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

What is the significance of the term 'Gerstmann–Sträussler–Scheinker syndrome' in the medical field?

Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, usually familial, fatal neurodegenerative disease that affects patients from 20 to 60 years in age. It is exclusively heritable, and is found in only a few families all over the world. It is, however, classified with the transmissible spongiform encephalopathies (TSE) due to the causative role played by PRNP, the human prion protein. GSS was first reported by the Austrian physicians Josef Gerstmann, Ernst Sträussler and Ilya Scheinker in 1936.Familial cases are associated with autosomal-dominant inheritance.Certain symptoms are common to GSS, such as progressive ataxia, pyramidal signs, and dementia; they worsen as the disease progresses. Symptoms and signs Symptoms start with slowly developing dysarthria (difficulty speaking) and cerebellar truncal ataxia (unsteadiness) and then the progressive dementia becomes more evident. Loss of memory can be the first symptom of GSS. Extrapyramidal and pyramidal symptoms and signs may occur and the disease may mimic spinocerebellar ataxias in the beginning stages. Myoclonus (spasmodic muscle contraction) is less frequently seen than in Creutzfeldt–Jakob disease. Many patients also exhibit nystagmus (involuntary movement of the eyes), visual disturbances, and even blindness or deafness. The neuropathological findings of GSS include widespread deposition of amyloid plaques composed of abnormally folded prion protein.Four clinical phenotypes are recognized: typical GSS, GSS with areflexia and paresthesia, pure dementia GSS and Creutzfeldt-Jakob disease-like GSS. Causes GSS is part of a group of diseases called transmissible spongiform encephalopathies. These diseases are caused by prions, which are a class of pathogenic proteins that are resistant to proteases. These prions then form clusters in the brain, which are responsible for the neurodegenerative effects seen in patients.The P102L mutation, which causes a substitution of proline to a leucine in codon 102, has been found in the prion protein gene (PRNP, on chromosome 20) of most affected individuals. Therefore, it appears this genetic change is usually required for the development of the disease. Diagnosis GSS can be identified through genetic testing. Testing for GSS involves a blood and DNA examination in order to attempt to detect the mutated gene at certain codons. If the genetic mutation is present, the patient will eventually develop GSS. Treatment There is no cure for GSS, nor is there any known treatment to slow the progression of the disease. Therapies and medication are aimed at treating or slowing down the effects of the symptoms. The goal of these treatments is to try to improve the patients quality of life as much as possible. There is some ongoing research to find a cure, with one of the most prominent examples being the PRN100 monoclonal antibody. Prognosis GSS is a disease that progresses slowly, lasting roughly 2–10 years, with an average of approximately five years. The disease ultimately results in death, most commonly from the patient either going into a coma, or from a secondary infection due to the patients loss of bodily functions. Research Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are neurodegenerative diseases of the brain thought to be caused by a protein that converts to an abnormal form called a prion. GSS is a very rare TSE, making its genetic origin nearly impossible to determine. It is also challenging to find any patients with GSS, as the disease tends to be underreported, due to its clinical similarity to other diseases, and has been found in only a few countries. In 1989, the first mutation of the prion protein gene was identified in a GSS family. The largest of these families affected by GSS is the Indiana Kindred, spanning over 8 generations, and includes over 3,000 people, with 57 individuals known to be affected. GSS was later realized to have many different gene mutation types, varying in symptom severity, timing and progression. Doctors in different parts of the world are in the process of uncovering more generations and families who have the mutation. Notes External links Gerstmann–Sträussler–Scheinker syndrome, MedicineNet.com

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

Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning. It is taken by mouth, injection into a muscle, or injection into a vein.Side effects may include trouble sleeping, allergic reactions, or fever. Use in pregnancy or breastfeeding is generally regarded as safe. When used for anemia it is recommended that pernicious anemia as a cause be ruled out first. Folinic acid is a form of folic acid that does not require activation by dihydrofolate reductase to be useful to the body.Folinic acid was first made in 1945. It is on the World Health Organizations List of Essential Medicines. Medical use Folinic acid is given following methotrexate as part of a total chemotherapeutic plan, where it may protect against bone marrow suppression or gastrointestinal mucosa inflammation. No apparent effect is seen on pre-existing methotrexate-induced nephrotoxicity. Folinic acid can be taken as a pill (orally) or injected into a vein (intravenously) or muscle (intramuscularly).While not specifically an antidote for methotrexate, folinic acid may also be useful in the treatment of acute methotrexate overdose. Different dosing protocols are used, but folinic acid should be redosed until the methotrexate level is less than 5 x 10−8 M.Additionally, folinic acid is sometimes used to reduce the side effects of methotrexate in rheumatoid arthritis patients. This includes reductions in nausea, abdominal pain, abnormal liver blood tests, and mouth sores.Folinic acid is also used in combination with the chemotherapy agent 5-fluorouracil in treating colon cancer. In this case, folinic acid is not used for "rescue" purposes; rather, it enhances the effect of 5-fluorouracil by inhibiting thymidylate synthase. Folinic acid is also sometimes used to prevent toxic effects of high doses of antimicrobial dihydrofolate reductase inhibitors such as trimethoprim and pyrimethamine. It may be prescribed in the treatment of toxoplasmosis retinitis, in combination with the folic acid antagonists pyrimethamine and sulfadiazine. Folinic acid is also used in the treatment of cerebral folate deficiency, a syndrome in which the use of folic acid cannot normalize cerebrospinal fluid levels of 5-MTHF. Side effects Folinic acid should not be administered intrathecally. This may produce severe adverse effects or even death.In cancer patients, rare hypersensitivity reactions to folinic acid have been described. Drug interactions Fluorouracil: Folinic acid may increase the toxicity associated with fluorouracil if the two are administered together. Some adverse effects that have occurred, particularly in elderly patients, include severe enterocolitis, diarrhea, and dehydration.Sulfamethoxazole-trimethoprim: A potential drug interaction exists with concomitant use of sulfamethoxazole-trimethoprim and folinic acid. Folinic acid has been shown to decrease the efficacy of sulfamethoxazole-trimethoprim in the treatment of Pneumocystis jirovecii (formerly known as Pneumocystis carinii), a common cause of pneumonia in AIDS patients. Mechanism of action Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., 5,10-methylenetetrahydrofolate, 5-methyltetrahydrofolate), thus has vitamin activity equivalent to that of folic acid. Since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate. This is the classical view of folinic acid rescue therapy. In 1980s, however, folinic acid was found to reactivate the dihydrofolate reductase itself even when methotrexate exists. Although the mechanism is not very clear, the polyglutamylation of methotrexate and dihydrofolate in malignant cells is considered to play an important role in the selective reactivation of dihydrofolate reductase by folinic acid in normal cells.Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of dihydrofolate reductase inhibition, so some normal DNA replication processes can proceed. Folinic acid has dextro- and levorotary isomers. Both levoleucovorin (the levorotary isomer) and racemic folinic acid (a mixture of both isomers) have similar efficacy and tolerability. Levoleucovorin was approved by the FDA in 2008. History Folinic acid was discovered as a needed growth factor for the bacterium Leuconostoc citrovorum in 1948, by Sauberlich and Baumann. This resulted in it being called "citrovorum factor," meaning citrovorum growth factor. It had an unknown structure, but was found to be a derivative of folate that had to be metabolized in the liver before it could support growth of L. citrovorum. The synthesis of citrovorum factor by liver cells in culture was eventually accomplished from pteroylglutamic acid in the presence of suitable concentrations of ascorbic acid. The simultaneous addition of sodium formate to such systems resulted in increased citrovorum factor activity in the cell-free supernatants (producing, as now known, the 5-formyl derivative), and from this method of preparation of large amounts of the factor, its structure as levo-folinic acid (5-formyl tetrahydrofolic acid) was eventually deduced. Names Folinic acid should be distinguished from folic acid (vitamin B9). However, folinic acid is a vitamer for folic acid and has the full vitamin activity of this vitamin. Levofolinic acid and its salts are the 2S- form of the molecule. They are the only forms of the molecule that are known to be biologically active. It is generally administered as the calcium or sodium salt (calcium folinate (INN), sodium folinate, leucovorin calcium, leucovorin sodium). References External links "Leucovorin". Drug Information Portal. U.S. National Library of Medicine. "Leucovorin". MedlinePlus.

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

Could you provide a brief overview of 'Ephedrine' in a medical context?

Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection it lasts about an hour and when taken by mouth it can last up to four hours.Common side effects include trouble sleeping, anxiety, headache, hallucinations, high blood pressure, fast heart rate, loss of appetite, and inability to urinate. Serious side effects include stroke and heart attack. While likely safe in pregnancy, its use in this population is poorly studied. Use during breastfeeding is not recommended. Ephedrine works by increasing the activity of the α and β adrenergic receptors.Ephedrine was first isolated in 1885 and came into commercial use in 1926. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. It can normally be found in plants of the Ephedra genus. Dietary supplements containing ephedrine are illegal in the United States, with the exception of those used in traditional Chinese medicine, where its presence is noted by má huáng. Medical use Both ephedrine and pseudoephedrine increase blood pressure and act as bronchodilators, with pseudoephedrine having considerably less effect.Ephedrine may decrease motion sickness, but it has mainly been used to decrease the sedating effects of other medications used for motion sickness.Ephedrine is also found to have quick and long-lasting responsiveness in congenital myasthenic syndrome in early childhood and also even in the adults with a novel COLQ mutation. Weight loss Ephedrine promotes modest short-term weight loss, specifically fat loss, but its long-term effects are unknown. In mice, ephedrine is known to stimulate thermogenesis in the brown adipose tissue, but because adult humans have only small amounts of brown fat, thermogenesis is assumed to take place mostly in the skeletal muscle. Ephedrine also decreases gastric emptying. Methylxanthines such as caffeine and theophylline have a synergistic effect with ephedrine with respect to weight loss. This led to creation and marketing of compound products. One of them, known as the ECA stack, contains ephedrine with caffeine and aspirin. It is a popular supplement taken by bodybuilders seeking to cut body fat before a competition. Recreational use As a phenethylamine, ephedrine has a similar chemical structure to amphetamines and is a methamphetamine analogue having the methamphetamine structure with a hydroxyl group at the β position. Because of ephedrines structural similarity to methamphetamine, it can be used to create methamphetamine using chemical reduction in which ephedrines hydroxyl group is removed; this has made ephedrine a highly sought-after chemical precursor in the illicit manufacture of methamphetamine. The most popular method for reducing ephedrine to methamphetamine is similar to the Birch reduction, in that it uses anhydrous ammonia and lithium metal in the reaction. The second-most popular method uses red phosphorus and iodine in the reaction with ephedrine. Moreover, ephedrine can be synthesized into methcathinone via simple oxidation. As such, ephedrine is listed as a table-I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. Detection of use Ephedrine may be quantified in blood, plasma, or urine to monitor possible abuse by athletes, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Many commercial immunoassay screening tests directed at the amphetamines cross-react appreciably with ephedrine, but chromatographic techniques can easily distinguish ephedrine from other phenethylamine derivatives. Blood or plasma ephedrine concentrations are typically in the 20–200 µg/L range in persons taking the drug therapeutically, 300–3000 µg/L in abusers or poisoned patients and 3–20 mg/L in cases of acute fatal overdosage. The current World Anti-Doping Agency (WADA) limit for ephedrine in an athletes urine is 10 µg/mL. Contraindications Ephedrine should not be used in conjunction with certain antidepressants, namely norepinephrine-dopamine reuptake inhibitors (NDRIs), as this increases the risk of symptoms due to excessive serum levels of norepinephrine. Bupropion is an example of an antidepressant with an amphetamine-like structure similar to ephedrine, and it is an NDRI. Its action bears more resemblance to amphetamine than to fluoxetine in that its primary mode of therapeutic action involves norepinephrine and to a lesser degree dopamine, but it also releases some serotonin from presynaptic clefts. It should not be used with ephedrine, as it may increase the likelihood of side effects. Ephedrine should be used with caution in patients with inadequate fluid replacement, impaired adrenal function, hypoxia, hypercapnia, acidosis, hypertension, hyperthyroidism, prostatic hypertrophy, diabetes mellitus, cardiovascular disease, during delivery if maternal blood pressure is >130/80 mmHg, and during lactation.Contraindications for the use of ephedrine include: closed-angle glaucoma, phaeochromocytoma, asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis), concomitant or recent (previous 14 days) monoamine oxidase inhibitor (MAOI) therapy, general anaesthesia with halogenated hydrocarbons (particularly halothane), tachyarrhythmias or ventricular fibrillation, or hypersensitivity to ephedrine or other stimulants. Ephedrine should not be used at any time during pregnancy unless specifically indicated by a qualified physician and only when other options are unavailable. Adverse effects Ephedrine is a potentially dangerous natural compound; as of 2004 the US Food and Drug Administration had received over 18,000 reports of adverse effects in people using it.Adverse drug reactions (ADRs) are more common with systemic administration (e.g. injection or oral administration) compared to topical administration (e.g. nasal instillations). ADRs associated with ephedrine therapy include: Cardiovascular: tachycardia, cardiac arrhythmias, angina pectoris, vasoconstriction with hypertension Dermatological: flushing, sweating, acne vulgaris Gastrointestinal: nausea Genitourinary: decreased urination due to vasoconstriction of renal arteries, difficulty urinating is not uncommon, as alpha-agonists such as ephedrine constrict the internal urethral sphincter, mimicking the effects of sympathetic nervous system stimulation Nervous system: restlessness, confusion, insomnia, mild euphoria, mania/hallucinations (rare except in previously existing psychiatric conditions), delusions, formication (may be possible, but lacks documented evidence) paranoia, hostility, panic, agitation Respiratory: dyspnea, pulmonary edema Miscellaneous: dizziness, headache, tremor, hyperglycemic reactions, dry mouthThe neurotoxicity of l-ephedrine is disputed. Other uses In chemical synthesis, ephedrine is used in bulk quantities as a chiral auxiliary group. In saquinavir synthesis, the half-acid is resolved as its salt with l-ephedrine. Chemistry and nomenclature Ephedrine is a sympathomimetic amine and substituted amphetamine. It is similar in molecular structure to phenylpropanolamine, methamphetamine, and epinephrine (adrenaline). Chemically, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra (family Ephedraceae). It works mainly by increasing the activity of norepinephrine (noradrenaline) on adrenergic receptors. It is most usually marketed as the hydrochloride or sulfate salt. Ephedrine exhibits optical isomerism and has two chiral centres, giving rise to four stereoisomers. By convention, the pair of enantiomers with the stereochemistry (1R,2S) and (1S,2R) is designated ephedrine, while the pair of enantiomers with the stereochemistry (1R,2R) and (1S,2S) is called pseudoephedrine. Ephedrine is a substituted amphetamine and a structural methamphetamine analogue. It differs from methamphetamine only by the presence of a hydroxyl group (—OH). The isomer which is marketed is (−)-(1R,2S)-ephedrine.Ephedrine hydrochloride has a melting point of 187−188 °C.In the outdated D/L system (+)-ephedrine is also referred to as D-ephedrine and (−)-ephedrine as L-ephedrine (in which case, in the Fisher projection, the phenyl ring is drawn at the bottom).Often, the D/L system (with small caps) and the d/l system (with lower-case) are confused. The result is that the levorotary l-ephedrine is wrongly named L-ephedrine and the dextrorotary d-pseudoephedrine (the diastereomer) wrongly D-pseudoephedrine. The IUPAC names of the two enantiomers are (1R,2S)- respectively (1S,2R)-2-methylamino-1-phenylpropan-1-ol. A synonym is erythro-ephedrine. Sources Agricultural Ephedrine is obtained from the plant Ephedra sinica and other members of the genus Ephedra, from which the name of the substance is derived. Raw materials for the manufacture of ephedrine and traditional Chinese medicines are produced in China on a large scale. As of 2007, companies produced for export US$13 million worth of ephedrine from 30,000 tons of ephedra annually, or about ten times the amount used in traditional Chinese medicine. Synthetic Most of the l-ephedrine produced today for official medical use is made synthetically as the extraction and isolation process from E. sinica is tedious and no longer cost effective. Biosynthetic Ephedrine was long thought to come from modifying the amino acid L-phenylalanine. L-Phenylalanine would be decarboxylated and subsequently attacked with ω-aminoacetophenone. Methylation of this product would then produce ephedrine. This pathway has since been disproven. A new pathway proposed suggests that phenylalanine first forms cinnamoyl-CoA via the enzymes phenylalanine ammonia-lyase and acyl CoA ligase. The cinnamoyl-CoA is then reacted with a hydratase to attach the alcohol functional group. The product is then reacted with a retro-aldolase, forming benzaldehyde. Benzaldehyde reacts with pyruvic acid to attach a 2 carbon unit. This product then undergoes transamination and methylation to form ephedrine and its stereoisomer, pseudoephedrine. Mechanism of action Ephedrine, a sympathomimetic amine, acts on part of the sympathetic nervous system (SNS). The principal mechanism of action relies on its indirect stimulation of the adrenergic receptor system by increasing the activity of norepinephrine at the postsynaptic α and β receptors. The presence of direct interactions with α receptors is unlikely, but still controversial. L-ephedrine, and particularly its stereoisomer norpseudoephedrine (which is also present in Catha edulis) has indirect sympathomimetic effects and due to its ability to cross the blood-brain barrier, it is a CNS stimulant similar to amphetamines, but less pronounced, as it releases noradrenaline and dopamine in the substantia nigra.The presence of an N-methyl group decreases binding affinities at α receptors, compared with norephedrine. Ephedrine, though, binds better than N-methylephedrine, which has an additional methyl group at the nitrogen atom. Also the steric orientation of the hydroxyl group is important for receptor binding and functional activity. Compounds with decreasing α-receptor affinity History Asia Ephedrine in its natural form, known as máhuáng (麻黄) in traditional Chinese medicine, has been documented in China since the Han dynasty (206 BC – 220 AD) as an antiasthmatic and stimulant. In traditional Chinese medicine, máhuáng has been used as a treatment for asthma and bronchitis for centuries.In 1885, the chemical synthesis of ephedrine was first accomplished by Japanese organic chemist Nagai Nagayoshi based on his research on traditional Japanese and Chinese herbal medicines. The industrial manufacture of ephedrine in China began in the 1920s, when Merck began marketing and selling the drug as ephetonin. Ephedrine exports from China to the West grew from 4 to 216 tonnes between 1926 and 1928. Western medicine Introduced in 1948 Vicks Vatronol nose drops (now discontinued) contained ephedrine sulfate as the active ingredient for rapid nasal decongestion. Legality Canada In January 2002, Health Canada issued a voluntary recall of all ephedrine products containing more than 8 mg per dose, all combinations of ephedrine with other stimulants such as caffeine, and all ephedrine products marketed for weight-loss or bodybuilding indications, citing a serious risk to health. Ephedrine is still sold as an oral nasal decongestant in 8 mg pills as a natural health product, with a limit of 0.4g per package, the limit established by the Controlled Drugs and Substances Act as it is considered as Class A Precursor. United States In 1997, the FDA proposed a regulation on ephedra (the herb from which ephedrine is obtained), which limited an ephedra dose to 8 mg (of active ephedrine) with no more than 24 mg per day. This proposed rule was withdrawn, in part, in 2000 because of "concerns regarding the agencys basis for proposing a certain dietary ingredient level and a duration of use limit for these products." In 2004, the FDA created a ban on ephedrine alkaloids marketed for reasons other than asthma, colds, allergies, other disease, or traditional Asian use. On April 14, 2005, the U.S. District Court for the District of Utah ruled the FDA did not have proper evidence that low dosages of ephedrine alkaloids are actually unsafe, but on August 17, 2006, the U.S. Court of Appeals for the Tenth Circuit in Denver upheld the FDAs final rule declaring all dietary supplements containing ephedrine alkaloids adulterated, and therefore illegal for marketing in the United States. Furthermore, ephedrine is banned by the NCAA, MLB, NFL, and PGA. Ephedrine is, however, still legal in many applications outside of dietary supplements. Purchasing is currently limited and monitored, with specifics varying from state to state. The House passed the Combat Methamphetamine Epidemic Act of 2005 as an amendment to the renewal of the USA PATRIOT Act. Signed into law by President George W. Bush on March 6, 2006, the act amended the US Code (21 USC 830) concerning the sale of products containing ephedrine and the closely related drug pseudoephedrine. Both substances are used as precursors in the illicit production of methamphetamine, and to discourage that use the federal statute included the following requirements for merchants who sell these products: A retrievable record of all purchases identifying the name and address of each party to be kept for two years Required verification of proof of identity of all purchasers Required protection and disclosure methods in the collection of personal information Reports to the Attorney General of any suspicious payments or disappearances of the regulated products Non-liquid dose form of regulated product may only be sold in unit-dose blister packs Regulated products are to be sold behind the counter or in a locked cabinet in such a way as to restrict access Daily sales of regulated products not to exceed 3.6 g to a single purchaser, without regard to the number of transactions Monthly sales to a single purchaser not to exceed 9 g of pseudoephedrine base in regulated productsThe law gives similar regulations to mail-order purchases, except the monthly sales limit is 7.5 g. As a pure herb or tea, má huáng, containing ephedrine, is still sold legally in the US. The law restricts/prohibits its being sold as a dietary supplement (pill) or as an ingredient/additive to other products, like diet pills. Australia Ephedrine and all Ephedra species which contain it are considered Schedule 4 substances under the Poisons Standard (October 2015). A Schedule 4 drug is considered a Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription under the Poisons Standard (October 2015). South Africa In South Africa, ephedrine was moved to schedule 6 on 27 May 2008, which makes pure ephedrine tablets prescription only. Pills containing ephedrine up to 30mg per tablet in combination with other medications are still available OTC, schedule 1 and 2, for sinus, head colds and influenza. Germany Ephedrine was freely available in pharmacies in Germany until 2001. Afterwards, access was restricted since it was mostly bought for unindicated uses. Similarly, ephedra can only be bought with a prescription. Since April 2006, all products, including plant parts, that contain ephedrine are only available with a prescription. See also Amphetamine Methamphetamine Phenylephrine Propylhexedrine Pyrovalerone Norephedrine Halostachine Metaraminol Oxyfedrine Pseudoephedrine Synephrine References External links "Ephedrine". Drug Information Portal. U.S. National Library of Medicine. "Ephedrine sulfate". Drug Information Portal. U.S. National Library of Medicine. "Ephedrine Hhydrochloride". Drug Information Portal. U.S. National Library of Medicine.

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

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

Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during labour. It is also available in pharmaceutical form. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in bonding with the baby and milk production. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity. Oxytocin is derived by enzymatic splitting from the peptide precursor encoded by the human OXT gene. The deduced structure of the active nonapeptide is: Cys – Tyr – Ile – Gln – Asn – Cys – Pro – Leu – Gly – NH2, or CYIQNCPLG-NH2. Etymology The term "oxytocin" derives from the Greek "ὠκυτόκος" (ōkutókos), based on ὀξύς (oxús), meaning "sharp" or "swift", and τόκος (tókos), meaning "childbirth". The adjective form is "oxytocic", which refers to medicines which stimulate uterine contractions, to speed up the process of childbirth. History The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist Henry Hallett Dale in 1906, and its milk ejection property was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911.In the 1920s, oxytocin and vasopressin were isolated from pituitary tissue and given their current names. Oxytocins molecular structure was determined in 1952. In the early 1950s, American biochemist Vincent du Vigneaud found that oxytocin is made up of nine amino acids, and he identified its amino acid sequence, the first polypeptide hormone to be sequenced. In 1953, du Vigneaud carried out the synthesis of oxytocin, the first polypeptide hormone to be synthesized. Du Vigneaud was awarded the Nobel Prize in 1955 for his work.Further work on different synthetic routes for oxytocin, as well as the preparation of analogues of the hormone (e.g. 4-deamido-oxytocin) was performed in the following decade by Iphigenia Photaki. Biochemistry Estrogen has been found to increase the secretion of oxytocin and to increase the expression of its receptor, the oxytocin receptor, in the brain. In women, a single dose of estradiol has been found to be sufficient to increase circulating oxytocin concentrations. Biosynthesis Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, that act locally. The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects. The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene. This precursor protein also includes the oxytocin carrier protein neurophysin I. The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM).The activity of the PAM enzyme system is dependent upon vitamin C (ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner. Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.Oxytocin is known to be metabolized by the oxytocinase, leucyl/cystinyl aminopeptidase. Other oxytocinases are also known to exist. Amastatin, bestatin (ubenimex), leupeptin, and puromycin have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as vasopressin, met-enkephalin, and dynorphin A. Neural sources In the hypothalamus, oxytocin is made in magnocellular neurosecretory cells of the supraoptic and paraventricular nuclei, and is stored in Herring bodies at the axon terminals in the posterior pituitary. It is then released into the blood from the posterior lobe (neurohypophysis) of the pituitary gland. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate neurons in the nucleus accumbens, a brain structure where oxytocin receptors are expressed. The endocrine effects of hormonal oxytocin and the cognitive or behavioral effects of oxytocin neuropeptides are thought to be coordinated through its common release through these collaterals. Oxytocin is also produced by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord. Depending on the species, oxytocin receptor-expressing cells are located in other areas, including the amygdala and bed nucleus of the stria terminalis. In the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin I as shown in the inset of the figure; neurophysin is a large peptide fragment of the larger precursor protein molecule from which oxytocin is derived by enzymatic cleavage. Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the oxytocin cells in the hypothalamus. These cells generate action potentials that propagate down axons to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by exocytosis when the nerve terminals are depolarised. Non-neural sources Endogenous oxytocin concentrations in the brain have been found to be as much as 1000-fold higher than peripheral levels.Outside the brain, oxytocin-containing cells have been identified in several diverse tissues, including in females in the corpus luteum and the placenta; in males in the testicles interstitial cells of Leydig; and in both sexes in the retina, the adrenal medulla, the thymus and the pancreas. The finding of significant amounts of this classically "neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these diverse tissues. Male The Leydig cells in some species have been shown to possess the biosynthetic machinery to manufacture testicular oxytocin de novo, to be specific, in rats (which can synthesize vitamin C endogenously), and in guinea pigs, which, like humans, require an exogenous source of vitamin C (ascorbate) in their diets. Female Oxytocin is synthesized by corpora lutea of several species, including ruminants and primates. Along with estrogen, it is involved in inducing the endometrial synthesis of prostaglandin F2α to cause regression of the corpus luteum. Evolution Virtually all vertebrates have an oxytocin-like nonapeptide hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are usually located close to each other (less than 15,000 bases apart) on the same chromosome, and are transcribed in opposite directions (however, in fugu, the homologs are further apart and transcribed in the same direction). The two genes are believed to result from a gene duplication event; the ancestral gene is estimated to be about 500 million years old and is found in cyclostomata (modern members of the Agnatha). Biological function Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. Its actions are mediated by specific oxytocin receptors. The oxytocin receptor is a G-protein-coupled receptor, OT-R, which requires magnesium and cholesterol and is expressed in myometrial cells. It belongs to the rhodopsin-type (class I) group of G-protein-coupled receptors.Studies have looked at oxytocins role in various behaviors, including orgasm, social recognition, pair bonding, anxiety, in-group bias, situational lack of honesty, autism, and maternal behaviors. Oxytocin is believed to have a significant role in social learning. There are indicators that oxytocin may help to decrease noise in the brains auditory system, increase perception of social cues and support more targeted social behavior. It may also enhance reward responses. However, its effects may be influenced by context, such as the presence of familiar or unfamiliar individuals. Physiological The peripheral actions of oxytocin mainly reflect secretion from the pituitary gland. The behavioral effects of oxytocin are thought to reflect release from centrally projecting oxytocin neurons, different from those that project to the pituitary gland, or that are collaterals from them. Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including the amygdala, ventromedial hypothalamus, septum, nucleus accumbens, and brainstem, although the distribution differs markedly between species. Furthermore, the distribution of these receptors changes during development and has been observed to change after parturition in the montane vole. Milk ejection reflex/Letdown reflex: in lactating (breastfeeding) mothers, oxytocin acts at the mammary glands, causing milk to be let down into lactiferous ducts, from where it can be excreted via the nipple. Suckling by the infant at the nipple is relayed by spinal nerves to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland. Uterine contraction: important for cervical dilation before birth, oxytocin causes contractions during the second and third stages of labor. Oxytocin release during breastfeeding causes mild but often painful contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition are normal. In male rats, oxytocin may induce erections. A burst of oxytocin is released during ejaculation in several species, including human males; its suggested function is to stimulate contractions of the reproductive tract, aiding sperm release. Human sexual response: Oxytocin levels in plasma rise during sexual stimulation and orgasm. At least two uncontrolled studies have found increases in plasma oxytocin at orgasm – in both men and women. Plasma oxytocin levels are increased around the time of self-stimulated orgasm and are still higher than baseline when measured five minutes after self arousal. The authors of one of these studies speculated that oxytocins effects on muscle contractibility may facilitate sperm and egg transport.In a study measuring oxytocin serum levels in women before and after sexual stimulation, the author suggests it serves an important role in sexual arousal. This study found genital tract stimulation resulted in increased oxytocin immediately after orgasm. Another study reported increases of oxytocin during sexual arousal could be in response to nipple/areola, genital, and/or genital tract stimulation as confirmed in other mammals. Murphy et al. (1987), studying men, found that plasma oxytocin levels remain unchanged during sexual arousal, but that levels increase sharply after ejaculation, returning to baseline levels within 30 minutes. In contrast, vasopressin was increased during arousal but returned to baseline at the time of ejaculation. The study concludes that (in males) vasopressin is secreted during arousal, while oxytocin is only secreted after ejaculation. A more recent study of men found an increase in plasma oxytocin immediately after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted these changes "may simply reflect contractile properties on reproductive tissue".Due to its similarity to vasopressin, it can reduce the excretion of urine slightly, and so it can be classified as an antidiuretic. In several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and, in humans, high doses can result in low sodium levels (hyponatremia). Cardiac effects: oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting cardiomyocyte differentiation. However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies. Modulation of hypothalamic-pituitary-adrenal axis activity: oxytocin, under certain circumstances, indirectly inhibits release of adrenocorticotropic hormone and cortisol and, in those situations, may be considered an antagonist of vasopressin. Preparing fetal neurons for delivery (in rats): crossing the placenta, maternal oxytocin reaches the fetal brain and induces a switch in the action of neurotransmitter GABA from excitatory to inhibitory on fetal cortical neurons. This silences the fetal brain for the period of delivery and reduces its vulnerability to hypoxic damage. Feeding: a 2012 paper suggested that oxytocin neurons in the para-ventricular hypothalamus in the brain may play a key role in suppressing appetite under normal conditions and that other hypothalamic neurons may trigger eating via inhibition of these oxytocin neurons. This population of oxytocin neurons is absent in Prader-Willi syndrome, a genetic disorder that leads to uncontrollable feeding and obesity, and may play a key role in its pathophysiology. Research on the oxytocin-related neuropeptide asterotocin in starfish also showed that in echinoderms, the chemical induces muscle relaxation, and in starfish specifically caused the organisms to evert their stomach and react as though feeding on prey, even when none were present. Psychological Autism: Oxytocin has been implicated in the etiology of autism, with one report suggesting autism is correlated to a mutation on the oxytocin receptor gene (OXTR). Studies involving Caucasian, Finnish and Chinese Han families provide support for the relationship of OXTR with autism. Autism may also be associated with an aberrant methylation of OXTR. Protection of brain functions: Studies in rats have demonstrated that nasal application of oxytocin can alleviate impaired learning capabilities caused by restrained stress. The authors attributed this effect to an improved hippocampal response in Brain-Derived Neurotrophic Factor (BDNF) being observed. Accordingly, oxytocin has been shown to promote neural growth in the hippocampus in rats even during swim stress or glucocorticoid administration. In a mouse model of early onset of Alzheimers, the administration of oxytocin by a gel particularly designed to make the peptide accessible for the brain, the cognitive decline and hippocampal atrophy of these mice were delayed. Moreover, the amyloid β-protein deposit and nerve cell apoptosis were retarded. An observed inhibitory impact by oxytocin on the inflammatory activity of the microglia was proposed to be an important factor. Bonding In the prairie vole, oxytocin released into the brain of the female during sexual activity is important for forming a pair bond with her sexual partner. Vasopressin appears to have a similar effect in males. Oxytocin has a role in social behaviors in many species, so it likely also does in humans. In a 2003 study, both humans and dog oxytocin levels in the blood rose after a five to 24 minute petting session. This possibly plays a role in the emotional bonding between humans and dogs. Maternal behavior: Female rats given oxytocin antagonists after giving birth do not exhibit typical maternal behavior. By contrast, virgin female sheep show maternal behavior toward foreign lambs upon cerebrospinal fluid infusion of oxytocin, which they would not do otherwise. Oxytocin is involved in the initiation of human maternal behavior, not its maintenance; for example, it is higher in mothers after they interact with unfamiliar children rather than their own. Human ingroup bonding: Oxytocin can increase positive attitudes, such as bonding, toward individuals with similar characteristics, who then become classified as "in-group" members, whereas individuals who are dissimilar become classified as "out-group" members. Race can be used as an example of in-group and out-group tendencies because society often categorizes individuals into groups based on race (Caucasian, African American, Latino, etc.). One study that examined race and empathy found that participants receiving nasally administered oxytocin had stronger reactions to pictures of in-group members making pained faces than to pictures of out-group members with the same expression. Moreover, individuals of one race may be more inclined to help individuals of the same race than individuals of another race when they are experiencing pain. Oxytocin has also been implicated in lying when lying would prove beneficial to other in-group members. In a study where such a relationship was examined, it was found that when individuals were administered oxytocin, rates of dishonesty in the participants responses increased for their in-group members when a beneficial outcome for their group was expected. Both of these examples show the tendency of individuals to act in ways that benefit those considered to be members of their social group, or in-group.Oxytocin is not only correlated with the preferences of individuals to associate with members of their own group, but it is also evident during conflicts between members of different groups. During conflict, individuals receiving nasally administered oxytocin demonstrate more frequent defense-motivated responses toward in-group members than out-group members. Further, oxytocin was correlated with participant desire to protect vulnerable in-group members, despite that individuals attachment to the conflict. Similarly, it has been demonstrated that when oxytocin is administered, individuals alter their subjective preferences in order to align with in-group ideals over out-group ideals. These studies demonstrate that oxytocin is associated with intergroup dynamics. Further, oxytocin influences the responses of individuals in a particular group to those of another group. The in-group bias is evident in smaller groups; however, it can also be extended to groups as large as ones entire country leading toward a tendency of strong national zeal. A study done in the Netherlands showed that oxytocin increased the in-group favoritism of their nation while decreasing acceptance of members of other ethnicities and foreigners. People also show more affection for their countrys flag while remaining indifferent to other cultural objects when exposed to oxytocin. It has thus been hypothesized that this hormone may be a factor in xenophobic tendencies secondary to this effect. Thus, oxytocin appears to affect individuals at an international level where the in-group becomes a specific "home" country and the out-group grows to include all other countries. Drugs Drug interaction: According to several studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs (opiates, cocaine, alcohol), and reduces withdrawal symptoms. MDMA (ecstasy) may increase feelings of love, empathy, and connection to others by stimulating oxytocin activity primarily via activation of serotonin 5-HT1A receptors, if initial studies in animals apply to humans. The anxiolytic drug buspirone may produce some of its effects via 5-HT1A receptor-induced oxytocin stimulation as well. Addiction vulnerability: Concentrations of endogenous oxytocin can impact the effects of various drugs and ones susceptibility to substance use disorders, with higher concentrations associated with lower susceptibility. The status of the endogenous oxytocin system can enhance or reduce susceptibility to addiction through its bidirectional interaction with numerous systems, including the dopamine system, the hypothalamic–pituitary–adrenal axis and the immune system. Individual differences in the endogenous oxytocin system based on genetic predisposition, gender and environmental influences, may therefore affect addiction vulnerability. Oxytocin may be related to the place conditioning behaviors observed in habitual drug abusers. Fear and anxiety Oxytocin is typically remembered for the effect it has on prosocial behaviors, such as its role in facilitating trust and attachment between individuals. However, oxytocin has a more complex role than solely enhancing prosocial behaviors. There is consensus that oxytocin modulates fear and anxiety; that is, it does not directly elicit fear or anxiety. Two dominant theories explain the role of oxytocin in fear and anxiety. One theory states that oxytocin increases approach/avoidance to certain social stimuli and the second theory states that oxytocin increases the salience of certain social stimuli, causing the animal or human to pay closer attention to socially relevant stimuli.Nasally administered oxytocin has been reported to reduce fear, possibly by inhibiting the amygdala (which is thought to be responsible for fear responses). Indeed, studies in rodents have shown oxytocin can efficiently inhibit fear responses by activating an inhibitory circuit within the amygdala. Some researchers have argued oxytocin has a general enhancing effect on all social emotions, since intranasal administration of oxytocin also increases envy and Schadenfreude. Individuals who receive an intranasal dose of oxytocin identify facial expressions of disgust more quickly than individuals who do not receive oxytocin. Facial expressions of disgust are evolutionarily linked to the idea of contagion. Thus, oxytocin increases the salience of cues that imply contamination, which leads to a faster response because these cues are especially relevant for survival. In another study, after administration of oxytocin, individuals displayed an enhanced ability to recognize expressions of fear compared to the individuals who received the placebo. Oxytocin modulates fear responses by enhancing the maintenance of social memories. Rats that are genetically modified to have a surplus of oxytocin receptors display a greater fear response to a previously conditioned stressor. Oxytocin enhances the aversive social memory, leading the rat to display a greater fear response when the aversive stimulus is encountered again. Mood and depression Oxytocin produces antidepressant-like effects in animal models of depression, and a deficit of it may be involved in the pathophysiology of depression in humans. The antidepressant-like effects of oxytocin are not blocked by a selective antagonist of the oxytocin receptor, suggesting that these effects are not mediated by the oxytocin receptor. In accordance, unlike oxytocin, the selective non-peptide oxytocin receptor agonist WAY-267,464 does not produce antidepressant-like effects, at least in the tail suspension test. In contrast to WAY-267,464, carbetocin, a close analogue of oxytocin and peptide oxytocin receptor agonist, notably does produce antidepressant-like effects in animals. As such, the antidepressant-like effects of oxytocin may be mediated by modulation of a different target, perhaps the vasopressin V1A receptor where oxytocin is known to weakly bind as an agonist.Oxytocin mediates the antidepressant-like effects of sexual activity. A drug for sexual dysfunction, sildenafil enhances electrically evoked oxytocin release from the pituitary gland. In accordance, it may have promise as an antidepressant. Sex differences It has been shown that oxytocin differentially affects males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin. Additionally, after the administration of oxytocin, females show increased amygdala activity in response to threatening scenes; however, males do not show increased amygdala activation. This phenomenon can be explained by looking at the role of gonadal hormones, specifically estrogen, which modulate the enhanced threat processing seen in females. Estrogen has been shown to stimulate the release of oxytocin from the hypothalamus and promote receptor binding in the amygdala.It has also been shown that testosterone directly suppresses oxytocin in mice. This has been hypothesized to have evolutionary significance. With oxytocin suppressed, activities such as hunting and attacking invaders would be less mentally difficult as oxytocin is strongly associated with empathy. Social Affecting generosity by increasing empathy during perspective taking: In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80%, but had no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants into which role they would be placed. Serious methodological questions have arisen, however, with regard to the role of oxytocin in trust and generosity. Empathy in healthy males has been shown to be increased after intranasal oxytocin This is most likely due to the effect of oxytocin in enhancing eye gaze. There is some discussion about which aspect of empathy oxytocin might alter – for example, cognitive vs. emotional empathy. While studying wild chimpanzees, it was noted that after a chimpanzee shared food with a non-kin related chimpanzee, the subjects levels of oxytocin increased, as measured through their urine. In comparison to other cooperative activities between chimpanzees that were monitored including grooming, food sharing generated higher levels of oxytocin. This comparatively higher level of oxytocin after food sharing parallels the increased level of oxytocin in nursing mothers, sharing nutrients with their kin. Trust is increased by oxytocin. Study found that with the oxytocin nasal spray, people place more trust to strangers in handling their money. Disclosure of emotional events is a sign of trust in humans. When recounting a negative event, humans who receive intranasal oxytocin share more emotional details and stories with more emotional significance. Humans also find faces more trustworthy after receiving intranasal oxytocin. In a study, participants who received intranasal oxytocin viewed photographs of human faces with neutral expressions and found them to be more trustworthy than those who did not receive oxytocin. This may be because oxytocin reduces the fear of social betrayal in humans. Even after experiencing social alienation by being excluded from a conversation, humans who received oxytocin scored higher in trust on the Revised NEO Personality Inventory. Moreover, in a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects who were told they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting risk aversion. When there is a reason to be distrustful, such as experiencing betrayal, differing reactions are associated with oxytocin receptor gene (OXTR) differences. Those with the CT haplotype experience a stronger reaction, in the form of anger, to betrayal. Romantic attachment: In some studies, high levels of plasma oxytocin have been correlated with romantic attachment. For example, if a couple is separated for a long period of time, anxiety can increase due to the lack of physical affection. Oxytocin may aid romantically attached couples by decreasing their feelings of anxiety when they are separated. Group-serving dishonesty/deception: In a carefully controlled study exploring the biological roots of immoral behavior, oxytocin was shown to promote dishonesty when the outcome favored the group to which an individual belonged instead of just the individual. Oxytocin affects social distance between adult males and females, and may be responsible at least in part for romantic attraction and subsequent monogamous pair bonding. An oxytocin nasal spray caused men in a monogamous relationship, but not single men, to increase the distance between themselves and an attractive woman during a first encounter by 10 to 15 centimeters. The researchers suggested that oxytocin may help promote fidelity within monogamous relationships. For this reason, it is sometimes referred to as the "bonding hormone". There is some evidence that oxytocin promotes ethnocentric behavior, incorporating the trust and empathy of in-groups with their suspicion and rejection of outsiders. Furthermore, genetic differences in the oxytocin receptor gene (OXTR) have been associated with maladaptive social traits such as aggressive behavior. Social behavior and wound healing: Oxytocin is also thought to modulate inflammation by decreasing certain cytokines. Thus, the increased release in oxytocin following positive social interactions has the potential to improve wound healing. A study by Marazziti and colleagues used heterosexual couples to investigate this possibility. They found increases in plasma oxytocin following a social interaction were correlated with faster wound healing. They hypothesized this was due to oxytocin reducing inflammation, thus allowing the wound to heal more quickly. This study provides preliminary evidence that positive social interactions may directly influence aspects of health. According to a study published in 2014, silencing of oxytocin receptor interneurons in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice during the sexually receptive phase of the estrous cycle. Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security when in the company of the mate. This suggests oxytocin may be important for the inhibition of the brain regions associated with behavioral control, fear, and anxiety, thus allowing orgasm to occur. Research has also demonstrated that oxytocin can decrease anxiety and protect against stress, particularly in combination with social support. It is found, that endocannabinoid signaling mediates oxytocin-driven social reward. According to a study published in 2008, its results pointed to how a lack of oxytocin in mice saw a abnormalities in emotional behavior. Another study in conducted in 2014, saw similar results with a variation in the oxytocin receptor is connected with dopamine transporter and how levels of oxytocin are dependent on the levels of dopamine transporter levels. One study explored the effects of low levels of oxytocin and the other on possible explanation of what affects oxytocin receptors. As a lack of social skills and proper emotional behavior are common signs of Autism, low levels of oxytocin could become a new sign for individuals that fall into the Autism Spectrum. Chemistry Oxytocin is a peptide of nine amino acids (a nonapeptide) in the sequence cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amide (Cys – Tyr – Ile – Gln – Asn – Cys – Pro – Leu – Gly – NH2, or CYIQNCPLG-NH2); its C-terminus has been converted to a primary amide and a disulfide bridge joins the cysteine moieties. Oxytocin has a molecular mass of 1007 Da, and one international unit (IU) of oxytocin is the equivalent of 1.68 μg of pure peptide.While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was reported in 2011 in marmosets, tamarins, and other new world primates. Genomic sequencing of the gene for oxytocin revealed a single in-frame mutation (thymine for cytosine) which results in a single amino acid substitution at the 8-position (proline for leucine). Since this original Lee et al. paper, two other laboratories have confirmed Pro8-OT and documented additional oxytocin structural variants in this primate taxon. Vargas-Pinilla et al. sequenced the coding regions of the OXT gene in other genera in new world primates and identified the following variants in addition to Leu8- and Pro8-OT: Ala8-OT, Thr8-OT, and Val3/Pro8-OT. Ren et al. identified a variant further, Phe2-OT in howler monkeys.The biologically active form of oxytocin, commonly measured by RIA and/or HPLC techniques, is the oxidized octapeptide oxytocin disulfide, but oxytocin also exists as a reduced straight-chain (non-cyclic) dithiol nonapeptide called oxytoceine. It has been theorized that oxytoceine may act as a free radical scavenger, as donating an electron to a free radical allows oxytoceine to be re-oxidized to oxytocin via the dehydroascorbate / ascorbate redox couple.Recent advances in analytical instrumental techniques highlighted the importance of liquid chromatography (LC) coupled with mass spectrometry (MS) for measuring oxytocin levels in various samples derived from biological sources. Most of these studies optimized the oxytocin quantification in electrospray ionization (ESI) positive mode, using [M+H]+ as the parent ion at mass-to-charge ratio (m/z) 1007.4 and the fragment ions as diagnostic peaks at m/z 991.0, m/z 723.2 and m/z 504.2. These important ion selections paved the way for the development of current methods of oxytocin quantification using MS instrumentation. The structure of oxytocin is very similar to that of vasopressin. Both are nonapeptides with a single disulfide bridge, differing only by two substitutions in the amino acid sequence (differences from oxytocin bolded for clarity): Cys – Tyr – Phe – Gln – Asn – Cys – Pro – Arg – Gly – NH2. Oxytocin and vasopressin were isolated and their total synthesis reported in 1954, work for which Vincent du Vigneaud was awarded the 1955 Nobel Prize in Chemistry with the citation: "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone."Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone and dynorphin, for example, that act locally. The magnocellular neurosecretory cells that make oxytocin are adjacent to magnocellular neurosecretory cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials. In popular culture "Oxytocin" is the name of the fifth song on Billie Eilishs second album Happier Than Ever. In the novel The Fireman by Joe Hill, the hormone plays a role in neutralizing the danger posed by an infectious spore that causes a condition known as Dragonscale. If the spore enters an oxytocin-rich environment, it will enter a dormant state instead of causing its host to undergo spontaneous human combustion. The formula for Oxytocin is displayed as written on the fingers of Nina Zilli and appears in the opening shot of her video for "Sola". Jack (Steve Zahn), a character in the 2004 movie “Employee of the Month” explains how oxytocin performs in the female body at the 45m27s mark. A more detailed explanation on oxytocin begins at 44m40s. See also Oxytocin (medication) References Further reading External links Media related to Oxytocin at Wikimedia Commons

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

Neutropenic enterocolitis is inflammation of the cecum (part of the large intestine) that may be associated with infection. It is particularly associated with neutropenia, a low level of neutrophil granulocytes (the most common form of white blood cells) in the blood. Signs and symptoms Signs and symptoms of typhlitis may include diarrhea, a distended abdomen, fever, chills, nausea, vomiting, and abdominal pain or tenderness. Cause The condition is usually caused by Gram-positive enteric commensal bacteria of the gut (gut flora). Clostridium difficile is a species of Gram-positive bacteria that commonly causes severe diarrhea and other intestinal diseases when competing bacteria are wiped out by antibiotics, causing pseudomembranous colitis, whereas Clostridium septicum is responsible for most cases of neutropenic enterocolitis.Typhlitis most commonly occurs in immunocompromised patients, such as those undergoing chemotherapy, patients with AIDS, kidney transplant patients, or the elderly. Diagnosis Typhlitis is diagnosed with a radiograph CT scan showing thickening of the cecum and "fat stranding". Treatment Typhlitis is a medical emergency and requires prompt management. Untreated typhlitis has a poor prognosis, particularly if associated with pneumatosis intestinalis (air in the bowel wall) and/or bowel perforation, and has significant morbidity unless promptly recognized and aggressively treated.Successful treatment hinges on: Early diagnosis provided by a high index of suspicion and the use of CT scanning Nonoperative treatment for uncomplicated cases Empiric antibiotics, particularly if the patient is neutropenic or at other risk of infection.In rare cases of prolonged neutropenia and complications such as bowel perforation, neutrophil transfusions can be considered but have not been studied in a randomized control trial. Elective right hemicolectomy may be used to prevent recurrence but is generally not recommended"...The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however," as based on studies from the 1980s Prognosis Inflammation can spread to other parts of the gut in patients with typhlitis. The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis.Historically, the mortality rate for typhlitis was as high as 50%, mostly because it is frequently associated with bowel perforation. More recent studies have demonstrated better outcomes with prompt medical management, generally with resolution of symptoms with neutrophil recovery without death . See also Colitis 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 curious about the meaning of the medical term 'Epiblepharon.' Can you give me some insights?

Epiblepharon is a condition characterised by a congenital horizontal fold of skin near the margin of the upper or lower eyelid caused by the abnormal insertion of muscle fibres. This extra fold of skin redirects the lashes into a vertical position, where they may contact the globe of the eye. This is found most commonly in Asian individuals, especially children. One estimate puts the percentage of affected Asian children aged 7–14 years old at 12.6%. References == External links ==

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

Encounter or Encounters may refer to: Film Encounter, a 1997 Indian film by Nimmala Shankar Encounter (2013 film), a Bengali film Encounter (2018 film), an American sci-fi film Encounter (2021 film), a British sci-fi film Encounters, a section of the Berlin International Film Festival Encounters (film), a 1993 Australian thriller Music Encounter!, a 1968 album by Pepper Adams Coleman Hawkins Encounters Ben Webster or Encounters, an album by Coleman Hawkins and Ben Webster Encounter (Mark Holden album) (1977) Encounter (Michael Stearns album) (1988) Place Vendôme (Swingle Singers with MJQ album) or Encounter Encounter (Trio 3 album) (2000) Encounters (album), a 1984 album by Mal Waldron Encounters, an album by Sylvan "Encounter", a 2016 song by Chris Quilala from Split the Sky Encounter, a song in the video game Metal Gear Solid Ships HMS Encounter (1846) HMS Encounter (1873), a wooden-screw corvette HMS Encounter (H10), an E-class destroyer launched in 1934 HMAS Encounter (1902), a Challenger-class protected cruiser HMAS Encounter (naval base), a former naval depot in South Australia Television Encounter (1958 TV series), a 1958 CBC/ABC anthology television series Encounter (1960 TV program), a Canadian talk show television program Encounter (1970 TV program), a Canadian political affairs television program Encounters (TV series), a 1994 American television series Encounter (Indian TV series) (2014) Encounter (South Korean TV series) (2018) Other uses Encounter (psychology), an authentic, congruent meeting between individuals Encounter (magazine), a literary magazine Encounter Books, a book publisher in the United States, named after the magazine Encounter (game), an international network of active urban games Encounter (video game), a 1983 game by Novagen Encounters (anthology), a 2004 anthology of speculative fiction Encounter (sculpture), an bronze sculpture by Bruce Beasley See also Close encounter, a claimed UFO sighting The Encounter (disambiguation) Encounter Bay (disambiguation) Police encounter Encounter killings by police, killing in a gun fight with the police in the Indian subcontinent, sometimes an extrajudicial killing HMS Encounter, a list of ships All pages with titles containing Encounter

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

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

Casimersen, sold under the brand name Amondys 45, is an antisense oligonucleotide medication used for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping. It is an antisense oligonucleotide of phosphorodiamidate morpholino oligomer (PMO).The most common side effects include upper respiratory tract infections, cough, fever, headache, joint pain and throat pain.Casimersen was approved for medical use in the United States in February 2021, and it is the first FDA-approved targeted treatment for people who have a confirmed mutation of the DMD gene that is amenable to skipping exon 45. Medical uses Casimersen is indicated for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. History Casimersen was evaluated in a double-blind, placebo-controlled study in which 43 participants were randomized 2:1 to receive either intravenous casimersen or placebo. All participants were male, between 7 and 20 years of age, and had a genetically confirmed mutation of the DMD gene that is amenable to exon 45 skipping.The U.S. Food and Drug Administration (FDA) granted the application for casimersen fast track, priority review, and orphan drug designations. The FDA granted the approval of Amondys 45 to Sarepta Therapeutics, Inc. Pharmacodynamics Duchenne Muscular Dystrophy is an X-linked recessive disorder that results in the absence of a functional dystrophin protein. Dystrophin protein is a protein that consists of an N-terminal actin-binding domain, C-terminal B-dystroglycan- binding domain, and 24 internal spectrum-like repeats. Dystrophin plays a role in muscle function and without dystrophin, muscle tissue will be replaced with fibrous and adipose tissue. Casimersen is an antisense phosphorodiamidate morpholino oligonucleotide designed to bind to the exon 45 of the DMD pre-MRNA, which prevents its exclusion into the mature RNA before translation. This change causes the production of an internally truncated dysphotrophin protein. Dosage and administration The usual pediatric and adult dose for Casimersen, for treatment of muscular dystrophy is 30 mg/kg via IV infusion once a week. Adverse effects Patients on Casimersen are advised to immediately contact their healthcare team if they experience the following side effects: pink, brown, or foamy urine or swelling of the hands and feet. Common side effects include: headache, fever, joint pain, cough and cold symptoms. References External links "Casimersen". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02500381 for "Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)" at ClinicalTrials.gov

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.

I'm seeking clarification on the medical term 'Vitelliform macular dystrophy.' Could you explain it?

Vitelliform macular dystrophy is an irregular autosomal dominant eye disorder which can cause progressive vision loss. This disorder affects the retina, specifically cells in a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The condition is characterized by yellow (or orange), slightly elevated, round structures similar to the yolk (Latin vitellus) of an egg. Genetics Best disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. The inheritance pattern of adult-onset vitelliform macular dystrophy is definitively autosomal dominant. Many affected people, however, have no history of the disorder in their family and only a small number of affected families have been reported. This is because the penetrance of the condition is incomplete; therefore, it is possible for an individual to have a copy of the mutant allele and not display the VMD phenotype. The ratio of males to females is approximately 1:1. Pathophysiology Mutations in the RDS and VMD2 genes cause vitelliform macular dystrophy. Mutations in the VMD2 gene are responsible for Best disease. Changes in either the VMD2 or RDS gene can cause the adult-onset form of vitelliform macular dystrophy; however, fewer than a quarter of cases result from mutations in these two genes. In most cases, the cause of the adult-onset form is unknown. The VMD2 gene provides instructions for making a protein called bestrophin. Although its exact function is uncertain, this protein likely acts as a channel that controls the movement of negatively charged chlorine atoms (chloride ions) into or out of cells in the retina. Mutations in the VMD2 gene probably lead to the production of an abnormally shaped channel that cannot regulate the flow of chloride. Researchers have not determined how these malfunctioning channels are related to the buildup of lipofuscin in the macula and progressive vision loss. The RDS gene provides instructions for making a protein called peripherin. This protein is essential for the normal function of light-sensing (photoreceptor) cells in the retina. Mutations in the RDS gene disrupt the structures in these cells that contain light-sensing pigments, leading to vision loss. It is unclear why RDS mutations affect only central vision in people with adult-onset vitelliform macular dystrophy. Diagnosis Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. The retinal pigment epithelium also degenerates. Over time, the abnormal accumulation of this substance can damage the cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision and may experience blurry or distorted vision, and loss is rarely symmetric. Scotomata appear, first with red light and then for green; finally, relative (or in more serious cases, absolute) scotomata occur with white light. Vitelliform macular dystrophy does not affect side (peripheral) vision or the ability to see at night. Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood. The disease received its name from a German ophthalmologist Friedrich Best who defined a pedigree living with various stages of the disease in 1905. The onset of symptoms and the severity of vision loss vary widely. The adult-onset form begins later, usually in middle age, and tends to cause relatively mild vision loss. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination. In the Best disease, the paraclinic evaluations such as fundus fluorescein angiography or indocyanine green angiography, along with baseline and final electrooculography (EOG) results, may shed the light on the progression of disease. References Further reading External links Vitelliform macular dystrophy at NLM Genetics Home Reference Bests disease - eMedicine.com GeneReviews/NCBI/NIH/UW entry on Best Vitelliform Macular Dystrophy NCBI Genetic Testing Registry

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 seeking clarification on the medical term 'Hydrolethalus syndrome.' Could you explain it?

Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth.HLS is associated with HYLS1 mutations. The gene encoding HYLS1 is responsible for proper cilial development within the human body. Cilia are microscopic projections that allow sensory input and signalling output within cells, as well as cell motility. Dysfunction results in a range of abnormalities that are often the result of improper cell signalling. A variant form, HLS2, with additional mutations to the KIF7 gene, is less common. KIF7 also ensures correct cilia formation and function, specifically cilia stability and length.Hydrolethalus syndrome (HLS) was first mistakenly identified in Finland, during a study on Meckel syndrome. Like HLS, Meckel syndrome presents with severe physiological abnormalities, namely disruptions to the central nervous system and the presence of extra fingers or toes (polydactyly). HLS can be distinguished from Meckel syndrome by analysing kidney function, which is dysfunctional in Meckel syndrome as a result of cyst formation. Signs and symptoms HLS presents itself as various, lethal developmental abnormalities, which often result in either premature stillbirth or death shortly after birth. Rare cases of children born with HLS surviving for several months have been noted. A characteristic abnormality of HLS is an absence of brain tissue and midline structures, with the presence of excess brain fluid (hydrocephalus) as a result of abnormal development of the central nervous system. Other common defects include incomplete lung development, heart defects, a cleft lip or palate, polydactyly, and an abnormally small jaw. Stillbirth and an excess of amniotic fluid (polyhydramnios) are common during pregnancy with a HLS-affected foetus, with cases of up to 8 litres cited compared to the normal 1 litre. Less common symptoms such as abnormally small eyes and a broad nose are also possible. Cause Genetic HLS is caused by a genetic missense mutation of the HYLS1 gene, encoding for Hydrolethalus syndrome protein 1, on chromosome 11; a single base change to the amino acid sequence for HYLS1 in exon 6 involves the replacement of aspartic acid 211 with glycine (D211G) in the polypeptide chain. Exon 6 is the only protein coding exon in HYLS1; proper functioning of exons 1-5 ensures regulation and expression of the entire protein. HLS is an autosomal recessive syndrome; development is only possible if both parents carry the defective gene, and in that instance, the risk of the foetus developing the syndrome is 25%. HLS is a member of the Finnish disease heritage, with incidences more common in Finland than the rest of the world; roughly 1 in 20,000 developing foetuses are affected in Finland. Rare cases in other regions have also been documented, often with less severe phenotypes as a result of allele variability across countries, allowing survival of affected offspring for up to several months. Individuals of Finnish descent are advised to undergo genetic testing before attempting to conceive.Prior to the discovery of HLS, the HYLS1 gene was unknown, and similar genes within humans have not been identified. Orthologs, genes in other species with common ancestral heritage, have been examined to explain the pathophysiology of HLS; a similar gene within the roundworm, Caenorhabditis elegans, is responsible for the formation of cilia. Current hypotheses place a dysfunction of cilia as the main cause of HLS defects arising from the HYLS1 mutation in humans. Differences between wild type and mutant HYLS1 have been clearly observed; the wild type form is localised to the cytoplasm, while the mutant form is localised to the nucleus and forms small clusters, suggesting that the mutant gene disrupts cellular localisation. The protein encoded by the HYLS1 mutant form is unable to carry out essential targeting of centrioles to the plasma membrane, disrupting ciliary function, which results in ciliopathy. As cilia are located in almost all cells throughout the body, cilial dysfunction causes developmental defects in a range of organs and thus the phenotype of HLS can vary greatly, though brain malformation and polydactyly are most commonly observed. Environmental Currently, no environmental factors are known to increase the likelihood of HLS development or progression; HLS is caused only by genetic abnormalities. Pathophysiology The pathophysiology of HLS is abnormal cilia development arising from the inability of the mutated HYLS1 gene to correctly target centrioles to the plasma membrane. Specifically, transition fibres within the transition zone, at the base of the axoneme and adjoining to the plasma membrane, lack proper development. As these structures form the cilial gate, improper development results in a loss of selectivity for protein entry into the ciliary compartment. Variations and related pathologies Mutations in KIF7 have also been noted in patients that present a similar phenotype to HLS and the characteristic HYLS1 A to G transformation; homozygous deletion of the KIF7 gene causes a variant form of HLS, HLS2. KIF7 encodes a structural factor vital to cilial transport, and is also implicated in other developmental disorders, such as Joubert syndrome (JS). Additionally, mutations in HYLS1 are no longer explicitly connected to HLS in humans. Homozygous mutations removing the stop codon in exon 4 of HYLS1 result in a different genomic sequence disruption to the missense mutation of HLS, and phenotypically present as JS. The ‘molar tooth sign’ of the brain, an anomaly in which cerebellar volume is reduced but cerebellar shape is retained, resembles the molar tooth and is used to identify JS. JS presents with mutations in more than 30 genes, whilst the HYLS1 mutation is the sole cause of HLS, but is also present in the HLS2 variant form with the mutated KIF7 gene. Diagnosis HLS can be readily diagnosed during pregnancy through the use of ultrasound, which will often reveal hydrocephaly and an abnormal structure of the brain. Precise examination via ultrasound or at birth is necessary to rule out Meckel syndrome, Trisomy 13, or Smith–Lemli–Opitz syndrome, which present with similar physiological defects. HLS can be detected at the end of the first trimester, approximately 13 weeks gestation. Treatment No cure or treatment option for individuals with HLS currently exist. Due to the severity of the foetal defects and the poor prognosis for those with HLS, the pregnancy is often terminated. Certain prevention can only be achieved by avoiding conception if genetic testing indicates both prospective parents as carriers of the defective HYLS1 gene. See also •HYLS1 References == External links ==

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

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

Vaginismus is a condition in which involuntary muscle spasm interferes with vaginal intercourse or other penetration of the vagina. This often results in pain with attempts at sex. Often, it begins when vaginal intercourse is first attempted.The formal diagnostic criteria specifically requires interference during vaginal intercourse and a desire for intercourse. However, the term vaginismus is sometimes used more broadly to refer to any muscle spasms occurring during the insertion of some or all types of objects into the vagina, sexually motivated or otherwise, including the usage of speculums and tampons.The underlying cause is generally a fear that penetration will hurt. Risk factors include a history of sexual assault, endometriosis, vaginitis, or a prior episiotomy. Diagnosis is based on the symptoms and examination. It requires there to be no anatomical or physical problems and a desire for penetration on the part of the woman.Treatment may include behavior therapy such as graduated exposure therapy and gradual vaginal dilatation. Surgery is not generally indicated. Botulinum toxin (botox), a muscle spasm treatment, is being studied. Estimates of how common the condition is vary. One textbook estimates that 0.5% of women are affected. Outcomes are generally good with treatment. Signs and symptoms Severity and pain during vaginal penetration varies. Causes Primary vaginismus Vaginismus occurs when penetrative sex or other vaginal penetration cannot be experienced without pain. It is commonly discovered among teenage girls and women in their early twenties, as this is when many girls and young women first attempt to use tampons, have penetrative sex, or undergo a Pap smear. Awareness of vaginismus may not happen until vaginal penetration is attempted. Reasons for the condition may be unknown.A few of the main factors that may contribute to primary vaginismus include: chronic pain conditions and harm-avoidance behaviour negative emotional reaction towards sexual stimulation, e.g. disgust both at a deliberate level and also at a more implicit level strict conservative moral education, which also can elicit negative emotionsPrimary vaginismus is often unknown cause.Vaginismus has been classified by Lamont according to the severity of the condition. Lamont describes four degrees of vaginismus: In first degree vaginismus, the person has spasm of the pelvic floor that can be relieved with reassurance. In second degree, the spasm is present but maintained throughout the pelvis even with reassurance. In third degree, the person elevates the buttocks to avoid being examined. In fourth degree vaginismus (also known as grade 4 vaginismus), the most severe form of vaginismus, the person elevates the buttocks, retreats and tightly closes the thighs to avoid examination. Pacik expanded the Lamont classification to include a fifth degree in which the person experiences a visceral reaction such as sweating, hyperventilation, palpitations, trembling, shaking, nausea, vomiting, losing consciousness, wanting to jump off the table, or attacking the doctor.Although the pubococcygeus muscle is commonly thought to be the primary muscle involved in vaginismus, Pacik identified two additionally-involved spastic muscles in people who were treated under sedation. These include the entry muscle (bulbocavernosum) and the mid-vaginal muscle (puborectalis). Spasm of the entry muscle accounts for the common complaint that people often report when trying to have intercourse: "Its like hitting a brick wall". Secondary vaginismus Secondary vaginismus occurs when a person who has previously been able to achieve penetration develops vaginismus. This may be due to physical causes such as a yeast infection or trauma during childbirth, while in some cases it may be due to psychological causes, or to a combination of causes. The treatment for secondary vaginismus is the same as for primary vaginismus, although, in these cases, previous experience with successful penetration can assist in a more rapid resolution of the condition. Peri-menopausal and menopausal vaginismus, often due to a drying of the vulvar and vaginal tissues as a result of reduced estrogen, may occur as a result of "micro-tears" first causing sexual pain then leading to vaginismus. Mechanism Specific muscle involvement is unclear, but the condition may involve the pubococcygeus muscle, levator ani, bulbocavernosus, circumvaginal, or perivaginal muscles. Diagnosis The diagnosis of vaginismus, as well as other diagnoses of female sexual dysfunction, can be made when "symptoms are sufficient to result in personal distress." The DSM-IV-TR defines vaginismus as "recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with sexual intercourse, causing marked distress or interpersonal difficulty". Treatment A Cochrane review found little high quality evidence regarding the treatment of vaginismus in 2012. Specifically it is unclear if systematic desensitisation is better than other measures including nothing. Psychological According to a 2011 study, those with vaginismus are twice as likely to have a history of childhood sexual interference and held less positive attitudes about their sexuality, whereas no correlation was noted for lack of sexual knowledge or (nonsexual) physical abuse. Physical Often, when faced with a person experiencing painful intercourse, a gynecologist will recommend reverse Kegel exercises and provide some additional lubricants. Although vaginismus has not been shown to affect a persons ability to produce lubrication, providing additional lubricant can be helpful in achieving successful penetration. This is due to the fact that women may not produce natural lubrication if anxious or in pain. Achieving sufficient arousal during foreplay is crucial for the release of lubrication which can contribute to the ease of sexual penetration and pain-free intercourse. Though strengthening exercises such as Kegel exercises were previously considered to be a helpful intervention for pelvic pain, new research suggests that these exercises, which function to strengthen the pelvic floor, may not be helpful or may make conditions that are caused by over-active muscles such as vaginismus worse. Exercises that stretch or relax the pelvic floor may be a better treatment option for vaginismus.To help develop a treatment plan that best fits the needs of their patient, a gynecologist or general practitioner may refer a person experiencing painful intercourse to a Pelvic floor physical therapist or occupational therapist. These therapists specialize in the treatment of disorders of the pelvic floor muscles such as vaginismus, dyspareunia, vulvodynia, constipation, and fecal or urinary incontinence. After performing a manual exam both internally and externally to assess muscle function and to isolate possible trigger points for pain or tightness on the muscles, pelvic floor physical or occupational therapists develop a treatment plan consisting of muscle exercises, muscle stretches, dilator training, electrostimulation, and/or biofeedback interventions. Treatment of vaginismus often involves the use of Hegar dilators (sometimes called vaginal trainers), progressively increasing the size of the dilator inserted into the vagina. The technique is used to practice conscious diaphragmatic breathing (breathing in deeply allowing ones belly to expand) and allowing the pelvic floor muscles to lengthen during inhale; then exhale, bringing belly in and repeat. Research suggests pelvic floor physical or occupational therapy is one of the safest and most effective treatments for vaginismus. Neuromodulators Botulinum toxin A (Botox) has been considered as a treatment option, under the idea of temporarily reducing the hypertonicity of the pelvic floor muscles. Although no random controlled trials have been done with this treatment, experimental studies with small samples have shown it to be effective, with sustained positive results through 10 months. Similar in its mechanism of treatment, lidocaine has also been tried as an experimental option.Anxiolytics and antidepressants are other pharmacotherapies that have been offered to people in conjunction with other psychotherapy modalities, or if these peoples experience high levels of anxiety from their condition. Evidence for these medications, however, is limited. Epidemiology Estimates of how common the condition is varies. A 2016 textbook estimated about 0.5% of women are affected, while rates in Morocco and Sweden were estimated at 6%.Among those who attend clinics for sexual dysfunction, rates may be as high as 12 to 47%. See also Hymen Penis captivus Vulvodynia References Further reading Crowley T, Richardson D, Goldmeier D (January 2006). "Recommendations for the management of vaginismus: BASHH Special Interest Group for Sexual Dysfunction-free". Int J STD AIDS. 17 (1): 14–8. doi:10.1258/095646206775220586. PMID 16409672. S2CID 14152533.

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

I'd like to learn more about the medical term 'Light chain deposition disease.' Can you provide some details?

Light chain deposition disease (LCDD) is a rare blood cell disease which is characterized by deposition of fragments of infection-fighting immunoglobulins, called light chains (LCs), in the body. LCs are normally cleared by the kidneys, but in LCDD, these light chain deposits damage organs and cause disease. The kidneys are almost always affected and this often leads to kidney failure. About half of people with light chain deposition disease also have a plasma cell dyscrasia, a spectrum of diseases that includes multiple myeloma, Waldenströms macroglobulinemia, and the monoclonal gammopathy of undetermined significance premalignant stages of these two diseases. Unlike in AL amyloidosis, in which light chains are laid down in characteristic amyloid deposits, in LCDD, light chains are deposited in non-amyloid granules. Signs and symptoms The kidney is the organ most frequently affected. Proteinuria, the presence of protein in the urine, is characteristic. More than 90% of people with LCDD develop kidney failure, often with rapid progression of disease.Light chains may be deposited in many other organs and may or may not result in any symptoms. Other than the kidneys, liver and heart are the most commonly involved organs. Deposition of light chains in the liver may lead to hepatomegaly, an enlarged liver, or rarely portal hypertension or liver failure. The heart is affected in up to 80% of patients with LCDD, and may cause arrhythmias and congestive heart failure. Cause Diagnosis A number of laboratory tests are required in order to assist in diagnosing LCDD. Blood and urine samples are collected for evaluation of kidney and liver function and determination of the presence of a monoclonal protein. Imaging studies such as echocardiography and an ultrasound of the abdomen will be performed. A CT scan, magnetic resonance imaging (MRI) or positron emission tomography (PET) may also be indicated. In patients with LCDD, a biopsy of the affected organ will show deposited light chains. A bone marrow biopsy will be done in order to rule out multiple myeloma. Treatment Decreasing production of the organ-damaging light chains is the treatment goal. Options include chemotherapy using bortezomib, autologous stem cell transplantation, immunomodulatory drugs, and kidney transplant.There is no standard treatment for LCDD. High-dose melphalan in conjunction with autologous stem cell transplantation has been used in some patients. A regimen of bortezomib and dexamethasone has also been examined. Prognosis The median time to progression to end stage renal disease is 2.7 years. After 5 years, about 37% of patients with LCDD are alive and do not have end stage renal disease. References External links National Institutes of Health Genetic and Rare Diseases Information Center Emedicine

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 'Epoophoron.'

The epoophoron or epoöphoron (also called organ of Rosenmüller or the parovarium) is a remnant of the mesonephric tubules that can be found next to the ovary and fallopian tube. Anatomy It may contain 10–15 transverse small ducts or tubules that lead to the Gartner’s duct (also longitudinal duct of epoophoron) that represents the caudal remnant of the mesonephric duct and passes through the broad ligament and the lateral wall of the cervix and vagina. The epoophoron is a homologue to the epididymis in the male. While the epoophoron is located in the lateral portion of the mesosalpinx and mesovarium, the paroophoron (residual remnant of that part of the mesonephric duct that forms the paradidymis in the male) lies more medially in the mesosalpinx. Histology It has a unique histological profile. Clinical significance Clinically the organ may give rise to a local paraovarian cyst or adenoma. See also List of homologues of the human reproductive system Vesicular appendages of epoophoron References External links figures/chapter_35/35-8.HTM: Basic Human Anatomy at Dartmouth Medical School genital-016a—Embryo Images at University of North Carolina Swiss embryology (from UL, UB, and UF) ugenital/genitinterne05

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

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

Psoriasin may refer to: Coal tar, by-product of the production of coke and coal gas from coal. S100A7, S100 calcium-binding protein A7.

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.

Could you provide a brief overview of 'Frostbite' in a medical context?

