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You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I've encountered the term 'VACTERL association' while reading about medical topics. What does it refer to exactly?

The VACTERL association (also VATER association, and less accurately VACTERL syndrome) refers to a recognized group of birth defects which tend to co-occur (see below). This pattern is a recognized association, as opposed to a syndrome, because there is no known pathogenetic cause to explain the grouped incidence. Each child with this condition can be unique. At present this condition is treated after birth with issues being approached one at a time. Some infants are born with symptoms that cannot be treated and they do not survive. Also, VACTERL association can be linked to other similar conditions such as Klippel Feil and Goldenhar syndrome including crossovers of conditions. No specific genetic or chromosome problem has been identified with VACTERL association. VACTERL can be seen with some chromosomal defects such as Trisomy 18 and is more frequently seen in babies of diabetic mothers. VACTERL association, however, is most likely caused by multiple factors.VACTERL association specifically refers to the abnormalities in structures derived from the embryonic mesoderm. Signs and symptoms The following features are observed with VACTERL association: V - Vertebral anomalies A - Anorectal malformations C - Cardiovascular anomalies T - Tracheoesophageal fistula E - Esophageal atresia R - Renal (Kidney) and/or radial anomalies L - Limb defectsAlthough it was not conclusive whether VACTERL should be defined by at least two or three component defects, it is typically defined by the presence of at least three of the above congenital malformations. Spine Vertebral anomalies, or defects of the spinal column, usually consist of small (hypoplastic) vertebrae or hemivertebra where only one half of the bone is formed. About 80 percent of patients with VACTERL association will have vertebral anomalies. In early life these rarely cause any difficulties, although the presence of these defects on a chest x-ray may alert the physician to other defects associated with VACTERL. Later in life these spinal column abnormalities may put the child at risk for developing scoliosis, or curvature of the spine. Anal defects Anal atresia or imperforate anus is seen in about 55 to 90 percent of patients with VACTERL association. These anomalies are usually noted at birth. It often require surgery in the first days of life. Sometimes babies will require several surgeries to fully reconstruct the intestine and anal canal. Cardiac defects Up to 75 percent of patients with VACTERL association have been reported to have congenital heart disease. The most common heart defects seen with VACTERL association are ventricular septal defect (VSD), atrial septal defects and tetralogy of Fallot. Less common defects are truncus arteriosus and transposition of the great arteries. It is subsequently thought that cardiac defects should be considered an extension of VACTERL. Trachea and oesophagus Oesophageal atresia with tracheoesophageal fistula (TO fistula or TOF) is seen in about 70 percent of patients with VACTERL association, although it can frequently occur as an isolated defect. 15 to 33 percent of patients with TO fistulas will also have congenital heart disease. However these babies usually have uncomplicated heart defects, like a ventricular septal defect, which may not require any surgery. Kidneys Kidney defects are seen in approximately 50 percent of patients with VACTERL association. In addition, up to 35 percent of patients with VACTERL association have a single umbilical artery (there are usually two arteries and one vein) which is often associated with additional kidney or urologic problems. Renal abnormalities in VACTERL association can be severe, with incomplete formation of one or both kidneys or urologic abnormalities such as obstruction of outflow of urine from the kidneys or severe reflux (backflow) of urine into the kidneys from the bladder. These problems can cause kidney failure early in life and may require kidney transplant. Many of these problems can be corrected surgically before any damage can occur. Limbs Limb defects occur in up to 70 percent of babies with VACTERL association and include a displaced or hypoplastic thumb, extra digits (polydactyly), fusion of digits (syndactyly) and forearm defects such as radial aplasia. Babies with limb defects on both sides tend to have kidney or urologic defects on both sides, while babies with limb defects on only one side of the body tend to have kidney problems on that same side. Extension Features secondary to VACTERL components are frequent enough to be considered an extension of VACTERL. These include: single umbilical artery, ambiguous genitalia, abdominal wall defects, diaphragmatic hernia, intestinal and respiratory anomalies, and oligohydramnios sequence defects. Cardiac defects are thought to fit in this category. Growth Many babies with VACTERL are born small and have difficulty with gaining weight. Babies with VACTERL association, however, do tend to have normal development and normal intelligence. Pathology Patients with abnormal cardiac and kidney function may be more at risk for hemolytic uremic syndrome Diagnosis Differential diagnosis Baller–Gerold syndrome CHARGE syndrome Currarino syndrome DiGeorge syndrome Fanconi anemia Feingold syndrome Fryns syndrome MURCS association Oculo-auriculo-vertebral syndrome Opitz G/BBB syndrome Holt–Oram syndrome Pallister–Hall syndrome Townes–Brocks syndrome VACTERL with hydrocephalus Management Epidemiology The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to diabetic mothers. While most cases are sporadic, there are clearly families who present with multiple involved members. History The acronym VATER association was first described by Linda Quan, an emergency room physician, and David Smith, a man who was considered the father of dysmorphology in 1972, to define a non-random co-occurrence of the listed defects. Years later, research revealed that cardiac and renal abnormalities were common in the association, and the acronym was changed to VACTERL. However, no single cause was identified that links all these conditions together. Therefore, this VACTERL is termed as "association" instead of a "syndrome". The differentiation of the acronyms VACTERL and VATER is due to the variation in defects determined at or prior to birth. VACTERL contains vertebral, anal, cardiac, trachea-esophageal, renal/kidney, and limb defects where as VATER only has vertebral, anal, trachea-esophogeal, and renal defects. The "R" in VATER represented radial dysplasia. Though the differences are clear, the physical defects vary from case to case. See also 22q11 deletion syndrome Absent radius CHARGE Association Holt–Oram syndrome Feingold syndrome Pallister–Hall syndrome Townes–Brocks syndrome References Further reading McMullen, KP; Karnes, PS; Moir, CR; Michels, VV (Jun 28, 1996). "Familial recurrence of tracheoesophageal fistula and associated malformations". American Journal of Medical Genetics. 63 (4): 525–8. doi:10.1002/(sici)1096-8628(19960628)63:4<525::aid-ajmg3>3.0.co;2-n. PMID 8826429. == External links ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

The term 'Bempedoic acid/ezetimibe' keeps coming up in medical discussions. What does it stand for?

Bempedoic acid/ezetimibe, sold under the brand name Nexlizet among others, is a fixed-dose combination medication used for the treatment of high cholesterol. It is a combination of bempedoic acid and ezetimibe.The most common side effects are hyperuricemia (high blood levels of uric acid) and constipation.Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor and ezetimibe is a cholesterol absorption inhibitor. Bempedoic acid works by blocking an enzyme in the liver called adenosine triphosphate citrate lyase, which is involved in making cholesterol. Ezetimibe works by binding to a gut protein called Niemann-Pick C1 Like 1, preventing cholesterol from being absorbed into the blood from the gut.The combination was approved for medical use in the United States in February 2020, and in the European Union in March 2020. Medical uses In the US bempedoic acid/ezetimibe is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.In the EU bempedoic acid/ezetimibe is indicated in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to diet: in combination with a statin in people unable to reach LDL-C goals with the maximum tolerated dose of a statin in addition to ezetimibe alone in people who are either statin-intolerant or for whom a statin is contraindicated, and are unable to reach LDL-C goals with ezetimibe alone, in people already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin. Contraindications It the European Union it must not be used in pregnant or breast-feeding women. Use during pregnancy is not recommended in the US. History The European Medicines Agency (EMA) recommended approval of bempedoic acid/ezetimibe (Nustendi) in the EU in January 2020.Bempedoic acid/ezetimibe was approved in the United States in February 2020, and in the European Union in March 2020.Two studies showed that bempedoic acid and ezetimibe effectively reduced LDL cholesterol levels in participants with hypercholesterolemia and heart disease or who were at high risk of heart disease. High cholesterol is a risk factor for heart disease.The first study involved 382 participants also taking the maximum tolerated doses of statins. After three months, LDL cholesterol levels were reduced by 36% in participants taking bempedoic acid and ezetimibe compared with a reduction of 23% with ezetimibe alone, 17% with bempedoic acid alone and an increase of around 2% with placebo (a dummy treatment).The second study involved 269 participants with high cholesterol levels who were not able to take a statin or were taking a low dose of a statin. All the participants were also taking ezetimibe. After three months, LDL cholesterol levels were reduced by 23% in participants taking bempedoic acid in addition to ezetimibe compared with an increase of around 5% in participants taking placebo and ezetimibe. References External links "Bempedoic acid". Drug Information Portal. U.S. National Library of Medicine. "Ezetimibe". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03337308 for "A Study Evaluating the Safety and Efficacy of Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo in Patients Treated With Maximally Tolerated Statin Therapy" at ClinicalTrials.gov

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Could you provide a brief overview of 'Trifluridine/tipiracil' in a medical context?

Trifluridine/tipiracil, sold under the brand name Lonsurf, is a fixed-dose combination medication that is used as a third- or fourth-line treatment of metastatic colorectal cancer or gastric cancer, after chemotherapy and targeted therapeutics have failed. It is a combination of two active pharmaceutical ingredients: trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor. Tipiracil prevents rapid metabolism of trifluridine, increasing the bioavailability of trifluridine.The most common side effects include neutropenia (low levels of neutrophils, a type of white blood cell that fights infection), feeling sick, tiredness and anemia (low red blood cell counts). Medical uses It is used as a third- or fourth-line treatment for metastatic colorectal cancer or gastric cancer, after chemotherapy and biologic therapy. Contraindications The combination caused harm to the fetus of pregnant animals, and it was not tested in pregnant women. Pregnant women should not take it, and women should not become pregnant while taking it. Adverse effects The combination severely suppresses bone marrow function, resulting in fewer red blood cells, white blood cells, and platelets, so many people taking it are at risk for infections, anemia, and blood loss from lack of clotting. It also causes digestive problems, with more than 10% of people experiencing loss of appetite, diarrhea, nausea, and vomiting. More than 10% of people experience fatigue and fever.Between 1 and 10% of people have skin and mucosa issues, like rashes and itchiness, or mouth sores, as well as skin sloughing, numbness, redness, and swelling of their palms and soles. Dizziness and confusion are common as well. Interactions Only in vitro interaction studies are available. In these, trifluridine used the concentrative nucleoside transporter 1 (CNT1) and equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), and tipiracil was transported by the solute carrier proteins SLC22A2 and SLC47A1. Drugs that interact with these transporters could influence blood plasma concentrations of trifluridine and tipiracil. Trifluridine, being a thymidine phosphorylase inhibitor, could also interact with substrates of this enzyme such as zidovudine. Pharmacology Mechanism of action The drug consists of the cytotoxin trifluridine and the thymidine phosphorylase inhibitor (TPI) tipiracil. Trifluridine is incorporated into DNA during DNA synthesis and inhibits tumor cell growth. Trifluridine (TFT) is incorporated into DNA by phosphorylation by thymidylate kinase (TK) to TF-TMP; TF-TMP then covalently binds to tyrosine 146 of the active site of thymidylate synthase (TS) inhibiting the enzymes activity. TS is vital to the synthesis of DNA because it is an enzyme involved in the synthesis of the deoxynucleotide, thymidine triphosphate (dTTP). Inhibition of TS depletes the cell of dTTP and causes accumulation of deoxyuridine monophosphate (dUMP), which increases the likelihood that uracil gets misincorporated into the DNA. Also, subsequent phosphorylations of TF-TMP cause an increased level of TF-TTP within the cell, which results in it being incorporated into DNA. Even though the exact mechanism of how TFT causes DNA damage is not completely understood, it is hypothesized that the incorporation TF-TTP in DNA leads to DNA strand break formation.Tipiracil prevents the degradation of trifluridine via thymidine phosphorylase (TP) when taken orally and also has antiangiogenic properties. History Since the synthesis of 5-fluorouracil (5-FU) in 1957, fluoropyrimidines have been used to treat many types of cancer. Due to the drawbacks of 5-FU therapy, such as having to be administered over long periods of time via intravenous infusion and the development of resistance in tumors, more convenient and efficacious fluoropyrimidine therapy has been desired. The fluoropyrimidine component of this drug, trifluridine, was first synthesized in 1964 by Heidelberger et al.By the late 1960s, Phase I and Phase II clinical trials of intravenous trifluridine alone initially proved to be disappointing. Its pharmacokinetic profile during these clinical trials showed that the drug exhibited a very short half-life while in serum (12 minutes post-injection). Adjustments in the dosing regimen improved its effects in small studies, but the effect was short-lived.Researchers later found out that trifluridine, when taken orally, was broken down into the inactive metabolites 5-trifluoromethyluracil and 5-trifluoromethyl-2,4(1H,3,H)-pyrimidinedione (FTY) during its extensive first pass metabolism in the liver via the enzyme thymidine phosphorylase. It was then hypothesized that orally administered FTD concentrations could be increased and maintained if the drug was given with a thymidine phosphorylase inhibitor.Trifluridine/tipiracil was approved by the U.S. FDA in September 2015, and by the European Medicines Agency in April 2016. References External links "Tipiracil hydrochloride mixture with trifluridine". Drug Information Portal. U.S. National Library of Medicine.

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

I'm seeking clarification on the medical term 'Variant Creutzfeldt–Jakob disease.' Could you explain it?

Variant Creutzfeldt–Jakob disease (vCJD), commonly referred to as "mad cow disease" or "human mad cow disease" to distinguish it from its BSE counterpart, is a fatal type of brain disease within the transmissible spongiform encephalopathy family. Initial symptoms include psychiatric problems, behavioral changes, and painful sensations. In the later stages of the illness, patients may exhibit poor coordination, dementia and involuntary movements. The length of time between exposure and the development of symptoms is unclear, but is believed to be years to decades. Average life expectancy following the onset of symptoms is 13 months.It is caused by prions, which are misfolded proteins. Spread is believed to be primarily due to eating bovine spongiform encephalopathy (BSE)-infected beef. Infection is also believed to require a specific genetic susceptibility. Spread may potentially also occur via blood products or contaminated surgical equipment. Diagnosis is by brain biopsy but can be suspected based on certain other criteria. It is different from typical Creutzfeldt–Jakob disease, though both are due to prions.Treatment for vCJD involves supportive care. As of 2020, 178 cases of vCJD have been recorded in the United Kingdom, due to a 1990s outbreak, and 50 cases in the rest of the world. The disease has become less common since 2000. The typical age of onset is less than 30 years old. It was first identified in 1996 by the National CJD Surveillance Unit in Edinburgh, Scotland. Signs and symptoms Initial symptoms include psychiatric problems, behavioral changes, and painful sensations. In the later stages of the illness, patients may exhibit poor coordination, dementia and involuntary movements. The length of time between exposure and the development of symptoms is unclear, but is believed to be years. Average life expectancy following the onset of symptoms is 13 months. Cause Tainted beef In the UK, the primary cause of vCJD has been eating beef tainted with bovine spongiform encephalopathy. A 2012 study by the Health Protection Agency showed that around 1 in 2,000 people in the UK show signs of abnormal prion accumulation.Jonathan Quick, instructor of medicine at the Department of Global Health and Social Medicine at Harvard Medical School, stated that bovine spongiform encephalopathy or BSE is the first man-made epidemic, or "Frankenstein" disease, because a human decision to feed meat and bone meal to previously herbivorous cattle (as a source of protein) caused what was previously an animal pathogen to enter into the human food chain, and from there to begin causing humans to contract vCJD. Blood products As of 2018, evidence suggests that while there may be prions in the blood of individuals with vCJD this is not the case in individuals with sporadic CJD.In 2004, a report showed that vCJD can be transmitted by blood transfusions. The finding alarmed healthcare officials because a large epidemic of the disease could result in the near future. A blood test for vCJD infection is possible but is not yet available for screening blood donations. Significant restrictions exist to protect the blood supply. The UK government banned anyone who had received a blood transfusion since January 1980 from donating blood. Since 1999 there has been a ban in the UK for using UK blood to manufacture fractional products such as albumin. Whilst these restrictions may go some way to preventing a self-sustaining epidemic of secondary infections, the number of infected blood donations is unknown and could be considerable. In June 2013 the government was warned that deaths, then at 176, could rise five-fold through blood transfusions.On 28 May 2002, the United States Food and Drug Administration instituted a policy that excludes from blood donation anyone having spent at least six months in certain European countries (or three months in the United Kingdom) from 1980 to 1996. Given the large number of U.S. military personnel and their dependents residing in Europe, it was expected that over 7% of donors would be deferred due to the policy. Later changes to this policy have relaxed the restriction to a cumulative total of five years or more of civilian travel in European countries (six months or more if military). The three-month restriction on travel to the UK, however, has not been changed.In New Zealand, the New Zealand Blood Service (NZBS) in 2000 introduced measures to preclude permanently donors having resided in the United Kingdom (including the Isle of Man and the Channel Islands) for a total of six months or more between January 1980 and December 1996. The measure resulted in ten percent of New Zealands active blood donors at the time becoming ineligible to donate blood. In 2003, the NZBS further extended restrictions to permanently preclude donors having received a blood transfusion in the United Kingdom since January 1980, and in April 2006, restrictions were further extended to include the Republic of Ireland and France.Similar regulations are in place where anyone having spent more than six months for Germany or one year for France living in the UK between January 1980 and December 1996 is permanently banned from donating blood.In Canada, individuals are not eligible to donate blood or plasma if they have spent a cumulative total of three months or more in the UK, or France from 1 January 1980 to December 31, 1996. They are also ineligible if they have spent a cumulative total of five years or more in the Republic of Ireland since January 1, 1980 through 31 December 2001 or spent a cumulative total of six months or more in Saudi Arabia from January 1, 1980, through December 31, 1996 or if they have had a blood transfusion in the UK, France or Western Europe since 1980.In Poland, anyone having spent cumulatively six months or longer between 1 January 1980 and 31 December 1996 in the UK, Ireland, or France is permanently barred from donating.In France, anyone having lived or stayed in the United Kingdom a total of over one year between 1 January 1980 and 31 December 1996 is permanently barred from donating.In the Czech Republic, anyone having spent more than six months in the UK or France between the years 1980 and 1996 or received transfusion in the UK after the year 1980 is not allowed to donate blood.In Finland, anyone having lived or stayed in the British Isles a total of over six months between 1 January 1980 and 31 December 1996 is permanently barred from donating. Sperm donation In the U.S., the FDA has banned import of any donor sperm, motivated by a risk of variant Creutzfeldt-Jakob disease, inhibiting the once popular import of Scandinavian sperm. Despite this, the scientific consensus is that the risk is negligible, as there is no evidence Creutzfeldt–Jakob is sexually transmitted. Occupational contamination In France, the last two victims of variant Creutzfeldt-Jakob disease, who died in 2019 and 2021, were research technicians at the National Research Institute for Agriculture, Food and the Environment (INRAE). Emilie Jaumain, who died in 2019, at the age of 33, had been the victim of a work accident in 2010, during which she had pricked herself with a tool contaminated with infected brain. The efficacy of this route of contamination has been unambiguously demonstrated in primates. Pierrette C., who died in 2021, had been victim of the same type of work accident. After her diagnosis, a moratorium was initiated in all French laboratories on research activities on infectious prions. In March 2022, INRAE recognized the occupational cause of these two deaths. This raises serious questions about the safety of personnel in these laboratories. Indeed, inspections have noted serious failures in the protection of agents in the face of this deadly risk, and the long incubation period of this disease leads to fears of new cases in the future, hence great concern. Other causes Eating other types of brains such as those from squirrels is not recommended as one person contracted vCJD from eating the brain of a squirrel. Mechanism Despite the consumption of contaminated beef in the UK being high, vCJD has infected a small number of people. One explanation for this can be found in the genetics of people with the disease. The human PRNP protein which is subverted in prion disease can occur with either methionine or valine at amino acid 129, without any apparent physiological difference. Of the overall Caucasian population, about 40% have two methionine-containing alleles, 10% have two valine-containing alleles, and the other 50% are heterozygous at this position. Only a single person with vCJD tested was found to be heterozygous; most of those affected had two copies of the methionine-containing form. It is not yet known whether those unaffected are actually immune or only have a longer incubation period until symptoms appear. Diagnosis Definitive Examination of brain tissue is required to confirm a diagnosis of variant CJD. The following confirmatory features should be present: Numerous widespread kuru-type amyloid plaques surrounded by vacuoles in both the cerebellum and cerebrum – florid plaques. Spongiform change and extensive prion protein deposition shown by immunohistochemistry throughout the cerebellum and cerebrum. Suspected Current age or age at death less than 55 years (a brain autopsy is recommended, however, for all physician-diagnosed CJD cases). Psychiatric symptoms at illness onset and/or persistent painful sensory symptoms (frank pain and/or dysesthesia). Dementia, and development ≥4 months after illness onset of at least two of the following five neurologic signs: poor coordination, myoclonus, chorea, hyperreflexia, or visual signs. (If persistent painful sensory symptoms exist, ≥4 months delay in the development of the neurologic signs is not required). A normal or an abnormal EEG, but not the diagnostic EEG changes often seen in classic CJD. Duration of illness of over 6 months. Routine investigations do not suggest an alternative, non-CJD diagnosis. No history of getting human pituitary growth hormone or a dura mater graft from a cadaver. No history of CJD in a first degree relative or prion protein gene mutation in the person. Classification vCJD is a separate condition from classic Creutzfeldt–Jakob disease (though both are caused by PrP prions). Both classic and variant CJD are subtypes of Creutzfeldt–Jakob disease. There are three main categories of CJD disease: sporadic CJD, hereditary CJD, and acquired CJD, with variant CJD being in the acquired group along with iatrogenic CJD. The classic form includes sporadic and hereditary forms. Sporadic CJD is the most common type.ICD-10 has no separate code for vCJD and such cases are reported under the Creutzfeldt–Jakob disease code (A81.0). Epidemiology The Lancet in 2006 suggested that it may take more than 50 years for vCJD to develop, from their studies of kuru, a similar disease in Papua New Guinea. The reasoning behind the claim is that kuru was possibly transmitted through cannibalism in Papua New Guinea when family members would eat the body of a dead relative as a sign of mourning. In the 1950s, cannibalism was banned in Papua New Guinea. In the late 20th century, however, kuru reached epidemic proportions in certain Papua New Guinean communities, therefore suggesting that vCJD may also have a similar incubation period of 20 to 50 years. A critique to this theory is that while mortuary cannibalism was banned in Papua New Guinea in the 1950s, that does not necessarily mean that the practice ended. Fifteen years later Jared Diamond was informed by Papuans that the practice continued.These researchers noticed a genetic variation in some people with kuru that has been known to promote long incubation periods. They have also proposed that individuals having contracted CJD in the early 1990s represent a distinct genetic subpopulation, with unusually short incubation periods for bovine spongiform encephalopathy (BSE). This means that there may be many more people with vCJD with longer incubation periods, which may surface many years later.Prion protein is detectable in lymphoid and appendix tissue up to two years before the onset of neurological symptoms in vCJD. Large scale studies in the UK have yielded an estimated prevalence of 493 per million, higher than the actual number of reported cases. This finding indicates a large number of asymptomatic cases and the need to monitor. Society and culture In 1997, a number of people from Kentucky developed CJD. It was discovered that all had consumed squirrel brains. A coincidental relationship between the disease and this dietary practice may have been involved. In 2008, UK scientists expressed concern over the possibility of a second wave of human cases due to the wide exposure and long incubation of some cases of vCJD. In 2015, a man from New York developed vCJD after eating squirrel brains. From November 2017 to April 2018, four suspected cases of the disease arose in Rochester. United Kingdom Researchers believe one in 2,000 people in the UK is a carrier of the disease, linked to eating contaminated beef. The survey provides the most robust prevalence measure to date—and identifies abnormal prion protein across a wider age group than found previously and in all genotypes, indicating "infection" may be relatively common. This new study examined over 32,000 anonymous appendix samples. Of these, 16 samples were positive for abnormal prion protein, indicating an overall prevalence of 493 per million population, or one in 2,000 people are likely to be carriers. No difference was seen in different birth cohorts (1941–1960 and 1961–1985), in both sexes, and there was no apparent difference in abnormal prion prevalence in three broad geographical areas. Genetic testing of the 16 positive samples revealed a higher proportion of valine homozygous (VV) genotype on the codon 129 of the gene encoding the prion protein (PRNP) compared with the general UK population. This also differs from the 176 people with vCJD, all of whom to date have been methionine homozygous (MM) genotype. The concern is that individuals with this VV genotype may be susceptible to developing the condition over longer incubation periods. Human BSE foundation In 2000 a voluntary support group was formed by families of people who had died from vCJD. The goal was to support other families going through a similar experience. This support was provided through a National Helpline, a Carers Guide, a website and a network of family befriending. The support groups had an internet presence at the turn of the 21st century. The driving force behind the foundation was Lester Firkins, whose young son had died from the disease.In October 2000 the report of the government inquiry into BSE chaired by Lord Phillips was published. The BSE report criticised former Conservative Party Agriculture Ministers John Gummer, John MacGregor and Douglas Hogg. The report concluded that the escalation of BSE into a crisis was the result of intensive farming, particularly with cows being fed with cow and sheep remains. Furthermore, the report was critical of the way the crisis had been handled. There was a reluctance to consider the possibility that BSE could cross the species barrier. The government assured the public that British beef was safe to eat, with agriculture minister John Gummer famously feeding his daughter a burger. The British government were reactive more than proactive in response; the worldwide ban on all British beef exports in March 1996 was a serious economic blow.The foundation had been calling for compensation to include a care package to help relatives look after those with vCJD. There have been widespread complaints of inadequate health and social services support. Following the Phillips Report in October 2001, the government announced a compensation scheme for British people affected with vCJD. The multi-million-pound financial package was overseen by the vCJD Trust. A memorial plaque for those who have died due to vCJD was installed in central London in approximately 2000. It is located on the boundary wall of St Thomas Hospital in Lambeth facing the Riverside Walk of Albert Embankment. See also Jonathan Simms, a person who died from vCJD Mepacrine == References ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Could you please explain the term 'Adenosine deaminase deficiency' in simple language?

Adenosine deaminase deficiency (ADA deficiency) is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–15% of all cases of autosomal recessive forms of severe combined immunodeficiency (SCID) among non-inbred populations.ADA deficiency can present in infancy, childhood, adolescence, or adulthood. Age of onset and severity is related to some 29 known genotypes associated with the disorder. It occurs in fewer than one in 100,000 live births worldwide. Signs and symptoms The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread skin rashes. Affected children also grow much more slowly than healthy children and some have developmental delay. Most individuals with ADA deficiency are diagnosed with SCID in the first 6 months of life.An association with polyarteritis nodosa has been reported. Genetics The enzyme adenosine deaminase is encoded by the ADA gene on chromosome 20. ADA deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 20 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.Age of onset and severity is related to some 29 known genotypes associated with the disorder. Pathophysiology ADA deficiency is due to a lack of the enzyme adenosine deaminase. This deficiency results in an accumulation of deoxyadenosine, which, in turn, leads to: a buildup of dATP in all cells, which inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are highly susceptible to this condition. an increase in S-adenosylhomocysteine since the enzyme adenosine deaminase is important in the purine salvage pathway; both substances are toxic to immature lymphocytes, which thus fail to mature.Because T cells undergo proliferation and development in the thymus, affected individuals typically have a small, underdeveloped thymus. As a result, the immune system is severely compromised or completely lacking. Diagnosis The diagnosis is based on clinical features, with a concomitant decreased blood adenosine deaminase level supporting the diagnosis. Treatment Treatments include: bone marrow transplant ADA enzyme in PEG vehicle Gene therapy In September 1990, the first gene therapy to combat this disease was performed by Dr. William French Anderson on a four-year-old girl, Ashanti DeSilva, at the National Institutes of Health, Bethesda, Maryland, U.S.A. In April 2016 the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed and recommended for approval a stem cell gene therapy called Strimvelis, for children with ADA-SCID for whom no matching bone marrow donor is available. History ADA deficiency was discovered in 1972 by Eloise Giblett, a professor at the University of Washington. The ADA gene was used as a marker for bone marrow transplants. A lack of ADA activity was discovered by Giblett in an immunocompromised transplant candidate. After discovering a second case of ADA deficiency in an immunocompromised patient, ADA deficiency was recognized as the first immunodeficiency disorder. References Further reading Adenosine deaminase deficiency - Genetics Home Reference == External links ==

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I'm curious about the meaning of the medical term 'Olanzapine.' Can you give me some insights?

Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.Common side effects include weight gain, movement disorders, dizziness, feeling tired, constipation, and dry mouth. Other side effects include low blood pressure with standing, allergic reactions, neuroleptic malignant syndrome, high blood sugar, seizures, and tardive dyskinesia. In older people with dementia, its use increases the risk of death. Use in the later part of pregnancy may result in a movement disorder in the baby for some time after birth. Although how it works is not entirely clear, it blocks dopamine and serotonin receptors.Olanzapine was patented in 1991 and approved for medical use in the United States in 1996. It is available as a generic medication. In 2019, it was the 185th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Lilly also markets olanzapine in a fixed-dose combination with fluoxetine as olanzapine/fluoxetine (Symbyax). Medical uses Schizophrenia The first-line psychiatric treatment for schizophrenia is antipsychotic medication, with olanzapine being one such medication. Olanzapine appears to be effective in reducing symptoms of schizophrenia, treating acute exacerbations, and treating early-onset schizophrenia. The usefulness of maintenance therapy, however, is difficult to determine, as more than half of people in trials quit before the 6-week completion date. Treatment with olanzapine (like clozapine) may result in increased weight gain and increased glucose and cholesterol levels when compared to most other second-generation antipsychotic drugs used to treat schizophrenia. Comparison The National Institute for Health and Care Excellence, the British Association for Psychopharmacology, and the World Federation of Societies for Biological Psychiatry suggest that little difference in effectiveness is seen between antipsychotics in prevention of relapse, and recommend that the specific choice of antipsychotic be chosen based on a persons preference and the drugs side-effect profile. The U.S. Agency for Healthcare Research and Quality concludes that olanzapine is not different from haloperidol in the treatment of positive symptoms and general psychopathology, or in overall assessment, but that it is superior for the treatment of negative and depressive symptoms. It has a lower risk of causing movement disorders than typical antipsychotics.In a 2013 comparison of fifteen antipsychotic drugs in schizophrenia, olanzapine was ranked third in efficacy. It was 5% more effective than risperidone (fourth), 24-27% more effective than haloperidol, quetiapine, and aripiprazole, and 33% less effective than clozapine (first). A 2013 review of first-episode schizophrenia concluded that olanzapine is superior to haloperidol in providing a lower discontinuation rate, and in short-term symptom reduction, response rate, negative symptoms, depression, cognitive function, discontinuation due to poor efficacy, and long-term relapse, but not in positive symptoms or on the clinical global impressions (CGI) score. In contrast, pooled second-generation antipsychotics showed superiority to first-generation antipsychotics only against the discontinuation, negative symptoms (with a much larger effect seen among industry- compared to government-sponsored studies), and cognition scores. Olanzapine caused less extrapyramidal side effects and less akathisia, but caused significantly more weight gain, serum cholesterol increase, and triglyceride increase than haloperidol.A 2012 review concluded that among ten atypical antipsychotics, only clozapine, olanzapine, and risperidone were better than first-generation antipsychotics. A 2011 review concluded that neither first- nor second-generation antipsychotics produce clinically meaningful changes in CGI scores, but found that olanzapine and amisulpride produce larger effects on the PANSS and BPRS batteries than five other second-generation antipsychotics or pooled first-generation antipsychotics. A 2010 Cochrane systematic review found that olanzapine may have a slight advantage in effectiveness when compared to aripiprazole, quetiapine, risperidone, and ziprasidone. No differences in effectiveness were detected when comparing olanzapine to amisulpride and clozapine. A 2014 meta-analysis of nine published trials having minimum duration six months and median duration 52 weeks concluded that olanzapine, quetiapine, and risperidone had better effects on cognitive function than amisulpride and haloperidol. Bipolar disorder Olanzapine is recommended by the National Institute for Health and Care Excellence as a first-line therapy for the treatment of acute mania in bipolar disorder. Other recommended first-line treatments are haloperidol, quetiapine, and risperidone. It is recommended in combination with fluoxetine as a first-line therapy for acute bipolar depression, and as a second-line treatment by itself for the maintenance treatment of bipolar disorder.The Network for Mood and Anxiety Treatments recommends olanzapine as a first-line maintenance treatment in bipolar disorder and the combination of olanzapine with fluoxetine as second-line treatment for bipolar depression.A review on the efficacy of olanzapine as maintenance therapy in patients with bipolar disorder was published by Dando & Tohen in 2006. A 2014 meta-analysis concluded that olanzapine with fluoxetine was the most effective among nine treatments for bipolar depression included in the analysis. Other uses Olanzapine may be useful in promoting weight gain in underweight adult outpatients with anorexia nervosa. However, no improvement of psychological symptoms was noted.Olanzapine has been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and has since been used in the treatment of a range of mood and anxiety disorders. Olanzapine is no less effective than lithium or valproate and more effective than placebo in treating bipolar disorder. It has also been used for Tourette syndrome and stuttering.Olanzapine has been studied for the treatment of hyperactivity, aggressive behavior, and repetitive behaviors in autism.Olanzapine is frequently prescribed off-label for the treatment of insomnia, including difficulty falling asleep and staying asleep, even though such use is not recommended. The daytime sedation experienced with olanzapine is generally comparable to quetiapine and lurasidone, which is a frequent complaint in clinical trials. In some cases, the sedation due to olanzapine impaired the ability of people to wake up at a consistent time every day. Some evidence of efficacy for treating insomnia is seen; however, side effects such as dyslipidemia and neutropenia, which may possibly be observed even at low doses, outweigh any potential benefits for insomnia that is not due to an underlying mental health condition.Olanzapine has been recommended to be used in antiemetic regimens in people receiving chemotherapy that has a high risk for vomiting. Specific populations Pregnancy and lactation Olanzapine is associated with the highest placental exposure of any atypical antipsychotic. Despite this, the available evidence suggests it is safe during pregnancy, although the evidence is insufficiently strong to say anything with a high degree of confidence. Olanzapine is associated with weight gain, which according to recent studies, may put olanzapine-treated patients offspring at a heightened risk for neural tube defects (e.g. spina bifida). Breastfeeding in women taking olanzapine is advised against because olanzapine is secreted in breast milk, with one study finding that the exposure to the infant is about 1.8% that of the mother. Elderly Citing an increased risk of stroke, in 2004, the Committee on the Safety of Medicines in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis. A BBC investigation in June 2008 found that this advice was being widely ignored by British doctors. Evidence suggested that the elderly are more likely to experience weight gain on olanzapine compared to aripiprazole and risperidone. Adverse effects The principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangement in blood-lipid and blood-sugar profiles (see section metabolic effects). A 2013 meta-analysis of the efficacy and tolerance of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APDs compared with an SMD of 0.74. Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine, but may include tremors and muscle rigidity. Aripiprazole, asenapine, clozapine, quetiapine and olanzapine, in comparison to other antipsychotic drugs, are less frequently associated with hyperprolactinaemia. Although these drugs can cause transient or sustained hyperprolactinaemia, the risk is much lower. Owing to its partial dopaminergic agonist effect, aripiprazole is likely to reduce prolactin levels and, in some patients, can cause hypoprolactinaemia. Although olanzapine causes an early dose-related rise in prolactin, this is less frequent and less marked than that seen with haloperidol, and is usually transient. A rise in prolactin is seen in about half of patients on olanzapine compared to over 90% of those taking risperidone, and enduring increases were less frequent in those taking olanzapine.It is not recommended to be used by IM injection in acute myocardial infarction, bradycardia, recent heart surgery, severe hypotension, sick sinus syndrome, and unstable angina.Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce nontrivial high blood sugar in people with diabetes mellitus. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of dystonic reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the bodys natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur.Other side effects include galactorrhea, amenorrhea, gynecomastia, and erectile dysfunction (impotence). Paradoxical effects Olanzapine is used therapeutically to treat serious mental illness. Occasionally, it can have the opposite effect and provoke serious paradoxical reactions in a small subgroup of people, causing unusual changes in personality, thoughts, or behavior; hallucinations and excessive thoughts about suicide have also been linked to olanzapine use. Drug-induced OCD Many different types of medication can create or induce pure obsessive-compulsive disorder (OCD) in patients who have never had symptoms before. A new chapter about OCD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013) now specifically includes drug-induced OCD. Metabolic effects The US Food and Drug Administration (FDA) requires all atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome. These effects may be related to the drugs ability to induce weight gain, although some reports have been made of metabolic changes in the absence of weight gain. Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, risperidone. Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain based on various measures. The effect is dose dependent in humans and animal models of olanzapine-induced metabolic side effects. There are some case reports of olanzapine-induced diabetic ketoacidosis. Olanzapine may decrease insulin sensitivity, though one 3-week study seems to refute this. It may also increase triglyceride levels.Despite weight gain, a large multicenter, randomized National Institute of Mental Health study found that olanzapine was better at controlling symptoms because patients were more likely to remain on olanzapine than the other drugs. One small, open-label, nonrandomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain, but this has not been substantiated in a blinded experimental setting. Post-injection delirium/sedation syndrome Postinjection delirium/sedation syndrome (PDSS) is a rare syndrome that is specific to the long-acting injectable formulation of olanzapine, olanzapine pamoate. The incidence of PDSS with olanzapine pamoate is estimated to be 0.07% of administrations, and is unique among other second-generation, long-acting antipsychotics (e.g. paliperidone palmitate), which do not appear to carry the same risk. PDSS is characterized by symptoms of delirium (e.g. confusion, difficulty speaking, and uncoordinated movements) and sedation. Most people with PDSS exhibit both delirium and sedation (83%). Although less specific to PDSS, a majority of cases (67%) involved a feeling of general discomfort. PDSS may occur due to accidental injection and absorption of olanzapine pamoate into the bloodstream, where it can act more rapidly, as opposed to slowly distributing out from muscle tissue. Using the proper, intramuscular-injection technique for olanzapine pamoate helps to decrease the risk of PDSS, though it does not eliminate it entirely. This is why the FDA advises that people who are injected with olanzapine pamoate be watched for 3 hours after administration, in the event that PDSS occurs. Animal toxicology Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals. Discontinuation The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly, vertigo, numbness, or muscle pains may occur. Symptoms generally resolve after a short time.Tentative evidence indicates that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely, tardive dyskinesia can occur when the medication is stopped. Overdose Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness, and coma. Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 2000 mg. Fatalities generally have occurred with olanzapine plasma concentrations greater than 1000 ng/mL post mortem, with concentrations up to 5200 ng/mL recorded (though this might represent confounding by dead tissue, which may release olanzapine into the blood upon death). No specific antidote for olanzapine overdose is known, and even physicians are recommended to call a certified poison control center for information on the treatment of such a case. Olanzapine is considered moderately toxic in overdose, more toxic than quetiapine, aripiprazole, and the SSRIs, and less toxic than the monoamine oxidase inhibitors and tricyclic antidepressants. Interactions Drugs or agents that increase the activity of the enzyme CYP1A2, notably tobacco smoke, may significantly increase hepatic first-pass clearance of olanzapine; conversely, drugs that inhibit CYP1A2 activity (examples: ciprofloxacin, fluvoxamine) may reduce olanzapine clearance. Carbamazepine, a known enzyme inducer, has decreased the concentration/dose ration of olanzapine by 33% compared to olanzapine alone. Another enzyme inducer, ritonavir, has also been shown to decrease the bodys exposure to olanzapine, due to its induction of the enzymes CYP1A2 and uridine 5-diphospho-glucuronosyltransferase (UGT).Probenecid increases the total exposure (area under the curve) and maximum plasma concentration of olanzapine. Although olanzapines metabolism includes the minor metabolic pathway of CYP2D6, the presence of the CYP2D6 inhibitor fluoxetine does not have a clinically significant effect on olanzapines clearance. Pharmacology Pharmacodynamics Olanzapine was first discovered while searching for a chemical analog of clozapine that would not require hematological monitoring. Investigation on a series of thiophene isosteres on 1 of the phenyl rings in clozapine, a thienobenzodiazepine analog (olanzapine) was discovered.Olanzapine has a higher affinity for 5-HT2A serotonin receptors than D2 dopamine receptors, which is a common property of most atypical antipsychotics, aside from the benzamide antipsychotics such as amisulpride along with the nonbenzamides aripiprazole, brexpiprazole, blonanserin, cariprazine, melperone, and perospirone. Olanzapine had the highest affinity of any second-generation antipsychotic towards the P-glycoprotein in one in vitro study. P-glycoprotein transports a myriad of drugs across a number of different biological membranes (found in numerous body systems) including the blood-brain barrier (a semipermeable membrane that filters the contents of blood prior to it reaching the brain); P-GP inhibition could mean that less brain exposure to olanzapine results from this interaction with the P-glycoprotein. A relatively large quantity of commonly encountered foods and medications inhibit P-GP, and pharmaceuticals fairly commonly are either substrates of P-GP, or inhibit its action; both substrates and inhibitors of P-GP effectively increase the permeability of the blood-brain barrier to P-GP substrates and subsequently increase the central activity of the substrate, while reducing the local effects on the GI tract. The mediation of olanzapine in the central nervous system by P-GP means that any other substance or drug that interacts with P-GP increases the risk for toxic accumulations of both olanzapine and the other drug.Olanzapine is a potent antagonist of the muscarinic M3 receptor, which may underlie its diabetogenic side effects. Additionally, it also exhibits a relatively low affinity for serotonin 5-HT1, GABAA, beta-adrenergic receptors, and benzodiazepine binding sites.The antagonistic effects of olanzapine at 5-HT2c, histaminergic H1, and muscarinic M3 receptors have been implicated in weight gain.The mode of action of olanzapines antipsychotic activity is unknown. It may involve antagonism of dopamine and serotonin receptors. Antagonism of dopamine receptors is associated with extrapyramidal effects such as tardive dyskinesia (TD), and with therapeutic effects. Antagonism of muscarinic acetylcholine receptors is associated with anticholinergic side effects such as dry mouth and constipation; in addition, it may suppress or reduce the emergence of extrapyramidal effects for the duration of treatment, but it offers no protection against the development of TD. In common with other second-generation (atypical) antipsychotics, olanzapine poses a relatively low risk of extrapyramidal side effects including TD, due to its higher affinity for the 5HT2A receptor over the D2 receptor.Antagonizing H1 histamine receptors causes sedation and may cause weight gain, although antagonistic actions at serotonin 5-HT2C and dopamine D2 receptors have also been associated with weight gain and appetite stimulation. Pharmacokinetics Metabolism Olanzapine is metabolized by the cytochrome P450 (CYP) system; principally by isozyme 1A2 (CYP1A2) and to a lesser extent by CYP2D6. By these mechanisms, more than 40% of the oral dose, on average, is removed by the hepatic first-pass effect. Clearance of olanzapine appears to vary by sex; women have roughly 25% lower clearance than men. Clearance of olanzapine also varies by race; in self-identified African Americans or Blacks, olanzapines clearance was 26% higher. A difference in the clearance is not apparent between individuals identifying as Caucasian, Chinese, or Japanese. Routine, pharmacokinetic monitoring of olanzapine plasma levels is generally unwarranted, though unusual circumstances (e.g. the presence of drug-drug interactions) or a desire to determine if patients are taking their medicine may prompt its use. Chemistry Olanzapine is unusual in having four well-characterised crystalline polymorphs and many hydrated forms. Chemical synthesis The preparation of olanzapine was first disclosed in a series of patents from Eli Lilly & Co. in the 1990s. In the final two steps, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile was reduced with stannous chloride in ethanol to give the substituted thienobenzodiazepine ring system, and this was treated with methylpiperazine in a mixture of dimethyl sulfoxide and toluene as solvent to produce the drug. Society and culture Regulatory status Olanzapine is approved by the US FDA for: Treatment—in combination with fluoxetine—of depressive episodes associated with bipolar disorder (December 2003).Long-term treatment of bipolar I disorder (January 2004). Long-term treatment—in combination with fluoxetine—of resistant depression (March 2009) Oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or sodium valproate) Intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults Oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults Treatment of the manifestations of psychotic disorders (September 1996 – March 2000).Short-term treatment of acute manic episodes associated with bipolar I disorder (March 2000) Short-term treatment of schizophrenia instead of the management of the manifestations of psychotic disorders (March 2000) Maintaining treatment response in schizophrenic patients who had been stable for about eight weeks and were then followed for a period of up to eight months (November 2000)The drug became generic in 2011. Sales of Zyprexa in 2008 were $2.2 billion in the US and $4.7 billion worldwide. Controversy and litigation Eli Lilly has faced many lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa, as well as by various governmental entities, insurance companies, and others. Lilly produced a large number of documents as part of the discovery phase of this litigation, which started in 2004; the documents were ruled to be confidential by a judge and placed under seal, and later themselves became the subject of litigation.In 2006, Lilly paid $700 million to settle around 8,000 of these lawsuits, and in early 2007, Lilly settled around 18,000 suits for $500 million, which brought the total Lilly had paid to settle suits related to the drug to $1.2 billion.A December 2006 New York Times article based on leaked company documents concluded that the company had engaged in a deliberate effort to downplay olanzapines side effects. The company denied these allegations and stated that the article had been based on cherry-picked documents. The documents were provided to the Times by Jim Gottstein, a lawyer who represented mentally ill patients, who obtained them from a doctor, David Egilman, who was serving as an expert consultant on the case. After the documents were leaked to online peer-to-peer, file-sharing networks by Will Hall and others in the psychiatric survivors movement, who obtained copies, in 2007 Lilly filed a protection order to stop the dissemination of some of the documents, which Judge Jack B. Weinstein of the Brooklyn Federal District Court granted. Judge Weinstein also criticized the New York Times reporter, Gottstein, and Egilman in the ruling. The Times of London also received the documents and reported that as early as 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales. On October 9, 2000, senior Lilly research physician Robert Baker noted that an academic advisory board to which he belonged was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose."Lilly had threatened Egilman with criminal contempt charges regarding the documents he took and provided to reporters; in September 2007, he agreed to pay Lilly $100,000 in return for the companys agreement to drop the threat of charges.In September 2008, Judge Weinstein issued an order to make public Lillys internal documents about the drug in a different suit brought by insurance companies, pension funds, and other payors.In March 2008, Lilly settled a suit with the state of Alaska, and in October 2008, Lilly agreed to pay $62 million to 32 states and the District of Columbia to settle suits brought under state consumer protection laws.In 2009, Eli Lilly pleaded guilty to a US federal criminal misdemeanor charge of illegally marketing Zyprexa for off-label use and agreed to pay $1.4 billion. The settlement announcement stated "Eli Lilly admits that between September 1999 and March 31, 2001, the company promoted Zyprexa in elderly populations as treatment for dementia, including Alzheimer’s dementia. Eli Lilly has agreed to pay a $515 million criminal fine and to forfeit an additional $100 million in assets."The outcomes described here, and their legal ramifications, were fueled by motions and appeals that were not resolved until 2010. In 2021, Gottstein summarized this tangle of legal activities, and their impact on the political landscape of psychiatry and antipsychiatry in the US, in The Zyprexa Papers. Trade names Olanzapine is generic and available under many trade names worldwide. Dosage forms Olanzapine is marketed in a number of countries, with tablets ranging from 2.5 to 20 mg. Zyprexa (and generic olanzapine) is available as an orally disintegrating "wafer", which rapidly dissolves in saliva. It is also available in 10-mg vials for intramuscular injection. Research Olanzapine has been studied as an antiemetic, particularly for the control of chemotherapy-induced nausea and vomiting (CINV).In general, olanzapine appears to be about as effective as aprepitant for the prevention of CINV, though some concerns remain for its use in this population. For example, concomitant use of metoclopramide or haloperidol increases the risk for extrapyramidal symptoms. Otherwise, olanzapine appears to be fairly well tolerated for this indication, with somnolence being the most common side effect.Olanzapine has been considered as part of an early psychosis approach for schizophrenia. The Prevention through Risk Identification, Management, and Education study, funded by the National Institute of Mental Health and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The study examined 60 patients with prodromal schizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with placebo. In this study, patients receiving olanzapine did not have a significantly lower risk of progressing to psychosis. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain. References External links "Olanzapine". Drug Information Portal. U.S. National Library of Medicine. Alex B (5 January 2007). "Lilly Settles With 18,000 Over Zyprexa". The New York Times.

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I'm seeking clarification on the medical term 'Esophageal candidiasis.' Could you explain it?

Esophageal candidiasis is an opportunistic infection of the esophagus by Candida albicans. The disease usually occurs in patients in immunocompromised states, including post-chemotherapy and in AIDS. However, it can also occur in patients with no predisposing risk factors, and is more likely to be asymptomatic in those patients. It is also known as candidal esophagitis or monilial esophagitis. Signs and symptoms People with esophageal candidiasis typically present with difficult or painful swallowing. Longstanding esophageal candidiasis can result in weight loss. There is often concomitant thrush in the mouth. Some patients present with esophageal candidiasis as a first presentation of systemic candidiasis. Diagnosis In most cases, the diagnosis is established based on response to therapy. Patients in whom esophageal candidiasis is suspected should receive a brief course of antifungal therapy with fluconazole. If the infection resolves after treatment with fluconazole, then the diagnosis of esophageal candidiasis is made and no further investigation is needed. However, if the infection persists or if there are other factors involved which may warrant further investigation, then patient will undergo an esophagogastroduodenoscopy if it is safe to do so. Endoscopy often reveals classic diffuse raised plaques that characteristically can be removed from the mucosa by the endoscope. Brushing or biopsy of the plaques shows yeast and pseudohyphae by histology that are characteristic of Candida species. Treatment The current first-line treatment is fluconazole, 200 mg. on the first day, followed by daily dosing of 100 mg. for at least 21 days total. Treatment should continue for 14 days after relief of symptoms. Other therapy options include: Nystatin is an effective treatment for mild esophageal candidiasis. It can be used as (swish, do not swallow) treatment for oral candidiasis that occurs with the use of asthma pumps. Oral fluconazole can be used for moderate to severe esophageal candidiasis (and oropharyngeal candidiasis). Other oral triazoles, such as itraconazole Caspofungin, used in refractory or systemic cases Amphotericin, used in refractory or systemic cases Mimidis, K; Papadopoulos, V; Margaritis, V; Thomopoulos, K; Gatopoulou, A; Nikolopoulou, V; Kartalis, G (February 2005). "Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present?". International Journal of Clinical Practice. 59 (2): 210–3. doi:10.1111/j.1742-1241.2004.00249.x. PMID 15854199. References == External links ==

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I'm encountering the term 'Primary sclerosing cholangitis' in medical literature. What's its definition?

Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain. The bile duct scarring that occurs in PSC narrows the ducts of the biliary tree and impedes the flow of bile to the intestines. Eventually, it can lead to cirrhosis of the liver and liver failure. PSC increases the risk of various cancers, including liver cancer, gallbladder carcinoma, colorectal cancer, and cholangiocarcinoma. The underlying cause of PSC is unknown. Genetic susceptibility, immune system dysfunction, and abnormal composition of the gut flora may play a role. This is further suggested by the observation that around 75% of individuals with PSC also have inflammatory bowel disease (IBD), most often ulcerative colitis.No effective medical treatment for primary sclerosing cholangitis is known. Its most definitive treatment is a liver transplant, but it can recur after transplantation. Many people affected by PSC require a liver transplant. PSC is a rare disease and most commonly affects people with IBD. About 3.0 to 7.5% of people with ulcerative colitis have PSC, and 80% of people with PSC have some form of IBD. Diagnosis usually occurs in people in their 30s or 40s. Individuals of Northern European ancestry are affected more often than people of Southern European or Asian descent. Men are affected more often than women. The disease was initially described in the mid-1800s, but was not fully characterized until the 1970s with the advent of improved medical-imaging techniques such as endoscopic retrograde cholangiopancreatography. Signs and symptoms Nearly half of people with PSC do not have symptoms, and are often incidentally discovered to have PSC due to abnormal liver function tests; however, a substantial proportion have debilitating signs and symptoms of the disease. Signs and symptoms of PSC may include severe itching and nonspecific fatigue. Yellowing of the skin and white portion of the eyes may also be seen. Enlargement of the liver and spleen are seen in roughly 40% of affected individuals. Abdominal pain affects about 20% of people with PSC.Multiple episodes of life-threatening acute cholangitis (infection within the bile ducts) can be seen due to impaired drainage of the bile ducts, which increases the risk of infection. Dark urine due to excess conjugated bilirubin, which is water-soluble and excreted by the kidneys (i.e. choluria) Malabsorption, especially of fat, and steatorrhea (fatty stool), due to an inadequate amount of bile reaching the small intestine, leading to decreased levels of the fat-soluble vitamins, A, D, E, and K. Portal hypertension, a complication of cirrhosis, which can manifest with esophageal and parastomal varices as well as hepatic encephalopathy (mental status alteration/disturbance caused by liver dysfunction and shunting of blood away from the scarred liver; such that ammonia detoxification is reduced with concomitant encephalopathy) or ascites. Cause The exact cause of primary sclerosing cholangitis is unknown, and its pathogenesis is improperly understood. Although PSC is thought to be caused by autoimmune disease, it does not demonstrate a clear response to immunosuppressants. Thus, many experts believe it to be a complex, multifactorial (including immune-mediated) disorder and perhaps one that encompasses several different hepatobiliary diseases.Data have provided novel insights suggesting: an important association between the intestinal microbiota and PSC and a process referred to as cellular senescence and the senescence-associated secretory phenotype in the pathogenesis of PSC.In addition, longstanding, well-recognized associations are seen between PSC and human leukocyte antigen alleles (A1, B8, and DR3). Pathophysiology PSC is characterized by inflammation of the bile ducts (cholangitis) with consequent stricturing (i.e., narrowing) and hardening (sclerosis) of these ducts due to scar formation, be it inside and/or outside the liver. The resulting scarring of the bile ducts obstructs the flow of bile, which further perpetuates bile duct and liver injury. Chronic impairment of bile flow due to blockage and dysfunctional bile transport (cholestasis) causes progressive biliary fibrosis and ultimately biliary cirrhosis and liver failure.The primary physiological function of bile is to assist in the breakdown and absorption of fat in the intestinal tract; a relative deficiency of bile can lead to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).Liver enlargement is seen due to portal hypertension caused by compression of portal veins by the proximate sclerosed intrahepatic bile ducts, and leads to right upper quadrant abdominal pain. Diagnosis PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out: serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months cholangiography demonstrating biliary strictures or irregularity consistent with PSC liver biopsy consistent with PSC (if available)Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its noninvasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear antineutrophil cytoplasmic antibodies (P-ANCA); however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20-50% of PSC patients, and likewise are not specific for the disease,but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation nonanastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with IBD, which includes ulcerative colitis and Crohns disease, response to treatment, and risks of disease progression. Classification Primary sclerosing cholangitis is typically classified into three subgroups based on whether the small and/or large bile ducts are affected. The subgroups of PSC include: Classic PSC Small-duct PSC PSC associated with autoimmune hepatitis Management No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as cholestyramine); antibiotics to treat episodes of ascending cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (A, D, E, and K).ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile-duct cancer (cholangiocarcinoma).Liver transplantation is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial ascending cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some experience disease recurrence afterward. The reasons why some patients develop recurrent PSC remains largely obscure, but surprisingly, those without recurrence of disease (hence protected from recurrence) are characterized by an increased presence of the potentially pathogenic Shigella species. Prognosis Estimated median survival from diagnosis until liver transplant or PSC-related death is 21.3 years. Various models have been developed to help predict survival, but their use is generally best suited for research and not clinical purposes. A serum alkaline phosphatase less than 1.5 times the upper limit of normal has been associated with better outcomes, but its use in predicting long-term outcomes is unclear. An IgA isotype autoantibody to the pancreatic GP2 protein (anti-GP2 IgA antibody) is the first verified prognostic biomarker in PSC. The role of anti-GP2 IgA in PSC was simultaneously investigated and reported by two research groups, and later confirmed by others. Association was demonstrated between anti-GP2 IgA and progressive liver fibrosis, cholangiocarcinoma development and shorter transplantation free survival in PSC patients.Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent. Related diseases The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population. Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.PSC is strongly associated with IBD, in particular ulcerative colitis (UC) and to a lesser extent Crohns disease. As many as 5% of patients with IBD are co-diagnosed with PSC, and approximately 70% of people with PSC have IBD. Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital. Various forms of gallbladder disease such as gallstones and gallbladder polyps are also common in those with PSC. Approximately 25% of people with PSC have gallstones. Ultrasound surveillance of the gallbladder every year is recommended for people with PSC. Any person with PSC who is found to have a mass in the gallbladder should undergo surgical removal of the gallbladder due to the high risk of cholangiocarcinoma. Osteoporosis (hepatic osteodystrophy) and hypothyroidism are also associated with PSC.A 2–3:1 male-to-female predilection occurs in primary sclerosing cholangitis. PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of IBD. PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences. Relatively few data are available on the prevalence and incidence of PSC, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, the risk is likely higher in populations where UC is more common. In the United States, an estimated 29,000 individuals have PSC. Research Although no curative treatment is known, several clinical trials are underway that aim to slow progression of this liver disease. Obeticholic acid is being investigated as a possible treatment for PSC due to its antifibrotic effects. Simtuzumab is a monoclonal antibody against the profibrotic enzyme LOXL2 that is being developed as a possible therapy for PSC. Notable cases Chris Klug – professional snowboarder with PSC who had liver transplant Chris LeDoux – professional rodeo rider and country musician with PSC who died of cholangiocarcinoma Elena Baltacha – British professional tennis player, diagnosed with PSC at age 19 and died five months after being diagnosed with PSC-associated liver cancer (specifically cholangiocarcinoma) at the age of 30 Walter Payton – died of complications of PSC Kieron Dyer – professional footballer James Redford – director and son of Robert Redford who underwent two liver transplants due to PSC References External links Patient support organizations: www.pscpartners.org—based in the US www.pscpartners.ca—based in Canada www.pscsupport.org.au—based in Australia www.pscsupport.org.uk—based in the UK

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Could you please explain the term 'Werner syndrome' in simple language?

Werner syndrome (WS) or Werners syndrome, also known as "adult progeria", is a rare, autosomal recessive disorder which is characterized by the appearance of premature aging.Werner syndrome is named after the German scientist Otto Werner. He identified the syndrome in four siblings observed with premature aging, which he explored as the subject of his dissertation of 1904.It has a global incidence rate of less than 1 in 100,000 live births (although incidence in Japan and Sardinia is higher, affecting 1 in 20,000–40,000 and 1 in 50,000, respectively). 1,300 cases had been reported as of 2006. Affected individuals typically grow and develop normally until puberty; the mean age of diagnosis is twenty-four, often realized when the adolescent growth spurt is not observed. The youngest person diagnosed was six years old. The median and mean ages of death are 47–48 and 54 years, respectively. The main causes of death are cardiovascular disease and cancer. Presentation Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss), wrinkling, prematurely aged faces with beaked noses, skin atrophy (wasting away) with scleroderma-like lesions, lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli (around ankles). Other symptoms include change in voice (weak, hoarse, high-pitched), atrophy of gonads leading to reduced fertility, bilateral cataracts (clouding of lens), premature arteriosclerosis (thickening and loss of elasticity of arteries), calcinosis (calcium deposits in blood vessels), atherosclerosis (blockage of blood vessels), type 2 diabetes, osteoporosis (loss of bone mass), telangiectasia, and malignancies. The prevalence of rare cancers, such as meningiomas, are increased in individuals with Werner syndrome. Gene expression Gene transcription changes found in WS cells are strikingly similar to those observed in normal aging. At the level of gene expression, WRN protein deficiency causes changes in the pattern of gene expression that markedly resemble those of normal old age. DNA methylation The blood of WS patients exhibits accelerated DNA methylation changes that are similar to those observed in normal aging according to a molecular biomarker of aging known as epigenetic clock. Diagnosis and clinical symptoms The mutation in the WRN gene that causes Werner syndrome is autosomal and recessive, meaning that sufferers must inherit a copy of the gene from each parent. Patients display rapid premature aging beginning in young adulthood, usually in their early twenties. Diagnosis is based on six cardinal symptoms: premature graying of the hair or hair loss, presence of bilateral cataracts, atrophied or tight skin, soft tissue calcification, sharp facial features, and an abnormal, high-pitched voice. Patients are generally short-statured due to absence of the adolescent growth spurt. Patients also display decreased fertility. The most common symptom of the six is premature graying and loss of hair. This is also generally the earliest observed symptom, with hair loss occurring first on the scalp and the eyebrows.Werner syndrome patients often have skin that appears shiny and tight, and may also be thin or hardened. This is due to atrophy of the subcutaneous tissue and dermal fibrosis. Over time, the characteristic facial features may be more apparent due to these skin conditions. Other associated skin conditions include ulcers, which are very difficult to treat in Werner syndrome patients, and are caused in part by decreased potential of skin cells for replication.WS cataracts are distinctly different from those of normal aging. They are associated with problems in the lens posterior cortex and subcapsular regions. These cataracts are generally treatable with cataract surgery, which should restore normal vision.Symptoms become apparent in the late teens and early twenties and continue to progress. Most patients live to about fifty years of age. The most common causes of death for people are associated diseases and complications, especially atherosclerosis and cancer. Associated diseases Werner syndrome patients are at increased risk for several other diseases, many associated with aging. Atherosclerosis, the thickening of artery walls due to cholesterol buildup, is one common complication. While normal atherosclerosis generally involves the major arteries, smaller arterioles are more likely to be affected. It is possible nervous system disorders are associated. Brain atrophy is present in 40% of patients. Osteoporosis, the loss of bone mineral density common in post-menopausal women, is another common symptom. In contrast with the normal population, the rate of osteoporosis is especially high for male patients. Diabetes mellitus is another common accompaniment. Skin ulcers occur in about 75% of patients – and can be difficult to treat. If skin ulcers become badly infected or develop gangrene, they often require amputation. Unlike most other related diseases and complications, these ulcers are not associated with normal aging.Patients are also at an increased risk of cancer, especially malignant melanoma. Soft-tissue sarcomas are the most common cancer types. Other types of skin cancer, other epithelial cancers such as thyroid and liver cancers, MDS (myelodysplastic syndrome), and MFH (malignant fibrous histiocytoma) are also prevalent among. Mutations in the WRN gene, especially single-nucleotide polymorphisms (SNPs), are associated with many of the cancers and other associated diseases. WRN SNPs correlate with cancers such as sarcomas and non-Hodgkin lymphomas, as well as diabetes and cardiovascular problems including atherosclerosis. Causes Approximately 90% of individuals presenting Werner syndrome have any of a range of mutations in the gene, WRN, the only gene currently attributed to cause Werner syndrome. WRN, which lies on chromosome 8 in humans, encodes the WRNp protein, a 1432 amino acid protein with a central domain resembling members of the RecQ helicases. RecQ helicases are a special type of helicase that function at unique times during DNA repair of doubled stranded breaks, which are a form of DNA damage that results in a break of both strands of DNA. Thus, RecQ helicases are important for maintaining DNA stability, and loss of function of these helicases has important implications in the development of Werner syndrome. In addition to the central domain, there are three exonuclease domains at the N-terminus and a Helicase and Ribonuclease D C-terminal (HRDC) domain at the C-terminus.When functioning normally, the WRN gene and its associated protein (WRNp) are important for maintaining genome stability. WRNp is active in unwinding DNA, a step necessary in DNA repair and DNA replication. Specifically, it has an important role in responding to replication malfunctions, particularly double-stranded breaks, and stalled replication machinery. WRNp may reactivate replication by preventing unwanted recombination processes from occurring or by promoting recombination, depending on the type of DNA damage. In addition, WRNp physically interacts with or binds to several other proteins that are involved in processing DNA. For example, when WRNp binds to RPA, its helicase activity is stimulated. WRNp also physically interacts with p53, a tumor suppressor gene that stops the formation of tumors and the progression of cancers, which inhibits the exonuclease activity of the WRNp. Since WRNps function depends on DNA, it is only functional when localized to the nucleus.Surprisingly, complete loss of WRN helicase activity does not cause clinical Werner syndrome. DNA repair processes The finding that WRN protein interacts with DNA-PKcs and the Ku protein complex, combined with evidence that WRN deficient cells produce extensive deletions at sites of joining of non-homologous DNA ends, suggests a role for WRN protein in the DNA repair process of non-homologous end joining (NHEJ). WRN protein also physically interacts with the major NHEJ factor X4L4 (XRCC4-DNA ligase 4 complex). X4L4 stimulates WRN exonuclease activity that likely facilitates DNA end processing prior to final ligation by X4L4.WRN protein appears to play a role in resolving recombination intermediate structures during homologous recombinational repair (HRR) of DNA double-strand breaks.WRN protein participates in a complex with RAD51, RAD54, RAD54B and ATR proteins in carrying out the recombination step during inter-strand DNA cross-link repair.Evidence was presented that WRN protein plays a direct role in the repair of methylation induced DNA damage. This process likely involves the helicase and exonuclease activities of WRN protein that operate together with DNA polymerase beta in long patch base excision repair. Effects on cell structure and function Mutations which cause Werner syndrome all occur at the regions of the gene which encode for protein, and not at non-coding regions. There are 35 different known mutations of WRN, which correspond to stop codons, insertions, or deletions that result in a frameshift mutation. These mutations can have a range of effects. They may decrease the stability of the transcribed messenger RNA (mRNA), which increases the rate at which they are degraded. With less mRNA, less is available to be translated into the WRNp protein. Mutations may also lead to the truncation (shortening) of the WRNp protein, leading to the loss of its nuclear localization signal sequence, thus it is no longer transported into the nucleus where it interacts with the DNA. This leads to a reduction in DNA repair. Furthermore, mutated proteins are more likely to be degraded than normal WRNp. Apart from causing defects in DNA repair, its aberrant association with p53 down-regulates the function of p53, leading to a reduction in p53-dependent apoptosis and increasing the survival of these dysfunctional cells. Cells of affected individuals also have reduced lifespan in culture, have more chromosome breaks and translocations and have extensive deletions.Patients with Werner syndrome lose the RecQ helicase activity in the WRN protein because of the loss of its C-terminus region, but the mechanism by which this happens is unclear. The loss of the helicase activity can have far-reaching consequences in terms of cell stability and mutation. One instance of these consequences involves telomeres. It is thought that the WRN helicase activity is important not only for DNA repair and recombination, but also for maintaining telomere length and stability. Thus, WRN helicase is important for preventing catastrophic telomere loss during DNA replication. In a normal cell, the telomeres (the ends of chromosomes) undergo repeated shortening during the cell cycle, which can prevent the cell from dividing and multiplying. This event can be counteracted by telomerase, an enzyme that extends the ends of the chromosomes by copying the telomeres and synthesizing an identical, but new end that can be added to the existing chromosome. However, patients with Werner syndrome often exhibit accelerated telomere shortening, indicating that there may be a connection between the loss of the WRN helicase activity and telomere and cell instability. While evidence shows that telomere dysfunction is consistent with the premature aging in WS, it has yet to be determined if it is the actual cause of the genomic instability observed in cells and the high rate of cancer in WS patients.Without the WRN protein, the interwoven pathways of DNA repair and telomere maintenance fail to suppress cancer and the aging symptoms seen in patients with WS. Events such as rapid telomere shortening cause Werner syndrome cells to exhibit low responses to overall cellular stress. In addition to telomere dysfunction, over-expression of oncogenes and oxidation can induce this type of response. High stress causes a synergistic effect, where WS cells become even more sensitive to agents that increase cell stress and agents that damage DNA. As a result, WS cells show a drastic reduction in replicative lifespan and enter into a stage of aging prematurely. The accumulation of these damaged cells due to telomere shortening over many years may be indicative of why Werner syndrome symptoms only appear after an individual is about twenty years old. Protection of DNA against oxidative damage WRN protein was found to have a specific role in preventing or repairing DNA damages resulting from chronic oxidative stress, particularly in slowly replicating cells. This finding suggested that WRN may be important in dealing with oxidative DNA damage that underlies normal aging (see DNA damage theory of aging). Diagnosis Treatment A cure for Werner syndrome has not yet been discovered. It is often treated by managing the associated diseases and relieving symptoms to improve quality of life. The skin ulcers that accompany WS can be treated in several ways, depending on the severity. Topical treatments can be used for minor ulcers, but are not effective in preventing new ulcers from occurring. In the most severe cases, surgery may be required to implant a skin graft or amputate a limb if necessary. Diseases commonly associated with Werner syndrome such as diabetes and cancer are treated in generally the same ways as they would be for a non-Werner syndrome individual. A change in diet and exercise can help prevent and control arteriosclerosis, and regular cancer screenings can allow for early detection of cancer.There is evidence that suggests that the cytokine-suppressive anti-inflammatory drug SB203580 may be a possible therapeutic option for patients with Werners syndrome. This drug targets the p38 signaling pathway, which may become activated as a result of genomic instability and stalled replication forks that are characteristic mutations in WS. This activation of p38 may play a role in the onset of premature cell aging, skin aging, cataracts, and graying of the hair. The p38 pathway has also been implicated in the inflammatory response that causes atherosclerosis, diabetes, and osteoporosis, all of which are associated with Werners syndrome. This drug has shown to revert the aged characteristics of young WS cells to those seen in normal, young cells and improve the lifespan of WS cells in vitro. SB203580 is in the clinical trial stages, and the same results have not yet been seen in vivo.In 2010, vitamin C supplementation was found to reverse the premature aging and several tissue dysfunctions in a genetically modified mouse model of the disease. Vitamin C supplementation also appeared to normalize several age-related molecular markers such as the increased levels of the transcription factor NF-κB. In addition, it decreases activity of genes activated in human Werner syndrome and increases gene activity involved in tissue repair. Supplementation of vitamin C is suspected to be beneficial in the treatment of human Werner syndrome, although there was no evidence of anti-aging activity in nonmutant mice. In general, treatments are available for only the symptoms or complications and not for the disease itself. History Otto Werner was the first to observe Werner syndrome in 1904 as a part of his dissertation research. As a German ophthalmologist, Werner described several progeria-like features and juvenile cataracts in many of his patients. He noticed these symptoms particularly in a family with four sequential children who all showed the characteristics of the syndrome at around the same age. He assumed the cause to be genetic, though most of his evidence was clinical. Between 1934 and 1941, two internists from New York, Oppenheimer and Kugel, coined the term "Werner Syndrome," igniting a wave of interest and research on the disease. During that time, Agatson and Gartner suggested a possible link between Werners syndrome and cancer. However, it was not until 1966 that there was a general consensus on the autosomal recessive mode of inheritance for the syndrome. By 1981, geneticists had located the WRN gene on chromosome 8, leading to its cloning in 1996. This cloning of the WRN was significant because it revealed the predicted WRN protein was made from a family of DNA helicases. Prior to 1996, Werner syndrome was thought to be a model for accelerated aging. Since the discovery of the gene, it has become clear that the premature aging displayed in Werner syndrome is not the same, on a cellular level, as normal aging. The role of WRN in DNA repair and its exonuclease and helicase activities have been the subject of many studies in recent years.Since the initial discovery in 1904, several other cases of Werner syndrome have been recorded. Many of these cases have occurred in Japan, where a founder effect has caused a higher incidence rate than in other populations. The incidence rate of Werner syndrome in Japan is approximately 1 case per 100 thousand people (1:100,000), a large contrast with the rate of incidence for the rest of the world, which is between 1:1,000,000 and 1:10,000,000. A founder effect is also apparent in Sardinia, where there have been 18 recorded cases of Werner syndrome. Society and culture On the episode "Stargazer in a Puddle" from the television series Bones, the victim has Werner syndrome. The team discovers in the course of the investigation that her mother killed her because she was dying of another disease, and worried that her daughter would have nobody to look after her afterwards, with the tragic twist that the mother began to recover from her disease after her daughters death.Werner syndrome is featured in the 1989 film The Fly II, starring Eric Stoltz, in which his character is born as a 2 year old baby. He never sleeps and grows 5 times his normal age due to his biological father having half fly genes from the first 1986 film The Fly.Werner syndrome is also featured in the 1996 film Jack, starring Robin Williams, in which his character ages four times faster than normal.In an early cutscene from the game Metal Gear Solid 4, Otacon cites "classic Werner syndrome" as the most likely cause of Solid Snakes premature aging, though he goes on to say that testing had been inconclusive. It is however later said that Solid Snakes body, created as a genetically engineered clone, had been designed to break down quickly.In season 3 episode 9, "The Ballad of Kevin and Tess", of the TV series The 4400, Kevin is said to have Werner syndrome to hide his real condition from the public.In The Invisible Man season 1 episode 6, "Impetus", the new character Gloria has an experimentally altered type of Werner syndrome that causes it to become contagious.The central character in Gail Tsukiyamas novel DREAMING WATER (2002) has Werners syndrome.In season 1 episode 8 "Cold Comfort" from TV series Dark Angel, a character has a "form of progeria, similar to Werner syndrome", due to genetic manipulation. With an appropriate treatment, her condition seems to be stabilized.In Resident Evil: The Final Chapter (2016), the deadly "T-Virus", which causes the viral pandemic in the Resident Evil film series, is revealed to be the cure for "adult progeria". James Marcus originally develops the virus to cure his young daughter Alicia Marcus.Ratsasan (2018), a Tamil movie (as well as its Telugu remake Rakshasudu), features a young man born with Werners and is a victim of childhood bullying due to his appearance and has bad experience proposing to a girl, who turns into serial killer and hunts down and kills school girls. See also References External links This article incorporates public domain text from The U.S. National Library of Medicine Werner Syndrome from GeneReviews, contains extensive information on the disorder

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The term 'Treprostinil' keeps coming up in medical discussions. What does it stand for?

Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a synthetic analog of prostacyclin (PGI2). Treprostinil was approved for use in the United States in May 2002.The drug can be given in various forms: IV, subcutaneous injection, oral inhalation, as well as oral extended-release tablets. The subcutaneous administration tends to be very painful. Medical uses Treprostinil is indicated for the treatment of pulmonary arterial hypertension in people with NYHA Class II-IV symptoms to diminish symptoms associated with exercise. It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route, or in whom these risks are considered warranted. This medication is also available in inhaled and tablet forms. In people with pulmonary arterial hypertension requiring transition from epoprostenol sodium (Flolan), treprostinil is indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition. Treprostinil therapy may be effective in treating Degos disease. Adverse effects Since treprostinil is a vasodilator, its antihypertensive effect may be compounded by other medications that affect the blood pressure, including calcium channel blockers, diuretics, and other vasodilating agents. Because of treprostinils inhibiting effect on platelet aggregation, there is an increased risk of bleeding, especially among patients who are also taking anticoagulants. It is not known whether treprostinil is excreted in breast milk. Caution is advised when administering this medication to nursing women. Caution is advised when administering treprostinil to patients who have impaired kidney or liver function.Common side effects depending on route of administration: 85% of patients report pain or other reaction at the infusion site. Other side effects may include headache, cough, throat irritation, diarrhea, nausea, rash, jaw pain, vasodilatation, dizziness, edema (swelling), pruritus (itching), and hypotension.Warnings: Abrupt interruption of the treprostinil infusion can lead to worsening of pulmonary hypertension symptoms, and should be avoided. Pharmacology Mechanism of action Treprostinil binds to the IP receptor in the lung tissue which will cause G protein activation and lead to three major effects: vasodilation, decreased cell proliferation and inhibition of platelet aggregation. Pharmacokinetics The pharmacokinetics of continuous subcutaneous treprostinil are linear over the dose range of 1.25 to 125 ng/kg/min (corresponding to plasma concentrations of about 15 pg/mL to 18,250 pg/m) and can be described by a two-compartment model. Dose proportionality at infusion rates greater than 125 ng/kg/min has not been studied. Treprostinil is substantially metabolized by the liver, but the involved enzymes are not currently known. Five metabolites (HU1 through HU5) have been described thus far. Based on the results of in vitro human hepatic cytochrome P450 studies, Remodulin does not inhibit CYP-1A2, 2C9, 2C19, 2D6, 2E1, or 3A. Whether Remodulin induces these enzymes has not been studied. Dosage and administration For infusion Treprostinil may be administered as a continuous subcutaneous infusion or continuous intravenous infusion via a small infusion pump that the patient must wear at all times. Treprostinil can be given subcutaneously by continuous infusion using an infusion set connected to an infusion pump, but also may be given intravenously via a central venous catheter if the patient is unable to tolerate subcutaneous administration because of severe site pain or reaction. Remodulin is supplied in 20 mL vials, containing treprostinil in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL. Treprostinil can be administered subcutaneously as supplied. It must be diluted for intravenous infusion with either sterile water or a 0.9% sodium chloride solution prior to administration. The infusion rate is normally initiated at 1.25 ng/kg/min for new patients, but may be reduced to 0.625 ng/kg/min if the normal rate provokes unwanted side effects in the patient. The infusion rate of treprostinil should be increased no more than 1.25 ng/kg/min per week for the first month, then 2.5 ng/kg/min per week for the remaining duration of infusion. The infusion rate should ideally be high enough to improve symptoms of pulmonary hypertension, while minimizing unpleasant side effects (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction). Dosage adjustments may be undertaken more often if tolerated. There is little experience with doses >40 ng/kg/min. Abrupt cessation of infusion should be avoided. Restarting a Remodulin infusion within a few hours after an interruption can be done using the same dose rate. Interruptions for longer periods may require the dose of Remodulin to be re-titrated. In patients with mild or moderate liver dysfunction, the initial dose of Remodulin should be decreased to 0.625 ng/kg/min ideal body weight and should be increased cautiously. Remodulin has not been studied in patients with severe liver dysfunction. No studies have been performed in patients with kidney dysfunction. No specific advice about dosing in patients with renal impairment can be given. Inhaled form The inhaled form of treprostinil was approved by the FDA in July 2009 and is marketed as the trade name Tyvaso. The inhaled form is used with a proprietary inhalation device supplied by the manufacturer. Patients use one ampule with inhalation solution a day, four times a day at least four hours apart. Oral form The oral form of treprostinil was approved by the FDA in December 2013 and is marketed as the trade name Orenitram. Orenitram is taken 2 or 3 times daily with food. History During the 1960s a U.K. research team, headed by Professor John Vane began to explore the role of prostaglandins in anaphylaxis and respiratory diseases. Working with a team from the Royal College of Surgeons, Vane discovered that aspirin and other oral anti-inflammatory drugs worked by inhibiting the synthesis of prostaglandins. This finding opened the door to a broader understanding of the role of prostaglandins in the body. Vane and a team from the Wellcome Foundation had identified a lipid mediator they called “PG-X,” which inhibited platelet aggregation. PG-X, which later would become known as prostacyclin, was 30 times more potent than any other known anti-aggregatory agent.By 1976, Vane and fellow researcher Salvador Moncada published the first paper on prostacyclin, in the scientific journal Nature. The collaboration produced a synthetic molecule which was given the name epoprostenol. But like native prostacyclin, the structure of the epoprostenol molecule proved to be unstable in solution, prone to rapid degradation. This presented a challenge for both in vitro experiments and clinical applications. To overcome this challenge, the research team that discovered prostacyclin was determined to continue the research in an attempt to build upon the success they had seen with the prototype molecule. The research team synthesized nearly 1,000 analogs.Remodulin was approved for use in the United States in May 2002, and again in July 2018. Tyvaso, the inhaled form of treprostinil, was approved for use in the United States in July 2009. Orenitram was approved in December 2013.Trepulmix was approved for use in the European Union in April 2020. Effect on PPARs Treprostinil has demonstrated an effect on PPAR-γ, a transcription factor important in vascular pathogenesis as a mediator of proliferation, inflammation and apoptosis. Through a complementary, yet cyclic AMP-independent pathway, treprostinil activates PPARs, another mechanism that contributes to the anti-growth benefits of the prostacyclin class. References Further reading External links "Treprostinil". Drug Information Portal. U.S. National Library of Medicine.

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I'm encountering the term 'Burning mouth syndrome' in medical literature. What's its definition?

Burning mouth syndrome (BMS) is a burning, tingling or scalding sensation in the mouth, lasting for at least four to six months, with no underlying known dental or medical cause. No related signs of disease are found in the mouth. People with burning mouth syndrome may also have a subjective xerostomia (dry mouth sensation where no cause can be found such as reduced salivary flow), paraesthesia (altered sensation such as tingling in the mouth), or an altered sense of taste or smell.A burning sensation in the mouth can be a symptom of another disease when local or systemic factors are found to be implicated; this is not considered to be burning mouth syndrome, which is a syndrome of medically unexplained symptoms. The International Association for the Study of Pain defines burning mouth syndrome as "a distinctive nosological entity characterized by unremitting oral burning or similar pain in the absence of detectable mucosal changes" and "burning pain in the tongue or other oral mucous membranes", and the International Headache Society defines it as "an intra-oral burning sensation for which no medical or dental cause can be found". To ensure the correct diagnosis of burning mouth syndrome, Research Diagnostic Criteria (RDC/BMS) have been developed.Insufficient evidence leaves it unclear if effective treatments exist. Signs and symptoms By definition, BMS has no signs. Sometimes affected persons will attribute the symptoms to sores in the mouth, but these are in fact normal anatomic structures (e.g. lingual papillae, varices). Symptoms of BMS are variable, but the typical clinical picture is given below, considered according to the Socrates pain assessment method (see table). If clinical signs are visible, then another explanation for the burning sensation may be present. Erythema (redness) and edema (swelling) of papillae on the tip of the tongue may be a sign that the tongue is being habitually pressed against the teeth. The number and size of filiform papillae may be reduced. If the tongue is very red and smooth, then there is likely a local or systemic cause (e.g. eythematous candidiasis, anemia). Causes Theories In about 50% of cases of burning mouth sensation no identifiable cause is apparent; these cases are termed (primary) BMS. Several theories of what causes BMS have been proposed, and these are supported by varying degrees of evidence, but none is proven. As most people with BMS are postmenopausal women, one theory of the cause of BMS is of estrogen or progesterone deficit, but a strong statistical correlation has not been demonstrated. Another theory is that BMS is related to autoimmunity, as abnormal antinuclear antibody and rheumatoid factor can be found in the serum of more than 50% of persons with BMS, but these levels may also be seen in elderly people who do not have any of the symptoms of this condition. Whilst salivary flow rates are normal and there are no clinical signs of a dry mouth to explain a complaint of dry mouth, levels of salivary proteins and phosphate may be elevated and salivary pH or buffering capacity may be reduced.Depression and anxiety are strongly associated with BMS. It is not known if depression is a cause or result of BMS, as depression may develop in any setting of constant unrelieved irritation, pain, and sleep disturbance. It is estimated that about 20% of BMS cases involve psychogenic factors, and some consider BMS a psychosomatic illness, caused by cancerophobia, concern about sexually transmitted infections, or hypochondriasis.Chronic low-grade trauma due to parafunctional habits (e.g. rubbing the tongue against the teeth or pressing it against the palate), may be involved. BMS is more common in persons with Parkinsons disease, so it has been suggested that it is a disorder of reduced pain threshold and increased sensitivity. Often people with BMS have unusually raised taste sensitivity, termed hypergeusia ("super tasters"). Dysgeusia (usually a bitter or metallic taste) is present in about 60% of people with BMS, a factor which led to the concept of a defect in sensory peripheral neural mechanisms. Changes in the oral environment, such as changes in the composition of saliva, may induce neuropathy or interruption of nerve transduction. The onset of BMS is often spontaneous, although it may be gradual. There is sometimes a correlation with a major life event or stressful period in life. In women, the onset of BMS is most likely three to twelve years following menopause. Other causes of an oral burning sensation Several local and systemic factors can give a burning sensation in the mouth without any clinical signs, and therefore may be misdiagnosed as BMS. Some sources state that where there is an identifiable cause for a burning sensation, this can be termed "secondary BMS" to distinguish it from primary BMS. However, the accepted definitions of BMS hold that there are no identifiable causes for BMS, and where there are identifiable causes, the term BMS should not be used.Some causes of a burning mouth sensation may be accompanied by clinical signs in the mouth or elsewhere on the body. For example, burning mouth pain may be a symptom of allergic contact stomatitis. This is a contact sensitivity (type IV hypersensitivity reaction) in the oral tissues to common substances such as sodium lauryl sulfate, cinnamaldehyde or dental materials. However, allergic contact stomatitis is accompanied by visible lesions and gives positive response with patch testing. Acute (short term) exposure to the allergen (the substance triggering the allergic response) causes non-specific inflammation and possibly mucosal ulceration. Chronic (long term) exposure to the allergen may appear as chronic inflammatory, lichenoid (lesions resembling oral lichen planus), or plasma cell gingivitis, which may be accompanied by glossitis and cheilitis. Apart from BMS itself, a full list of causes of an oral burning sensation is given below: Deficiency of iron, folic acid or various B vitamins (glossitis e.g. due to anemia), or zinc Neuropathy, e.g. following damage to the chorda tympani nerve. Hypothyroidism. Medications ("scalded mouth syndrome", unrelated to BMS) - protease inhibitors and angiotensin-converting-enzyme inhibitors (e.g. captopril). Type 2 diabetes True xerostomia, caused by hyposalivation e.g. Sjögrens syndrome Parafunctional activity, e.g. nocturnal bruxism or a tongue thrusting habit. Restriction of the tongue by poorly constructed dentures. Geographic tongue. Oral candidiasis. Herpetic infection (herpes simplex virus). Fissured tongue. Lichen planus. Allergies and contact sensitivities to foods, metals, and other substances (see table). Hiatal hernia. Human immunodeficiency virus. Multiple myeloma Diagnosis BMS is a diagnosis of exclusion, i.e. all other explanations for the symptoms are ruled out before the diagnosis is made. There are no clinically useful investigations that would help to support a diagnosis of BMS (by definition all tests would have normal results), but blood tests and / or urinalysis may be useful to rule out anemia, deficiency states, hypothyroidism and diabetes. Investigation of a dry mouth symptom may involve sialometry, which objectively determines if there is any reduction of the salivary flow rate (hyposalivation). Oral candidiasis can be tested for with use of a swabs, smears, an oral rinse or saliva samples. It has been suggested that allergy testing (e.g., patch test) is inappropriate in the absence of a clear history and clinical signs in people with a burning sensation in the mouth. The diagnosis of a people with a burning symptom may also involve psychologic screening e.g. depression questionnaires.The second edition of the International Classification of Headache Disorders lists diagnostic criteria for "Glossodynia and Sore Mouth": A. Pain in the mouth present daily and persisting for most of the day, B. Oral mucosa is of normal appearance, C. Local and systemic diseases have been excluded. Classification A burning sensation in the mouth may be primary (i.e. burning mouth syndrome) or secondary to systemic or local factors. Other sources refer to a "secondary BMS" with a similar definition, i.e. a burning sensation which is caused by local or systemic factors, or "where oral burning is explained by a clinical abnormality". However this contradicts the accepted definition of BMS which specifies that no cause can be identified. "Secondary BMS" could therefore be considered a misnomer. BMS is an example of dysesthesia, or a distortion of sensation.Some consider BMS to be a variant of atypical facial pain. More recently, BMS has been described as one of the 4 recognizable symptom complexes of chronic facial pain, along with atypical facial pain, temporomandibular joint dysfunction and atypical odontalgia. BMS has been subdivided into three general types, with type two being the most common and type three being the least common. Types one and two have unremitting symptoms, whereas type three may show remitting symptoms. Type 1 - Symptoms not present upon waking, and then increase throughout the day Type 2 - Symptoms upon waking and through the day Type 3 - No regular pattern of symptomsSometimes those terms specific to the tongue (e.g. glossodynia) are reserved for when the burning sensation is located only on the tongue. Treatment If a cause can be identified for a burning sensation in the mouth, then treatment of this underlying factor is recommended. If symptom persist despite treatment a diagnosis of BMS is confirmed. BMS has been traditionally treated by reassurance and with antidepressants, anxiolytics or anticonvulsants. A 2016 Cochrane review of treatment for burning mouth syndrome concluded that strong evidence of an effective treatment was not available, however, a systematic review in 2018 found that the use of antidepressants and alpha-lipoic acids gave promising results.Other treatments which have been used include atypical antipsychotics, histamine receptor antagonists, and dopamine agonists. Supplementation with vitamin complexes and cognitive behavioral therapy may be helpful in the management of burning mouth syndrome. Prognosis BMS is benign (importantly, it is not a symptom of oral cancer), but as a cause of chronic pain which is poorly controlled, it can detriment quality of life, and may become a fixation which cannot be ignored, thus interfering with work and other daily activities. Two thirds of people with BMS have a spontaneous partial recovery six to seven years after the initial onset, but in others the condition is permanent. Recovery is often preceded by a change in the character of the symptom from constant to intermittent. No clinical factors predicting recovery have been noted.If there is an identifiable cause for the burning sensation, then psychologic dysfunctions such as anxiety and depression often disappear if the symptom is successfully treated. Epidemiology BMS is fairly uncommon worldwide, affecting up to five individuals per 100,000 general population. People with BMS are more likely to be middle aged or elderly, and females are three to seven times more likely to have BMS than males. Some report a female to male ratio of as much as 33 to 1. BMS is reported in about 10-40% of women seeking medical treatment for menopausal symptoms, and BMS occurs in about 14% of postmenopausal women. Males and younger individuals of both sexes are sometimes affected.Asian and Native American people have considerably higher risk of BMS. Notable cases Sheila Chandra, a singer of Indian heritage, retired due to this condition. References Scala A; Checchi L; Montevecchi M; Marini I; Giamberardino MA (2003). "Update on burning mouth syndrome: overview and patient management". Crit Rev Oral Biol Med. 14 (4): 275–91. doi:10.1177/154411130301400405. PMID 12907696. == External links ==

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I'm seeking clarification on the medical term 'Isocarboxazid.' Could you explain it?

