephalopathy (but it can be reversible with stopping use of the drug and starting the use of methylene blue). Bevacizumab and other anti–vascular endothelial growth factor medication can cause posterior reversible encephalopathy syndrome.

Toxicity from psychotropic medications
All therapeutic interventions are double-edged swords with benefits and adverse effects, and pharmacotherapy is not an exception. Shortly after the introduction of conventional antipsychotic drugs into clinical practice, relatively rare but serious complications with hyperthermia, muscle rigidity, autonomic instability, and disturbed mental status were recognized to develop in some patients treated with antipsychotics. This type of encephalopathy induced by the use of antipsychotics was referred to as neuroleptic malignant syndrome (NMS), and almost all physicians prescribing antipsychotics are nowadays aware of this adverse phenomenon. Another well-known type of encephalopathy associated with psychotropic drug therapy is serotonin toxicity (ST) or serotonin syndrome (SS), which is characterized by autonomic and neuromuscular symptoms and altered mental status. In contrast with the idiosyncratic nature of NMS, ST is a spectrum pathophysiological state assumed to derive from excess serotonergic neural transmission caused by serotonin-related psychotropic agents. In these two decades, pharmacotherapy with psychotropic drugs for mentally ill patients has been dramatically changed, and classical prototypal antipsychotics and antidepressants have been replaced with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs), respectively. These newly developed psychotropic drugs are generally safer and more tolerable than older drugs. However, atypical antipsychotics are not free of the risk of development of NMS, and the explosive prevalence of SSRIs prescribed not only for depression but also for a number of psychiatric diagnoses such as anxiety, eating, impulse-control, and personality disorders may increase the incidence of ST. Therefore, these two pathological states still remain as major adverse effects of psychotropic drugs involving altered functioning of the central nervous system (CNS), to which all clinicians prescribing psychoactive drugs should pay attention. The popularity of SSRIs also increased the case reports of patients experiencing discontinuation syndrome, which sometimes includes CNS symptoms like anxiety and irritability. In this chapter, the author provides a comprehensive overview of the above- mentioned adverse effects affecting the CNS function associated with psychotropic pharmacotherapy. In addition, several other pathological conditions potentially causing encephalopathic symptoms in psychiatric patients treated with psychotropic drugs, e.g., hyponatremia, valproate-induced hyperammonemia, transient splenial lesion of the corpus callosum, and so on, are also described.

Diagnosis
Blood tests, cerebrospinal fluid examination by lumbar puncture (also known as spinal tap), brain imaging studies, electroencephalography (EEG), neuropsychological testing and similar diagnostic studies may be used to differentiate the various causes of encephalopathy.
Diagnosis is frequently clinical. That is, no set of tests give the diagnosis, but the entire presentation of the illness with nonspecific test results informs the experienced clinician of the diagnosis.

Treatment
Treatment varies according to the type and severity of the encephalopathy. Anticonvulsants may be prescribed to reduce or halt any seizures. Changes to diet and nutritional supplements may help some people. In severe cases, dialysis or organ replacement surgery may be needed.
Sympathomimetic drugs can increase motivation, cognition, motor performance and alertness in persons with encephalopathy caused by brain injury, chronic infections, strokes, brain tumors.When the  encephalopathy is caused by untreated celiac disease or non-celiac gluten sensitivity, the gluten-free diet stops the progression of brain damage and improves the headaches.

Prognosis
Treating the underlying cause of the disorder may improve or reverse symptoms. However, in some cases, the encephalopathy may cause permanent structural changes and irreversible damage to the brain </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 Tubercle (bone) and can you explain it in depth? [/INST] In the skeleton of humans and other animals, a tubercle, tuberosity or apophysis is a protrusion or eminence that serves as an attachment for skeletal muscles. The muscles attach by tendons, where the enthesis is the connective tissue between the tendon and bone. A tuberosity is generally a larger tubercle.

Main tubercles
Humerus
The humerus has two tubercles, the greater tubercle and the lesser tubercle. These are situated at the proximal end of the bone, that is the end that connects with the scapula.  The greater/lesser tubercule is located from the top of the acromion laterally and inferiorly.  The radius has two, the radial tuberosity and Listers tubercle.

Ribs
On a rib, tubercle is an eminence on the back surface, at the junction between the neck and the body of the rib. It consists of an articular and a non-articular area </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 Phoria and can you explain it in depth? [/INST] Phoria are an English art rock band based in Brighton, consisting of Trewin Howard, Ed Sanderson, Jeb Hardwick, James "Cheese" Cheeseman, and Seryn Burden.
Phoria released their debut EP, Yourself Still, in 2010, followed by Bloodworks (2013) and Display (2014). The records earned the band international critical and popular acclaim.
The bands first full-length album, Volition, was released on 3 June 2016.
Their second album, Caught a Black Rabbit, came out on 13 November 2020.