Frostbite is a skin injury that occurs when exposed to extreme low temperatures, causing the freezing of the skin or other tissues, commonly affecting the fingers, toes, nose, ears, cheeks and chin areas. Most often, frostbite occurs in the hands and feet. The initial symptom is typically numbness. This may be followed by clumsiness with a white or bluish color to the skin. Swelling or blistering may occur following treatment. Complications may include hypothermia or compartment syndrome.People who are exposed to low temperatures for prolonged periods, such as winter sports enthusiasts, military personnel, and homeless individuals, are at greatest risk. Other risk factors include drinking alcohol, smoking, mental health problems, certain medications, and prior injuries due to cold. The underlying mechanism involves injury from ice crystals and blood clots in small blood vessels following thawing. Diagnosis is based on symptoms. Severity may be divided into superficial (1st and 2nd degree) or deep (3rd and 4th degree). A bone scan or MRI may help in determining the extent of injury.Prevention is by wearing proper, fully-covering clothing, maintaining hydration and nutrition, avoiding low temperatures, and minimizing strenuous physical activity while maintaining a sufficient core temperature. Treatment is by gradual rewarming, generally from cold to warm water, and should only be done when consistent temperature can be maintained and refreezing is not a concern. Rapid heating or cooling should be avoided since it could potentially cause heart stress or cause burning. Rubbing or applying force to the affected areas should be avoided as it may cause further damage such as abrasions. The use of ibuprofen and tetanus toxoid is recommended for pain relief or to reduce swelling or inflammation. For severe injuries, iloprost or thrombolytics may be used. Surgery is sometimes necessary. Amputation should be considered a few months after exposure in order to consider whether the extent of injury is permanent damage and thus necessitates drastic treatment.Evidence of frostbite occurring in people dates back 5,000 years. Evidence was documented in a pre-Columbian mummy discovered in the Andes. The number of cases of frostbite is unknown. Rates may be as high as 40% a year among those who mountaineer. The most common age group affected is those 30 to 50 years old. Frostbite has also played an important role in a number of military conflicts. The first formal description of the condition was in 1813 by Dominique Jean Larrey, a physician in Napoleons army, during its invasion of Russia. Signs and symptoms Areas that are usually affected include cheeks, ears, nose and fingers and toes. Frostbite is often preceded by frostnip. The symptoms of frostbite progress with prolonged exposure to cold. Historically, frostbite has been classified by degrees according to skin and sensation changes, similar to burn classifications. However, the degrees do not correspond to the amount of long term damage. A simplification of this system of classification is superficial (first or second degree) or deep injury (third or fourth degree). First degree First degree frostbite is superficial, surface skin damage that is usually not permanent. Early on, the primary symptom is loss of feeling in the skin. In the affected areas, the skin is numb, and possibly swollen, with a reddened border. In the weeks after injury, the skins surface may slough off. Second degree In second degree frostbite, the skin develops clear blisters early on, and the skins surface hardens. In the weeks after injury, this hardened, blistered skin dries, blackens, and peels. At this stage, lasting cold sensitivity and numbness can develop. Third degree In third degree frostbite, the layers of tissue below the skin freeze. Symptoms include blood blisters and "blue-grey discoloration of the skin". In the weeks after injury, pain persists and a blackened crust (eschar) develops. There can be longterm ulceration and damage to growth plates. Fourth degree In fourth degree frostbite, structures below the skin are involved like muscles, tendon, and bone. Early symptoms include a colorless appearance of the skin, a hard texture, and painless rewarming. Later, the skin becomes black and mummified. The amount of permanent damage can take one month or more to determine. Autoamputation can occur after two months. Causes Risk factors The major risk factor for frostbite is exposure to cold through geography, occupation and/or recreation. Inadequate clothing and shelter are major risk factors. Frostbite is more likely when the bodys ability to produce or retain heat is impaired. Physical, behavioral, and environmental factors can all contribute to the development of frostbite. Immobility and physical stress (such as malnutrition or dehydration) are also risk factors. Disorders and substances that impair circulation contribute, including diabetes, Raynauds phenomenon, tobacco and alcohol use. Homeless individuals and individuals with some mental illnesses may be at higher risk. Mechanism Freezing In frostbite, cooling of the body causes narrowing of the blood vessels (vasoconstriction). Temperatures below −23 °C (−9 °F) are required to form ice crystals in the tissues. The process of freezing causes ice crystals to form in the tissue, which in turn causes damage at the cellular level. Ice crystals can damage cell membranes directly. In addition, ice crystals can damage small blood vessels at the site of injury. Scar tissue forms when fibroblasts replace the dead cells. Rewarming Rewarming causes tissue damage through reperfusion injury, which involves vasodilation, swelling (edema), and poor blood flow (stasis). Platelet aggregation is another possible mechanism of injury. Blisters and spasm of blood vessels (vasospasm) can develop after rewarming. Non-freezing cold injury The process of frostbite differs from the process of non-freezing cold injury (NFCI). In NFCI, temperature in the tissue decreases gradually. This slower temperature decrease allows the body to try to compensate through alternating cycles of closing and opening blood vessels (vasoconstriction and vasodilation). If this process continues, inflammatory mast cells act in the area. Small clots (microthrombi) form and can cut off blood to the affected area (known as ischemia) and damage nerve fibers. Rewarming causes a series of inflammatory chemicals such as prostaglandins to increase localized clotting. Pathophysiology The pathological mechanism by which frostbite causes body tissue injury can be characterized by four stages: Prefreeze, freeze-thaw, vascular stasis, and the late ischemic stage. Prefreeze phase: involves the cooling of tissues without ice crystal formation. Freeze-thaw phase: ice-crystals form, resulting in cellular damage and death. Vascular stasis phase: marked by blood coagulation or the leaking of blood out of the vessels. Late ischemic phase: characterized by inflammatory events, ischemia and tissue death. Diagnosis Frostbite is diagnosed based on signs and symptoms as described above, and by patient history. Other conditions that can have a similar appearance or occur at the same time include: Frostnip is similar to frostbite, but without ice crystal formation in the skin. Whitening of the skin and numbness reverse quickly after rewarming. Trench foot is damage to nerves and blood vessels that results exposure to wet, cold (non-freezing) conditions. This is reversible if treated early. Pernio or chilblains are inflammation of the skin from exposure to wet, cold (non-freezing) conditions. They can appear as various types of ulcers and blisters. Bullous pemphigoid is a condition that causes itchy blisters over the body that can mimic frostbite. It does not require exposure to cold to develop. Levamisole toxicity is a vasculitis that can appear similar to frostbite. It is caused by contamination of cocaine by levamisole. Skin lesions can look similar those of frostbite, but do not require cold exposure to occur.People who have hypothermia often have frostbite as well. Since hypothermia is life-threatening this should be treated first. Technetium-99 or MR scans are not required for diagnosis, but might be useful for prognostic purposes. Prevention The Wilderness Medical Society recommends covering the skin and scalp, taking in adequate nutrition, avoiding constrictive footwear and clothing, and remaining active without causing exhaustion. Supplemental oxygen might also be of use at high elevations. Repeated exposure to cold water makes people more susceptible to frostbite. Additional measures to prevent frostbite include: Avoiding temperatures below −23 °C (-9 °F) Avoiding moisture, including in the form of sweat and/or skin emollients Avoiding alcohol and drugs that impair circulation or natural protective responses Layering clothing Using chemical or electric warming devices Recognizing early signs of frostnip and frostbite Treatment Individuals with frostbite or potential frostbite should go to a protected environment and get warm fluids. If there is no risk of re-freezing, the extremity can be exposed and warmed in the groin or underarm of a companion. If the area is allowed to refreeze, there can be worse tissue damage. If the area cannot be reliably kept warm, the person should be brought to a medical facility without rewarming the area. Rubbing the affected area can also increase tissue damage. Aspirin and ibuprofen can be given in the field to prevent clotting and inflammation. Ibuprofen is often preferred to aspirin because aspirin may block a subset of prostaglandins that are important in injury repair.The first priority in people with frostbite should be to assess for hypothermia and other life-threatening complications of cold exposure. Before treating frostbite, the core temperature should be raised above 35 °C. Oral or intravenous (IV) fluids should be given.Other considerations for standard hospital management include: wound care: blisters can be drained by needle aspiration, unless they are bloody (hemorrhagic). Aloe vera gel can be applied before breathable, protective dressings or bandages are put on. antibiotics: if there is trauma, skin infection (cellulitis) or severe injury tetanus toxoid: should be administered according to local guidelines. Uncomplicated frostbite wounds are not known to encourage tetanus. pain control: NSAIDs or opioids are recommended during the painful rewarming process. Rewarming If the area is still partially or fully frozen, it should be rewarmed in the hospital with a warm bath with povidone iodine or chlorhexidine antiseptic. Active rewarming seeks to warm the injured tissue as quickly as possible without burning. The faster tissue is thawed, the less tissue damage occurs. According to Handford and colleagues, "The Wilderness Medical Society and State of Alaska Cold Injury Guidelines recommend a temperature of 37–39 °C, which decreases the pain experienced by the patient whilst only slightly slowing rewarming time." Warming takes 15 minutes to 1 hour. The faucet should be left running so the water can circulate. Rewarming can be very painful, so pain management is important. Medications People with potential for large amputations and who present within 24 hours of injury can be given TPA with heparin. These medications should be withheld if there are any contraindications. Bone scans or CT angiography can be done to assess damage.Blood vessel dilating medications such as iloprost may prevent blood vessel blockage. This treatment might be appropriate in grades 2–4 frostbite, when people get treatment within 48 hours. In addition to vasodilators, sympatholytic drugs can be used to counteract the detrimental peripheral vasoconstriction that occurs during frostbite.A systematic review and metaanalysis revealed that iloprost alone or iloprost plus recombinant tissue plasminogen activator (rtPA) may decrease amputation rate in case of severe frostbite in comparison to buflomedil alone with no major adverse events reported from iloprost or iloprost plus rtPA in the included studies. Surgery Various types of surgery might be indicated in frostbite injury, depending on the type and extent of damage. Debridement or amputation of necrotic tissue is usually delayed unless there is gangrene or systemic infection (sepsis). This has led to the adage "Frozen in January, amputate in July". If symptoms of compartment syndrome develop, fasciotomy can be done to attempt to preserve blood flow. Prognosis Tissue loss and autoamputation are potential consequences of frostbite. Permanent nerve damage including loss of feeling can occur. It can take several weeks to know what parts of the tissue will survive. Time of exposure to cold is more predictive of lasting injury than temperature the individual was exposed to. The classification system of grades, based on the tissue response to initial rewarming and other factors is designed to predict degree of longterm recovery. Grades Grade 1: if there is no initial lesion on the area, no amputation or lasting effects are expected Grade 2: if there is a lesion on the distal body part, tissue and fingernails can be destroyed Grade 3: if there is a lesion on the intermediate or near body part, auto-amputation and loss of function can occur Grade 4: if there is a lesion very near the body (such as the carpals of the hand), the limb can be lost. Sepsis and/or other systemic problems are expected.A number of long term sequelae can occur after frostbite. These include transient or permanent changes in sensation, paresthesia, increased sweating, cancers, and bone destruction/arthritis in the area affected. Epidemiology There is a lack of comprehensive statistics about the epidemiology of frostbite. In the United States, frostbite is more common in northern states. In Finland, annual incidence was 2.5 per 100,000 among civilians, compared with 3.2 per 100,000 in Montreal. Research suggests that men aged 30–49 are at highest risk, possibly due to occupational or recreational exposures to cold. History Frostbite has been described in military history for millennia. The Greeks encountered and discussed the problem of frostbite as early as 400 BCE. Researchers have found evidence of frostbite in humans dating back 5,000 years, in an Andean mummy. Napoleons Army was the first documented instance of mass cold injury in the early 1800s. According to Zafren, nearly 1 million combatants fell victim to frostbite in the First and Second World Wars, and the Korean War. Society and culture Several notable cases of frostbite include: Captain Lawrence Oates, an English army captain and Antarctic explorer who in 1912 died of complications of frostbite; Harold Bride, the junior wireless operator of RMS Titanic, who suffered severe frostbite on his feet as he and other survivors stood for over an hour on the back of a capsized lifeboat knee-deep in freezing water--Bride had to be carried off from the rescue vessel RMS Carpathia after it arrived in New York; noted American rock climber Hugh Herr, who in 1982 lost both legs below the knee to frostbite after being stranded on Mount Washington (New Hampshire) in a blizzard; Beck Weathers, a survivor of the 1996 Mount Everest disaster who lost his nose and hands to frostbite; Scottish mountaineer Jamie Andrew, who in 1999 had all four limbs amputated due to sepsis from frostbite sustained after becoming trapped for four nights whilst climbing Les Droites in the Mont Blanc massif. Research directions Evidence is insufficient to determine whether or not hyperbaric oxygen therapy as an adjunctive treatment can assist in tissue salvage. Cases have been reported, but no randomized control trial has been performed on humans.Medical sympathectomy using intravenous reserpine has also been attempted with limited success. Studies have suggested that administration of tissue plasminogen activator (tPa) either intravenously or intra-arterially may decrease the likelihood of eventual need for amputation. References External links Mayo Clinic Definition

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

I'm encountering the term 'Postoperative nausea and vomiting' in medical literature. What's its definition?

Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the postanesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population undergoing general anaesthesia each year. PONV can be unpleasant and lead to a delay in mobilization and food, fluid, and medication intake following surgery. Cause Emetogenic drugs commonly used in anaesthesia include nitrous oxide, physostigmine, and opioids. The intravenous anaesthetic propofol is currently the least emetogenic general anaesthetic. These medications are thought to stimulate the chemoreceptor trigger zone. This area is on the floor of the fourth ventricle and is effectively outside of the blood-brain barrier, which makes it incredibly sensitive to toxin and pharmacological stimulation. Several neurotransmitters are known, such as histamine, dopamine, serotonin, acetylcholine, and the more recently discovered neurokinin-1 (substance P). Risk factors A 2008 study compared 121 Japanese patients who experienced PONV after being given the general anesthetic propofol to 790 people who were free of postoperative nausea after receiving it. Those with a G at both copies of rs1800497 were 1.6 times more likely to experience PONV within six hours of surgery compared to those with the AG or AA genotypes, but they were not significantly more likely to experience PONV more than six hours after surgery.PONV results from patient, surgical, and anesthetic factors.Surgical factors that confer increased risk for PONV include procedures of increased length and gynecological, abdominal, laparoscopic and ENT procedures, and strabismus procedures in children. Anesthetic risk factors include the use of volatile anesthetics, nitrous oxide (N2O), opioids, and longer duration of anesthesia. Patient factors that confer increased risk for PONV include female gender, obesity, age less than 16 years, past history of motion sickness or chemotherapy-induced nausea, high levels of preoperative anxiety, and patients with history of PONV. Smokers and the elderly often have a decreased risk for PONV. A risk-stratification method created by Apfel et al has been developed to determine a patients risk for PONV. The presence of 0, 1, 2, 3, or 4 of any of the following risk factors corresponds to a PONV respective risk of 10, 20, 40, 60, and 80%.- Female gender - Non-smoking - History of PONV or motion sickness - Expectant use of postoperative opioid medications Prevention Treatment options to prevent PONV include medications such as antiemetics (for example, ondansetron or dexamethasone) or other drugs including tropisetron, dolasetron, cyclizine, and granisetron. Droperidol may cause QT prolongation and is not frequently used. Other approaches to reduce PONV include decision on the types of anaesthetic used during surgery and intravenous (IV) dextrose solutions. Increasing the IV fluids during surgery by giving additional fluid while the person is under general anaesthesia may reduce the risk of nausea/vomiting after surgery. For minor surgical procedures, more research is needed to determine the risks and benefits of this approach. Management Because currently no single antiemetic available is especially effective on its own, experts recommend a multimodal approach. Anesthetic strategies to prevent vomiting include using regional anesthesia whenever possible and avoiding medications that cause vomiting. Medications to treat and prevent PONV are limited by both cost and the adverse effects. People with risk factors likely warrant preventive medication, whereas a "wait and see" strategy is appropriate for those without risk factors. Preoperative fasting Fasting guidelines often restrict the intake of any oral fluid 2-6 hours preoperatively, but in a large retrospective analysis in Torbay Hospital, unrestricted clear oral fluids until transfer to theatre could significantly reduce the incidence of postoperative nausea and vomiting without an increased risk in the adverse outcomes for which such conservative guidance exists. Medications A multimodal approach to treating a patient with PONV can be efficacious. Numerous patient factors and medication adverse effects must be taken into consideration when selecting a treatment regimen. Serotonin (5-HT3) receptor antagonists can be administered as a single dose at the end of surgery. Adverse effects include prolongation of the QT interval on electrocardiogram (EKG). Medications include ondansetron, granisetron, and dolasetron. Anticholinergics can be used as a long-acting patch placed behind the patients ear. Adverse effects include dry mouth and blurry vision. Care must be taken when handling the patch, as transfer of medication to the eye can induce pupillary dilation. Avoid use in elderly patients. Medications include scopolamine. Glucocorticoids have direct antiemetic effects and can reduce need for postoperative opioids. Adverse effects include a transient increase in serum glucose level, and poor wound healing (controversial). Medications include dexamethasone. Butyrophenones are typically administered as a single injection at the end of surgery. Adverse effects include prolongation of the QT interval on EKG. Medications include droperidol and haloperidol. Phenothiazines are particularly effective in treating opioid-induced PONV. Adverse effects are dose-dependent and include sedation and extrapyramidal symptoms. Medications include promethazine and prochlorperazine. Neurokinin 1 (NK1) receptor antagonists prevent an emetic signal from being transmitted. Medications include aprepitant and rolapitant. Histamine receptor antagonists can be administered by multiple routes, including orally, intramuscularly, or rectally. Adverse effects include dry mouth, sedation, and urinary retention. Medications include dimenhydrinate and diphenhydramine. Propofol, an anesthetic medication, confers its own antiemetic properties.The 2020 Cochrane Anaesthesia Review Group review of Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis (Review) demonstrated that combination therapy is more effective than single anti-emetic, and that dexamethasone and ondansetron (a commonly used combination) are two of the most effective anti-emetics for PONV. The review adds robust evidence of efficacy for drugs in newer classes, such as aprepitant or fosapreitant, or newer agents in familiar classes, such as ramosetron. The review does not cover the cost effectiveness of the agents included and, despite increased efficacy for newer novel agents, this may preclude their immediate utilisation in anaesthetic practice. Alternative medicine In conjunction with antiemetic medications, at least one study has found that application to the pericardium meridian 6 acupressure point produced a positive effect in relieving PONV. Another study found no statistically significant difference. The two general types of alternative pressure therapy are sham acupressure and the use of the P6 point. A 2015 study found no significant difference between the use of either therapy in the treatment or prevention of PONV. In a review of 59 studies, both therapies significantly affected the nausea aspect, but had no significant effect on vomiting. Cannabinoids have also been used for treatment of PONV, but its safety and efficacy are controversial. Epidemiology Typically, the incidence of nausea or vomiting after general anesthesia ranges between 25 and 30%. Nausea and vomiting can be extremely distressing for patients, and so is one of their major concerns. Vomiting has been associated with major complications, such as pulmonary aspiration of gastric content, and might endanger surgical outcomes after certain procedures, for example after maxillofacial surgery with wired jaws. Nausea and vomiting can delay discharge, and about 1% of patients scheduled for day surgery require unanticipated overnight admission because of uncontrolled PONV. References Further reading Blackburn, J., Spencer, R. (2015). Postoperative nausea and vomiting. Pleuvry, B. (2015). Physiology and pharmacology of nausea and vomiting. == External links ==

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.

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

Adenomyomatosis is a benign condition characterized by hyperplastic changes of unknown cause involving the wall of the gallbladder. Adenomyomatosis is caused by an overgrowth of the mucosa, thickening of the muscular wall, and formation of intramural diverticula or sinus tracts termed Rokitansky–Aschoff sinuses, also called entrapped epithelial crypts. Signs and symptoms Pathophysiology Rokitansky–Aschoff sinuses Rokitansky–Aschoff sinuses are pseudodiverticula or pockets in the wall of the gallbladder. They may be microscopic or macroscopic. Histologically, they are outpouchings of gallbladder mucosa into the gallbladder muscle layer and subserosal tissue as a result of hyperplasia and herniation of epithelial cells through the fibromuscular layer of the gallbladder wall.Rokitansky–Aschoff sinuses are not of themselves considered abnormal but they can be associated with cholecystitis.They form as a result of increased pressure in the gallbladder and recurrent damage to the wall of the gallbladder. Associations Black pigment gallstones can form in Rokitansky–Aschoff sinuses of the gallbladder after the fourth to fifth decades of life in absence of the typical risk factors for bilirubin supersaturation of bile. Hence, they are associated with gallstones (cholelithiasis). Cases of gall bladder cancer have also been reported to arise from Rokitansky–Aschoff sinuses. Diagnosis Abdominal ultrasound has low accuracy in differentiating gall bladder adenomyomatosis from cancer and is operator dependent. However, it is used as the exam of the first-line due to its wide availability. Ultrasound findings may show thickened gall bladder wall, tiny anechoic spaces (Rokitansky–Aschoff sinuses or RAS), and twinkling artifact (or comet-tail reverberation). Comet tail reverberation, which is due to reflections from cholesterol crystals, is a highly specific sign for adenomyomatosis.On CT scan, it may show rosary sign, showing mucosal epithelium with intramural diverticula.Magnetic resonance imaging also plays an important role in the diagnosis of Rokitansky–Aschoff sinuses. In fat-suppression MRI, RAS present with small, rounded, high signal intensity foci, called “pearl necklace sign”. Eponym Rokitansky–Aschoff sinuses are named after Carl Freiherr von Rokitansky (1804–1878), a pathologist in Vienna, Austria and Ludwig Aschoff (1866–1942), a pathologist in Bonn, Germany. See also Cholecystectomy Strawberry gallbladder Diverticulum Hyperplasia Gallbladder References External links 00859 at CHORUS

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 'Oxycodone/paracetamol' while reading about medical topics. What does it refer to exactly?

Oxycodone/paracetamol, sold under the brand name Percocet among others, is a combination of the opioid oxycodone with paracetamol (acetaminophen), used to treat moderate to severe pain. In 2019, it was the 59th most commonly prescribed medication in the United States, with more than 11 million prescriptions. History The United States Food and Drug Administration (FDA) first approved Percocet in 1976, under application ANDA 085106. Implicated in deaths On June 30, 2009, an FDA advisory panel recommended that Percocet, Vicodin, and every other combination of acetaminophen with narcotic analgesics be limited in their sales because of their contributions to an alleged 400 acetaminophen-related deaths in the U.S. each year, that were attributed to acetaminophen overdose and associated liver damage.In December 2009, the Canadian Medical Association Journal reported a study finding a fivefold increase in oxycodone-related deaths in Ontario (mostly accidental) between 1991 and 2007 that led to a doubling of all opioid-related deaths in Ontario over the same period.In March 2017, U.S. President Donald Trump initiated the Opioid and Drug Abuse Commission. In July 2017, an interim report was published. Some excerpts: References External links "Acetaminophen mixture with Oxycodone". Drug Information Portal. U.S. National Library of Medicine. "Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure". U.S. Food and Drug Administration. 13 January 2011. "FDA warns about several safety issues with opioid pain medicines; requires label changes". U.S. Food and Drug Administration. 22 March 2016. "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning". U.S. Food and Drug Administration. 31 August 2016.

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

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

Ethinylestradiol/drospirenone (EE/DRSP), sold under the brand name Yasmin among others, is a combination of ethinylestradiol (EE), an estrogen, and drospirenone (DRSP), a progestin, antimineralocorticoid, and antiandrogen, which is used as a birth control pill to prevent pregnancy in women. It is also indicated for the treatment of moderate acne, premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and dysmenorrhea (painful menstruation) in women. The medication is taken by mouth and contains 30 μg EE and 3 mg DRSP per tablet (brand names Yasmin, others) or 20 μg EE and 3 mg DRSP per tablet (brand names Yaz, Yasminelle, Nikki, others). A formulation with levomefolic acid (vitamin B9) has also been marketed (brand names Beyaz, Safyral, others), with similar indications. EE/DRSP is marketed widely throughout the world.In 2019, it was the 148th most commonly prescribed medication in the United States, with more than 4 million prescriptions. See also Ethinylestradiol/drospirenone/levomefolic acid Ethinylestradiol/drospirenone/prasterone Estradiol/drospirenone List of combined sex-hormonal preparations § Estrogens and progestogens References External links "Drospirenone mixture with estradiol". Drug Information Portal. U.S. National Library of Medicine.

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 seeking clarification on the medical term 'Paraneoplastic pemphigus.' Could you explain it?

Paraneoplastic pemphigus (PNP) is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes. While patients with malignant and benign tumors are both at risk, malignancy is associated with high mortality rates (near 90%). Current treatment focuses on general wound healing and administering corticosteroids, which has not demonstrated a high success rate. Recent research developments aim to treat the underlying tumor in order to alleviate the symptoms of PNP. Signs and symptoms While the presence of lesions is the denominator among patients with PNP, the characteristics of the lesions differ. The five clinical presentations of lesions associated with PNP include: "Pemphigus-like": Flaccid blister (discrete), crusts over the raw exuding skin lesions "Pemphigoid-like": Tense blister(s) on brick red erythema "Erythema multiforme-like": Severe polymorphic skin and/or mucous membrane lesions "Graft-vs.-host disease-like": Widespread lichenoid eruption with severe mucous membrane involvement "Lichen planus-like": Small red flat-topped scaly papulesIt is most common that mucous membrane lesions of the oral cavity are presented first. They can involve the oropharynx, nasopharynx, tongue, and vermilion (red portion) of the lips. They are also known to develop in the conjunctiva of the eye, anogenital (perineum) region, and esophagus. Cutaneous lesions tend to follow the onset of mucosal lesions. The blisters often erupt in waves, usually affecting the upper trunk, head, neck, and proximal extremities. Pemphigoid-like lesions are seen more often on the extremities. Lichenoid lesions are more common among children, presenting on the trunk and limbs, ranging from small red scaly papules to extensive violet to brown papules extending to the face and neck. Within the spectrum of lichenoid presentations are wounds that have features of erythema multiforme and graft-vs.-host disease. Scaly lesions on the palms of the hand and soles of the feet have been noted to coincide with the lichenoid lesions. Lesions of varying morphology may present simultaneously and transform from one type to another as the disease progresses. Mechanism Underlying cause PNP is ultimately caused by the presence of a tumor. There is a strong association between the development of PNP and malignancy of the tumor. However, it is not uncommon for the tumor to be benign, as in the case of afflictions such as thymoma and Castlemans disease. Only one patient without a tumor has met the diagnostic criteria for PNP. However, they rapidly reached their demise and it is suggested they may have had an undiagnosed tumor. Mechanism behind display of major symptoms The underlying tumor causes circulating and tissue-bound antibodies to direct themselves against antigens in the plakin family, which are involved in the intracellular attachment structures in various levels of the skin/respiratory tract/membranes (keeping skin tissue together throughout the body). The number of target antigens varies on a case by case basis. The variability is likely what accounts for the different presentations of PNP. Through immunoprecipitation, target antigens have been found to include desmoglein-3, desmoglein-1, envoplakin, periplakin, desmoplakin 1, desmoplakin 2, and bullous pemphigoid antigen I.The precise mechanism for how tumors are able to induce autoantibodies toward the plakin proteins is unknown. Suggested theories include tumor production of plakin proteins which initiate an autoimmune response against them, and cross-reactivity of tumor antigens and epidermal antigens.Once the molecules that hold the various levels of the membranes together are attacked, they are unable to function properly, and the tissue breaks apart. This is manifested as the associated blistering and lesions of PNP. Diagnosis In order to diagnose paraneoplastic pemphigus, several tests may be performed. Initially, samples are obtained via skin biopsy for routine microscopy and direct immunofluorescence (DIF) testing. The skin sample needs to be obtained from an unaffected area adjacent to a lesion. Testing in more detail follows depending on the results from the DIF. Prompt diagnosis of PNP is crucial due to the high mortality rate of the disease. Camisa and Helm revised the original criteria from Anhalt et al. into major and minor signs indicating PNP:Major: Polymorphic mucocutaneous eruption Concurrent internal tumor Serum antibodies with a specific immunoprecipitation patternMinor: Histologic evidence of acantholysis (loss of intercellular connections leading to breaking apart of the skin; lesion) Direct immunofluorescence showing intercellular and basement membrane staining Indirect immunofluorescence staining with rat bladder epithelium Microscopy Microscopy of the skin sample obtained from the biopsy is used to detect the presence of cleavage within the dermis, epidermal acantholysis (breaking apart of the skin), dyskeratotic keratinocytes and vacuolar changes in the layers of the skin, interfacial dermatitis, and epidermal exocytosis. Presentation of these characteristics suggests PNP. Direct immunofluorescence testing The presence of Immunoglobulin G, A, or M in the epidermis is normal. Detection in other locations such as intercellular and areas below the epidermis (subepidermal), as well as along the dermoepidermal junction (area that joins the epidermis and dermis), suggests paraneoplastic pemphigus. Follow-up tests for confirmation Indirect immunofluorescence (IDIF) Patients with high concentration of antibodies show intercellular, intraepidermal antibodies as well as along the dermoepidermal junction. Patients with low concentration of antibodies only present with them inside the cells (intercellular).If the results are negative, perform the additional assays regardless. Cases have been confirmed that reported with initial negative DIF and IDIF tests. Assays Immunoprecipitation, immunoblotting and enzyme-link immunosorbent assay (ELISA) Poot et al. 2013 determined that immunoprecipitation for antibodies against envoplakin and periplakin or alpha2-macroglobulin-like–1 is the most sensitive test. However, alpha2-macroglobulin-like-1 can also be detected in patients with toxic epidermal necrosis. Similar diseases with overlapping symptoms Bullous Pemphigoid, Cicatricial Pemphigoid, Drug Eruptions. Epidermolysis Bullosa, Epidermolysis Bullosa Acquisita, Erythema Multiforme, Lichen Planus, pemphigus vulgaris, Stevens–Johnson syndrome and toxic epidermal necrolysis.PNP is most commonly mistaken for pemphigus vulgaris, due to the extreme similarities of the lesions that develop. However, the difference lies in the specificity of the autoreactive antibodies in each case. Treatment Wound healing Initial treatment involves addressing any existing infections that may have occurred due to the broken state of the skin. Existing wounds are treated with warm compresses, non-adherent (non-stick) dressing, and topical antibiotic ointment. Immunosuppressive agents are administered in attempt to decrease blistering; this is not often effective. The first medication given aiming to heal the wounds are high dose corticosteroids. This is followed by steroid sparing agents which may reduce steroid intake and therefore lessen the side effects. Skin lesions are more likely to respond to this line of treatment than mucosal lesions. However, a high level of caution is advised in patients with a confirmed malignancy, where immunosuppression is vital and dictates treatment options. If the initial therapy fails to control the symptoms of PNP, and the condition of the patient deteriorates, a more aggressive approach may be necessary. Medication Prednisone Prednisone is an immunosuppressive agent which affects all of the organ systems. Effects on the cellular level include cell activation, replication, differentiation, and mobility. The overall goal is to decrease blistering (inhibition of immediate and delayed hypersensitivity) through decreasing the production of autoantibodies. In order to suppress the production of antibodies, higher doses must be administered. Lesser doses can be prescribed in order to achieve suppression of monocyte function. Azathioprine Azathioprine is a steroid-sparing agent used in combination with Prednisone. It functions by inhibiting RNA and DNA synthesis. Ciclosporin Ciclosporin is an immunosuppressive agent most often used in organ transplantation that has demonstrated to be effective with skin disorders. It functions by lessening production of autoantibodies and therefore diminishing the development of blisters and erosions. The mechanism of action is by inhibiting the production of T lymphocytes and lymphokines. Cyclophosphamide Cyclophosphamide is an immunomodulator used in combination with systemic steroids to remove bone marrow. This is followed by transplanting peripheral blood stem cells. Prognosis Quality of life/ Life expectancy If the lesions are mild, the patient will be subject to a good deal of pain. If the lesions are severe, the overall quality of life is devastating. The impaired skin barrier function commonly leads to localized infection, which sepsis and death may follow. The pain from the oral and pharyngeal ulcers interfere with eating, which can compromise nutritional health.The general prognosis for PNP is poor. It is more hopeful if the tumor is benign, but in the case of malignant tumors, the mortality rate is roughly 90%. The two most commonly associated types of tumors are non-Hodgkin lymphoma and chronic lymphocytic lymphoma; nearly all of these patients die within two years of diagnosis. This is attributed to the effects of the tumor combined with the negative side effects of the medication administered to treat PNP.Roughly 1/3 of the deaths from PNP stem from pulmonary insufficiency which is brought about by the action of PNP on the respiratory mucosa. It manifests as dyspnea and progresses to bronchiolitis obliterans (non-reversible obstructive lung disease) via an unknown mechanism. Risk Factors As PNP is ultimately caused by the presence of a tumor, it is not contagious. There is no known way to predict who will become afflicted with it. Patients with cancer are therefore a group at risk. Although PNP has been known to affect all age groups, it is more likely to afflict middle-aged to older patients. Recent research The Development of ELISA testing for specific diagnosis of PNP was released in 2009. The research focuses on the specific determination of autoantibodies involved in the mechanism of PNP. Specifically, antibodies against envoplakin and periplakin were being investigated. Further use of ELISA testing on these antibodies confirmed the presence of anti-envoplakin and anti-periplakin autoantibodies in patients with PNP.Further research in 2013 outlined the various types of assays that could be used to determine which antibodies were involved in PNP. Demonstration of certain antibodies in the serum was named as the basis for diagnosis of PNP. This piece labeled PNP as a "multiorgan disease characterized by antibodies against plakins, desmogleins and the α2-macroglobulin-like-1 (A2ML1) protein, in association with an underlying neoplasm".A study concluded in 2009, summarized in 2010, surrounded the surgical removal of the associated tumor as a means to treat PNP. While 7/22 of the subjects perished due to resulting infection from the bodys inability to heal itself after surgery, the other 15 cases survived. This study outlined the importance of early detection and prompt treatment as of utmost important in the treatment of PNP.In 2011, a case study of a woman with ulcers on the back of her leg reported as being diagnosed with PNP. The underlying tumors are almost exclusively of B-cell lineage. However, T-cells and CD56+ Natural Killer cells have also been postulated to be associated effectors of paraneoplastic pemphigus. This case demonstrated the rare association between Natural Killer cell lymphoma and PNP, suggesting that Natural Killer cells could be involved in the pathogenesis of PNP. The article warned clinicians to be alert to the possibility that paraneoplastic pemphigus in lymphomas not of B-cell lineage. This added to the already complex, not fully understood pathogenesis of PNP.A study in 2013 outlined the effectiveness of plasma exchange in PNP patients with benign tumors.The University of Toronto has been working to develop a form of treatment that improves the patients overall quality of life while remaining economically achievable. They believe they have achieved this through fixed-dose rituximab. It has proven to be effective among auto-immune diseases, but the correct administration process for treating PNP is yet to be defined. The results of the study demonstrated varying levels of remission. References Notes == 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 trying to understand 'Carditis' within a medical context. Could you shed some light on it?

Carditis (pl. carditides) is the inflammation of the heart.It is usually studied and treated by specifying it as: Pericarditis is the inflammation of the pericardium Myocarditis is the inflammation of the heart muscle Endocarditis is the inflammation of the endocardium Pancarditis, also called perimyoendocarditis, is the inflammation of the entire heart: the pericardium, the myocardium and the endocardium Reflux carditis refers to a possible outcome of esophageal reflux (also known as GERD), and involves inflammation of the esophagus/stomach mucosa == References ==

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 'Triplegia' in a medical context, but I'm not sure what it means. Can you clarify?

Triplegia is a medical condition characterized by the paralysis of three limbs. While there is no typical pattern of involvement, it is usually associated with paralysis of both legs and one arm—but can also involve both arms and one leg. Triplegia can sometimes be considered a combination of hemiplegia (paralysis of arm and leg of one side of the body) overlaying diplegia (paralysis of both legs), or as quadriplegia (paralysis of four limbs) with less involvement in one extremity.The condition is commonly associated with cerebral palsy, although conditions such as strokes can also lead to it. Triplegia has also been found to be due to an increase in intracranial pressure associated with hydrocephalus resulting from traumatic brain injury.A similar condition is triparesis, in which a person has paresis in three limbs, meaning that the limbs are very weak, but not completely paralyzed. In a case reported only due to its rarity, triplegia was reported following a surgical removal of the tonsils. An eight-year-old boy was sent to Willard Parker Hospital on August 12, 1929, and had been diagnosed with poliomyelitis. After an unrelated, and routine, tonsillectomy there was complete flaccid paralysis and loss of feeling in both the legs, right arm, and muscles in the trunk. == References ==

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

A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functioning properly.Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours, the stroke is a transient ischemic attack (TIA), also called a mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia and loss of bladder control.The main risk factor for stroke is high blood pressure. Other risk factors include high blood cholesterol, tobacco smoking, obesity, diabetes mellitus, a previous TIA, end-stage kidney disease, and atrial fibrillation. An ischemic stroke is typically caused by blockage of a blood vessel, though there are also less common causes. A hemorrhagic stroke is caused by either bleeding directly into the brain or into the space between the brains membranes. Bleeding may occur due to a ruptured brain aneurysm. Diagnosis is typically based on a physical exam and supported by medical imaging such as a CT scan or MRI scan. A CT scan can rule out bleeding, but may not necessarily rule out ischemia, which early on typically does not show up on a CT scan. Other tests such as an electrocardiogram (ECG) and blood tests are done to determine risk factors and rule out other possible causes. Low blood sugar may cause similar symptoms.Prevention includes decreasing risk factors, surgery to open up the arteries to the brain in those with problematic carotid narrowing, and warfarin in people with atrial fibrillation. Aspirin or statins may be recommended by physicians for prevention. A stroke or TIA often requires emergency care. An ischemic stroke, if detected within three to four and half hours, may be treatable with a medication that can break down the clot. Some hemorrhagic strokes benefit from surgery. Treatment to attempt recovery of lost function is called stroke rehabilitation, and ideally takes place in a stroke unit; however, these are not available in much of the world.In 2013, approximately 6.9 million people had an ischemic stroke and 3.4 million people had a hemorrhagic stroke. In 2015, there were about 42.4 million people who had previously had a stroke and were still alive. Between 1990 and 2010 the number of strokes which occurred each year decreased by approximately 10% in the developed world and increased by 10% in the developing world. In 2015, stroke was the second most frequent cause of death after coronary artery disease, accounting for 6.3 million deaths (11% of the total). About 3.0 million deaths resulted from ischemic stroke while 3.3 million deaths resulted from hemorrhagic stroke. About half of people who have had a stroke live less than one year. Overall, two thirds of strokes occurred in those over 65 years old. Classification Strokes can be classified into two major categories: ischemic and hemorrhagic. Ischemic strokes are caused by interruption of the blood supply to the brain, while hemorrhagic strokes result from the rupture of a blood vessel or an abnormal vascular structure. About 87% of strokes are ischemic, the rest being hemorrhagic. Bleeding can develop inside areas of ischemia, a condition known as "hemorrhagic transformation." It is unknown how many hemorrhagic strokes actually start as ischemic strokes. Definition In the 1970s the World Health Organization defined stroke as a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours", although the word "stroke" is centuries old. This definition was supposed to reflect the reversibility of tissue damage and was devised for the purpose, with the time frame of 24 hours being chosen arbitrarily. The 24-hour limit divides stroke from transient ischemic attack, which is a related syndrome of stroke symptoms that resolve completely within 24 hours. With the availability of treatments that can reduce stroke severity when given early, many now prefer alternative terminology, such as brain attack and acute ischemic cerebrovascular syndrome (modeled after heart attack and acute coronary syndrome, respectively), to reflect the urgency of stroke symptoms and the need to act swiftly. Ischemic In an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that area. There are four reasons why this might happen: Thrombosis (obstruction of a blood vessel by a blood clot forming locally) Embolism (obstruction due to an embolus from elsewhere in the body), Systemic hypoperfusion (general decrease in blood supply, e.g., in shock) Cerebral venous sinus thrombosis.A stroke without an obvious explanation is termed cryptogenic (of unknown origin); this constitutes 30–40% of all ischemic strokes.There are various classification systems for acute ischemic stroke. The Oxford Community Stroke Project classification (OCSP, also known as the Bamford or Oxford classification) relies primarily on the initial symptoms; based on the extent of the symptoms, the stroke episode is classified as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) or posterior circulation infarct (POCI). These four entities predict the extent of the stroke, the area of the brain that is affected, the underlying cause, and the prognosis. The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based on clinical symptoms as well as results of further investigations; on this basis, a stroke is classified as being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) an embolism originating in the heart, (3) complete blockage of a small blood vessel, (4) other determined cause, (5) undetermined cause (two possible causes, no cause identified, or incomplete investigation). Users of stimulants such as cocaine and methamphetamine are at a high risk for ischemic strokes. Hemorrhagic There are two main types of hemorrhagic stroke: Intracerebral hemorrhage, which is basically bleeding within the brain itself (when an artery in the brain bursts, flooding the surrounding tissue with blood), due to either intraparenchymal hemorrhage (bleeding within the brain tissue) or intraventricular hemorrhage (bleeding within the brains ventricular system). Subarachnoid hemorrhage, which is basically bleeding that occurs outside of the brain tissue but still within the skull, and precisely between the arachnoid mater and pia mater (the delicate innermost layer of the three layers of the meninges that surround the brain).The above two main types of hemorrhagic stroke are also two different forms of intracranial hemorrhage, which is the accumulation of blood anywhere within the cranial vault; but the other forms of intracranial hemorrhage, such as epidural hematoma (bleeding between the skull and the dura mater, which is the thick outermost layer of the meninges that surround the brain) and subdural hematoma (bleeding in the subdural space), are not considered "hemorrhagic strokes".Hemorrhagic strokes may occur on the background of alterations to the blood vessels in the brain, such as cerebral amyloid angiopathy, cerebral arteriovenous malformation and an intracranial aneurysm, which can cause intraparenchymal or subarachnoid hemorrhage.In addition to neurological impairment, hemorrhagic strokes usually cause specific symptoms (for instance, subarachnoid hemorrhage classically causes a severe headache known as a thunderclap headache) or reveal evidence of a previous head injury. Signs and symptoms Stroke symptoms typically start suddenly, over seconds to minutes, and in most cases do not progress further. The symptoms depend on the area of the brain affected. The more extensive the area of the brain affected, the more functions that are likely to be lost. Some forms of stroke can cause additional symptoms. For example, in intracranial hemorrhage, the affected area may compress other structures. Most forms of stroke are not associated with a headache, apart from subarachnoid hemorrhage and cerebral venous thrombosis and occasionally intracerebral hemorrhage. Early recognition Various systems have been proposed to increase recognition of stroke. Different findings are able to predict the presence or absence of stroke to different degrees. Sudden-onset face weakness, arm drift (i.e., if a person, when asked to raise both arms, involuntarily lets one arm drift downward) and abnormal speech are the findings most likely to lead to the correct identification of a case of stroke, increasing the likelihood by 5.5 when at least one of these is present. Similarly, when all three of these are absent, the likelihood of stroke is decreased (– likelihood ratio of 0.39). While these findings are not perfect for diagnosing stroke, the fact that they can be evaluated relatively rapidly and easily make them very valuable in the acute setting. A mnemonic to remember the warning signs of stroke is FAST (facial droop, arm weakness, speech difficulty, and time to call emergency services), as advocated by the Department of Health (United Kingdom) and the Stroke Association, the American Stroke Association, the National Stroke Association (US), the Los Angeles Prehospital Stroke Screen (LAPSS) and the Cincinnati Prehospital Stroke Scale (CPSS). Use of these scales is recommended by professional guidelines. FAST is less reliable in the recognition of posterior circulation strokes.For people referred to the emergency room, early recognition of stroke is deemed important as this can expedite diagnostic tests and treatments. A scoring system called ROSIER (recognition of stroke in the emergency room) is recommended for this purpose; it is based on features from the medical history and physical examination. Subtypes If the area of the brain affected includes one of the three prominent central nervous system pathways—the spinothalamic tract, corticospinal tract, and the dorsal column–medial lemniscus pathway, symptoms may include: hemiplegia and muscle weakness of the face numbness reduction in sensory or vibratory sensation initial flaccidity (reduced muscle tone), replaced by spasticity (increased muscle tone), excessive reflexes, and obligatory synergies.In most cases, the symptoms affect only one side of the body (unilateral). Depending on the part of the brain affected, the defect in the brain is usually on the opposite side of the body. However, since these pathways also travel in the spinal cord and any lesion there can also produce these symptoms, the presence of any one of these symptoms does not necessarily indicate a stroke. In addition to the above CNS pathways, the brainstem gives rise to most of the twelve cranial nerves. A brainstem stroke affecting the brainstem and brain, therefore, can produce symptoms relating to deficits in these cranial nerves: altered smell, taste, hearing, or vision (total or partial) drooping of eyelid (ptosis) and weakness of ocular muscles decreased reflexes: gag, swallow, pupil reactivity to light decreased sensation and muscle weakness of the face balance problems and nystagmus altered breathing and heart rate weakness in sternocleidomastoid muscle with inability to turn head to one side weakness in tongue (inability to stick out the tongue or move it from side to side)If the cerebral cortex is involved, the CNS pathways can again be affected, but also can produce the following symptoms: aphasia (difficulty with verbal expression, auditory comprehension, reading and writing; Brocas or Wernickes area typically involved) dysarthria (motor speech disorder resulting from neurological injury) apraxia (altered voluntary movements) visual field defect memory deficits (involvement of temporal lobe) hemineglect (involvement of parietal lobe) disorganized thinking, confusion, hypersexual gestures (with involvement of frontal lobe) lack of insight of his or her, usually stroke-related, disabilityIf the cerebellum is involved, ataxia might be present and this includes: altered walking gait altered movement coordination vertigo and or disequilibrium Associated symptoms Loss of consciousness, headache, and vomiting usually occur more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing the brain. If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage or an embolic stroke. Causes Thrombotic stroke In thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower than that of a hemorrhagic stroke. A thrombus itself (even if it does not completely block the blood vessel) can lead to an embolic stroke (see below) if the thrombus breaks off and travels in the bloodstream, at which point it is called an embolus. Two types of thrombosis can cause stroke: Large vessel disease involves the common and internal carotid arteries, the vertebral artery, and the Circle of Willis. Diseases that may form thrombi in the large vessels include (in descending incidence): atherosclerosis, vasoconstriction (tightening of the artery), aortic, carotid or vertebral artery dissection, various inflammatory diseases of the blood vessel wall (Takayasu arteritis, giant cell arteritis, vasculitis), noninflammatory vasculopathy, Moyamoya disease and fibromuscular dysplasia. Small vessel disease involves the smaller arteries inside the brain: branches of the circle of Willis, middle cerebral artery, stem, and arteries arising from the distal vertebral and basilar artery. Diseases that may form thrombi in the small vessels include (in descending incidence): lipohyalinosis (build-up of fatty hyaline matter in the blood vessel as a result of high blood pressure and aging) and fibrinoid degeneration (a stroke involving these vessels is known as a lacunar stroke) and microatheroma (small atherosclerotic plaques).Anemia causes increase blood flow in the blood circulatory system. This causes the endothelial cells of the blood vessels to express adhesion factors which encourages the clotting of blood and formation of thrombus. Sickle-cell anemia, which can cause blood cells to clump up and block blood vessels, can also lead to stroke. A stroke is the second leading cause of death in people under 20 with sickle-cell anemia. Air pollution may also increase stroke risk. Embolic stroke An embolic stroke refers to an arterial embolism (a blockage of an artery) by an embolus, a traveling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g., from bone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually from infectious endocarditis).Because an embolus arises from elsewhere, local therapy solves the problem only temporarily. Thus, the source of the embolus must be identified. Because the embolic blockage is sudden in onset, symptoms usually are maximal at the start. Also, symptoms may be transient as the embolus is partially resorbed and moves to a different location or dissipates altogether. Emboli most commonly arise from the heart (especially in atrial fibrillation) but may originate from elsewhere in the arterial tree. In paradoxical embolism, a deep vein thrombosis embolizes through an atrial or ventricular septal defect in the heart into the brain.Causes of stroke related to the heart can be distinguished between high and low-risk: High risk: atrial fibrillation and paroxysmal atrial fibrillation, rheumatic disease of the mitral or aortic valve disease, artificial heart valves, known cardiac thrombus of the atrium or ventricle, sick sinus syndrome, sustained atrial flutter, recent myocardial infarction, chronic myocardial infarction together with ejection fraction <28 percent, symptomatic congestive heart failure with ejection fraction <30 percent, dilated cardiomyopathy, Libman-Sacks endocarditis, Marantic endocarditis, infective endocarditis, papillary fibroelastoma, left atrial myxoma and coronary artery bypass graft (CABG) surgery. Low risk/potential: calcification of the annulus (ring) of the mitral valve, patent foramen ovale (PFO), atrial septal aneurysm, atrial septal aneurysm with patent foramen ovale, left ventricular aneurysm without thrombus, isolated left atrial "smoke" on echocardiography (no mitral stenosis or atrial fibrillation), complex atheroma in the ascending aorta or proximal arch.Among those who have a complete blockage of one of the carotid arteries, the risk of stroke on that side is about one percent per year.A special form of embolic stroke is the embolic stroke of undetermined source (ESUS). This subset of cryptogenic stroke is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. About one out of six ischemic strokes could be classified as ESUS. Cerebral hypoperfusion Cerebral hypoperfusion is the reduction of blood flow to all parts of the brain. The reduction could be to a particular part of the brain depending on the cause. It is most commonly due to heart failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion. Because the reduction in blood flow is global, all parts of the brain may be affected, especially vulnerable "watershed" areas—border zone regions supplied by the major cerebral arteries. A watershed stroke refers to the condition when the blood supply to these areas is compromised. Blood flow to these areas does not necessarily stop, but instead it may lessen to the point where brain damage can occur. Venous thrombosis Cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, which exceeds the pressure generated by the arteries. Infarcts are more likely to undergo hemorrhagic transformation (leaking of blood into the damaged area) than other types of ischemic stroke. Intracerebral hemorrhage It generally occurs in small arteries or arterioles and is commonly due to hypertension, intracranial vascular malformations (including cavernous angiomas or arteriovenous malformations), cerebral amyloid angiopathy, or infarcts into which secondary hemorrhage has occurred. Other potential causes are trauma, bleeding disorders, amyloid angiopathy, illicit drug use (e.g., amphetamines or cocaine). The hematoma enlarges until pressure from surrounding tissue limits its growth, or until it decompresses by emptying into the ventricular system, CSF or the pial surface. A third of intracerebral bleed is into the brains ventricles. ICH has a mortality rate of 44 percent after 30 days, higher than ischemic stroke or subarachnoid hemorrhage (which technically may also be classified as a type of stroke). Other Other causes may include spasm of an artery. This may occur due to cocaine. Silent stroke A silent stroke is a stroke that does not have any outward symptoms, and people are typically unaware they have had a stroke. Despite not causing identifiable symptoms, a silent stroke still damages the brain and places the person at increased risk for both transient ischemic attack and major stroke in the future. Conversely, those who have had a major stroke are also at risk of having silent strokes. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as MRI. Silent strokes are estimated to occur at five times the rate of symptomatic strokes. The risk of silent stroke increases with age, but may also affect younger adults and children, especially those with acute anemia. Pathophysiology Ischemic Ischemic stroke occurs because of a loss of blood supply to part of the brain, initiating the ischemic cascade. Atherosclerosis may disrupt the blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow by causing the formation of blood clots within the vessel or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a consequence of atrial fibrillation, or in the carotid arteries, break off, enter the cerebral circulation, then lodge in and block brain blood vessels. Since blood vessels in the brain are now blocked, the brain becomes low in energy, and thus it resorts to using anaerobic metabolism within the region of brain tissue affected by ischemia. Anaerobic metabolism produces less adenosine triphosphate (ATP) but releases a by-product called lactic acid. Lactic acid is an irritant which could potentially destroy cells since it is an acid and disrupts the normal acid-base balance in the brain. The ischemia area is referred to as the "ischemic penumbra".As oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energy phosphate compounds such as adenosine triphosphate (ATP) fails, leading to failure of energy-dependent processes (such as ion pumping) necessary for tissue cell survival. This sets off a series of interrelated events that result in cellular injury and death. A major cause of neuronal injury is the release of the excitatory neurotransmitter glutamate. The concentration of glutamate outside the cells of the nervous system is normally kept low by so-called uptake carriers, which are powered by the concentration gradients of ions (mainly Na+) across the cell membrane. However, stroke cuts off the supply of oxygen and glucose which powers the ion pumps maintaining these gradients. As a result, the transmembrane ion gradients run down, and glutamate transporters reverse their direction, releasing glutamate into the extracellular space. Glutamate acts on receptors in nerve cells (especially NMDA receptors), producing an influx of calcium which activates enzymes that digest the cells proteins, lipids, and nuclear material. Calcium influx can also lead to the failure of mitochondria, which can lead further toward energy depletion and may trigger cell death due to programmed cell death.Ischemia also induces production of oxygen free radicals and other reactive oxygen species. These react with and damage a number of cellular and extracellular elements. Damage to the blood vessel lining or endothelium may occur. These processes are the same for any type of ischemic tissue and are referred to collectively as the ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has little respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs. Hemorrhagic Hemorrhagic strokes are classified based on their underlying pathology. Some causes of hemorrhagic stroke are hypertensive hemorrhage, ruptured aneurysm, ruptured AV fistula, transformation of prior ischemic infarction, and drug-induced bleeding. They result in tissue injury by causing compression of tissue from an expanding hematoma or hematomas. In addition, the pressure may lead to a loss of blood supply to affected tissue with resulting infarction, and the blood released by brain hemorrhage appears to have direct toxic effects on brain tissue and vasculature. Inflammation contributes to the secondary brain injury after hemorrhage. Diagnosis Stroke is diagnosed through several techniques: a neurological examination (such as the NIHSS), CT scans (most often without contrast enhancements) or MRI scans, Doppler ultrasound, and arteriography. The diagnosis of stroke itself is clinical, with assistance from the imaging techniques. Imaging techniques also assist in determining the subtypes and cause of stroke. There is yet no commonly used blood test for the stroke diagnosis itself, though blood tests may be of help in finding out the likely cause of stroke. In deceased people, an autopsy of stroke may help establishing the time between stroke onset and death. Physical examination A physical examination, including taking a medical history of the symptoms and a neurological status, helps giving an evaluation of the location and severity of a stroke. It can give a standard score on e.g., the NIH stroke scale. Imaging For diagnosing ischemic (blockage) stroke in the emergency setting: CT scans (without contrast enhancements)sensitivity= 16% (less than 10% within first 3 hours of symptom onset) specificity= 96%MRI scansensitivity= 83% specificity= 98%For diagnosing hemorrhagic stroke in the emergency setting: CT scans (without contrast enhancements)sensitivity= 89% specificity= 100%MRI scansensitivity= 81% specificity= 100%For detecting chronic hemorrhages, an MRI scan is more sensitive.For the assessment of stable stroke, nuclear medicine scans SPECT and PET/CT may be helpful. SPECT documents cerebral blood flow, whereas PET with an FDG isotope shows cerebral glucose metabolism. CT scans may not detect an ischemic stroke, especially if it is small, of recent onset, or in the brainstem or cerebellum areas (posterior circulation infarct). MRI is better at detecting a posterior circulation infarct with diffusion-weighted imaging. A CT scan is used more to rule out certain stroke mimics and detect bleeding. The presence of leptomeningeal collateral circulation in the brain is associated with better clinical outcomes after recanalization treatment. Cerebrovascular reserve capacity is another factor that affects stroke outcome – it is the amount of increase in cerebral blood flow after a purposeful stimulation of blood flow by the physician, such as by giving inhaled carbon dioxide or intravenous acetazolamide. The increase in blood flow can be measured by PET scan or transcranial doppler sonography. However, in people with obstruction of the internal carotid artery of one side, the presence of leptomeningeal collateral circulation is associated with reduced cerebral reserve capacity. Underlying cause When a stroke has been diagnosed, various other studies may be performed to determine the underlying cause. With the current treatment and diagnosis options available, it is of particular importance to determine whether there is a peripheral source of emboli. Test selection may vary since the cause of stroke varies with age, comorbidity and the clinical presentation. The following are commonly used techniques: an ultrasound/doppler study of the carotid arteries (to detect carotid stenosis) or dissection of the precerebral arteries; an electrocardiogram (ECG) and echocardiogram (to identify arrhythmias and resultant clots in the heart which may spread to the brain vessels through the bloodstream); a Holter monitor study to identify intermittent abnormal heart rhythms; an angiogram of the cerebral vasculature (if a bleed is thought to have originated from an aneurysm or arteriovenous malformation); blood tests to determine if blood cholesterol is high, if there is an abnormal tendency to bleed, and if some rarer processes such as homocystinuria might be involved.For hemorrhagic strokes, a CT or MRI scan with intravascular contrast may be able to identify abnormalities in the brain arteries (such as aneurysms) or other sources of bleeding, and structural MRI if this shows no cause. If this too does not identify an underlying reason for the bleeding, invasive cerebral angiography could be performed but this requires access to the bloodstream with an intravascular catheter and can cause further strokes as well as complications at the insertion site and this investigation is therefore reserved for specific situations. If there are symptoms suggesting that the hemorrhage might have occurred as a result of venous thrombosis, CT or MRI venography can be used to examine the cerebral veins. Misdiagnosis Among people with ischemic strokes, misdiagnosis occurs 2 to 26% of the time. A "stroke chameleon" (SC) is stroke which is diagnosed as something else.People not having a stroke may also be misdiagnosed as a stroke. Giving thrombolytics (clot-busting) in such cases causes intracerebral bleeding 1 to 2% of the time, which is less than that of people with strokes. This unnecessary treatment adds to health care costs. Even so, the AHA/ASA guidelines state that starting intravenous tPA in possible mimics is preferred to delaying treatment for additional testing.Women, African-Americans, Hispanic-Americans, Asian and Pacific Islanders are more often misdiagnosed for a condition other than stroke when in fact having a stroke. In addition, adults under 44 years of age are seven times more likely to have a stroke missed than are adults over 75 years of age. This is especially the case for younger people with posterior circulation infarcts. Some medical centers have used hyperacute MRI in experimental studies for persons initially thought to have a low likelihood of stroke. And in some of these persons, strokes have been found which were then treated with thrombolytic medication. Prevention Given the disease burden of strokes, prevention is an important public health concern. Primary prevention is less effective than secondary prevention (as judged by the number needed to treat to prevent one stroke per year). Recent guidelines detail the evidence for primary prevention in stroke. In those who are otherwise healthy, aspirin does not appear beneficial and thus is not recommended. In people who have had a myocardial infarction or those with a high cardiovascular risk, it provides some protection against a first stroke. In those who have previously had a stroke, treatment with medications such as aspirin, clopidogrel, and dipyridamole may be beneficial. The U.S. Preventive Services Task Force (USPSTF) recommends against screening for carotid artery stenosis in those without symptoms. Risk factors The most important modifiable risk factors for stroke are high blood pressure and atrial fibrillation although the size of the effect is small; 833 people have to be treated for 1 year to prevent one stroke. Other modifiable risk factors include high blood cholesterol levels, diabetes mellitus, end-stage kidney disease, cigarette smoking (active and passive), heavy alcohol use, drug use, lack of physical activity, obesity, processed red meat consumption, and unhealthy diet. Smoking just one cigarette per day increases the risk more than 30%. Alcohol use could predispose to ischemic stroke, as well as intracerebral and subarachnoid hemorrhage via multiple mechanisms (for example, via hypertension, atrial fibrillation, rebound thrombocytosis and platelet aggregation and clotting disturbances). Drugs, most commonly amphetamines and cocaine, can induce stroke through damage to the blood vessels in the brain and acute hypertension. Migraine with aura doubles a persons risk for ischemic stroke. Untreated, celiac disease regardless of the presence of symptoms can be an underlying cause of stroke, both in children and adults.High levels of physical activity reduce the risk of stroke by about 26%. There is a lack of high quality studies looking at promotional efforts to improve lifestyle factors. Nonetheless, given the large body of circumstantial evidence, best medical management for stroke includes advice on diet, exercise, smoking and alcohol use. Medication is the most common method of stroke prevention; carotid endarterectomy can be a useful surgical method of preventing stroke. Blood pressure High blood pressure accounts for 35–50% of stroke risk. Blood pressure reduction of 10 mmHg systolic or 5 mmHg diastolic reduces the risk of stroke by ~40%. Lowering blood pressure has been conclusively shown to prevent both ischemic and hemorrhagic strokes. It is equally important in secondary prevention. Even people older than 80 years and those with isolated systolic hypertension benefit from antihypertensive therapy. The available evidence does not show large differences in stroke prevention between antihypertensive drugs—therefore, other factors such as protection against other forms of cardiovascular disease and cost should be considered. The routine use of beta-blockers following a stroke or TIA has not been shown to result in benefits. Blood lipids High cholesterol levels have been inconsistently associated with (ischemic) stroke. Statins have been shown to reduce the risk of stroke by about 15%. Since earlier meta-analyses of other lipid-lowering drugs did not show a decreased risk, statins might exert their effect through mechanisms other than their lipid-lowering effects. Diabetes mellitus Diabetes mellitus increases the risk of stroke by 2 to 3 times. While intensive blood sugar control has been shown to reduce small blood vessel complications such as kidney damage and damage to the retina of the eye it has not been shown to reduce large blood vessel complications such as stroke. Anticoagulation drugs Oral anticoagulants such as warfarin have been the mainstay of stroke prevention for over 50 years. However, several studies have shown that aspirin and other antiplatelets are highly effective in secondary prevention after a stroke or transient ischemic attack. Low doses of aspirin (for example 75–150 mg) are as effective as high doses but have fewer side effects; the lowest effective dose remains unknown. Thienopyridines (clopidogrel, ticlopidine) might be slightly more effective than aspirin and have a decreased risk of gastrointestinal bleeding, but are more expensive. Both aspirin and clopidogrel may be useful in the first few weeks after a minor stroke or high risk TIA. Clopidogrel has less side effects than ticlopidine. Dipyridamole can be added to aspirin therapy to provide a small additional benefit, even though headache is a common side effect. Low-dose aspirin is also effective for stroke prevention after having a myocardial infarction.Those with atrial fibrillation have a 5% a year risk of stroke, and this risk is higher in those with valvular atrial fibrillation. Depending on the stroke risk, anticoagulation with medications such as warfarin or aspirin is useful for prevention. Except in people with atrial fibrillation, oral anticoagulants are not advised for stroke prevention—any benefit is offset by bleeding risk.In primary prevention, however, antiplatelet drugs did not reduce the risk of ischemic stroke but increased the risk of major bleeding. Further studies are needed to investigate a possible protective effect of aspirin against ischemic stroke in women. Surgery Carotid endarterectomy or carotid angioplasty can be used to remove atherosclerotic narrowing of the carotid artery. There is evidence supporting this procedure in selected cases. Endarterectomy for a significant stenosis has been shown to be useful in preventing further strokes in those who have already had one. Carotid artery stenting has not been shown to be equally useful. People are selected for surgery based on age, gender, degree of stenosis, time since symptoms and the persons preferences. Surgery is most efficient when not delayed too long—the risk of recurrent stroke in a person who has a 50% or greater stenosis is up to 20% after 5 years, but endarterectomy reduces this risk to around 5%. The number of procedures needed to cure one person was 5 for early surgery (within two weeks after the initial stroke), but 125 if delayed longer than 12 weeks.Screening for carotid artery narrowing has not been shown to be a useful test in the general population. Studies of surgical intervention for carotid artery stenosis without symptoms have shown only a small decrease in the risk of stroke. To be beneficial, the complication rate of the surgery should be kept below 4%. Even then, for 100 surgeries, 5 people will benefit by avoiding stroke, 3 will develop stroke despite surgery, 3 will develop stroke or die due to the surgery itself, and 89 will remain stroke-free but would also have done so without intervention. Diet Nutrition, specifically the Mediterranean-style diet, has the potential for decreasing the risk of having a stroke by more than half. It does not appear that lowering levels of homocysteine with folic acid affects the risk of stroke. Women A number of specific recommendations have been made for women including taking aspirin after the 11th week of pregnancy if there is a history of previous chronic high blood pressure and taking blood pressure medications during pregnancy if the blood pressure is greater than 150 mmHg systolic or greater than 100 mmHg diastolic. In those who have previously had preeclampsia other risk factors should be treated more aggressively. Previous stroke or TIA Keeping blood pressure below 140/90 mmHg is recommended. Anticoagulation can prevent recurrent ischemic strokes. Among people with nonvalvular atrial fibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. However, a recent meta-analysis suggests harm from anticoagulation started early after an embolic stroke. Stroke prevention treatment for atrial fibrillation is determined according to the CHA2DS2–VASc score. The most widely used anticoagulant to prevent thromboembolic stroke in people with nonvalvular atrial fibrillation is the oral agent warfarin while a number of newer agents including dabigatran are alternatives which do not require prothrombin time monitoring.Anticoagulants, when used following stroke, should not be stopped for dental procedures.If studies show carotid artery stenosis, and the person has a degree of residual function on the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after stroke. Management Ischemic stroke Aspirin reduces the overall risk of recurrence by 13% with greater benefit early on. Definitive therapy within the first few hours is aimed at removing the blockage by breaking the clot down (thrombolysis), or by removing it mechanically (thrombectomy). The philosophical premise underlying the importance of rapid stroke intervention was summed up as Time is Brain! in the early 1990s. Years later, that same idea, that rapid cerebral blood flow restoration results in fewer brain cells dying, has been proved and quantified.Tight blood sugar control in the first few hours does not improve outcomes and may cause harm. High blood pressure is also not typically lowered as this has not been found to be helpful. Cerebrolysin, a mixture of pig-derived neurotrophic factors used to treat acute ischemic stroke in many Asian and European countries, does not improve outcomes and may increase the risk of severe adverse events. Thrombolysis Thrombolysis, such as with recombinant tissue plasminogen activator (rtPA), in acute ischemic stroke, when given within three hours of symptom onset, results in an overall benefit of 10% with respect to living without disability. It does not, however, improve chances of survival. Benefit is greater the earlier it is used. Between three and four and a half hours the effects are less clear. The AHA/ASA recommend it for certain people in this time frame. A 2014 review found a 5% increase in the number of people living without disability at three to six months; however, there was a 2% increased risk of death in the short term. After four and a half hours thrombolysis worsens outcomes. These benefits or lack of benefits occurred regardless of the age of the person treated. There is no reliable way to determine who will have an intracranial bleed post-treatment versus who will not. In those with findings of savable tissue on medical imaging between 4.5 hours and 9 hours or who wake up with a stroke, alteplase results in some benefit.Its use is endorsed by the American Heart Association, the American College of Emergency Physicians and the American Academy of Neurology as the recommended treatment for acute stroke within three hours of onset of symptoms as long as there are no other contraindications (such as abnormal lab values, high blood pressure, or recent surgery). This position for tPA is based upon the findings of two studies by one group of investigators which showed that tPA improves the chances for a good neurological outcome. When administered within the first three hours thrombolysis improves functional outcome without affecting mortality. 6.4% of people with large strokes developed substantial brain bleeding as a complication from being given tPA thus part of the reason for increased short term mortality. The American Academy of Emergency Medicine had previously stated that objective evidence regarding the applicability of tPA for acute ischemic stroke was insufficient. In 2013 the American College of Emergency Medicine refuted this position, acknowledging the body of evidence for the use of tPA in ischemic stroke; but debate continues. Intra-arterial fibrinolysis, where a catheter is passed up an artery into the brain and the medication is injected at the site of thrombosis, has been found to improve outcomes in people with acute ischemic stroke. Endovascular treatment Mechanical removal of the blood clot causing the ischemic stroke, called mechanical thrombectomy, is a potential treatment for occlusion of a large artery, such as the middle cerebral artery. In 2015, one review demonstrated the safety and efficacy of this procedure if performed within 12 hours of the onset of symptoms. It did not change the risk of death, but reduced disability compared to the use of intravenous thrombolysis which is generally used in people evaluated for mechanical thrombectomy. Certain cases may benefit from thrombectomy up to 24 hours after the onset of symptoms. Craniectomy Strokes affecting large portions of the brain can cause significant brain swelling with secondary brain injury in surrounding tissue. This phenomenon is mainly encountered in strokes affecting brain tissue dependent upon the middle cerebral artery for blood supply and is also called "malignant cerebral infarction" because it carries a dismal prognosis. Relief of the pressure may be attempted with medication, but some require hemicraniectomy, the temporary surgical removal of the skull on one side of the head. This decreases the risk of death, although some people – who would otherwise have died – survive with disability. Hemorrhagic stroke People with intracerebral hemorrhage require supportive care, including blood pressure control if required. People are monitored for changes in the level of consciousness, and their blood sugar and oxygenation are kept at optimum levels. Anticoagulants and antithrombotics can make bleeding worse and are generally discontinued (and reversed if possible). A proportion may benefit from neurosurgical intervention to remove the blood and treat the underlying cause, but this depends on the location and the size of the hemorrhage as well as patient-related factors, and ongoing research is being conducted into the question as to which people with intracerebral hemorrhage may benefit.In subarachnoid hemorrhage, early treatment for underlying cerebral aneurysms may reduce the risk of further hemorrhages. Depending on the site of the aneurysm this may be by surgery that involves opening the skull or endovascularly (through the blood vessels). Stroke unit Ideally, people who have had a stroke are admitted to a "stroke unit", a ward or dedicated area in a hospital staffed by nurses and therapists with experience in stroke treatment. It has been shown that people admitted to a stroke unit have a higher chance of surviving than those admitted elsewhere in hospital, even if they are being cared for by doctors without experience in stroke. Nursing care is fundamental in maintaining skin care, feeding, hydration, positioning, and monitoring vital signs such as temperature, pulse, and blood pressure. Rehabilitation Stroke rehabilitation is the process by which those with disabling strokes undergo treatment to help them return to normal life as much as possible by regaining and relearning the skills of everyday living. It also aims to help the survivor understand and adapt to difficulties, prevent secondary complications, and educate family members to play a supporting role. Stroke rehabilitation should begin almost immediately with a multidisciplinary approach. The rehabilitation team may involve physicians trained in rehabilitation medicine, neurologists, clinical pharmacists, nursing staff, physiotherapists, occupational therapists, speech-language pathologists, and orthotists. Some teams may also include psychologists and social workers, since at least one-third of affected people manifests post stroke depression. Validated instruments such as the Barthel scale may be used to assess the likelihood of a person who has had a stroke being able to manage at home with or without support subsequent to discharge from a hospital.Stroke rehabilitation should be started as quickly as possible and can last anywhere from a few days to over a year. Most return of function is seen in the first few months, and then improvement falls off with the "window" considered officially by U.S. state rehabilitation units and others to be closed after six months, with little chance of further improvement. However, some people have reported that they continue to improve for years, regaining and strengthening abilities like writing, walking, running, and talking. Daily rehabilitation exercises should continue to be part of the daily routine for people who have had a stroke. Complete recovery is unusual but not impossible and most people will improve to some extent: proper diet and exercise are known to help the brain to recover. Spatial neglect The current body of evidence is uncertain on the efficacy of cognitive rehabilitation for reducing the disabling effects of neglect and increasing independence remains unproven. However, there is limited evidence that cognitive rehabilitation may have an immediate beneficial effect on tests of neglect. Overall, no rehabilitation approach can be supported by evidence for spatial neglect. Automobile driving The current body of evidence is uncertain whether the use of rehabilitation can improve on-road driving skills following stroke. There is limited evidence that training on a driving simulator will improve performance on recognizing road signs after training. The findings are based on low-quality evidence as further research is needed involving large numbers of participants. Yoga Based on low quality evidence, it is currently uncertain whether yoga has a significant benefit for stroke rehabilitation on measures of quality of life, balance, strength, endurance, pain, and disability scores. Yoga may reduce anxiety and could be included as part of patient-centred stroke rehabilitation. Further research is needed assessing the benefits and safety of yoga in stroke rehabilitation. Action observation for upper limbs The latest scientific evidence indicates that action observation is beneficial in improving upper limb motor function and dependence in activities of daily living in patients with stroke. Thus, action observation therapy is generally associated with better arm and hand function, with no significant adverse events. The findings are based on low to moderate quality evidence. Cognitive rehabilitation for attention deficits The current body of scientific evidence is uncertain on the effectiveness of cognitive rehabilitation for attention deficits in patients following stroke. While there may be an immediate effect after treatment on attention, the findings are based on low to moderate quality and small number of studies. Further research is needed to assess whether the effect can be sustained in day-to-day tasks requiring attention. Motor imagery for gait rehabilitation The latest evidence supports the short-term benefits of motor imagery (MI) on walking speed in individuals who have had a stroke, in comparison to other therapies. MI does not improve motor function after stroke and does not seem to cause significant adverse events. The findings are based on low-quality evidence as further research is needed to estimate the effect of MI on walking endurance and the dependence on personal assistance. Physical and occupational therapy Physical and occupational therapy have overlapping areas of expertise; however, physical therapy focuses on joint range of motion and strength by performing exercises and relearning functional tasks such as bed mobility, transferring, walking and other gross motor functions. Physiotherapists can also work with people who have had a stroke to improve awareness and use of the hemiplegic side. Rehabilitation involves working on the ability to produce strong movements or the ability to perform tasks using normal patterns. Emphasis is often concentrated on functional tasks and peoples goals. One example physiotherapists employ to promote motor learning involves constraint-induced movement therapy. Through continuous practice the person relearns to use and adapt the hemiplegic limb during functional activities to create lasting permanent changes. Physical therapy is effective for recovery of function and mobility after stroke. Occupational therapy is involved in training to help relearn everyday activities known as the activities of daily living (ADLs) such as eating, drinking, dressing, bathing, cooking, reading and writing, and toileting. Approaches to helping people with urinary incontinence include physical therapy, cognitive therapy, and specialized interventions with experienced medical professionals, however, it is not clear how effective these approaches are at improving urinary incontinence following a stroke.Treatment of spasticity related to stroke often involves early mobilizations, commonly performed by a physiotherapist, combined with elongation of spastic muscles and sustained stretching through various different positions. Gaining initial improvement in range of motion is often achieved through rhythmic rotational patterns associated with the affected limb. After full range has been achieved by the therapist, the limb should be positioned in the lengthened positions to prevent against further contractures, skin breakdown, and disuse of the limb with the use of splints or other tools to stabilize the joint. Cold in the form of ice wraps or ice packs have been proven to briefly reduce spasticity by temporarily dampening neural firing rates. Electrical stimulation to the antagonist muscles or vibrations has also been used with some success. Physical therapy is sometimes suggested for people who experience sexual dysfunction following a stroke. Interventions for age-related visual problems in patients with stroke With the prevalence of vision problems increasing with age in stroke patients, the overall effect of interventions for age-related visual problems is currently uncertain. It is also not sure whether people with stroke respond differently from the general population when treating eye problems. Further research in this area is needed as current body of evidence is very low quality. Speech and language therapy Speech and language therapy is appropriate for people with the speech production disorders: dysarthria and apraxia of speech, aphasia, cognitive-communication impairments, and problems with swallowing. Speech and language therapy for aphasia following stroke compared to no therapy improves functional communication, reading, writing and expressive language. There may be benefit in high intensity and high doses over a longer period, but these higher intensity doses may not be acceptable to everyone.People who have had a stroke may have particular problems, such as dysphagia, which can cause swallowed material to pass into the lungs and cause aspiration pneumonia. The condition may improve with time, but in the interim, a nasogastric tube may be inserted, enabling liquid food to be given directly into the stomach. If swallowing is still deemed unsafe, then a percutaneous endoscopic gastrostomy (PEG) tube is passed and this can remain indefinitely. Swallowing therapy has mixed results as of 2018. Devices Often, assistive technology such as wheelchairs, walkers and canes may be beneficial. Many mobility problems can be improved by the use of ankle foot orthoses. Physical fitness A stroke can also reduce peoples general fitness. Reduced fitness can reduce capacity for rehabilitation as well as general health. Physical exercises as part of a rehabilitation program following a stroke appear safe. Cardiorespiratory fitness training that involves walking in rehabilitation can improve speed, tolerance and independence during walking, and may improve balance. There are inadequate long-term data about the effects of exercise and training on death, dependence and disability after a stroke. The future areas of research may concentrate on the optimal exercise prescription and long-term health benefits of exercise. The effect of physical training on cognition also may be studied further. The ability to walk independently in their community, indoors or outdoors, is important following stroke. Although no negative effects have been reported, it is unclear if outcomes can improve with these walking programs when compared to usual treatment. Other therapy methods Some current and future therapy methods include the use of virtual reality and video games for rehabilitation. These forms of rehabilitation offer potential for motivating people to perform specific therapy tasks that many other forms do not. While virtual reality and interactive video gaming are not more effective than conventional therapy for improving upper limb function, when used in conjunction with usual care these approaches may improve upper limb function and ADL function. There are inadequate data on the effect of virtual reality and interactive video gaming on gait speed, balance, participation and quality of life. Many clinics and hospitals are adopting the use of these off-the-shelf devices for exercise, social interaction, and rehabilitation because they are affordable, accessible and can be used within the clinic and home.Mirror therapy is associated with improved motor function of the upper extremity in people who have had a stroke.Other non-invasive rehabilitation methods used to augment physical therapy of motor function in people recovering from a stroke include transcranial magnetic stimulation and transcranial direct-current stimulation. and robotic therapies. Constraint‐induced movement therapy (CIMT), mental practice, mirror therapy, interventions for sensory impairment, virtual reality and a relatively high dose of repetitive task practice may be effective in improving upper limb function. However, further primary research, specifically of CIMT, mental practice, mirror therapy and virtual reality is needed. Orthotics Clinical studies confirm the importance of orthoses in stroke rehabilitation. The orthosis supports the therapeutic applications and also helps to mobilize the patient at an early stage. With the help of an orthosis, physiological standing and walking can be learned again, and late health consequences caused by a wrong gait pattern can be prevented. A treatment with an orthosis can therefore be used to support the therapy. Self-management A stroke can affect the ability to live independently and with quality. Self-management programs are a special training that educates stroke survivors about stroke and its consequences, helps them acquire skills to cope with their challenges, and helps them set and meet their own goals during their recovery process. These programs are tailored to the target audience, and led by someone trained and expert in stroke and its consequences (most commonly professionals, but also stroke survivors and peers). A 2016 review reported that these programs improve the quality of life after stroke, without negative effects. People with stroke felt more empowered, happy and satisfied with life after participating in this training. Prognosis Disability affects 75% of stroke survivors enough to decrease their ability to work. Stroke can affect people physically, mentally, emotionally, or a combination of the three. The results of stroke vary widely depending on size and location of the lesion. Physical effects Some of the physical disabilities that can result from stroke include muscle weakness, numbness, pressure sores, pneumonia, incontinence, apraxia (inability to perform learned movements), difficulties carrying out daily activities, appetite loss, speech loss, vision loss and pain. If the stroke is severe enough, or in a certain location such as parts of the brainstem, coma or death can result. Up to 10% of people following a stroke develop seizures, most commonly in the week subsequent to the event; the severity of the stroke increases the likelihood of a seizure. An estimated 15% of people experience urinary incontinence for more than a year following a stroke. 50% of people have a decline in sexual function (sexual dysfunction) following a stroke. Emotional and mental effects Emotional and mental dysfunctions correspond to areas in the brain that have been damaged. Emotional problems following a stroke can be due to direct damage to emotional centers in the brain or from frustration and difficulty adapting to new limitations. Post-stroke emotional difficulties include anxiety, panic attacks, flat affect (failure to express emotions), mania, apathy and psychosis. Other difficulties may include a decreased ability to communicate emotions through facial expression, body language and voice.Disruption in self-identity, relationships with others, and emotional well-being can lead to social consequences after stroke due to the lack of ability to communicate. Many people who experience communication impairments after a stroke find it more difficult to cope with the social issues rather than physical impairments. Broader aspects of care must address the emotional impact speech impairment has on those who experience difficulties with speech after a stroke. Those who experience a stroke are at risk of paralysis which could result in a self disturbed body image which may also lead to other social issues.30 to 50% of stroke survivors develop post-stroke depression, which is characterized by lethargy, irritability, sleep disturbances, lowered self-esteem and withdrawal.Depression can reduce motivation and worsen outcome, but can be treated with social and family support, psychotherapy and, in severe cases, antidepressants. Psychotherapy sessions may have a small effect on improving mood and preventing depression after a stroke, however psychotherapy does not appear to be effective at treating depression after a stroke. Antidepressant medications may be useful for treating depression after a stroke.Emotional lability, another consequence of stroke, causes the person to switch quickly between emotional highs and lows and to express emotions inappropriately, for instance with an excess of laughing or crying with little or no provocation. While these expressions of emotion usually correspond to the persons actual emotions, a more severe form of emotional lability causes the affected person to laugh and cry pathologically, without regard to context or emotion. Some people show the opposite of what they feel, for example crying when they are happy. Emotional lability occurs in about 20% of those who have had a stroke. Those with a right hemisphere stroke are more likely to have an empathy problems which can make communication harder.Cognitive deficits resulting from stroke include perceptual disorders, aphasia, dementia, and problems with attention and memory. A stroke survivor may be unaware of their own disabilities, a condition called anosognosia. In a condition called hemispatial neglect, the affected person is unable to attend to anything on the side of space opposite to the damaged hemisphere. Cognitive and psychological outcome after a stroke can be affected by the age at which the stroke happened, pre-stroke baseline intellectual functioning, psychiatric history and whether there is pre-existing brain pathology. Epidemiology Stroke was the second most frequent cause of death worldwide in 2011, accounting for 6.2 million deaths (~11% of the total). Approximately 17 million people had a stroke in 2010 and 33 million people have previously had a stroke and were still alive. Between 1990 and 2010 the number of strokes decreased by approximately 10% in the developed world and increased by 10% in the developing world. Overall, two-thirds of strokes occurred in those over 65 years old. South Asians are at particularly high risk of stroke, accounting for 40% of global stroke deaths. Incidence of ischemic stroke is ten times more frequent than haemorrhagic stroke.It is ranked after heart disease and before cancer. In the United States stroke is a leading cause of disability, and recently declined from the third leading to the fourth leading cause of death. Geographic disparities in stroke incidence have been observed, including the existence of a "stroke belt" in the southeastern United States, but causes of these disparities have not been explained. The risk of stroke increases exponentially from 30 years of age, and the cause varies by age. Advanced age is one of the most significant stroke risk factors. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65.A persons risk of dying if he or she does have a stroke also increases with age. However, stroke can occur at any age, including in childhood.Family members may have a genetic tendency for stroke or share a lifestyle that contributes to stroke. Higher levels of Von Willebrand factor are more common amongst people who have had ischemic stroke for the first time. The results of this study found that the only significant genetic factor was the persons blood type. Having had a stroke in the past greatly increases ones risk of future strokes. Men are 25% more likely to develop strokes than women, yet 60% of deaths from stroke occur in women. Since women live longer, they are older on average when they have their strokes and thus more often killed. Some risk factors for stroke apply only to women. Primary among these are pregnancy, childbirth, menopause, and the treatment thereof (HRT). History Episodes of stroke and familial stroke have been reported from the 2nd millennium BC onward in ancient Mesopotamia and Persia. Hippocrates (460 to 370 BC) was first to describe the phenomenon of sudden paralysis that is often associated with ischemia. Apoplexy, from the Greek word meaning "struck down with violence", first appeared in Hippocratic writings to describe this phenomenon. The word stroke was used as a synonym for apoplectic seizure as early as 1599, and is a fairly literal translation of the Greek term. The term apoplectic stroke is an archaic, nonspecific term, for a cerebrovascular accident accompanied by haemorrhage or haemorrhagic stroke. Martin Luther was described as having an apoplectic stroke that deprived him of his speech shortly before his death in 1546.In 1658, in his Apoplexia, Johann Jacob Wepfer (1620–1695) identified the cause of hemorrhagic stroke when he suggested that people who had died of apoplexy had bleeding in their brains. Wepfer also identified the main arteries supplying the brain, the vertebral and carotid arteries, and identified the cause of a type of ischemic stroke known as a cerebral infarction when he suggested that apoplexy might be caused by a blockage to those vessels. Rudolf Virchow first described the mechanism of thromboembolism as a major factor.The term cerebrovascular accident was introduced in 1927, reflecting a "growing awareness and acceptance of vascular theories and (...) recognition of the consequences of a sudden disruption in the vascular supply of the brain". Its use is now discouraged by a number of neurology textbooks, reasoning that the connotation of fortuitousness carried by the word accident insufficiently highlights the modifiability of the underlying risk factors. Cerebrovascular insult may be used interchangeably.The term brain attack was introduced for use to underline the acute nature of stroke according to the American Stroke Association, which has used the term since 1990, and is used colloquially to refer to both ischemic as well as hemorrhagic stroke. Research As of 2017, angioplasty and stents were under preliminary clinical research to determine the possible therapeutic advantages of these procedures in comparison to therapy with statins, antithrombotics, or antihypertensive drugs. See also References Further reading External links Stroke at Curlie DRAGON Score for Post-Thrombolysis Archived 2020-10-27 at the Wayback Machine THRIVE score for stroke outcome Archived 2016-09-13 at the Wayback Machine National Institute of Neurological Disorders and Stroke

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 'Plantar wart.' Could you provide some insights?