Isocarboxazid (Marplan, Marplon, Enerzer) is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. Along with phenelzine and tranylcypromine, it is one of only three classical MAOIs still available for clinical use in the treatment of psychiatric disorders in the United States, though it is not as commonly employed in comparison to the others.Isocarboxazid is primarily used to treat mood and anxiety disorders. It has also been investigated in the treatment of schizophrenia, Parkinsons disease and other dementia-related disorders. Isocarboxazid, as well as other MAOIs, increase the levels of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine in the brain.Classical MAOIs, including isocarboxazid, are used only rarely due to prominent food and drug interactions and have been largely superseded by newer antidepressants such as the selective serotonin reuptake inhibitors (SSRIs). The cause of the interactions is because MAOIs inhibit the metabolism of dietary amines (e.g., tyramine) and the monoamine neurotransmitters. In combination with other drugs that increase the levels of the monoamine neurotransmitters such as the SSRIs, or with certain foods high in dietary amines such as aged cheeses, MAOIs can produce dangerous elevations of monoamine neurotransmitters resulting in potentially life-threatening syndromes such as hypertensive crisis and serotonin syndrome. See also Hydrazine (antidepressant) == References ==

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I've encountered the term 'Terbinafine' while reading about medical topics. What does it refer to exactly?

Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athletes foot. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment are not effective for nail infections.Common side effects when taken by mouth include nausea, diarrhea, headache, cough, rash, and elevated liver enzymes. Severe side effects include liver problems and allergic reactions. Liver injury is, however, unusual. Use during pregnancy is not typically recommended. The cream and ointment may result in itchiness but are generally well tolerated. Terbinafine is in the allylamines family of medications. It works by decreasing the ability of fungi to synthesize sterols. It appears to result in fungal cell death.Terbinafine was discovered in 1991. It is on the World Health Organizations List of Essential Medicines. In 2017, it was the 307th most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses Terbinafine is mainly effective on fungi of the group Onygenales and some yeasts in the genus Candida (e.g. Candida glabrata) As a cream or powder, it is used topically for superficial skin infections such as jock itch (tinea cruris), athletes foot (tinea pedis), and other types of ringworm (tinea corporis).Tablets by mouth are often prescribed for the treatment of onychomycosis, a fungal nail infection, typically by a dermatophyte or Candida species. Fungal nail infections are located deep under the nail in the cuticle to which topically applied treatments are unable to penetrate in sufficient amounts. The tablets may, rarely, cause hepatotoxicity, so patients are warned of this and may be monitored with liver function tests. Alternatives to oral administration have been studied. Terbinafine may induce or exacerbate subacute cutaneous lupus erythematosus. Persons with lupus erythematosus should first discuss possible risks with their doctor before initiation of therapy. Side effects Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride possibly due to its extensive biodistribution and the often extended durations involved in antifungal treatment (longer than two months). A comprehensive list of adverse events associated with terbinafine use includes: Gastrointestinal problems: Diarrhea, constipation, nausea, fullness, abdominal pain, indigestion, dyspepsia, gastritis, cholestasis, flatulence, altered stool colour, abdominal muscular pain Central nervous system or neurological problems: Headaches, dizziness, vertigo, light-headedness, decreased concentration levels, paraesthesia (pins and needles) Hepatic problems: Raised liver enzyme levels, liver inflammation (hepatitis), liver damage, liver failure Immune system problems: Decreased white blood cell counts including pancytopenia, leukopenia, lymphopenia, thrombocytopenia, agranulocytosis, and neutropenia, autoimmune reactions such as lupus erythematosus Psychological problems: Depression, anxiety, insomnia, increased or unusual dream activity, malaise Sensory problems: Complete loss of taste (ageusia), decreased taste (hypogeusia) and distorted taste (dysgeusia), often involving a metallic taste sensation and dry mouth, visual disturbances including blurred vision, green vision and double vision. In extremely rare cases, the loss or impairment of taste is permanent Skin problems: Rashes, hives (urticaria), skin irritation, itching, jaundice, Stevens–Johnson syndrome Other side effects: Fatigue, increased heart rate (tachycardia), hair loss (alopecia), decreased red blood cell count (anemia), muscle pain (myalgia), joint pain (arthralgia)In 2015 physicians reported that a patient with an MTHFR enzyme mutation (specifically the C677T variant) had developed an adverse reaction to Lamisil (headache, fatigue, and dizziness). Genetic testing revealed the MTHFR C677T mutation. It was noted that Lamisil interferes with the methylation cycle and that this can cause side effects in individuals with the MTHFR C677T mutation. Pharmacology Like other allylamines, terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase, an enzyme that catalyzes the conversion of squalene to lanosterol. In fungi, lanosterol is then converted to ergosterol; in humans, lanosterol becomes cholesterol. However, as fungi and animals diverged around 1.1 billion years ago - there is enough difference in this enzyme that terbinafine preferentially binds fungal squalene epoxidase, making it selective for inhibiting ergosterol production in fungi without significantly affecting cholesterol production in mammals. This is thought to fatally disrupt the fungal cell membrane. Terbinafine is highly lipophilic and tends to accumulate in hair, skin, nails, and fat cells. This accumulation results in therapeutic levels of terbinafine even after 80 days following one week treatment of 250 mg/day. Different dosing schedules have been proposed such as 500 mg/day for one week or 250 mg/day for two weeks each followed by a drug-free period of three or two weeks, totaling 3 months of treatment including the drug-free periods. Such intermittent dosing schedules appear to be as effective as continuous regimes. Chemistry Terbinafine hydrochloride is a white crystalline powder that is freely soluble in methanol and dichloromethane, soluble in ethanol, and slightly soluble in water.Terbinafine is produced from olefin metathesis of 1,3-dichloropropene and neohexene followed by reaction with N-methyl-1-naphthalenemethanamine.Despite its name it does not contain terbium. History Terbinafine first became available in Europe in 1991 and in the United States in 1996. The U.S. Food and Drug Administration has approved the first generic versions of prescription Lamisil (terbinafine hydrochloride) tablets. The remaining patent or exclusivity for Lamisil expired on June 30, 2007. On September 28, 2007, the FDA stated that terbinafine is a new treatment approved for use by children age four and up. The antifungal granules can be sprinkled on a childs food to treat ringworm of the scalp, tinea capitis.In the United States the price in 1999 was $547 for a 12-week course; this fell to $10 by 2015, after the patent had expired. Society and culture Brand names Terbinafine is sold in India as Terboderm by Omega Pharma and Tyza (Abbott Healthcare). Lamisil in Argentina, Australia, Bangladesh, Belgium, Brazil, Canada, Chile, Colombia, Croatia, Egypt, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Mexico, the Netherlands, New Zealand, Norway, Pakistan (لیمسل), Peru, the Philippines, Romania, Russia, Slovakia, Slovenia, South Africa, Sweden, Thailand, the United Kingdom, the United States, and Venezuela Corbinal and Terbisil in Turkey, Pakistan, Undofen in Poland, and Terbistad (Stada Arzneimittel). As a generic oral medication, it is sold as Sebifin, Tinasil, Terbisil, Terbicor, and Tamsil in Australia, whilst the generic topical medication is sold there as SolvEasyTinea and Tamsil. It is also available as a generic medication in the United States, the United Kingdom, Belgium, Switzerland, Brazil, Mexico, Canada and France. In India, terbinafine hydrochloride is available in topical form under the brand names Triabin by Medley Pharmaceuticals, Sebifin (Sun Pharma), Zimig (GSK Pharma) and mycoCeaze (Progreś Laboratories). MycoVa, developed by Apricus Biosciences, is a topical nail solution of terbinafine and DDAIP, which has completed three phase-III studies for the treatment of onychomycosis. Other names include Terbinaforce (Mankind Pharma) and Tafine (Deurali Janta Pharmaceuticals Pvt Ltd.) Turbo (Apex Pharmaceuticals Pvt Ltd) in Nepal. The topical form is sold as Lamisil AT in the United States. References External links "Terbinafine". Drug Information Portal. U.S. National Library of Medicine.

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I'm not familiar with the medical term 'High-altitude cerebral edema.' Could you provide some insights?

High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves disorientation, lethargy, and nausea among other symptoms. It occurs when the body fails to acclimatize while ascending to a high altitude. It appears to be a vasogenic edema (fluid penetration of the blood–brain barrier), although cytotoxic edema (cellular retention of fluids) may play a role as well. Individuals with the condition must immediately descend to a lower altitude or coma and death can occur. Patients are usually given supplemental oxygen and dexamethasone as well. HACE can be prevented by ascending to heights slowly to allow the body more time to acclimatize. Acetazolamide also helps prevent the condition. Untreated patients usually die within 48 hours. Those who receive treatment may take weeks to fully recover. It is a rare condition, occurring in less than one percent of people who ascend to 4,000 metres (13,000 ft). Although it was first described in 1913, little was known about the cause of the condition until MRI studies were performed in the 1990s. Signs and symptoms Early symptoms of HACE generally correspond with those of moderate to severe acute mountain sickness (AMS). Initial symptoms of HACE commonly include confusion, loss of consciousness, fever, ataxia, photophobia, rapid heart beat, lassitude, and an altered mental state. Those affected generally attempt to cease physical activities, regardless of their necessity for survival. Severe headaches develop and people lose the ability to sit up. Retinal venous dilation occurs in 59% of people with HACE. Rarer symptoms include brisk deep tendon reflexes, retinal hemorrhages, blurred vision, extension plantar reflexes, and ocular paralysis. Cranial nerve palsies occur in some unusual cases.In the bestselling 1996 non-fiction book Into Thin Air: A Personal Account of the Mt. Everest Disaster, Jon Krakauer describes the effects of HACE upon Dale Kruse, a forty-four-year-old dentist and one of the members of Scott Fischers team: Kruse was having an incredibly difficult time simply trying to dress himself. He put his climbing harness on inside out, threaded it through the fly of his wind suit, and failed to fasten the buckle; fortunately, Fischer and Neal Beidleman noticed the screwup before Kruse started to descend. "If hed tried to rappel down the ropes like that," says Beidleman, "he would have immediately popped out of his harness and fallen to the bottom of the Lhotse Face." "It was like I was very drunk," Kruse recollects. "I couldnt walk without stumbling, and completely lost the ability to think or speak. It was a really strange feeling. Id have some word in my mind, but I couldnt figure out how to bring it to my lips. So Scott and Neal had to get me dressed and make sure my harness was on correctly, then Scott lowered me down the fixed ropes." By the time Kruse arrived in Base Camp, he says, "it was still another three or four days before I could walk from my tent to the mess tent without stumbling all over the place." Patients with HACE have an elevated white blood cell count, but otherwise their blood count and biochemistry are normal. If a lumbar puncture is performed, it will show normal cerebral spinal fluid and cell counts but an increase in pressure. In one study, CT scans of patients with HACE exhibited ventricle compression and low density in the cerebellum. Only a few autopsies have been performed on fatal cases of HACE; they showed swollen gyri, spongiosis of white matter, and compressed sulci. There was some variation between individuals, and the results may not be typical of HACE deaths. Mechanism Most people who travel to high altitudes acclimatize. Acclimatization precludes the development of HACE by maintaining adequate levels of cerebral oxygen. The primary cause of HACE is hypoxia (oxygen deprivation). This occurs after the body is exposed to a low-oxygen environment and before it acclimatizes. The rate of change from a normal oxygen environment and how little oxygen is in the new environment can be used to predict the chance of developing HACE. Prolonged exertion in low oxygen also causes serious hypocapnia, lower carbon dioxide in the bloodstream, which may play a role in HACE. These factors cause the brain to swell with fluid, resulting in severe impairment. If the swelling is untreated, it causes death by brain herniation.The brain swelling is likely a result of vasogenic edema, the penetration of the blood–brain barrier by fluids. This process has been observed in MRI studies. Hypoxia increases extracellular fluid, which passes through the vasogenic endothelium in the brain. The leaking may be caused by increased pressure, or it may be caused by inflammation that makes the endothelium vulnerable to leaking. An MRI study found microhemorrhages in the corpus callosum of HACE patients, and hypoxia may also cause microvascular permeability. It has been hypothesized that vascular endothelial growth factor may cause the vascular permeability at the root of HACE. MRI scans of patients with HACE showed increased T2 in the corpus callosum, although grey matter was unchanged. This demonstrated that the blood-brain barrier was broken by cerebral blood vessels, thus interfering with white matter metabolism. Another study looked at the brains of people with HACE several months after their recovery; it showed hemosiderin deposits in the corpus callosum, evidence of vascular permeability.While there is strong evidence that vasogenic edema plays a major role in HACE, cytotoxic edema, cellular retention of fluids, may contribute as well. Cytotoxic edema may be caused by the failure of cellular ion pumps, which results from hypoxia. Then intracellular sodium and osmolarity increase, and there is an influx of water that causes cellular swelling. After the failure of the ATPase pumps, free radicals form and cause damage that complicates the edema. Evidence against cytotoxic edema includes the high levels of hypoxemia (low bloodstream oxygen) needed to cause it.It is not known why some are more vulnerable to HACE than others. One theory is that variations in brain size play a role, but the increase in brain volume from edema does not likely cause cranial vault impingement. The presence of large sulci indicate the condition may be influenced by the brain tightly fitting. Elevated intracranial pressure is generally accepted to be a late effect of HACE. High central venous pressure may also occur late in the conditions progression.One study demonstrated that normal autorelation of cerebral blood flow does not cause HACE. What role the sympathetic nervous system plays in determining who gets HACE is unclear, but it may have an effect.Another theory about the cause of HACE is that hypoxia may induce nitrous oxide synthase. Vasodilation is caused by the release of nitric oxide and adenosine. This in turn can increase vascular permeability and causes edema. This may combine with low levels of cytokines to cause HACE. Diagnosis Generally, high-altitude pulmonary edema (HAPE) or AMS precede HACE. In patients with AMS, the onset of HACE is usually indicated by vomiting, headache that does not respond to non-steroidal anti-inflammatory drugs, hallucinations, and stupor. In some situations, however, AMS progresses to HACE without these symptoms. HACE must be distinguished from conditions with similar symptoms, including stroke, intoxication, psychosis, diabetic symptoms, meningitis, or ingestion of toxic substances. It should be the first diagnosis ruled out when sickness occurs while ascending to a high altitude. Prevention HACE is generally preventable by ascending gradually with frequent rest days while climbing or trekking. Not ascending more than 1,000 metres (3,300 ft) daily and not sleeping at a greater height than 300 metres (980 ft) more than the previous night is recommended. The risk of developing HACE is diminished if acetazolamide or dexamethasone are administered. Generally, the use of acetazolamide is preferred, but dexamethasone can be used for prevention if there are side effects or contraindications. Some individuals are more susceptible to HACE than others, and physical fitness is not preventive. Age and sex do not by themselves affect vulnerability to HACE. Treatment Patients with HACE should be brought to lower altitudes and provided supplemental oxygen, and rapid descent is sometimes needed to prevent mortality. Early recognition is important because as the condition progresses patients are unable to descend without assistance. Dexamethasone should also be administered, although it fails to ameliorate some symptoms that can be cured by descending to a lower altitude. It can also mask symptoms, and they sometimes resume upon discontinuation. Dexamethasones prevention of angiogenesis may explain why it treats HACE well. Three studies that examined how mice and rat brains react to hypoxia gave some credence to this idea.If available, supplemental oxygen can be used as an adjunctive therapy, or when descent is not possible. FiO2 should be titrated to maintain arterial oxygen saturation of greater than 90%, bearing in mind that oxygen supply is often limited in high altitude clinics/environments.In addition to oxygen therapy, a portable hyperbaric chamber (Gamow bag) can by used as a temporary measure in the treatment of HACE. These devices simulate a decrease in altitude of up to 7000 ft, but they are resource intensive and symptoms will often return after discontinuation of the device. Portable hyperbaric chambers should not be used in place of descent or evacuation to definitive care.Diuretics may be helpful, but pose risks outside of a hospital environment. Sildenafil and tadalafil may help HACE, but there is little evidence of their efficacy. Theophylline is also theorized to help the condition.Although AMS is not life-threatening, HACE is usually fatal within 24 hours if untreated. Without treatment, the patient will enter a coma and then die. In some cases, patients have died within a few hours, and a few have survived for two days. Descriptions of fatal cases often involve climbers who continue ascending while experiencing the conditions symptoms. Prognosis Recovery varies between days and weeks, but most recover in a few days. After the condition is successfully treated, it is possible for climbers to reascend. Dexamethesone should be discontinued, but continual acetazolamide is recommended. In one study, it took patients between one week and one month to display a normal CT scan following HACE. Epidemiology HACE occurs in 0.5% to 1% of people who climb or trek between 4,000 metres (13,000 ft) and 5,000 metres (16,000 ft). In some unusual cases, up to 30% of members of expeditions have had the condition. The condition is seldom seen below 3,000 metres (9,800 ft), but in some rare cases it has developed as low as 2,500 metres (8,200 ft). The condition generally does not occur until an individual has spent 48 hours at an altitude of 4,000 metres (13,000 ft). History HACE was first described by a medical officer stationed in Chile in 1913, but few took note of it. Later, access to air travel made the condition more common because it allowed more people access to high mountains, such as those in the Himalayas. One early description of HACE may have been published in 1969 after a group of Indian soldiers made a rapid ascent to almost 6,000 metres (20,000 ft). It is not definitely established whether they had HACE or acute decompression sickness. MRI has been used to study the effects of high altitude on the brain, providing the best evidence about the condition. A 1998 MRI study of nine climbers with HACE clearly demonstrated vasogenic edema.Data about HACE are lacking because it generally occurs in remote areas, far from hospitals and is generally rare. It is uncommon for doctors to be able to study victims within six days of the conditions development. Animal models of HACE have not been developed. Several genes are being examined for the role they may play in the development of the condition.Increased education and helicopter capabilities have combined to cut the number of deaths from the condition. Symptoms of HACE have been reported in many cases of deaths while descending Mount Everest, although HACE may not be the only problem they experienced. HACE also posed a threat to workers on the Qinghai–Tibet Railway. References Bibliography Bärtsch, Peter; Swenson, Erik (2013). "Acute High-Altitude Illnesses". The New England Journal of Medicine. 368 (24): 2294–302. doi:10.1056/NEJMcp1214870. PMID 23758234. Imray, Chris; Wright, Alex; Subudhi, Andrew; Roach, Robert (2010). "Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment". Progress in Cardiovascular Diseases. 52 (6): 467–484. doi:10.1016/j.pcad.2010.02.003. PMID 20417340. Rosenberg, Gary (2012). Molecular Physiology and Metabolism of the Nervous System (5 ed.). Oxford University Press. ISBN 978-0-19-539427-6. Schoene, Robert (2008). "Illnesses at High Altitude". Chest. 134 (2): 402–16. doi:10.1378/chest.07-0561. PMID 18682459. Schoene, Robert; Milledge, James; Luks, Andrew; West, John (2012). High Altitude Medicine and Physiology. CRC Press. ISBN 978-1-4441-5432-0. Wilson, Mark; Newman, Stanton; Imray, Chris (2009). "The Cerebral Effects of Ascent to High Altitudes". Lancet Neurology. 8 (2): 175–91. doi:10.1016/S1474-4422(09)70014-6. PMID 19161909. S2CID 268646. == External links ==

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The term 'White sponge nevus' keeps coming up in medical discussions. What does it stand for?

White sponge nevus (WSN) is an autosomal dominant condition of the oral mucosa (the mucous membrane lining of the mouth). It is caused by a mutations in certain genes coding for keratin, which causes a defect in the normal process of keratinization of the mucosa. This results in lesions which are thick, white and velvety on the inside of the cheeks within the mouth. Usually, these lesions are present from birth or develop during childhood. The condition is entirely harmless, and no treatment is required. Signs and symptoms It presents itself in the mouth, most frequently as a thick, bilateral, symmetrical white plaques with a spongy, corrugated or velvety texture. Most usually, the lesions are on the buccal mucosa, but sometimes on the labial mucosa, alveolar ridge, floor of the mouth, ventral surface of the tongue or soft palate. The gingival margin and dorsum of the tongue are almost never affected. Less commonly, sites outside the mouth are affected, including the nasal, esophageal, laryngeal, anal and genital mucosae. It usually is present from birth, or develops during childhood. Rarely, the lesions may develop during adolescence. Apart from the appearance of the affected areas, there are usually no other signs or symptoms. Pathophysiology WSN is caused by a mutation of the keratin 4 or keratin 13 genes, located respectively at human chromosomes 12q13 and 17q21-q22. The condition is inherited in an autosomal dominant manner. This indicates that the defective gene responsible for a disorder is located on an autosome (chromosomes 12 and 17 are autosomes), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. Diagnosis Differential diagnosis It is often mistaken for leukoplakia.The differential diagnosis also includes hyperplastic candidiasis and frictional keratosis Classification The ICD-10 lists WSN under "other congenital malformations of mouth". It could be classified as a skin condition, or more precisely as a genodermatosis (a genetically determined skin disorder). Treatment There is no treatment, but because this is a benign condition with no serious clinical complications, prognosis is excellent. See also Oral melanosis List of cutaneous conditions caused by mutations in keratins Hereditary benign intraepithelial dyskeratosis References External links White sponge nevus of cannon; Leukokeratosis, hereditary mucosal at NIHs Office of Rare Diseases

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What does the medical term 'Migraine' encompass?

Migraine (UK: , US: ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hours to three days. Non-headache symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity during an attack, although regular physical exercise may prevent future attacks. Up to one-third of people affected have aura: typically, it is a short period of visual disturbance that signals that the headache will soon occur. Occasionally, aura can occur with little or no headache following, but not everyone has this symptom.Migraine is believed to be due to a mixture of environmental and genetic factors. About two-thirds of cases run in families. Changing hormone levels may also play a role, as migraine affects slightly more boys than girls before puberty and two to three times more women than men. The risk of migraine usually decreases during pregnancy and after menopause. The underlying mechanisms are not fully known. They are, however, believed to involve the nerves and blood vessels of the brain.Initial recommended treatment is with simple pain medication such as ibuprofen and paracetamol (acetaminophen) for the headache, medication for the nausea, and the avoidance of triggers. Specific medications such as triptans or ergotamines may be used in those for whom simple pain medications are not effective. Caffeine in combination with other analgesics is safe and effective in treatment of acute migraine. A number of medications are useful to prevent attacks including metoprolol, valproate, and topiramate.Globally, approximately 15% of people are affected by migraine. In the Global Burden of Disease Study of 2010, it was ranked as the third most prevalent disorder in the world. It most often starts at puberty and is worst during middle age. As of 2016, it is one of the most common causes of disability. An early description consistent with migraines is contained in the Ebers papyrus, written around 1500 BC in ancient Egypt. The word migraine is from the Greek ἡμικρᾱνίᾱ (hēmikrāníā), pain in half of the head, from ἡμι- (hēmi-), half and κρᾱνίον (krāníon), skull. Signs and symptoms Migraine typically presents with self-limited, recurrent severe headache associated with autonomic symptoms. About 15–30% of people living with migraine experience episodes with aura, and they also frequently experience episodes without aura. The severity of the pain, duration of the headache, and frequency of attacks are variable. A migraine attack lasting longer than 72 hours is termed status migrainosus. There are four possible phases to a migraine attack, although not all the phases are necessarily experienced: The prodrome, which occurs hours or days before the headache The aura, which immediately precedes the headache The pain phase, also known as headache phase The postdrome, the effects experienced following the end of a migraine attackMigraine is associated with major depression, bipolar disorder, anxiety disorders, and obsessive–compulsive disorder. These psychiatric disorders are approximately 2–5 times more common in people without aura, and 3–10 times more common in people with aura. Prodrome phase Prodromal or premonitory symptoms occur in about 60% of those with migraines, with an onset that can range from two hours to two days before the start of pain or the aura. These symptoms may include a wide variety of phenomena, including altered mood, irritability, depression or euphoria, fatigue, craving for certain food(s), stiff muscles (especially in the neck), constipation or diarrhea, and sensitivity to smells or noise. This may occur in those with either migraine with aura or migraine without aura. Neuroimaging indicates the limbic system and hypothalamus as the origin of prodromal symptoms in migraine. Aura phase Aura is a transient focal neurological phenomenon that occurs before or during the headache. Aura appears gradually over a number of minutes (usually occurring over 5–60 minutes) and generally lasts less than 60 minutes. Symptoms can be visual, sensory or motoric in nature, and many people experience more than one. Visual effects occur most frequently: they occur in up to 99% of cases and in more than 50% of cases are not accompanied by sensory or motor effects.Visual disturbances often consist of a scintillating scotoma (an area of partial alteration in the field of vision which flickers and may interfere with a persons ability to read or drive). These typically start near the center of vision and then spread out to the sides with zigzagging lines which have been described as looking like fortifications or walls of a castle. Usually the lines are in black and white but some people also see colored lines. Some people lose part of their field of vision known as hemianopsia while others experience blurring.Sensory aura are the second most common type; they occur in 30–40% of people with auras. Often a feeling of pins-and-needles begins on one side in the hand and arm and spreads to the nose–mouth area on the same side. Numbness usually occurs after the tingling has passed with a loss of position sense. Other symptoms of the aura phase can include speech or language disturbances, world spinning, and less commonly motor problems. Motor symptoms indicate that this is a hemiplegic migraine, and weakness often lasts longer than one hour unlike other auras. Auditory hallucinations or delusions have also been described. Pain phase Classically the headache is unilateral, throbbing, and moderate to severe in intensity. It usually comes on gradually and is aggravated by physical activity during a migraine attack. However, the effects of physical activity on migraine are complex, and some researchers have concluded that, while exercise can trigger migraine attacks, regular exercise may have a prophylactic effect and decrease frequency of attacks. The feeling of pulsating pain is not in phase with the pulse. In more than 40% of cases, however, the pain may be bilateral (both sides of the head), and neck pain is commonly associated with it. Bilateral pain is particularly common in those who have migraine without aura. Less commonly pain may occur primarily in the back or top of the head. The pain usually lasts 4 to 72 hours in adults; however, in young children frequently lasts less than 1 hour. The frequency of attacks is variable, from a few in a lifetime to several a week, with the average being about one a month.The pain is frequently accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, sensitivity to smells, fatigue and irritability. Many thus seek a dark and quiet room. In a basilar migraine, a migraine with neurological symptoms related to the brain stem or with neurological symptoms on both sides of the body, common effects include a sense of the world spinning, light-headedness, and confusion. Nausea occurs in almost 90% of people, and vomiting occurs in about one-third. Other symptoms may include blurred vision, nasal stuffiness, diarrhea, frequent urination, pallor, or sweating. Swelling or tenderness of the scalp may occur as can neck stiffness. Associated symptoms are less common in the elderly. Silent migraine Sometimes, aura occurs without a subsequent headache. This is known in modern classification as a typical aura without headache, or acephalgic migraine in previous classification, or commonly as a silent migraine. However, silent migraine can still produce debilitating symptoms, with visual disturbance, vision loss in half of both eyes, alterations in color perception, and other sensory problems, like sensitivity to light, sound, and odors, and aura sudden outbreak without headache can be scary. It can last from 15 to 30 minutes, usually no longer than 60 minutes, and it can recur or appear as an isolated event. Postdrome The migraine postdrome could be defined as that constellation of symptoms occurring once the acute headache has settled. Many report a sore feeling in the area where the migraine was, and some report impaired thinking for a few days after the headache has passed. The person may feel tired or "hung over" and have head pain, cognitive difficulties, gastrointestinal symptoms, mood changes, and weakness. According to one summary, "Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise." For some individuals this can vary each time. Cause The underlying causes of migraines are unknown. However, they are believed to be related to a mix of environmental and genetic factors. They run in families in about two-thirds of cases and rarely occur due to a single gene defect. While migraines were once believed to be more common in those of high intelligence, this does not appear to be true. A number of psychological conditions are associated, including depression, anxiety, and bipolar disorder, as are many biological events or triggers. Genetics Studies of twins indicate a 34% to 51% genetic influence of likelihood to develop migraine. This genetic relationship is stronger for migraine with aura than for migraines without aura. A number of specific variants of genes increase the risk by a small to moderate amount.Single gene disorders that result in migraines are rare. One of these is known as familial hemiplegic migraine, a type of migraine with aura, which is inherited in an autosomal dominant fashion. Four genes have been shown to be involved in familial hemiplegic migraine. Three of these genes are involved in ion transport. The fourth is an axonal protein associated with the exocytosis complex. Another genetic disorder associated with migraine is CADASIL syndrome or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. One meta-analysis found a protective effect from angiotensin converting enzyme polymorphisms on migraine. The TRPM8 gene, which codes for a cation channel, has been linked to migraines. Triggers Migraine may be induced by triggers, with some reporting it as an influence in a minority of cases and others the majority. Many things such as fatigue, certain foods, alcohol, and weather have been labeled as triggers; however, the strength and significance of these relationships are uncertain. Most people with migraines report experiencing triggers. Symptoms may start up to 24 hours after a trigger. Physiological aspects Common triggers quoted are stress, hunger, and fatigue (these equally contribute to tension headaches). Psychological stress has been reported as a factor by 50 to 80% of people. Migraine has also been associated with post-traumatic stress disorder and abuse. Migraine episodes are more likely to occur around menstruation. Other hormonal influences, such as menarche, oral contraceptive use, pregnancy, perimenopause, and menopause, also play a role. These hormonal influences seem to play a greater role in migraine without aura. Migraine episodes typically do not occur during the second and third trimesters of pregnancy, or following menopause. Dietary aspects Between 12 and 60% of people report foods as triggers.There are many reports that tyramine – which is naturally present in chocolate, alcoholic beverages, most cheeses, processed meats, and other foods – can trigger migraine symptoms in some individuals. Likewise, monosodium glutamate (MSG) is frequently reported as a trigger for migraine symptoms. Environmental aspects A 2009 review on potential triggers in the indoor and outdoor environment concluded that while there were insufficient studies to confirm environmental factors as causing migraine, "migraineurs worldwide consistently report similar environmental triggers". The article suggests that people living with migraine take some preventive measures related to indoor air quality and lighting. Pathophysiology Migraine is believed to be primarily a neurological disorder, while others believe it to be a neurovascular disorder with blood vessels playing the key role, although current evidence does not support this completely. Others believe both are likely important. One theory is related to increased excitability of the cerebral cortex and abnormal control of pain neurons in the trigeminal nucleus of the brainstem. Aura Cortical spreading depression, or spreading depression according to Leão, is a burst of neuronal activity followed by a period of inactivity, which is seen in those with migraines with aura. There are a number of explanations for its occurrence, including activation of NMDA receptors leading to calcium entering the cell. After the burst of activity, the blood flow to the cerebral cortex in the area affected is decreased for two to six hours. It is believed that when depolarization travels down the underside of the brain, nerves that sense pain in the head and neck are triggered. Pain The exact mechanism of the head pain which occurs during a migraine episode is unknown. Some evidence supports a primary role for central nervous system structures (such as the brainstem and diencephalon), while other data support the role of peripheral activation (such as via the sensory nerves that surround blood vessels of the head and neck). The potential candidate vessels include dural arteries, pial arteries and extracranial arteries such as those of the scalp. The role of vasodilatation of the extracranial arteries, in particular, is believed to be significant. Neuromodulators Adenosine, a neuromodulator, may be involved. Released after the progressive cleavage of adenosine triphosphate (ATP), adenosine acts on adenosine receptors to put the body and brain in a low activity state by dilating blood vessels and slowing the heart rate, such as before and during the early stages of sleep. Adenosine levels have been found to be high during migraine attacks. Caffeines role as an inhibitor of adenosine may explain its effect in reducing migraine. Low levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine (5-HT), are also believed to be involved.Calcitonin gene-related peptides (CGRPs) have been found to play a role in the pathogenesis of the pain associated with migraine, as levels of it become elevated during an attack. Diagnosis The diagnosis of a migraine is based on signs and symptoms. Neuroimaging tests are not necessary to diagnose migraine, but may be used to find other causes of headaches in those whose examination and history do not confirm a migraine diagnosis. It is believed that a substantial number of people with the condition remain undiagnosed.The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria": Five or more attacks—for migraine with aura, two attacks are sufficient for diagnosis. Four hours to three days in duration Two or more of the following: Unilateral (affecting one side of the head) Pulsating Moderate or severe pain intensity Worsened by or causing avoidance of routine physical activity One or more of the following: Nausea and/or vomiting Sensitivity to both light (photophobia) and sound (phonophobia)If someone experiences two of the following: photophobia, nausea, or inability to work or study for a day, the diagnosis is more likely. In those with four out of five of the following: pulsating headache, duration of 4–72 hours, pain on one side of the head, nausea, or symptoms that interfere with the persons life, the probability that this is a migraine attack is 92%. In those with fewer than three of these symptoms, the probability is 17%. Classification Migraine was first comprehensively classified in 1988. The International Headache Society updated their classification of headaches in 2004. A third version was published in 2018. According to this classification, migraine is a primary headache disorder along with tension-type headaches and cluster headaches, among others.Migraine is divided into seven subclasses (some of which include further subdivisions): Migraine without aura, or "common migraine", involves migraine headaches that are not accompanied by aura. Migraine with aura, or "classic migraine", usually involves migraine headaches accompanied by aura. Less commonly, aura can occur without a headache, or with a nonmigraine headache. Two other varieties are familial hemiplegic migraine and sporadic hemiplegic migraine, in which a person has migraine with aura and with accompanying motor weakness. If a close relative has had the same condition, it is called "familial", otherwise it is called "sporadic". Another variety is basilar-type migraine, where a headache and aura are accompanied by difficulty speaking, world spinning, ringing in ears, or a number of other brainstem-related symptoms, but not motor weakness. This type was initially believed to be due to spasms of the basilar artery, the artery that supplies the brainstem. Now that this mechanism is not believed to be primary, the symptomatic term migraine with brainstem aura (MBA) is preferred. Childhood periodic syndromes that are commonly precursors of migraine include cyclical vomiting (occasional intense periods of vomiting), abdominal migraine (abdominal pain, usually accompanied by nausea), and benign paroxysmal vertigo of childhood (occasional attacks of vertigo). Retinal migraine involves migraine headaches accompanied by visual disturbances or even temporary blindness in one eye. Complications of migraine describe migraine headaches and/or auras that are unusually long or unusually frequent, or associated with a seizure or brain lesion. Probable migraine describes conditions that have some characteristics of migraines, but where there is not enough evidence to diagnose it as a migraine with certainty (in the presence of concurrent medication overuse). Chronic migraine is a complication of migraines, and is a headache that fulfills diagnostic criteria for migraine headache and occurs for a greater time interval. Specifically, greater or equal to 15 days/month for longer than 3 months. Abdominal migraine The diagnosis of abdominal migraine is controversial. Some evidence indicates that recurrent episodes of abdominal pain in the absence of a headache may be a type of migraine or are at least a precursor to migraines. These episodes of pain may or may not follow a migraine-like prodrome and typically last minutes to hours. They often occur in those with either a personal or family history of typical migraine. Other syndromes that are believed to be precursors include cyclical vomiting syndrome and benign paroxysmal vertigo of childhood. Differential diagnosis Other conditions that can cause similar symptoms to a migraine headache include temporal arteritis, cluster headaches, acute glaucoma, meningitis and subarachnoid hemorrhage. Temporal arteritis typically occurs in people over 50 years old and presents with tenderness over the temple, cluster headache presents with one-sided nose stuffiness, tears and severe pain around the orbits, acute glaucoma is associated with vision problems, meningitis with fevers, and subarachnoid hemorrhage with a very fast onset. Tension headaches typically occur on both sides, are not pounding, and are less disabling.Those with stable headaches that meet criteria for migraines should not receive neuroimaging to look for other intracranial disease. This requires that other concerning findings such as papilledema (swelling of the optic disc) are not present. People with migraines are not at an increased risk of having another cause for severe headaches. Prevention Preventive treatments of migraine include medications, nutritional supplements, lifestyle alterations, and surgery. Prevention is recommended in those who have headaches more than two days a week, cannot tolerate the medications used to treat acute attacks, or those with severe attacks that are not easily controlled. Recommended lifestyle changes include stopping tobacco use and reducing behaviors that interfere with sleep.The goal is to reduce the frequency, painfulness, and duration of migraine episodes, and to increase the effectiveness of abortive therapy. Another reason for prevention is to avoid medication overuse headache. This is a common problem and can result in chronic daily headache. Medication Preventive migraine medications are considered effective if they reduce the frequency or severity of the migraine attacks by at least 50%. Due to few medications being approved specifically for the preventative treatment of migraine headaches; many medications such as beta-blockers, anticonvulsive agents such as topiramate or sodium valproate, antidepressants such as amitriptyline and calcium channel blockers such as flunarizine are used off label for the preventative treatment of migraine headaches. Guidelines are fairly consistent in rating the anticonvulsants topiramate and divalproex/sodium valproate, and the beta blockers propranolol and metoprolol as having the highest level of evidence for first-line use for migraine prophylaxis in adults. Propranolol and topiramate have the best evidence in children; however, evidence only supports short-term benefit as of 2020.The beta blocker timolol is also effective for migraine prevention and in reducing migraine attack frequency and severity. While beta blockers are often used for first-line treatment, other antihypertensives also have a proven efficiency in migraine prevention, namely the calcium channel blocker verapamil and the angiotensin receptor blocker candesartan.Tentative evidence also supports the use of magnesium supplementation. Increasing dietary intake may be better. Recommendations regarding effectiveness varied for the anticonvulsants gabapentin and pregabalin. Frovatriptan is effective for prevention of menstrual migraine.The antidepressants amitriptyline and venlafaxine are probably also effective. Angiotensin inhibition by either an angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist may reduce attacks.Medications in the anti-calcitonin gene-related peptide, including eptinezumab, erenumab, fremanezumab, and galcanezumab, appear to decrease the frequency of migraines by one to two per month. They are, however, expensive: a year of erenumab costs $6,900 as of 2019. Alternative therapies Acupuncture has a small effect in reducing migraine frequency, compared to sham acupuncture, a practice where needles are placed randomly or do not penetrate the skin. Physiotherapy, massage and relaxation, and chiropractic manipulation might be as effective as propranolol or topiramate in the prevention of migraine headaches; however, the research had some problems with methodology. Another review, however, found evidence to support spinal manipulation to be poor and insufficient to support its use.Tentative evidence supports the use of stress reduction techniques such as cognitive behavioral therapy, biofeedback, and relaxation techniques. Regular physical exercise may decrease the frequency. Numerous psychological approaches have been developed that are aimed at preventing or reducing the frequency of migraine in adults including educational approaches, relaxation techniques, assistance in developing coping strategies, strategies to change the way one thinks of a migraine attack, and strategies to reduce symptoms. The medical evidence supporting the effectiveness of these types of psychological approaches is very limited.Among alternative medicines, butterbur has the best evidence for its use. However, unprocessed butterbur contains chemicals called pyrrolizidine alkaloids (PAs) which can cause liver damage, however there are versions that are PA free. In addition, butterbur may cause allergic reactions in people who are sensitive to plants such as ragweed. There is tentative evidence that coenzyme Q10 reduces migraine frequency.Feverfew has traditionally been used as a treatment for fever, headache and migraine, womens conditions such as difficulties in labour and regulation of menstruation, relief of stomach ache, toothache and insect bites. During the last decades, it has mainly been used for headache and as a preventive treatment for migraine. The plant parts used for medicinal use are the dried leaves or the dried aerial parts. Several historical data supports feverfews traditional medicinal uses. In addition, several clinical studies have been performed assessing the efficacy and safety of feverfew monotherapy in the prevention of migraine. The majority of the clinical trials favoured feverfew over placebo. The data also suggest that feverfew is associated with only mild and transient adverse effects. The frequency of migraine was positively affected after treatment with feverfew. Reduction of migraine severity was also reported after intake of feverfew and incidence of nausea and vomiting decreased significantly. No effect of feverfew was reported in one study.There is tentative evidence for melatonin as an add-on therapy for prevention and treatment of migraine. The data on melatonin are mixed and certain studies have had negative results. The reasons for the mixed findings are unclear but may stem from differences in study design and dosage. Melatonins possible mechanisms of action in migraine are not completely clear, but may include improved sleep, direct action on melatonin receptors in the brain, and anti-inflammatory properties. Devices and surgery Medical devices, such as biofeedback and neurostimulators, have some advantages in migraine prevention, mainly when common anti-migraine medications are contraindicated or in case of medication overuse. Biofeedback helps people be conscious of some physiological parameters so as to control them and try to relax and may be efficient for migraine treatment. Neurostimulation uses noninvasive or implantable neurostimulators similar to pacemakers for the treatment of intractable chronic migraine with encouraging results for severe cases. A transcutaneous electrical nerve stimulator and a transcranial magnetic stimulator are approved in the United States for the prevention of migraines. There is also tentative evidence for transcutaneous electrical nerve stimulation decreases the frequency of migraines. Migraine surgery, which involves decompression of certain nerves around the head and neck, may be an option in certain people who do not improve with medications. Management There are three main aspects of treatment: trigger avoidance, acute symptomatic control, and medication for prevention. Medications are more effective if used earlier in an attack. The frequent use of medications may result in medication overuse headache, in which the headaches become more severe and more frequent. This may occur with triptans, ergotamines, and analgesics, especially opioid analgesics. Due to these concerns simple analgesics are recommended to be used less than three days per week at most. Analgesics Recommended initial treatment for those with mild to moderate symptoms are simple analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) or the combination of paracetamol (also known as acetaminophen), aspirin, and caffeine. Several NSAIDs, including diclofenac and ibuprofen have evidence to support their use. Aspirin (900 to 1000 mg) can relieve moderate to severe migraine pain, with an effectiveness similar to sumatriptan. Ketorolac is available in intravenous and intramuscular formulations.Paracetamol, either alone or in combination with metoclopramide, is another effective treatment with a low risk of adverse effects. Intravenous metoclopramide is also effective by itself. In pregnancy, paracetamol and metoclopramide are deemed safe as are NSAIDs until the third trimester.Naproxen by itself may not be effective as a stand-alone medicine to stop a migraine headache as it is only weakly better than a placebo medication in clinical trials. Antiemetics Triptans Triptans such as sumatriptan are medications used to stop an active migraine headache (an abortive medication). Triptans are the initially recommended treatments for those with moderate to severe pain from an acute migraine headache or those with milder symptoms who do not respond to simple analgesics. Triptans have been shown to be effective for both pain and nausea in up to 75% of people. There are different methods or routes of administration to take sumatriptan including oral (by mouth), injectable (subcutaneous), rectal, nasal spray, and oral dissolving tablets. For people with migraine symptoms such as nausea or vomiting, taking the abortive medicine by mouth or through the nose may be difficult. All route of administration have been shown to be effective at reducing migraine symptoms, however, nasal and injectable subcutaneous administration may result in more side effects. The adverse effects associated with rectal administration have not been well studied. Some people may find that they respond to one type of sumatriptan better than another.Most side effects are mild, including flushing; however, rare cases of myocardial ischemia have occurred. They are thus not recommended for people with cardiovascular disease, who have had a stroke, or have migraines that are accompanied by neurological problems. In addition, triptans should be prescribed with caution for those with risk factors for vascular disease. While historically not recommended in those with basilar migraines there is no specific evidence of harm from their use in this population to support this caution. Triptans are not addictive, but may cause medication-overuse headaches if used more than 10 days per month.Sumatriptan does not prevent other migraine headaches from starting in the future. For increased effectiveness at stopping migraine symptoms, a combined therapy that includes sumatriptan and naproxen may be suggested. CGRP receptor antagonists CGRP receptor antagonists target calcitonin gene-related peptide or its receptor to prevent migraine headaches or reduce their severity. CGRP is a signaling molecule as well as a potent vasodilator that is involved in the development of a migraine headache. There are four injectable monoclonal antibodies that target CGRP or its receptor (eptinezumab, erenumab, fremanezumab and galcanezumab) and the medications have demonstrated efficacy in the preventative treatment of episodic and chronic migraine headaches in phase 3 randomized clinical trials. Eptinezumab is available as an infusion every three months, Erenumab and galcanezumab are once monthly injections and fremanezumab is a monthly or quarterly injection. Ergotamines Ergotamine and dihydroergotamine are older medications still prescribed for migraines, the latter in nasal spray and injectable forms. They appear equally effective to the triptans and experience adverse effects that typically are benign. In the most severe cases, such as those with status migrainosus, they appear to be the most effective treatment option. They can cause vasospasm including coronary vasospasm and are contraindicated in people with coronary artery disease. Magnesium Magnesium is recognized as an inexpensive, over-the-counter supplement which some studies have shown to be effective in both preventing and treating migraine in intravenous form. Other Intravenous metoclopramide, intravenous prochlorperazine, or intranasal lidocaine are other potential options. Metoclopramide or prochlorperazine are the recommended treatment for those who present to the emergency department. Haloperidol may also be useful in this group. A single dose of intravenous dexamethasone, when added to standard treatment of a migraine attack, is associated with a 26% decrease in headache recurrence in the following 72 hours. Spinal manipulation for treating an ongoing migraine headache is not supported by evidence. It is recommended that opioids and barbiturates not be used due to questionable efficacy, addictive potential, and the risk of rebound headache. There is tentative evidence that propofol may be useful if other measures are not effective.Occipital nerve stimulation, may be effective but has the downsides of being cost-expensive and has a significant amount of complications.There is modest evidence for the effectiveness of non-invasive neuromodulatory devices, behavioral therapies and acupuncture in the treatment of migraine headaches. There is little to no evidence for the effectiveness of physical therapy, chiropractic manipulation and dietary approaches to the treatment of migraine headaches. Behavioral treatment of migraine headaches may be helpful for those who may not be able to take medications (for example pregnant women).Feverfew is registered as a traditional herbal medicine in the Nordic countries under the brand name Glitinum, only powdered feverfew is approved in the Herbal community monograph issued by European Medicines Agency (EMA). Sexual activity, particularly orgasm, may provide relief for some migraineurs. Children Ibuprofen helps decrease pain in children with migraines and is the initially recommended treatment. Paracetamol does not appear to be effective in providing pain relief. Triptans are effective, though there is a risk of causing minor side effects like taste disturbance, nasal symptoms, dizziness, fatigue, low energy, nausea, or vomiting. Ibuprofen should be used less than half the days in a month and triptans less than a third of the days in a month to decrease the risk of medication overuse headache. Chronic migraine Topiramate and botulinum toxin (Botox) have evidence in treating chronic migraine. Botulinum toxin has been found to be useful in those with chronic migraine but not those with episodic ones. The anti-CGRP monoclonal antibody erenumab was found in one study to decrease chronic migraines by 2.4 days more than placebo. Prognosis "Migraine exists on a continuum of different attack frequencies and associated levels of disability." For those with occasional, episodic migraine, a "proper combination of drugs for prevention and treatment of migraine attacks" can limit the diseases impact on patients personal and professional lives. But fewer than half of people with migraine seek medical care and more than half go undiagnosed and undertreated. "Responsive prevention and treatment of migraine is incredibly important" because evidence shows "an increased sensitivity after each successive attack, eventually leading to chronic daily migraine in some individuals." Repeated migraine results in "reorganization of brain circuitry," causing "profound functional as well as structural changes in the brain." "One of the most important problems in clinical migraine is the progression from an intermittent, self-limited inconvenience to a life-changing disorder of chronic pain, sensory amplification, and autonomic and affective disruption. This progression, sometimes termed chronification in the migraine literature, is common, affecting 3% of migraineurs in a given year, such that 8% of migraineurs have chronic migraine in any given year." Brain imagery reveals that the electrophysiological changes seen during an attack become permanent in people with chronic migraine; "thus, from an electrophysiological point of view, chronic migraine indeed resembles a never-ending migraine attack." Severe migraine ranks in the highest category of disability, according to the World Health Organization, which uses objective metrics to determine disability burden for the authoritative annual Global Burden of Disease report. The report classifies severe migraine alongside severe depression, active psychosis, quadriplegia, and terminal-stage cancer.Migraine with aura appears to be a risk factor for ischemic stroke doubling the risk. Being a young adult, being female, using hormonal birth control, and smoking further increases this risk. There also appears to be an association with cervical artery dissection. Migraine without aura does not appear to be a factor. The relationship with heart problems is inconclusive with a single study supporting an association. Migraine does not appear to increase the risk of death from stroke or heart disease. Preventative therapy of migraines in those with migraine with aura may prevent associated strokes. People with migraine, particularly women, may develop higher than average numbers of white matter brain lesions of unclear significance. Epidemiology Worldwide, migraine affects nearly 15% or approximately one billion people. It is more common in women at 19% than men at 11%. In the United States, about 6% of men and 18% of women experience a migraine attack in a given year, with a lifetime risk of about 18% and 43% respectively. In Europe, migraines affect 12–28% of people at some point in their lives with about 6–15% of adult men and 14–35% of adult women getting at least one yearly. Rates of migraine are slightly lower in Asia and Africa than in Western countries. Chronic migraine occurs in approximately 1.4 to 2.2% of the population.These figures vary substantially with age: onset of migraine is most commonly between 15 and 24 years of age, and occur most frequently in those 35 to 45 years of age. In children, about 1.7% of 7 year olds and 3.9% of those between 7 and 15 experience migraine, with the condition being slightly more common in boys before puberty. Children as young as two years may be affected. During adolescence, migraine becomes more common among women and this persists for the rest of the lifespan, being twice as common among elderly females than males. In women migraine without aura are more common than migraine with aura; however in men the two types occur with similar frequency.During perimenopause symptoms often get worse before decreasing in severity. While symptoms resolve in about two thirds of the elderly, in 3 to 10% they persist. History An early description consistent with migraine is contained in the Ebers papyrus, written around 1500 BCE in ancient Egypt. In 200 BCE, writings from the Hippocratic school of medicine described the visual aura that can precede the headache and a partial relief occurring through vomiting.A second-century description by Aretaeus of Cappadocia divided headaches into three types: cephalalgia, cephalea, and heterocrania. Galen of Pergamon used the term hemicrania (half-head), from which the word migraine was eventually derived. He also proposed that the pain arose from the meninges and blood vessels of the head. Migraine was first divided into the two now used types – migraine with aura (migraine ophthalmique) and migraine without aura (migraine vulgaire) in 1887 by Louis Hyacinthe Thomas, a French Librarian. The mystical visions of Hildegard von Bingen, which she described as “reflections of the living light", are consistent with the visual aura experienced during migraines. Trepanation, the deliberate drilling of holes into a skull, was practiced as early as 7,000 BCE. While sometimes people survived, many would have died from the procedure due to infection. It was believed to work via "letting evil spirits escape". William Harvey recommended trepanation as a treatment for migraines in the 17th century.While many treatments for migraine have been attempted, it was not until 1868 that use of a substance which eventually turned out to be effective began. This substance was the fungus ergot from which ergotamine was isolated in 1918. Methysergide was developed in 1959 and the first triptan, sumatriptan, was developed in 1988. During the 20th century with better study-design, effective preventive measures were found and confirmed. Society and culture Migraine is a significant source of both medical costs and lost productivity. It has been estimated that migraine is the most costly neurological disorder in the European Community, costing more than €27 billion per year. In the United States, direct costs have been estimated at $17 billion, while indirect costs — such as missed or decreased ability to work — is estimated at $15 billion. Nearly a tenth of the direct cost is due to the cost of triptans. In those who do attend work during a migraine attack, effectiveness is decreased by around a third. Negative impacts also frequently occur for a persons family. Research Potential prevention mechanisms Transcranial magnetic stimulation shows promise as does transcutaneous supraorbital nerve stimulation. There is preliminary evidence that a ketogenic diet may help prevent episodic and long-term migraine. Potential gender dependency While no definitive proof has been found linking migraine to gender, statistical data indicates that women may be more prone to having migraine, showing migraine incidence three times higher among women than men. The Society for Womens Health Research has also mentioned hormonal influences, mainly estrogen, as having a considerable role in provoking migraine pain. Studies and research related to the gender dependencies of migraine are still ongoing, and conclusions have yet to be achieved. References Notes Olesen J (2006). The headaches (3 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 9780781754002. Further reading Ashina M (November 2020). Ropper AH (ed.). "Migraine". The New England Journal of Medicine. 383 (19): 1866–1876. doi:10.1056/nejmra1915327. PMID 33211930. S2CID 227078662. Oskoui M, Pringsheim T, Billinghurst L, Potrebic S, Gersz EM, Gloss D, et al. (September 2019). "Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 93 (11): 500–509. doi:10.1212/WNL.0000000000008105. PMC 6746206. PMID 31413170. Oskoui M, Pringsheim T, Holler-Managan Y, Potrebic S, Billinghurst L, Gloss D, et al. (September 2019). "Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 93 (11): 487–499. doi:10.1212/WNL.0000000000008095. PMID 31413171. S2CID 199662718. External links Migraine at Curlie

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Please help me grasp the concept behind the medical term 'Lathosterolosis.'

Lathosterolosis is a defect in cholesterol biosynthesis. See also SC5DL Lathosterol References == External links ==

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I need a basic explanation for the medical term 'Generalized tonic–clonic seizure.'

A generalized tonic–clonic seizure, or GTCS, previously known as a Grand mal seizure, is a type of generalized seizure that produces bilateral, convulsive tonic and then clonic muscle contractions. Tonic-clonic seizures are the seizure type most commonly associated with epilepsy and seizures in general and the most common seizure associated with metabolic imbalances. It is a misconception that they are the sole type of seizure, as they are the main seizure type in approximately 10% of those with epilepsy.These seizures typically initiate abruptly with either a focal or generalized onset, the former being known as focal to bilateral tonic-clonic seizure. The seizure itself includes tonic (sustained) and then clonic (repetitive short) contractions. In some seizures, the tonic phase may be preceded by brief, arrhythmic muscle jerks (myoclonus), by a clonic phase or by an absence seizure. After the GTCS, there is an extended postictal state where the person is unresponsive and commonly sleeping with loud snoring. There is usually pronounced confusion upon awakening. Causes The vast majority of generalized tonic-clonic seizures have a focal origin they start as a smaller seizure that occurs solely on one side of the brain and is referred to as a focal (or partial) seizure. These unilateral seizure types (formerly known as simple partial seizure or a complex partial seizure and now referred to as focal aware seizure and focal impaired awareness seizure, respectively) can then spread to both hemispheres of the brain and cause a generalized tonic-clonic seizure. This type of seizure has a specific term called "focal to a bilateral tonic-clonic seizure. Other generalized tonic-clonic seizures are idiopathic, start in large networks involving both hemispheres, and have a presumed genetic cause. Precipitating factors include chemical and neurotransmitter imbalances and a genetically or situationally determined seizure threshold, both of which have been implicated. The seizure threshold can be altered by fatigue, malnutrition, lack of sleep or rest, hypertension, stress, diabetes, the presence of strobe-flashes or simple light/dark patterns, raised estrogen levels at ovulation, fluorescent lighting, rapid motion or flight, blood sugar imbalances, anxiety, antihistamines and other factors. Tonic–clonic seizures can also be induced deliberately with electroconvulsive therapy.In the case of symptomatic focal epilepsy, the cause is often determined by MRI or other neuroimaging techniques showing that there is some degree of damage to a large number of neurons. The lesions (i.e., scar tissue) caused by the loss of these neurons can result in groups of neurons forming a seizure "focus" area with episodic abnormal firing that can cause seizures if the focus is not abolished or suppressed via anticonvulsant drugs. Mechanism Prodrome Most generalized tonic–clonic seizures begin without warning and abruptly, but some epileptic patients describe a prodrome. The prodrome of a generalized tonic–clonic seizure is a sort of premonitory feeling hours before a seizure. This type of prodrome is distinct from stereotypic aura of focal seizures that become generalized seizures. Phases A tonic–clonic seizure comprises three phases: the tonic phase, clonic phase and postictal phase. Tonic phaseThe tonic phase is usually the first phase. Consciousness will quickly be lost and the skeletal muscles will suddenly tense, often causing the extremities to be pulled towards the body or rigidly pushed away from it, which will cause the patient to fall if standing or sitting. There may also be upward deviation of the eyes with the mouth open. The tonic phase is usually the shortest part of the seizure, normally lasting only 10–20 seconds. The patient typically expresses brief vocalizations like a loud moan upon entering the tonic stage, due to air being forcefully expelled from the lungs. This vocalization is commonly referred to as an "ictal cry." Starting in the tonic phase, there may also be bluing of the skin from respiration impairment as well as pooling of saliva in the back of the throat. Increased blood pressure, pupillary size and heart rate (sympathetic response) may also be noted with clenching of the jaw possibly resulting in biting the tongue. The initial tonic phase may be preceded by repetitive rhythmic or arrhythmic jerks or by the absence seizure. Clonic phaseThe clonic phase is an evolution of the tonic phase and is caused by muscle relaxations superimposed on the tonic phase muscle contractions. This phase is longer than the tonic phase with the total ictal period usually lasting no longer than 1 min. Skeletal muscles will start to contract and relax rapidly, causing convulsions. These may range from exaggerated twitches of the limbs to violent shaking or vibrating of the stiffened extremities. The patient may roll and stretch as the seizure spreads. Initially, these contractions are of a high frequency and low amplitude, which will gradually progress to decreased frequency and high amplitude. An eventual decrease in contraction amplitude just before seizure cessation is also typical.Postictal phaseThe postictal phase causes are multifactorial to include alteration of cerebral blood flow and effects on multiple neurotransmitters. These changes after a generalized tonic–clonic seizure cause a period of postictal sleep with stertorous breathing. Confusion and total amnesia upon regaining consciousness are also usually experienced and slowly wear off as the patient becomes gradually aware that a seizure occurred and remembers their identity and location. Most often, patients regain consciousness within 30 minutes. Rarely, impaired consciousness duration can last several hours after a seizure, especially with a compounding central nervous system condition or a prolonged seizure. Occasionally the patient may vomit or burst into tears from the experienced mental trauma. An additional smaller seizure can also occur several minutes after the main seizure, particularly if the patients seizure threshold has been brought unusually low by known factors or combinations of such. Examples include: severe hangovers, sleep deprivation, elevated estrogen at ovulation, prolonged physical tiredness, and drug use or abuse (including, but not limited to, stimulants, alcohol and caffeine). Rarely, the respiration is inhibited during the postictal phase, leading to sudden unexpected death in epilepsy (SUDEP). Generalized tonic–clonic seizures represent the most important risk factor for SUDEP, especially in patients with nocturnal seizures, who are living alone or do not share a bedroom. Diagnosis Diagnosis can be made definitively by video recordings of the seizures and Electroencephalography (EEG), which records the electrical activity of the brain. This is typically done after a seizure episode in a clinical setting with an attempt to "capture" a seizure while it happens. According to the "Harrisons Manual of Medicine," the EEG during the tonic phase will show a "progressive increase in low-voltage fast wave activity, followed by generalized high-amplitude, poly spike discharges." The clonic phase EEG will show "high amplitude activity that is typically interrupted by slow waves to create a spike-and-slow-wave pattern." Additionally, the postictal phase will show suppression of all brain activity, then slowing that gradually recovers as the patient awakens. Management For a person experiencing a tonic–clonic seizure, first-aid treatment includes rolling the person over into the recovery position, which can prevent asphyxiation by preventing fluid from entering the lungs. Other general actions to take as recommended by the Epilepsy Foundation include staying with a person until a seizure is over, paying attention to length of seizure as a possible indication for status epilepticus and/or indication to give rescue medication and call for emergency help, moving close objects out of the way to prevent injury. It is also not recommended to hold a person down that is having a seizure, as that can lead to injury. Nor should anything be put in a persons mouth, as these items can become choking hazards and, depending on what is put in, can potentially break the persons teeth. Long-term therapy may include the use of antiepileptic drugs, surgical therapy, diet therapy (ketogenic diet), vagus nerve stimulation, or deep brain stimulation. Terminology Generalized tonic–clonic seizures can have a focal onset (described above) that progresses into a generalized seizure or be a generalized seizure at the onset. The term "Grand Mal" is outdated and nonspecific, referring to generalized tonic-clonic seizures with either a focal or generalized onset. See also Focal seizure Absence seizure Epileptic seizure Non-epileptic seizure Tonic (physiology) Clonus Postictal state Electroencephalography References External links Generalized tonic–clonic seizure at Curlie

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I'm trying to understand 'Congenital dermal sinus' within a medical context. Could you shed some light on it?

Congenital dermal sinus is an uncommon form of cranial or spinal dysraphism. It occurs in 1 in 2500 live births. It occurs as a dermal indentation, found along the midline of the neuraxis and often presents alongside infection and neurological deficit. Congenital dermal sinus form due to a focal failure of dysjunction between the cutaneous ectoderm and neuroectoderm during the third to eight week of gestation. Typically observed in the lumbar and lumbosacral region, congenital dermal sinus can occur from the nasion and occiput region down.Early diagnosis and treatment is crucial for cases of congenital dermal sinus. It ensures that neurological condition does not degrade and prevents infection. Diagnosis can be confirmed through the use of advanced neuroimaging to observe the tract and associated lesions. Embryogenesis During normal development, cutaneous ectoderm separates from neuroectoderm to allow for the insertion of mesoderm. That is, the skin separates from the tissue of the spinal cord to allow proper formation of the vertebral column. In cases of congenital dermal sinus there is a failure in this process, resulting in formation of a persistent connection between the skin and neural tissue. This manifests as a tract extending from the surface of the skin to the spinal cord lined with stratified squamous epithelium, surrounded by dermal and neurological tissue. The tract may terminate in the deep fascia, or even make contact with neural elements. Congenital dermal sinus may form at any point along the midline of the neuraxis, however, the majority form in the lumbar and lumbosacral region (41% and 35% of cases respectively). Diagnosis Congenital dermal sinus is often diagnosed in infants and children. Early diagnosis is important in congenital dermal sinus, so that treatment can be provided early, to prevent progression of associated complications. Clinical features There three key hallmarks of congenital dermal sinus: cutaneous abnormalities, infection, and neurological deficits. Cutaneous abnormalities Congenital dermal sinus is a tract from the surface layer of the skin, through the deeper tissues into the cranial or spinal cavity. The skin findings of this tract can include: Pit along neuraxis Flat capillary hemangioma Hypertrichosis Skin tag Abnormal pigmentation Subcutaneous lipoma Signs of local infection Infection The stratified squamous epithelium of the congenital dermal sinus tract can extend to the spinal fascia of the dura mater or all the way to the spinal cord. Thus, the congenital dermal sinus forms a point of entry for infection, this can allow for the formation of an abscess, especially among children. Infection can then travel up the spinal cord to result in meningitis, which can be fatal if left untreated. Neurological deficit Congenital dermal sinus is often also associated with spinal fluid drainage, intradural cysts and spinal cord tethering; conveying neurological deficit. Neurological deficit can occur due to spinal cord compression from intradural dermoid cyst growth in the epidermis and dermis. Tethered spinal cord can result in gait difficulties and sphincter dysfunction, as well as compressing the spine. Neurological deficits are more likely to occur where diagnosis has not been timely, allowing cysts and or infection. Imaging Magnetic Resonance Imaging (MRI) is the preferred tool for diagnostic and preoperative imaging of congenital dermal sinus. MRI allows the neural structures to be observed, visualizing the tract and its anomalies and lesions. For example, exposing tethered cord, inclusion tumors or spinal cord malformations. Observation by X-ray is limited in diagnosis, especially due to immature calcification of infants less than 18 months. X-ray may be used in conjunction with MRI or sonogram images to assist preoperatively. Treatment Treatment of congenital dermal sinus involves complete resection of the tract as well as intradural exploration. Prophylactic surgical removal of the congenital dermal sinus tract is beneficial for the patient, allowing neurological and bladder function to be maintained. Early surgical intervention results decreases the risk of infection and/or tumour progression – factors typically associated with delayed presentation of congenital dermal sinus. ] Intradural exploration is necessary as excision of the entire tract, as well as any of its intradural connections, reduces need for further surgical intervention.The surgical technique involves ‘removing the cutaneous lesion in ellipse’. The tract of the congenital dermal sinus must then be explored and excised, with intradural lesions dissected. If not all epithelial tissue is removed, there is a possibility for the dermoid cyst to reoccur and require further operation. Further operations are limited by postoperative and post-infection scarring. History Prior to pervasive use and availability of advanced methods of neuroimaging, it is possible that the rate of incidence of congenital dermal sinus has been supplemented by the incidence of coccygeal pits. Coccygeal pits are distinct from congenital dermal sinus as they are found within the gluteal cleft, rather than above the gluteal cleft. The caudally orientated coccygeal pits are not associated with intradural pathology and do not need to be excised, unlike the cephalically oriented tracts of the congenital dermal sinus which confer great intradural pathology and require surgical intervention. While coccygeal pits occur in 4% of neonate population, congenital dermal sinus is only found in 1 in 2500 live births. == References ==

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I'm looking for a concise explanation of the medical term 'Polio vaccine.'

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccines cause about three cases of vaccine-associated paralytic poliomyelitis per million doses given. This compares with 5,000 cases per million who are paralysed following a polio infection. Both types of vaccine are generally safe to give during pregnancy and in those who have HIV/AIDS but are otherwise well. However, the emergence of circulating vaccine-derived poliovirus (cVDPV), a form of the vaccine virus that has reverted to causing poliomyelitis, has led to the development of novel oral polio vaccine type 2 (nOPV2) which aims to make the vaccine safer and thus stop further outbreaks of cVDPV2.The first successful demonstration of a polio vaccine was by Hilary Koprowski in 1950, with a live attenuated virus which people drank. The vaccine was not approved for use in the United States, but was used successfully elsewhere. The success of an inactivated (killed) polio vaccine, developed by Jonas Salk, was announced in 1955. Another attenuated live oral polio vaccine was developed by Albert Sabin and came into commercial use in 1961.Polio vaccine is on the World Health Organizations List of Essential Medicines. Medical uses Interruption of person-to-person transmission of the virus by vaccination is important in global polio eradication, since no long-term carrier state exists for poliovirus in individuals with normal immune function, polio viruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote. There are two types of vaccine: inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Inactivated When the IPV (injection) is used, 90% or more of individuals develop protective antibodies to all three serotypes of polio virus after two doses of inactivated polio vaccine (IPV), and at least 99% are immune to polio virus following three doses. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to provide protection for many years. IPV replaced the oral vaccine in many developed countries in the 1990s mainly due to the (small) risk of vaccine-derived polio in the oral vaccine. Attenuated Oral polio vaccines were easier to administer than IPV, as it eliminated the need for sterile syringes and therefore was more suitable for mass vaccination campaigns. OPV also provided longer-lasting immunity than the Salk vaccine, as it provides both humoral immunity and cell-mediated immunity.One dose of OPV produces immunity to all three poliovirus serotypes in roughly 50% of recipients. Three doses of live-attenuated OPV produce protective antibodies to all three poliovirus types in more than 95% of recipients. OPV produces excellent immunity in the intestine, the primary site of wild poliovirus entry, which helps prevent infection with wild virus in areas where the virus is endemic. The live virus used in the vaccine can rarely shed in the stool and can rarely spread to others within a community. The live virus also has stringent requirements for transport and storage, which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is probably lifelong.The trivalent (against wild types 1, 2, and 3) OPV has been used to nearly eradicate polio infection worldwide. Led by the Global Polio Eradication Initiative, 155 countries switched to use the bivalent (against wild types 1 and 3) between 17 April and 1 May 2016. The bivalent OPV is more effective against types 1 and 3, but does not cover type 2. The United States as of 2017 continues to recommend the use of a trivalent version, but a fully inactivated version. The switch to the bivalent vaccine and associated missing immunity against type 2 strains, among other factors, led to outbreaks of circulating vaccine-derived poliovirus type 2(cVDPV2), which increased from 2 cases in 2016 to 1037 cases in 2020. As a response, a novel oral polio vaccine type 2 (nOPV2) was developed with the aim to provide a safer form of vaccination against type 2 strains with less risk of reverting to infectious polio. Schedule In countries with endemic polio or where the risk of imported cases is high, the WHO recommends OPV vaccine at birth followed by a primary series of three OPV doses and at least one IPV dose starting at 6 weeks of age, with a minimum of 4 weeks between OPV doses. In countries with >90% immunization coverage and low risk of importation, the WHO recommends one or two IPV doses starting at 2 months of age followed by at least two OPV doses, with the doses separated by 4–8 weeks depending on the risk of exposure. In countries with the highest levels of coverage and the lowest risks of importation and transmission, the WHO recommends a primary series of three IPV injections, with a booster dose after an interval of six months or more if the first dose was administered before 2 months of age. Side effects The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccine results in vaccine-associated paralytic poliomyelitis in about three per million doses. They are generally safe to give to those who are pregnant, and those who have HIV/AIDS, but who are otherwise well. Allergic reaction to the vaccine Inactivated polio vaccine can cause an allergic reaction in a few people since the vaccine contains trace amounts of antibiotics, streptomycin, polymyxin B, and neomycin. It should not be given to anyone who has an allergic reaction to these medicines. Signs and symptoms of an allergic reaction, which usually appear within minutes or a few hours after receiving the injected vaccine, include breathing difficulties, weakness, hoarseness or wheezing, heart rate fluctuations, skin rash and dizziness. Vaccine-induced polio A potential, adverse effect of the OPV is its known ability to recombine to a form that causes neurological infection and paralysis. This genetic reversal of the pathogen to a virulent form takes a considerable time (at least 12 months) and does not affect the person who was originally vaccinated. The vaccine-derived attenuated virus is normally excreted from vaccinated people for a limited period. Thus, in areas with poor sanitation and low vaccination coverage, the spontaneous reversal of the vaccine-derived virus to a virulent form and its spreading in the environment can lead to unvaccinated people becoming infected. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. Outbreaks of vaccine-associated paralytic poliomyelitis (VAPP), caused by a circulating vaccine-derived poliovirus (cVDPV), have been reported, and tend to occur in areas of low coverage by OPV, presumably because the OPV is itself protective against the related outbreak strain. With wild polio cases at record lows, 2017 was the first year where more cases of cVDPV were recorded than the wild poliovirus, a trend that is expected to continue.To combat this, the WHO in 2016, decided to switch from the trivalent polio vaccine to the bivalent polio vaccine. This vaccine no longer contains the type 2 polio virus because it was eradicated in 1999. Contamination concerns In 1960, the rhesus monkey kidney cells used to prepare the poliovirus vaccines were determined to be infected with the simian virus-40 (SV40), which was also discovered in 1960 and is a naturally occurring virus that infects monkeys. In 1961, SV40 was found to cause tumors in rodents. More recently, the virus was found in certain forms of cancer in humans, for instance brain and bone tumors, pleural and peritoneal mesothelioma, and some types of non-Hodgkin lymphoma. However, SV40 has not been determined to cause these cancers.SV40 was found to be present in stocks of the injected form of the IPV in use between 1955 and 1963. It is not found in the OPV form. Over 98 million Americans received one or more doses of polio vaccine between 1955 and 1963 when a proportion of vaccine was contaminated with SV40; an estimated 10–30 million Americans may have received a dose of vaccine contaminated with SV40. Later analysis suggested that vaccines produced by the former Soviet bloc countries until 1980, and used in the USSR, China, Japan, and several African countries, may have been contaminated, meaning hundreds of millions more may have been exposed to SV40.In 1998, the National Cancer Institute undertook a large study, using cancer case information from the institutes SEER database. The published findings from the study revealed no increased incidence of cancer in persons who may have received vaccine containing SV40. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial, however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy. During the race to develop an oral polio vaccine, several large-scale human trials were undertaken. By 1958, the National Institutes of Health had determined that OPV produced using the Sabin strains were the safest. Between 1957 and 1960, however, Hilary Koprowski continued to administer his vaccine around the world. In Africa, the vaccines were administered to roughly one million people in the Belgian territories (now the Democratic Republic of the Congo, Rwanda, and Burundi). The results of these human trials have been controversial, and unfounded accusations in the 1990s arose that the vaccine had created the conditions necessary for transmission of simian immunodeficiency virus from chimpanzees to humans, causing HIV/AIDS. These hypotheses, however, have been conclusively refuted. By 2004, cases of poliomyelitis in Africa had been reduced to just a small number of isolated regions in the western portion of the continent, with sporadic cases elsewhere. Recent local opposition to vaccination campaigns have evolved due to lack of adequate information, often relating to fears that the vaccine might induce sterility. The disease has since resurged in Nigeria and in several other African nations without necessary information, which epidemiologists believe is due to refusals by certain local populations to allow their children to receive the polio vaccine. Manufacture Inactivated The Salk vaccine, IPV, is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome. In the United States, vaccine is administered along with the tetanus, diphtheria, and acellular pertussis vaccines (DTaP) and a pediatric dose of hepatitis B vaccine. In the UK, IPV is combined with tetanus, diphtheria, pertussis, and Haemophilus influenzae type b vaccines. Attenuated OPV is an attenuated vaccine, produced by the passage of the virus through nonhuman cells at a subphysiological temperature, which produces spontaneous mutations in the viral genome. Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin. Other groups, led by Hilary Koprowski and H.R. Cox, developed their own attenuated vaccine strains. In 1958, the National Institutes of Health created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio, while retaining a low incidence of neuropathogenicity in monkeys. Large-scale clinical trials performed in the Soviet Union in late 1950s to early 1960s by Mikhail Chumakov and his colleagues demonstrated safety and high efficacy of the vaccine. Based on these results, the Sabin strains were chosen for worldwide distribution. Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. The primary attenuating factor common to all three Sabin vaccines is a mutation located in the viruss internal ribosome entry site, which alters stem-loop structures and reduces the ability of poliovirus to translate its RNA template within the host cell. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV (TOPV) was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. A second wave of mass immunizations led to a further dramatic decline in the number of polio cases. Between 1962 and 1965, about 100 million Americans (roughly 56% of the population at that time) received the Sabin vaccine. The result was a substantial reduction in the number of poliomyelitis cases, even from the much-reduced levels following the introduction of the Salk vaccine.OPV is usually provided in vials containing 10–20 doses of vaccine. A single dose of oral polio vaccine (usually two drops) contains 1,000,000 infectious units of Sabin 1 (effective against PV1), 100,000 infectious units of the Sabin 2 strain, and 600,000 infectious units of Sabin 3. The vaccine contains small traces of antibiotics—neomycin and streptomycin—but does not contain preservatives. History In a generic sense, vaccination works by priming the immune system with an immunogen. Stimulating immune response, by use of an infectious agent, is known as immunization. The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community.The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest states. 1930s In the 1930s, poliovirus was perceived as especially terrifying, as little was known of how the disease was transmitted or how it could be prevented. This virus was also notable for primarily impacting affluent children, making it a prime target for vaccine development, despite its relatively low mortality and morbidity. Despite this, the community of researchers in the field thus far had largely observed an informal moratorium on any vaccine development as it was perceived to present too high a risk for too little likelihood of successThis shifted in the early 1930s when American groups took up the challenge: Maurice Brodie led a team from the public health laboratory of the city of New York and Dr. John A. Kolmer collaborated with the Research Institute of Cutaneous Medicine in Philadelphia. The rivalry between these two researchers lent itself to a race-like mentality which, combined with a lack of oversight of medical studies, was reflected in the methodology and outcomes of each of these early vaccine development ventures. Kolmers live vaccine Kolmer began his vaccine development project in 1932 and ultimately focused on producing an attenuated or live virus vaccine. Inspired by the success of vaccines for rabies and yellow fever, he hoped to use a similar process to denature the polio virus. In order to go about attenuating his polio vaccine, he repeatedly passed the virus through monkeys. Using methods of production that were later described as "hair-raisingly amateurish, the therapeutic equivalent of bath-tub gin," Kolmer ground the spinal cords of his infected monkeys and soaked them in a salt solution. He then filtered the solution through mesh, treated it with ricinolate, and refrigerated the product for 14 days to ultimately create what would later be prominently critiqued as a "veritable witches brew".In keeping with the norms of the time, Kolmer completed a relatively small animal trial with 42 monkeys before proceeding to self experimentation in 1934. He tested his vaccine upon himself, his two children, and his assistant. He gave his vaccine to just 23 more children before declaring it safe and sending it out to doctors and health departments for a larger test of efficacy. By April 1935, he was able to report having tested the vaccine on 100 children without ill effect. Kolmers first formal presentation of results would not come about until November 1935 where he presented the results of 446 children and adults he had vaccinated with his attenuated vaccine. He also reported that together the Research Institute of Cutaneous Medicine and the Merrell Company of Cincinnati (the manufacturer who held the patent for his ricinoleating process) had distributed 12,000 doses of vaccine to some 700 physicians across the United States and Canada. Kolmer did not describe any monitoring of this experimental vaccination program nor did he provide these physicians with instructions in how to administer the vaccine or how to report side effects. Kolmer dedicated the bulk of his publications thereafter to explaining what he believed to be the cause of the 10+ reported cases of paralytic polio following vaccination, in many cases in towns where no polio outbreak had occurred. Six of these cases had been fatal. Kolmer had no control group but asserted that many more children would have gotten sick. Brodies inactivated vaccine At nearly the same time as Kolmers project, Maurice Brodie had joined immunologist Dr. William H. Park at the New York City Health Department where they worked together on poliovirus. With the aid of grant funding from the Presidents Birthday Ball Commission (a predecessor to what would become the March of Dimes), Brodie was able to pursue development of an inactivated or "killed virus" vaccine. Brodies process also began by grinding the spinal cords of infectious monkeys and then treating the cords with various germicides, ultimately finding a solution of formaldehyde to be the most effective. By the June 1, 1934, Brodie was able to publish his first scholarly article describing his successful induction of immunity in three monkeys with inactivated polio virus. Through continued study on an additional 26 monkeys, Brodie ultimately concluded that administration of live virus vaccine tended to result in humoral immunity while administration of killed virus vaccine tended to result in tissue immunity.Soon after, following a similar protocol to Kolmer, Brodie proceeded with self experimentation upon himself and his co-workers at the NYC Health Department laboratory. Brodies progress was eagerly covered by popular press as the public hoped for a successful vaccine to become available. Such reporting did not make mention of the 12 children in a New York City Asylum who were subjected to early safety trials. As none of the subjects experienced ill effects, Dr. Park, described by contemporaries as "never one to let grass grow under his feet," declared the vaccine safe. When a severe polio outbreak overwhelmed Kern County, California it became the first trial site for the new vaccine on very short notice. Between November 1934 - May 1935, over 1,500 doses of the vaccine were administered in Kern County. While initial results were very promising, insufficient staffing and poor protocol design left Brodie open to criticism when he published the California results in August 1935. Through private physicians, Brodie also conducted a broader field study, including 9,000 children who received the vaccine and 4,500 age- and location-matched controls who did not receive a vaccine. Again, results were promising. Of those who received the vaccine, only a few went on to develop polio. Most had been exposed prior to vaccination and none had received the full series of vaccine doses being studied. Additionally, a polio epidemic in Raleigh, North Carolina provided an opportunity for the U.S. Public Health Service to conduct a highly structured trial of the Brodie vaccine using funding from the Birthday Ball Commission. Academic reception While their work was ongoing, the larger community of bacteriologists began to raise concerns regarding the safety and efficacy of the new poliovirus vaccines. At this time there was very little oversight of medical studies, and ethical treatment of study participants largely relied upon moral pressure from peer academic scientists. Brodies inactivated vaccines faced scrutiny from many who felt killed virus vaccines could not be efficacious. While researchers were able to replicate the tissue immunity he had produced in his animal trials, prevailing wisdom was that humoral immunity was essential for an efficacious vaccine. Kolmer directly questioned the killed virus approach in scholarly journals. Kolmers studies however had raised even more concern with increasing reports of children becoming paralysed following vaccination with his live virus vaccine and notably, with paralysis beginning at the arm rather than the foot in many cases. Both Kolmer and Brodie were called to present their research at the Annual Meeting of the American Public Health Association in Milwaukee WI in October 1935. Additionally, Dr. Thomas M. Rivers was asked to discuss each of the presented papers as a prominent critic of the vaccine development effort. This resulted in the APHA arranging a Symposium on Poliomyelitis to be delivered at the Annual Meeting of their Southern Branch the following month. It was during the discussion at this meeting that Dr. James Leake of the U.S. Public Health Service stood to immediately present clinical evidence that the Kolmer vaccine had caused several deaths and then allegedly accused Kolmer of being a murderer. As Rivers recalled in his oral history, "All hell broke loose, and it seemed as if everybody was trying to talk at the same time....Jimmy Leake used the strongest language that I have ever heard used at a scientific meeting." In response to the attacks from all sides, Brodie was reported to have stood up and stated, "It looks as though, according to Dr. Rivers, my vaccine is no good, and, according to Dr. Leake, Dr Kolmers is dangerous." Kolmer simply responded by stating, "Gentlemen, this is one time I wish the floor would open up and swallow me." Ultimately, Kolmers live vaccine was undoubtedly shown to be dangerous and had already been withdrawn in September 1935 prior to the Milwaukee meeting. While the consensus of the symposium was largely sceptical of the efficacy of Brodies vaccine, its safety was not in question and the recommendation was for a much larger well-controlled trial. However, when three children became ill with paralytic polio following a dose of the vaccine, the directors of the Warm Springs Foundation in Georgia (acting as the primary funders for the project) requested it be withdrawn in December 1935. Following its withdrawal, the previously observed moratorium on human poliomyelitis vaccine development resumed and there would not be another attempt for nearly 20 years.While Brodie had arguably made the most progress in the pursuit of a poliovirus vaccine, he suffered the most significant career repercussions due to his status as a less widely known researcher. Modern researchers recognize that Brodie may well have developed an effective polio vaccine, however the basic science and technology of the time was insufficient to understand and utilize this breakthrough. Brodies work using formalin-inactivated virus would later become the basis for the Salk vaccine, but he would not live to see this success. Brodie was fired from his position within three months of the symposiums publication. While he was able to find another laboratory position, he died of a heart attack only three years later at age 36. By contrast, Park, who was believed in the community to be reaching senility at this point in his older age, was able to retire from his position with honors prior to his death in 1939. Kolmer, already an established and well respected researcher, returned to Temple University as a professor of medicine. Kolmer had a very productive career, receiving multiple awards, and publishing countless papers, articles, and textbooks up until his retirement in 1957. 1948 A breakthrough came in 1948 when a research group headed by John Enders at the Childrens Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948, Thomas H. Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that there were a few unused tubes. He retrieved a sample of mouse brain infected with poliovirus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow, but the polio cultures were successful. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized in 1954 for their efforts with a Nobel Prize in Physiology or Medicine. Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotypes (Poliovirus type 1 – PV1, or Mahoney; PV2, Lansing; and PV3, Leon); the finding that prior to paralysis, the virus must be present in the blood; and the demonstration that administration of antibodies in the form of gamma globulin protects against paralytic polio. 1950–1955 During the early 1950s, polio rates in the U.S. were above 25,000 annually; in 1952 and 1953, the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, respectively, up from a typical number of some 20,000 a year, with deaths in those years numbering 3,200 and 1,400. Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox. Also working at Lederle was Polish-born virologist and immunologist Hilary Koprowski of the Wistar Institute in Philadelphia, who tested the first successful polio vaccine, in 1950. His vaccine, however, being a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salks polio vaccine (a dead-virus injectable vaccine) had reached the market. Koprowskis attenuated vaccine was prepared by successive passages through the brains of Swiss albino mice. By the seventh passage, the vaccine strains could no longer infect nervous tissue or cause paralysis. After one to three further passages on rats, the vaccine was deemed safe for human use. On 27 February 1950, Koprowskis live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village, an institution for physically and mentally disabled people located in New York. After the child had no side effects, Koprowski enlarged his experiment to include 19 other children. Jonas Salk The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, which required years of subsequent testing. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later, the results were published in JAMA. Leone N. Farrell invented a key laboratory technique that enabled the mass production of the vaccine by a team she led in Toronto. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania.Salks vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis, the largest medical experiment in history at that time. The test began with about 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and eventually involved 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio.The results of the field trial were announced 12 April 1955 (the tenth anniversary of the death of President Franklin D. Roosevelt, whose paralytic illness was generally believed to have been caused by polio). The Salk vaccine had been 60–70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. Soon after Salks vaccine was licensed in 1955, childrens vaccination campaigns were launched. In the U.S, following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States.A week before the announcement of the Francis Field Trial results in April 1955, Pierre Lépine at the Pasteur Institute in Paris had also announced an effective polio vaccine. Safety incidents In April 1955, soon after mass polio vaccination began in the US, the Surgeon General began to receive reports of patients who contracted paralytic polio about a week after being vaccinated with Salk polio vaccine from the Cutter pharmaceutical company, with the paralysis limited to the limb the vaccine was injected into. The Cutter vaccine had been used in vaccinating 200,000 children in the western and midwestern United States. Later investigations showed that the Cutter vaccine had caused 40,000 cases of polio, killing 10. In response the Surgeon General pulled all polio vaccines made by Cutter Laboratories from the market, but not before 250 cases of paralytic illness had occurred. Wyeth polio vaccine was also reported to have paralyzed and killed several children. It was soon discovered that some lots of Salk polio vaccine made by Cutter and Wyeth had not been properly inactivated, allowing live poliovirus into more than 100,000 doses of vaccine. In May 1955, the National Institutes of Health and Public Health Services established a Technical Committee on Poliomyelitis Vaccine to test and review all polio vaccine lots and advise the Public Health Service as to which lots should be released for public use. These incidents reduced public confidence in polio vaccine, leading to a drop in vaccination rates. 1961 At the same time that Salk was testing his vaccine, both Albert Sabin and Hilary Koprowski continued working on developing a vaccine using live virus. During a meeting in Stockholm to discuss polio vaccines in November 1955, Sabin presented results obtained on a group of 80 volunteers, while Koprowski read a paper detailing the findings of a trial enrolling 150 people. Sabin and Koprowski both eventually succeeded in developing vaccines. Because of the commitment to the Salk vaccine in America, Sabin and Koprowski both did their testing outside the United States, Sabin in Mexico and the Soviet Union, Koprowski in the Congo and Poland. In 1957, Sabin developed a trivalent vaccine containing attenuated strains of all three types of poliovirus. In 1959, ten million children in the Soviet Union received the Sabin oral vaccine. For this work, Sabin was given the medal of the Order of Friendship of Peoples, described as the Soviet Unions highest civilian honor. Sabins oral vaccine using live virus came into commercial use in 1961.Once Sabins oral vaccine became widely available, it supplanted Salks injected vaccine, which had been tarnished in the publics opinion by the Cutter incident of 1955, in which Salk vaccines improperly prepared by one company resulted in several children dying or becoming paralyzed. 1987 An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice there. The first dose of polio vaccine is given shortly after birth, usually between 1 and 2 months of age, and a second dose is given at 4 months of age. The timing of the third dose depends on the vaccine formulation, but should be given between 6 and 18 months of age. A booster vaccination is given at 4 to 6 years of age, for a total of four doses at or before school entry. In some countries, a fifth vaccination is given during adolescence. Routine vaccination of adults (18 years of age and older) in developed countries is neither necessary nor recommended because most adults are already immune and have a very small risk of exposure to wild poliovirus in their home countries. In 2002, a pentavalent (five-component) combination vaccine (called Pediarix) containing IPV was approved for use in the United States. 1988 A global effort to eradicate polio, led by the World Health Organization (WHO), UNICEF, and the Rotary Foundation, began in 1988, and has relied largely on the oral polio vaccine developed by Albert Sabin and Mikhail Chumakov (Sabin-Chumakov vaccine). After 1990 Polio was eliminated in the Americas by 1994. The disease was officially eliminated in 36 Western Pacific countries, including China and Australia, in 2000. Europe was declared polio-free in 2002. Since January 2011, no cases of the disease have been reported in India, hence in February 2012, the country was taken off the WHO list of polio-endemic countries. In March 2014, India was declared a polio-free country.Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occur, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained. In November 2013, the WHO announced a polio outbreak in Syria. In response, the Armenian government put out a notice asking Syrian Armenians under age 15 to get the polio vaccine. As of 2014, polio virus had spread to 10 countries, mainly in Africa, Asia, and the Middle East, with Pakistan, Syria, and Cameroon advising vaccinations to outbound travellers.Polio vaccination programs have been resisted by some people in Pakistan, Afghanistan, and Nigeria - the three countries as of 2017 with remaining polio cases. Almost all Muslim religious and political leaders have endorsed the vaccine, but a fringe minority believes that the vaccines are secretly being used for sterilization of Muslims. The fact that the CIA organized a fake vaccination program in 2011 to help find Osama Bin Laden is an additional cause of distrust. In 2015, the WHO announced a deal with the Taliban to encourage them to distribute the vaccine in areas they control. However, the Pakistani Taliban was not supportive. On 11 September 2016, two unidentified gunmen associated with the Pakistani Taliban, Jamaat-ul-Ahrar, shot Zakaullah Khan, a doctor who was administering polio vaccines in Pakistan. The leader of the Jamaat-ul-Ahrar claimed responsibility for the shooting and stated that the group would continue this type of attack. Such resistance to and scepticism of vaccinations has consequently slowed down the polio eradication process within the two remaining endemic countries. Travel requirements Travellers who wish to enter or leave certain countries must be vaccinated against polio, usually at most 12 months and at least 4 weeks before crossing the border, and be able to present a vaccination record/certificate at the border checks.: 25–27  Most requirements apply only to travel to or from so-called polio-endemic, polio-affected, polio-exporting, polio-transmission, or high-risk countries. As of August 2020, Afghanistan and Pakistan are the only polio-endemic countries in the world (where wild polio has not yet been eradicated). Several countries have additional precautionary polio vaccination travel requirements, for example to and from key at-risk countries, which as of December 2020 include China, Indonesia, Mozambique, Myanmar, and Papua New Guinea. Society and culture Cost As of 2015, the Global Alliance for Vaccines and Immunization supplies the inactivated vaccine to developing countries for as little as €0.75 (about US$0.89) per dose in 10-dose vials. Misconceptions A misconception has been present in Pakistan that polio vaccine contained haram ingredients and could cause impotence and infertility in male children, leading some parents not to have their children vaccinated. This belief is most common in the Khyber Pakhtunkhwa province and the FATA region. Attacks on polio vaccination teams have also occurred, thereby hampering international efforts to eradicate polio in Pakistan and globally. References Further reading Ramsay M, ed. (2013). "Polio: the green book, chapter 26". Immunisation against infectious disease. London: Public Health England. Wallace G, Alexander J (2015). "Chapter 18: Poliomyelitis". In Hamborsky J, Kroger A, Wolfe S (eds.). Epidemiology and Prevention of Vaccine-Preventable Diseases (13th ed.). Washington D.C.: U.S. Centers for Disease Control and Prevention (CDC). ISBN 978-0990449119. Routh JA, Oberste MS, Patel M (2018). "Chapter 12: Poliomyelitis". In Roush SW, Baldy LM, Hall MH (eds.). Manual for the surveillance of vaccine-preventable diseases. Atlanta, Georgia: U.S. Centers for Disease Control and Prevention (CDC). External links "Polio Vaccine Information Statement". Centers for Disease Control and Prevention (CDC). 10 August 2021. History of Vaccines Website – History of Polio History of Vaccines, a project of the College of Physicians of Philadelphia PBS.org – People and Discoveries: Salk Produces Polio Vaccine 1952, Public Broadcasting Service (PBS) "IPOL – Poliovirus Vaccine Inactivated (Monkey Kidney Cell)". U.S. Food and Drug Administration (FDA). 11 December 2019. STN: 103930. Poliovirus Vaccines at the US National Library of Medicine Medical Subject Headings (MeSH)

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Could you please explain the term 'Episodic ataxia' in simple language?

Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recognized entities. Ataxia can be provoked by psychological stress or startle, or heavy exertion, including exercise. Symptoms can first appear in infancy. There are at least six loci for EA, of which 4 are known genes. Some patients with EA also have migraine or progressive cerebellar degenerative disorders, symptomatic of either familial hemiplegic migraine or spinocerebellar ataxia. Some patients respond to acetazolamide though others do not. Signs and symptoms Typically, episodic ataxia presents as bouts of ataxia induced by startle, stress, or exertion. Some patients also have continuous tremors of various motor groups, known as myokymia. Other patients have nystagmus, vertigo, tinnitus, diplopia or seizures. Cause The various symptoms of EA are caused by dysfunction of differing areas. Ataxia, the most common symptom, is due to misfiring of Purkinje cells in the cerebellum. This is either due to direct malfunction of these cells, such as in EA2, or improper regulation of these cells, such as in EA1. Seizures are likely due to altered firing of hippocampal neurons (KCNA1 null mice have seizures for this reason). Pathophysiology EA1: KCNA1 Type 1 episodic ataxia (EA1) is characterized by attacks of generalized ataxia induced by emotion or stress, with myokymia both during and between attacks. This disorder is also known as episodic ataxia with myokymia (EAM), hereditary paroxysmal ataxia with neuromyotonia and Isaacs-Mertens syndrome. Onset of EA1 occurs during early childhood to adolescence and persists throughout the patients life. Attacks last from seconds to minutes. Mutations of the gene KCNA1, which encodes the voltage-gated potassium channel KV1.1, are responsible for this subtype of episodic ataxia. KV1.1 is expressed heavily in basket cells and interneurons that form GABAergic synapses on Purkinje cells. The channels aid in the repolarization phase of action potentials, thus affecting inhibitory input into Purkinje cells and, thereby, all motor output from the cerebellum. EA1 is an example of a synaptopathy. There are currently 17 KV1.1 mutations associated with EA1, Table 1 and Figure 1. 15 of these mutations have been at least partly characterized in cell culture based electrophysiological assays wherein 14 of these 15 mutations have demonstrated drastic alterations in channel function. As described in Table 1, most of the known EA1 associated mutations result in a drastic decrease in the amount of current through KV1.1 channels. Furthermore, these channels tend to activate at more positive potentials and slower rates, demonstrated by positive shifts in their V½ values and slower τ activation time constants, respectively. Some of these mutations, moreover, produce channels that deactivate at faster rates (deactivation τ), which would also result in decreased current through these channels. While these biophysical changes in channel properties likely underlie some of the decrease in current observed in experiments, many mutations also seem to result in misfolded or otherwise mistrafficked channels, which is likely to be the major cause of dysfunction and disease pathogenesis. It is assumed, though not yet proven, that decrease in KV1.1 mediated current leads to prolonged action potentials in interneurons and basket cells. As these channels are important in the regulation of Purkinje cell activity, it is likely that this results increased and aberrant inhibitory input into Purkinje cells and, thus, disrupted Purkinje cell firing and cerebellum output. EA2: CACNA1A Type 2 episodic ataxia (EA2) is characterized by acetazolamide-responsive attacks of ataxia with or without migraine. Patients with EA2 may also present with progressive cerebellar atrophy, nystagmus, vertigo, visual disturbances and dysarthria. These symptoms last from hours to days, in contrast with EA1, which lasts from seconds to minutes. Attacks can be accompanied by increased heart rate and blood pressure, moderate to severe shaking, and stuttering. Like EA1, attacks can be precipitated by exercise, emotional stress/agitation, physical stress, or heat (overheated body temperature) but also by coffee and alcohol. EA2 is caused by mutations in CACNA1A, which encodes the P/Q-type voltage-gated calcium channel CaV2.1, and is also the gene responsible for causing spinocerebellar ataxia type-6 and familial hemiplegic migraine type-1. EA2 is also referred to as episodic ataxia with nystagmus, hereditary paroxysmal cerebellopathy, familial paroxysmal ataxia and acetazolamide-responsive hereditary paroxysmal cerebellar ataxia (AHPCA). There are currently 19 mutations associated with EA2, though only 3 have been characterized electrophysiologically, table 2 and figure 2. Of these, all result in decreased current through these channels. It is assumed that the other mutations, especially the splicing and frameshift mutations, also result in a drastic decrease in CaV2.1 currents, though this may not be the case for all mutations. CACNA1A is heavily expressed in Purkinje cells of the cerebellum where it is involved in coupling action potentials with neurotransmitter release. Thus, decrease in Ca2+ entry through CaV2.1 channels is expected to result in decreased output from Purkinje cells, even though they will fire at an appropriate rate. The tottering mouse is a widely used model to study EA2, as it developed a spontaneous homologous mutation in Cacna1a in the early 1960s. Alternatively, some CACNA1A mutations, such as those seen in familial hemiplegic migraine type-1, result in increased Ca2+ entry and, thereby, aberrant transmitter release. This can also result in excitotoxicity, as may occur in some cases of spinocerebellar ataxia type-6. EA3: 1q42 Episodic ataxia type-3 (EA3) is similar to EA1 but often also presents with tinnitus and vertigo. Patients typically present with bouts of ataxia lasting less than 30 minutes and occurring once or twice daily. During attacks, they also have vertigo, nausea, vomiting, tinnitus and diplopia. These attacks are sometimes accompanied by headaches and precipitated by stress, fatigue, movement and arousal after sleep. Attacks generally begin in early childhood and last throughout the patients lifetime. Acetazolamide administration has proved successful in some patients. As EA3 is extremely rare, there is currently no known causative gene. The locus for this disorder has been mapped to the long arm of chromosome 1 (1q42). EA4 Also known as periodic vestibulocerebellar ataxia, type-4 episodic ataxia (EA4) is an extremely rare form of episodic ataxia differentiated from other forms by onset in the third to sixth generation of life, defective smooth pursuit and gaze-evoked nystagmus. Patients also present with vertigo and ataxia. There are only two known families with EA4, both located in North Carolina. The locus for EA4 is unknown. EA5: CACNB4 There are two known families with type-5 episodic ataxia (EA5).These patients can present with an overlapping phenotype of ataxia and seizures similar to juvenile myoclonic epilepsy. In fact, juvenile myoclonic epilepsy and EA5 are allelic and produce proteins with similar dysfunction.Patients with pure EA5 present with recurrent episodes of ataxia with vertigo. Between attacks they have nystagmus and dysarthria. These patients are responsive to acetazolamide. Both juvenile myoclonic epilepsy and EA5 are a result of mutations in CACNB4, a gene that encodes the calcium channel β4 subunit. This subunit coassembles with α-subunits and produces channels that slowly inactivate after opening.EA5 patients have a cysteine to phenylalanine mutation at position 104.Thus results in channels with 30% greater current than wild-type. As this subunit is expressed in the cerebellum, it is assumed that such increased current results in neuronal hyperexcitability Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. EA6: SLC1A3 Type-6 episodic ataxia (EA6) is a rare form of episodic ataxia, identified initially in a 10-year-old boy who first presented with 30 minute bouts of decreased muscle tone during infancy. He required "balance therapy" as a young child to aid in walking and has a number of ataxic attacks, each separated by months to years. These attacks were precipitated by fever. He has cerebellar atrophy and subclinical seizures. During later attacks, he also presented with distortions of the left hemifield, ataxia, slurred speech, followed by headache. After enrolling in school, he developed bouts of rhythmic arm jerking with concomitant confusion, also lasting approximately 30 minutes. He also has presented, at various times, with migraines. This patient carries a proline to arginine substitution in the fifth transmembrane-spanning segment of the gene SLC1A3. This gene encodes the excitatory amino acid transporter 1 (EAAT1) protein, which is responsible for glutamate uptake. In cell culture assays, this mutation results in drastically decreased glutamate uptake in a dominant-negative manner. This is likely due to decreased synthesis or protein stability. As this protein is expressed heavily in the brainstem and cerebellum, it is likely that this mutation results in excitotoxicity and/or hyperexcitability leading to ataxia and seizures. Mutations in EAAT1 (GLAST) have subsequently been identified in a family with episodic ataxia. Diagnosis Treatment Depending on subtype, many patients find that acetazolamide therapy is useful in preventing attacks. In some cases, persistent attacks result in tendon shortening, for which surgery is required. References External links GeneReviews/NCBI/NIH/UW entry on Episodic Ataxia Type 1, Episodic Ataxia with Myokymia, Hereditary Cerebellar Ataxia with Neuromyotonia GeneReviews/NCBI/NIH/UW entry on Episodic ataxia type 2

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I'm seeking clarification on the medical term 'Ovarian pregnancy.' Could you explain it?

Ovarian pregnancy refers to an ectopic pregnancy that is located in the ovary. Typically the egg cell is not released or picked up at ovulation, but fertilized within the ovary where the pregnancy implants. Such a pregnancy usually does not proceed past the first four weeks of pregnancy. An untreated ovarian pregnancy causes potentially fatal intra-abdominal bleeding and thus may become a medical emergency. Cause and pathology The cause of ovarian pregnancy is unknown, specifically as the usual causative factors – pelvic inflammatory disease and pelvic surgery – implicated in tubal ectopic pregnancy seem to be uninvolved. There appears to be a link to the intrauterine device (IUD), however, it cannot be concluded that this is causative as it could be that IUDs prevent other but not ovarian pregnancies. Some have suggested that patients who undergo IVF therapy are at higher risk for ovarian pregnancy.An ovarian pregnancy is usually understood to begin when a mature egg cell is not expelled or picked up from its follicle and a sperm enters the follicle and fertilizes the egg, giving rise to an intrafollicular pregnancy. It has also been debated that an egg cell fertilized outside of the ovary could implant on the ovarian surface, perhaps aided by a decidual reaction or endometriosis. Ovarian pregnancies rarely go longer than 4 weeks; nevertheless, there is the possibility that the trophoblast finds further support outside the ovary and thus may affect the tube and other organs. In very rare occasions the pregnancy may find a sufficient foothold outside the ovary to continue as an abdominal pregnancy, and an occasional delivery has been reported.y Diagnosis The diagnosis is made in asymptomatic pregnant women by obstetric ultrasonography. On pelvic examination a unilateral adnexal mass may be found. Typical symptoms are abdominal pain and, to a lesser degree, vaginal bleeding during pregnancy. Patients may present with hypovolemia or be in circulatory shock because of internal bleeding.Ideally, ultrasound will show the location of the gestational sac in the ovary, while the uterine cavity is "empty", and if there is internal bleeding, it can be identified. Because of the proximity of the tube, the sonographic distinction between a tubal and an ovarian pregnancy may be difficult. Serial hCG levels generally show not the normal progressive rise. In a series of 12 patients the mean gestation age was 45 days.Histologically, the diagnosis has been made by Spiegelberg criteria on the surgical specimen of the removed ovary and tube. However, the tube and ovary are not usually removed as sonography allows for earlier diagnosis and surgeons strive to preserve the ovary. Prior to the introduction of Spiegelbergs criteria in 1878, the existence of ovarian pregnancy was in doubt; his criteria helped to identify the ovarian pregnancy from other ectopics: The gestational sac is located in the region of the ovary. The gestational sac is attached to the uterus by the ovarian ligament. Ovarian tissue is histologically proven in the wall of the gestational sac. The oviduct on the affected side is intact (this criterion, however, holds not true for a longer ongoing ovarian pregnancy).An ovarian pregnancy can be mistaken for a tubal pregnancy or a hemorrhagic ovarian cyst or corpus luteum prior to surgery. Sometimes, only the presence of trophoblastic tissue during the histologic examination of material of a bleeding ovarian cyst shows that an ovarian pregnancy was the cause of the bleeding. Management Ovarian pregnancies are dangerous and prone to internal bleeding. Thus, when suspected, intervention is called for. Traditionally, an explorative laparotomy was performed, and once the ovarian pregnancy was identified, an oophorectomy or salpingo-oophorectomy was performed, including the removal of the pregnancy. Today, the surgery can often be performed via laparoscopy. The extent of surgery varies according to the amount of tissue destruction that has occurred. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. Further, in attempts to preserve ovarian tissue, surgery may involve just the removal of the pregnancy with only a part of the ovary. This can be accomplished by an ovarian wedge resection.Ovarian pregnancies have been successfully treated with methotrexate since it was introduced in the management of ectopic pregnancy in 1988.An ovarian pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as not to endanger the intrauterine pregnancy. Epidemiology Ovarian pregnancies are rare: the vast majority of ectopic pregnancies occur in the fallopian tube; only about 0.15-3% of ectopics occur in the ovary. The incidence has been reported to be about 1:3,000 to 1:7,000 deliveries. History In 1614 Mercier (also shown as Mercerus) described ovarian pregnancy for the first time, as a condition separate from a tubal pregnancy. Once the study of physiology emerged, Boehmer classified extra-uterine pregnancy into three classes: abdominal, ovarian, and tubal. There were many doubters that such a condition existed, particularly Mayer, who wrote an essay not only denying the existence of ovarian pregnancy, but demonstrating that recorded cases to that time were other conditions. Then Cohnstein proposed four criteria that would need to be present for ovarian pregnancy exist. His requirements were: 1) absence of the ovary on the side in which the alleged pregnancy was located; 2) connection of the uterus and sac via an ovarian ligament; 3) cylindrical tissue must line the layers of the sac with direct connection between the tunica albuginea and sac wall; and 4) evidence of the amniotic cavity connection to the ovarian follicle or corpus luteum. These were replaced by Otto Spiegelbergs criteria in 1878, which have been used into the 20th century with additions and modifications.Up to 1845, about 80 cases of ovarian pregnancy were proposed. With Mayers 1845 denial that ovarian pregnancy could exist, physicians began taking more care in their descriptions and analysis of cases. Though numerous cases were evaluated, some failed to provide microscopic evidence and others failed to show the necessary histological changes of pregnancy, or failed on one or more of the criteria. In 1899, Catharine van Tussenbroek finally settled the question of the existence of ovarian pregnancy, by providing the first accurate clinical and histological description of a case. Though doubted, her results were confirmed three years later in a case by Thompson. References Citations Sources Jacobson, Sidney D. (1908). "True Primary Ovarian Pregnancy: Operation; Recovery". In Brooks, Henry T. (ed.). Contributions to the Science of Medicine and Surgery: In celebration of the twenty-fifth anniversary, 1882-1907, of the founding of the New York Post-Graduate Medical School and Hospital. New York: Jacobson New York Post-graduate Medical School and Hospital Faculty / Royal College of Physicians of Edinburgh. McDonald, Ellice (1914). Studies in gynecology and obstetrics. New York: American Medical Publishing Co. OCLC 11339026. Ray, Henry M. (June 1921). "Primary Ovarian and Primary Abdominal Pregnancy: Their Morphological Possibility". Surgery, Gynecology & Obstetrics. Chicago: Journal of the American College of Surgeons / Franklin H. Martin Memorial Foundation. 32. Retrieved 21 March 2016. Rizk, Botros R. M. B. (2010). Ultrasonography in Reproductive Medicine and Infertility. Cambridge, England: Cambridge University Press. ISBN 978-1-139-48457-2. Thorek, Max (February 1926). "Case of Ovarian Pregnancy with Histological Findings". The Illinois Medical Journal. Chicago: Illinois State Medical Society. 49: 106–111. Retrieved 6 April 2016. "Obstetrical Society of London". The British Medical Journal. London: Royal Medical and Chirurgical Society. 2 (2081): 1442. 17 November 1900. PMC 2463948. External links The Ectopic Pregnancy Trust - Information and support for those who have suffered the condition by a medically overseen and moderated UK based charity, recognised by the National Health Service (UK) Department of Health (UK) and the Royal College of Obstetricians and Gynaecologists

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I need a basic explanation for the medical term 'Overweight.'

Being overweight or fat is having more body fat than is optimally healthy. Being overweight is especially common where food supplies are plentiful and lifestyles are sedentary. As of 2003, excess weight reached epidemic proportions globally, with more than 1 billion adults being either overweight or obese. In 2013, this increased to more than 2 billion. Increases have been observed across all age groups. A healthy body requires a minimum amount of fat for proper functioning of the hormonal, reproductive, and immune systems, as thermal insulation, as shock absorption for sensitive areas, and as energy for future use; however, the accumulation of too much storage fat can impair movement, flexibility, and alter the appearance of the body. Classification The degree to which a person is overweight is generally described by the body mass index (BMI). Overweight is defined as a BMI of 25 or more, thus it includes pre-obesity defined as a BMI between 25 and 29.9 and obesity as defined by a BMI of 30 or more. Pre-obese and overweight however are often used interchangeably, thus giving overweight a common definition of a BMI of between 25 and 29.9. There are, however, several other common ways to measure the amount of adiposity or fat present in an individuals body. Body mass indexThe body mass index (BMI) is a measure of a persons weight taking into account their height. It is given by the following formula: BMI equals a persons weight (mass) in kilograms divided by the square of the persons height in metres. The units therefore are kg/m2 but BMI measures are typically used and written without units.BMI provides a significantly more accurate representation of body fat content than simply measuring a persons weight. It is only moderately correlated with both body fat percentage and body fat mass (R2 of 0.68). It does not take into account certain factors such as pregnancy or bodybuilding; however, the BMI is an accurate reflection of fat percentage in the majority of the adult population.Body volume indexThe body volume index (BVI) was devised in 2000 as a computer, rather than manual, measurement of the human body for obesity and an alternative to the BMIBVI uses 3D software to create an accurate image of a person so BVI can differentiate between people with the same BMI rating, but who have a different shape and different weight distribution. BVI measures where a persons weight and the fat are located on the body, rather than total weight or total fat content and places emphasis on the weight carried around the abdomen, commonly known as central obesity. There has been an acceptance in recent years that abdominal fat and weight around the abdomen constitute a greater health risk.Simple weighingA persons weight is measured and compared to an estimated ideal weight. This is the easiest and most common method, but by far the least accurate, as it only measures one quantity (weight) and often does not take into account many factors such as height, body type, and relative amount of muscle mass.Skinfold calipers or "pinch test"The skin at several specific points on the body is pinched and the thickness of the resulting fold is measured. This measures the thickness of the layers of fat located under the skin, from which a general measurement of total amount of fat in the body is calculated. This method can be reasonably accurate for many people, but it assumes particular fat distribution patterns over the body—which may not apply to all individuals, and does not account for fat deposits not directly under the skin. Also, as the measurement and analysis generally involves a high degree of practice and interpretation, an accurate result requires that a professional perform it. It cannot generally be done by patients themselves.Bioelectrical impedance analysisA small electric current is passed through the body to measure its electrical resistance. As fat and muscle conduct electricity differently, this method can provide a direct measurement of the body fat percentage, in relation to muscle mass. In the past, this technique could only be performed reliably by trained professionals with specialized equipment, but it is now possible to buy home testing kits that let people do this themselves with a minimum of training. Despite the improved simplicity of this process over the years, however, a number of factors can affect the results, including hydration and body temperature, so it still needs some care when taking the test to ensure that the results are accurate.Hydrostatic weighingConsidered one of the more accurate methods of measuring body fat, this technique involves complete submersion of a person in water, with special equipment to measure the persons weight while submerged. This weight is then compared with "dry weight" as recorded outside the water to determine overall body density. As fat is less dense than muscle, careful application of this technique can provide a reasonably close estimate of fat content in the body. This technique does, however, require expensive specialized equipment and trained professionals to administer it properly.Dual-energy X-ray absorptiometry (DEXA)Originally developed to measure bone density, DEXA imaging is also used to precisely determine body fat content by using the density of various body tissues to identify which portions of the body are fat. This test is generally considered very accurate, but requires a great deal of expensive medical equipment and trained professionals to perform.The most common method for discussing this subject and the one used primarily by researchers and advisory institutions is BMI. Definitions of what is considered overweight vary by ethnicity. The current definition proposed by the US National Institutes of Health (NIH) and the World Health Organization (WHO) designates whites, Hispanics and blacks with a BMI of 25 or more as overweight. For Asians, overweight is a BMI between 23 and 29.9 and obesity for all groups is a BMI of 30 or more. BMI, however, does not account extremes of muscle mass, some rare genetic factors, the very young, and a few other individual variations. Thus it is possible for an individuals with a BMI of less than 25 to have excess body fat, while others may have a BMI that is significantly higher without falling into this category. Some of the above methods for determining body fat are more accurate than BMI but are less convenient to measure. If an individual is overweight and has excess body fat it can create or lead to health risks. Reports are surfacing, however, that being mildly overweight to slightly obese – BMI being between 24 and 31.9 – may be actually beneficial and that people with a BMI between 24 and 31.9 could actually live longer than normal weight or underweight persons. Health effects While some negative health outcomes associated with obesity are accepted within the medical community, the health implications of the overweight category are more controversial. A 2016 review estimated that the risk of death increases by seven percent among overweight people with a BMI of 25 to 27.5 and 20 percent among overweight people with a BMI of 27.5 to 30. Katherine Flegal et al., however, found that the mortality rate for individuals who are classified as overweight (BMI 25 to 29.9) may actually be lower than for those with an "ideal" weight (BMI 18.5 to 24.9), noting that many studies show that the lowest mortality rate is at a BMI close to 25. The specific conclusions appear to depend on what other factors are controlled for, and Flegal has accordingly alleged that the findings from the 2016 review are driven by bias toward preconceived opinions.Being overweight has been identified as a risk factor for cancer, and Walter Willett predicts that being overweight will overtake smoking as the primary cause of cancer in developed countries as cases of smoking-related cancer dwindle. Being overweight also increases the risk of oligospermia and azoospermia in men.Psychological well-being is also at risk in the overweight individual due to social discrimination. Being overweight has been shown not to increase mortality in older people: in a study of 70 to 75-year old Australians, mortality was lowest for "overweight" individuals (BMI 25 to 29.9), while a study of Koreans found that, among those initially aged 65 or more, an increase in BMI to above 25 was not associated with increased risk of death. Causes Being overweight is generally caused by the intake of more calories (by eating) than are expended by the body (by exercise and everyday activity). Factors that may contribute to this imbalance include: Alcoholism Eating disorders (such as binge eating) Genetic predisposition Hormonal imbalances (e.g. hypothyroidism) Insufficient or poor-quality sleep Limited physical exercise and a sedentary lifestyle Poor nutrition Metabolic disorders, which could be caused by repeated attempts to lose weight by weight cycling Overeating Psychotropic medication (e.g. olanzapine) Smoking cessation and other stimulant withdrawal StressPeople who have insulin dependent diabetes and chronically overdose insulin may gain weight, while people who already are overweight may develop insulin tolerance, and in the long run develop type II diabetes. Treatment The usual treatments for overweight individuals is diet and physical exercise. Dietitians generally recommend eating several balanced meals dispersed through the day, with a combination of progressive, primarily aerobic, physical exercise. In fact, some research found benefits from physical activity, diet and behaviour changes on BMI in children from 12 to 17 years old.Considering that most of the treatment strategies are directed to change lifestyle-related behaviours of individuals (namely in dietary and physical activity), the transtheoretical model (TTM) has been used as a framework to design weight management interventions. A systematic review assessed the effectiveness of dietary and physical activity interventions based on the TTM in producing sustainable (one year or longer) weight loss in overweight and obese adults. The included studies did not allow to produce conclusive evidence about the impact of the use of this model combined with these interventions on sustainable weight loss. Nevertheless, very low quality scientific evidence suggests that this approach may lead to improvements in physical activity and dietary habits, namely increased in both exercise duration and frequency, and fruits and vegetables consumption, along with reduced dietary fat intake. Epidemiology The World Health Organization (WHO) estimated that nearly 2 billion adults worldwide, aged 18 years and older, were overweight in 2016.According to the National Health and Nutrition Examination Survey (NHANES), an estimated 71.6% of the United States adult population aged 20 and over is considered either overweight or obese, and this percentage has increased over the last four decades. See also Body image Canadian Obesity Network Fat acceptance movement Physical attractiveness References External links Obesity Epidemic: U.S. Temporal Trends 1985–2004 at the Wayback Machine (archived December 8, 2006) Ranking of Most Overweight Countries in the World 2005 at the Wayback Machine (archived June 29, 2007) World Health Organization fact sheet on obesity and overweight

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I'm encountering the term 'Dural arteriovenous fistula' in medical literature. What's its definition?

A dural arteriovenous fistula (DAVF) or malformation is an abnormal direct connection (fistula) between a meningeal artery and a meningeal vein or dural venous sinus. Signs and symptoms The most common signs/symptoms of DAVFs are: Pulsatile tinnitus Occipital bruit Headache Visual impairment PapilledemaPulsatile tinnitus is the most common symptom in patients, and it is associated with transverse-sigmoid sinus DAVFs. Carotid-cavernous DAVFs, on the other hand, are more closely associated with pulsatile exophthalmos. DAVFs may also be asymptomatic (e.g. cavernous sinus DAVFs). Location Most commonly found adjacent to dural sinuses in the following locations: Transverse (lateral) sinus, left-sided slightly more common than right Intratentorial From the posterior cavernous sinus, usually draining to the transverse or sigmoid sinuses Vertebral artery (posterior meningeal branch) Causes It is still unclear whether DAVFs are congenital or acquired. Current evidence supports transverse-sigmoid sinus junction dural malformations are acquired defects, occurring in response to thrombosis and collateral revascularization of a venous sinus. Diagnosis Cerebral angiography is the diagnostic standard. MRIs are typically normal but can identify venous hypertension as a result of arterial-venous shunting. Classification Borden Classification The Borden Classification of dural arteriovenous malformations or fistulas, groups into three types based upon their venous drainage: Type I: dural arterial supply drains anterograde into venous sinus. Type II: dural arterial supply drains into venous sinus. High pressure in sinus results in both anterograde drainage and retrograde drainage via subarachnoid veins. Type III: dural arterial supply drains retrograde into subarachnoid veins. Type I Type I dural arteriovenous fistulas are supplied by meningeal arteries and drain into a meningeal vein or dural venous sinus. The flow within the draining vein or venous sinus is anterograde. Type Ia – simple dural arteriovenous fistulas have a single meningeal arterial supply Type Ib – more complex arteriovenous fistulas are supplied by multiple meningeal arteriesThe distinction between Types Ia and Ib is somewhat specious as there is a rich system of meningeal arterial collaterals. Type I dural fistulas are often asymptomatic, do not have a high risk of bleeding and do not necessarily need to be treated. Type II The high pressure within a Type II dural AV fistula causes blood to flow in a retrograde fashion into subarachnoid veins which normally drain into the sinus. Typically this is because the sinus has outflow obstruction. Such draining veins form venous varices or aneurysms which can bleed. Type II fistulas need to be treated to prevent hemorrhage. The treatment may involve embolization of the draining sinus as well as clipping or embolization of the draining veins. Type III Type III dural AV fistulas drain directly into subarachnoid veins. These veins can form aneurysms and bleed. Type III dural fistulas need to be treated to prevent hemorrhage. Treatment can be as simple as clipping the draining vein at the site of the dural sinus. If treatment involves embolization, it will only typically be effective if the glue traverses the actual fistula and enters, at least slightly, the draining vein.The Cognard et al. Classification correlates venous drainage patterns with increasingly aggressive neurological clinical course. To simplify the above systems of DAVF classification, the two main factors that should be considered to determine aggressiveness of these lesions are: DAVF that have bleed (as opposed to those that have not before) DAVF resulting in cortical venous refluxTreatment decisions are more complicated and require consultation with a neurosurgeon and team familiar with these lesions. Treatment Indications Hemorrhage Neurologic dysfunction or refractory symptoms Interventions Embolization One approach used for treatment is embolization. A six-vessel angiogram is employed to determine the vascular supply to the fistula. Detachable coils, liquid embolic agents like NBCA, and onyx, or combinations of both are injected into the blood vessel to occlude the DAVF. Preoperative embolization can also be used to supplement surgery. Surgery DAVFs are also managed surgically. The operative approach varies depending on the location of the lesion. Stereotactic radiosurgery Stereotactic radiosurgery is used for obliterating DAVFs sometimes in conjunction with embolization or surgery, and is considered an important adjunct and sometimes a primary treatment method for non-aggressive DAVFs. Use of this method, however, is limited as obliteration occurs over the course of up to 2–3 years after the delivery of radiation. Epidemiology 10–15% of intracranial AV malformations are DAVFs. There is a higher preponderance in females (61–66%), and typically patients are in their fourth or fifth generation of life. DAVFs are rarer in children. Research External Manual Carotid Compression is Effective in Patients with Cavernous Sinus Dural Arteriovenous Fistulaetreatment. The patients were instructed to compress the carotid artery and jugular vein with the contralateral hand for ten seconds several times each hour (about 6 to 15 times per day).[1] See also Arteriovenous fistula References == External links ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

Can you demystify the medical term 'Famciclovir' for me?

Famciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis). Famciclovir was patented in 1983 and approved for medical use in 1994. In 2007, the United States Food and Drug Administration approved the first generic version of famciclovir. Generic tablets are manufactured by TEVA Pharmaceuticals and Mylan Pharmaceuticals. Medical uses Famciclovir is indicated for the treatment of herpes zoster (shingles), treatment of herpes simplex virus 2 (genital herpes), herpes labialis (cold sores) in immunocompetent patients and for the suppression of recurring episodes of herpes simplex virus 2. It is also indicated for treatment of recurrent episodes of herpes simplex in HIV patients. Adverse effects Side effects: mild to extreme stomach upset, headaches, mild fever. Herpes Early treatment Several studies in humans and mice provide evidence that early treatment with famciclovir soon after the first infection with herpes can significantly lower the chance of future outbreaks. Use of famciclovir in this manner has been shown to reduce the amount of latent virus in the neural ganglia compared to no treatment or treatment with valaciclovir. A review of human subjects treated for five days with famciclovir 250 mg three times daily during their first herpes episode found that only 4.2 percent experienced a recurrence within six months after the first outbreak, a fivefold decrease compared to the 19 percent recurrence in acyclovir-treated patients. Neither drug affected latency if treatment was delayed for several months. See also Penciclovir Valaciclovir References External links Famvir product website run by Novartis

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

I'd like to learn more about the medical term 'Seasonal affective disorder.' Can you provide some details?

Seasonal affective disorder (SAD) is a mood disorder subset, in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year, most commonly in winter. Common symptoms include sleeping too much, having little to no energy, and overeating. The condition in the summer can include heightened anxiety.In the Diagnostic and Statistical Manual of Mental Disorders DSM-IV and DSM-5, its status was changed. It is no longer classified as a unique mood disorder, but is now a specifier, called "with seasonal pattern", for recurrent major depressive disorder that occurs at a specific time of the year, and fully remits otherwise. Although experts were initially skeptical, this condition is now recognized as a common disorder. However, the validity of SAD has been questioned by a 2016 analysis by the Center for Disease Control, in which no links were detected between depression and seasonality or sunlight exposure. In the United States, the percentage of the population affected by SAD ranges from 1.4% of the population in Florida, to 9.9% in Alaska. SAD was formally described and named in 1984, by Norman E. Rosenthal and colleagues at the National Institute of Mental Health. History SAD was first systematically reported and named in the early 1980s, by Norman E. Rosenthal, M.D., and his associates at the National Institute of Mental Health (NIMH). Rosenthal was initially motivated by his desire to discover the cause of his own experience of depression during the dark days of the northern US winter, called polar night. He theorized that the reduction in available natural light during winter was the cause. Rosenthal and his colleagues then documented the phenomenon of SAD in a placebo-controlled study utilizing light therapy. A paper based on this research was published in 1984. Although Rosenthals ideas were initially greeted with skepticism, SAD has become well recognized, and his 1993 book, Winter Blues has become the standard introduction to the subject.Research on SAD in the United States began in 1979, when Herb Kern, a research engineer, had also noticed that he felt depressed during the winter months. Kern suspected that scarcer light in winter was the cause, and discussed the idea with scientists at the NIMH who were working on bodily rhythms. They were intrigued, and responded by devising a lightbox to treat Kerns depression. Kern felt much better within a few days of treatments, as did other patients treated in the same way. Signs and symptoms SAD is a type of major depressive disorder, and those with the condition may exhibit any of the associated symptoms, such as feelings of hopelessness and worthlessness, thoughts of suicide, loss of interest in activities, withdrawal from social interaction, sleep and appetite problems, difficulty with concentrating and making decisions, decreased libido, a lack of energy, or agitation. Symptoms of winter SAD often include falling asleep earlier or in less than 5 minutes in the evening, oversleeping or difficulty waking up in the morning, nausea, and a tendency to overeat, often with a craving for carbohydrates, which leads to weight gain. SAD is typically associated with winter depression, but springtime lethargy or other seasonal mood patterns are not uncommon. Although each individual case is different, in contrast to winter SAD, people who experience spring and summer depression may be more likely to show symptoms such as insomnia, decreased appetite and weight loss, and agitation or anxiety. Bipolar disorder With seasonal pattern is a specifier for bipolar and related disorders, including bipolar I disorder and bipolar II disorder. Most people with SAD experience major depressive disorder, but as many as 20% may have a bipolar disorder. It is important to distinguish between diagnoses because there are important treatment differences. In these cases, people who have the With seasonal pattern specifier may experience a depressive episode either due to major depressive disorder or as part of bipolar disorder during the winter and remit in the summer. Around 25% of patients with bipolar disorder may present with a depressive seasonal pattern, which is associated with bipolar II disorder, rapid cycling, eating disorders, and more depressive episodes. Differences in biological sex display distinct clinical characteristics associated to seasonal pattern: males present with more Bipolar II disorder and a higher number of depressive episodes, and females with rapid cycling and eating disorders. Cause In many species, activity is diminished during the winter months, in response to the reduction in available food, the reduction of sunlight (especially for diurnal animals), and the difficulties of surviving in cold weather. Hibernation is an extreme example, but even species that do not hibernate often exhibit changes in behavior during the winter. The preponderance of women with SAD suggests that the response may also somehow regulate reproduction.Various proximate causes have been proposed. One possibility is that SAD is related to a lack of serotonin, and serotonin polymorphisms could play a role in SAD, although this has been disputed. Mice incapable of turning serotonin into N-acetylserotonin (by serotonin N-acetyltransferase) appear to express "depression-like" behavior, and antidepressants such as fluoxetine increase the amount of the enzyme serotonin N-acetyltransferase, resulting in an antidepressant-like effect. Another theory is that the cause may be related to melatonin, which is produced in dim light and darkness by the pineal gland, since there are direct connections, via the retinohypothalamic tract and the suprachiasmatic nucleus, between the retina and the pineal gland. Melatonin secretion is controlled by the endogenous circadian clock, but can also be suppressed by bright light.One study looked at whether some people could be predisposed to SAD based on personality traits. Correlations between certain personality traits, higher levels of neuroticism, agreeableness, openness, and an avoidance-oriented coping style, appeared to be common in those with SAD. Pathophysiology Seasonal mood variations are believed to be related to light. An argument for this view is the effectiveness of bright-light therapy. SAD is measurably present at latitudes in the Arctic region, such as northern Finland (64°00′N), where the rate of SAD is 9.5%. Cloud cover may contribute to the negative effects of SAD. There is evidence that many patients with SAD have a delay in their circadian rhythm, and that bright light treatment corrects these delays which may be responsible for the improvement in patients.The symptoms of it mimic those of dysthymia or even major depressive disorder. There is also potential risk of suicide in some patients experiencing SAD. One study reports 6–35% of people with the condition required hospitalization during one period of illness. At times, patients may not feel depressed, but rather lack energy to perform everyday activities.Subsyndromal Seasonal Affective Disorder is a milder form of SAD experienced by an estimated 14.3% (vs. 6.1% SAD) of the U.S. population. The blue feeling experienced by both those with SAD and with SSAD can usually be dampened or extinguished by exercise and increased outdoor activity, particularly on sunny days, resulting in increased solar exposure. Connections between human mood, as well as energy levels, and the seasons are well documented, even in healthy individuals. Diagnosis According to the American Psychiatric Association DSM-IV criteria, Seasonal Affective Disorder is not regarded as a separate disorder. It is called a "course specifier" and may be applied as an added description to the pattern of major depressive episodes in patients with major depressive disorder or patients with bipolar disorder. The "Seasonal Pattern Specifier" must meet four criteria: depressive episodes at a particular time of the year; remissions or mania/hypomania at a characteristic time of year; these patterns must have lasted two years with no nonseasonal major depressive episodes during that same period; and these seasonal depressive episodes outnumber other depressive episodes throughout the patients lifetime. The Mayo Clinic describes three types of SAD, each with its own set of symptoms. Management Treatments for classic (winter-based) seasonal affective disorder include light therapy, medication, ionized-air administration, cognitive-behavioral therapy, and carefully timed supplementation of the hormone melatonin. Light therapy Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy may be an effective treatment for SAD. Light therapy uses a lightbox, which emits far more lumens than a customary incandescent lamp. Bright white "full spectrum" light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green (actually cyan or blue-green) light at a wavelength of 500 nm at 350 lux are used, with the first-mentioned historically preferred.Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30–60 cm, in front of the box with her/his eyes open, but not staring at the light source, for 30–60 minutes. A study published in May 2010 suggests that the blue light often used for SAD treatment should perhaps be replaced by green or white illumination. Discovering the best schedule is essential. One study has shown that up to 69% of patients find lightbox treatment inconvenient, and as many as 19% stop use because of this.Dawn simulation has also proven to be effective; in some studies, there is an 83% better response when compared to other bright light therapy. When compared in a study to negative air ionization, bright light was shown to be 57% effective vs. dawn simulation 50%. Patients using light therapy can experience improvement during the first week, but increased results are evident when continued throughout several weeks. Certain symptoms like hypersomnia, early insomnia, social withdrawal, and anxiety resolve more rapidly with light therapy than with cognitive behavioral therapy. Most studies have found it effective without use year round, but rather as a seasonal treatment lasting for several weeks, until frequent light exposure is naturally obtained.Light therapy can also consist of exposure to sunlight, either by spending more time outside or using a computer-controlled heliostat to reflect sunlight into the windows of a home or office. Although light therapy is the leading treatment for seasonal affective disorder, prolonged direct sunlight or artificial lights that dont block the ultraviolet range should be avoided, due to the threat of skin cancer.The evidence base for light therapy as a preventive treatment for seasonal affective disorder is limited. The decision to use light therapy to treat people with a history of winter depression before depressive symptoms begin should be based on a persons preference of treatment. Medication SSRI (selective serotonin reuptake inhibitor) antidepressants have proven effective in treating SAD. Effective antidepressants are fluoxetine, sertraline, or paroxetine. Both fluoxetine and light therapy are 67% effective in treating SAD, according to direct head-to-head trials conducted during the 2006 Can-SAD study. Subjects using the light therapy protocol showed earlier clinical improvement, generally within one week of beginning the clinical treatment. Bupropion extended-release has been shown to prevent SAD for one in four people, but has not been compared directly to other preventive options in trials. In a 2021 updated Cochrane review of second-generation antidepressant medications for the treatment of SAD, a definitive conclusion could not be drawn, due to lack of evidence, and the need for larger randomized controlled trials.Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.Another explanation is that vitamin D levels are too low when people do not get enough Ultraviolet-B on their skin. An alternative to using bright lights is to take vitamin D supplements. However, studies did not show a link between vitamin D levels and depressive symptoms in elderly Chinese, nor among elderly British women given only 800IU when 6,000IU is needed. 5-HTP (an amino acid that helps to produce serotonin, and is often used to help those with depression) has also been suggested as a supplement that may help treat the symptoms of SAD, by lifting mood, and regulating sleep schedule for those with the condition. However, those who take antidepressants are not advised to take 5-HTP, as antidepressant medications may combine with the supplement to create dangerously high levels of serotonin – potentially resulting in serotonin syndrome. Other treatments Depending upon the patient, one treatment (e.g., lightbox) may be used in conjunction with another (e.g., medication).Negative air ionization, which involves releasing charged particles into the sleep environment, has been found effective, with a 47.9% improvement if the negative ions are in sufficient density (quantity).Physical exercise has shown to be an effective form of depression therapy, particularly when in addition to another form of treatment for SAD. One particular study noted marked effectiveness for treatment of depressive symptoms, when combining regular exercise with bright light therapy. Patients exposed to exercise which had been added to their treatments in 20 minutes intervals on the aerobic bike during the day, along with the same amount of time underneath the UV light were seen to make a quick recovery.Of all the psychological therapies aimed at the prevention of SAD, cognitive-behaviour therapy, typically involving thought records, activity schedules and a positive data log, has been the subject of the most empirical work. However, evidence for CBT or any of the psychological therapies aimed at preventing SAD remains inconclusive. Epidemiology Nordic countries Winter depression is a common slump in the mood of some inhabitants of most of the Nordic countries. Iceland, however, seems to be an exception. A study of more than 2000 people there found the prevalence of seasonal affective disorder and seasonal changes in anxiety and depression to be unexpectedly low in both sexes. The studys authors suggested that propensity for SAD may differ due to some genetic factor within the Icelandic population. A study of Canadians of wholly Icelandic descent also showed low levels of SAD. It has more recently been suggested that this may be attributed to the large amount of fish traditionally eaten by Icelandic people. In 2007, about 90 kilograms of fish per person was consumed per year in Iceland, as opposed to about 24 kilograms in the US and Canada, rather than to genetic predisposition; a similar anomaly is noted in Japan, where annual fish consumption in recent years averages about 60 kilograms per capita. Fish are high in vitamin D. Fish also contain docosahexaenoic acid (DHA), which help with a variety of neurological dysfunctions. Other countries In the United States, a diagnosis of seasonal affective disorder was first proposed by Norman E. Rosenthal, M.D. in 1984. Rosenthal wondered why he became sluggish during the winter after moving from sunny South Africa to (cloudy in winter) New York. He started experimenting increasing exposure to artificial light, and found this made a difference. In Alaska it has been established that there is a SAD rate of 8.9%, and an even greater rate of 24.9% for subsyndromal SAD. Around 20% of Irish people are affected by SAD, according to a survey conducted in 2007. The survey also shows women are more likely to be affected by SAD than men. An estimated 3% of the population in the Netherlands experience winter SAD. See also Diurnal Cycle Seasonal effects on suicide rates Seasonal Pattern Assessment Questionnaire Vitamin D deficiency References External links Seasonal Affective Disorder at Curlie USA National Institute of Mental Health webpages https://www.nimh.nih.gov/health/topics/seasonal-affective-disorder/index.shtml

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

Can you break down the meaning of the medical term 'Typhoid fever' for me?

Typhoid fever, also known as typhoid, is a disease caused by Salmonella serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry the bacterium without being affected, but they are still able to spread the disease. Typhoid fever is a type of enteric fever, along with paratyphoid fever. S. enterica Typhi is believed to infect and replicate only within humans.Typhoid is caused by the bacterium Salmonella enterica subsp. enterica serovar Typhi growing in the intestines, peyers patches, mesenteric lymph nodes, spleen, liver, gallbladder, bone marrow and blood. Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person. Risk factors include limited access to clean drinking water and poor sanitation. Those who have not yet been exposed to the pathogen and ingest contaminated drinking water or food are most at risk for developing symptoms. Only humans can be infected; there are no known animal reservoirs.Diagnosis is by culturing and identifying S. enterica Typhi from patient samples or detecting an immune response to the pathogen from blood samples. Recently, new advances in large-scale data collection and analysis have allowed researchers to develop better diagnostics, such as detecting changing abundances of small molecules in the blood that may specifically indicate typhoid fever. Diagnostic tools in regions where typhoid is most prevalent are quite limited in their accuracy and specificity, and the time required for a proper diagnosis, the increasing spread of antibiotic resistance, and the cost of testing are also hardships for under-resourced healthcare systems.A typhoid vaccine can prevent about 40% to 90% of cases during the first two years. The vaccine may have some effect for up to seven years. For those at high risk or people traveling to areas where the disease is common, vaccination is recommended. Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing. Until an infection is confirmed as cleared, the infected person should not prepare food for others. Typhoid is treated with antibiotics such as azithromycin, fluoroquinolones, or third-generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment more difficult.In 2015, 12.5 million new typhoid cases were reported. The disease is most common in India. Children are most commonly affected. Typhoid decreased in the developed world in the 1940s as a result of improved sanitation and the use of antibiotics. Every year about 400 cases are reported in the U.S. and an estimated 6,000 people have typhoid. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990. Without treatment, the risk of death may be as high as 20%. With treatment, it is between 1% and 4%.Typhus is a different disease. Owing to their similar symptoms, they were not recognized as distinct diseases until the 1800s. "Typhoid" means "resembling typhus". Signs and symptoms Classically, the progression of untreated typhoid fever has three distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated. In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for S. enterica subsp. enterica serovar Typhi. The Widal test is usually negative. In the second week, the person is often too tired to get up, with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium can occur, where the patient is often calm, but sometimes becomes agitated. This delirium has given typhoid the nickname "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi (rattling breathing sounds) are heard in the base of the lungs. The abdomen is distended and painful in the right lower quadrant, where a rumbling sound can be heard. Diarrhea can occur in this stage, but constipation is also common. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive. In the third week of typhoid fever, a number of complications can occur: The fever is still very high and oscillates very little over 24 hours. Dehydration ensues along with malnutrition, and the patient is delirious. A third of affected people develop a macular rash on the trunk. Intestinal haemorrhage due to bleeding in congested Peyers patches occurs; this can be very serious, but is usually not fatal. Intestinal perforation in the distal ileum is a very serious complication and often fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in. Respiratory diseases such as pneumonia and acute bronchitis Encephalitis Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects. Metastatic abscesses, cholecystitis, endocarditis, and osteitis. Low platelet count (thrombocytopenia) is sometimes seen. Causes Bacteria The Gram-negative bacterium that causes typhoid fever is Salmonella enterica subsp. enterica serovar Typhi. Based on MLST subtyping scheme, the two main sequence types of the S. Typhi are ST1 and ST2, which are widespread globally. Global phylogeographical analysis showed dominance of a haplotype 58 (H58), which probably originated in India during the late 1980s and is now spreading through the world with multi-drug resistance. A more detailed genotyping scheme was reported in 2016 and is now being used widely. This scheme reclassified the nomenclature of H58 to genotype 4.3.1. Transmission Unlike other strains of Salmonella, no animal carriers of typhoid are known. Humans are the only known carriers of the bacterium. S. enterica subsp. enterica serovar Typhi is spread by the fecal-oral route from people who are infected and from asymptomatic carriers of the bacterium. An asymptomatic human carrier is someone who is still excreting typhoid bacteria in their stool a year after the acute stage of the infection. Diagnosis Diagnosis is made by any blood, bone marrow, or stool cultures and with the Widal test (demonstration of antibodies against Salmonella antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery, or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and blood and stool cultures. Widal test The Widal test is used to identify specific antibodies in the serum of people with typhoid by using antigen-antibody interactions.In this test, the serum is mixed with a dead bacterial suspension of salmonella with specific antigens. If the patients serum contains antibodies against those antigens, they get attached to them, forming clumps. If clumping does not occur, the test is negative. The Widal test is time-consuming and prone to significant false positives. It may also be falsely negative in recently infected people. But unlike the Typhidot test, the Widal test quantifies the specimen with titres. Rapid diagnostic tests Rapid diagnostic tests such as Tubex, Typhidot, and Test-It have shown moderate diagnostic accuracy. Typhidot Typhidot is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen. This test is carried out on a cellulose nitrate membrane where a specific S. typhi outer membrane protein is attached as fixed test lines. It separately identifies IgM and IgG antibodies. IgM shows recent infection; IgG signifies remote infection. The sample pad of this kit contains colloidal gold-anti-human IgG or gold-anti-human IgM. If the sample contains IgG and IgM antibodies against those antigens, they will react and turn red. The typhidot test becomes positive within 2–3 days of infection. Two colored bands indicate a positive test. A single control band indicates a negative test. A single first fixed line or no band at all indicates an invalid test. Typhidots biggest limitation is that it is not quantitative, just positive or negative. Tubex test The Tubex test contains two types of particles: brown magnetic particles coated with antigen and blue indicator particles coated with O9 antibody. During the test, if antibodies are present in the serum, they will attach to the brown magnetic particles and settle at the base, while the blue indicator particles remain in the solution, producing a blue color, which means the test is positive.If the serum does not have an antibody in it, the blue particles attach to the brown particles and settle at the bottom, producing a colorless solution, which means the test is negative. Prevention Sanitation and hygiene are important to prevent typhoid. It can spread only in environments where human feces can come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid. Industrialization contributed greatly to the elimination of typhoid fever, as it eliminated the public-health hazards associated with having horse manure in public streets, which led to a large number of flies, which are vectors of many pathogens, including Salmonella spp. According to statistics from the U.S. Centers for Disease Control and Prevention, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever. Vaccination Two typhoid vaccines are licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif by Crucell Switzerland AG) and the injectable typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are efficacious and recommended for travelers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form. An older, killed whole-cell vaccine is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has more side effects (mainly pain and inflammation at the site of the injection). To help decrease rates of typhoid fever in developing nations, the World Health Organization (WHO) endorsed the use of a vaccination program starting in 1999. Vaccination has proven effective at controlling outbreaks in high-incidence areas and is also very cost-effective: prices are normally less than US$1 per dose. Because the price is low, poverty-stricken communities are more willing to take advantage of the vaccinations. Although vaccination programs for typhoid have proven effective, they alone cannot eliminate typhoid fever. Combining vaccines with public-health efforts is the only proven way to control this disease.Since the 1990s, the WHO has recommended two typhoid fever vaccines. The ViPS vaccine is given by injection, and the Ty21a by capsules. Only people over age two are recommended to be vaccinated with the ViPS vaccine, and it requires a revaccination after 2–3 years, with a 55%–72% efficacy. The Ty21a vaccine is recommended for people five and older, lasting 5–7 years with 51%–67% efficacy. The two vaccines have proved safe and effective for epidemic disease control in multiple regions.A version of the vaccine combined with a hepatitis A vaccine is also available.Results of a phase 3 trial of typhoid conjugate vaccine (TCV) in December 2019 reported 81% fewer cases among children. Treatment Oral rehydration therapy The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general. Antibiotics Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.Properly treated, typhoid fever is not fatal in most cases. Antibiotics such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin have been commonly used to treat it. Treatment with antibiotics reduces the case-fatality rate to about 1%.Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms, and occasionally pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in 10%–20% of cases. The highest case fatality rates are reported in children under 4. Around 2%–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved. Surgery Surgery is usually indicated if intestinal perforation occurs. One study found a 30-day mortality rate of 9% (8/88), and surgical site infections at 67% (59/88), with the disease burden borne predominantly by low-resource countries.For surgical treatment, most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations. If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is sometimes successful, especially in patients with gallstones, but is not always successful in eradicating the carrier state because of persisting hepatic infection. Resistance As resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, these agents are no longer used as first–line treatment of typhoid fever. Typhoid resistant to these agents is known as multidrug-resistant typhoid.Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are shifting from ciprofloxacin to ceftriaxone as the first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. Also, it has been suggested that azithromycin is better at treating resistant typhoid than both fluoroquinolone drugs and ceftriaxone. Azithromycin can be taken by mouth and is less expensive than ceftriaxone, which is given by injection.A separate problem exists with laboratory testing for reduced susceptibility to ciprofloxacin; current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), that isolates sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", and that isolates sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". But an analysis of 271 isolates found that around 18% of isolates with a reduced susceptibility to fluoroquinolones, the class which CIP belongs (MIC 0.125–1.0 mg/L), would not be detected by this method. Epidemiology In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths. It occurs most often in children and young adults between 5 and 19 years old. In 2013, it resulted in about 161,000 deaths – down from 181,000 in 1990. Infants, children, and adolescents in south-central and Southeast Asia have the highest rates of typhoid. Outbreaks are also often reported in sub-Saharan Africa and Southeast Asia. In 2000, more than 90% of morbidity and mortality due to typhoid fever occurred in Asia. In the U.S., about 400 cases occur each year, 75% of which are acquired while traveling internationally.Before the antibiotic era, the case fatality rate of typhoid fever was 10%–20%. Today, with prompt treatment, it is less than 1%, but 3%–5% of people who are infected develop a chronic infection in the gall bladder. Since S. enterica subsp. enterica serovar Typhi is human-restricted, these chronic carriers become the crucial reservoir, which can persist for decades for further spread of the disease, further complicating its identification and treatment. Lately, the study of S. enterica subsp. enterica serovar Typhi associated with a large outbreak and a carrier at the genome level provides new insight into the pathogenesis of the pathogen.In industrialized nations, water sanitation and food handling improvements have reduced the number of typhoid cases. Developing nations, such as those in parts of Asia and Africa, have the highest rates. These areas lack access to clean water, proper sanitation systems, and proper health-care facilities. In these areas, such access to basic public-health needs is not expected in the near future.In 2004–2005 an outbreak in the Democratic Republic of Congo resulted in more than 42,000 cases and 214 deaths. Since November 2016, Pakistan has had an outbreak of extensively drug-resistant (XDR) typhoid fever.In Europe, a report based on data for 2017 retrieved from The European Surveillance System (TESSy) on the distribution of confirmed typhoid and paratyphoid fever cases found that 22 EU/EEA countries reported a total of 1,098 cases, 90.9% of which were travel-related, mainly acquired during travel to South Asia. History Early descriptions The plague of Athens, during the Peloponnesian War, was most likely an outbreak of typhoid fever. During the war, Athenians retreated into a walled-in city to escape attack from the Spartans. This massive influx of humans into a concentrated space overwhelmed the water supply and waste infrastructure, likely leading to unsanitary conditions as fresh water became harder to obtain and waste became more difficult to collect and remove beyond the city walls. In 2006, examining the remains for a mass burial site from Athens from around the time of the plague (~430 B.C.) revealed that fragments of DNA similar to modern day S. Typhi DNA were detected, whereas Yersinia pestis (plague), Rickettsia prowazekii (typhus), Mycobacterium tuberculosis, cowpox virus, and Bartonella henselae were not detected in any of the remains tested.It is possible that the Roman emperor Augustus Caesar had either a liver abscess or typhoid fever, and survived by using ice baths and cold compresses as a means of treatment for his fever. There is a statue of the Greek physician, Antonius Musa, who treated his fever. Definition and evidence of transmission The French doctors Pierre-Fidele Bretonneau and Pierre-Charles-Alexandre Louis are credited with describing typhoid fever as a specific disease, unique from typhus. Both doctors performed autopsies on individuals who died in Paris due to fever – and indicated that many had lesions on the Peyers patches which correlated with distinct symptoms before death. British medics were skeptical of the differentiation between typhoid and typhus because both were endemic to Britain at that time. However, in France only typhoid was present circulating in the population. Pierre-Charlles-Alexandre Louis also performed case studies and statistical analysis to demonstrate that typhoid was contagious - and that persons who already had the disease seemed to be protected. Afterward, several American doctors confirmed these findings, and then Sir William Jenner convinced any remaining skeptics that typhoid is a specific disease recognizable by lesions in the Peyers patches by examining sixty six autopsies from fever patients and concluding that the symptoms of headaches, diarrhea, rash spots, and abdominal pain were only present in patients which then had intestinal lesions after death; which solidified the association of the disease with the intestinal tract and gave the first clue to the route of transmission.In 1847 William Budd learned of an epidemic of typhoid fever in Clifton, and identified that all 13 of 34 residents who had contracted the disease drew their drinking water from the same well. Notably, this observation was two years prior to John Snow discovering the route of contaminated water as the cause for a cholera outbreak. Budd later became health officer of Bristol and ensured a clean water supply, and documented further evidence of typhoid as a water-borne illness throughout his career. Cause Polish scientist Tadeusz Browicz described a short bacillus in the organs and feces of typhoid victims in 1874. Browicz was able to isolate and grow the bacilli but did not go as far as to insinuate or prove that they caused the disease.In April 1880, three months prior to Eberths publication, Edwin Klebs described short and filamentous bacilli in the Peyers patches in typhoid victims. The bacteriums role in disease was speculated but not confirmed.In 1880, Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid. Eberth is given credit for discovering the bacterium definitively by successfully isolating the same bacterium from 18 of 40 typhoid victims and failing to discover the bacterium present in any "control" victims of other diseases. In 1884, pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberths findings. Gaffky isolated the same bacterium as Eberth from the spleen of a typhoid victim, and was able to grow the bacterium on solid media. The organism was given names such as Eberths bacillus, Eberthella Typhi, and Gaffky-Eberth bacillus. Today, the bacillus that causes typhoid fever goes by the scientific name Salmonella enterica serovar Typhi. Chlorination of water Most developed countries had declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1893 attempts were made to chlorinate the water supply in Hamburg, Germany and in 1897 Maidstone, England, was the first town to have its entire water supply chlorinated. In 1905, following an outbreak of typhoid fever, the City of Lincoln, England, instituted permanent water chlorination. The first permanent disinfection of drinking water in the US was made in 1908 to the Jersey City, New Jersey, water supply. Credit for the decision to build the chlorination system has been given to John L. Leal. The chlorination facility was designed by George W. Fuller.Outbreaks in traveling military groups led to the creation of the Lyster bag in 1915; a bag with a faucet which can be hung from a tree or pole, filled with water, and comes with a chlorination tablet to drop into the water. The Lyster bag was essential for the survival of American soldiers in the Vietnam War. Direct transmission and carriers There were several occurrences of milk delivery men spreading typhoid fever throughout the communities they served. Although typhoid is not spread through milk itself, there were several examples of milk distributors in many locations watering their milk down with contaminated water, or cleaning the glass bottles the milk was placed in with contaminated water. Boston had two such cases around the turn of the 20th century. In 1899 there were 24 cases of typhoid traced to a single milkman, whose wife had died of typhoid fever a week before the outbreak. In 1908, J.J. Fallon, who was also a milkman, died of typhoid fever. Following his death and confirmation of the typhoid fever diagnosis, the city conducted an investigation of typhoid symptoms and cases along his route and found evidence of a significant outbreak. A month after the outbreak was first reported, the Boston Globe published a short statement declaring the outbreak over, stating "[a]t Jamaica Plain there is a slight increase, the total being 272 cases. Throughout the city there is a total of 348 cases." There was at least one death reported during this outbreak: Mrs. Sophia S. Engstrom, aged 46. Typhoid continued to ravage the Jamaica Plain neighborhood in particular throughout 1908, and several more people were reported dead due to typhoid fever, although these cases were not explicitly linked to the outbreak. The Jamaica Plain neighborhood at that time was home to many working-class and poor immigrants, mostly from Ireland.The most notorious carrier of typhoid fever, but by no means the most destructive, was Mary Mallon, known as Typhoid Mary. Although other cases of human-to-human spread of typhoid were known at the time, the concept of an asymptomatic carrier, who was able to transmit disease, had only been hypothesized and not yet identified or proven. Mary Mallon became the first known example of an asymptomatic carrier of an infectious disease, making typhoid fever the first known disease being transmissible through asymptomatic hosts. The cases and deaths caused by Mallon were mainly upper-class families in New York City. At the time of Mallons tenure as a personal cook for upper-class families, New York City reported 3,000 to 4,500 cases of typhoid fever annually. In the summer of 1906 two daughters of a wealthy family and maids working in their home became ill with typhoid fever. After investigating their home water sources and ruling out water contamination, the family hired civil engineer George Soper to conduct an investigation of the possible source of typhoid fever in the home. Soper described himself as an "epidemic fighter". His investigation ruled out many sources of food, and led him to question if the cook the family hired just prior to their household outbreak, Mallon, was the source. Since she had already left and begun employment elsewhere, he proceeded to track her down in order to obtain a stool sample. When he was able to finally meet Mallon in person he described her by saying "Mary had a good figure and might have been called athletic had she not been a little too heavy." In recounts of Sopers pursuit of Mallon, his only remorse appears to be that he was not given enough credit for his relentless pursuit and publication of her personal identifying information, stating that the media "rob[s] me of whatever credit belongs to the discovery of the first typhoid fever carrier to be found in America." Ultimately, 51 cases and 3 deaths were suspected to be caused by Mallon.In 1924 the city of Portland, Oregon, experienced an outbreak of typhoid fever, consisting of 26 cases and 5 deaths, all deaths due to intestinal hemorrhage. All cases were concluded to be due to a single milk farm worker, who was shedding large amounts of the typhoid pathogen in his urine. Misidentification of the disease, due to inaccurate Widal test results, delayed identification of the carrier and proper treatment. Ultimately, it took four samplings of different secretions from all of the dairy workers in order to successfully identify the carrier. Upon discovery, the dairy worker was forcibly quarantined for seven weeks, and regular samples were taken, most of the time the stool samples yielding no typhoid and often the urine yielding the pathogen. The carrier was reported as being 72 years old and appearing in excellent health with no symptoms. Pharmaceutical treatment decreased the amount of bacteria secreted, however, the infection was never fully cleared from the urine, and the carrier was released "under orders never again to engage in the handling of foods for human consumption." At the time of release, the authors noted "for more than fifty years he has earned his living chiefly by milking cows and knows little of other forms of labor, it must be expected that the closest surveillance will be necessary to make certain that he does not again engage in this occupation."Overall, in the early 20th century the medical profession began to identify carriers of the disease, and evidence of transmission independent of water contamination. In a 1933 American Medical Association publication, physicians treatment of asymptomatic carriers is best summarized by the opening line "Carriers of typhoid bacilli are a menace". Within the same publication, the first official estimate of typhoid carriers is given: 2 to 5% of all typhoid patients, and distinguished between temporary carriers and chronic carriers. The authors further estimate that there are four to five chronic female carriers to every one male carrier, although offered no data to explain this assertion of a gender difference in the rate of typhoid carriers. As far as treatment, the authors suggest: "When recognized, carriers must be instructed as to the disposal of excreta as well as to the importance of personal cleanliness. They should be forbidden to handle food or drink intended for others, and their movements and whereabouts must be reported to the public health officers". Today, typhoid carriers exist all over the world, but the highest incidence of asymptomatic infection is likely to occur in South/Southeast Asian and Sub-Saharan countries. The Los Angeles County department of public health tracks typhoid carriers and reports the number of carriers identified within the county yearly; between 2006 and 2016 0-4 new cases of typhoid carriers were identified per year. Cases of typhoid fever must be reported within one working day from identification. As of 2018, chronic typhoid carriers must sign a "Carrier Agreement" and are required to test for typhoid shedding twice yearly, ideally every 6 months. Carriers may be released from their agreements upon fulfilling "release" requirements, based on completion of a personalized treatment plan designed with medical professionals. Fecal or gallbladder carrier release requirements: 6 consecutive negative feces and urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. Urinary or kidney carrier release requirements: 6 consecutive negative urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. As of 2016 the male:female ratio of carriers in Los Angeles county was 3:1.Due to the nature of asymptomatic cases, many questions remain about how individuals are able to tolerate infection for long periods of time, how to identify such cases, and efficient options for treatment. Researchers are currently working to understand asymptomatic infection with Salmonella species by studying infections in laboratory animals, which will ultimately lead to improved prevention and treatment options for typhoid carriers. In 2002, Dr. John Gunn described the ability of Salmonella sp. to form biofilms on gallstones in mice, providing a model for studying carriage in the gallbladder. Dr. Denise Monack and Dr. Stanley Falkow described a mouse model of asymptomatic intestinal and systemic infection in 2004, and Dr. Monack went on to demonstrate that a sub-population of superspreaders are responsible for the majority of transmission to new hosts, following the 80/20 rule of disease transmission, and that the intestinal microbiota likely plays a role in transmission. Dr. Monacks mouse model allows long-term carriage of salmonella in mesenteric lymph nodes, spleen and liver. Vaccine development British bacteriologist Almroth Edward Wright first developed an effective typhoid vaccine at the Army Medical School in Netley, Hampshire. It was introduced in 1896 and used successfully by the British during the Second Boer War in South Africa. At that time, typhoid often killed more soldiers at war than were lost due to enemy combat. Wright further developed his vaccine at a newly opened research department at St Marys Hospital Medical School in London from 1902, where he established a method for measuring protective substances (opsonin) in human blood. Wrights version of the typhoid vaccine was produced by growing the bacterium at body temperature in broth, then heating the bacteria to 60 °C to "heat inactivate" the pathogen, killing it, while keeping the surface antigens intact. The heat-killed bacteria was then injected into a patient. To show evidence of the vaccines efficacy, Wright then collected serum samples from patients several weeks post-vaccination, and tested their serums ability to agglutinate live typhoid bacteria. A "positive" result was represented by clumping of bacteria, indicating that the body was producing anti-serum (now called antibodies) against the pathogen.Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the British Army that 10 million vaccine doses should be produced for the troops being sent to the Western Front, thereby saving up to half a million lives during World War I. The British Army was the only combatant at the outbreak of the war to have its troops fully immunized against the bacterium. For the first time, their casualties due to combat exceeded those from disease.In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wrights typhoid vaccine for use with the Army, and two years later, his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military. Typhoid vaccination for members of the American military became mandatory in 1911. Before the vaccine, the rate of typhoid fever in the military was 14,000 or greater per 100,000 soldiers. By World War I, the rate of typhoid in American soldiers was 37 per 100,000.During the second world war, the United States army authorized the use of a trivalent vaccine – containing heat-inactivated Typhoid, Paratyphi A and Paratyphi B pathogens.In 1934, discovery of the Vi capsular antigen by Arthur Felix and Miss S. R. Margaret Pitt enabled development of the safer Vi Antigen vaccine – which is widely in use today. Arthur Felix and Margaret Pitt also isolated the strain Ty2, which became the parent strain of Ty21a, the strain used as a live-attenuated vaccine for typhoid fever today. Antibiotics and resistance Chloramphenicol was isolated from Streptomyces by Dr. David Gotlieb during the 1940s. In 1948 American army doctors tested its efficacy in treating typhoid patients in Kuala Lumpur, Malaysia. Individuals who received a full course of treatment cleared the infection, whereas patients given a lower dose had a relapse. Asymptomatic carriers continued to shed bacilli despite chloramphenicol treatment - only ill patients were improved with chloramphenicol. Resistance to chloramphenicol became frequent in Southeast Asia by the 1950s, and today chloramphenicol is only used as a last resort due to the high prevalence of resistance. Terminology The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, pythogenic fever, drain fever and low fever. Notable people Emperor Augustus of Rome (suspected based on historical record but not confirmed), survived. Albert, Prince Consort, husband of Queen Victoria of the United Kingdom, died in 24 days after first record of "feeling horribly ill". Died 14 December 1861 after suffering loss of appetite, insomnia, fever, chills, profuse sweating, vomiting, rash spots, delusions, inability to recognize family members, worsening rash on abdomen, a change in tongue color, then finally a state of extreme fatigue. Attending physician William Jenner, an expert on Typhoid fever at the time, diagnosed him. Edward VII of the UK, son of Queen Victoria, while still Prince of Wales, had a near fatal case of typhoid fever. Tsar Nicholas II of Russia, survived, illness was circa 1900–1901. William Henry Harrison, the 9th President of the United States of America, died 32 days into his term, in 1841. This is the shortest term served by a United States President. Wilbur Wright, co-inventor of the plane with his brother Orville died from typhoid 32 years before Orville. Stephen A. Douglas, political opponent of Abraham Lincoln in 1858 and 1860, died of typhoid on June 3, 1861. Ignacio Zaragoza, Mexican general and politician, died at the age of 33 of typhoid fever on September 8, 1862. William Wallace Lincoln, the son of US president Abraham and Mary Todd Lincoln, died of typhoid in 1862. Martha Bulloch Roosevelt, mother of president Theodore Roosevelt and paternal grandmother of Eleanor Roosevelt, died of typhoid fever in 1884. Mary Mallon, "Typhoid Mary" - see history section, "carriers" for further details Leland Stanford Jr., son of American tycoon and politician A. Leland Stanford and eponym of Leland Stanford Junior University, died of typhoid fever in 1884 at the age of 15. Three of Louis Pasteurs five children died of typhoid fever. Gerard Manley Hopkins, English poet, died of typhoid fever in 1889. Lizzie van Zyl, South African child inmate of the Bloemfontein concentration camp during the Second Boer War, died of typhoid fever in 1901. Dr HJH Tup Scott, captain of the 1886 Australian cricket team that toured England, died of typhoid in 1910. Arnold Bennett, English novelist, died in 1932 of typhoid, two months after drinking a glass of water in a Paris hotel to prove it was safe. Hakaru Hashimoto, Japanese medical scientist, died of typhoid fever in 1934. Outbreaks Plague of Athens (suspected) "Burning Fever" outbreak among indigenous Americans. Between 1607 and 1624, 85% of the population at the James River died from a typhoid epidemic. The World Health Organization estimates the death toll was over 6,000 during this time. Maidstone, Kent outbreak in 1897–1898: 1,847 patients were recorded to have typhoid fever. This outbreak is notable because it was the first time a typhoid vaccine was deployed during a civilian outbreak. Almoth Edward Wrights vaccine was offered to 200 healthcare providers, and of the 84 individuals who received the vaccine none developed typhoid whereas 4 who had not been vaccinated became ill. American army in the Spanish-American war: government records estimate over 21,000 troops had typhoid, resulting in 2,200 deaths. In 1902, guests at mayoral banquets in Southampton and Winchester, England, became ill and four died, including the Dean of Winchester, after consuming oysters. The infection was due to oysters sourced from Emsworth, where the oyster beds had been contaminated with raw sewage. Jamaica Plain neighborhood, Boston in 1908 - linked to milk delivery. See history section, "carriers" for further details. Outbreak in upperclass New Yorkers who employed Mary Mallon - 51 cases and 3 deaths from 1907 to 1915. Aberdeen, Scotland, in summer 1964 - traced back to contaminated canned beef sourced from Argentina sold in markets. More than 500 patients were quarantined in the hospital for a minimum of four weeks, and the outbreak was contained without any deaths. Dushanbe, Tajikistan, in 1996–1997: 10,677 cases reported, 108 deaths Kinshasa, Democratic Republic of the Congo, in 2004: 43,000 cases and over 200 deaths. A prospective study of specimens collected in the same region between 2007 and 2011 revealed about one third of samples obtained from patient samples were resistant to multiple antibiotics. Kampala, Uganda in 2015: 10,230 cases reported See also Typhus fever References == Further reading ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

The term 'Pigmented purpuric dermatosis' keeps coming up in medical discussions. What does it stand for?

Pigmented purpuric dermatosis refers to one of the three major classes of skin conditions characterized by purpuric skin eruptions. Pigmented purpuric dermatosis are distinguished from other purpura by size (0.3–1 cm) and are most often seen in the lower extremities.: 829  Pigmentary purpuric eruptions may present with one of several clinical patterns. There may be overlapping characteristics among pigmented purpuric dermatosis and between their signs and those of other purpuric eruptions.: 829  Examples of the pigmented purpuric dermatosis group include:: 829–30  Schambergs disease Majocchis disease (Purpura annularis telangiectodes) Gougerot-Blum syndrome (Pigmented purpuric lichenoid dermatitis) Ducas and Kapetanakis pigmented purpura Lichen aureusAlthough vascular damage may be present, it is insufficient for these conditions to be considered forms of vasculitis.A few very small non-blinded studies of treatment with narrow-band ultraviolet light have been reported as promising. See also Purpura Skin lesion List of cutaneous conditions References == External links ==

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I'm curious about the meaning of the medical term 'Idiopathic interstitial pneumonia.' Can you give me some insights?

Idiopathic interstitial pneumonia (IIP), or noninfectious pneumonia are a class of diffuse lung diseases. These diseases typically affect the pulmonary interstitium, although some also have a component affecting the airways (for instance, cryptogenic organizing pneumonitis). There are seven recognized distinct subtypes of IIP. Diagnosis Classification can be complex, and the combined efforts of clinicians, radiologists, and pathologists can help in the generation of a more specific diagnosis.Idiopathic interstitial pneumonia can be subclassified based on histologic appearance into the following patterns: Usual interstitial pneumonia is the most common type. Development Table 1: Development of the (histologic) idiopathic interstitial pneumonia classification UIP=usual interstitial pneumonia; DAD=diffuse alveolar damage; NSIP=non-specific interstitial pneumonia; DIP=desquamative interstitial pneumonia; RB=respiratory bronchiolitis; BIP=bronchiolitis obliterans interstitial pneumonia; OP=organizing pneumonia; LIP=lymphoid interstitial pneumonia; LPD=lymphoproliferative disease (not considered a diffuse lung disease); GIP=giant cell interstitial pneumonia; HMF=heavy metal fibrosis, no longer grouped with diffuse lung disease Lymphoid interstitial pneumonia was originally included in this category, then excluded, then included again. References == External links ==

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I'm encountering the term 'Bruck syndrome' in medical literature. What's its definition?

Bruck syndrome is characterized as the combination of arthrogryposis multiplex congenita and osteogenesis imperfecta. Both diseases are uncommon, but concurrence is extremely rare which makes Bruck syndrome very difficult to research. Bruck syndrome is thought to be an atypical variant of osteogenesis imperfecta most resembling type III, if not its own disease. Multiple gene mutations associated with osteogenesis imperfecta are not seen in Bruck syndrome. Many affected individuals are within the same family, and pedigree data supports that the disease is acquired through autosomal recessive inheritance. Bruck syndrome has features of congenital contractures, bone fragility, recurring bone fractures, flexion joint and limb deformities, pterygia, short body height, and progressive kyphoscoliosis. Individuals encounter restricted mobility and pulmonary function. A reduction in bone mineral content and larger hydroxyapatite crystals are also detectable Joint contractures are primarily bilateral and symmetrical, and most prone to ankles. Bruck syndrome has no effect on intelligence, vision, or hearing. Genetics The genetics of Bruck syndrome differs from osteogenesis imperfecta. Osteogenesis imperfecta involves autosomal dominant mutations to Col 1A2 or Col 1A2 which encode type 1 procollagen. Bruck syndrome is linked to mutations in two genes, and therefore is divided in two types. Bruck syndrome type 1 is caused by a homozygous mutation in the FKBP10 gene. Type 2 is caused by a homozygous mutation in the PLOD2 gene. Mechanism Type 1 encodes FKBP65, an endoplasmic reticulum associated peptidyl-prolyl cis/trans isomerase (PPIase) that functions as a chaperone in collagen biosynthesis. Osteoblasts deficient in FKBP65 have a buildup of procollagen aggregates in the endoplasmic reticulum which reduces their ability to form bone. Furthermore, Bruck syndrome type 1 patients have under-hydroxylated lysine residues in the collagen telopeptide and as a result show diminished hydroxylysylpyridinoline cross-links.Type 2 encodes the enzyme, lysyl hydroxylase 2, which catalyzes hydroxylation of lysine residues in collagen cross-links. PLOD2 is most expressed in active osteoblasts since collagen cross-linking is tissue-specific. Mutation in PLOD2 alters the structure of telopeptide lysyl hydroxylase and prevents fibril formation of collagen type 1. Bone analysis shows the lysine residues of telopeptides in collagen type 1 are under-hydroxylated. Diagnosis Diagnosis of Bruck syndrome must distinguish the association of contractures and skeletal fragility. Ultrasound is used for prenatal diagnosis. The diagnosis of a neonate bears resemblance to arthrogryposis multiplex congenital, and later in childhood to osteogenesis imperfecta. Management Until more molecular and clinical studies are performed there will be no way to prevent the disease. Treatments are directed towards alleviating the symptoms. To treat the disease it is crucial to diagnose it properly. Orthopedic therapy and fracture management are necessary to reduce the severity of symptoms. Bisphosphonate drugs are also an effective treatment. History The first case was in 1897 of a male who was described by Bruck as having bone fragility and bone contractures. Bruck was credited with the first description and the diseases eponym. References Further reading Breslau-Siderius, E. J.; et al. (1998). "Brack syndrome: a rare combination of bone fragility and multiple congenital joint contractures". Journal of Pediatric Orthopaedics B. 7 (1): 35–38. doi:10.1097/01202412-199801000-00006. == External links ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

Can you demystify the medical term 'Tenofovir alafenamide' for me?

Tenofovir alafenamide, sold under the brand name Vemlidy, is a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor medication for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease. It is taken by mouth.Tenofovir alafenamide is a prodrug of tenofovir. It was developed by Gilead Sciences based on the protide technology of Chris McGuigan for use in the treatment of HIV/AIDS and chronic hepatitis B, and is applied in the form of tenofovir alafenamide fumarate (TAF). Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (TDF), TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent. Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016. Fixed-dose combinations containing tenofovir alafenamide Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya) — approved both in the United States and in the European Union in November 2015 (compare elvitegravir/cobicistat/emtricitabine/tenofovir; (Stribild)) Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) — approved in the United States in March 2016, and in the European Union in June 2016 (compare Emtricitabine/rilpivirine/tenofovir; (Complera)) Emtricitabine/tenofovir alafenamide (Descovy) — approved in the United States in April 2016 (compare emtricitabine/tenofovir; (Truvada)). In October 2019, Descovy was approved in the United States for HIV-1 pre-exposure prophylaxis (PrEP). Bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) — approved in the United States in February 2018. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza) — approved in the European Union in September 2017, in the United States in July 2018, and in Australia in November 2019. Dolutegravir/emtricitabine/tenofovir alafenamide. Dolutegravir/lamivudine/tenofovir alafenamide. Research Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir. In a 48-week study comparing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (Stribild) to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya), the results showed the newer drugs effects to be non-inferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function. The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015. Genvoya is the first TAF-based regimen to receive approval. References External links "Tenofovir alafenamide". Drug Information Portal. U.S. National Library of Medicine. "Tenofovir alafenamide fumarate". Drug Information Portal. U.S. National Library of Medicine.

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

Can you demystify the medical term 'Renpennings syndrome' for me?

Renpennings syndrome is a neurodevelopmental disorder recognised in males that causes intellectual disability, mild growth retardation with examples in the testes and head, and a somewhat short stature. The condition only affects males, starting at birth. Presentation People with Renpennings typically begin learning language at an ordinary pace, but by the age of 3–4 they experience a regression in mental and physical development, such as mild low muscle tone resulting in elongated faces and rapid loss in the normal growth of the head (microcephaly). Small testes and short stature are also known to commonly occur. Genetics It is associated with mutations in the PQBP1 gene. The gene product is a polyglutamine-binding protein involved in transcription and pre-mRNA splicing. The gene itself is located on the short arm of the X chromosome (Xp11.23). The most common mutations causing this condition occur in exon 4. Diagnosis This diagnosis may be suspected on clinical grounds but should be confirmed by sequencing the PQBP1 gene. Treatment There is no specific or curative treatment for this condition at present. Management is supportive Epidemiology This condition normally only occurs in males but a case in a female has been reported. History This condition was first characterized in 1962. and later described by Hans Renpenning in 1963 after he documented these traits on many children in one family alone. See also Lujan-Fryns syndrome Fragile x syndrome References == External links ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm not familiar with the medical term 'Saddle nose.' Could you provide some insights?

Saddle nose is a condition associated with nasal trauma, congenital syphilis, relapsing polychondritis, granulomatosis with polyangiitis, cocaine abuse, and leprosy, among other conditions. The most common cause is nasal trauma. It is characterized by a loss of height of the nose, because of the collapse of the bridge. The depressed nasal dorsum may involve bony, cartilaginous or both bony and cartilaginous components of the nasal dorsum. It can usually be corrected with augmentation rhinoplasty by filling the dorsum of nose with cartilage, bone or synthetic implant. If the depression is only cartilaginous, cartilage is taken from the nasal septum or auricle and laid in single or multiple layers. If deformity involves both cartilage and bone, cancellous bone from iliac crest is the best replacement. Autografts are preferred over allografts. Saddle deformity can also be corrected by synthetic implants of teflon or silicon, but they are likely to be extruded. See also Saber shin List of cutaneous conditions References == External links ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

What is the significance of the term 'Anorexia (symptom)' in the medical field?

Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others indicate a serious clinical condition or pose a significant risk. Anorexia is a symptom, not a diagnosis. Anorexia is not to be confused with the mental health disorder anorexia nervosa. Because the term anorexia is often used as a short-form of anorexia nervosa, to avoid confusion a provider must clarify to a patient whether they are simply referring to a decreased appetite or the mental health disorder. Anyone can manifest anorexia as a loss of appetite, regardless of their gender, age, or weight. The symptom also occurs in other animals, such as cats, dogs, cattle, goats, and sheep. In these species, anorexia may be referred to as inappetence. As in humans, loss of appetite can be due to a range of diseases and conditions, as well as environmental and psychological factors. Etymology The term is from Ancient Greek: ανορεξία (ἀν-, without + όρεξις, spelled órexis, meaning appetite). Common manifestations Anorexia simply manifests as a decreased or loss of appetite. This can present as not feeling hungry or lacking the desire to eat. Sometimes people do not even notice they lack an appetite until they begin to lose weight from eating less. In other cases, it can be more noticeable, such as when a person becomes nauseated from just the thought of eating. Any form of decreased appetite that leads to changes in the body (such as weight loss or muscle loss) that is not done intentionally as part of dieting is clinically significant. Physiology of anorexia Appetite stimulation and suppression is a complex process involving many different parts of the brain and body by the use of various hormones and signals. Appetite is thought to be stimulated by interplay between peripheral signals to the brain (taste, smell, sight, gut hormones) as well as the balance of neurotransmitters and neuropeptides in the hypothalamus. Examples of these signals or hormones include neuropeptide Y, leptin, ghrelin, insulin, serotonin, and orexins (also called hypocretins). Anything that causes an imbalance of these signals or hormones can lead to the symptom of anorexia. While it is known that these signals and hormones help control appetite, the complicated mechanisms regarding a pathological increase or decrease in appetite are still being explored. Common causes Acute radiation syndrome Addisons disease Alcoholism Alcohol withdrawal Anemia Anorexia nervosa Anxiety Appendicitis Babesiosis Benzodiazepine withdrawal Bipolar disorder Cancer Cannabinoid hyperemesis syndrome Cannabis withdrawal Celiac disease Chronic kidney disease Chronic pain Common cold Constipation COPD COVID-19 Crohns disease Dehydration Dementia Depression Ebola Fatty liver disease Fever Food poisoning Gastroparesis Hepatitis HIV/AIDS Hypercalcemia Hyperglycemia Hypervitaminosis D Hypothyroidism and sometimes hyperthyroidism Irritable bowel syndrome Ketoacidosis Kidney failure Low blood pressure Mania Metabolic disorders, particularly urea cycle disorders MELAS syndrome Nausea Opioid use disorder Pancreatitis Pernicious anemia Psychosis Schizophrenia Side effect of drugs Stimulant use disorder Stomach flu Stress Sickness behavior Superior mesenteric artery syndrome Syndrome of inappropriate antidiuretic hormone secretion Tuberculosis Thalassemia Ulcerative colitis Uremia Vitamin B12 deficiency Zinc deficiency Infection: Anorexia of infection is part of the acute phase response (APR) to infection. The APR can be triggered by lipopolysaccharides and peptidoglycans from bacterial cell walls, bacterial DNA, and double-stranded viral RNA, and viral glycoproteins, which can trigger production of a variety of proinflammatory cytokines. These can have an indirect effect on appetite by a number of means, including peripheral afferents from their sites of production in the body, by enhancing production of leptin from fat stores. Inflammatory cytokines can also signal to the central nervous system more directly by specialized transport mechanisms through the blood–brain barrier, via circumventricular organs (which are outside the barrier), or by triggering production of eicosanoids in the endothelial cells of the brain vasculature. Ultimately, the control of appetite by this mechanism is thought to be mediated by the same factors normally controlling appetite, such as neurotransmitters (serotonin, dopamine, histamine, norepinephrine, corticotropin releasing factor, neuropeptide Y, and α-melanocyte-stimulating hormone). Drugs Stimulants, such as ephedrine, amphetamine, methamphetamine, MDMA, cathinone, methylphenidate, nicotine, cocaine, caffeine, etc. Narcotics, such as heroin, morphine, codeine, hydrocodone, oxycodone, etc. Antidepressants can have anorexia as a side effect, primarily selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Byetta, a type II diabetes drug, will cause moderate nausea and loss of appetite. Abruptly stopping appetite-increasing drugs, such as cannabis and corticosteroids. Chemicals that are members of the phenethylamine group. (Individuals with anorexia nervosa may seek them to suppress appetite.) Topiramate may cause anorexia as a side effect. Other drugs may be used to intentionally cause anorexia in order to help a patient preoperative fasting prior to general anesthesia. It is important to avoid food before surgery to mitigate the risk of pulmonary aspiration, which can be fatal. Other During the post-operative recovery period for a tonsillectomy or adenoidectomy, it is common for adult patients to experience a lack of appetite until their throat significantly heals (usually 10–14 days). Altitude sickness Significant emotional pain caused by an event (rather than a mental disorder) can cause an individual to temporarily lose all interest in food. Several Twelve-step programs including Overeaters Anonymous tackle psychological issues members believe lead to forms of deprivation Psychological stress Experiencing grotesque or unappealing thoughts or conversations, or viewing similar images Being in the presence of unappealing things such as waste matter, dead organisms, or bad smells Complications Complications of anorexia may result due to poor food intake. Poor food intake can lead to dehydration, electrolyte imbalances, anemia and nutritional deficiencies. These imbalances will worsen the longer that food is avoided. Sudden cardiac death Anorexia is a relatively common condition that can lead patients to have dangerous electrolyte imbalances, leading to acquired long QT syndrome which can result in sudden cardiac death. This can develop over a prolonged period of time, and the risk is further heightened when feeding resumes after a period of abstaining from consumption. Refeeding syndrome Care must be taken when a patient begins to eat after prolonged starvation to avoid the potentially fatal complications of refeeding syndrome. The initial signs of refeeding syndrome are minimal, but can rapidly progress to death. Thus, the reinitiation of food or oral intake is usually started slowly and requires close observation under supervision by trained healthcare professionals. This is usually done in a hospital or nutritional rehabilitation center. Management Anorexia can be treated with the help of orexigenic drugs. "Anorexia" vs "anorexic" vs anorexia nervosa Anorexic is a description of somebody with the stereotypical thin, frail, malnourished appearance. The appearance is classically associated with anorexia, although in rare cases do patients end up becoming anorexic. An anorexic or anorectic is also a description given to substances that cause anorexia for weight loss purposes. Anorexia nervosa is an eating disorder characterized by food restriction due to the strong desire to remain thin. It is considered a mental health diagnosis where people see themselves as obese regardless of their weight or appearance. The person does not necessarily exhibit anorexia as a symptom in their quest to restrict food intake. References == External links ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

What does the medical term 'Mouth and genital ulcers with inflamed cartilage syndrome' encompass?

Mouth and genital ulcers with inflamed cartilage syndrome (also known as "MAGIC syndrome") is a cutaneous condition with features of both Behçets disease and relapsing polychondritis. Recently, it has been questioned whether these two conditions are linked in the same individual or are two separate disorders. See also Cartilage Nicolau–Balus syndrome List of cutaneous conditions References == External links ==

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

Could you please explain the term 'Ethylenediaminetetraacetic acid' in simple language?

Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula [CH2N(CH2CO2H)2]2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes even at neutral pH. It is thus used to remove (dissolve) Fe- and Ca-containing scale as well as to delivery Fe ions under conditions where its oxides are insoluble. EDTA is available as several salts, notably disodium EDTA, sodium calcium edetate, and tetrasodium EDTA, but these all function similarly. Uses Textile industry In industry, EDTA is mainly used to sequester (bind or confine) metal ions in aqueous solution. In the textile industry, it prevents metal ion impurities from modifying colours of dyed products. In the pulp and paper industry, EDTA inhibits the ability of metal ions, especially Mn2+, from catalysing the disproportionation of hydrogen peroxide, which is used in chlorine-free bleaching. In a similar manner, EDTA is added to some food as a preservative or stabiliser to prevent catalytic oxidative decolouration, which is catalysed by metal ions.In soft drinks containing ascorbic acid and sodium benzoate, EDTA mitigates formation of benzene (a carcinogen). Water softener The reduction of water hardness in laundry applications and the dissolution of scale in boilers both rely on EDTA and related complexants to bind Ca2+, Mg2+, as well as other metal ions. Once bound to EDTA, these metal complexes are less likely to form precipitates or to interfere with the action of the soaps and detergents. For similar reasons, cleaning solutions often contain EDTA. In a similar manner EDTA is used in the cement industry for the determination of free lime and free magnesia in cement and clinkers.The solubilisation of Fe3+ ions at or below near neutral pH can be accomplished using EDTA. This property is useful in agriculture including hydroponics. However, given the pH dependence of ligand formation, EDTA is not helpful for improving iron solubility in above neutral soils. Otherwise, at near-neutral pH and above, iron(III) forms insoluble salts, which are less bioavailable to susceptible plant species. Scrubbing Aqueous [Fe(EDTA)]− is used for removing ("scrubbing") hydrogen sulfide from gas streams. This conversion is achieved by oxidising the hydrogen sulfide to elemental sulfur, which is non-volatile: 2 [Fe(EDTA)]− + H2S → 2 [Fe(EDTA)]2− + S + 2 H+In this application, the iron(III) centre is reduced to its iron(II) derivative, which can then be reoxidised by air. In similar manner, nitrogen oxides are removed from gas streams using [Fe(EDTA)]2−. The oxidising properties of [Fe(EDTA)]− are also exploited in photography, where it is used to solubilise silver particles. Ion-exchange chromatography EDTA was used in separation of the lanthanide metals by ion-exchange chromatography. Perfected by F. H. Spedding et al. in 1954, the method relies on the steady increase in stability constant of the lanthanide EDTA complexes with atomic number. Using sulfonated polystyrene beads and Cu2+ as a retaining ion, EDTA causes the lanthanides to migrate down the column of resin while separating into bands of pure lanthanides. The lanthanides elute in order of decreasing atomic number. Due to the expense of this method, relative to countercurrent solvent extraction, ion exchange is now used only to obtain the highest purities of lanthanides (typically greater than 99.99%). Medicine Sodium calcium edetate, an EDTA derivative, is used to bind metal ions in the practice of chelation therapy, such as for treating mercury and lead poisoning. It is used in a similar manner to remove excess iron from the body. This therapy is used to treat the complication of repeated blood transfusions, as would be applied to treat thalassaemia. Dentistry Dentists and endodontists use EDTA solutions to remove inorganic debris (smear layer) and lubricate the root canals in endodontics. This procedure helps prepare root canals for obturation. Furthermore, EDTA solutions with the addition of a surfactant loosen up calcifications inside a root canal and allow instrumentation (canal shaping) and facilitate apical advancement of a file in a tight or calcified root canal towards the apex. Eyedrops It serves as a preservative (usually to enhance the action of another preservative such as benzalkonium chloride or thiomersal) in ocular preparations and eyedrops. Analysis In evaluating kidney function, the chromium(III) complex [Cr(EDTA)]− (as radioactive chromium-51 (51Cr)) is administered intravenously and its filtration into the urine is monitored. This method is useful for evaluating glomerular filtration rate (GFR) in nuclear medicine.EDTA is used extensively in the analysis of blood. It is an anticoagulant for blood samples for CBC/FBCs, where the EDTA chelates the calcium present in the blood specimen, arresting the coagulation process and preserving blood cell morphology. Tubes containing EDTA are marked with lavender (purple) or pink tops. EDTA is also in tan top tubes for lead testing and can be used in royal blue top tubes for trace metal testing.EDTA is a slime dispersant, and has been found to be highly effective in reducing bacterial growth during implantation of intraocular lenses (IOLs). Alternative medicine Some alternative practitioners believe EDTA acts as an antioxidant, preventing free radicals from injuring blood vessel walls, therefore reducing atherosclerosis. These ideas are unsupported by scientific studies, and seem to contradict some currently accepted principles. The U.S. FDA has not approved it for the treatment of atherosclerosis. Cosmetics In shampoos, cleaners, and other personal care products, EDTA salts are used as a sequestering agent to improve their stability in air. Laboratory applications In the laboratory, EDTA is widely used for scavenging metal ions: In biochemistry and molecular biology, ion depletion is commonly used to deactivate metal-dependent enzymes, either as an assay for their reactivity or to suppress damage to DNA, proteins, and polysaccharides. EDTA also acts as a selective inhibitor against dNTP hydrolyzing enzymes (Taq polymerase, dUTPase, MutT), liver arginase and horseradish peroxidase independently of metal ion chelation. These findings urge the rethinking of the utilisation of EDTA as a biochemically inactive metal ion scavenger in enzymatic experiments. In analytical chemistry, EDTA is used in complexometric titrations and analysis of water hardness or as a masking agent to sequester metal ions that would interfere with the analyses. EDTA finds many specialised uses in the biomedical labs, such as in veterinary ophthalmology as an anticollagenase to prevent the worsening of corneal ulcers in animals. In tissue culture EDTA is used as a chelating agent that binds to calcium and prevents joining of cadherins between cells, preventing clumping of cells grown in liquid suspension, or detaching adherent cells for passaging. In histopathology, EDTA can be used as a decalcifying agent making it possible to cut sections using a microtome once the tissue sample is demineralised. EDTA is also known to inhibit a range of metallopeptidases, the method of inhibition occurs via the chelation of the metal ion required for catalytic activity. EDTA can also be used to test for bioavailability of heavy metals in sediments. However, it may influence the bioavailability of metals in solution, which may pose concerns regarding its effects in the environment, especially given its widespread uses and applications. EDTA is also used to remove crud (corroded metals) from fuel rods in nuclear reactors. Side effects EDTA exhibits low acute toxicity with LD50 (rat) of 2.0 g/kg to 2.2 g/kg. It has been found to be both cytotoxic and weakly genotoxic in laboratory animals. Oral exposures have been noted to cause reproductive and developmental effects. The same study also found that both dermal exposure to EDTA in most cosmetic formulations and inhalation exposure to EDTA in aerosolised cosmetic formulations would produce exposure levels below those seen to be toxic in oral dosing studies. Synthesis The compound was first described in 1935 by Ferdinand Münz, who prepared the compound from ethylenediamine and chloroacetic acid. Today, EDTA is mainly synthesised from ethylenediamine (1,2-diaminoethane), formaldehyde, and sodium cyanide. This route yields the tetrasodium EDTA, which is converted in a subsequent step into the acid forms: H2NCH2CH2NH2 + 4 CH2O + 4 NaCN + 4 H2O → (NaO2CCH2)2NCH2CH2N(CH2CO2Na)2 + 4 NH3(NaO2CCH2)2NCH2CH2N(CH2CO2Na)2 + 4 HCl → (HO2CCH2)2NCH2CH2N(CH2CO2H)2 + 4 NaClThis process is used to produce about 80,000 tonnes of EDTA each year. Impurities cogenerated by this route include glycine and nitrilotriacetic acid; they arise from reactions of the ammonia coproduct. Nomenclature To describe EDTA and its various protonated forms, chemists distinguish between EDTA4−, the conjugate base that is the ligand, and H4EDTA, the precursor to that ligand. At very low pH (very acidic conditions) the fully protonated H6EDTA2+ form predominates, whereas at very high pH or very basic condition, the fully deprotonated EDTA4− form is prevalent. In this article, the term EDTA is used to mean H4−xEDTAx−, whereas in its complexes EDTA4− stands for the tetraanion ligand. Coordination chemistry principles In coordination chemistry, EDTA4− is a member of the aminopolycarboxylic acid family of ligands. EDTA4− usually binds to a metal cation through its two amines and four carboxylates, i.e., it is It a hexadentate ("six-toothed") chelating agent. Many of the resulting coordination compounds adopt octahedral geometry. Although of little consequence for its applications, these octahedral complexes are chiral. The cobalt(III) anion [Co(EDTA)]− has been resolved into enantiomers. Many complexes of EDTA4− adopt more complex structures due to either the formation of an additional bond to water, i.e. seven-coordinate complexes, or the displacement of one carboxylate arm by water. The iron(III) complex of EDTA is seven-coordinate. Early work on the development of EDTA was undertaken by Gerold Schwarzenbach in the 1940s. EDTA forms especially strong complexes with Mn(II), Cu(II), Fe(III), Pb(II) and Co(III).Several features of EDTAs complexes are relevant to its applications. First, because of its high denticity, this ligand has a high affinity for metal cations: [Fe(H2O)6]3+ + H4EDTA ⇌ [Fe(EDTA)]− + 6 H2O + 4 H+ Keq = 1025.1Written in this way, the equilibrium quotient shows that metal ions compete with protons for binding to EDTA. Because metal ions are extensively enveloped by EDTA, their catalytic properties are often suppressed. Finally, since complexes of EDTA4− are anionic, they tend to be highly soluble in water. For this reason, EDTA is able to dissolve deposits of metal oxides and carbonates. The pKa values of free EDTA are 0, 1.5, 2, 2.66 (deprotonation of the four carboxyl groups) and 6.16, 10.24 (deprotonation of the two amino groups). Environmental fate Abiotic degradation EDTA is in such widespread use that questions have been raised whether it is a persistent organic pollutant. While EDTA serves many positive functions in different industrial, pharmaceutical and other avenues, the longevity of EDTA can pose serious issues in the environment. The degradation of EDTA is slow. It mainly occurs abiotically in the presence of sunlight.The most important process for the elimination of EDTA from surface waters is direct photolysis at wavelengths below 400 nm. Depending on the light conditions, the photolysis half-lives of iron(III) EDTA in surface waters can range as low as 11.3 minutes up to more than 100 hours. Degradation of FeEDTA, but not EDTA itself, produces iron complexes of the triacetate (ED3A), diacetate (EDDA), and monoacetate (EDMA) – 92% of EDDA and EDMA biodegrades in 20 hours while ED3A displays significantly higher resistance. Many environmentally-abundant EDTA species (such as Mg2+ and Ca2+) are more persistent. Biodegradation In many industrial wastewater treatment plants, EDTA elimination can be achieved at about 80% using microorganisms. Resulting byproducts are ED3A and iminodiacetic acid (IDA) – suggesting that both the backbone and acetyl groups were attacked. Some microorganisms have even been discovered to form nitrates out of EDTA, but they function optimally at moderately alkaline conditions of pH 9.0–9.5.Several bacterial strains isolated from sewage treatment plants efficiently degrade EDTA. Specific strains include Agrobacterium radiobacter ATCC 55002 and the sub-branches of Pseudomonadota like BNC1, BNC2, and strain DSM 9103. The three strains share similar properties of aerobic respiration and are classified as gram-negative bacteria. Unlike photolysis, the chelated species is not exclusive to iron(III) in order to be degraded. Rather, each strain uniquely consumes varying metal–EDTA complexes through several enzymatic pathways. Agrobacterium radiobacter only degrades Fe(III) EDTA while BNC1 and DSM 9103 are not capable of degrading iron(III) EDTA and are more suited for calcium, barium, magnesium and manganese(II) complexes. EDTA complexes require dissociation before degradation. Alternatives to EDTA Interest in environmental safety has raised concerns about biodegradability of aminopolycarboxylates such as EDTA. These concerns incentivize the investigation of alternative aminopolycarboxylates. Candidate chelating agents include nitrilotriacetic acid (NTA), iminodisuccinic acid (IDS), polyaspartic acid, S,S-ethylenediamine-N,N′-disuccinic acid (EDDS), methylglycinediacetic acid (MGDA), and L-Glutamic acid N,N-diacetic acid, tetrasodium salt (GLDA). Iminodisuccinic acid (IDS) Commercially used since 1998, iminodisuccinic acid (IDS) biodegrades by about 80% after only 7 days. IDS binds to calcium exceptionally well and forms stable compounds with other heavy metal ions. In addition to having a lower toxicity after chelation, IDS is degraded by Agrobacterium tumefaciens (BY6), which can be harvested on a large scale. The enzymes involved, IDS epimerase and C−N lyase, do not require any cofactors. Polyaspartic acid Polyaspartic acid, like IDS, binds to calcium and other heavy metal ions. It has many practical applications including corrosion inhibitors, wastewater additives, and agricultural polymers. A Polyaspartic acid-based laundry detergent was the first laundry detergent in the world to receive the EU flower ecolabel. Calcium binding ability of polyaspartic acid has been exploited for targeting of drug-loaded nanocarriers to bone. Preparation of hydrogels based on polyaspartic acid, in a variety of physical forms ranging from fiber to particle, can potentially enable facile separation of the chelated ions from a solution. Therefore, despite being weaker than EDTA, polyaspartic acid can still be regarded as a viable alternative due to these features as well as biocompatibility, and biodegradability. S,S-Ethylenediamine-N,N′-disuccinic acid (EDDS) A structural isomer of EDTA, ethylenediamine-N,N′-disuccinic acid (EDDS) is readily biodegradable at high rate in its S,S form. Methylglycinediacetic acid (MGDA) Trisodium dicarboxymethyl alaninate, also known as methylglycinediacetic acid (MGDA), has a high rate of biodegradation at over 68%, but unlike many other chelating agents can degrade without the assistance of adapted bacteria. Additionally, unlike EDDS or IDS, MGDA can withstand higher temperatures while maintaining a high stability as well as the entire pH range. MGDA has been shown to be an effective chelating agent, with a capacity for mobilization comparable with that of nitrilotriacetic acid (NTA), with application to water for industrial use and for the removal of calcium oxalate from urine from patients with kidney stones. Methods of detection and analysis The most sensitive method of detecting and measuring EDTA in biological samples is selected reaction monitoring capillary electrophoresis mass spectrometry (SRM-CE/MS), which has a detection limit of 7.3 ng/mL in human plasma and a quantitation limit of 15 ng/mL. This method works with sample volumes as small as 7–8 nL.EDTA has also been measured in non-alcoholic beverages using high performance liquid chromatography (HPLC) at a level of 2.0 μg/mL. In popular culture In the movie Blade (1998), EDTA is used as a weapon to kill vampires, exploding when in contact with vampire blood. References External links EDTA: Molecule of the Month EDTA Determination of Total Water Hardness Oviedo, Claudia; Rodríguez, Jaime (2003). "EDTA: The chelating agent under environmental scrutiny". Química Nova. 26 (6): 901–905. doi:10.1590/S0100-40422003000600020.

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I'm encountering the term 'Blister' in medical literature. What's its definition?

A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid, either serum or plasma. However, blisters can be filled with blood (known as "blood blisters") or with pus (for instance, if they become infected). The word "blister" entered English in the 14th century. It came from the Middle Dutch bluyster and was a modification of the Old French blostre, which meant a leprous nodule—a rise in the skin due to leprosy. In dermatology today, the words vesicle and bulla refer to blisters of smaller or greater size, respectively. To heal properly, a blister should not be popped unless medically necessary. If popped, the excess skin should not be removed because the skin underneath needs the top layer to heal properly. Causes A blister may form when the skin has been damaged by friction or rubbing, heat, cold or chemical exposure. Fluid collects between the upper layers of skin (the epidermis) and the layers below (the dermis). This fluid cushions the tissue underneath, protecting it from further damage and allowing it to heal. Friction Intense rubbing can cause a blister, as can any friction on the skin if continued long enough. This kind of blister is most common after walking long distances or by wearing old or poorly fitting shoes. Blisters are most common on the hands and feet, as these extremities are susceptible while walking, running, or performing repetitive motions, such as joystick manipulation whilst playing certain video games, certain sports (e.g., baseball pitching), digging with a shovel, playing guitar or bass, etc. Blisters form more easily on damp skin than on dry or soaked skin, and are more common in warm conditions. Less-aggressive rubbing over long periods of time may cause calluses to form rather than a blister. Both blisters and calluses can lead to more serious complications, such as foot ulceration and infection, particularly when sensation or circulation is impaired, as in the case of diabetes, neuropathy or peripheral artery disease (PAD). Burning This type of blistering is one of the tools used to determine the degree of burns sustained. First and second degree burns may result in blistered skin; however, it is characteristic of second degree burns to blister immediately, whereas first degree burns can have blisters after a couple of days. Sunburn can also result in blisters. Blisters can also form on the hands and feet as a result of tissue damage incurred by frostbite. Chemical exposure Sometimes, the skin will blister when it comes into contact with a cosmetic, detergent, solvent, or other chemical such as nickel sulfate, Balsam of Peru, or urushiol (poison ivy, poison oak, poison sumac). This is known as contact dermatitis. Blisters can also develop as a result of an allergic reaction to an insect bite or sting. Some chemical warfare agents, known as blister agents or vesicants, cause large, painful blisters wherever they contact skin; an example is mustard gas. Blood blister A blood blister usually forms when a minute blood vessel close to the surface of the skin ruptures (breaks), and blood leaks into a tear between the layers of skin. This can happen if the skin is crushed, pinched or aggressively squeezed. Medical conditions There are also a number of medical conditions that cause blisters. The most common are chickenpox, herpes, impetigo, and a form of eczema called dyshidrosis. Other, much rarer conditions that cause blisters include: Bullous pemphigoid: a skin disease that causes large, tightly filled blisters to develop, usually affecting people over the age of 60. Pemphigus: a serious skin disease in which blisters develop if pressure is applied to the skin; the blisters burst easily, leaving raw areas that can become infected. Dermatitis herpetiformis: a skin disease that causes intensely itchy blisters, usually on the elbows, knees, back and buttocks. The blisters usually develop in patches of the same shape and size on both sides of the body. Chronic bullous dermatosis: a disease that causes clusters of blisters on the face, mouth or genitals. Cutaneous radiation syndrome Epidermolysis bullosa Pathophysiology Friction blisters Friction blisters are caused by excess shear stress between the bottom and surface of the skin and the body. The strata of skin around the stratum spinosum are most susceptible to shear. As the stratum spinosum tears away from the connecting tissues below, plasma from the cells diffuses out. This plasma solution helps new cells divide and grow into new connective tissues and epidermal layers. The clear fluid will be reabsorbed as new cells develop and the swollen appearance will subside. Painful blisters located on hands (palmar surface) and feet (plantar surface) are due to tissue shearing deeper in the epidermis, near nerve endings. Lower tissues are more susceptible to infection. Prevention Friction blisters Friction blisters, caused by rubbing against the skin, can be prevented by reducing the friction to a level where blisters will not form. This can be accomplished in a variety of ways. Blisters on the feet can be prevented by wearing comfortable, well-fitting shoes and clean socks. Inherently ill-fitting or stiffer shoes, such as high heels and dress shoes, present a larger risk of blistering. Blisters are more likely to develop on skin that is moist, so socks that manage moisture or frequent sock changes will aid those with particularly sweaty feet. While exercising or playing sports, special sports socks can help keep feet drier and reduce the chance of blisters. Before going for a long walk, it is also important to ensure that shoes or hiking boots have been properly broken in. Even before a "hot" or irritated area on the foot is felt, taping a protective layer of padding or a friction-reducing interface between the affected area and the footwear can prevent the formation of a blister. Bandages, moleskin and tapes generally must be applied to the foot daily, and most have a very high coefficient of friction (COF), but a friction-management patch applied to the shoe will remain in place much longer, throughout many changes of socks and insoles. This type of intervention may be used with footwear that is worn daily, with specialty shoes and boots like hockey skates, ice skates, inline skates, ski boots and cleats, or even with orthotic braces and splints. For periods of sustained use such as hiking and trail running, especially where water ingress or moisture build up in the shoe or boot can occur, moisture wicking liner socks can provide the required friction protection. To avoid friction blisters on the hands, gloves should be worn when using tools such as a shovel or pickaxe, doing manual work such as gardening, or using sports equipment like golf clubs or baseball bats. Oars used for competitive rowing are known for causing frequent blisters on the hands of oarsmen. Weightlifters are also prone to blisters as are gymnasts from the friction developed by the rubbing against the bars. To further reduce the occurrence one can tape the hands, and there are also a number of products on the market that claim to reduce the occurrence of blisters. These are all intended to be worn as a liner underneath a glove. The majority of these offerings simply add padding, and create a layer that reduces the coefficient of friction between the skin and the glove. A lubricant, typically talcum powder, can be used to reduce friction between skin and apparel in the short term. People put talcum powder inside gloves or shoes for this purpose, although this type of lubricant can actually increase the friction in the long term as it absorbs moisture. Increased friction makes blisters more likely. Other Sunscreen and protective clothing should also be used during the hottest part of the day to avoid blisters from sunburn. Avoiding sunlight during midday is the best way to avoid blisters from sunburn. Protective gloves should be worn when handling detergents, cleaning products, solvents and other chemicals. References External links Media related to blisters at Wikimedia Commons The dictionary definition of blister at Wiktionary

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I'm seeking clarification on the medical term 'Violence.' Could you explain it?

Violence is the use of physical force so as to injure, abuse, damage, or destroy. Other definitions are also used, such as the World Health Organizations definition of violence as "the intentional use of physical force or power, threatened or actual, against oneself, another person, or against a group or community, which either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment, or deprivation."Internationally, violence resulted in deaths of an estimated 1.28 million people in 2013 up from 1.13 million in 1990. However, global population grew by roughly 1.9 billion during those years, showing a dramatic reduction in violence per capita. Of the deaths in 2013, roughly 842,000 were attributed to self-harm (suicide), 405,000 to interpersonal violence, and 31,000 to collective violence (war) and legal intervention. For each single death due to violence, there are dozens of hospitalizations, hundreds of emergency department visits, and thousands of doctors appointments. Furthermore, violence often has lifelong consequences for physical and mental health and social functioning and can slow economic and social development. In 2013, of the estimated 405,000 deaths due to interpersonal violence globally, assault by firearm was the cause in 180,000 deaths, assault by sharp object was the cause in 114,000 deaths, and the remaining 110,000 deaths from other causes.Violence in many forms can be preventable. There is a strong relationship between levels of violence and modifiable factors in a country such as an concentrated (regional) poverty, income and gender inequality, the harmful use of alcohol, and the absence of safe, stable, and nurturing relationships between children and parents. Strategies addressing the underlying causes of violence can be relatively effective in preventing violence, although mental and physical health and individual responses, personalities, etc. have always been decisive factors in the formation of these behaviors. Types The World Health Organization divides violence into three broad categories: self-directed violence interpersonal violence collective violenceThis initial categorization differentiates between violence that a person inflicts upon themself, violence inflicted by another individual or by a small group of individuals, and violence inflicted by larger groups such as states, organized political groups, militia groups and terrorist organizations. Alternatively, violence can primarily be classified as either instrumental or reactive / hostile. Self-directed Self-directed violence is subdivided into suicidal behaviour and self-abuse. The former includes suicidal thoughts, attempted suicides—also called para suicide or deliberate self-injury in some countries—and suicide itself. Self-abuse, in contrast, includes acts such as self-mutilation. Collective Unlike the other two broad categories, the subcategories of collective violence suggest possible motives for violence committed by larger groups of individuals or by states. Collective violence that is committed to advance a particular social agenda includes, for example, crimes of hate committed by organized groups, terrorist acts and mob violence. Political violence includes war and related violent conflicts, state violence and similar acts carried out by armed groups. There may be multiple determinants of violence against civilians in such situations. Economic violence includes attacks motivated by economic gain—such as attacks carried out with the purpose of disrupting economic activity, denying access to essential services, or creating economic division and fragmentation. Clearly, acts committed by domestic and subnational groups can have multiple motives. Slow violence is a long-duration form of violence which is often invisible (at least to those not impacted by it), such as environmental degradation, pollution and climate change. Warfare War is a state of prolonged violent large-scale conflict involving two or more groups of people, usually under the auspices of government. It is the most extreme form of collective violence. War is fought as a means of resolving territorial and other conflicts, as war of aggression to conquer territory or loot resources, in national self-defence or liberation, or to suppress attempts of part of the nation to secede from it. There are also ideological, religious and revolutionary wars.Since the Industrial Revolution the lethality of modern warfare has grown. World War I casualties were over 40 million and World War II casualties were over 70 million. Interpersonal Interpersonal violence is divided into two subcategories: Family and intimate partner violence—that is, violence largely between family members and intimate partners, usually, though not exclusively, taking place in the home. Community violence—violence between individuals who are unrelated, and who may or may not know each other, generally taking place outside the home. The former group includes forms of violence such as child abuse and child corporal punishment, intimate partner violence and abuse of the elderly. The latter includes youth violence, random acts of violence, rape or sexual assault by strangers, and violence in institutional settings such as schools, workplaces, prisons and nursing homes. When interpersonal violence occurs in families, its psychological consequences can affect parents, children, and their relationship in the short- and long-terms. Child maltreatment Child maltreatment is the abuse and neglect that occurs to children under 18 years of age. It includes all types of physical and/or emotional ill-treatment, sexual abuse, neglect, negligence and commercial or other child exploitation, which results in actual or potential harm to the childs health, survival, development or dignity in the context of a relationship of responsibility, trust, or power. Exposure to intimate partner violence is also sometimes included as a form of child maltreatment.Child maltreatment is a global problem with serious lifelong consequences, which is, however, complex and difficult to study.There are no reliable global estimates for the prevalence of child maltreatment. Data for many countries, especially low- and middle-income countries, are lacking. Current estimates vary widely depending on the country and the method of research used. Approximately 20% of women and 5–10% of men report being sexually abused as children, while 25–50% of all children report being physically abused.Consequences of child maltreatment include impaired lifelong physical and mental health, and social and occupational functioning (e.g. school, job, and relationship difficulties). These can ultimately slow a countrys economic and social development. Preventing child maltreatment before it starts is possible and requires a multisectoral approach. Effective prevention programmes support parents and teach positive parenting skills. Ongoing care of children and families can reduce the risk of maltreatment reoccurring and can minimize its consequences. Youth Following the World Health Organization, youth are defined as people between the ages of 10 and 29 years. Youth violence refers to violence occurring between youths, and includes acts that range from bullying and physical fighting, through more severe sexual and physical assault to homicide.Worldwide some 250,000 homicides occur among youth 10–29 years of age each year, which is 41% of the total number of homicides globally each year ("Global Burden of Disease", World Health Organization, 2008). For each young person killed, 20–40 more sustain injuries requiring hospital treatment. Youth violence has a serious, often lifelong, impact on a persons psychological and social functioning. Youth violence greatly increases the costs of health, welfare and criminal justice services; reduces productivity; decreases the value of property; and generally undermines the fabric of society.Prevention programmes shown to be effective or to have promise in reducing youth violence include life skills and social development programmes designed to help children and adolescents manage anger, resolve conflict, and develop the necessary social skills to solve problems; schools-based anti-bullying prevention programmes; and programmes to reduce access to alcohol, illegal drugs and guns. Also, given significant neighbourhood effects on youth violence, interventions involving relocating families to less poor environments have shown promising results. Similarly, urban renewal projects such as business improvement districts have shown a reduction in youth violence.Different types of youth on youth violence include witnessing or being involved in physical, emotional and sexual abuse (e.g. physical attacks, bullying, rape), and violent acts like gang shootings and robberies. According to researchers in 2018, "More than half of children and adolescents living in cities have experienced some form of community violence." The violence "can also all take place under one roof, or in a given community or neighborhood and can happen at the same time or at different stages of life." Youth violence has immediate and long term adverse impact whether the individual was the recipient of the violence or a witness to it.Youth violence impacts individuals, their families, and society. Victims can have lifelong injuries which means ongoing doctor and hospital visits, the cost of which quickly add up. Since the victims of youth-on-youth violence may not be able to attend school or work because of their physical and/or mental injuries, it is often up to their family members to take care of them, including paying their daily living expenses and medical bills. Their caretakers may have to give up their jobs or work reduced hours to provide help to the victim of violence. This causes a further burden on society because the victim and maybe even their caretakers have to obtain government assistance to help pay their bills. Recent research has found that psychological trauma during childhood can change a childs brain. "Trauma is known to physically affect the brain and the body which causes anxiety, rage, and the ability to concentrate. They can also have problems remembering, trusting, and forming relationships." Since the brain becomes used to violence it may stay continually in an alert state (similar to being stuck in the fight or flight mode). "Researchers claim that the youth who are exposed to violence may have emotional, social, and cognitive problems. They may have trouble controlling emotions, paying attention in school, withdraw from friends, or show signs of post-traumatic stress disorder".It is important for youth exposed to violence to understand how their bodies may react so they can take positive steps to counteract any possible short- and long-term negative effects (e.g., poor concentration, feelings of depression, heightened levels of anxiety). By taking immediate steps to mitigate the effects of the trauma theyve experienced, negative repercussions can be reduced or eliminated. As an initial step, the youths need to understand why they may be feeling a certain way and to understand how the violence they have experienced may be causing negative feelings and making them behave differently. Pursuing a greater awareness of their feelings, perceptions, and negative emotions is the first step that should be taken as part of recovering from the trauma they have experienced. "Neuroscience research shows that the only way we can change the way we feel is by becoming aware of our inner experience and learning to befriend what is going on inside ourselves".Some of the ways to combat the adverse effects of exposure to youth violence would be to try various mindfulness and movement activities, deep breathing exercises and other actions that enable youths to release their pent up emotions. Using these techniques will teach body awareness, reduce anxiety and nervousness, and reduce feelings of anger and annoyance. Over time these types of activities will help these younger victims of violence to have greater control over their feelings and behaviors and avoid unhealthy ways of coping. Another way to help trauma victims of youth violence is through the arts. This can be accomplished by giving them the opportunity to engage in drawing, painting, music, and singing which will give them an outlet to express themselves and their emotions in a positive way.Youth who have experienced violence benefit from having a close relationship with one or more people. This is important because the trauma victims need to have people who are safe and trustworthy that they can relate and talk to about their horrible experiences. Some youth do not have adult figures at home or someone they can count on for guidance and comfort. Schools in bad neighborhoods where youth violence is prevalent should assign counselors to each student so that they receive regular guidance. In addition to counseling/therapy sessions and programs, it has been recommended that schools offer mentoring programs where students can interact with adults who can be a positive influence on them. Another way is to create more neighborhood programs to ensure that each child has a positive and stable place to go when school in not in session. Many children have benefited from formal organizations now which aim to help mentor and provide a safe environment for the youth especially those living in neighborhoods with higher rates of violence. This includes organizations such as Becoming a Man, CeaseFire Illinois, Chicago Area Project, Little Black Pearl, and Rainbow House". These programs are designed to help give the youth a safe place to go, stop the violence from occurring, offering counseling and mentoring to help stop the cycle of violence. If the youth do not have a safe place to go after school hours they will likely get into trouble, receive poor grades, drop out of school and use drugs and alcohol. The gangs look for youth who do not have positive influences in their life and need protection. This is why these programs are so important for the youth to have a safe environment rather than resorting to the streets. Intimate partner Intimate partner violence refers to behaviour in an intimate relationship that causes physical, sexual or psychological harm, including physical aggression, sexual coercion, psychological abuse and controlling behaviours.Population-level surveys based on reports from victims provide the most accurate estimates of the prevalence of intimate partner violence and sexual violence in non-conflict settings. A study conducted by WHO in 10 mainly developing countries found that, among women aged 15 to 49 years, between 15% (Japan) and 70% (Ethiopia and Peru) of women reported physical and/or sexual violence by an intimate partner. A growing body of research on men and intimate partner violence focuses on men as both perpetrators and victims of violence, as well as on how to involve men and boys in anti-violence work.Intimate partner and sexual violence have serious short- and long-term physical, mental, sexual and reproductive health problems for victims and for their children, and lead to high social and economic costs. These include both fatal and non-fatal injuries, depression and post-traumatic stress disorder, unintended pregnancies, sexually transmitted infections, including HIV.Factors associated with the perpetration and experiencing of intimate partner violence are low levels of education, history of violence as a perpetrator, a victim or a witness of parental violence, harmful use of alcohol, attitudes that are accepting of violence as well as marital discord and dissatisfaction. Factors associated only with perpetration of intimate partner violence are having multiple partners, and antisocial personality disorder. A recent theory named "The Criminal Spin" suggests a mutual flywheel effect between partners that is manifested by an escalation in the violence. A violent spin may occur in any other forms of violence, but in Intimate partner violence the added value is the mutual spin, based on the unique situation and characteristics of intimate relationship. The primary prevention strategy with the best evidence for effectiveness for intimate partner violence is school-based programming for adolescents to prevent violence within dating relationships. Evidence is emerging for the effectiveness of several other primary prevention strategies—those that: combine microfinance with gender equality training; promote communication and relationship skills within communities; reduce access to, and the harmful use of alcohol; and change cultural gender norms. Sexual Sexual violence is any sexual act, attempt to obtain a sexual act, unwanted sexual comments or advances, or acts to traffic, or otherwise directed against a persons sexuality using coercion, by any person regardless of their relationship to the victim, in any setting. It includes rape, defined as the physically forced or otherwise coerced penetration of the vulva or anus with a penis, other body part or object.Population-level surveys based on reports from victims estimate that between 0.3 and 11.5% of women reported experiencing sexual violence. Sexual violence has serious short- and long-term consequences on physical, mental, sexual and reproductive health for victims and for their children as described in the section on intimate partner violence. If perpetrated during childhood, sexual violence can lead to increased smoking, drug and alcohol misuse, and risky sexual behaviors in later life. It is also associated with perpetration of violence and being a victim of violence. Many of the risk factors for sexual violence are the same as for domestic violence. Risk factors specific to sexual violence perpetration include beliefs in family honor and sexual purity, ideologies of male sexual entitlement and weak legal sanctions for sexual violence. Few interventions to prevent sexual violence have been demonstrated to be effective. School-based programmes to prevent child sexual abuse by teaching children to recognize and avoid potentially sexually abusive situations are run in many parts of the world and appear promising, but require further research. To achieve lasting change, it is important to enact legislation and develop policies that protect women; address discrimination against women and promote gender equality; and help to move the culture away from violence. Elder maltreatment Elder maltreatment is a single or repeated act, or lack of appropriate action, occurring within any relationship where there is an expectation of trust which causes harm or distress to an older person. This constitutes a violation of human rights and includes physical, sexual, psychological, emotional; financial and material abuse; abandonment; neglect; and serious loss of dignity and respect.While there is little information regarding the extent of maltreatment in elderly populations, especially in developing countries, it is estimated that 4–6% of elderly people in high-income countries have experienced some form of maltreatment at home However, older people are often afraid to report cases of maltreatment to family, friends, or to the authorities. Data on the extent of the problem in institutions such as hospitals, nursing homes and other long-term care facilities are scarce. Elder maltreatment can lead to serious physical injuries and long-term psychological consequences. Elder maltreatment is predicted to increase as many countries are experiencing rapidly ageing populations. Many strategies have been implemented to prevent elder maltreatment and to take action against it and mitigate its consequences including public and professional awareness campaigns, screening (of potential victims and abusers), caregiver support interventions (e.g. stress management, respite care), adult protective services and self-help groups. Their effectiveness has, however, not so far been well-established. Targeted Several rare but painful episodes of assassination, attempted assassination and school shootings at elementary, middle, high schools, as well as colleges and universities in the United States, led to a considerable body of research on ascertainable behaviors of persons who have planned or carried out such attacks. These studies (1995–2002) investigated what the authors called "targeted violence," described the "path to violence" of those who planned or carried out attacks and laid out suggestions for law enforcement and educators. A major point from these research studies is that targeted violence does not just "come out of the blue". Everyday As an anthropological concept, "everyday violence" may refer to the incorporation of different forms of violence (mainly political violence) into daily practices. Latin America and the Caribbean, the region with the highest murder rate in the world, experienced more than 2.5 million murders between 2000 and 2017. Philosophical perspectives Some philosophers have argued that any interpretation of reality is intrinsically violent. Slavoj Žižek in his book Violence stated that "something violent is the very symbolization of a thing." An ontological perspective considers the harm inflicted by the very interpretation of the world as a form of violence that is distinct from physical violence in that it is possible to avoid physical violence whereas some ontological violence is intrinsic to all knowledge.Both Foucault and Arendt considered the relationship between power and violence but concluded that while related they are distinct.: 46 In feminist philosophy, epistemic violence is the act of causing harm by an inability to understand the conversation of others due to ignorance. Some philosophers think this will harm marginalized groups.Brad Evans (author) states that "violence" "represents a violation in the very conditions constituting what it means to be human as such", "is always an attack upon a persons dignity, their sense of selfhood, and their future", and "is both an ontological crime ... and a form of political ruination". Factors and models of understanding Violence cannot be attributed to solely protective factors or risk factors. Both of these factor groups are equally important in the prevention, intervention, and treatment of violence as a whole. The CDC outlines several risk and protective factors for youth violence at the individual, family, social and community levels. Individual risk factors include poor behavioral control, high emotional stress, low IQ, and antisocial beliefs or attitudes. Family risk factors include authoritarian childrearing attitudes, inconsistent disciplinary practices, low emotional attachment to parents or caregivers, and low parental income and involvement. Social risk factors include social rejection, poor academic performance and commitment to school, and gang involvement or association with delinquent peers. Community risk factors include poverty, low community participation, and diminished economic opportunities.On the other hand, individual protective factors include an intolerance towards deviance, higher IQ and GPA, elevated popularity and social skills, as well as religious beliefs. Family protective factors include a connectedness and ability to discuss issues with family members or adults, parent/family use of constructive coping strategies, and consistent parental presence during at least one of the following: when awakening, when arriving home from school, at dinner time, or when going to bed. Social protective factors include quality school relationships, close relationships with non-deviant peers, involvement in prosocial activities, and exposure to school climates that are: well supervised, use clear behavior rules and disciplinary approaches, and engage parents with teachers.With many conceptual factors that occur at varying levels in the lives of those impacted, the exact causes of violence are complex. To represent this complexity, the ecological, or social ecological model is often used. The following four-level version of the ecological model is often used in the study of violence: The first level identifies biological and personal factors that influence how individuals behave and increase their likelihood of becoming a victim or perpetrator of violence: demographic characteristics (age, education, income), genetics, brain lesions, personality disorders, substance abuse, and a history of experiencing, witnessing, or engaging in violent behaviour.The second level focuses on close relationships, such as those with family and friends. In youth violence, for example, having friends who engage in or encourage violence can increase a young persons risk of being a victim or perpetrator of violence. For intimate partner violence, a consistent marker at this level of the model is marital conflict or discord in the relationship. In elder abuse, important factors are stress due to the nature of the past relationship between the abused person and the care giver. The third level explores the community context—i.e., schools, workplaces, and neighbourhoods. Risk at this level may be affected by factors such as the existence of a local drug trade, the absence of social networks, and concentrated poverty. All these factors have been shown to be important in several types of violence. Finally, the fourth level looks at the broad societal factors that help to create a climate in which violence is encouraged or inhibited: the responsiveness of the criminal justice system, social and cultural norms regarding gender roles or parent-child relationships, income inequality, the strength of the social welfare system, the social acceptability of violence, the availability of weapons, the exposure to violence in mass media, and political instability. Child-rearing While studies showing associations between physical punishment of children and later aggression cannot prove that physical punishment causes an increase in aggression, a number of longitudinal studies suggest that the experience of physical punishment has a direct causal effect on later aggressive behaviors. Cross-cultural studies have shown that greater prevalence of corporal punishment of children tends to predict higher levels of violence in societies. For instance, a 2005 analysis of 186 pre-industrial societies found that corporal punishment was more prevalent in societies which also had higher rates of homicide, assault, and war. In the United States, domestic corporal punishment has been linked to later violent acts against family members and spouses. The American family violence researcher Murray A. Straus believes that disciplinary spanking forms "the most prevalent and important form of violence in American families", whose effects contribute to several major societal problems, including later domestic violence and crime. Psychology The causes of violent behavior in people are often a topic of research in psychology. Neurobiologist Jan Vodka emphasizes that, for those purposes, "violent behavior is defined as overt and intentional physically aggressive behavior against another person."Based on the idea of human nature, scientists do agree violence is inherent in humans. Among prehistoric humans, there is archaeological evidence for both contentions of violence and peacefulness as primary characteristics.Since violence is a matter of perception as well as a measurable phenomenon, psychologists have found variability in whether people perceive certain physical acts as "violent". For example, in a state where execution is a legalized punishment we do not typically perceive the executioner as "violent", though we may talk, in a more metaphorical way, of the state acting violently. Likewise, understandings of violence are linked to a perceived aggressor-victim relationship: hence psychologists have shown that people may not recognise defensive use of force as violent, even in cases where the amount of force used is significantly greater than in the original aggression.The concept of violence normalization is known as socially sanctioned, or structural violence and is a topic of increasing interest to researchers trying to understand violent behavior. It has been discussed at length by researchers in sociology, medical anthropology, psychology, psychiatry, philosophy, and bioarchaeology.Evolutionary psychology offers several explanations for human violence in various contexts, such as sexual jealousy in humans, child abuse, and homicide. Goetz (2010) argues that humans are similar to most mammal species and use violence in specific situations. He writes that "Buss and Shackelford (1997a) proposed seven adaptive problems our ancestors recurrently faced that might have been solved by aggression: co-opting the resources of others, defending against attack, inflicting costs on same-sex rivals, negotiating status and hierarchies, deterring rivals from future aggression, deterring mate from infidelity, and reducing resources expended on genetically unrelated children."Goetz writes that most homicides seem to start from relatively trivial disputes between unrelated men who then escalate to violence and death. He argues that such conflicts occur when there is a status dispute between men of relatively similar status. If there is a great initial status difference, then the lower status individual usually offers no challenge and if challenged the higher status individual usually ignores the lower status individual. At the same an environment of great inequalities between people may cause those at the bottom to use more violence in attempts to gain status. Media Research into the media and violence examines whether links between consuming media violence and subsequent aggressive and violent behaviour exists. Although some scholars had claimed media violence may increase aggression, this view is coming increasingly in doubt both in the scholarly community and was rejected by the US Supreme Court in the Brown v EMA case, as well as in a review of video game violence by the Australian Government (2010) which concluded evidence for harmful effects were inconclusive at best and the rhetoric of some scholars was not matched by good data. Prevention The threat and enforcement of physical punishment has been a tried and tested method of preventing some violence since civilisation began. It is used in various degrees in most countries. Public awareness campaigns Cities and counties throughout the United States organize "Violence Prevention Months" where the mayor, by proclamation, or the county, by a resolution, encourage the private, community and public sectors to engage in activities that raise awareness that violence is not acceptable through art, music, lectures and events. For example, Violence Prevention Month coordinator, Karen Earle Lile in Contra Costa County, California created a Wall of Life, where children drew pictures that were put up in the walls of banks and public spaces, displaying a childs view of violence they had witnessed and how it affected them, in an effort to draw attention to how violence affects the community, not just the people involved. Interpersonal violence A review of scientific literature by the World Health Organization on the effectiveness of strategies to prevent interpersonal violence identified the seven strategies below as being supported by either strong or emerging evidence for effectiveness. These strategies target risk factors at all four levels of the ecological model. Child–caregiver relationships Among the most effective such programmes to prevent child maltreatment and reduce childhood aggression are the Nurse Family Partnership home-visiting programme and the Triple P (Parenting Program). There is also emerging evidence that these programmes reduce convictions and violent acts in adolescence and early adulthood, and probably help decrease intimate partner violence and self-directed violence in later life. Life skills in youth Evidence shows that the life skills acquired in social development programmes can reduce involvement in violence, improve social skills, boost educational achievement and improve job prospects. Life skills refer to social, emotional, and behavioural competencies which help children and adolescents effectively deal with the challenges of everyday life. Gender equality Evaluation studies are beginning to support community interventions that aim to prevent violence against women by promoting gender equality. For instance, evidence suggests that programmes that combine microfinance with gender equity training can reduce intimate partner violence. School-based programmes such as Safe Dates programme in the United States of America and the Youth Relationship Project in Canada have been found to be effective for reducing dating violence. Cultural norms Rules or expectations of behaviour – norms – within a cultural or social group can encourage violence. Interventions that challenge cultural and social norms supportive of violence can prevent acts of violence and have been widely used, but the evidence base for their effectiveness is currently weak. The effectiveness of interventions addressing dating violence and sexual abuse among teenagers and young adults by challenging social and cultural norms related to gender is supported by some evidence. Support programmes Interventions to identify victims of interpersonal violence and provide effective care and support are critical for protecting health and breaking cycles of violence from one generation to the next. Examples for which evidence of effectiveness is emerging includes: screening tools to identify victims of intimate partner violence and refer them to appropriate services; psychosocial interventions—such as trauma-focused cognitive behavioural therapy—to reduce mental health problems associated with violence, including post-traumatic stress disorder; and protection orders, which prohibit a perpetrator from contacting the victim, to reduce repeat victimization among victims of intimate partner violence. Collective violence Not surprisingly, scientific evidence about the effectiveness of interventions to prevent collective violence is lacking. However, policies that facilitate reductions in poverty, that make decision-making more accountable, that reduce inequalities between groups, as well as policies that reduce access to biological, chemical, nuclear and other weapons have been recommended. When planning responses to violent conflicts, recommended approaches include assessing at an early stage who is most vulnerable and what their needs are, co-ordination of activities between various players and working towards global, national and local capabilities so as to deliver effective health services during the various stages of an emergency. Criminal justice One of the main functions of law is to regulate violence. Sociologist Max Weber stated that the state claims the monopoly of the legitimate use of force practised within the confines of a specific territory. Law enforcement is the main means of regulating nonmilitary violence in society. Governments regulate the use of violence through legal systems governing individuals and political authorities, including the police and military. Civil societies authorize some amount of violence, exercised through the police power, to maintain the status quo and enforce laws. However, German political theorist Hannah Arendt noted: "Violence can be justifiable, but it never will be legitimate ... Its justification loses in plausibility the farther its intended end recedes into the future. No one questions the use of violence in self-defence, because the danger is not only clear but also present, and the end justifying the means is immediate". Arendt made a clear distinction between violence and power. Most political theorists regarded violence as an extreme manifestation of power whereas Arendt regarded the two concepts as opposites. In the 20th century in acts of democide governments may have killed more than 260 million of their own people through police brutality, execution, massacre, slave labour camps, and sometimes through intentional famine.Violent acts that are not carried out by the military or police and that are not in self-defense are usually classified as crimes, although not all crimes are violent crimes. Damage to property is classified as violent crime in some jurisdictions but not in all. The Federal Bureau of Investigation (FBI) classifies violence resulting in homicide into criminal homicide and justifiable homicide (e.g. self-defense).The criminal justice approach sees its main task as enforcing laws that proscribe violence and ensuring that "justice is done". The notions of individual blame, responsibility, guilt, and culpability are central to criminal justices approach to violence and one of the criminal justice systems main tasks is to "do justice", i.e. to ensure that offenders are properly identified, that the degree of their guilt is as accurately ascertained as possible, and that they are punished appropriately. To prevent and respond to violence, the criminal justice approach relies primarily on deterrence, incarceration and the punishment and rehabilitation of perpetrators.The criminal justice approach, beyond justice and punishment, has traditionally emphasized indicated interventions, aimed at those who have already been involved in violence, either as victims or as perpetrators. One of the main reasons offenders are arrested, prosecuted, and convicted is to prevent further crimes—through deterrence (threatening potential offenders with criminal sanctions if they commit crimes), incapacitation (physically preventing offenders from committing further crimes by locking them up) and through rehabilitation (using time spent under state supervision to develop skills or change ones psychological make-up to reduce the likelihood of future offences).In recent decades in many countries in the world, the criminal justice system has taken an increasing interest in preventing violence before it occurs. For instance, much of community and problem-oriented policing aims to reduce crime and violence by altering the conditions that foster it—and not to increase the number of arrests. Indeed, some police leaders have gone so far as to say the police should primarily be a crime prevention agency. Juvenile justice systems—an important component of criminal justice systems—are largely based on the belief in rehabilitation and prevention. In the US, the criminal justice system has, for instance, funded school- and community-based initiatives to reduce childrens access to guns and teach conflict resolution. Despite this, force is used routinely against juveniles by police. In 1974, the US Department of Justice assumed primary responsibility for delinquency prevention programmes and created the Office of Juvenile Justice and Delinquency Prevention, which has supported the "Blueprints for violence prevention" programme at the University of Colorado Boulder. Public health The public health approach is a science-driven, population-based, interdisciplinary, intersectoral approach based on the ecological model which emphasizes primary prevention. Rather than focusing on individuals, the public health approach aims to provide the maximum benefit for the largest number of people, and to extend better care and safety to entire populations. The public health approach is interdisciplinary, drawing upon knowledge from many disciplines including medicine, epidemiology, sociology, psychology, criminology, education and economics. Because all forms of violence are multi-faceted problems, the public health approach emphasizes a multi-sectoral response. It has been proved time and again that cooperative efforts from such diverse sectors as health, education, social welfare, and criminal justice are often necessary to solve what are usually assumed to be purely "criminal" or "medical" problems. The public health approach considers that violence, rather than being the result of any single factor, is the outcome of multiple risk factors and causes, interacting at four levels of a nested hierarchy (individual, close relationship/family, community and wider society) of the Social ecological model. From a public health perspective, prevention strategies can be classified into three types: Primary prevention – approaches that aim to prevent violence before it occurs. Secondary prevention – approaches that focus on the more immediate responses to violence, such as pre-hospital care, emergency services or treatment for sexually transmitted infections following a rape. Tertiary prevention – approaches that focus on long-term care in the wake of violence, such as rehabilitation and reintegration, and attempt to lessen trauma or reduce long-term disability associated with violence.A public health approach emphasizes the primary prevention of violence, i.e. stopping them from occurring in the first place. Until recently, this approach has been relatively neglected in the field, with the majority of resources directed towards secondary or tertiary prevention. Perhaps the most critical element of a public health approach to prevention is the ability to identify underlying causes rather than focusing upon more visible "symptoms". This allows for the development and testing of effective approaches to address the underlying causes and so improve health. The public health approach is an evidence-based and systematic process involving the following four steps: Defining the problem conceptually and numerically, using statistics that accurately describe the nature and scale of violence, the characteristics of those most affected, the geographical distribution of incidents, and the consequences of exposure to such violence. Investigating why the problem occurs by determining its causes and correlates, the factors that increase or decrease the risk of its occurrence (risk and protective factors) and the factors that might be modifiable through intervention. Exploring ways to prevent the problem by using the above information and designing, monitoring and rigorously assessing the effectiveness of programmes through outcome evaluations. Disseminating information on the effectiveness of programmes and increasing the scale of proven effective programmes. Approaches to prevent violence, whether targeted at individuals or entire communities, must be properly evaluated for their effectiveness and the results shared. This step also includes adapting programmes to local contexts and subjecting them to rigorous re-evaluation to ensure their effectiveness in the new setting.In many countries, violence prevention is still a new or emerging field in public health. The public health community has started only recently to realize the contributions it can make to reducing violence and mitigating its consequences. In 1949, Gordon called for injury prevention efforts to be based on the understanding of causes, in a similar way to prevention efforts for communicable and other diseases. In 1962, Gomez, referring to the WHO definition of health, stated that it is obvious that violence does not contribute to "extending life" or to a "complete state of well-being". He defined violence as an issue that public health experts needed to address and stated that it should not be the primary domain of lawyers, military personnel, or politicians.However, it is only in the last 30 years that public health has begun to address violence, and only in the last fifteen has it done so at the global level. This is a much shorter period of time than public health has been tackling other health problems of comparable magnitude and with similarly severe lifelong consequences. The global public health response to interpersonal violence began in earnest in the mid-1990s. In 1996, the World Health Assembly adopted Resolution WHA49.25 which declared violence "a leading worldwide public health problem" and requested that the World Health Organization (WHO) initiate public health activities to (1) document and characterize the burden of violence, (2) assess the effectiveness of programmes, with particular attention to women and children and community-based initiatives, and (3) promote activities to tackle the problem at the international and national levels. The World Health Organizations initial response to this resolution was to create the Department of Violence and Injury Prevention and Disability and to publish the World report on violence and health (2002).The case for the public health sector addressing interpersonal violence rests on four main arguments. First, the significant amount of time health care professionals dedicate to caring for victims and perpetrators of violence has made them familiar with the problem and has led many, particularly in emergency departments, to mobilize to address it. The information, resources, and infrastructures the health care sector has at its disposal are an important asset for research and prevention work. Second, the magnitude of the problem and its potentially severe lifelong consequences and high costs to individuals and wider society call for population-level interventions typical of the public health approach. Third, the criminal justice approach, the other main approach to addressing violence (link to entry above), has traditionally been more geared towards violence that occurs between male youths and adults in the street and other public places—which makes up the bulk of homicides in most countries—than towards violence occurring in private settings such as child maltreatment, intimate partner violence and elder abuse—which makes up the largest share of non-fatal violence. Fourth, evidence is beginning to accumulate that a science-based public health approach is effective at preventing interpersonal violence. Human rights The human rights approach is based on the obligations of states to respect, protect and fulfill human rights and therefore to prevent, eradicate and punish violence. It recognizes violence as a violation of many human rights: the rights to life, liberty, autonomy and security of the person; the rights to equality and non-discrimination; the rights to be free from torture and cruel, inhuman and degrading treatment or punishment; the right to privacy; and the right to the highest attainable standard of health. These human rights are enshrined in international and regional treaties and national constitutions and laws, which stipulate the obligations of states, and include mechanisms to hold states accountable. The Convention on the Elimination of All Forms of Discrimination Against Women, for example, requires that countries party to the Convention take all appropriate steps to end violence against women. The Convention on the Rights of the Child in its Article 19 states that States Parties shall take all appropriate legislative, administrative, social and educational measures to protect the child from all forms of physical or mental violence, injury or abuse, neglect or negligent treatment, maltreatment or exploitation, including sexual abuse, while in the care of parent(s), legal guardian(s) or any other person who has the care of the child. Geographical context Violence, as defined in the dictionary of human geography, "appears whenever power is in jeopardy" and "in and of itself stands emptied of strength and purpose: it is part of a larger matrix of socio-political power struggles". Violence can be broadly divided into three broad categories—direct violence, structural violence and cultural violence. Thus defined and delineated, it is of note, as Hyndman says, that "geography came late to theorizing violence" in comparison to other social sciences. Social and human geography, rooted in the humanist, Marxist, and feminist subfields that emerged following the early positivist approaches and subsequent behavioral turn, have long been concerned with social and spatial justice. Along with critical geographers and political geographers, it is these groupings of geographers that most often interact with violence. Keeping this idea of social/spatial justice via geography in mind, it is worthwhile to look at geographical approaches to violence in the context of politics. Derek Gregory and Alan Pred assembled the influential edited collection Violent Geographies: Fear, Terror, and Political Violence, which demonstrates how place, space, and landscape are foremost factors in the real and imagined practices of organized violence both historically and in the present. Evidently, political violence often gives a part for the state to play. When "modern states not only claim a monopoly of the legitimate means of violence; they also routinely use the threat of violence to enforce the rule of law", the law not only becomes a form of violence but is violence. Philosopher Giorgio Agambens concepts of state of exception and homo sacer are useful to consider within a geography of violence. The state, in the grip of a perceived, potential crisis (whether legitimate or not) takes preventative legal measures, such as a suspension of rights (it is in this climate, as Agamben demonstrates, that the formation of the Social Democratic and Nazi governments lager or concentration camp can occur). However, when this "in limbo" reality is designed to be in place "until further notice…the state of exception thus ceases to be referred to as an external and provisional state of factual danger and comes to be confused with juridical rule itself". For Agamben, the physical space of the camp "is a piece of land placed outside the normal juridical order, but it is nevertheless not simply an external space". At the scale of the body, in the state of exception, a person is so removed from their rights by "juridical procedures and deployments of power" that "no act committed against them could appear any longer as a crime"; in other words, people become only homo sacer. Guantanamo Bay could also be said to represent the physicality of the state of exception in space, and can just as easily draw man as homo sacer. In the 1970s, genocides in Cambodia under the Khmer Rouge and Pol Pot resulted in the deaths of over two million Cambodians (which was 25% of the Cambodian population), forming one of the many contemporary examples of state-sponsored violence. About fourteen thousand of these murders occurred at Choeung Ek, which is the best-known of the extermination camps referred to as the Killing Fields. The killings were arbitrary; for example, a person could be killed for wearing glasses, since that was seen as associating them with intellectuals and therefore as making them part of the enemy. People were murdered with impunity because it was no crime; Cambodians were made homo sacer in a condition of bare life. The Killing Fields—manifestations of Agambens concept of camps beyond the normal rule of law—featured the state of exception. As part of Pol Pots "ideological intent…to create a purely agrarian society or cooperative", he "dismantled the countrys existing economic infrastructure and depopulated every urban area". Forced movement, such as this forced movement applied by Pol Pot, is a clear display of structural violence. When "symbols of Cambodian society were equally disrupted, social institutions of every kind…were purged or torn down", cultural violence (defined as when "any aspect of culture such as language, religion, ideology, art, or cosmology is used to legitimize direct or structural violence") is added to the structural violence of forced movement and to the direct violence, such as murder, at the Killing Fields. Vietnam eventually intervened and the genocide officially ended. However, ten million landmines left by opposing guerillas in the 1970s continue to create a violent landscape in Cambodia. Human geography, though coming late to the theorizing table, has tackled violence through many lenses, including anarchist geography, feminist geography, Marxist geography, political geography, and critical geography. However, Adriana Cavarero notes that, "as violence spreads and assumes unheard-of forms, it becomes difficult to name in contemporary language". Cavarero proposes that, in facing such a truth, it is prudent to reconsider violence as "horrorism"; that is, "as though ideally all the…victims, instead of their killers, ought to determine the name". With geography often adding the forgotten spatial aspect to theories of social science, rather than creating them solely within the discipline, it seems that the self-reflexive contemporary geography of today may have an extremely important place in this current (re)imaging of violence, exemplified by Cavarero. Epidemiology As of 2010, all forms of violence resulted in about 1.34 million deaths up from about 1 million in 1990. Suicide accounts for about 883,000, interpersonal violence for 456,000 and collective violence for 18,000. Deaths due to collective violence have decreased from 64,000 in 1990.By way of comparison, the 1.5 millions deaths a year due to violence is greater than the number of deaths due to tuberculosis (1.34 million), road traffic injuries (1.21 million), and malaria (830000), but slightly less than the number of people who die from HIV/AIDS (1.77 million).For every death due to violence, there are numerous nonfatal injuries. In 2008, over 16 million cases of non-fatal violence-related injuries were severe enough to require medical attention. Beyond deaths and injuries, forms of violence such as child maltreatment, intimate partner violence, and elder maltreatment have been found to be highly prevalent. Self-directed violence In the last 45 years, suicide rates have increased by 60% worldwide. Suicide is among the three leading causes of death among those aged 15–44 years in some countries, and the second leading cause of death in the 10–24 years age group. These figures do not include suicide attempts which are up to 20 times more frequent than completed suicide. Suicide was the 16th leading cause of death worldwide in 2004 and is projected to increase to the 12th in 2030. Although suicide rates have traditionally been highest among the male elderly, rates among young people have been increasing to such an extent that they are now the group at highest risk in a third of countries, in both developed and developing countries. Interpersonal violence Rates and patterns of violent death vary by country and region. In recent years, homicide rates have been highest in developing countries in Sub-Saharan Africa and Latin America and the Caribbean and lowest in East Asia, the western Pacific, and some countries in northern Africa. Studies show a strong, inverse relationship between homicide rates and both economic development and economic equality. Poorer countries, especially those with large gaps between the rich and the poor, tend to have higher rates of homicide than wealthier countries. Homicide rates differ markedly by age and sex. Gender differences are least marked for children. For the 15 to 29 age group, male rates were nearly six times those for female rates; for the remaining age groups, male rates were from two to four times those for females.Studies in a number of countries show that, for every homicide among young people age 10 to 24, 20 to 40 other young people receive hospital treatment for a violent injury.Forms of violence such as child maltreatment and intimate partner violence are highly prevalent. Approximately 20% of women and 5–10% of men report being sexually abused as children, while 25–50% of all children report being physically abused. A WHO multi-country study found that between 15 and 71% of women reported experiencing physical and/or sexual violence by an intimate partner at some point in their lives. Collective violence Wars grab headlines, but the individual risk of dying violently in an armed conflict is today relatively low—much lower than the risk of violent death in many countries that are not suffering from an armed conflict. For example, between 1976 and 2008, African Americans were victims of 329,825 homicides. Although there is a widespread perception that war is the most dangerous form of armed violence in the world, the average person living in a conflict-affected country had a risk of dying violently in the conflict of about 2.0 per 100,000 population between 2004 and 2007. This can be compared to the average world homicide rate of 7.6 per 100,000 people. This illustration highlights the value of accounting for all forms of armed violence rather than an exclusive focus on conflict related violence. Certainly, there are huge variations in the risk of dying from armed conflict at the national and subnational level, and the risk of dying violently in a conflict in specific countries remains extremely high. In Iraq, for example, the direct conflict death rate for 2004–07 was 65 per 100,000 people per year and, in Somalia, 24 per 100,000 people. This rate even reached peaks of 91 per 100,000 in Iraq in 2006 and 74 per 100,000 in Somalia in 2007. History Scientific evidence for warfare has come from settled, sedentary communities. Some scholars argue humans may have a predisposition for violence (chimpanzees, also great apes, have been known to kill members of competing groups for resources like food), placing the origins of organized violence prior to modern settled societies. However, actual evidence suggests that organized, large-scale, militaristic, or regular human-on-human violence was absent for the vast majority of the human timeline, and is first documented to have started only relatively recently in the Holocene, an epoch that began about 11,700 years ago, probably with the advent of higher population densities due to sedentism. Social anthropologist Douglas P. Fry writes that scholars are divided on the origins of this greater degree of violence—in other words, war-like behavior: There are basically two schools of thought on this issue. One holds that warfare... goes back at least to the time of the first thoroughly modern humans and even before then to the primate ancestors of the hominid lineage. The second positions on the origins of warfare sees war as much less common in the cultural and biological evolution of humans. Here, warfare is a latecomer on the cultural horizon, only arising in very specific material circumstances and being quite rare in human history until the development of agriculture in the past 10,000 years. Jared Diamond in his books Guns, Germs and Steel and The Third Chimpanzee posits that the rise of large-scale warfare is the result of advances in technology and city-states. For instance, the rise of agriculture provided a significant increase in the number of individuals that a region could sustain over hunter-gatherer societies, allowing for development of specialized classes such as soldiers, or weapons manufacturers. In academia, the idea of the peaceful pre-history and non-violent tribal societies gained popularity with the post-colonial perspective. The trend, starting in archaeology and spreading to anthropology reached its height in the late half of the 20th century. However, some newer research in archaeology and bioarchaeology may provide evidence that violence within and among groups is not a recent phenomenon. According to the book "The Bioarchaeology of Violence" violence is a behavior that is found throughout human history.Lawrence H. Keeley at the University of Illinois writes in War Before Civilization that 87% of tribal societies were at war more than once per year, and that 65% of them were fighting continuously. He writes that the attrition rate of numerous close-quarter clashes, which characterize endemic warfare, produces casualty rates of up to 60%, compared to 1% of the combatants as is typical in modern warfare. "Primitive Warfare" of these small groups or tribes was driven by the basic need for sustenance and violent competition.Fry explores Keeleys argument in depth and counters that such sources erroneously focus on the ethnography of hunters and gatherers in the present, whose culture and values have been infiltrated externally by modern civilization, rather than the actual archaeological record spanning some two million years of human existence. Fry determines that all present ethnographically studied tribal societies, "by the very fact of having been described and published by anthropologists, have been irrevocably impacted by history and modern colonial nation states" and that "many have been affected by state societies for at least 5000 years."The relatively peaceful period since World War II is known as the Long Peace. The Better Angels of Our Nature Steven Pinkers 2011 book, The Better Angels of Our Nature, argued that modern society is less violent than in periods of the past, whether on the short scale of decades or long scale of centuries or millennia. Steven Pinker argues that by every possible measure, every type of violence has drastically decreased since ancient and medieval times. A few centuries ago, for example, genocide was a standard practice in all kinds of warfare and was so common that historians did not even bother to mention it. Cannibalism and slavery have been greatly reduced in the last thousand years, and capital punishment is now banned in many countries. According to Pinker, rape, murder, warfare and animal cruelty have all seen drastic declines in the 20th century. Pinkers analyses have also been criticized, concerning the statistical question of how to measure violence and whether it is in fact declining.Pinkers observation of the decline in interpersonal violence echoes the work of Norbert Elias, who attributes the decline to a "civilizing process", in which the states monopolization of violence, the maintenance of socioeconomic interdependencies or "figurations", and the maintenance of behavioural codes in culture all contribute to the development of individual sensibilities, which increase the repugnance of individuals towards violent acts. According to a 2010 study, non-lethal violence, such as assaults or bullying appear to be declining as well.Some scholars disagree with the argument that all violence is decreasing arguing that not all types of violent behaviour are lower now than in the past. They suggest that research typically focuses on lethal violence, often looks at homicide rates of death due to warfare, but ignore the less obvious forms of violence. Society and culture Beyond deaths and injuries, highly prevalent forms of violence (such as child maltreatment and intimate partner violence) have serious lifelong non-injury health consequences. Victims may engage in high-risk behaviours such as alcohol and substance misuse and smoking, which in turn can contribute to cardiovascular disorders, cancers, depression, diabetes and HIV/AIDS, resulting in premature death. The balances of prevention, mitigation, mediation and exacerbation are complex, and vary with the underpinnings of violence. Economic effects In countries with high levels of violence, economic growth can be slowed down, personal and collective security eroded, and social development impeded. Families edging out of poverty and investing in schooling their sons and daughters can be ruined through the violent death or severe disability of the main breadwinner. Communities can be caught in poverty traps where pervasive violence and deprivation form a vicious circle that stifles economic growth. For societies, meeting the direct costs of health, criminal justice, and social welfare responses to violence diverts many billions of dollars from more constructive societal spending. The much larger indirect costs of violence due to lost productivity and lost investment in education work together to slow economic development, increase socioeconomic inequality, and erode human and social capital. Additionally, communities with high level of violence do not provide the level of stability and predictability vital for a prospering business economy. Individuals will be less likely to invest money and effort towards growth in such unstable and violent conditions. One of the possible proves might be the study of Baten and Gust that used "regicide" as measurement unit to approximate the influence of interpersonal violence and depict the influence of high interpersonal violence on economic development and level of investments. The results of the research prove the correlation of the human capital and the interpersonal violence.In 2016, the Institute for Economics and Peace, released the Economic Value of Peace report, which estimates the economic impact of violence and conflict on the global economy, the total economic impact of violence on the world economy in 2015 was estimated to be $13.6 trillion in purchasing power parity terms. Religion and politics Religious and political ideologies have been the cause of interpersonal violence throughout history. Ideologues often falsely accuse others of violence, such as the ancient blood libel against Jews, the medieval accusations of casting witchcraft spells against women, and modern accusations of satanic ritual abuse against day care center owners and others.Both supporters and opponents of the 21st-century War on Terrorism regard it largely as an ideological and religious war.Vittorio Bufacchi describes two different modern concepts of violence, one the "minimalist conception" of violence as an intentional act of excessive or destructive force, the other the "comprehensive conception" which includes violations of rights, including a long list of human needs.Anti-capitalists say that capitalism is violent, that private property and profit survive only because police violence defends them, and that capitalist economies need war to expand. In this view, capitalism results in a form of structural violence that stems from inequality, environmental damage, and the exploitation of women and people of color.Frantz Fanon critiqued the violence of colonialism and wrote about the counter violence of the "colonized victims."Throughout history, most religions and individuals like Mahatma Gandhi have preached that humans are capable of eliminating individual violence and organizing societies through purely nonviolent means. Gandhi himself once wrote: "A society organized and run on the basis of complete non-violence would be the purest anarchy." Modern political ideologies which espouse similar views include pacifist varieties of voluntarism, mutualism, anarchism and libertarianism. Terence Fretheim writing about the Old Testament: For many people, ... only physical violence truly qualifies as violence. But, certainly, violence is more than killing people, unless one includes all those words and actions that kill people slowly. The effect of limitation to a "killing fields" perspective is the widespread neglect of many other forms of violence. We must insist that violence also refers to that which is psychologically destructive, that which demeans, damages, or depersonalizes others. In view of these considerations, violence may be defined as follows: any action, verbal or nonverbal, oral or written, physical or psychical, active or passive, public or private, individual or institutional/societal, human or divine, in whatever degree of intensity, that abuses, violates, injures, or kills. Some of the most pervasive and most dangerous forms of violence are those that are often hidden from view (against women and children, especially); just beneath the surface in many of our homes, churches, and communities is abuse enough to freeze the blood. Moreover, many forms of systemic violence often slip past our attention because they are so much a part of the infrastructure of life (e.g., racism, sexism, ageism). See also Aestheticization of violence Aggression Communal violence Corporal punishment Domestic violence Fight-or-flight response Hunting Legislative violence Martial arts Parasitism Predation Religious violence Resentment Sectarian violence War Notes References Sources Barzilai, Gad (2003). Communities and Law: Politics and Cultures of Legal Identities. Ann Arbor: University of Michigan Press. ISBN 0472113151. Benjamin, Walter, Critique of Violence Flannery, D.J., Vazsonyi, A.T. & Waldman, I.D. (Eds.) (2007). The Cambridge handbook of violent behavior and aggression. Cambridge University Press. ISBN 052160785X. James, Paul; Sharma, RR (2006). Globalization and Violence, Vol. 4: Transnational Conflict. London: Sage Publications. Malešević, Siniša The Sociology of War and Violence. Cambridge University Press; 2010 [cited October 17, 2011]. ISBN 978-0521731690. Nazaretyan, A.P. (2007). Violence and Non-Violence at Different Stages of World History: A view from the hypothesis of techno-humanitarian balance. In: History & Mathematics. Moscow: KomKniga/URSS. pp. 127–48. ISBN 978-5484010011. External links Violence prevention at World Health Organization Violence prevention at Centers for Disease Control and Prevention Violence prevention at American Psychological Association World Report on Violence Against Children Archived 2016-01-11 at the Wayback Machine at Secretary-General of the United Nations Hidden in Plain Sight: A statistical analysis of violence against children Archived 2017-11-15 at the Wayback Machine at UNICEF Heat and Violence

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I've come across the term 'Marshall syndrome' in a medical context, but I'm not sure what it means. Can you clarify?

Marshall syndrome is a genetic disorder of the connective tissue which can cause hearing loss. The three most common areas to be affected are the eyes which are uncommonly large, joints and the mouth and facial structures. Marshall syndrome and Stickler syndrome closely resemble each other; in fact they are so similar, some say they are the same. Presentation Eyes Myopia is the most common eye problem in Marshall syndrome. Cataracts also occur more frequently and detached retina less frequently than in Stickler syndrome. Myopia also is the most common problem with the eyes in Stickler syndrome. In the latter syndrome, extreme myopia may lead to severe eye problems such as detached retina more frequently than in Marshall syndrome. Joints The joint changes include hyperextensibility (double-jointedness) and arthritis. Babies and young children with Stickler syndrome usually have very hyperextensible joints. As an affected child gets older, they may experience pain and stiffness from overuse of a joint. Osteoarthritis of the large joints often develops during the third or fourth decade. The joint changes in Marshall syndrome are of the same type but to a lesser degree. There also may be changes in the bones that show up on X-ray but generally are not a problem. Orofacial Structure The most severe problem associated with Stickler syndrome is Pierre Robin syndrome. This refers to a cleft palate resulting from a very small lower jaw. During early fetal life, the roof of the mouth is normally open and the sides of the palate have to come together to close. If the jaw is too small, there is not enough room for the tongue which is then pushed up and gets in the way of the closing palate. Sometimes the chin is so small the baby has problems with eating and breathing if the tongue blocks the back of the throat. Cleft palate is found less frequently in Marshall Syndrome than in Stickler syndrome but still more frequently than in the general population.The facial features of Marshall Syndrome include a flat midface, the appearance of large eyes, short upturned nose, and a round face. The facial features of Stickler syndrome are less prominent but include a rather long flat face, and depressed nasal bridge. Hearing loss The hearing loss associated with Stickler syndrome can be progressive and usually involves the high frequencies. Sensorineural hearing loss has been reported in as many as 100% and as low as 20% of affected individuals. A conductive loss due to otitis can magnify an existing sensorineural loss and is a frequent problem for children with Stickler or Marshall Syndrome. Genetics Stickler syndrome and Marshall syndrome have an autosomal dominant pattern of inheritance. However, there is a great deal of variation within and among families with regard to gene expression. Some may be more severely affected and others may be very mildly affected. Often these syndromes are not recognized in a family until a baby is born with Pierre Robin syndrome or some members have detached retinas or cataracts at a young age.Both syndromes where correlated with mutations in the COL11A1 gene. Diagnosis Diagnosis is made based on features as well as by the very early onset of serious eye and ear disease. Because Marshall syndrome is an autosomal dominant hereditary disease, physicians can also note the characteristic appearance of the biological parent of the child. A genetic test can be performed in Stickler syndrome diagnosis is made by doing a genetic test for the several collagen genes as well as other genes that are associated with Stickler as well as considering the presence and severity of Spondyloepiphyseal Dysplasia with association of reduced height and growth rate as well as other connective tissue features like skin hyperextensibility and poor wound healing. It is an area of active research, also the genetic testing being expensive supports that the diagnosis is made depending on the features. Treatment There is no medical treatment for either syndrome but there are some recommendations that can help with prevention or early identification of some of the problems. Children with either syndrome should have their hearing tested, and adults should be aware that the hearing loss may not develop until the adult years. Yearly visits to an ophthalmologist or other eye care professional who has been informed of the diagnosis of Stickler or Marshall syndrome is important for all affected individuals. Children should have the opportunity to have myopia corrected as early as possible, and treatment for cataracts or detached retinas may be more effective with early identification. Support for the joints is especially important during sports, and some recommend that contact sports should be avoided by those who have very loose joints. References == External links ==

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I've encountered the term 'Cholesterolosis of gallbladder' while reading about medical topics. What does it refer to exactly?

In surgical pathology, strawberry gallbladder, more formally cholesterolosis of the gallbladder and gallbladder cholesterolosis, is a change in the gallbladder wall due to excess cholesterol.The name strawberry gallbladder comes from the typically stippled appearance of the mucosal surface on gross examination, which resembles a strawberry. Cholesterolosis results from abnormal deposits of cholesterol esters in macrophages within the lamina propria (foam cells) and in mucosal epithelium. The gallbladder may be affected in a patchy localized form or in a diffuse form. The diffuse form macroscopically appears as a bright red mucosa with yellow mottling (due to lipid), hence the term strawberry gallbladder. It is not tied to cholelithiasis (gallstones) or cholecystitis (inflammation of the gallbladder). Additional images See also Cholecystectomy Rokitansky-Aschoff sinuses References Further reading Izzo L, Boschetto A, Brachini G, et al. (2001). "["Strawberry" gallbladder: review of the literature and our experience]". Il Giornale di Chirurgia (in Italian). 22 (1–2): 33–6. PMID 11272434. == External links ==

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Could you please explain the term 'Ischiopagi' in simple language?

Ischiopagi comes from the Greek word ischio- meaning hip (ilium) and -pagus meaning fixed or united. It is the medical term used for conjoined twins (Class V) who are united at the pelvis. The twins are classically joined with the vertebral axis at 180°. However, the most frequent cases usually structures the ischiopagus twins with two separate spines forming a lateral angle smaller than 90°. The conjoined twins usually have four arms; two, three or four legs; and typically one external genitalia and anus.It is mostly confused with pygopagus where the twins are joined dorsally at the buttocks facing away from each other, whereas ischiopagus twins are joined ventrally and caudally at the sacrum and coccyx. Parapagus is also similar to ischiopagus; however, parapagus twins are joined side-by-side whereas ischiopagus twins typically have spines connected at a 180° angle, facing away from one another. Classification Ischiopagus Dipus: This is the rarest variety with the twins sharing two legs with no lower extremities on one side. Ischiopagus Tripus: This is the most common variety. These twins share three legs, the third leg is often two fused legs, or is non-functioning. The twins also usually share only one set of external genitalia. Ischiopagus Tetrapus/Quadripus: This variety has the twins at a symmetrical continuous longitudinal axis with their area of union not broken anteriorly. The axes extends in a straight line but in opposite directions. The lower extremities are oriented at right angles to the axes of the thorax and the adjacent limbs near the union of the ischium belong to the opposite twin. Embryology During embryonic development, twins can form from the splitting of a single embryo (monozygotic) which forms identical twins or the twins can arise from separate oocytes in the same menstrual cycle (dizygotic) which forms fraternal twins. Although the latter is more frequent, monozygotic is the reason conjoined twins can develop. In monozygotic twinning for conjoined twins such as ischiopagi, the twins form by the splitting of a bi-laminar embryonic disc after the formation of the inner cell masses. Thus, making the twins occupy the same amnion which can lead to a conjoining of the twins as a result of the twins not separating properly during the twinning process. Separation occurring between the seventh and thirteenth days should result in a monochorionic, monoamniotic identical twins sharing a yolk sac. If separation of the twins occur in the later stages of development prior to the appearance of the primitive streak and axial orientation, then it can be predicted that conjoined twins will develop. The origin of exactly what goes wrong to produce ischiopagus or any conjoined twin is a result by either incomplete fission or double overlapping inducing centers on the same germ disc. Various studies suggest that mechanical disturbances such as shaking of the blastomeres, exposure of the embryo to cold or insufficient oxygen during the early process of cleavage, grafting organizer onto gastrula or half a gastrula together, or constricting the blastula or early gastrula can cause the incomplete separation of monozygotic twins. However, studies have shown that these disturbances must happen at critical times in the pregnancy for the conjoined twins to develop. Complications Conjoined twins are at high risk to being stillborn or dying shortly after birth. In some cases, a healthy twin and a parasitic twin are born. The parasitic twin has no hope for survival and dies and is then surgically separated from its twin. Depending upon how the twins are attached and what is shared among them, complications can arise from surgically separating the live twin from the dead twin. In Ischiopagus cases, the children share a pelvic region along with the gastrointestinal tract and genital region. Ischiopagus twins need reconstructive surgery for the genitals and gastrointestinal tract in order for normal bowel movements and reproductive possibilities in adulthood. For the Ischiopagus twins that both survive from birth, complications and risks also arise. Usually if both twins survive labor, one twin will be healthy and strong, while the other is malnourished and weak. Thus, surgery would have to be planned in advance to understand the best option and how to keep both children alive during surgery as well as afterwards. Treatment Separation is the only treatment for Ischiopagus. The rarity of the condition as well as the challenge it presents in separating the twins has been difficult to understand. In recent years, with advancing medical technology, physicians have been able to successfully separate Ischiopagus twins. However, it depends on the organs shared, how closely joined the twins are, and what risks could rise from separating the twins during surgery. Since Ischiopagus twins usually share a gastrointestinal tract and other organs in the pelvic region, it takes months of planning to decide whether or not separation of the twins outweighs the complications and risks associated with surgery and reconstruction of organs. Surgery to separate conjoined twins has allowed surgeons to be able to study the mechanisms of embryogenesis as well as the physiological consequences of parabiosis.Separating ischiopagus tripus conjoined twins usually leaves the twins with one leg each. Prognosis Depending upon what organs are shared among the twins and if they are surgically separable, usually only one of the twins makes it through the surgery or they both die due to complications either before or during the surgery. Now that successful surgery has been reported and more findings are becoming available due to research and pre-surgery evaluation, better surgery techniques and procedures will be available in the future to help increase the survival rate of ischiopagus twins as well as other conjoined twins. Epidemiology Ischiopagus is a rare anomaly occurring in about 1 in every 100,000 live births and occurring in 1 out of 10 conjoined twin births. Most Ischiopagus cases are common in the areas of India and Africa. Of the varieties of Ischiopagus twins, Ischiopagus Tetrapus is more prevalent, happening in 68.75% of all Ischiopagus cases. Ischiopagus Tripus occurs in 31.25% of cases while Ischiopagus Dipus occurs in only 6.25% of all Ischiopagus cases. == References ==

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I'd like to learn more about the medical term 'Transient erythroblastopenia of childhood.' Can you provide some details?

Transient erythroblastopenia of childhood (TEC) is a slowly developing anemia of early childhood characterized by gradual onset of pallor. Signs and symptoms Individuals with TEC have a median age of presentation of 18–26 months; however, the disorder may occur in infants younger than 6 months and in children as old as age 10 years. Because of the gradual onset of the anemia, children are often healthier than expected from their low hemoglobin levels. Cause The cause of TEC is unknown, but it thought to be triggered by a viral infection. While rare cases have been attributed to infection with Parvovirus B19, the majority of cases are not related to Parvovirus infection. This is in contrast to transient aplastic crisis, seen in patients with hemoglobinopathies such as sickle cell disease, which is usually caused by Parvovirus infection. Diagnosis Children typically present with a moderate normocytic anemia (usual range: Hemoglobin 5-8 g/dL) and reticulocytopenia. Mean corpuscular volume (MCV) is usually normal for age. Hemoglobin F levels are also typically normal. Prognosis Most patients recover completely within 1–2 months. However many reported cases have lasted 18–24 months and longer. References External links ped/2279 at eMedicine

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What does the medical term 'Black heel and palm' encompass?

Black heel and palm is a skin condition characterized by a sudden shower of minute, black, punctate macules occurring most often on the posterior edge of the plantar surface of one or both heels.: 43 See also Skin lesion List of cutaneous conditions == References ==

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Orthostatic albuminuria'?

Orthostatic proteinuria (synonyms: orthostatic albuminuria, postural proteinuria) is a benign condition. A change in renal hemodynamics, which in some otherwise normal individuals, causes protein (mostly albumin) to appear in urine when they are in the standing position. Urine formed when these individuals are lying down is protein-free.There is normal urinary protein excretion during the night but increased excretion during the day, associated with activity and upright posture. Total urinary protein excretion may be increased but levels above 1 g per 24 hours are more likely to be associated with underlying renal disease. The exact cause for orthostatic proteinuria is not known. == References ==

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I'd like to learn more about the medical term 'Erythema ab igne.' Can you provide some details?