Biography
Phoria members Trewin, Jeb and Ed went to primary as school together in Salisbury, where they learned cello, classical guitar, and violin respectively.
As friends, they spent their youth making music together before leaving for university in 2005.
Jeb and Ed both attended the University of Southampton. Ed continued to study music, specialising in violin and piano. Jeb studied for a sociology degree, though spent much of his time experimenting with music and visual arts.
Trewin attended the Dartington College of Arts in Devon. He  had initially enrolled on as fine arts course but was soon drawn back to music.
Having completed their studies, Trewin, Ed, and Jeb returned to Salisbury and took full time jobs. Jebs included a brief spell as an insurance agent. Ed, with a passion for acting, took large but unfulfilling parts in a series of niche-market films.
It was not long before the three of them realised that their future lay elsewhere, and moved to Brighton to start their musical careers.
While studying at Southampton, Jeb and Ed had met Tim Douglas through a mutual friend. Following successful spells playing guitar in bands across the South West, Tim moved to Brighton to play bass, and complete the Phoria line-up along with then drummer, Ross Crick.
Seryn Burden joined the band in August 2011, twelve months after the release of Yourself Still, following Rosss departure.
In 2016, following the release of Volition, and a string of successful EPs and UK and international tours, Jeb Hardwick left Phoria to pursue a career in filmmaking. He was replaced by James Cheeseman.
Jeb returned for the recording of the second album Caught A Black Rabbit (2020).

Yourself Still EP (2010)
The bands first EP Yourself Still was released in 2010 and earned positive reviews from various music blogs. The blog The Sirens Sound reviewed the EP, stating that [Yourself Still]...carries various musical vibes from cinematic orchestra to post-rock and indie-rock to a stunning pop environment leading the overall outcome of this record to blazed emotion.  Describing Phoria as A band you definitely want to keep an eye on.

Bloodworks EP (2013)
Bloodworks was released through Akira Records in Spring 2013.
Lead single "Red" hit number 2 in The Hype Machine blog aggregator charts within only a few days, cementing the track as one of the standout singles of 2013 from a relatively unknown band. With the single released just days before the EP, ThisIsFakeDIY said of the track [It gives] the impression that this here EPs going to be a game-changer. Glossy production is met midway by a startling, intimate style of songwriting, half Youth Lagoon, half something grander and more orchestral.Several tracks from the EP have been licensed to festival-featured European cinema, and Canadian television series Saving Hope.

Display EP (2014)
Display was released in June 2014. The lead single Emanate received 250,000 plays across YouTube and Soundcloud in the first two weeks.

Volition (2016)
Volition was released in June 2016 following several delays. It received positive reviews across the critical sphere, with The 405 describing the album as gigantic...[yet] effortlessly intimate, praising the cohesion in sound and vision. Ben Yung of therevue.ca gave a glowing review, stating: Volition is stunning, an absolute emotional roller coaster from start to finish. It is easy to understand why it took two years for the Brighton-based five-piece to complete their debut, as every single detail has been given the utmost attention and the production is refined and masterful. Every note, every vocal component, every lyric, every instrumental texture has been attended to and nothing feels out of place. With the precision of a surgeon and the steely aim of an assassin, Phoria hits every mark, including piercing a hole through our hearts with their visceral and emotional electronica.
The album was supported by festival appearances throughout 2016 and a UK and European tour.
In 2018, the song "Evolve" was featured in an episode of the Syfy original show, The Magicians.
Tim Douglas left the band in 2019 citing personal reasons.
Saving Us A Riot was used in Season 3 of Killing Eve. It was announced Jeb Hardwick had rejoined the band in August 2019

Caught A Black Rabbit (2020)
In August 2019, photos were shared of the band recording at Abbey Road Studios. On the 23rd June the band shared the first track from the upcoming album, Intro </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 Vestibular papillomatosis 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 Chalicosis 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 Beckwith–Wiedemann syndrome and can you explain it in depth? [/INST] Beckwith–Wiedemann syndrome (; abbreviated BWS) is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features. A minority (<15%) cases of BWS are familial, meaning that a close relative may also have BWS, and parents of an affected child may be at increased risk of having other children with BWS. While children with BWS are at increased risk of childhood cancer, most children with BWS do not develop cancer and the vast majority of children who do develop cancer can be treated successfully.

Presentation
No consensus clinical diagnostic criteria for Beckwith–Wiedemann syndrome (BWS) exist. Beckwith–Wiedemann syndrome (BWS) should be suspected in individuals who have one or more of the following major and/or minor findings.Major findings associated with BWS
Macrosomia (traditionally defined as weight and length/height >97th centile)
Macroglossia
Hemihyperplasia (asymmetric overgrowth of one or more regions of the body)
Omphalocele (also called exomphalos) or umbilical hernia
Embryonal tumor (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma) in childhood
Visceromegaly involving one or more intra-abdominal organs including liver, spleen, kidneys, adrenal glands, and/or pancreas
Cytomegaly of the fetal adrenal cortex (pathognomonic)
Renal abnormalities including structural abnormalities, nephromegaly, nephrocalcinosis, and/or later development of medullary sponge kidney
Anterior linear ear lobe creases and/or posterior helical ear pits
Placental mesenchymal dysplasia
Cleft palate (rare in BWS)
Cardiomyopathy (rare in BWS)
Positive family history (≥1 family members with a clinical diagnosis of BWS or a history or features suggestive of BWS)Minor findings associated with BWS