A plantar wart, or verruca, is a wart occurring on the bottom of the foot or toes. Its color is typically similar to that of the skin. Small black dots often occur on the surface. One or more may occur in an area. They may result in pain with pressure such that walking is difficult.They are caused by the human papillomavirus (HPV). A break in the skin is required for infection to occur. Risk factors include use of communal showers, having had prior warts, and poor immune function. Diagnosis is typically based on symptoms.Treatment is only needed if it is causing symptoms. This may include salicylic acid, cryotherapy, chemo-based fluorouracil or bleomycin, and surgical removal. The skin atop the lesion should generally be removed before treatment. In about a third to two-thirds of cases, they go away without specific treatment, but this may take a few years. Plantar warts are common. Children and young adults are most often affected. Signs and symptoms Their colors are typically similar to that of the nearby skin. Small, black dots may occur on their surfaces. One or more may occur in an area. They may result in pain with pressure such that walking may be difficult. Cause Plantar warts are benign epithelial tumors generally caused by infection by human papillomavirus types 1, 2, 4, 60, or 63, but have also been caused by types 57, 65, 66, and 156. These types are classified as clinical (visible symptoms). The virus attacks compromised skin through direct contact, possibly entering through tiny cuts and abrasions in the stratum corneum (outermost layer of skin). After infection, warts may not become visible for several weeks or months. Because of pressure on the sole of the foot or finger, the wart is pushed inward and a layer of hard skin may form over the wart. A plantar wart can be painful if left untreated.Warts may spread through autoinoculation, by infecting nearby skin, or by contaminated walking surfaces. They may fuse or develop into clusters called mosaic warts. Diagnosis A plantar wart is a small lesion that appears on the surface of the skin and typically resembles a cauliflower, with tiny black petechiae (tiny hemorrhages under the skin) in the center. Pinpoint bleeding may occur when these are scratched. Plantar warts occur on the soles of feet and toes. They may be painful when standing or walking.Plantar warts are often similar to calluses or corns, but can be differentiated by close observation of skin striations. Feet are covered in friction ridges, which are akin to fingerprints of the feet. Friction ridges are disrupted by plantar warts; if the lesion is not a plantar wart, the striations continue across the top layer of the skin. Plantar warts tend to be painful on application of pressure from either side of the lesion rather than direct pressure, unlike calluses (which tend to be painful on direct pressure, instead). Prevention HPV is spread by direct and indirect contact from an infected host. Avoiding direct contact with contaminated surfaces such as communal changing rooms and shower floors and benches, avoiding sharing of shoes and socks and avoiding contact with warts on other parts of the body and on the bodies of others may help reduce the spread of infection. Infection is less common among adults than children.As all warts are contagious, precautions should be taken to avoid spreading them. Recommendations include: Cover them with an adhesive bandage while swimming Wear latex swimming socks Wear flip-flops when using communal showers Do not share towels.Plantar warts are not prevented by inoculation with HPV vaccines because the warts are caused by different strains of HPV. Gardasil protects against strains 6, 11, 16, and 18, and Cervarix protects against 16 and 18, whereas plantar warts are caused by strains 1, 2, 4, and 63. Treatment A number of treatments have been found to be effective. A 2012 review of different treatments for skin warts in otherwise healthy people concluded modest benefit from salicylic acid, and cryotherapy appears similar to salicylic acid. Medications Salicylic acid, the treatment of warts by keratolysis, involves the peeling away of dead surface skin cells with keratolytic chemicals such as salicylic acid or trichloroacetic acid. These are available in over-the-counter products, or in higher concentrations, may need to be prescribed by a physician. A 12-week daily treatment with salicylic acid has been shown to lead to a complete clearance of warts in 10–15% of the cases.Formic acid, topical, is a common treatment for plantar warts, which works by being applied over a period of time, causing the body to reject the wart.Fluorouracil cream, a chemotherapy agent sometimes used to treat skin cancer, can be used on particularly resistant warts, by blocking viral DNA and RNA production and repair.Bleomycin, a more potent chemotherapy drug, can be injected into deep warts, destroying the viral DNA or RNA. Bleomycin is notably not US FDA approved for this purpose. Possible side effects include necrosis of the digits, nail loss, and Raynaud syndrome. The usual treatment is one or two injections.Immunotherapy, as intralesional injection of antigens (mumps, candida or trichophytin antigens USP), is a wart treatment that may trigger a host immune response to the wart virus, resulting in wart resolution. It is now recommended as a second-line therapy. Surgery Liquid nitrogen and similar cryosurgery methods are common surgical treatments, which act by freezing the external cell structure of the warts, destroying the live tissue.Electrodesiccation and surgical excision may produce scarring.Laser surgery is generally a last resort treatment, as it is expensive and painful, but may be necessary for large, hard-to-cure warts.Cauterization may be effective as a prolonged treatment. As a short-term treatment, cauterization of the base with anesthetic can be effective, but this method risks scarring or keloids. Subsequent surgical removal, if necessary, also risks keloids and/or recurrence in the operative scar. References External links Plantar warts at the Mayo Clinic website Warts at The Merck Manual

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 'Brinzolamide/brimonidine' within a medical context. Could you shed some light on it?

Brinzolamide/brimonidine, sold under the brand name Simbrinza, is a fixed-dose combination medication used to reduce intra-ocular pressure (pressure inside the eye) in adults with ocular hypertension (high intra-ocular pressure) or in those with an eye condition known as open-angle glaucoma. It contains brinzolamide and brimonidine tartrate. It is used as an eye drop.The most common side effects include ocular hyperaemia (red eye), allergic reactions in the eye, and dysgeusia (taste disturbances).Open-angle glaucoma (a condition where the aqueous humour, the watery fluid inside the eyeball, cannot drain away properly) and other causes of high pressure in the eye increase the risk of damage to the retina and the optic nerve (the nerve that sends signals from the eye to the brain). This can result in serious vision loss and even blindness.The active substances, brinzolamide and brimonidine tartrate, help to reduce intra-ocular pressure by reducing the production of aqueous humour. Brinzolamide works by blocking an enzyme called carbonic anhydrase, which produces bicarbonate needed for the production of the aqueous humour, while brimonidine tartrate blocks another enzyme known as adenylate cyclase, which is also involved in the production of the aqueous humour. Brimonidine also increases the drainage of aqueous humour from the front of the eye.Brinzolamide/brimonidine was approved for medical use in the United States in April 2013, and in the European Union in July 2014. Medical uses Brinzolamide/brimonidine is indicated to decrease of elevated intraocular pressure (IOP) in adults with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction. History Brinzolamide/brimonidine was approved for medical use in the United States in April 2013, and in the European Union in July 2014. References Further reading Li T, Lindsley K, Rouse B, Hong H, Shi Q, Friedman DS, Wormald R, Dickersin K (January 2016). "Comparative Effectiveness of First-Line Medications for Primary Open-Angle Glaucoma: A Systematic Review and Network Meta-analysis". Ophthalmology. 123 (1): 129–40. doi:10.1016/j.ophtha.2015.09.005. PMC 4695285. PMID 26526633. Lusthaus JA, Goldberg I (September 2017). "Brimonidine and brinzolamide for treating glaucoma and ocular hypertension; a safety evaluation". Expert Opin Drug Saf. 16 (9): 1071–1078. doi:10.1080/14740338.2017.1346083. PMID 28656780. S2CID 205825340. External links "Brinzolamide". Drug Information Portal. U.S. National Library of Medicine. "Brimonidine". Drug Information Portal. U.S. National Library of Medicine. "Brimonidine tartrate". 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 encountering the term 'Erysipeloid' in medical literature. What's its definition?

In humans, Erysipelothrix rhusiopathiae infections most commonly present in a mild cutaneous form known as erysipeloid or fish poisoning. E. rhusiopathiae can cause an indolent cellulitis, more commonly in individuals who handle fish and raw meat. Erysipelothrix rhusiopathiae also causes Swine Erysipelas. It is common in domestic pigs and can be transmitted to humans who work with swine. It gains entry typically by abrasions in the hand. Bacteremia and endocarditis are uncommon but serious sequelae. Due to the rarity of reported human cases, E. rhusiopathiae infections are frequently misidentified at presentation. Diagnosis Violaceous swelling with severe pain but without pus (Which differentiates from pus forming streptococcal and staphylococcal erysipelas) Erysipeloid of Rosenbach Erysipeloid of Rosenbach is a cutaneous condition most frequently characterized by a purplish marginated swelling on the hands.: 264  The eponym Rosenbachs disease is in reference to the milder type of the condition and is named after Friedrich Julius Rosenbach. Early work on the condition in US fishermen was carried out by Klaunders and colleagues. Treatment The treatment of choice is a single dose of benzathine benzylpenicillin given by intramuscular injection, or a five-day to one-week course of either oral penicillin or intramuscular procaine benzylpenicillin. Erythromycin or doxycycline may be given instead to people who are allergic to penicillin. E. rhusiopathiae is intrinsically resistant to vancomycin. See also Erysipeloid of Rosenbach References == External links ==

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

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

Meclizine, sold under the brand name Bonine, among others, is an antihistamine used to treat motion sickness and dizziness (vertigo). It is taken by mouth. Effects generally begin in an hour and last for up to a day.Common side effects include sleepiness and dry mouth. Serious side effects may include allergic reactions. Use in pregnancy appears safe, but has not been well studied while use in breastfeeding is of unclear safety. It is believed to work in part by anticholinergic and antihistamine mechanisms.Meclizine was patented in 1951 and came into medical use in 1953. It is available as a generic medication and often over the counter. In 2019, it was the 150th most commonly prescribed medication in the United States, with more than 4 million prescriptions. Medical uses Meclizine is used to treat symptoms of motion sickness. Safety and efficacy in children younger than twelve years of age has not been established; therefore, use in this population is not recommended. Meclizine should be taken with caution in the elderly due to increased risk of confusion and amnesia. Motion sickness Meclizine is effective in inhibiting nausea, vomiting, and dizziness caused by motion sickness.The drug is safe for treating nausea in pregnancy and is a first-line therapy for this use. Doxylamine is similarly safe. Meclizine may not be strong enough for especially sickening motion stimuli and second-line defenses should be tried in those cases. Vertigo Meclizine may be used to treat motion sickness or vertigo such as in those with Ménières disease. Side effects Some common side effects such as drowsiness, dry mouth, and tiredness may occur. Meclizine has been shown to have fewer dry mouth side effects than the traditional treatment for motion sickness, transdermal scopolamine. A very serious allergic reaction to this drug is unlikely, but immediate medical attention should be sought if it occurs. Symptoms of a serious allergic reaction may include rash, itching, swelling, severe dizziness, and trouble breathing. Drowsiness Drowsiness may result as a side effect of taking meclizine. Users are advised not to operate heavy machinery while under the influence. The consumption of alcohol while under the influence of meclizine may result in additional drowsiness. Elderly As with any anticholinergic agent, meclizine may cause confusion or aggravate symptoms in those with dementia in the geriatric population (older than 65 years). Therefore, caution should be used when administering meclizine to the elderly. Mechanism of action Meclizine is an antagonist at H1 receptors. It possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Its antiemetic and antivertigo effects are not fully understood, but its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It has however been suggested that meclizine only has an inhibitory effect under normal viewing-circumstances, as the drug has been shown to enhance an isolated vestibular response. Much like motion-sickness arises from a discrepancy between multiple senses, Meclizine most likely affects a wide array of sensory mechanisms related to self-motion. Meclizine also is a dopamine antagonist at D1-like and D2-like receptors but does not cause catalepsy in mice, perhaps because of its anticholinergic activity. Chemistry Meclizine is a first-generation antihistamine (nonselective H1 antagonist) of the piperazine class. It is structurally and pharmacologically similar to buclizine, cyclizine, and hydroxyzine, but has a shorter half-life of six hours compared to cyclizine and hydroxyzine with about 20 hours (though half-life should not be confused with duration). It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Meclizine is sometimes combined with opioids, especially ones of the open-chain class like methadone, dextropropoxyphene, and dipipanone. Similarly, Diconal is a combination drug containing dipipanone and cyclizine. Synthesis (4-Chlorphenyl)-phenylmethanol is halogenated with thionyl chloride before adding acetylpiperazine. The acetyl group is cleaved with diluted sulfuric acid. An N-alkylation of the piperazine ring with 3-methylbenzylchloride completes the synthesis. Alternatively, the last step can be replaced by a reductive N-alkylation with 3-methylbenzaldehyde. The reductive agent is hydrogen, and Raney nickel is used as a catalyst. Meclizine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the racemic dihydrochloride. Names Meclizine is an international nonproprietary name.It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine II (Less Drowsy Formulation). Emesafene is a combination of meclizine (1/3) and pyridoxine (2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclizine and nicotinic acid. Notes References External links "Meclizine". Drug Information Portal. U.S. National Library of Medicine. "Meclizine dihydrochloride". Drug Information Portal. U.S. National Library of Medicine.

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Can you demystify the medical term 'Cutaneous meningioma' for me?

Cutaneous meningioma (also known as "Heterotopic meningeal tissue," and "Rudimentary meningocele") is a developmental defect, and results from the presence of meningocytes outside the calvarium.: 622 See also List of cutaneous conditions == References ==

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 'Dacryocystitis' within a medical context. Could you shed some light on it?

Dacryocystitis is an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. The term derives from the Greek dákryon (tear), cysta (sac), and -itis (inflammation). It causes pain, redness, and swelling over the inner aspect of the lower eyelid and epiphora. When nasolacrimal duct obstruction is secondary to a congenital barrier it is referred to as dacryocystocele. It is most commonly caused by Staphylococcus aureus and Streptococcus pneumoniae. The most common complication is corneal ulceration, frequently in association with S. pneumoniae. The mainstays of treatment are oral antibiotics, warm compresses, and relief of nasolacrimal duct obstruction by dacryocystorhinostomy. Signs and symptoms Pain, swelling, redness over the lacrimal sac at medial canthus Tearing, crusting, fever Digital pressure over the lacrimal sac may extrude pus through the punctum In chronic cases, tearing may be the only symptom Pathophysiology A variety of causes may lead to dacryocystitis. Most notably, obstruction of the nasolacrimal duct leads to stasis of the nasolacrimal fluid, which predisposes to infection. Staphylococcus aureus is a common bacterial pathogen causing infectious dacryocystitis. Sometimes, especially in women, stones may develop in the lacrimal gland, causing recurrent bouts of dacryocystitis; this condition is called "acute dacryocystic retention syndrome." Also due to pneumococcus, infection due to surrounding structure such as paranasal sinuses. Prognosis About 60 percent of initial attacks of dacryocystitis will recur. Individuals with a poorly functioning immune system (immunocompromised) may develop orbital cellulitis, which may lead to optic neuritis, proptosis, motility abnormalities, or blindness. See also Dacryocystocele Canaliculitis References == External links ==

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

Pentamidine is an antimicrobial medication used to treat African trypanosomiasis, leishmaniasis, Balamuthia infections, babesiosis, and to prevent and treat pneumocystis pneumonia (PCP) in people with poor immune function. In African trypanosomiasis it is used for early disease before central nervous system involvement, as a second line option to suramin. It is an option for both visceral leishmaniasis and cutaneous leishmaniasis. Pentamidine can be given by injection into a vein or muscle or by inhalation.Common side effects of the injectable form include low blood sugar, pain at the site of injection, nausea, vomiting, low blood pressure, and kidney problems. Common side effects of the inhaled form include wheezing, cough, and nausea. It is unclear if doses should be changed in those with kidney or liver problems. Pentamidine is not recommended in early pregnancy but may be used in later pregnancy. Its safety during breastfeeding is unclear. Pentamidine is in the aromatic diamidine family of medications. While the way the medication works is not entirely clear, it is believed to involve decreasing the production of DNA, RNA, and protein.Pentamidine came into medical use in 1937. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In regions of the world where the disease is common pentamidine is provided for free by the World Health Organization (WHO). Medical uses Treatment of PCP caused by Pneumocystis jirovecii Prevention of PCP in adults with HIV who have one or both of the following: History of PCP CD4+ count ≤ 200mm³ Treatment of leishmaniasis Treatment of African trypanosomiasis caused by Trypanosoma brucei gambiense Balamuthia infections Pentamidine is classified as an orphan drug by the U.S. Food and Drug Administration Other uses Use as an antitumor drug has also been proposed. Pentamidine is also identified as a potential small molecule antagonist that disrupts this interaction between S100P and RAGE receptor. Special Populations Pregnancy It has not been shown to cause birth defects in animal studies when given intravenously. There are no controlled studies to show if pentamidine can harm the fetus in pregnant women. It is only recommended if the drug of choice trimethoprim-sulfamethoxazole is contraindicated. Breastfeeding There is no information regarding the excretion of pentamidine in breast milk, but since the adverse effects on breastfed infants are unknown currently, it is recommended by the manufacturer for the infant to not be breastfed or for the mother to stop the drug. Risks versus benefits for the mother should be considered when making this decision. Children Pentamidine can be used in the prevention of PCP in children with HIV who cannot tolerate Trimethoprim/Sulfamethoxazole and can use a nebulizer. Intranvenous solutions of pentamidine should only be used in children with HIV older than 2 years old when other treatments are unavailable Elderly There is no data for the use of pentamidine in this specific population. Contraindications Patients with a history of anaphylaxis or hypersensitivity to pentamidine isethionate Side effects Common Burning pain, dryness, or sensation of lump in throat Chest pain Coughing difficulty in breathing difficulty in swallowing skin rash wheezing Rare Nausea and vomiting Pain in upper abdomen, possibly radiating to the back Severe pain in side of chest Shortness of breath Others Blood: Pentamidine frequently causes leukopenia and less often thrombopenia, which may cause symptomatic bleeding. Some cases of anemia, possibly related to folic acid deficiency, have been described. Cardiovascular: Hypotension, which may be severe. Severe or fatal arrhythmias and heart failure are quite frequent. Kidney: 25 percent develop signs of nephrotoxicity ranging from mild, asymptomatic azotemia (increased serum creatinine and urea) to irreversible renal failure. Ample fluids or intravenous hydration may prevent some nephrotoxicity. Liver: Elevated liver enzymes are associated with intravenous use of pentamidine. Hepatomegaly and hepatitis have been encountered with long term prophylactic use of pentamidine inhalation. Neurological: Dizziness, drowsiness, neuralgia, confusion, hallucinations, seizures and other central side effects are reported. Pancreas: Hypoglycemia that requires symptomatic treatment is frequently seen. On the other hand, pentamidine may cause or worsen diabetes mellitus. Respiratory: Cough and bronchospasm, most frequently seen with inhalation. Skin: Severe local reactions after extravasculation of intravenous solutions or following intramuscular injection treatment have been seen. Pentamidine itself may cause rash, or rarely Stevens–Johnson syndrome or Lyell syndrome. Eye discomfort, conjunctivitis, throat irritation, splenomegaly, Herxheimer reaction, electrolyte imbalances (e.g. hypocalcemia). Drug interactions The additional or sequential use of other nephrotoxic drugs like aminoglycosides, amphotericin B, capreomycin, colistin, polymyxin B, vancomycin, foscarnet, or cisplatin should be closely monitored, or whenever possible completely avoided. Mechanism of action The mechanism seems to vary with different organisms and is not well understood. However, pentamidine is suspected to work through various methods of interference of critical functions in DNA, RNA, phospholipid and protein synthesis. Pentamidine binds to adenine-thymine-rich regions of the Trypanosoma parasite DNA, forming a cross-link between two adenines four to five base pairs apart. The drug also inhibits topoisomerase enzymes in the mitochondria of Pneumocystis jirovecii. Similarly, pentamidine inhibits type II topoisomerase in the mitochondria of the Trypanosoma parasite, resulting in a broken and unreadable mitochondrial genome. Resistance Strains of the Trypanosoma brucei parasite that are resistant to pentamidine have been discovered. Pentamidine is brought into the mitochondria through carrier proteins, and the absence of these carriers prevents the drug from reaching its site of action. Pharmacokinetics Absorption: Pentamidine is completely absorbed when given intravenously or intramuscularly. When inhaled through a nebulizer, pentamidine accumulates in the bronchoalveolar fluid of the lungs at a higher concentration compared to injections. The inhaled form is minimally absorbed in the blood. Absorption is unreliable when given orally.Distribution: When injected, pentamidine binds to tissues and proteins in the plasma. It accumulates in the kidney, liver, lungs, pancreas, spleen, and adrenal glands. Additionally, pentamidine does not reach curative levels in the cerebrospinal fluid. It has a volume of distribution of 286-1356 liters when given intravenously and 1658-3790 liters when given intramuscularly. Inhaled pentamidine is mainly deposited into the bronchoalveolar lavage fluid of the lungs.Metabolism: Pentamidine is primarily metabolized by Cytochrome P450 enzymes in the liver. Up to 12% of pentamidine is eliminated in the urine unchanged.Elimination: Pentamidine has an average half-life of 5–8 hours when given intravenously and 7–11 hours when given intramuscularly. However, these may increase with severe kidney problems. Pentamidine can remain in the system for as long as 8 months after the first injection. Chemistry Pentamidine isethionate for injection is commercially available as a lyophilized, white crystalline powder for reconstitution with sterile water or 5% Dextrose. After reconstitution, the mixture should be free from discoloration and precipitation. Reconstitution with sodium chloride should be avoided due to formation of precipitates. Intravenous solutions of pentamidine can be mixed with intravenous HIV medications like zidovidine and intravenous heart medications like diltiazem. However, intravenous solutions of antiviral foscarnet and antifungal fluconazole are incompatible with pentamidine. To avoid side-effects associated with intravenous administration, the solution should be slowly infused to minimize the release of histamine. History Pentamidine was first used to treat African trypanosomiasis in 1937 and leishmaniasis in 1940 before it was registered as pentamidine mesylate in 1950. Its efficacy against Pneumocystis jirovecii was demonstrated in 1987, following its re-emergence on the drug market in 1984 in the current isethionate form. Trade names and dose form For oral inhalation and for nebulizer use: NebuPent Nebulizer (APP Pharmaceuticals LLC - US)For intravenous and intramuscular use: US and Canada: Pentacarinat 300 injection powder 300 mg vial (Avantis Pharma Inc - Canada) Pentam 300 (APP Pharmaceuticals LLC - US) Pentamidine isethionate 300 mg for injection (David Bull Laboratories LTD - Canada, Hospira Healthcare Corporation - Canada) International Brands:Pentamidine isethionate (Abbott) Pentacarinat (Sanofi-Aventis) Pentacrinat (Abbott) Pentam (Abbott) Pneumopent See also Netropsin Lexitropsin References External links "Pentamidine". Drug Information Portal. U.S. National Library of Medicine.

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

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

Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock. Toxic megacolon is usually a complication of inflammatory bowel disease, such as ulcerative colitis and, more rarely, Crohns disease, and of some infections of the colon, including Clostridium difficile infections, which have led to pseudomembranous colitis. Other forms of megacolon exist and can be congenital (present since birth, such as Hirschsprungs disease). It can also be caused by Entamoeba histolytica and Shigella. It may also be caused by the use of loperamide. Signs and symptoms Abdominal pain Abdominal bloating Abdominal tenderness Fever Tachycardia (rapid heart rate) DehydrationThere may be signs of septic shock. A physical examination reveals abdominal tenderness and possible loss of bowel sounds. An abdominal radiography shows colonic dilation. White blood cell count is usually elevated. Severe sepsis may present with hypothermia or leukopenia. Complications Perforation of the colon Sepsis ShockEmergency action may be required if severe abdominal pain develops, particularly if it is accompanied by fever, rapid heart rate, tenderness when the abdomen is pressed, bloody diarrhea, frequent diarrhea, or painful bowel movements. Colonoscopy is contraindicated, as it may rupture the dilated colon resulting in peritonitis and septic shock. Pathophysiology The pathological process involves inflammation and damage to the colonic wall with unknown toxins breaking down the protective mucosal barrier and exposing the muscularis propria. There is relative destruction of the ganglion cells and swelling of the nerve fibers in the myenteric plexus, with concomitant damage to the colonic musculature. This results in almost complete paralysis of the diseased segment of the colon with loss of smooth muscle substance, tone and motility. This can lead to further complications as pressure builds up in the colon due to relative fecal stasis including sepsis, intestinal hemorrhage or free perforation and spontaneous decompression. Diagnosis "Abdominal X-ray with the features of Air-fluid level can be shown or CT Scan with Contrast can be done if the patient is stable." Treatment The objective of treatment is to decompress the bowel and to prevent swallowed air from further distending the bowel. If decompression is not achieved or the patient does not improve within 24 hours, a colectomy (surgical removal of all or part of the colon) is indicated. When surgery is required the recommended procedure is a subtotal colectomy with end ileostomy. Fluid and electrolyte replacement help to prevent dehydration and shock. Use of corticosteroids may be indicated to suppress the inflammatory reaction in the colon if megacolon has resulted from active inflammatory bowel disease. Antibiotics may be given to prevent sepsis. Prognosis If the condition does not improve, the risk of death is significant. In case of poor response to conservative therapy, a colectomy is usually required. References This article incorporates text from the United States National Library of Medicine (Toxic megacolon), which is in the public domain. Further reading Ausch, C; Madoff, RD; Gnant, M; Rosen, HR; Garcia-Aguilar, J; Hölbling, N; Herbst, F; Buxhofer, V; Holzer, B; Rothenberger, DA; Schiessel, R (March 2006). "Aetiology and surgical management of toxic megacolon". Colorectal Disease. 8 (3): 195–201. doi:10.1111/j.1463-1318.2005.00887.x. PMID 16466559. S2CID 36384160. Toxic Megacolon at eMedicine == External links ==

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.

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

Acrodysostosis is a rare congenital malformation syndrome which involves shortening of the interphalangeal joints of the hands and feet, intellectual disability in approximately 90% of affected children, and peculiar facies. Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur. Signs and Symptoms Acrodysostosis presents with a wide spectrum of clinical manifestations. The following is a list of conditions and complications associated with acrodysostosis. Bone issues Skeletal dysplasia (dwarfism, short stature) Brachydactyly Advanced bone age Bone plate fusing Scoliosis Pain – joint, hip, lower back, wrist Endocrine Hypothyroidism Hypoparathyroidism Pseudohypoparathyroidism Vitamin D deficiency Thyroid cysts Type 1 diabetes Behavioural / Developmental / Emotional Autism Spectrum Disorder (ASD) Childhood Apraxia of Speech Cognitive impairment Sensory issues Gross motor delays Fine motor delays Craniofacial and dental Cranial frontal nasal syndrome Midface hypoplasia Depressed nasal bridge Retrognathia Glossoptosis High palate Mandibular distraction surgery Jaw surgery Underbite Chalky teeth Overcrowded teeth Early eruption of adult teeth Small, unaligned teeth Cardiology Hypertension Atrial Septal Defect (ASD) Aortic Coarctation Middle Aortic Syndrome (MAS) Coarctation of abdominal aorta Bradycardia Bicuspid aortic valve Causes Acrodysostosis is believed to be caused by mutations in the PRKAR1A gene (type 1) or the PDE4D gene (type 2). It has been suggested that the condition might be genetically related i.e. in an autosomal dominant mode of transmission. Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception. A PRKAR1A mutation has been identified in acrodysostosis with hormone resistance. Diagnosis Treatment There are currently no approved treatments or standardised treatment guidelines for acrodysostosis. Management of acrodysostosis typically focuses on addressing specific symptoms that occur in each individual and may include surgery, physical therapy and special education. Research A number of transgenic mouse models have been generated that harbour genetic mutations within genes linked to the condition in humans. These mouse models exhibit phenotypes similar to that observed in Acrodysostosis in humans. Media The actress Olivia Colman partnered with the charity Acrodysostosis Support and Research to raise awareness for the disease. She participated in a promotional video campaign in December 2020. References External links "Acrodysostosis: Support and Research". "Acrodysostosis: Disease Information from NORD". National Organization for Rare Disorders. Acrodysostosis at NIHs Office of Rare Diseases

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

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants urine and earwax, particularly prior to diagnosis and during times of acute illness. Signs and symptoms The disease is named for the presence of sweet-smelling urine, similar to maple syrup, when the person goes into metabolic crisis. The smell is also detected in ear wax of an affected individual during metabolic crisis. In populations to whom maple syrup is unfamiliar, the aroma can be likened to fenugreek, and fenugreek ingestion may impart the aroma to urine. Symptoms of MSUD varies between patients and is greatly related to the amount of residual enzyme activity. Classic MSUD Infants with classic MSUD will display subtle symptoms within the first 24–48 hours. Subtle symptoms include poor feeding, either bottle or breast, lethargy, and irritability. The infant will then experience increased focal neurologic signs. These neurologic signs include athetoid, hypertonia, spasticity, and opisthotonus that lead to convulsions and coma. If MSUD is left untreated, central neurologic function and respiratory failure will occur and lead to death. Although MSUD can be stabilized, there are still threats of metabolic decompensation and loss of bone mass that can lead to osteoporosis, pancreatitis, and intracranial hypertension. Additional signs and symptoms that can be associated with classic MSUD include intellectual limitation and behavioral issues. Intermediate MSUD Intermediate MSUD has greater levels of residual enzyme activity than classic MSUD. The majority of children with intermediate MSUD are diagnosed between the ages of 5 months and 7 years. Symptoms associated with classic MSUD also appear in intermediate MSUD. Intermittent MSUD Contrary to classic and intermediate MSUD, intermittent MSUD individuals will have normal growth and intellectual development. Symptoms of lethargy and characterized odor of maple syrup will occur when the individual experiences stress, does not eat, or develops an infection. Metabolic crisis leading to seizures, coma, and brain damage is still a possibility. Thiamine-response MSUD Symptoms associated with thiamine-response MSUD are similar to intermediate MSUD. Newborns rarely present with symptoms. Later onset The symptoms of MSUD may also present later depending on the severity of the disease. Untreated in older individuals, and during times of metabolic crisis, symptoms of the condition include uncharacteristically inappropriate, extreme or erratic behaviour and moods, hallucinations, lack of appetite, weight loss, anemia, diarrhea, vomiting, dehydration, lethargy, oscillating hypertonia and hypotonia, ataxia, seizures, hypoglycaemia, ketoacidosis, opisthotonus, pancreatitis, rapid neurological decline, and coma. Death from cerebral edema will likely occur if there is no treatment. Additionally, MSUD patients experience an abnormal course of diseases in simple infections that can lead to permanent damage. Causes Mutations in the following genes cause maple syrup urine disease: BCKDHA (OMIM: 608348) BCKDHB (OMIM: 248611) DBT (OMIM: 248610) DLD (OMIM: 238331)These four genes produce proteins that work together as the branched-chain alpha-keto acid dehydrogenase complex. The complex is essential for breaking down the amino acids leucine, isoleucine, and valine. These are present in some quantity in almost all kinds of food, but in particular, protein-rich foods such as dairy products, meat, fish, soy, gluten, eggs, nuts, whole grains, seeds, avocados, algae, edible seaweed, beans, and pulses. Mutation in any of these genes reduces or eliminates the function of the enzyme complex, preventing the normal breakdown of isoleucine, leucine, and valine. As a result, these amino acids and their by-products build up in the body. Because high levels of these substances are toxic to the brain and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease.This condition has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene – one from each parent – must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder. Pathophysiology MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKAD), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The buildup of these BCAAS will lead to the maple syrup odor that is associated with MSUD. The BCKAD complex begins by breaking down leucine, isoleucine, and valine through the use of branch-chain aminotransferase into their relevant α-ketoacids. The second step involves the conversion of α-ketoacids into acetoacetate, acetyl-CoA, and succinyl-CoA through oxidative decarboxylation of α-ketoacids. The BCKAD complex consists of four subunits designated E1α, E1β, E2, and E3. The E3 subunit is also a component of pyruvate dehydrogenase complex and oxoglutarate dehydrogenase complex. MSUD can result from mutations in any of the genes that code for these enzyme subunits, E1α, E1β, E2, and E3. Mutations of these enzyme subunits will lead to the BCKAD complex unable to break down leucine, isoleucine, and valine. The levels of these branched chain amino acids will become elevated and lead to the symptoms associated with MSUD. Glutamate levels are maintained in the brain by BCAA metabolism functions and if not properly maintained can lead to neurological problems that are seen in MSUD individuals. High levels of leucine has also been shown to affect water homeostasis within subcortical gray matter leading to cerebral edema, which occurs in MSUD patients if left untreated. Diagnosis Prior to the easy availability of plasma amino acid measurement, diagnosis was commonly made based on suggestive symptoms and odor. Affected individuals are now often identified with characteristic elevations on plasma amino acids which do not have the characteristic odor. The compound responsible for the odor is sotolon (sometimes spelled sotolone).On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four further genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including maple syrup urine disease. The disease is estimated to affect 1 out of 185,000 infants worldwide and its frequency increases with certain heritages.Newborn screening for maple syrup urine disease involves analyzing the blood of 1–2 day-old newborns through tandem mass spectrometry. The blood concentration of leucine and isoleucine is measured relative to other amino acids to determine if the newborn has a high level of branched-chain amino acids. Once the newborn is 2–3 days old the blood concentration of branched-chain amino acids like leucine is greater than 1000 μmol/L and alternative screening methods are used. Instead, the newborns urine is analyzed for levels of branched-chain alpha-hydroxyacids and alpha-ketoacids.The amount and type of enzyme activity in an affected individual with MSUD will determine which classification the affected individual will identify with: Classic MSUD: Less than 2% of normal enzyme activity Intermediate MSUD: 3-8% normal enzyme activity Intermittent MSUD: 8-15% of normal enzyme activity Thiamine-Responsive MSUD: Large doses of thiamine will increase enzyme activity. Classification Maple syrup urine disease can be classified by its pattern of signs and symptoms, or by its genetic cause. The most common and severe form of this disease is the classic type, which appears soon after birth, and as long as it remains untreated, gives rise to progressive and unremitting symptoms. Variant forms of the disorder may become apparent only later in infancy or childhood, with typically less severe symptoms that may only appear during times of fasting, stress or illness, but still involve mental and physical problems if left untreated.Sub-divisions of MSUD: Classic MSUD Intermediate MSUD Intermittent MSUD Thiamine-responsive MSUDGenerally, majority of patients will be classified into one of these four categories but some patients affected by MSUD do not fit the criteria for the listed sub-divisions and will be deemed unclassified MSUD. Prevention There are no methods for preventing the manifestation of the pathology of MSUD in infants with two defective copies of the BCKD gene. However, genetic counselors may consult with couples to screen for the disease via DNA testing. DNA testing is also available to identify the disease in an unborn child in the womb. Treatment Monitoring Keeping MSUD under control requires careful monitoring of blood chemistry, both at home and in a hospital setting. DNPH or specialised dipsticks may be used to test the patients urine for ketones (a sign of metabolic decompensation), when metabolic stress is likely or suspected. Fingerstick tests are performed regularly and sent to a laboratory to determine blood levels of leucine, isoleucine, and valine. Regular metabolic consultations, including blood-draws for full nutritional analysis, are recommended; especially during puberty and periods of rapid growth. MSUD management also involves a specially tailored metabolic formula, a modified diet, and lifestyle precautions such as avoiding fatigue and infections, as well as consuming regular, sufficient calories in proportion to physical stress and exertion. Without sufficient calories, catabolism of muscle protein will result in metabolic crisis. Those with MSUD must be hospitalised for intravenous infusion of sugars and nasogastric drip-feeding of formula, in the event of metabolic decompensation, or lack of appetite, diarrhea or vomiting. Food avoidance, rejection of formula and picky eating are all common problems with MSUD. Some patients may need to receive all or part of their daily nutrition through a feeding tube. Toxin removal Following diagnosis, rapid removal of excess leucine from the body reduces the impact of the disease on development. Exchange transfusion, hemodialysis, or hemofiltration may be used. Diet control A diet with carefully controlled levels of the amino acids leucine, isoleucine, and valine must be maintained at all times in order to prevent neurological damage. Since these three amino acids occur in all natural protein, and most natural foods contain some protein, any food intake must be closely monitored, and day-to-day protein intake calculated on a cumulative basis, to ensure individual tolerance levels are not exceeded at any time. As the MSUD diet is so protein-restricted, and adequate protein is a requirement for all humans, tailored metabolic formula containing all the other essential amino acids, as well as any vitamins, minerals, omega-3 fatty acids and trace elements (which may be lacking due to the limited range of permissible foods), are an essential aspect of MSUD management. These complement the MSUD patients natural food intake to meet normal nutritional requirements without causing harm. If adequate calories cannot be obtained from natural food without exceeding protein tolerance, specialised low protein products such as starch-based baking mixtures, imitation rice and pasta may be prescribed, often alongside a protein-free carbohydrate powder added to food and/or drink, and increased at times of metabolic stress. MSUD patients with thiamine- responsive MSUD can have a higher protein intake diet with administration of high doses of thiamine, a cofactor of the enzyme that causes the condition. The typical dosage amount of thiamine-responsive MSUD depends on the enzyme activity present and can range from 10 mg - 100 mg daily. Liver transplantation Usually MSUD patients are monitored by a dietitian. Liver transplantation is a treatment option that can completely and permanently normalise metabolic function, enabling discontinuation of nutritional supplements and strict monitoring of biochemistry and caloric intake, relaxation of MSUD-related lifestyle precautions, and an unrestricted diet. This procedure is most successful when performed at a young age, and weaning from immunosuppressants may even be possible in the long run. However, the surgery is a major undertaking requiring extensive hospitalisation and rigorous adherence to a tapering regimen of medications. Following transplant, the risk of periodic rejection will always exist, as will the need for some degree of lifelong monitoring in this respect. Despite normalising clinical presentation, liver transplantation is not considered a cure for MSUD. The patient will still carry two copies of the mutated BKAD gene in each of their own cells, which will consequently still be unable to produce the missing enzyme. They will also still pass one mutated copy of the gene on to each of their biological children. As a major surgery the transplant procedure itself also carries standard risks, although the odds of its success are greatly elevated when the only indication for it is an inborn error of metabolism. In absence of a liver transplant, the MSUD diet must be adhered to strictly and permanently. However, in both treatment scenarios, with proper management, those affected are able to live healthy, normal lives without experiencing the severe neurological damage associated with the disease. Pregnancy Control of metabolism is vital during pregnancy of women with MSUD. To prevent detrimental abnormalities in development of the embryo or fetus, dietary adjustments should be made and plasma amino acid concentrations of the mother should be observed carefully and frequently. Amino acid deficiency can be detected through fetal growth, making it essential to monitor development closely. Prognosis If left untreated, MSUD will lead to death due to central neurological function failure and respiratory failure. Early detection, diet low in branched-chain amino acids, and close monitoring of blood chemistry can lead to a good prognosis with little or no abnormal developments. Average intellectual development is below that of the general population and the severity of the deficit is a related to the time the condition remained undiagnosed and the effectiveness of dietary control including during metabolic crises. Epidemiology Maple syrup urine disease (MSUD) is a rare, inherited metabolic disorder. Its prevalence in the United States population is approximately 1 newborn out of 180,000 live births. However, in populations where there is a higher frequency of consanguinity, such as the Mennonites in Pennsylvania or the Amish, the frequency of MSUD is significantly higher at 1 newborn out of 176 live births. In Austria, 1 newborn out of 250,000 live births inherits MSUD. It also is believed to have a higher prevalence in certain populations due in part to the founder effect since MSUD has a much higher prevalence in children of Amish, Mennonite, and Jewish descent. Research directions Gene therapy Gene therapy to overcome the genetic mutations that cause MSUD have already been proven safe in animals studies with MSUD. The gene therapy involves a healthy copy of the gene causing MSUD is produced and inserted into a viral vector. The adeno-associated virus vector is delivered one-time to the patient intravenously. Hepatocytes will take up vector and functional copies of the affected gene is MSUD patients will be expressed. This will allow BCAA to be broken down properly and prevent toxic build up. Phenylbutyrate therapy Sodium phenylacetate/benzoate or sodium phenylbutyrate has been shown to reduce BCAA in a clinical trial done February 2011. Phenylbutyrate treatment reduced the blood concentration of BCAA and their corresponding BCKA in certain groups of MSUD patients and may be a possible adjunctive treatment. See also Isovaleric acidemia Methylmalonic acidemia Propionic acidemia John Menkes References External links Maple syrup urine disease at NLM Genetics Home Reference msud at NIH/UW GeneTests

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

Streptozotocin or streptozocin (INN, USP) (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the islets of Langerhans and used in medical research to produce an animal model for hyperglycemia and Alzheimers in a large dose, as well as type 2 diabetes or type 1 diabetes with multiple low doses. Usage Streptozotocin is approved by the U.S. Food and Drug Administration (FDA) for treating metastatic cancer of the pancreatic islet cells. Since it carries a substantial risk of toxicity and rarely cures the cancer, its use is generally limited to patients whose cancer cannot be removed by surgery. In these patients, streptozotocin can reduce the tumor size and reduce symptoms (especially hypoglycemia due to excessive insulin secretion by insulinomas). A typical dose is 500 mg/m2/day by intravenous injection, for 5 days, repeated every 4–6 weeks. Due to its high toxicity to beta cells, in scientific research, streptozotocin has also been long used for inducing insulitis and diabetes on experimental animals. Streptozotocin has also been used for modeling Alzheimers disease through memory loss in mice. Mechanism Streptozotocin is a glucosamine-nitrosourea compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute. DNA damage induces activation of PARP which is likely more important for diabetes induction than the DNA damage itself. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2. History Streptozotocin was originally identified in the late 1950s as an antibiotic. The drug was discovered in a strain of the soil microbe Streptomyces achromogenes by scientists at the drug company Upjohn (now part of Pfizer) in Kalamazoo, Michigan. The soil sample in which the microbe turned up had been taken from Blue Rapids, Kansas, which can therefore be considered the birthplace of streptozotocin. Upjohn filed for patent protection for the drug in August 1958 and U.S. Patent 3,027,300 was granted in March 1962. In the mid-1960s, streptozotocin was found to be selectively toxic to the beta cells of the pancreatic islets, the cells that normally regulate blood glucose levels by producing the hormone insulin. This suggested the drugs use as an animal model of diabetes, and as a medical treatment for cancers of the beta cells. In the 1960s and 1970s, the National Cancer Institute investigated streptozotocins use in cancer chemotherapy. Upjohn filed for FDA approval of streptozotocin as a treatment for pancreatic islet cell cancer in November 1976, and approval was granted in July 1982. The drug was subsequently marketed as Zanosar. More recently, a growing body of studies has provided evidence that derangement of insulin signaling underlying type-2 diabetes significantly increase the risk of cognitive impairment and Alzheimers disease (AD) progression (12). On this ground, the direct administration of STZ in the brain (i.e., by intracerebroventricular (ICV) infusion) has been used to develop an animal model of brain insulin resistance to mimic in rodents the pathophysiology of sporadic AD, which represents the most common form of AD in humans. STZ infusion in the brain induced accumulation of Amyloid beta (Aβ) protein (13), oxidative stress and cognitive impairment (14). Notably, there is now evidence that STZ infusion within the brain produced up-regulation of amyloid precursor protein (APP), tau hyperphosphorylation and neuroinflammation (15). This study (15), also shows that treatment with the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) can relieve APP upregulation, neuroinflammation and reduce cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations, as well as induce a nearly complete recovery of cognitive impairment in the STZ-induced SAD mouse model. Streptozotocin is now long off patent and many generic formulations are available. Biosynthesis Recent advancements in understanding the biosynthesis of this natural product have been made by Balskus et al. In short, the authors found the gene cluster responsible for production of Streptozotocin in Streptomyces achromogenes and identified novel function of a non-heme iron enzyme, SznF, which forms the N-N bond in the N-nitrosourea pharmacophore by oxidative rearrangement. See also Alloxan References 12. Velayudhan, L. et al. Risk of developing dementia in people with diabetes and mild cognitive impairment. Br. J. Psychiatry 2010, 196, 36–40. 13. Knezovic, A.; Osmanovic-Barilar, J.; Curlin, M.; Hof, P.R.; Šimić, G.; Riederer, P.; Salkovic-Petrisic, M. et al. Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimers disease. J. Neural Transm. 2015, 122, 577–592. 14. Sharma, M. et al. Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci. 2001, 68, 1021–1029. 15. Latina, V. et al., Tau Cleavage Contributes to Cognitive Dysfunction in Streptozotocin-Induced Sporadic Alzheimers Disease (sAD) Mouse Model. Int. J. Mol. Sci. 2021, 22, 12158. https://doi.org/10.3390/ijms222212158. External links U.S. Patent 3,027,300 FDA drug details

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

Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move ones legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This is often described as aching, tingling, or crawling in nature. Occasionally, arms may also be affected. The feelings generally happen when at rest and therefore can make it hard to sleep. Due to the disturbance in sleep, people with RLS may have daytime sleepiness, low energy, irritability and a depressed mood. Additionally, many have limb twitching during sleep. RLS is not the same as habitual foot tapping or leg rocking.Risk factors for RLS include low iron levels, kidney failure, Parkinsons disease, diabetes mellitus, rheumatoid arthritis, pregnancy and celiac disease. A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers. There are two main types. One is early onset RLS which starts before age 45, runs in families and worsens over time. The other is late onset RLS which begins after age 45, starts suddenly, and does not worsen. Diagnosis is generally based on a persons symptoms after ruling out other potential causes.Restless legs syndrome may resolve if the underlying problem is addressed. Otherwise treatment includes lifestyle changes and medication. Lifestyle changes that may help include stopping alcohol and tobacco use, and sleep hygiene. Medications used include a dopamine agonist such as pramipexole. RLS affects an estimated 2.5–15% of the American population. Females are more commonly affected than males, and it becomes increasingly common with age. Signs and symptoms RLS sensations range from pain or an aching in the muscles, to "an itch you cant scratch", a "buzzing sensation", an unpleasant "tickle that wont stop", a "crawling" feeling, or limbs jerking while awake. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep.It is a "spectrum" disease with some people experiencing only a minor annoyance and others having major disruption of sleep and impairments in quality of life.The sensations—and the need to move—may return immediately after ceasing movement or at a later time. RLS may start at any age, including childhood, and is a progressive disease for some, while the symptoms may remit in others. In a survey among members of the Restless Legs Syndrome Foundation, it was found that up to 45% of patients had their first symptoms before the age of 20 years. "An urge to move, usually due to uncomfortable sensations that occur primarily in the legs, but occasionally in the arms or elsewhere."The sensations are unusual and unlike other common sensations. Those with RLS have a hard time describing them, using words or phrases such as uncomfortable, painful, antsy, electrical, creeping, itching, pins and needles, pulling, crawling, buzzing, and numbness. It is sometimes described similar to a limb falling asleep or an exaggerated sense of positional awareness of the affected area. The sensation and the urge can occur in any body part; the most cited location is legs, followed by arms. Some people have little or no sensation, yet still, have a strong urge to move."Motor restlessness, expressed as activity, which relieves the urge to move."Movement usually brings immediate relief, although temporary and partial. Walking is most common; however, stretching, yoga, biking, or other physical activity may relieve the symptoms. Continuous, fast up-and-down movements of the leg, and/or rapidly moving the legs toward then away from each other, may keep sensations at bay without having to walk. Specific movements may be unique to each person."Worsening of symptoms by relaxation."Sitting or lying down (reading, plane ride, watching TV) can trigger the sensations and urge to move. Severity depends on the severity of the persons RLS, the degree of restfulness, duration of the inactivity, etc."Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night."Some experience RLS only at bedtime, while others experience it throughout the day and night. Most people experience the worst symptoms in the evening and the least in the morning."restless legs feel similar to the urge to yawn, situated in the legs or arms."These symptoms of RLS can make sleeping difficult for many patients and a 2005 National Sleep Foundation poll shows the presence of significant daytime difficulties resulting from this condition. These problems range from being late for work to missing work or events because of drowsiness. Patients with RLS who responded reported driving while drowsy more than patients without RLS. These daytime difficulties can translate into safety, social and economic issues for the patient and for society.RLS may contribute to higher rates of depression and anxiety disorders in RLS patients. Primary and secondary RLS is categorized as either primary or secondary. Primary RLS is considered idiopathic or with no known cause. Primary RLS usually begins slowly, before approximately 40–45 years of age and may disappear for months or even years. It is often progressive and gets worse with age. RLS in children is often misdiagnosed as growing pains. Secondary RLS often has a sudden onset after age 40, and may be daily from the beginning. It is most associated with specific medical conditions or the use of certain drugs (see below). Causes While the cause is generally unknown, it is believed to be caused by changes in the nerve transmitter dopamine resulting in an abnormal use of iron by the brain. RLS is often due to iron deficiency (low total body iron status). Other associated conditions may include end-stage kidney disease and hemodialysis, folate deficiency, magnesium deficiency, sleep apnea, diabetes, peripheral neuropathy, Parkinsons disease, and certain autoimmune diseases, such as multiple sclerosis. RLS can worsen in pregnancy, possibly due to elevated estrogen levels. Use of alcohol, nicotine products, and caffeine may be associated with RLS. A 2014 study from the American Academy of Neurology also found that reduced leg oxygen levels were strongly associated with restless legs Syndrome symptom severity in untreated patients. ADHD An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder. Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine, and common medications for both conditions among other systems, affect dopamine levels in the brain. A 2005 study suggested that up to 44% of people with ADHD had comorbid (i.e. coexisting) RLS, and up to 26% of people with RLS had confirmed ADHD or symptoms of the condition. Medications Certain medications may cause or worsen RLS, or cause it secondarily, including: certain antiemetics (antidopaminergic ones) certain antihistamines (especially the sedating, first generation H1 antihistamines often in over-the-counter cold medications) many antidepressants (both older TCAs and newer SSRIs) antipsychotics and certain anticonvulsants a rebound effect of sedative-hypnotic drugs such as a benzodiazepine withdrawal syndrome from discontinuing benzodiazepine tranquilizers or sleeping pills alcohol withdrawal can also cause restless legs syndrome and other movement disorders such as akathisia and parkinsonism usually associated with antipsychotics opioid withdrawal is associated with causing and worsening RLSBoth primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS.The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses) is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS. Genetics More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra. Iron is well understood to be an essential cofactor for the formation of L-dopa, the precursor of dopamine. Six genetic loci found by linkage are known and listed below. Other than the first one, all of the linkage loci were discovered using an autosomal dominant model of inheritance. The first genetic locus was discovered in one large French Canadian family and maps to chromosome 12q. This locus was discovered using an autosomal recessive inheritance model. Evidence for this locus was also found using a transmission disequilibrium test (TDT) in 12 Bavarian families. The second RLS locus maps to chromosome 14q and was discovered in one Italian family. Evidence for this locus was found in one French Canadian family. Also, an association study in a large sample 159 trios of European descent showed some evidence for this locus. This locus maps to chromosome 9p and was discovered in two unrelated American families. Evidence for this locus was also found by the TDT in a large Bavarian family, in which significant linkage to this locus was found. This locus maps to chromosome 20p and was discovered in a large French Canadian family with RLS. This locus maps to chromosome 2p and was found in three related families from population isolated in South Tyrol. The sixth locus is located on chromosome 16p12.1 and was discovered by Levchenko et al. in 2008.Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to RLS. Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated with RLS.There is also some evidence that periodic limb movements in sleep (PLMS) are associated with BTBD9 on chromosome 6p21.2, MEIS1, MAP2K5/SKOR1, and PTPRD. The presence of a positive family history suggests that there may be a genetic involvement in the etiology of RLS. Mechanism Although it is only partly understood, pathophysiology of restless legs syndrome may involve dopamine and iron system anomalies. There is also a commonly acknowledged circadian rhythm explanatory mechanism associated with it, clinically shown simply by biomarkers of circadian rhythm, such as body temperature. The interactions between impaired neuronal iron uptake and the functions of the neuromelanin-containing and dopamine-producing cells have roles in RLS development, indicating that iron deficiency might affect the brain dopaminergic transmissions in different ways.Medial thalamic nuclei may also have a role in RLS as part as the limbic system modulated by the dopaminergic system which may affect pain perception. Improvement of RLS symptoms occurs in people receiving low-dose dopamine agonists. Diagnosis There are no specific tests for RLS, but non-specific laboratory tests are used to rule out other causes such as vitamin deficiencies. Five symptoms are used to confirm the diagnosis: A strong urge to move the limbs, usually associated with unpleasant or uncomfortable sensations. It starts or worsens during inactivity or rest. It improves or disappears (at least temporarily) with activity. It worsens in the evening or night. These symptoms are not caused by any medical or behavioral condition.These symptoms are not essential, like the ones above, but occur commonly in RLS patients: genetic component or family history with RLS good response to dopaminergic therapy periodic leg movements during day or sleep most strongly affected are people who are middle-aged or older other sleep disturbances are experienced decreased iron stores can be a risk factor and should be assessedAccording to the International Classification of Sleep Disorders (ICSD-3), the main symptoms have to be associated with a sleep disturbance or impairment in order to support RLS diagnosis. As stated by this classification, RLS symptoms should begin or worsen when being inactive, be relieved when moving, should happen exclusively or mostly in the evening and at night, not be triggered by other medical or behavioral conditions, and should impair ones quality of life. Generally, both legs are affected, but in some cases there is an asymmetry. Differential diagnosis The most common conditions that should be differentiated with RLS include leg cramps, positional discomfort, local leg injury, arthritis, leg edema, venous stasis, peripheral neuropathy, radiculopathy, habitual foot tapping/leg rocking, anxiety, myalgia, and drug-induced akathisia.Peripheral artery disease and arthritis can also cause leg pain but this usually gets worse with movement.There are less common differential diagnostic conditions included myelopathy, myopathy, vascular or neurogenic claudication, hypotensive akathisia, orthostatic tremor, painful legs, and moving toes. Treatment If RLS is not linked to an underlying cause, its frequency may be reduced by lifestyle modifications such as adopting improving sleep hygiene, regular exercise, and stopping smoking. Medications used may include dopamine agonists or gabapentin in those with daily restless legs syndrome, and opioids for treatment of resistant cases.Treatment of RLS should not be considered until possible medical causes are ruled out. Secondary RLS may be cured if precipitating medical conditions (anemia) are managed effectively. Physical measures Stretching the leg muscles can bring temporary relief. Walking and moving the legs, as the name "restless legs" implies, brings temporary relief. In fact, those with RLS often have an almost uncontrollable need to walk and therefore relieve the symptoms while they are moving. Unfortunately, the symptoms usually return immediately after the moving and walking ceases. A vibratory counter-stimulation device has been found to help some people with primary RLS to improve their sleep. Iron There is some evidence that intravenous iron supplementation moderately improves restlessness for people with RLS. Medications For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be useful. Evidence supports the use of dopamine agonists including: pramipexole, ropinirole, rotigotine, and cabergoline. They reduce symptoms, improve sleep quality and quality of life. Levodopa is also effective. However, pergolide and cabergoline are less recommended due to their association with increased risk of valvular heart disease. Ropinirole has a faster onset with shorter duration. Rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout the day. One 2008 review found pramipexole to be better than ropinirole.There are, however, issues with the use of dopamine agonists including augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound when symptoms increase as the drug wears off. In many cases, the longer dopamine agonists have been used the higher the risk of augmentation and rebound as well as the severity of the symptoms. Also, a recent study indicated that dopamine agonists used in restless legs syndrome can lead to an increase in compulsive gambling. Gabapentin or pregabalin, a non-dopaminergic treatment for moderate to severe primary RLS Opioids are only indicated in severe cases that do not respond to other measures due to their very high abuse liability and high rate of side effects, which may include constipation, fatigue and headache.One possible treatment for RLS is dopamine agonists, unfortunately patients can develop dopamine dysregulation syndrome, meaning that they can experience an addictive pattern of dopamine replacement therapy. Additionally, they can exhibit some behavioral disturbances such as impulse control disorders like pathologic gambling, compulsive purchasing and compulsive eating. There are some indications that stopping the dopamine agonist treatment has an impact on the resolution or at least improvement of the impulse control disorder, even though some people can be particularly exposed to dopamine agonist withdrawal syndrome.Benzodiazepines, such as diazepam or clonazepam, are not generally recommended, and their effectiveness is unknown. They however are sometimes still used as a second line, as add on agents. Quinine is not recommended due to its risk of serious side effects involving the blood. Prognosis RLS symptoms may gradually worsen with age, although more slowly for those with the idiopathic form of RLS than for people who also have an associated medical condition. Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some people have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear. Being diagnosed with RLS does not indicate or foreshadow another neurological disease, such as Parkinsons disease. RLS symptoms can worsen over time when dopamine-related drugs are used for therapy, an effect called "augmentation" which may represent symptoms occurring throughout the day and affect movements of all limbs. There is no cure for RLS. Epidemiology RLS affects an estimated 2.5–15% of the American population. A minority (around 2.7% of the population) experience daily or severe symptoms. RLS is twice as common in women as in men, and Caucasians are more prone to RLS than people of African descent. RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern regions, and in 1–5% of those from East Asia, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome. RLS diagnosed at an older age runs a more severe course. RLS is even more common in individuals with iron deficiency, pregnancy, or end-stage kidney disease. The National Sleep Foundations 1998 Sleep in America poll showed that up to 25 percent of pregnant women developed RLS during the third trimester. Poor general health is also linked.There are several risk factors for RLS, including old age, family history, and uremia. The prevalence of RLS tends to increase with age, as well as its severity and longer duration of symptoms. People with uremia receiving renal dialysis have a prevalence from 20% to 57%, while those having kidney transplant improve compared to those treated with dialysis.RLS can occur at all ages, although it typically begins in the third or fourth decade. Genome‐wide association studies have now identified 19 risk loci associated with RLS. Neurological conditions linked to RLS include Parkinsons disease, spinal cerebellar atrophy, spinal stenosis, lumbosacral radiculopathy and Charcot–Marie–Tooth disease type 2. History The first known medical description of RLS was by Sir Thomas Willis in 1672. Willis emphasized the sleep disruption and limb movements experienced by people with RLS. Initially published in Latin (De Anima Brutorum, 1672) but later translated to English (The London Practice of Physick, 1685), Willis wrote: Wherefore to some, when being abed they betake themselves to sleep, presently in the arms and legs, leapings and contractions on the tendons, and so great a restlessness and tossings of other members ensue, that the diseased are no more able to sleep, than if they were in a place of the greatest torture. The term "fidgets in the legs" has also been used as early as the early nineteenth century.Subsequently, other descriptions of RLS were published, including those by François Boissier de Sauvages (1763), Magnus Huss (1849), Theodur Wittmaack (1861), George Miller Beard (1880), Georges Gilles de la Tourette (1898), Hermann Oppenheim (1923) and Frederick Gerard Allison (1943). However, it was not until almost three centuries after Willis, in 1945, that Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, restless legs: clinical study of hitherto overlooked disease. Ekbom coined the term "restless legs" and continued work on this disorder throughout his career. He described the essential diagnostic symptoms, differential diagnosis from other conditions, prevalence, relation to anemia, and common occurrence during pregnancy.Ekboms work was largely ignored until it was rediscovered by Arthur S. Walters and Wayne A. Hening in the 1980s. Subsequent landmark publications include 1995 and 2003 papers, which revised and updated the diagnostic criteria. Journal of Parkinsonism and RLS is the first peer-reviewed, online, open access journal dedicated to publishing research about Parkinsons disease and was founded by a Canadian neurologist Dr. Abdul Qayyum Rana. Nomenclature In 2013, the Restless Legs Syndrome Foundation renamed itself the Willis–Ekbom Disease Foundation; however, it reverted to its original name in 2015 “to better support its mission”.A point of confusion is that RLS and delusional parasitosis are entirely different conditions that have both been called "Ekbom syndrome", as both syndromes were described by the same person, Karl-Axel Ekbom. Today, calling WED/RLS "Ekbom syndrome" is outdated usage, as the unambiguous names (WED or RLS) are preferred for clarity. Controversy Some doctors express the view that the incidence of restless legs syndrome is exaggerated by manufacturers of drugs used to treat it. Others believe it is an underrecognized and undertreated disorder. Further, GlaxoSmithKline (GSK) ran advertisements that, while not promoting off-licence use of their drug (ropinirole) for treatment of RLS, did link to the Ekbom Support Group website. That website contained statements advocating the use of ropinirole to treat RLS. The Association of the British Pharmaceutical Industry (ABPI) ruled against GSK in this case. Research Different measurements have been used to evaluate treatments in RLS. Most of them are based on subjective rating scores, such as IRLS rating scale (IRLS), Clinical Global Impression (CGI), Patient Global Impression (PGI), and Quality of life (QoL). These questionnaires provide information about the severity and progress of the disease, as well as the persons quality of life and sleep. Polysomnography (PSG) and actigraphy (both related to sleep parameters) are more objective resources that provide evidences of sleep disturbances associated with RLS symptoms. See also Periodic limb movement disorder References External links Restless legs syndrome at Curlie

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

I need a basic explanation for the medical term 'Half and half nail.'