Erythema ab igne (EAI), also known as hot water bottle rash, is a skin condition caused by long-term exposure to heat (infrared radiation). Prolonged thermal radiation exposure to the skin can lead to the development of reticulated erythema, hyperpigmentation, scaling, and telangiectasias in the affected area. Some people may complain of mild itchiness and a burning sensation, but often, unless a change in pigmentation is seen, it can go unnoticed. Causes Different types of heat sources can cause this condition such as: Repeated application of hot water bottles, heating blankets, or heat pads to treat chronic pain—e.g., chronic back pain. Repeated exposure to heated car seats, space heaters, or fireplaces. Repeated or prolonged exposure to a heater is a common cause of this condition in elderly individuals. Occupational hazards of silversmiths and jewelers (face exposed to heat), bakers, and chefs (arms, face) Resting a laptop computer on the thigh (laptop computer-induced erythema ab igne). In a 2012 review, Riahi and Cohen describe the characteristics of laptop computer-induced erythema ab igne. Temperatures between 43 and 47 °C can cause this skin condition; modern laptops can generate temperatures in this range. Indeed, laptops with powerful processors can reach temperatures of 50 °C and be associated with burns. Positioning the laptop on the thighs can allow for direct exposure to the heating elements of the laptop, which include the central processing unit (CPU) and the graphics processing unit (GPU). At least 15 cases have been reported by 2012 with the condition usually affecting the left anterior thigh. In these reports, 9 of the 15 patients were women (60%) with an average age of 25 years at diagnosis. In Kashmir, due to the use of a kanger which also causes kangri cancer. It is a classic finding in chronic pancreatitis and may also be seen in people with hypothyroidism or lymphedema Pathogenesis The pathogenesis of erythema ab igne remains unknown. It has been proposed that thermal radiation exposure can induce damage to superficial blood vessels that subsequently leads to epidermal vascular dilation. The dilation of vessels presents morphologically as the initially observed erythema. Red blood cell extravasation and deposition of hemosiderin that follows clinically appear as hyperpigmentation, which can occur in a reticular distribution. It has also been proposed that the distribution of affected blood vessels—predominantly in the superficial subcutaneous plexus (found in the papillary dermis)—results in the net-like pattern of erythema ab igne skin lesions. Diagnosis Differential diagnosis Livedo reticularis Vasculitis Treatment Discontinuing contact with the heat source is the initial treatment of erythema ab igne. If the area is only mildly affected with slight redness, the condition may resolve after a few months. If the condition is severe and the skin pigmented and atrophic, then it is unlikely to resolve. In this case, there is a possibility that a squamous cell carcinoma or a neuroendocrine carcinoma such as a Merkel cell carcinoma may form. If there is a persistent sore that does not heal or a growing lump within the rash, a skin biopsy should be performed to rule out the possibility of skin cancer. If the erythema ab igne lesions demonstrate pre-cancerous changes, the use of 5-fluorouracil cream has been recommended. Abnormally pigmented skin may persist for years. Treatment with topical tretinoin or laser treatment may improve the appearance. Epidemiology Erythema ab igne was once commonly seen in the elderly who stood or sat closely to open fires or electric heaters; however, erythema ab igne has been reported in both young and elderly individuals. Women have a higher incidence of erythema ab igne than men. Although wide use of central heating has reduced the overall incidence of erythema ab igne, it is still sometimes found in people exposed to heat from other sources such as heating pads, space heaters, hot water bottles, and electronic devices. References External links DermNet vascular/erythema-ab-igneNew England Journal of Medicine Image Challenge

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Could you please explain the term 'Immunodeficiency' in simple language?

Immunodeficiency, also known as immunocompromisation, is a state in which the immune systems ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patients immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID. In clinical settings, immunosuppression by some drugs, such as steroids, can either be an adverse effect or the intended purpose of the treatment. Examples of such use is in organ transplant surgery as an anti-rejection measure and in patients with an overactive immune system, as in autoimmune diseases. Some people are born with intrinsic defects in their immune system, or primary immunodeficiency.A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised individual may particularly be vulnerable to opportunistic infections, in addition to normal infections that could affect anyone. It also decreases cancer immunosurveillance, in which the immune system scans the bodys cells and kills neoplastic ones. They are also more susceptible to infectious diseases owing to reduced protection afforded by vaccines. Types By affected component Humoral immune deficiency (including B cell deficiency or dysfunction), with signs or symptoms depending on the cause, but generally include signs of hypogammaglobulinemia (decrease of one or more types of antibodies) with presentations including repeated mild respiratory infections, and/or agammaglobulinemia (lack of all or most antibody production) which results in frequent severe infections and is often fatal. T cell deficiency, often causes secondary disorders such as acquired immune deficiency syndrome (AIDS). Granulocyte deficiency, including decreased numbers of granulocytes (called as granulocytopenia or, if absent, agranulocytosis) such as of neutrophil granulocytes (termed neutropenia). Granulocyte deficiencies also include decreased function of individual granulocytes, such as in chronic granulomatous disease. Asplenia, where there is no function of the spleen Complement deficiency is where the function of the complement system is deficientIn reality, immunodeficiency often affects multiple components, with notable examples including severe combined immunodeficiency (which is primary) and acquired immune deficiency syndrome (which is secondary). Primary or secondary The distinction between primary versus secondary immunodeficiencies is based on, respectively, whether the cause originates in the immune system itself or is, in turn, due to insufficiency of a supporting component of it or an external decreasing factor of it. Primary immunodeficiency A number of rare diseases feature a heightened susceptibility to infections from childhood onward. Primary Immunodeficiency is also known as congenital immunodeficiencies. Many of these disorders are hereditary and are autosomal recessive or X-linked. There are over 95 recognised primary immunodeficiency syndromes; they are generally grouped by the part of the immune system that is malfunctioning, such as lymphocytes or granulocytes.The treatment of primary immunodeficiencies depends on the nature of the defect, and may involve antibody infusions, long-term antibiotics and (in some cases) stem cell transplantation. The characteristics of lacking and/or impaired antibody functions can be related to illnesses such as X-Linked Agammaglobulinemia and Common Variable Immune Deficiency Secondary immunodeficiencies Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from various immunosuppressive agents, for example, malnutrition, aging, particular medications (e.g., chemotherapy, disease-modifying antirheumatic drugs, immunosuppressive drugs after organ transplants, glucocorticoids) and environmental toxins like mercury and other heavy metals, pesticides and petrochemicals like styrene, dichlorobenzene, xylene, and ethylphenol. For medications, the term immunosuppression generally refers to both beneficial and potential adverse effects of decreasing the function of the immune system, while the term immunodeficiency generally refers solely to the adverse effect of increased risk for infection. Many specific diseases directly or indirectly cause immunosuppression. This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections. Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV). HIV directly infects a small number of T helper cells, and also impairs other immune system responses indirectly. Various hormonal and metabolic disorders can also result in immune deficiency including anemia, hypothyroidism and hyperglycemia. Smoking, alcoholism and drug abuse also depress immune response. Heavy schedules of training and competition in athletes increases their risk of immune deficiencies. Diagnosis Patients with immune deficiencies can present with variable clinical phenotypes. This often translates into a significant delay in their diagnosis, and resultant patient morbidity. A structured approach on when to suspect an immunodeficiency and the initial investigations pathway is given in the publication by Grammatikos et al. Immunodeficiency and autoimmunity There are a large number of immunodeficiency syndromes that present clinical and laboratory characteristics of autoimmunity. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual immune system activation. One example is common variable immunodeficiency (CVID) where multiple autoimmune diseases are seen, e.g., inflammatory bowel disease, autoimmune thrombocytopenia, and autoimmune thyroid disease. Familial hemophagocytic lymphohistiocytosis, an autosomal recessive primary immunodeficiency, is another example. Low blood levels of red blood cells, white blood cells, and platelets, rashes, lymph node enlargement, and enlargement of the liver and spleen are commonly seen in these patients. Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible. In addition to chronic and/or recurrent infections many autoimmune diseases including arthritis, autoimmune hemolytic anemia, scleroderma and type 1 diabetes are also seen in X-linked agammaglobulinemia (XLA). Recurrent bacterial and fungal infections and chronic inflammation of the gut and lungs are seen in chronic granulomatous disease (CGD) as well. CGD is caused by a decreased production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by neutrophils. Hypomorphic RAG mutations are seen in patients with midline granulomatous disease; an autoimmune disorder that is commonly seen in patients with granulomatosis with polyangiitis and NK/T cell lymphomas. Wiskott–Aldrich syndrome (WAS) patients also present with eczema, autoimmune manifestations, recurrent bacterial infections and lymphoma. In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) also autoimmunity and infections coexist: organ-specific autoimmune manifestations (e.g., hypoparathyroidism and adrenocortical failure) and chronic mucocutaneous candidiasis. Finally, IgA deficiency is also sometimes associated with the development of autoimmune and atopic phenomena. Causes The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be either genetic or acquired by malnutrition and poor sanitary conditions. Only for some genetic causes, the exact genes are known. Treatment Available treatment falls into two modalities: treating infections and boosting the immune system. Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised. In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administrated, resulting in higher Ig levels for about three to four weeks, although this varies with each patient. Prognosis Prognosis depends greatly on the nature and severity of the condition. Some deficiencies cause early mortality (before age one), others with or even without treatment are lifelong conditions that cause little mortality or morbidity. Newer stem cell transplant technologies may lead to gene based treatments of debilitating and fatal genetic immune deficiencies. Prognosis of acquired immune deficiencies depends on avoiding or treating the causative agent or condition (like AIDS). See also Acquired immune deficiency syndrome (AIDS) Immune disorder Autoimmune disease, immune response to self-proteins Allergy, immune response to harmless non-self proteins Histamine Immunosenescence, age-associated immune deficiency Steroids, commonly administered drugs like prednisone that suppress the immune system Human genetic enhancement Immune system Immunology References External links Immune Deficiency Foundation The European Society of Immunodeficiencies

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I'd like to learn more about the medical term 'Larotrectinib.' Can you provide some details?

Larotrectinib, sold under the brand name Vitrakvi, is a medication for the treatment of cancer. It is an inhibitor of tropomyosin kinase receptors TrkA, TrkB, and TrkC. It was discovered by Array BioPharma and licensed to Loxo Oncology in 2013. Larotrectinib was initially awarded orphan drug status in 2015, for soft tissue sarcoma, and breakthrough therapy designation in 2016 for the treatment of metastatic solid tumors with NTRK fusion. Some clinical trial results were announced in 2017. On 26 November 2018, Larotrectinib was approved by the FDA.Larotrectinib was the first drug to be specifically developed and approved to treat any cancer containing certain mutations, as opposed to cancers of specific tissues (i.e., the approval is "tissue agnostic"). Several earlier drugs, including pembrolizumab, were eventually approved by the FDA for treatment of specific mutations independent of the type of cancer, but those drugs had been initially developed for specific cancer types. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.Phase II clinical trials evaluating the drug for efficacy and safety in treating several types of solid tumors are ongoing.Larotrectinib was approved for medical use in the European Union in September 2019. It was approved for medical use in Australia in August 2020. References External links "Larotrectinib". Drug Information Portal. U.S. National Library of Medicine. "Larotrectinib sulfate". National Cancer Institute. "Larotrectinib sulfate". NCI Dictionary of Cancer Terms. National Cancer Institute.

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Cycloserine'?

Cycloserine, sold under the brand name Seromycin, is a GABA transaminase inhibitor and an antibiotic, used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It is given by mouth.Common side effects include allergic reactions, seizures, sleepiness, unsteadiness, and numbness. It is not recommended in people who have kidney failure, epilepsy, depression, or are alcoholics. It is unclear if use during pregnancy is safe for the baby. Cycloserine is similar in structure to the amino acid D-alanine and works by interfering with the formation of the bacterias cell wall.Cycloserine was discovered in 1954 from a type of Streptomyces. It is on the World Health Organizations List of Essential Medicines. Medical uses Tuberculosis For the treatment of tuberculosis, cycloserine is classified as a second-line drug, i.e. its use is only considered if one or more first-line drugs cannot be used. Hence, cycloserine is restricted for use only against multiple drug-resistant and extensively drug-resistant strains of M. tuberculosis. Another reason for limited use of this drug is the neurological side effects it causes, since it is able to penetrate into the central nervous system (CNS) and cause headaches, drowsiness, depression, dizziness, vertigo, confusion, paresthesias, dysarthria, hyperirritability, psychosis, convulsions, and shaking (tremors). Overdose of cycloserine may result in paresis, seizures, and coma, while alcohol consumption may increase the risk of seizures. Coadministration of pyridoxine can reduce the incidence of some of these CNS side effects (e.g. convulsions) caused by cycloserine. Psychiatry A 2015 Cochrane review found no evidence of benefit in anxiety disorders as of 2015. Another review found preliminary evidence of benefit. Evidence for use in addiction is tentative but also unclear. Mechanism of action Cycloserine works as an antibiotic by inhibiting cell-wall biosynthesis in bacteria. As a cyclic analogue of D-alanine, cycloserine acts against two crucial enzymes important in the cytosolic stages of peptidoglycan synthesis: alanine racemase (Alr) and D-alanine:D-alanine ligase (Ddl). The first enzyme is a pyridoxal 5-phosphate-dependent enzyme which converts the L-alanine to the D-alanine form. The second enzyme is involved in joining two of these D-alanine residues together by catalyzing the formation of the ATP-dependent D-alanine-D-alanine dipeptide bond between the resulting D-alanine molecules. If both of these enzymes are inhibited, then D-alanine residues cannot form and previously formed D-alanine molecules cannot be joined together. This effectively leads to inhibition of peptidoglycan synthesis. Chemical properties Under mildly acidic conditions, cycloserine hydrolyzes to give hydroxylamine and D-serine. Cycloserine can be conceptualized as a cyclized version of serine, with an oxidative loss of dihydrogen to form the nitrogen-oxygen bond.Cycloserine is stable under basic conditions, with the greatest stability at pH = 11.5. History The compound was first isolated nearly simultaneously by two teams. Workers at Merck isolated the compound, which they called oxamycin, from a species of Streptomyces. The same team prepared the molecule synthetically. Workers at Eli Lilly isolated the compound from strains of Streptomyces orchidaceus. It was shown to hydrolyze to serine and hydroxylamine. Economics In the U.S., the price of cycloserine increased from $500 for 30 pills to $10,800 in 2015 after the Chao Center for Industrial Pharmacy and Contract Manufacturing changed ownership to Rodelis Therapeutics in August 2015.The price increase was rescinded after the previous owner, the Purdue University Research Foundation, which retained "oversight of the manufacturing operation" intervened and Rodelis returned the drug to an NGO of Purdue University. The foundation now will charge $1,050 for 30 capsules, twice what it charged before". Eli Lilly has been criticised for not ensuring that the philanthropic initiative continued. Due to US antitrust laws, however, no company may control the price of a product after it is outlicensed.In 2015, the cost in the United States was increased to US$3,150 a month and then decreased to US$1,050 per month. Research There is some experimental evidence to suggest that D-cycloserine aids in learning by helping form stronger neural connections. It has been investigated as an aid to facilitate exposure therapy in people with PTSD and anxiety disorders as well as treatment with schizophrenia. In a clinical trial, a course of D-cycloserine combined with a single dose of ketamine was investigated for treatment resistant bipolar depression. When administered for 8 weeks after a ketamine infusion, cycloserine appeared to potentiate the antidepressant effects in all trial participants. References External links "Cycloserine". Drug Information Portal. U.S. National Library of Medicine.

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I've come across the term 'Intractability' in a medical context, but I'm not sure what it means. Can you clarify?

Intractable may refer to: Intractable conflict, a form of complex, severe, and enduring conflict Intractable pain, pain which cannot be controlled/cured by any known treatment Intractability (complexity), in computational complexity theory

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I've encountered the term 'Ibrexafungerp' while reading about medical topics. What does it refer to exactly?

Ibrexafungerp, sold under the brand name Brexafemme, is an antifungal medication used to treat vulvovaginal candidiasis (VVC) (vaginal yeast infection). It is taken by mouth. An estimated 75% of women will have at least one episode and 40 to 45% will have two or more episodes in their lifetime.Ibrexafungerp is a triterpenoid antifungal. It acts via inhibition of glucan synthase, which prevents formation of the fungal cell wall.Ibrexafungerp was approved for medical use in the United States in June 2021. It is the first approved drug in a novel antifungal class. Medical uses Ibrexafungerp is indicated for the treatment of adult and postmenarchal pediatric females with vulvovaginal candidiasis (VVC). Pharmacology Pharmacodynamics Ibrexafungerp is a triterpenoid antifungal agent. It acts via inhibition of the enzyme glucan synthase, which is involved in the formation of 1,3-β-D-glucan—an essential component of the fungal cell wall. The compound has concentration-dependent fungicidal activity against Candida species. Pharmacokinetics Ibrexafungerp has a time to maximal concentrations of 4 to 6 hours. It is metabolized by hydroxylation via CYP3A4 and subsequently by glucuronidation and sulfation. The medication has an elimination half-life of approximately 20 hours. References Further reading Azie N, Angulo D, Dehn B, Sobel JD (September 2020). "Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis". Expert Opin Investig Drugs. 29 (9): 893–900. doi:10.1080/13543784.2020.1791820. PMID 32746636. Davis MR, Donnelley MA, Thompson GR (July 2020). "Ibrexafungerp: A novel oral glucan synthase inhibitor". Med Mycol. 58 (5): 579–592. doi:10.1093/mmy/myz083. PMID 31342066. Petraitis V, Petraitiene R, Katragkou A, Maung BB, Naing E, Kavaliauskas P, et al. (May 2020). "Combination Therapy with Ibrexafungerp (Formerly SCY-078), a First-in-Class Triterpenoid Inhibitor of (1→3)-β-d-Glucan Synthesis, and Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis". Antimicrob Agents Chemother. 64 (6). doi:10.1128/AAC.02429-19. PMC 7269506. PMID 32179521. External links "Ibrexafungerp". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03734991 for "Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs. Placebo in Subjects With Acute Vulvovaginal Candidiasis (VANISH 303)" at ClinicalTrials.gov Clinical trial number NCT03987620 for "Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs. Placebo in Subjects With Acute Vulvovaginal Candidiasis (Vanish 306)" at ClinicalTrials.gov

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I'm trying to understand 'Myelopathy' within a medical context. Could you shed some light on it?

Myelopathy describes any neurologic deficit related to the spinal cord. When due to trauma, it is known as (acute) spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy. The most common form of myelopathy in humans, cervical spondylotic myelopathy (CSM), also called degenerative cervical myelopathy is caused by arthritic changes (spondylosis) of the cervical spine, which result in narrowing of the spinal canal (spinal stenosis) ultimately causing compression of the spinal cord. In Asian populations, spinal cord compression often occurs due to a different, inflammatory process affecting the posterior longitudinal ligament. Presentation Clinical signs and symptoms depend on which spinal cord level (cervical, thoracic, or lumbar) is affected and the extent (anterior, posterior, or lateral) of the pathology, and may include: Upper motor neuron signs—weakness, spasticity, clumsiness, altered tonus, hyperreflexia and pathological reflexes, including Hoffmanns sign and inverted plantar reflex (positive Babinski sign) Lower motor neuron signs—weakness, clumsiness in the muscle group innervated at the level of spinal cord compromise, muscle atrophy, hyporeflexia, muscle hypotonicity or flaccidity, fasciculations Sensory deficits Bowel/bladder symptoms and sexual dysfunction Diagnosis Diagnosis of myelopathy Myelopathy is primarily diagnosed by clinical exam findings. Because the term myelopathy describes a clinical syndrome that can be caused by many pathologies the differential diagnosis of myelopathy is extensive. In some cases the onset of myelopathy is rapid, in others, such as CSM, the course may be insidious with symptoms developing slowly over a period of months. As a consequence, the diagnosis of CSM is often delayed. As the disease is thought to be progressive, this may impact negatively on outcome. Diagnosis of etiology Once the clinical diagnosis myelopathy is established, the underlying cause must be investigated. Most commonly this involves medical imaging. The best way to visualize the spinal cord is magnetic resonance imaging (MRI). Apart from T1 and T2 MRI images, which are commonly used for routine diagnosis, more recently researchers are exploring quantitative MRI signals. Further imaging modalities used for evaluating myelopathy include plain X-rays for detecting arthritic changes of the bones, and Computer Tomography, which is often used for pre-operative planning of surgical interventions for cervical spondylotic myelopathy. Angiography is used to examine blood vessels in suspected cases of vascular myelopathy.The presence and severity of myelopathy can also be evaluated by means of transcranial magnetic stimulation (TMS), a neurophysiological method that allows the measurement of the time required for a neural impulse to cross the pyramidal tracts, starting from the cerebral cortex and ending at the anterior horn cells of the cervical, thoracic or lumbar spinal cord. This measurement is called Central Conduction Time (CCT). TMS can aid physicians to: Determine whether myelopathy exists Identify the level of the spinal cord where myelopathy is located. This is especially useful in cases where more than two lesions may be responsible for the clinical symptoms and signs, such as in patients with two or more cervical disc hernias Follow-up the progression of myelopathy in time, for example before and after cervical spine surgeryTMS can also help in the differential diagnosis of different causes of pyramidal tract damage. Treatment The treatment and prognosis of myelopathy depends on the underlying cause: myelopathy caused by infection requires medical treatment with pathogen specific antibiotics. Similarly, specific treatments exist for multiple sclerosis, which may also present with myelopathy. As outlined above, the most common form of myelopathy is secondary to degeneration of the cervical spine. Newer findings have challenged the existing controversy with respect to surgery for cervical spondylotic myelopathy by demonstrating that patients benefit from surgery. See also Surfers myelopathy References == External links ==

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I need a basic explanation for the medical term 'Neutropenia.'

Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening (neutropenic sepsis).Neutropenia can be divided into congenital and acquired, with severe congenital neutropenia (SCN) and cyclic neutropenia (CyN) being autosomal dominant and mostly caused by heterozygous mutations in the ELANE gene (neutrophil elastase). Neutropenia can be acute (temporary) or chronic (long lasting). The term is sometimes used interchangeably with "leukopenia" ("deficit in the number of white blood cells").Decreased production of neutrophils is associated with deficiencies of vitamin B12 and folic acid, aplastic anemia, tumors, drugs, metabolic disease, nutritional deficiency and immune mechanisms. In general, the most common oral manifestations of neutropenia include ulcer, gingivitis, and periodontitis. Agranulocytosis can be presented as whitish or greyish necrotic ulcer in oral cavity, without any sign of inflammation. Acquired agranulocytosis is much more common than the congenital form. The common causes of acquired agranulocytosis including drugs (non-steroidal anti-inflammatory drugs, antiepileptics, antithyroid and antibiotics) and viral infection. Agranulocytosis has a mortality rate of 7–10%. To manage this, the application of granulocyte colony stimulating factor (G-CSF) or granulocyte transfusion and the use of broad-spectrum antibiotics to protect against bacterial infections are recommended. Signs and symptoms Signs and symptoms of neutropenia include fever, painful swallowing, gingival pain, skin abscesses, and otitis. These symptoms may exist because individuals with neutropenia often have infection.Children may show signs of irritability and poor feeding. Additionally, hypotension has also been observed in individuals who have this condition. Causes The causes of neutropenia can be divided between problems that are transient and those that are chronic. Causes can be divided into these groups: Severe bacterial infections, especially in people with underlying hematological diseases or alcoholism, can deplete neutrophil reserves and lead to neutropenia. Gram-positive bacteria are present in 60–70% of bacterial infections. There are serious concerns regarding antibiotic-resistant organisms. These would include as methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE).Nutritional deficiencies, such as deficiency in vitamin B12, folate, copper or protein-calorie malnutrition are associated with chronic neutropenia. However, nutritional deficiencies are usually associated with decreases in other cell lines (multiple cytopenia or pancytopenia) rather than isolated neutropenia.Other causes of congenital neutropenia are Shwachman–Diamond syndrome, Cyclic neutropenia, bone marrow failure syndromes, cartilage–hair hypoplasia, reticular dysgenesis, and Barth syndrome. Viruses that infect neutrophil progenitors can also be the cause of neutropenia. Viruses identified that have an effect on neutrophils are rubella and cytomegalovirus. Though the body can manufacture a normal level of neutrophils, in some cases the destruction of excessive numbers of neutrophils can lead to neutropenia. These are: Pathophysiology The pathophysiology of neutropenia can be divided into congenital and acquired. The congenital neutropenia (severe and cyclic type) is autosomal dominant, with mutations in the ELA2 gene (neutrophil elastase) as the most common genetic reason for this condition. Acquired neutropenia (immune-associated neutropenia) is due to anti-neutrophil antibodies that target neutrophil-specific antigens, ultimately altering neutrophil function. Furthermore, emerging research suggests neutropenia without an identifiable etiology (idiopathic neutropenia) may be the result of a low-grade, chronic inflammatory process with an abnormal excessive production of myelosuppressive cytokines in a study conducted in the island of Crete.Neutropenia fever can complicate the treatment of cancers. Observations of children noted that fungal infections are more likely to develop in those with neutropenia. Mortality increases during cancer treatments if neutropenia is also present. Congenital neutropenia is determined by blood neutrophil counts (absolute neutrophil counts or ANC) < 0.5 × 109/L and recurrent bacterial infections beginning very early in childhood. Congenital neutropenia is related to alloimmunization, sepsis, maternal hypertension, twin-to-twin transfusion syndrome, and Rh hemolytic disease. Diagnosis Neutropenia can be the result of a variety of consequences, including from certain types of drugs, environmental toxins, vitamin deficiencies, metabolic abnormalities, as well as cancer or infections. Neutropenia itself is a rare entity, but can be clinically common in oncology and immunocompromised individuals as a result of chemotherapy (drug-induced neutropenia). Additionally, acute neutropenia can be commonly seen from people recovering from a viral infection or in a post-viral state. Meanwhile, several subtypes of neutropenia exist which are rarer and chronic, including acquired (idiopathic) neutropenia, cyclic neutropenia, autoimmune neutropenia, and congenital neutropenia.Neutropenia that is developed in response to chemotherapy typically becomes evident in seven to fourteen days after treatment, this period is known as the Nadir. Conditions that indicate the presence of neutropenic fever are implanted devices; leukemia induction; the compromise of mucosal, mucociliary and cutaneous barriers; a rapid decline in absolute neutrophil count, duration of neutropenia >7–10 days, and other illnesses that exist in the patient.Signs of infection can be subtle. Fevers are a common and early observation. Sometimes overlooked is the presence of hypothermia, which can be present in sepsis. Physical examination and accessing the history and physical examination is focused on sites of infection. Indwelling line sites, areas of skin breakdown, sinuses, nasopharynx, bronchi and lungs, alimentary tract, and skin are assessed.The diagnosis of neutropenia is done via the low neutrophil count detection on a complete blood count. Generally, other investigations are required to arrive at the right diagnosis. When the diagnosis is uncertain, or serious causes are suspected, bone marrow biopsy may be necessary. A bone marrow biopsy can identify abnormalities in myelopoesis contributing to neutropenia such as the stage of arrest in the development of myeloid progenitor cells. Bone marrow biopsies can also be used to monitor the development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with chronic neutropenia (especially in those with severe congenital neutropenia (SCN) which carries a higher risk of MDS and AML)). Other investigations commonly performed: serial neutrophil counts for suspected cyclic neutropenia, tests for antineutrophil antibodies, autoantibody screen (and investigations for systemic lupus erythematosus), vitamin B12 and folate assays. Rectal examinations are usually not performed due to the increased risk of introducing bacteria into the blood stream and the possible development of rectal abscesses. Classification Generally accepted reference range for absolute neutrophil count (ANC) in adults is 1500 to 8000 cells per microliter (µl) of blood. Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/µl): Mild neutropenia (1000 <= ANC < 1500): minimal risk of infection Moderate neutropenia (500 <= ANC < 1000): moderate risk of infection Severe neutropenia (ANC < 500): severe risk of infection.Each of these are either derived from laboratory tests or via the formula below: ANC = ( % n e u t r o p h i l s + % b a n d s ) × ( W B C ) ( 100 ) {\displaystyle (\%neutrophils+\%bands)\times (WBC) \over (100)} Treatment A fever, when combined with profound neutropenia (febrile neutropenia), is considered a medical emergency and requires broad spectrum antibiotics. An absolute neutrophil count less than 200 is also considered a medical emergency and almost always requires hospital admission and initiation of broad spectrum antibiotics with selection of specific antibiotics based on local resistance patterns.Precautions to avoid opportunistic infections in those with chronic neutropenia include maintaining proper soap and water hand hygiene, good dental hygiene and avoiding highly contaminated sources that may contain a large fungal reservoirs such as mulch, construction sites and bird or other animal waste.Neutropenia can be treated with the hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF). These are cytokines that are present naturally in the body. The factors promote neutrophil recovery following anticancer therapy or in chronic neutropenia. Recombinant G-CSF factor preparations, such as filgrastim can be effective in people with congenital forms of neutropenia including severe congenital neutropenia and cyclic neutropenia; the amount needed (dosage) to stabilize the neutrophil count varies considerably (depending on the individuals condition). Guidelines for neutropenia regarding diet are currently being studied. Those who have chronic neutropenia and fail to respond to G-CSF or who have an increased risk of developing MDS or AML (due to increased dosage requirements of G-CSF or having abnormal precursor cells in the bone marrow) often require hematopoietic stem cell transplantation as a treatment.Most cases of neonatal neutropenia are temporary. Antibiotic prophylaxis is not recommended because of the possibility of encouraging the development of multidrug-resistant bacterial strains.These are cytokines that are present naturally in the body. The factors promote neutrophil recovery following anticancer therapy.The administration of intravenous immunoglobulins (IVIGs) has had some success in treating neutropenias of alloimmune and autoimmune origins with a response rate of about 50%. Blood transfusions have not been effective.Patients with neutropenia caused by cancer treatment can be given antifungal drugs. A Cochrane review found that lipid formulations of amphotericin B had fewer side effects than conventional amphotericin B, though it is not clear whether there are particular advantages over conventional amphotericin B if given under optimal circumstances. Another Cochrane review was not able to detect a difference in effect between amphotericin B and fluconazole because available trial data analysed results in a way that disfavoured amphotericin B. Trilaciclib, a CDK4/6 inhibitor, administered approximately thirty minutes before chemotherapy, has been shown in three clinical trials to significantly reduce the occurrence of chemotherapy-induced neutropenia and the associated need for interventions such as the administration of G-CSFs. The drug is currently under review by the FDA for use in small cell lung cancer with a decision expected by February 15, 2021. Prognosis If left untreated, people with fever and absolute neutrophil count <500 have a mortality of up to 70% within 24 hours. The prognosis of neutropenia depends on the cause. Antibiotic agents have improved the prognosis for individuals with severe neutropenia. Neutropenic fever in individuals treated for cancer has a mortality of 4–30%. Epidemiology Neutropenia is usually detected shortly after birth, affecting 6% to 8% of all newborns in neonatal intensive care units (NICUs). Out of the approximately 600,000 neonates annually treated in NICUs in the United States, 48,000 may be diagnosed as neutropenic. The incidence of neutropenia is greater in premature infants. Six to fifty-eight percent of preterm neonates are diagnosed with this auto-immune disease. The incidence of neutropenia correlates with decreasing birth weight. The disorder is seen up to 38% in infants that weigh less than 1000g, 13% in infants weighing less than 2500g, and 3% of term infants weighing more than 2500 g. Neutropenia is often temporary, affecting most newborns in only first few days after birth. In others, it becomes more severe and chronic indicating a deficiency in innate immunity.Furthermore, the prevalence of chronic neutropenia in the general public is rare. In a study conducted in Denmark, over 370,000 people were assessed for the presence of neutropenia. Results published demonstrated only 1% of those evaluated were neutropenic, and were commonly seen in those with HIV, viral infections, acute leukemias, and myelodysplastic syndromes. The study concluded the presence of neutropenia is an ominous sign that warrants further investigation and follow-up. See also Pancytopenia Thrombocytopenia References == External links ==

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I need a basic explanation for the medical term 'Stiripentol.'

Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder.The most common side effects include loss of appetite, weight loss, insomnia (difficulty sleeping), drowsiness, ataxia (inability to co‑ordinate muscle movements), hypotonia (low muscle strength) and dystonia (muscle disorders). Medical uses In the European Union, stiripentol is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in people with severe myoclonic epilepsy in infancy (SMEI, Dravets syndrome) whose seizures are not adequately controlled with clobazam and valproate.In the United States, stiripentol is indicated for the treatment of seizures associated with Dravet syndrome in people two years of age and older taking clobazam. There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome.It is used in some countries as an add-on therapy with sodium valproate and clobazam for treating children with Dravet syndrome whose seizures are not adequately controlled. As of 2017, it was not known whether stiripentol remains useful as children become adolescents or adults. Contraindications Stiripentol must not be used in people who have had psychoses (a serious mental state with a distorted sense of reality) with attacks of delirium (a mental state with confusion, excitement, restlessness and hallucinations). Adverse effects Very common (more than 10% of people) adverse effects include loss of appetite, weight loss, insomnia, drowsiness, ataxia, hypotonia, and dystonia.Common (between 1% and 10% of people) adverse effects include neutropenia (sometimes severe), aggressiveness, irritability, behavior disorders, opposing behavior, hyperexcitability, sleep disorders, hyperkinesias, nausea, vomiting, and elevated gamma-glutamyltransferase. Interactions Stiripentol inhibits several cytochrome P450 isoenzymes and so interacts with many anticonvulsants and other medicines. Pharmacology As with most anticonvulsants, the precise mechanism of action is unknown. Regardless, stiripentol has been shown to have anticonvulsant effects of its own. Stiripentol increases GABAergic activity. At clinically relevant concentrations, it enhances central GABA neurotransmission through a barbiturate-like effect, since it increases the duration of opening of GABA-A receptor channels in hippocampal slices. It has also been shown to increase GABA levels in brain tissues by interfering with its reuptake and metabolism. Specifically, it has been shown to inhibit lactate dehydrogenase, which is an important enzyme involved in the energy metabolism of neurons. Inhibition of this enzyme can make neurons less prone to fire action potentials, likely through activation of ATP-sensitive potassium channels.Stiripentol also improves the effectiveness of many other anticonvulsants, possibly due to its inhibition of certain enzymes, slowing the drugs metabolism and increasing blood plasma levels. Chemistry Stiripentol is an α-ethylene alcohol; its chemical formula is 4,4-dimethyl-1-[3,4-(methylendioxy)-phenyl]-1penten-3-ol. It is chiral and used medically as the racemate. The R enantiomer appears to be around 2.5 times more active than the S enantiomer. History Stiripentol was discovered in 1978 by scientists at Biocodex and clinical trials started over the next few years. It was originally developed for adults with focal seizures, but failed a Phase III trial.In December 2001, the European Medicines Agency (EMA) granted stiripentol orphan drug status (designation number EU/3/01/071) for the treatment of severe myoclonic epilepsy of infancy (SMEI, also known as Dravets syndrome) in children and in January 2007, the EMA granted the drug a marketing authorisation for use of the drug as an add-on to other anti-seizure drugs. It was approved in Canada for this use in May 2013. As of 2017, it was also approved for this use in Japan.In August 2018, stiripentol was approved by the US Food and Drug Administration (FDA) as an adjunctive therapy for Dravet Syndrome. Society and culture Economics Prior to approval in the US, parents of children with Dravet Syndrome were paying around $1,000 for a month supply to obtain it from Europe. References External links "Stiripentol". Drug Information Portal. U.S. National Library of Medicine.

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I'm trying to understand 'Spinocerebellar ataxia' within a medical context. Could you shed some light on it?

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder. Signs and symptoms Spinocerebellar ataxia (SCA) is one of a group of genetic disorders characterized by slowly progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. A review of different clinical features among SCA subtypes was recently published describing the frequency of non-cerebellar features, like parkinsonism, chorea, pyramidalism, cognitive impairment, peripheral neuropathy, seizures, among others. As with other forms of ataxia, SCA frequently results in atrophy of the cerebellum, loss of fine coordination of muscle movements leading to unsteady and clumsy motion, and other symptoms. The symptoms of an ataxia vary with the specific type and with the individual patient. In many cases a person with ataxia retains full mental capacity but progressively loses physical control. Cause The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Many types of autosomal dominant cerebellar ataxias for which specific genetic information is available are now known. Synonyms for autosomal-dominant cerebellar ataxias (ADCA) used prior to the current understanding of the molecular genetics were Maries ataxia, inherited olivopontocerebellar atrophy, cerebello-olivary atrophy, or the more generic term "spinocerebellar degeneration." (Spinocerebellar degeneration is a rare inherited neurological disorder of the central nervous system characterized by the slow degeneration of certain areas of the brain. There are three forms of spinocerebellar degeneration: Types 1, 2, 3. Symptoms begin during adulthood.) There are five typical autosomal-recessive disorders in which ataxia is a prominent feature: Friedreich ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, ataxia with oculomotor apraxia (AOA), spastic ataxia. Disorder subdivisions: Friedreichs ataxia, Spinocerebellar ataxia, Ataxia telangiectasia, Vasomotor ataxia, Vestibulocerebellar, Ataxiadynamia, Ataxiophemia, and Olivopontocerebellar atrophy. There have been reported cases where a polyglutamine expansion may lengthen when passed down, which often can result in an earlier age-of-onset and a more severe disease phenotype for individuals who inherit the disease allele. This falls under the category of genetic anticipation. Several types of SCA are characterized by repeat expansion of the trinucleotide sequence CAG in DNA that encodes a polyglutamine repeat tract in protein. The expansion of CAG repeats over successive generations appears to be due to slipped strand mispairing during DNA replication or DNA repair. Diagnosis Classification A few SCAs remain unspecified and can not be precisely diagnosed, but in the last decade genetic testing has allowed precise identification of dozens of different SCAs and more tests are being added each year. In 2008, a genetic ataxia blood test developed to test for 12 types of SCA, Friedreichs ataxia, and several others. However, since not every SCA has been genetically identified some SCAs are still diagnosed by neurological examination, which may include a physical exam, family history, MRI scanning of the brain and spine, and spinal tap.Many SCAs below fall under the category of polyglutamine diseases, which are caused when a disease-associated protein (i.e., ataxin-1, ataxin-3, etc.) contains a large number of repeats of glutamine residues, termed a polyQ sequence or a "CAG trinucleotide repeat" disease for either the one-letter designation or codon for glutamine respectively. The threshold for symptoms in most forms of SCA is around 35, though for SCA3 it extends beyond 50. Most polyglutamine diseases are dominant due to the interactions of resulting polyQ tail.The first ataxia gene was identified in 1993 and called "Spinocerebellar ataxia type 1" (SCA1); later genes were called SCA2, SCA3, etc. Usually, the "type" number of "SCA" refers to the order in which the gene was found. At this time, there are at least 29 different gene mutations that have been found.The following is a list of some of the many types of Spinocerebellar ataxia. Others include SCA18, SCA20, SCA21, SCA23, SCA26, SCA28, and SCA29. Four X-linked types have been described ( 302500, 302600, 301790, 301840), but only the first of these has so far been tied to a gene (SCAX1). Treatment Medication There is no cure for spinocerebellar ataxia, which is currently considered to be a progressive and irreversible disease, although not all types cause equally severe disability.In general, treatments are directed towards alleviating symptoms, not the disease itself. Many patients with hereditary or idiopathic forms of ataxia have other symptoms in addition to ataxia. Medications or other therapies might be appropriate for some of these symptoms, which could include tremor, stiffness, depression, spasticity, and sleep disorders, among others. Both onset of initial symptoms and duration of disease are variable. If the disease is caused by a polyglutamine trinucleotide repeat CAG expansion, a longer expansion may lead to an earlier onset and a more radical progression of clinical symptoms. Typically, a person with this disease will eventually be unable to perform daily tasks (ADLs). However, rehabilitation therapists can help patients to maximize their ability of self-care and delay deterioration to certain extent. Researchers are exploring multiple avenues for a cure including RNAi and the use of Stem Cells and several other avenues.On January 18, 2017, BioBlast Pharma announced completion of Phase 2a clinical trials of their medication, Trehalose, in the treatment of SCA3. BioBlast has received FDA Fast Track status and Orphan Drug status for their treatment. The information provided by BioBlast in their research indicates that they hope this treatment may prove efficacious in other SCA treatments that have similar pathology related to PolyA and PolyQ diseases.In addition, Dr. Beverly Davidson has been working on a methodology using RNAi technology to find a potential cure for over 2 decades. Her research began in the mid-1990s and progressed to work with mouse models about a decade later and most recently has moved to a study with non-human primates. The results from her most recent research "are supportive of clinical application of this gene therapy".Finally, another gene transfer technology discovered in 2011 has also been shown by Boudreau et al. to hold great promise and offers yet another avenue to a potential future cure. N-Acetyl-Leucine N-Acetyl-Leucine is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and common neurological disorders by IntraBio Inc (Oxford, United Kingdom).N-Acetyl-Leucine has been granted multiple orphan drug designations from the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of various genetic diseases, including Spinocerebellar Ataxias. N-Acetyl-Leucine has also been granted Orphan Drug Designations in the US and EU for the related inherited cerebellar ataxia Ataxia-Telangiectasia U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA).Published case series studies have demonstrated the effects of acute treatment with N-Acetyl-Leucine for the treatment of inherited cerebellar ataxias, including Spinocerebellar Ataxias. These studies further demonstrated that the treatment is well tolerated, with a good safety profile. A multinational clinical trial investigating N-Acetyl-L-Leucine for the treatment of a related inherited cerebellar ataxia, Ataxia-Telangiectasia, began in 2019.IntraBio is also conducting parallel clinical trials with N-Acetyl-L-Leucine for the treatment of Niemann-Pick disease type C and GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). Future opportunities to develop N-Acetyl-Leucine include Lewy Body Dementia, Amyotrophic lateral sclerosis, Restless Leg Syndrome, Multiple Sclerosis, and Migraine. Rehabilitation Physical therapists can assist patients in maintaining their level of independence through therapeutic exercise programmes. One recent research report demonstrated a gain of 2 SARA points (Scale for the Assessment and Rating of Ataxia) from physical therapy. In general, physical therapy emphasises postural balance and gait training for ataxia patients. General conditioning such as range-of-motion exercises and muscle strengthening would also be included in therapeutic exercise programmes. Research showed that spinocerebellar ataxia 2 (SCA2) patients with a mild stage of the disease gained significant improvement in static balance and neurological indices after six months of a physical therapy exercise training program. Occupational therapists may assist patients with incoordination or ataxia issues through the use of adaptive devices. Such devices may include a cane, crutches, walker, or wheelchair for those with impaired gait. Other devices are available to assist with writing, feeding, and self care if hand and arm coordination are impaired. A randomised clinical trial revealed that an intensive rehabilitation program with physical and occupational therapies for patients with degenerative cerebellar diseases can significantly improve functional gains in ataxia, gait, and activities of daily living. Some level of improvement was shown to be maintained 24 weeks post-treatment. Speech language pathologists may use both behavioral intervention strategies as well as augmentative and alternative communication devices to help patients with impaired speech. References Further reading Nikonishyna, Yuliia V.; et al. (2022). ""Novel CACNA1A Variant p.Cys256Phe Disrupts Disulfide Bonds and Causes Spinocerebellar Ataxia."". Movement Disorders. Movement disorders: official journal of the Movement Disorder Society. 37 (2): 401–404. doi:10.1002/mds.28835. PMID 34647648. S2CID 238859984. External links ataxia at NINDS msa at NINDS opca_doc at NINDS MedlinePlus Encyclopedia: Olivopontocerebellar atrophy Spinocerebellar ataxia 27 at NIHs Office of Rare Diseases Spinocerebellar ataxia dysmorphism at NIHs Office of Rare Diseases

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm looking for a concise explanation of the medical term 'Dermatitis repens.'

Dermatitis repens (also known as Acrodermatitis continua,: 1026  Acrodermatitis perstans, Pustular acrodermatitis, Acrodermatitis continua of Hallopeau, Acrodermatitis continua suppurativa Hallopeau, Hallopeaus acrodermatitis, Hallopeaus acrodermatitis continua, and Dermatitis repens Crocker) is a rare, sterile, pustular eruption of the fingers and toes that slowly extends proximally.: 1026 : 631 : 195 See also List of cutaneous conditions François Henri Hallopeau Psoriasis Skin lesion == References ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm encountering the term 'Nevus comedonicus' in medical literature. What's its definition?

Nevus comedonicus (also known as a comedo nevus) is characterized by closely arranged, grouped, often linear, slightly elevated papules that have at their center keratinous plugs resembling comedones.: 634 : 774 See also Nevus comedonicus syndrome Skin lesion List of cutaneous conditions == References ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

Can you demystify the medical term 'Sitosterolemia' for me?

Sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder. It is characterized by hyperabsorption and decreased biliary excretion of dietary sterols (including the plant phytosterol beta-sitosterol). Healthy persons absorb only about 5% of dietary plant sterols, but sitosterolemia patients absorb 15% to 60% of ingested sitosterol without excreting much into the bile. The phytosterol campesterol is more readily absorbed than sitosterol.Sitosterolemia patients develop hypercholesterolemia, tendon and tuberous xanthomas, premature development of atherosclerosis, and abnormal hematologic and liver function test results. Signs and symptoms Sitosterolemia may share several clinical characteristics with the well-characterized familial hypercholesterolemia (FH), such as the development of tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis. However, in contrast to FH patients, sitosterolemia patients usually have normal to moderately elevated total sterol levels and very high levels of plant sterols (sitosterol, campesterol, stigmasterol, avenosterol) and 5α-saturated stanols in their plasma. Plasma sitosterol levels in sitosterolemia patients are 10–25 times higher than in normal individuals (8–60 mg/dl). Not all patients with sitosterolemia have tendon xanthomas, thus absence of this should not be used to exclude this diagnosis. Xanthomas may appear at any age, even in childhood. These may be present as subcutaneous xanthomas on the buttocks in children or in usual locations (e.g., Achilles tendon, extensor tendons of the hand) in children and adults. Xanthelasma and corneal arcus are less common. Decreased range of motion with possible redness, swelling, and warmth of joints due to arthritis may be present. In addition, sitosterolemia patients may develop hemolytic episodes and splenomegaly. Untreated, the condition causes a significant increase in morbidity and mortality. Coronary heart disease and its inherent health consequences are the primary causes of illness and premature death in untreated patients. Pathogenesis Mammalian cells cannot use plant sterols. Normally, plant sterols are poorly absorbed from the gastrointestinal tract; fewer than 5% of plant sterols are absorbed compared to approximately 40% of cholesterol absorbed. The liver preferentially excretes plant sterols over cholesterol. Dietary sterols have recently been shown to passively enter intestinal cells, and subsequently the vast majority are pumped back into the gut lumen by ATP-binding cassette transporter (ABC transporter) proteins. Sitosterolemia is inherited as a rare autosomal recessive condition. It has been shown to result from mutations in either of two adjacent and oppositely oriented genes (ABCG5 and ABCG8) located in chromosome 2 in band 2p21 and encode for ABC transporter proteins named sterolin-1 and sterolin-2, respectively. Thus, the active pumping back into the intestine of passively absorbed plant sterols is disrupted, and hepatic secretion of the resultant accumulation of these sterols is decreased. The ability of the liver to preferentially excrete plant sterols into the bile is apparently impaired. While bile acid synthesis remains the same as in healthy people, the total excretion of sterols in the bile is reportedly less than 50% in subjects with sitosterolemia compared to control subjects. The mechanism for decreased hepatic secretion is unknown. Patients have markedly reduced whole-body cholesterol biosynthesis associated with suppressed hepatic, ileal, and mononuclear leukocyte hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-controlling enzyme in the cholesterol biosynthetic pathway. Whether or not the down-regulation is due to accumulated sitosterol is still debatable, but most recent data indicate that secondary effects of unknown regulators other than sitosterol can lead to reduced HMG-CoA reductase activity in the disease. This is coupled with significantly increased low-density lipoprotein (LDL) receptor expression. Diagnosis Diagnosis is made by measuring serum plant sterol concentrations. Treatment The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone. If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins. Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe. Epidemiology Around 80 cases have been reported in the literature worldwide, hence this condition appears to be relatively rare. More than likely, sitosterolemia is significantly underdiagnosed and many patients are probably misdiagnosed with hyperlipidemia. See also ABCG5 and ABCG8 Genes Cerebrotendinous xanthomatosis Notes References Lee M, Lu K, Patel SB (2001). "Genetic basis of sitosterolemia". Current Opinion in Lipidology. 12 (2): 141–149. doi:10.1097/00041433-200104000-00007. PMC 1350992. PMID 11264985. Steiner R D. Sitosterolemia .[online] Available from : http://www.emedicine.com/ped/topic2110.htm [Accessed :12 July 2006] Bazerbachi F.; et al. (2017). "Cryptogenic Cirrhosis and Sitosterolemia: A Treatable Disease If Identified but Fatal If Missed". Annals of Hepatology. 16 (6): 970–978. doi:10.5604/01.3001.0010.5290. PMID 29055934. == External links ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

What does the medical term 'Mirtazapine' encompass?

Mirtazapine, sold under the brand name Remeron amongst others, is an atypical antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is often used in cases of depression complicated by anxiety or insomnia. The effectiveness of Mirtazapine is comparable to other commonly prescribed antidepressants. It is taken by mouth.Common side effects include sleepiness, dizziness, increased appetite and weight gain. Serious side effects may include mania, low white blood cell count, and increased suicide among children. Withdrawal symptoms may occur with stopping. It is not recommended together with an MAO inhibitor, although evidence supporting the danger of this combination has been refuted. It is unclear if use during pregnancy is safe. How it works is not clear, but it may involve blocking certain adrenergic and serotonin receptors. Chemically, it is a tetracyclic antidepressant (TeCA), and is closely related to mianserin. It also has strong antihistaminergic effects.Mirtazapine came into medical use in the United States in 1996. The patent expired in 2004, and generic versions are available. In 2019, it was the 106th most commonly prescribed medication in the United States, with more than 6 million prescriptions. Medical uses Depression Mirtazapine is primarily used for major depressive disorder and other mood disorders. Onset of action appears faster than some selective serotonin reuptake inhibitors (SSRI) and similar to tricyclic antidepressants.In 2010, NICE recommended generic SSRIs as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio." With respect to mirtazapine, it found: "There is no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over selective serotonin reuptake inhibitors in terms of reducing symptoms of depression, but the difference is not clinically significant. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason."A 2011 Cochrane review that compared mirtazapine to other antidepressants found that, while it appears to have a faster onset in people for whom it works (measured at two weeks), its efficacy is about the same as other antidepressants after six weeks use.A 2012 review focused on antidepressants and sleep found that in many people with sleep disorders caused by depression, mirtazapine reduces the time it takes to fall asleep and increases the quality of sleep, but that in some people it can disturb sleep, especially at higher doses, causing restless leg syndrome in 8 to 28% of people and in rare cases causes REM sleep behavior disorder. This seemingly paradoxical dose–response curve of mirtazapine with respect to somnolence is owed to the exceptionally high affinity of the drug for the histamine H1, 5-HT2A, and 5-HT2C receptors; exhibiting near exclusive occupation of these receptors at doses ≤15 mg. However, at higher doses, inverse antagonism and constitutive activation of the α2A-, α2B-, and α2C-adrenergic receptors begins to offset activity at H1 receptors leading to decreased somnolence and even a subjective sensation of "activation" in treated patients.A 2018 analysis of 21 antidepressants found them to be fairly similar overall. It found tentative evidence for mirtazapine being in the more effective group and middle in tolerability.After one week of usage, mirtazapine was found to have an earlier onset of action compared to SSRIs. Other There is also some evidence supporting its use in treating the following conditions, for which it is sometimes prescribed off-label: Doses of mirtazapine used for sleep range from 7.5 to 45 mg. Doses of 7.5 to 15 mg are recommended as mirtazapine may become more stimulating at higher doses. Side effects A 2011 Cochrane review found that, compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite (17%) and weight gain (>7% increase in <50% of children).Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, fasciculations (muscle twitches), peripheral edema (swelling, usually of the lower limbs), and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them. (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.) In general, some antidepressants, especially selective serotonin reuptake inhibitors (SSRI), can paradoxically exacerbate some peoples depression or anxiety or cause suicidal ideation. Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects, especially for people under the age of 25.Mirtazapine may induce arthralgia (non-inflammatory joint pain)A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.In a study comparing 32 antidepressants of all pharmacological classes, mirtazapine was one of the antidepressants most likely to cause nightmare disorder, sleepwalking, restless legs syndrome, night terrors and sleep paralysis.Mirtazapine has been associated with an increased risk of death compared to other antidepressants in several studies. However, it is more likely that the residual differences between people prescribed mirtazapine rather than an SSRI account for the difference in risk of mortality. Withdrawal Mirtazapine and other antidepressants may cause withdrawal symptoms upon cessation. A gradual and slow reduction in dose is recommended to minimize withdrawal symptoms. Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, tinnitus, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms, allergy-like symptoms such as pruritus, headaches, and sometimes mania or hypomania. Overdose Mirtazapine is considered to be relatively safe in the event of an overdose, although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram). Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose. Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.Twelve reported fatalities have been attributed to mirtazapine overdose. The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs. Interactions Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism. As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them. Liver impairment and moderate chronic kidney disease have been reported to decrease the oral clearance of mirtazapine by about 30%; severe kidney disease decreases it by 50%.Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically, with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel". Several case reports document serotonin syndrome induced by the combination of mirtazapine with other agents (olanzapine, quetiapine, tramadol and venlafaxine). According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor (MAOI) usage; likewise, MAOIs should not be administered within two weeks of discontinuing mirtazapine.The addition of mirtazapine to a monoamine oxidase inhibitor (MAOI), while potentially having typical or idiosyncratic (unique to the individual) reactions not herein described, does not appear to cause serotonin syndrome. This is in accordance with the fact that the 5-HT2A receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT1A receptor seeming to be protective). Mirtazapine is a potent 5-HT2A receptor antagonist, and cyproheptadine, a medication that shares this property, mediates recovery from serotonin syndrome and is an antidote against it.There is a possible interaction that results in a hypertensive crisis when mirtazapine is given to a patient that has already been on steady doses of clonidine. This involves a subtle consideration, when patients have been on chronic therapy with clonidine and suddenly stop the dosing, a rapid hypertensive rebound sometimes (20%) occurs from increased sympathetic outflow. Clonidines blood pressure lowering effects are due to stimulation of presynaptic α2 autoreceptors in the CNS which suppress sympathetic outflow. Mirtazapine itself blocks these same α2 autoreceptors, so the effect of adding mirtazapine to a patient stabilized on clonidine may precipitate withdrawal symptoms. Pharmacology Pharmacodynamics Mirtazapine is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA), although the actual evidence in support of this label has been regarded as poor. It is a tetracyclic piperazine-azepine.Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity. It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and the histamine H1 receptor. Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine, nor does it inhibit monoamine oxidase. Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most TCAs. In accordance, it has better tolerability and low toxicity in overdose. As an H1 receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the TCAs and TeCAs. Antagonism of the H1 receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H1 receptor antagonist at low concentrations.The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT2A and 5-HT2C receptors, while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT3 receptor. Both enantiomers are involved in antagonism of the H1 and α2-adrenergic receptors, although the (S)-(+) enantiomer is the stronger antihistamine.Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC50 = 7.2 μM). α2-Adrenergic receptor Antagonism of the α2-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT1A receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapines classification as a NaSSA. Indirect α1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α2 heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1A receptor. Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs. 5-HT2 receptor Antagonism of the 5-HT2 subfamily of receptors and inverse agonism of the 5-HT2C receptor appears to be in part responsible for mirtazapines efficacy in the treatment of depressive states. Mirtazapine increases dopamine release in the prefrontal cortex. Accordingly, it was shown that by blocking the α2-adrenergic receptors and 5-HT2C receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats. In addition, mirtazapines antagonism of 5-HT2A receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor. Mirtazapine has been shown to lower drug seeking behaviour (more specifically to methamphetamine) in various human and animal studies. It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.Mirtazapine significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in affected individuals. Mirtazapine may be used as an inexpensive antiemetic alternative to Ondansetron. In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success. In contrast to mirtazapine, the selective serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), Monoamine oxidase inhibitors (MAOI), and some Tricyclic antidepressants (TCA) increase the general activity of the 5-HT2A, 5-HT2C, and 5-HT3 receptors leading to a host of negative changes and side effects, the most prominent of which including anorexia, insomnia, nausea, and diarrhea, among others. Its reduced incidence of sexual dysfunction (such as loss of libido and anorgasmia) could be a product of negligible binding to the serotonin transporter (as is generally the cause of sexual dysfunction with most SSRIs) and antagonism of the 5-HT2A receptors; however, Mirtazapines high affinity towards and inverse agonism of the 5-HT2C receptors may greatly attenuate those pro-sexual factors (as evidenced by the pro-sexual effects of drugs like m-CPP and Lorcaserin which agonize 5-HT2C receptors in a reasonably selective manner). As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.Mirtazapine does not have pro-serotonergic activity and thus does not cause serotonin syndrome. This is in accordance with the fact that it is not a serotonin reuptake inhibitor or monoamine oxidase inhibitor (MAOI), nor a serotonin receptor agonist. There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose. However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like SSRIs, although such reports are very rare, and do not necessarily implicate mirtazapine as causative. 5-HT3 receptor It is a potent 5-HT3 blocker. It may relieve chemotherapy-related and advanced cancer-related nausea. H1 receptor Mirtazapine is a very strong H1 receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects. A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H1 receptor and to induce intense sleepiness. After a short period of chronic treatment, however, the H1 receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H1 receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in affected individuals. It may also contribute to weight gain, however. In contrast to the H1 receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors, although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice. Pharmacokinetics The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes, CYP1A2, CYP2D6, CYP3A4. One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. It is conjugated in the kidney for excretion in the urine, where 75% of the drug is excreted, and about 15% is eliminated in feces.: 430 Chemistry Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings.: 429  It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine. Analogues of mirtazapine include mianserin, setiptiline, and aptazapine. Synthesis A chemical synthesis of mirtazapine has been published. The first step of synthesis is a condensation reaction between the molecule 2-chloro 3-cyanopyridine and the molecule 1-methyl-3-phenylpiperazine. History Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron.: 429 Society and culture Generic names Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN. Its generic name in Spanish, Italian and Portuguese is mirtazapina and in German and Swedish is Mirtazapin. Brand names Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Axit, Azapin, Beron, Bilanz, Blumirtax, Calixta, Ciblex, Combar, Comenter, Depreram, Divaril, Esprital, Maz, Menelat, Mepirzapine, Merdaten, Meronin, Mi Er Ning, Milivin, Minelza, Minivane, Mirastad, Mirazep, Miro, Miron, Mirrador, Mirt, Mirta, Mirtabene, Mirtadepi, Mirtagamma, Mirtagen, Mirtalan, Mirtamor, Mirtamylan, Mirtan, Mirtaneo, Mirtapax, Mirtapil, Mirtapine, Mirtaron, Mirtastad, Mirtax, Mirtaz, Mirtazap, Mirtazapin, Mirtazapina, Mirtazapine, Mirtazapinum, Mirtazelon, Mirtazon, Mirtazonal, Mirtel, Mirtimash, Mirtin, Mirtine, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Rapizapine, Ramure, Razapina, Redepra, Reflex, Remergil, Remergon, Remeron, Remirta, Rexer, Saxib, Sinmaron, Smilon, Tazepin, Tazimed, Tetrazic, Tifona, U-Mirtaron, U-zepine, Valdren, Vastat, Velorin, Yarocen, Zania, Zapex, Zestat, Zismirt, Zispin, Zuleptan, and Zulin. Research The use of mirtazapine has been explored in several additional conditions: Sleep apnea/hypopnea Secondary symptoms of autistic spectrum conditions and other pervasive developmental disorders Antipsychotic-induced akathisia. Drug withdrawal, dependence and detoxification Negative, depressive and cognitive symptoms of schizophrenia (as an adjunct) A case report has been published in which mirtazapine reduced visual hallucinations in a patient with Parkinsons disease psychosis (PDP). This is in alignment with recent findings that inverse agonists at the 5-HT2A receptors are efficacious in attenuating the symptoms of Parkinsons disease psychosis. As is supported by the common practice of prescribing low-dose quetiapine and clozapine for PDP at doses too low to antagonize the D2 receptor, but sufficiently high doses to inversely agonize the 5-HT2A receptors. Eight case reports have been reported in five papers on the use of mirtazapine in the treatment of hives as of 2017. Veterinary use Mirtazapine also has some veterinary use in cats and dogs. Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing loss of appetite due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.Mirtazapine is indicated for bodyweight gain in cats experiencing poor appetite and weight loss resulting from chronic medical conditions.There are two options for administration: tablets given orally, and an ointment applied topically to the inner surface of the ear.The most common side effects include signs of local irritation or inflammation at the site where the ointment is applied and behavioural changes (increased meowing, hyperactivity, disoriented state or inability to co-ordinate muscle movements, lack of energy/weakness, attention-seeking, and aggression). References External links "Mirtazapine". Drug Information Portal. U.S. National Library of Medicine.

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

Can you break down the meaning of the medical term 'Cryptosporidiosis' for me?

Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by Cryptosporidium, a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in both immunocompetent (i.e., individuals with a normal functioning immune system) and immunocompromised (e.g., persons with HIV/AIDS or autoimmune disorders) individuals, resulting in watery diarrhea with or without an unexplained cough. In immunosuppressed individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through the fecal-oral route, often through contaminated water; recent evidence suggests that it can also be transmitted via fomites contaminated with respiratory secretions.Cryptosporidium is commonly isolated in HIV-positive patients presenting with diarrhea. Despite not being identified until 1976, it is one of the most common waterborne diseases and is found worldwide. The infection begins when a human consumes food or water containing cysts of the Cryptosporidium organism. Signs and symptoms Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), as recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and as a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent. It may be fatal in individuals with a severely compromised immune system. Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals; symptoms are usually more severe and persist longer in immunocompromised individuals. Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection. The likelihood of re-infection is high in immunocompromised adults, and low in those with normal immune systems.In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well. In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder; pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis. Intestinal cryptosporidiosis Common signs and symptoms of intestinal cryptosporidiosis include: Moderate to severe watery diarrhea, sometimes contains mucus and rarely contains blood or leukocytesIn very severe cases, diarrhea may be profuse and cholera-like with malabsorption and hypovolemia Low-grade fever Crampy abdominal pain Dehydration Weight loss Fatigue Nausea and vomiting – suggests upper GI tract involvement and may lead to respiratory cryptosporidiosis Epigastric or right upper quadrant tendernessLess common or rare signs and symptoms include: Reactive arthritis (may affect the hands, knees, ankles, and feet) Jaundice – suggests hepatobiliary involvement Ascites – suggests pancreatic involvement Respiratory cryptosporidiosis Symptoms of upper respiratory cryptosporidiosis include: Inflammation of the nasal mucosa, sinuses, larynx, or trachea Nasal discharge Voice change (e.g., hoarseness)Symptoms of lower respiratory cryptosporidiosis include: Cough Shortness of breath Fever Hypoxemia Reason Cryptosporidium is a genus of protozoan pathogens which is categorized under the phylum Apicomplexa. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. A number of Cryptosporidium infect mammals. In humans, the main causes of disease are C. parvum and C. hominis (previously C. parvum genotype 1). C. canis, C. felis, C. meleagridis, and C. muris can also cause disease in humans. Cryptosporidium is capable of completing its life cycle within a single host, resulting in microbial cyst stages that are excreted in feces and are capable of transmission to a new host via the fecal-oral route. Other vectors of disease transmission also exist.The pattern of Cryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborder Eimeriina: macro- and microgamonts develop independently; a microgamont gives rise to numerous male gametes; and oocysts serving for parasites spreading in the environment. Electron microscopic studies made from the 1970s have shown the intracellular, although extracytoplasmic localization of Cryptosporidium species.These species possess a number of unusual features: an endogenous phase of development in microvilli of epithelial surfaces two morphofunctional types of oocysts the smallest number of sporozoites per oocyst a multi-membraneous "feeder" organelleDNA studies suggest a relationship with the gregarines rather than the coccidia. The taxonomic position of this group has not yet been finally agreed upon. The genome of Cryptosporidium parvum was sequenced in 2004 and was found to be unusual amongst Eukaryotes in that the mitochondria seem not to contain DNA. A closely related species, C. hominis, also has its genome sequence available. CryptoDB.org is a NIH-funded database that provides access to the Cryptosporidium genomics data sets. Transfer Infection is through contaminated material such as earth, water, uncooked or cross-contaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces. The high resistance of Cryptosporidium oocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective. Some outbreaks have happened in day care related to diaper changes.The following groups have an elevated risk of being exposed to Cryptosporidium: Child care workers Parents of infected children People who take care of other people with cryptosporidiosis International travelers Backpackers, hikers, and campers who drink unfiltered, untreated water People, including swimmers, who swallow water from contaminated sources People who handle infected cattle People exposed to human feces through sexual contactCases of cryptosporidiosis can occur even in cities that have a properly de-contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have other origins. Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. Cryptosporidium is causing serious illness more frequently in immunocompromised than in apparently healthy individuals. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviors can transmit the parasite directly. Life cycle Cryptosporidium spp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage). As an oocyst – a type of hardy, thick-walled spore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants. After being ingested, the sporozoites within oocysts excyst (i.e., are released) in the small intestine. The released sporozoites subsequently attach to the microvilli of the epithelial cells of the small intestine. From there they become trophozoites that reproduce asexually by multiple fission, a process known as schizogony. The trophozoites develop into Type 1 meronts [1] that contain 8 daughter cells.These daughter cells are Type 1 merozoites, which get released by the meronts. Some of these merozoites can cause autoinfection by attaching to epithelial cells. Others of these merozoites become Type II meronts, which contain 4 Type II merozoites. These merozoites get released and they attach to the epithelial cells. From there they become either macrogamonts or microgamonts. These are the female and male sexual forms, respectively. This stage, when sexual forms arise, is called gametogony.Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts. The zygotes develop into oocysts of two types. 20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again. The thick-walled oocysts are excreted into the environment. The oocysts are mature and infective upon being excreted. Pathogenesis The oocysts are ovoid or spherical and measure 5 to 6 micrometers across. When in flotation preparations they appear highly refractile. The oocysts contains up to 4 sporozoites that are bow-shaped.As few as 2 to 10 oocysts can initiate an infection. The parasite is located in the brush border of the epithelial cells of the small intestine. They are mainly located in the jejunum. When the sporozoites attach the epithelial cells membrane envelops them. Thus, they are "intracellular but extracytoplasmic". The parasite can cause damage to the microvilli where it attaches. The infected human excretes the most oocysts during the first week. Oocysts can be excreted for weeks after the diarrhea subsides from infections by C. parvum or C. hominis; however, immunocompetent individuals with C. muris infections have been observed excreting oocysts for seven months.The immune system reduces the formation of Type 1 merozoites as well as the number of thin-walled oocysts. This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite. Previous infection in immunocompetent individuals produces little resistance to future infection, however it may decrease the severity of disease and the number of oocysts excreted. Diagnosis There are many diagnostic tests for Cryptosporidium. They include microscopy, staining, and detection of antibodies. Microscopy can help identify oocysts in fecal matter. To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples. There are several techniques to concentrate either the stool sample or the oocysts. The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool. Both the modified zinc sulfate centrifugal flotation technique and the Sheathers sugar flotation procedure can concentrate the oocysts by causing them to float. Another form of microscopy is fluorescent microscopy done by staining with auramine.Other staining techniques include acid-fast staining, which will stain the oocysts red. One type of acid-fast stain is the Kinyoun stain. Giemsa staining can also be performed. Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.Detecting antigens is yet another way to diagnose the disease. This can be done with direct fluorescent antibody (DFA) techniques. It can also be achieved through indirect immunofluorescence assay. Enzyme-linked immunosorbent assay (ELISA) also detects antigens.Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis. It can even identify the specific species of Cryptosporidium. If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique is ultrasonography. If that returns normal results, the next step would be to perform endoscopic retrograde cholangiopancreatography. Prevention Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. This involves a series of processes, including coagulation, flocculation, sedimentation, and filtration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration, but not sedimentation. Other common filtration processes, including slow sand filters, diatomaceous earth filters and membranes will remove 99% of Cryptosporidium. Membranes and bag and cartridge filters remove Cryptosporidium product-specifically.While Cryptosporidium is highly resistant to chlorine disinfection, with high enough concentrations and contact time, Cryptosporidium will be inactivated by chlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to control Cryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivate Cryptosporidium. Water Research Foundation-funded research originally discovered UVs efficacy in inactivating Cryptosporidium.One of the largest challenges in identifying outbreaks is the ability to identify Cryptosporidium in the laboratory. Real-time monitoring technology is now able to detect Cryptosporidium with online systems, unlike the spot and batch testing methods used in the past.The most reliable way to decontaminate drinking water that may be contaminated by Cryptosporidium is to boil it.In the US the law requires doctors and labs to report cases of cryptosporidiosis to local or state health departments. These departments then report to the Center for Disease Control and Prevention. The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation. An example would be hand-washing. Prevention is through washing hands carefully after going to the bathroom or contacting stool, and before eating. People should avoid contact with animal feces. They should also avoid possibly contaminated food and water. In addition, people should refrain from engaging in sexual activities that can expose them to feces.Standard water filtration may not be enough to eliminate Cryptosporidium; boiling for at least 1 minute (3 minutes above 6,500 feet (2,000 m) of altitude) will decontaminate it. Heating milk at 71.7 °C (161 °F) for 15 seconds pasteurizes it and can destroy the oocysts ability to infect. Water can also be made safe by filtering with a filter with pore size not greater than 1 micrometre, or by filters that have been approved for "cyst removal" by NSF International National Sanitation Foundation. Bottled drinking water is less likely to contain Cryptosporidium, especially if the water is from an underground source.People with cryptosporidiosis should not swim in communal areas because the pathogen can reside in the anal and genital areas and be washed off. They should wait until at least two weeks after diarrhea stops before entering public water sources, since oocysts can still be shed for a while. Also, they should stay away from immunosuppressed people. Immunocompromised people should take care to protect themselves from water in lakes and streams. They should also stay away from animal stools and wash their hands after touching animals. To be safe, they should boil or filter their water. They should also wash and cook their vegetables.The US CDC notes the recommendation of many public health departments to soak contaminated surfaces for 20 minutes with a 3% hydrogen peroxide (99% kill rate) and then rinse them thoroughly, with the caveat that no disinfectant is guaranteed to be completely effective against Cryptosporidium. However, hydrogen peroxide is more effective than standard bleach solutions. Treatment Symptomatic treatment primarily involves fluid rehydration, electrolyte replacement (sodium, potassium, bicarbonate, and glucose), and antimotility agents (e.g., loperamide). Supplemental zinc may improve symptoms, particularly in recurrent or persistent infections or in others at risk for zinc deficiency. Immunocompetent Immunocompetent individuals with cryptosporidiosis typically experience a short (i.e., duration of less than 2 weeks) self-limiting course of diarrhea that may require symptomatic treatment and ends with spontaneous recovery; in some circumstances, antiparasitic medication may be required (e.g., recurrent, severe, or persistent symptoms); however reinfection frequently occurs.As of 2015, nitazoxanide is the only antiparasitic drug treatment with proven efficacy for cryptosporidiosis in immunocompetent individuals; however, it lacks efficacy in severely immunocompromised patients. Certain agents such as paromomycin and azithromycin are sometimes used as well, but they only have partial efficacy. Immunocompromised In immunocompromised individuals, such as AIDS patients, cryptosporidiosis resolves slowly or not at all, and frequently causes a particularly severe and persistent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. As a result, infected individuals may experience severe dehydration, electrolyte imbalances, malnutrition, wasting, and potentially death. In general, the mortality rate for infected AIDS patients is based on CD4+ marker counts. Patients with CD4+ counts over 180 cells/mm³ recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within 3 to 6 months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4+ counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.The best treatment approach is to improve the immune status in immunodeficient individuals using highly active antiretroviral therapy that includes an HIV protease inhibitor along with continued use of antiparasitic medication. Antiparasitic drug treatment for immunocompromised individuals usually involves the combination of nitazoxanide, paromomycin, and azithromycin together; these drugs are only partially active in HIV/AIDS patients compared to their effect in immunocompetent persons. A Cochrane Collaboration review recommended that nitazoxanide be considered for use in treatment despite its reduced effectiveness in immunocompromised individuals.Currently, research is being done in molecular-based immunotherapy. For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum both in vitro and in animal studies. Derivates of nitazoxanide, known as thiazolides, have also shown promising results in vitro. rifaximin is also sometimes used for immunocompromised patients/patients with severe disease. Epidemiology Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites. In developing countries, 8–19% of diarrheal diseases can be attributed to Cryptosporidium. Ten percent of the population in developing countries excretes oocysts. In developed countries, the number is lower at 1–3%. The age group most affected are children from 1 to 9 years old.In Eastern Europe cryptosporidiosis in humans and animals is common, but there are considerable gaps in surveillance and a lack of comparable methods which is limit the understanding of the disease and detection of outbreaks. Research show a rich diversity of zoonotic subtypes of the parasite in animals indicating a rich potential of animal to human transmission. Roughly 30% of adults in the United States are seropositive for cryptosporidiosis, meaning that they contracted the infection at some point in their lives. History The organism was first described in 1907 by Tyzzer, who recognised it was a coccidian. Research A recombinant Cryptosporidium parvum oocyst surface protein (rCP15/60) vaccine has produced an antibody response in a large group of cows and also antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. This is very promising. Human Cryptosporidium parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDS patients. There is no commercially available effective vaccine against Cryptosporidium parvum, although passive immunization utilizing different zoite surface (glyco)proteins has shown promise. Developmental stages of the life cycle of the parasite might act as possible targets for vaccine development. The organism is detected in 65–97% of the surface-water supply in the United States and is resistant to most disinfectants used for the treatment of drinking water. Antibodies in the serum of humans and animals infected with Cryptosporidium parvum react with several antigens, one of which is a 15 kDa protein (CP15) located on the surface of the organism. This protein is a good candidate for use as a molecular vaccine because previous studies have shown that a monoclonal antibody to CP15 confers passive immunity to mice. Currently, there is no vaccine or completely effective drug therapy against Cryptosporidium parvum in HIV/AIDS individuals.A summary of discoveries presented at the most recent (June 2019) international symposium on Cryptosporidium has been published in 2020. Other animals The most important zoonotic reservoirs are cattle, sheep and goats. In addition, in recent years, cryptosporidiosis has plagued many commercial leopard gecko breeders. Several species of the Cryptosporidium family (C. serpentes and others) are involved, and outside of geckos it has been found in monitor lizards, iguanas and tortoises, as well as several snake species. Notable cases Before 2000 In 1987, 13,000 people in Carrollton, Georgia, United States, became ill with cryptosporidiosis. This was the first report of its spread through a municipal water system that met all state and federal drinking water standards. In 1993, a waterborne cryptosporidiosis outbreak occurred in Milwaukee, Wisconsin, US. An estimated 403,000 people became ill, including 4,400 people hospitalized. The source of the Cryptosporidium is believed to be overflow from the Milwaukee area combined sanitary and storm sewer system into Lake Michigan, which was then taken into the Howard Avenue Water Purification Plant and distributed to an estimated 880,000 residents (of the 1.61 million residents in the Milwaukee area who receive their drinking water from Lake Michigan). These residents, who receive their drinking water from Lake Michigan, were told to boil their water before drinking it. More people were affected in this one outbreak than the combined number of people affected in every cryptosporidiosis outbreak in the 24 years since then. An estimated 69 people died during the outbreak, according to the CDC. The UKs biggest outbreak occurred in Torbay in Devon in 1995. In the summer of 1996, Cryptosporidium affected approximately 2,000 people in Cranbrook, British Columbia, Canada. Weeks later, a separate incident occurred in Kelowna, British Columbia, where 10,000 to 15,000 people got sick. 2001–2009 In April 2001, an outbreak occurred in the city of North Battleford, Saskatchewan, Canada. Between 5800 and 7100 people had diarrheal illness, and 1907 cases of cryptosporidiosis were confirmed. Equipment failures at the citys antiquated water filtration plant following maintenance were found to have caused the outbreak. In the summer of 2005, after numerous reports by patrons of gastrointestinal upset, a water park at Seneca Lake State Park, in the Finger Lakes region of upstate New York was found to have two water storage tanks infected with Cryptosporidium. By early September 2005, over 3,800 people reported symptoms of a Cryptosporidium infection. The "Sprayground" was ordered closed for the season on 15 August. In October 2005, the Gwynedd and Anglesey areas of North Wales, the United Kingdom, suffered an outbreak of cryptosporidiosis. The outbreak may have been linked to the drinking water supply from Llyn Cwellyn, but this is not yet confirmed. As a result, 231 people fell ill and the company Welsh Water (Dwr Cymru) advised 61,000 people to boil their water before use. In March 2007, a suspected outbreak occurred in Galway, Ireland, after the source of water for much of the county, Lough Corrib, was suspected to be contaminated with the parasite. A large population (90,000 people), including areas of both Galway City and County, were advised to boil water for drinking, food preparation and for brushing teeth. On 21 March 2007, it was confirmed that the city and countys water supply was contaminated with the parasite. The areas water supply was finally given approval on 20 August 2007, five months after Cryptosporidium was first detected. Around 240 people are known to have contracted the disease; experts say the true figure could be up to 5,000. Hundreds of public pools in 20 Utah counties were closed to young children in 2007, as children under 5 are most likely to spread the disease, especially children wearing diapers. As of 10 September 2007 the Utah Department of Health had reported 1302 cases Archived 25 September 2007 at the Wayback Machine of cryptosporidiosis in the year; a more usual number would be 30. On 25 September the pools were reopened to those not requiring diapers, but hyperchlorination requirements were not lifted. On 21 September 2007, a Cryptosporidium outbreak attacked the Western United States: 230 Idaho residents, with hundreds across the Rocky Mountain area; in the Boise and Meridian areas; Utah, 1,600 illnesses; Colorado and other Western states — Montana, decrease. On 25 June 2008, Cryptosporidium was found in England in water supplies in Northampton, Daventry, and some surrounding areas supplied from the Pitsford Reservoir, as reported on the BBC. People in the affected areas were warned not to drink tap water unless it had been boiled. Anglian Water confirmed that 108,000 households were affected, about 250,000 people. They advised that water might not be fit for human consumption for many weeks. The boil notice was lifted for all the affected customers on 4 July 2008. Throughout the summer of 2008; many public swimming areas, water parks, and public pools in the Dallas/Fort Worth Metroplex of Texas suffered an outbreak of cryptosporidiosis. Burgers Lake in Fort Worth was the first to report such an outbreak. This prompted some, if not all, city-owned and private pools to close and hyperchlorinate. To the 13 August 2008 there were 400 reported cases of Cryptosporidium. In September 2008, a gym in Cambridge, the United Kingdom, was forced to close its swimming pool until further notice after health inspectors found an outbreak of cryptosporidiosis. Environmental Health authorities requested that the water be tested after it was confirmed that a young man had been infected. 2010 and later In May 2010, the Behana creek water supply south of Cairns, Australia, was found to be contaminated by cryptosporidium. In July 2010, a local sports center in Cumbernauld (Glasgow, UK) detected traces of cryptosporidium in its swimming pools, causing a temporary closure of the swimming pools. In November 2010, over 4000 cases of cryptosporidiosis were reported in Östersund, Sweden. The source of contamination was the tap water. In mid December 2010 the number of reported cases was 12,400 according to local media. As of April 2011, there has been an ongoing outbreak in Skellefteå, Sweden. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Several tests have been taken around the water treatment unit "Abborren", but so far no results have turned up positive. Residents are being advised to boil the tap water as they continue to search for the contaminating source. Since May 2011, there has been an ongoing outbreak in South Roscommon in Ireland. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Testing continues and Roscommon County Council are now considering introducing Ultra Violet Filtration to their water treatment process in the next 12 months. Residents are being advised to boil the tap water and there is no sign of this boil notice being lifted in the near future. In May 2013, in Roscommon, Ireland, another outbreak of the cryptosporidiosis was reported and a boil water notice was issued. This was the second time the parasite was detected in a month in the Roscommon water supply. The source of one of the outbreaks had been linked to the agricultural community. At least 13 people were treated for Cryptosporidiosis. See also Cryptosporidium was the basis of the 1998 television film, Thirst, in which it mutates and passes through a towns water filters. Cryptosporidium was shown on three episodes in three seasons of the television show, Monsters Inside Me References White, A. Clinton Jr. (2005). "Cryptosporidiosis". In Mandell, G; et al. (eds.). Principles and Practice of Infectious Diseases (6th ed.). Elsevier. pp. 3215–28. Upton, Steve J. (12 September 2003). "Basic Biology of Cryptosporidium" (Website). Kansas State University: Parasitology Laboratory. S.J. Brands (Compiler) (2000). "The Taxonomicon & Systema Naturae" (Website database). Taxon: Genus Cryptosporidium. Universal Taxonomic Services, Amsterdam, The Netherlands. Heymann, David (2015). Control of communicable diseases manual : an official report of the American Public Health Association. APHA Press, the American Public Health Association. ISBN 9780875530185. External links Cryptosporidiosis — Centers for Disease Control and Prevention Aquatics International Article Regarding Infection via Spray Parks CryptoDB: The Cryptosporidium Genome Resource

You serve as an encyclopedia of medical terms. Deliver clear, detailed explanations, making medical language understandable to a diverse audience.

Could you offer a clear explanation of the term 'Blau syndrome' as used in the medical field?

Blau syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and joints. It is caused by a mutation in the NOD2 (CARD15) gene. Symptoms usually begin before the age of four, and the disease manifests as early onset cutaneous sarcoidosis, granulomatous arthritis, and uveitis. Presentation Cause The elucidation that the gene defect in Blau syndrome (BS) involves the CARD15/NOD2 gene has stimulated many investigators to define how this gene operates as part of the innate immune system. The innate immune system recognizes pathogen-associated molecular patterns (PMAPs), including bacterial polysaccharides such as muramyl dipeptide, via its pattern recognition receptors (PRRs), such as NOD2, to induce signaling pathways that activate cytokine responses and protect the organism. In BS the genetic defect seems to lead to over activation and poor control of the inflammatory response leading to widespread granulomatous inflammation and tissue damage. Diagnosis Treatment Treatment has included the usual anti-inflammatory drugs such as adrenal glucocorticoids, anti-metabolites and also biological agents such as anti-TNF and infliximab all with varying degrees of success. History In 1981, Malleson et al. reported a family that had autosomal dominant synovitis, camptodactyly, and iridocyclitis. One member died of granulomatous arteritis of the heart and aorta. In 1982, Rotenstein reported a family with granulomatous arteritis, rash, iritis, and arthritis transmitted as an autosomal dominant trait over three generations.In 1985, Edward Blau, a pediatrician in Marshfield, Wisconsin, reported a family that over four generations had granulomatous inflammation of the skin, eyes and joints. The condition was transmitted as an autosomal dominant trait. In the same year Jabs et al. reported a family that over two generations had granulomatous synovitis, uveitis and cranial neuropathies. The condition was transmitted in an autosomal dominant fashion.Then in 1990 Pastores et al. reported a kindred with a phenotype very similar to what Blau described and suggested that the condition be called Blau Syndrome (BS). They also pointed out the similarities in the families noted above to BS but also pointed out the significant differences in the phenotypes.In 1996 Tromp et al. conducted a genome wide search using affected and non affected members of the original family. A marker, D16S298, gave a maximum logarithm of odds (LOD) score of 3.75 and put the BS susceptibility locus within the 16p12-q21 interval. Hugot et al. found a susceptibility locus for Crohn disease, a granulomatous inflammation of the bowel, on chromosome 16 close to the locus for BS. Based on the above information Blau suggested in 1998 that the genetic defect in BS and Crohn Disease might be the same or similar. Finally in 2001 Miceli-Richard et al. found the defect in BS to be in the nucleotide-binding domain of CARD15/NOD2. They commented in their article that mutations in CARD15 had also been found in Crohns disease. Confirmation of the defect in BS being in the CARD15 gene was made by Wang et al. in 2002 using the BS family and others. With that information the diagnosis of BS was not only determined by phenotype but now by genotype.Early onset sarcoidosis is BS without a family history, BS has been diagnosed in patients who have not only the classic triad but granuloma in multiple organs. See also List of cutaneous conditions References Further reading Wouters CH, Maes A, Foley KP, Bertin J, and Rose CD: Blau Syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatric Rheumatology 2014;12:33. PMID 25136265. PMC 4136643. doi:10.1186/1546-0096-12-33. Blau EB : Familial Granulomatous Arthritis, Iritis, and Rash. The Journal of Pediatrics 1985; 107: 689-693. PMID 4056967. doi:10.1016/s0022-3476(85)80394-2. Jabs DA, Houk JL, Bias WB, and Arnett FC: Familial Granulomatous Synovitis, Uveitis, and Cranial Neuropathies. The American Journal of Medicine 1985; 78: 801–804. PMID 3993660. doi:10.1016/0002-9343(85)90286-4. Malleson P, Schaller JG, Dega F, Cassidy SB, and Pagon RA : Familial Arthritis and Camplodactyly. Arthritis and Rheumatism 1981; 24: 1199–1204. PMID 7306244. doi:10.1002/art.1780240915. Rotenstein D, Gibbas DL, Majmudar B, and Chastain EA: Familial Granulomatous Arteritis with Polyarthritis of Juvenile Onset. The New England Journal of Medicine 1982; 306: 85–90. PMID 7053492. doi:10.1056/NEJM198201143060208. Pastores GM, Michels VV, Stickler GB, Su WP, Nelson AM, and Bovenmyer DA: Autosomal dominant granulomatous arthritis, uveitis, skin rash, and synovial cysts. The Journal of Pediatrics 1990; 117: 403–408. PMID 2391595. doi:10.1016/s0022-3476(05)81080-7. Tromp G, Kuivaniemi H, Raphael S, et al.: Genetic Linkage of Familial Granulomatous Inflammatory Arthritis, Skin Rash, and Uveitis to Chromosome 16. The American Journal of Human Genetics 1996; 59: 1097-1107. PMID 8900239. PMC 1914842. Hugot JP, Chamaillard M, Zouali H, et al.: Association of NOD2 leucine-rich repeat variants with susceptibility to Crohns disease. Nature 2001; 411:599-603. PMID 11385576. doi:10.1038/35079107. Blau EB : Autosomal dominant granulomatous disease of childhood: The naming of things. The Journal of Pediatrics 1998; 133: 322–323. PMID 9738710. doi:10.1016/s0022-3476(98)70263-x. Miceli-Richard C, Lesage S, Rybojad M, Prieur A-M, Manouvrier-Hanu S, Häfner R, Chamaillard M, Zouali H, Thomas G, and Hugot J-P: CARD15 mutations in Blau syndrome. Nature Genetics 2001; 29: 19-20. PMID 11528384. doi:10.1038/ng720. Wang X, Kuivaniemi H, Bonavita G, Mutkus L, Mau U, Blau E, Inohara N, Nunez G, Tromp G, and Williams CJ: CARD15 Mutations in Familial Granulomatous Syndromes: A Study of the Original Blau Syndrome Kindred and Other Families with Large-Vessel Arteritis and Cranial Neuropathy. Arthritis and Rheumatism 2002; 46: 3041-3045. PMID 12428248. doi:10.1002/art.10618. Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, and Punzi L; Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohns disease. RMD Open 2015; 1: e000097. PMID 26509073. PMC 4612691. doi:10.1136/rmdopen-2015-000097. External links Blau Syndrome in Orpha website

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Hydroxyzine'?