Pregnancy-related findings including polyhydramnios and prematurity in fetuses with the condition.
Neonatal hypoglycemia
Vascular lesions including nevus simplex (typically appearing on the forehead, glabella, and/or back of the neck) or hemangiomas (cutaneous or extracutaneous)
Characteristic facies including midface retrusion and infraorbital creases
Structural cardiac anomalies or cardiomegaly
Diastasis recti
Advanced bone age (common in overgrowth/endocrine disorders)The diagnosis of BWS is established in a proband with either of the following:

Three major or two major plus at least one minor criteria  Note: BWS should be considered a clinical spectrum, with some affected individuals having only one or two suggestive clinical findings. Therefore, the generally accepted clinical criteria proposed here should not be viewed as absolute but rather as guidelines. In other words, they cannot be used to rule out a diagnosis of BWS and cannot substitute for clinical judgment.
An epigenetic or genomic alteration leading to abnormal methylation at 11p15.5 or a heterozygous BWS-causing pathogenic variant in CDKN1C in the presence of one or more clinical findingsMost children with BWS do not have all of these features. In addition, some children with BWS have other findings including: nevus flammeus, prominent occiput, midface hypoplasia, hemihypertrophy, genitourinary anomalies (enlarged kidneys), cardiac anomalies, musculoskeletal abnormalities, and hearing loss. Also, some premature newborns with BWS do not have macroglossia until closer to their anticipated delivery date.Given the variation among individuals with BWS and the lack of a simple diagnostic test, identifying BWS can be difficult. In an attempt to standardize the classification of BWS, DeBaun et al. have defined a child as having BWS if the child has been diagnosed by a physician as having BWS and if the child has at least two of the five common features associated with BWS (macroglossia, macrosomia, midline abdominal wall defects, ear creases, neonatal hypoglycemia).  Another definition presented by Elliot et al. includes the presence of either three major features (anterior abdominal wall defect, macroglossia, or prepostnatal overgrowth) or two major plus three minor findings (ear creases, nevus flammeus, neonatal hypoglycemia, nephromegaly, or hemihyperplasia).In general, children with BWS do very well and grow up to become adults of normal size and intelligence, usually without the syndromic features of their childhood.

Neoplasms
Most children (>80%) with BWS do not develop cancer; however, children with BWS are much more likely (~600 times more) than other children to develop certain childhood cancers, particularly Wilms tumor (nephroblastoma), pancreatoblastoma and hepatoblastoma. Individuals with BWS appear to only be at increased risk for cancer during childhood (especially before age four) and do not have an increased risk of developing cancer in adulthood. If 100 children with BWS were followed from birth until age ten, about 10 cases of cancer would be expected in the group before age four, and about 1 case of cancer in the group would be expected between age four and ten.
In addition to Wilms tumor and hepatoblastoma, children with BWS have been shown in individual case reports to develop ganglioneuroma, adrenocortical carcinoma, acute lymphoid leukemia, liver sarcoma, thyroid carcinoma, melanoma, rhabdomyosarcoma, and mesoblastic nephroma.Wilms tumor, hepatoblastoma, and mesoblastic nephroma can usually be cured if diagnosed early. Early diagnosis allows physicians to treat the cancer when it is at an early stage. In addition, there is less toxic treatment. Given the importance of early diagnosis, all children with BWS should receive cancer screening.An abdominal ultrasound every 3 months until at least eight years of age is recommended and a blood test to measure alpha-fetoprotein (AFP) every 6 weeks until at least four years of age. Families and physicians should determine screening schedules for specific patients, especially the age at which to discontinue screening, based upon their own evaluation of the risk-benefit ratio.

Genetics
Most (>85%) cases of BWS are sporadic, meaning that, typically, no one else in that family has BWS, and parents of an affected child are not at increased risk of having other children with BWS. However, some (<15%) cases of BWS are familial, meaning that a close relative may also have BWS, and parents of an affected child may be at increased risk of having other children with BWS. BWS has been shown to specifically involve mutations in a defined region on the short arm of chromosome 11 referred to as 11p15.5, that leads to overactivity of the IGF-2 gene (growth factor) and/or no active copy of CDKN1C (inhibitor of cell proliferation gene).BWS can be caused by a range of different genetic defects. Over five distinct errors involving 11p15.5 have been identified in different BWS patients. Some patients have maternal chromosomal rearrangements of 11p15.5. Other patients have paternal uniparental disomy (UPD) of chromosome 11, meaning that the maternal copy of this chromosome is replaced with an extra paternal copy. Many other patients have abnormal DNA methylation in different areas of 11p15.5, meaning that normal epigenetic marks that regulate imprinted genes in this region are altered. A few other patients have a single gene copy located within 11p15, instead of two copies.The absence of a mutation in a child with clinical findings suggestive of BWS should not preclude a diagnosis of BWS. Even after extensive molecular testing, the specific defect causing BWS in an affected individual may remain unknown. BWS remains a clinical, rather than genetic, diagnosis, since physicians cannot identify and test for all the genetic causes of BWS. The clinical definition used for BWS is limited, because no standard diagnostic criteria exist that have been independently verified with patients who have either genetic or epigenetic mutations. When molecular analyses were completed in 10 children who met a research criterion for BWS, only 7 of the 10 children had genetic or epigenetic mutations.Given that the genetics of BWS are complex, a child with BWS should be under the medical care of a geneticist or an expert in the management of BWS.
Genes involved are IGF-2, CDKN1C, H19, and KCNQ1OT1.