Half and half nails (also known as "Lindsays nails") show the proximal portion of the nail white and the distal half red, pink, or brown, with a sharp line of demarcation between the two halves.: 785  Seventy percent of hemodialysis patients and 56% of renal transplant patients have at least one type of nail abnormality. Absence of lunula, splinter hemorrhage, and half and half nails were significantly more common in hemodialysis patients, while leukonychia was significantly more common in transplant patients.: 785 : 659 See also List of cutaneous conditions References == External links ==

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

The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates has been replaced by a segmented series of bone: vertebrae separated by intervertebral discs. Individual vertebrae are named according to their region and position, and can be used as anatomical landmarks in order to guide procedures such as lumbar punctures. The vertebral column houses the spinal canal, a cavity that encloses and protects the spinal cord. There are about 50,000 species of animals that have a vertebral column. The human vertebral column is one of the most-studied examples. Many different diseases in humans can affect the spine, with spina bifida and scoliosis being recognisable examples. The general structure of human vertebrae is fairly typical of that found in mammals, reptiles, and birds. The shape of the vertebral body does, however, vary somewhat between different groups. Structure The number of vertebrae in a region can vary but overall the number remains the same. In a human vertebral column, there are normally 33 vertebrae. The upper 24 pre-sacral vertebrae are articulating and separated from each other by intervertebral discs, and the lower nine are fused in adults, five in the sacrum and four in the coccyx, or tailbone. The articulating vertebrae are named according to their region of the spine. There are 7 cervical vertebrae, 12 thoracic vertebrae and 5 lumbar vertebrae. The number of those in the cervical region, however, is only rarely changed, while that in the coccygeal region varies most. One study of 908 human adults found 43 individuals with 23 pre-sacral vertebrae (4.7%), 826 individuals with 24 pre-sacral vertebrae (91%), and 39 with 25 pre-sacral vertebrae (4.3%).There are ligaments extending the length of the column at the front and the back, and in between the vertebrae joining the spinous processes, the transverse processes and the vertebral laminae. Vertebrae The vertebrae in the human vertebral column is divided into different regions, which correspond to the curves of the vertebral column. The articulating vertebrae are named according to their region of the spine. Vertebrae in these regions are essentially alike, with minor variation. These regions are called the cervical spine, thoracic spine, lumbar spine, sacrum, and coccyx. There are seven cervical vertebrae, twelve thoracic vertebrae, and five lumbar vertebrae. The number of vertebrae in a region can vary but overall the number remains the same. The number of those in the cervical region, however, is only rarely changed. The vertebrae of the cervical, thoracic, and lumbar spines are independent bones and generally quite similar. The vertebrae of the sacrum and coccyx are usually fused and unable to move independently. Two special vertebrae are the atlas and axis, on which the head rests. A typical vertebra consists of two parts: the vertebral body and the vertebral arch. The vertebral arch is posterior, meaning it faces the back of a person. Together, these enclose the vertebral foramen, which contains the spinal cord. Because the spinal cord ends in the lumbar spine, and the sacrum and coccyx are fused, they do not contain a central foramen. The vertebral arch is formed by a pair of pedicles and a pair of laminae, and supports seven processes, four articular, two transverse, and one spinous, the latter also being known as the neural spine. Two transverse processes and one spinous process are posterior to (behind) the vertebral body. The spinous process comes out the back, one transverse process comes out the left, and one on the right. The spinous processes of the cervical and lumbar regions can be felt through the skin. Above and below each vertebra are joints called facet joints. These restrict the range of movement possible, and are joined by a thin portion of the neural arch called the pars interarticularis. In between each pair of vertebrae are two small holes called intervertebral foramina. The spinal nerves leave the spinal cord through these holes. Individual vertebrae are named according to their region and position. From top to bottom, the vertebrae are: Cervical spine: 7 vertebrae (C1–C7) Thoracic spine: 12 vertebrae (T1–T12) Lumbar spine: 5 vertebrae (L1–L5) Sacrum: 5 (fused) vertebrae (S1–S5) Coccyx: 4 (3–5) (fused) vertebrae (Tailbone)The combined region of the thoracic and lumbar vertebrae is known as the thoracolumbar division, or region. Shape The vertebral column is curved in several places, a result of human bipedal evolution. The curves allow the human spine to better stabilize the body in the upright position.The upper cervical spine has a curve, convex forward, that begins at the axis (second cervical vertebra) at the apex of the odontoid process or dens and ends at the middle of the second thoracic vertebra; it is the least marked of all the curves. This inward curve is known as a lordotic curve. The thoracic curve, concave forward, begins at the middle of the second and ends at the middle of the twelfth thoracic vertebra. Its most prominent point behind corresponds to the spinous process of the seventh thoracic vertebra. This curve is known as a kyphotic curve. The lumbar curve is more marked in the female than in the male; it begins at the middle of the last thoracic vertebra, and ends at the sacrovertebral angle. It is convex anteriorly, the convexity of the lower three vertebrae being much greater than that of the upper two. This curve is described as a lordotic curve. The sacral curve begins at the sacrovertebral articulation, and ends at the point of the coccyx; its concavity is directed downward and forward as a kyphotic curve. The thoracic and sacral kyphotic curves are termed primary curves, because they are present in the fetus. The cervical and lumbar curves are compensatory, or secondary, and are developed after birth. The cervical curve forms when the infant is able to hold up its head (at three or four months) and sit upright (at nine months). The lumbar curve forms later from twelve to eighteen months, when the child begins to walk. Surfaces Anterior surfaceWhen viewed from in front, the width of the bodies of the vertebrae is seen to increase from the second cervical to the first thoracic; there is then a slight diminution in the next three vertebrae. Below this, there is again a gradual and progressive increase in width as low as the sacrovertebral angle. From this point there is a rapid diminution, to the apex of the coccyx. Posterior surfaceFrom behind, the vertebral column presents in the median line the spinous processes. In the cervical region (with the exception of the second and seventh vertebrae), these are short, horizontal, and bifid. In the upper part of the thoracic region they are directed obliquely downward; in the middle they are almost vertical, and in the lower part they are nearly horizontal. In the lumbar region they are nearly horizontal. The spinous processes are separated by considerable intervals in the lumbar region, by narrower intervals in the neck, and are closely approximated in the middle of the thoracic region. Occasionally one of these processes deviates a little from the median line — which can sometimes be indicative of a fracture or a displacement of the spine. On either side of the spinous processes is the vertebral groove formed by the laminae in the cervical and lumbar regions, where it is shallow, and by the laminae and transverse processes in the thoracic region, where it is deep and broad; these grooves lodge the deep muscles of the back. Lateral to the spinous processes are the articular processes, and still more laterally the transverse processes. In the thoracic region, the transverse processes stand backward, on a plane considerably behind that of the same processes in the cervical and lumbar regions. In the cervical region, the transverse processes are placed in front of the articular processes, lateral to the pedicles and between the intervertebral foramina. In the thoracic region they are posterior to the pedicles, intervertebral foramina, and articular processes. In the lumbar region they are in front of the articular processes, but behind the intervertebral foramina. Lateral surfacesThe sides of the vertebral column are separated from the posterior surface by the articular processes in the cervical and thoracic regions and by the transverse processes in the lumbar region. In the thoracic region, the sides of the bodies of the vertebrae are marked in the back by the facets for articulation with the heads of the ribs. More posteriorly are the intervertebral foramina, formed by the juxtaposition of the vertebral notches, oval in shape, smallest in the cervical and upper part of the thoracic regions and gradually increasing in size to the last lumbar. They transmit the special spinal nerves and are situated between the transverse processes in the cervical region and in front of them, in the thoracic and lumbar regions. Ligaments There are different ligaments involved in the holding together of the vertebrae in the column, and in the columns movement. The anterior and posterior longitudinal ligaments extend the length of the vertebral column along the front and back of the vertebral bodies. The interspinous ligaments connect the adjoining spinous processes of the vertebrae. The supraspinous ligament extends the length of the spine running along the back of the spinous processes, from the sacrum to the seventh cervical vertebra. From there it is continuous with the nuchal ligament. Development The striking segmented pattern of the spine is established during embryogenesis when somites are rhythmically added to the posterior of the embryo. Somite formation begins around the third week when the embryo begins gastrulation and continues until all somites are formed. Their number varies between species: there are 42 to 44 somites in the human embryo and around 52 in the chick embryo. The somites are spheres, formed from the paraxial mesoderm that lies at the sides of the neural tube and they contain the precursors of spinal bone, the vertebrae ribs and some of the skull, as well as muscle, ligaments and skin. Somitogenesis and the subsequent distribution of somites is controlled by a clock and wavefront model acting in cells of the paraxial mesoderm. Soon after their formation, sclerotomes, which give rise to some of the bone of the skull, the vertebrae and ribs, migrate, leaving the remainder of the somite now termed a dermamyotome behind. This then splits to give the myotomes which will form the muscles and dermatomes which will form the skin of the back. Sclerotomes become subdivided into an anterior and a posterior compartment. This subdivision plays a key role in the definitive patterning of vertebrae that form when the posterior part of one somite fuses to the anterior part of the consecutive somite during a process termed resegmentation. Disruption of the somitogenesis process in humans results in diseases such as congenital scoliosis. So far, the human homologues of three genes associated to the mouse segmentation clock, (MESP2, DLL3 and LFNG), have been shown to be mutated in cases of congenital scoliosis, suggesting that the mechanisms involved in vertebral segmentation are conserved across vertebrates. In humans the first four somites are incorporated in the base of the occipital bone of the skull and the next 33 somites will form the vertebrae, ribs, muscles, ligaments and skin. The remaining posterior somites degenerate. During the fourth week of embryogenesis, the sclerotomes shift their position to surround the spinal cord and the notochord. This column of tissue has a segmented appearance, with alternating areas of dense and less dense areas. As the sclerotome develops, it condenses further eventually developing into the vertebral body. Development of the appropriate shapes of the vertebral bodies is regulated by HOX genes. The less dense tissue that separates the sclerotome segments develop into the intervertebral discs. The notochord disappears in the sclerotome (vertebral body) segments but persists in the region of the intervertebral discs as the nucleus pulposus. The nucleus pulposus and the fibers of the anulus fibrosus make up the intervertebral disc. The primary curves (thoracic and sacral curvatures) form during fetal development. The secondary curves develop after birth. The cervical curvature forms as a result of lifting the head and the lumbar curvature forms as a result of walking. Function Spinal cord The vertebral column surrounds the spinal cord which travels within the spinal canal, formed from a central hole within each vertebra. The spinal cord is part of the central nervous system that supplies nerves and receives information from the peripheral nervous system within the body. The spinal cord consists of grey and white matter and a central cavity, the central canal. Adjacent to each vertebra emerge spinal nerves. The spinal nerves provide sympathetic nervous supply to the body, with nerves emerging forming the sympathetic trunk and the splanchnic nerves. The spinal canal follows the different curves of the column; it is large and triangular in those parts of the column that enjoy the greatest freedom of movement, such as the cervical and lumbar regions, and is small and rounded in the thoracic region, where motion is more limited. The spinal cord terminates in the conus medullaris and cauda equina. Clinical significance Disease Spina bifida is a congenital disorder in which there is a defective closure of the vertebral arch. Sometimes the spinal meninges and also the spinal cord can protrude through this, and this is called spina bifida cystica. Where the condition does not involve this protrusion it is known as spina bifida occulta. Sometimes all of the vertebral arches may remain incomplete.Another, though rare, congenital disease is Klippel–Feil syndrome, which is the fusion of any two of the cervical vertebrae. Spondylolisthesis is the forward displacement of a vertebra and retrolisthesis is a posterior displacement of one vertebral body with respect to the adjacent vertebra to a degree less than a dislocation. Spondylolysis, also known as a pars defect, is a defect or fracture at the pars interarticularis of the vertebral arch. Spinal disc herniation, more commonly called a "slipped disc", is the result of a tear in the outer ring (anulus fibrosus) of the intervertebral disc, which lets some of the soft gel-like material, the nucleus pulposus, bulge out in a hernia. Spinal stenosis is a narrowing of the spinal canal which can occur in any region of the spine though less commonly in the thoracic region. The stenosis can constrict the spinal canal giving rise to a neurological deficit. Pain at the coccyx (tailbone) is known as coccydynia.Spinal cord injury is damage to the spinal cord that causes changes in its function, either temporary or permanent. Spinal cord injuries can be divided into categories: complete transection, hemisection, central spinal cord lesions, posterior spinal cord lesions, and anterior spinal cord lesions. Scalloping vertebrae is the increase in the concavity of the posterior vertebral body. It can be seen on lateral X-ray and sagittal views of CT and MRI scans. Its concavity is due to the increased pressure exerting on the vertebrae due to a mass. Internal spinal mass such as spinal astrocytoma, ependymoma, schwannoma, neurofibroma, and achondroplasia causes vertebrae scalloping. Curvature Excessive or abnormal spinal curvature is classed as a spinal disease or dorsopathy and includes the following abnormal curvatures: Kyphosis is an exaggerated kyphotic (convex) curvature of the thoracic region in the sagittal plane, also called hyperkyphosis. This produces the so-called "humpback" or "dowagers hump", a condition commonly resulting from osteoporosis. Lordosis is an exaggerated lordotic (concave) curvature of the lumbar region in the sagittal plane, is known as lumbar hyperlordosis and also as "swayback". Temporary lordosis is common during pregnancy. Scoliosis, lateral curvature, is the most common abnormal curvature, occurring in 0.5% of the population. It is more common among females and may result from unequal growth of the two sides of one or more vertebrae, so that they do not fuse properly. It can also be caused by pulmonary atelectasis (partial or complete deflation of one or more lobes of the lungs) as observed in asthma or pneumothorax. Kyphoscoliosis, a combination of kyphosis and scoliosis. Anatomical landmarks Individual vertebrae of the human vertebral column can be felt and used as surface anatomy, with reference points are taken from the middle of the vertebral body. This provides anatomical landmarks that can be used to guide procedures such as a lumbar puncture and also as vertical reference points to describe the locations of other parts of human anatomy, such as the positions of organs. Other animals Variations in vertebrae The general structure of vertebrae in other animals is largely the same as in humans. Individual vertebrae are composed of a centrum (body), arches protruding from the top and bottom of the centrum, and various processes projecting from the centrum and/or arches. An arch extending from the top of the centrum is called a neural arch, while the haemal arch or chevron is found underneath the centrum in the caudal (tail) vertebrae of fish, most reptiles, some birds, some dinosaurs and some mammals with long tails. The vertebral processes can either give the structure rigidity, help them articulate with ribs, or serve as muscle attachment points. Common types are transverse process, diapophyses, parapophyses, and zygapophyses (both the cranial zygapophyses and the caudal zygapophyses). The centrum of the vertebra can be classified based on the fusion of its elements. In temnospondyls, bones such as the spinous process, the pleurocentrum and the intercentrum are separate ossifications. Fused elements, however, classify a vertebra as having holospondyly. A vertebra can also be described in terms of the shape of the ends of the centrum. Centra with flat ends are acoelous, like those in mammals. These flat ends of the centra are especially good at supporting and distributing compressive forces. Amphicoelous vertebra have centra with both ends concave. This shape is common in fish, where most motion is limited. Amphicoelous centra often are integrated with a full notochord. Procoelous vertebrae are anteriorly concave and posteriorly convex. They are found in frogs and modern reptiles. Opisthocoelous vertebrae are the opposite, possessing anterior convexity and posterior concavity. They are found in salamanders, and in some non-avian dinosaurs. Heterocoelous vertebrae have saddle-shaped articular surfaces. This type of configuration is seen in turtles that retract their necks, and birds, because it permits extensive lateral and vertical flexion motion without stretching the nerve cord too extensively or wringing it about its long axis. In horses, the Arabian (breed) can have one less vertebrae and pair of ribs. This anomaly disappears in foals that are the product of an Arabian and another breed of horse. Regional vertebrae Vertebrae are defined by the regions of the vertebral column that they occur in, as in humans. Cervical vertebrae are those in the neck area. With the exception of the two sloth genera (Choloepus and Bradypus) and the manatee genus, (Trichechus), all mammals have seven cervical vertebrae. In other vertebrates, the number of cervical vertebrae can range from a single vertebra in amphibians to as many as 25 in swans or 76 in the extinct plesiosaur Elasmosaurus. The dorsal vertebrae range from the bottom of the neck to the top of the pelvis. Dorsal vertebrae attached to the ribs are called thoracic vertebrae, while those without ribs are called lumbar vertebrae. The sacral vertebrae are those in the pelvic region, and range from one in amphibians, to two in most birds and modern reptiles, or up to three to five in mammals. When multiple sacral vertebrae are fused into a single structure, it is called the sacrum. The synsacrum is a similar fused structure found in birds that is composed of the sacral, lumbar, and some of the thoracic and caudal vertebra, as well as the pelvic girdle. Caudal vertebrae compose the tail, and the final few can be fused into the pygostyle in birds, or into the coccygeal or tail bone in chimpanzees (and humans). Fish and amphibians The vertebrae of lobe-finned fishes consist of three discrete bony elements. The vertebral arch surrounds the spinal cord, and is of broadly similar form to that found in most other vertebrates. Just beneath the arch lies a small plate-like pleurocentrum, which protects the upper surface of the notochord, and below that, a larger arch-shaped intercentrum to protect the lower border. Both of these structures are embedded within a single cylindrical mass of cartilage. A similar arrangement was found in the primitive Labyrinthodonts, but in the evolutionary line that led to reptiles (and hence, also to mammals and birds), the intercentrum became partially or wholly replaced by an enlarged pleurocentrum, which in turn became the bony vertebral body. In most ray-finned fishes, including all teleosts, these two structures are fused with, and embedded within, a solid piece of bone superficially resembling the vertebral body of mammals. In living amphibians, there is simply a cylindrical piece of bone below the vertebral arch, with no trace of the separate elements present in the early tetrapods.In cartilaginous fish, such as sharks, the vertebrae consist of two cartilaginous tubes. The upper tube is formed from the vertebral arches, but also includes additional cartilaginous structures filling in the gaps between the vertebrae, and so enclosing the spinal cord in an essentially continuous sheath. The lower tube surrounds the notochord, and has a complex structure, often including multiple layers of calcification.Lampreys have vertebral arches, but nothing resembling the vertebral bodies found in all higher vertebrates. Even the arches are discontinuous, consisting of separate pieces of arch-shaped cartilage around the spinal cord in most parts of the body, changing to long strips of cartilage above and below in the tail region. Hagfishes lack a true vertebral column, and are therefore not properly considered vertebrates, but a few tiny neural arches are present in the tail. Other vertebrates The general structure of human vertebrae is fairly typical of that found in mammals, reptiles, and birds. The shape of the vertebral body does, however, vary somewhat between different groups. In mammals, such as humans, it typically has flat upper and lower surfaces, while in reptiles the anterior surface commonly has a concave socket into which the expanded convex face of the next vertebral body fits. Even these patterns are only generalisations, however, and there may be variation in form of the vertebrae along the length of the spine even within a single species. Some unusual variations include the saddle-shaped sockets between the cervical vertebrae of birds and the presence of a narrow hollow canal running down the centre of the vertebral bodies of geckos and tuataras, containing a remnant of the notochord.Reptiles often retain the primitive intercentra, which are present as small crescent-shaped bony elements lying between the bodies of adjacent vertebrae; similar structures are often found in the caudal vertebrae of mammals. In the tail, these are attached to chevron-shaped bones called haemal arches, which attach below the base of the spine, and help to support the musculature. These latter bones are probably homologous with the ventral ribs of fish. The number of vertebrae in the spines of reptiles is highly variable, and may be several hundred in some species of snake.In birds, there is a variable number of cervical vertebrae, which often form the only truly flexible part of the spine. The thoracic vertebrae are partially fused, providing a solid brace for the wings during flight. The sacral vertebrae are fused with the lumbar vertebrae, and some thoracic and caudal vertebrae, to form a single structure, the synsacrum, which is thus of greater relative length than the sacrum of mammals. In living birds, the remaining caudal vertebrae are fused into a further bone, the pygostyle, for attachment of the tail feathers.Aside from the tail, the number of vertebrae in mammals is generally fairly constant. There are almost always seven cervical vertebrae (sloths and manatees are among the few exceptions), followed by around twenty or so further vertebrae, divided between the thoracic and lumbar forms, depending on the number of ribs. There are generally three to five vertebrae with the sacrum, and anything up to fifty caudal vertebrae. Dinosaurs The vertebral column in dinosaurs consists of the cervical (neck), dorsal (back), sacral (hips), and caudal (tail) vertebrae. Saurischian dinosaur vertebrae sometimes possess features known as pleurocoels, which are hollow depressions on the lateral portions of the vertebrae, perforated to create an entrance into the air chambers within the vertebrae, which served to decrease the weight of these bones without sacrificing strength. These pleurocoels were filled with air sacs, which would have further decreased weight. In sauropod dinosaurs, the largest known land vertebrates, pleurocoels and air sacs may have reduced the animals weight by over a ton in some instances, a handy evolutionary adaption in animals that grew to over 30 metres in length. In many hadrosaur and theropod dinosaurs, the caudal vertebrae were reinforced by ossified tendons. The presence of three or more sacral vertebrae, in association with the hip bones, is one of the defining characteristics of dinosaurs. The occipital condyle is a structure on the posterior part of a dinosaurs skull that articulates with the first cervical vertebra. See also Low back pain Neuromechanics of idiopathic scoliosis Neutral spine References External links Spinal Term Glossary VIRTUAL Spine - online learning resource

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

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

Erythropoietic protoporphyria (or commonly called EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the red blood cells (erythrocytes), plasma, skin, and liver. The severity varies significantly from individual to individual. A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008. Presentation EPP usually presents in childhood with the most common mode of presentation as acute photosensitivity of the skin. It affects areas exposed to the sun and tends to be intractable. A few minutes of exposure to the sun induces pruritus, erythema, swelling and pain. Longer periods of exposure may induce second degree burns. After repetitive exposure, patients may present with lichenification, hypopigmentation, hyperpigmentation and scarring of the skin.EPP usually first presents in childhood, and most often affects the face and the upper surfaces of the arms, hands, and feet and the exposed surfaces of the legs. Most patients, if the EPP is not as severe, manifest symptoms with onset of puberty when the male and female hormone levels elevate during sexual development and maintenance. More severe EPP can manifest in infancy. EPP can be triggered through exposure to sun even though the patient is behind glass. Even the UV emissions from arc welding with the use of full protective mask have been known to trigger EPP. EPP can also manifest between the ages of 3 and 6.Prolonged exposure to the sun can lead to edema of the hands, face, and feet, rarely with blistering and petechiae. Skin thickening can sometimes occur over time.People with EPP are also at increased risk to develop gallstones. One study has noted that EPP patients suffer from vitamin D deficiency. Liver failure Protoporphyrin accumulates to toxic levels in the liver in 5–20% of EPP patients, leading to liver failure. The spectrum of hepatobiliary disease associated with EPP is wide. It includes cholelithiasis, mild parenchymal liver disease, progressive hepatocellular disease and end-stage liver disease.A lack of diagnostic markers for liver failure makes it difficult to predict which patients may experience liver failure, and the mechanism of liver failure is poorly understood. A retrospective European study identified 31 EPP patients receiving a liver transplant between 1983 and 2008, with phototoxic reactions in 25% of patients who were unprotected by surgical light filters. The same study noted a 69% recurrence of the disease in the grafted organ. Five UK liver transplants for EPP have been identified between 1987 and 2009. Frequent liver testing is recommended in EPP patients where no effective therapy has been identified to manage liver failure to date. Pregnancy EPP photosensitivity symptoms are reported to lessen in some female patients during pregnancy and menstruation, although this phenomenon is not consistent, and the mechanism is not understood. Genetics Most cases of EPP are results of inborn errors of metabolism but the metabolic defect in some patients may be acquired. Mutation of the gene that encodes for ferrochelatase in the long arm of chromosome 18 is found in majority of the cases. Ferrochelatase (FECH) catalyzes the insertion of ferrous iron into the protoporphyrin IX ring to form heme. EPP exhibits both recessive and dominant patterns of inheritance and a high degree of allelic heterogeneity with incomplete penetrance. Most heterozygotes are asymptomatic. Symptoms do not occur unless FECH activity is less than 30% of normal, but such low levels are not present in a majority of patients. Pathophysiology Cells which synthesize heme are predominantly erythroblasts/reticulocytes in the bone marrow (80%) and hepatocytes (20%). Deficiency of FECH results in increased release of protoporphyrin, which binds to albumin in plasma and subsequently undergoes hepatic extraction. Normally, most protoporphyrin in hepatocytes is secreted into bile; the remainder undergoes transformation into heme. Some protoporphyrin in bile is returned to the liver as a consequence of the enterohepatic circulation; the remaining protoporphyrin in the intestine undergoes fecal excretion. Protoporphyrin is insoluble and hence unavailable for renal excretion. In EPP, subnormal biotransformation of protoporphyrin into heme results in accumulation of protoporphyrin in hepatocytes.Since FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes, plasma, skin and liver, retention of protoporphyrin in skin predisposes to acute photosensitivity. As a result of absorption of ultraviolet and visible light (peak sensitivity at 400 nm, with lesser peaks between 500-625 nm) by protoporphyrin in plasma and erythrocytes when blood circulates through the dermal vessels, free radicals are formed, erythrocytes become unstable and injury to the skin is induced.A significant increase in the hepatobiliary excretion of protoporphyrin can damage the liver through both cholestatic phenomena and oxidative stress - predisposing to hepatobiliary disease of varying degrees of severity Diagnosis EPP is generally suspected by the presence of acute photosensitivity of the skin and can be confirmed by detection of a plasmatic fluorescence peak at 634 nm. It is also useful to find increased levels of protoporphyrin in feces and the demonstration of an excess of free protoporphyrin in erythrocytes.Screening for FECH mutation on one allele or aminolevulinic acid synthase 2 gain-of-function mutation in selected family members may be useful, especially in genetic counseling. Liver biopsy confirms hepatic disease in EPP by the presence of protoporphyrin deposits in the hepatocytes that can be observed as a brown pigment within the biliary canaliculi and the portal macrophages. Macroscopically, the cirrhotic liver can have a black color due to protoporphyrin deposits. Using polarized light the characteristic Maltese cross shape of birefringent crystalline pigment deposits is found. The examination of liver tissue under a Wood’s lamp reveals a red fluorescence due to protoporphyrin. Liver biopsy is not helpful for estimation of prognosis of liver disease. Treatment There is no cure for this disorder; however, symptoms can usually be managed by limiting exposure to daytime sun and some types of artificial lighting. Most types of artificial lighting emit light in the problematic wavelengths, with fluorescent lighting being the worst offender. Color temperature can be a good indicator of what light is most detrimental, as the higher the color temperature, the more violet light (380–450 nm) is emitted. Incandescent and LED lighting in the soft white range (2700–3000 K) produce the least problematic light. Additionally, selecting lower wattage bulbs can reduce the overall output of light. Since the photosensitivity results from light in the visible spectrum, most sunscreens are of little use (with the exception of non-nano zinc oxide which provides uniform protection between 290–400 nm and some protection up to 700 nm). Sun protective clothing can also be very helpful, although clothing with UPF values are only rated based on their UV protection (up to 400 nm) and not on their protection from the visible spectrum. Some sun protective clothing manufacturers use zinc oxide in their fabrics, such as Coolibars ZnO Suntect line, which will offer protection from visible light.Some patients gradually build a protective layer of melanin by regularly exposing themselves for short times to ultraviolet radiation.Window films which block UV and visible light up to 450 nm can provide relief from symptoms if applied to the patients automobile and home windows. An example of such would be Madico Amber 81 which can protect through the 500 nm range. Blue blocking screen protectors can help provide relief from symptoms caused by televisions, phones, tablets and computer screens. EPP is considered one of the least severe of the porphyrias. Unless there is liver failure, it is not a life-threatening disease. Approved therapies Afamelanotide, developed by Australian-based Clinuvel Pharmaceuticals, was approved in Europe in December 2014 and in the United States in October 2019 for treatment or prevention of phototoxicity in adults with EPP. Off-label therapies Several drugs are used off label by patients with EPP: Ursodeoxycholic acid is a bile acid that is administered to promote biliary secretion of protoporphyrin. Results of its use in EPP are controversial. However, it is known to alter the composition of bile, to protect hepatocytes from the cytotoxic effect of hydrophobic bile acids, and to stimulate biliary secretion by several distinct mechanisms. Hematin appears to reduce excess protoporphyrin production in the bone marrow. It has been administered to patients with EPP (3–4 mg/kg iv) who develop a crisis after liver transplantation. Plasmapheresis can also decrease the levels of protoporphyrin in plasma, however its use in treating acute episodes is controversial. Cholestyramine is an orally administered resin which reduces circulating levels of protoporphyrin by binding to protoporphyrin in the intestine and, hence, interrupting the enterohepatic circulation. It is usually used in combination with other treatment approaches. Activated carbon, like cholestyramine, binds to protoporphyrin in the intestine and prevents its absorption. It is cheap and readily available. It seems to be effective in reducing circulating protoporphyrin levels.Bone marrow transplantation, liver transplantation, acetylcysteine, extracorporeal albumin dialysis, parenteral iron and transfusion of erythrocytes are alternative plans for treatment of EEP. Over-the-counter drug Some over-the-counter drugs may help: Proferrin is an oral heme supplement which may work similarly to Hematin. B. subtilis (a gram-positive soil probiotic) produces ferrochelatase, which may be able to convert some of the protoporphyrin in the intestine into heme. Beta carotene, though a recent meta analysis of carotene treatment has called its effectiveness into question. Epidemiology Case reports suggest that EPP is prevalent globally. The prevalence has been estimated somewhere between 1 in 75,000 and 1 in 200,000 however it has been noted that the prevalence of EPP may be increasing due to a better understanding of the disease and improved diagnosis. An estimated 5,000–10,000 individuals worldwide have EPP. EPP is considered the most common form of porphyria in children. The prevalence in Sweden has been published as 1:180,000. History Erythropoietic protoporphyria was first described in 1953 by Kosenow and Treibs and completed in 1960 by Magnus et al. at the St Johns Institute of Dermatology in London. See also Xeroderma pigmentosum Porphyria cutanea tarda List of cutaneous conditions References External links Erythropoietic protoporphyria at NLM Genetics Home Reference

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

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

Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin culex meaning "gnat"). The word "mosquito" (formed by mosca and diminutive -ito) is Spanish and Portuguese for "little fly". Mosquitoes have a slender segmented body, one pair of wings, one pair of halteres, three pairs of long hair-like legs, and elongated mouthparts. The mosquito life cycle consists of egg, larva, pupa, and adult stages. Eggs are laid on the water surface; they hatch into motile larvae that feed on aquatic algae and organic material. These larvae are important food sources for many freshwater animals, such as dragonfly nymphs, many fish, and some birds such as ducks. The adult females of most species have tube-like mouthparts (called a proboscis) that can pierce the skin of a host and feed on blood, which contains protein and iron needed to produce eggs. Thousands of mosquito species feed on the blood of various hosts ⁠— vertebrates, including mammals, birds, reptiles, amphibians, and some fish; along with some invertebrates, primarily other arthropods. The mosquitos saliva is transferred to the host during the bite, and can cause an itchy rash. In addition, many species can ingest pathogens while biting, and transmit them to future hosts. In this way, mosquitoes are important vectors of parasitic diseases such as malaria and filariasis, and arboviral diseases such as yellow fever, Chikungunya, West Nile, dengue fever, and Zika. By transmitting diseases, mosquitoes cause the deaths of more people than any other animal taxon: over 700,000 each year. It has been claimed that almost half of the people who have ever lived have died of mosquito-vectored disease, but this claim is disputed, with more conservative estimates placing the death toll closer to 5% of all humans. Mosquitoes cannot live or function properly when the air temperature is below 10 degrees Celsius (50 degrees Fahrenheit). They are mostly active at 15–25 degrees Celsius (60–80 degrees Fahrenheit). Fossil record and evolutionary history The oldest known mosquitoes are known from amber dating to the Late Cretaceous. Three species of Cretaceous mosquito are currently known, Burmaculex antiquus and Priscoculex burmanicus are known from Burmese amber from Myanmar, which dates to the earliest part of the Cenomanian stage of the Late Cretaceous, around 99 million years ago. Paleoculicis minutus, is known from Canadian amber from Alberta, Canada, which dates to the Campanian stage of the Late Cretaceous, around 79 million years ago. Priscoculex burmanicus can be definitively assigned to Anophelinae, one of the two subfamilies of mosquitoes alongside Culicinae, indicating the split between these two subfamilies occurred over 99 million years ago. Molecular estimates suggest that the split between the two subfamilies occurred 197.5 million years ago, during the Early Jurassic, but that major diversification did not take place until the Cretaceous.The mosquito Anopheles gambiae is currently undergoing speciation into the M(opti) and S(avanah) molecular forms. Consequently, some pesticides that work on the M form no longer work on the S form. Over 3,500 species of the Culicidae have already been described. They are generally divided into two subfamilies which in turn comprise some 43 genera. These figures are subject to continual change, as more species are discovered, and as DNA studies compel rearrangement of the taxonomy of the family. The two main subfamilies are the Anophelinae and Culicinae, with their genera as shown in the subsection below. The distinction is of great practical importance because the two subfamilies tend to differ in their significance as vectors of different classes of diseases. Roughly speaking, arboviral diseases such as yellow fever and dengue fever tend to be transmitted by Culicine species, not necessarily in the genus Culex. Some transmit various species of avian malaria, but it is not clear that they ever transmit any form of human malaria. Some species transmit various forms of filariasis, much as many Simuliidae do. Taxonomy Family Mosquitoes are members of a family of nematoceran flies: the Culicidae (from the Latin culex, genitive culicis, meaning "midge" or "gnat"). Superficially, mosquitoes resemble crane flies (family Tipulidae) and chironomid flies (family Chironomidae). Subfamilies Anophelinae Culicinae Genera Mosquitoes have been classified into 112 genera, some of the more common of which appear below. Species Over 3,500 species of mosquitoes have thus far been described in the scientific literature. Genomics An analysis by Matthews et al 2018 suggests mosquito species all carry a large and diverse number of transposable elements. Morphology As true flies, mosquitoes have one pair of wings, with distinct scales on the surface. Their wings are long and narrow, as are their long, thin legs. They have slender and dainty bodies of length typically 3–6 mm, with dark grey to black coloring. Some species harbor specific morphological patterns. When at rest they tend to hold their first pair of legs outward. They are similar in appearance to midges (Chironomidae), another ancient family of flies. Tokunagayusurika akamusi, for example, is a midge fly that looks very much like mosquitoes in that they also have slender and dainty bodies of similar colors, though larger in size. They also have only one pair of wings, but without scales on the surface. Another distinct feature to tell the two families of flies apart is the way they hold their first pair of legs – mosquitoes hold them outward, while midges hold them forward. Life cycle Overview Like all flies, mosquitoes go through four stages in their life cycles: egg, larva, pupa, and adult or imago. The first three stages—egg, larva, and pupa—are largely aquatic. Each of the stages typically lasts 5 to 14 days, depending on the species and the ambient temperature, but there are important exceptions. Mosquitoes living in regions where some seasons are freezing or waterless spend part of the year in diapause; they delay their development, typically for months, and carry on with life only when there is enough water or warmth for their needs. For instance, Wyeomyia larvae typically get frozen into solid lumps of ice during winter and only complete their development in spring. The eggs of some species of Aedes remain unharmed in diapause if they dry out, and hatch later when they are covered by water. Eggs hatch to become larvae, which grow until they are able to change into pupae. The adult mosquito emerges from the mature pupa as it floats at the water surface. Bloodsucking mosquitoes, depending on species, sex, and weather conditions, have potential adult lifespans ranging from as short as a week to as long as several months. Some species can overwinter as adults in diapause. Breeding In most species, adult females lay their eggs in stagnant water: some lay near the waters edge while others attach their eggs to aquatic plants. Each species selects the situation of the water into which it lays its eggs and does so according to its own ecological adaptations. Some breed in lakes, some in temporary puddles. Some breed in marshes, some in salt-marshes. Among those that breed in salt water (such as Opifex fuscus), some are equally at home in fresh and salt water up to about one-third the concentration of seawater, whereas others must acclimatize themselves to the salinity. Such differences are important because certain ecological preferences keep mosquitoes away from most humans, whereas other preferences bring them right into houses at night. Some species of mosquitoes prefer to breed in phytotelmata (natural reservoirs on plants), such as rainwater accumulated in holes in tree trunks, or in the leaf-axils of bromeliads. Some specialize in the liquid in pitchers of particular species of pitcher plants, their larvae feeding on decaying insects that had drowned there or on the associated bacteria; the genus Wyeomyia provides such examples — the harmless Wyeomyia smithii breeds only in the pitchers of Sarracenia purpurea.Some of the species of mosquitoes that are adapted to breeding in phytotelmata are dangerous disease vectors. In nature, they might occupy anything from a hollow tree trunk to a cupped leaf. Such species typically take readily to breeding in artificial water containers. Such casual puddles are important breeding places for some of the most serious disease vectors, such as species of Aedes that transmit dengue and yellow fever. Some with such breeding habits are disproportionately important vectors because they are well-placed to pick up pathogens from humans and pass them on. In contrast, no matter how voracious, mosquitoes that breed and feed mainly in remote wetlands and salt marshes may well remain uninfected, and if they do happen to become infected with a relevant pathogen, might seldom encounter humans to infect, in turn. Eggs and oviposition Mosquito habits of oviposition, the ways in which they lay their eggs, vary considerably between species, and the morphologies of the eggs vary accordingly. The simplest procedure is that followed by many species of Anopheles; like many other gracile species of aquatic insects, females just fly over the water, bobbing up and down to the water surface and dropping eggs more or less singly. The bobbing behavior occurs among some other aquatic insects as well, for example mayflies and dragonflies; it is sometimes called "dapping". The eggs of Anopheles species are roughly cigar-shaped and have floats down their sides. Females of many common species can lay 100–200 eggs during the course of the adult phase of their life cycles. Even with high egg and intergenerational mortality, over a period of several weeks, a single successful breeding pair can create a population of thousands. Some other species, for example members of the genus Mansonia, lay their eggs in arrays, attached usually to the under-surfaces of waterlily pads. Their close relatives, the genus Coquillettidia, lay their eggs similarly, but not attached to plants. Instead, the eggs form layers called "rafts" that float on the water. This is a common mode of oviposition, and most species of Culex are known for the habit, which also occurs in some other genera, such as Culiseta and Uranotaenia. Anopheles eggs may on occasion cluster together on the water, too, but the clusters do not generally look much like compactly glued rafts of eggs. In species that lay their eggs in rafts, rafts do not form adventitiously; the female Culex settles carefully on still water with its hind legs crossed, and as it lays the eggs one by one, it twitches to arrange them into a head-down array that sticks together to form the raft.Aedes females generally drop their eggs singly, much as Anopheles do, but not as a rule into water. Instead, they lay their eggs on damp mud or other surfaces near the waters edge. Such an oviposition site commonly is the wall of a cavity such as a hollow stump or a container such as a bucket or a discarded vehicle tire. The eggs generally do not hatch until they are flooded, and they may have to withstand considerable desiccation before that happens. They are not resistant to desiccation straight after oviposition, but must develop to a suitable degree first. After that, they can enter diapause for several months if they dry out. Clutches of eggs of the majority of mosquito species hatch as soon as possible, and all the eggs in the clutch hatch at much the same time. In contrast, a batch of Aedes eggs in diapause tends to hatch irregularly over an extended period of time. This makes it much more difficult to control such species than those mosquitoes whose larvae can be killed all together as they hatch. Some Anopheles species do also behave in such a manner, though not to the same degree of sophistication. Larva The mosquito larva has a well-developed head with mouth brushes used for feeding, a large thorax with no legs, and a segmented abdomen. Larvae breathe through spiracles located on their eighth abdominal segments, or through a siphon, so must come to the surface frequently. The larvae spend most of their time feeding on algae, bacteria, and other microbes in the surface microlayer. Mosquito larvae have been investigated as prey of other Dipteran flies. Species such as Bezzia nobilis within the family Ceratopogonidae have been observed in experiments to prey upon mosquito larvae.They dive below the surface when disturbed. Larvae swim either through propulsion with their mouth brushes, or by jerky movements of their entire bodies, giving them the common name of "wigglers" or "wrigglers". Larvae develop through four stages, or instars, after which they metamorphose into pupae. At the end of each instar, the larvae molt, shedding their skins to allow for further growth. Pupa As seen in its lateral aspect, the mosquito pupa is comma-shaped. The head and thorax are merged into a cephalothorax, with the abdomen curving around underneath. The pupa can swim actively by flipping its abdomen, and it is commonly called a "tumbler" because of its swimming action. As with the larva, the pupa of most species must come to the surface frequently to breathe, which they do through a pair of respiratory trumpets on their cephalothoraxes. They do not feed during this stage; typically they pass their time hanging from the surface of the water by their respiratory trumpets. If alarmed, say by a passing shadow, they nimbly swim downwards by flipping their abdomens in much the same way as the larvae do. If undisturbed, they soon float up again. After a few days or longer, depending on the temperature and other circumstances, the dorsal surface of its cephalothorax splits, and the adult mosquito emerges. The pupa is less active than the larva because it does not feed, whereas the larva feeds constantly. Adult The period of development from egg to adult varies among species and is strongly influenced by ambient temperature. Some species of mosquitoes can develop from egg to adult in as few as five days, but a more typical period of development in tropical conditions would be some 40 days or more for most species. The variation of the body size in adult mosquitoes depends on the density of the larval population and food supply within the breeding water. Adult mosquitoes usually mate within a few days after emerging from the pupal stage. In most species, the males form large swarms, usually around dusk, and the females fly into the swarms to mate. Males typically live for about 5–7 days, feeding on nectar and other sources of sugar. After obtaining a full blood meal, the female will rest for a few days while the blood is digested and eggs are developed. This process depends on the temperature, but usually takes two to three days in tropical conditions. Once the eggs are fully developed, the female lays them and resumes host-seeking. The cycle repeats itself until the female dies. While females can live longer than a month in captivity, most do not live longer than one to two weeks in nature. Their lifespans depend on temperature, humidity, and their ability to successfully obtain a blood meal while avoiding host defenses and predators. The length of the adult is typically between 3 mm and 6 mm. The smallest known mosquitoes are around 2 mm (0.1 in), and the largest around 19 mm (0.7 in). Mosquitoes typically weigh around 5 mg. All mosquitoes have slender bodies with three segments: a head, a thorax and an abdomen. The head is specialized for receiving sensory information and for feeding. It has eyes and a pair of long, many-segmented antennae. The antennae are important for detecting host odors, as well as odors of breeding sites where females lay eggs. In all mosquito species, the antennae of the males in comparison to the females are noticeably bushier and contain auditory receptors to detect the characteristic whine of the females. The compound eyes are distinctly separated from one another. Their larvae only possess a pit-eye ocellus. The compound eyes of adults develop in a separate region of the head. New ommatidia are added in semicircular rows at the rear of the eye. During the first phase of growth, this leads to individual ommatidia being square, but later in development they become hexagonal. The hexagonal pattern will only become visible when the carapace of the stage with square eyes is molted.The head also has an elongated, forward-projecting, stinger-like proboscis used for feeding, and two sensory palps. The maxillary palps of the males are longer than their proboscises, whereas the females’ maxillary palps are much shorter. In typical bloodsucking species, the female has an elongated proboscis. The thorax is specialized for locomotion. Three pairs of legs and a pair of wings are attached to the thorax. The insect wing is an outgrowth of the exoskeleton. The Anopheles mosquito can fly for up to four hours continuously at 1 to 2 km/h (0.6–1 mph), traveling up to 12 km (7.5 mi) in a night. Males beat their wings between 450 and 600 times per second.The abdomen is specialized for food digestion and egg development; the abdomen of a mosquito can hold three times its own weight in blood. This segment expands considerably when a female takes a blood meal. The blood is digested over time, serving as a source of protein for the production of eggs, which gradually fill the abdomen. Feeding by adults Typically, both male and female mosquitoes feed on nectar, aphid honeydew, and plant juices, but in many species the mouthparts of the females are adapted for piercing the skin of animal hosts and sucking their blood as ectoparasites. In many species, the female needs to obtain nutrients from a blood meal before it can produce eggs, whereas in many other species, obtaining nutrients from a blood meal enables the mosquito to lay more eggs. A mosquito has a variety of ways of finding nectar or its prey, including chemical, visual, and heat sensors. Both plant materials and blood are useful sources of energy in the form of sugars, and blood also supplies more concentrated nutrients, such as lipids, but the most important function of blood meals is to obtain proteins as materials for egg production.When a female reproduces without such parasitic meals, it is said to practice autogenous reproduction, as in Toxorhynchites; otherwise, the reproduction may be termed anautogenous, as occurs in mosquito species that serve as disease vectors, particularly Anopheles and some of the most important disease vectors in the genus Aedes. In contrast, some mosquitoes, for example, many Culex, are partially anautogenous: they do not need a blood meal for their first cycle of egg production, which they produce autogenously; subsequent clutches of eggs are produced anautogenously, at which point their disease vectoring activity becomes operative.Among humans, the feeding preferences of mosquitoes typically include: those with type O blood, heavy breathers, an abundance of skin bacteria, high body heat, and pregnant women. Individuals attractiveness to mosquitoes also has a heritable, genetically-controlled component.Female mosquitoes hunt their blood host by detecting organic substances such as carbon dioxide (CO2) and 1-octen-3-ol (mushroom alcohol, found in exhaled breath) produced from the host, and through visual recognition. Mosquitoes prefer some people over others. The preferred victims sweat smells more attractive than others because of the proportions of the carbon dioxide, octenol, and other compounds that make up body odor. The most powerful semiochemical that triggers the keen sense of smell of Culex quinquefasciatus is nonanal. Another compound identified in human blood that attracts mosquitoes is sulcatone or 6-methyl-5-hepten-2-one, especially for Aedes aegypti mosquitoes with the odor receptor gene Or4. A large part of the mosquitos sense of smell, or olfactory system, is devoted to sniffing out blood sources. Of 72 types of odor receptors on its antennae, at least 27 are tuned to detect chemicals found in perspiration. In Aedes, the search for a host takes place in two phases. First, the mosquito exhibits a nonspecific searching behavior until the perception of a hosts stimulants, then it follows a targeted approach.Most mosquito species are crepuscular (dawn or dusk) feeders. During the heat of the day, most mosquitoes rest in a cool place and wait for the evenings, although they may still bite if disturbed. Some species, such as the Asian tiger mosquito, are known to fly and feed during daytime.Prior to and during blood feeding, blood-sucking mosquitoes inject saliva into the bodies of their source(s) of blood. This saliva serves as an anticoagulant; without it the female mosquitos proboscis might become clogged with blood clots. The saliva also is the main route by which mosquito physiology offers passenger pathogens access to the hosts bloodstream. The salivary glands are a major target to most pathogens, whence they find their way into the host via the saliva. A mosquito bite often leaves an itchy weal, a raised bump, on the victims skin, which is caused by histamines trying to fight off the protein left by the attacking insect.Mosquitoes of the genus Toxorhynchites never drink blood. This genus includes the largest extant mosquitoes, the larvae of which prey on the larvae of other mosquitoes. These mosquito eaters have been used in the past as mosquito control agents, with varying success. Host animals Many, if not all, blood-sucking species of mosquitoes are fairly selective feeders that specialise in particular host species, though they often relax their selectivity when they experience severe competition for food, defensive activity on the part of the hosts, or starvation. Some species feed selectively on monkeys, while others prefer particular kinds of birds, but they become less selective as conditions become more difficult. For example, Culiseta melanura sucks the blood of passerine birds for preference, and such birds are typically the main reservoir of the Eastern equine encephalitis virus in North America. Early in the season while mosquito numbers are low, they concentrate on passerine hosts, but as mosquito numbers rise and the birds are forced to defend themselves more vigorously, the mosquitoes become less selective of hosts. Soon the mosquitoes begin attacking mammals more readily, thereby becoming the major vector of the virus, and causing epidemics of the disease, most conspicuously in humans and horses. Multiple mosquitoes withdrawal of blood from a host can add up to a large volume. In rare cases, heavy mosquito densities have directly killed livestock as large as cattle and horses.Even more dramatically, in most of its range in North America, the main vector for the Western equine encephalitis virus is Culex tarsalis, because it is known to feed variously on mammals, birds, reptiles, and amphibians. Even fish may be attacked by some mosquito species if they expose themselves above water level, as mudskippers do.In 1969 it was reported that some species of anautogenous mosquitoes would feed on the haemolymph of caterpillars although its nutritional value is questionable. Other observations include mosquitoes feeding on cicadas and mantids. In 2014, it was shown that malaria-transmitting mosquitoes actively seek out some species of caterpillars and feed on their haemolymph, and do so to the caterpillars apparent physical detriment. Mouthparts Mosquito mouthparts are very specialized, particularly those of the females, which in most species are adapted to piercing skin and then sucking blood. Apart from bloodsucking, the females generally also drink assorted fluids rich in dissolved sugar, such as nectar and honeydew, to obtain the energy they need. For this, their blood-sucking mouthparts are perfectly adequate. In contrast, male mosquitoes are not bloodsuckers; they only drink sugary fluids. Accordingly, their mouthparts do not require the same degree of specialization as those of females.Externally, the most obvious feeding structure of the mosquito is the proboscis. More specifically, the visible part of the proboscis is the labium, which forms the sheath enclosing the rest of the mouthparts. When the mosquito first lands on a potential host, its mouthparts are enclosed entirely in this sheath, and it will touch the tip of the labium to the skin in various places. Sometimes, it will begin to bite almost straight away, while other times, it will prod around, apparently looking for a suitable place. Occasionally, it will wander for a considerable time, and eventually fly away without biting. Presumably, this probing is a search for a place with easily accessible blood vessels, but the exact mechanism is not known. It is known that there are two taste receptors at the tip of the labium which may well play a role.The female mosquito does not insert its labium into the skin; it bends back into a bow when the mosquito begins to bite. The tip of the labium remains in contact with the skin of the host, acting as a guide for the other mouthparts. In total, there are six mouthparts besides the labium: two mandibles, two maxillae, the hypopharynx, and the labrum. The mandibles and the maxillae are used for piercing the skin. The mandibles are pointed, while the maxillae end in flat, toothed "blades". To force these into the skin, the mosquito moves its head backwards and forwards. On one movement, the maxillae are moved as far forward as possible. On the opposite movement, the mandibles are pushed deeper into the skin by levering against the maxillae. The maxillae do not slip back because the toothed blades grip the skin. The hypopharynx and the labrum are both hollow. Saliva with anticoagulant is pumped down the hypopharynx to prevent clotting, and blood is drawn up the labrum. To understand the mosquito mouthparts, it is helpful to draw a comparison with an insect that chews food, such as a dragonfly. A dragonfly has two mandibles, which are used for chewing, and two maxillae, which are used to hold the food in place as it is chewed. The labium forms the floor of the dragonflys mouth, the labrum forms the top, while the hypopharynx is inside the mouth and is used in swallowing. Conceptually, then, the mosquitos proboscis is an adaptation of the mouthparts that occur in other insects. The labium still lies beneath the other mouthparts, but also enfolds them, and it has been extended into a proboscis. The maxillae still "grip" the "food" while the mandibles "bite" it. The top of the mouth, the labrum, has developed into a channeled blade the length of the proboscis, with a cross-section like an inverted "U". Finally, the hypopharynx has extended into a tube that can deliver saliva at the end of the proboscis. Its upper surface is somewhat flattened so, when the lower part of the hypopharynx is pressed against it, the labrum forms a closed tube for conveying blood from the host. Saliva For the mosquito to obtain a blood meal, it must circumvent the vertebrates physiological responses. The mosquito, as with all blood-feeding arthropods, has mechanisms to effectively block the hemostasis system with their saliva, which contains a mixture of secreted proteins. Saglin is a protein produced by the salivary glands of mosquitoes. Mosquito saliva acts to reduce vascular constriction, blood clotting, platelet aggregation, angiogenesis and immunity, and creates inflammation. Universally, hematophagous arthropod saliva contains at least one anti-clotting, one anti-platelet, and one vasodilatory substance. Mosquito saliva also contains enzymes that aid in sugar feeding, and antimicrobial agents to control bacterial growth in the sugar meal. The composition of mosquito saliva is relatively simple, as it usually contains fewer than 20 dominant proteins. As of the early 2000s, scientists still were unable to ascribe functions to more than half of the molecules found in arthropod saliva. One promising application of components of mosquito saliva is the development of anti-clotting drugs, such as clotting inhibitors and capillary dilators, that could be useful for managing cardiovascular disease. It is now well recognized that feeding ticks, sandflies, and, more recently, mosquitoes, have an ability to modulate the immune response of the animals (hosts) on which they feed. The presence of this activity in vector saliva is a reflection of the inherent overlapping and interconnected nature of the host hemostatic and inflammatory/immunological responses and the intrinsic need to prevent these host defenses from disrupting successful feeding. The mechanism for mosquito saliva-induced alteration of the host immune response is unclear, but the data have become increasingly convincing that such an effect occurs. Early work described a factor in saliva that directly suppresses TNF-α release, but not antigen-induced histamine secretion, from activated mast cells. Experiments by Cross et al. (1994) demonstrated that the inclusion of Ae. aegypti mosquito saliva into naïve cultures led to a suppression of interleukin (IL)-2 and IFN-γ production, while the cytokines IL-4 and IL-5 are unaffected. Cellular proliferation in response to IL-2 is clearly reduced by prior treatment of cells with mosquito salivary gland extract. Correspondingly, activated splenocytes isolated from mice fed upon by either Ae. aegypti or Cx. pipiens mosquitoes produce markedly higher levels of IL-4 and IL-10 concurrent with suppressed IFN-γ production. Unexpectedly, this shift in cytokine expression is observed in splenocytes up to 10 days after mosquito exposure, suggesting natural feeding of mosquitoes can have a profound, enduring, and systemic effect on the immune response.T cell populations are decidedly susceptible to the suppressive effect of mosquito saliva, showing increased mortality and decreased division rates. Parallel work by Wasserman et al. (2004) demonstrated that T and B cell proliferation was inhibited in a dose dependent manner with concentrations as low as 1/7 of the saliva in a single mosquito. Depinay et al. (2005) observed a suppression of antibody-specific T cell responses mediated by mosquito saliva and dependent on mast cells and IL-10 expression.A 2006 study suggests mosquito saliva can also decrease expression of interferon−α/β during early mosquito-borne virus infection. The contribution of type I interferons (IFN) in recovery from infection with viruses has been demonstrated in vivo by the therapeutic and prophylactic effects of administration of IFN inducers or IFN itself, and different research suggests mosquito saliva exacerbates West Nile virus infection, as well as other mosquito-transmitted viruses.Studies in humanized mice bearing a reconstituted human immune system have suggested potential impact of mosquito saliva in humans. Work published in 2018 from the Baylor College of Medicine using such humanized mice came to several conclusions, among them being that mosquito saliva led to an increase in natural killer T cells in peripheral blood; to an overall decrease in ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs); changes to proportions of subsets of PBMCs; changes in the prevalence of T cell subtypes across organs; and changes to circulating levels of cytokines. Egg development and blood digestion Most species of mosquito require a blood meal to begin the process of egg development. Females with poor larval nutrition may need to ingest sugar or a preliminary blood meal before their ovarian follicles can reach their resting stage. Once the follicles have reached the resting stage, digestion of a sufficiently large blood meal triggers a hormonal cascade that leads to egg development. Upon completion of feeding, the mosquito withdraws her proboscis, and as the gut fills up, the stomach lining secretes a peritrophic membrane that surrounds the blood. This membrane keeps the blood separate from anything else in the stomach. Like many Hemiptera and other insects that survive on dilute liquid diets, many adult mosquitoes must excrete unwanted aqueous fractions even as they feed. (See the photograph of a feeding Anopheles stephensi: Note that the excreted droplet patently is not whole blood, being far more dilute). As long as they are not disturbed, this permits mosquitoes to continue feeding until they have accumulated a full meal of nutrient solids. As a result, a mosquito replete with blood can continue to absorb sugar, even as the blood meal is slowly digested over a period of several days. Once blood is in the stomach, the midgut of the female synthesizes proteolytic enzymes that hydrolyze the blood proteins into free amino acids. These are used as building blocks for the synthesis of vitellogenin, which are the precursors for egg yolk protein.In the mosquito Anopheles stephensi, trypsin activity is restricted entirely to the posterior midgut lumen. No trypsin activity occurs before the blood meal, but activity increases continuously up to 30 hours after feeding, and subsequently returns to baseline levels by 60 hours. Aminopeptidase is active in the anterior and posterior midgut regions before and after feeding. In the whole midgut, activity rises from a baseline of approximately three enzyme units (EU) per midgut to a maximum of 12 EU at 30 hours after the blood meal, subsequently falling to baseline levels by 60 hours. A similar cycle of activity occurs in the posterior midgut and posterior midgut lumen, whereas aminopeptidase in the posterior midgut epithelium decreases in activity during digestion. Aminopeptidase in the anterior midgut is maintained at a constant, low level, showing no significant variation with time after feeding. Alpha-glucosidase is active in anterior and posterior midguts before and at all times after feeding. In whole midgut homogenates, alpha-glucosidase activity increases slowly up to 18 hours after the blood meal, then rises rapidly to a maximum at 30 hours after the blood meal, whereas the subsequent decline in activity is less predictable. All posterior midgut activity is restricted to the posterior midgut lumen. Depending on the time after feeding, greater than 25% of the total midgut activity of alpha-glucosidase is located in the anterior midgut. After blood meal ingestion, proteases are active only in the posterior midgut. Trypsin is the major primary hydrolytic protease and is secreted into the posterior midgut lumen without activation in the posterior midgut epithelium. Aminopeptidase activity is also luminal in the posterior midgut, but cellular aminopeptidases are required for peptide processing in both anterior and posterior midguts. Alpha-glucosidase activity is elevated in the posterior midgut after feeding in response to the blood meal, whereas activity in the anterior midgut is consistent with a nectar-processing role for this midgut region. Ecology Distribution Mosquitoes are cosmopolitan (world-wide): they are in every land region except Antarctica and a few islands with polar or subpolar climates. Iceland is such an island, being essentially free of mosquitoes.The absence of mosquitoes in Iceland and similar regions is probably because of quirks of their climate, which differs in some respects from mainland regions. At the start of the uninterrupted continental winter of Greenland and the northern regions of Eurasia and America, the pupa enters diapause under the ice that covers sufficiently deep water. The imago emerges only after the ice breaks in late spring. In Iceland, the weather is less predictable. In mid-winter it frequently warms up suddenly, causing the ice to break, but then to freeze again after a few days. By that time the mosquitoes will have emerged from their pupae, but the new freeze sets in before they can complete their life cycle. Any anautogenous adult mosquito would need a host to supply a blood meal before it could lay viable eggs; it would need time to mate, mature the eggs and oviposit in suitable wetlands. These requirements would not be realistic in Iceland and in fact the absence of mosquitoes from such subpolar islands is in line with the islands low insect biodiversity; Iceland has fewer than 1,500 described species of insects, many of them probably accidentally introduced by human agency. In Iceland most ectoparasitic insects live in sheltered conditions or actually on mammals; examples include lice, fleas and bedbugs, in whose living conditions freezing is no concern, and most of which were introduced inadvertently by humans.Some other aquatic Diptera, such as Simuliidae, do survive in Iceland, but their habits and adaptations differ from those of mosquitoes; Simuliidae for example, though they, like mosquitoes, are bloodsuckers, generally inhabit stones under running water that does not readily freeze and which is totally unsuited to mosquitoes; mosquitoes are generally not adapted to running water.Eggs of species of mosquitoes from the temperate zones are more tolerant of cold than the eggs of species indigenous to warmer regions. Many even tolerate subzero temperatures. In addition, adults of some species can survive the winter by taking shelter in suitable microhabitats such as buildings or hollow trees. Pollination Several flowers are pollinated by mosquitoes, including some members of the Asteraceae, Roseaceae and Orchidaceae. Activity In warm and humid tropical regions, some mosquito species are active for the entire year, but in temperate and cold regions they hibernate or enter diapause. Arctic or subarctic mosquitoes, like some other arctic midges in families such as Simuliidae and Ceratopogonidae may be active for only a few weeks annually as melt-water pools form on the permafrost. During that time, though, they emerge in huge numbers in some regions and may take up to 300 ml of blood per day from each animal in a caribou herd. Means of dispersal Worldwide introduction of various mosquito species over large distances into regions where they are not indigenous has occurred through human agencies, primarily on sea routes, in which the eggs, larvae, and pupae inhabiting water-filled used tires and cut flowers are transported. They have also been carried by personal vehicles, delivery trucks, trains, and aircraft. Man-made areas such as storm water retention basins, or storm drains also provide sprawling sanctuaries. Sufficient quarantine measures have proven difficult to implement. In addition, outdoor pool areas make a perfect place for them to grow. Climate and global distribution Seasonality In order for a mosquito to transmit a disease to the host there must be favorable conditions, referred to as transmission seasonality. Seasonal factors that impact the prevalence of mosquitoes and mosquito-borne diseases are primarily humidity, temperature, and precipitation. A positive correlation between malaria outbreaks and these climatic variables has been demonstrated in China; and El Niño has been shown to impact the location and number of outbreaks of mosquito-borne diseases observed in East Africa, Latin America, Southeast Asia and India. Climate change impacts each of these seasonal factors and in turn impacts the dispersal of mosquitoes. Past and future patterns Climatology and the study of mosquito-borne disease have been developed only over the past 100 years. Historical records of weather patterns and distinct symptoms associated with mosquito-borne diseases can be utilized to trace the prevalence of these diseases in relation to the climate over longer time periods. Further, statistical models are being created to predict the impact of climate change on vector-borne diseases using these past records, and these models can be utilized in the field of public health in order to create interventions to reduce the impact of these predicted outcomes. Two types of models are used to predict mosquito-borne disease spread in relation to climate: correlative models and mechanistic models. Correlative models focus primarily on vector distribution, and generally function in 3 steps. First, data is collected regarding geographical location of a target mosquito species. Next, a multivariate regression model establishes the conditions under which the target species can survive. Finally, the model determines the likelihood of the mosquito species to become established in a new location based on similar living conditions. The model can further predict future distributions based on environmental emissions data. Mechanistic models tend to be broader and include the pathogens and hosts in the analysis. These models have been used to recreate past outbreaks as well as predict the potential risk of a vector-borne disease based on an areas forecasted climate.Mosquito-borne diseases are currently most prevalent in East Africa, Latin America, Southeast Asia, and India. An emergence in Europe was recently observed. A weighted risk analysis demonstrated associations to climate for 49% of infectious diseases in Europe including all transmission routes. One statistical model predicts by 2030, the climate of southern Great Britain will be climatically suitable for malaria transmission Plasmodium vivax for 2 months of the year. By 2080 it is predicted that the same will be true for southern Scotland. Vectors of disease Mosquitoes can act as vectors for many disease-causing viruses and parasites. Infected mosquitoes carry these organisms from person to person without exhibiting symptoms themselves. Mosquito-borne diseases include: Viral diseases, such as yellow fever, dengue fever, and chikungunya, transmitted mostly by Aedes aegypti. Dengue fever is the most common cause of fever in travelers returning from the Caribbean, Central America, South America, and South Central Asia. This disease is spread through the bites of infected mosquitoes and cannot be spread person to person. Severe dengue can be fatal, but with good treatment, fewer than 1% of patients die from dengue. Work published in 2012 from Baylor College of Medicine suggested that for some diseases, such as dengue fever, which can be transmitted via mosquitoes and by other means, the severity of the mosquito-transmitted disease could be greater. The parasitic diseases collectively called malaria, caused by various species of Plasmodium, carried by female mosquitoes of the genus Anopheles. Lymphatic filariasis (the main cause of elephantiasis) which can be spread by a wide variety of mosquito species. West Nile virus is a significant concern in the United States but there are no reliable statistics on worldwide cases. Dengue viruses are a significant health risk globally. Severe cases of dengue often require hospitalization and can be life-threatening shortly after infection. Symptoms include a high fever, aches and pains, vomiting, and rashes. Warning signs of severe dengue infection include vomiting blood, bleeding from the gums or nose, and stomach tenderness/pain. Equine encephalitis viruses, such as Eastern equine encephalitis virus, Western equine encephalitis virus, and Venezuelan equine encephalitis virus, can be spread by mosquito vectors such as Aedes taeniorhynchus. Tularemia, a bacterial disease caused by Francisella tularensis, is variously transmitted, including by biting flies. Culex and Culiseta are vectors of tularemia, as well as arbovirus infections such as West Nile virus. Zika, recently notorious, though rarely deadly, causes fever, joint pain, rashes and conjunctivitis. The most serious consequence appears when the infected person is a pregnant woman, since during pregnancy this virus can originate a birth defect called microcephaly. St. Louis Encephalitis, a mosquito-borne disease that is characterized by fever and headaches upon initial onset of infection, arises from mosquitoes who feed on birds who are infected with the illness, and can result in death. The most common vector of this disease is Culex pipiens, also known as the common house mosquito. Heartworm disease, a parasitic roundworm infection that affects dogs and other canids. Mosquitoes transmit larvae to the definitive host through bites. Adult heart worms infest the right heart and pulmonary artery, where they can cause serious complications including congestive heart failure.Potential transmission of HIV was originally a public health concern, but practical considerations and detailed studies of epidemiological patterns suggest that any transmission of the HIV virus by mosquitoes is at worst extremely unlikely.Various species of mosquitoes are estimated to transmit various types of disease to more than 700 million people annually in Africa, South America, Central America, Mexico, Russia, and much of Asia, with millions of resultant deaths. At least two million people annually die of these diseases, and the morbidity rates are many times higher still. Methods used to prevent the spread of disease, or to protect individuals in areas where disease is endemic, include: Vector control aimed at mosquito control or eradication Disease prevention, using prophylactic drugs and developing vaccines Prevention of mosquito bites, with insecticides, nets, and repellentsSince most such diseases are carried by "elderly" female mosquitoes, some scientists have suggested focusing on these to avoid the evolution of resistance. Control Many measures have been tried for mosquito control, including the elimination of breeding places, exclusion via window screens and mosquito nets, biological control with parasites such as fungi and nematodes, or predators such as fish, copepods, dragonfly nymphs and adults, and some species of lizard and gecko. Another approach is to introduce large numbers of sterile males. Genetic modification methods including cytoplasmic incompatibility, chromosomal translocations, sex distortion and gene replacement, solutions seen as inexpensive and not subject to vector resistance, have been explored.According to an article in Nature discussing the idea of totally eradicating mosquitoes, "Ultimately, there seem to be few things that mosquitoes do that other organisms can’t do just as well—except perhaps for one. They are lethally efficient at sucking blood from one individual and mainlining it into another, providing an ideal route for the spread of pathogenic microbes." The control of disease-carrying mosquitoes may in the future be possible using gene drives. Repellents Insect repellents are applied on skin and give short-term protection against mosquito bites. The chemical DEET repels some mosquitoes and other insects. Some CDC-recommended repellents are picaridin, eucalyptus oil (PMD), and ethyl butylacetylaminopropionate (IR3535). Pyrethrum (from Chrysanthemum species, particularly C. cinerariifolium and C. coccineum) has been reviewed favorably in research published in 2021. Others are indalone, dimethyl phthalate, dimethyl carbate, and ethyl hexanediol. Electronic insect repellent devices that produce ultrasounds intended to keep away insects (and mosquitoes) are marketed. No EPA or university study has shown that these devices prevent a human from being bitten by a mosquito. Bites Mosquito bites lead to a variety of mild, occasionally serious, and, rarely, life-threatening allergic reactions. These include ordinary wheal and flare reactions and mosquito bite allergies (MBA). The MBA, also termed hypersensitivity to mosquito bites (HMB), are excessive reactions to mosquito bites that are not caused by any toxin or pathogen in the saliva injected by a mosquito at the time it takes its blood-meal. Rather, they are allergic hypersensitivity reactions caused by the non-toxic allergenic proteins contained in the mosquitos saliva. Studies have shown or suggest that numerous species of mosquitoes can trigger ordinary reactions as well as MBA. These include Aedes aegypti, Aedes vexans, Aedes albopictus, Anopheles sinensis, Culex pipiens, Aedes communis, Anopheles stephensi, Culex quinquefasciatus, Ochlerotatus triseriatus, and Culex tritaeniorhynchus. Furthermore, there is considerable cross-reactivity between the salivary proteins of mosquitoes in the same family and, to a lesser extent, different families. It is therefore assumed that these allergic responses may be caused by virtually any mosquito species (or other biting insect). The mosquito bite allergies are informally classified as 1) the Skeeter syndrome, i.e. severe local skin reactions sometimes associated with low-grade fever; 2) systemic reactions that range from high-grade fever, lymphadenopathy, abdominal pain, and/or diarrhea to, very rarely, life-threatening symptoms of anaphylaxis; and 3) severe and often systemic reactions occurring in individuals that have an Epstein-Barr virus-associated lymphoproliferative disease, Epstein-Barr virus-negative lymphoid malignancy, or another predisposing condition such as Eosinophilic cellulitis or chronic lymphocytic leukemia. Mechanism Visible, irritating bites are due to an immune response from the binding of IgG and IgE antibodies to antigens in the mosquitos saliva. Some of the sensitizing antigens are common to all mosquito species, whereas others are specific to certain species. There are both immediate hypersensitivity reactions (types I and III) and delayed hypersensitivity reactions (type IV) to mosquito bites. Both reactions result in itching, redness and swelling. Immediate reactions develop within a few minutes of the bite and last for a few hours. Delayed reactions take around a day to develop, and last for up to a week. Treatment Several anti-itch medications are commercially available, including those taken orally, such as diphenhydramine, or topically applied antihistamines and, for more severe cases, corticosteroids, such as hydrocortisone and triamcinolone. Aqueous ammonia (3.6%) has also been shown to provide relief.Both topical heat and cool may be useful to treat mosquito bites. In human culture Greek mythology Ancient Greek beast fables including "The Elephant and the Mosquito" and "The Bull and the Mosquito", with the general moral that the large beast does not even notice the small one, derive ultimately from Mesopotamia. Origin myths The peoples of Siberia have origin myths surrounding the mosquito. One Ostiak myth tells of a man-eating giant, Punegusse, who is killed by a hero but will not stay dead. The hero eventually burns the giant, but the ashes of the fire become mosquitoes that continue to plague mankind. Other myths from the Yakuts, Goldes (Nanai people), and Samoyed have the insect arising from the ashes or fragments of some giant creature or demon. Similar tales found in Native North American myth, with the mosquito arising from the ashes of a man-eater, suggest a common origin. The Tatars of the Altai had a similar myth, thought to be of Native North American origin, involving the fragments of the dead giant, Andalma-Muus, becoming mosquitoes and other insects. Modern era Winsor McCays 1912 film How a Mosquito Operates was one of the earliest works of animation, which has been described as far ahead of its time in technical quality. It depicts a giant mosquito tormenting a sleeping man.The de Havilland Mosquito was a high-speed aircraft manufactured between 1940 and 1950, and used in many roles. References Further reading External links Mosquito at Curlie Mosquito Information Website Mosquitoes chapter in United States Environmental Protection Agency National Public Health Pesticide Applicator Training Manual A film clip describing The Life Cycle of the Mosquito is available at the Internet Archive "Mosquitoes: The Worst". Stuff You Should Know (Podcast). Retrieved 2015-06-30. Parasitic Insects, Mites and Ticks: Genera of Medical and Veterinary Importance Wikibooks

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.

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

Cerebellar stroke syndrome is a condition in which the circulation to the cerebellum is impaired due to a lesion of the superior cerebellar artery, anterior inferior cerebellar artery or the posterior inferior cerebellar artery.Cardinal signs include vertigo, headache, vomiting, and ataxia. Cerebellar strokes account for only 2-3% of the 600,000 strokes that occur each year in the United States. They are far less common than strokes which occur in the cerebral hemispheres. In recent years mortality rates have decreased due to advancements in health care which include earlier diagnosis through MRI and CT scanning. Advancements have also been made which allow earlier management for common complications of cerebellar stroke such as brainstem compression and hydrocephalus.Research is still needed in the area of cerebellar stroke management; however, several factors may lead to poor outcomes in individuals who have a cerebellar stroke. These factors include: Declining levels of consciousness New signs of brainstem involvement Progressing Hydrocephalus Stroke to the midline of the cerebellum (a.k.a. the vermis) References Further reading Macdonell, R.A.; Kalnins, R.M.; Donnan, G.A. (1987). "Cerebellar infarction: Natural history, prognosis, and pathology". Stroke. 18 (5): 849–55. doi:10.1161/01.STR.18.5.849. PMID 3629642. Edlow, J.A.; Newman-Toker, D.E.; Savitz, S.I. (2008). "Diagnosis and initial management of cerebellar infarction". The Lancet Neurology. 7 (10): 951–64. doi:10.1016/S1474-4422(08)70216-3. PMID 18848314. S2CID 25118582. Norrving, Bo (2014). Oxford Textbook of Stroke and Cerebrovascular Disease. Oxford University Press. pp. 90–1. ISBN 9780199641208. Nowe, Tim; Jütter, Eric (2014). "Ch. 17: Critical Care of Cerebellar Stroke". In Schwab, Stefan; Hanley, Daniel; Mendelow, A. David (eds.). Critical Care of the Stroke Patient. Cambridge University Press. pp. 206–25. ISBN 9780521762564. Manto, Mario Ubaldo (2010). "Ch. 8: Cerebellar Stroke". Cerebellar Disorders: A Practical Approach to Diagnosis and Management. Cambridge University Press. pp. 88–101. ISBN 9780521878135. External links Image of cerebellar stroke Images of cerebellar stroke at MedPix

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

Could you provide a brief overview of 'Suberosis' in a medical context?

Suberosis is a type of hypersensitivity pneumonitis usually caused by the fungus Penicillium glabrum (formerly called Penicillium frequentans) from exposure to moldy cork dust. Chrysonilia sitophilia, Aspergillus fumigatus, uncontaminated cork dust, and Mucor macedo may also have significant roles in the pathogenesis of the disease. Cause Cork is often harvested from the cork oak (Quercus suber) and stored in slabs in a hot and humid environment until covered in mold. Cork workers may be exposed to organic dusts in this process, leading to this disease. Diagnosis Chest radiography, high-resolution chest CT, pulmonary function testing, bronchofibroscopy with BAL and transbronchial biopsy, delayed cutaneous hypersensitivity tests, fungal and suberin antigen testing, immediate hypersensitivity specific skin tests, and specific bronchial challenge tests can all be used for diagnosis. Chest radiography can show fine miliary mottling. Obtaining a history of antigen exposure and asking about symptoms (e.g. dyspnea, cough) can also be useful. Treatment Avoidance of antigen exposure is beneficial. History Vinte-e-Um Mendes first reported respiratory disease in Portuguese cork workers in 1947 at the Portuguese Medical Reunion. Cancella dAbreu first described the disease in 1955. See also Hypersensitivity pneumonitis References Further reading Cancella de Abreu, LC (1955) On a special kind of pneumoconiosis: the suberosis [in Portuguese]. Med Contemp 73,235-243 == 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 'Fibrosing colonopathy' encompass?

Fibrosing colonopathy is a disease that arises in people with cystic fibrosis treated with high doses of pancreatic enzyme supplements. Symptoms are non-specific with abdominal pain, abdominal swelling, vomiting, and constipation.Risk factors include being young, prior surgery of the intestines, and the use of certain medications including corticosteroids and H2 blockers. It may appear similar to distal intestinal obstruction syndrome or inflammatory colitis such as Crohns disease.A maximum dose of 10,000 IU of lipase per kilogram per day is recommended for pancreatic enzyme supplementation to prevent this condition. More than 60 cases have been described as of 1999. The disease was suggested to be caused by methacrylic acid copolymer which is used as coating for delayed release of enzymes but there is no reliable evidence for that. == References ==

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 provide a brief overview of 'Vortioxetine' in a medical context?