Hydroxyzine, sold under the brand names Atarax, Vistaril and others, is an antihistamine medication. It is used in the treatment of itchiness, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.Common side effects include sleepiness, headache, and a dry mouth. Serious side effects may include QT prolongation. It is unclear if use during pregnancy or breastfeeding is safe. Hydroxyzine works by blocking the effects of histamine. It is a first-generation antihistamine in the piperazine family of chemicals.It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year. In 2019, it was the 75th most commonly prescribed medication in the United States, with more than 9 million prescriptions. Medical uses Hydroxyzine is used in the treatment of itchiness, anxiety, and nausea due to motion sickness.A systematic review concluded that hydroxyzine outperforms placebo in treating generalized anxiety disorder. Insufficient data were available to compare the drug with benzodiazepines and buspirone.Hydroxyzine can also be used for the treatment of allergic conditions, such as chronic urticaria, atopic or contact dermatoses, and histamine-mediated pruritus. These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system, or urinary tract.Use of hydroxyzine for premedication as a sedative has no effects on tropane alkaloids, such as atropine, but may, following general anesthesia, potentiate meperidine and barbiturates, and use in pre-anesthetic adjunctive therapy should be modified depending upon the state of the individual.Hydroxyzine is used as a non-barbiturate tranquilizer and for the treatment of neurological disorders, such as psychoneurosis and other forms of anxiety or tension states.Doses of hydroxyzine hydrochloride used for sleep range from 25 to 100 mg. As with other antihistamine sleep aids, hydroxyzine is usually only prescribed for short term or "as-needed" use since tolerance to the CNS effects of hydroxyzine can develop in as little as a few days. Contraindications The administration of hydroxyzine in large amounts by ingestion or intramuscular administration during the onset of pregnancy can cause fetal abnormalities. When administered to pregnant rats, mice and rabbits, hydroxyzine caused abnormalities such as hypogonadism with doses significantly above that of the human therapeutic range.In humans, a significant dose has not yet been established in studies and, by default, the Food and Drug Administration (FDA) has introduced contraindication guidelines in regard to hydroxyzine. Use by those at risk for or showing previous signs of hypersensitivity is also contraindicated. Hydroxyzine is contraindicated for intravenous (IV) injection, as it has shown to cause hemolysis. Other contraindications include the administration of hydroxyzine alongside depressants and other compounds which affect the central nervous system; if absolutely necessary, it should only be administered concomitantly in small doses. If administered in small doses with other substances, such as mentioned, then patients should refrain from using dangerous machinery, motor vehicles or any other practice requiring absolute concentration, in accordance with safety law.Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to tardive dyskinesia after years of use, but effects related to dyskinesia have also anecdotally been reported after periods of 7.5 months, such as continual head rolling, lip licking and other forms of athetoid movement. In certain cases, elderly patients previous interactions with phenothiazine derivatives or pre-existing neuroleptic treatment may have contributed to dyskinesia at the administration of hydroxyzine due to hypersensitivity caused by prolonged treatment, and therefore some contraindication is given for short-term administration of hydroxyzine to those with previous phenothiazine use. Side effects Several reactions have been noted in manufacturer guidelines—deep sleep, incoordination, sedation, calmness, and dizziness have been reported in children and adults, as well as others such as hypotension, tinnitus, and headaches. Gastrointestinal effects have also been observed, as well as less serious effects such as dryness of the mouth and constipation caused by the mild antimuscarinic properties of hydroxyzine.Central nervous system effects such as hallucinations or confusion have been observed in rare cases, attributed mostly to overdosage. Such properties have been attributed to hydroxyzine in several cases, particularly in patients treated for neuropsychological disorders, as well as in cases where overdoses have been observed. While there are reports of the "hallucinogenic" or "hypnotic" properties of hydroxyzine, several clinical data trials have not reported such side effects from the sole consumption of hydroxyzine, but rather, have described its overall calming effect described through the stimulation of areas within the reticular formation. The hallucinogenic or hypnotic properties have been described as being an additional effect from overall central nervous system suppression by other CNS agents, such as lithium or ethanol.Hydroxyzine exhibits anxiolytic and sedative properties in many psychiatric patients. One study showed that patients reported very high levels of subjective sedation when first taking the drug, but that levels of reported sedation decreased markedly over 5-7 days, likely due to CNS receptor desensitization. Other studies have suggested that hydroxyzine acts as an acute hypnotic, reducing sleep onset latency and increasing sleep duration — also showing that some drowsiness did occur. This was observed more in female patients, who also had greater hypnotic response. The use of sedating drugs alongside hydroxyzine can cause oversedation and confusion if administered at high doses—any form of hydroxyzine treatment alongside sedatives should be done under supervision of a doctor.Because of the potential for more severe side effects, this drug is on the list to avoid in the elderly.In 2015, the European Medicines Agency (EMA) announced a small but definite risk of QT prolongation associated with the use of hydroxyzine. This side effect is more likely to occur in people with pre-existing cardiac disease, or with the use of other medicines known to prolong the QT interval. Pharmacology Pharmacodynamics Hydroxyzines predominant mechanism of action is as a potent and selective histamine H1 receptor inverse agonist. This action is responsible for its antihistamine and sedative effects. Unlike many other first-generation antihistamines, hydroxyzine has a lower affinity for the muscarinic acetylcholine receptors, and in accordance, has a lower risk of anticholinergic side effects. In addition to its antihistamine activity, hydroxyzine has also been shown to act more weakly as an antagonist of the serotonin 5-HT2A receptor, the dopamine D2 receptor, and the α1-adrenergic receptor. The weak antiserotonergic effects of hydroxyzine likely underlie its usefulness as an anxiolytic, as other antihistamines without such properties have not been found to be effective in the treatment of anxiety.Hydroxyzine crosses the blood–brain barrier easily and exerts effects in the central nervous system. A positron emission tomography (PET) study found that brain occupancy of the H1 receptor was 67.6% for a single 30 mg dose of hydroxyzine. In addition, subjective sleepiness correlated well with the brain H1 receptor occupancy. PET studies with antihistamines have found that brain H1 receptor occupancy of more than 50% is associated with a high prevalence of somnolence and cognitive decline, whereas brain H1 receptor occupancy of less than 20% is considered to be non-sedative. Pharmacokinetics Hydroxyzine can be administered orally or via intramuscular injection. When given orally, hydroxyzine is rapidly absorbed from the gastrointestinal tract. The effect of hydroxyzine is notable in 30 minutes.Hydroxyzine is rapidly absorbed and distributed with oral and intramuscular administration, and is metabolized in the liver; the main metabolite (45%), cetirizine, is formed through oxidation of the alcohol moiety to a carboxylic acid by alcohol dehydrogenase, and overall effects are observed within one hour of administration. Higher concentrations are found in the skin than in the plasma. Cetirizine, although less sedating, is non-dialyzable and possesses similar antihistamine properties. The other metabolites identified include a N-dealkylated metabolite, and an O-dealkylated 1/16 metabolite with a plasma half-life of 59 hours. These pathways are mediated principally by CYP3A4 and CYP3A5. "In animals, hydroxyzine and its metabolites are excreted in feces via biliary elimination."The Tmax of hydroxyzine is about 2.0 hours in both adults and children and its elimination half-life is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children. Its elimination half-life is shorter in children compared to adults. In another study, the elimination half-life of hydroxyzine in elderly adults was 29.3 hours. One study found that the elimination half-life of hydroxyzine in adults was as short as 3 hours, but this may have just been due to methodological limitations. Although hydroxyzine has a long elimination half-life and produces antihistamine for as long as 24 hours, the CNS effects of hydroxyzine and other antihistamines with long half-lives seem to diminish after 8 hours.Administration in geriatrics differs from the administration of hydroxyzine in younger patients; according to the FDA, there have not been significant studies made (2004), which include population groups over 65, which provide a distinction between elderly aged patients and other younger groups. Hydroxyzine should be administered carefully in the elderly with consideration given to possible reduced elimination. Chemistry Hydroxyzine is a member of the diphenylmethylpiperazine class of antihistamines. Hydroxyzine is supplied mainly as a dihydrochloride salt (hydroxyzine hydrochloride) but also to a lesser extent as an embonate salt (hydroxyzine pamoate). The molecular weights of hydroxyzine, hydroxyzine dihydrochloride, and hydroxyzine pamoate are 374.9 g/mol, 447.8 g/mol, and 763.3 g/mol, respectively. Due to their differences in molecular weight, 1 mg hydroxyzine dihydrochloride is equivalent to about 1.7 mg hydroxyzine pamoate. Analogues Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others. Synthesis Hydroxyzine is synthesized by the alkylation of 1-(4-chlorobenzhydryl)piperazine with 2-(2-chloroethoxy)ethanol: Society and culture Brand names Hydroxyzine preparations require a doctors prescription. The drug is available in two formulations, the pamoate (anxiolytic) and the dihydrochloride or hydrochloride salts (antihistamine). Vistaril, Equipose, Masmoran, and Paxistil are preparations of the pamoate salt, while Atarax, Alamon, Aterax, Durrax, Tran-Q, Orgatrax, Quiess, and Tranquizine are of the hydrochloride salt. References External links "Hydroxyzine". Drug Information Portal. U.S. National Library of Medicine.

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Ethinylestradiol/norethisterone acetate'?

Ethinylestradiol/norethisterone acetate (EE/NETA), or ethinylestradiol/norethindrone acetate, is a combination of ethinylestradiol (EE) and norethisterone acetate (NETA) which is used as birth control and menopausal hormone therapy. EE is an estrogen, while norethisterone acetate (NETA) is a progestin. It is taken by mouth. Some preparations of EE/NETA used in birth control additionally contain an iron supplement in the form of ferrous fumarate.In 2019, it was the 42nd most commonly prescribed medication in the United States, with more than 16 million prescriptions. Society and culture Brand names Brand names of EE/NETA include Anovlar, Blisovi, Cumorit, Estrostep, FemHRT, Fyavolv, Gildess, Junel, Larin, Leribane, Loestrin, Lo Loestrin (Lo Lo), Mibelas, Microgestin, Minastrin, Norlestrin, Primodos, Taytulla, and Tri-Legest, among others.In addition, the combination is sold in the United States under the brand name FemHRT for use in menopausal hormone therapy. See also Estradiol/norethisterone acetate Oral contraceptive formulations List of combined sex-hormonal preparations Nand Peeters References External links "Ethinyl estradiol mixture with norethindrone acetate". Drug Information Portal. U.S. National Library of Medicine.

You are a conduit for medical education. Your task is to offer detailed explanations of medical terms, ensuring they are understandable and precise.

What does the medical term 'Ileitis' encompass?

Ileitis is an inflammation of the ileum, a portion of the small intestine. Crohns ileitis is a type of Crohns disease affecting the ileum. Ileitis is caused by the bacterium Lawsonia intracellularis. Inflammatory bowel disease does not associate with Lawsonia intracellularis infection. References == External links ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

I'm looking for a concise explanation of the medical term 'Fatal insomnia.'

Fatal familial insomnia is an extremely rare genetic (and even more rarely, sporadic) disorder that results in trouble sleeping as its hallmark symptom. The problems with sleeping typically start out gradually and worsen over time. Other symptoms may include speech problems, coordination problems, and dementia. It results in death within a few months to a few years.Fatal familial insomnia is a prion disease of the brain. It is usually caused by a mutation to the gene encoding protein PrPC. It has two forms: fatal familial insomnia (FFI), which is autosomal dominant, and sporadic fatal insomnia (sFI), which lacks the gene mutation. Diagnosis is suspected based on symptoms and can be supported by a sleep study, a PET scan, and genetic testing if the patients family has a history of the disease. Similar to other prion diseases, the diagnosis can only be confirmed by a brain autopsy at post-mortem.Fatal insomnia has no known cure and involves progressively worsening insomnia, which leads to hallucinations, delirium, and confusional states like that of dementia, until the patient slips into a stupor and eventually dies. The average survival time from onset of symptoms is 18 months. The first recorded case was an Italian man who died in Venice in 1765. Signs and symptoms The disease has four stages: Characterized by worsening insomnia, resulting in panic attacks, paranoia, and phobias. This stage lasts for about four months. Hallucinations and panic attacks become noticeable, continuing for about five months. Complete inability to sleep is followed by rapid loss of weight. This lasts for about three months. Dementia, during which the person becomes unresponsive or mute over the course of six months, is the final stage of the disease, after which death follows.Other symptoms include: profuse sweating, miosis (pinpoint pupils), sudden entrance into menopause or impotence, neck stiffness, and elevation of blood pressure and heart rate. The sporadic form of the disease often presents with double vision. Constipation is common as well. As the disease progresses, the person becomes stuck in a state of pre-sleep limbo, or hypnagogia, which is the state just before sleep in healthy individuals. During these stages, people commonly and repeatedly move their limbs as if dreaming.The age of onset is variable, ranging from 13 to 60 years, with an average of 50. The disease can be detected prior to onset by genetic testing. Death usually occurs between 6–36 months from onset. The presentation of the disease varies considerably from person to person, even among people within the same family; in the sporadic form, for example, sleep problems are not commonly reported and early symptoms are ataxia, cognitive impairment, and double vision. Cause The gene PRNP that provides instructions for making the prion protein PrPC is located on the short (p) arm of chromosome 20 at position p13. Both people with FFI and those with familial Creutzfeldt–Jakob disease (fCJD) carry a mutation at codon 178 of the prion protein gene. FFI is also invariably linked to the presence of the methionine codon at position 129 of the mutant allele, whereas fCJD is linked to the presence of the valine codon at that position. "The disease is where there is a change of amino acid at position 178 when an asparagine (N) is found instead of the normal aspartic acid (D). This has to be accompanied with a methionine at position 129." Pathophysiology In itself, the presence of prions causes reduced glucose use by the thalamus and a mild hypo-metabolism of the cingulate cortex. The extent of this symptom varies between two variations of the disease, these being those presenting methionine homozygotes at codon 129 and methionine/valine heterozygotes being the most severe in the latter one. Given the relationship between the involvement of the thalamus in regulating sleep and alertness, a causal relationship can be drawn, and is often mentioned as the cause. Diagnosis Diagnosis is suspected based on symptoms. Further work up often include a sleep study and PET scan. Confirmation of the familial form is by genetic testing. Differential diagnosis Other diseases involving the mammalian prion protein are known. Some are transmissible (TSEs, including FFI) such as kuru, bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle, and chronic wasting disease in American deer and American elk in some areas of the United States and Canada, as well as Creutzfeldt–Jakob disease (CJD). Until recently, prion diseases were only thought to be transmissible by direct contact with infected tissue, such as from eating infected tissue, transfusion, or transplantation; research suggests that prions can be transmitted by aerosols, but that the general public is not at risk of airborne infection. Treatments Treatment involves palliative care. There is conflicting evidence over the use of sleeping pills, including barbiturates, as a treatment for the disease. Prognosis Similar to other prion diseases, the disease is invariably fatal. Life expectancy ranges from seven months to six years, with an average of 18 months. Epidemiology In 1998, 40 families were known to carry the gene for FFI globally: eight German, five Italian, four American, two French, two Australian, two British, one Japanese, and one Austrian. In the Basque Country, Spain, 16 family cases of the 178N mutation were seen between 1993 and 2005 related to two families with a common ancestor in the 18th century. In 2011, another family was added to the list when researchers found the first man in the Netherlands with FFI. While he had lived in the Netherlands for 19 years, he was of Egyptian descent. Other prion diseases are similar to FFI and could be related, but are missing the D178N gene mutation.As of 2016, 24 cases of sporadic fatal insomnia have been diagnosed. Unlike in FFI, those with sFI do not have the D178N mutation in the PRNP-prion gene; they all have a different mutation in the same gene causing methionine homozygosity at codon 129. Nonetheless, the methionine presence in lieu of the valine (Val129) is what causes the sporadic form of disease. The targeting of this mutation is another strategy that has been suggested as possible for treatment, or hopefully as cure for the disease. Silvano, 1983, Bologna, Italy In late 1983, Italian neurologist/sleep expert Dr. Ignazio Roiter received a patient at the University of Bologna hospitals sleep institute. The man, known only as Silvano, decided in a rare moment of consciousness to be recorded for future studies and to donate his brain for research in hopes of finding a cure for future victims. Unnamed American patient, 2001 In a 2006 published article, Schenkein and Montagna wrote of a 52-year-old American man who was able to exceed the average survival time by nearly one year with various strategies that included vitamin therapy and meditation, different stimulants and hypnotics, and even complete sensory deprivation in an attempt to induce sleep at night and increase alertness during the day. He managed to write a book and drive hundreds of miles in this time, but nonetheless, over the course of his trials, the man succumbed to the classic four-stage progression of the illness. Egyptian man, 2011, Netherlands In 2011, the first reported case in the Netherlands was of a 57-year-old man of Egyptian descent. The man came in with symptoms of double vision and progressive memory loss, and his family also noted he had recently become disoriented, paranoid, and confused. While he tended to fall asleep during random daily activities, he experienced vivid dreams and random muscular jerks during normal slow-wave sleep. After four months of these symptoms, he began to have convulsions in his hands, trunk, and lower limbs while awake. The person died at age 58, seven months after the onset of symptoms. An autopsy revealed mild atrophy of the frontal cortex and moderate atrophy of the thalamus. The latter is one of the most common signs of FFI. Research Still with unclear benefit in humans, a number of treatments have had tentative success in slowing disease progression in animal models, including pentosan polysulfate, mepacrine, and amphotericin B. As of 2016, a study investigating doxycycline is being carried out.In 2009, a mouse model was made for FFI. These mice expressed a humanized version of the PrP protein that also contains the D178N FFI mutation. These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the thalamus, and early deaths, similar to humans with FFI.The Prion Alliance was established by husband and wife duo Eric Minikel and Sonia Vallabh after Vallabhs mother was diagnosed with the fatal disease. They conduct research at the Broad Institute to develop therapeutics for human prion diseases. Other research interests involve identifying biomarkers to track the progression of prion disease in living people. References External links "AFIFF Fatal Familial Insomnia Families Association".

You serve as a guide in the medical field. Explain medical terms thoroughly, ensuring the information is both insightful and comprehensible.

I'm looking for a concise explanation of the medical term 'Pruritus ani.'

Pruritus ani is the irritation of the skin at the exit of the rectum, known as the anus, causing the desire to scratch. The intensity of anal itching increases from moisture, pressure, and rubbing caused by clothing and sitting. At worst, anal itching causes intolerable discomfort that often is accompanied by burning and soreness. It is estimated that up to 5% of the population of the United States experiences this type of discomfort daily. Causes If a specific cause for pruritus ani is found it is classified as "secondary pruritus ani". If a specific cause is not found it is classified as "idiopathic pruritus ani". The irritation can be caused by intestinal parasites, anal perspiration, frequent liquid stools, diarrhea, residual stool deposits, or the escape of small amounts of stool as a result of incontinence or flatulence. Another cause is yeast infection or candidiasis. Some diseases increase the possibility of yeast infections, such as diabetes mellitus or HIV infection. Treatment with antibiotics can bring about a disturbance of the natural balance of intestinal flora, and lead to perianal thrush, a yeast infection affecting the anus. Psoriasis also can be present in the anal area and cause irritation. Abnormal passageways (fistulas) from the small intestine or colon to the skin surrounding the anus can form as a result of disease (such as Crohns disease), acting as channels which may allow leakage of irritating fluids to the anal area. Other problems that can contribute to anal itching include pinworms, hemorrhoids, tears of the anal skin near the mucocutaneous junction (fissures), and skin tags (abnormal local growth of anal skin). Aside from diseases relative to the condition, a common view suggests that the initial cause of the itch may have passed, and that the illness is in fact prolonged by what is known as an itch-scratch-itch cycle. It states that scratching the itch encourages the release of inflammatory chemicals, which worsen redness, intensifies itchiness and increases the area covered by dry skin, thereby causing a snowball effect. Some authorities describe “psychogenic pruritus” or "functional itch disorder", where psychological factors may contribute to awareness of itching. Ingestion of pinworm eggs leads to enterobiasis, indicative of severe itching around the anus from migration of gravid females from the bowel. Severe cases of enterobiasis result in hemorrhage and eczema. Diagnosis Diagnosis is usually done with a careful examination of the anus and the patients history. If the presentation or physical findings are atypical, biopsies can be done.In case of long-lasting symptoms, above all in patients over 50 years of age, a colonoscopy is useful to rule out a colonic polyp or tumor, that can show pruritus ani as first symptom. Treatment The goal of treatment is asymptomatic, intact, dry, clean perianal skin with reversal of morphological changes. For pruritus ani of unknown cause (idiopathic pruritus ani) treatment typically begins with measures to reduce irritation and trauma to the perianal area. Stool softeners can help prevent constipation. If this is not effective topical steroids or injected methylene blue may be tried. Another treatment option that has been met with success in small-scale trials is the application of a very mild (.006) topical capsaicin cream. This strength cream is not typically commercially available and therefore must be diluted by a pharmacist or end-user. If the itchiness is secondary to another condition such as infection or psoriasis these are typically treated.A successful treatment option for chronic idiopathic pruritus ani has been documented using a clean, dry and apply (if necessary) method. The person is instructed to follow this procedure every time the urge to scratch occurs. The treatment makes the assumption that there is an unidentified bacteria in the feces that causes irritation and itching when the feces makes contact with the anal and perianal skin during defecation, flatulation or anal leakage (particularly during sleep). Cleaning the area with warm water, avoiding all soaps and even baby wipes, then drying the area, ideally with a hair dryer to avoid irritation or failing that simply patting gently with a clean, dry, towel. If persons with pruritus ani do not need to scratch after these steps they are instructed to do nothing else. If the urge to scratch is still present they are instructed to apply a topical steroid cream which has antibiotic and antifungal properties. This will address a skin condition which may have become infected. Apply such a cream as directed by your medical professional but usually twice a day for one to two weeks. After this, they must maintain their clean and dry regime and apply an emollient ointment (not cream) to moisturize the skin. This should be applied after each bowel movement and at night. Continue until no longer needed. At any time, persons may use antihistamine treatments orally, to control the itching. See also Pruritus scroti Pruritus vulvae Perianal candidiasis References External links Siddiqi S, Vijay V, Ward M, Mahendran R, Warren S (September 2008). "Pruritus ani". Annals of the Royal College of Surgeons of England. 90 (6): 457–463. doi:10.1308/003588408X317940. PMC 2647235. PMID 18765023.

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

Can you demystify the medical term 'Optic neuritis' for me?

Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.It is also known as optic papillitis (when the head of the optic nerve is involved), neuroretinitis (when there is a combined involvement of optic disc and surrounding retina in the macular area) and retrobulbar neuritis (when the posterior part of the nerve is involved). Prelaminar optic neuritis describes involvement of the non-myelinated axons in the retina. It is most often associated with multiple sclerosis, and it may lead to complete or partial loss of vision in one or both eyes. Other causes include: Hereditary optic neuritis (Lebers disease) Parainfectious optic neuritis (associated with viral infections such as measles, mumps, chickenpox, whooping cough and glandular fever) Infectious optic neuritis (sinus related or associated with cat scratch fever, tuberculosis, lyme disease and cryptococcal meningitis in AIDS patients Autoimmune causes (sarcoidosis, systemic lupus erythematosus, PAN, MOG Antibody disease, granulomatosis with polyangiitis) Diabetes Mellitus Low phosphorus levels HyperkalaemiaPartial, transient vision loss (lasting less than one hour) can be an indication of early onset multiple sclerosis. Signs and symptoms Major symptoms are sudden loss of vision (partial or complete), sudden blurred or "foggy" vision, and pain on movement of the affected eye. Early symptoms that require investigation include symptoms from multiple sclerosis (twitching, lack of coordination, slurred speech, frequent episodes of partial vision loss or blurred vision), episodes of "disturbed/blackened" rather than blurry indicate moderate stage and require immediate medical attention to prevent further loss of vision. Other early symptoms are reduced night vision, photophobia and red eyes. Many patients with optic neuritis may lose some of their color vision in the affected eye (especially red), with colors appearing subtly washed out compared to the other eye. Patients may also experience difficulties judging movement in depth which can be particular troublesome during driving or sport (Pulfrich effect). Likewise transient worsening of vision with increase of body temperature (Uhthoffs phenomenon) and glare disability are a frequent complaint. However, several case studies in children have demonstrated the absence of pain in more than half of cases (approximately 60%) in their pediatric study population, with the most common symptom reported simply as "blurriness." Other remarkable differences between the presentation of adult optic neuritis as compared to pediatric cases include more often unilateral optic neuritis in adults, while children much predominantly present with bilateral involvement. On medical examination the head of the optic nerve can easily be visualized by a slit lamp with a high positive lens or by using direct ophthalmoscopy; however, frequently there is no abnormal appearance of the nerve head in optic neuritis (in cases of retrobulbar optic neuritis), though it may be swollen in some patients (anterior papillitis or more extensive optic neuritis). In many cases, only one eye is affected and patients may not be aware of the loss of color vision until they are asked to close or cover the healthy eye. Cause The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the brain to be processed into vision. Inflammation of the optic nerve causes loss of vision, usually because of the swelling and destruction of the myelin sheath covering the optic nerve. The most common cause is multiple sclerosis or ischemic optic neuropathy due to thrombosis or embolism of the vessel that supplies the optic nerve. Up to 50% of patients with MS will develop an episode of optic neuritis, and 20-30% of the time optic neuritis is the presenting sign of MS. The presence of demyelinating white matter lesions on brain MRI at the time of presentation of optic neuritis is the strongest predictor for developing clinically definite MS. Almost half of the patients with optic neuritis have white matter lesions consistent with multiple sclerosis. Some other common causes of optic neuritis include infection (e.g. a tooth abscess in the upper jaw, syphilis, Lyme disease, herpes zoster), autoimmune disorders (e.g. lupus, neurosarcoidosis, neuromyelitis optica), methanol poisoning, Vitamin B12 deficiency, beriberi, dysautonomia (i.e. autonomic nervous system dysfunction), and diabetes, or an injury to the eye. In neuromyelitis optica higher AQP4 autoantibody levels are associated with the occurrence of optic neuritis.Less common causes are: papilledema, brain tumor or abscess in the occipital region, cerebral trauma or hemorrhage, meningitis, arachnoidal adhesions, sinus thrombosis, liver dysfunction, or late stage kidney disease. Demyelinating recurrent optic neuritis and non-demyelinating (CRION) The repetition of an idiopathic optic neuritis is considered a distinct clinical condition, and when it shows demyelination, it has been found to be associated to anti-MOG and AQP4-negative neuromyelitis opticaWhen an inflammatory recurrent optic neuritis is not demyelinating, it is called "Chronic relapsing inflammatory optic neuropathy" (CRION)When it is anti-MOG related, it is demyelinating and it is considered inside the anti-MOG associated inflammatory demyelinating diseases. Some reports point to the possibility to establish a difference via OCT Treatment In most MS-associated optic neuritis, visual function spontaneously improves over 2–3 months, and there is evidence that corticosteroid treatment does not affect the long term outcome. However, for optic neuritis that is not MS-associated (or atypical optic neuritis) the evidence is less clear and therefore the threshold for treatment with intravenous corticosteroids is lower. Intravenous corticosteroids also reduce the risk of developing MS in the following two years in patients with MRI lesions; but this effect disappears by the third year of follow up.Paradoxically, oral administration of corticosteroids in this situation may lead to more recurrent attacks than in non-treated patients (though oral steroids are generally prescribed after the intravenous course, to wean the patient off the medication). This effect of corticosteroids seems to be limited to optic neuritis and has not been observed in other diseases treated with corticosteroids.A Cochrane Systematic Review studied the effect of corticosteroids for treating people with acute optic neuritis. Specific corticosteroids studied included intravenous and oral methylprednisone, and oral prednisone. The authors conclude that current evidence does not show a benefit of either intravenous or oral corticosteroids for rate of recovery of vision (in terms of visual acuity, contrast sensitivity, or visual fields). There are a number of reasons why this might be the case. Epidemiology Optic neuritis typically affects young adults ranging from 18–45 years of age, with a mean age of 30–35 years. There is a strong female predominance. The annual incidence is approximately 5/100,000, with a prevalence estimated to be 115/100,000. Society and culture In Charles Dickens Bleak House, the main character, Esther Summerville, has a transient episode of visual loss, the symptoms of which are also seen in people who have optic neuritis. Legal historian Sir William Searle Holdsworth, suggested that the events in Bleak House took place in 1827. In an episode of Dr. Quinn, Medicine Woman ("Season of Miracles", season five), Reverend Timothy Johnson is struck blind by optic neuritis on Christmas Day 1872. He remains blind for the duration of the series. See also Optic neuropathy Visual snow References == External links ==

You are a conduit for medical education. Your task is to offer detailed explanations of medical terms, ensuring they are understandable and precise.

I've encountered the term 'Tobacco smoking' while reading about medical topics. What does it refer to exactly?

Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed to have begun as early as 5000–3000 BC in Mesoamerica and South America. Tobacco was introduced to Eurasia in the late 17th century by European colonists, where it followed common trade routes. The practice encountered criticism from its first import into the Western world onwards but embedded itself in certain strata of a number of societies before becoming widespread upon the introduction of automated cigarette-rolling apparatus.Smoking is the most common method of consuming tobacco, and tobacco is the most common substance smoked. The agricultural product is often mixed with additives and then combusted. The resulting smoke is then inhaled and the active substances absorbed through the alveoli in the lungs or the oral mucosa. Many substances in cigarette smoke trigger chemical reactions in nerve endings, which heighten heart rate, alertness and reaction time, among other things. Dopamine and endorphins are released, which are often associated with pleasure.German scientists identified a link between smoking and lung cancer in the late 1920s, leading to the first anti-smoking campaign in modern history, albeit one truncated by the collapse of Nazi Germany at the end of World War II. In 1950, British researchers demonstrated a clear relationship between smoking and cancer. Evidence continued to mount in the 1960s, which prompted political action against the practice. Rates of consumption since 1965 in the developed world have either peaked or declined. However, they continue to climb in the developing world. As of 2008 to 2010, tobacco is used by about 49% of men and 11% of women aged 15 or older in fourteen low-income and middle-income countries (Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Russia, Thailand, Turkey, Ukraine, Uruguay and Vietnam), with about 80% of this usage in the form of smoking. The gender gap tends to be less pronounced in lower age groups.Many smokers begin during adolescence or early adulthood. During the early stages, a combination of perceived pleasure acting as positive reinforcement and desire to respond to social peer pressure may offset the unpleasant symptoms of initial use, which typically include nausea and coughing. After an individual has smoked for some years, the avoidance of withdrawal symptoms and negative reinforcement become the key motivations to continue. A 2009 study of first smoking experiences of seventh-grade students found out that the most common factor leading students to smoke is cigarette advertisements. Smoking by parents, siblings and friends also encourages students to smoke. History Use in ancient cultures Smokings history dates back to as early as 5000–3000 BC, when the agricultural product began to be cultivated in Mesoamerica and South America; consumption later evolved into burning the plant substance either by accident or with intent of exploring other means of consumption. The practice worked its way into shamanistic rituals. Many ancient civilizations – such as the Babylonians, the Indians, and the Chinese – burnt incense during religious rituals. Smoking in the Americas probably had its origins in the incense-burning ceremonies of shamans but was later adopted for pleasure or as a social tool. The smoking of tobacco and various hallucinogenic drugs was used to achieve trances and to come into contact with the spirit world. Also, to stimulate respiration, tobacco smoke enemas were used.Eastern North American tribes would carry large amounts of tobacco in pouches as a readily accepted trade item and would often smoke it in ceremonial pipes, either in sacred ceremonies or to seal bargains. Adults as well as children enjoyed the practice. It was believed that tobacco was a gift from the Creator and that the exhaled tobacco smoke was capable of carrying ones thoughts and prayers to heaven.Apart from smoking, tobacco had uses as medicine. As a pain killer it was used for earache and toothache and occasionally as a poultice. Smoking was said by the desert Indians to be a cure for colds, especially if the tobacco was mixed with the leaves of the small Desert sage, Salvia dorrii, or the root of Indian balsam or cough root, Leptotaenia multifida, the addition of which was thought to be particularly good for asthma and tuberculosis. Popularization In 1612, six years after the settlement of Jamestown, Virginia, John Rolfe was credited as the first settler to successfully raise tobacco as a cash crop. The demand quickly grew as tobacco, referred to as "brown gold", revived the Virginia joint stock company from its failed gold expeditions. In order to meet demands from the Old World, tobacco was grown in succession, quickly depleting the soil. This became a motivator to settle west into the unknown continent, and likewise an expansion of tobacco production. Indentured servitude became the primary labor force up until Bacons Rebellion, from which the focus turned to slavery. This trend abated following the American Revolution as slavery became regarded as unprofitable. However, the practice was revived in 1794 with the invention of the cotton gin.Frenchman Jean Nicot (from whose name the word nicotine is derived) introduced tobacco to France in 1560, and tobacco then spread to England. The first report of a smoking Englishman is of a sailor in Bristol in 1556, seen "emitting smoke from his nostrils". Like tea, coffee and opium, tobacco was just one of many intoxicants that was originally used as a form of medicine. Tobacco was introduced around 1600 by French merchants in what today is modern-day Gambia and Senegal. At the same time, caravans from Morocco brought tobacco to the areas around Timbuktu, and the Portuguese brought the commodity (and the plant) to southern Africa, establishing the popularity of tobacco throughout all of Africa by the 1650s. Soon after its introduction to the Old World, tobacco came under frequent criticism from state and religious leaders. James VI and I, King of Scotland and England, produced the treatise A Counterblaste to Tobacco in 1604, and also introduced excise duty on the product. Murad IV, sultan of the Ottoman Empire 1623–40 was among the first to attempt a smoking ban by claiming it was a threat to public morals and health. The Chongzhen Emperor of China issued an edict banning smoking two years before his death and the overthrow of the Ming dynasty. Later, the Manchu rulers of the Qing dynasty, would proclaim smoking "a more heinous crime than that even of neglecting archery". In Edo period Japan, some of the earliest tobacco plantations were scorned by the shogunate as being a threat to the military economy by letting valuable farmland go to waste for the use of a recreational drug instead of being used to plant food crops. Religious leaders have often been prominent among those who considered smoking immoral or outright blasphemous. In 1634, the Patriarch of Moscow forbade the sale of tobacco, and sentenced men and women who flouted the ban to have their nostrils slit and their backs flayed. Pope Urban VIII likewise condemned smoking on holy places in a papal bull of 1624. Despite some concerted efforts, restrictions and bans were largely ignored. When James I of England, a staunch anti-smoker and the author of A Counterblaste to Tobacco, tried to curb the new trend by enforcing a 4000% tax increase on tobacco in 1604 it was unsuccessful, as suggested by the presence of around 7,000 tobacco outlets in London by the early 17th century. From this point on for some centuries, several administrations withdrew from efforts at discouragement and instead turned tobacco trade and cultivation into sometimes lucrative government monopolies.By the mid-17th century most major civilizations had been introduced to tobacco smoking and in many cases had already assimilated it into the native culture, despite some continued attempts upon the parts of rulers to eliminate the practice with penalties or fines. Tobacco, both product and plant, followed the major trade routes to major ports and markets, and then on into the hinterlands. The English language term smoking appears to have entered currency in the late 18th century, before which less abbreviated descriptions of the practice such as drinking smoke were also in use.Growth in the US remained stable until the American Civil War in 1860s, when the primary agricultural workforce shifted from slavery to sharecropping. This, along with a change in demand, accompanied the industrialization of cigarette production as craftsman James Bonsack created a machine in 1881 to partially automate their manufacture. Social attitudes and public health In Germany, anti-smoking groups, often associated with anti-liquor groups, first published advocacy against the consumption of tobacco in the journal Der Tabakgegner (The Tobacco Opponent) in 1912 and 1932. In 1929, Fritz Lickint of Dresden, Germany, published a paper containing formal statistical evidence of a lung cancer–tobacco link. During the Great Depression Adolf Hitler condemned his earlier smoking habit as a waste of money, and later with stronger assertions. This movement was further strengthened with Nazi reproductive policy as women who smoked were viewed as unsuitable to be wives and mothers in a German family. In the 20th century, smoking was common. There were social events like the smoke night which promoted the habit. The anti-tobacco movement in Nazi Germany did not reach across enemy lines during the Second World War, as anti-smoking groups quickly lost popular support. By the end of the Second World War, American cigarette manufacturers quickly reentered the German black market. Illegal smuggling of tobacco became prevalent, and leaders of the Nazi anti-smoking campaign were silenced. As part of the Marshall Plan, the United States shipped free tobacco to Germany; with 24,000 tons in 1948 and 69,000 tons in 1949. Per capita yearly cigarette consumption in post-war Germany steadily rose from 460 in 1950 to 1,523 in 1963. By the end of the 20th century, anti-smoking campaigns in Germany were unable to exceed the effectiveness of the Nazi-era climax in the years 1939–41 and German tobacco health research was described by Robert N. Proctor as "muted". In 1950, Richard Doll published research in the British Medical Journal showing a close link between smoking and lung cancer. Beginning in December 1952, the magazine Readers Digest published "Cancer by the Carton", a series of articles that linked smoking with lung cancer.In 1954, the British Doctors Study, a prospective study of some 40 thousand doctors for about 2.5 years, confirmed the suggestion, based on which the government issued advice that smoking and lung cancer rates were related. In January 1964, the United States Surgeon Generals Report on Smoking and Health likewise began suggesting the relationship between smoking and cancer.As scientific evidence mounted in the 1980s, tobacco companies claimed contributory negligence as the adverse health effects were previously unknown or lacked substantial credibility. Health authorities sided with these claims up until 1998, from which they reversed their position. The Tobacco Master Settlement Agreement, originally between the four largest US tobacco companies and the Attorneys General of 46 states, restricted certain types of tobacco advertisement and required payments for health compensation; which later amounted to the largest civil settlement in United States history.Social campaigns have been instituted in many places to discourage smoking, such as Canadas National Non-Smoking Week. From 1965 to 2006, rates of smoking in the United States declined from 42% to 20.8%. The majority of those who quit were professional, affluent men. Although the per-capita number of smokers decreased, the average number of cigarettes consumed per person per day increased from 22 in 1954 to 30 in 1978. This paradoxical event suggests that those who quit smoked less, while those who continued to smoke moved to smoke more light cigarettes. The trend has been paralleled by many industrialized nations as rates have either leveled-off or declined. In the developing world, however, tobacco consumption continues to rise at 3.4% in 2002. In Africa, smoking is in most areas considered to be modern, and many of the strong adverse opinions that prevail in the West receive much less attention. Today Russia leads as the top consumer of tobacco followed by Indonesia, Laos, Ukraine, Belarus, Greece, Jordan, and China.As a result of public pressure and the FDA, Walmart and Sams club announced that they were raising the minimum age to purchase tobacco products, including all e-cigarettes, to 21 starting 1 July 2019. Consumption Methods Tobacco is an agricultural product processed from the fresh leaves of plants in the genus Nicotiana. The genus contains several species, of which Nicotiana tabacum is the most commonly grown. Nicotiana rustica follows second, containing higher concentrations of nicotine. The leaves are harvested and cured to allow the slow oxidation and degradation of carotenoids in tobacco leaf. This produces certain compounds in the tobacco leaves which can be attributed to sweet hay, tea, rose oil, or fruity aromatic flavors. Before packaging, the tobacco is often combined with other additives in order to increase the addictive potency, shift the products pH, or improve the effects of smoke by making it more palatable. In the United States these additives are regulated to 599 substances. The product is then processed, packaged, and shipped to consumer markets. Beedi Beedis are thin South Asian cigarettes filled with tobacco flakes and wrapped in a tendu leaf tied with a string at one end. They produce higher levels of carbon monoxide, nicotine, and tar than cigarettes typical in the United States. Cigars Cigars are tightly rolled bundles of dried and fermented tobacco which are ignited so that smoke may be drawn into the smokers mouth. They are generally not inhaled because of the high alkalinity of the smoke, which can quickly become irritating to the trachea and lungs. The prevalence of cigar smoking varies depending on location, historical period, and population surveyed, and prevalence estimates vary somewhat depending on the survey method. The United States is the top consuming country by far, followed by Germany and the United Kingdom; the US and Western Europe account for about 75% of cigar sales worldwide. As of 2005 it is estimated that 4.3% of men and 0.3% of women smoke cigars in the USA.Cigarettes Cigarettes, French for "small cigar", are a product consumed through smoking and manufactured out of cured and finely cut tobacco leaves and reconstituted tobacco, often combined with other additives, which are then rolled or stuffed into a paper-wrapped cylinder. Cigarettes are ignited and inhaled, usually through a cellulose acetate filter, into the mouth and lungs. Hookah Hookah are a single or multi-stemmed (often glass-based) water pipe for smoking. Originally from India. The hookah was a symbol of pride and honor for the landlords, kings and other such high class people. Now, the hookah has gained immense popularity, especially in the Middle East. A hookah operates by water filtration and indirect heat. It can be used for smoking herbal fruits, tobacco, or cannabis. Kretek Kretek are cigarettes made with a complex blend of tobacco, cloves and a flavoring "sauce". It was first introduced in the 1880s in Kudus, Java, to deliver the medicinal eugenol of cloves to the lungs. The quality and variety of tobacco play an important role in kretek production, from which kretek can contain more than 30 types of tobacco. Minced dried clove buds weighing about one-third of the tobacco blend are added to add flavoring. In 2004 the United States prohibited cigarettes from having a "characterizing flavor" of certain ingredients other than tobacco and menthol, thereby removing kretek from being classified as cigarettes. Pipe smoking Pipe smoking is done with a tobacco pipe, typically consisting of a small chamber (the bowl) for the combustion of the tobacco to be smoked and a thin stem (shank) that ends in a mouthpiece (the bit). Shredded pieces of tobacco are placed into the chamber and ignited. Roll-your-own Roll-your-own or hand-rolled cigarettes, often called "rollies", "cigi" or "Roll-ups", are very popular particularly in European countries and the UK. These are prepared from loose tobacco, cigarette papers, and filters all bought separately. They are usually much cheaper than ready-made cigarettes and small contraptions can be bought making the process easier. Vaporizer A vaporizer is a device used to sublimate the active ingredients of plant material. Rather than burning the herb, which produces potentially irritating, toxic, or carcinogenic by-products; a vaporizer heats the material in a partial vacuum so that the active compounds contained in the plant boil off into a vapor. This method is often preferable when medically administrating the smoke substance, as opposed to directly pyrolyzing the plant material. Physiology The active substances in tobacco, especially cigarettes, are administered by burning the leaves and inhaling the vaporized gas that results. This quickly and effectively delivers substances into the bloodstream by absorption through the alveoli in the lungs. The lungs contain some 300 million alveoli, which amounts to a surface area of over 70 m2 (about the size of a tennis court). This method is not completely efficient as not all of the smoke will be inhaled, and some amount of the active substances will be lost in the process of combustion, pyrolysis. Pipe and Cigar smoke are not inhaled because of its high alkalinity, which are irritating to the trachea and lungs. However, because of its higher alkalinity (pH 8.5) compared to cigarette smoke (pH 5.3), non-ionized nicotine is more readily absorbed through the mucous membranes in the mouth. Nicotine absorption from cigar and pipe, however, is much less than that from cigarette smoke. Nicotine and cocaine activate similar patterns of neurons, which supports the existence of common substrates among these drugs.The absorbed nicotine mimics nicotinic acetylcholine which when bound to nicotinic acetylcholine receptors prevents the reuptake of acetylcholine thereby increasing that neurotransmitter in those areas of the body. These nicotinic acetylcholine receptors are located in the central nervous system and at the nerve-muscle junction of skeletal muscles; whose activity increases heart rate, alertness, and faster reaction times. Nicotine acetylcholine stimulation is not directly addictive. However, since dopamine-releasing neurons are abundant on nicotine receptors, dopamine is released; and, in the nucleus accumbens, dopamine is associated with motivation causing reinforcing behavior. Dopamine increase, in the prefrontal cortex, may also increase working memory.When tobacco is smoked, most of the nicotine is pyrolyzed. However, a dose sufficient to cause mild somatic dependency and mild to strong psychological dependency remains. There is also a formation of harmane (an MAO inhibitor) from the acetaldehyde in tobacco smoke. This may play a role in nicotine addiction, by facilitating a dopamine release in the nucleus accumbens as a response to nicotine stimuli. Using rat studies, withdrawal after repeated exposure to nicotine results in less responsive nucleus accumbens cells, which produce dopamine responsible for reinforcement. Demographics As of 2000, smoking was practiced by around 1.22 billion people. At current rates of smoker replacement and market growth, this may reach around 1.9 billion in 2025.Smoking may be up to five times more prevalent among men than women in some communities, although the gender gap usually declines with younger age. In some developed countries smoking rates for men have peaked and begun to decline, while for women they continue to climb.As of 2002, about twenty percent of young teenagers (13–15) smoked worldwide. 80,000 to 100,000 children begin smoking every day, roughly half of whom live in Asia. Half of those who begin smoking in adolescent years are projected to go on to smoke for 15 to 20 years. As of 2019 in the United States, roughly 800,000 high school students smoke.The World Health Organization (WHO) states that "Much of the disease burden and premature mortality attributable to tobacco use disproportionately affect the poor". Of the 1.22 billion smokers, 1 billion of them live in developing or transitional economies. Rates of smoking have leveled off or declined in the developed world. In the developing world, however, tobacco consumption is rising by 3.4% per year as of 2002.The WHO in 2004 projected 58.8 million deaths to occur globally, from which 5.4 million are tobacco-attributed, and 4.9 million as of 2007. As of 2002, 70% of the deaths are in developing countries. As of 2017, smoking causes one in ten deaths worldwide, with half of those deaths in the US, China, India and Russia. Psychology Takeup Most smokers begin smoking during adolescence or early adulthood. Some studies also show that smoking can also be linked to various mental health complications. Smoking has elements of risk-taking and rebellion, which often appeal to young people. The presence of peers that smoke and media featuring high-status models smoking may also encourage smoking. Because teenagers are influenced more by their peers than by adults, attempts by parents, schools, and health professionals at preventing people from trying cigarettes are often unsuccessful.Children of smoking parents are more likely to smoke than children with non-smoking parents. Children of parents who smoke are less likely to quit smoking. One study found that parental smoking cessation was associated with less adolescent smoking, except when the other parent currently smoked. A current study tested the relation of adolescent smoking to rules regulating where adults are allowed to smoke in the home. Results showed that restrictive home smoking policies were associated with lower likelihood of trying smoking for both middle and high school students.Behavioural research generally indicates that teenagers begin their smoking habits due to peer pressure, and cultural influence portrayed by friends. However, one study found that direct pressure to smoke cigarettes played a less significant part in adolescent smoking, with adolescents also reporting low levels of both normative and direct pressure to smoke cigarettes. Mere exposure to tobacco retailers may motivate smoking behaviour in adults. A similar study suggested that individuals may play a more active role in starting to smoke than has previously been thought and that social processes other than peer pressure also need to be taken into account. Another studys results indicated that peer pressure was significantly associated with smoking behavior across all age and gender cohorts, but that intrapersonal factors were significantly more important to the smoking behavior of 12- to 13-year-old girls than same-age boys. Within the 14- to 15-year-old age group, one peer pressure variable emerged as a significantly more important predictor of girls than boys smoking. It is debated whether peer pressure or self-selection is a greater cause of adolescent smoking. Psychologist Hans Eysenck (who later was questioned for nonplausible results and unsafe publications) developed a personality profile for the typical smoker. Extraversion is the trait that is most associated with smoking, and smokers tend to be sociable, impulsive, risk taking, and excitement seeking individuals. Persistence The reasons given by some smokers for this activity have been categorized as addictive smoking, pleasure from smoking, tension reduction/relaxation, social smoking, stimulation, habit/automatism, and handling. There are gender differences in how much each of these reasons contribute, with females more likely than males to cite tension reduction/relaxation, stimulation and social smoking.Some smokers argue that the depressant effect of smoking allows them to calm their nerves, often allowing for increased concentration. However, according to the Imperial College London, "Nicotine seems to provide both a stimulant and a depressant effect, and it is likely that the effect it has at any time is determined by the mood of the user, the environment and the circumstances of use. Studies have suggested that low doses have a depressant effect, while higher doses have stimulant effect." Patterns A number of studies have established that cigarette sales and smoking follow distinct time-related patterns. For example, cigarette sales in the United States of America have been shown to follow a strongly seasonal pattern, with the high months being the months of summer, and the low months being the winter months.Similarly, smoking has been shown to follow distinct circadian patterns during the waking day—with the high point usually occurring shortly after waking in the morning, and shortly before going to sleep at night. Impact Health Tobacco smoking is the leading cause of preventable death and a global public health concern. There are 1.1 billion tobacco users in the world. One person dies every six seconds from a tobacco related disease. Tobacco use leads most commonly to diseases affecting the heart and lungs, with smoking being a major risk factor for heart attacks, strokes, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), emphysema, and various types and subtypes of cancers (particularly lung cancer, cancers of the oropharynx, larynx, and mouth, esophageal and pancreatic cancer). Cigarette smoking increases the risk of Crohns disease as well as the severity of the course of the disease. It is also the number one cause of bladder cancer. Cigarette smoking has also been associated with sarcopenia, the age-related loss of muscle mass and strength. The smoke from tobacco elicits carcinogenic effects on the tissues of the body that are exposed to the smoke. Regular cigar smoking is known to carry serious health risks, including increased risk of developing various types and subtypes of cancers, respiratory diseases, cardiovascular diseases, cerebrovascular diseases, periodontal diseases and teeth loss, and malignant diseases.Tobacco smoke is a complex mixture of over 7,000 toxic chemicals, 98 of which are associated with an increased risk of cardiovascular disease and 69 of which are known to be carcinogenic. The most important chemicals causing cancer are those that produce DNA damage, since such damage appears to be the primary underlying cause of cancer. Cunningham et al. combined the microgram weight of the compound in the smoke of one cigarette with the known genotoxic effect per microgram to identify the most carcinogenic compounds in cigarette smoke: acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide, and isoprene. In addition to the aforementioned toxic chemicals, flavored tobacco contains flavorings which upon heating release toxic chemicals and carcinogens such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), furans, phenols, aldehydes (such as acrolein), and acids, in addition to nitrogenous carcinogens, alcohols, and heavy metals, all of which are dangerous to human health. A comparison of 13 common hookah flavors found that melon flavors are the most dangerous, with their smoke containing four classes of hazards in high concentrations.The World Health Organization estimates that tobacco caused 5.4 million deaths in 2004 and 100 million deaths over the course of the 20th century. Similarly, the United States Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide." Although 70% of smokers state their intention to quit only 3–5% are actually successful in doing so.The probabilities of death from lung cancer before age 75 in the United Kingdom are 0.2% for men who never smoked (0.4% for women), 5.5% for male former smokers (2.6% in women), 15.9% for current male smokers (9.5% for women) and 24.4% for male "heavy smokers" defined as smoking more than 5 cigarettes per day (18.5% for women). Tobacco smoke can combine with other carcinogens present within the environment in order to produce elevated degrees of lung cancer. The risk of lung cancer decreases almost from the first day someone quits smoking. Healthy cells that have escaped mutations grow and replace the damaged ones in the lungs. In the research dated December 2019, 40% of cells in former smokers looked like those of people who had never smoked.Rates of smoking have generally leveled-off or declined in the developed world. Smoking rates in the United States have dropped by half from 1965 to 2006, falling from 42% to 20.8% in adults. In the developing world, tobacco consumption is rising by 3.4% per year.Smoking alters the transcriptome of the lung parenchyma; the expression levels of a panel of seven genes (KMO, CD1A, SPINK5, TREM2, CYBB, DNASE2B, FGG) are increased in the lung tissue of smokers.Passive smoking is the inhalation of tobacco smoke by individuals who are not actively smoking. This smoke is known as second-hand smoke (SHS) or environmental tobacco smoke (ETS) when the burning end is present, and third-hand smoke after the burning end has been extinguished. Because of its negative implications, exposure to SHS has played a central role in the regulation of tobacco products. Six hundred thousand deaths were attributed to SHS in 2004. It also has been known to produce skin conditions such as freckles and dryness.In 2015, a meta-analysis found that smokers were at greater risk of developing psychotic disorder. Tobacco has also been described an anaphrodisiac due to its propensity for causing erectile dysfunction. There is a correlation between tobacco smoking and a reduced risk of Parkinsons disease. Economic In countries where there is a universally funded healthcare system, the government covers the cost of medical care for smokers who become ill through smoking in the form of increased taxes. Two broad debating positions exist on this front, the "pro-smoking" argument suggesting that heavy smokers generally do not live long enough to develop the costly and chronic illnesses which affect the elderly, reducing societys healthcare burden, and the "anti-smoking" argument suggests that the healthcare burden is increased because smokers get chronic illnesses younger and at a higher rate than the general population. Data on both positions has been contested. The Centers for Disease Control and Prevention published research in 2002 claiming that the cost of each pack of cigarettes sold in the United States was more than $7 in medical care and lost productivity. The cost may be higher, with another study putting it as high as $41 per pack, most of which however is on the individual and his/her family. This is how one author of that study puts it when he explains the very low cost for others: "The reason the number is low is that for private pensions, Social Security, and Medicare — the biggest factors in calculating costs to society — smoking actually saves money. Smokers die at a younger age and dont draw on the funds theyve paid into those systems." Other research demonstrates that premature death caused by smoking may redistribute Social Security income in unexpected ways that affect behavior and reduce the economic well-being of smokers and their dependents. To further support this, whatever the rate of smoking consumption is per day, smokers have a greater lifetime medical cost on average compared to a non-smoker by an estimated $6000 Between the cost for lost productivity and health care expenditures combined, cigarette smoking costs at least 193 billion dollars (Research also shows that smokers earn less money than nonsmokers). As for secondhand smoke, the cost is over 10 billion dollars.By contrast, some non-scientific studies, including one conducted by Philip Morris in the Czech Republic called Public Finance Balance of Smoking in the Czech Republic and another by the Cato Institute, support the opposite position. Philip Morris has explicitly apologised for the former study, saying: "The funding and public release of this study which, among other things, detailed purported cost savings to the Czech Republic due to premature deaths of smokers, exhibited terrible judgment as well as a complete and unacceptable disregard of basic human values. For one of our tobacco companies to commission this study was not just a terrible mistake, it was wrong. All of us at Philip Morris, no matter where we work, are extremely sorry for this. No one benefits from the very real, serious and significant diseases caused by smoking."Between 1970 and 1995, per-capita cigarette consumption in poorer developing countries increased by 67 percent, while it dropped by 10 percent in the richer developed world. Eighty percent of smokers now live in less developed countries. By 2030, the World Health Organization (WHO) forecasts that 10 million people a year will die of smoking-related illness, making it the single biggest cause of death worldwide, with the largest increase to be among women. WHO forecasts the 21st centurys death rate from smoking to be ten times the 20th centurys rate ("Washingtonian" magazine, December 2007). The tobacco industry is known to be one of the largest global enterprises in the world. The six biggest tobacco companies made a combined profit of $35.1 billion (Jha et al., 2014) in 2010. Social Famous smokers of the past used cigarettes or pipes as part of their image, such as Jean-Paul Sartres Gauloises-brand cigarettes; Albert Einsteins, Douglas MacArthurs, Bertrand Russells, and Bing Crosbys pipes; or the news broadcaster Edward R. Murrows cigarette. Writers in particular seem to be known for smoking, for example, Cornell Professor Richard Kleins book Cigarettes are Sublime for the analysis, by this professor of French literature, of the role smoking plays in 19th and 20th century letters. The popular author Kurt Vonnegut addressed his addiction to cigarettes within his novels. British Prime Minister Harold Wilson was well known for smoking a pipe in public as was Winston Churchill for his cigars. Sherlock Holmes, the fictional detective created by Sir Arthur Conan Doyle, smoked a pipe, cigarettes, and cigars. The DC Vertigo comic book character John Constantine, created by Alan Moore, is synonymous with smoking, so much so that the first storyline by Preacher creator Garth Ennis centered around John Constantine contracting lung cancer. Professional wrestler James Fullington, while in character as "The Sandman", is a chronic smoker in order to appear "tough". The problem of smoking at home is particularly difficult for women in many cultures (especially Arab cultures), where it may not be acceptable for a woman to ask her husband not to smoke at home or in the presence of her children. Studies have shown that pollution levels for smoking areas indoors are higher than levels found on busy roadways, in closed motor garages, and during fire storms. Furthermore, smoke can spread from one room to another, even if doors to the smoking area are closed.The ceremonial smoking of tobacco, and praying with a sacred pipe, is a prominent part of the religious ceremonies of a number of Native American Nations. Sema, the Anishinaabe word for tobacco, is grown for ceremonial use and considered the ultimate sacred plant since its smoke is believed to carry prayers to the spirits. In most major religions, however, tobacco smoking is not specifically prohibited, although it may be discouraged as an immoral habit. Before the health risks of smoking were identified through controlled study, smoking was considered an immoral habit by certain Christian preachers and social reformers. The founder of the Latter Day Saint movement, Joseph Smith, recorded that on 27 February 1833, he received a revelation which discouraged tobacco use. This "Word of Wisdom" was later accepted as a commandment, and faithful Latter-day Saints abstain completely from tobacco. Jehovahs Witnesses base their stand against smoking on the Bibles command to "clean ourselves of every defilement of flesh" (2 Corinthians 7:1). The Jewish Rabbi Yisrael Meir Kagan (1838–1933) was one of the first Jewish authorities to speak out on smoking. In Ahmadiyya Islam, smoking is highly discouraged, although not forbidden. During the month of fasting however, it is forbidden to smoke tobacco. In the Baháʼí Faith, smoking tobacco is discouraged though not forbidden. Public policy On 27 February 2005 the WHO Framework Convention on Tobacco Control, took effect. The FCTC is the worlds first public health treaty. Countries that sign on as parties agree to a set of common goals, minimum standards for tobacco control policy, and to cooperate in dealing with cross-border challenges such as cigarette smuggling. Currently the WHO declares that 4 billion people will be covered by the treaty, which includes 168 signatories. Among other steps, signatories are to put together legislation that will eliminate secondhand smoke in indoor workplaces, public transport, indoor public places and, as appropriate, other public places. Taxation Many governments have introduced excise taxes on cigarettes in order to reduce the consumption of cigarettes. The World Health Organisation finds that: The structure of tobacco excise taxes varies considerably across countries, with lower income countries more likely to rely more on ad valorem excises and higher income countries more likely to rely more on specific excise taxes, while many countries at all income levels use a mix of specific and ad valorem excises. Tobacco excise tax systems are quite complex in several countries, where different tax rates are applied based on prices, product characteristics such as presence/absence of a filter or length, packaging, weight, tobacco content, and/or production or sales volume. These complex systems are difficult to administer, create opportunities for tax avoidance, and are less effective from a public health perspective. Globally, cigarette excise taxes account for less than 45 percent of cigarette prices, on average, while all taxes applied to cigarettes account for just over half of half of price. Higher income countries levy higher taxes on tobacco products and these taxes account for a greater share of price, with both the absolute tax and share of price accounted for by tax falling as country incomes fall. In 2002, the Centers for Disease Control and Prevention said that each pack of cigarettes sold in the United States costs the nation more than $7 in medical care and lost productivity, around $3400 per year per smoker. Another study by a team of health economists finds the combined price paid by their families and society is about $41 per pack of cigarettes.Substantial scientific evidence shows that higher cigarette prices result in lower overall cigarette consumption. Most studies indicate that a 10% increase in price will reduce overall cigarette consumption by 3% to 5%. Youth, minorities, and low-income smokers are two to three times more likely to quit or smoke less than other smokers in response to price increases. Smoking is often cited as an example of an inelastic good, however, i.e. a large rise in price will only result in a small decrease in consumption. Many nations have implemented some form of tobacco taxation. As of 1997, Denmark had the highest cigarette tax burden of $4.02 per pack. Taiwan only had a tax burden of $0.62 per pack. The federal government of the United States charges $1.01 per pack.Cigarette taxes vary widely from state to state in the United States. For example, Missouri has a cigarette tax of only 17 cents per pack, the nations lowest, while New York has the highest cigarette tax in the U.S.: $4.35 per pack. In Alabama, Illinois, Missouri, New York City, Tennessee, and Virginia, counties and cities may impose an additional limited tax on the price of cigarettes. Sales taxes are also levied on tobacco products in most jurisdictions. In the United Kingdom, a packet of 20 cigarettes has a tax added of 16.5% of the retail price plus £4.90. The UK has a significant black market for tobacco, and it has been estimated by the tobacco industry that 27% of cigarette and 68% of handrolling tobacco consumption is non-UK duty paid (NUKDP).In Australia total taxes account for 62.5% of the final price of a packet of cigarettes (2011 figures). These taxes include federal excise or customs duty and Goods and Services Tax. Restrictions In June 1967, the US Federal Communications Commission ruled that programmes broadcast on a television station which discussed smoking and health were insufficient to offset the effects of paid advertisements that were broadcast for five to ten minutes each day. In April 1970, the US Congress passed the Public Health Cigarette Smoking Act banning the advertising of cigarettes on television and radio starting on 2 January 1971.The Tobacco Advertising Prohibition Act 1992 expressly prohibited almost all forms of Tobacco advertising in Australia, including the sponsorship of sporting or other cultural events by cigarette brands. All tobacco advertising and sponsorship on television has been banned within the European Union since 1991 under the Television Without Frontiers Directive (1989). This ban was extended by the Tobacco Advertising Directive, which took effect in July 2005 to cover other forms of media such as the internet, print media, and radio. The directive does not include advertising in cinemas and on billboards or using merchandising – or tobacco sponsorship of cultural and sporting events which are purely local, with participants coming from only one Member State as these fall outside the jurisdiction of the European Commission. However, most member states have transposed the directive with national laws that are wider in scope than the directive and cover local advertising. A 2008 European Commission report concluded that the directive had been successfully transposed into national law in all EU member states, and that these laws were well implemented.Some countries also impose legal requirements on the packaging of tobacco products. For example, in the countries of the European Union, Turkey, Australia and South Africa, cigarette packs must be prominently labeled with the health risks associated with smoking. Canada, Australia, Thailand, Iceland and Brazil have also imposed labels upon cigarette packs warning smokers of the effects, and they include graphic images of the potential health effects of smoking. Cards are also inserted into cigarette packs in Canada. There are sixteen of them, and only one comes in a pack. They explain different methods of quitting smoking. Also, in the United Kingdom, there have been a number of graphic NHS advertisements, one showing a cigarette filled with fatty deposits, as if the cigarette is symbolizing the artery of a smoker. Some countries have also banned advertisement at point of sale. United Kingdom and Ireland have limited the advertisement of tobacco at retailers. This includes storing of cigarettes behind a covered shelf not visible to the public. They do however allow some limited advertising at retailers. Norway has a complete ban of point of sale advertising. This includes smoking products and accessories. Implementing these policies can be challenging, all of these countries experienced resistance and challenges from the tobacco industry. The World Health Organisation recommends the complete ban of all types of advertisement or product placement, including at vending machines, at airports and on internet shops selling tobacco. The evidence is as yet unclear as to the impact of such bans. Many countries have a smoking age. In many countries, including the United States, most European Union member states, New Zealand, Canada, South Africa, Israel, India, Brazil, Chile, Costa Rica and Australia, it is illegal to sell tobacco products to minors and in the Netherlands, Austria, Belgium, Denmark and South Africa it is illegal to sell tobacco products to people under the age of 16. On 1 September 2007 the minimum age to buy tobacco products in Germany rose from 16 to 18, as well as in the United Kingdom where on 1 October 2007 it rose from 16 to 18. Underlying such laws is the belief that people should make an informed decision regarding the risks of tobacco use. These laws have a lax enforcement in some nations and states. In China, Turkey, and many other countries usually a child will have little problem buying tobacco products, because they are often told to go to the store to buy tobacco for their parents. Several countries such as Ireland, Latvia, Estonia, the Netherlands, Finland, Norway, Canada, Australia, Sweden, Portugal, Singapore, Italy, Indonesia, India, Lithuania, Chile, Spain, Iceland, United Kingdom, Slovenia, Turkey and Malta have legislated against smoking in public places, often including bars and restaurants. Restaurateurs have been permitted in some jurisdictions to build designated smoking areas (or to prohibit smoking). In the United States, many states prohibit smoking in restaurants, and some also prohibit smoking in bars. In provinces of Canada, smoking is illegal in indoor workplaces and public places, including bars and restaurants. As of 31 March 2008 Canada has introduced a smoke-free law in all public places, as well as within 10 metres of an entrance to any public place. In Australia, smoke-free laws vary from state to state. Currently, Queensland has completely smoke-free indoor public places (including workplaces, bars, pubs and eateries) as well as patrolled beaches and some outdoor public areas. There are, however, exceptions for designated smoking areas. In Victoria, smoking is restricted in railway stations, bus stops and tram stops as these are public locations where second-hand smoke can affect non-smokers waiting for public transport, and since 1 July 2007 is now extended to all indoor public places. In New Zealand and Brazil, smoking is restricted in enclosed public places including bars, restaurants and pubs. Hong Kong restricted smoking on 1 January 2007 in the workplace, public spaces such as restaurants, karaoke rooms, buildings, and public parks (bars which do not admit minors were exempt until 2009). In Romania smoking is illegal in trains, metro stations, public institutions (except where designated, usually outside) and public transport. In Germany, in addition to smoking bans in public buildings and transport, an anti-smoking ordinance for bars and restaurants was implemented in late 2007. A study by the University of Hamburg (Ahlfeldt and Maennig 2010) demonstrates, that the smoking ban had, if any, only short run impacts on bar and restaurant revenues. In the medium and long run no negative effect was measurable. The results suggest either, that the consumption in bars and restaurants is not affected by smoking bans in the long run, or, that negative revenue impacts by smokers are compensated by increasing revenues through non-smokers. Ignition safety An indirect public health problem posed by cigarettes is that of accidental fires, usually linked with consumption of alcohol. Enhanced combustion using nitrates was traditionally used but cigarette manufacturers have been silent on this subject claiming at first that a safe cigarette was technically impossible, then that it could only be achieved by modifying the paper. Roll your own cigarettes contain no additives and are fire safe. Numerous fire safe cigarette designs have been proposed, some by tobacco companies themselves, which would extinguish a cigarette left unattended for more than a minute or two, thereby reducing the risk of fire. Among American tobacco companies, some have resisted this idea, while others have embraced it. RJ Reynolds was a leader in making prototypes of these cigarettes in 1983 and will make all of their U.S. market cigarettes to be fire-safe by 2010. Phillip Morris is not in active support of it. Lorillard (purchased by RJ Reynolds), the US 3rd-largest tobacco company, seems to be ambivalent. Gateway drug theory The relationship between tobacco and other drug use has been well-established, however the nature of this association remains unclear. The two main theories are the phenotypic causation (gateway) model and the correlated liabilities model. The causation model argues that smoking is a primary influence on future drug use, while the correlated liabilities model argues that smoking and other drug use are predicated on genetic or environmental factors. One study published by the NIH found that tobacco use may be linked to cocaine addiction and marijuana use. The study stated that 90% of adults who used cocaine had smoked cigarettes before (this was for people ages 18–34). This study could support the gateway drug theory. Cessation Smoking cessation, referred to as "quitting", is the action leading towards abstinence of tobacco smoking. Methods of "quitting" include advice from physicians or social workers, cold turkey, nicotine replacement therapy, contingent vouchers, antidepressants, hypnosis, self-help (mindfulness meditation), and support groups. A meta-analysis from 2018, conducted on 61 RCT, showed that one year after people quit smoking with the assistance of first‐line smoking cessation medications (and some behavioral help), only a little under 20% of smokers remained sustained abstinence.In the United States, about 70% of smokers would like to quit smoking, and 50% report having made an attempt to do so in the past year. In recent years, especially in Canada and the United Kingdom, many smokers have switched to use electronic cigarettes in order to quit smoking tobacco. See also Cannabis smoking Cigarette smoking among college students Cigarette smoking for weight loss Electronic cigarette Herbal cigarette List of cigarette smoke carcinogens Snuff (tobacco) Smokers paradox Tobacco advertising Tobacco control References Bibliography == External links ==

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

I'm curious about the meaning of the medical term 'Cholesterol embolism.' Can you give me some insights?

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. Affected organs show the characteristic histologic changes in 50-75% of the clinically diagnosed cases. Non-specific tissue findings suggestive of a cholesterol embolization include ischemic changes, necrosis and unstable-appearing complex atherosclerotic plaques (that are cholesterol-laden and have a thin fibrous cap). While biopsy findings may not be diagnostic, they have significant value, as they help exclude alternate diagnoses, e.g. vasculitis, that often cannot be made confidently based on clinical criteria. Treatment Treatment of an episode of cholesterol emboli is generally symptomatic, i.e. it deals with the symptoms and complications but cannot reverse the phenomenon itself. In kidney failure resulting from cholesterol crystal emboli, statins (medication that reduces cholesterol levels) have been shown to halve the risk of requiring hemodialysis. History The phenomenon of embolisation of cholesterol was first recognized by the Danish pathologist Dr. Peter Ludvig Panum and published in 1862. Further evidence that eroded atheroma was the source of emboli came from American pathologist Dr. Curtis M. Flory, who in 1945 reported the phenomenon in 3.4% of a large autopsy series of older individuals with severe atherosclerosis of the aorta. References External links Patient.info - Cholesterol Embolism Summary MedlinePlus - atheroembolic renal disease

You serve as an encyclopedia of medical terms. Deliver clear, detailed explanations, making medical language understandable to a diverse audience.

Could you please explain the term 'Monomelic amyotrophy' in simple language?

Monomelic amyotrophy (MMA) is a rare motor neuron disease first described in 1959 in Japan. Its symptoms usually appear about two years after adolescent growth spurt and is significantly more common in males, with an average age of onset between 15 and 25 years. MMA is reported most frequently in Asia but has a global distribution. It is typically marked by insidious onset of muscle atrophy of an upper limb, which plateaus after two to five years from which it neither improves nor worsens. There is no pain or sensory loss associated with MMA. MMA is not believed to be hereditary.Both the names for the disorder and its possible causes have been evolving since first reported in 1959. It is most commonly believed the condition occurs by asymmetrical compression of the cervical spinal column by the cervical dural sac, especially when the neck is flexed. However, the disease is uncommon and diagnosis is confused by several atypical reports. Symptoms In terms of the signs and symptoms that are consistent for an individual who has monomelic amyotrophy are the following (although this does not reflect a complete list): Initially most people notice weakness in one hand; they may feel contracture of middle and ring finger and notice a thinning of the subdigital palm of the affected fingers. Progress of the condition varies, and weakness in the arm ranges from minimal to significant. Fasciculations are uncommon (>20%); increased weakness under cold conditions is commonly reported (cold paresis). Cause The disability originates with impaired functioning of the anterior horn cells of the lower cervical cord (lower neck), but the cause of the decline is not fully understood and is still considered unknown. Researchers, including Hirayama, believe that "forward displacement of the cervical dural sac and compressive flattening of the lower cervical cord during neck flexion" is the contributing factor. Studies consistently note a loss of normal neck curvature (the cervical lordosis) and compression of the cervical chord by the dural sac in forward flexion. "There is a debate about whether this condition represents a focal form of primary LMN degeneration (ie, a focal form of spinal muscular atrophy) or a local consequence of chronic compression from a dural expansion in the cervical spine."A familial link has been found in a minor percentage of cases, including parent-child and sibling-sibling. Because of the unusual distribution of the disease, some researchers speculate that there could be an ethnic link. Diagnosis The condition presents almost exclusively in 15- to 25-year-old adults experiencing weakness in hand and arm. A patient history and a neurological exam narrows down the possible diagnosis; this preliminary exam typically includes strength and reflex tests. Cold paresis (increased weakness in cold weather) is reported by most patients (> 80%). Fasciculations are reported as uncommon (< 20%) to common; larger tremors are more consistently cited. Males are far more likely to be diagnosed with the condition.The disease is rare and several cited cases deviate from the expected norm, making diagnosis more difficult. Proposed diagnostic criteria: Distal predominant muscle weakness and atrophy in forearm and hand Involvement of the unilateral upper extremity almost always all the time Onset between the ages of 10 to early 20s Insidious onset with gradual progression for the first several years, followed by stabilization No lower extremity involvement No sensory disturbance and tendon reflex abnormalities Exclusion of other diseases (e.g., motor neuron disease, multifocal motor neuropathy, brachial plexopathy, spinal cord tumors, syringomyelia, cervical vertebral abnormalities, anterior interosseous, or deep ulnar neuropathy) A neurological exam can suggest different motor neuron diseases (such as MMA), but to more confidently distinguish MMA from the diseases it mimics, advanced diagnostic tools are called for. These include exam tools such as magnetic resonance imaging (MRI), and electromyography (EMG) and nerve conduction velocity (NCV) tests. An MRI examination of the neck would typically reveal—for a positive MMA diagnosis—some constriction of the cervical cord and an abnormal forward extension of the neck, ("loss of cervical lordosis"); pressure by the dura on the nerve cord apparently causes the flattening / narrowing. An EMG test reveals loss of the nerve supply, or denervation, in the affected limb without a conduction block (a nerve blockage restricted to a small segment of the nerve).In early stages of the disease MMA may be confused for amyotrophic lateral sclerosis (ALS), cervical spondylotic amyotrophy (CSA), and other challenging neurological diseases, as well as conditions that are minor but that call for very different treatments, such as advanced carpal tunnel syndrome (CTS). Symptoms somewhat differ. Pain and tingling in the hand is typically present in CTS and absent from MMA; loss of function presents differently; with careful electrophysiological study and neurological exams the two are distinguished. In early stages, ALS, SCA, and MMA, presentation may be similar. Both CSA and ALS ultimately have more extensive symptoms. MMA is more prevalent in young people while ALS and CSA are more common in older populations. With ALS, hand symptoms usually more commonly both proximal and distal vs in MMA mostly distal only, and with ALS fasciculations (twitching) are often present in upper extremities, but rarely in MMA. MMA is usually eliminated from consideration if disability expresses itself in more than one extremity or in lower extremities (legs), but symptomatic absence may not rule out ALS for three to five years after initial onset. Electrophysiological texts and reflex tests tend to yield different results, but interpretation is at times subjective. Treatment At present there is no cure for MMA. The impact on the affected individual ranges from minimal to significant depending on the extent of the weakness. Physical and occupational therapies include muscle strengthening exercises and training in hand coordination. Early use of a cervical collar is increasingly encouraged as therapeutic for arresting further compression of the cervical spinal cord. Spinal surgery on patients with more advanced symptoms has met with reported success, but is still regarded as experimental. Prognosis The symptoms of MMA usually progress slowly for two to five years and then remain stable for many years. The weakness can progress to the opposite limb, although whether this progression is typical or rare is under discussion. Cases of patient improvement and deterioration have both been described, but are atypical. Initially MMA can be confused for slowly progressing case of other neurological diseases such as amyotrophic lateral sclerosis (ALS); initial symptoms can be similar, but their causes are apparently different, and their outcomes markedly so. Diagnostic tools have improved since first described, and a few therapies are being introduced. But sometimes several years of observation are needed before a definitive diagnosis can be made.Use of a cervical collar may afford relief, and some researchers advocate its therapeutic use. There is also a slowly progressive variant of MMA known as OSullivan-McLeod syndrome, which only affects the small muscles of the hand and forearm and has a slowly progressive course. Epidemiology MMA is described most frequently in Asia, with studies of a few hundred individuals emerging from Japan, China and India; it is much less commonly seen in North America and Europe. The disease (disorder) was first described by Keizo Hirayama in 1959 as "juvenile muscular atrophy of unilateral upper extremity". In 1984 Mandavilli Gourie-Devi (et al.) introduced the term "monomelic amyotrophy". The disease primarily (but not exclusively) affects young (15- to 25-year-old) males. As of 2014 there had been less than 1500 described cases, starting with the patients in Hirayamas 1959 study. The condition is disproportionately high in Asia but no conclusive reason has been found for this. To date the largest studies recorded are Japan (333 cases), India (279 cases), and China (179 cases). Etymology Both the names for the disorder and its possible causes have been evolving since first reported. Because this condition has been found almost exclusively in healthy young adults and stabilizes after a few years, a span of 23 years elapsed between the time Hirayama first described the condition, and the first death (from cancer), and autopsy. Over the several decades since first reported, a majority of researchers now describe this as a biomechanical condition linked to adolescent growth spurt. However, this is not yet a universal conclusion and there are anomalous reports that suggest an incomplete understanding of the condition. See also Lower motor neuron lesion Notes References External links monomelic_amyotrophy at NINDS

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I've come across the term 'Herpetic whitlow' in a medical context, but I'm not sure what it means. Can you clarify?

A herpetic whitlow is a lesion (whitlow) on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2. HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions. It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion, and in adults aged 20 to 30 following contact with HSV-2-infected genitals. Symptoms and signs Symptoms of herpetic whitlow include swelling, reddening and tenderness of the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form individually, then merge and become cloudy, unlike in bacterial whitlow when there is pus. Associated pain often seems largely relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks. It may reside in axillary sensory ganglia to cause recurrent herpetic lesions on that arm or digits. Blistering can occur in severe cases. Causes In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.Contact sports are also a potential source of infection with herpetic whitlows. Treatment Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. It is usually given when the condition fails to improve on its own. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes. Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis. Prognosis Even though the disease is self-limiting, as with many herpes infections, the virus lies dormant in the peripheral nervous system. The disease recurs in about 20-50% of people. The most severe infection is usually the first one, with recurrences subsequently getting milder. The lesions the disease makes will either dry out, or burst, followed by healing. If the infected area is not touched, scars usually do not occur. The immunocompromised may have a hard time recovering, and have more frequent recurrences. Gallery See also Herpes simplex List of cutaneous conditions References External links Herpetic Whitlow Medscape Klotz, R. W. (Feb 1990). "Herpetic whitlow: an occupational hazard" (PDF). AANA J. 58 (1): 8–13. PMID 2316323. Archived from the original (PDF) on 2016-06-05. Retrieved 2014-05-12.

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

Could you offer a clear explanation of the term 'Pemphigus vulgaris' as used in the medical field?

Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. Pemphigus was derived from the Greek word pemphix, meaning blister. It is classified as a type II hypersensitivity reaction in which antibodies are formed against desmosomes, components of the skin that function to keep certain layers of skin bound to each other. As desmosomes are attacked, the layers of skin separate and the clinical picture resembles a blister. These blisters are due to acantholysis, or breaking apart of intercellular connections through an autoantibody-mediated response. Over time the condition inevitably progresses without treatment: lesions increase in size and distribution throughout the body, behaving physiologically like a severe burn. Before the advent of modern treatments, mortality for the disease was close to 90%. Today, the mortality rate with treatment is between 5-15% due to the introduction of corticosteroids as primary treatment. Nevertheless, in 1998, pemphigus vulgaris was the fourth most common cause of death due to a skin disorder. The disease mainly affects middle-aged and older adults between 50–60 years old. There has historically been a higher incidence in women. Signs and symptoms Pemphigus vulgaris most commonly presents with oral blisters (buccal and palatine mucosa, especially), but also includes cutaneous blisters. Other mucosal surfaces, the conjunctiva, nose, esophagus, penis, vulva, vagina, cervix, and anus, may also be affected. Flaccid blisters over the skin are frequently seen with sparing of the skin covering the palms and soles.Blisters commonly erode and leave ulcerated lesions and erosions. A positive Nikolsky sign (induction of blistering in normal skin or at the edge of a blister) is indicative of the disease.Severe pain with chewing can lead to weight loss and malnutrition. Pathophysiology Pemphigus is an autoimmune disease caused by antibodies directed against both desmoglein 1 and desmoglein 3 present in desmosomes. Loss of desmosomes results in loss of cohesion between keratinocytes in the epidermis, and a disruption of the barrier function served by intact skin. The process is classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the bodys own tissues). On histology, the basal keratinocytes are usually still attached to the basement membrane leading to a characteristic appearance called "tombstoning". Transudative fluid accumulates in between the keratinocytes and the basal layer (suprabasal split), forming a blister and resulting in what is known as a positive Nikolskys sign. This is a contrasting feature from bullous pemphigoid, which is thought to be due to anti-hemidesmosome antibodies, and where the detachment occurs between the epidermis and dermis (subepidermal bullae). Clinically, pemphigus vulgaris is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and erythematoses) are more anti-desmoglein 1 heavy. The disease arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. It can also start with blisters in the mouth. The lesions can become quite extensive. Diagnosis Because it is a rare disease, diagnosis is often complicated and takes a long time. Early in the disease patients may have erosions in the mouth or blisters on the skin. These blisters can be itchy or painful. Theoretically, the blisters should demonstrate a positive Nikolskys sign, in which the skin sloughs off from slight rubbing, but this is not always reliable. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, in which cells are acantholytic, that is, lacking the normal intercellular connections that hold them together. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein desmoglein. Pemphigus vulgaris is easily confused with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment. Treatment Corticosteroids and other immunosuppressive medications have historically been employed to reduce pemphigus symptoms, yet steroids are associated with serious and long-lasting side effects and their use should be limited as much as possible. Intravenous immunoglobulin, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success. An established alternative to steroids are monoclonal antibodies such as rituximab, which are increasingly being used as first-line treatment. In summer 2018, the FDA granted full approval to rituximab for this application, following successful fast track evaluation. In numerous case series, many patients achieve remission after one cycle of rituximab. Treatment is more successful if initiated early on in the course of disease, perhaps even at diagnosis. Rituximab treatment combined with monthly IV immunoglobulin infusions has resulted in long-term remission with no recurrence of disease in 10 years after treatment was halted. This was a small trial study of 11 patients with 10 patients followed to completion. Rituximab demonstrated superior efficacy compared to mycophenolate mofetil in a Phase III clinical trial, results of which were published in 2021. Epidemiology Pemphigus vulgaris is a relatively rare disease that only affects about 1 to 5 people in 1 million in the United Kingdom, with an incidence of 1-10 cases per 1 million people across the world. There is an estimated prevalence of 30,000-40,000 cases in the United States. Cases of P. vulgaris usually dont develop until after the age of 50 or so. The disease is not contagious which means it cannot be spread from person to person. There is currently no way of knowing who will be affected with P. vulgaris in their life as it is usually not a genetic disorder and is usually triggered later in life by environmental factors. Men and women are both equally affected and the disease has been found to affect people of many different cultures and racial backgrounds, especially Ashkenazi Jews, people of Mediterranean, North Indian and Persian descent. There has been no found difference in the rate of disease when looking at socioeconomic factors as well.If left untreated, 8 of 10 people with the disease die within a year with a cause of death being infection or loss of fluids, which is very common for raw, open sores that are characteristic of P. vulgaris. With treatment, only about 1 in 10 people with the disease die, either from the condition, or side effects of the medicine.An effect of the disease being so rare is that there is not enough evidence to prove that the treatments currently being used are actually as effective as they could be. Doctors are trying to find effective steroid-sparing agents to use in the treatment, to decrease the side effects of long term steroid treatment. The small amount of case numbers make it hard to test statistical significance between the affected and the control groups when testing if these types of systematic treatments are effective. Research Research into using genetically modified T-cells to treat pemphigus vulgaris in mice was reported in 2016. Rituximab indiscriminately attacks all B cells, which reduces the bodys ability to control infections. In the experimental treatment, human T cells are genetically engineered to recognize only those B cells that produce antibodies to desmoglein. In PV, autoreactive B cells produce antibodies against Dsg3, disrupting its adhesive function and causing skin blistering. By expressing Dsg3 on their surfaces, the CAAR-T cells lure those B cells in and kill them. The Dsg 3 CAAR-T cells eliminated Dsg3-specific B cells in lab dishes and in mice, the researchers reported at the time. Penns Aimee Payne, M.D., Ph.D., and Michael Milone, M.D., Ph.D., a co-inventor of Novartis’ CAR-T cancer therapy Kymriah, pioneered the CAAR-T idea and have founded biotech Cabaletta Bio, hoping to bring their therapies through clinical studies to the market. The MuSK-CAAR-T is the second candidate in its pipeline; the company has already received FDA clearance to test its lead project, DSG3-CAAR-T, in patients with mucosal pemphigus vulgaris (PV), and a phase 1 trial is expected to start in 2020. See also List of conditions caused by problems with junctional proteins List of cutaneous conditions List of immunofluorescence findings for autoimmune bullous conditions References External links Pemphigus vulgaris - DermNet New Zealand

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I'm seeking clarification on the medical term 'Cetirizine/pseudoephedrine.' Could you explain it?

Cetirizine/pseudoephedrine (Zyrtec-D) is an antihistamine and decongestant formulation. It is a fixed-dose combination drug containing cetirizine hydrochloride and pseudoephedrine hydrochloride for symptoms related to seasonal allergic rhinitis. == References ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Neck pain'?

Neck pain, also known as cervicalgia, is a common problem, with two-thirds of the population having neck pain at some point in their lives.Neck pain, although felt in the neck, can be caused by numerous other spinal problems. Neck pain may arise due to muscular tightness in both the neck and upper back, or pinching of the nerves emanating from the cervical vertebrae. Joint disruption in the neck creates pain, as does joint disruption in the upper back. The head is supported by the lower neck and upper back, and it is these areas that commonly cause neck pain. The top three joints in the neck allow for most movement of the neck and head. The lower joints in the neck and those of the upper back create a supportive structure for the head to sit on. If this support system is affected adversely, then the muscles in the area will tighten, leading to neck pain. Neck pain affects about 5% of the global population as of 2010. Differential diagnosis Neck pain may come from any of the structures in the neck including: vascular, nerve, airway, digestive, and musculature / skeletal, or be referred from other areas of the body.Major and severe causes of neck pain (roughly in order of severity) include: Carotid artery dissection Referred pain from acute coronary syndrome Head and neck cancer Infections, including: Meningitis of several types including sudden onset of severe neck or back pain particularly in teens and young adults which may be fatal if not treated quickly Retropharyngeal abscess Epiglottitis Spinal disc herniation – protruding or bulging discs, or if severe prolapse. Spondylosis - degenerative arthritis and osteophytes Spinal stenosis – a narrowing of the spinal canalMore common and lesser neck pain causes include: Stress – physical and emotional stresses Prolonged postures – many people fall asleep on sofas and chairs and wake up with sore necks. Minor injuries and falls – car accidents, sporting events, and day to day injuries that are really minor. Referred pain – mostly from upper back problems Over-use – muscular strain is one of the most common causes Whiplash Pinched nerveAlthough the causes are numerous, most are easily rectified by either professional help or using self help advice and techniques. More causes can include: poor sleeping posture, torticollis, head injury, rheumatoid arthritis, Carotidynia, congenital cervical rib, mononucleosis, rubella, certain cancers, ankylosing spondylitis, cervical spine fracture, esophageal trauma, subarachnoid hemorrhage, lymphadenitis, thyroid trauma, and tracheal trauma. Treatment Treatment of neck pain depends on the cause. For the vast majority of people, neck pain can be treated conservatively. Recommendations in which it helps alleviate symptoms include applying heat or cold. Other common treatments could include medication, body mechanics training, ergonomic reform, and physical therapy. Treatments may also include patient education, but existing evidence shows a lack of effectiveness. Medication Analgesics such as acetaminophen or NSAIDs are generally recommended for pain. A 2017 review, however found that paracetamol was not efficacious and that NSAIDs are minimally effective.Muscle relaxants may also be recommended. However, one study showed that one muscle relaxant called cyclobenzaprine was not effective for treatment of acute cervical strain (as opposed to neck pain from other etiologies or chronic neck pain). Surgery Surgery is usually not indicated for mechanical causes of neck pain. If neck pain is the result of instability, cancer, or other disease process surgery may be necessary. Surgery is usually not indicated for "pinched nerves" or herniated discs unless there is spinal cord compression or pain and disability have been protracted for many months and refractory to conservative treatment such as physical therapy. Alternative medicine Exercise plus joint manipulation has been found to be beneficial in both acute and chronic mechanical neck disorders. In particular, specific strengthening exercise may improve function and pain. Motor control using cranio-cervical flexion exercises has been shown to be effective for non-specific chronic neck pain. Both cervical manipulation and cervical mobilization produce similar immediate-, and short-term changes. Multiple cervical manipulation sessions may provide better pain relief and functional improvement than certain medications at immediate to long-term follow-up. Thoracic manipulation may also improve pain and function. Low-level laser therapy has been shown to reduce pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in patients that experience chronic neck pain. Low quality evidence suggests that cognitive-behavioural therapy may be effective at reducing pain in the short-term. Massaging the area may provide immediate and short-lived benefits, but long term effects are unknown. There is a lack of high-quality evidence to support the use of mechanical traction, and side effects include headaches, nausea and injury to tissue. Radiofrequency denervation may provide temporary relief for specific affected areas in the neck. Transcutaneous electrical nerve stimulation (TENS), the noninvasive use of electrical stimulation on the skin, is of unclear benefit in chronic neck pain. Epidemiology Neck pain affects about 330 million people globally as of 2010 (4.9% of the population). It is more common in women (5.7%) than men (3.9%). It is less common than low back pain. Prognosis About one-half of episodes resolve within one year and around 10% become chronic. Prevention Prevalence of neck pain in the population suggests it is a common condition. For cervicalgia associated with bad posture the treatment is usually corrective in nature (i.e. ensure shoulders are in one line above the hips) and relating to interventions that provide ergonomic improvement. There is also growing research in how neck pain caused by mobile devices (see iHunch) can be prevented using embedded warning systems. References External links 6 Ways to Ease Neck Pain - Harvard Medical School Neck pain - Symptoms and causes - Mayo Clinic

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I'd like to learn more about the medical term 'Cystinosis.' Can you provide some details?

Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosomal recessive disorder resulting from accumulation of free cystine in lysosomes, eventually leading to intracellular crystal formation throughout the body. Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group. Fanconi syndrome occurs when the function of cells in renal tubules is impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates. Cystinosis was the first documented genetic disease belonging to the group of lysosomal storage disease disorders. Cystinosis is caused by mutations in the CTNS gene that codes for cystinosin, the lysosomal membrane-specific transporter for cystine. Intracellular metabolism of cystine, as it happens with all amino acids, requires its transport across the cell membrane. After degradation of endocytosed protein to cystine within lysosomes, it is normally transported to the cytosol. But if there is a defect in the carrier protein, cystine is accumulated in lysosomes. As cystine is highly insoluble, when its concentration in tissue lysosomes increases, its solubility is immediately exceeded and crystalline precipitates are formed in almost all organs and tissues.However, the progression of the disease is not related to the presence of crystals in target tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Increased intracellular cystine profoundly disturbs cellular oxidative metabolism and glutathione status, leading to altered mitochondrial energy metabolism, autophagy, and apoptosis.Cystinosis is usually treated with cysteamine, which is prescribed to decrease intralysosomal cystine accumulation. However, the discovery of new pathogenic mechanisms and the development of an animal model of the disease may open possibilities for the development of new treatment modalities to improve long-term prognosis. Symptoms There are three distinct types of cystinosis each with slightly different symptoms: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis. Infants affected by nephropathic cystinosis initially exhibit poor growth and particular kidney problems (sometimes called renal Fanconi syndrome). The kidney problems lead to the loss of important minerals, salts, fluids, and other nutrients. The loss of nutrients not only impairs growth, but may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about age two, cystine crystals may also be present in the cornea. The buildup of these crystals in the eye causes an increased sensitivity to light (photophobia). Without treatment, children with cystinosis are likely to experience complete kidney failure by about age ten. With treatment this may be delayed into the patients teens or 20s. Other signs and symptoms that may occur in patients include muscle deterioration, blindness, inability to swallow, impaired sweating, decreased hair and skin pigmentation, diabetes, and thyroid and nervous system problems. The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically begins to affect individuals around age twelve to fifteen. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid twenties. People with non-nephropathic or ocular cystinosis do not usually experience growth impairment or kidney malfunction. The only symptom is photophobia due to cystine crystals in the cornea. Crystal morphology and identification Cystine crystals are hexagonal in shape and are colorless. They are not found often in alkaline urine due to their high solubility. The colorless crystals can be difficult to distinguish from uric acid crystals which are also hexagonal. Under polarized examination, the crystals are birefringent with a polarization color interference. Genetics Cystinosis occurs due to a mutation in the gene CTNS, located on chromosome 17, which codes for cystinosin, the lysosomal cystine transporter. Symptoms are first seen at about 3 to 18 months of age with profound polyuria (excessive urination), followed by poor growth, photophobia, and ultimately kidney failure by age 6 years in the nephropathic form. All forms of cystinosis (nephropathic, juvenile and ocular) are autosomal recessive, which means that the trait is located on an autosomal chromosome, and only an individual who inherits two copies of the gene – one from both parents – will have the disorder. There is a 25% risk of having a child with the disorder, when both parents are carriers of an autosomal recessive trait. Cystinosis affects approximately 1 in 100,000 to 200,000 newborns. and there are only around 2,000 known individuals with cystinosis in the world. The incidence is higher in the province of Brittany, France, where the disorder affects 1 in 26,000 individuals. Diagnosis Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes.The accumulation is caused by abnormal transport of cystine from lysosomes, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter apoptosis in such a way that cells die inappropriately, leading to loss of renal epithelial cells. This results in renal Fanconi syndrome, and similar loss in other tissues can account for the short stature, retinopathy, and other features of the disease. Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell cystine level using tandem mass spectrometry. Types Online Mendelian Inheritance in Man (OMIM): 219800 – Infantile nephropathic Online Mendelian Inheritance in Man (OMIM): 219900 – Adolescent nephropathic Online Mendelian Inheritance in Man (OMIM): 219750 – Adult nonnephropathic Treatment Cystinosis is normally treated with cysteamine, which is available in capsules and in eye drops. People with cystinosis are also often given sodium citrate to treat the blood acidosis, as well as potassium and phosphorus supplements as well as others. If the kidneys become significantly impaired or fail, then treatment must be begun to ensure continued survival, up to and including renal transplantation. See also Hartnup disease Cystinuria CTNS References External links Cystinosis at NLM Genetics Home Reference GeneReviews/NCBI/NIH/UW entry on Cystinosis

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I need a basic explanation for the medical term 'Sodium bicarbonate.'

Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation (Na+) and a bicarbonate anion (HCO3−). Sodium bicarbonate is a white solid that is crystalline, but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda (sodium carbonate). The natural mineral form is nahcolite. It is a component of the mineral natron and is found dissolved in many mineral springs. Nomenclature Because it has long been known and widely used, the salt has many different names such as baking soda, bread soda, cooking soda, and bicarbonate of soda and can often be found near baking powder in stores. The term baking soda is more common in the United States, while bicarbonate of soda is more common in Australia, United Kingdom and Ireland. and in many northern/central European countries it is called Natron. Abbreviated colloquial forms such as sodium bicarb, bicarb soda, bicarbonate, and bicarb are common.The word saleratus, from Latin sal æratus (meaning "aerated salt"), was widely used in the 19th century for both sodium bicarbonate and potassium bicarbonate.Its E number food additive code is E500.The prefix bi in bicarbonate comes from an outdated naming system predating molecular knowledge in reference to the two molar equivalents of carbon dioxide (known as carbonic acid in the ancient chemistry language) that potassium hydrocarbonate/bicarbonate releases upon decomposition to (di)potassium carbonate and to potassium oxide (potash). The modern chemical formulas of these compounds now express their precise chemical compositions which were unknown when the name bi-carbonate of potash was coined (see also: bicarbonate). Uses Cooking Leavening In cooking, baking soda is primarily used in baking as a leavening agent. When it reacts with acid, carbon dioxide is released, which causes expansion of the batter and forms the characteristic texture and grain in cakes, quick breads, soda bread, and other baked and fried foods. The acid–base reaction can be generically represented as follows: NaHCO3 + H+ → Na+ + CO2 + H2OAcidic materials that induce this reaction include hydrogen phosphates, cream of tartar, lemon juice, yogurt, buttermilk, cocoa, and vinegar. Baking soda may be used together with sourdough, which is acidic, making a lighter product with a less acidic taste.Heat can also by itself cause sodium bicarbonate to act as a raising agent in baking because of thermal decomposition, releasing carbon dioxide at temperatures above 80 °C (180 °F), as follows: 2 NaHCO3 → Na2CO3 + H2O + CO2When used this way on its own, without the presence of an acidic component (whether in the batter or by the use of a baking powder containing acid), only half the available CO2 is released (one CO2 molecule is formed for every two equivalents of NaHCO3). Additionally, in the absence of acid, thermal decomposition of sodium bicarbonate also produces sodium carbonate, which is strongly alkaline and gives the baked product a bitter, "soapy" taste and a yellow color. Since the reaction occurs slowly at room temperature, mixtures (cake batter, etc.) can be allowed to stand without rising until they are heated in the oven. Baking powder Baking powder, also sold for cooking, contains around 30% of bicarbonate, and various acidic ingredients which are activated by the addition of water, without the need for additional acids in the cooking medium. Many forms of baking powder contain sodium bicarbonate combined with calcium acid phosphate, sodium aluminium phosphate, or cream of tartar. Baking soda is alkaline; the acid used in baking powder avoids a metallic taste when the chemical change during baking creates sodium carbonate. Pyrotechnics Sodium bicarbonate is one of the main components of the common "black snake" firework. The effect is caused by the thermal decomposition, which produces carbon dioxide gas to produce a long snake-like ash as a combustion product of the other main component, sucrose. Sodium bicarbonate is also used to delay combustion reactions by releasing CO2 and H2O when heated, both of which are flame retardants. Mild disinfectant It has weak disinfectant properties, and it may be an effective fungicide against some organisms. Because baking soda will absorb musty smells, it has become a reliable method for used book sellers when making books less malodorous. Fire extinguisher Sodium bicarbonate can be used to extinguish small grease or electrical fires by being thrown over the fire, as heating of sodium bicarbonate releases carbon dioxide. However, it should not be applied to fires in deep fryers; the sudden release of gas may cause the grease to splatter. Sodium bicarbonate is used in BC dry chemical fire extinguishers as an alternative to the more corrosive monoammonium phosphate in ABC extinguishers. The alkaline nature of sodium bicarbonate makes it the only dry chemical agent, besides Purple-K, that was used in large-scale fire suppression systems installed in commercial kitchens. Because it can act as an alkali, the agent has a mild saponification effect on hot grease, which forms a smothering, soapy foam. Neutralization of acids Sodium bicarbonate reacts spontaneously with acids, releasing CO2 gas as a reaction product. It is commonly used to neutralize unwanted acid solutions or acid spills in chemical laboratories. It is not appropriate to use sodium bicarbonate to neutralize base even though it is amphoteric, reacting with both acids and bases. Agriculture Sodium bicarbonate when applied on leaves, can prevent the growth of fungi; however, it does not kill the fungus. Excessive amount of sodium bicarbonate can cause discolouration of fruits (two percent solution) and chlorosis (one percent solution). Medical uses and health Sodium bicarbonate mixed with water can be used as an antacid to treat acid indigestion and heartburn. Its reaction with stomach acid produces salt, water, and carbon dioxide: NaHCO3 + HCl → NaCl + H2O + CO2(g)A mixture of sodium bicarbonate and polyethylene glycol such as PegLyte, dissolved in water and taken orally, is an effective gastrointestinal lavage preparation and laxative prior to gastrointestinal surgery, gastroscopy, etc.Intravenous sodium bicarbonate in an aqueous solution is sometimes used for cases of acidosis, or when insufficient sodium or bicarbonate ions are in the blood. In cases of respiratory acidosis, the infused bicarbonate ion drives the carbonic acid/bicarbonate buffer of plasma to the left, and thus raises the pH. For this reason, sodium bicarbonate is used in medically supervised cardiopulmonary resuscitation. Infusion of bicarbonate is indicated only when the blood pH is markedly low (< 7.1–7.0).HCO3− is used for treatment of hyperkalemia, as it will drive K+ back into cells during periods of acidosis. Since sodium bicarbonate can cause alkalosis, it is sometimes used to treat aspirin overdoses. Aspirin requires an acidic environment for proper absorption, and a basic environment will diminish aspirin absorption in cases of overdose. Sodium bicarbonate has also been used in the treatment of tricyclic antidepressant overdose. It can also be applied topically as a paste, with three parts baking soda to one part water, to relieve some kinds of insect bites and stings (as well as accompanying swelling).Some alternative practitioners, such as Tullio Simoncini, have promoted baking soda as a cancer cure, which the American Cancer Society has warned against due to both its unproven effectiveness and potential danger in use. Edzard Ernst has called the promotion of sodium bicarbonate as a cancer cure "one of the more sickening alternative cancer scams I have seen for a long time".Sodium bicarbonate can be added to local anesthetics, to speed up the onset of their effects and make their injection less painful. It is also a component of Moffetts solution, used in nasal surgery.It has been proposed that acidic diets weaken bones. One systematic meta-analysis of the research shows no such effect. Another also finds that there is no evidence that alkaline diets improve bone health, but suggests that there "may be some value" to alkaline diets for other reasons.Antacid (such as baking soda) solutions have been prepared and used by protesters to alleviate the effects of exposure to tear gas during protests.Similarly to its use in baking, sodium bicarbonate is used together with a mild acid such as tartaric acid as the excipient in effervescent tablets: when such a tablet is dropped in a glass of water, the carbonate leaves the reaction medium as carbon dioxide gas (HCO3− + H+ → H2O + CO2↑ or, more precisely, HCO3− + H3O+ → 2 H2O + CO2↑). This makes the tablet disintegrate, leaving the medication suspended and/or dissolved in the water together with the resulting salt (in this example, sodium tartrate). Personal hygiene Sodium bicarbonate is also used as an ingredient in some mouthwashes. It has anticaries and abrasive properties. It works as a mechanical cleanser on the teeth and gums, neutralizes the production of acid in the mouth, and also acts as an antiseptic to help prevent infections. Sodium bicarbonate in combination with other ingredients can be used to make a dry or wet deodorant. Sodium bicarbonate may be used as a buffering agent, combined with table salt, when creating a solution for nasal irrigation.It is used in eye hygiene to treat blepharitis. This is done by addition of a teaspoon of sodium bicarbonate to cool water that was recently boiled, followed by gentle scrubbing of the eyelash base with a cotton swab dipped in the solution. Veterinary uses Sodium bicarbonate is used as a cattle feed supplement, in particular as a buffering agent for the rumen. Cleaning agent Sodium bicarbonate is used in a process for removing paint and corrosion called sodablasting. As a blasting medium, sodium bicarbonate is used to remove surface contamination from softer and less resilient substrates such as aluminium, copper or timber which could be damaged by silica sand abrasive media.A manufacturer recommends a paste made from baking soda with minimal water as a gentle scouring powder, and is useful in removing surface rust, as the rust forms a water-soluble compound when in a concentrated alkaline solution; cold water should be used, as hot-water solutions can corrode steel. Sodium bicarbonate attacks the thin protective oxide layer that forms on aluminium, making it unsuitable for cleaning this metal. A solution in warm water will remove the tarnish from silver when the silver is in contact with a piece of aluminium foil. Baking soda is commonly added to washing machines as a replacement for water softener and to remove odors from clothes. It is also almost as effective in removing heavy tea and coffee stains from cups as Sodium hydroxide, when diluted with warm water. During the Manhattan Project to develop the nuclear bomb in the early 1940s, the chemical toxicity of uranium was an issue. Uranium oxides were found to stick very well to cotton cloth, and did not wash out with soap or laundry detergent. However, the uranium would wash out with a 2% solution of sodium bicarbonate. Clothing can become contaminated with toxic dust of depleted uranium (DU), which is very dense, hence used for counterweights in a civilian context, and in armour-piercing projectiles. DU is not removed by normal laundering; washing with about 6 ounces (170 g) of baking soda in 2 gallons (7.5 L) of water will help to wash it out. Odor control It is often claimed that baking soda is an effective odor remover, and it is often recommended that an open box be kept in the refrigerator to absorb odor. This idea was promoted by the leading U.S. brand of baking soda, Arm & Hammer, in an advertising campaign starting in 1972. Though this campaign is considered a classic of marketing, leading within a year to more than half of American refrigerators containing a box of baking soda, there is little evidence that it is in fact effective in this application. Chemistry Sodium bicarbonate is an amphoteric compound. Aqueous solutions are mildly alkaline due to the formation of carbonic acid and hydroxide ion: HCO−3 + H2O → H2CO3 + OH−Sodium bicarbonate can often be used as a safer alternative to sodium hydroxide, and as such can be used as a wash to remove any acidic impurities from a "crude" liquid, producing a purer sample. Reaction of sodium bicarbonate and an acid produces a salt and carbonic acid, which readily decomposes to carbon dioxide and water: NaHCO3 + HCl → NaCl + H2CO3 H2CO3 → H2O + CO2(g)Sodium bicarbonate reacts with acetic acid (found in vinegar), producing sodium acetate, water, and carbon dioxide: NaHCO3 + CH3COOH → CH3COONa + H2O + CO2(g)Sodium bicarbonate reacts with bases such as sodium hydroxide to form carbonates: NaHCO3 + NaOH → Na2CO3 + H2O Thermal decomposition At temperatures from 80–100 °C (176–212 °F), sodium bicarbonate gradually decomposes into sodium carbonate, water, and carbon dioxide. The conversion is faster at 200 °C (392 °F): 2 NaHCO3 → Na2CO3 + H2O + CO2Most bicarbonates undergo this dehydration reaction. Further heating converts the carbonate into the oxide (above 850 °C/1,560 °F): Na2CO3 → Na2O + CO2These conversions are relevant to the use of NaHCO3 as a fire-suppression agent ("BC powder") in some dry-powder fire extinguishers. Stability and shelf life If kept cool (room temperature) and dry (an airtight container is recommended to keep out moist air), sodium bicarbonate can be kept without a significant amount of decomposition for at least two or three years. History The word natron has been in use in many languages throughout modern times (in the forms of anatron, natrum and natron) and originated (like Spanish, French and English natron as well as sodium) via Arabic naṭrūn (or anatrūn; cf. the Lower Egyptian “Natrontal” Wadi El Natrun, where a mixture of sodium carbonate and sodium hydrogen carbonate for the dehydration of mummies was used ) from Greek nítron (νίτρον) (Herodotus; Attic lítron (λίτρον)), which can be traced back to ancient Egyptian ntr. The Greek nítron (soda, saltpeter) was also used in Latin (sal) nitrum and in German Salniter (the source of Nitrogen, Nitrat etc.).In 1791, French chemist Nicolas Leblanc produced sodium carbonate, also known as soda ash. The pharmacist Valentin Rose the Younger is credited with the discovery of sodium bicarbonate in 1801 in Berlin. In 1846, two American bakers, John Dwight and Austin Church, established the first factory in the United States to produce baking soda from sodium carbonate and carbon dioxide.Saleratus, potassium or sodium bicarbonate, is mentioned in the novel Captains Courageous by Rudyard Kipling as being used extensively in the 1800s in commercial fishing to prevent freshly caught fish from spoiling.In 1919, US Senator Lee Overman declared that bicarbonate of soda could cure the Spanish flu. In the midst of the debate on 26 January 1919, he interrupted the discussion to announce the discovery of a cure. "I want to say, for the benefit of those who are making this investigation," he reported, "that I was told by a judge of a superior court in the mountain country of North Carolina they have discovered a remedy for this disease." The purported cure implied a critique of modern science and an appreciation for the simple wisdom of simple people. "They say that common baking soda will cure the disease," he continued, "that they have cured it with it, that they have no deaths up there at all; they use common baking soda, which cures the disease." Production Sodium bicarbonate is produced industrially from sodium carbonate: Na2CO3 + CO2 + H2O → 2 NaHCO3It is produced on the scale of about 100,000 tonnes/year (as of 2001) with a worldwide production capacity of 2.4 million tonnes per year (as of 2002). Commercial quantities of baking soda are also produced by a similar method: soda ash, mined in the form of the ore trona, is dissolved in water and treated with carbon dioxide. Sodium bicarbonate precipitates as a solid from this solution.Regarding the Solvay process, sodium bicarbonate is an intermediate in the reaction of sodium chloride, ammonia, and carbon dioxide. The product however shows low purity (75pc). NaCl + CO2 + NH3 + H2O → NaHCO3 + NH4ClAlthough of no practical value, NaHCO3 may be obtained by the reaction of carbon dioxide with an aqueous solution of sodium hydroxide: CO2 + NaOH → NaHCO3 Mining Naturally occurring deposits of nahcolite (NaHCO3) are found in the Eocene-age (55.8–33.9 Mya) Green River Formation, Piceance Basin in Colorado. Nahcolite was deposited as beds during periods of high evaporation in the basin. It is commercially mined using common underground mining techniques such as bore, drum, and longwall mining in a fashion very similar to coal mining.It is also produced by solution mining, pumping heated water through nahcolite beds and crystalizing the dissolved nahcolite through a cooling crystallization process. In popular culture Sodium bicarbonate, as "bicarbonate of soda", was a frequent source of punch lines for Groucho Marx in Marx Brothers movies. In Duck Soup, Marx plays the leader of a nation at war. In one scene, he receives a message from the battlefield that his general is reporting a gas attack, and Groucho tells his aide: "Tell him to take a teaspoonful of bicarbonate of soda and a half a glass of water." In A Night at the Opera, Grouchos character addresses the opening night crowd at an opera by saying of the lead tenor: "Signor Lassparri comes from a very famous family. His mother was a well-known bass singer. His father was the first man to stuff spaghetti with bicarbonate of soda, thus causing and curing indigestion at the same time."In the Joseph L. Mankewicz classic All About Eve, the Max Fabian character (Gregory Ratoff) has an extended scene with Margo Channing (Bette Davis) in which, suffering from heartburn, he requests and then drinks bicarbonate of soda, eliciting a prominent burp. Channing promises to always keep a box of bicarb with Maxs name on it. See also References Bibliography External links International Chemical Safety Card 1044

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I'm encountering the term 'Pustular psoriasis' in medical literature. What's its definition?

The term pustular psoriasis is used for a heterogeneous group of diseases that share pustular skin characteristics. Signs and symptoms Characteristics may vary according to the subtype of pustular psoriasis. For example, it can be localized, commonly to the hands and feet (localized pustular psoriasis), or generalized with widespread patches appearing randomly on any part of the body (generalized pustular psoriasis). However, all forms of pustular psoriasis share in common the presence of red and tender blotchy skin covered with pustules.Pustular psoriasis can be localized, commonly to the hands and feet (palmoplantar pustulosis), or generalized with widespread patches occurring randomly on any part of the body. Acrodermatitis continua is a form of localized psoriasis limited to the fingers and toes that may spread to the hands and feet. Pustulosis palmaris et plantaris is another form of localized pustular psoriasis similar to acrodermatitis continua with pustules erupting from red, tender, scaly skin found on the palms of the hands and the soles of the feet.Generalized pustular psoriasis (GPP) is also known as (von Zumbusch) acute generalized pustular psoriasis in acute cases, and as impetigo herpetiformis during pregnancy. GPP is a rare and severe form of psoriasis that may require hospitalization. This form of psoriasis is characterized by an acute onset of numerous pustules on top of tender red skin. This skin eruption is often accompanied by a fever, muscle aches, nausea, and an elevated white blood cell count. Annular pustular psoriasis (APP), a rare form of GPP, is the most common type seen during childhood. APP tends to occur in women more frequently than in men, and is usually less severe than other forms of generalized pustular psoriasis such as impetigo herpetiformis. This form of psoriasis is characterized by ring-shaped plaques with pustules around the edges and yellow crusting. APP most often affects the torso, neck, arms, and legs. Diagnosis Classification Pustular psoriasis is classified into two major forms: localized and generalized pustular psoriasis. Within these two categories there are several variants: Management injection of methotrexate References == External links ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm curious about the meaning of the medical term 'Supermarket.' Can you give me some insights?

A supermarket is a self-service shop offering a wide variety of food, beverages and household products, organized into sections. This kind of store is larger and has a wider selection than earlier grocery stores, but is smaller and more limited in the range of merchandise than a hypermarket or big-box market. In everyday U.S. usage, however, "grocery store" is synonymous with supermarket, and is not used to refer to other types of stores that sell groceries.The supermarket typically has places for fresh meat, fresh produce, dairy, deli items, baked goods, etc. Shelf space is also reserved for canned and packaged goods and for various non-food items such as kitchenware, household cleaners, pharmacy products and pet supplies. Some supermarkets also sell other household products that are consumed regularly, such as alcohol (where permitted), medicine, and clothing, and some sell a much wider range of non-food products: DVDs, sporting equipment, board games, and seasonal items (e.g., Christmas wrapping paper in December). A larger full-service supermarket combined with a department store is sometimes known as a hypermarket. Other services may include those of banks, cafés, childcare centers/creches, insurance (and other financial services), mobile phone services, photo processing, video rentals, pharmacies, and gas stations. If the eatery in a supermarket is substantial enough, the facility may be called a "grocerant", a blend of "grocery" and "restaurant".The traditional supermarket occupies a large amount of floor space, usually on a single level. It is usually situated near a residential area in order to be convenient to consumers. The basic appeal is the availability of a broad selection of goods under a single roof, at relatively low prices. Other advantages include ease of parking and frequently the convenience of shopping hours that extend into the evening or even 24 hours of the day. Supermarkets usually allocate large budgets to advertising, typically through newspapers. They also present elaborate in-shop displays of products. Supermarkets typically are chain stores, supplied by the distribution centers of their parent companies, thus increasing opportunities for economies of scale. Supermarkets usually offer products at relatively low prices by using their buying power to buy goods from manufacturers at lower prices than smaller stores can. They also minimise financing costs by paying for goods at least 30 days after receipt and some extract credit terms of 90 days or more from vendors. Certain products (typically staple foods such as bread, milk and sugar) are very occasionally sold as loss leaders so as to attract shoppers to their store. Supermarkets make up for their low margins by a high volume of sales, and with of higher-margin items bought by the attracted shoppers. Self-service with shopping carts (trolleys) or baskets reduces labor costs, and many supermarket chains are attempting further reduction by shifting to self-service check-out. History In the early days of retailing, generally an assistant fetched products from shelves behind the merchants counter while customers waited in front of the counter, indicating the items they wanted. Most foods and merchandise did not come in individually wrapped consumer-sized packages, so an assistant measured out and wrapped the precise amount requested by the consumer. This offered opportunities for social interaction: many regarded this style of shopping as "a social occasion" and would often "pause for conversations with the staff or other customers". These practices were by nature slow and had high labor intensity and therefore also quite expensive. The number of customers who could be attended to at one time was limited by the number of staff employed in the store. Shopping for groceries also often involved trips to multiple specialty shops, such as a greengrocer, butcher, bakery, fishmonger and dry goods store, in addition to a general store. Milk and other items of short shelf life were delivered by a milkman. The concept of an inexpensive food market relying on economies of scale was developed by Vincent Astor. He founded the Astor Market in 1915, investing $750,000 of his fortune into a 165′ by 125′ (50×38-metre) corner of 95th and Broadway, Manhattan, creating, in effect, an open-air mini-mall that sold meat, fruit, produce and flowers. The expectation was that customers would come from great distances ("miles around"), but in the end, even attracting people from ten blocks away was difficult, and the market folded in 1917.The concept of a self-service grocery store was developed by entrepreneur Clarence Saunders and his Piggly Wiggly stores, the first of which opened in 1916. Saunders was awarded several patents for the ideas he incorporated into his stores. The stores were a financial success and Saunders began to offer franchises. The Great Atlantic & Pacific Tea Company, which was established in 1859, was another successful early grocery store chain in Canada and the United States, and became common in North American cities in the 1920s. Early self-service grocery stores did not sell fresh meats or produce. Combination stores that sold perishable items were developed in the 1920s. The general trend since then has been to stock shelves at night so that customers, the following day, can obtain their own goods and bring them to the front of the store to pay for them. Although there is a higher risk of shoplifting, the costs of appropriate security measures ideally will be outweighed by reduced labor costs.Historically, there has been debate about the origin of the supermarket, with King Kullen and Ralphs of California having strong claims. Other contenders included Weingartens and Henke & Pillot. To end the debate, the Food Marketing Institute in conjunction with the Smithsonian Institution and with funding from H.J. Heinz, researched the issue. They defined the attributes of a supermarket as "self-service, separate product departments, discount pricing, marketing and volume selling".They determined that the first true supermarket in the United States was opened by a former Kroger employee, Michael J. Cullen, on 4 August 1930, inside a 6,000-square-foot (560 m2) former garage in Jamaica, Queens in New York City. The store, King Kullen, operated under the slogan "Pile it high. Sell it low." At the time of Cullens death in 1936, there were seventeen King Kullen stores in operation. Although Saunders had brought the world self-service, uniform stores, and nationwide marketing, Cullen built on this idea by adding separate food departments, selling large volumes of food at discount prices and adding a parking lot. Other established American grocery chains in the 1930s, such as Kroger and Safeway Inc. at first resisted Cullens idea, but eventually were forced to build their own supermarkets as the economy sank into the Great Depression, while consumers were becoming price-sensitive at a level never experienced before. Kroger took the idea one step further and pioneered the first supermarket surrounded on all four sides by a parking lot.As larger chain supermarkets began to dominate the market in the US, able to supply consumers with the desired lower prices as opposed to the smaller "mom and pop" stands with considerably more overhead costs, the backlash of this infrastructure alteration was seen through numerous anti-chain campaigns. The idea of "monopsony", proposed by Cambridge economist Joan Robinson in 1933, that a single buyer could out-power the market of multiple sellers, became a strong anti-chain rhetorical device. With public backlash came political pressure to even the playing field for smaller vendors lacking the luxury of economies of scale. In 1936, the Robinson-Patman Act was implemented as a way of preventing such larger chains from using this buying power to reap advantages over smaller stores, although the act was not well enforced and did not have much impact on the prevention of larger chains overtaking power in the markets.Supermarkets proliferated across Canada and the United States with the growth of automobile ownership and suburban development after World War II. Most North American supermarkets are located in suburban strip shopping centers as an anchor store along with other smaller retailers. They are generally regional rather than national in their company branding. Kroger is perhaps the most nationally oriented supermarket chain in the United States but it has preserved most of its regional brands, including Ralphs, City Market, King Soopers, Frys, Smiths, and QFC. In Canada, the largest such company is Loblaw, which operates stores under a variety of banners targeted to different segments and regions, including Fortinos, Zehrs, No Frills, the Real Canadian Superstore, and Loblaws, the foundation of the company. Sobeys is Canadas second largest supermarket with locations across the country, operating under many banners (Sobeys IGA in Quebec). Québecs first supermarket opened in 1934 in Montréal, under the banner Steinbergs.In the United Kingdom, self-service shopping took longer to become established. Even in 1947, there were just ten self-service shops in the country. In 1951, ex-US Navy sailor Patrick Galvani, son-in-law of Express Dairies chairman, made a pitch to the board to open a chain of supermarkets across the country. The UKs first supermarket under the new Premier Supermarkets brand opened in Streatham, South London, taking ten times as much per week as the average British general store of the time. Other chains caught on, and after Galvani lost out to Tescos Jack Cohen in 1960 to buy the 212 Irwins chain, the sector underwent a large amount of consolidation, resulting in the big four dominant UK of today: Tesco, Asda, Sainsburys and Morrisons. In the 1950s, supermarkets frequently issued trading stamps as incentives to customers. Today, most chains issue store-specific "membership cards", "club cards", or "loyalty cards". These typically enable the cardholder to receive special members-only discounts on certain items when the credit card-like device is scanned at check-out. Sales of selected data generated by club cards is becoming a significant revenue stream for some supermarkets. Traditional supermarkets in many countries face intense competition from discounters such as Wal-Mart, Aldi and Lidl, which typically is non-union and operates with better buying power. Other competition exists from warehouse clubs such as Costco that offer savings to customers buying in bulk quantities. Superstores, such as those operated by Wal-Mart and Asda, often offer a wide range of goods and services in addition to foods. In Australia, Aldi, Woolworths and Coles are the major players running the industry with fierce competition among all the three. The rising market share of Aldi has forced the other two to cut prices and increase their private label product ranges. The proliferation of such warehouse and superstores has contributed to the continuing disappearance of smaller, local grocery stores; increased dependence on the automobile; suburban sprawl because of the necessity for large floor space and increased vehicular traffic. For example, in 2009 51% of Wal-Marts $251 billion domestic sales were recorded from grocery goods. Some critics consider the chains common practice of selling loss leaders to be anti-competitive. They are also wary of the negotiating power that large, often multinationals have with suppliers around the world. Online-only supermarkets (21st century) During the dot-com boom, Webvan, an online-only supermarket, was formed and went bankrupt after three years and was acquired by Amazon. The British online supermarket Ocado, which uses a high degree of automation in its warehouses, was the first successful online-only supermarket. Ocado expanded into providing services to other supermarket firms such as Waitrose and Morrisons. Grocery stores such as Walmart employ food delivery services offered by third parties such as DoorDash. Other online food delivery services, such as Deliveroo in the United Kingdom, have begun to pay specific attention to supermarket delivery.Delivery robots are offered by various companies partnering with supermarkets. Micro-fulfillment centers (MFC) are relatively small warehouses with sophisticated automated rack-and-tote systems which prepare orders for pickup and delivery. Once the order is complete, the customer will pick it up (i.e. "click-and-collect") or have it fulfilled via home delivery. Supermarkets are investing in micro-fulfillment centers with the hope that automation can help reduce the costs of online commerce and ecommerce by shortening the distances from store to home and speeding up deliveries. In short, MFCs are said by many to be the key to profitably fulfilling online orders. Types U.S. categorization The U.S. FMI food industry association, drawing on research by Willard Bishop, defines the following formats (store types) that sell groceries: Organic and environmentally-friendly supermarkets Some supermarkets are focusing on selling more (or even exclusively) organically certified produce. Others are trying to differentiate themselves by selling fewer (or no) products containing palm oil. This as the demand of palm oil is a main driver for the destruction of rainforests. As a response to the growing concern on the heavy use of petroleum-based plastics for food packaging, so-called "zero waste" and "plastic-free" supermarkets and groceries are on the rise. Growth in developing countries Beginning in the 1990s, the food sector in developing countries has rapidly transformed, particularly in Latin America, South-East Asia, India, China and South Africa. With growth, has come considerable competition and some amount of consolidation. The growth has been driven by increasing affluence and the rise of a middle class; the entry of women into the workforce; with a consequent incentive to seek out easy-to-prepare foods; the growth in the use of refrigerators, making it possible to shop weekly instead of daily; and the growth in car ownership, facilitating journeys to distant stores and purchases of large quantities of goods. The opportunities presented by this potential have encouraged several European companies to invest in these markets (mainly in Asia) and American companies to invest in Latin America and China. Local companies also entered the market. Initial development of supermarkets has now been followed by hypermarket growth. In addition there were investments by companies such as Makro and Metro Cash and Carry in large-scale Cash-and-Carry operations. While the growth in sales of processed foods in these countries has been much more rapid than the growth in fresh food sales, the imperative nature of supermarkets to achieve economies of scale in purchasing means that the expansion of supermarkets in these countries has important repercussions for small farmers, particularly those growing perishable crops. New supply chains have developed involving cluster formation; development of specialized wholesalers; leading farmers organizing supply, and farmer associations or cooperatives. In some cases supermarkets have organized their own procurement from small farmers; in others wholesale markets have adapted to meet supermarket needs. Typical supermarket merchandise Larger supermarkets in North America and in Europe typically sell many items among many brands, sizes and varieties. U.S. publisher Supermarket News lists the following categories, for example: Hypermarkets have a larger range of non-food categories such as clothing, electronics, household decoration and appliances. Bakery (packaged and sometimes a service bakery and/or onsite bakery) Beverages (non-alcoholic packaged, sometimes also alcoholic if laws permit) Nonfood & Pharmacy (e.g. cigarettes, lottery tickets and over-the-counter medications (as laws permit), DVD rentals, books and magazines, including supermarket tabloids, greeting cards, toys, small selection of home goods like light bulbs, housewares (typically limited) Personal care e.g. cosmetics, soap, shampoo Produce (fresh fruits and vegetables) Floral (flowers and plants) Deli (sliced meats, cheeses, etc.) Prepared Foods (packaged and frozen foods) Meat (fresh packaged, frozen, sometimes with a butcher service counter) Seafood (fresh packaged, frozen, sometimes with a butcher service counter) Dairy (milk products and eggs) Center store (e.g. detergent, paper products, household cleaning supplies) Multicultural (ethnic foods) Bulk dried foods Animal foods, toys and products Layout strategies Most merchandise is already packaged when it arrives at the supermarket. Packages are placed on shelves, arranged in aisles and sections according to type of item. Some items, such as fresh produce, are stored in bins. Those requiring an intact cold chain are in temperature-controlled display cases. While branding and store advertising will differ from company to company, the layout of a supermarket remains virtually unchanged. Although big companies spend time giving consumers a pleasant shopping experience, the design of a supermarket is directly connected to the in-store marketing that supermarkets must conduct to get shoppers to spend more money while there. Every aspect of the store is mapped out and attention is paid to color, wording and even surface texture. The overall layout of a supermarket is a visual merchandising project that plays a major role. Stores can creatively use a layout to alter customers perceptions of the atmosphere. Alternatively, they can enhance the stores atmospherics through visual communications (signs and graphics), lighting, colors, and even scents. For example, to give a sense of the supermarket being healthy, fresh produce is deliberately located at the front of the store. In terms of bakery items, supermarkets usually dedicate 30 to 40 feet of store space to the bread aisle.Supermarkets are designed to "give each product section a sense of individual difference and this is evident in the design of what is called the anchor departments; fresh produce, dairy, delicatessen, meat and the bakery". Each section has different floor coverings, style, lighting and sometimes even individual services counters to allow shoppers to feel as if there are a number of markets within this one supermarket. Marketers use well-researched techniques to try to control purchasing behavior. The layout of a supermarket is considered by some to consist of a few rules of thumb and three layout principles. The high-draw products are placed in separate areas of the store to keep drawing the consumer through the store. High impulse and high margin products are placed in the most predominant areas to grab attention. Power products are placed on both sides of the aisle to create increased product awareness, and end caps are used to receive a high exposure of a certain product whether on special, promotion or in a campaign, or a new line. The first principle of the layout is circulation. Circulation is created by arranging product so the supermarket can control the traffic flow of the consumer. Along with this path, there will be high-draw, high-impulse items that will influence the consumer to make purchases which they did not originally intend. Service areas such as restrooms are placed in a location which draws the consumer past certain products to create extra buys. Necessity items such as bread and milk are found at the rear of the store to increase the start of circulation. Cashiers desks are placed in a position to promote circulation. In most supermarkets, the entrance will be on the right-hand side because some research suggests that consumers who travel in a counter-clockwise direction spend more. However, other researchers have argued that consumers moving in a clockwise direction can form better mental maps of the store leading to higher sales in turn.The second principle of the layout is coordination. Coordination is the organized arrangement of product that promotes sales. Products such as fast-selling and slow-selling lines are placed in strategic positions in aid of the overall sales plan. Managers sometimes place different items in fast-selling places to increase turnover or to promote a new line. The third principle is consumer convenience. The layout of a supermarket is designed to create a high degree of convenience to the consumer to make the shopping experience pleasant and increase customer spending. This is done through the character of merchandising and product placement. There are many different ideas and theories in relation to layout and how product layout can influence the purchases made. One theory suggests that certain products are placed together or near one another that are of a similar or complementary nature to increase the average customer spend. This strategy is used to create cross-category sales similarity. In other words, the toothpaste is next to or adjacent the toothbrushes and the tea and coffee are down the same aisle as the sweet biscuits. These products complement one another and placing them near is one-way marketers try to increase purchases.For vertical placement, cheap generic brands tend to be on the lowest shelves, products appealing to children are placed at the mid-thigh level, and the most profitable brands are placed at eye level.The fourth principle is the use of color psychology, and the locations of the food, similar to its use in fast food branding. Consumer psychologists suggest that most buyers tend to enter the store and shop to their right first. Some supermarkets, therefore, choose to place the entrance to the left-hand side as the consumer will likely turn right upon entry, and this allows the consumer to do a full anticlockwise circle around the store before returning to the checkouts. This suggests that supermarket marketers should use this theory to their advantage by placing their temporary displays of products on the right-hand side to entice you to make an unplanned purchase. Furthermore, aisle ends are extremely popular with product manufacturers, who pay top dollar to have their products located there. These aisle ends are used to lure customers into making a snap purchase and to also entice them to shop down the aisle. The most obvious place supermarket layout influences consumers are at the checkout. Small displays of chocolates, magazines, and drinks are located at each checkout to tempt shoppers while they wait to be served. Criticisms The large scale of supermarkets, while often improving cost and efficiency for customers, can place significant economic pressure on suppliers and smaller shopkeepers. Supermarkets often generate considerable food waste, although modern technologies such as biomethanation units may be able to process the waste into an economical source of energy. Also, purchases tracking may help as supermarkets then become better able to size their stock (of perishable goods), reducing food spoilage. See also Hypermarket List of grocers Short food supply chains Farmers markets Types of retail outlets Effects of the car on societies References Further reading Greer, William R.; Logan, John A.; Willis, Paul S. (1986). America the Bountiful: How the Supermarket Came to Main Street : an Oral History. Washington, D.C.: Food Marketing Institute in cooperation with Beatrice Companies. OCLC 14357784. Longstreth, R. W. (1999). The Drive-In, the Supermarket, and the Transformation of Commercial Space in Los Angeles, 1914-1941. The MIT Press. Lorr, B. (2020). The Secret Life of Groceries: The Dark Miracle of the American Supermarket. Avery. Newman, K. (2012). The Secret Financial Life of Food: From Commodities Markets to Supermarkets (Illustrated edition). Columbia University Press. Petroski, Henry (November–December 2005). "Shopping by Design". American Scientist 93 (6): 491. Sowell, Thomas. Basic Economics (Third Edition, 2007 Basic Books). Pages 92–94 describe the competition between the dominant grocery chains in the United States through the 20th century and beyond. Yee, A. (2003). Shopping at Giant Foods: Chinese American Supermarkets in Northern California (Illustrated edition). University of Washington Press. External links Food Stories – Explore a century of revolutionary change in UK food culture on the British Librarys Food Stories website groceteria.com – supermarket history and architecture from the 1920s to the 1970s Scrambling for customers, 4 August 2005, San Francisco Chronicle

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm not familiar with the medical term 'Iron overload.' Could you provide some insights?

Iron overload or haemochromatosis (also spelled hemochromatosis in American English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosis (HH or HHC), a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions. Signs and symptoms Organs most commonly affected by haemochromatosis include the liver, heart, and endocrine glands.Haemochromatosis may present with the following clinical syndromes: liver: chronic liver disease and cirrhosis of the liver. heart: heart failure, cardiac arrhythmia. hormones: diabetes (see below) and hypogonadism (insufficiency of the sex hormone producing glands) which leads to low sex drive and/or loss of fertility in men and loss of menstrual cycle in women. metabolism: diabetes in people with iron overload occurs as a result of selective iron deposition in islet beta cells in the pancreas leading to functional failure and cell death. skeletal: arthritis, from calcium pyrophosphate deposition in joints leading to joint pains. The most commonly affected joints are those of the hands, particularly the knuckles of the second and third fingers. skin: melanoderma (darkening or bronzing of the skin).The skins deep tan color, in concert with insulin insufficiency due to pancreatic damage, is the source of a nickname for this condition: "bronze diabetes" (for more information, see the history of haemochromatosis). Causes The term haemochromatosis was initially used to refer to what is now more specifically called haemochromatosis type 1 (or HFE-related hereditary haemochromatosis). Currently, haemochromatosis (without further specification) is mostly defined as iron overload with a hereditary or primary cause, or originating from a metabolic disorder. However, the term is currently also used more broadly to refer to any form of iron overload, thus requiring specification of the cause, for example, hereditary haemochromatosis. Hereditary haemochromatosis is an autosomal recessive disorder with estimated prevalence in the population of 1 in 200 among patients with European ancestry, with lower incidence in other ethnic groups. The gene responsible for hereditary haemochromatosis (known as HFE gene) is located on chromosome 6; the majority of hereditary haemochromatosis patients have mutations in this HFE gene.Hereditary haemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues. This typically begins to be expressed in the third to fifth decades of life, but may occur in children. The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disorder if left untreated, and recognizing that treatment is relatively simple, early diagnosis before symptoms or signs appear is important.In general, the term haemosiderosis is used to indicate the pathological effect of iron accumulation in any given organ, which mainly occurs in the form of the iron-storage complex haemosiderin. Sometimes, the simpler term siderosis is used instead. Other definitions distinguishing haemochromatosis or haemosiderosis that are occasionally used include: Haemosiderosis is haemochromatosis caused by excessive blood transfusions, that is, haemosiderosis is a form of secondary haemochromatosis. Haemosiderosis is haemosiderin deposition within cells, while haemochromatosis is haemosiderin within cells and interstitium. Haemosiderosis is iron overload that does not cause tissue damage, while haemochromatosis does. Haemosiderosis is arbitrarily differentiated from haemochromatosis by the reversible nature of the iron accumulation in the reticuloendothelial system.The causes of haemochromatosis broken down into two subcategories: primary cases (hereditary or genetically determined) and less frequent secondary cases (acquired during life). People of Celtic (Irish, Scottish, Welsh, Cornish, Breton etc.), English, and Scandinavian origin have a particularly high incidence, with about 10% being carriers of the principal genetic variant, the C282Y mutation on the HFE gene, and 1% having the condition. This has been recognised in several laymans alternative names such as Celtic curse, Irish illness, British gene, and Scottish sickness. The overwhelming majority depend on mutations of the HFE gene discovered in 1996, but since then others have been discovered and sometimes are grouped together as "non-classical hereditary haemochromatosis", "non-HFE related hereditary haemochromatosis", or "non-HFE haemochromatosis". Most types of hereditary haemochromatosis have autosomal recessive inheritance, while type 4 has autosomal dominant inheritance. Secondary haemochromatosis Severe chronic haemolysis of any cause, including intravascular haemolysis and ineffective erythropoiesis (haemolysis within the bone marrow) Multiple frequent blood transfusions (either whole blood or just red blood cells), which are usually needed either by individuals with hereditary anaemias (such as beta-thalassaemia major, sickle cell anaemia, and Diamond–Blackfan anaemia) or by older patients with severe acquired anaemias such as in myelodysplastic syndromes. Excess parenteral (non-ingested) iron supplements, such as what can acutely happen in iron poisoning Excess dietary iron Some disorders do not normally cause haemochromatosis on their own, but may do so in the presence of other predisposing factors. These include cirrhosis (especially related to alcohol use disorder), steatohepatitis of any cause, porphyria cutanea tarda, prolonged haemodialysis, and post-portacaval shunting Diagnosis There are several methods available for diagnosing and monitoring iron loading. Blood test Blood tests are usually the first test if there is a clinical suspicion of iron overload. Serum ferritin testing is a low-cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of iron overload is that it can be elevated in a variety of other medical conditions including infection, inflammation, fever, liver disease, kidney disease, and cancer. Also, total iron binding capacity may be low, but can also be normal. In males and postmenopausal females, normal range of serum ferritin is between 12 and 300 ng/mL (670 pmol/L) . In premenopausal females, normal range of serum ferritin is between 12 and 150 or 200 ng/mL (330 or 440 pmol/L). If the person is showing the symptoms, they may need to be tested more than once throughout their lives as a precaution, most commonly in women after menopause. Transferrin saturation is a more specific test. Genetics DNA/screening: the current standard of practice in diagnosis of haemochromatosis, places emphasis on genetic testing. Positive HFE analysis confirms the clinical diagnosis of haemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals with a family history of haemochromatosis. The alleles evaluated by HFE gene analysis are evident in ~80% of patients with haemochromatosis; a negative report for HFE gene does not rule out haemochromatosis. First degree relatives of those with primary haemochromatosis should be screened to determine if they are a carrier or if they could develop the disease. This can allow preventive measures to be taken. Screening the general population is not recommended. Biopsy Liver biopsy is the removal of small sample in order to be studied and can determine the cause of inflammation or cirrhosis. In someone with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated. In this case, diagnosis of haemochromatosis is based on biochemical analysis and histologic examination of a liver biopsy. Assessment of the hepatic iron index (HII) is considered the "gold standard" for diagnosis of haemochromatosis.Magnetic resonance imaging (MRI) is used as a noninvasive way to accurately estimate iron deposition levels in the liver as well as heart, joints, and pituitary gland. Treatment Phlebotomy Phlebotomy/venesection: routine treatment consists of regularly scheduled phlebotomies (bloodletting or erythrocytapheresis). When first diagnosed, the phlebotomies may be performed every week or fortnight, until iron levels can be brought to within normal range. Once the serum ferritin and transferrin saturation are within the normal range, treatments may be scheduled every two to three months depending upon the rate of reabsorption of iron. A phlebotomy session typically draws between 450 and 500 mL of blood. The blood drawn is sometimes donated. Diet A diet low in iron is generally recommended, but has little effect compared to venesection. The human diet contains iron in two forms: heme iron and non-heme iron. Heme iron is the most easily absorbed form of iron. People with iron overload may be advised to avoid food that are high in heme iron. Highest in heme iron is red meat such as beef, venison, lamb, buffalo, and fish such as bluefin tuna. A strict low-iron diet is usually not necessary. Non-heme iron is not as easily absorbed in the human system and is found in plant-based foods such as grains, beans, vegetables, fruits, nuts, and seeds. Medication Medication: For those unable to tolerate routine blood draws, there are chelating agents available for use. The drug deferoxamine binds with iron in the bloodstream and enhances its elimination in urine and faeces. Typical treatment for chronic iron overload requires subcutaneous injection over a period of 8–12 hours daily. Two newer iron-chelating drugs that are licensed for use in patients receiving regular blood transfusions to treat thalassaemia (and, thus, who develop iron overload as a result) are deferasirox and deferiprone. Chelating polymers A minimally invasive approach to hereditary haemochromatosis treatment is the maintenance therapy with polymeric chelators. These polymers or particles have a negligible or null systemic biological availability and they are designed to form stable complexes with Fe2+ and Fe3+ in the GIT and thus limiting their uptake and long-term accumulation. Although this method has only a limited efficacy, unlike small-molecular chelators, the approach has virtually no side effects in sub-chronic studies. Interestingly, the simultaneous chelation of Fe2+ and Fe3+ increases the treatment efficacy. Prognosis In general, provided there has been no liver damage, patients should expect a normal life expectancy if adequately treated by venesection. If the serum ferritin is greater than 1000 ug/L at diagnosis there is a risk of liver damage and cirrhosis which may eventually shorten their life. The presence of cirrhosis increases the risk of hepatocellular carcinoma. Epidemiology HHC is most common in certain European populations (such as those of Irish or Scandinavian descent) and occurs in 0.6% of some unspecified population. Men have a 24-fold increased rate of iron-overload disease compared with women. Stone Age Diet and the environment are thought to have had large influence on the mutation of genes related to iron overload. Starting during the Mesolithic era, communities of people lived in an environment that was fairly sunny, warm and had the dry climates of the Middle East. Most humans who lived at that time were foragers and their diets consisted largely of game, fish and wild plants. Archaeologists studying dental plaque have found evidence of tubers, nuts, plantains, grasses and other foods rich in iron. Over many generations, the human body became well-adapted to a high level of iron content in the diet. Neolithic In the Neolithic era, significant changes are thought to have occurred in both the environment and diet. Some communities of foragers migrated north, leading to changes in lifestyle and environment, with a decrease in temperatures and a change in the landscape which the foragers then needed to adapt to. As people began to develop and advance their tools, they learned new ways of producing food, and farming also slowly developed. These changes would have led to serious stress on the body and a decrease in the consumption of iron-rich foods. This transition is a key factor in the mutation of genes, especially those that regulated dietary iron absorption. Iron, which makes up 70% of red blood cell composition, is a critical micronutrient for effective thermoregulation in the body. Iron deficiency will lead to a drop in the core temperature. In the chilly and damp environments of Northern Europe, supplementary iron from food was necessary to keep temperatures regulated, however, without sufficient iron intake the human body would have started to store iron at higher rates than normal. In theory, the pressures caused by migrating north would have selected for a gene mutation that promoted greater absorption and storage of iron. Viking hypothesis Studies and surveys conducted to determine the frequencies of haemochromatosis help explain how the mutation migrated around the globe. In theory, the disease initially evolved from travelers migrating from the north. Surveys show a particular distribution pattern with large clusters and frequencies of gene mutations along the western European coastline. This led the development of the "Viking Hypothesis". Cluster locations and mapped patterns of this mutation correlate closely to the locations of Viking settlements in Europe established c.700 AD to c.1100 AD. The Vikings originally came from Norway, Sweden and Denmark. Viking ships made their way along the coastline of Europe in search of trade, riches, and land. Genetic studies suggest that the extremely high frequency patterns in some European countries are the result of migrations of Vikings and later Normans, indicating a genetic link between hereditary haemochromatosis and Viking ancestry. Modern times In 1865, Armand Trousseau (a French internist) was one of the first to describe many of the symptoms of a diabetic patient with cirrhosis of the liver and bronzed skin color. The term haemochromatosis was first used by German pathologist Friedrich Daniel von Recklinghausen in 1889 when he described an accumulation of iron in body tissues. Identification of genetic factors Although it was known most of the 20th century that most cases of haemochromatosis were inherited, they were incorrectly assumed to depend on a single gene.In 1935 J.H. Sheldon, a British physician, described the link to iron metabolism for the first time as well as demonstrating its hereditary nature.In 1996 Felder and colleagues identified the haemochromatosis gene, HFE gene. Felder found that the HFE gene has two main mutations, C282Y and H63D, which were the main cause of hereditary haemochromatosis. The next year the CDC and the National Human Genome Research Institute sponsored an examination of haemochromatosis following the discovery of the HFE gene, which helped lead to the population screenings and estimates that are still being used today. See also Human iron metabolism Iron deficiency References External links Iron overload at Curlie GeneReview/NCBI/NIH/UW entry on HFE-Associated Hereditary Hemochromatosis GeneReview/NCBI/NIH/UW entry on TFR2-Related Hereditary Hemochromatosis GeneReview/NCBI/NIH/UW entry on Juvenile Hereditary Hemochromatosis GeneReview/NCBI/NIH/UW entry on Aceruloplasminemia

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

I'm curious about the meaning of the medical term 'Clonorchiasis.' Can you give me some insights?

Clonorchiasis is an infectious disease caused by the Chinese liver fluke (Clonorchis sinensis) and two related species. Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary system.Symptoms of opisthorchiasis caused by Opisthorchis viverrini and by O. felineus are indistinguishable from clonorchiasis caused by Clonorchis sinensis, leading some to argue that the disease by these three parasites should be referred to collectively as clonorchiasis. Signs and symptoms Cause Clonorchiasis sinensis is a trematode (fluke) which is part of the phylum Platyhelminthes. The parasitic worm is as long as 10 to 25 mm and lives in the bile ducts of the liver. It is a hermaphroditic fluke that requires two intermediate hosts. The eggs of the worms are passed in fecal matter into a body of water and are then ingested by mollusks. The water snail is the first intermediate host, in which a miracidium (an embryonated egg discharged in stool) goes through its developmental stages (sporocyst, rediae and cercariae). Freshwater fish are a second intermediate host for the parasitic worm. They become infected when the larva (cercaria) of the worm leaves the snail and penetrates the flesh of the fish. Humans then become infected by eating infected fish that has been undercooked, smoked, pickled, or salted, and from there the cycle repeats. Clonorchiasis is endemic in the Far East, especially in Korea, Japan, Taiwan, and Southern China. Clonorchiasis has been reported in areas to which it is not endemic (including the United States). In such cases, the infection follows the ingestion of undercooked or pickled freshwater fish imported from one of the endemic areas and containing metacercariae. Diagnosis Adult C. sinensis worms can inhabit the bile ducts of humans for 20–25 years without any clear clinical symptoms. This, in addition to the nonspecific symptoms infected persons may develop, can lead to missed diagnoses.Patients are diagnosed when C. sinensis eggs are found in stools. The formalin-ether concentration technique (FECT) method of stool examination is most effective at diagnosing light cases of infection, while the Kato-Katz (KK) method is more suitable for the diagnosing of persons with clonorchiasis. Serological methods that use enzyme-linked immunosorbent assay (ELISA) can help differentiate the eggs of C. sinensis from other flukes. Treatment Praziquantel is the treatment of choice for clonorchiasis. References == External links ==

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Could you provide a brief overview of 'Large plaque parapsoriasis' in a medical context?

Large plaque parapsoriasis are skin lesions that may be included in the modern scheme of cutaneous conditions described as parapsoriasis. These lesions, called plaques, may be irregularly round-shaped to oval and are 10 cm (4 in) or larger in diameter. They can be very thin plaques that are asymptomatic or mildly pruritic. Large-plaque parapsoriasis is a common associate of retiform parapsoriasis, can be accompanied by poikiloderma vasculare atrophicans, and can in rare occasions be a precursor to cutaneous T-cell lymphoma. Cause Diagnosis Treatment Parapsoriasis treatment consists primarily of light therapy (more specifically PUVA therapy or UVB therapy) possibly in combination with topical steroids. Large plaque parapsoriasis is usually a chronic condition that needs long-term treatment. See also List of cutaneous conditions Mycosis fungoides References == External links ==

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I'm not familiar with the medical term 'Coalworkers pneumoconiosis.' Could you provide some insights?

Coal workers pneumoconiosis (CWP), also known as black lung disease or black lung, is an occupational type of pneumoconiosis caused by long-term exposure to coal dust. It is common in coal miners and others who work with coal. It is similar to both silicosis from inhaling silica dust and asbestosis from inhaling asbestos dust. Inhaled coal dust progressively builds up in the lungs and leads to inflammation, fibrosis, and in worse cases, necrosis. Coal workers pneumoconiosis, severe state, develops after the initial, milder form of the disease known as anthracosis (from the Greek άνθρακας, or anthracas —coal, carbon). This is often asymptomatic and is found to at least some extent in all urban dwellers due to air pollution. Prolonged exposure to large amounts of coal dust can result in more serious forms of the disease, simple coal workers pneumoconiosis and complicated coal workers pneumoconiosis (or progressive massive fibrosis, or PMF). More commonly, workers exposed to coal dust develop industrial bronchitis, clinically defined as chronic bronchitis (i.e. productive cough for 3 months per year for at least 2 years) associated with workplace dust exposure. The incidence of industrial bronchitis varies with age, job, exposure, and smoking. In nonsmokers (who are less prone to develop bronchitis than smokers), studies of coal miners have shown a 16% to 17% incidence of industrial bronchitis. In 2013 CWP resulted in 25,000 deaths globally—down from 29,000 deaths in 1990. However, a later 2018 study by the National Institute of Occupational Safety and Health shows a resurgence, recording the highest rate of CWP in roughly two decades. Pathogenesis Coal dust is not as fibrogenic as silica dust. Coal dust that enters the lungs can neither be destroyed nor removed by the body. The particles are engulfed by resident alveolar or interstitial macrophages and remain in the lungs, residing in the connective tissue or pulmonary lymph nodes. Coal dust provides a sufficient stimulus for the macrophage to release various products, including enzymes, cytokines, oxygen radicals, and fibroblast growth factors, which are important in the inflammation and fibrosis of CWP. Aggregations of carbon-laden macrophages can be visualized under a microscope as granular, black areas. In serious cases, the lung may grossly appear black. These aggregations can cause inflammation and fibrosis, as well as the formation of nodular lesions within the lungs. The centers of dense lesions may become necrotic due to ischemia, leading to large cavities within the lung. Appearance Simple CWP is marked by the presence of 1–2 mm nodular aggregations of anthracotic macrophages, supported by a fine collagen network, within the lungs. Those 1–2 mm in diameter are known as coal macules, with larger aggregations known as coal nodules. These structures occur most frequently around the initial site of coal dust accumulation—the upper regions of the lungs around respiratory bronchioles. The coal macule is the basic pathological feature of CWP and has a surrounding area of enlargement of the airspace, known as focal emphysema. Focal emphysema extends into progressive centrilobular emphysema. Less commonly a variant of panacinar emphysema develops.Continued exposure to coal dust following the development of simple CWP may progress to complicated CWP with progressive massive fibrosis (PMF), wherein large masses of dense fibrosis develop, usually in the upper lung zones, measuring greater than 1 cm in diameter, with accompanying decreased lung function. These cases generally require a number of years to develop. Grossly, the lung itself appears blackened. Pathologically, these consist of fibrosis with haphazardly-arranged collagen and many pigment-laden macrophages and abundant free pigment. Radiographically, CWP can appear strikingly similar to silicosis. In simple CWP, small rounded nodules (see ILO Classification) predominate, tending to first appear in the upper lung zones. The nodules may coalesce and form large opacities (>1 cm), characterizing complicated CWP, or PMF. Diagnosis There are three basic criteria for the diagnosis of CWP: Chest radiography consistent with CWP An exposure history to coal dust (typically underground coal mining) of sufficient amount and latency Exclusion of alternative diagnoses (mimics of CWP)Symptoms and pulmonary function testing relate to the degree of respiratory impairment but are not part of the diagnostic criteria. As noted above, the chest X-ray appearance for CWP can be virtually indistinguishable from silicosis. Chest CT, particularly high-resolution scanning (HRCT), are more sensitive than plain X-ray for detecting the small round opacities. Treatment There is no cure or discovered treatments for pneumoconiosis. Some patients are given oxygen to help with their breathing and are advised to stop smoking to prevent further decline in lung function. In the most extreme cases a lung transplant could be done to help prolong the patients life expectancy. Prevention of pneumoconiosis The main way to avoid contracting coal workers pneumoconiosis is to avoid the inhalation of coal dust. Some of the ways to prevent this disease include: not smoking, wearing ventilated masks when coming in contact with potentially dangerous airborne particles, regular pulmonary exams, and becoming educated about the risks of lung diseases in your work environment. Epidemiology In 2013 CWP resulted in 25,000 deaths down from 29,000 deaths in 1990. Between 1970 and 1974, prevalence of CWP among US coal miners who had worked over 25 years was 32%; the same group saw a prevalence of 9% in 2005–2006. In Australia, CWP was considered to be eliminated in the 1970s due to strict hazard control measures. However, there has been a resurgence of CWP in Australia, with the first new cases being detected in May 2015. From 1999 to 2016, the average years of life lost due to CWP increased from 8.1 to 12.6 years, most likely due to the increased severity and progression of CWP. History Black lung is actually a set of conditions and until the 1950s its dangers were not well understood. The prevailing view was that silicosis was very serious but it was solely caused by silica and not coal dust. The miners union, the United Mine Workers of America, realized that rapid mechanization meant drills that produced much more dust, but under John L. Lewis they decided not to raise the black lung issue because it might impede the mechanization that was producing higher productivity and higher wages. Union priorities were to maintain the viability of the long-fought-for welfare and retirement fund, which would be sustained by higher outputs of coal. After the death of Lewis, the union dropped its opposition to calling black lung a disease and realized the financial advantages of a fund for its disabled members. In the Federal Coal Mine Health and Safety Act of 1969, the US Congress set up standards to reduce dust and created the Black Lung Disability Trust. The mining companies agreed to a clause, by which a ten-year history of mine work, coupled with X-ray or autopsy evidence of severe lung damage, guaranteed compensation. Equally important was a "rate retention" clause that allowed workers with progressive lung disease to transfer to jobs with lower exposure without loss of pay, seniority, or benefits. Financed by a federal tax on coal, the Trust by 2009 had distributed over $44 billion in benefits to miners disabled by the disease and their widows. A miner who has spent 25 years in underground coal mines has a 5–10% risk of contracting the disease. 21st century After the Federal Coal Mine Health and Safety Act of 1969 became law in the United States, the percentage of American miners with black lung disease decreased by about 90 percent. More recently, however, rates of the disease have been on the rise. The National Institute for Occupational Safety and Health (NIOSH) reported that close to 9 percent of miners with 25 years or more experience tested positive for black lung in 2005–2006, compared with 4 percent in the late 1990s.New findings have shown that CWP can be a risk for surface coal miners, who are 48% of the workforce. Data from the Coal Workers Health Surveillance Program of NIOSH, which examined chest X-rays from more than 2,000 miners in 16 US states from 2010 to 2011, showed that 2% of miners with greater than one year of surface mining experience developed CWP. 0.5% of these miners had PMF. Most of these workers had never worked in an underground mine prior to surface mining. A high proportion of the X-rays suggested that these miners had developed silicosis. NIOSH, with support from the Mine Safety and Health Administration (MSHA), operates a Mobile Health Screening Program, which travels to mining regions around the United States. Miners who participate in the Program receive health evaluations once every five years, at no cost to themselves. Chest x-rays can detect the early signs of and changes in CWP, often before the miner is aware of any lung problems.A 2016-17 investigation by National Public Radio found that the National Institute for Occupational Safety and Health had under-reported cases of progressive massive fibrosis (a complication of black lung) by at least a factor of 20. NPR identified over 2,000 cases at certain clinics in Kentucky, Virginia, West Virginia, Pennsylvania, and Ohio, compared to 99 that NIOSH reported. NIOSH confirmed in 2018 the largest cluster of PMF ever scientifically documented, despite near-elimination of the disease in the 1990s. The causes of the spike are believed to include longer working shifts, mining of thinner coal seams (which causes mining machines to put more non-coal silica dust in the air), and retirements and layoffs that have prompted more former employees to visit health clinics.New U.S. Mine Safety and Health Administration rules took effect in August, 2016, that lowered maximum allowed dust concentrations for surface and underground mines, and exposure by miners who have been found to be developing pneumoconiosis. Research Work to investigate the relationship between respirable dust exposure and coal workers pneumoconiosis was carried out in Britain by the Institute of Occupational Medicine. This research was known as the Pneumoconiosis Field Research (PFR). The research underpinned the recommendations for more stringent airborne dust standards in British coalmines and the PFR was ultimately used as the basis for many national dust standards around the world. See also Black Lung Benefits Act of 1972 Caplan syndrome References External links Faces of Black Lung - USDHHS on YouTube NIOSH Mining Topic: Respiratory Diseases NIOSH Coal Workers Health Surveillance Program Mine Safety and Health Administration 42CFR27 Specifications of Medical Examinations of Underground Coal Miners Institute of Occupational Medicines pneumoconiosis research

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Could you offer a clear explanation of the term 'Imiglucerase' as used in the medical field?

Imiglucerase is a medication used in the treatment of Gauchers disease.It is a recombinant DNA-produced analogue of the human enzyme β-glucocerebrosidase. Cerezyme is a freeze-dried medicine containing imiglucerase, manufactured by Genzyme Corporation. It is given intravenously after reconstitution as a treatment for Type 1 and Type 3 Gauchers disease. It is available in formulations containing 200 or 400 units per vial. The specific activity of highly purified human enzyme is 890,000 units/mg, meanwhile the enzyme activity produced by recombinant DNA technology is approximately 40 units/mg. A typical dose is 2.5U/kg every two weeks, up to a maximum of 60 U/kg once every two weeks, and safety has been established from ages 2 and up. It is one of more expensive medications, with an annual cost of $200,000 per person in the United States. Imiglucerase has been granted orphan drug status in the United States, Australia, and Japan.Cerezyme was one of the drugs manufactured at Genzymes Allston, Massachusetts plant, for which production was disrupted in 2009 after contamination with Vesivirus 2017. Side effects The most common side effect is hypersensitivity, which occurs in about 3% of patients. It is associated with symptoms such as cough, shortness of breath, rashes, itching, and angiooedema. Less common side effects include dizziness, headache, nausea, diarrhoea, and reactions at the injection site; they are found in less than 1% of patients. Interactions No clinical interaction studies have been conducted. Miglustat appears to increase the clearance of imiglucerase by 70%, resulting in decreased enzyme activity. See also Other drugs for the treatment of Gauchers disease Afegostat (development terminated) Eliglustat Miglustat Velaglucerase alfa taliglucerase alfa == References ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

What is the significance of the term 'Dysequilibrium syndrome' in the medical field?

Dysequilibrium syndrome may refer to: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1 (CAMRQ1), an autosomal recessive cerebellar ataxia associated with the VLDLR gene Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 (CAMRQ2), an autosomal recessive cerebellar ataxia associated with the WDR81 gene Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ3), an autosomal recessive cerebellar ataxia associated with the CA8 gene Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 (CAMRQ4), an autosomal recessive cerebellar ataxia associated with the ATP8A2 gene

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I'm seeking clarification on the medical term 'Nortriptyline.' Could you explain it?

Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18-24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.Common side effects include dry mouth, constipation, blurry vision, sleepiness, low blood pressure with standing, and weakness. Serious side effects may include seizures, an increased risk of suicide in those less than 25 years of age, urinary retention, glaucoma, mania, and a number of heart issues. Nortriptyline may cause problems if taken during pregnancy. Use during breastfeeding appears to be relatively safe. It is a tricyclic antidepressant (TCA) and is believed to work by altering levels of serotonin and norepinephrine.Nortriptyline was approved for medical use in the United States in 1964. It is available as a generic medication. In 2019, it was the 153rd most commonly prescribed medication in the United States, with more than 4 million prescriptions. Medical uses Nortriptyline is used to treat depression. This medication is in capsule or liquid and is taken by the mouth one to four times a day, with or without food. Usually people are started on a low dose and it is gradually increased. A level between 50 and 150 ng/mL of nortriptyline in the blood generally corresponds with an antidepressant effect.In the United Kingdom, it may also be used for treating nocturnal enuresis, with courses of treatment lasting no more than three months. It is also used off-label for the treatment of panic disorder, irritable bowel syndrome, migraine prophylaxis and chronic pain or neuralgia modification, particularly temporomandibular joint disorder. Neuropathic pain Although not approved by the FDA for neuropathic pain, many randomized controlled trials have demonstrated the effectiveness of TCAs for the treatment of this condition in both depressed and non-depressed individuals. In 2010, an evidence-based guideline sponsored by the International Association for the Study of Pain recommended nortriptyline as a first-line medication for neuropathic pain. However, in a 2015 Cochrane systematic review the authors did not recommend nortriptyline as a first-line agent for neuropathic pain. Irritable Bowel Syndrome Nortriptyline has also been used as an off-label treatment for Irritable Bowel Syndrome, or IBS. Contraindications Nortriptyline should not be used in the acute recovery phase after myocardial infarction (viz, heart attack). Use of tricyclic antidepressants along with a monoamine oxidase (MAO) inhibitor, linezolid, and IV methylene blue are contraindicated as it can cause an increased risk of developing serotonin syndrome.Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma, or seizures, as well as in persons with hyperthyroidism or receiving thyroid hormones. Side effects The most common side effects include dry mouth, sedation, constipation, increased appetite, blurred vision and tinnitus. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects. Overdose The symptoms and the treatment of an overdose are generally the same as for the other TCAs, including anticholinergic effects, serotonin syndrome and adverse cardiac effects. TCAs, particularly nortriptyline, have a relatively narrow therapeutic index, which increase the chance of an overdose (both accidental and intentional). Symptoms of overdose include: irregular heartbeat, seizures, coma, confusion, hallucination, widened pupils, drowsiness, agitation, fever, low body temperature, stiff muscles and vomiting. Interactions Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicidal attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation. It may interact with the following drugs: heart rhythm medications such as flecainide (Tambocor), propafenone (Rhythmol), or quinidine (Cardioquin, Quinidex, Quinaglute) cimetidine guanethidine reserpine Pharmacology Nortriptyline is a strong norepinephrine reuptake inhibitor and a moderate serotonin reuptake inhibitor. Its pharmacologic profile is as the table shows with (inhibition or antagonism of all sites). Pharmacodynamics Nortriptyline is an active metabolite of amitriptyline by demethylation in the liver. Chemically, it is a secondary amine dibenzocycloheptene and pharmacologically it is classed as a first-generation antidepressant.Nortriptyline may also have a sleep-improving effect due to antagonism of the H1 and 5-HT2A receptors. In the short term, however, nortriptyline may disturb sleep due to its activating effect. In one study, nortriptyline had the highest affinity for the dopamine transporter among the TCAs (KD = 1,140 nM) besides amineptine (a norepinephrine–dopamine reuptake inhibitor), although its affinity for this transporter was still 261- and 63-fold lower than for the norepinephrine and serotonin transporters (KD = 4.37 and 18 nM, respectively). Pharmacokinetics Pharmacogenetics Nortriptyline is metabolized in the liver by the hepatic enzyme CYP2D6, and genetic variations within the gene coding for this enzyme can affect its metabolism, leading to changes in the concentrations of the drug in the body. Increased concentrations of nortriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drugs efficacy.Individuals can be categorized into different types of CYP2D6 metabolizers depending on which genetic variations they carry. These metabolizer types include poor, intermediate, extensive, and ultrarapid metabolizers. Most individuals (about 77–92%) are extensive metabolizers, and have "normal" metabolism of nortriptyline. Poor and intermediate metabolizers have reduced metabolism of the drug as compared to extensive metabolizers; patients with these metabolizer types may have an increased probability of experiencing side effects. Ultrarapid metabolizers use nortriptyline much faster than extensive metabolizers; patients with this metabolizer type may have a greater chance of experiencing pharmacological failure.The Clinical Pharmacogenetics Implementation Consortium recommends avoiding nortriptyline in persons who are CYP2D6 ultrarapid or poor metabolizers, due to the risk of a lack of efficacy and side effects, respectively. A reduction in starting dose is recommended for patients who are CYP2D6 intermediate metabolizers. If use of nortriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments. The Dutch Pharmacogenetics Working Group recommends reducing the dose of nortriptyline in CYP2D6 poor or intermediate metabolizers, and selecting an alternative drug or increasing the dose in ultrarapid metabolizers. Chemistry Nortriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzocycloheptadiene TCAs include amitriptyline (N-methylnortriptyline), protriptyline, and butriptyline. Nortriptyline is a secondary amine TCA, with its N-methylated parent amitriptyline being a tertiary amine. Other secondary amine TCAs include desipramine and protriptyline. The chemical name of nortriptyline is 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine and its free base form has a chemical formula of C19H21N1 with a molecular weight of 263.384 g/mol. The drug is used commercially mostly as the hydrochloride salt; the free base form is used rarely. The CAS Registry Number of the free base is 72-69-5 and of the hydrochloride is 894-71-3. History Nortriptyline was developed by Geigy. It first appeared in the literature in 1962 and was patented the same year. The drug was first introduced for the treatment of depression in 1963. Society and culture Generic names Nortriptyline is the English and French generic name of the drug and its INN, BAN, and DCF, while nortriptyline hydrochloride is its USAN, USP, BANM, and JAN. Its generic name in Spanish and Italian and its DCIT are nortriptilina, in German is nortriptylin, and in Latin is nortriptylinum. Brand names Brand names of nortriptyline include Allegron, Aventyl, Noritren, Norpress, Nortrilen, Norventyl, Norzepine, Pamelor, and Sensoval, among many others. References External links "Nortriptyline". Drug Information Portal. U.S. National Library of Medicine.

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I'm trying to understand 'Hip dysplasia' within a medical context. Could you shed some light on it?

Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation. Hip dysplasia may occur at birth or develop in early life. Regardless, it does not typically produce symptoms in babies less than a year old. Occasionally one leg may be shorter than the other. The left hip is more often affected than the right. Complications without treatment can include arthritis, limping, and low back pain.Risk factors for hip dysplasia include family history, certain swaddling practices, and breech birth. If one identical twin is affected, there is a 40% risk the other will also be affected. Screening all babies for the condition by physical examination is recommended. Ultrasonography may also be useful.Many of those with mild instability resolve without specific treatment. In more significant cases, if detected early, bracing may be all that is required. In cases that are detected later, surgery and casting may be needed. About 7.5% of hip replacements are done to treat problems which have arisen from hip dysplasia.About 1 in 1,000 babies have hip dysplasia. Hip instability of meaningful importance occurs in one to two percent of babies born at term. Females are affected more often than males. Hip dysplasia was described at least as early as the 300s BC by Hippocrates. Signs and symptoms Hip dysplasia can range from barely detectable to severely malformed or dislocated. The congenital form, teratologic or non-reducible dislocation occurs as part of more complex conditions.The condition can be bilateral or unilateral: If both hip joints are affected, one speaks of "bilateral" dysplasia. In this case, some diagnostic indicators like asymmetric folds and leg-length inequality do not apply. In unilateral dysplasia only one joint shows deformity, the contralateral side may show resulting effects. In the majority of unilateral cases, the left hip has the dysplasia.If the joint is fully dislocated a false acetabulum often forms (often higher up on the pelvis) opposite the dislocated femoral head position. In acetabular dysplasia, the acetabulum (socket) is too shallow or deformed. The center-edge angle is measured as described by Wiberg. Two forms of femoral dysplasia are coxa vara, in which the femur head grows at too narrow an angle to the shaft, and coxa valga, in which the angle is too wide. A rare type, the "Beukes familial hip dysplasia" is found among Afrikaners that are members of the Beukes family. The femur head is flat and irregular. People develop osteoarthritis at an early age. Causes Hip dysplasia is considered to be a multifactorial condition. That means that several factors are involved in causing the condition to manifest.The cause of this condition is unknown; however, some factors of congenital hip dislocation are through heredity and racial background. It is also thought that the higher rates in some ethnic groups (such as some Native American groups) is due to the practice of swaddling of infants, which is known to be a potential risk factor for developing dysplasia. It also has a low risk in African Americans and southern Chinese. Congenital Some studies suggest a hormonal link. Specifically, the hormone relaxin has been indicated.A genetic factor is indicated since the trait runs in families and there is an increased occurrence in some ethnic populations (e.g., Native Americans, Lapps / Sami people). A locus has been described on chromosome 13. Beukes familial dysplasia, on the other hand, was found to map to an 11-cM region on chromosome 4q35, with nonpenetrant carriers not affected. Acquired As an acquired condition it has often been linked to traditions of swaddling infants, use of overly restrictive baby seats, carriers and other methods of transporting babies, or use of a cradle board which locks the hip joint in an "adducted" position (pulling the knees together tends to pull the heads of the femur bone out of the sockets or acetabulae) for extended periods. Modern swaddling techniques, such as the hip healthy swaddle have been developed to relieve stress on hip joints caused by traditional swaddling methods.Further risk factors include breech birth, gender, genetics (family history), and firstborns. In breech position the femoral head tends to get pushed out of the socket. A narrow uterus also facilitates hip joint dislocation during fetal development and birth. Diagnosis Most countries have standard newborn exams that include a hip joint exam screening for early detection of hip dysplasia. Sometimes during an exam a "click" or more precisely "clunk" in the hip may be detected (although not all clicks indicate hip dysplasia). When a hip click (also known as "clicky hips" in the UK) is detected, the childs hips are tracked with additional screenings to determine if developmental dysplasia of the hip is caused.Two maneuvers commonly employed for diagnosis in neonatal exams are the Ortolani maneuver and the Barlow maneuver.In order to do the Ortolani maneuver it is recommended that the examiner put the newborn baby in a position in which the contralateral hip is held still while the thigh of the hip being tested is abducted and gently pulled anteriorly. If a "clunk" is heard (the sound of the femoral head moving over the acetabulum), the joint is normal, but absence of the "clunk" sound indicates that the acetabulum is not fully developed. The next method that can be used is called the Barlow maneuver. It is done by adducting the hip while pushing the thigh posteriorly. If the hip goes out of the socket it means it is dislocated, and the newborn has a congenital hip dislocation. The baby is laid on its back for examination by separation of its legs. If a clicking sound can be heard, it indicates that the baby may have a dislocated hip. It is highly recommended that these maneuvers be done when the baby is not fussing, because the baby may inhibit hip movement.Asymmetrical gluteal folds and an apparent limb-length inequality can further indicate unilateral hip dysplasia. Most vexingly, many newborn hips show a certain ligamentous laxity, on the other hand severely malformed joints can appear stable. That is one reason why follow-up exams and developmental monitoring are important. Frequency and methods of routine screenings in children is still in debate however physical examination of newborns followed by appropriate use of hip ultrasound is widely accepted.The Harris hip score (developed by William H. Harris MD, an orthopedist from Massachusetts) is one way to evaluate hip function following surgery. Other scoring methods are based on patients evaluation like e.g. the Oxford hip score, HOOS and WOMAC score. Childrens Hospital Oakland Hip Evaluation Scale (CHOHES) is a modification of the Harris hip score that is currently being evaluated.Hip dysplasia can develop in older age. Adolescents and adults with hip dysplasia may present with hip pain and in some cases hip labral tears. X-rays are used to confirm a diagnosis of hip dysplasia. CT scans and MRI scans are occasionally used too. Terminology Some sources prefer "developmental dysplasia of the hip" (DDH) to "congenital dislocation of the hip" (CDH), finding the latter term insufficiently flexible in describing the diversity of potential complications.The use of the word congenital can also imply that the condition already exists at birth. This terminology introduces challenges, because the joint in a newborn is formed from cartilage and is still malleable, making the onset difficult to ascertain. The newer term DDH also encompasses occult dysplasia (e.g. an underdeveloped joint) without dislocation and a dislocation developing after the "newborn" phase.The term is not used consistently. In pediatric/neonatal orthopedics it is used to describe unstable/dislocatable hips and poorly developed acetabula. For adults it describes hips showing abnormal femur head or acetabular x-rays.Some sources prefer the term "hip dysplasia" over DDH, considering it to be "simpler and more accurate", partly because of the redundancy created by the use of the terms developmental and dysplasia. Types of DDH include subluxation, dysplasia, and dislocation. The main types are the result of either laxity of the supporting capsule or an abnormal acetabulum. Imaging Hip dysplasia diagnosed by ultrasound and projectional radiography ("X-ray"). Ultrasound imaging is generally preferred at up to 4 months due to limited ossification of the skeleton.Despite the widespread of ultrasound, pelvis X-ray is still frequently used to diagnose or monitor hip dysplasia or for assessing other congenital conditions or bone tumors. The most useful lines and angles that can be drawn in the pediatric pelvis assessing hip dysplasia are as follows: Different measurements are used in adults. Treatment Hip dysplasia presents a nearly perfect equilibrium between the arthritis, movement/mobility problems and pain associated with the developmental malformation, and the arthritis, movement/mobility problems and pain that are, as often as not in moderate to severe cases, inflicted by the treatment itself.However, given the very real possibility of a limp, constant and/or debilitating pain, complicated treatment and impaired mobility later in life, careful developmental monitoring is indicated and early intervention is often the best result. The worst possible consequence of non treatment is developing early arthritis, sometimes even during teenage years. All treatment aims to delay the onset of arthritis, but no treatment is fully successful in avoiding it; and, all available treatments bear the risk of inflicting equivalent damage. Most unfortunately, studies have as yet been unable to find a method of predicting outcomes in either the surgical/orthopedic treatment of the condition in infants and young children, or the surgical treatment of these early treatments negative outcomes later in life (such as arthritis, avascular necrosis, trochanteric bursitis, and bone spurs of up to 3.5 cm just medial of the gluteus maximus insertion point on the greater trochanter due to excessive friction). Harnesses, casts, and traction Early hip dysplasia can often be treated using a Pavlik harness (see photograph) or the Frejka pillow/splint in the first year of life with usually normal results. Complications can occur when using the Pavlik harness. Cases of femoral nerve palsy and avascular necrosis of the femoral head have been reported with the use of the Pavlik harness, but whether these cases were due to improper application of the device or a complication encountered in the course of the disorder remains unresolved. Complications arise mainly because the sheet of the iliopsoas muscle pushes the circumflex artery against the neck of the femur and decreases blood flow to the femoral head, so the Frejka pillow is not indicated in all the forms of the developmental dysplasia of the hip. Other devices employed include the spica cast, particularly following surgical closed reduction, open reduction, or osteotomy in babies and young children. Traction is sometimes used in the weeks leading up to a surgery to help stretch ligaments in the hip joint, although its use is controversial and varies amongst physicians. Surgery In older children the adductor and iliopsoas muscles may have to be treated surgically because they adapt to the dislocated joint position (contracture). Braces and splints are often used following either of these methods to continue treatment. Although some children "outgrow" untreated mild hip dysplasia and some forms of untreated dysplasia cause little or no impairment of quality of life, studies have as yet been unable to find a method of predicting outcomes. On the other hand, it has often been documented that starting treatment late leads to complications and ends in poor results. Hip replacement and osteotomy Hip dysplasia is often cited as causing osteoarthritis of the hip at a comparatively young age. Dislocated load bearing surfaces lead to increased and unusual wear, although there are studies that contradict these findings (see). Peri-acetabular osteotomy (PAO) surgery can be used to realign the hip joint in some adolescents and adults. Subsequent treatment with total hip arthroplasty (hip replacement) is complicated by a need for revision surgery (replacing the artificial joint) owing to skeletal changes as the body matures, loosening/wear or bone resorption. Hip resurfacing is another option for correcting hip dysplasia in adults. It is a type of hip replacement that preserves more bone, and may work for younger hip dysplasia patients.Osteotomies are either used in conjunction with arthroplasty or by themselves to correct misalignment. Epidemiology Determining the incidence can be difficult. In addition there is a wide margin in diagnostic results. A German study comparing two methods resulted in twice the usual rate for one method. The condition is eight times more frequent in females than in males.Native Americans are more likely to have congenital hip dislocation than any of the other races. The risk for Native Americans is about 25–50 in 1000. The overall frequency of developmental dysplasia of the hip is approximately 1 case per 1000 individuals; however, Barlow believed that the incidence of hip instability in newborns can be as high as 1 case for every 60 newborns, with the rate dropping to 1:240 at one week. History The Frejka pillow splint was named after Dr. Bedrich Frejka (1890-1972), a Czech orthopedic surgeon. The Pavlik harness was named after Dr. Arnold Pavlik (1902-1962), also a Czech orthopedic surgeon. Society and culture In the television program ER, Kerry Weaver uses a crutch owing to congenital hip dysplasia. In season 12, she undergoes a hip replacement to cure her dysplasia when her previously untreated joint worsens. Research One avenue of research is using stem cells. They are applied in grafting (bone grafting) or by seeding porous arthroplasty prosthesis with autologous fibroblasts or chondrocyte progenitor cells to assist in firmly anchoring the artificial material in the bone bed. Other animals In dogs, hip dysplasia is an abnormal formation of the hip socket that, in its more severe form, can eventually cause crippling lameness and painful arthritis of the joints. It is a genetic (polygenic) trait that is affected by environmental factors. It is common in many dog breeds, particularly the larger breeds.Hip dysplasia is one of the most studied veterinary conditions in dogs, and the most common single cause of arthritis of the hips. Cats are also known to have this condition, especially Siamese. Notes References External links Online orthopedic textbook

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

Can you demystify the medical term 'Familial benign copper deficiency' for me?

Familial benign copper deficiency, also known as Familial benign hypocupremia is a rare genetic disorder which is characterized by hypocupremia that causes symptoms such as epilepsy, hypotonia, seborrheic skin, thriving failure and mild anemia. Radiological findings include tibia and femur spurring. Transmission is thought to be either autosomal dominant or X-linked dominant.Symptoms are caused by a familial tendency of having low levels of copper within the body and can be improved (treated and managed) with oral supplements of copper.It has been described in members of a 3-generation Hungarian family. == References ==

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Could you please explain the term 'Abdomen' in simple language?