Association with CDKN1C
CDKN1C is a protein coding gene that encodes a cyclin-dependent kinase inhibitor that acts as a negative regulator of cell proliferation, effectively making CDKN1C a tumor suppressor gene. CDKN1C also works during fetal development, preventing the fetus from becoming too large. It is located on the short arm of the human chromosome 11 in the ICR2 region, along with many other imprinted genes. Since CDKN1C is preferentially maternally expressed, hypomethylation in the ICR2 region of the maternal allele can result in pathologies such as cancer or a defect known as Beckwith-Weidemann Syndrome. Beckwith-Weidemann Syndrome (BWS) may also be brought about by CDKN1C 11p15 epimutations. It may also be a result of deletions of small amounts of DNA that cause chromosomal abnormalities, rendering the gene inactive. This leaves only the paternally expressed IGF2 to promote cell proliferation. The reduction of growth restriction results in the overgrowth of many tissues, leading to the common symptoms of BWS. These symptoms may include macroglossia, organomegaly, periorbital fullness, and hernias. Knockout models for CDKN1C in mice do exist; in fact, many of the affected offspring exhibit fetal and neonatal lethality and have most of the features related to Beckwith-Weidemann Syndrome.

Diagnosis
Management
Abdominal wall defects are common in newborns with BWS and may require surgical treatment. These defects can range in severity from omphalocele (most serious) to umbilical hernia and diastasis recti (least serious). An omphalocele is a congenital malformation in which a newborns intestines, and sometimes other abdominal organs, protrude out of the abdomen through the umbilicus. Newborns with an omphalocele typically require surgery to place the abdominal contents back into the abdomen in order to prevent serious infection or shock. An umbilical hernia is also a defect in which abdominal contents come through weak abdominal wall muscle at the umbilicus. In general, newborns with umbilical hernias do not require treatment because often these hernias spontaneously close by age four. If, after this time, a hernia is still present, surgery may be recommended. Diastasis recti is a separation of the left and right sides of the rectus abdominis muscle that are normally joined. Children with diastasis recti usually require no treatment because the condition resolves as the child grows.Neonatal hypoglycemia, low blood glucose in the first month of life, occurs in about half of children with BWS. Most of these hypoglycemic newborns are asymptomatic and have a normal blood glucose level within days. However, untreated persistent hypoglycemia can lead to permanent brain damage. Hypoglycemia in newborns with BWS should be managed according to standard protocols for treating neonatal hypoglycemia. Usually this hypoglycemia can easily be treated with more frequent feedings or medical doses of glucose. Rarely (<5%) children with BWS will continue to have hypoglycemia after the neonatal period and require more intensive treatment. Such children may require tube feedings, oral hyperglycemic medicines, or a partial pancreatectomy.Macroglossia, a large tongue, is a very common (>90%) and prominent feature of BWS. Infants with BWS and macroglossia typically cannot fully close their mouth in front of their large tongue, causing it to protrude out. Macroglossia in BWS becomes less noticeable with age and often requires no treatment; but it does cause problems for some children with BWS. In severe cases, macroglossia can cause respiratory, feeding, and speech difficulties. Children with BWS and significant macroglossia should be evaluated by a craniofacial team.The best time to perform surgery for a large tongue is not known. Some surgeons recommend performing the surgery between 3 and 6 months of age. Surgery for macroglossia involves removing a small part of the tongue so that it fits within the mouth  to allow for proper jaw and tooth development.These children are often managed by a multidisciplinary craniofacial team. These teams include speech and language therapists, Craniofacial and Paediatric Plastic Surgeons and Orthodontists who decide the appropriateness and timing of tongue reduction surgery. Some countries have designated centres for the management of macroglossia. For example, in the United Kingdom, children who have macroglossia associated with Beckwith Wiedemann Syndrome are managed in a national specialised service. The service is commissioned as highly specialised service by NHS England and is located at Great Ormond Street Hospital.Nevus flammeus (port-wine stain) is a flat, red birthmark caused by a capillary (small blood vessel) malformation. Children with BWS often have nevus flammeus on their forehead or the back of their neck. Nevus flammeus is benign and commonly does not require any treatment.
Hemihypertrophy (hemihyperplasia) is an abnormal asymmetry between the left and right sides of the body occurring when one part of the body grows faster than normal. Children with BWS and hemihypertrophy can have an isolated asymmetry of one body part, or they can have a difference affecting the entire one side of the body. Individuals who do not have BWS can also have hemihypertrophy. Isolated hemihypertrophy is associated with a higher risk for cancer.  The types of cancer and age of the cancers are similar to children with BWS. As a result, children with hemihypertrophy should follow the general cancer screening protocol for BWS.
Hemihypertrophy can also cause various orthopedic problems, so children with significant limb hemihyperplasia should be evaluated and followed by an orthopedic surgeon.
Hemihyperplasia affecting the face can sometimes cause significant cosmetic concerns that may be addressed by a cranial facial team.