Vortioxetine, sold under the brand names Trintellix and Brintellix among others, is a medication used to treat major depressive disorder. Effectiveness is viewed as similar to that of other antidepressants. In the United Kingdom, it is only recommended in people who have not improved sufficiently on two other antidepressants. It is taken by mouth.Common side effects include nausea, vomiting, constipation, and sexual dysfunction. Serious side effects may include suicide in those under the age of 25, serotonin syndrome, bleeding, mania, and SIADH. A withdrawal syndrome may occur if the medication is abruptly stopped or the dose is decreased. Use during pregnancy and breastfeeding is not generally recommended. It is classified as a serotonin modulator and stimulator. How it works is not entirely clear but is believed to be related to increasing serotonin levels and possibly interacting with certain receptors for serotonin.It was approved for medical use in the United States in 2013. In 2017, it was the 312th most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses Vortioxetine is used as a treatment for major depressive disorder. Effectiveness appears to be similar to other antidepressants and in terms of effect size has been described as modest. Vortioxetine may be used when other treatments have failed. A 2017 Cochrane review on vortioxetine determined that the place for it in the treatment of severe depression is unclear due to low-quality evidence and that more study is needed comparing vortioxetine to selective serotonin reuptake inhibitors (SSRIs) which are typical first-line treatments.Vortioxetine is also used off-label for anxiety. A 2016 review found it was not useful in generalized anxiety disorder at 2.5, 5, and 10 mg doses (15 and 20 mg doses were not tested). A 2019 meta-analysis found that vortioxetine didnt produce statistically significant results over placebo in the symptoms, quality of life and remission rates of generalized anxiety disorder, but it was well-tolerated. However, a 2018 meta-analysis supported use and efficacy of vortioxetine for generalized anxiety disorder, though stated that more research was necessary to strengthen the evidence. A 2021 systematic review and meta-analysis concluded that there was uncertainty about the effectiveness of vortioxetine for anxiety due to existing evidence being very low-quality. In a 2020 network meta-analysis of randomized controlled trials, vortioxetine was associated with among the lowest remission rates for generalized anxiety disorder of the included medications (odds ratio = 1.30 for vortioxetine, range of odds ratios for other agents = 1.13–2.70). Dosage The recommended starting dosage of vortioxetine is 10 mg/day. The dosage should then be increased as tolerated to 20 mg/day. For individuals who dont tolerate higher doses, 5 mg/day may be considered. The maximum recommended dose of vortioxetine in known CYP2D6 poor metabolizers is 10 mg/day. Similarly, the dose should be reduced by half in those taking strong CYP2D6 inhibitors. Vortioxetine can be discontinued abruptly without tapering, but it is recommended that at doses of 15 to 20 mg/day it be tapered first to 10 mg/day one week prior to full discontinuation if possible. Available forms Vortioxetine is available in the form of 5, 10, and 20 mg immediate-release, film-coated oral tablets. Contraindications Vortioxetine is contraindicated in those with hypersensitivity to vortioxetine or to any other components of vortioxetine tablets. It is also contraindicated in those taking monoamine oxidase inhibitors (MAOIs) due to the possibility of serotonin syndrome. Adverse effects The most common side effects reported with vortioxetine are nausea, vomiting, constipation, and sexual dysfunction, among others. With the exceptions of nausea and sexual dysfunction, these side effects were reported by less than or equal to 10% of study participants given vortioxetine. Significant percentages of placebo-treated participants also report these side effects. Discontinuation of treatment due to adverse effects in clinical trials was 8% with vortioxetine versus 3% with placebo.Sexual dysfunction, such as decreased libido, abnormal orgasm, delayed ejaculation, and erectile dysfunction, are well-known side effects of SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs). In clinical trials, sexual dysfunction occurred more often with vortioxetine than with placebo and appeared to be dose-dependent. The specific incidences of treatment-emergent sexual dysfunction as measured with the Arizona Sexual Experience Scale (ASEX) were 14 to 20% for placebo and 16 to 34% for vortioxetine over a dosage range of 5 to 20 mg/day. The incidence of sexual dysfunction with vortioxetine was similar to that with the SNRI duloxetine, which had an incidence of 26 to 28% at the used dosage of 60 mg/day. However, treatment-emergent sexual dysfunction caused by a prior SSRI was better improved by switching to vortioxetine than by switching to the SSRI escitalopram. In another study, vortioxetine at a dosage of 10 mg/day though not at 20 mg/day produced less sexual dysfunction than the SSRI paroxetine. These findings suggest that although vortioxetine can still cause sexual dysfunction itself, it may cause somewhat less sexual dysfunction than SSRIs and might be a useful alternative option for people experiencing sexual dysfunction with these medications. The rates of voluntarily or spontaneously reported sexual dysfunction with vortioxetine are much lower than with the ASEX, ranging from <1 to 5% for vortioxetine versus <1 to 2% for placebo in clinical trials. Significant changes in body weight (gain or loss) were not observed with vortioxetine in clinical trials. Vortioxetine might cause less emotional blunting than SSRIs and SNRIs based on a couple of preliminary clinical studies.If vortioxetine is used in combination with other serotonergic drugs like MAOIs or SSRIs, this may result in serotonin syndrome. Interactions Vortioxetine is metabolized primarily by the cytochrome P450 enzyme CYP2D6. Inhibitors and inducers of CYP2D6 may modify the pharmacokinetics of vortioxetine and necessitate dosage adjustments.Bupropion, a strong CYP2D6 inhibitor, has been found to increase peak levels of vortioxetine by 2.1-fold and total vortioxetine levels by 2.3-fold (bupropion dosed at 300 mg/day and vortioxetine dosed at 10 mg/day). The incidence of side effects with vortioxetine, like nausea, headache, vomiting, and insomnia, was correspondingly increased with the combination. Other strong CYP2D6 inhibitors, like fluoxetine, paroxetine, and quinidine, may have similar influences on the pharmacokinetics of vortioxetine, and it is recommended that the dosage of vortioxetine be reduced by half when it is administered in combination with such medications. Lesser interactions have additionally been identified for vortioxetine with the cytochrome P450 inhibitors ketoconazole and fluconazole.Rifampicin, a strong and broad cytochrome P450 inducer (though notably not of CYP2D6), has been found to decrease peak levels of vortioxetine by 51% and total levels of vortioxetine by 72% (rifampicin dosed at 600 mg/day and vortioxetine at 20 mg/day). Similar influences on vortioxetine pharmacokinetics may also occur with other strong cytochrome P450 inducers like carbamazepine and phenytoin. As such, it is recommended that increasing vortioxetine dosage be considered when it is given in combination with strong cytochrome P450 inducers. The maximum recommended dose should not exceed three times the original vortioxetine dose.Vortioxetine and its metabolites show no meaningful interactions with a variety of assessed cytochrome P450 enzymes and transporters (e.g., P-glycoprotein) and hence vortioxetine is not expected to importantly influence the pharmacokinetics of other medications.The combination of vortioxetine with MAOIs, including other MAOIs like linezolid and intravenous methylene blue, may cause serotonin syndrome and is contraindicated. The risk of serotonin syndrome may also be increased when vortioxetine is combined with other serotonergic drugs, like SSRIs, SNRIs, tricyclic antidepressants (TCAs), triptans, tramadol, tryptophan, buspirone, St Johns wort, fentanyl, and lithium, among others. However, vortioxetine is not considered to be contraindicated with serotonergic medications besides MAOIs. Pharmacology Pharmacodynamics Vortioxetine increases serotonin concentrations in the brain by inhibiting its reuptake in the synapse, and also modulates (activates or blocks) certain serotonin receptors. This puts it in the class of serotonin modulators and stimulators, which also includes vilazodone. More specifically, vortioxetine is a serotonin reuptake inhibitor, agonist of the serotonin 5-HT1A receptor, partial agonist of the 5-HT1B receptor, and antagonist of the serotonin 5-HT1D, 5-HT3, and 5-HT7 receptors, as well as an apparent ligand of the β1-adrenergic receptor. In terms of functional activity however, vortioxetine appears to be much more potent on serotonin reuptake inhibition and 5-HT3 receptor antagonism than for its interactions with the other serotonin receptors. Whereas vortioxetine has IC50 or EC50 values of 5.4 nM for the SERT and 12 nM for the 5-HT3 receptor, its values are 120 to 450 nM for the 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT7 receptors. This translates to about 22- to 83-fold selectivity for SERT inhibition and 10- to 38-fold selectivity for 5-HT3 antagonism over activities at the other serotonin receptors.It has been claimed that the serotonin transporter (SERT) and 5-HT3 receptor may be primarily occupied at lower clinical doses of vortioxetine and that the 5-HT1B, 5-HT1A, and 5-HT7 receptors may additionally be occupied at higher doses. Occupancy of the serotonin transporter with vortioxetine in young men was found to be highest in the raphe nucleus with median occupancies of 25%, 53%, and 98% after 9 days of administration with 2.5, 10, and 60 mg/day vortioxetine. In another study, serotonin transporter occupancy in men was 50%, 65%, and ≥80% for 5, 10, and 20 mg/day vortioxetine.Based on its clinical efficacy (e.g., at 5 mg/day), it appears that vortioxetine may produce antidepressant effects at SERT occupancy as low as 50%. This is in apparent contrast to SSRIs and SNRIs, which appear to require a minimum of 70 to 80% occupancy for antidepressant efficacy. These findings are suggestive that the antidepressant effects of vortioxetine may be mediated by serotonin receptor interactions in addition to serotonin reuptake inhibition. A study found no significant occupancy of the 5-HT1A receptor with vortioxetine at 30 mg/day for 9 days, which suggests that at least this specific serotonin receptor may not be involved in the clinical pharmacology of vortioxetine. However, methodological concerns were noted that may limit the interpretability of this result. Occupancy of other serotonin receptors like 5-HT3 and 5-HT7 by vortioxetine in humans does not seem to have been studied. In relation to the preceding, the contribution of serotonin receptor interactions to the antidepressant effects of vortioxetine is unknown and remains to be established. Uncertainties remain about whether vortioxetine is indeed a clinically multimodal antidepressant or whether it is effectively "[just] another selective serotonin reuptake inhibitor".Antagonism of the 5-HT3 receptor has been found to enhance the increase in brain serotonin levels produced by serotonin reuptake inhibition in animal studies. Whether or not the 5-HT3 receptor antagonism of vortioxetine likewise does this in humans or contributes to its clinical antidepressant efficacy is unclear. SSRIs and 5-HT1A receptor agonists often produce nausea as a side effect, whereas 5-HT3 receptor antagonists like ondansetron are antiemetics and have been found to be effective in treating SSRI-induced nausea. It was thought that the 5-HT3 receptor antagonism of vortioxetine would reduce the incidence of nausea relative to SSRIs. However, clinical trials found significant and dose-dependent rates of nausea with vortioxetine that appeared to be comparable to those found with the SNRI duloxetine. Pharmacokinetics Vortioxetine is well-absorbed when taken orally and has an oral bioavailability of 75%. It is systemically detectable after a single oral dose by 0.781 hours. Peak levels of vortioxetine are reached within 7 to 11 hours post-dose with single or multiple doses. Steady-state levels of vortioxetine are generally reached within 2 weeks of administration, with 90% of individuals reaching 90% of steady state after 12 days of administration. Steady-state peak levels of vortioxetine with doses of 5, 10, and 20 mg/day were 9, 18, and 33 ng/mL, respectively. The accumulation index of vortioxetine (area-under-the-curve levels after a single dose versus at steady state) is 5 to 6. A loading dose given intravenously has been found to achieve steady-state levels more rapidly with oral vortioxetine therapy. The pharmacokinetics of vortioxetine are known to be linear and dose proportional over a range of 2.5 to 75 mg for single doses and 2.5 to 60 mg for multiple doses. Food has no influence on the pharmacokinetics of vortioxetine.The apparent volume of distribution of vortioxetine is large and ranges from 2,500 to 3,400 L after single or multiple doses of 5 to 20 mg vortioxetine, with extensive extravascular distribution. The plasma protein binding of vortioxetine is approximately 98 or 99%, with about 1.25 ± 0.48% free or unbound.Vortioxetine is extensively metabolized by oxidation via cytochrome P450 enzymes and subsequent glucuronidation via UDP-glucuronosyltransferase. CYP2D6 is the primary enzyme involved in the metabolism of vortioxetine, but others including CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5 are also involved. It is also metabolized by alcohol dehydrogenase, aldehyde dehydrogenase, and aldehyde oxidase. Six metabolites of vortioxetine have been identified. The major metabolite of vortioxetine (Lu AA34443) is inactive and its minor active metabolite (Lu AA39835) is not thought to cross the blood–brain barrier. The remaining metabolites are glucuronide conjugates. Hence, vortioxetine itself is thought to be primarily responsible for its pharmacological activity.The estimated total clearance of vortioxetine ranges from 30 to 41 L/h. The elimination half-life of vortioxetine is 66 hours, with a range of 59 to 69 hours after single or multiple doses. Elimination of vortioxetine is almost entirely via the liver (99%) rather than the kidneys (<1%). Approximately 85% of vortioxetine was recovered in a single-dose excretion study after 15 days, with 59% in urine and 26% in feces. Pharmacogenomics Genetic variations in cytochrome P450 enzymes can influence exposure to vortioxetine. CYP2D6 extensive metabolizers have approximately 2-fold higher clearance of vortioxetine than CYP2D6 poor metabolizers. The estimated clearance rates were 52.9, 34.1, 26.6, and 18.1 L/h for CYP2D6 ultra-rapid metabolizers, extensive metabolizers, intermediate metabolizers, and poor metabolizers. Area-under-the-curve levels of vortioxetine were 35.5% lower in CYP2D6 ultra-rapid metabolizers than in extensive metabolizers, though with significant overlap due to interindividual variability. Dosage adjustment for CYP2D6 ultra-rapid metabolizers is considered to not be necessary. Vortioxetine exposure in CYP2D6 poor metabolizers is expected to be approximately twice as high as in extensive metabolizers. Depending on the individual response, dosage adjustment may be considered for CYP2D6 poor metabolizers, with a maximum recommended dosage of 10 mg/day for known such individuals. In addition to CYP2D6, CYP2C19 extensive metabolizers have 1.4-fold higher clearance of vortioxetine than poor metabolizers. However, this is not considered to be clinically important and dose adjustment is not considered to be necessary based on CYP2C19 status. Chemistry Vortioxetine (1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine) is a bis-aryl-sulfanyl amine as well as piperazine derivative. The acid dissociation constant (pKa) values for vortioxetine hydrobromide were determined to be 9.1 (± 0.1) and 3.0 (± 0.2) according to an Australian Public Assessment Report. History Vortioxetine was discovered by scientists at Lundbeck who reported the rationale and synthesis for the drug (then called Lu AA21004) in a 2011 paper.In 2007, the compound was in Phase II clinical trials, and Lundbeck and Takeda entered into a partnership in which Takeda paid Lundbeck $40 million up-front, with promises of up to $345 million in milestone payments, and Takeda agreed to pay most of the remaining cost of developing the drug. The companies agreed to co-promote the drug in the US and Japan, and that Lundbeck would receive a royalty on all such sales. The deal included another drug candidate, tedatioxetine (Lu AA24530), and could be expanded to include two other Lundbeck compounds.Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in adults in September 2013, and it was approved in Europe later that year. Society and culture It is made by the pharmaceutical companies Lundbeck and Takeda. Names Vortioxetine was previously sold under the brand name Brintellix in the United States, but on May 2, 2016, the US FDA approved a name change to Trintellix in order to avoid confusion with the blood-thinning medication Brilinta (ticagrelor). Research Vortioxetine was under development for the treatment of generalized anxiety disorder and attention-deficit hyperactivity disorder (ADHD) but development for these indications was discontinued. As of August 2021, vortioxetine remains in development for the treatment of anxiety disorders, binge-eating disorder, and bipolar disorder. It is in phase II clinical trials for these indications. There is also interest in vortioxetine for the potential treatment of social phobia, neuropathic pain, and for cognitive enhancement in major depression. References External links "Vortioxetine". Drug Information Portal. U.S. National Library of Medicine. "Vortioxetine hydrobromide". Drug Information Portal. U.S. National Library of Medicine.

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

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

Clubfoot is a birth defect where one or both feet are rotated inward and downward. Congenital clubfoot, is the most common congenital malformation of the foot with an incidence of 1 per 1000 births. In approximately 50% of cases, clubfoot affects both feet, but it can present unilaterally causing one leg or foot to be shorter than the other. Most of the time, it is not associated with other problems. Without appropriate treatment, the foot deformity will persist and lead to pain and impaired ability to walk, which can have a dramatic impact on the quality of life.The exact cause is usually not identified. Both genetic and environmental factors are believed to be involved. There are two main types of congenital clubfoot: idiopathic (80% of cases) and secondary clubfoot (20% of cases). The idiopathic congenital clubfoot is a multifactorial condition that includes environmental, vascular, positional, and genetic factors. There appears to be hereditary component for this birth defect given that the risk of developing congenital clubfoot is 25% when a first-degree relative is affected. In addition, if one identical twin is affected, there is a 33% chance the other one will be as well. The underlying mechanism involves disruption of the muscles or connective tissue of the lower leg, leading to joint contracture. Other abnormalities are associated 20% of the time, with the most common being distal arthrogryposis and myelomeningocele. The diagnosis may be made at birth by physical examination or before birth during an ultrasound exam.The most common initial treatment is the Ponseti method, which is divided into two phases: 1) correcting of foot position and 2) casting at repeated weekly intervals. If the clubfoot deformity does not improve by the end of the casting phase, an Achilles tendon tenotomy can be performed. The procedure consists of a small posterior skin incision through which the tendon cut is made. In order to maintain the correct position of the foot, it is necessary to wear an orthopedic brace until 5 years of age.Initially, the brace is worn nearly continuously and then just at night. In about 20% of cases, further surgery is required. Treatment can be carried out by a range of healthcare providers and can generally be achieved in the developing world with few resources.Clubfoot occurs in 1 to 4 of every 1,000 live births, making it one of the most common birth defects affecting the legs. About 80% of cases occur in developing countries where there is limited access to care. Clubfoot is more common in firstborn children and males. It is more common among Māori people, and less common among Chinese people. Epidemiology Birth prevalence of clubfoot varies between 0.51 and 2.03/1,000 live births in Low to middle income countries. It is one of the most common birth defects affecting the legs. Clubfoot is more common in firstborn children and males, who are twice as likely to be affected as females. It is more common among Māori people, and less common among Chinese people.Clubfoot disproportionally affects those in low and middle-income countries (LMICs). About 80% of those with clubfoot, or approximately 100,000 children per year as of 2018, are born in LMICs. History Pharaohs Siptah and Tutankhamun had clubfoot, and the condition appeared in Egyptian paintings. Indian texts (c. 1000 BC) and Hippocrates (c. 400 BC) described treatment. In 1823, Delpech presented another way to treat patient with clubfoot. This new way was tenotomy, which means the cut of the Achilles tendon in those patients. As a surgical procedure it had its complications like infections. Signs and symptoms In clubfoot, feet are rotated inward and downward. The affected foot and leg may be smaller than the other, while in about half of cases, clubfoot affects both feet. Most of the time clubfoot is not associated with other problems.Clubfoot can be diagnosed by ultrasound of the fetus in more than 60% of cases. The earliest week of gestation in which the condition is diagnosed with a high degree of confidence was the 12th and the latest was the 32nd. Not all patients were diagnosed at an early stage. In 29% of fetuses the first ultrasound examination failed to detect the deformity which subsequently became obvious at a later examination. Clubfoot was diagnosed between 12 and 23 weeks of gestation in 86% of children and between 24 and 32 weeks of gestation in the remaining 14%.Without treatment the foot remains deformed and people walk on the sides or tops of their feet, which can cause calluses, foot infections, trouble fitting into shoes, pain, difficulty walking, and disability. Causes Hypotheses about the precise cause of clubfoot vary. However, research has found that genetics, environmental factors or a combination of both are associated with this condition. Evidence suggests that the etiology of clubfoot is most likely multifactorial. A meta-analysis and systematic review found that the most clinically relevant risk factors for clubfoot were family history, paternal and maternal smoking, birthing parent obesity, gestational diabetes, amniocentesis, and the use of selective serotonin re-uptake inhibitors (SSRIS). Many findings agree that "it is likely there is more than one different cause and at least in some cases the phenotype may occur as a result of a threshold effect of different factors acting together." The most commonly associated conditions are distal arthrogryposis or myelomeningocele. The factors contributing to the development of clubfoot can be categorized as extrinsic and intrinsic factors.Extrinsic Factors Factors that can influence the positioning of the fetal foot in uteru include oligohydramnios, breech presentation, Müllerian anomalies, multiple gestation, amniotic band sequence, or amniocentesis at <15 weeks of gestation. In cases that impede normal growth and position for longstanding period of times, clubfoot can be accompanied with other deformations and may be associated with developmental hip dysplasia. The theory of fetal growth arrest was proposed by Von Volkmann in 1863, and has been verified by other authors since. According to this theory, intrinsic errors or environmental insults during gestation prevents the correction of a equinovarus to pronated foot. Other researchers hypothesize that clubfoot may derive from external insults during gestation. For example, a research study found an alarming high incidence of club foot and limb contractures associated with iatrogenic amniotic leakage cause by early amniocentesis between the 11th and 12th week of gestation.Intrinsic Factors Chromosomal abnormalities found in 30% and 2% of complex clubfoot and isolated clubfoot respectively. These include trisomy 18, 13, 21, sex chromosome abnormalities, micro-deletions and duplications. Genetic Syndromes: Larsen, Gordon, Pierre-Robin, Meckel-Gruber, Roberts, Smith-Lemli-Opitz, TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, Persistence of left superior vena cava). Skeletal Dysplasias: Ellis van Creveld syndrome, diastrophic dysplasia, chondrodysplasia punctata, camptomelic dysplasia, atelosteogenesis, and mesomelic dysplasia. Neuromuscular and Neurologic abnormalities: arthrogryposis multiplex congenita, myotonic dystrophy, spinal muscular atrophy, neural tube defects, holoprosencephaly, and hydranencephaly. Genetics Clubfoot can be diagnosed prenatally as early as 13 weeks of gestation via ultrasound. According to the Society of Maternal-Fetal Medicine, a diagnostic testing for genetic causes is recommended when clubfoot is diagnoses prenatally. If prenatal screening is suspicious for aneuploidy, karyotype analysis or chromosomal microarray (CMA) may be performed. However, if patients decline diagnostic testing, Cell-Free DNA is another screening option to identify high-risk pregnancies for aneuploidy and it is not diagnostic. The incidence of chromosomal abnormalities in fetuses with prenatal diagnosis of clubfoot is relatively low. Overall, fetal ultrasound should be performed with a prenatal diagnosis of clubfoot in order to classify the condition as either complex or isolated because of the significant differences in rates of chromosomal abnormalities and outcomes between these two groups.If one identical twin is affected, there is a 33% chance the other one will be as well.Mutations in genes involved in muscle development are risk factors for clubfoot, specifically those encoding the muscle contractile complex (MYH3, TPM2, TNNT3, TNNI2 and MYH8). These can cause congenital contractures, including clubfoot, in distal arthrogryposis (DA) syndromes. Clubfoot can also be present in people with genetic conditions such as Loeys–Dietz syndrome and Ehlers-Danlos syndrome.Genetic mapping and the development of models of the disease have improved understanding of developmental processes. Its inheritance pattern is explained as a heterogenous disorder using a polygenic threshold model. The PITX1-TBX4 transcriptional pathway has become key to the study of clubfoot. PITX1 and TBX4 are uniquely expressed in the hind limb. Diagnosis Clubfoot is diagnosed through physical examination. Typically, babies are examined from head-to-toe shortly after they are born. There are four components of the clubfoot deformity: Factors used to assess severity include the stiffness of the deformity (how much it can be corrected by manually manipulating the foot), the presence of skin creases at the arch and heel, and poor muscle consistency. Sometimes, it is possible to detect clubfoot before birth using ultrasound. Prenatal diagnosis by ultrasound can allow parents to learn more about this condition and plan ahead for treatment after their baby is born.More testing and imaging is typically not needed, unless there is concern for other associated conditions. Treatment Treatment is usually with some combination of the Ponseti method and French method. The Ponseti method involves a combination of casting, Achilles tendon release, and bracing. It is widely used and highly effective under the age of two. The French method involves realignment, taping, and long-term home exercises and night splinting. It is also effective but outcomes vary and rely on heavy involvement of caregivers. Generally, the Ponseti method is preferred. Another technique, the Kite method, does not appear to be as effective. In about 20% of cases, additional surgery is required after initial treatment. Ponseti method The Ponseti method corrects clubfoot over the course of several stages. Serial casting: First, the foot is manually manipulated into an improved position and held in place with a long leg cast which extends from the toes up to the thigh. After a week this cast is removed, the foot is re-manipulated, and placed into a new cast. This process repeats and the foot is gradually reshaped over the course of 4-6 serial casts, although some feet may require additional casts. The goal of the initial cast is to align the forefoot with the hindfoot. Ponseti describes the forefoot as pronated in relation to the hindfoot, so supinating the forefoot and elevating the first metatarsal improves this alignment. Subsequent casts are applied after stretching the foot with a focus on abducting the forefoot with lateral pressure at the talus, to bring the navicular laterally and improve the alignment of the talonavicular joint. In contrast to the Kite method of casting, it is important to avoid constraining the calcanocuboid joint. With each additional cast, the abduction is increased and this moves the hindfoot from varus into valgus. It is important to leave the ankle in equinus until the forefoot and hindfoot are corrected. The final stage of casting is to correct the equinus. After fully abducting the forefoot with spontaneous correction of the hindfoot, an attempt is made to bring the ankle up and into dorsiflexion. The foot must have the ability to dorsiflex to at least 10 degrees past 0 (neutral, or L position), although 15 degrees or more is better and preferred. If the foot can not dorsiflex enough, the brace will not work/be tolerated. If it is determined the foot can not dorsiflex at least 10 degrees, the Achilles Tenotomy surgical procedure is performed. Achilles tendon release: At the end of the serial casting, most children have corrected cavus, adductus and varus deformities, but continue to have equinus deformity. To correct this, a procedure called an Achilles tendon release (commonly called Achilles tenotomy) is performed. Before the procedure, many centers place the child under sedation or monitored anesthesia care, although Ponseti recommended using local anesthetic alone. Next, the area around the heel is cleansed and numbed, and a small scalpel is used to cut the Achilles tendon. The incision is small so there is minimal bleeding and no need for stitches. The skin is covered with a small dressing, and the foot is placed into a final long leg cast in a fully corrected position. This cast is typically left in place for three weeks. During this time, the Achilles tendon will regrow in a lengthened position. Bracing: After successful correction is achieved through serial casting and Achilles tenotomy, the foot must be kept in a brace to prevent it from returning to the deformed position over the first few years of a childs life. The brace is made up of two shoes or boots that are connected to each other by a bar that is bent under the shoes at 10-15 degrees, or curved to create 10-15 degrees dorsiflexion. This device is also called a foot abduction brace (FAB) or more generally boots and bar (BnB). At first, the brace is worn full-time (23 hours per day) on both feet, regardless of whether the clubfoot affects one or two feet. After 3 months of 23/7 wear, the brace is worn less frequently by gradually reducing hours a couple at a time, every couple months so that hours are down to 12-14 per day at or around a year old. From this point on until at least 4–5 years, or even longer (6–9 years if needed), the brace is worn mostly while sleeping at night and during naps (12–14 hours per day). Bracing is essential in preventing recurrence of the deformity and is a major determinant of a childs long-term outcome.The Ponseti method is highly effective with short-term success rates of 90%. However, anywhere from 14% to 41% of children experience a recurrence of the deformity. The most common reason for this is inadequate adherence to bracing, such as not wearing the brace properly, not keeping it on for the recommended length of time, or not using it every day. Children who do not follow proper bracing protocol have up to seven times higher recurrence rates than those who follow bracing protocol, as the muscles around the foot can pull it back into the abnormal position. Low parental education level and failure to understand the importance of bracing is a major contributor to non-adherence. Relapses are managed by repeating the casting process. Relapsed feet may also require additional, more extensive surgeries and have a reduced chance of achieving subsequent correction.Another reason for recurrence is a congenital muscle imbalance between the muscles that invert the ankle (tibialis posterior and tibialis anterior muscles) and the muscles that evert the ankle (peroneal muscles). This imbalance is present in approximately 20% of infants successfully treated with the Ponseti casting method, and makes them more prone to recurrence. This relapse is usually treated with Ponseti casting and can be done multiple times before resorting to surgery. If after all non-surgical casting and bracing options have been exhausted, and when the child is over four years of age (many doctors prefer to wait until after seven years old), this can be addressed with a surgery to transfer the tibialis anterior tendon from its medial attachment (on the navicula) to a more lateral position (on the lateral cuneiform). The surgery requires general anesthesia and subsequent casting while the tendon heals, but it is a relatively minor surgery that re-balances the muscles of the foot without disturbing any joints. French method The French method is a conservative, non-operative method of clubfoot treatment that involves daily physical therapy for the first two months followed by thrice-weekly physical therapy for the next four months and continued home exercises following the conclusion of formal physical therapy. During each physical therapy session the feet are manipulated, stretched, then taped to maintain any gains made to the feets range of motion. Exercises may focus on strengthening the peroneal muscles, which is thought to contribute to long-term correction. After the two month mark, the frequency of physical therapy sessions can be weaned down to three times a week instead of daily, until the child reaches six months. After the conclusion of the physical therapy program, caregivers must continue performing exercises at home and splinting at night in order to maintain long-term correction. Compared to the Ponseti method which uses rigid casts and braces, the French method uses tape which allows for some motion in the feet. Despite its goal to avoid surgery, the success rate varies and surgery may still be necessary. The Ponseti method is generally preferred over the French method. Surgery If non-operative treatments are unsuccessful or achieve incomplete correction of the deformity, surgery is sometimes needed. Surgery was more common prior to the widespread acceptance of the Ponseti method. The extent of surgery depends on the severity of the deformity. Usually, surgery is done at 9 to 12 months of age and the goal is to correct all the components of the clubfoot deformity at the time of surgery. For feet with the typical components of deformity (cavus, forefoot adductus, hindfoot varus, and ankle equinus), the typical procedure is a Posteromedial Release (PMR) surgery. This is done through an incision across the medial side of the foot and ankle, that extends posteriorly, and sometimes around to the lateral side of the foot. In this procedure, it is typically necessary to release (cut) or lengthen the plantar fascia, several tendons, and joint capsules/ligaments. Typically, the important structures are exposed and then sequentially released until the foot can be brought to an appropriate plantigrade position. Specifically, it is important to bring the ankle to neutral, the heel into neutral, the midfoot aligned with the hindfoot (navicula aligned with the talus, and the cuboid aligned with the calcaneus). Once these joints can be aligned, thin wires are usually placed across these joints to hold them in the corrected position. These wires are temporary and left out through the skin for removal after 3–4 weeks. Once the joints are aligned, tendons (typically the Achilles, posterior tibialis, and flexor halluces longus) are repaired at an appropriate length. The incision (or incisions) are closed with dissolvable sutures. The foot is then casted in the corrected position for 6–8 weeks. It is common to do a cast change with anesthesia after 3–4 weeks, so that pins can be removed and a mold can be made to fabricate a custom AFO brace. The new cast is left in place until the AFO is available. When the cast is removed, the AFO is worn to prevent the foot from returning to the old position.For feet with partial correction of deformity with non-operative treatment, surgery may be less extensive and may involve only the posterior part of the foot and ankle. This might be called a posterior release. This is done through a smaller incision and may involve releasing only the posterior capsule of the ankle and subtalar joints, along with lengthening the Achilles tendon. Surgery leaves residual scar tissue and typically there is more stiffness and weakness than with nonsurgical treatment. As the foot grows, there is potential for asymmetric growth that can result in recurrence of foot deformity that can affect the forefoot, midfoot, or hindfoot. Many patients do fine, but some require orthotics or additional surgeries. Long-term studies of adults with post-surgical clubfeet, especially those needing multiple surgeries, show that they may not fare as well in the long term. Some people may require additional surgeries as they age, though there is some dispute as to the effectiveness of such surgeries, in light of the prevalence of scar tissue present from earlier surgeries. Developing world Despite effective treatments, children in LMICs face many barriers such as limited access to equipment (specifically casting materials and abduction braces), shortages of healthcare professionals, and low education levels and socioeconomic status amongst caregivers and families. These factors make it difficult to detect and diagnose children with clubfoot, connect them to care, and train their caregivers to follow the proper treatment and return for follow-up visits. It is estimated that only 15% of those diagnosed with clubfoot receive treatment.In an effort to reduce the burden of clubfoot in LMICs, there have been initiatives to improve early diagnosis, organize high-volume Ponseti casting centers, utilize mid-level practitioners and non-physician health workers, engage families in care, and provide local follow-up in the persons community. Cultural references Hippolyte Tautain, the stableman at the Lion DOr public house in the 1856 novel Madame Bovary by Gustave Flaubert, has clubfoot. Charles Bovary tries to correct it, but the procedure is unsuccessful, and Tautain must have an amputation. Philip Carey, the main character of the 1915 novel Of Human Bondage by W. Somerset Maugham, has clubfoot. It is a central theme of the work. Velma, a character in the 1941 film High Sierra, has clubfoot. It is successfully treated with surgery. Gimpy, a coworker of the main character in the 1959 science fiction short story "Flowers for Algernon" by Daniel Keyes, has clubfoot. Kashiwagi, a character in the 1956 novel The Temple of the Golden Pavilion by Yukio Mishima, has clubfoot. It parallels the main character, Mizoguchi, who has a stutter. Johnson, a character in the 1965 short story "The Lame Shall Enter First" by Flannery OConnor, has clubfoot. It is a major symbol in the story. The main character of the 1974 science fiction novel The Bladerunner by Alan E. Nourse has clubfoot. The main character of the 1985 novel Perfume: The Story of a Murderer by Patrick Süskind, has clubfoot. It causes a limp. Senji, a character in the 1987 to 1991 fantasy book series The Mallorean by David Eddings, has clubfoot. Kwai Geuk-Chat, a character in the 1993 film Once Upon a Time in China III, which is part of the 1991 to 1997 Once Upon a Time in China series, has clubfoot. He is nicknamed "Clubfoot Seven Chiu-Tsat" – "Clubfoot" because of his foot, and "Seven Chiu-Tsat" because he is the seventh member of the character Chiu Tin-baks apprentices, disciples, and henchmen. Mordred, King of Dumonia, a character in the 1995 to 1997 historical fantasy book series The Warlord Chronicles by Bernard Cornwell, has clubfoot. It is often used as a symbol for his weakness as a ruler. Charlie Wilcox, the main character of the 2000 childrens book of the same name by Sharon McKay, has clubfoot. Vulcan the blacksmith, a character in the 2001 novel The Secrets of Vesuvius, which is part of the 2001 to 2009 historical fiction series The Roman Mysteries by Caroline Lawrence, has clubfoot. Princess Matilda, the main character of Handbook for Dragon Slayers by Merrie Haskell, a 2013 novel published by HarperCollins, has a clubfoot. Ada, the main character of the 2016 childrens book The War That Saved My Life by Kimberly Brubaker Bradley, has clubfoot. Her mother emotionally and physically abuses her because of it. 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 trying to understand 'Mediastinitis' within a medical context. Could you shed some light on it?

Mediastinitis is inflammation of the tissues in the mid-chest, or mediastinum. It can be either acute or chronic. It is thought to be due to four different etiologies:direct contamination hematogenous or lymphatic spread extension of infection from the neck or retroperitoneum extension from the lung or pleuraAcute mediastinitis is usually caused by bacteria and is most often due to perforation of the esophagus. As the infection can progress rapidly, this is considered a serious condition. Chronic sclerosing (or fibrosing) mediastinitis, while potentially serious, is caused by a long-standing inflammation of the mediastinum, leading to growth of acellular collagen and fibrous tissue within the chest and around the central vessels and airways. It has a different cause, treatment, and prognosis than acute infectious mediastinitis. Space infections: Pretracheal space – lies anterior to trachea. Pretracheal space infection leads to mediastinitis. Here, the fascia fuses with the pericardium and the parietal pleura, which explains the occurrence of empyema and pericardial effusion in mediastinitis. However, infectious of other spaces can also lead to mediastinitis. Symptoms Acute Acute mediastinitis is an infectious process and can cause fever, chills, tachycardia. Pain can occur with mediastinitis but the location of the pain depends on which part of the mediastinum is involved. When the upper mediastinum is involved, the pain is typically retro-sternal pain. When the lower mediastinum is involved, pain can be located between in the scapulae and radiate around to the chest. Chronic Symptoms depend on what organs of the mediastinum the disease is affecting. They might be caused by a constricted airway, constricted esophagus, or constricted blood vessels. Symptoms also depend on how mush fibrosis has occurred. There may be cough, shortness of breath, coughing up blood, pain in the chest, and difficulty in swallowing. Causes Acute Esophageal perforation, a form of direct contamination, accounts for 90% of acute mediastinal infections. Esophageal perforation can arise from vomiting, incidental trauma from a procedure or operation, external trauma, ingestion of corrosive substances, malignancy, or other esophageal disease.Other causes of acute mediastinitis include infection secondary to cervical disease which arises from dental procedures, skin infections of the neck, neck trauma, or neck procedures.Descending necrotizing mediastinitis (DNM) was first described by Herman E. Pearse Jr., M.D. in 1938 and he stated, "the term mediastinitis means little unless qualified by a description of its type and kind." Although Descending Necrotizing Mediastinitis is an acute mediastinitis, it is distinct because it does not originate from structures within the mediastinum. Therefore, the term Descending Necrotizing Mediastinitis implies that the infection of the mediastinum originated from a primary site in the head or neck and descended through fascial spaces into the mediastinum.Though rare in developed countries, acute mediastinitis can be caused by inhalation of bacterial spores such as Anthrax. Historically, this infection was referred to as Wool-sorters Disease. In the lungs, spores can spread via lymphatics to mediastinal lymph nodes, where the mature rods can release exotoxins promoting edema and tissue necrosis. Clinically, persons infected with anthrax can develop a hemorrhagic mediastinitis, which manifests as acute pulmonary hemorrhage and meningitis. Hallmark finding of disease is a widened mediastinum visualized on chest x-ray. Once clinical symptoms of anthrax induced mediastinitis appear, disease is nearly 100% fatal. Individuals with known exposure to spores may be treated prophylactically with antibiotics (fluoroquinolones or tetracycline) to prevent disease progression. Chronic There are two types of fibrosing mediastinitis: granulomatous and non-granulomatous. Granulomatous mediastinitis is due to a granulomatous process of the mediastinal lymph nodes leading to fibrosis and chronic abscesses in the mediastinum. The most common causes are histoplasmosis and tuberculosis infections. Non-granulomatous fibrosing mediastinitis is caused by an idiopathic reaction to drugs and radiation therapy. Autoimmune disease and Behcets disease are also causes. Etiology An observational retrospective study of 17 patients diagnosed with DNM found that the infections most often originated from neck infections including tonsillar abscess, pharyngitis, and epiglottitis. The study also found that most infections are poly-microbial. Often the culprits are usually Gram-positive bacteria and anaerobes, though rarely, Gram-negative bacteria are also present. This severe form represents 20% of acute mediastinitis cases. Diagnosis Acute Acute mediastinitis can be confirmed by contrast x-rays since most cases of acute mediastinitis are due to esophageal perforation. Other studies that can be used include endoscopic visualization, Chest CT scan with oral and intravenous contrast.With regards to CT Imaging, the extent of involvement of the mediastinum can be evaluated. Therefore, acute mediastinitis can be classified into three categories: diffuse mediastinitis isolated mediastinal abscess mediastinitis or mediastinal abscess complicated by empyema or subphrenic abscess. Chronic Most cases of granulomatous mediastinitis (75%) are incidentally found on chest x-rays which show a mediastinal mass, or widening of the mediastinum. Treatment Treatment for acute mediastinitis usually involves aggressive intravenous antibiotic therapy and hydration. If discrete fluid collections or grossly infected tissue have formed (such as abscesses), they may have to be surgically drained or debrided.Treatment for DNM usually requires an operation to remove and drain infected necrotic tissue. Broad spectrum intravenous antibiotics are also given to treat the infection. Patients are typically managed in the intensive care unit due to the severity of the disease.Treatment for chronic fibrosing mediastinitis is somewhat controversial, and may include steroids or surgical decompression of affected vessels. Prognosis Fibrosing mediastinitis can lead to entrapment of mediastinal structures. The mortality of DNM ranges from 10 to 40% due to sepsis and multi-organ failure if not recognized and intervened upon early. References External links Mediastinitis at the US National Library of Medicine Medical Subject Headings (MeSH)

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

I'm not familiar with the medical term 'Guaifenesin/phenylephrine.' Could you provide some insights?

Guaifenesin/phenylephrine is a combination of the drugs guaifenesin and phenylephrine and is a preparation against the symptoms of cold, flu and allergy. Guaifenesine is an expectorant, phenylephrine is a decongestant. The drug is sold under the brand name Entex and as generic brands. Entex La is 400 mg guaifenesin and 30 mg phenylephrine hydrochloride. Entex Pse is 600 mg guaifenesin and 120 mg phenylephrine hydrochloride. Both are extended release products, meaning that the non-active ingredients are chosen to dissolve slowly to provide a prolonged therapeutic effect. Guaifenesin Guaifenesin is an oral medication used to try to help cough out phlegm from the airways. It is often used in combination with other medications. It is believed to work by making airway secretions more liquid. Side effects may include dizziness, sleepiness, skin rash, and nausea. Guaifenesin has been used medically since at least 1933. It is available as a generic medication and an over-the-counter drug. Phenylephrine Phenylephrine is an oral medication primarily used as a decongestant. It is a selective α1-adrenergic receptor activator which results in the constriction of both arteries and veins. Common side effects include nausea, headache, and anxiety. Phenylephrine was patented in 1927 and came into medical use in 1938. It is available as a generic medication. == References ==

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

I'm trying to expand my medical knowledge. Can you elucidate the term 'Posner–Schlossman syndrome'?

Posner–Schlossman syndrome (PSS) also known as glaucomatocyclitic crisis (GCC) is a rare acute ocular condition with unilateral attacks of mild granulomatous anterior uveitis and elevated intraocular pressure. It is sometimes considered as a secondary inflammatory glaucoma. Signs and symptoms Ocular hypertension (IOP 30 - 70 mmHg) with open angle of anterior chamber and unilateral mild granulomatous anterior uveitis are hallmark signs of Posner–Schlossman syndrome. On slit-lamp examination, conjunctival injections, epithelial corneal edema, small to medium-sized fine keratitic precipitates, aqueous cells and flare may also be noted. Blurring of vision, eye pain and discomfort are the main symptoms. Colored halos may occur due to elevated IOP. Symptoms last from several hours to weeks and may be recurrent. IOP and aqueous humor outflow return to normal in the remission periods. Etiology Exact etiology of PSS is unknown. Since it was first described, A number of noninfectious etiological theories have been proposed including autonomic dysregulation, allergy, variation of developmental glaucoma, autoimmune/HLA-Bw54 and abnormality of the ciliary vasculature. Initially, infectious etiologies were not considered because of the episodic nature of the acute attacks. Recently, infectious theories associated with organisms like H. pylori, Herpes simplex virus, Varicella zoster virus, Cytomegalovirus, B. burgdorferi etc. are also emerged in medical literature. Treatment Main aim of treatment is to reduce IOP and decrease inflammation. Medical Topical steroids, such as prednisolone acetate can be used to decrease the uveal inflammation. Topical or oral non-steroidal anti-inflammatory agents may be used to avoid steroid-induced complications like secondary glaucoma. Prostaglandin analogs such as latanoprost or bimatoprost, beta-blockers such as timolol, alpha-2 agonists such as brimonidine, muscarinic agents such as pilocarpine, hyperosmotic agents such as mannitol and carbonic anhydrase inhibitors such as acetazolamide, methazolamide or dorzolamide are the drugs used to decrease IOP. Surgical If the elevated IOP is not responsive to medical treatment, glaucoma surgeries may be considered to prevent visual field loss. Epidemiology It usually affects adults between the ages of twenty and fifty and is common in males than females. One study from Finland found that the incidence of disease is 0.4 and its prevalence is 1.9 out of 100,000. History Posner and Schlossman first identified and described the syndrome in 1948. They first reported a series of 9 cases and given the name glaucomatocyclitic crisis to describe this condition. == References ==

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

Can you break down the meaning of the medical term 'High-grade prostatic intraepithelial neoplasia' for me?

High-grade prostatic intraepithelial neoplasia (HGPIN) is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).It may be referred to simply as prostatic intraepithelial neoplasia (PIN). It is considered to be a pre-malignancy, or carcinoma in situ, of the prostatic glands. Signs and symptoms HGPIN in isolation is asymptomatic. It is typically discovered in prostate biopsies taken to rule-out prostate cancer and very frequently seen in prostates removed for prostate cancer. Relation to prostate cancer There are several reasons why PIN is the most likely prostate cancer precursor. PIN is more common in men with prostate cancer. High grade PIN can be found in 85 to 100% of radical prostatectomy specimens, nearby or even in connection with prostate cancer. It tends to occur in the peripheral zone of the prostate. With age, it becomes increasingly multifocal, like prostate cancer. Molecular analysis has shown that high grade PIN and prostate cancer share many genetic abnormalities.The risk for men with high grade PIN of being diagnosed with prostate cancer after repeat biopsy has decreased since the introduction of biopsies at more than six locations (traditional sextant biopsies). Histology HGPIN typically has one of four different histologic patterns: tufted, micropapillary, cribriform and, flat.Its cytologic features are that of prostatic adenocarcinoma: presence of nucleoli, increased nuclear-to-cytoplasmic ratio and, increased nuclear size.Microscopically, PIN is a collection of irregular, atypical epithelial cells. The architecture of the glands and ducts remains normal. The epithelial cells proliferate and crowding results in a pseudo-multilayer appearance. They remain fully contained within a prostate acinus (the berry-shaped termination of a gland, where the secretion is produced) or duct. The latter can be demonstrated with special staining techniques (immunohistochemistry for cytokeratins) to identify the basal cells forming the supporting layer of the acinus. In prostate cancer, the abnormal cells spread beyond the boundaries of the acinus and form clusters without basal cells. In HGPIN, the basal cell layer is disrupted but present. PIN is primarily found in the peripheral zone of the prostate (75-80%), rarely in the transition zone (10-15%) and very rarely in the central zone (5%), a distribution that parallels the zonal distribution for prostate carcinoma.Because it is thought to be a premalignant state, PIN is often considered the prostate equivalent of what is called carcinoma in situ (localized cancer) in other organs. However, PIN differs from carcinoma in situ in that it may remain unchanged or even spontaneously regress.Several architectural variants of PIN have been described, and many cases have multiple patterns. The main ones are tufting, micropapillary, cribriform, and flat. Although these different appearances may cause confusion with other conditions, they have not been found to be of clinical importance. Rarer types are signet-ring-cell, small-cell-neuroendocrine, mucinous, foamy, inverted, and with squamous differentiation. Diagnosis HGPIN is diagnosed from tissue by a pathologist, which may come from: a needle biopsy taken via the rectum and, surgical removal of prostate tissue: transurethral resection of the prostate - removal of extra prostate tissue to improve urination (a treatment for benign prostatic hyperplasia), radical prostatectomy - complete removal of prostate and seminal vesicles (a treatment for prostate cancer).Blood tests for prostate specific antigen (PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum, fine needle aspiration or medical imaging studies (such as magnetic resonance imaging) are not useful for diagnosing HGPIN. Treatment HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood. Prognosis On a subsequent biopsy, given a history of a HGPIN diagnosis, the chance of finding prostatic adenocarcinoma is approximately 30%. History PIN was historically subdivided into different stages, based on the level of cell atypia. PIN was formerly classified as PIN 1, 2 or 3, in order of increasing cell irregularities. Nowadays, PIN 1 is referred to as low grade PIN, and PIN 2 and PIN 3 are grouped together as high grade PIN. Only high grade PIN has been shown to be a risk factor for prostate cancer. Because low grade PIN has no significance and does not require repeat biopsies or treatment, it is not mentioned in pathology reports. As such, PIN has become synonymous with high grade PIN. See also Atypical small acinar proliferation 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've encountered the term 'Cluttons joints' while reading about medical topics. What does it refer to exactly?

Cluttons joints is a term describing the finding of symmetrical joint swelling seen in patients with congenital syphilis. It most commonly affects the knees, presenting with synovitis and joint effusions (collections of fluid within the joint capsules) lasting up to a year. It has also been reported affecting the ankles, elbows, wrists and fingers. It is usually painless, although pain in the absence of trauma can occur in a few cases. There is usually no disability associated with the joint swelling, and recovery is usually complete. It occurs between 5 and 20 years of age in both sexes.The condition was described in 1886 by Henry Hugh Clutton in The Lancet. == References ==

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

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

A phytobezoar is a type of bezoar, or trapped mass in the gastrointestinal system, that consists of components of indigestible plant material, such as fibres, skins and seeds. While phytobezoars may be discovered incidentally on barium x-ray or endoscopic testing of the stomach, individuals with phytobezoars may develop symptoms: nausea, vomiting, gastric outlet obstruction, perforation, abdominal pain, and bleeding have been reported. Conditions that lead to decreased motility in the stomach (gastroparesis) and surgeries on the stomach (such as vagotomy or gastric bypass) are associated with the development of phytobezoars. A specific type of phytobezoar, termed a diospyrobezoar, is associated with ingestion of unripe persimmons, which contain a soluble tannin called shibuol that polymerizes into a coagulative cellulose-protein compound in the acid environment of the stomach, to form the bezoar. In addition to their presence in human stomachs, phytobezoars have been documented in the stomachs of slaughtered plant-eating animals. Cause Gastric phytobezoars are a form of intestinal blockage and are seen in those with poor gastric motility. The preferred treatment of bezoars includes different therapies and/or fragmentation to avoid surgery. Phytobezoars are most common and consist of undigested lignin, cellulose, tannins, celery, pumpkin skin, grape skins, prunes, raisins, vegetables and fruits. Phytobezoars can form after eating persimmons and pineapples. These are more difficult to treat and are referred to as diospyrobezoars. Phytobezoars are more likely to form due to the ingestion of raw plant foods, even in persons without predisposing factors, as cooking softens them for easier digestion. Treatment Several treatments for phytobezoars have been described. Endoscopy involves using a fibre-optic flexible camera to identify the phytobezoar, that can be evacuated from the stomach using various assisted devices (such as Roth baskets, snares, or Dormia baskets). If the phytobezoar cannot be removed due to size, electrohydraulic lithotripsy, mechanical lithotripsy, snares, or Nd:YAG laser therapy may be used to fragment the mass. Papain (meat tenderizer) and cellulase enzymes have been used to help reduce the size of phytobezoars. Carbonated soda ingestion has also been found to be useful to decrease the size of diospyrobezoars. A systematic review regarding initial treatment of phytobezoars with Coca-Cola found that Coca-Cola alone completely dissolved phytobezoars in half of cases, and that Coca-Cola combined with other endoscopic methods (particularly endoscopic fragmentation) was successful more than 90% of the time. The same review found that diospyrobezoars (which are considered more difficult to dissolve because of their hard consistency) were successfully treated with Coca-Cola alone in only 23% of cases, but that follow-up endoscopic fragmentation was successful in 84.6% of cases in the publications reviewed. When all other measures have failed, surgical gastrectomy is required to evacuate the bezoar. Physical and chemical properties Generally, bezoars can be found in the stomach in less than 0.5% of patients having an esophagogastroduodenoscopy. The formation of phytobezoars from persimmons is due to a chemical reaction between stomach acid and phlobatannin contained in the persimmon. Tannin and shibuol found in the skin of unripe persimmons reacts with gastric acid and forms a coagulum. This structure then accumulates cellulose, hemicellulose and protein. References == External links ==

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 'Zidovudine.'

Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.Common side effects include headaches, fever, and nausea. Serious side effects include liver problems, muscle damage, and high blood lactate levels. It is commonly used in pregnancy and appears to be safe for the baby. ZDV is of the nucleoside analog reverse-transcriptase inhibitor (NRTI) class. It works by inhibiting the enzyme reverse transcriptase that HIV uses to make DNA and therefore decreases replication of the virus.Zidovudine was first described in 1964. It was approved in the United States in 1987 and was the first treatment for HIV. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. Medical uses HIV treatment AZT is usually dosed twice a day in combination with other antiretroviral therapies. This approach is referred to as Highly Active Antiretroviral Therapy (HAART) and is used to prevent the likelihood of HIV resistance. HIV prevention AZT has been used for post-exposure prophylaxis (PEP) in combination with another antiretroviral drug called lamivudine. Together they work to substantially reduce the risk of HIV infection following the first single exposure to the virus. More recently, AZT has been replaced by other antiretrovirals such as tenofovir to provide PEP.AZT is now a principal part of the clinical pathway for both pre-exposure prophylaxis and post-exposure treatment of mother-to-child transmission of HIV during pregnancy, labor, and delivery and has been proven to be integral to uninfected siblings perinatal and neonatal development. Without AZT, 10 to 15% of fetuses with HIV-infected mothers will themselves become infected. AZT has been shown to reduce this risk to 8% when given in a three-part regimen post-conception, delivery, and six weeks post-delivery. Consistent and proactive precautionary measures, such as the rigorous use of antiretroviral medications, cesarean section, face masks, heavy-duty rubber gloves, clinically segregated disposable diapers, and avoidance of mouth contact will further reduce child-attendant transmission of HIV to as little as 1–2%.During 1994 to 1999, AZT was the primary form of prevention of mother-to-child HIV transmission. AZT prophylaxis prevented more than 1000 parental and infant deaths from AIDS in the United States. In the U.S. at that time, the accepted standard of care for HIV-positive mothers was known as the 076 regimen and involved five daily doses of AZT from the second trimester onwards, as well as AZT intravenously administered during labour. As this treatment was lengthy and expensive, it was deemed unfeasible in the Global South, where mother-to-child transmission was a significant problem. A number of studies were initiated in the late 1990s that sought to test the efficacy of a shorter, simpler regimen for use in resource-poor countries. This AZT short course was an inferior standard of care and would have been considered malpractice if trialed in the US; however, it was nonetheless a treatment that would improve the care and survival of impoverished subjects. Antibacterial properties Zidovudine also has antibacterial properties, though not routinely used in clinical settings. It acts on bacteria with a mechanism of action still not fully explained. Promising results from in vitro and in vivo studies showed the efficacy of AZT also against multidrug-resistant gram-negative bacteria (including mcr-1 carrying and metallo-β-lactamase producing isolates), especially in combination with other active agents (e.g. fosfomycin, colistin, tigecycline). Side effects Most common side-effects include nausea, vomiting, acid reflux (heartburn), headache, cosmetic reduction in abdominal body fat, light sleeping, and loss of appetite. Less common side effects include faint discoloration of fingernails and toenails, mood elevation, occasional tingling or transient numbness of the hands or feet, and minor skin discoloration. Allergic reactions are rare.Early long-term higher-dose therapy with AZT was initially associated with side effects that sometimes limited therapy, including anemia, neutropenia, hepatotoxicity, cardiomyopathy, and myopathy. All of these conditions were generally found to be reversible upon reduction of AZT dosages. They have been attributed to several possible causes, including transient depletion of mitochondrial DNA, sensitivity of the γ-DNA polymerase in some cell mitochondria, the depletion of thymidine triphosphate, oxidative stress, reduction of intracellular L-carnitine or apoptosis of the muscle cells. Anemia due to AZT was successfully treated using erythropoetin to stimulate red blood cell production. Drugs that inhibit hepatic glucuronidation, such as indomethacin, nordazepam, acetylsalicylic acid (aspirin) and trimethoprim decreased the elimination rate and increased the therapeutic strength of the medication. Today, side-effects are much less common with the use of lower doses of AZT. According to IARC, there is sufficient evidence in experimental animals for the carcinogenicity of zidovudine; it is possibly carcinogenic to humans (Group 2B). In 2009, the State of California added zidovudine to its list of chemicals "known to the state of California to cause cancer and other reproductive harm." Viral resistance Even at the highest doses that can be tolerated in patients, AZT is not potent enough to prevent all HIV replication and may only slow the replication of the virus and progression of the disease. Prolonged AZT treatment can lead to HIV developing resistance to AZT by mutation of its reverse transcriptase. To slow the development of resistance, physicians generally recommend that AZT be given in combination with another reverse-transcriptase inhibitor and an antiretroviral from another group, such as a protease inhibitor, non-nucleoside reverse-transcriptase inhibitor, or integrase inhibitor; this type of therapy is known as HAART (Highly Active Anti Retroviral Therapy). Mechanism of action AZT is a thymidine analogue. AZT works by selectively inhibiting HIVs reverse transcriptase, the enzyme that the virus uses to make a DNA copy of its RNA. Reverse transcription is necessary for production of HIVs double-stranded DNA, which would be subsequently integrated into the genetic material of the infected cell (where it is called a provirus).Cellular enzymes convert AZT into the effective 5-triphosphate form. Studies have shown that the termination of HIVs forming DNA chains is the specific factor in the inhibitory effect.At very high doses, AZTs triphosphate form may also inhibit DNA polymerase used by human cells to undergo cell division, but regardless of dosage AZT has an approximately 100-fold greater affinity for HIVs reverse transcriptase. The selectivity has been suggested to be due to the cells ability to quickly repair its own DNA chain if it is disrupted by AZT during its formation, whereas the HIV virus lacks that ability. Thus AZT inhibits HIV replication without affecting the function of uninfected cells. At sufficiently high dosages, AZT begins to inhibit the cellular DNA polymerase used by mitochondria to replicate, accounting for its potentially toxic but reversible effects on cardiac and skeletal muscles, causing myositis. Chemistry Enantiopure AZT crystallizes in the monoclinic space group P21. The primary intermolecular bonding motif is a hydrogen bonded dimeric ring formed from two N-H...O interactions. History Initial cancer research In the 1960s, the theory that most cancers were caused by environmental retroviruses gained clinical support and funding. It had recently become known, due to the work of Nobel laureates Howard Temin and David Baltimore, that nearly all avian cancers were caused by bird retroviruses, but corresponding human retroviruses had not yet been found. In parallel work, other compounds that successfully blocked the synthesis of nucleic acids had been proven to be both antibacterial, antiviral, and anticancer agents, the leading work being done at the laboratory of Nobel laureates George Hitchings and Gertrude Elion, leading to the development of the antitumor agent 6-mercaptopurine.Jerome Horwitz of the Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine first synthesized AZT in 1964 under a US National Institutes of Health (NIH) grant. Development was shelved after it proved biologically inert in mice. In 1974, Wolfram Ostertag of the Max Planck Institute for Experimental Medicine in Göttingen, Germany reported that AZT specifically targeted Friend virus (strain of murine leukemia virus).This report attracted little interest from other researchers as the Friend leukemia virus is a retrovirus, and at the time, there were no known human diseases caused by retroviruses. HIV/AIDS research In 1983, researchers at the Institut Pasteur in Paris identified the retrovirus now known as the Human Immunodeficiency Virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) in humans. Shortly thereafter, Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan of the United States National Cancer Institute (NCI) initiated a program to develop therapies for HIV/AIDS. Using a line of CD4+ T cells that they had made, they developed an assay to screen drugs for their ability to protect CD4+ T cells from being killed by HIV. In order to expedite the process of discovering a drug, the NCI researchers actively sought collaborations with pharmaceutical companies having access to libraries of compounds with potential antiviral activity. This assay could simultaneously test both the anti-HIV effect of the compounds and their toxicity against infected T cells. In June 1984, Burroughs-Wellcome virologist Marty St. Clair set up a program to discover drugs with the potential to inhibit HIV replication. Burroughs-Wellcome had expertise in nucleoside analogs and viral diseases, led by researchers including George Hitchings, Gertrude Elion, David Barry, Paul (Chip) McGuirt Jr., Philip Furman, Martha St. Clair, Janet Rideout, Sandra Lehrman and others. Their research efforts were focused in part on the viral enzyme reverse transcriptase. Reverse transcriptase is an enzyme that retroviruses, including HIV, utilize to replicate themselves. Secondary testing was performed in mouse cells infected with the retroviruses Friend virus or Harvey sarcoma virus, as the Wellcome group did not have a viable in-house HIV antiviral assay in place at that time, and these other retroviruses were believed to represent reasonable surrogates. AZT proved to be a remarkably potent inhibitor of both Friend virus and Harvey sarcoma virus, and a search of the companys records showed that it had demonstrated low toxicity when tested for its antibacterial activity in rats many years earlier. Based in part on these results, AZT was selected by nucleoside chemist Janet Rideout as one of 11 compounds to send to the NCI for testing in that organizations HIV antiviral assay.In February 1985, the NCI scientists found that AZT had potent efficacy in vitro. Several months later, a phase 1 clinical trial of AZT at the NCI was initiated at the NCI and Duke University,. In doing this Phase I trial, they built on their experience in doing an earlier trial, with suramin, another drug that had shown effective anti-HIV activity in the laboratory. This initial trial of AZT proved that the drug could be safely administered to patients with HIV, that it increased their CD4 counts, restored T cell immunity as measured by skin testing, and that it showed strong evidence of clinical effectiveness, such as inducing weight gain in AIDS patients. It also showed that levels of AZT that worked in vitro could be injected into patients in serum and suppository form, and that the drug penetrated deeply only into infected brains. Patent filed and FDA approval A rigorous double-blind, placebo-controlled randomized trial of AZT was subsequently conducted by Burroughs-Wellcome and proved that AZT safely prolongs the lives of people with HIV. Burroughs-Wellcome filed for a patent for AZT in 1985. The Anti-Infective Advisory Committee to United States Food and Drug Administration (FDA) voted ten to one to recommend the approval of AZT. The FDA approved the drug (via the then-new FDA accelerated approval system) for use against HIV, AIDS, and AIDS Related Complex (ARC, a now-obsolete medical term for pre-AIDS illness) on March 20, 1987. The time between the first demonstration that AZT was active against HIV in the laboratory and its approval was 25 months, the shortest period of drug development in recent history.AZT was subsequently approved unanimously for infants and children in 1990. AZT was initially administered in significantly higher dosages than today, typically 400 mg every four hours, day and night, compared to modern dosage of 300 mg twice daily. The paucity of alternatives for treating HIV/AIDS at that time unambiguously affirmed the health risk/benefit ratio, with inevitable slow, disfiguring, and painful death from HIV outweighing the drugs side-effect of transient anemia and malaise. Society and culture In 1991, the advocacy group Public Citizen filed a lawsuit claiming that the patents were invalid. Subsequently, Barr Laboratories and Novopharm Ltd. also challenged the patent, in part based on the assertion that NCI scientists Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan should have been named as inventors, and those two companies applied to the FDA to sell AZT as a generic drug. In response, Burroughs Wellcome Co. filed a lawsuit against the two companies. The United States Court of Appeals for the Federal Circuit ruled in 1992 in favor of Burroughs Wellcome, ruling that even though they had never tested it against HIV, they had conceived of it working before they sent it to the NCI scientists. This suit was appealed up to the Supreme Court of the US, but in 1996 they declined to formally review it. The case, Burroughs Wellcome Co. v. Barr Laboratories, was a landmark in US law of inventorship.In 2002, another lawsuit was filed challenging the patent by the AIDS Healthcare Foundation, which also filed an antitrust case against GSK as well. The patent case was dismissed in 2003 and AHF filed a new case challenging the patent.GSKs patents on AZT expired in 2005, and in September 2005, the FDA approved three generic versions. References External links "Zidovudine". Drug Information Portal. U.S. National Library of Medicine.

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

Opsismodysplasia is a type of skeletal dysplasia (a bone disease that interferes with bone development) first described by Zonana and associates in 1977, and designated under its current name by Maroteaux (1984). Derived from the Greek opsismos ("late"), the name "opsismodysplasia" describes a delay in bone maturation. In addition to this delay, the disorder is characterized by micromelia (short or undersized bones), particularly of the hands and feet, delay of ossification (bone cell formation), platyspondyly (flattened vertebrae), irregular metaphyses, an array of facial aberrations and respiratory distress related to chronic infection. Opsismodysplasia is congenital, being apparent at birth. It has a variable mortality, with some affected individuals living to adulthood. The disorder is rare, with an incidence of less than 1 per 1,000,000 worldwide. It is inherited in an autosomal recessive pattern, which means the defective (mutated) gene that causes the disorder is located on an autosome, and the disorder occurs when two copies of this defective gene are inherited. No specific gene has been found to be associated with the disorder. It is similar to spondylometaphyseal dysplasia, Sedaghatian type. Presentation Opsismodysplasia can be characterized by a delay in bone maturation, which refers to "bone aging", an expected sequence of developmental changes in the skeleton corresponding to the chronological age of a person. Factors such as gender and ethnicity also play a role in bone age assessment. The only indicator of physical development that can be applied from birth through mature adulthood is bone age. Specifically, the age and maturity of bone can be determined by its state of ossification, the age-related process whereby certain cartilaginous and soft tissue structures are transformed into bone. The condition of epiphyseal plates (growth plates) at the ends of the long bones (which includes those of the arms, hands, legs and feet) is another measurement of bone age. The evaluation of both ossification and the state of growth plates in children is often reached through radiography (X-rays) of the carpals (bones of the hand and wrist). In opsismodysplasia, the process of ossification in long bones can be disrupted by a failure of ossification centers (a center of organization in long bones, where cartilage cells designated to await and undergo ossification gather and align in rows) to form. This was observed in a 16-month-old boy with the disorder, who had no apparent ossification centers in the carpals (bones of the hand and wrist) or tarsals (bones of the foot). This was associated with an absence of ossification in these bones, as well as disfigurement of the hands and feet at age two. The boy also had no ossification occurring in the lower femur (thigh bone) and upper tibia (the shin bone). Genetics Opsismodysplasia is inherited in an autosomal recessive manner. This means the defective gene(s) responsible for the disorder is located on 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. Currently, no specific mutation in any gene has been found to cause the disorder.It appears that the gene inositol polyphosphate phosphatase-like 1 is the cause of this condition in at least some cases. Diagnosis Epidemiology Opsismodysplasia is a very rare disorder, and is estimated to occur in less than 1 in 1,000,000 people. History The disorder was first described by Jonathan Zonana and associates in 1977. Further observation of four cases of it was reported by Pierre Maroteaux and colleagues in 1982, and Maroteaux was the first to call the disorder "opsismodysplasia", in a 1984 journal report of three affected individuals. The name derives from the Greek opsismos, meaning "late", while the term dysplasia refers to development. References == External links ==

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I'm curious about the meaning of the medical term 'Infantile neuronal ceroid lipofuscinosis.' Can you give me some insights?

Infantile neuronal ceroid lipofuscinoses (INCL) or Santavuori disease or Hagberg-Santavuori disease or Santavuori-Haltia disease or Infantile Finnish type neuronal ceroid lipofuscinosis or Balkan disease is a form of NCL and inherited as a recessive autosomal genetic trait. The disorder is progressive, degenerative and fatal, extremely rare worldwide – with approximately 60 official cases reported by 1982, perhaps 100 with the condition in total today – but relatively common in Finland due to the local founder effect. Presentation The development of children born with INCL is normal for the first 8–18 months, but will then flounder and start to regress both physically and mentally. Motor skills and speech are lost, and optic atrophy causes blindness. A variety of neurological symptoms, such as epilepsy and myoclonic seizures, appear. The senses of hearing and touch remain unaffected. The average lifespan of an INCL child is 9–11 years. Causes It has been associated with palmitoyl-protein thioesterase. Diagnosis Treatment Treatment is limited. Drugs can alleviate the symptoms, such as sleep difficulties and epilepsy. Physiotherapy helps affected children retain the ability to remain upright for as long as possible, and prevents some of the pain. Recent attempts to treat INCL with cystagon have been unsuccessful. See also FAIDD (The Finnish Association on Intellectual and Developmental Disabilities) References External links GeneReviews/NCBI/NIH/UW entry on Neuronal Ceroid-Lipofuscinosis An overview (in Finnish) The INCL organization of Finland (in Finnish)

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

I'm seeking clarification on the medical term 'Low milk supply.' Could you explain it?

In breastfeeding women, low milk supply, also known as lactation insufficiency, insufficient milk syndrome, agalactia, agalactorrhea, hypogalactia or hypogalactorrhea, is the production of breast milk in daily volumes that do not fully meet the nutritional needs of her infant. Breast milk supply augments in response to the babys demand for milk, and decreases when milk is allowed to remain in the breasts. Low milk supply is usually caused by allowing milk to remain in the breasts for long periods of time, or insufficiently draining the breasts during feeds. It is usually preventable, unless caused by medical conditions that have been estimated to affect five to fifteen percent of women.Several common misconceptions often lead mothers to believe they have insufficient milk when they are in fact producing enough. Actual low milk supply is likely if the baby is latching and swallowing well at the breast, is nevertheless not growing well or is showing signs of dehydration or malnutrition, and does not have a medical condition that would explain the lack of growth. The main method for increasing milk supply is improved breastfeeding practices and/or expressing milk through pumping or hand expression. The medication domperidone increases milk supply for some women. For mothers who cannot breastfeed exclusively, breastfeeding as much as possible, with supplementary formula feeding as necessary, offers many benefits over formula alone. Causes Low milk supply can be either primary (caused by medical conditions or anatomical issues in the mother), secondary (caused by not thoroughly and regularly removing milk from the breasts) or both. Secondary causes are far more common than primary ones. One study found that 15% of healthy first-time mothers had low milk supply 2–3 weeks after birth, with secondary causes accounting for at least two-thirds of those cases.Breastfeeding management issues that can interfere with regular milk drainage from the breast include poor latch, unnecessary use of supplemental formula, timed or scheduled feedings (as opposed to on-demand feedings), and overuse of pacifiers. Medical conditions in the infant that result in weak or unco-ordinated sucking can cause low milk supply by inhibiting the transfer of milk to the baby. These conditions include tongue-tie, congenital heart defects, prematurity, and Down syndrome.Primary causes of low milk supply include: insufficient glandular tissue, also known as primary lactation failure. Breasts with insufficient glandular tissue often have a tubular shape, with a large space between the breasts, and often do not grow during pregnancy. retained placenta Sheehans syndrome prior breast surgery (especially breast reduction) prior nipple piercing polycystic ovary syndrome (PCOS) hypothyroidism hypoprolactinemia theca lutein cysts hypertension pregnancySmoking more than 15 cigarettes per day is associated with reduced milk production. Many medications are known to significantly suppress milk production, including pseudoephedrine, diuretics, and contraceptives that contain estrogen. It is suspected that some herbs, particularly sage and peppermint, suppress milk production. Mechanism The physiological mechanisms that regulate breast milk supply are poorly understood. High levels of prolactin are necessary for lactation, however there is no direct correlation between baseline levels of prolactin and quantity of milk production. One aspect of supply regulation that has been identified is that breast milk contains a peptide called feedback inhibitor of lactation (FIL). When milk is present in the breast, FIL inhibits the secretion of milk. After a mothers milk comes in, a reduction in supply is inevitable unless milk is removed regularly and thoroughly from the breasts.Surgery or injury to the breast can decrease supply by disrupting milk ducts that carry milk from the alveoli, where milk is produced, to the nipple. Retained placenta results in high levels of progesterone, a hormone that inhibits lactation. Diagnosis A womans belief that her milk supply is insufficient is one of the most common reasons for discontinuing breastfeeding. In many of those cases, the womans milk supply is actually normal. After a few weeks or months of breastfeeding, changes that are commonly mistaken for signs of low milk supply include breasts feeling softer (this is normal after 1–3 months), more frequent demands by the infant to feed, feeds becoming shorter over time, baby colic, the perception that the baby is more satisfied after being fed infant formula, and a slowdown in growth after three months.To evaluate whether milk supply is actually insufficient, qualitative parameters should be used such as the following: By 3–5 days, of age, the infant should be stooling 3–4 times per day and urinating 3—5 times per day. By 5–7 days of age, there should be 3—6 stools per day and 4—6 urines. The infant should be alert, have good muscle tone, and show no signs of dehydration. The infant should be consistently gaining weight and growing. In newborns, a loss of more than 5 to 7 percent of birth weight warrants investigation. The use of IV fluids in labour tends to artificially increase the birth weight of the baby, and subsequently inflate the babys weight loss. Newborns should regain their birth weight by two weeks of age, and gain at least 150 g per week.If an infant is not showing these signs of growing well, other possible causes include: Poor milk transfer due to tongue-tie, or cleft palate. Medical conditions in the infant, such as malabsorption of nutrients. Definition A mother is considered to have low milk supply if she produces less breast milk than her infant requires. The term is used only after a mothers milk "comes in", which usually occurs around 30–40 hours after delivery of a full-term infant. Low milk supply is distinct from the scenario in which the mothers milk comes in later than normal but is thereafter produced in sufficient quantities; this is known as delayed onset of lactation (delayed lactogenesis II). Prevention The first week after birth is a critical window for establishing milk supply. The Ten Steps of the Baby Friendly Hospital Initiative describe some maternity hospital practices that promote the development of a good milk supply, such as rooming in (allowing mothers and infants to remain together 24 hours a day) and having trained staff available to help mothers with breastfeeding. Supplemental formula or donor milk should be given only when medically necessary. There is increasing evidence that suggests that early skin-to-skin contact between mother and baby stimulates breastfeeding behavior in the baby. Newborns who are immediately placed on their mothers skin have a natural instinct to latch on to the breast and start nursing, typically within one hour of birth. Immediate skin-to-skin contact may provide a form of imprinting that makes subsequent feeding significantly easier. Interrupting the process, such as removing the baby to weigh him/her, may complicate subsequent feeding.Frequent suckling in the first days of life is correlated with higher milk production. Infants should be fed when they show signs of hunger. It is common for breastfed babies to feed during the night for the first six months. Usually feedings last 10–15 minutes in the early days.If the infant is unable to breastfeed, it is recommended that pumping or hand expression of milk begin within two hours of delivery, and be done at least eight times every 24 hours. Management Attempts to increase milk supply should begin promptly as the longer low supply continues, the more difficult it is to reverse. The primary method for increasing milk supply is to increase the frequency and the thoroughness of milk drainage from the breasts, and to increase breast stimulation.For mothers of healthy term infants who are able to nurse, very strong evidence supports improving breastfeeding practices as a primary treatment. Increasing skin-to-skin contact between mother and baby, and allowing unrestricted breastfeeding, aid in stimulating the milk ejection reflex and promote frequent feeds. If the babys latch is not optimal, improving the latch will help the baby drink more milk. Making the mother comfortable, particularly by resolving nipple pain, is essential. Breast self-massage is recommended to stimulate the milk ejection reflex and to physically promote the flow of milk. Some experts recommend using a breast pump after each breastfeeding session.If the baby cannot nurse effectively, frequent drainage of milk from the breasts through hand expression and/or an electric double breast pump is recommended.The mothers use of medications and herbs should be evaluated, as some substance suppress lactation. The Academy of Breastfeeding Medicine protocol for low milk supply recommends that the mother be evaluated for medical causes of the problem, however health professionals and breastfeeding counsellors often do not do this. Medications and herbs After the above treatment methods have been attempted, many breastfeeding specialists and lactation consultants recommend medications or herbs that are believed to increase milk supply (galactagogues). In 2010, a randomized, double-blinded, placebo-controlled study demonstrated that domperidone increased milk production in mothers of preterm infants. Another very small study of domperidone found that some women respond to it and others do not. As the effects of domperidone stop when use of the drug is stopped, it is sometimes used for months. Domperidone is available by prescription in Canada, Australia, many parts of Europe, and other countries, but not in the United States. Several herbs, including fenugreek and milk thistle are traditionally and widely used with the intention of promoting milk supply. For these herbs, there are anecdotal reports of efficacy which may be due to placebo effect. Scientific evidence for the efficacy of herbal galactagogues is insufficient or nonexistent. The Academy of Breastfeeding Medicine protocol for low milk supply says that there is insufficient data to recommend specific medicinal or herbal galactagogues, but that some substances may be useful in some cases.A Cochrane review showed that, despite the relatively large number of randomised controlled trials investigating medical and natural galactogogues, it is uncertain whether galactogogues have any effect on breastfeeding rates. Supplementary feeding If the mothers milk supply is insufficient, formula or (preferably) donor milk is necessary in order for the infant to obtain adequate nutrients. Supplements should be given immediately after a breastfeeding session, rather than in place of a breastfeeding session.The use of supplements is gradually tapered off as the mothers own milk supply rebounds. In some cases, especially when low supply is caused by medical conditions such as insufficient glandular tissue, long-term use of supplements is necessary. For mothers who cannot breastfeed exclusively, breastfeeding as much as possible, with formula feeding as necessary, offers many benefits over formula alone. See also Breastfeeding difficulties Lactation References Bibliography Lawrence, Ruth (2016). Breastfeeding : a guide for the medical profession, 8th edition. Philadelphia, PA: Elsevier. ISBN 978-0-323-35776-0.

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

What is the significance of the term 'Webbed neck' in the medical field?

A webbed neck, or pterygium colli, is a congenital skin fold that runs along the sides of the neck down to the shoulders. There are many variants. Signs and symptoms On babies, webbed neck may look like loose folds of skin on the neck. As the child grows, the skin may stretch out to look like there is little or no neck. Associated conditions It is a feature of Turner syndrome (only found in girls) and Noonan syndrome, as well as the rarer Klippel–Feil syndrome, or Diamond–Blackfan anemia References == External links ==

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Can you demystify the medical term 'Imipenem/cilastatin' for me?