The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. The area occupied by the abdomen is called the abdominal cavity. In arthropods it is the posterior tagma of the body; it follows the thorax or cephalothorax.In humans, the abdomen stretches from the thorax at the thoracic diaphragm to the pelvis at the pelvic brim. The pelvic brim stretches from the lumbosacral joint (the intervertebral disc between L5 and S1) to the pubic symphysis and is the edge of the pelvic inlet. The space above this inlet and under the thoracic diaphragm is termed the abdominal cavity. The boundary of the abdominal cavity is the abdominal wall in the front and the peritoneal surface at the rear. In vertebrates, the abdomen is a large body cavity enclosed by the abdominal muscles, at front and to the sides, and by part of the vertebral column at the back. Lower ribs can also enclose ventral and lateral walls. The abdominal cavity is continuous with, and above, the pelvic cavity. It is attached to the thoracic cavity by the diaphragm. Structures such as the aorta, inferior vena cava and esophagus pass through the diaphragm. Both the abdominal and pelvic cavities are lined by a serous membrane known as the parietal peritoneum. This membrane is continuous with the visceral peritoneum lining the organs. The abdomen in vertebrates contains a number of organs belonging to, for instance, the digestive system, urinary system, and muscular system. Contents The abdominal cavity contains most organs of the digestive system, including the stomach, the small intestine, and the colon with its attached appendix. Other digestive organs are known as the accessory digestive organs and include the liver, its attached gallbladder, and the pancreas, and these communicate with the rest of the system via various ducts. The spleen, and organs of the urinary system including the kidneys, and adrenal glands also lie within the abdomen, along with many blood vessels including the aorta and inferior vena cava. The urinary bladder, uterus, fallopian tubes, and ovaries may be seen as either abdominal organs or as pelvic organs. Finally, the abdomen contains an extensive membrane called the peritoneum. A fold of peritoneum may completely cover certain organs, whereas it may cover only one side of organs that usually lie closer to the abdominal wall. This is called the retroperitoneum, and the kidneys and ureters are known as retroperitoneal organs. Abdominal organs can be highly specialized in some animals. For example, the stomach of ruminants, (a suborder of mammals that includes cattle and sheep), is divided into four chambers – rumen, reticulum, omasum and abomasum. Muscles There are three layers of muscles in the abdominal wall. They are, from the outside to the inside: external oblique, internal oblique, and transverse abdominal. The first three layers extend between the vertebral column, the lower ribs, the iliac crest and pubis of the hip. All of their fibers merge towards the midline and surround the rectus abdominis in a sheath before joining up on the opposite side at the linea alba. Strength is gained by the criss-crossing of fibers, such that the external oblique runs downward and forward, the internal oblique upward and forward, and the transverse abdominal horizontally forward.The transverse abdominal muscle is flat and triangular, with its fibers running horizontally. It lies between the internal oblique and the underlying transverse fascia. It originates from the inguinal ligament, costal cartilages 7-12, the iliac crest and thoracolumbar fascia. Inserts into the conjoint tendon, xiphoid process, linea alba and the pubic crest. The rectus abdominis muscles are long and flat. The muscle is crossed by three fibrous bands called the tendinous intersections. The rectus abdominis is enclosed in a thick sheath, formed as described above, by fibers from each of the three muscles of the lateral abdominal wall. They originate at the pubis bone, run up the abdomen on either side of the linea alba, and insert into the cartilages of the fifth, sixth, and seventh ribs. In the region of the groin, the inguinal canal, is a passage through the layers. This gap is where the testes can drop through the wall and where the fibrous cord from the uterus in the female runs. This is also where weakness can form, and cause inguinal hernias.The pyramidalis muscle is small and triangular. It is located in the lower abdomen in front of the rectus abdominis. It originates at the pubic bone and is inserted into the linea alba halfway up to the navel. Function Functionally, the human abdomen is where most of the digestive tract is placed and so most of the absorption and digestion of food occurs here. The alimentary tract in the abdomen consists of the lower esophagus, the stomach, the duodenum, the jejunum, ileum, the cecum and the appendix, the ascending, transverse and descending colons, the sigmoid colon and the rectum. Other vital organs inside the abdomen include the liver, the kidneys, the pancreas and the spleen. The abdominal wall is split into the posterior (back), lateral (sides), and anterior (front) walls. Movement, breathing and other functions The abdominal muscles have different important functions. They assist as muscles of exhalation in the breathing process during forceful exhalation. Moreover, these muscles serve as protection for the inner organs. Furthermore, together with the back muscles they provide postural support and are important in defining the form. When the glottis is closed and the thorax and pelvis are fixed, they are integral in the cough, urination, defecation, childbirth, vomit, and singing functions. When the pelvis is fixed, they can initiate the movement of the trunk in a forward motion. They also prevent hyperextension. When the thorax is fixed, they can pull up the pelvis and finally, they can bend the vertebral column sideways and assist in the trunks rotation. Posture The transverse abdominis muscle is the deepest muscle, therefore, it cannot be touched from the outside. It can greatly affect the bodys posture. The internal obliques are also deep and also affect body posture. Both of them are involved in rotation and lateral flexion of the spine and are used to bend and support the spine from the front. The external obliques are more superficial and they are also involved in rotation and lateral flexion of the spine. Also they stabilize the spine when upright. The rectus abdominis muscle is not the most superficial abdominal muscle. The tendonous sheath extending from the external obliques cover the rectus abdominis. The rectus abdominis is the muscle that very fit people develop into the 6-pack ab look. Although it should really be a 10 pack as there are 5 vertical sections on each side. The 2 bottom sections are just above the pubic bone and usually not visible, hence, the 6 pack abs. The rectus abdominals function is to bend ones back forward (flexion). The main work of the abdominal muscles is to bend the spine forward when contracting concentrically. Society and culture Social and cultural perceptions of the outward appearance of the abdomen has varying significance around the world. Depending on the type of society, excess weight can be perceived as an indicator of wealth and prestige due to excess food, or as a sign of poor health due to lack of exercise. In many cultures, bare abdomens are distinctly sexualized and perceived similarly to breast cleavage. Exercise Being key elements of spinal support, and contributors to good posture, it is important to properly exercise the abdominal muscles together with the back muscles because when these are weak or overly tight they can suffer painful spasms and injuries. When properly exercised, abdominal muscles contribute to improved posture and balance, reduce the likelihood of back pain episodes, reduce the severity of back pain, protect against injury by responding efficiently to stresses, help avoid some back surgeries, and help with the healing of back problems, or after spine surgery. When strengthened, the abdominal muscles provide flexibility as well. The abdominal muscles can be worked by practicing disciplines of general body strength such as Pilates, yoga, Tai chi, and jogging. There are also specific routines which target each of these muscles. Clinical significance Abdominal obesity is a condition where abdominal fat or visceral fat, has built up excessively between the abdominal organs. This is associated with a higher risk of heart disease, asthma and type 2 diabetes. Abdominal trauma is an injury to the abdomen and can involve damage to the abdominal organs. There is an associated risk of severe blood loss and infection. Injury to the lower chest can cause injuries to the spleen and liver.A scaphoid abdomen is when the abdomen is sucked inwards. In a newborn, it may represent a diaphragmatic hernia. In general, it is indicative of malnutrition. Disease Many gastrointestinal diseases affect the abdominal organs. These include stomach disease, liver disease, pancreatic disease, gallbladder and bile duct disease; intestinal diseases include enteritis, coeliac disease, diverticulitis, and IBS. Examination Different medical procedures can be used to examine the organs of the gastrointestinal tract. These include endoscopy, colonoscopy, sigmoidoscopy, enteroscopy, oesophagogastroduodenoscopy and virtual colonoscopy. There are also a number of medical imaging techniques that can be used. Surface landmarks are important in the examination of the abdomen. Surface landmarks In the mid-line a slight furrow extends from the xiphoid process above to the pubic symphysis below, representing the linea alba in the abdominal wall. At about its midpoint sits the umbilicus or navel. The rectus abdominis on each side of the linea alba stands out in muscular people. The outline of these muscles is interrupted by three or more transverse depressions indicating the tendinous intersections. There is usually one about the xiphoid process, one at the navel, and one in between. It is the combination of the linea alba and the tendinous intersections which form the abdominal "six-pack" sought after by many people. The upper lateral limit of the abdomen is the subcostal margin (at or near the subcostal plane) formed by the cartilages of the false ribs (8, 9, 10) joining one another. The lower lateral limit is the anterior crest of the ilium and Pouparts ligament, which runs from the anterior superior spine of the ilium to the spine of the pubis. These lower limits are marked by visible grooves. Just above the pubic spines on either side are the external abdominal rings, which are openings in the muscular wall of the abdomen through which the spermatic cord emerges in the male, and through which an inguinal hernia may rupture. One method by which the location of the abdominal contents can be appreciated is to draw three horizontal and two vertical lines. Horizontal lines The highest of the former is the transpyloric line of C. Addison, which is situated halfway between the suprasternal notch and the top of the pubic symphysis, and often cuts the pyloric opening of the stomach an inch to the right of the mid-line. The hilum of each kidney is a little below it, while its left end approximately touches the lower limit of the spleen. It corresponds to the first lumbar vertebra behind. The second line is the subcostal line, drawn from the lowest point of the subcostal arch (tenth rib). It corresponds to the upper part of the third lumbar vertebra, and it is an inch or so above the umbilicus. It indicates roughly the transverse colon, the lower ends of the kidneys, and the upper limit of the transverse (3rd) part of the duodenum. The third line is called the intertubercular line, and runs across between the two rough tubercles, which can be felt on the outer lip of the crest of the ilium about two and a half inches (64 mm) from the anterior superior spine. This line corresponds to the body of the fifth lumbar vertebra, and passes through or just above the ileo-caecal valve, where the small intestine joins the large intestine. Vertical lines The two vertical or mid-Poupart lines are drawn from the point midway between the anterior superior spine and the pubic symphysis on each side, vertically upward to the costal margin. The right one is the most valuable, as the ileo-caecal valve is situated where it cuts the intertubercular line. The orifice of the appendix lies an inch lower, at McBurneys point. In its upper part, the vertical line meets the transpyloric line at the lower margin of the ribs, usually the ninth, and here the gallbladder is situated. The left mid-Poupart line corresponds in its upper three-quarters to the inner edge of the descending colon.The right subcostal margin corresponds to the lower limit of the liver, while the right nipple is about half an inch above its upper limit. Quadrants and regions The abdomen can be divided into quadrants or regions to describe the location of an organ or structure. Classically, quadrants are described as the left upper, left lower, right upper, and right lower. Quadrants are also often used in describing the site of an abdominal pain.The abdomen can also be divided into nine regions. These terms stem from "hypo" meaning "below" and "epi" means "above", while "chondron" means "cartilage" (in this case, the cartilage of the rib) and "gaster" means stomach. The reversal of "left" and "right" is intentional, because the anatomical designations reflect the patients own right and left.) The "right iliac fossa" (RIF) is a common site of pain and tenderness in patients who have appendicitis. The fossa is named for the underlying iliac fossa of the hip bone, and thus is somewhat imprecise. Most of the anatomical structures that will produce pain and tenderness in this region are not in fact in the concavity of the ileum. However, the term is in common usage. Other animals In arthropods the abdomen is built up of a series of upper plates known as tergites and lower plates known as sternites, the whole being held together by a tough yet stretchable membrane. The abdomen contains the insects digestive tract and reproductive organs, it consists of eleven segments in most orders of insects though the eleventh segment is absent in the adult of most higher orders. The number of these segments does vary from species to species with the number of segments visible reduced to only seven in the common honeybee. In the Collembola (Springtails) the abdomen has only six segments. The abdomen is sometimes highly modified. In Apocrita (bees, ants and wasps), the first segment of the abdomen is fused to the thorax and is called the propodeum. In ants the second segment forms the narrow petiole. Some ants have an additional postpetiole segment, and the remaining segments form the bulbous gaster. The petiole and gaster (abdominal segments 2 and onward) are collectively called the metasoma. Unlike other arthropods, insects possess no legs on the abdomen in adult form, though the Protura do have rudimentary leg-like appendages on the first three abdominal segments, and Archaeognatha possess small, articulated "styli" which are sometimes considered to be rudimentary appendages. Many larval insects including the Lepidoptera and the Symphyta (Sawflies) have fleshy appendages called prolegs on their abdominal segments (as well as their more familiar thoracic legs), which allow them to grip onto the edges of plant leaves as they walk around. In arachnids (spiders, scorpions and relatives), the term "abdomen" is used interchangeably with "opisthosoma" ("hind body"), which is the body section posterior to that bearing the legs and head (the prosoma or cephalothorax). See also Abdominal fat References External links "Abdomen" . Colliers New Encyclopedia. 1921.

You function as a medical dictionary. Offer comprehensive and accurate descriptions of medical terms, ensuring clarity and depth in your explanations.

I'm looking for a concise explanation of the medical term 'Median nerve.'

The median nerve is a nerve in humans and other animals in the upper limb. It is one of the five main nerves originating from the brachial plexus. The median nerve originates from the lateral and medial cords of the brachial plexus, and has contributions from ventral roots of C5-C7 (lateral cord) and C8 and T1 (medial cord).The median nerve is the only nerve that passes through the carpal tunnel. Carpal tunnel syndrome is the disability that results from the median nerve being pressed in the carpal tunnel. Structure The median nerve arises from the branches from lateral and medial cords of the brachial plexus, courses through the anterior part of arm, forearm, and hand, and terminates by supplying the muscles of the hand. Arm After receiving inputs from both the lateral and medial cords of the brachial plexus, the median nerve enters the arm from the axilla at the inferior margin of the teres major muscle. It then passes vertically down and courses lateral to the brachial artery between biceps brachii (above) and brachialis (below). At first, it is lateral to the artery and lies anterior to the shoulder joint; it then crosses anteriorly to run medial to the artery in the distal arm and into the cubital fossa. Inside the cubital fossa, the median nerve passes medial to the brachial artery. The median nerve gives off an articular branch to the elbow joint. A branch to pronator teres muscle arise from the median nerve immediately above the elbow joint. Forearm The median nerve continues in the cubital fossa medial to the brachial artery and passes between the two heads of the pronator teres, deep to the bicipital aponeurosis (aponeurosis of biceps) and superficial the brachialis muscle. It crosses the ulnar artery (branch of brachial artery) while being separated by the deep head of the pronator teres. It then travels between the flexor digitorum superficialis (above) and flexor digitorum profundus (below). The median nerve is accompanied by the median artery (a branch of anterior interosseous artery) during this course. Then, about 5 cm above the flexor retinaculum (wrist), it emerges between the flexor digitorum superficialis (medially) and the flexor carpi radialis (laterally) into the hand.The main trunk of the median nerve innervates the superficial and deep groups of the muscles in the anterior compartment of the forearm with the exception of flexor carpi ulnaris. The median nerve does this by giving off two branches as it courses through the forearm: Muscular branches are given off in the cubital fossa to supply flexor carpi radialis, palmaris longus, and flexor digitorum superficialis. The anterior interosseous branch is given off in the upper part of the forearm, courses with the anterior interosseous artery and innervates flexor pollicis longus and the lateral half of flexor digitorum profundus (the ulnar half is supplied by ulnar nerve, as is the flexor carpi ulnaris muscle). It ends with its innervation of pronator quadratus. In addition to its supply to muscles, this nerve also supplies the distal radioulnar joint and wrist joint.The median nerve also gives off sensory and other branches in the forearm. The palmar cutaneous branch of the median nerve arises at the distal part of the forearm. It supplies sensory innervation to the thenar eminence of the palm and the central palm. Articular branches are given to the elbow joint and proximal radioulnar joint. Vascular branches supply the radial and ulnar arteries. Meanwhile, a communicating branch is given to the ulnar nerve. Hand The median nerve enters the hand through the carpal tunnel, deep to the flexor retinaculum along with the tendons of flexor digitorum superficialis, flexor digitorum profundus, and flexor pollicis longus. From there, it is divided into recurrent muscular branch and digital cutaneous branch: The muscular branch (also known as recurrent branch) supplies the thenar muscles (opponens pollicis, abductor pollicis brevis, and superficial part of flexor pollicis brevis) Digital cutaneous to the proper palmar digital branch and the common palmar digital branch: The proper palmar digital branch gives out three digital branches to the lateral one and a half digits (two digital branches to the thumb, one digital branch to the lateral side of the index finger). The digital branch to the index finger also supplies the first lumbrical. The common palmar digital branch divides further into two branches. Both the medial and lateral branches supply the second and third interdigital clefts with adjoining index, middle, and lateral half of ring finger. The lateral branch also supplies the second lumbrical. Variation The naturally occurring anomalies of the median nerve are: Bifurcation of the median nerve typically occurs after the nerve exits the carpal tunnel; however, in a small percentage (5-10%) of individuals, the median nerve bifurcates more proximal in the carpal tunnel, wrist, or forearm. During gestation, a median artery that serves the hand retracts. However, in some individuals, the median artery does not retract and follows the course next to the median nerve into the hand. Martin-Gruber anastomoses can occur when branches of the median nerve cross-over in the forearm and merge with the ulnar nerve to innervate portions of the forehand. Riche-Cannieu anastomosis can occur when a connection exists between recurrent branch of the median nerve and deep branch of the ulnar nerve of the hand. Function The median nerve is the main nerve of the front of the forearm. It supplies the muscles of the front of the forearm and muscles of the thenar eminence, thus controlling the coarse movements of the hand. Therefore, it is also called "labourers nerve". Arm The median nerve has no voluntary motor or cutaneous function in the brachium. It gives vascular branches to the wall of the brachial artery. These vascular branches carry sympathetic fibers. Forearm It innervates all of the flexors in the forearm, except flexor carpi ulnaris and that part of flexor digitorum profundus that supplies the fourth and fifth digits. The latter two muscles are supplied by the ulnar nerve (specifically the muscular branches of ulnar nerve). The main portion of the median nerve supplies these muscles: Superficial group: Pronator teres Flexor carpi radialis Palmaris longusIntermediate group: Flexor digitorum superficialis muscleThe anterior interosseus branch of the median nerve supplies these muscles: Deep group: Flexor digitorum profundus (only the lateral half) Flexor pollicis longus Pronator quadratus Hand In the hand, the median nerve supplies motor innervation to the first and second lumbrical muscles. It also supplies the muscles of the thenar eminence by a recurrent thenar branch. The rest of the intrinsic muscles of the hand are supplied by the ulnar nerve. The median nerve innervates the skin of the palmar (volar) side of the index finger, thumb, middle finger, and half the ring finger, and the nail bed. The radial aspect of the palm is supplied by the palmar cutaneous branch of the median nerve, which leaves the nerve proximal to the wrist creases. This palmar cutaneous branch travels in a separate fascial groove adjacent to the flexor carpi radialis and then superficial to the flexor retinaculum. It is, therefore, spared in carpal tunnel syndrome. Clinical significance Injury Injury of median nerve at different levels causes different syndromes with varying motor and sensory deficits. At the shoulder Injury can occur at the brachial plexusAbove the elbow Common mechanism of injury: A supracondylar humerus fracture Motor deficit: Loss of pronation of forearm, weakness in flexion of the hand at the wrist, loss of flexion of radial half of digits and thumb, loss of abduction and opposition of thumb. Presence of an ape hand deformity when the hand is at rest, due to an hyperextension of index finger and thumb, and an adducted thumb Presence of benediction sign when attempting to form a fist, due to loss of flexion of radial half of digits Sensory deficit: Loss of sensation in lateral 3+1⁄2 digits including their nail beds, and the thenar areaAt the elbow Entrapment at the level of the elbow or the proximal forearm could be due to the pronator teres syndrome.Within the proximal forearm: Anterior interosseous syndrome Injury to the anterior interosseous branch in the forearm causes the anterior interosseous syndrome Common mechanisms: Tight cast, forearm bone fracture Motor deficit: Loss of pronation of forearm, loss of flexion of radial half of digits and thumb Sensory deficit: NoneAt the wrist Common mechanism: Wrist laceration Motor deficit: Weakness in flexion of radial half of digits and thumb, loss of abduction and opposition of thumb Presence of an ape hand deformity when the hand is at rest may be likely, due to an hyperextension of index finger and thumb, and an adducted thumb. Nevertheless, an ape hand deformity is not a requirement for a carpal tunnel syndrome diagnosis. Presence of a benediction sign when attempting to form a fist, due to weakness in flexion of radial half of digits Sensory deficit: Loss of sensation in lateral 3+1⁄2 digits including their nail beds, and the thenar areaWithin the wrist: Carpal tunnel syndrome Common mechanism: Carpal tunnel syndrome, an injury by compression in the carpal tunnel, without transection of the median nerve, due to overuse by activities such as keyboard typing and cooking Motor deficit: Weakness in flexion of radial half of digits and thumb, weakness in abduction and opposition of thumb Presence of an ape hand deformity or when attempting to form a fist, the benediction sign, due to compression of the median nerve, as opposed to complete median nerve palsy Sensory deficit: Numbness and tingling in lateral 3+1⁄2 digits including their nail beds, but excluding the thenar eminence which is supplied by the palmar cutaneous branch of the median nerve Unlike in wrist laceration, sensation still occurs in the area of the central palm. Sensation is not lost because the palmar cutaneous branch runs above the flexor retinaculum, and is not affected in compression in carpal tunnel syndrome. Additional images See also References This article incorporates text in the public domain from page 938 of the 20th edition of Grays Anatomy (1918) External links Median nerve at the Duke University Health Systems Orthopedics program Median+Nerve at the US National Library of Medicine Medical Subject Headings (MeSH) Hand kinesiology at the University of Kansas Medical Center Atlas image: hand_plexus at the University of Michigan Health System - "Axilla, dissection, anterior view"

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm not familiar with the medical term 'Lepromatous leprosy.' Could you provide some insights?

Lepromatous leprosy is a form of leprosy characterized by pale macules in the skin.: 346 It results from the failure of Th1 cell activation which is necessary to eradicate the mycobacteria (Th1 response is required to activate macrophages that engulf and contain the disease). In lepromatous leprosy, TH2 response is turned on, and because of reciprocal inhibition (IL-4; IL-10), the cell-mediated response (TH1) is depressed. Lepromatous leprosy, in contrast to the tuberculoid form of leprosy, is characterized by the absence of epithelioid cells in the lesions. In this form of leprosy Mycobacterium leprae are found in lesion in large numbers. This is the most unfavorable clinical variant of leprosy.This debilitating form of leprosy begins to spread causing the eyebrows to disappear and spongy tumor like swellings appear on the face and body. The disease attacks the internal organs, bones, joints and marrow of the body resulting in physical degeneration. The result is deformity with loss of feeling in the fingers and toes which eventually fall off. Contrary to popular belief, both forms of leprosy are curable, with the lepromatous form classically treated with antibiotics dapsone, rifampin and clofazimine for as long as 2–5 years, but if left untreated the person may die up to 20 or 30 years from its inception.Early detection of the disease is of utmost importance, since severe physical and neurological damage are irreversible even if cured (e.g. blindness, loss of digits/limbs/sensation). Early infection is characterized by a well demarcated, usually pale, skin lesion which has lost its hair, and there may be many of these lesions if the infection is more severe (most commonly found on the cooler parts of the body such as the elbows, knees, fingers, or scrotum, as the bacteria thrive in cooler environments). This early presentation is the same for both tuberculous and lepromatous forms of leprosy as they are a spectrum of the same disease (lepromatous being the more contagious and severe form in patients with impaired Th1 response). Disease progression is extremely slow, and signs of infection may not appear for years.Family members of those with the disease, and especially children, are most at risk. The disease is believed to be spread through respiratory droplets in close quarters like its relative Mycobacterium tuberculosis, and similarly requires extended exposure to an individual in most situations, so outsiders and healthcare workers are normally not infected (except with the most infective individuals such as those in the most progressed lepromatous forms, as those patients have the highest bacterial loads). See also Tuberculoid leprosy Diffuse leprosy of Lucio and Latapí References == External links ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I've come across the term 'Essential thrombocythemia' in a medical context, but I'm not sure what it means. Can you clarify?

Essential thrombocythemia (ET) is a rare chronic blood cancer (myeloproliferative neoplasm) characterised by the overproduction of platelets (thrombocytes) by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid leukemia or myelofibrosis. It is a type of myeloproliferative neoplasm (blood cancers) wherein the body makes too many white or red blood cells, or platelets). Signs and symptoms Most people with essential thrombocythemia are without symptoms at the time of diagnosis, which is usually made after noting an elevated platelet level on a routine complete blood count (CBC). The most common symptoms are bleeding (due to dysfunctional platelets), blood clots (e.g., deep vein thrombosis or pulmonary embolism), fatigue, headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities; the most common signs are increased white blood cell count, reduced red blood cell count, and an enlarged spleen. Cause In ET, megakaryocytes are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes are activated, which, along with the elevated platelet count, contributes to the likelihood of forming blood clots. The increased possibility of bleeding when the platelet count is over 1 million is due to von Willebrand factor (vWF) sequestration by the increased mass of platelets, leaving insufficient vWF for platelet adhesion. A mutation in the JAK2 kinase (V617F) is present in 40–50% of cases and is diagnostic if present. JAK2 is a member of the Janus kinase family.In 2013, two groups detected calreticulin mutations in a majority of JAK2-negative/MPL-negative patients with essential thrombocythemia and primary myelofibrosis, which makes CALR mutations the second most common in myeloproliferative neoplasms. All mutations (insertions or deletions) affected the last exon, generating a reading frame shift of the resulting protein, that creates a novel terminal peptide and causes a loss of endoplasmic reticulum KDEL retention signal. Diagnosis The following revised diagnostic criteria for essential thrombocythemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6. The criteria are as follows: A1. Platelet count > 400 × 103/µL for at least 2 months. A2. Acquired V617F JAK2 mutation present B1. No cause for a reactive thrombocytosis normal inflammatory indices B2. No evidence of iron deficiency stainable iron in the bone marrow or normal red cell mean corpuscular volume B3. No evidence of polycythemia vera hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores B4. No evidence of chronic myeloid leukemia But the Philadelphia chromosome may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially acute lymphocytic leukemia. B5. No evidence of myelofibrosis no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale) B6. No evidence of a myelodysplastic syndrome no significant dysplasia no cytogenetic abnormalities suggestive of myelodysplasia Treatment Indications Not all those affected will require treatment at presentation. People are usually split up into low and high risk for bleeding/blood clotting groups (based on their age, their medical history, their blood counts and their lifestyles), low risk individuals are usually treated with aspirin, whereas those at high risk are given hydroxycarbamide and/or other treatments that reduce platelet count (such as interferon-α and anagrelide). Agents Hydroxycarbamide, interferon-α and anagrelide can lower the platelet count. Low-dose aspirin is used to reduce the risk of blood clot formation unless the platelet count is very high, where there is a risk of bleeding from the disease, and hence this measure would be counter-productive as aspirin-use increases the risk of bleeding.The PT1 study compared hydroxyurea plus aspirin to anagrelide plus aspirin as initial therapy for ET. Hydroxyurea treated patients had a lower incidence of arterial thrombosis, lower incidence of severe bleeding and lower incidence of transformation to myelofibrosis, but the risk of venous thrombosis was higher with hydroxycarbamide than with anagrelide. It is unknown whether the results are applicable to all ET patients. In people with symptomatic ET and extremely high platelet counts (exceeding 1 million), plateletpheresis can be used to remove platelets from the blood to reduce the risk of thrombosis. Prognosis Essential thrombocythemia is sometimes described as a slowly progressive disorder with long asymptomatic periods punctuated by thrombotic or hemorrhagic events. However, well-documented medical regimens can reduce and control the number of platelets, which reduces the risk of these thrombotic or hemorrhagic events. The lifespan of a well-controlled ET person is well within the expected range for a person of similar age but without ET. ET is the myeloproliferative neoplasm least likely to progress to acute myeloid leukemia. Epidemiology The incidence of ET is 0.6-2.5/100,000 per year, the median age at onset is 65–70 years and it is more frequent in females than in males. The incidence in children is 0.09/100,000 per year. Pregnancy Hydroxycarbamide and anagrelide are contraindicated during pregnancy and nursing. Essential thrombocythemia can be linked with a three-fold increase in risk of miscarriage. Throughout pregnancy, close monitoring of the mother and fetus is recommended. Low-dose low molecular weight heparin (e.g. enoxaparin) may be used. For life-threatening complications, the platelet count can be reduced rapidly using plateletpheresis, a procedure that removes platelets from the blood and returns the remainder to the patient. References == External links ==

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

Could you provide a brief overview of 'Drospirenone/estetrol' in a medical context?

Drospirenone/estetrol, sold under the brand name Nextstellis among others, is a fixed-dose combination medication containing drospirenone, a progestin, and estetrol, an estrogen, which is used as a combined birth control pill for the prevention of pregnancy in women. It is taken by mouth.It was approved for medical use in Canada in March 2021, and in the United States in April 2021. Medical uses Drospirenone/estetrol is used as a combined birth control pill to prevent pregnancy in women. Side effects Estetrol-containing birth control pills, similarly to estradiol-containing birth control pills, may have a lower risk of venous thromboembolism (VTE) than ethinylestradiol-containing birth control pills based on studies of coagulation. However, it is likely that another decade will be required before post-marketing epidemiological studies of VTE incidence with these birth control pills are completed and able to confirm this. Pharmacology Pharmacodynamics Drospirenone/estetrol has a much lower impact on liver protein synthesis, including of sex hormone-binding globulin, angiotensinogen, and coagulation factors, than does ethinylestradiol/drospirenone. Society and culture Legal status Drospirenone/estetrol is approved for the use of hormonal contraception in the European Union, the United States, and Canada. Brand names Drospirenone/estetrol in sold under the brand names Nexstellis, Drovelis, and Lydisilka. See also Birth control pill formulations List of combined sex-hormonal preparations § Estrogens and progestogens References External links "Drospirenone". Drug Information Portal. U.S. National Library of Medicine. "Estetrol". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02817828 for "E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - EU/Russia Study" at ClinicalTrials.gov Clinical trial number NCT02817841 for "E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - United States/Canada Study" at ClinicalTrials.gov

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

Could you please explain the term 'Chemical burn' in simple language?

A chemical burn occurs when living tissue is exposed to a corrosive substance (such as a strong acid, base or oxidizer) or a cytotoxic agent (such as mustard gas, lewisite or arsine). Chemical burns follow standard burn classification and may cause extensive tissue damage. The main types of irritant and/or corrosive products are: acids, bases, oxidizers / reducing agents, solvents, and alkylants. Additionally, chemical burns can be caused by some types of cytotoxic chemical weapons, e.g., vesicants such as mustard gas and Lewisite, or urticants such as phosgene oxime. Chemical burns may: need no source of heat occur immediately on contact not be immediately evident or noticeable be extremely painful diffuse into tissue and damage cellular structures under skin without immediately apparent damage to skin surface Presentation The exact symptoms of a chemical burn depend on the chemical involved. Symptoms include itching, bleaching or darkening of skin, burning sensations, trouble breathing, coughing blood and/or tissue necrosis. Common sources of chemical burns include sulfuric acid (H2SO4), hydrochloric acid (HCl), sodium hydroxide (NaOH), lime (CaO), silver nitrate (AgNO3), and hydrogen peroxide (H2O2). Effects depend on the substance; hydrogen peroxide removes a bleached layer of skin, while nitric acid causes a characteristic color change to yellow in the skin, and silver nitrate produces noticeable black stains. Chemical burns may occur through direct contact on body surfaces, including skin and eyes, via inhalation, and/or by ingestion. Lipophilic substances that diffuse efficiently in human tissue, e.g., hydrofluoric acid, sulfur mustard, and dimethyl sulfate, may not react immediately, but instead produce the burns and inflammation hours after the contact. Chemical fabrication, mining, medicine, and related professional fields are examples of occupations where chemical burns may occur. Hydrofluoric acid leaches into the bloodstream, reacts with calcium and magnesium, and the resulting salts can cause cardiac arrest after eating through skin. Prevention In Belgium, the Conseil Supérieur de la Santé gives a scientific advisory report on public health policy. The Superior Health Council of Belgium provides an overview of products that are authorized in Belgium for consumer use and that contain caustic substances, as well as of the risks linked to exposure to these products. This report aims at suggesting protection measures for the consumers, and formulates recommendations that apply to the different stages of the chain, which begins with the formulation of the product, followed by its regulation, marketing, application, post-application and ends with its monitoring. Gallery See also Acid throwing References == External links ==

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Pituitary adenoma'?

Pituitary adenomas are benign tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%.Non-invasive and non-secreting pituitary adenomas are considered to be benign in the literal as well as the clinical sense; however a recent meta-analysis (Fernández-Balsells, et al. 2011) of available research has shown there are to date scant studies – of poor quality – to either support or refute this assumption. Adenomas exceeding 10 mm (0.39 in) in size are defined as macroadenomas, with those smaller than 10 mm (0.39 in) referred to as microadenomas. Most pituitary adenomas are microadenomas and have an estimated prevalence of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies). A majority of pituitary microadenomas often remain undiagnosed, and those that are diagnosed are often found as an incidental finding and are referred to as incidentalomas. Pituitary macroadenomas are the most common cause of hypopituitarism.While pituitary adenomas are common, affecting approximately one in 6 of the general population, clinically active pituitary adenomas that require surgical treatment are more rare, affecting approximately one in 1,000 of the general population. Signs and symptoms Physical Hormone secreting pituitary adenomas cause one of several forms of hyperpituitarism. The specifics depend on the type of hormone. Some tumors secrete more than one hormone, the most common combination being GH and prolactin, which present as unexpected bone growth and unexpected lactation (in both men and women).A patient with pituitary adenoma may present with visual field defects, classically bitemporal hemianopsia. It arises from the compression of the optic nerve by the tumor. The specific area of the visual pathway at which compression by these tumours occurs is at the optic chiasma. The anatomy of this structure causes pressure on it to produce a defect in the temporal visual field on both sides, a condition called bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia, if originating inferior to the optic chiasm the visual field defect will first appear as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also compress the abducens nerve, causing a lateral rectus palsy.Also, a pituitary adenoma can cause symptoms of increased intracranial pressure. Prolactinomas often start to give symptoms especially during pregnancy, when the increased hormone level estrogen can increase the tumors growth rate.Various types of headaches are common in patients with pituitary adenomas. The adenoma may be the prime causative factor behind the headache or may serve to exacerbate a headache caused by other factors. Amongst the types of headaches experienced are both chronic and episodic migraine, and more uncommonly various unilateral headaches; primary stabbing headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) - another type of stabbing headache characterized by short stabs of pain -, cluster headache, and hemicrania continua (HS).Compressive symptoms of pituitary adenomas (visual field deficits, decreased visual acuity, headaches) are more commonly seen with macroadenomas (which are greater than 10 mm in diameter) than with microadenomas (which are less than 10 mm in diameter).Non-secreting adenomas can go undetected for an extended time because no obvious abnormalities are seen; the gradual reduction in normal activities due to decreased production of hormones is rather less evident. For example, insufficient adrenocorticotropic hormone means that the adrenal glands will not produce sufficient cortisol, resulting in slow recovery from illness, inflammation, and chronic fatigue; insufficient growth hormone in children and adolescents leads to diminished stature but which can have many other explanations. Psychiatric Various psychiatric manifestations have been associated with pituitary disorders including pituitary adenomas. Psychiatric symptoms such as depression, anxiety apathy, emotional instability, easy irritability and hostility have been noted. Complications Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone (GH). Approximately 90–95% of acromegaly cases are caused by a pituitary adenoma and it most commonly affects middle aged adults, Acromegly can result in severe disfigurement, serious complicating conditions, and premature death if unchecked. The disease which is often also associated with gigantism, is difficult to diagnose in the early stages and is frequently missed for many years, until changes in external features, especially of the face, become noticeable with the median time from the development of initial symptoms to diagnosis being twelve years. Cushings syndrome is a hormonal disorder that causes hypercortisolism, which is elevated levels of cortisol in the blood. Cushings disease (CD) is the most frequent cause of Cushings syndrome, responsible for approximately 70% of cases. CD results when a pituitary adenoma causes excessive secretion of adrenocorticotropic hormone (ACTH) that stimulates the adrenal glands to produce excessive amounts of cortisol.Cushings disease may cause fatigue, weight gain, fatty deposits around the abdomen and lower back (truncal obesity) and face ("moon face"), stretch marks (striae) on the skin of the abdomen, thighs, breasts, and arms, hypertension, glucose intolerance, and various infections. In women, it may cause excessive growth of facial hair (hirsutism) and in men erectile dysfunction. Psychiatric manifestations may include depression, anxiety, easy irritability, and emotional instability. It may also result in various cognitive difficulties.Hyperpituitarism is a disease of the anterior lobe of the pituitary gland which is usually caused by a functional pituitary adenoma and results in hypersecretion of adenohypophyseal hormones such as growth hormone; prolactin; thyrotropin; luteinizing hormone; follicle-stimulating hormone; and adrenocorticotropic hormone. Pituitary apoplexy is a condition that occurs when pituitary adenomas suddenly hemorrhage internally, causing a rapid increase in size or when the tumor outgrows its blood supply which causes tissue necrosis and subsequent swelling of the dead tissue. Pituitary apoplexy often presents with visual loss and sudden onset headache and requires timely treatment often with corticosteroids and if necessary surgical intervention. Central diabetes insipidus is caused by diminished production of the antidiuretic hormone vasopressin that causes severe thirst and excessive production of very dilute urine (polyuria) which can lead to dehydration. Vasopressin is produced in the hypothalamus and is then transported down the pituitary stalk and stored in the posterior lobe of the pituitary gland which then secretes it into the bloodstream.As the pituitary gland is in close proximity to the brain, invasive adenomas may invade the dura mater, cranial bone, or sphenoid bone. Risk factors Multiple endocrine neoplasia Adenomas of the anterior pituitary gland are a major clinical feature of multiple endocrine neoplasia type 1 (MEN1), a rare inherited endocrine syndrome that affects 1 person in every 30,000. MEN causes various combinations of benign or malignant tumors in various glands in the endocrine system or may cause the glands to become enlarged without forming tumors. It often affects the parathyroid glands, pancreatic islet cells, and anterior lobe of the pituitary gland. MEN1 may also cause non-endocrine tumors such as facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas. Approximately 25 percent of patients with MEN1 develop pituitary adenomas. Carney complex Carney complex (CNC), also known as LAMB syndrome and NAME syndrome is an autosomal dominant condition comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity and is distinct from Carneys triad. Approximately 7% of all cardiac myxomas are associated with Carney complex. Patients with CNC develop growth hormone (GH)-producing pituitary tumors and in some instances these same tumors also secrete prolactin. There are however no isolated prolactinomas or any other type of pituitary tumor. In some patients with CNC, the pituitary gland is characterized by hyperplastic areas with the hyperplasia most likely preceding the formation of GH-producing adenomas. Familial isolated pituitary adenoma Familial isolated pituitary adenoma (FIPA) is a term that is used to identify a condition that displays an autosomal dominant inheritance and is characterised by the presence of two or more related patients affected by adenomas of the pituitary gland only, with no other associated symptoms that occur in multiple endocrine neoplasia type 1 (MEN-1), Carney complex and with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. FIPA was first described in a limited cohort of families by Albert Beckers group in Liège, Belgium; later FIPA was fully characterized in a multicenter international study of 64 families. FIPA families are divided into those that are homogenous and have the same type of pituitary adenoma in all the affected family members (e.g. only acromegaly, only prolactinoma, etc.), while heterogeneous FIPA families can have different pituitary adenomas in affected family members. Genetics of FIPA FIPA has two known genetic causes, mutations in the AH receptor-interacting protein (AIP) gene and duplications in chromosome Xq26.3 that include the GPR101 gene that also causes X-linked acrogigantism (X-LAG) syndrome. About 15-20% of FIPA families carry a germline AIP gene mutation or deletion, and the disease occurs as autosomal dominant with incomplete penetrance, meaning that about 20% of AIP mutation carriers will develop a pituitary adenoma. AIP mutation associated pituitary adenomas (either presenting as FIPA or as individual, non familial cases) are usually growth hormone-secreting (acromegaly) or prolactin-secreting (prolactinoma) adenomas that are large (macroadenomas) and often occur in children, adolescents and young adults. Daly and colleagues showed that acromegaly cases with AIP mutations occurred about 20 years before acromegaly cases without AIP mutations and these tumors are large and relatively treatment-resistant. Due to their young age at onset, AIP mutations are the most frequent genetic cause of pituitary gigantism (29% of cases).X-LAG is a rare syndrome of very early childhood onset pituitary tumors/hyperplasia that leads to growth hormone excess and severe overgrowth and pituitary gigantism. Three FIPA families with X-LAG have been reported to date all of which had transmission of a chromosome Xq26.3 duplication from affected mother to affected son. The disease characteristics of very young onset pituitary gigantism leads to severe overgrowth if not treated adequately; many of the tallest humans in history (e.g. Robert Pershing Wadlow; Sandy Allen, André Rousimoff (Andre the Giant), Zeng Jinlian) had a similar clinical history to patients with X-LAG syndrome. The tallest historical individual with a known genetic cause was Julius Koch (Geant Constantin) who was found to have X-LAG on genetic study of his skeleton. X-LAG has 100% penetrance so far (all affected with the Xq26.3 duplication have the disease and it affects predominantly females. Isolated non familial cases of X-LAG can either have a constitutional duplication of a chromosome Xq26.3 including GPR101, or mosaicism for the duplication (present in a minority of cells) in the case of isolated male patients. X-LAG causes about 10% of cases of pituitary gigantism. Mechanism The pituitary gland or hypophysis is often referred to as the "master gland" of the human body. Part of the hypothalamic-pituitary axis, it controls most of the bodys endocrine functions via the secretion of various hormones into the circulatory system. The pituitary gland is located below the brain in a depression (fossa) of the sphenoid bone known as the sella turcica. Although anatomically and functionally connected to the brain, the pituitary gland sits outside the blood–brain barrier. It is separated from the subarachnoid space by the diaphragma sella, therefore the arachnoid mater and thus cerebral spinal fluid cannot enter the sella turcica.The pituitary gland is divided into two lobes, the anterior lobe (which accounts for two thirds of the volume of the gland), and the posterior lobe (one third of the volume) separated by the pars intermedia.The posterior lobe (the neural lobe or neurohypophysis) of the pituitary gland is not, despite its name, a true gland. The posterior lobe contains axons of neurons that extend from the hypothalamus to which it is connected via the pituitary stalk. The hormones vasopressin and oxytocin, produced by the neurons of the supraoptic and paraventricular nuclei of the hypothalamus, are stored in the posterior lobe and released from axon endings (dendrites) within the lobe.The pituitary glands anterior lobe (adenohypophysis) is a true gland which produces and secretes six different hormones: thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and prolactin (PRL). Diagnosis Diagnosis of pituitary adenoma can be made, or at least suspected, by a constellation of related symptoms presented above.The differential diagnosis includes pituitary tuberculoma, especially in developing countries and in immumocompromised patients. The diagnosis is confirmed by testing hormone levels, and by radiographic imaging of the pituitary (for example, by CT scan or MRI). Classification Unlike tumors of the posterior Pituitary, Pituitary adenomas are classified as endocrine tumors (not brain tumors). Pituitary adenomas are classified based upon anatomical, histological and functional criteria. Anatomically pituitary tumors are classified by their size based on radiological findings; either microadenomas (less than <10 mm) or macroadenomas (equal or greater than ≥10 mm).Classification based on radioanatomical findings places adenomas into 1 of 4 grades (I–IV):Stage I: microadenomas (<1 cm) without sella expansion.Stage II: macroadenomas (≥1 cm) and may extend above the sella.Stage III: macroadenomas with enlargement and invasion of the floor or suprasellar extension.Stage IV: destruction of the sella.Histological classification utilizes an immunohistological characterization of the tumors in terms of their hormone production. Historically they were classed as either basophilic, acidophilic, or chromophobic on the basis of whether or not they took up the tinctorial stains hematoxylin and eosin. This classification has fallen into disuse, in favor of a classification based on what type of hormone is secreted by the tumor. Approximately 20–25% of adenomas do not secrete any readily identifiable active hormones (non-functioning tumors) yet they are still sometimes referred to as chromophobic. Functional classification is based upon the tumors endocrine activity as determined by serum hormone levels and pituitary tissue cellular hormone secretion detected via immunohistochemical staining. The "Percentage of hormone production cases" values are the fractions of adenomas producing each related hormone of each tumor type as compared to all cases of pituitary tumors, and does not directly correlate to the percentages of each tumor type because of smaller or greater incidences of absence of secretion of the expected hormone. Thus, non secretive adenomas may be either null cell adenomas or a more specific adenoma that, however, remains non-secretive. Any type of pituitary adenocarcinoma listed in the table below may cause compressive symptoms due to local expansion in addition to the systemic effects of secreted hormones listed in the pathology column. Null cell adenomas by definition do not secrete hormones, but they commonly cause compressive effects on the pituitary stalk (stalk effect). This leads to decreased levels of dopamine from the hypothalamus reaching the anterior pituitary gland. Dopamine exerts an inhibitory effect on prolactin secretion. With the absence of this inhibitory effect, prolactin levels increase and are often increased in null cell adenomas. This leads to symptoms of hypogonadism. Pituitary incidentalomas Pituitary incidentalomas are pituitary tumors that are characterized as an incidental finding. They are often discovered by computed tomography (CT) or magnetic resonance imaging (MRI), performed in the evaluation of unrelated medical conditions such as suspected head trauma, in cancer staging or in the evaluation of nonspecific symptoms such as dizziness and headache. It is not uncommon for them to be discovered at autopsy. In a meta-analysis, adenomas were found in an average of 16.7% in postmortem studies, with most being microadenomas (<10mm); macrodenomas accounted for only 0.16% to 0.2% of the decedents. While non-secreting, noninvasive pituitary microadenomas are generally considered to be literally as well as clinically benign, there are to date scant studies of low quality to support this assertion.It has been recommended in the current Clinical Practice Guidelines (2011) by the Endocrine Society - a professional, international medical organization in the field of endocrinology and metabolism – that all patients with pituitary incidentalomas undergo a complete medical history and physical examination, laboratory evaluations to screen for hormone hypersecretion and for hypopituitarism. If the lesion is in close proximity to the optic nerves or optic chiasm, a visual field examination should be performed. For those with incidentalomas which do not require surgical removal, follow up clinical assessments and neuroimaging should be performed as well follow-up visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm and follow-up endocrine testing for macroincidentalomas. Ectopic pituitary adenoma An ectopic (occurring in an abnormal place) pituitary adenoma is a rare type of tumor which occurs outside of the sella turcica, most often in the sphenoid sinus, suprasellar region, nasopharynx and the cavernous sinuses. Metastases to the pituitary gland Carcinomas that metastasize into the pituitary gland are uncommon and typically seen in the elderly, with lung and breast cancers being the most prevalent, In breast cancer patients, metastases to the pituitary gland occur in approximately 6-8% of cases.Symptomatic pituitary metastases account for only 7% of reported cases. In those who are symptomatic Diabetes insipidus often occurs with rates approximately 29–71%. Other commonly reported symptoms include anterior pituitary dysfunction, visual field defects, headache/pain, and ophthalmoplegia. Treatment Treatment options depend on the type of tumor and on its size: Prolactinomas are most often treated with cabergoline or bromocriptine (both dopamine agonists), which decrease tumor size as well as alleviates symptoms, followed by serial imaging to detect any increase in size. Treatment, where the tumor is large, can be with radiation therapy, proton therapy or surgery, and patients generally respond well. Unlike prolactinomas, thyrotrophic adenomas characteristically respond poorly to dopamine agonist treatment. Somatotrophic adenomas respond to octreotide or lanreotide, which are long-acting somatostatin analogs. These somatostatin receptor analogs inhibit secretion of growth hormone. They were found to be about 50–55% effective in reducing tumor mass and reducing growth hormone and insulin like growth factor 1 (IGF-1) levels in studies. The growth hormone receptor antagonist pegvisomant is also used in the treatment of somatotrophic adenomas. Pegvisomant blocks the action of growth hormone. It can either be used as monotherapy or combined with a somatostatin analog. Surgery is a common treatment for pituitary tumors. The normal approach is trans-sphenoidal adenectomy, which usually can remove the tumor without affecting the brain or optic nerves. Radiation is also used to treat pituitary adenomas. Examples include external beam or proton beam radiation therapy or stereotactic radiosurgery. External radiation of pituitary adenomas can arrest tumor growth for several years but pituitary failure develops within 10 years in most patients necessitating lifelong hormone replacement. Radiation therapy for pituitary adenomas is associated with a 4 fold increase in mortality due to cerebrovascular disease. See also Pituitary disease References External links Cancer.gov: pituitary tumors

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

Could you please explain the term 'Thymoma' in simple language?

A thymoma is a tumor originating from the epithelial cells of the thymus that is considered a rare malignancy. Thymomas are frequently associated with neuromuscular disorders such as myasthenia gravis; thymoma is found in 20% of patients with myasthenia gravis. Once diagnosed, thymomas may be removed surgically. In the rare case of a malignant tumor, chemotherapy may be used. Signs and symptoms A third of all people with a thymoma have symptoms caused by compression of the surrounding organs by an expansive mass. These problems may take the form of superior vena cava syndrome, dysphagia (difficulty swallowing), cough, or chest pain.One-third of patients have their tumors discovered because they have an associated autoimmune disorder. As mentioned earlier, the most common of those conditions is myasthenia gravis (MG); 10–15% of patients with MG have a thymoma and, conversely, 30–45% of patients with thymomas have MG. Additional associated autoimmune conditions include thymoma-associated multiorgan autoimmunity, pure red cell aplasia and Good syndrome (thymoma with combined immunodeficiency and hypogammaglobulinemia). Other reported disease associations are with acute pericarditis, agranulocytosis, alopecia areata, ulcerative colitis, Cushings disease, hemolytic anemia, limbic encephalopathy, myocarditis, nephrotic syndrome, panhypopituitarism, pernicious anemia, polymyositis, rheumatoid arthritis, sarcoidosis, scleroderma, sensorimotor radiculopathy, stiff person syndrome, systemic lupus erythematosus and thyroiditis.One-third to one-half of all persons with thymoma have no symptoms at all, and the mass is identified on a chest X-ray or CT/CAT scan performed for an unrelated problem. Pathology Thymoma originates from the epithelial cell population in the thymus, and several microscopic subtypes are now recognized. There are three principal histological types of thymoma, depending on the appearance of the cells by microscopy: Type A if the epithelial cells have an oval or fusiform shape (less lymphocyte count); Type B if they have an epithelioid shape (Type B has three subtypes: B1 (lymphocyte-rich), B2 (cortical) and B3 (epithelial).); Type AB if the tumor contains a combination of both cell types.Thymic cortical epithelial cells have abundant cytoplasm, vesicular nucleus with finely divided chromatin and small nucleoli and cytoplasmic filaments contact adjacent cells. Thymic medullary epithelial cells in contrast are spindle shaped with oval dense nucleus and scant cytoplasm thymoma if recapitulates cortical cell features more, is thought to be less benign. Diagnosis When a thymoma is suspected, a CT/CAT scan is generally performed to estimate the size and extent of the tumor, and the lesion is sampled with a CT-guided needle biopsy. Increased vascular enhancement on CT scans can be indicative of malignancy, as can be pleural deposits. Limited biopsies are associated with a very small risk of pneumomediastinum or mediastinitis and an even-lower risk of damaging the heart or large blood vessels. Sometimes thymoma metastasize for instance to the abdomen.The diagnosis is made via histologic examination by a pathologist, after obtaining a tissue sample of the mass. Final tumor classification and staging is accomplished pathologically after formal surgical removal of the thymic tumor. Selected laboratory tests can be used to look for associated problems or possible tumor spread. These include: full blood count, protein electrophoresis, antibodies to the acetylcholine receptor (indicative of myasthenia), electrolytes, liver enzymes and renal function. Staging The Masaoka Staging System is used widely and is based on the anatomic extent of disease at the time of surgery: I: Completely encapsulated IIA: Microscopic invasion through the capsule into surrounding fatty tissue IIB: Macroscopic invasion into capsule III: Macroscopic invasion into adjacent organs IVA: Pleural or pericardial implants IVB: Lymphogenous or hematogenous metastasis to distant (extrathoracic) sites Treatment Surgery is the mainstay of treatment for thymoma. If the tumor is apparently invasive and large, preoperative (neoadjuvant) chemotherapy and/or radiotherapy may be used to decrease the size and improve resectability, before surgery is attempted. When the tumor is an early stage (Masaoka I through IIB), no further therapy is necessary. Removal of the thymus in adults does not appear to induce immune deficiency. In children, however, postoperative immunity may be abnormal and vaccinations for several infectious agents are recommended. Invasive thymomas may require additional treatment with radiotherapy and chemotherapy (cyclophosphamide, doxorubicin and cisplatin).. Recurrences of thymoma are described in 10-30% of cases up to 10 years after surgical resection, and in the majority of cases also pleural recurrences can be removed. Recently, surgical removal of pleural recurrences can be followed by hyperthermic intrathoracic perfusion chemotherapy or intrathoracic hyperthermic perfused chemotherapy (ITH). Prognosis Prognosis is much worse for stage III or IV thymomas as compared with stage I and II tumors. Invasive thymomas uncommonly can also metastasize, generally to pleura, bones, liver or brain in approximately 7% of cases. A study found that slightly over 40% of observed patients with stage III and IV tumors survived for at least 10 years after diagnosis. The median age of these patients at the time of thymoma diagnosis was 57 years. Patients who have undergone thymectomy for thymoma should be warned of possible severe side effects after yellow fever vaccination. This is probably caused by inadequate T-cell response to live attenuated yellow fever vaccine. Deaths have been reported. Epidemiology Men and women are equally affected by thymomas. The typical age at diagnosis is 30–40, although cases have been described in every age group, including children. Gallery See also Mediastinal tumor References == External links ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

I'm trying to understand 'Browns syndrome' within a medical context. Could you shed some light on it?

Browns syndrome is a rare form of strabismus characterized by limited elevation of the affected eye. The disorder may be congenital (existing at or before birth), or acquired. Brown syndrome is caused by a malfunction of the superior oblique muscle, causing the eye to have difficulty moving up, particularly during adduction (when eye turns towards the nose). Harold W. Brown first described the disorder in 1950 and initially named it the "superior oblique tendon sheath syndrome". Presentation A simple definition of the syndrome is "limited elevation in adduction from mechanical causes around the superior oblique". This definition indicates that when the head is upright, the eye is restricted in movement due to problems with muscles and tendons that surround the eye.Harold W. Brown characterized the syndrome in many ways such as: Limited elevation in the eye when head is straight up Eyes point out in a straight up gaze (divergence in up gaze) Widening of the eyelids in the affected eye on adduction Head tilts backwards (compensatory chin elevation to avoid double vision) Near normal elevation in abductionHe concluded that all of these features of Brown syndrome were due to the shortening or tightening of the anterior superior oblique tendon. Because this syndrome can be acquired or occur at random and has spontaneous resolution, Brown hypothesized one major truth for this disorder — that the short tendon sheath was due to a complete separation, congenital paresis, of the ipsilateral (on the same side) inferior oblique muscle and secondary to a permanent shortening.After further research, he redefined the sheath syndrome into the following divisions: true sheath syndrome, which categorized only the cases that had a congenital short anterior sheath of the superior oblique tendon, and simulated sheath syndrome, which characterized all cases in which the clinical features of a sheath syndrome caused by something different other than a congenital short anterior sheath of the tendon. The clinical features of the two categories are correct but true sheath syndrome is always congenital. However, in 1970 it was discovered that a tight sheath tendon was not the cause of Browns Syndrome. The real cause was a tight or short superior oblique tendon; studies have confirmed this and have labeled the tendon inelastic. Causes Browns syndrome can be divided in two categories based on the restriction of movement on the eye itself and how it affects the eye excluding the movement: Congenital (present at birth) Browns syndrome results from structural anomalies other than a short tendon sheath but other fibrous adhesions may be present around the trochlear area. Acquired cases arise from trauma, surgery, sinusitis and inflammation of the superior oblique tendon sheath in rheumatoid arthritis. Orbital floor fractures may trap the orbital tissue in such a way as to simulate Browns syndrome. Intermittent forms of vertical retraction syndrome have been associated with click, which occurs as the restriction is released (superior oblique click syndrome). Diagnosis Diagnosis of Browns syndrome usually happens during a routine ophthalmologic appointment. Treatments If binocular vision is present and head position is correct, treatment is not obligatory. Treatment is required for: visual symptoms, strabismus, or incorrect head position.Acquired cases that have active inflammation of the superior oblique tendon may benefit from local corticosteroid injections in the region of the trochlea. The goal of surgery is to restore free ocular rotations. Various surgical techniques have been used: Harold Brown advocated that the superior oblique tendon be stripped. A procedure named sheathotomy. The results of such a procedure are frequently unsatisfactory because of reformation of scar tissue. Tenotomy of the superior oblique tendon (with or without a tendon spacer) has also been advocated. This has the disadvantage that it frequently produces a superior oblique paresis. Weakening of the inferior oblique muscle of the affected eye may be needed to compensate for iatrogenic fourth nerve palsy.During surgery, a traction test is repeated until the eye rotations are free and the eye is anchored in an elevated adducted position for about two weeks after the surgery. This maneuver is intended to prevent the reformation of scar tissue in the same places. Normalization of head position may occur but restoration of full motility is seldom achieved. A second procedure may be required. Epidemiology In Browns original series there was a 3:2 predominance of women to men and nearly twice as many cases involved the right eye as the left. 10% of cases showed bilaterality. Familial occurrence of Browns syndrome has been reported. See also Strabismus Strabismus surgery Pediatric ophthalmology Duane syndrome References == External links ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'd like to learn more about the medical term 'Sacroiliitis.' Can you provide some details?

Sacroiliitis is inflammation within the sacroiliac joint. It is a feature of spondyloarthropathies, such as axial spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis, reactive arthritis or arthritis related to inflammatory bowel diseases, including ulcerative colitis or Crohns disease. It is also the most common presentation of arthritis from brucellosis. Symptoms and signs People suffering from sacroiliitis can often experience symptoms in a number of different ways, however it is commonly related to the amount of pressure that is put onto the sacroiliac joint. Sacroiliitis pain is typically axial, meaning that the location of the condition is also where the pain is occurring. Symptoms commonly include prolonged, inflammatory pain in the lower back region, hips or buttocks.However, in more severe cases, pain can become more radicular and manifest itself in seemingly unrelated areas of the body including the legs, groin and feet.Symptoms are typically aggravated by: Transitioning from sitting to standing Walking or standing for extended periods of time Running Climbing stairs Taking long strides Rolling over in bed Bearing more weight on one leg Cause Sacroiliitis is a condition caused by inflammation within the sacroiliac joint. This joint is located where the base of the spine, known as the sacrum, and the pelvis, known as the ilium, intersect. "Itis" is a Latin term denoting inflammation.Since sacroiliitis can describe any type of inflammation found within the sacroiliac joint, there can be a number of issues that cause it. These include: Degenerative arthritis, or osteoarthritis of the spine, can cause degeneration within the sacroiliac joints and lead to inflammation and joint pain. Any form of spondyloarthropathies, which includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis or arthritis related to inflammatory bowel diseases, including ulcerative colitis or Crohns disease. Pregnancy can cause inflammation as a result of the widening and stretching of the sacroiliac joints to prepare for childbirth. Additionally, the added weight carried during childbearing can put an extra amount of stress on the SI joints, leading to abnormal wear. Traumatic injury such as a fall or car crash that affects the lower back, hips, buttocks or legs. Though rare, infection within the sacroiliac joints or another part of the body, such as a urinary tract infection, can cause inflammation. Diagnosis Sacroiliitis can be somewhat difficult to diagnose because the symptoms it manifests can also be caused by other, more common, conditions. If a physician suspects sacroiliitis, they will typically begin their diagnosis by performing a physical exam. Since the condition is axial, they can often pinpoint the affected joint by putting pressure on different places within the legs, hips, spine and buttocks. They may also ask a patient to perform some stretches that will put gentle stress on the sacroiliac joints.X-rays, MRIs and other medical imaging tests can be used to show signs of inflammation and damage within the SI joints. Typically, a spine specialist will order a medical imaging test if they suspect ankylosing spondylitis or another form of arthritis to be the primary cause of inflammation and pain. Treatment Treatment of sacroiliitis can vary depending on the severity of the condition and the amount of pain the patient is currently experiencing. However, it typically falls into one of two categories non-surgical and surgical: Non-surgical In most cases sacroiliitis can be treated without surgery. Often patients will find relief through a combination of rest, heat / ice therapy, physical therapy and anti-inflammatory medication, like ibuprofen. Together these simple treatments help reduce inflammation in the affected SI joints.For more severe forms of sacroiliitis, sacroiliac joint injections might be recommended to help combat symptoms. If chosen, a physician will inject a numbing agent, usually lidocaine, and a steroid containing powerful anti-inflammatory medication into the joint using fluoroscopic guidance. These steroid injections can be delivered up to three or four times a year and should be accompanied with physical therapy to help rehabilitate the affected joint. Surgical Surgery is often the last resort when dealing with sacroiliitis and is rarely required. However, it may be a viable option for patients who are suffering from severe pain that is unresponsive to nonsurgical treatments and is significantly impacting their quality of life. In these cases, a minimally invasive procedure known as Sacroiliac Joint Fusion can effectively stabilize the joint and increase its load-bearing capacity by fusing it together. See also Sacroiliac joint dysfunction Surgery for the dysfunctional sacroiliac joint References == External links ==

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I'm looking for a concise explanation of the medical term 'Craniopagus twins.'

Craniopagus twins are conjoined twins that are fused at the cranium. The union may occur on any portion of the cranium, but does not primarily involve either the face or the foramen magnum; their brains are usually separate, but they may share some brain tissue. Conjoined twins are genetically identical and always share the same sex. The thorax and abdomen are separate and each twin has its own umbilicus and umbilical cord.The condition is extremely rare, with an incidence of approximately 1 in 2.5 million live births. An estimated 50 craniopagus twins born around the world every year as of 2021, with only 15 twins surviving beyond the first 30 days of life. Relatively few craniopagus twins survive the perinatal period; approximately 40% of conjoined twins are stillborn and an additional 33% die within the immediate perinatal period, usually from organ abnormalities and failure.However, 25% of craniopagus twins survive and may be considered for a surgical separation; several such attempts occur yearly worldwide. Advances in neuroimaging, neuroanesthesia, and neurosurgery have proven that a successful outcome is possible. Among all conjoined twins, craniopagus twins account for a mere 2% to 6%. Classification The first classification system was developed by OConnell in 1976, where craniopagus twins were classified as total and partial. In the former, twins shared an "extensive surface area with widely connected cranial cavities", while in the latter, only a "limited, superficial surface area" was connected.In 2006, Stone and Goodrich came up with a more nuanced classification system, which is the "most commonly used" system. Partial CPT was defined as "lacking substantial shared dural venous sinuses", whereas total CPT "share a large portion of their dural venous sinuses and present with pronounced brain compression, which leads to distortion within the cranium". Total Total craniopagus twins share a large portion of dural venous sinuses and present with pronounced brain compression, leading to distortion within the cranium. Stone and Goodrich also defined two main subtypes, based on whether the long-axis angle between the twins was angular or vertical. The angular subtype has a higher rate of comorbidities than the vertical subtype.Vertical craniopagus calvaria is continuous and is further subdivided on the basis of intertwin axial facial rotation: Type 1: both children face in the same general directional axis so that the angle between twins is less than 40 degrees. These twins show relatively symmetric superior bi-parietal or vertex compressional flattening. Type 2: both children face opposite directions so that the deformity shows an axial rotation between 140 and 180 degrees. Type 3: in this variety axial rotation is intermediate between the first two types with a rotation of being between 40 and 140.Another classification system divides total craniopagus twins into four categories: Frontal: twins are facing each other with the axis of the bodies forming an acute angle Temporoparietal: joined immediately above the external auditory meatus Occipital: twins are connected in the occipital lobe causing the twins to face away from each other Parietal: twins fuse at the vertex with the axis of the twins forming an obtuse angle; this leads to a situation where the twins share the most veins, lobes, and neural circuitry and thus is often described as one brain shared by two individuals Having this kind of juncture means that there would be one common continuous cranium housing four cerebral hemispheres. An incomplete dural septum typically separates the flattened cerebral hemispheres. In total vertical craniopagus, the major cerebral arterial supply is usually confined to each respective twin and in some cases conjoined brain tissue may contain a larger artery. Within this category there are three smaller subdivisions that basically outline the different rotational symmetry of the junction. Partial Stone and Goodrich define partial craniopagus twins as lacking substantial shared dural venous sinuses, with limited surface area involvement, with either intact crania or cranial defects. It is less common than total craniopagus twins. In partial craniopagus twins, the unions are usually frontal and less commonly occipital and vertical. Angular frontal junctions occur when the two twins are joined at any part of the forehead. Occipital twins are joined at the occipital lobe in the back of the head and vertical are joined on the top of the head and usually face opposite directions. The junctional diameter is often smaller in partial forms and occasionally an incomplete layer of bone may be present between the twins. Each child maintains independent calvarial convexities except at the common area of skull junction. The dura of both children may be intact or deficient and cortical gyri may interdigitate. Additionally, shared dural venous sinuses is usually absent, or, if it is present, negligible. These twins usually undergo successful separation and both twins may live to lead normal lives. Gestation and embryology The exact nature of how conjoined twins develop in utero remains unclear. Embryologists have traditionally attributed identical twinning as "splitting or fission" of either the inner cell mass of pleuripotential cells or early embryonic disc at 13–14 days of gestation just before the primitive streak. Some theorists suggested that conjoined twins develop as a result of the failed fusion of a single fertilized ovum. However a new hypothesis suggests that cranial fusion occurs between two separate embryos before the end of the 4th week of gestation. This can happen because the cranial neuropore is still open, which is responsible for the ultimate fusion and formation of the brain stem and central nervous system. Furthermore, this secondary fusion of embryonic discs could implicate that intact skin will not fuse to other intact skin, including the ectoderm of the embryo. This means that two embryonic discs could only unite in locations where the ectoderm is absent. Moreover, the fusion occurs from neural folds of two separate, dorsally oriented embryonic discs, and the union can occur only after the ectoderm is disrupted to allow the neural and surface ectodermal layers to separate from each other. The union in craniopagus twins may happen at any portion of the calvarium. The juncture can involve either the entire diameter of the head or any portion of the head and can be positioned at a multitude of rotational angles. In fact, craniopagus twins are rarely found in a symmetrical union. Apart from this, the vertebral axes may have a straight line. Despite this, the angle of the vertebrae is the ultimate dictator in how the individuals heads actually face. The majority of twins face either the same way or the exact opposite direction. Medical procedures Diagnosis Conjoined twins, including craniopagus twins, can be diagnosed using standard ultrasound procedures during a pregnancy. In part because treatment of conjoined twins varies largely, many parents make the decision to terminate pregnancy due to the prognosis and quality-of -life issues. If the parents choose to continue the pregnancy, mother and babies will be closely monitored. In almost all cases, a C-section delivery is planned, often two to three weeks before the due date. Separation surgeries After the twins are born, parents and doctors decide whether or not separation surgery is possible. The doctors also must consider the possibility of reconstructive surgery and the social and learning issues the twins may have to face after they are separated. Due to advances in neuroimaging, neuroanesthesia, and neurosurgical techniques, successful separation operations have become more common. Physical traits like joined brain tissue, shared arteries and veins, as well as defects in the skull and dura mater complicate a separation operation.Neuroimaging especially plays an important role because it is imperative in surgical planning to understand the shared vascular anatomy—including the brain parenchyma, calvaria, and dura mater—because separating shared vessels can lead to thrombosis, air embolism, cerebral infarction, and hemorrhage. Technologies such as CT scans, MRIs, and angiography are used to map the shared vascular structures. Cases Emilie and Elisabeth Stoll were born on January 17, 1912. Their parents exhibited them until their death in July 1912. Their cause of death is unknown, but they were probably weakened by the stress of travelling and exhibition. Rodney and Roger Brodie were born in Rock Island, Illinois, in 1951. In December 1952 a medical team led by neurosurgeon Oscar Sugar attempted to separate the 15-month old twins in a surgery that lasted 12 hours. During surgery, the doctors discovered that the twins shared the superior sagittal sinus, the canal that drains blood from the brain to the heart. This vessel was retained by Rodney Brodie. Both twins survived the surgery, although Roger did not regain consciousness and died 34 days later. Rodney recovered but suffered neurological damage; because his skull was never closed, he wore a helmet until his death at age 11. This was the first case where craniopagual twins were separated and one survived. Lotti and Rosemarie Knaack, who were born in Germany in 1951, were separated at age 6, with Lotti dying in surgery. Rosemarie survived until 2008. Lori and George Schappell, born in 1961, are believed to be the longest-surviving craniopagus twins still living. Ladan and Laleh Bijani, who were born in Iran, were separated in 2003 at age 29, only to die 90 minutes apart after surgery. Ahmed and Mohamed Ibrahim, who were born in Egypt, were successfully separated in Dallas, Texas, in October 2001, when they were 28 months old. Lea and Tabea Block, who were born in Germany in 2003, were separated in September 2004 at Johns Hopkins Hospital in Baltimore, Maryland. Tabea died of cardiac arrest an hour after separation. Anastasia and Tatiana Dogaru were born in 2004 with the crown of Tatianas head joined to the back of Anastasias. Doctors determined in 2007 that they could not be separated. Krista and Tatiana Hogan, born on October 25, 2006. After a series of tests doctors also determined these twins could also not be separated. Joseph and Luka Banda from Zambia, born in 1997, were separated successfully the same year in South Africa by a team of surgeons led by Ben Carson. Trishna and Krishna from Bangladesh born in December 2006, joined on the tops of their skulls and sharing a small amount of brain tissue. In 2009, they were separated in Melbourne, Australia. Ganga and Jamuna Shreshta, born in Kathmandu, Nepal in 2000, were successfully separated by Dr. Chumpon Chan and his team from the Singapore General Hospital in 2001 Rital and Ritaj Gaboura of Sudan, were separated at 11 months old in 2011 at the Great Ormond Street Hospital in London. As of 2019 they lived in Ireland. Jadon and Anias McDonald were separated at 13 months old in 2016 in a crowdfunded operation costing $2.5million (USD) at Montefiore Hospital in New York. Maria Ysadora and Maria Ysabelle, born in July 2016, were successfully separated on October 27, 2018, after a five-step surgery in São Paulo, Brazil by a multidisciplinary team of neurosurgeons and plastic surgeons led by Helio Machado and James Tait Goodrich. Safa and Marwa Bibi, born in Peshawar, Pakistan, on January 7, 2017, were separated in February 2019 during the third of three surgeries. Erin and Abby Delaney, born on July 24, 2016 in North Carolina, were successfully separated by a team led by Dr. Jesse Taylor and Dr. Gregory Heuer at the Childrens Hospital of Philadelphia on June 6, 2017. Jaga and Kalia, twins from Odisha, India, were separated successfully in September 2017 at All India Institutes of Medical Sciences in New Delhi and kept at SCB Medical College for monitoring. Kalia died on 25 November 2020 from cardiac arrest while Jaga continues to live. Rabeya and Rukaya Islam, born in Pabna, Bangladesh in July 2016, were successfully separated after a 33-hour surgery in Dhaka, Bangladesh, by a medical team from a Hungarian nonprofit called the Action for Defenseless People Foundation led by renowned neurosurgeon András Csókay. Two unnamed year-old twins conjoined at the back of their heads were separated successfully in a surgery performed by Dr. Mickey Gideon at the Soroka Medical Center in Beersheba, Israel, in September 2021. Bernado and Arthur Lima, three-year-old twins from Roraima, Brazil, were separated by a team led by Owase Jeelani in a Rio de Janeiro hospital. Seven surgeries were needed, the last of which alone took 27 hours. The operation was particularly notable in that Jeelani received assistance from Great Ormond Street Hospital in London via the use of virtual reality, as well as the twins being the oldest craniopagus twins to be separated. Tatiana and Krista Throughout history, the fascination about craniopagus twins has continually increased as neurobiology and the field of neuroscience has become more interesting to the public. In 2011, The New York Times Magazine covered a story of two craniopagus twin girls who share a brain and seem to show all different kinds of physiological and emotional responses due to their condition. Though Krista and Tatiana Hogan share a brain, the two girls showed distinct personalities and behavior. One example was when Krista started drinking her juice Tatiana felt it physically going through her body. In any other set of twins the natural conclusion about the two events would be that Kristas drinking and Tatianas reaction would be coincidental. But because Krista and Tatiana are connected at their heads, whatever the girls do they do it together. In this case, brain images revealed that there was an attenuated line stretching between the two brains and forming a "thalamic bridge", a bridge connecting the two thalami. Knowing that the thalamus acts as a major control panel within the body, it is believed that the girls share part of this control panel and so when one girl drinks the other one feels it. This along with many other cases, has advanced social media and neurological related research concerning this kind of link between craniopagus twins. Unfortunately, no controlled studies have been done because the twins are so young and their brains are still very malleable and plastic. Although there is not an overwhelming amount of research surrounding how the union between craniopagus twins leads to different personality, cognitive and motor traits, there have been some studies exploring what it actually means to share a brain. In the case of Tatiana and Krista, it is possible that the twins shared some conscious thought. Studies of the thalamus’ role in the brain provide neurological data that help explain these behavioral observations that these two twins experience. Thalamo-cortico-thalamic circuits are the looped neural pathways that connect the thalamus to the cerebral cortex, and then the cerebral cortex back to the thalamus. Because the thalamus is mainly responsible for relaying sensory messages from the body to the brain, it is possible that there is a lot of overlap between the twins’ sensory reception and the actual response it creates within the brain. One study examines this by studying the thalamus when it is at a persistent vegetative state that is when the patient is awake but not conscious. This study proved that the cortical activity on its own is not conscious and that all the activity between the loops of the thalamus, the cerebral cortex and the thalamus itself are all conscious actions. Another study of the thalamus reaffirms that the thalamus does not answer yes/no questions but instead acts as a mediator between different parts of the cerebral cortex and systemic sensory reception.These loops actually may account for the relationship between Tatiana and Krista. At the neuronal level, communication is dense network of neurons linked between themselves and the coordinator (in this case the thalamus) that finally sends a message to the cortex. On top of this, there are links between the cortex that send messages back through the coordinator and finally to the rest of the body. The brains ability to function through loops and circuits is a good model to explain why Tatiana “consciously” feels what Krista is “physically” experiencing. Additionally there is some level of synchronization between the two twins. Another study found that for craniopagus twins, their connection to each other is comparable to our normal appendages and that their bodies have obvious overlapping physically and psychologically. Because most cases of craniopagus twins are unique, the research outlining general connections between craniopagus twins is limited. However, this example provides insight into the effects of a union between twins who essentially share the same sensory relay system in the thalamus. History Conjoined twinning is one of the oldest known birth defects in history and examples with humans fascination with twins is extremely evident throughout historical literature. Although there are cases of conjoined twins dating back to as early as the 10th century, it was not until 1491 that the first case was documented. Apart from that, Sebastian Münster’s Cosmographia universalis provides the true first account of craniopagus twins who happened to live for ten years, exceeding many expectations during that time. He describes the set of twins as being a unique malformation and a punishment from their mothers mistake. In French barber surgeon Ambroise Paré’s 16th-century book, On Monsters and Marvels, various types of "supernatural" twinning are illustrated and described as "monstrous and marvelous creatures that proceed from the judgment of God", suggesting that conjoined twins and specifically craniopagus twins were viewed as literal monsters in the 16th century. See also Conjoined twins Parasitic twin Twin References == External links ==

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I've encountered the term 'Foreign body aspiration' while reading about medical topics. What does it refer to exactly?

Foreign body aspiration occurs when a foreign body enters the airway which can cause difficulty breathing or choking. Objects may reach the respiratory tract and the digestive tract from the mouth and nose, but when an object enters the respiratory tract it is termed aspiration. The foreign body can then become lodged in the trachea or further down the respiratory tract such as in a bronchus. Regardless of the type of object, any aspiration can be a life-threatening situation and requires timely recognition and action to minimize risk of complications. While advances have been made in management of this condition leading to significantly improved clinical outcomes, there were still 2,700 deaths resulting from foreign body aspiration in 2018. Approximately one child dies every five days due to choking on food in the United States, highlighting the need for improvements in education and prevention. Signs and symptoms Signs and symptoms of foreign body aspiration vary based on the site of obstruction, the size of the foreign body, and the severity of obstruction. 20% of foreign bodies become lodged in the upper airway, while 80% become lodged in a bronchus. Signs of foreign body aspiration are usually abrupt in onset and can involve coughing, choking, and/or wheezing; however, symptoms can be slower in onset if the foreign body does not cause a large degree of obstruction of the airway. With this said, aspiration can also be asymptomatic on rare occasions.Classically, patients present with acute onset of choking. In these cases, the obstruction is classified as a partial or complete obstruction. Signs of partial obstruction include choking with drooling, stridor, and the patient maintains the ability to speak. Signs of complete obstruction include choking with inability to speak or absence of bilateral breath sounds among other signs of respiratory distress such as cyanosis. A fever may be present. When this is the case, it is possible the object may be chemically irritating or contaminated.Foreign bodies above the larynx often present with stridor, while objects below the larynx present with wheezing. Foreign bodies above the vocal cords often present with difficulty and pain with swallowing and excessive drooling. Foreign bodies below the vocal cords often present with pain and difficulty with speaking and breathing. Increased respiratory rate may be the only sign of foreign body aspiration in a child who cannot verbalize or report if they have swallowed a foreign body.If the foreign body does not cause a large degree of obstruction, patients may present with chronic cough, asymmetrical breath sounds on exam, or recurrent pneumonia of a specific lung lobe. If the aspiration occurred weeks or even months ago, the object may lead to an obstructive pneumonia or even a lung abscess. Therefore, it is important to consider chronic foreign body aspiration in patients whose histories include unexplained recurrent pneumonia or lung abscess with or without fever.In adults, the right lower lobe of the lung is the most common site of recurrent pneumonia in foreign body aspiration. This is due to the fact that the anatomy of the right main bronchus is wider and steeper than that of the left main bronchus, allowing objects to enter more easily than the left side. Unlike adults, there is only a slight propensity towards objects lodging in the right bronchus in children. This is likely due to the bilateral bronchial angles being symmetric until about 15 years of age when the aortic knob fully develops and displaces the left main bronchus.Signs and symptoms of foreign body aspiration in adults may also mimic other lung disorders such as asthma, COPD, and lung cancer. { Causes Most cases of foreign body aspiration are in children ages 6 months to 3 years due to the tendency for children to place small objects in the mouth and nose. Children of this age usually lack molars and cannot grind up food into small pieces for proper swallowing. Small, round objects including nuts, hard candy, popcorn kernels, beans, and berries are common causes of foreign body aspiration. Latex balloons are also a serious choking hazard in children that can result in death. A latex balloon will conform to the shape of the trachea, blocking the airway and making it difficult to expel with the Heimlich maneuver. In addition, if the foreign body is able to absorb water, such as a bean, seed, or corn, among other things, it may swell over time leading to a more severe obstruction. In adults, foreign body aspiration is most prevalent in populations with impaired swallowing mechanisms such as the following: neurological disorders, alcohol use, advanced age leading to senility (most common in the 6th decade of life), and loss of consciousness. This inadequate airway protection may also be attributed to poor dentition, seizure, general anesthesia, or sedative drug use. Diagnosis The most important aspect of the assessment for a clinician is an accurate history provided by an event witness. Unfortunately, this is not always available. Physical examination A physical examination by a clinician should include, at a minimum, a general assessment in addition to cardiac and pulmonary exams. Auscultation of breath sounds may give additional information regarding object location and the degree of airway obstruction. The presence of drooling and dysphagia (drooling) should always be noted alongside the classic signs of airway obstruction as these can indicate involvement of the esophagus and impact management. Diagnostic Imaging Radiography is the most common form of imaging used in the initial assessment of a foreign body presentation. Most patients receive a chest x-ray to determine the location of the foreign body. Lateral neck, chest, and bilateral decubitus end-expiratory chest x-rays should be obtained in patients suspected of having aspirated a foreign body. However, the presence of normal findings on chest radiography should not rule out foreign body aspiration as not all objects can be visualized. In fact, up to 50% of cases can have normal findings on radiography. This is because visibility of an object depends on many factors, such as the objects material, size, anatomic location and surrounding structures, as well as the patients body habitus. X-ray beams only show an object if that objects composition blocks the rays from traveling through, making it radiopaque and appearing lighter or white on the image. This also requires it to not be stuck behind something that blocks the beams first. Objects that are radiopaque include items made of most metals except aluminum, bones except most fish bones, and glass. If the material does not block the x-ray beams it is considered radiolucent and will appear dark which prevents visualization. This includes material such as most plastics, most fish bones, wood, and most aluminum objects.Other diagnostic imaging modalities, such as magnetic resonance imaging, computed tomography, and ventilation perfusion scans play a limited role in the diagnosis of foreign body aspiration.Signs on x-ray that are more commonly seen than the object itself and can be indicative of foreign body aspiration include visualization of the foreign body or hyperinflation of the affected lung. Other x-ray findings that can be seen with foreign body aspiration include obstructive emphysema, atelectasis, and consolidation.While, x-ray can be used to visualize the location and identity of a foreign body, rigid bronchoscopy under general anesthesia is the gold-standard for diagnosis since the foreign body can be visualized and removed with this intervention. Rigid bronchoscopy is indicated when two of the three following criteria are met: report of foreign body aspiration by the patient or a witness, abnormal lung exam findings, or abnormal chest x-ray findings. Management See also: Choking § Treatment, Basic Life Support, Advanced Cardiovascular Life Support Treatment of foreign body aspiration is determined by the age of the patient and the severity of obstruction of the airway involved. Basic management An airway obstruction can be partial or complete. In partial obstruction, the patient can usually clear the foreign body with coughing. In complete obstruction, acute intervention is required to remove the foreign body.If foreign body aspiration is suspected, finger sweeping in the mouth is not recommended due to the increased risk of displacing the foreign object further into the airway.For choking children less than 1 year of age, the child should be placed face down over the rescuers arm. Back blows should be delivered with the heel of the hand, then the patient should be turned face-up and chest thrusts should be administered. The rescuer should alternate five back blows followed by five chest thrusts until the object is cleared. The Heimlich maneuver should be used in choking patients older than 1 year of age to dislodge a foreign body. If the patient becomes unresponsive during physical intervention, cardiopulmonary resuscitation (CPR) should be started. Advanced management In the event that the basic measures do not remove the foreign body, and adequate ventilation cannot be restored, need for treatment by trained personnel becomes necessary. Laryngoscopy should be performed in unresponsive patients if non-invasive airway clearance techniques are unsuccessful. Laryngoscopy involves placing a device in the mouth to visualize the back of the airway. If the foreign body can be seen, it can be removed with forceps. An endotracheal tube should then be placed in order to prevent airway compromise from resulting inflammation after the procedure. If the foreign body cannot be visualized, intubation, tracheotomy, or needle cricothyrotomy can be done to restore an airway for patients who have become unresponsive due to airway compromise.If non-invasive measures do not dislodge the foreign body, and the patient can maintain adequate ventilation, rigid bronchoscopy under general anesthesia should be performed. Supplemental oxygen, cardiac monitoring, and a pulse oximeter should be applied to the patient. Efforts should be made to keep the patient calm and avoid agitating the patient to prevent further airway compromise. Flexible rather than rigid bronchoscopy might be used when the diagnosis or object location are unclear. When flexible bronchoscope is used, rigid bronchoscope is typically on standby and readily available as this is the preferred approach for removal. Rigid bronchoscopy allows good airway control, ready bleeding management, better visualization, and ability to manipulate the aspirated object with a variety of forceps. Flexible bronchoscopy may be used for extraction when distal access is needed and the operator is experienced in this technique. Potential advantages include avoidance of general anesthesia as well as the ability to reach subsegmental bronchi which are smaller in diameter and further down the respiratory tract than the main bronchi. The main disadvantage of using a flexible scope is the risk of further dislodging the object and causing airway compromise. Bronchoscopy is successful in removing the foreign body in approximately 95% of cases with a complication rate of only 1%.After the foreign body is removed, patients should receive nebulized beta-adrenergic medication and chest physiotherapy to further protect the airway. Steroidal anti-inflammatories and antibiotics are not routinely administered except in certain scenarios. These include situations such as when the foreign body is difficult or impossible to extract, when there is a documented respiratory tract infection, and when swelling within the airway occurs after removal of the object. Glucocorticoids may be administered when the foreign body is surrounded by inflamed tissue and extraction is difficult or impossible. In such cases, extraction may be delayed for a short course of glucocorticoids so that the inflammation may be reduced before subsequent attempts. These patients should remain under observation in the hospital until successful extraction as this practice can result in dislodgement of the foreign body. Antibiotics are appropriate when an infection has developed but should not delay extraction. In fact, removal of the object may improve infection control by removing the infectious source as well as using cultures taken during the bronchoscopy to guide antibiotic choice. When airway edema or swelling occur, the patient may have stridor. In these cases, glucocorticoids, aerosolized epinephrine, or helium oxygen therapy may be considered as part of the management plan.Patients who are clinically stable with no need for supplemental oxygen after extraction may be discharged from the hospital the same day as the procedure. Routine imaging such as a follow-up chest x-ray are not needed unless symptoms persist or worsen, or if the patient had imaging abnormalities previously to verify return to normal. Most children are discharged within 24 hours of the procedure. Complications Many complications can develop if a foreign body remains in the airway. There are also complications that may occur after removal of the object depending on the timeline of events. Cardiac arrest and death are possible complications if a sudden complete obstruction occurs and immediate medical care is not performed. The most common complication from a foreign body aspiration is a pulmonary infection, such as pneumonia or a lung abscess. This can be more difficult to overcome in the elderly population and lead to even further complications. Patients may develop inflammation of the airway walls from a foreign body remaining in the airway. Airway secretions can be retained behind the obstruction which creates an ideal environment for subsequent bacterial overgrowth. Hyperinflation of the airway distal to the obstruction can also occur if the foreign body is not removed. Episodes of recurrent pneumonia in the same lung field should prompt evaluation for a possible foreign body in the airway.Whether or not the foreign body is removed, complications such as chemical bronchitis, mucosal reactions, and the development of granulation tissue are possible.Complications can also arise from interventions used to remove a foreign body from the airway. Rigid bronchoscopy is the gold standard for removal of a foreign body, however this intervention does have potential risks. The most common complication from rigid bronchoscopy is damage to the patients teeth. Other less common complications include cuts to the mouth or esophagus, perforation of the bronchial tree, damage to the vocal cords, pneumothorax, atelectasis, stricture, and perforation. Prevention There are many factors to consider when determining how to decrease the likelihood of aspiration, especially in the extremely young and elderly populations.The major considerations in children are their developmental level in terms of swallowing and protecting their airway via mechanisms such as coughing and the gag reflex. Also, certain object characteristics such as size, shape, and material can increase their potential to cause choking among children. When there are multiple children in a shared environment, toys and foods that are acceptable for older children often pose a choking risk to the younger children. Education for parents and caretakers should continue to be prioritized when possible. This can be through positions such as pediatricians, dentists, and school teachers as well as media advertisements and printed materials. This education should include educating caretakers on how to recognize choking and perform first aid and cardiopulmonary resuscitation, check for warning labels and toy recalls, and avoid high risk objects and foods.Thanks to numerous public advancements, such as the Child Safety Protection Act and the Federal Hazardous Substance Act (FHSA), warning labels for choking hazards are required on packaging for small balls, marbles, balloons, and toys with small parts when these are intended for use by children in at-risk age groups. Also, the Consumer Product Safety Improvement Act of 2008 amended the FHSA to also require advertisements on websites, catalogues, and other printed materials to include the choking hazard warnings. == References ==

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Please help me grasp the concept behind the medical term 'Masticatory muscle myositis.'

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. The disease is usually bilateral. MMM is caused by the presence of 2M fibers in the muscles of the jaw. 2M fibers are not found elsewhere in the body. The immune system recognizes these proteins as foreign to the body and attacks them, resulting in inflammation. Diagnosis of MMM is through either biopsy of the temporalis or masseter muscles or the 2M antibody assay, in which blood serum of the possible MMM-dog is reacted with temporalis tissue of a normal dog, or both. False negatives by the 2M antibody assay may be obtained if MMM is end-stage with destruction of type 2M fibers and marked fibrosis. Treatment is usually with corticosteroids such as prednisone, often with decreasing doses for up to 4–6 months, and in the case of trismus, manual opening of the mouth under anesthesia. Feeding very soft or liquid food during this time is usually necessary. The ultimate degree of recovery of jaw function and muscle mass will depend upon the extent of damage to the muscle tissue. Recurrence of MMM may occur. Misdiagnosis of MMM as a retroorbital abscess based on physical examination and finding of trismus leads to inappropriate treatment with antibiotics, which will not impede the progress of MMM. References External links Most Commonly Asked Questions about Masticatory Muscle Myositis Masticatory muscle myositis (MMM), Dogs Masticatory Muscle Myositis in the Cavalier King Charles Spaniel

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Could you offer a clear explanation of the term 'Polyradiculoneuropathy' as used in the medical field?

Polyradiculoneuropathy describes a condition in which polyneuropathy and polyradiculopathy occur together. An example is Guillain–Barré syndrome.Treatment with a single course of intravenous immunoglobulin (IVIG) infusions has been demonstrated to be a potentially effective treatment (reported to have caused prolonged remission in a case associated with systemic lupus (Systemic lupus erythematosus) ). References External links Polyradiculoneuropathy at the US National Library of Medicine Medical Subject Headings (MeSH)