Prognosis
In general, the prognosis is very good. Children with BWS usually do very well and grow up to become the heights expected based on their parents heights. While they are at increased risk of childhood cancer, most of them do not develop the disease, and the vast majority of the children who do can be treated successfully.Children with BWS for the most part had no significant delays when compared to their siblings. However, some of them do have speech problems that could be related to macroglossia or hearing loss.Advances in treating neonatal complications and premature infants in the last twenty years have significantly improved the true infant mortality rate associated with BWS. In a review of pregnancies that resulted in 304 children with BWS, no neonatal deaths were reported. This is compared to a previously reported mortality rate of 20%. The data from the former study was derived from a BWS registry, a database that may be slightly biased towards involving living children; however, death was not an exclusion criterion to join the registry. This suggests that while infants with BWS are likely to have a higher than normal infant mortality risk, it may not be as high as 20%.

Assisted reproductive technology
Assisted reproductive technology (ART) is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. According to the CDC, in general, ART procedures involve surgically removing eggs from a womans ovaries, combining them with sperm in the laboratory, and returning them to the womans body or donating them to another woman. ART has been associated with epigenetic syndromes, specifically BWS and Angelman syndrome. Three groups have shown an increased rate of ART conception in children with BWS.  A retrospective case control study from Australia found a 1 in 4000 risk of BWS in their in-vitro population, several times higher than the general population.  Another study found that children conceived by in vitro fertilisation (IVF) are three to four times more likely to develop the condition. No specific type of ART has been more closely associated with BWS. The mechanism by which ART produces this effect is still under investigation.

Epidemiology
Beckwith–Wiedemann syndrome has an estimated incidence of one in 13,700; about 300 children with BWS are born each year in the United States </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 Dissociative disorder and can you explain it in depth? [/INST] Dissociative disorders (DD) are conditions that involve disruptions or breakdowns of memory, awareness, identity, or perception. People with dissociative disorders use dissociation as a defense mechanism, pathologically and involuntarily. The individual experiences these dissociations to protect themselves. Some dissociative disorders are triggered by psychological trauma, but depersonalization-derealization disorder may be preceded only by stress, psychoactive substances, or no identifiable trigger at all.The dissociative disorders listed in the American Psychiatric Associations DSM-5 are as follows:
Dissociative identity disorder (formerly multiple personality disorder): the alternation of two or more distinct personality states with impaired recall among personality states. In extreme cases, the host personality is unaware of the other, alternating personalities; however, the alternate personalities can be aware of all the existing personalities.
Dissociative amnesia (formerly psychogenic amnesia): the temporary loss of recall memory, specifically episodic memory, due to a traumatic or stressful event. It is considered the most common dissociative disorder amongst those documented. This disorder can occur abruptly or gradually and may last minutes to years depending on the severity of the trauma and the patient. Dissociative fugue was previously a separate category but is now treated as a specifier for dissociative amnesia.
Depersonalization-derealization disorder: periods of detachment from self or surrounding which may be experienced as "unreal" (lacking in control of or "outside" self) while retaining awareness that this is only a feeling and not a reality.
The old category of dissociative disorder not otherwise specified is now split into two: other specified dissociative disorder, and unspecified dissociative disorder. These categories are used for forms of pathological dissociation that do not fully meet the criteria of the other specified dissociative disorders; or if the correct category has not been determined; or the disorder is transient.The ICD11 lists dissociative disorders as:

Dissociative neurological symptom disorder
Dissociative amnesia
Dissociative amnesia with dissociative fugue
Trance disorder
Possession trance disorder
Dissociative identity disorder
Partial dissociative identity disorder
Depersonalization-derealization disorder

Cause and treatment
Dissociative identity disorder
Cause: Dissociative identity disorder is caused by ongoing childhood trauma that occurs before the ages of six to nine. People with dissociative identity disorder usually have close relatives who have also had similar experiences.Treatment: Long-term psychotherapy to improve the patients quality of life.

Dissociative amnesia
Cause: A way to cope with trauma.
Treatment: Psychotherapy (e.g. talk therapy) counseling or psychosocial therapy which involves talking about your disorder and related issues with a mental health provider. Psychotherapy often involves hypnosis (help you remember and work through the trauma); creative art therapy (using creative process to help a person who cannot express his or her thoughts); cognitive therapy (talk therapy to identify unhealthy and negative beliefs/behaviors); and medications (antidepressants, anti-anxiety medications, or sedatives). These medications help control the symptoms associated with the dissociative disorders, but there are no medications yet that specifically treat dissociative disorders. However, the medication pentothal can sometimes help to restore the memories. The length of an event of dissociative amnesia may be a few minutes or several years. If an episode is associated with a traumatic event, the amnesia may clear up when the person is removed from the traumatic situation. Dissociative fugue was a separate category but is now listed as a specifier for dissociative amnesia.