Imipenem/cilastatin, sold under the brand name Primaxin among others, is an antibiotic useful for the treatment of a number of bacterial infections. It is made from a combination of imipenem and cilastatin. Specifically it is used for pneumonia, sepsis, endocarditis, joint infections, intra-abdominal infections, and urinary tract infections. It is given by injection into a vein or muscle.Common side effects include nausea, diarrhea, and pain at the site of injection. Other side effects may include Clostridium difficile diarrhea and allergic reactions including anaphylaxis. It is unclear if use during pregnancy is safe for the baby. Imipenem is in the carbapenem family of medications and works by interfering with the bacterias cell wall. Cilastatin blocks the activity of dehydropeptidase I which prevents the breakdown of imipenem.Imipenem/cilastatin was first sold in 1987. It is on the World Health Organizations List of Essential Medicines. Medical uses Imipenem/cilastatin is used for lower respiratory tract infections, urinary tract infections, intra-abdominal infections, gynecologic infections, bacterial sepsis, bone and joint infections, skin and skin structure infections, endocarditis and polymicrobic infections.It is a broad-spectrum beta-lactam containing equal quantities of imipenem and cilastatin. Side effects Common side effects for both forms are: Upset stomach Vomiting Stomach painMajor side effects requiring medical attention: Diarrhea Rash Fever Facial swelling Difficulty breathing Unusual bleeding SeizuresThis medicine is passed through breast milk, so its use during pregnancy or breastfeeding should only be done when clearly needed. Primaxin is cleared from the body by the kidneys, so it is important to tell ones doctor about any other drugs being taken that are also cleared through the kidneys (such as other antibiotics), especially for older patients, as kidney function declines with age.Patients who are allergic to penicillin, cephalosporins, and related drugs may react to imipenem. It is important tell ones doctor or pharmacist ones medical history, especially of brain disorders (e.g., seizures, head injury, tumor), kidney disease, liver disease, and stomach/intestinal diseases (e.g., colitis). Hepatotoxicity In large clinical trials, imipenem was associated with transient and asymptomatic elevations in serum aminotransferase levels in about 6% of patients given the drug for five to 14 days. More serious hepatic injury from imipenem/cilastatin is rare, but jaundice and liver test abnormalities have been reported in 0.1% of patients in prospective trials of the agent. Several instances of cholestatic jaundice arising during or shortly after therapy have been reported with imipenem-cilastatin and other carbapenems. The latency to onset has been within one to three weeks, and the pattern of enzyme elevations is usually cholestatic. Immunoallergic features can occur, but autoantibodies are rare. The course is usually self-limiting, but at least one case of vanishing bile duct syndrome related to the carbapenems has been reported. Imipenem and other carbapenems have not been linked to cases of acute liver failure. Mechanism of liver injury The cause of the mild, transient serum enzyme elevations during imipenem-cilastatin therapy is not known. The cholestatic hepatitis attributed to imipenem-cilastatin and the carbapenems is probably immunoallergic and resembles the rare, clinically apparent liver injury that has been linked to penicillins and cephalosporins. Outcome and management The liver injury due to the carbapenems is usually mild and self-limited. Rarely, the carbapenems can cause a clinically apparent acute cholestatic hepatitis that is usually self-limiting and not requiring therapy or intervention. In patients with vanishing bile duct syndrome, corticosteroids are often used but have not been shown to be beneficial and are best avoided. Some patients may benefit from symptomatic therapy of the pruritus associated with cholestasis using antihistamines, ursodiol, or cholestyramine. Little information is available on possible cross-sensitivity to liver injury among the different betalactam antibiotics, but patients with clinically apparent liver injury due to imipenem should probably avoid the other carbapenems. Interactions valproic acid (Depakene, Stavzor) ganciclovir (Cytovene) probenecid (Benemid) penicillin antibiotics such as amoxicillin (Amoxil, Augmentin), ampicillin (Omnipen, Principen), dicloxacillin (Dycill, Dynapen), oxacillin (Bactocill), or penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others); or cephalosporin antibiotics such as cefaclor (Ceclor), cefuroxime (Ceftin), cefadroxil (Duricef), cephalexin (Keflex), and others. Mechanism of action Imipenem/cilastatin has the ability to kill a wide variety of bacteria. Imipenem is the active antibiotic agent and works by interfering with their ability to form cell walls, so the bacteria break up and die. Imipenem is rapidly degraded by the renal enzyme dehydropeptidase if administered alone (making it less effective); the metabolites can cause kidney damage. Imipenem is a broad-spectrum betalactam antibiotic used for severe bacterial infections caused by susceptible organisms. Because imipenem is rapidly inactivated by renal dehydropeptidase I, it is given in combination with cilastatin, a DHP-I inhibitor which increases half-life and tissue penetration of imipenem. Imipenem/cilastatin, like other carbapenems, binds to bacterial penicillin-binding proteins and interferes with bacterial cell wall integrity and synthesis. It has activity against many aerobic and anaerobic Gram-positive and Gram-negative organisms, including Staphylococcus aureus, Streptococcus pyogenes, S. agalactiae, S. viridans- group streptococci, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and Peptostreptococcus species. Imipenem/cilastatin was approved for use in the United States in 1985. Imipenem/cilastatin is indicated for the treatment of severe or complicated skin, tissue, joint, respiratory tract, intra-abdominal, urinary tract and urogenital infections, but not meningitis (as it does not pass through the blood brain barrier), endocarditis, and sepsis due to susceptible organisms. Its use is generally restricted to severe infections largely in hospitalized patients. The recommended dosage is 250 mg to 1 gram given intravenously every 6 to 8 hours or in intramuscular doses of no more than 1.5 gm daily, usually for five to 14 days. It is commercially available as Primaxin as 250-mg or 500-mg infusion bottles for IV use or 500-mg or 750-mg vials of lyophilized powder for IM injection. The most common side effects of imipenem are diarrhea, nausea, vomiting, skin rash, pruritus, and injection-site reactions. Pharmacology Mechanism of action Imipenem inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins; cilastatin prevents renal metabolism of imipenem. Bioavailability Intramuscular injection: imipenem: 60–75% cilastatin: 95–100% Distribution The drug is distributed rapidly and widely to most tissues and fluids, including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, reproductive organs, and bone; highest concentrations occur in pleural fluid, interstitial fluid, peritoneal fluid, and reproductive organs; low concentrations occur in CSF; it crosses the placenta, and enters breast milk Protein binding imipenem: 13–21% cilastatin, 40% Metabolism Imipenem is metabolized in the kidney by dehydropeptidase 1; activity is blocked by cilastatin. Elimination Half-life (both drugs): 60 min; prolonged with renal impairment. Excretion (both drugs): Urine (~70% as unchanged drug) Availability and description Primaxin IV is a combination of imipenem, cilastatin sodium, and sodium bicarbonate which is added as a buffer. Primaxin IM lacks the sodium bicarbonate buffer. See also Imipenem/cilastatin/relebactam References External links "Cilastatin mixture with Imipenem". Drug Information Portal. U.S. National Library of Medicine.

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

Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows: A distinctive abnormality in skeletal muscle fibres on the cellular level; observable via light microscope Symptoms of muscle weakness and hypotonia Is a congenital disorder, meaning it occurs during development and symptoms present themselves at birth or in early life. Is a genetic disorder. Classification Myopathies with inclusion bodies and abnormal protein accumulation Congenital myopathies with inclusion bodies and protein accumulation is a broad category, and some congenital myopathies that fall within this group are well understood, such as nemaline myopathy (see below). Typically, the development error in this category occurs when muscle proteins aggregate and build up in the sarcoplasm, which leads to muscle dysfunction. Myopathies with cores Core myopathies such as multicore myopathy and central core disease are characterized by sharply-demarcated areas devoid of oxidative enzymes NADH, SDH, and COX, in muscle fibres. Myopathies with central nuclei Myopathies with central nuclei, such as myotubular myopathy, involves an error in the gene involved in vesicle movement throughout the cell. This creates problems in vesicles reaching the plasma membrane with the cellular components necessary to fuse myoblast, a major step in the formation of the skeletal muscle. This creates structural problems throughout the skeletal muscle and in the Z line of the sarcomere, creating the weakness in the muscle. Myopathies with fiber size variation Myopathies with varying fiber size, such as congenital fiber type disproportion, occurs when type 1 fibers, the slow twitch fibers involved in sustaining activity, are smaller than type 2 fibers, the fast twitch fibers involved in quick activity. Since smaller type 1 fibers is not associated with nemaline myopathy, the most common type of congenital myopathy, it has not been studied in as great detail as many of the others. However, the smaller type 1 fibers explains why patients typically can participate in activities for shorter periods of time, but struggle with extended activity. Cause Diagnosis There are rarely any specific tests for the congenital myopathies except for muscle biopsy. Tests can be run to check creatine kinase in the blood, which is often normal or mildly elevated in congenital myopathies. Electromyography can be run to check the electrical activity of the muscle. Diagnosis heavily relies on muscle pathology, where a muscle biopsy is visualised on the cellular level. Diagnosis usually relies on this method, as creatine kinase levels and electromyography can be unreliable and non-specific. Since congenital myopathies are genetic, there have been advancements in prenatal screenings. Types The conditions included under the term "congenital myopathy" can vary. One source includes nemaline myopathy, myotubular myopathy, central core myopathy, congenital fiber type disproportion, and multicore myopathy. The term can also be used more broadly, to describe conditions present from birth. Nemaline myopathy Nemaline myopathy was first described in 1963 and is the most common congenital myopathy. It is characterized by generalized muscle weakness and low muscle tone. In its severest form, affected babies often die from respiratory failure. To date, 9 gene mutations have been found to cause nemaline myopathy. 6 of the identified genes are associated with the actin filament, which is the basis for muscle contraction. Histologically, nemaline rods stain red with Gomoris trichrome and are mostly seen in the subsarcolemmal region of muscle fibres. Nemaline rods have also been observed in the intermyofibrillar region of muscle fibres and within the nucleus. Nemaline myopathy is an autosomal dominant and sometimes an autosomal recessive genetic disorder. Sporadic cases have also been described. Myotubular myopathy Myotubular myopathy, also known as centeronuclear myopathy, is recognized by pain during exercise and difficulty walking. People affected by this disease typically are wheelchair-reliant by middle adulthood, have weakness in the muscles involved in eye movement, nerve function disorders, and some form of intellectual disability. Myotubular myopathy is very rare, with less than 50 families currently affected. Genetically, myotubular myopathy can have two causes: autosomal dominant and autosomal recessive. When caused by a mutation in the DNM2 gene, the disorder is autosomal dominant, meaning it can be passed on by one mutated gene. When the mutation takes place in the BIN1 gene, the disease is instead autosomal recessive, and both genes must be mutated for the disease to be inherited. Autosomal recessive onset is most common. Central core disease Central core disease or central core myopathy was first described in 1956 and usually presents in infancy or early childhood as non-progressive mild proximal weakness that persists throughout life. Central core disease is believed to be more prevalent than currently reported, as it is hard to recognize and often misdiagnosed in early childhood. Central core disease has been found to be allelic with malignant hyperthermia, which is a life-threatening anesthetic reaction that causes a rise in body temperature, muscular rigidity and muscular breakdown, grossly elevated creatine kinase, and acidosis. Central core disease is caused by a mutation in the RYR1 gene. Congenital fiber type disproportion Congenital fiber type disproportion affects skeletal muscle, typically causing weakness in the shoulders, upper arms, thighs, and hips. Skeletal muscle is made up of two kinds of fiber, type 1 and type 2. In congenital fiber type disproportion, type 1 fibers are not only smaller but often more abundant than type 2 fibers. This leads to affected individuals being able to maintain an active lifestyle, though they usually have lower levels of stamina. Severity with this disease varies greatly, but people typically present symptoms by the age of one. Individuals do not usually worsen with time, and cases have even been reported of improvements. Multicore myopathy Multicore myopathy also referred to as minicore myopathy, is associated with small areas of decreased oxidative activities, resulting in areas that appear in this histology as "cores". These appear through microscopy very similar to central core, however the cores are typically smaller in multicore myopathy. As with congenital fiber type disproportion, patients have a greater number of type 1 fibers. Overall, approximately half of diagnosed individuals report no progression of muscle weakness, while half report a very slow progression. Cylindrical spirals myopathy Cylindrical spirals myopathy is very rare with only 18 individual cases described as of 2013. The majority of cases are sporadic, and has been observed in only 3 families. It is characterized by the presence of cylindrical spirals as the main pathological finding in muscle biopsies. Cylindrical spirals are unusual membrane structures that have a spiral pattern. These membrane structures are seen during electron microscopic examination of the affected muscle. These structures merge into or are surrounded by tubular structures that resemble tubular aggregates. Tubular aggregates are abnormal accumulations of membranous tubules and have been observed in a wide variety of muscle diseases and originate from the sarcoplasmic reticulum. Cylindrical spirals were first described in 1979 and were thought to be a non-specific reaction of skeletal muscle secondary to a metabolic disturbance or muscle fibre injury. The molecular basis of cylindrical spiral myopathy is currently unknown, however a genetic mutation affecting the sarcoplasmic reticulum in some patients seems likely, as SERCA1, calsequestrin, and RYR1 have been shown to bind to cylindrical spirals. Cylindrical spirals have also been shown to react with the mitochondrial enzyme succinate dehydrogenase, which suggests that cylindrical spirals originate from mitochondria. Phenotypes are quite variable, and manifestations can include weakness, abnormal gait, myotonia, cramps, and scoliosis. Treatment Currently, there are no treatments for any of the congenital myopathies. Depending on the severity, there are different therapies available to help alleviate any pain and aid patients in performing varying activities. For example, many congenital myopathy patients are involved in physical or occupational therapy in an attempt to strengthen their skeletal muscles. Orthopedic surgery is usually necessary to correct skeletal deformities secondary to muscle weakness, such as scoliosis. Survival is typically determined by the level of respiratory muscle insufficiency. References Further reading GeneReviews/NCBI/NIH/UW entry on Congenital Fiber-Type Disproportion == 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 expand my medical knowledge. Can you elucidate the term 'Glomeruloid hemangioma'?

Glomeruloid hemangioma is a distinctive vascular tumor first described in 1990 when found to be associated with POEMS syndrome and Castleman disease.: 595 See also List of cutaneous conditions == References ==

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What is the significance of the term 'Agenesis of the corpus callosum' in the medical field?

Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the development of the corpus callosum, the band of white matter connecting the two hemispheres in the brain, in the embryo is disrupted. The result of this is that the fibers that would otherwise form the corpus callosum are instead longitudinally oriented along the ipsilateral ventricular wall and form structures called Probst bundles. In addition to agenesis, other degrees of callosal defects exist, including hypoplasia (underdevelopment or thinness), hypogenesis (partial agenesis) or dysgenesis (malformation).ACC is found in many syndromes and can often present alongside hypoplasia of the cerebellar vermis. When this is the case, there can also be an enlarged fourth ventricle or hydrocephalus; this is called Dandy–Walker malformation. Signs and symptoms Signs and symptoms of ACC and other callosal disorders vary greatly among individuals. However, some characteristics common in individuals with callosal disorders include vision impairments, low muscle tone (hypotonia), poor motor coordination, delays in motor milestones such as sitting and walking, delayed toilet training and dysautonomic symptoms such as low perception of pain or chewing and swallowing difficulties.Laboratory research has demonstrated that individuals with ACC have difficulty transferring more complex information from one hemisphere to the other. They also have been shown to have some cognitive disabilities (difficulty in complex problem solving) and social difficulties (missing subtle social cues), even when their intelligence quotient is normal. Recent research suggests that specific social difficulties may be a result of impaired face processing. The unusual social behavior in childhood often resembles that of an autism spectrum disorder.Other characteristics sometimes associated with callosal disorders include seizures, spasticity, early feeding difficulties and/or gastric reflux, hearing impairments, abnormal head and facial features, and intellectual disability. Associated brain anomalies Brain anomalies that can sometimes occur in syndromes that cause callosal disorders include: Aplasia of the cerebellar vermis Chiari malformation Colpocephaly Dandy–Walker syndrome Holoprosencephaly Hydrocephalus Neuronal migration disorders such as grey matter heterotopia Schizencephaly Associated syndromes and conditions Some syndromes that frequently include ACC are: Acrocallosal syndrome Aicardi syndrome Andermann syndrome Donnai–Barrow syndrome Dwarfism FG syndrome L1CAM syndrome Microcephalic osteodysplastic primordial dwarfism type II Mowat–Wilson syndrome Oculocerebrocutaneous syndrome Saal Bulas syndrome Septo-optic dysplasia (optic nerve hypoplasia) Shapiro syndrome Vici syndromeSome conditions that can sometimes be associated with ACC or other callosal disorders include: 1p36 deletion syndrome 13q deletion syndrome CDK13-related disorder Craniofacial abnormalities and other oral and maxillofacial pathologies Fetal alcohol syndrome Fetal warfarin syndrome Genitopatellar syndrome Gomez-Lopez-Hernandez syndrome Joubert syndrome Lujan–Fryns syndrome Marden–Walker syndrome Maternal nutritional deficiencies or infections Metabolic disorders Okamoto syndrome Opitz G/BBB syndrome Pascual-Castroviejo syndrome Pitt–Hopkins syndrome Sensenbrenner syndrome Strømme syndrome Triploid syndrome Trisomy 9 Xia-Gibbs syndrome Causes Agenesis of the corpus callosum is caused by disruption to development of the fetal brain between the 3rd and 12th weeks of pregnancy. In most cases, it is not possible to know what caused an individual to have ACC or another callosal disorder. However, research suggests that some possible causes may include chromosome errors, inherited genetic factors, prenatal infections or injuries, prenatal toxic exposures, structural blockage by cysts or other brain abnormalities and metabolic disorders. Ciliopathies: rare genetic disorders Until recently, the medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying symptoms apparent on clinical examination. Agenesis of the corpus callosum is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell organelles that are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration. Cocaine and other street drugs In utero exposure to cocaine, heroin, amphetamines and phenylpropanolamine can lead to agenesis of corpus callosum. Diagnosis Callosal disorders can be diagnosed through brain imaging studies or during autopsy. They may be diagnosed through an MRI, CT scan, Sonography, prenatal ultrasound, or prenatal MRI. Treatment There are currently no specific medical treatments for callosal disorders, but individuals with ACC and other callosal disorders may benefit from a range of developmental therapies, educational support, and services. It is important to consult with a variety of medical, health, educational, and social work professionals. Such professionals include neurologists, neuropsychologists, occupational therapists, physical therapists, speech and language pathologists, pediatricians, recreation therapists, music therapists, geneticists, social workers, special educators, early childhood intervention specialists, and caregivers for adults. Prognosis Prognosis varies depending on the type of callosal abnormality and associated conditions or syndromes. It is not possible for the corpus callosum to regenerate. Neuropsychological testing reveals subtle differences in higher cortical function compared to individuals of the same age and education without ACC, although some individuals with callosal disorders have average intelligence and live normal lives. Culture Kim Peek, inspiration for the film Rain Man and renowned for his savant abilities, was born with agenesis of the corpus callosum, along with macrocephaly and damage to the cerebellum. Notes == External links ==

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What does the medical term 'Segesterone acetate/ethinylestradiol' encompass?

Segesterone acetate/ethinylestradiol (EE/SGA), sold under the brand name Annovera, is a contraceptive vaginal ring and combined form of hormonal birth control which contains segesterone acetate, a progestin and ethinylestradiol, an estrogen. It contains 17.4 mg ethinylestradiol and 103 mg segesterone acetate, releases an average of 13 μg ethinylestradiol and 0.15 mg segesterone acetate per day.Annovera is inserted into the vagina and left for 21 days, then removed, washed and stored for seven days, during which the user experiences a period (withdrawal bleeding.) This can be repeated thirteen times, for one full year of use. Unlike NuvaRing, another vaginal ring contraceptive, Annovera does not need to be refrigerated before being dispensed and can be stored at temperatures up to 30 degrees Celsius.The medication was developed by the Population Council, an international non-profit organization, and licensed to TherapeuticsMD. It was approved for medical use in the United States in August 2018. See also Combined injectable birth control § Available forms List of combined sex-hormonal preparations References External links "Segesterone acetate". Drug Information Portal. U.S. National Library of Medicine. "Ethinylestradiol". 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've come across the term 'Erythropoiesis-stimulating agent' in a medical context, but I'm not sure what it means. Can you clarify?

Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In these situations they decrease the need for blood transfusions. The different agents are more or less equivalent. They are given by injection.Common side effects may include joint pain, rash, vomiting, and headache. Serious side effects may include heart attacks, stroke, increased cancer growth, or pure red cell aplasia. It is unclear if use is safe during pregnancy. They work similar to naturally occurring erythropoietin.They were first approved for medical use in the United States in 1989. It is on the World Health Organizations List of Essential Medicines. Commercially available agents include epoetin alfa and darbepoetin alfa, and biosimilars. Use among athletes is prohibited by the World Anti-Doping Agency. Medical uses ESAs are used to maintain hemoglobin at the lowest level that both minimizes transfusions and best meets a persons needs. Medical speciality professional organizations do not recommend the use of ESAs in people with chronic kidney disease (CKD) who have hemoglobin levels greater than 10 g/dL and do not have anemia symptoms. In preterm babies ESAs may help reduce the need for red blood cell transfusions.The 2020 Cochrane Anaesthesia Review Group review of Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non‐cardiac surgery demonstrated that patients were much less likely to require red cell transfusion and in those transfused, the volumes were unchanged (mean difference -0.09, 95% CI -0.23 to 0.05). Pre-op Hb concentration was increased in those receiving high dose EPO, but not low dose.There is no evidence that one agent is better than another in the setting of CKD. Failure ESAs may fail to achieve an adequate therapeutic response when one or more of the following is present: Occult blood loss and/or iron deficiency Vitamin B12 or folate deficiency Infection and inflammation Inadequate dialysis Hyperparathyroidism Aluminum toxicity Patient adherence Hypothyroidism Primary disease activity Transplant rejection Malignancy Pure red cell aplasia Types The following types of ESAs are available: Erythropoietin (Epo) Epoetin alfa (Procrit, Epogen) Epoetin beta (NeoRecormon) Epoetin zeta (Silapo, Retacrit) Darbepoetin alfa (Aranesp) Methoxy polyethylene glycol-epoetin beta (Mircera) Available forms Recombinant erythropoietin has a variety of glycosylation patterns giving rise to alpha, beta, delta, and omega forms: Darbepoetin alfa, which early literature during its development often termed as novel erythropoiesis-stimulating protein (NESP), is a form created by five substitutions (Asn-30, Thr-32, Val-87, Asn-88 and Thr-90) that create two new N-glycosylation sites. This glycoprotein has a longer terminal half-life, meaning it is possible to administer it less frequently. Misuse Erythropoiesis-stimulating agents have a history of use as blood doping agents in endurance sports, such as horseracing, boxing, cycling, rowing, distance running, race walking, snowshoeing, cross country skiing, biathlon, mixed martial arts, and triathlon. The overall oxygen delivery system (blood oxygen levels, as well as heart stroke volume, vascularization, and lung function) is one of the major limiting factors to muscles ability to perform endurance exercise. Therefore, the primary reason athletes may use ESAs is to improve oxygen delivery to muscles, which directly improves their endurance capacity. With the advent of recombinant erythropoietin in the 1990s, the practice of autologous and homologous blood transfusion has been partially replaced by injecting erythropoietin such that the body naturally produces its own red cells. ESAs increase hematocrit (% of blood volume that is red cell mass) and total red cell mass in the body, providing a good advantage in sports where such practice is banned. In addition to ethical considerations in sports, providing an increased red cell mass beyond the natural levels reduces blood flow due to increased viscosity, and increases the likelihood of thrombosis and stroke. Due to dangers associated with using ESAs, their use should be limited to the clinic where anemic patients are boosted back to normal hemoglobin levels (as opposed to going above the normal levels for performance advantage, leading to an increased risk of death).Though EPO was believed to be widely used in the 1990s in certain sports, there was no way at the time to directly test for it, until in 2000, when a test developed by scientists at the French national antidoping laboratory (LNDD) and endorsed by the World Anti-Doping Agency (WADA) was introduced to detect pharmaceutical EPO by distinguishing it from the nearly identical natural hormone normally present in an athletes urine. The first EPO-doping cases were found by the Swiss Laboratory for Doping Analyses.In 2002, at the Winter Olympic Games in Salt Lake City, Dr. Don Catlin, the founder and then-director of the UCLA Olympic Analytical Lab, reported finding darbepoetin alfa, a form of erythropoietin, in a test sample for the first time in sports. At the 2012 Summer Olympics in London, Alex Schwazer, the gold medalist in the 50-kilometer race walk in the 2008 Summer Olympics in Beijing, tested positive for EPO and was disqualified.Since 2002, EPO tests performed by US sports authorities have consisted of only a urine or "direct" test. From 2000 to 2006, EPO tests at the Olympics were conducted on both blood and urine. However, several compounds have been identified that can be taken orally to stimulate endogenous EPO production. Most of the compounds stabilize the hypoxia-inducible transcription factors which activate the EPO gene. The compounds include oxo-glutarate competitors, but also simple ions such as cobalt(II) chloride.Inhalation of a xenon/oxygen mixture activates production of the transcription factor HIF-1-alpha, which leads to increased production of erythropoietin and improved performance. It has been used for this purpose in Russia since at least 2004. Cycling Recombinant EPO is believed to have come into use in cycling about 1990. In theory, EPO use can increase VO2max by a significant amount, making it useful for endurance sports like cycling. Italian antidoping advocate Sandro Donati has claimed that the history of doping in cycling can be traced to the Italian Dr Francesco Conconi at the University of Ferrara. Conconi had worked on the idea of giving athletes transfusions of their own blood in the 1980s. Donati felt this work "opened the road to EPO . . . because blood doping was a trial to understand the role of EPO".Dr. Michele Ferrari, a former student and protege of Conconi, had a controversial interview mentioning the drug in 1994, just after his Gewiss-Ballan team had a remarkable performance in the La Flèche Wallonne race. Ferrari told lEquipe journalist Jean-Michel Rouet that EPO had no "fundamental" effect on performance and that if his riders used it, it would not "scandalize" himself. After the journalist pointed out several riders were suspected of dying from EPO, Ferrari said EPO was not dangerous, and only abuse of it was dangerous, saying, "Its also dangerous to drink 10 liters of orange juice." The orange juice comment has been widely misquoted. Ferrari was fired shortly after, but continued to work in the industry with top riders, allegedly including Lance Armstrong. That same year, Sandro Donati, working for the Italian National Olympic Committee, presented a report accusing Conconi of being linked to the use of EPO in the sport.In 1997, the Union Cycliste Internationale (UCI) instituted a new rule that riders testing above 50% haematocrit were not only immediately disqualified, but banned from racing for two weeks. Robert Millar, former racer, later wrote for Cycling News that the 50% limit was "an open invitation to dope to that level", pointing out that normally haematocrit levels would start "around 40-42%" and drop during the course of a "grand tour", but after EPO, they were staying at 50% for "weeks at a time". By 1998, EPO use had become widespread, and the Festina affair tarnished the 1998 Tour de France. One manager offered a 270,000-franc-per-month raise to Christophe Bassons if he would use EPO, but Bassons refused.In the 1998 Tour de France Stuart OGrady won one stage, held the Tour de France yellow jersey for three days, and came second in the points classification with the assistance of EPO. In 2010, Floyd Landis admitted to using performance-enhancing drugs, including EPO, throughout his career as a professional cyclist. In 2012, the USADA released a report on its investigation into massive doping by the US Postal Service cycling team under the leadership of Lance Armstrong. The report contained affidavits from numerous riders on the team, including Frankie Andreu, Tyler Hamilton, George Hincapie, Floyd Landis, Levi Leipheimer, and others, outlining that they and Armstrong used a cocktail of performance-enhancing substances for the Tour de France, most notably EPO, during Armstrongs seven consecutive Tour wins. It detailed how Armstrong and the Postal manager, Johan Bruyneel, forced other team members to dope as well. It also went to the root of their doping network, targeting the shadowy doctors and back room enablers who helped cyclists procure and administer drugs as well as highly placed executives who helped to avoid doping controls and hide positive test results. Armstrong was subsequently stripped of all of his victories from 1998 onward—including his Tour wins and his performance in the 2000 Summer Olympics. The UCI concurred with the decision. While several of the doping offenses took place outside the normal eight-year statute of limitations for doping offenses, USADA contended the statute of limitations did not apply due to Armstrongs "fraudulent concealment" of his doping. Longstanding precedent in U.S. law holds that the statute of limitations does not apply in cases of fraudulent conduct by a defendant. In accordance with this decision, Tour organizers removed Armstrongs name and results from the races history.Witnesses testified that code words used for EPO included "Edgar", "Poe", "Edgar Allan Poe", and "Zumo" (Spanish for juice). Dynepo Dynepo is the brand name for a form of EPO developed by Shire Pharmaceuticals. The first development steps were performed by HMR and Aventis. Aventis obtained the license in Europe in 2002. The company expected to launch the product in Europe in 2006, although patents held by the American biotechnology company Amgen, Inc. may have precluded its sale in the United States.Dynepo was made in cultured human cells. It was therefore expected to have an authentic human form of sialic acid and other oligosaccharide residues. It was hoped that this would make a longer-acting product than existing brands. There were concerns that such production would also make Dynepo undetectable in the urine tests for EPO used, at that time, to detect doping by athletes. Dynepo was withdrawn from European markets on 17 February 2009, for commercial reasons. On July 1, 2009, professional cycling team Silence–Lotto announced that Thomas Dekker was tested positive for Dynepo on a test taken on December 24, 2007, while Dekker was riding for Rabobank. References External links Media related to Erythropoiesis-stimulating agents at Wikimedia Commons "Erythropoietin". Drug Information Portal. U.S. National Library of Medicine. "Epoetin alfa". Drug Information Portal. U.S. National Library of Medicine. "Epoetin beta". Drug Information Portal. U.S. National Library of Medicine. "Darbepoetin Alfa". Drug Information Portal. U.S. National Library of Medicine. "Methoxy polyethylene glycol-epoetin beta". Drug Information Portal. U.S. National Library of Medicine.

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

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

Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated. Pathophysiology The innate immune system responds quickly to infection, with neutrophils (a type of white blood cells) being the first responders. Neutrophils enter the site of infection and begin to phagocytose (take up) pathogens. Once engulfed, the neutrophils must then degrade the captured pathogens–a process known as intracellular killing.One method of intracellular killing which takes place in the phagolysosomes of neutrophils involves the reaction of myeloperoxidase with hydrogen peroxide (H2O2) acquired in the cells from NADPH oxidase through the respiratory bursts. This reaction generates several acidic products including hypochlorous acid (HClO), which can break down pathogens. Bacteria such as Pseudomonas aeruginosa and fungi such as Candida albicans are killed in this manner.Neutrophils are also involved in killing extracellular pathogens (pathogens outside of the cell) through the release of NETs. These NETs contain myeloperoxidase, among other antimicrobial proteins. Once released outside of the cell, NETs trap pathogens and may in some cases kill them. Although myeloperoxidase is not required for all NET formation/release, NETs are only formed and released in response to Candida albicans when myeloperoxidase is present. Myeloperoxidase proteins in NETs can still react with H2O2 to form HClO and break down some extracellular pathogens. In myeloperoxidase deficient individuals, this extracellular pathogen killing doesn’t typically occur.Finally, during infection, neutrophils can migrate to the lymph nodes, where they deposit myeloperoxidase. Although the mechanisms of this process aren’t well understood, there is evidence that this extracellular myeloperoxidase interacts with dendritic cells (cells of the adaptive immune system) in the lymph nodes, leading to a decrease in adaptive immune system activity in response to infection. Presentation About 1:1,000 to 1:4,000 individuals in the United States and Europe and 1:55,000 individuals in Japan experience myeloperoxidase deficiency. The most common symptom of myeloperoxidase deficiency is frequent infections, particularly by the fungus Candida albicans. This symptom is especially frequent in individuals who also experience diabetes mellitus.The majority of myeloperoxidase-deficient individuals, however, do not display any significant tendencies towards chronic infections from most bacteria. This is likely due to the fact that the absence of myeloperoxidase leads to increased neutrophil phagocytosis and degranulation as well as increased development of the adaptive immune system. That is, other aspects of the immune system typically compensate for the lack of myeloperoxidase, leading to relatively mild symptoms. Nonetheless, myeloperoxidase-deficient individuals have been found to experience more chronic inflammatory conditions (such as rheumatoid arthritis, pulmonary/skin inflammation, kidney/heart disease, etc.) than individuals with sufficient myeloperoxidase. Researchers hypothesize this may be a result of heightened adaptive immune system activity in individuals with myeloperoxidase deficiency. There is also some evidence that congenital myeloperoxidase deficiency is correlated with higher rates of malignant tumors. Types MPO deficiency is broken down into two categories: primary/congenital and secondary/acquired. Primary MPO deficiency is an autosomal recessive genetic disorder, which is caused by mutations in the myeloperoxidase gene on chromosome 17q23. There are several different known mutations of this gene which all lead to myeloperoxidase deficiency.Secondary MPO deficiency, on the other hand, occurs in various clinical situations as a result of hematological neoplasm, disseminated cancers, some drugs, iron deficiency, lead intoxication, thrombotic disease, renal transplantation, severe infectious disease, diabetes mellitus, neuronal lipofuscinosis, or pregnancy. Secondary MPO deficiency is typically partial, meaning only a portion of the affected individual’s neutrophils lack functional myeloperoxidase. Diagnosis Myeloperoxidase deficiency can be diagnosed via flow cytometry and cytochemical stains. Various devices can divide up leukocyte (white blood cell) populations based on their size and peroxidase activity. Specific stains bind to myeloperoxidase, and individuals who display large, granulated cells without this stain through flow cytometry typically have myeloperoxidase deficiency. In this way, it’s apparent when neutrophils are present in an individual but peroxidase activity is absent.Note, myeloperoxidase deficiency can cause false positives in the diagnosis of chronic granulomatous disease, a condition which includes dysfunctional NADPH oxidase. Both disorders interfere with neutrophils’ abilities to kill pathogens through reaction with oxidative species. However, chronic granulomatous disease leads to inadequate H2O2 production, while myeloperoxidase deficiency is characterized by a lack of myeloperoxidase to interact with present H2O2. Testing with NADPH oxidase-specific assays can lead to positive results for chronic granulomatous disease and negative results for myeloperoxidase deficiency. Treatment Most individuals with myeloperoxidase deficiency do not need regular treatment, as they experience only mild symptoms, if any at all. Continued antibiotic use is not recommended in myeloperoxidase-deficient patients who don’t experience recurrent infections.Acquired myeloperoxidase deficiency typically goes away when the underlying condition is treated. In particular, when myeloperoxidase deficiency is caused by severe iron deficiency, treatment with iron returns myeloperoxidase function to normal. 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.

Could you please explain the term 'Klatskin tumor' in simple language?

A Klatskin tumor (or hilar cholangiocarcinoma) is a cholangiocarcinoma (cancer of the biliary tree) occurring at the confluence of the right and left hepatic bile ducts. The disease was named after Gerald Klatskin, who in 1965 described 15 cases and found some characteristics for this type of cholangiocarcinoma Cause The cause of cholangiocarcinoma has not been defined. A number of pathologic conditions, however, resulting in either acute or chronic biliary tract epithelial injury may predispose to malignant change. Primary sclerosing cholangitis, an idiopathic inflammatory condition of the biliary tree, has been associated with the development of cholangiocarcinoma in up to 40% of patients. Congenital biliary cystic disease, such as choledochal cysts or Carolis disease, has also been associated with malignant transformation in up to 25% of cases. These conditions appear to be related to an anomalous pancreatico-biliary duct junction and, perhaps, are related to the reflux of pancreatic secretions into the bile duct. Chronic biliary tract parasitic infection, seen commonly in Southeast Asia due to Clonorchis sinensis and Opisthorchis viverrini, has also been identified as a risk factor. Although gallstones and cholecystectomy are not thought to be associated with an increased incidence of cholangiocarcinoma, hepatolithiasis and choledocholithiasis may predispose to malignant change. Further, industrial exposure to asbestos and nitrosamines, and the use of the radiologic contrast agent, Thorotrast (thorium dioxide), are considered to be risk factors for the development of cholangiocarcinoma. Diagnosis Levels of the tumor markers carbohydrate antigen 19-9 (CA 19–9), carcinoembryonic antigen (CEA) and CA 125 are abnormally high in the bloodstreams of patients with intrahepatic cholangiocarcinoma and Klatskin tumor. The serum CA 19–9 in particular may be very high. The ultrasonography (and the use of Doppler modes) permit definitive diagnosis of a large number of lesions and the involvement of hepatic hilum, but it is less sensitive than CT or MRI in detecting focal lesions. Ultrasonography always detects dilatation of the bile ducts, but more rarely the tumor itself.Magnetic resonance cholangiopancreatography (MRCP) is a good non-invasive alternative to these other procedure. This technique demonstrates hepatic parenchyma and its accurate for detecting nodular carcinomas and infiltrating lesions. Treatment Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. Complete resection of the tumor, especially in early-stage disease, offers hope of long-term survival. However, patients that are candidates for resectability are few and moreover many of these patients will have a relapse despite apparent removal of the tumor. The type of surgery and the extent of the resection depend on the location of the tumor and the degree of extension. In some cases, the obstruction, jaundice may present early and compel the patient to seek help. More often, liver resection is not a viable option because many patients are of advanced age, have multiple co-pathologies and are therefore at high risk. Of late there has been renewed interest in liver transplantation from deceased donors along with add on therapy. Prognosis remains poor. Epidemiology Approximately 15,000 new cases of liver and biliary tract carcinoma are diagnosed annually in the United States, with roughly 10% of these cases being Klatskin tumors. Cholangiocarcinoma accounts for approximately 2% of all cancer diagnoses, with an overall incidence of 1.2/100,000 individuals. Two-thirds of cases occur in patients over the age of 65, with a nearly ten-fold increase in patients over 80 years of age. The incidence is similar in both men and women. References == External links ==

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Could you provide a brief overview of 'Meconium' in a medical context?

Meconium is the earliest stool of a mammalian infant resulting from defecation. Unlike later feces, meconium is composed of materials ingested during the time the infant spends in the uterus: intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile, and water. Meconium, unlike later feces, is viscous and sticky like tar – its color usually being a very dark olive green and it is almost odorless. When diluted in amniotic fluid, it may appear in various shades of green, brown, or yellow. It should be completely passed by the end of the first few days after birth, with the stools progressing toward yellow (digested milk). Clinical significance Meconium in amniotic fluid Meconium is normally retained in the infants bowel until after birth, but sometimes it is expelled into the amniotic fluid (also called "amniotic liquor") prior to birth or during labor and delivery. The stained amniotic fluid (called "meconium liquor" or "meconium-stained liquor") is recognized by medical staff as a possible sign of fetal distress. Some post-dates pregnancies (when they are more than 40 weeks pregnant) may also have meconium-stained liquor without fetal distress. Medical staff may aspirate the meconium from the nose and mouth of a newborn immediately after delivery in the event the baby shows signs of respiratory distress to decrease the risk of meconium aspiration syndrome, which can occur in meconium-stained amniotic fluid. Most of the time that the amniotic fluid is stained with meconium, it will be homogeneously distributed throughout the fluid, making it brown. This indicates that the fetus passed the meconium some time ago such that sufficient mixing occurred as to establish the homogeneous mixture. Terminal meconium occurs when the fetus passes the meconium a short enough time before birth/cesarean section that the amniotic fluid remains clear, but individual clumps of meconium are in the fluid. Failure to pass meconium The failure to pass meconium is a symptom of several diseases including Hirschsprungs disease and cystic fibrosis. The meconium sometimes becomes thickened and congested in the intestines, a condition known as meconium ileus. Meconium ileus is often the first sign of cystic fibrosis. In cystic fibrosis, the meconium can form a bituminous black-green mechanical obstruction in a segment of the ileum. Beyond this, there may be a few separate grey-white globular pellets. Below this level, the bowel is a narrow and empty micro-colon. Above the level of the obstruction, there are several loops of hypertrophied bowel distended with fluid. No meconium is passed, and abdominal distension and vomiting appear soon after birth. About 20% of cases of cystic fibrosis present with meconium ileus, while approximately 20% of one series of cases of meconium ileus did not have cystic fibrosis. The presence of meconium ileus is not related to the severity of the cystic fibrosis. The obstruction can be relieved in a number of different ways.Meconium ileus should be distinguished from meconium plug syndrome, in which a tenacious mass of mucus prevents the meconium from passing and there is no risk of intestinal perforation. Meconium ileus has a significant risk of intestinal perforation. In a barium enema, meconium plug syndrome shows a normal or dilated colon as compared to micro-colon in meconium ileus. Testing meconium for drugs Meconium can be tested for various drugs, to check for in utero exposure. Using meconium, a Canadian research group showed that by measuring a by-product of alcohol, fatty acid ethyl esters (FAEE) they could objectively detect excessive maternal drinking of alcohol during pregnancy. In the US, the results of meconium testing may be used by child protective services and other law enforcement agencies to determine the eligibility of the parents to keep the newborn. Meconium can also be analyzed to detect the tobacco use of mothers during their pregnancy, which is commonly under-reported. Sterility The issue of whether meconium is sterile remains debated and is an area of ongoing research. Although some researchers have reported evidence of bacteria in meconium, this has not been consistently confirmed. Other researchers have raised questions about whether these findings may be due to contamination after sample collection and that meconium is, in fact, sterile until after birth. Further researchers have hypothesized that there may be bacteria in the womb, but these are a normal part of pregnancy and could have an important role in shaping the developing immune system and are not harmful to the baby. Etymology The Latin term meconium derives from the Greek μηκώνιον, mēkōnion, a diminutive of μήκων, mēkōn, i.e. poppy, in reference either to its tar-like appearance that may resemble some raw opium preparations or to Aristotles belief that it induces sleep in the fetus. Other uses In biology, meconium describes the metabolic waste product from the pupal stage of an insect that is expelled through the anal opening of the adult upon eclosion from the pupa. Other insects, such as beetles and some Hymenoptera (Aculeata) expel the meconium at the end of the larval stage, before becoming a pupa. Gallery References External links Media related to Meconium at Wikimedia Commons

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What is the significance of the term 'Atenolol' in the medical field?

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken by mouth or by injection into a vein. It can also be used with other blood pressure medications.Common side effects include feeling tired, heart failure, dizziness, depression, and shortness of breath. Other serious side effects include bronchospasm. Use is not recommended during pregnancy and alternative drugs are preferred when breastfeeding. It works by blocking β1-adrenergic receptors in the heart, thus decreasing the heart rate and workload.Atenolol was patented in 1969 and approved for medical use in 1975. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2020, it was the 53rd most commonly prescribed medication in the United States, with more than 12 million prescriptions. Medical uses Atenolol is used for a number of conditions including hyperthyroidism, hypertension, angina, long QT syndrome, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, and the symptoms of alcohol withdrawal.The role for β-blockers in general in hypertension was downgraded in June 2006 in the United Kingdom, and later in the United States, as they are less appropriate than other agents such as ACE inhibitors, calcium channel blockers, thiazide diuretics and angiotensin receptor blockers, particularly in the elderly. Side effects Hypertension treated with a β-blocker such as atenolol, alone or in conjunction with a thiazide diuretic, is associated with a higher incidence of new onset type 2 diabetes mellitus compared to those treated with an ACE inhibitor or angiotensin receptor blocker. β-blockers, of which atenolol is mainly studied, provides weaker protection against stroke and mortality in patients over 60 years old compared to other antihypertensive medications. Diuretics may be associated with better cardiovascular and cerebrovascular outcomes than β-blockers in the elderly. Overdose Symptoms of overdose are due to excessive pharmacodynamic actions on β1 and also β2-receptors. These include bradycardia (slow heartbeat), severe hypotension with shock, acute heart failure, hypoglycemia and bronchospastic reactions. Treatment is largely symptomatic. Hospitalization and intensive monitoring is indicated. Activated charcoal is useful to absorb the drug. Atropine will counteract bradycardia, glucagon helps with hypoglycemia, dobutamine can be given against hypotension and the inhalation of a β2-mimetic as hexoprenalin or salbutamol will terminate bronchospasms. Blood or plasma atenolol concentrations may be measured to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 3 mg/L during therapeutic administration, but can range from 3–30 mg/L in overdose victims. Society and culture Atenolol has been given as an example of how slow healthcare providers are to change their prescribing practices in the face of medical evidence that indicates that a drug is not as effective as others in treating some conditions. In 2012, 33.8 million prescriptions were written to American patients for this drug. In 2014, it was in the top (most common) 1% of drugs prescribed to Medicare patients. Although the number of prescriptions has been declining steadily since limited evidence articles contesting its efficacy was published, it has been estimated that it would take 20 years for doctors to stop prescribing it for hypertension. Despite its diminished efficacy when compared to newer antihypertensive drugs, atenolol and other beta blockers are still a relevant clinical choice for treating some conditions, since beta blockers are a diverse group of medicines with different properties that still requires further research. As consequence, reasons for the popularity of beta blockers cannot be fully attributed to a slow healthcare system – patient compliance factor, such as treatment cost and duration, also affect adherence and popularity of therapy. References External links "Atenolol". Drug Information Portal. U.S. National Library of Medicine.

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

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

Oligomenorrhea is infrequent (or, in occasional usage, very light) menstruation. More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Menstrual periods should have been regularly established before the development of infrequent flow. The duration of such events may vary. Causes Oligomenorrhea can be a result of prolactinomas (adenomas of the anterior pituitary). It may be caused by thyrotoxicosis, hormonal changes in perimenopause, Prader–Willi syndrome, and Graves disease. Endurance exercises such as running or swimming can affect the reproductive physiology of female athletes. Female runners, swimmers and ballet dancers either menstruate infrequently in comparison to non-athletic females of comparable age or exhibit amenorrhea. A more recent study shows that athletes competing in sports that emphasise thinness or a specific weight exhibit a higher rate of menstrual dysfunction than either athletes competing in sports with less focus on these or control subjects.Breastfeeding has been linked to irregularity of menstrual cycles due to hormones that delay ovulation. People with polycystic ovary syndrome (PCOS) are also likely to have oligomenorrhea. PCOS is a condition in which excessive androgens (male sex hormones) are released by the ovaries. People with PCOS show menstrual irregularities that range from oligomenorrhea and amenorrhea, to very heavy, irregular periods. The condition affects about 6% of premenopausal females. Eating disorders can result in oligomenorrhea. Although menstrual disorders are most strongly associated with anorexia nervosa, bulimia nervosa may also result in oligomenorrhea or amenorrhea. There is some controversy regarding the mechanism for the menstrual dysregulation, since amenorrhea may sometimes precede substantial weight loss in some anorexics. See also Amenorrhea: a total cessation of the menstrual period Menorrhagia: unusually heavy periods 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'd like to learn more about the medical term 'Hydrocortisone sodium succinate.' Can you provide some details?

Hydrocortisone sodium succinate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester. == References ==

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

I'm looking for a concise explanation of the medical term 'Bouffée délirante.'

Bouffée délirante (BD) is an acute and transient psychotic disorder. It is a uniquely French psychiatric diagnostic term with a long history in France and various French speaking nations: Caribbean, e.g. Haiti, Guadeloupe, Antilles and Francophone Africa. The term BD was originally coined and described by Valentin Magnan (1835–1916), fell into relative disuse and was later revived by Henri Ey (1900–1977). Terminology The French word bouffée is often translated as a puff or waft (as of air), but can also mean a flash, rush or surge. Chabrol translates the word délirante as "delusional". Other common dictionary definitions include less useful meanings such as "crazy" or "incoherent". A reasonable English translation of the term bouffée délirante is "delusional flash". Description Bouffée délirante is "an acute, brief nonorganic psychosis that typically presents with a sudden onset of fully formed, thematically variable delusions and hallucinations against a background of some degree of clouding of consciousness, unstable and fluctuating affect, and spontaneous recovery with some probability of relapse." The following criteria have been suggested for a diagnosis of BD: a) abrupt onset, b) polymorphic delusions, emotional changes, mood swings, depersonalization, derealization and/or hallucinations, c) complete remission within weeks or a few months, d) exclusion of organic causation, alcohol or drug use, e) no psychiatric antecedents with the exception of a previous episode of bouffée délirante. American academic investigators proposed the following definition in 2011: "The French concept of bouffée délirante refers to conditions with a sudden onset marked by prominent delusions with hallucinations, confusion, anxiety and affective symptoms. Symptoms vary rapidly, perhaps even by the hour, and there is a rapid return to the premorbid state of health." A frequently quoted authority on BD, P. Pichot (Hôpital Sainte Anne, Paris) provides this description of BD: sudden onset: a bolt from the blue. manifold delusions without recognizable structure and cohesiveness with/without hallucinations. clouding of consciousness associated with emotional instability. absence of physical signs. rapid return to pre-morbid level of functioning.Pichots criteria can be refined further with these typical clinical characteristics: age: usually between 20 and 40 years of age. onset: acute without prior mental illness (with the exception of previous episodes of bouffée délirante). past history: no chronic mental disturbance after resolution of the BD episode. typical symptoms: delusions and/or hallucinations of any type. Depersonalization/derealization and/or confusion depression and/or elation. symptoms quite variable from day to day and even hour to hour. not due to alcohol, drug use, or organic mental disorder. Formal classification In 1968 the French national organization INSERM (Institut National de la Santé et de la Recherche Médicale) classification of mental illness referenced two types of BD in their category acute delusional psychoses and confusional states viz. reactive bouffée délirante and bouffée délirante (Magnans type). This classification scheme has been largely replaced by the two nosological systems discussed below. The World Health Organization edition of the International Classification of Diseases 10th edition:version 2019 (ICD-10, CIM-10 en français), lists BD as the subentry "Bouffée délirante without symptoms of schizophrenia or unspecified" under diagnosis code F23: Acute and Transient Psychotic Disorders subsection, F23.0: Acute polymorphic psychotic disorder without symptoms of schizophrenia. It is likely that the use of the term BD in French clinical psychiatry will decline further with the proposed 2022 implementation of ICD-11 (which was released in May 2019.) In contrast to the ICD-10, the term BD does not appear anywhere in ICD-11. The closest clinical match for BD in the ICD-11 is code 6A23, Acute and transient psychotic disorder which is defined as acute onset of psychotic symptoms that emerge without a prodrome and reach their maximal severity within two weeks. Symptoms may include delusions, hallucinations, disorganization of thought processes, perplexity or confusion, and disturbances of affect and mood. Catatonia-like psychomotor disturbances may be present. Symptoms typically change rapidly, both in nature and intensity, from day to day, or even within a single day. The duration of the episode does not exceed 3 months, and most commonly lasts from a few days to 1 month. The symptoms are not a manifestation of another health condition (e.g., a brain tumor) and are not due to the effect of a substance or medication on the central nervous system (e.g., corticosteroids), including withdrawal (e.g., alcohol withdrawal). The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnostic category brief psychotic disorder is probably the closest analog of BD. The French term BD is nowhere mentioned in DSM-5. The diagnosis of Bouffée Délirante is still in use in the Classification Française des Troubles Mentaux (French Classification of Mental Disorder, CFTM) under the name Bouffée délirante aiguë. Incidence The frequency of BD diagnoses in French hospitals has been declining due to the widespread acceptance of international classification systems such as the ICD-10 and DSM-5. However, the BD diagnosis has been used as recently as 2019 in Le Groupe Hospitalier Universitaire Paris psychiatrie & neurosciences (GHU Paris), Maison Blanche Bichat XVIII. Older estimates of the incidence of BD in psychiatric hospitalizations ranges from 1–5%. Psychiatric admission reviews show that 2–7% of first episode psychotic episodes are due to brief psychotic disorder; here serving as a surrogate diagnosis for BD. Some authors state that the diagnostic category of BD can be eliminated because it can be fully integrated into the Polymorphic subgroup of Acute and Transient Psychotic Disorders of the ICD-10. Treatment There are no current published guidelines in the English language psychiatric literature that discuss treatment for BD. A 2019 case of BD from GHU Paris treated the patient with largactil (chlorpromazine). Assuming that BPD is an equivalent diagnosis, treatment depends on the severity of the episode. Mildly affected patients may receive supportive management and observation with additional outpatient therapy. More severe illness may require inpatient hospitalization and pharmacologic treatment with benzodiazepines and/or antipsychotic medication, for example: risperidone, though no clinical trials have examined the efficacy of therapy for BPD. Prognosis It is difficult to firmly establish the prognosis of first episode BD patients with respect to progression to other psychiatric illness or relapse to another psychotic episode. This is due to the fact that high quality follow-up studies of large cohorts of BD patients are unavailable in part because of the uncommon nature of the illness and non-standardization of diagnostic methods. Investigators attempting to define the prognosis in BD have used data from similar conditions, i.e. acute transient psychotic disorder (ATPD) and brief psychotic disorder (BPD). A meta-analysis involving 11,000 patients estimated the rate of recurrent psychotic episodes in ATPD and BPD patients was 51% at 30 months compared to first episode schizophrenia patients who had an 84% recurrence rate at 36 months. As suggested by the various definitions of BD discussed above, rapid recovery and return to pre-morbid level of function is expected, though quantitative data is lacking. Society Psychiatric illnesses comparable to the unique French BD can be seen in the cycloid psychosis of German speaking countries and the psychogenic psychosis in Scandinavia. It has been argued that acute and transient psychoses are more common in African and Afro-Caribbean populations and may be attributable to socio-cultural factors. This has led to the term "culture-bound syndrome." It must be stressed that the term BD long predates any such socio-cultural, ethnic, or regional uses. The African and Caribbean nuances of the diagnosis and presentation of BD has been extensively reviewed by Henry MB Murphy. Note that DSM-5 does not use the term culture-bound and the term BD is not listed in the "Glossary of Cultural Concepts of Distress" in DSM-5. Summary BD is a psychotic disorder of short duration generally considered to have a relatively good prognosis. The diagnosis has undergone numerous changes and re-evaluations since its description by Magnan in 1886. Though becoming replaced by more internationally recognized terminology, BD as a diagnostic category is still in use in France and other French speaking nations. See also Brief psychotic disorder == References ==

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

I'm looking for a concise explanation of the medical term 'Alcohol abuse.'

Alcohol abuse encompasses a spectrum of unhealthy alcohol drinking behaviors, ranging from binge drinking to alcohol dependence, in extreme cases resulting in health problems for individuals and large scale social problems such as alcohol-related crimes. Alcohol abuse was a psychiatric diagnosis in the DSM-IV, and has been merged with alcohol dependence into alcohol use disorder in the DSM-5.Globally, excessive alcohol consumption is the seventh leading risk factor for both death and the burden of disease and injury. In short, except for tobacco, alcohol accounts for a higher burden of disease than any other drug. Alcohol use is a major cause of preventable liver disease worldwide, and alcoholic liver disease is the main alcohol-related chronic medical illness. Millions of people of all ages, from adolescents to the elderly, engage in unhealthy drinking. Alcohol use disorder can affect people from all walks of life. There are many factors that play a role in causing someone to have an alcohol use disorder: genetics, psychiatric conditions, trauma, environmental issues, and even parental drinking habits. Definitions Risky drinking (also called hazardous drinking) is defined by drinking above the recommended limits: greater than 14 standard drinks units per week or greater than 4 standard drinks on a single occasion in men greater than 7 standard drinks units per week or greater than 3 standard drinks on a single occasion in women any drinking in pregnant women or persons < 21 years oldBinge drinking is a pattern of alcohol consumption that brings blood alcohol concentration ≥ 0.08%, usually corresponding to ≥ 5 standard drinks on a single occasion in men ≥ 4 standard drinks on a single occasion in womenIn the DSM-IV, alcohol abuse and alcohol dependence were defined as distinct disorders from 1994 to 2013. The DSM-5 combined those two disorders into alcohol use disorder with sub-classifications of severity. The DSM-IV definition is no longer used. There is no "alcoholism" diagnosis in medical care. Alcohol misuse is a term used by United States Preventive Services Task Force to describe a spectrum of drinking behaviors that encompass risky drinking, alcohol abuse, and alcohol dependence (similar meaning to alcohol use disorder but not a term used in DSM). Signs and symptoms Individuals with an alcohol use disorder will often complain of difficulty with interpersonal relationships, problems at work or school, and legal problems. Additionally, people may complain of irritability and insomnia. Alcohol abuse is also an important cause of chronic fatigue. Signs of alcohol abuse are related to alcohols effects on organ systems. However, while these findings are often present, they are not necessary to make a diagnosis of alcohol abuse. Signs of alcohol abuse show its drastic effects on the central nervous system, including inebriation and poor judgment; chronic anxiety, irritability, and insomnia. Alcohols effects on the liver include elevated liver function tests (classically AST is at least twice as high as ALT). Prolonged use leads to cirrhosis and liver failure. With cirrhosis, patients develop an inability to process hormones and toxins. The skin of a patient with alcoholic cirrhosis can feature spider angiomas, palmar erythema and — in acute liver failure — jaundice and ascites. The derangements of the endocrine system lead to the enlargement of the male breasts. The inability to process toxins leads to liver disease, such as hepatic encephalopathy.Alcohol abuse can result in brain damage which causes impairments in executive functioning such as impairments to working memory and visuospatial function, and can cause an abnormal personality as well as affective disorders to develop. Binge drinking is associated with individuals reporting fair to poor health compared to non-binge drinking individuals and which may progressively worsen over time. Alcohol also causes impairment in a persons critical thinking. A persons ability to reason in stressful situations is compromised, and they seem very inattentive to what is going on around them. Social skills are significantly impaired in people who have alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The prefrontal cortex is responsible for cognitive functions such as working memory, impulse control and decision making. This region of the brain is vulnerable to chronic alcohol-induced oxidative DNA damage. The social skills that are impaired by alcohol abuse include impairments in perceiving facial emotions, difficulty with perceiving vocal emotions and theory of mind deficits; the ability to understand humour is also impaired in alcohol abusers. Adolescent binge drinkers are most sensitive to damaging neurocognitive functions especially executive functions and memory. People who abuse alcohol are less likely to survive critical illness with a higher risk for having sepsis and were more likely to die during hospitalization.A smaller volume of consumed alcohol has a greater impact on the older adult than it does on a younger individual. As a result, the American Geriatrics Society recommends for an older adult with no known risk factors less than one drink a day or fewer than two drinks per occasion regardless of gender. Violence Alcohol abuse is significantly associated with suicide and violence. Alcohol is the most significant health concern in Native American communities because of very high rates of alcohol dependence and abuse; up to 80 percent of suicides and 60 percent of violent acts are a result of alcohol abuse in Native American communities.In the United States alcohol-related violence is related to more severe injuries and chronic cases. Pregnancy Alcohol abuse among pregnant women causes their baby to develop fetal alcohol syndrome. Fetal alcohol syndrome is the pattern of physical abnormalities and the impairment of mental development which is seen with increasing frequency among children with alcoholic mothers. Alcohol exposure in a developing fetus can result in slowed development of the fetal brain, resulting in severe retardation or death. Surviving infants may have severe abnormalities such as abnormal eyes, fissures, lips and incomplete cerebella. Some infants may develop lung disease. It is even possible that the baby throughout pregnancy will develop heart defects such as ventricular septal defect or atrial septal defect. Experts suggest that pregnant women take no more than one unit of alcohol per day. However, other organizations advise complete abstinence from alcohol while pregnant. Adolescence Adolescence and the onset of puberty have both a physiological and social impact on a developing person. About half of grade 12 students have been drunk, and a third binge drink. About 3% drink every day. One of these social impacts is the increase in risk-taking behaviors, such as the emergence of alcohol use. Children aged 16 and under who consume alcohol heavily display symptoms of conduct disorder. Its symptoms include troublesome behaviour in school, constantly lying, learning disabilities and social impairments.Alcohol abuse during adolescence greatly increases the risk of developing an alcohol use disorder in adulthood due to changes to neurocircuitry that alcohol abuse causes in the vulnerable adolescent brain. Younger ages of initial consumption among males in recent studies has shown to be associated with increased rates of alcohol abuse within the general population.Societal inequalities (among other factors) have influenced an adolescents decision to consume alcohol. One study suggests that girls were scrutinized for "drinking like men", whereas magazines that target the male population sent underlying messages to boys and or men that drinking alcohol was "masculine". (Bogren, 2010) Causes The cause of alcohol abuse is complex. Alcohol abuse is related to economic and biological origins and is associated with adverse health consequences. Peer pressure influences individuals to abuse alcohol; however, most of the influence of peers is due to inaccurate perceptions of the risks of alcohol abuse. According to Gelder, Mayou and Geddes (2005) easy accessibility of alcohol is one of the reasons people engage in alcohol abuse as this substance is easily obtained in shops. Another influencing factor among adolescents and college students are the perceptions of social norms for drinking; people will often drink more to keep up with their peers, as they believe their peers drink more than they actually do. They might also expect to drink more given the context (e.g. sporting event, house party, etc.). This perception of norms results in higher alcohol consumption than is normal. Alcohol abuse is also associated with acculturation, because social and cultural factors such as an ethnic groups norms and attitudes can influence alcohol abuse. Mental illness A person misusing alcohol may be doing so because they find alcohols effects provide relief from a psychological problem, such as anxiety or depression. Often both the alcohol misuse and psychological problems need to be treated at the same time.The numbing effects of alcohol and narcotics can become a coping strategy for traumatized people who are unable to dissociate themselves from the trauma. However, the altered or intoxicated state of the abuser prevents the full consciousness necessary for healing. Puberty Gender differences may affect drinking patterns and the risk for developing alcohol use disorders. Sensation-seeking behaviors have been previously shown to be associated with advanced pubertal maturation, as well as the company of deviant peers. Early pubertal maturation, as indicated by advanced morphological and hormonal development, has been linked to increased alcohol usage in both male and female individuals. Additionally, when controlling for age, this association between advanced development and alcohol use still held true. Mechanisms Excessive alcohol use causes neuroinflammation and leads to myelin disruptions and white matter loss. The developing adolescent brain is at increased risk of brain damage and other long-lasting alterations to the brain. Adolescents with an alcohol use disorder damage the hippocampal, prefrontal cortex, and temporal lobes. Chronic alcohol exposure can result in increased DNA damage in the brain, as well as reduced DNA repair and increased neuronal cell death. Alcohol metabolism generates genotoxic acetaldehyde and reactive oxygen species.Until recently, the underlying mechanisms mediating the link between pubertal maturation and increased alcohol use in adolescence was poorly understood. Now research has suggested that sex steroid hormone levels may play a role in this interaction. When controlling for age, it was demonstrated that elevated estradiol and testosterone levels in male teenagers undergoing pubertal development was linked to increased alcohol consumption. It has been suggested that sex hormones promote alcohol consumption behaviors in teens by stimulating areas in the male adolescent brain associated with reward processing. The same associations with hormone levels were not demonstrated in females undergoing pubertal development. It is hypothesized that sex steroid hormones, such as testosterone and estradiol, are stimulating areas in the male brain that function to promote sensation-seeking and status-seeking behaviors and result in increased alcohol usage.Additionally, the enzyme TTTan aromatase, which functions in the male brain to convert testosterone to estradiols, has been linked to addictive and reward-seeking behaviors. Therefore, the increased activity of the enzyme may be influencing male adolescent alcohol-usage behaviors during pubertal development. The underlying mechanisms for female alcohol consumption and abuse is still under examination, but is believed to be largely influenced by morphological, rather than hormonal, changes during puberty as well as the presence of deviant peer groups.The brain goes through dynamic changes during adolescence as a result of advancing pubertal maturation, and alcohol can damage long- and short-term growth processes in teenagers. The rapid effect of drugs releases the neurotransmitter dopamine which acts as reinforcement for the behavior.Alcohol is the most recreationally used drug internationally, throughout history it has played a variety of roles, from medicine to a mood enhancer. Alcoholism and alcohol abuse however have undergone rigorous examination as a disease which has pervasive physiological and biosocial implications. The genesis and maintenance of the disease involves the mind, body, society and culture. A common anthropological approach to understanding alcoholism is one which relates to a social factor, and this is cross-cultural studies. The description and analysis of the degree of possibilities in drinking and its results among various populations indeed constitutes one of anthropologys major contributions to the field of alcohol studies. Understanding interactions between factors and evaluating ideas regarding how alcohol usage correlates to other cultural elements requires a number of cross-cultural comparisons. Anthropologists have analyzed a large global sample of cultures examining the association between particular traits for each which relate to the cultural components of alcoholism, these include significant measures which emphasize the social system, reliance and anxiety and strength as physical and social measures. These are the primary drivers of consuming alcohol affecting individuals on a psychosocial level.Individualistic cultures such as the United States or Australia are amongst some of the highest consumers of alcohol in the whole world, however this rate of consumption does not necessarily coincide with the rate of abuse as countries like Russia which are highly collectivist see the highest rates of Alcoholism. Research suggests that people who score highly on individualism, a trait commonly fostered by the culture, report a lower rate of alcohol abuse and alcohol related disorders so much so that the association was negative, however a higher average consumption of alcohol per week. It is implied that individuals will drink more in a given setting, or on average because they are less receptive towards negative social attitudes surrounding excessive consumption. This however acts on another component, by where individualism protects from maladaptive consumption by lowering the need to drink socially. The final axis by which individualism protects from abusive consumption is that it promotes higher degrees of individualization and achievement values which promote personally suited rewards, this allow the individual to be more cognizant of potential alcohol abuse, and therefore protect from damaging mentalities in those who already identify as drinkers.Alcohol abuse also has a variety of biosocial implications, such as the physiologically effects of a detox, how the detox period interacts with ones social life and how these interactions can make beating alcoholism a complex, difficult process. Alcohol abuse can lead to a number of physical issues and may even create a mental health condition, leading to a double classification for the alcoholic. The stress, the social perceptions of these issues may reinforce abusive drinking habits. Alcoholism is the most severe form of alcohol dependence and abuse, it is often in fact a complicated hereditary disease. While it can run it families this is only a correlation and does not prove that the inherited factors play a role. Genetic influences on its genesis are suggested by numerous different sources of evidence. Alcoholism among adopted people has a stronger correlation with their biological parents than with their adopted parents, according to adoption research. Alcohol especially has a large effect on young and developing brains and chances of further abuse, the culture surrounding the acceptable age of drinking therefore can be a biosocial factor. This however isnt always preventable, alcohol when consumed during pregnancy is profoundly damaging. The umbilical cord allows the mothers blood alcohol to reach the infant. Consumption of alcohol during pregnancy can result in miscarriage, and a number of physical and cognitive that can last a lifetime to the child. Therefore the biological implications of alcohol abuse are also further reaching than just the physical issues experienced by the consumer. Diagnosis DSM-IV Alcohol abuse was defined in the DSM-IV as a maladaptive pattern of drinking. For its diagnosis, at least one of the following criteria had to be fulfilled in the last 12 months: Recurrent use of alcohol resulting in a failure to fulfill major role obligations at work, school, or home Recurrent alcohol use in situations in which it is physically hazardous Recurrent alcohol-related legal problems Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol DSM-5 The alcohol abuse diagnosis is no longer used in the DSM-5 (released in 2013), it is now part of the alcohol use disorder diagnosis. Of the four alcohol abuse criteria, all except the one referring to alcohol-related legal problems are included in the alcohol use disorder criteria. Screening The Alcohol Use Disorders Identification Test (AUDIT) is considered the most accurate alcohol screening tool for identifying potential alcohol misuse, including dependence. It was developed by the World Health Organisation, designed initially for use in primary healthcare settings with supporting guidance. Prevention Preventing or reducing the harm has been called for via increased taxation of alcohol, stricter regulation of alcohol advertising, and the provision of brief Interventions. Brief Interventions for alcohol abuse reduce the incidence of unsafe sex, sexual violence, unplanned pregnancy, and, likely, STD transmission. Information and education on social norms and the harms associated with alcohol abuse delivered via the internet or face-to-face has not been found to result in any meaningful benefit in changing harmful drinking behaviours in young people.According to European law, individuals who are suffering from alcohol abuse or other related problems cannot be given a drivers license, or if in possession of a license cannot get it renewed. This is a way to prevent individuals driving under the influence of alcohol, but does not prevent alcohol abuse per se.An individuals need for alcohol can depend on their familys alcohol use history. For instance, if it is discovered that their family history with alcohol has a strong pattern, there might be a need for education to be set in place to reduce the likelihood of reoccurrence (Powers, 2007). However, studies have established that those with alcohol abuse tend to have family members who try to provide help. On many of these occasions, the family members would try to help the individual to change or to help improve the individuals lifestyle. Treatment Youth treatment and intervention should focus on eliminating or reducing the effects of adverse childhood experiences, like childhood maltreatment, since these are common risk factors contributing to the early development of alcohol abuse. Approaches like contingency management and motivational interviewing have shown to be effective means of treating substance abuse in impulsive adolescents by focusing on positive rewards and redirecting them towards healthier goals. Educating youth about what is considered heavy drinking along with helping them focus on their own drinking behaviors has been shown to effectively change their perceptions of drinking and could potentially help them to avoid alcohol abuse. Completely stopping the use of alcohol, or "abstinence", is the ideal goal of treatment. The motivation required to achieve abstinence is dynamic; family, friends and health practitioners play a role in affecting this motivation.Some people who abuse alcohol may be able to reduce the amount they drink, also called "drinking in moderation". If this method does not work, the person may need to try abstinence. Abstinence has been regularly achieved by many alcoholics in Alcoholics Anonymous.Mindfulness-based intervention programs (that encourage people to be aware of their own experiences in the present moment and of emotions that arise from thoughts) can reduce the consumption of alcohol.A major barrier to seeking treatment for those struggling with alcohol abuse is the stigma associated with alcohol abuse itself. Those who struggle with alcohol abuse are less likely to utilize substance (or alcohol) abuse treatment services when they perceived higher stigma with alcohol abuse. The stigmatization of individuals who abuse alcohol has been linked to increased levels of depression, increased levels of anxiety, decreased levels of self-esteem, and poor sleeping habits. While negative thoughts and views around the subject of alcohol abuse can keep those struggling with this issue from seeking the treatment they need, there have been several things that have been found to reduce this stigma. Social support can be an effective tool for counteracting the harmful effects of stigma and shame on those struggling with alcohol abuse. Social support can help push those struggling with alcohol abuse to overcome the negative connotation associated with their struggle and finally seek the treatment that they need. Prognosis Alcohol abuse during adolescence, especially early adolescence (i.e. before age 15), may lead to long-term changes in the brain which leaves them at increased risk of alcoholism in later years; genetic factors also influence age of onset of alcohol abuse and risk of alcoholism. For example, about 40 percent of those who begin drinking alcohol before age 15 develop alcohol dependence in later life, whereas only 10 percent of those who did not begin drinking until 20 years or older developed an alcohol problem in later life. It is not entirely clear whether this association is causal, and some researchers have been known to disagree with this view.Alcohol use disorders often cause a wide range of cognitive impairments that result in significant impairment of the affected individual. If alcohol-induced neurotoxicity has occurred a period of abstinence for on average a year is required for the cognitive deficits of alcohol abuse to reverse.College/university students who are heavy binge drinkers (three or more times in the past two weeks) are 19 times more likely to be diagnosed with alcohol dependence, and 13 times more likely to be diagnosed with alcohol abuse compared to non-heavy episodic drinkers, though the direction of causality remains unclear. Occasional binge drinkers (one or two times in the past two weeks), were found to be four times more likely to be diagnosed with alcohol abuse or dependence compared to non-heavy episodic drinkers. Epidemiology Alcohol abuse is said to be most common in people aged between 15 and 24 years, according to Moreira 2009. However, this particular study of 7275 college students in England collected no comparative data from other age groups or countries. Causes of alcohol abuse are complex and are likely the combination of many factors, from coping with stress to childhood development. The US Department of Health & Human Services identifies several factors influencing adolescent alcohol use, such as risk-taking, expectancies, sensitivity and tolerance, personality and psychiatric comorbidity, hereditary factors, and environmental aspects.Studies show that child maltreatment such as neglect, physical, and/or sexual abuse, as well as having parents with alcohol abuse problems, increases the likelihood of that child developing alcohol use disorders later in life. According to Shin, Edwards, Heeren, & Amodeo (2009), underage drinking is more prevalent among teens that experienced multiple types of childhood maltreatment regardless of parental alcohol abuse, putting them at a greater risk for alcohol use disorders. Genetic and environmental factors play a role in the development of alcohol use disorders, depending on age. The influence of genetic risk factors in developing alcohol use disorders increase with age ranging from 28% in adolescence and 58% in adults. Societal and economic costs Alcohol abuse is associated with many accidents, fights, and offences, including criminal. Alcohol is responsible in the world for 1.8 million deaths and results in disability in approximately 58.3 million people. Approximately 40 percent of the 58.3 million people disabled through alcohol abuse are disabled due to alcohol-related neuropsychiatric disorders. Alcohol abuse is highly associated with adolescent suicide. Adolescents who abuse alcohol are 17 times more likely to commit suicide than adolescents who dont drink. Additionally, alcohol abuse increases the risk of individuals either experiencing or perpetrating sexual violence. Alcohol availability and consumption rates and alcohol rates are positively associated with violent crimes, through specifics differ between particular countries and cultures. By country According to studies of present and former alcoholic drinkers in Canada, 20% of them are aware that their drinking has negatively impacted their lives in various vital areas including finances, work and relationships.Problems caused by alcohol abuse in Ireland cost about 3.7 billion euro in 2007.In South Africa, where HIV infection is epidemic, alcohol abusers exposed themselves to double the risk of this infection.The introduction of alcopops, sweet and pleasantly flavoured alcoholic drinks, was responsible for half of the increase in alcohol abuse in 15- and 16-year-olds, according to one survey in Sweden. In the case of girls, the alcopops, which disguise the taste of alcohol, were responsible for two thirds of the increase. The introduction of alcopops to Sweden was a result of Sweden joining the European Union and adopting the entire European Union law.Alcohol misuse costs the United Kingdoms National Health Service £3 billion per year. The cost to employers is 6.4 billion pounds sterling per year. These figures do not include the crime and social problems associated with alcohol misuse. The number of women regularly drinking alcohol has almost caught up with men.In the United States, many people are arrested for drinking and driving. Also, people under the influence of alcohol commit a large portion of various violent crimes, including child abuse, homicide and suicide. In addition, people of minority groups are affected by alcohol-related problems disproportionately, with the exception of Asian Americans. According to criminologist Hung‐En Sung "alcohol is the most widely abused psychoactive substance in the United States". See also 0-0-1-3 – a United States Air Force program for alcohol abuse prevention Drunken monkey hypothesis References Further reading Christopher M. Finan (2017). Drunks: An American History. Beacon Press. ISBN 978-0807001790. External links dassa.sa.gov.au Rethinking Drinking, National Institute on Alcohol Abuse and Alcoholism Alcohol and Crime: Data from 2002 to 2008 Bureau of Justice Statistics Healthy Youth! Alcohol & Drug Abuse – U.S. Centers for Disease Control (CDC)

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

Please help me grasp the concept behind the medical term 'Breast development.'

Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a females life. It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, breast development ceases and the breasts atrophy. Breast development results in prominent and developed structures on the chest known as breasts in primates, which serve primarily as mammary glands. The process is mediated by an assortment of hormones (and growth factors), the most important of which include estrogen, progesterone, prolactin, and growth hormone. Biochemistry Hormones The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin. These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.At puberty, gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile manner from the hypothalamus. GnRH induces the secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland. The secreted gonadotropins travel through the bloodstream to the ovaries and trigger the secretion of estrogen and progesterone in fluctuating amounts during each menstrual cycle. Growth hormone (GH), which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response to GH, are growth-mediating hormones. During prenatal development, infancy, and childhood, GH and IGF-1 levels are low, but progressively increase and reach a peak at puberty, with a 1.5- to 3-fold increase in pulsatile GH secretion and a 3-fold or greater increase in serum IGF-1 levels being capable of occurring at this time. In late adolescence and early adulthood, GH and IGF-1 levels significantly decrease, and continue to decrease throughout the rest of life. It has been found that both estrogen and GH are essential for breast development at puberty – in the absence of either, no development will take place. Moreover, most of the role of GH in breast development has been found to be mediated by its induction of IGF-1 production and secretion, as IGF-1 administration rescues breast development in the absence of GH. GH induction of IGF-1 production and secretion occurs in almost all types of tissue in the body, but especially in the liver, which is the source of approximately 80% of circulating IGF-1, as well as locally in the breasts. Although IGF-1 is responsible for most of the role of GH in mediating breast development, GH itself has been found to play a direct, augmenting role as well, as it increases estrogen receptor (ER) expression in breast stromal (connective) tissue, while IGF-1, in contrast, has been found to not do this. In addition to estrogen and GH/IGF-1 both being essential for pubertal breast development, they are synergistic in bringing it about.Despite the apparent necessity of GH/IGF-1 signaling in pubertal breast development however, women with Laron syndrome, in whom the growth hormone receptor (GHR) is defective and insensitive to GH and serum IGF-1 levels are very low, puberty, including breast development, is delayed, although full sexual maturity is always eventually reached. Moreover, breast development and size are normal (albeit delayed) in spite of GH/IGF-1 axis insufficiency, and in some the breasts may actually be large in relation to body size. The relatively large breasts in women with Laron syndrome have been suggested to be due to increased secretion of prolactin (which is known to produce breast enlargement) caused by a drift phenomenon from somatomammotrophic cells in the pituitary gland with a high GH secretion. An animal model of Laron syndrome, the GHR knockout mouse, shows severely impaired ductal outgrowth at 11 weeks of age. However, by 15 weeks, ductal development has caught up with that of normal mice and the ducts have fully distributed throughout the mammary fat pad, although the ducts remain narrower than those of wild-type mice. In any case, female GHR knockout mice can lactate normally. As such, it has been said that the phenotypes of women with Laron syndrome and GHR knockout mice are identical, with diminished body size and delayed sexual maturation accompanied by normal lactation. These data indicate that very low circulating levels of IGF-1 can nonetheless allow for full pubertal breast development. Development of the breasts during the prenatal stage of life is independent of biological sex and sex hormones. During embryonic development, the breast buds, in which networks of tubules are formed, are generated from the ectoderm. These rudimentary tubules will eventually become the matured lactiferous (milk) ducts, which connect the lobules (milk "containers") of the breast, grape-like clusters of alveoli, to the nipples. Until puberty, the tubule networks of the breast buds remain rudimentary and quiescent, and the male and female breast do not show any differences. During puberty in females, estrogen, in conjunction with GH/IGF-1, through activation of ERα specifically (and notably not ERβ or GPER), causes growth of and transformation of the tubules into the matured ductal system of the breasts. Under the influence of estrogen, the ducts sprout and elongate, and terminal end buds (TEBs), bulbous structures at the tips of the ducts, penetrate into the fat pad and branch as the ducts elongate. This continues until a tree-like network of branched ducts that is embedded into and fills the entire fat pad of the breast is formed. In addition to its role in mediating ductal development, estrogen causes stromal tissue to grow and adipose (fat) tissue to accumulate, as well as the nipple-areolar complex to increase in size.Progesterone, in conjunction with GH/IGF-1 similarly to estrogen, affects the development of the breasts during puberty and thereafter as well. To a lesser extent than estrogen, progesterone contributes to ductal development at this time, as evidenced by the findings that progesterone receptor (PR) knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen acting on its own) ductal growth during puberty and by the fact that progesterone has been found to induce ductal growth on its own in the mouse mammary gland mainly via the induction of the expression of amphiregulin, the same growth factor that estrogen primarily induces to mediate its actions on ductal development. In addition, progesterone produces modest lobuloalveolar development (alveolar bud formation or ductal sidebranching) starting at puberty, specifically through activation of PRB (and notably not PRA), with growth and regression of the alveoli occurring to some degree with each menstrual cycle. However, only rudimentary alveoli develop in response to pre-pregnancy levels of progesterone and estrogen, and lobuloalveolar development will remain at this stage until pregnancy occurs, if it does. In addition to GH/IGF-1, estrogen is required for progesterone to affect the breasts, as estrogen primes the breasts by inducing the expression of the progesterone receptor (PR) in breast epithelial tissue. In contrast to the case of the PR, ER expression in the breast is stable and differs relatively little in the contexts of reproductive status, stage of the menstrual cycle, or exogenous hormonal therapy.During pregnancy, pronounced breast growth and maturation occurs in preparation of lactation and breastfeeding. Estrogen and progesterone levels increase dramatically, reaching levels by late pregnancy that are several hundred-fold higher than usual menstrual cycle levels. Estrogen and progesterone cause the secretion of high levels of prolactin from the anterior pituitary, which reach levels as high as 20 times greater than normal menstrual cycle levels. IGF-1 and IGF-2 levels also increase dramatically during pregnancy, due to secretion of placental growth hormone (PGH). Further ductal development, by estrogen, again in conjunction with GH/IGF-1, occurs during pregnancy. In addition, the concert of estrogen, progesterone (again specifically through PRB), prolactin, and other lactogens such as human placental lactogen (hPL) and PGH, in conjunction with GH/IGF-1, as well as insulin-like growth factor 2 (IGF-2), acting together, mediate the completion of lobuloalveolar development of the breasts during pregnancy. Both PR and prolactin receptor (PRLR) knockout mice fail to show lobuloalveolar development, and progesterone and prolactin have been found to be synergistic in mediating growth of alveoli, demonstrating the essential role of both of these hormones in this aspect of breast development. Growth hormone receptor (GHR) knockout mice also show greatly impaired lobuloalveolar development. In addition to their role in lobuloalveolar growth, prolactin and hPL act to increase the size of the nipple-areolar complex during pregnancy. By the end of the fourth month of pregnancy, at which time lobuloalveolar maturation is complete, the breasts are fully prepared for lactation and breastfeeding.Insulin, glucocorticoids such as cortisol (and by extension adrenocorticotropic hormone (ACTH)), and thyroid hormones such as thyroxine (and by extension thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH)) also play permissive but less well-understood/poorly-characterized roles in breast development during both puberty and pregnancy, and are required for full functional development. Leptin has also been found to be an important factor in mammary gland development, and has been found to promote mammary epithelial cell proliferation.In contrast to the female-associated sex hormones, estrogen and progesterone, the male-associated sex hormones, the androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts. At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue. In the absence of androgenic activity, such as in women with complete androgen insensitivity syndrome (CAIS), modest levels of estrogen (50 pg/mL) are capable of mediating significant breast development, with CAIS women showing breast volumes that are even above-average. The combination of much higher levels of androgens (about 10-fold higher) and much lower levels of estrogen (about 10-fold less), due to the ovaries in females producing high amounts of estrogens but low amounts of androgens and the testes in males producing high amounts of androgens but low amounts of estrogens, are why males generally do not grow prominent or well-developed breasts relative to females.Calcitriol, the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR), has, like the androgens, been reported to be a negative regulator of mammary gland development in mice, for instance, during puberty. VDR knockout mice show more extensive ductal development relative to wild-type mice, as well as precocious mammary gland development. In addition, VDR knockout has also been shown to result in increased responsiveness of mouse mammary gland tissue to estrogen and progesterone, which was represented by increased cell growth in response to these hormones. Conversely however, it has been found that VDR knockout mice show reduced ductal differentiation, represented by an increased number of undifferentiated TEBs, and this finding has been interpreted as indicating that vitamin D may be essential for lobuloalveolar development. As such, calcitriol, via the VDR, may be a negative regulator of ductal development but a positive regulator of lobuloalveolar development in the mammary gland.A possible mechanism of the negative regulatory effects of the VDR on breast development may be indicated by a study of vitamin D3 supplementation in women which found that vitamin D3 suppresses cyclooxygenase-2 (COX-2) expression in the breast, and by doing so, reduces and increases, respectively, the levels of prostaglandin E2 (PGE2) and transforming growth factor β2 (TGF-β2), a known inhibitory factor in breast development. Moreover, suppression of PGE2 in breast tissue is relevant because, via activation of prostaglandin EP receptors, PGE2 potently induces amphiregulin expression in breast tissue, and activation of the EGFR by amphiregulin increases COX-2 expression in breast tissue, in turn resulting in more PGE2, and thus, a self-perpetuating, synergistic cycle of growth amplification due to COX-2 appears to potentially be present in normal breast tissue. Accordingly, overexpression of COX-2 in mammary gland tissue produces mammary gland hyperplasia as well as precocious mammary gland development in female mice, mirroring the phenotype of VDR knockout mice, and demonstrating a strong stimulatory effect of COX-2, which is downregulated by VDR activation, on the growth of the mammary glands. Also in accordance, COX-2 activity in the breasts has been found to be positively associated with breast volume in women. Growth factors Estrogen, progesterone, and prolactin, as well as GH/IGF-1, produce their effects on breast development by modulating the local expression in breast tissue of an assortment of autocrine and paracrine growth factors, including IGF-1, IGF-2, amphiregulin, EGF, FGF, hepatocyte growth factor (HGF), tumor necrosis factor α (TNF-α), tumor necrosis factor β (TNF-β), transforming growth factor α (TGF-α), transforming growth factor β (TGF-β), heregulin, Wnt, RANKL, and leukemia inhibitory factor (LIF). These factors regulate cellular growth, proliferation, and differentiation via activation of intracellular signaling cascades that control cell function, such as Erk, Akt, JNK, and Jak/Stat.Based on research with epidermal growth factor receptor (EGFR) knockout mice, the EGFR, which is the molecular target of EGF, TGF-α, amphiregulin, and heregulin, has, similarly to the insulin-like growth factor-1 receptor (IGF-1R), been found to be essential for mammary gland development. Estrogen and progesterone mediate ductal development mainly through induction of amphiregulin expression, and thus downstream EGFR activation. Accordingly, ERα, amphiregulin, and EGFR knockout mice copy each other phenotypically in regards to their effects on ductal development. Also in accordance, treatment of mice with amphiregulin or other EGFR ligands like TGF-α or heregulin induces ductal and lobuloalveolar development in the mouse mammary gland, actions that occur even in the absence of estrogen and progesterone. As both the IGF-1R and the EGFR are independently essential for mammary gland development, and as combined application of IGF-1 and EGF, through their respective receptors, has been found to synergistically stimulate the growth of human breast epithelial cells, these growth factor systems appear to work together in mediating breast development.Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in macromastia, a very rare condition of extremely and excessively large breast size. Exposure of macromastic breast stromal tissue to non-macromastic breast epithelial tissue was found to cause increased alveolar morphogenesis and epithelial proliferation in the latter. A neutralizing antibody for HGF, but not for IGF-1 or EGF, was found to attenuate the proliferation of breast epithelial tissue caused by exposure to macromastic breast stromal cells, potentially directly implicating HGF in the breast growth and enlargement seen in macromastia. Also, a genome-wide association study has highly implicated HGF and its receptor, c-Met, in breast cancer aggressiveness. Lactation Upon parturition (childbirth), estrogen and progesterone rapidly drop to very low levels, with progesterone levels being undetectable. Conversely, prolactin levels remain elevated. As estrogen and progesterone block prolactin-induced lactogenesis by suppressing prolactin receptor (PRLR) expression in breast tissue, their sudden absence results in the commencement of milk production and lactation by prolactin. Expression of the PRLR in breast tissue may increase by as much as 20-fold when estrogen and progesterone levels drop upon childbirth. With suckling from the infant, prolactin and oxytocin are secreted and mediate milk production and letdown, respectively. Prolactin suppresses the secretion of LH and FSH, which in turn results in continued low levels of estrogen and progesterone, and temporary amenorrhea (absence of menstrual cycles) occurs. In the absence of regular, episodic suckling, which keeps prolactin concentrations high, levels of prolactin will quickly drop, the menstrual cycle will resume and hence normal estrogen and progesterone levels will return, and lactation will cease (that is, until next parturition, or until induced lactation (i.e., with a galactogogue), occurs). Breast size and cancer risk Some factors of breast morphology, including their density, are clearly implicated in breast cancer. While breast size is moderately heritable, the relationship between breast size and cancer is uncertain. The genetic variants influencing breast size have not been identified.Through genome-wide association studies, a variety of genetic polymorphisms have been linked to breast size. Some of these include rs7816345 near ZNF703 (zinc finger protein 703); rs4849887 and rs17625845 flanking INHBB (inhibin βB); rs12173570 near ESR1 (ERα); rs7089814 in ZNF365 (zinc finger protein 365); rs12371778 near PTHLH (parathyroid hormone-like hormone); rs62314947 near AREG (amphiregulin); as well as rs10086016 at 8p11.23 (which is in complete linkage disequilibrium with rs7816345) and rs5995871 at 22q13 (contains the MKL1 gene, which has been found to modulate the transcriptional activity of ERα). Many of these polymorphisms are also associated with the risk of developing breast cancer, revealing a potential positive association between breast size and breast cancer risk. However, conversely, some polymorphisms show a negative association between breast size and breast cancer risk. In any case, a meta-analysis concluded that breast size and risk of breast cancer are indeed importantly related.Circulating IGF-1 levels are positively associated with breast volume in women. In addition, the absence of the common 19-repeat allele in the IGF1 gene is also positively associated with breast volume in women, as well as with high IGF-1 levels during oral contraceptive use and with lessening of the normal age-associated decline in circulating IGF-1 concentrations in women. There is great variation in the prevalence of the IGF1 19-repeat allele between ethnic groups, and its absence has been reported to be highest among African-American women.Genetic variations in the androgen receptor (AR) have been linked to both breast volume (as well as body mass index) and breast cancer aggressiveness.COX-2 expression has been positively associated with breast volume and inflammation in breast tissue, as well as with breast cancer risk and prognosis. Rare mutations Women with CAIS, who are completely insensitive to the AR-mediated actions of androgens, have, as a group, above-average sized breasts. This is true despite the fact that they simultaneously have relatively low levels of estrogen, which demonstrates the powerful suppressant effect of androgens on estrogen-mediated breast development.Aromatase excess syndrome, an extremely rare condition characterized by marked hyperestrogenism, is associated with precocious breast development and macromastia in females and similarly precocious gynecomastia (womens breasts) in males. In complete androgen insensitivity syndrome, a condition in which the AR is defective and insensitive to androgens, there is full breast development with breast volumes that are in fact above average in spite of relatively low levels of estrogen (50 pg/mL estradiol). In aromatase deficiency, a form of hypoestrogenism in which aromatase is defective and cannot synthesize estrogen, and in complete estrogen insensitivity syndrome, a condition in which ERα is defective and insensitive to estrogen, breast development is completely absent. See also Breast augmentation Breast enlargement Mammoplasia Premenstrual water retention Thelarche References Further reading Hovey, Russell C.; Aimo, Lucila (2010). "Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function". Journal of Mammary Gland Biology and Neoplasia. 15 (3): 279–290. doi:10.1007/s10911-010-9187-8. ISSN 1083-3021. PMC 2941079. PMID 20717712. Sun, Susie X.; Bostanci, Zeynep; Kass, Rena B.; Mancino, Anne T.; Rosenbloom, Arlan L.; Klimberg, V. Suzanne; Bland, Kirby I. (2018). "Breast Physiology". The Breast. pp. 37–56.e6. doi:10.1016/B978-0-323-35955-9.00003-9. ISBN 9780323359559.

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

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

Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the major symptom of gastroesophageal reflux disease (GERD).Other common descriptors for heartburn (besides burning) are belching, nausea, squeezing, stabbing, or a sensation of pressure on the chest. The pain often rises in the chest (directly behind the breastbone) and may radiate to the neck, throat, or angle of the arm. Because the chest houses other important organs besides the esophagus (including the heart and lungs), not all symptoms related to heartburn are esophageal in nature.The cause will vary depending on ones family and medical history, genetics, if a person is pregnant or lactating, and age. As a result, the diagnosis will vary depending on the suspected organ and the inciting disease process. Work-up will vary depending on the clinical suspicion of the provider seeing the patient, but generally includes endoscopy and a trial of antacids to assess for relief.Treatment for heartburn may include medications and dietary changes. Medication include antacids. Dietary changes may require avoiding foods that are high in fats, spicy, high in artificial flavors, heavily reducing NSAID use, heavy alcohol consumption, and decreasing peppermint consumption. Lifestyle changes may help such as reducing weight. Definition The term indigestion includes heartburn along with a number of other symptoms. Indigestion is sometimes defined as a combination of epigastric pain and heartburn. Heartburn is commonly used interchangeably with gastroesophageal reflux disease (GERD) rather than just to describe a symptom of burning in ones chest. Differential diagnosis Heartburn-like symptoms and/or lower chest or upper abdomen may be indicative of much more sinister and/or deadly disease. Of greatest concern is to confuse heartburn (generally related to the esophagus) with a heart attack as these organs share a common nerve supply. Numerous abdominal and thoracic organs are present in that region of the body. Many different organ systems might explain the discomfort called heartburn. Heart The most common symptom for a heart attack is chest pain. However, as many as 30% of chest pain patients undergoing cardiac catheterization have findings that do not account for their chest discomfort. These are often defined as having "atypical chest pain" or chest pain of undetermined origin. Women experiencing heart attacks may also deny classic signs and symptoms and instead complain of GI symptoms. One article estimates that ischemic heart disease may appear to be GERD in 0.6% of people. Esophagus GERD (most common cause of heartburn) occurs when acid refluxes from the stomach and inflames the esophagus. Esophageal spasms typically occur after eating or drinking and may be combined with difficulty swallowing. Esophageal strictures Esophageal cancers Esophagitis GERD Eosinophilic esophagitis – a disease commonly associated with other atopic diseases such as asthma, food allergies, seasonal allergies, and atopic skin disease Mallory-Weis tears – tears of the superficial mucosa of the esophagus that are subsequently exposed to gastric acid commonly due to vomiting and/or retching Chemical esophagitis – related to the intake of caustic substances, excessive amounts of hot liquids, alcohol, or tobacco smoke Infections may explain heartburn symptoms. These especially include CMV and certain fungal infections, most common in immunocompromised persons Stomach Peptic ulcer disease – can be secondary to H. Pylori infection or heavy NSAID use that weakens stomach mucosal layer. Pain often worsens with eating. Stomach cancer Intestines Intestinal ulcers – generally secondary to other conditions such as H. Pylori infection or cancers of the GI tract. Pain often improves with eating. Duodenitis – inflammation of the small intestine. May be the result of several conditions Gallbladder Gallstones Pancreas Pancreatitis – can be autoimmune, due to a gallstone obstructing the lumen, related to alcohol consumption. Hematology Pernicious anemia – can be autoimmune, due to atrophic gastritis. Pregnancy Heartburn is common during pregnancy having been reported in as high as 80% of pregnancies. It is most often due to GERD and results from relaxation of the lower esophageal sphincter (LES), changes in gastric motility, and/or increasing intra-abdominal pressure. The onset of symptoms can be during any trimester of pregnancy. Hormonal – related to the increasing amounts of estrogen and progesterone and their effect on the LES Mechanical – the enlarging uterus increasing intra-abdominal pressure, inducing reflux of gastric acid Behavioral – as with other instances of heartburn, behavioral modifications can exacerbate or alleviate symptoms Unknown origin Functional heartburn is heartburn of unknown cause. It is commonly associated with psychiatric conditions like depression, anxiety, and panic attacks. It is also seen with other functional gastrointestinal disorders like irritable bowel syndrome and is the primary cause of lack of improvement post treatment with proton pump inhibitors (PPIs). Despite this, PPIs are still the primary treatment with response rates in about 50% of people. The diagnosis is one of elimination, based upon the Rome III criteria. It was found to be present in 22.3% of Canadians in one survey. Diagnostic approach Heartburn can be caused by several conditions and a preliminary diagnosis of GERD is based on additional signs and symptoms. The chest pain caused by GERD has a distinct burning sensation, occurs after eating or at night, and worsens when a person lies down or bends over. It also is common in pregnant women, and may be triggered by consuming food in large quantities, or specific foods containing certain spices, high fat content, or high acid content. In young persons (typically <40 years) who present with heartburn symptoms consistent with GERD (onset after eating, when laying down, when pregnant), a physician may begin a course of PPIs to assess clinical improvement before additional testing is undergone. Resolution or improvement of symptoms on this course may result in a diagnosis of GERD.Other tests or symptoms suggesting acid reflux is causing heartburn include: Onset of symptoms after eating or drinking, at night, and/or with pregnancy, and improvement with PPIs Endoscopy looking for erosive changes of the esophagus consistent with prolonged acid exposure (e.g. - Barretts esophagus) Upper GI series looking for the presence of acid reflux GI cocktail Relief of symptoms 5 to 10 minutes after the administration of viscous lidocaine and an antacid increases the suspicion that the pain is esophageal in origin. This however does not rule out a potential cardiac cause as 10% of cases of discomfort due to cardiac causes are improved with antacids. Biochemical Esophageal pH monitoring: a probe can be placed via the nose into the esophagus to record the level of acidity in the lower esophagus. Because some degree of variation in acidity is normal, and small reflux events are relatively common, esophageal pH monitoring can be used to document reflux in real-time. Patients are able to record symptom onset to correlate lower esophageal pH with time of symptom onset. Mechanical Manometry: in this test, a pressure sensor (manometer) is passed via the mouth into the esophagus and measures the pressure of the LES directly.Endoscopy: the esophageal mucosa can be visualized directly by passing a thin, lighted tube with a tiny camera known as an endoscope attached through the mouth to examine the oesophagus and stomach. In this way, evidence of esophageal inflammation can be detected, and biopsies taken if necessary. Since an endoscopy allows a doctor to visually inspect the upper digestive tract the procedure may help identify any additional damage to the tract that may not have been detected otherwise.Biopsy: a small sample of tissue from the oesophagus is removed. It is then studied to check for inflammation, cancer, or other problems. Treatment Treatment plans are tailored to the specific diagnosis and etiology of the heartburn. Management of heartburn can be sorted into various categories. Pharmacologic management Antacids (i.e. calcium carbonate) are often taken to treat the immediate problem H2 receptor antagonists or proton pump inhibitors are effective for the two most common causes of heartburn (e.g. gastritis and GERD) Antibiotics are used if H. pylori is present. Behavioral management Taking medications 30–45 minutes before eating suppresses the stomachs acid generating response to food Avoiding spicy foods, foods high in fats, peppermint, and chocolate Avoiding reclining 2.5–3.5 hours after a meal to prevent the reflux of stomachs contents Lifestyle modifications Early studies show that diets that are high in fiber may show evidence in decreasing symptoms of dyspepsia. Weight loss can decrease abdominal pressure that both delays gastric emptying and increases gastric acid reflux into the esophagus Alternative and complementary therapies Symptoms of heartburn may not always be the result of an organic cause. Patients may respond better to therapies targeting anxiety and symptoms of hyper-vigilance, through medications aimed towards a psychiatric etiology, osteopathic manipulation and acupuncture. Psychotherapy may show a positive role in treatment of heartburn and the reduction of distress experienced during symptoms. Acupuncture - in cases of functional heartburn (e.g. heartburn of unknown origin) acupuncture may be as effective if not more than PPIs alone. Surgical management In the case of GERD causing heartburn symptoms, surgery may be required if PPI is not effective. Surgery is not undergone if functional heartburn is the leading diagnosis. Epidemiology About 42% of the United States population has had heartburn at some point. == References ==

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

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

Transient neonatal diabetes mellitus (TNDM) is a form of neonatal diabetes presenting at birth that is not permanent. This disease is considered to be a type of maturity onset diabetes of the young (MODY). Types Cause This condition has to do with genetics and is often associated with having an added Chromosome 7 gene (mostly from the paternal side).The form on chromosome 6 can involve imprinting. Diagnosis Management See also Permanent neonatal diabetes mellitus References Further reading GeneReview/NIH/UW entry on 6q24-Related Transient Neonatal Diabetes Mellitus == External links ==

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

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

Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties. It was patented in 1959 and came into medical use in 1961. Medical uses Cyproheptadine is used to treat allergic reactions (specifically hay fever). The evidence for its use for this purpose indicates its effectiveness but second generation antihistamines such as ketotifen and loratadine have shown equal results with fewer side effects.It is also used as a preventive treatment against migraine. In a 2013 study the frequency of migraine was dramatically reduced in patients within 7 to 10 days after starting treatment. The average frequency of migraine attacks in these patients before administration was 8.7 times per month, this was decreased to 3.1 times per month at 3 months after the start of treatment. This use is on the label in the UK and some other countries. It is also used off-label in the treatment of cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies.Cyproheptadine is sometimes used off-label to improve akathisia in people on antipsychotic medications.It is used off-label to treat various dermatological conditions, including psychogenic itch drug-induced hyperhidrosis (excessive sweating), and prevention of blister formation for some people with epidermolysis bullosa simplex.One of the effects of the drug is increased appetite and weight gain, which has led to its use (off-label in the USA) for this purpose in children who are wasting as well as people with cystic fibrosis.It is also used off-label in the management of moderate to severe cases of serotonin syndrome, a complex of symptoms associated with the use of serotonergic drugs, such as selective serotonin reuptake inhibitors (and monoamine oxidase inhibitors), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor.Cyproheptadine has sedative effects and can be used to treat insomnia similarly to other centrally-acting antihistamines. The recommended dose for this use is 4 to 8 mg. Adverse effects Adverse effects include: Overdose Gastric decontamination measures such as activated charcoal are sometimes recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD50 in mice is 123 mg/kg and 295 mg/kg in rats. Pharmacology Pharmacodynamics Cyproheptadine is a very potent antihistamine or inverse agonist of the H1 receptor. At higher concentrations, it also has anticholinergic, antiserotonergic, and antidopaminergic activities. Of the serotonin receptors, it is an especially potent antagonist of the 5-HT2 receptors. This is thought to underlie its effectiveness in the treatment of serotonin syndrome. However, it is possible that blockade of 5-HT1 receptors may also contribute to its effectiveness in serotonin syndrome. Cyproheptadine has been reported to block 85% of 5-HT2 receptors in the human brain at a dose of 4 mg three times per day (12 mg/day total) and to block 95% of 5-HT2 receptors in the human brain at a dose of 6 mg three times per day (18 mg/day total) as measured with positron emission tomography (PET). The dose of cyproheptadine recommended to ensure blockade of the 5-HT2 receptors for serotonin syndrome is 20 to 30 mg. Besides its activity at neurotransmitter targets, cyproheptadine has been reported to possess weak antiandrogenic activity. Pharmacokinetics Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours. Its terminal half-life when taken orally is approximately 8 hours. Chemistry Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants. Research Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from. It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect.There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications.Cyproheptadine has been studied for the treatment of posttraumatic stress disorder. Veterinary use Cyproheptadine is used in cats as an appetite stimulant: 1371  and as an adjunct in the treatment of asthma. Possible adverse effects include excitement and aggressive behavior. The elimination half-life of cyproheptadine in cats is 12 hours.Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses. == References ==

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

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

Sputum is mucus that is coughed up from the lower airways (the trachea and bronchi). In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigations of respiratory systems. It is crucial that the specimen does not include any mucoid material from the nose or oral cavity. A naked eye exam of the sputum can be done at home by a patient in order to note the various colors (see below). Any hint of yellow or green color (pus) suggests an airway infection (but does not indicate the type of organism causing it). Such color hints are best detected when the sputum is viewed on a very white background such as white paper, a white pot or a white sink surface. The more intense the yellow color, the more likely it is a caused by an infection (bronchitis, bronchopneumonia or pneumonia). Having green, yellow, or thickened phlegm (sputum) does not always indicate the presence of an infection. Also, if an infection is present, the color of the phlegm (sputum) does not determine whether a virus, a bacterium or another pathogen has caused it. Simple allergies can also cause changes in the color of the mucus. Description The best sputum samples contain very little saliva, as saliva contaminates the sample with oral bacteria. This is especially true for samples for laboratory testing in cytology or microbiology. Specimen adequacy is assessed by the laboratory technologists by examining a Gram stain or cytology stain of the sputum. More than 25 squamous epithelial cells at low power magnification exam under the microscope strongly suggest salivary contamination. Sputum samples have been used to quantify the degree of airway inflammation in human diseases such as asthma. Specifically, this work has demonstrated that a subgroup of severe asthma patients has airway inflammation that is resistant to treatment with corticosteroids.When a sputum specimen is plated out in microbiology, it is best to get the portion of the sample that almost looks like yellow pus onto the swab. If there is any blood in the sputum, this should also be on the swab. Microbiological sputum samples are used to look for infections, such as Moraxella catarrhalis, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Haemophilus influenzae. Other pathogens can also be found. Purulent sputum contains pus, composed of white blood cells, cellular debris, dead tissue, serous fluid, and viscous liquid (mucus). Purulent sputum is typically yellow or green. It is seen in cases of pneumonia, bronchiectasis, lung abscess, or an advanced stage of bronchitis. Interpretation Sputum can be (when examined by the naked eye): Bloody (hemoptysis) Blood-streaked sputum –an indicator of possible inflammation of the throat (larynx and/or trachea) or bronchi; lung cancer; other bleeding erosions, ulcers, or tumors of the lower airway. Pink sputum – it indicates sputum evenly mixed with blood from alveoli and/or small peripheral bronchi as is seen in potential pulmonary edema. Massive blood – an indicator of possible cavitary tuberculosis or tumor such as lung cancer, or lung abscess; bronchiectasis; lung infarction; pulmonary embolism. Red, jelly-like sputum - an indicator of possible pneumonia caused by Klebsiella. Green or greenish colored - indicative of potential longstanding respiratory infection (green from degenerative changes in cell debris) as in pneumonia, ruptured lung abscess, chronic infectious bronchitis, and infected bronchiectasis or cystic fibrosis. Rust colored – usually caused by pneumococcal bacteria (in pneumonia), pulmonary embolism, lung cancer or pulmonary tuberculosis. Brownish –potential indicator of chronic bronchitis (greenish/yellowish/brown); chronic pneumonia (whitish-brown); tuberculosis; lung cancer. Yellow, yellowish purulent – an indicator of the sample containing pus. "The sputum color of patients with acute cough and no underlying chronic lung disease does not imply therapeutic consequences such as prescription of antibiotics." The color can provide hints as to effective treatment in chronic bronchitis patients:A yellow-greenish (mucopurulent) color suggests that treatment with antibiotics can reduce symptoms. The green color is caused by degenerating neutrophil verdoperoxidase. Whitish gray sputum color against a white color background (such as a white sink surface) tends to indicate either a specimen from someone who is dehydrated, and/or from an older person, and/or a specimen with a mixed, modest number of eosinophils and maybe some acute inflammatory neutrophil cells (this last choice tends to suggest chronic allergic bronchitis). A white, milky, or opaque (mucoid) appearance means that antibiotics are less likely to be effective in treatment because the likelihood is greater of a viral infection or allergy (even asthma...thick sputum) than of antibiotic-responsive micro-organisms. Foamy white – may come from earlier-phase pulmonary edema. Frothy pink – may indicate more severe pulmonary edema. Antibiotics may not be necessary at this time. Clear – pulmonary embolism (clear to frothy); COPD chronic obstructive pulmonary disease (clear to gray); viral respiratory infection (clear to whitish and sometimes a hint of yellow); asthma (thick and white to yellowish). See also Phlegm 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.

Could you provide a brief overview of 'Anastrozole' in a medical context?

Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast cancer in those at high risk. It is taken by mouth.Common side effects of anastrozole include hot flashes, altered mood, joint pain, and nausea. Severe side effects include an increased risk of heart disease and osteoporosis. Use during pregnancy may harm the baby. Anastrozole is in the aromatase-inhibiting family of medications. It works by blocking the production of estrogens in the body, and hence has antiestrogenic effects.Anastrozole was patented in 1987 and was approved for medical use in 1995. It is on the World Health Organizations List of Essential Medicines. Anastrozole is available as a generic medication. In 2019, it was the 176th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses Breast cancer Anastrozole is used in the treatment and prevention of breast cancer in women. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial was of localized breast cancer and women received either anastrozole, the selective estrogen receptor modulator tamoxifen, or both for five years, followed by five years of follow-up. After more than 5 years the group that received anastrozole had better results than the tamoxifen group. The trial suggested that anastrozole is the preferred medical therapy for postmenopausal women with localized estrogen receptor-positive breast cancer. Early puberty Anastrozole is used at a dosage of 0.5 to 1 mg/day in combination with the antiandrogen bicalutamide in the treatment of peripheral precocious puberty, for instance due to familial male-limited precocious puberty (testotoxicosis) and McCune–Albright syndrome, in boys. Available forms Anastrozole is available in the form of 1 mg oral tablets. No alternative forms or routes are available. Contraindications Contraindications of anastrozole include hypersensitivity to anastrozole or any other component of anastrozole formulations, pregnancy, and breastfeeding. Hypersensitivity reactions to anastrozole including anaphylaxis, angioedema, and urticaria have been observed. Side effects Common side effects of anastrozole (≥10% incidence) include hot flashes, asthenia, arthritis, pain, arthralgia, hypertension, depression, nausea and vomiting, rash, osteoporosis, bone fractures, back pain, insomnia, headache, bone pain, peripheral edema, coughing, dyspnea, pharyngitis, and lymphedema. Serious but rare adverse effects (<0.1% incidence) include skin reactions such as lesions, ulcers, or blisters; allergic reactions with swelling of the face, lips, tongue, and/or throat that may cause difficulty swallowing or breathing; and abnormal liver function tests as well as hepatitis. Interactions Anastrozole is thought to have clinically negligible inhibitory effects on the cytochrome P450 enzymes CYP1A2, CYP2A6, CYP2D6, CYP2C8, CYP2C9, and CYP2C19. As a result, it is thought that drug interactions of anastrozole with cytochrome P450 substrates are unlikely. No clinically significant drug interactions have been reported with anastrozole as of 2003.Anastrozole does not affect circulating levels of tamoxifen or its major metabolite N-desmethyltamoxifen. However, tamoxifen has been found to decrease steady-state area-under-the-curve levels of anastrozole by 27%. But estradiol levels were not significantly different in the group that received both anastrozole and tamoxifen compared to the anastrozole alone group, so the decrease in anastrozole levels is not thought to be clinically important. Pharmacology Pharmacodynamics Anastrozole works by reversibly binding to the aromatase enzyme, and through competitive inhibition blocks the conversion of androgens to estrogens in peripheral (extragonadal) tissues. The medication has been found to achieve 96.7% to 97.3% inhibition of aromatase at a dosage of 1 mg/day and 98.1% inhibition of aromatase at a dosage of 10 mg/day in humans. As such, 1 mg/day is considered to be the minimal dosage required to achieve maximal suppression of aromatase with anastrozole. This decrease in aromatase activity results in an at least 85% decrease in estradiol levels in postmenopausal women. Levels of corticosteroids and other adrenal steroids are unaffected by anastrozole. Pharmacokinetics The bioavailability of anastrozole in humans is unknown, but it was found to be well-absorbed in animals. Absorption of anastrozole is linear over a dosage range of 1 to 20 mg/day in humans and does not change with repeated administration. Food does not significantly influence the extent of absorption of anastrozole. Peak levels of anastrozole occur a median 3 hours after administration, but with a wide range of 2 to 12 hours. Steady-state levels of anastrozole are achieved within 7 to 10 days of continuous administration, with 3.5-fold accumulation. However, maximal suppression of estradiol levels occurs within 3 or 4 days of therapy.Active efflux of anastrozole by P-glycoprotein at the blood–brain barrier has been found to limit the central nervous system penetration of anastrozole in rodents, whereas this was not the case with letrozole and vorozole. As such, anastrozole may have peripheral selectivity in humans, although this has yet to be confirmed. In any case, estradiol is synthesized peripherally and readily crosses the blood–brain barrier, so anastrozole would still expected to reduce estradiol levels in the central nervous system to a certain degree. The plasma protein binding of anastrozole is 40%.The metabolism of anastrozole is by N-dealkylation, hydroxylation, and glucuronidation. Inhibition of aromatase is due to anastrozole itself rather than to metabolites, with the major circulating metabolite being inactive. The elimination half-life of anastrozole is 40 to 50 hours (1.7 to 2.1 days). This allows for convenient once-daily administration. The medication is eliminated predominantly by metabolism in the liver (83 to 85%) but also by residual excretion by the kidneys unchanged (11%). Anastrozole is excreted primarily in urine but also to a lesser extent in feces. Chemistry Anastrozole is a nonsteroidal benzyltriazole. It is also known as α,α,α,α-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile. Anastrozole is structurally related to letrozole, fadrozole, and vorozole, with all being classified as azoles. History Anastrozole was patented by Imperial Chemical Industries (ICI) in 1987 and was approved for medical use, specifically the treatment of breast cancer, in 1995. Society and culture Generic names Anastrozole is the generic name of the drug and its INN, USAN, BAN, and JAN. Brand names Anastrozole is primarily sold under the brand name Arimidex. However, it is also marketed under a variety of other brand names throughout the world. Availability Anastrozole is available widely throughout the world. Research Anastrozole is surprisingly ineffective at treating gynecomastia, in contrast to selective estrogen receptor modulators like tamoxifen.Anastrozole was under development for the treatment of female infertility but did not complete development and hence was never approved for this indication.An anastrozole and levonorgestrel vaginal ring (developmental code name BAY 98–7196) was under development for use as a hormonal contraceptive and treatment for endometriosis, but development was discontinued in November 2018 and the formulation was never marketed.Anastrozole increases testosterone levels in males and has been studied as an alternative method of androgen replacement therapy in men with hypogonadism. However, there are concerns about its long-term influence on bone mineral density in this patient population, as well as other adverse effects. References External links "Anastrozole". 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.

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

Amblyopia, also called lazy eye, is a disorder of sight in which the brain fails to fully process input from one eye and over time favors the other eye. It results in decreased vision in an eye that typically appears normal in other respects. Amblyopia is the most common cause of decreased vision in a single eye among children and younger adults.The cause of amblyopia can be any condition that interferes with focusing during early childhood. This can occur from poor alignment of the eyes (strabismic), an eye being irregularly shaped such that focusing is difficult, one eye being more nearsighted or farsighted than the other (refractive), or clouding of the lens of an eye (deprivational). After the underlying cause is addressed, vision is not restored right away, as the mechanism also involves the brain. Amblyopia can be difficult to detect, so vision testing is recommended for all children around the ages of four to five.Early detection improves treatment success. Glasses may be all the treatment needed for some children. If this is not sufficient, treatments which encourage or force the child to use the weaker eye are used. This is done by either using a patch or putting atropine in the stronger eye. Without treatment, amblyopia typically persists. Treatment in adulthood is usually much less effective.Amblyopia begins by the age of five. In adults, the disorder is estimated to affect 1–5% of the population. While treatment improves vision, it does not typically restore it to normal in the affected eye. Amblyopia was first described in the 1600s. The condition may make people ineligible to be pilots or police officers. The word amblyopia is from Greek ἀμβλύς amblys, meaning "blunt", and ὤψ ōps, meaning "sight". Signs and symptoms Many people with amblyopia, especially those who only have a mild form, are not aware they have the condition until tested at older ages, since the vision in their stronger eye is normal. People with amblyopia typically have poor stereo vision, since it requires both eyes. They further may have, on the affected eye, poor pattern recognition, poor visual acuity, and low sensitivity to contrast and motion.Amblyopia is characterized by several functional abnormalities in spatial vision, including reductions in visual acuity, contrast sensitivity function, and vernier acuity, as well as spatial distortion, abnormal spatial interactions, and impaired contour detection. In addition, individuals with amblyopia have binocular abnormalities such as impaired stereoacuity (stereoscopic acuity) and abnormal binocular summation. Also, central vision in amblyopes is more crowded than central vision in normal observers.These deficits are usually specific to the amblyopic eye. Subclinical deficits of the "better" eye have also been demonstrated.People with amblyopia also have problems of binocular vision such as limited stereoscopic depth perception and usually have difficulty seeing the three-dimensional images in hidden stereoscopic displays such as autostereograms. Perception of depth, from monocular cues such as size, perspective, and motion parallax remains normal. Cause Amblyopia has three main causes: Strabismic: by strabismus (misaligned eyes) Refractive: by anisometropia (difference of a certain degree of nearsightedness, farsightedness, or astigmatism), or by significant amount of equal refractive error in both eyes Deprivational: by deprivation of vision early in life by vision-obstructing disorders such as congenital cataract Strabismus Strabismus, sometimes also incorrectly called lazy eye, is a condition in which the eyes are misaligned. Strabismus usually results in normal vision in the preferred sighting (or "fellow") eye (the eye that the person prefers to use), but may cause abnormal vision in the deviating or strabismic eye due to the difference between the images projecting to the brain from the two eyes. Adult-onset strabismus usually causes double vision (diplopia), since the two eyes are not fixed on the same object. Childrens brains are more neuroplastic, so can more easily adapt by suppressing images from one of the eyes, eliminating the double vision. This plastic response of the brain, interrupts the brains normal development, resulting in the amblyopia. Recent evidence points to a cause of infantile strabismus lying with the input to the visual cortex.Those with strabismic amblyopia tend to show ocular motion deficits when reading, even when they use the nonamblyopic eye. In particular, they tend to make more saccades per line than persons with normal stereo vision, and to have a reduced reading speed, especially when reading a text with small font size.Strabismic amblyopia is treated by clarifying the visual image with glasses, or encouraging use of the amblyopic eye with an eyepatch over the dominant eye or pharmacologic penalization of the better eye. Penalization usually consists of applying atropine drops to temporarily paralyze the accommodation reflex, leading to the blurring of vision in the good eye. It also dilates the pupil. This helps to prevent the bullying and teasing associated with wearing a patch, although sometimes application of the eye drops is challenging. The ocular alignment itself may be treated with surgical or nonsurgical methods, depending on the type and severity of the strabismus. Refractive Refractive amblyopia may result from anisometropia (unequal refractive error between the two eyes). Anisometropia exists when there is a difference in the power between the two eyes. The eye which provides the brain with a clearer image typically becomes the dominant eye. The image in the other eye is blurred, which results in abnormal development of one half of the visual system. Refractive amblyopia is usually less severe than strabismic amblyopia and is commonly missed by primary care physicians because of its less dramatic appearance and lack of obvious physical manifestation, such as with strabismus. Given that the refractive correction of anisometropia by means of spectacles typically leads to different image magnification for the two eyes, which may in turn prevent binocular vision, a refractive correction using contact lenses is to be considered. Also pediatric refractive surgery is a treatment option, in particular if conventional approaches have failed due to aniseikonia or lack of compliance or both.Frequently, amblyopia is associated with a combination of anisometropia and strabismus. In some cases, the vision between the eyes can differ to the point where one eye has twice average vision while the other eye is completely blind. Deprivation and occlusion Deprivation amblyopia (amblyopia ex anopsia) results when the ocular media become opaque, such as is the case with congenital cataract or corneal haziness. These opacities prevent adequate visual input from reaching the eye, and disrupt development. If not treated in a timely fashion, amblyopia may persist even after the cause of the opacity is removed. Sometimes, drooping of the eyelid (ptosis) or some other problem causes the upper eyelid to physically occlude a childs vision, which may cause amblyopia quickly. Occlusion amblyopia may be a complication of a hemangioma that blocks some or all of the eye. Other possible causes of deprivation and occlusion amblyopia include obstruction in the vitreous and aphakia. Deprivation amblyopia accounts for less than 3% of all individuals affected by amblyopia. Pathophysiology Amblyopia is a developmental problem in the brain, not any intrinsic, organic neurological problem in the eyeball (although organic problems can lead to amblyopia which can continue to exist after the organic problem has resolved by medical intervention). The part of the brain receiving images from the affected eye is not stimulated properly and does not develop to its full visual potential. This has been confirmed by direct brain examination. David H. Hubel and Torsten Wiesel won the Nobel Prize in Physiology or Medicine in 1981 for their work in showing the extent of the damage to ocular dominance columns produced in kittens by sufficient visual deprivation during the so-called "critical period". The maximum "critical period" in humans is from birth to two years old. Diagnosis Amblyopia is diagnosed by identifying low visual acuity in one or both eyes, out of proportion to the structural abnormality of the eye and excluding other visual disorders as causes for the lowered visual acuity. It can be defined as an interocular difference of two lines or more in acuity (e.g. on Snellen chart) when the eye optics are maximally corrected. In young children, visual acuity is difficult to measure and can be estimated by observing the reactions of the patient when one eye is covered, including observing the patients ability to follow objects with one eye. Stereotests like the Lang stereotest are not reliable exclusion tests for amblyopia. A person who passes the Lang stereotest test is unlikely to have strabismic amblyopia, but could nonetheless have refractive or deprivational amblyopia. Binocular retinal birefringence scanning may be able to identify, already in very young children, amblyopia that is associated with strabismus, microstrabismus, or reduced fixation accuracy. Diagnosis and treatment of amblyopia as early as possible is necessary to keep the vision loss to a minimum. Screening for amblyopia is recommended in all people between three and five years of age. Treatment Treatment of strabismic or anisometropic amblyopia consists of correcting the optical deficit (wearing the necessary spectacle prescription) and often forcing use of the amblyopic eye, by patching the good eye, or instilling topical atropine in the good eye, or both.: 130  Atropine appears to result in similar outcomes to patching. If there is overpatching or overpenalizing the good eye when treating amblyopia, "reverse amblyopia" can result. Eye patching is usually done on a part-time schedule of about 4–6 hours a day. Treatment is continued as long as vision improves. It is not worthwhile continuing to patch for more than 6 months if no improvement continues.Deprivation amblyopia is treated by removing the opacity as soon as possible followed by patching or penalizing the good eye to encourage the use of the amblyopic eye. The earlier the treatment is initiated, the easier and faster the treatment is and the less psychologically damaging. Also, the chance of achieving 20/20 vision is greater if treatment is initiated early.One of the German public health insurance providers, Barmer, has changed its policy to cover, as of 1 April 2014, the cost of software for amblyopic children whose condition did not improve through patching. The app offers dedicated eye exercises that the patient performs while wearing an eyepatch.Evidence for vision therapy is unclear as of 2011. Older age Treatment of individuals age 9 through to adulthood is possible through applied perceptual learning. Tentative evidence shows that perceptual training may be beneficial in adults. Epidemiology Amblyopia occurs in between 2 and 5% of the population in Western countries. In the UK, 90% of visual health appointments in the child concern amblyopia.Depending on the chosen criterion for diagnosis, between 1 and 4% of the children have amblyopia. Research A 2009 study, widely reported in the popular press, has suggested that repetitive transcranial magnetic stimulation may temporarily improve contrast sensitivity and spatial resolution in the affected eye of adults with amblyopia. This approach is still under development, and the results await verification by other researchers. Comparable results may be achieved using different types of brain stimulation, such as anodal transcranial direct current stimulation and theta burst rTMS.A 2013 study concluded that converging evidence indicates decorrelated binocular experience plays a pivotal role in the genesis of amblyopia and the associated residual deficits. Another study of 2013 suggests that playing a version of the popular game Tetris that is modified such that each eye sees separate components of the game may also help to treat this condition in adults. Furthermore, the effects of this kind of therapy may be further enhanced by noninvasive brain stimulation as shown by a recent study using anodal tDCS.A 2014 Cochrane review sought to determine the effectiveness of occlusion treatment on patients with sensory deprivation amblyopia, but no trials were found eligible to be included in the review. However, good outcomes from occlusion treatment for sensory deprivation amblyopia likely rely on compliance with the treatment. References Further reading External links National Eye Institute (NEI) Resource Guide Lazy Eye Site from the National Health Service, UK Look After Your Eyes - patient information on Amblyopia or lazy eye by College of Optometrists

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

I'm not familiar with the medical term 'Endovascular aneurysm repair.' Could you provide some insights?

Endovascular aneurysm repair (EVAR) is a type of minimally-invasive endovascular surgery used to treat pathology of the aorta, most commonly an abdominal aortic aneurysm (AAA). When used to treat thoracic aortic disease, the procedure is then specifically termed TEVAR for "thoracic endovascular aortic/aneurysm repair." EVAR involves the placement of an expandable stent graft within the aorta to treat aortic disease without operating directly on the aorta. In 2003, EVAR surpassed open aortic surgery as the most common technique for repair of AAA, and in 2010, EVAR accounted for 78% of all intact AAA repair in the United States. Medical uses Standard EVAR is appropriate for aneurysms that begin below the renal arteries, where there exists an adequate length of normal aorta (the "proximal aortic neck") for reliable attachment of the endograft without leakage of blood around the device ("endoleak"). If the proximal aortic neck is also involved with the aneurysm, the patient may be a candidate for complex visceral EVAR with a fenestrated or branched EVAR. Patients with aneurysms require elective repair of their aneurysm when it reaches a diameter large enough (typically greater than 5.5 cm) such that the risk of rupture is greater than the risk of surgery. Repair is also warranted for aneurysms that rapidly enlarge or those that have been the source of emboli (debris from the aneurysm that dislodges and travel into other arteries). Lastly, the repair is also indicated for aneurysms that are the source of pain and tenderness, which may indicate impending rupture. The options for repair include traditional open aortic surgery or endovascular repair.Endovascular procedures aim to reduce the morbidity and mortality of treating arterial disease in a patient population that is increasingly older and less fit than when major open repairs were developed and popularized. Even in the early days, significant risks were accepted in the understanding that the large open operation was the only option. That is not the case in most patients today.Studies that assign aneurysm patients to treatment with EVAR or traditional open surgery have demonstrated fewer early complications with the minimally invasive approach. Some studies have also observed a lower mortality rate with EVAR. The reduction in death, however, does not persist long-term. After a few years, the survival after repair is similar to EVAR or open surgery. This observation may be the result of durability problems with early endograft, with a corresponding need for additional procedures to repair endoleaks and other device-related issues. Newer, improved technology may reduce the need for such secondary procedures. If so, the results of EVAR may improve to the point where long-term survival benefit becomes evident.EVAR is also used for rupture of the abdominal and descending thoracic aorta, and in rare cases used to treat pathology of the ascending aorta. Aortic dissection Endografts have been used in patients with aortic dissection, noting the extremely complex nature of open surgical repair in these patients. In uncomplicated aortic dissections, no benefit has been demonstrated over medical management alone. In uncomplicated type B aortic dissection, TEVAR does not seem either to improve or compromise 2-year survival and adverse event rates. Its use in complicated aortic dissection is under investigation. In the Clinical Practice Guidelines of the European Society for Vascular Surgery, it is recommended that in patients with complicated acute type B aortic dissection, endovascular repair with thoracic endografting should be the first line intervention.Before people are deemed to be suitable candidates for this treatment, they have to go through a rigorous set of tests. These include a CT scan of the complete thorax/abdomen/pelvis and blood tests. The CT scan gives precise measurements of the aneurysm and the surrounding anatomy. In particular, the calibre/tortuosity of the iliac arteries and the relationship of the neck of the aneurysm to the renal arteries are important determinants of whether the aneurysm is amenable to endoluminal repair. In certain occasions where the renal arteries are too close to the aneurysm, the custom-made fenestrated graft stent is now an accepted alternative to doing open surgery. Relative contraindications A patients anatomy can be unsuitable for EVAR in several ways. Most commonly, in an infrarenal aneurysm, a potential EVAR candidate lacks adequate length of the normal-diameter aorta between the aneurysm and the takeoff of the renal arteries, the "infra-renal neck". Another relative contraindications include prohibitively small iliac arteries, aneurysmal iliac arteries, prohibitively small femoral arteries, or circumferential calcification of the femoral or iliac arteries.In addition to a short proximal aortic neck, the neck may be angulated, large in diameter, or shaped like a funnel (conical) where the neck diameter at the top is larger than the neck diameter at the bottom. Along with a short proximal aortic neck, necks with any of these characteristics are called "hostile necks" and endovascular repair can be either contraindicated or associated with early-late complications of endoleak, or endograft migration, or both.Many of the advances in EVAR technique aim to adapt EVAR for these situations, and advanced techniques allow EVAR to be employed in patients who previously were not candidates. Technique The procedure is carried out in a sterile environment under fluoroscopic guidance. It is usually carried out by a vascular surgeon, interventional radiologist or cardiac surgeon, and occasionally, general surgeon or interventional cardiologist. The procedure can be performed under general, regional (spinal or epidural) or even local anesthesia. Access to the patients femoral arteries can be with surgical incisions or percutaneously in the groin on both sides. Vascular sheaths are introduced into the patients femoral arteries, through which guidewires, catheters, and the endograft are passed.Diagnostic angiography images are captured of the aorta to determine the location of the patients renal arteries, so the stent-graft can be deployed without blocking these. Failure to achieve this will cause kidney failure. With most devices, the "main body" of the endograft is placed first, followed by the "limbs" which join the main body and extend to the iliac arteries, effectively protecting the aneurysm sac from blood pressure.The abdominal aneurysm extends down to the common iliac arteries in about 25%-30% of patients. In such cases, the iliac limbs can be extended into the external iliac artery to bypass a common iliac aneurysm. Alternatively, a specially designed endograft, (an iliac branch device) can be used to preserve flow to the internal iliac arteries. The preservation of the hypogastric (internal iliac) arteries is important to prevent buttock claudication and impotence, and every effort should be made to preserve flow to at least one hypogastric artery.The endograft acts as an artificial lumen for blood to flow through, protecting the surrounding aneurysm sac. This reduces the pressure in the aneurysm, which itself will usually thrombose and shrink in size over time.Staging such procedures is common, particularly to address aortic branch points near the diseased aortic segment. One example in the treatment of thoracic aortic disease is revascularization of the left common carotid artery and/or the left subclavian artery from the innominate artery or the right common carotid artery to allow treatment of a thoracic aortic aneurysm that encroaches proximally into the aortic arch. These "extra-anatomic bypasses" can be performed without an invasive thoracotomy. Another example in the abdominal aorta is the embolization of the internal iliac artery on one side prior to coverage by an iliac limb device. Continued improvement in stent-graft design, including branched endografts, will reduce but not eliminate multi-stage procedures. Percutaneous EVAR Standard EVAR involves a surgical cut-down on either the femoral or iliac arteries, with the creation of a 4–6 cm incision. Like many surgical procedures, EVAR has advanced to a more minimally invasive technique, by accessing the femoral arteries percutaneously In percutaneous EVAR (PEVAR), small, sub-centimeter incisions are made over the femoral artery, and endovascular techniques are used to place the device over a wire. Percutaneous EVAR has been systematically compared to the standard EVAR cut-down femoral artery approach. Moderate quality evidence suggests that there are no differences in short-term mortality, aneurysm sealing, long and short-term complications, or infections at the wound site. Higher quality evidence suggests that there are no differences in post-repair bleeding complications or haematoma between the two approaches. The percutaneous approach may have reduced surgical time. Fenestrated EVAR In certain circumstances, a specially designed custom-made graft, which has holes, or fenestrations, on the graft body to maintain the patency of the visceral arteries, is used for the procedure, which is called FEVAR (fenestrated endovascular aortic/aneurysm repair). When the aneurysm begins close to the renal arteries, standard EVAR may be contraindicated since there will be an inadequate length of suitable aorta for the endograft attachment. In these cases, a fenestrated endograft may be useful, where the attachment of the endograft to the aorta may be placed above the renal arteries with each fenestration aligned with a renal artery so that blood flow to the kidneys is maintained. Fenestrated EVAR has been in use in the United Kingdom for over a decade and early results were published in Jun 2012. Branched EVAR Thoracoabdominal aortic aneurysms (TAAA) involve the aorta in the chest and abdomen. As such, major branch arteries to the head, arms, spinal cord, intestines, and kidneys may originate from the aneurysm. An endovascular repair of a TAAA is only possible if blood flow to these critical arteries is preserved. Hybrid procedures offer one option, but a more direct approach involves the use of a branched endograft. However, the complex anatomy associated with the supra-aortic vessels is particularly difficult to accommodate with branched endograft devices. Dr. Timothy Chuter pioneered this approach, with a completely endovascular solution. After partial deployment of the main body of an endograft, separate endograft limbs are deployed from the main body to each major aortic branch. This procedure is long, technically difficult, and currently only performed in a few centers. When the aneurysm begins above the renal arteries, neither fenestrated endografts nor "EndoAnchoring" of an infrarenal endograft is useful (an open surgical repair may be necessary). Alternatively, a "branched" endograft may be used. A branched endograft has graft limbs that branch off of the main portion of the device to directly provide blood flow to the kidneys or the visceral arteries. Hybrid procedures On occasion, there is inadequate length or quality of the proximal or distal aortic neck. In these cases, a fully minimally invasive option is not possible. One solution, however, is a hybrid repair, which combines an open surgical bypass with EVAR or TEVAR. In hybrid procedures, the endograft is positioned over major aortic branches. While such a position would normally cause problems from disruption of blood flow to the covered branches (renal, visceral, or branches to the head or arms), the prior placement of bypass grafts to these critical vessels allowed the deployment of the endograft at a level that would otherwise not be possible.If a patient has calcified or narrow femoral arteries that prohibit the introduction of the endograft transfemorally, an iliac conduit may be used. This is typically a piece of PTFE that is sewn directly to the iliac arteries, which are exposed via an open retroperitoneal approach. The endograft is then introduced into the aorta through the conduit.In patients with thoracic aortic disease involving the arch and descending aorta, it is not always possible to perform a completely endovascular repair. This is because head vessels of the aortic arch supplying blood to the brain cannot be covered and for this reason, there is often an inadequate landing zone for stent-graft delivery. A hybrid repair strategy offers a reasonable choice for treating such patients. A commonly used hybrid repair procedure is the "frozen elephant trunk repair". This technique involves midline sternotomy. The aortic arch is transected and the stent-graft device is delivered in an ante-grade fashion in the descending aorta. The aortic arch is subsequently reconstructed and the proximal portion of the stent-graft device is then directly sutured into the surgical graft. Patients with anomalies of the arch and some disease extension into the descending aorta are often ideal candidates. Studies have reported successful use of hybrid techniques for treating Kommerell diverticulum and descending aneurysms in patients with previous coarctation repairs.In addition, hybrid techniques combining both open and endovascular repair are also used in managing emergency complications in the aortic arch, such as retrograde ascending dissection and endoleaks from previous stent grafting of descending aorta. A "reverse frozen elephant trunk repair" is shown to be particularly effective. Adjunctive procedures Snorkel: A covered stent placed into a visceral vessel adjacent to the main body of the EVAR device. The aortic lumen of the visceral stent is directed superiorly, resembling a snorkel. Chimney: In TEVAR, a covered stent placed from the ascending aorta to a great vessel (e.g., innominate artery) and adjacent to the main body of the EVAR is termed a chimney. In anatomic position, blood flows superiorly through a chimney-stent graft into the great vessel, just as smoke flows up a chimney. Periscope: Like a snorkel, a periscope stent graft provides flow to a visceral vessel, but in a retrograde fashion, with the aortic lumen inferior to the main body of the EVAR device. Stents: Large bare-metal stents have been used to treat proximal endoleaks, as have aortic extension cuffs to treat endograft migration. Glue: Trans-catheter embolic glue has been used to treat type I endoleaks, with inconsistent success. EndoAnchors: Small, helically shaped devices are screwed through the endograft and into the aortic wall. EndoAnchors have been used successfully to treat endoleaks and, in concert with an aortic extension endograft, to treat migration of the original endograft. Rigorous evaluations and long-term outcomes of this technique are not yet available. Risks The complications of EVAR can be divided into those that are related to the repair procedure and those related to the endograft device. For example, a myocardial infarction that occurs immediately after the repair is normally related to the procedure and not the device. By contrast, the development of an endoleak from degeneration of endograft fabric would be a device-related complication.Durability and problems such as endoleaks may require careful surveillance and adjuvant procedures to ensure the success of the EVAR or EVAR/hybrid procedure. CT angiography (CTA) imaging has, in particular, made a key contribution to planning, success, durability in this complex area of vascular surgery.A major cause of complications in EVAR is the failure of the seal between the proximal, infra-renal aneurysm neck and the endovascular graft. Risk of this form of failure is especially elevated in adverse or challenging proximal neck anatomies, where this seal could be compromised by unsuitable geometric fit between the graft and vessel wall, as well as instability of the anatomy. New recent techniques have been introduced to address these risks by utilizing a segment of the supra-renal portion of the aorta to increase the sealing zone, such as with fenestrated EVAR, chimneys and snorkels. These techniques may be suitable in certain patients with qualifying factors, e.g., configuration of renal arteries, renal function. However, these are more complex procedures than standard EVAR and may be subject to further complications.An approach that directly augments the fixation and sealing between the graft and aorta to mimic the stability of a surgical anastomosis is EndoAnchoring. EndoAnchors are small, helically shaped implants that directly lock the graft to the aortic wall with the goal to prevent complications of the seal, especially in adverse neck anatomies. These EndoAnchors may also be used to treat identified leaks between the graft and proximal neck. Procedure-related Arterial dissection, contrast-induced kidney failure, thromboembolizaton, ischemic colitis, groin hematoma, wound infection, type II endoleaks, myocardial infarction, congestive heart failure, cardiac arrhythmias, respiratory failure. Device-related Endograft migration, aneurysm rupture, graft limb stenosis/kinking, type I/III/IV endoleaks, stent graft thrombosis, or infection. Endoleaks An endoleak is a leak into the aneurysm sac after endovascular repair. Five types of endoleaks exist: Type I - Perigraft leakage at proximal or distal graft attachment sites (near the renal and iliac arteries) Type II - Retrograde flow to the aneurysm sac from branches such as the lumbar and inferior mesenteric arteries. Type II endoleaks are the most common, and least serious type of endoleak. Type II endoleaks do not require immediate treatment, as a portion will resolve spontaneously. Type III - Leakage between overlapping parts of the stent (i.e., the connection between overlapping components) or rupture through graft material. Type IV - Leakage through the graft wall due to the quality (porosity) of the graft material. As seen in first-generation grafts, changes in graft material in modern devices have decreased the prevalence of type IV leaks. Type V - Expansion of the aneurysm sac without an identifiable leak. Also called "endotension".Type I and III leaks are considered high-pressure leaks and are more concerning than other leak types. Depending on the aortic anatomy, they may require further intervention to treat. Type 2 leaks are common and often can be left untreated unless the aneurysm sac continues to expand after EVAR. Spinal cord injury Spinal cord injury is a devastating complication after aortic surgery, specifically for thoracoabdominal aortic aneurysm repair; severe injury could lead to urine and fecal incontinence, paresthesia and even paraplegia. The risk varies between studies with two metanalysis demonstrating a pooled incidence of spinal cord injury 2.2% and 11%. Predictive factors include increasing extent of coverage, hypogastric artery occlusion, prior aortic repair and perioperative hypotension. Spinal cord injury related to aortic repair occurs due to impaired blood flow to the spine after coverage of blood vessels, important to the blood circulation of the spine, namely intercostal- and lumbar arteries. A few methods exist for potentially reversing spinal cord injury, if it arises, elevated blood pressure, increased oxygenation, blood transfusion and cerebrospinal fluid drainage. Cerebrospinal fluid drainage Cerebrospinal fluid drainage is one of the adjunct methods used to reverse spinal cord injury. With increased drainage of spinal fluid, the intrathecal pressure decreases which allows for increase blood perfusion to the spine, possibly reversing the ischemic injury of the spinal tissue due to lessened blood supply. The benefits of this procedure have been established in open aortic repair and suggested in endovascular aortic repair. Recovery after EVAR Unlike traditional aortic repair, standard recovery after EVAR is remarkably straightforward. Patients who have undergone EVAR typically spend one night in the hospital to be monitored, although it has been suggested that EVAR can be performed as a same-day procedure.Patients are advised to slowly return to normal activity. There are no specific activity restrictions after EVAR, however, patients typically are seen by their surgeon within one month after EVAR to begin post-EVAR surveillance.There is limited research looking at patients experience of recovery after more complex and staged EVAR for thoracoabdominal aortic diseases. One qualitative study found that patients with complex aortic diseases struggle with physical and psychological setbacks, continuing years after their operations. History Dr. Juan C. Parodi introduced the minimally-invasive endovascular aneurysm repair (EVAR) to the world and performed the first successful endovascular repair of an abdominal aortic aneurysm on 7 September 1990 in Buenos Aires on a friend of Carlos Menem, the then President of Argentina. The first device was simple, according to Parodi: "It was a graft I designed with expandable ends, the extra-large Palmaz stent, a Teflon sheath with a valve, a wire, and the valvuloplasty balloon, which I took from the cardiologists." Parodis first patient lived for nine years after the procedure and died from pancreatic cancer. The first EVAR performed in the United States was in 1992 by Drs. Frank Veith, Michael Marin, Juan Parodi and Claudio Schonholz at Montefiore Medical Center affiliated with Albert Einstein College of Medicine.The modern endovascular device used to repair abdominal aortic aneurysms, which is bifurcated and modular, was pioneered and first employed by Dr. Timothy Chuter while a fellow at the University of Rochester. The first clinical series of his device was published from Nottingham in 1994. The first endovascular repair of a ruptured abdominal aortic aneurysm was also reported from Nottingham in 1994.By 2003, four devices were on the market in the United States. Each of these devices has since been either abandoned or further refined to improve its characteristics in vivo. Special populations Women Women are known to have smaller aortas on average than men, so are potential candidates for AAA treatment at smaller maximum aneurysm diameters than men. Transplant candidates As immunosuppressive medications are known to increase the rate of aneurysm growth, transplant candidates are AAA repair candidates at smaller maximum aneurysm diameters than the general population. Other animals Due to the expense associated with EVAR stent-graft devices and their specificity to human aortic anatomy, EVAR is not used in other animals. Videos == References ==

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 please explain the term 'Fexinidazole' in simple language?

Fexinidazole is a medication used to treat African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense. It is effective against both first and second stage disease. Some evidence also supports its use in Chagas disease. It is taken by mouth.Common side effects include nausea, vomiting, headache, and trouble sleeping. Other side effects may include QT prolongation, psychosis, and low white blood cells. It is unclear if use during pregnancy or breast feeding is safe. Fexinidazole is in the antiparasitic and the nitroimidazole family of medications. It is believed to work by turning on certain enzymes within the parasites that result in their death.Fexinidazole was first described in 1978. It was given a positive opinion by the European Medicines Agency in 2018. It is on the World Health Organizations List of Essential Medicines. Development for sleeping sickness was funded by the Drugs for Neglected Diseases initiative in collaboration with Sanofi. Fexinidazole was approved for medical use in the United States in July 2021. Medical use Sleeping sickness A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness. Though less effective than nifurtimox with eflornithine in severe disease, fexinidazole has the benefit that it can be taken by mouth.Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years. Other It has activity against Trypanosoma cruzi, Tritrichomonas foetus, Trichomonas vaginalis, Entamoeba histolytica, and Trypanosoma brucei. It has not been found to be useful for visceral leishmaniasis. Mechanism of action The biologically relevant active metabolites in vivo are the sulfoxide and sulfone. History Fexinidazole was discovered by the German pharmaceutical company Hoechst AG, but its development as a pharmaceutical was halted in the 1980s. Society and culture Fexinidazole Winthrop, a Sanofi-Aventis product developed with the Drugs for Neglected Diseases Initiative (DNDi), received a positive endorsement from the European Medicines Agency in 2018, for use in non-European markets. It was approved for the treatment of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) in December 2018. Fexinidazole was included in the role of honour in Préscrire magazines 2020 prize list.[1] Veterinary use Fexinidazole is promising in African animal trypanosomiasis. Torreele et al. 2010 found the drug to be effective against T. b. gambiense infection of mice, rats, rabbits and beagles. They also found no toxicity in any of them, including a lack of mutagenicity despite in vitro mutagenicity. References External links "Fexinidazole". Drug Information Portal. U.S. National Library of Medicine.

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

Early childhood caries (ECC), formerly known as nursing bottle caries, baby bottle tooth decay, night bottle mouth and night bottle caries, is a disease that affects teeth in children aged between birth and 71 months. ECC is characterized by the presence of 1 or more decayed (noncavitated or cavitated lesions), missing (due to caries), or filled tooth surfaces in any primary tooth. ECC has been shown to be a very common, transmissible bacterial infection, usually passed from the primary caregiver to the child. The main bacteria responsible for dental caries are Streptococcus mutans (S. mutans) and Lactobacillus. There is also evidence that supports that those who are in lower socioeconomic populations are at greater risk of developing ECC. Aetiology Early childhood caries (ECC) is a multi-factorial disease, referring to various risk factors that inter-relate to increase risk of developing the disease. These risk factors include but not limits to, cariogenic bacteria, diet practices and socioeconomic factors. Normally after 6 months, deciduous teeth begin to erupt means, they are susceptible to tooth decay or dental caries. In some unfortunate cases, infants and young children have experienced severe tooth decay called ECC. This can result in the child experiencing severe pain, extensive dental restorations or extractions. The good news is that ECC is preventable, however, still remains a large burden particularly towards health care expenditure. Microbial factors The primary cariogenic bacteria involved in ECC are S. mutans and Lactobacillus. The oral flora in an infant oral cavity is not colonised with normal oral flora until the eruption of the primary dentition at approximately 6 to 30 months of age. The colonisation of S. Mutans from mother to infant is well documented. Over time this combination of food debris and bacteria form a biofilm on the tooth surface called plaque. In plaque, the cariogenic microorganisms are those that produce lactic acid as a by-product from fermentable carbohydrates. Examples of these fermentable carbohydrates include fructose, sucrose and glucose. Cariogenic bacteria thrive on these sugars and help them to weaken the adjacent tooth surface. A poor oral care routine and a diet that is high in fermentable carbohydrates favour acidic attack in the oral cavity. This prolonged acidic exposure allows the net loss of minerals from the tooth. This diminishes the strength of the tooth and is called demineralisation. For the outer layer of the tooth (enamel) to reach cavitation, there is a breakdown of the enamel matrix that allows the influx of the cariogenic bacteria. As cavitation progresses into dentine, the dental caries is classified severe, this causes ECC. Dietary factors Diet plays a key role in the process of dental caries. The type of foods along with the frequency at which they are consumed can determine the risk it puts for also developing carious lesions. With new products being put on supermarket shelves with irresistible prices, this can largely influence what people buy. It is common for infants and young children to frequently consume fermentable carbohydrates, in the form of liquids. The consumption of liquids containing fermentable carbohydrate, include drinks such as: juice, breast milk, formula, soda. These consumables all have the potential to increase the risk of dental caries due to prolonged contact between sugars in the liquid and cariogenic bacteria on the tooth surface. Recent research has shown that breastfeeding does not increase caries risk up to 12 months of age. Poor feeding practices without appropriate preventive measures can lead to a distinctive pattern of caries in susceptible infants and toddlers commonly known as baby bottle tooth decay or ECC. Frequent and long duration bottle feeding, especially at night, is associated with ECC. This finding can be attributed to the fact that there is less salivary flow at night and hence less capacity for buffering and remineralisation. Each time a child drinks these liquids, acids attack for 20 minutes or longer. A parents education and health awareness has a major influence on the caries experience of their child - feeding practices, dietary habits and food choices. Socioeconomic factors Dental caries still today, remains the most prevalent disease worldwide. This means the disease is highly preventable, yet it is still burdening millions of children and into adulthood with pain and potentially lower quality of life. There are several studies by Locker and Mota-Veloso reporting that there is a two-way relationship that exists between dental caries and levels of education, household income that effect quality of life and social positioning. Locker suggested that the relationship between oral disease and health-related quality of life outcomes can be mediated by personal and environmental variables. Previous studies have also mentioned that the rate of ECC has decreased. However, these results can tend to dis-include communities where equity still exists. More health promotion initiatives and policy-making that collaborate directly with the community to increase meeting their needs, should be implemented.While the primary aetiology is due to microbial factors, it is also largely influenced by the social, behavioral and economic determinants in which children are surrounded by. such factors include living in a low income earning family that may not have the budget to afford visiting a dental clinic. Secondly, having limited access to healthcare and education where important messages about the consumption of carcinogenic foods are not being transferred to children or their parents. Distribution of budget should be made to reach rural and remote communities to implement health promotion strategies to increase awareness about diet and oral hygiene. The education, occupation and income of families also greatly affects the quality of life. Children greatly rely on their parents or guardians for help concerning their health and well-being. Studies have shown that families of lower socioeconomic status are less likely to regularly attend the dentist and access preventive dental resources. ECC also has an accumulative effect for those that live in rural areas. Prevention Early childhood caries can be prevented through the combination of the following: adhering to a healthy nutritional diet, optimal plaque removal, use of fluoridation on the tooth surface once erupted, care taken by the mother during the pre-natal and peri-natal period and regular dental visits. The following are recommendations to help prevent ECC. Adequate diet Dietary habits and the presence of cariogenic bacteria within the oral cavity are an important factor in the risk of ECC. ECC is commonly caused by bottle feeding, frequent snacking and a high sugar diet In regards to preventing ECC through bottle feeding, it is fundamental not to allow the child to sleep using ‘sippy cups’ or bottles as this is a large factor contributing to baby bottle decay/caries. This is highly encouraged as it prevents continuous exposure to non-milk extrinsic sugars and therefore the potential progression of caries – this means the oral cavity can return to a neutral pH and therefore decreased acidity. These researches also suggest trying to introduce cups to children as they approach their first birthday and to reduce the use of a bottle. A low-sugar and high nutritional diet is recommended for both the mother and the child especially during breastfeeding, and it is also recommended to avoid frequent snackingA 2019 Cochrane review concluded that there is a 15% drop in risk of developing ECC, when mother with infants or pregnant women were given advice on a healthy child diet and feeding practices. Consequently, resulting in less decay for the child. Optimal plaque removal On eruption of the first primary tooth in a child, tooth brushing and cleaning should be performed by an adult. This is important as the plaque that attaches to the surface of the tooth has bacteria that have the ability to cause caries (decay) on the tooth surface. It is recommended to brush childrens teeth using a soft bristled, age and size appropriate toothbrush and age appropriate toothpaste twice daily, however children below the age of two usually dont require toothpaste. These researches also suggest that it is suitable to brush childrens teeth until they reach the approximate age of 6; where they will begin to learn adequate dexterity and cognition needed for adequate brushing by themselves. It is encouraged to watch children brushing their teeth until they are competently able to brush appropriately alone. Fluoride Fluoride is a natural mineral that naturally occurs throughout the world – it is also the active ingredient of many toothpastes specifically for its remineralizing effects on enamel, often repairing the tooth surface and reducing the risk of caries. The use of fluoridated toothpaste is highly recommended by dental professionals; whereby studies suggest that the correct daily use of fluoride on the dentition of children has a high caries-preventive effect and therefore prevents has potential to prevent ECC. However, it is important to use fluoridated toothpastes correctly; children below the age of two do not usually require toothpaste unless they are already at a high risk of ECC as diagnosed by a dental professional, and therefore it is recommended to use a small sized ‘smear’ of toothpaste to incorporate fluoride, with caution removing the toothpaste from within the mouth and not allowing the child to swallow the substances. Pre-natal and peri-natal period Prevention of early childhood caries begins before the baby is born; women are advised to maintain a well-balanced diet of high nutritional value, especially during the third trimester and within the infants first year of life. This is since enamel undergoes maturation; if the diet is not sufficient, a common condition that may occur is enamel hypoplasia. Enamel hypoplasia is a developmental defect of enamel that occurs during tooth development, mainly pre-natally or during early childhood. Teeth affected by enamel hypoplasia are commonly at a higher risk of caries since there is an increased loss of minerals and therefore the tooth surface is able to breakdown more easily than in comparison to a non-hypoplastic tooth. It is therefore suggested to the mother to maintain a healthy diet since evidence suggests malnourishment during the perinatal period increases the risk of hypoplastic teeth in an infant. Dental visits It is recommended to parents and caregivers to take their children to a dental professional for examination as soon as the first few teeth start to erupt into the oral cavity. The dental professional will assess all the present dentition for early carious demineralization and may provide recommendations to the parents or caregivers the best way to prevent ECC and what actions to take. Studies suggest that children who have attended visits within the first few years of life (an early preventive dental visit) potentially experience less dental related issues and incur lower dental related costs throughout their lives. Treatment The current standard of care for Severe Early Childhood Caries includes restoration and extraction of carious teeth and, where possible, includes early intervention which includes application of topical fluoride, oral hygiene instructions and education. The initial visit is important as it allows dental professionals to flag unfavourable behaviour or eating habits. This will also allow dental clinician, working in a collaborative team, to perform diagnostic testing to determine the rate and progression of the disease. This is done by performing risk assessment based on the childs age, as well as the social, behavioural, and medical history of the child. Children at low risk may not need any restorative therapy, and frequent visits should be made to detect possible early lesions. Children at moderate risk may require restoration of progressing and cavitated lesions, while white spot and enamel proximal lesions should be treated by preventive techniques and monitored for progression. Children at high risk, however, may require earlier restorative intervention of enamel proximal lesions, as well as intervention of progressing and cavitated lesions to minimize continual caries development. As Early Childhood Caries occurs in children under the age of 5, restorative treatment is conventionally performed under general anesthetic to prevent a traumatic experience for the child. Still, the literature shows a high rate of caries relapse after treatment under general anesthesia, sometimes as early as 6 months after treatment was rendered.Dental professionals now have a safe, inexpensive, and less invasive option to manage Early Childhood Caries: Silver Diamine Fluoride (SDF) is a liquid containing silver and fluoride that can be brushed on teeth to stop decay, relieve sensitivity, and prevent cavities from getting worse. Silver kills the bacteria that cause tooth decay and fluoride helps strengthen the tooth. SDF is applied directly to the area of decay without first having to drill the tooth. SDF is an inexpensive option that is simple to apply; however, although it stops the decay from progressing, it does not fill the cavity, and the tooth may still need to be restored with a filling or crown. After treatment with SDF, arrested decay will become black, but a dental provider can cover the treated area with a white filling material if needed. This may be less of a problem in baby teeth, which will be lost as the child ages, than for permanent teeth. Even so, because applying SDF is quick, it may be especially helpful for young children and other patients who have trouble sitting still during dental treatments, avoiding the need for sedation or general anesthesia. However, the use of SDF remains controversial and more good quality research is needed to be conclusive on its effectiveness, its need and its adverse effects on early caries and childrens health especially for those in developed countries. This is particularly important in light of the FDA warnings about using general anesthetics and sedation in young children. The American Dental Association recognizes SDF as an effective approach to conservatively manage dental decay.Depending on the level of cavitation of the teeth, different types of restorations may be employed. Stainless steel (preformed) crowns are pre-fabricated crown forms which can be adapted to individual primary molars and cemented in place to provide a definitive restoration or can be fitted using the Hall Technique. They have been indicated for the restoration of primary and permanent teeth with caries where a normal filling may not last. Another approach of treating dental caries in young children is Atraumatic Restorative Treatment (ART). The ART is a procedure based on removing carious tooth tissues using hand instruments alone and restoring the cavity with an adhesive restorative material. This is useful to prevent trauma and requires less chair time for the young patients. This is used in cases where the teeth are being maintained in the mouth to maintain space for the future teeth to come through. Low quality evidence indicates that ART may have a higher risk of filling failure when compared to usual care. Despite the potential for filling failure, ART is still recommended for children when access to electricity, drills, dentists, or other dental resources are limited. References 16.Maternal Perception about Early Childhood Caries in Nigeria in Kalipeni, E.; Iwelunmor, J.; Grigsby-Toussaint, D.; and Moise, I. K. (eds.) (In Press, June 2018). Public Health, Disease and Development in Africa. London: Routledge Publishers. External links American Academy of Pediatric Dentistry American Dental Association ADA page on early childhood tooth decay Columbia Center Comparison of Dental Surgery versus Caries Suppression with other treatments Childrens Dental Health Project

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

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

Factor I deficiency, also known as fibrinogen deficiency, is a rare inherited bleeding disorder related to fibrinogen function in the blood coagulation cascade. It is typically subclassified into four distinct fibrinogen disorders: afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. Afibrinogenemia is defined as a lack of fibrinogen in the blood, clinically <20 mg/deciliter of plasma. The frequency of this disorder is estimated at between 0.5 and 2 per million. Within the United States, afibrinogenemia accounts for 24% of all inherited abnormalities of fibrinogen, while hypofibrinogenemia and dysfibrinogenemia account for 38% each. Congenital hypofibrinogenemia is defined as a partial deficiency of fibrinogen, clinically 20–80/deciliter of plasma. Estimated frequency varies from <0.5 to 3 per million. Dysfibrinogenemia is defined as malfunctioning or non-functioning fibrinogen in the blood, albeit at normal concentrations: 200–400 mg/deciliter of plasma. Dysfibrinogenemia may be an inherited disease and therefore termed congenital dysfibrinogenemia or secondary to another disease and therefore termed acquired dysfibrinogenemia. The congenital disorder is estimated to a frequency varying between 1 and 3 per million. Hypodysfibrinogenemia is a partial deficiency of fibrinogen that is also malfunctioning. Hypodysfibrinogenemia is an extremely rare inherited disease.Clinically, these disorders are generally associated with an increased diathesis, i.e. propensity, to develop spontaneous bleeding episodes and excessive bleeding after even minor tissue injuries and surgeries; however, individuals with any of these disorders may also exhibit a propensity to pathological thrombosis episodes.Treatment of these disorders generally involves specialized centers and the establishment of preventive measures designed based on each individuals personal and family histories of the frequency and severity of previous bleeding and thrombosis episodes, and, in a select few cases, the predicted propensity of the genetic mutations which underlie their disorders to cause bleeding and thrombosis. Signs and symptoms Afibrinogenemia is typically the most severe of the three disorders. Common symptoms include bleeding of the umbilical cord at birth, traumatic and surgical bleeding, GI tract, oral and mucosal bleeding, spontaneous splenic rupture, and rarely intracranial hemorrhage and articular bleeding. Symptoms of hypofibrinogenemia varies from mild to severe, but can include bleeding of the GI tract, oral and mucosal bleeding, and very rarely intracranial bleeding. More commonly it presents during traumatic bleeding or surgical procedures. Most cases (60%) of dysfibrinogenemia are asymptomatic, but 28% exhibit hemorrhaging similar to that described above while 20% exhibit thrombosis (i.e. excessive clotting). Causes The disorders associated with Factor I deficiency are generally inherited, although certain liver diseases can also affect fibrinogen levels and function (e.g. cirrhosis). Afibrinogenemia is a recessive inherited disorder, where both parents must be carriers. Hypofibrinogenemia and dysfibrinogenemia can be dominant (i.e. only one parent needs to be a carrier) or recessive. The origin of the disorders is traced back to three possible genes: FGA, FGB, or FGG. Because all three are involved in forming the hexameric glycoprotein fibrinogen, mutations in any one of the three genes can cause the deficiency. Diagnosis Treatment The most common type of treatment is cryoprecipitate or fibrinogen concentrate drip to increase fibrinogen levels to normal during surgical procedures or after trauma. RiaSTAP, a factor I concentrate, was approved by the U.S. FDA in 2009 for use when the fibrinogen level was below 50 mg/deciliter of plasma. Recently, antifibrinolytics have also been used to inhibit fibrinolysis (breaking down of the fibrin clot). In the case of dysfibrinogenemia that manifests by thrombosis, anticoagulants can be used. Due to the inhibited clotting ability associated with a- and hypofibrinogenemia, physicians advise against the use of Aspirin as it inhibits platelet function. See also Congenital afibrinogenemia Hypodysfibrinogenemia References == External links ==

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What does the medical term 'Herpesviral meningitis' encompass?