Depersonalization-derealization disorder
Cause: Dissociative disorders usually develop as a way to cope with trauma. The disorders most often form in children subjected to chronic physical, sexual or emotional abuse or, less frequently, a home environment that is otherwise frightening or highly unpredictable; however, this disorder can also acutely form due to severe traumas such as war or the death of a loved one.
Treatment: Same treatment as dissociative amnesia. An episode of depersonalization-derealization disorder can be as brief as a few seconds or continue for several years.Dissociative disorders, especially dissociative identity disorder (DID), while being the result of extraordinary abuse and trauma in childhood, it should not be attributed exotic status. DID would be better examined through a more holistic lens, taking into considering the social, cognitive, and neural components, and how they interact with one another.

Medications
There are no medications to treat dissociative disorders, however, drugs to treat anxiety and depression that may accompany the disorders can be given.

Diagnosis and prevalence
The lifetime prevalence of dissociative disorders varies from 10% in the general population to 46% in psychiatric inpatients. Diagnosis can be made with the help of structured clinical interviews such as the Dissociative Disorders Interview Schedule (DDIS) and the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D-R), and behavioral observation of dissociative signs during the interview. Additional information can be helpful in diagnosis, including the Dissociative Experiences Scale or other questionnaires, performance-based measures, records from doctors or academic records, and information from partners, parents, or friends. A dissociative disorder cannot be ruled out in a single session and it is common for patients diagnosed with a dissociative disorder to not have a previous dissociative disorder diagnosis due to a lack of clinician training. Some diagnostic tests have also been adapted or developed for use with children and adolescents such as the Adolescent Dissociative Experiences Scale, Childrens Version of the Response Evaluation Measure (REM-Y-71), Child Interview for Subjective Dissociative Experiences, Child Dissociative Checklist (CDC), Child Behavior Checklist (CBCL) Dissociation Subscale, and the Trauma Symptom Checklist for Children Dissociation Subscale.Dissociative disorders have been found to be quite prevalent in outpatient populations, as well as within low-income communities. One study found that in a population of poor inner-city outpatients, there was a 29% prevalence of dissociative disorders.There are problems with classification, diagnosis and therapeutic strategies of dissociative and conversion disorders which can be understood by the historic context of hysteria. Even current systems used to diagnose DD such as the DSM-IV and ICD-10 differ in the way the classification is determined. In most cases mental health professionals are still hesitant to diagnose patients with Dissociative Disorder, because before they are considered to be diagnosed with Dissociative Disorder these patients have more than likely been diagnosed with major depressive disorder, anxiety disorder, and most often post-traumatic stress disorder. It has been found from interviews with those who may be afflicted with dissociative disorders may be more effective at getting an accurate diagnosis than self-scoring assessments and scales.The prevalence of dissociative disorders is not completely understood due to the many difficulties in diagnosing dissociative disorders. Many of these difficulties stem from a misunderstanding of dissociative disorders, from an unfamiliarity diagnosis or symptoms to disbelief in some dissociative disorders entirely. Due to this it has been found that only 28% to 48% of people diagnosed with a dissociative disorder receive treatment for their mental health. Patients who are misdiagnosed are often those more likely to be hospitalised repeatedly, and lack of treatment can result in intensive outpatient treatment and higher rates of disability.An important concern in the diagnosis of dissociative disorders in forensic interviews is the possibility that the patient may be feigning symptoms in order to escape negative consequences. Young criminal offenders report much higher levels of dissociative disorders, such as amnesia. In one study it was found that 1% of young offenders reported complete amnesia for a violent crime, while 19% claimed partial amnesia. There have also been cases in which people with dissociative identity disorder provide conflicting testimonies in court, depending on the personality that is present.
The world-wide prevalence of dissociative disorders is not well understood due to different cultural beliefs surrounding human emotions and the human brain.

Children and adolescents
Dissociative disorders (DD) are widely believed to have roots in adverse childhood experiences including abuse and loss, but the symptoms often go unrecognized or are misdiagnosed in children and adolescents. However, a recent western Chinese study showed a increase in awareness of dissociative disorders present in children These studies show that DDs have an intricate relationship with the patients mental, physical and socio-cultural environments. This study suggested that dissociative disorders are more common in Western, or developing countries, however, some cases have been seen in both clinical and non-clinical Chinese populations. There are several reasons why recognizing symptoms of dissociation in children is challenging: it may be difficult for children to describe their internal experiences; caregivers may miss signals or attempt to conceal their own abusive or neglectful behaviors; symptoms can be subtle or fleeting; disturbances of memory, mood, or concentration associated with dissociation may be misinterpreted as symptoms of other disorders.Another resource, Beacon House, informs us of dissociative disorder in children, suggesting that it is a survival mechanism that often goes unnoticed in children that have been traumatised. Dr. Shoshanah Lyons suggests that traumatised children often continue to dissociate even though they might not be in any danger, and that they are often unaware that they are dissociating. In addition to developing diagnostic tests for children and adolescents (see above), a number of approaches have been developed to improve recognition and understanding of dissociation in children. Recent research has focused on clarifying the neurological basis of symptoms associated with dissociation by studying neurochemical, functional and structural brain abnormalities that can result from childhood trauma. Others in the field have argued that recognizing disorganized attachment (DA) in children can help alert clinicians to the possibility of dissociative disorders. In their 2008 article, Rebecca Seligman and Laurence Kirmayer suggest the existence of evidence of linkages between trauma experienced in childhood and the capacity for dissociation or depersonalisation. They also suggest that individuals who are able to utilise dissociative techniques are able to keep this as an extended strategy to cope with stressful situations.Clinicians and researchers stress the importance of using a developmental model to understand both symptoms and the future course of DDs. In other words, symptoms of dissociation may manifest differently at different stages of child and adolescent development and individuals may be more or less susceptible to developing dissociative symptoms at different ages. Further research into the manifestation of dissociative symptoms and vulnerability throughout development is needed. Related to this developmental approach, more research is required to establish whether a young patients recovery will remain stable over time.

Current debates and the DSM-5
A number of controversies surround DD in adults as well as children. First, there is ongoing debate surrounding the etiology of dissociative identity disorder (DID). The crux of this debate is if DID is the result of childhood trauma and disorganized attachment. A proposed view is that dissociation has a physiological basis, in that it involves automatically triggered mechanisms such as increased blood pressure and alertness, that would, as Lynn contends, imply its existence as a cross-species disorder. A second area of controversy surrounds the question of whether or not dissociation as a defense versus pathological dissociation are qualitatively or quantitatively different. Experiences and symptoms of dissociation can range from the more mundane to those associated with posttraumatic stress disorder (PTSD) or acute stress disorder (ASD) to dissociative disorders. Mirroring this complexity, the DSM-5 workgroup considered grouping dissociative disorders with other trauma/stress disorders, but instead decided to put them in the following chapter to emphasize the close relationship </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 Contact dermatitis and can you explain it in depth? [/INST] Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are not contagious or life-threatening, but can be very uncomfortable.
Contact dermatitis results from either exposure to allergens (allergic contact dermatitis), or irritants (irritant contact dermatitis). Allergic contact dermatitis involves a delayed type of hypersensitivity and previous exposure to an allergen to produce a reaction. Irritant contact dermatitis is the most common type and represents 80% of all cases. It is caused by prolonged exposure to irritants, leading to direct injury of the epidermal cells of the skin, which activates an immune response, resulting in an inflammatory cutaneous reaction. Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight. Diagnosis of allergic contact dermatitis can often be supported by patch testing.

Epidemiology
Contact dermatitis constitutes 95% of all occupational skin disorders. There are few accurate statistics on the incidence and prevalence of contact dermatitis. The results of the few studies that have been undertaken cannot be compared because of methodological differences.

Signs and symptoms
Contact dermatitis is a localized rash or irritation of the skin caused by contact with a foreign substance. Only the superficial regions of the skin are affected in contact dermatitis. Inflammation of the affected tissue is present in the epidermis (the outermost layer of skin) and the outer dermis (the layer beneath the epidermis).Contact dermatitis results in large, burning, and itchy rashes. These can take anywhere from several days to weeks to heal. This differentiates it from contact urticaria (hives), in which a rash appears within minutes of exposure and then fades away within minutes to hours. Even after days, contact dermatitis fades only if the skin no longer comes in contact with the allergen or irritant.  Chronic contact dermatitis can develop when the removal of the offending agent no longer provides expected relief.
Irritant dermatitis is usually confined to the area where the trigger actually touched the skin, whereas allergic dermatitis may be more widespread on the skin. Irritant dermatitis usually found on hands whereas exposed areas of skin. Symptoms of both forms include the following:

Red rash. This is the usual reaction. The rash appears immediately in irritant contact dermatitis; in allergic contact dermatitis, the rash sometimes does not appear until 24–72 hours after exposure to the allergen.
Blisters or wheals. Blisters, wheals (welts), and urticaria (hives) often form in a pattern where skin was directly exposed to the allergen or irritant.
Itchy, burning skin. Irritant contact dermatitis tends to be more painful than itchy, while allergic contact dermatitis often itches.
The surface appearance of skin is dry and fissured in the irritant contact dermatitis whereas vesicles and bullae are seen in allergic contact dermatitis.
lichenified lesions.While either form of contact dermatitis can affect any part of the body, irritant contact dermatitis often affects the hands, which have been exposed by resting in or dipping into a container (sink, pail, tub, swimming pools with high chlorine) containing the irritant.

Causes
The percentage of cases attributable to occupational contact dermatitis varies substantially depending on the industries that predominate, the employment that people have, the risks to which they are exposed, the centers that record cases, and variances in defining and confirming diagnoses.Common causes of allergic contact dermatitis include: nickel allergy, 14K or 18K gold, Balsam of Peru (Myroxylon pereirae), and chromium.  In the Americas they include the oily coating from plants of the genus Toxicodendron: poison ivy, poison oak, and poison sumac. Millions of cases occur each year in North America alone.  The alkyl resorcinols in Grevillea banksii and Grevillea Robyn Gordon are responsible for contact dermatitis. Bilobol, another alkyl resorcinol found in Ginkgo biloba fruits, is also a strong skin irritant.Common causes of irritant contact dermatitis include solvents, metalworking fluids, latex, kerosene, ethylene oxide, paper, especially papers coated with chemicals and printing inks, certain foods and drink, food flavorings and spices, perfume, surfactants in topical medications and cosmetics, alkalis, low humidity from air conditioning, and many plants.  Other common causes of irritant contact dermatitis are harsh alkaline soaps, detergents, and cleaning products.There are three types of contact dermatitis:  irritant contact dermatitis; allergic contact dermatitis; and photocontact dermatitis. Photocontact dermatitis is divided into two categories: phototoxic and photoallergic.

Irritant contact dermatitis
The irritants direct cytotoxic impact on epidermal keratinocytes causes Irritant contact dermatitis. This disrupts the skin barrier and activates the innate immune system. Keratinocytes in the epidermis can be actually affected by irritants. It is a complicated reaction that is influenced by genetic and environmental elements, both of which have a role in the pathogenesis of the disease. It can be seen in both occupational and non-occupational environments but its more common in the occupations dealing in low humidity conditions.
Irritant contact dermatitis (ICD) can be divided into forms caused by chemical irritants, and those caused by physical irritants. Common chemical irritants implicated include: solvents (alcohol, xylene, turpentine, esters, acetone, ketones, and others); metalworking fluids (neat oils, water-based metalworking fluids with surfactants); latex; kerosene; ethylene oxide; surfactants in topical medications and cosmetics (sodium lauryl sulfate); and alkalis (drain cleaners, strong soap with lye residues).
Physical irritant contact dermatitis may most commonly be caused by low humidity from air conditioning. Also, many plants directly irritate the skin.

Allergic contact dermatitis
Allergic contact dermatitis (ACD) is accepted to be the most prevalent form of immunotoxicity found in humans, and is a common occupational and environmental health problem. By its allergic nature, this form of contact dermatitis is a hypersensitive reaction that is atypical within the population. The development of the disease occurs in two phases, which are induction and elicitation. The process of skin sensitization begins when a susceptible subject is exposed to the allergen in sufficient concentration to elicit the required cutaneous immune response. This causes sensitization and when exposure to the same allergen at a later time at the same or different skin site leads to a secondary immune response at the point of contact. The mechanisms by which this reaction occurs are complex, with many levels of fine control. Their immunology centres on the interaction of immunoregulatory cytokines and discrete subpopulations of T lymphocytes.
Allergens include nickel, gold, Balsam of Peru (Myroxylon pereirae), chromium, and the oily coating from plants of the genus Toxicodendron, such as poison ivy, poison oak, and poison sumac.  Acrylates, rubber chemicals, emulsifiers and dyes, epoxy resin chemicals are just several of the substances that might induce Allergic Contact Dermatitis. Much of the allergic contact dermatitis that arises is caused by occupational exposure. Non-occupational exposure to allergens in medicaments, clothing, cosmetics, and plants are also a significant cause of allergic contact dermatitis.

Photocontact dermatitis
Sometimes termed "photoaggravated", and divided into two categories, phototoxic and photoallergic, PCD is the eczematous condition which is triggered by an interaction between an otherwise unharmful or less harmful substance on the skin and ultraviolet light (320–400 nm UVA) (ESCD 2006), therefore manifesting itself only in regions where the affected person has been exposed to such rays.
Without the presence of these rays, the photosensitiser is not harmful. For this reason, this form of contact dermatitis is usually associated only with areas of skin that are left uncovered by clothing, and it can be soundly defeated by avoiding exposure to sunlight.  The mechanism of action varies from toxin to toxin, but is usually due to the production of a photoproduct. Toxins which are associated with PCD include the psoralens. Psoralens are in fact used therapeutically for the treatment of psoriasis, eczema, and vitiligo.
Photocontact dermatitis is another condition in which the distinction between forms of contact dermatitis is not clear-cut. Immunological mechanisms can also play a part, causing a response similar to ACD.

Diagnosis
Since contact dermatitis relies on an irritant or an allergen to initiate the reaction, it is important for the patient to identify the responsible agent and avoid it. This can be accomplished by having patch tests, one of various methods commonly known as allergy testing.  The patch tests were based on the concept of a type IV hypersensitivity reaction where there is exposure of allergens to skin and checking for the development of contact dermatitis in that area. This test involves the application of suspected irritant to a part of the skin and cover it with impermeable material and attached to the skin with the help of adhesive plaster. The top three allergens found in patch tests from 2005 to 2006 were:  nickel sulfate (19.0%), Myroxylon pereirae (Balsam of Peru, 11.9%), and fragrance mix I (11.5%).The patient must know where the irritant or allergen is found to be able to avoid it. It is important to also note that chemicals sometimes have several different names, and do not always appear on labels.The distinction between the various types of contact dermatitis is based on a number of factors. The morphology of the tissues, the histology, and immunologic findings are all used in diagnosis of the form of the condition. However, as suggested previously, there is some confusion in the distinction of the different forms of contact dermatitis. Using histology on its own is insufficient, as these findings have been acknowledged not to distinguish, and even positive patch testing does not rule out the existence of an irritant form of dermatitis as well as an immunological one.

Prevention
In an industrial setting the employer has a duty of care to its worker to provide the correct level of safety equipment to mitigate exposure to harmful irritants </s>