Herpesviral meningitis is meningitis associated with herpes simplex virus (HSV).HSV-2 is the most common cause of Mollarets meningitis, a type of recurrent viral meningitis. This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few weeks, and resolve without treatment. They may recur weekly or monthly for approximately 5 years following primary infection. Diagnosis Although DNA analysis techniques such as polymerase chain reaction can be used to look for DNA of herpesviruses in spinal fluid or blood, the results may be negative, even in cases where other definitive symptoms exist. Treatment See also Herpesviral encephalitis References == External links ==

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

A tear of a meniscus is a rupturing of one or more of the fibrocartilage strips in the knee called menisci. When doctors and patients refer to "torn cartilage" in the knee, they actually may be referring to an injury to a meniscus at the top of one of the tibiae. Menisci can be torn during innocuous activities such as walking or squatting. They can also be torn by traumatic force encountered in sports or other forms of physical exertion. The traumatic action is most often a twisting movement at the knee while the leg is bent. In older adults, the meniscus can be damaged following prolonged wear and tear. Especially acute injuries (typically in younger, more active patients) can lead to displaced tears which can cause mechanical symptoms such as clicking, catching, or locking during motion of the joint. The joint will be in pain when in use, but when there is no load, the pain goes away. A tear of the medial meniscus can occur as part of the unhappy triad, together with a tear of the anterior cruciate ligament and medial collateral ligament. Signs and symptoms The common signs and symptoms of a torn meniscus are knee pain, particularly along the joint line, and swelling. These are worse when the knee bears more weight (for example, when running). Another typical complaint is joint locking, when the affected person is unable to straighten the leg fully. This can be accompanied by a clicking feeling. Sometimes, a meniscal tear also causes a sensation that the knee gives way.A person with a torn meniscus can sometimes remember a specific activity during which the injury was sustained. A tear of the meniscus commonly follows a trauma that involves rotation of the knee while it was slightly bent. These maneuvers also exacerbate the pain after the injury; for example, getting out of a car is often reported as painful. Causes There are two menisci in the knee. They sit between the thigh bone and the shin bone. While the ends of the thigh bone and the shin bone have a thin covering of soft hyaline cartilage, the menisci are made of tough fibrocartilage and conform to the surfaces of the bones they rest on. One meniscus rests on the medial tibial plateau; this is the medial meniscus. The other meniscus rests on the lateral tibial plateau; this is the lateral meniscus.These menisci act to distribute body weight across the knee joint. Without the menisci, the weight of the body would be unevenly applied to the bones in the legs (the femur and tibia). This uneven weight distribution would cause the development of abnormal excessive forces leading to early damage of the knee joint. The menisci also contribute to the stability of the joint.The menisci are nourished by small blood vessels but have a large area in the center with no direct blood supply (avascular). This presents a problem when there is an injury to the meniscus, as the avascular areas tend not to heal. Without the essential nutrients supplied by blood vessels, healing cannot take place.The two most common causes of a meniscal tear are traumatic injury (often seen in athletes) and degenerative processes, which are the most common tear seen in all ages of patients. Meniscal tears can occur in all age groups. Traumatic tears are most common in active people aged 10–45. Traumatic tears are usually radial or vertical in the meniscus and more likely to produce a moveable fragment that can catch in the knee and therefore require surgical treatment.A meniscus can tear due to an internally or externally rotated knee in a flexed position, with the foot in a flexed position. It is not uncommon for a meniscal tear to occur along with injuries to the anterior cruciate ligament ACL and the medial collateral ligament MCL — these three problems occurring together are known as the "unhappy triad," which is seen in sports such as football when the player is hit on the outside of the knee. Individuals who experience a meniscal tear usually experience pain and swelling as their primary symptoms. Another common complaint is joint locking, or the inability to completely straighten the joint. This is due to a piece of the torn cartilage preventing the normal functioning of the knee joint.Degenerative tears are most common in people from age 40 upward but can be found at any age, especially with obesity. Degenerative meniscal tears are thought to occur as part of the aging process when the collagen fibers within the meniscus start to break down and lend less support to the structure of the meniscus. Degenerative tears are usually horizontal, producing both an upper and a lower segment of the meniscus. These segments do not usually move out of place and are therefore less likely to produce mechanical symptoms of catching or locking. Risk factors The meniscus is made of cartilage, a viscoelastic material, which makes it more susceptible to rate of loading injuries. Repetitive loading can also lead to injury. Recent studies have shown people who experience rapid rate of loading and/or repetitive loading to be the most susceptible to meniscus tears. People over the age of 60 who have working conditions in which squatting and kneeling are common are more susceptible to degenerative meniscal tears. Athletes who constantly experience a high rate of loading (e.g. soccer, rugby) are also susceptible to meniscus tears. Studies have also shown with increasing time between ACL injury and ACL reconstruction, there is an increasing chance of meniscus tears. This study showed meniscus tears occurring at a rate of 50–70% depending on how long after the ACL injury the surgery occurred. Meniscal ramp lesions (tears of the medial meniscus posterior horn at the menisco-capsular junction) occur in approximately 25% of ACL-injured knees. Lateral meniscal root tears occur in approximately 7% of ACL injured knees Pathophysiology The force distribution is across the knee joint, increasing force concentration on the cartilage and other joint structures.Damage to the meniscus due to rotational forces directed to a flexed knee (as may occur with twisting sports) is the usual underlying mechanism of injury. A valgus force applied to a flexed knee with the foot planted and the femur rotated externally can result in a lateral meniscus tear. A varus force applied to the flexed knee when the foot is planted and the femur rotated internally result in a tear of the medial meniscus.Tears produce rough surfaces inside the knee, which cause catching, locking, buckling, pain, or a combination of these symptoms. Abnormal loading patterns and rough surfaces inside the knee, especially when coupled with return to sports, significantly increase the risk of developing arthritis if not already present. Anatomy The menisci are C-shaped wedges of fibrocartilage located between the tibial plateau and femoral condyles. The menisci contain 70% type I collagen. The larger semilunar medial meniscus is attached more firmly than the loosely fixed, more circular lateral meniscus. The anterior and posterior horns of both menisci are secured to the tibial plateaus. Anteriorly, the transverse ligament connects the 2 menisci; posteriorly, the meniscofemoral ligament helps stabilize the posterior horn of the lateral meniscus to the femoral condyle. The coronary ligaments connect the peripheral meniscal rim loosely to the tibia. Although the lateral collateral ligament (LCL) passes in close proximity, the lateral meniscus has no attachment to this structure.The joint capsule attaches to the entire periphery of each meniscus but adheres more firmly to the medial meniscus. An interruption in the attachment of the joint capsule to the lateral meniscus, forming the popliteal hiatus, allows the popliteus tendon to pass through to its femoral attachment site. Contraction by the popliteus during knee flexion pulls the lateral meniscus posteriorly, avoiding entrapment within the joint space. The medial meniscus does not have a direct muscular connection. The medial meniscus may shift a few millimeters, while the less stable lateral meniscus may move at least 1 cm.In 1978, Shrive et al. reported that the collagen fibers of the menisci are oriented in a circumferential pattern. When a compressive force is applied in the knee joint, a tensile force is transmitted to the menisci. The femur attempts to spread the menisci anteroposteriorly in extension and mediolaterally in flexion. Shrive et al. further studied the effects of a radial cut in the peripheral rim of the menisci during loading. In joints with intact menisci, the force was applied through the menisci and articular cartilage; however, a lesion in the peripheral rim disrupted the normal mechanics of the menisci and allowed it to spread when a load was applied. The load now was distributed directly to the articular cartilage. In light of these findings, it is essential to preserve the peripheral rim during partial meniscectomy to avoid irreversible disruption of the structures hoop tension capability. Diagnosis Physical examination After noting symptoms, a physician can perform clinical tests to determine if the pain is caused by compression and impingement of a torn meniscus. The knee is examined for swelling. In meniscal tears, pressing on the joint line on the affected side typically produces tenderness. The McMurray test involves pressing on the joint line while stressing the meniscus (using flexion–extension movements and varus or valgus stress). Similar tests are the Steinmann test (with the patient sitting) and the Apley grind test (a grinding maneuver while the person lies prone and the knee is bent 90°) and the Thessaly test (flexing the affected knee to 20 degrees, pivoting on the knee to see if the pain is reproduced). Bending the knee (into hyperflexion if tolerable), and especially squatting, is typically a painful maneuver if the meniscus is torn. The range of motion of the joint is often restricted. Coopers sign is present in over 92% of tears. It is a subjective symptom of pain in the affected knee when turning over in bed at night. Osteoarthritic pain is present with weightbearing, but the meniscal tear causes pain with a twisting motion of the knee as the meniscal fragment gets pinched, and the capsular attachment gets stretched causing the complaint of pain. Radiology X-ray images (normally during weightbearing) can be obtained to rule out other conditions or to see if the patient also has osteoarthritis. The menisci themselves cannot be visualised with plain radiographs. If the diagnosis is not clear from the history and examination, the menisci can be imaged with magnetic resonance imaging (an MRI scan). This technique has replaced previous arthrography, which involved injecting contrast medium into the joint space. In straightforward cases, knee arthroscopy allows quick diagnosis and simultaneous treatment. Recent clinical data shows that MRI and clinical testing are comparable in sensitivity and specificity when looking for a meniscal tear. Classification A meniscal tear can be classified in various ways, such as by anatomic location or by proximity to blood supply. Various tear patterns and configurations have been described. These include: Radial tears Flap or parrot-beak tears Peripheral, longitudinal tears Bucket-handle tears Horizontal cleavage tears Complex, degenerative tearsThese tears can then be further classified by their proximity to the meniscus blood supply, namely whether they are located in the “red-red,” “red-white,” or “white-white” zones. The functional importance of these classifications, however, is to ultimately determine whether a meniscus is repairable. The repairability of a meniscus depends on a number of factors. These include: Age/strength Activity level Tear pattern Chronicity of the tear Associated injuries (anterior cruciate ligament injury) Healing potential Prevention Tear of a meniscus is a common injury in many sports. The menisci hold 30–50% of the body load in standing position. Some sports where a meniscus tear is common are American football, association football, ice hockey and tennis. Regardless of what the activity is, it is important to take the correct precautions to prevent a meniscus tear from happening. Footwear There are three major ways of preventing a meniscus tear. The first of these is wearing the correct footwear for the sport and surface that the activity is taking place on. This means that if the sport being played is association football, cleats are an important item in reducing the risk of a meniscus tear. The proper footwear is imperative when engaging in physical activity because one off-balanced step could mean a meniscus tear. It is highly advised that cleats contain a sole that molds around the foot, no fewer than fourteen cleats per shoe, no lower than a half inch diameter of the cleat tip, and at most, a three-eighths inch of cleat length. Stretches The second way to prevent a meniscus tear is to strengthen and stretch the major leg muscles. Those muscles include the hamstrings, quadriceps, and calf muscles. One popular exercise used to strengthen the hamstrings is the leg curl. It is also important to properly stretch the hamstrings; doing standing toe touches can do this. Seated leg extensions strengthen the quadriceps and doing the quadriceps stretch will help loosen the muscles. Toe raises are used to strengthen and stretch the calves. Adequate muscle mass and strength may also aid in maintaining healthy knees. The use of the parallel squat increases much needed stability in the knee if executed properly. Execution of the parallel squat will develop the lower body muscles that will strengthen the hips, knees, and ankles. Technique The last major way to prevent a tear in the meniscus is learning proper technique for the movement that is taking place. For the sports involving quick powerful movements it is important to learn how to cut, turn, land from a jump, and stop correctly. It is important to take the time out to perfect these techniques when used. These three major techniques will significantly prevent and reduce the risk of a meniscus tear. Treatment Presently, treatments make it possible for quicker recovery. If the tear is not serious, physical therapy, compression, elevation and icing the knee can heal the meniscus. Meniscus tears are more likely to heal on their own if they are in what physicians call the "red zone," or the outer edge of the meniscus where blood supply is present. More serious tears may require surgical procedures. Surgery, however, does not appear to be better than non-surgical care. In the long term, degenerative meniscal tears are often associated with osteoarthritis. This leads to poor outcomes regardless of treatment type. In the short term, studies have shown arthroscopic partial meniscectomy (APM) is a more effective treatment with regards to function and pain management. Conservative treatments Initial treatment may include physical therapy, bracing, anti-inflammatory drugs, or corticosteroid injections to increase flexibility, endurance, and strength.Common anti-inflammatory drugs and painkillers prescribed for meniscus tears include acetaminophen, non-steroidal inflammatory drugs, and corticosteroids.Exercises can strengthen the muscles around the knee, especially the quadriceps. Stronger and bigger muscles will protect the meniscus cartilage by absorbing a part of the weight. The patient may be given paracetamol or anti-inflammatory medications. For patients selecting non-surgical treatment, physical therapy may reduce symptoms of pain and swelling. This type of rehabilitation focuses on maintenance of full range of motion and functional progression without aggravating symptoms. Physical therapists can employ electric stimulation, cold therapy, and ultrasonography. Accelerated rehabilitation programs can be as successful as the conservative program. The program reduces the time the patient spends using crutches and allows weight bearing activities. The less conservative approach allows the patient to apply a small amount of stress while protecting range of motion. It is likely that a patient with a peripheral tear can pursue the accelerated program, while a patient with a larger tear adopts the conservative program. The use of platelet rich plasma (PRP) to aid in the healing process has become widely accepted among US athletes. Although the procedure has grown in popularity, studies assessing the efficacy of PRP treatment have yielded contradictory results. Surgery Arthroscopy is a surgical technique in which a joint is operated on using an endoscopic camera as opposed to open surgery on the joint. The meniscus can either be repaired or completely removed. Surgery is not appropriate for a degenerative meniscus tear, absent locking or catching of the knee, recurrent effusion or persistent pain. Evidence suggests that it is no better than conservative management in those with and without osteoarthritis. Surgery appears to offer no benefit to adults who have mild arthritis.An independent international guideline panel recommended against arthroscopy for degenerative meniscus tears; this conclusion derived from evidence of no lasting benefit and that less than 15% of patients experience even a short-term benefit. Disadvantages include a two to six week recovery time and rare but serious adverse effects that can occur, including blood clots in the legs, surgical site infections, and nerve damage. The BMJ Rapid Recommendation includes infographics and shared decision-making tools to facilitate a conversation between doctors and patients about the risks and benefits of arthroscopic surgery.If the injury is isolated, then the knee would be relatively stable. However, if an injury such as an anterior cruciate ligament injury (torn ACL) is coupled with a torn meniscus, then an arthroscopy is recommended. A meniscal repair has a higher success rate given an adequate blood supply to the peripheral rim. The interior of the meniscus is avascular, but the blood supply can penetrate up to about 6 millimetres (0.24 in). Therefore, meniscus tears that occur near the peripheral rim are able to heal after a meniscal repair. One study found that repair is better than removal (meniscectomy). The amount of rehabilitation time required for a repair is longer, but removing the meniscus can induce osteoarthritis. Meniscectomy rehab requires four to six weeks. Repair requires four to six months. If conservative treatment is ineffective, surgical intervention may be required. Younger patients are typically more resilient and respond well to this treatment, while older, more sedentary patients do not have a favorable outcome after a repair. Transplants Meniscus transplants are regularly successful, although the procedure is not common and many questions surrounding its use remain. Side effects of meniscectomy include: The knee loses its ability to transmit and distribute load and absorb mechanical shock. Persistent and significant swelling and stiffness in the knee. The knee may be not be fully mobile; there may be the sensation of knee locking or buckling in the knee. The full knee may be in full motion after tear of meniscus. Increases progression of arthritis and time to knee replacement. Implants Another treatment approach in development is a meniscus implant or "artificial meniscus." While many artificial joints and bionic body parts are available, including arms, legs, joints and other body parts, a prosthetic meniscus replacement.The first to be implanted in humans is called the NUsurface Meniscus Implant. The implant is made from medical grade plastic and is designed not to require fixation to bone or soft tissue. The implant could be a good option for younger, active patients who are considered too young for knee replacement because that surgery lasts only about 10 years. The implant has been used in clinical trials in Europe since 2008. The first surgery as part of US clinical trials took place in January 2015 at Ohio State Universitys Wexner Medical Center. Two FDA-approved clinical trials evaluating the implant completed enrollment in June 2018. In September 2019, the manufacturer received breakthrough designation from the U.S. Food and Drug Administration, and the company expected to file for regulatory approval within the following year. In November 2019, the implant became commercially available in Israel.Other implants include TRAMMPOLIN and Orthonika.Scientists are working to grow an artificial meniscus in the lab. Scientists from Cornell and Columbia universities grew a meniscus inside the knee joint of a sheep using a 3-D printer and the sheeps stem cells. Similarly, researchers at Scripps Research Shiley Center for Orthopaedic Research and Education reported growing a meniscus. Post-surgical rehabilitation After a successful surgery for treating the destroyed part of the meniscus, patients must follow a rehabilitation program to have the best result. The rehabilitation following a meniscus surgery depends on whether the entire meniscus was removed or repaired. If the destroyed part of the meniscus was removed, patients can usually start walking using a crutch a day or two after surgery. Although each case is different, patients return to their normal activities on average after a few weeks (2 or 3). Still, a completely normal walk will resume gradually, and its not unusual to take 2–3 months for the recovery to reach a level where a patient will walk totally smoothly. Many meniscectomy patients dont ever feel a 100% functional recovery, but even years after the procedure they sometimes feel tugging or tension in a part of their knee. There is little medical follow-up after meniscectomy and official medical documentation tends to ignore the imperfections and side-effects of this procedure. If the meniscus was repaired, the rehabilitation program that follows is a lot more intensive. After the surgery, a hinged knee brace is sometimes placed on the patient. This brace allows controlled movement of the knee. The patient is encouraged to walk using crutches from the first day, and most of the times can put partial weight on the knee. Improving symptoms, restoring function, and preventing further injuries are the main goals when rehabilitating. By the end of rehabilitation, normal range of motion, function of muscles and coordination of the body are restored. Personalized rehabilitation programs are designed considering the patients surgery type, location repaired (medial or lateral), simultaneous knee injuries, type of meniscal tear, age of patient, condition of the knee, loss of strength and ROM, and the expectations and motivations of the patient. Phase I There are three phases that follow meniscal surgery. Each phase consists of rehabilitation goals, exercises, and criteria to move on to the next phase. Phase I starts immediately following surgery to 4–6 weeks or until the patient is able meet progression criteria. The goals are to restore normal knee extension, reduce and eliminate swelling, regain leg control, and protect the knee (Fowler, PJ and D. Pompan, 1993). During the first 5 days following the surgery, a passive continuous motion machine is used to prevent a prolonged period of immobilization which leads to muscular atrophy and delays functional recovery. During the 4–6 weeks post-surgical, active and passive non-weight bearing motions which flex the knee up to 90° are recommended. For patients with meniscal transplantation, further knee flexion can damage the allograft because of the increased shear forces and stresses. If any weight-bearing exercises are applied, a controlled brace should be worn on the knee to keep the knee at near (<10°) or full extension. The suggested exercises target increasing the patients ROM, muscular and neuromuscular strength, and cardiovascular endurance. Aquatic therapy, or swimming, can be used to rehab patients because it encompasses ROM, strength, and cardiovascular exercises while relieving stress on the body. It has also been shown to significantly improve dependent edema and pain symptoms. No pain gait without crutches, swelling and 4–6 weeks after surgery are the criteria to begin the next phase (Ulrich G.S., and S Aroncyzk, 1993). Phase II This phase of the rehabilitation program is 6 to 14 weeks after the surgery. The goals for Phase II include being able to restore full ROM, normalized gait, and performing functional movements with control and no pain (Fowler, PJ and D. Pompan, 1993). Also, muscular strengthening and neuromuscular training are emphasized using progressive weight bearing and balance exercises. Exercises in this phase can increase knee flexion for more than 90°. Advised exercises include stationary bicycle, standing on foam surface with two and one leg, abdominal and back strengthening, and quadriceps strengthening. The proposed criteria include normal gait on all surfaces and single leg balance longer than 15 seconds (Ulrich G.S., and S Aroncyzk, 1993). Phase III Patients begin exercises in phase III 14 to 22 weeks after surgery. Phase IIIs goal and final criterion is to perform sport/work specific movements with no pain or swelling (Fowler, PJ and D. Pompan, 1993). Drills for maximal muscle control, strength, flexibility, movements specific to patients work/sport, low to high rate exercises, and abdominal and back strengthening exercises are all recommended exercises (Ulrich G.S., and S Aroncyzk, 1993). Exercises to increase cardiovascular fitness are also applied to fully prepare the patients to return to their desired activities. If the progression criteria are met, the patient can gradually return to "high-impact" activities (like running). However, "heavier activities", like running, skiing, basketball etc., generally any activities where knees bear sudden changes of the direction of movement can lead to repeated injuries. When planning sport activities it makes sense to consult a physical therapist and check how much impact the sport will have on the knee. Epidemiology The meniscal tear is the most common knee injury. It tends to be more frequent in sports that have rough contact or pivoting sports such as soccer. It is more common in males than females, with a ratio of about two and a half males to one female. Males between the ages of 31 and 40 tend to tear their meniscus more frequently than younger men. Females seem to be more likely to tear their meniscus between the ages of 11 and 20. People who work in physically demanding jobs such as construction or professional sports are more at risk of a meniscal tear because of the different stresses to which their knees are subjected. According to the United States National Library of Medicine, the isolated medial meniscal tear occurs more frequently than any other tear associated with the meniscus. The prevalence of meniscus tears is the same for both knees. In a few studies the having a higher BMI puts more weight on the joints, which can cause the knee to be non-aligned, resulting in an easier tear.In 2008 the U.S Department of Health and Human Services reported a combined total of 2,295 discharges for the principal diagnosis of tear of lateral cartilage/meniscus (836.0), tear of medial cartilage/meniscus (836.1), and tear of cartilage/meniscus (836.2). Females had a total of 53.49% discharges, while males had 45.72%. Individuals between the ages of 45 and 68 had an average of 31.73% discharges followed by age group 65–84, with 28.82%. The average length of stay for a patient diagnosed with torn menisci was 2.7 days for males and 3.7 days for females. There was a report of 6,941 hospital discharges for knee repair. Individuals between age 18 and 44 were among the highest with 37.37% total of discharges, followed by the age group 45–64, with a percentage of 36.34%. Males had a slightly higher number of discharges (50.78%) than females (48.66%). The average length of stay for both male and female patients in a hospital setting was 3.1. References == External links ==

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

Couvade is a term which was coined by anthropologist E. B. Tylor in 1865 to refer to certain rituals in several cultures that fathers adopt during pregnancy. Couvade can be traced to Ancient Egypt as a "sacred birth custom, of when a child is born, the man experiences the ritual of "labor" in which he takes to his bed, and undergoes periods of fasting and purification, and the observance of certain taboos".The term "couvade" is borrowed from French (where it is derived from the verb couver "to brood, hatch"); the use in the modern sense derives from a misunderstanding of an earlier idiom faire la couvade, which meant "to sit doing nothing."An example of couvade is that the Cantabri people had a custom in which the father, during or immediately after the birth of a child, took to bed, complained of having labour pains, and was accorded the treatment usually shown to women during pregnancy or after childbirth. Similarly, in Papua New Guinea, fathers built a hut outside the village and mimicked the pains of labour until the baby is born. Similar rituals occur in other cultural groups in Thailand, Russia, China, India and many indigenous groups in the Americas. In some cultures, "sympathetic pregnancy" is attributed to efforts to ward off demons or spirits from the mother or seek favour of supernatural beings for the child. Couvade has been reported by travelers throughout history, including the Greek geographer Strabo (3.4.17). According to Claude Levi-Strauss, the custom of couvade reinforces the institution of the family in some societies by "welding" together men and their wives and future children. See also Couvade syndrome References External links Chisholm, Hugh, ed. (1911). "Couvade" . Encyclopædia Britannica. Vol. 7 (11th ed.). Cambridge University Press. pp. 337–338. Couvade in Tribal Cultures

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What is the significance of the term 'Paclitaxel' in the medical field?

Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposis sarcoma, cervical cancer, and pancreatic cancer. It is administered by intravenous injection. There is also an albumin-bound formulation.Common side effects include hair loss, bone marrow suppression, numbness, allergic reactions, muscle pains, and diarrhea. Other serious side effects include heart problems, increased risk of infection, and lung inflammation. There are concerns that use during pregnancy may cause birth defects. Paclitaxel is in the taxane family of medications. It works by interference with the normal function of microtubules during cell division.Paclitaxel was first isolated in 1971 from the Pacific yew and approved for medical use in 1993. It is on the World Health Organizations List of Essential Medicines. It has been made from precursors, and more recently through cell culture. Medical use Paclitaxel is approved in the UK for ovarian, breast, lung, bladder, prostate, melanoma, esophageal, and other types of solid tumor cancers as well as Kaposis sarcoma.It is recommended in National Institute for Health and Care Excellence (NICE) guidance of June 2001 that it should be used for non-small-cell lung cancer in patients unsuitable for curative treatment, and in first-line and second-line treatment of ovarian cancer. In September 2001, NICE recommended paclitaxel should be available for the treatment of advanced breast cancer after the failure of anthracyclic chemotherapy, but that its first-line use should be limited to clinical trials. In September 2006, NICE recommended paclitaxel should not be used in the adjuvant treatment of early node-positive breast cancer. In 2018, it is approved in the United States for the treatment of breast, pancreatic, ovarian, Kaposis sarcoma and non-small-cell lung cancers. Similar compounds Albumin-bound paclitaxel (trade name Abraxane, also called nab-paclitaxel) is an alternative formulation where paclitaxel is bound to albumin nanoparticles. Much of the clinical toxicity of paclitaxel is associated with the solvent Cremophor EL in which it is dissolved for delivery.Abraxis BioScience developed Abraxane, in which paclitaxel is bonded to albumin as an alternative delivery agent to the often toxic solvent delivery method. This was approved by the FDA in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. It has since been approved for locally advanced or metastatic non-small cell lung cancer and metastatic adenocarcinoma of the pancreas as well.Synthetic approaches to paclitaxel production led to the development of docetaxel. Docetaxel has a similar set of clinical uses to paclitaxel, and it is marketed under the brand name Taxotere. Taxanes, including paclitaxel, 10-deacetylbaccatin III, baccatin III, paclitaxel C, and 7-epipaclitaxel, have been found in the leaves and shells of hazel. The finding of these compounds in shells, which are considered discarded material and are mass-produced by many food industries, is of interest for the future availability of paclitaxel. Restenosis Paclitaxel is used as an antiproliferative agent for the prevention of restenosis (recurrent narrowing) of coronary and peripheral stents; locally delivered to the wall of the artery, a paclitaxel coating limits the growth of neointima (scar tissue) within stents. Paclitaxel drug-eluting stents for coronary artery placement are sold under the trade name Taxus by Boston Scientific in the United States. Paclitaxel drug-eluting stents for femoropopliteal artery placement are also available. Side effects Common side effects include nausea and vomiting, loss of appetite, change in taste, thinned or brittle hair, pain in the joints of the arms or legs lasting two to three days, changes in the color of the nails, and tingling in the hands or toes. More serious side effects such as unusual bruising or bleeding, pain, redness or swelling at the injection site, hand-foot syndrome, change in normal bowel habits for more than two days, fever, chills, cough, sore throat, difficulty swallowing, dizziness, shortness of breath, severe exhaustion, skin rash, facial flushing, female infertility by ovarian damage, and chest pain can also occur. Neuropathy may also occur.Dexamethasone is given prior to paclitaxel infusion to mitigate some of the side effects.A number of these side effects are associated with the excipient used, Cremophor EL, a polyoxyethylated castor oil, and allergies to cyclosporine, teniposide, and other drugs containing polyoxyethylated castor oil may increase the risk of adverse reactions to paclitaxel. Mechanism of action Paclitaxel is one of several cytoskeletal drugs that target tubulin. Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-targeting drugs, such as colchicine, that inhibit microtubule assembly, paclitaxel stabilizes the microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a metaphase spindle configuration. This blocks the progression of mitosis and prolonged activation of the mitotic checkpoint triggers apoptosis or reversion to the G0-phase of the cell cycle without cell division.The ability of paclitaxel to inhibit spindle function is generally attributed to its suppression of microtubule dynamics, but other studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher therapeutic concentrations, paclitaxel appears to suppress microtubule detachment from centrosomes, a process normally activated during mitosis. Paclitaxel binds to the beta-tubulin subunits of microtubules. Chemistry The nomenclature for paclitaxel is structured on a tetracyclic 17-atom skeleton. There are a total of 11 stereocenters. The active stereoisomer is (−)-paclitaxel (shown here). Production Bark processing From 1967 to 1993, almost all paclitaxel produced was derived from bark of the Pacific yew, Taxus brevifolia, the harvesting of which kills the tree in the process. The processes used were descendants of the original isolation method of Monroe Wall and Mansukh Wani; by 1987, the U.S. National Cancer Institute (NCI) had contracted Hauser Chemical Research of Boulder, Colorado, to handle bark on the scale needed for phase II and III trials. While both the size of the wild population of the Pacific yew and the magnitude of the eventual demand for paclitaxel were uncertain, it was clear that an alternative, sustainable source of the natural product would be needed. Initial attempts to broaden its sourcing used needles from the tree, or material from other related Taxus species, including cultivated ones, but these attempts were challenged by the relatively low and often highly variable yields obtained. Early in the 1990s, coincident with increased sensitivity to the ecology of the forests of the Pacific Northwest, paclitaxel was successfully extracted on a clinically useful scale from these sources. Semisynthesis Concurrently, synthetic chemists in the U.S. and France had been interested in paclitaxel, beginning in the late 1970s. As noted, by 1992 extensive efforts were underway to accomplish the total synthesis of paclitaxel, efforts motivated by the desire to generate new chemical understanding rather than to achieve practical commercial production. In contrast, the French group of Pierre Potier at the Centre national de la recherche scientifique (CNRS) addressed the matter of overall process yield, showing that it was feasible to isolate relatively large quantities of the compound 10-deacetylbaccatin from the European yew, Taxus baccata, which grew on the CNRS campus and whose needles were available in large quantity. By virtue of its structure, 10-deacetylbaccatin was seen as a viable starting material for a short semisynthesis to produce paclitaxel. By 1988, Poitier and collaborators had published a semisynthetic route from needles of the European yew to paclitaxel.The view of the NCI, however, was that even this route was not practical. The group of Robert A. Holton had also pursued a practical semisynthetic production route; by late 1989, Holtons group had developed a semisynthetic route to paclitaxel with twice the yield of the Potier process. Florida State University, where Holton worked, signed a deal with Bristol-Myers Squibb (BMS) to license their semisynthesis and future patents. In 1992, Holton patented an improved process with an 80% yield, and BMS took the process in-house and started to manufacture paclitaxel in Ireland from 10-deacetylbaccatin isolated from the needles of the European yew. In early 1993, BMS announced that it would cease reliance on Pacific yew bark by the end of 1995, effectively terminating ecological controversy over its use. This announcement also made good their commitment to develop an alternative supply route, made to the NCI in their cooperative research and development agreement (CRADA) application of 1989. As of 2013, BMS was using the semisynthetic method utilizing needles from the European yew to produce paclitaxel. Another company which worked with BMS until 2012, Phyton Biotech, Inc., uses plant cell fermentation (PCF) technology. By cultivating a specific Taxus cell line in fermentation tanks, they no longer need ongoing sourcing of material from actual yew tree plantations. Paclitaxel is then captured directly from the suspension broth by a resin allowing concentration to highly enriched powder containing about 40% paclitaxel. The compound is then purified by one chromatographic step followed by crystallization. Compared to the semisynthesis method, PCF eliminates the need for many hazardous chemicals and saves a considerable amount of energy.In 1993, paclitaxel was discovered as a natural product in a newly described endophytic fungus living in the yew tree. It has since been reported in a number of other endophytic fungi, including Nodulisporium sylviforme, Alternaria taxi, Cladosporium cladosporioides MD2, Metarhizium anisopliae, Aspergillus candidus MD3, Mucor rouxianus, Chaetomella raphigera, Phyllosticta tabernaemontanae, Phomopsis, Pestalotiopsis pauciseta, Phyllosticta citricarpa, Podocarpus sp., Fusarium solani, Pestalotiopsis terminaliae, Pestalotiopsis breviseta, Botryodiplodia theobromae, Gliocladium sp., Alternaria alternata var. monosporus, Cladosporium cladosporioides, Nigrospora sp., Pestalotiopsis versicolor, and Taxomyces andreanae. However, there has been contradictory evidence for its production by endophytes, with other studies finding independent production is unlikely. Biosynthesis Taxol is a tetracyclic diterpene, and the biosynthesis of diterpenes starts with a FPP molecule being elongated by the addition of an IPP molecule in order to form geranylgeranyl diphosphate (GGPP). The biosynthesis of Taxol contains nineteen steps. These 19 steps can be considered in several steps, with the first step being the formation of the taxane skeleton, which then undergoes a series of oxygenations. Following the oxygenations, two acetylations and a benzoylation occur on the intermediate. The oxygenation of the taxane core is believed to occur on C5 and C10, C2 and C9, C13 followed by C7, and a C1 hydroxylation later on in the pathway. Later in the pathway, an oxidation at C9 forms a ketone functional group and an oxetane, forming the intermediate baccatin III. The final steps of the pathway include the formation of a C13-side chain which is attached to baccatin III. The biosynthesis of Taxol is illustrated in more detail in the figure, with steps 1-7 all occurring in the enzyme taxadiene synthase (TS on the figure). Taxols biosynthesis begins with E,E,E-GGPP losing pyrophosphate via an SN1 mechanism (step 1 in the figure). The double-bond attacks the cation via electrophilic addition, yielding a tertiary cation and creating the first ring closure (step 2). Another electrophilic attack occurs, further cyclizing the structure by creating the first 6-membered ring and creating another tertiary cation (step 3). An intramolecular proton transfer occurs, attacking the verticillyl cation (step 4) and creating a double bond, yielding a tertiary cation. An electrophilic cyclization occurs in step 5, and an intramolecular proton transfer attacks the taxenyl cation (step 6). This forms the fused ring structure intermediate known as taxadiene. Taxadiene then undergoes a series of 10 oxidations via NADPH, forming the intermediate taxadiene-5α-acetoxy-10β-ol (multiple steps later in the figure). A series of hydroxylations and esterficiations occur, forming the intermediate 10-deacetyl-baccatin III, which undergoes a further series of esterifications and a side-chain hydroxylation. This finally yields the product taxol. Total synthesis By 1992, at least thirty academic research teams globally were working to achieve a total synthesis of this natural product, with the synthesis proceeding from simple natural products and other readily available starting materials. This total synthesis effort was motivated primarily by the desire to generate new chemical understanding, rather than with an expectation of the practical commercial production of paclitaxel. The first laboratories to complete the total synthesis from much less complex starting materials were the research groups of Robert A. Holton, who had the first article to be accepted for publication, and of K. C. Nicolaou who had the first article to appear in print (by a week, on 7 February 1994). Though the Holton submission preceded the Nicolaou by a month (21 December 1993 versus 24 January 1994), the near coincidence of the publications arising from each of these massive, multiyear efforts—11–18 authors appearing on each of the February 1994 publications—has led the ending of the race to be termed a "tie" or a "photo finish", though each group has argued that their synthetic strategy and tactics were superior.As of 2006, five additional research groups had reported successful total syntheses of paclitaxel: Wender et al. in 1997, and Kuwajima et al. and Mukaiyama et al. in 1998 with further linear syntheses, and Danishefsky et al. in 1996 and Takahashi et al. in 2006 with further convergent syntheses. As of that date, all strategies had aimed to prepare a 10-deacetylbaccatin-type core containing the ABCD ring system, followed generally by last stage addition of the "tail" to the 13-hydroxyl group.While the "political climate surrounding [paclitaxel] and [the Pacific yew] in the early 1990s ... helped bolster [a] link between total synthesis and the [paclitaxel] supply problem," and though total synthesis activities were a requisite to explore the structure-activity relationships of paclitaxel via generation of analogs for testing, the total synthesis efforts were never seen "as a serious commercial route" to provide significant quantities of the natural product for medical testing or therapeutic use. History The discovery of paclitaxel began in 1962 as a result of a NCI-funded screening program. A number of years later it was isolated from the bark of the Pacific yew, Taxus brevifolia, hence its name "taxol".The discovery was made by Monroe E. Wall and Mansukh C. Wani at the Research Triangle Institute, Research Triangle Park, North Carolina, in 1971. These scientists isolated the natural product from the bark of the Pacific yew tree, determined its structure and named it "taxol", and arranged for its first biological testing. The compound was then developed commercially by BMS, who had the generic name assigned as "paclitaxel". Plant screening program In 1955, the NCI in the United States set up the Cancer Chemotherapy National Service Center (CCNSC) to act as a public screening center for anticancer activity in compounds submitted by external institutions and companies. Although the majority of compounds screened were of synthetic origin, one chemist, Jonathan Hartwell, who was employed there from 1958 onwards, had experience with natural product derived compounds, and began a plant screening operation. After some years of informal arrangements, in July 1960, the NCI commissioned the United States Department of Agriculture (USDA) botanists to collect samples from about 1,000 plant species per year. On 21 August 1962, one of those botanists, Arthur S. Barclay, collected bark from a single Pacific yew tree in a forest north of the town of Packwood, Washington, as part of a four-month trip to collect material from over 200 different species. The material was then processed by a number of specialist CCNSC subcontractors, and one of the trees samples was found to be cytotoxic in a cellular assay on 22 May 1964.Accordingly, in late 1964 or early 1965, the fractionation and isolation laboratory run by Monroe E. Wall in Research Triangle Park, North Carolina, began work on fresh Taxus samples, isolating the active ingredient in September 1966 and announcing their findings at an April 1967 American Chemical Society meeting in Miami Beach. They named the pure compound taxol in June 1967. Wall and his colleague Wani published their results, including the chemical structure, in 1971.The NCI continued to commission work to collect more Taxus bark and to isolate increasing quantities of taxol. By 1969, 28 kg (62 lb) of crude extract had been isolated from almost 1,200 kg (2,600 lb) of bark, although this ultimately yielded only 10 g (0.35 oz) of pure material, but for several years, no use was made of the compound by the NCI. In 1975, it was shown to be active in another in vitro system; two years later, a new department head reviewed the data and finally recommended taxol be moved on to the next stage in the discovery process. This required increasing quantities of purified taxol, up to 600 g (21 oz), and in 1977 a further request for 7,000 lb (3,200 kg) of bark was made. In 1978, two NCI researchers published a report showing taxol was mildly effective in leukaemic mice. In November 1978, taxol was shown to be effective in xenograft studies. Meanwhile, taxol began to be well known in the cell biology, as well as the cancer community, with a publication in early 1979 by Susan B. Horwitz, a molecular pharmacologist at Albert Einstein College of Medicine, showing taxol had a previously unknown mechanism of action involving the stabilization of microtubules. Together with formulation problems, this increased interest from researchers meant that, by 1980, the NCI envisaged needing to collect 20,000 lb (9,100 kg) of bark. Animal toxicology studies were complete by June 1982, and in November NCI applied for the IND necessary to begin clinical trials in humans. Early clinical trials, supply and the transfer to BMS Phase I clinical trials began in April 1984, and the decision to start Phase II trials was made a year later. These larger trials needed more bark and collection of a further 12,000 pounds was commissioned, which enabled some phase II trials to begin by the end of 1986. But by then it was recognized that the demand for taxol might be substantial and that more than 60,000 pounds of bark might be needed as a minimum. This unprecedentedly large amount brought ecological concerns about the impact on yew populations into focus for the first time, as local politicians and foresters expressed unease at the program.The first public report from a phase II trial in May 1988 showed promising effects in melanoma and refractory ovarian cancer. At this point, Gordon Cragg of the NCIs Natural Product Branch calculated the synthesis of enough taxol to treat all the ovarian cancer and melanoma cases in the US would require the destruction of 360,000 trees annually. For the first time, serious consideration was given to the problem of supply. Because of the practical and, in particular, the financial scale of the program needed, the NCI decided to seek association with a pharmaceutical company, and in August 1989, it published a Cooperative Research and Development Agreement (CRADA) offering its current stock and supply from current bark stocks, and proprietary access to the data so far collected, to a company willing to commit to providing the funds to collect further raw material, isolate taxol, and fund a large proportion of clinical trials. In the words of Goodman and Welsh, authors of a substantial scholarly book on taxol, "The NCI was thinking, not of collaboration, ... but of a hand-over of taxol (and its problems)".Although the offer was widely advertised, only four companies responded to the CRADA, including the American firm Bristol-Myers Squibb (BMS), which was selected as the partner in December 1989. The choice of BMS later became controversial and was the subject of Congressional hearings in 1991 and 1992. While it seems clear the NCI had little choice but to seek a commercial partner, there was also controversy about the terms of the deal, eventually leading to a report by the General Accounting Office in 2003, which concluded the NIH had failed to ensure value for money. In related CRADAs with the USDA and Department of the Interior, Bristol-Myers Squibb was given exclusive first refusal on all Federal supplies of Taxus brevifolia. This exclusive contract lead to some criticism for giving BMS a "cancer monopoly". Eighteen months after the CRADA, BMS filed a new drug application (NDA), which was given FDA approval at the very end of 1992. Although there was no patent on the compound, the provisions of the Waxman-Hatch Act gave Bristol-Myers Squibb five years exclusive marketing rights. In 1990, BMS applied to trademark the name taxol as Taxol(R). This was controversially approved in 1992. At the same time, paclitaxel replaced taxol as the generic (INN) name of the compound. Critics, including the journal Nature, argued the name taxol had been used for more than two decades and in more than 600 scientific articles and suggested the trademark should not have been awarded and the BMS should renounce its rights to it. BMS argued changing the name would cause confusion among oncologists and possibly endanger the health of patients. BMS has continued to defend its rights to the name in the courts. BMS has also been criticized for misrepresentation by Goodman and Walsh, who quote from a company report saying "It was not until 1971 that ... testing ... enabled the isolation of paclitaxel, initially described as compound 17". This quote is, strictly speaking, accurate: the objection seems to be that this misleadingly neglects to explain that it was the scientist doing the isolation who named the compound taxol and it was not referred to in any other way for more than twenty years. Annual sales peaked in 2000, reaching US$1.6 billion; paclitaxel is now available in generic form. Society and culture As of 2006, the cost to the NHS per patient in early breast cancer, assuming four cycles of treatment, was about £4,000 (approx. $6,000). Research Caffeine has been speculated to inhibit paclitaxel-induced apoptosis in colorectal cancer cells.Aside from its direct clinical use, paclitaxel is used extensively in biological and biomedical research as a microtubule stabilizer. In general, in vitro assays involving microtubules, such as motility assays, rely on paclitaxel to maintain microtubule integrity in the absence of the various nucleating factors and other stabilizing elements found in the cell. For example, it is used for in vitro tests of drugs that aim to alter the behavior of microtubule motor proteins, or for studies of mutant motor proteins. Moreover, Paclitaxel has been used in vitro to inhibit insulin fibrillation; in a molar ratio of 10:1 (insulin:paclitaxel), it hindered insulin fibrillation near 70%. Iso-thermal titration calorimetry (ITC) findings indicated a spontaneous tendency of paclitaxel to interact with insulin through hydrogen bonds and van der Waals forces. Also, the inhibitory role of paclitaxel is attributed to its impact on the colloidal stability of protein solution, as it was observed that paclitaxel inhibited lysozyme fibrillation by inducing the formation of "off-pathway" oligomeric intermediates and increasing the colloidal stability subsequently. Paclitaxel is sometimes used for in vivo studies as well; it can be fed to test organisms, such as fruit flies, or injected into individual cells, to inhibit microtubule disassembly or to increase the number of microtubules in the cell. Paclitaxel induces remyelination in a demyelinating mouse in vivo and inhibits hPAD2 in vitro though its methyl ester side chain. Angiotech Pharmaceuticals Inc. began phase II clinical trials in 1999 as a multiple sclerosis treatment but in 2002, reported that the results showed no statistical significance.In 2016 in vitro multi-drug resistant mouse tumor cells were treated with paclitaxel encased in exosomes. Doses 98% less than common dosing had the same effect. Also, dye-marked exosomes were able to mark tumor cells, potentially aiding in diagnosis. Additional images References Further reading External links "Paclitaxel". Drug Information Portal. U.S. National Library of Medicine. "Paclitaxel". National Cancer Institute. 5 October 2006. "Paclitaxel". NCI Drug Dictionary. 2 February 2011. Molecule of the Month: TAXOL by Neil Edwards, University of Bristol. A Tale of Taxol from Florida State University. Berenson, Alex (October 1, 2006). "Hope, at $4,200 a Dose". The New York Times. Retrieved 2007-03-31.

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

Please help me grasp the concept behind the medical term 'Acquired progressive lymphangioma.'

Acquired progressive lymphangioma is a group of lymphangiomas that occur anywhere in young individuals, grow slowly, and present as bruise-like lesions or erythematous macules.: 597 See also List of cutaneous conditions References == External links ==

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Could you please explain the term 'Loin pain hematuria syndrome' in simple language?

Loin pain hematuria syndrome (LPHS) is the combination of debilitating unilateral or bilateral flank pain and microscopic or macroscopic amounts of blood in the urine that is otherwise unexplained.Loin pain-hematuria syndrome (LPHS) is a poorly defined disorder characterized by recurrent or persistent loin (flank) pain and hematuria that appears to represent glomerular bleeding. Most patients present with both manifestations, but some present with loin pain or hematuria alone. Pain episodes are rarely associated with low-grade fever and dysuria, but urinary tract infection is not present. The major causes of flank pain and hematuria, such as nephrolithiasis and blood clot, are typically not present. Renal arteriography may suggest focally impaired cortical perfusion, while renal biopsy may show interstitial fibrosis and arterial sclerosis.The pain is typically severe, and narcotic therapy is often prescribed as a way to manage chronic pain. Sleep can be difficult because the supine position increases pressure on the flank. The onset of pain is often associated with nausea and vomiting, making pain management by oral opiates complicated. Cause The cause of LPHS is not known. One theory proposes that it is caused by a thin glomerular basement membrane and red blood cell (RBC) renal tubular congestion that leads to swelling of the kidney and distension of the renal fascia resulting in pain.Researchers have hypothesized that the syndrome may be due to blood vessel diseases of the kidney, spasms of the kidney vessels, or other bleeding disorders (coagulopathy). The hematuria in LPHS may be due to an abnormal (thick or thin) glomerular basement membrane. The glomerular basement membrane is a tissue in the kidney that filters the blood. An abnormal glomerular basement membrane may allow red blood cells into the urinary space. Because kidney stones are so common in people with LPHS, crystals in the kidney tubules may also play a part in bleeding and pain.Other speculations on cause include IgA nephropathy. This is a condition in which small amount of a type of normal antibody (called IgA) get stuck in the kidney as it passes through in the bloodstream. This is a chronic condition, which sometimes goes away on its own but occasionally can cause damage to the kidneys. A related condition called IgM nephropathy can sometimes cause pain. Thin membrane disease. In this condition the membrane that filters the blood to make urine is too thin, and blood can pass across it in very small amounts. In a few cases of this condition, there is pain in the kidneys, usually occurring in attacks every so often. Although this condition can be painful, kidney failure does not seem to occur in the long term, so that the only real problem is the symptoms. Infection. In some cases, loin pain-haematuria syndrome occurs after a bladder infection with involvement of the kidney. Even when the infection has been treated and bugs can no longer be found in the urine, pain may persist for 6 months, or even longer in some cases. "Classic loin pain-haematuria syndrome". Some patients have none of the above diagnoses. In these cases there may be minor abnormalities on a kidney biopsy. Angiogram tests to look at the blood vessels in the kidney may show abnormal blood flow, perhaps causing a cramp like pain. The cause is not fully understood. It certainly is [more common] in women than in men, and there may be hormonal influences. Some women find the pain is worse at different times of their menstrual cycle, or comes on during pregnancy, or if they are taking [oral contraceptives].It has also been reported to be caused by microscopic granules of calcium oxylate into the glomerulus itself, causing blood vessels to rupture and increase the distention of the renal capsule.This condition may persist for some years, and can be lifelong. Damage to the kidneys leading to kidney failure does not occur. However, because LPHS is unusual in patients older than 60 years, some clinicians believe that LPHS eventually resolves.At this time no cure has been found for this disease. LPHS is a debilitating disease due to chronic pain and the inability to know how to control the glomerular aspect. The pain of LPHS can be worsened by acts as simple as riding in the car and undertaking daily activities. Many people with this disease are unable to maintain employment due to the debilitating pain. Unpublished research by Dr. Ahmed Ghanem (who has cared for well over 100 women with LPHS found that untreated Symptomatic Nephroptosis - SN (Hypermobile kidney) can lead to LPHS. Nephropexy can help to relieve symptoms. Severe renal colic caused by kinking ureter. Pain classically relieved a little by going on all fours with hips higher than head. Diagnosis LPHS is considered a diagnosis of exclusion. The syndrome presents with hematuria (blood in the urine) and flank (a region of the lower back beneath the ribs and above the ilium) pain which can result from a number of causes. Nonglomerular causes of bleeding (e.g., urinary infection, tumor, or nephrolithiasis) must be excluded. Obstruction of the urinary tract should not be present, confirmed by at least two imaging procedures while pain is present. Diagnosis of loin pain-hematuria syndrome (LPHS) occurs when hematuria is present, recurrent or persistent pain is severe, and other causes of bleeding are excluded. Urine testing can be performed to detect microscopic levels of hematuria. Protein is also commonly found in the urine of patients with LPHS. Kidney biopsies are sometimes performed to look for evidence of glomerular hematuria, excess red blood cells in the kidney tubules, and to assess the width of the glomerular basement membrane. Hematuria (more than 5 red blood cells per high power field) should be present in virtually every urinalysis and is typically characterized by dysmorphic red cells. Recurrent or persistent severe pain for six months or more, occurring in the costovertebral angles. Relation to chronic pelvic pain LPHS has considerable overlap with chronic pelvic pain syndrome. Relation to thin basement membrane disease A thin glomerular basement membrane, as in thin basement membrane disease, is proposed to be the characteristic finding on renal biopsy, but not part of the syndrome definition. Differential diagnosis Kidney stones Nutcracker syndrome IgA nephropathy Cancer of the genitourinary tract Chronic pelvic pain Endometriosis Pyelonephritis Treatment The treatment of LPHS varies considerably from centre to centre. As the condition is rare and poorly understood, a widely adopted standard of care is not existent.Treatment of loin pain-hematuria syndrome (LPHS) typically consists of pain management. Narcotics or oral opioids may be prescribed to help control pain. Patients with severe pain may need high-dose opioids daily or almost daily. Occasionally, people with LPHS require hospitalization for intravenous opioid therapy and control of nausea. Other treatments may include denervation, autotransplantation, renal neurectomy, or nephrectomy. Unfortunately symptoms often recur following these procedures. Limited evidence suggests that drugs that inhibit angiotensin may reduce the frequency and severity of episodes of loin pain and gross hematuria.Pain management with opiate and non-opiate analgesia is common. Angiotensin converting enzyme inhibitors are thought to be beneficial, as they reduce intraglomerular pressure and, presumably, reduce renal tubular congestion with RBCs.Possible treatment regimens General Angiotensin inhibition Reduce the risk of nephrolithiasis Pain control Opioid therapy Inpatient therapy Intravenous opioid regimen Antiemetic drugs Pruritus management Maintenance therapy between pain exacerbations Invasive therapy Implantable drug delivery system Surgical renal denervation Renal autotransplantation Nephrectomy (NOT recommended) Other invasive therapies (but not proven effective) Pulse radio frequency Celiac plexus block Intraureteric capsaicin infusionSurgery (autotransplantation) is thought by some to be of benefit in selected individuals and advocated in some centres, but usually considered the last resort.Physicians discourage surgery, as LPHS symptoms often re-occur after autotransplantation. Epidemiology LPHS is listed as a rare disease in the US National Institute of Health Rare Diseases database. While exact numbers worldwide are not available, the primary LPHS research clinic located in Ohio has over 200 patients. In addition, several hundred other patients have been reported in one study as of 2006. The prevalence of LPHS is estimated at about 0.012 percent, which qualifies LPHS as a rare disease (prevalence less than 0.07 percent) according to the Rare Diseases Act of 2002. Those affected are usually young, with an average age of 31 years, and 70% to 80% are women. See also Pelvic pain References External links Loin Pain - Patient UK

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I need a basic explanation for the medical term 'Heterotopic ossification.'

Heterotopic ossification (HO) is the process by which bone tissue forms outside of the skeleton in muscles and soft tissue. Symptoms In traumatic heterotopic ossification (traumatic myositis ossificans), the patient may complain of a warm, tender, firm swelling in a muscle and decreased range of motion in the joint served by the muscle involved. There is often a history of a blow or other trauma to the area a few weeks to a few months earlier. Patients with traumatic neurological injuries, severe neurologic disorders or severe burns who develop heterotopic ossification experience limitation of motion in the areas affected. Causes Heterotopic ossification of varying severity can be caused by surgery or trauma to the hips and legs. About every third patient who has total hip arthroplasty (joint replacement) or a severe fracture of the long bones of the lower leg will develop heterotopic ossification, but is uncommonly symptomatic. Between 50% and 90% of patients who developed heterotopic ossification following a previous hip arthroplasty will develop additional heterotopic ossification.Heterotopic ossification often develops in patients with traumatic brain or spinal cord injuries, other severe neurologic disorders or severe burns, most commonly around the hips. The mechanism is unknown. This may account for the clinical impression that traumatic brain injuries cause accelerated fracture healing.There are also rare genetic disorders causing heterotopic ossification such as fibrodysplasia ossificans progressiva (FOP), a condition that causes injured bodily tissues to be replaced by heterotopic bone. Characteristically exhibiting in the big toe at birth, it causes the formation of heterotopic bone throughout the body over the course of the sufferers life, causing chronic pain and eventually leading to the immobilisation and fusion of most of the skeleton by abnormal growths of bone.Another rare genetic disorder causing heterotopic ossification is progressive osseous heteroplasia (POH), is a condition characterized by cutaneous or subcutaneous ossification. Diagnosis During the early stage, an x-ray will not be helpful because there is no calcium in the matrix. (In an acute episode which is not treated, it will be 3– 4 weeks after onset before the x-ray is positive.) Early laboratory tests are not very helpful. Alkaline phosphatase will be elevated at some point, but initially may be only slightly elevated, rising later to a high value for a short time. Unless weekly tests are done, this peak value may not be detected. It is not useful in patients who have had fractures or spine fusion recently, as they will cause elevations.The only definitive diagnostic test in the early acute stage is a bone scan, which will show heterotopic ossification 7 – 10 days earlier than an x-ray. The three-phase bone scan may be the most sensitive method of detecting early heterotopic bone formation. However, an abnormality detected in the early phase may not progress to the formation of heterotopic bone. Another finding, often misinterpreted as early heterotopic bone formation, is an increased (early) uptake around the knees or the ankles in a patient with a very recent spinal cord injury. It is not clear exactly what this means, because these patients do not develop heterotopic bone formation. It has been hypothesized that this may be related to the autonomic nervous system and its control over circulation.When the initial presentation is swelling and increased temperature in a leg, the differential diagnosis includes thrombophlebitis. It may be necessary to do both a bone scan and a venogram to differentiate between heterotopic ossification and thrombophlebitis, and it is even possible that both could be present simultaneously. In heterotopic ossification, the swelling tends to be more proximal and localized, with little or no foot/ankle edema, whereas in thrombophlebitis the swelling is usually more uniform throughout the leg. Treatment There is no clear form of treatment. Originally, bisphosphonates were expected to be of value after hip surgery but there has been no convincing evidence of benefit, despite having been used prophylactically.Depending on the growths location, orientation and severity, surgical removal may be possible. Radiation Therapy. Prophylactic radiation therapy for the prevention of heterotopic ossification has been employed since the 1970s. A variety of doses and techniques have been used. Generally, radiation therapy should be delivered as close as practical to the time of surgery. A dose of 7-8 Gray in a single fraction within 24–48 hours of surgery has been used successfully. Treatment volumes include the peri-articular region, and can be used for hip, knee, elbow, shoulder, jaw or in patients after spinal cord trauma. Single dose radiation therapy is well tolerated and is cost effective, without an increase in bleeding, infection or wound healing disturbances.Other possible treatments. Certain antiinflammatory agents, such as indomethacin, ibuprofen and aspirin, have shown some effect in preventing recurrence of heterotopic ossification after total hip replacement. Conservative treatments such as passive range of motion exercises or other mobilization techniques provided by physical therapists or occupational therapists may also assist in preventing HO. A review article looked at 114 adult patients retrospectively and suggested that the lower incidence of HO in patients with a very severe TBI may have been due to early intensive physical and occupational therapy in conjunction with pharmacological treatment. Another review article also recommended physiotherapy as an adjunct to pharmacological and medical treatments because passive range of motion exercises may maintain range at the joint and prevent secondary soft tissue contractures, which are often associated with joint immobility. See also Intramembranous ossification Myositis ossificans Fibrodysplasia ossificans progressiva Progressive osseous heteroplasia References External links pmr/112 at eMedicine radio/336 at eMedicine

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

Causality (also referred to as causation, or cause and effect) is influence by which one event, process, state, or object (a cause) contributes to the production of another event, process, state, or object (an effect) where the cause is partly responsible for the effect, and the effect is partly dependent on the cause. In general, a process has many causes, which are also said to be causal factors for it, and all lie in its past. An effect can in turn be a cause of, or causal factor for, many other effects, which all lie in its future. Some writers have held that causality is metaphysically prior to notions of time and space.Causality is an abstraction that indicates how the world progresses. As such a basic concept, it is more apt as an explanation of other concepts of progression than as something to be explained by others more basic. The concept is like those of agency and efficacy. For this reason, a leap of intuition may be needed to grasp it. Accordingly, causality is implicit in the logic and structure of ordinary language.In English studies of Aristotelian philosophy, the word "cause" is used as a specialized technical term, the translation of Aristotles term αἰτία, by which Aristotle meant "explanation" or "answer to a why question". Aristotle categorized the four types of answers as material, formal, efficient, and final "causes". In this case, the "cause" is the explanans for the explanandum, and failure to recognize that different kinds of "cause" are being considered can lead to futile debate. Of Aristotles four explanatory modes, the one nearest to the concerns of the present article is the "efficient" one. David Hume, as part of his opposition to rationalism, argued that pure reason alone cannot prove the reality of efficient causality; instead, he appealed to custom and mental habit, observing that all human knowledge derives solely from experience. The topic of causality remains a staple in contemporary philosophy. Concept Metaphysics The nature of cause and effect is a concern of the subject known as metaphysics. Kant thought that time and space were notions prior to human understanding of the progress or evolution of the world, and he also recognized the priority of causality. But he did not have the understanding that came with knowledge of Minkowski geometry and the special theory of relativity, that the notion of causality can be used as a prior foundation from which to construct notions of time and space. Ontology A general metaphysical question about cause and effect is what kind of entity can be a cause, and what kind of entity can be an effect. One viewpoint on this question is that cause and effect are of one and the same kind of entity, with causality an asymmetric relation between them. That is to say, it would make good sense grammatically to say either "A is the cause and B the effect" or "B is the cause and A the effect", though only one of those two can be actually true. In this view, one opinion, proposed as a metaphysical principle in process philosophy, is that every cause and every effect is respectively some process, event, becoming, or happening. An example is his tripping over the step was the cause, and his breaking his ankle the effect. Another view is that causes and effects are states of affairs, with the exact natures of those entities being less restrictively defined than in process philosophy.Another viewpoint on the question is the more classical one, that a cause and its effect can be of different kinds of entity. For example, in Aristotles efficient causal explanation, an action can be a cause while an enduring object is its effect. For example, the generative actions of his parents can be regarded as the efficient cause, with Socrates being the effect, Socrates being regarded as an enduring object, in philosophical tradition called a substance, as distinct from an action. Epistemology Since causality is a subtle metaphysical notion, considerable intellectual effort, along with exhibition of evidence, is needed to establish knowledge of it in particular empirical circumstances. According to David Hume, the human mind is unable to perceive causal relations directly. On this ground, the scholar distinguished between the regularity view on causality and the counterfactual notion. According to the counterfactual view, X causes Y if and only if, without X, Y would not exist. Hume interpreted the latter as an ontological view, i.e., as a description of the nature of causality but, given the limitations of the human mind, advised using the former (stating, roughly, that X causes Y if and only if the two events are spatiotemporally conjoined, and X precedes Y) as an epistemic definition of causality. Having an epistemic concept of causality is needed to distinguish between causal and noncausal relations. The contemporary philosophical literature on causality can be divided into five big approaches to causality. These include the (mentioned above) regularity, probabilistic, counterfactual, mechanistic, and manipulationist views. The five approaches can be shown to be reductive, i.e., define causality in terms of relations of other types. According to this reading, they define causality in terms of, respectively, empirical regularities (constant conjunctions of events), changes in conditional probabilities, counterfactual conditions, mechanisms underlying causal relations, and invariance under intervention. Geometrical significance Causality has the properties of antecedence and contiguity. These are topological, and are ingredients for space-time geometry. As developed by Alfred Robb, these properties allow the derivation of the notions of time and space. Max Jammer writes "the Einstein postulate ... opens the way to a straightforward construction of the causal topology ... of Minkowski space." Causal efficacy propagates no faster than light.Thus, the notion of causality is metaphysically prior to the notions of time and space. In practical terms, this is because use of the relation of causality is necessary for the interpretation of empirical experiments. Interpretation of experiments is needed to establish the physical and geometrical notions of time and space. Volition The deterministic world-view holds that the history of the universe can be exhaustively represented as a progression of events following one after as cause and effect. The incompatibilist version of this holds that there is no such thing as "free will". Compatibilism, on the other hand, holds that determinism is compatible with, or even necessary for, free will. Necessary and sufficient causes Causes may sometimes be distinguished into two types: necessary and sufficient. A third type of causation, which requires neither necessity nor sufficiency in and of itself, but which contributes to the effect, is called a "contributory cause". Necessary causes If x is a necessary cause of y, then the presence of y necessarily implies the prior occurrence of x. The presence of x, however, does not imply that y will occur. Sufficient causes If x is a sufficient cause of y, then the presence of x necessarily implies the subsequent occurrence of y. However, another cause z may alternatively cause y. Thus the presence of y does not imply the prior occurrence of x. Contributory causes For some specific effect, in a singular case, a factor that is a contributory cause is one among several co-occurrent causes. It is implicit that all of them are contributory. For the specific effect, in general, there is no implication that a contributory cause is necessary, though it may be so. In general, a factor that is a contributory cause is not sufficient, because it is by definition accompanied by other causes, which would not count as causes if it were sufficient. For the specific effect, a factor that is on some occasions a contributory cause might on some other occasions be sufficient, but on those other occasions it would not be merely contributory.J. L. Mackie argues that usual talk of "cause" in fact refers to INUS conditions (insufficient but non-redundant parts of a condition which is itself unnecessary but sufficient for the occurrence of the effect). An example is a short circuit as a cause for a house burning down. Consider the collection of events: the short circuit, the proximity of flammable material, and the absence of firefighters. Together these are unnecessary but sufficient to the houses burning down (since many other collections of events certainly could have led to the house burning down, for example shooting the house with a flamethrower in the presence of oxygen and so forth). Within this collection, the short circuit is an insufficient (since the short circuit by itself would not have caused the fire) but non-redundant (because the fire would not have happened without it, everything else being equal) part of a condition which is itself unnecessary but sufficient for the occurrence of the effect. So, the short circuit is an INUS condition for the occurrence of the house burning down. Contrasted with conditionals Conditional statements are not statements of causality. An important distinction is that statements of causality require the antecedent to precede or coincide with the consequent in time, whereas conditional statements do not require this temporal order. Confusion commonly arises since many different statements in English may be presented using "If ..., then ..." form (and, arguably, because this form is far more commonly used to make a statement of causality). The two types of statements are distinct, however. For example, all of the following statements are true when interpreting "If ..., then ..." as the material conditional: If Barack Obama is president of the United States in 2011, then Germany is in Europe. If George Washington is president of the United States in 2011, then ⟨arbitrary statement⟩.The first is true since both the antecedent and the consequent are true. The second is true in sentential logic and indeterminate in natural language, regardless of the consequent statement that follows, because the antecedent is false. The ordinary indicative conditional has somewhat more structure than the material conditional. For instance, although the first is the closest, neither of the preceding two statements seems true as an ordinary indicative reading. But the sentence: If Shakespeare of Stratford-on-Avon did not write Macbeth, then someone else did.intuitively seems to be true, even though there is no straightforward causal relation in this hypothetical situation between Shakespeares not writing Macbeth and someone elses actually writing it. Another sort of conditional, the counterfactual conditional, has a stronger connection with causality, yet even counterfactual statements are not all examples of causality. Consider the following two statements: If A were a triangle, then A would have three sides. If switch S were thrown, then bulb B would light.In the first case, it would not be correct to say that As being a triangle caused it to have three sides, since the relationship between triangularity and three-sidedness is that of definition. The property of having three sides actually determines As state as a triangle. Nonetheless, even when interpreted counterfactually, the first statement is true. An early version of Aristotles "four cause" theory is described as recognizing "essential cause". In this version of the theory, that the closed polygon has three sides is said to be the "essential cause" of its being a triangle. This use of the word cause is of course now far obsolete. Nevertheless, it is within the scope of ordinary language to say that it is essential to a triangle that it has three sides. A full grasp of the concept of conditionals is important to understanding the literature on causality. In everyday language, loose conditional statements are often enough made, and need to be interpreted carefully. Questionable cause Fallacies of questionable cause, also known as causal fallacies, non-causa pro causa (Latin for "non-cause for cause"), or false cause, are informal fallacies where a cause is incorrectly identified. Theories Counterfactual theories Counterfactual theories define causation in terms of a counterfactual relation. These theories can often be seeing as "floating" their account of causality on top of an account of the logic of counterfactual conditionals. This approach can be traced back to David Humes definition of the causal relation as that "where, if the first object had not been, the second never had existed." More full-fledged analysis of causation in terms of counterfactual conditionals only came in the 20th century after development of the possible world semantics for the evaluation of counterfactual conditionals. In his 1973 paper "Causation," David Lewis proposed the following definition of the notion of causal dependence: An event E causally depends on C if, and only if, (i) if C had occurred, then E would have occurred, and (ii) if C had not occurred, then E would not have occurred.Causation is then defined as a chain of causal dependence. That is, C causes E if and only if there exists a sequence of events C, D1, D2, ... Dk, E such that each event in the sequence depends on the previous. This chain may be called a mechanism. Note that the analysis does not purport to explain how we make causal judgements or how we reason about causation, but rather to give a metaphysical account of what it is for there to be a causal relation between some pair of events. If correct, the analysis has the power to explain certain features of causation. Knowing that causation is a matter of counterfactual dependence, we may reflect on the nature of counterfactual dependence to account for the nature of causation. For example, in his paper "Counterfactual Dependence and Times Arrow," Lewis sought to account for the time-directedness of counterfactual dependence in terms of the semantics of the counterfactual conditional. If correct, this theory can serve to explain a fundamental part of our experience, which is that we can only causally affect the future but not the past. Probabilistic causation Interpreting causation as a deterministic relation means that if A causes B, then A must always be followed by B. In this sense, war does not cause deaths, nor does smoking cause cancer or emphysema. As a result, many turn to a notion of probabilistic causation. Informally, A ("The person is a smoker") probabilistically causes B ("The person has now or will have cancer at some time in the future"), if the information that A occurred increases the likelihood of Bs occurrence. Formally, P{B|A}≥ P{B} where P{B|A} is the conditional probability that B will occur given the information that A occurred, and P{B} is the probability that B will occur having no knowledge whether A did or did not occur. This intuitive condition is not adequate as a definition for probabilistic causation because of its being too general and thus not meeting our intuitive notion of cause and effect. For example, if A denotes the event "The person is a smoker," B denotes the event "The person now has or will have cancer at some time in the future" and C denotes the event "The person now has or will have emphysema some time in the future," then the following three relationships hold: P{B|A} ≥ P{B}, P{C|A} ≥ P{C} and P{B|C} ≥ P{B}. The last relationship states that knowing that the person has emphysema increases the likelihood that he will have cancer. The reason for this is that having the information that the person has emphysema increases the likelihood that the person is a smoker, thus indirectly increasing the likelihood that the person will have cancer. However, we would not want to conclude that having emphysema causes cancer. Thus, we need additional conditions such as temporal relationship of A to B and a rational explanation as to the mechanism of action. It is hard to quantify this last requirement and thus different authors prefer somewhat different definitions. Causal calculus When experimental interventions are infeasible or illegal, the derivation of a cause-and-effect relationship from observational studies must rest on some qualitative theoretical assumptions, for example, that symptoms do not cause diseases, usually expressed in the form of missing arrows in causal graphs such as Bayesian networks or path diagrams. The theory underlying these derivations relies on the distinction between conditional probabilities, as in P ( c a n c e r | s m o k i n g ) {\displaystyle P(cancer|smoking)} , and interventional probabilities, as in P ( c a n c e r | d o ( s m o k i n g ) ) {\displaystyle P(cancer|do(smoking))} . The former reads: "the probability of finding cancer in a person known to smoke, having started, unforced by the experimenter, to do so at an unspecified time in the past", while the latter reads: "the probability of finding cancer in a person forced by the experimenter to smoke at a specified time in the past". The former is a statistical notion that can be estimated by observation with negligible intervention by the experimenter, while the latter is a causal notion which is estimated in an experiment with an important controlled randomized intervention. It is specifically characteristic of quantal phenomena that observations defined by incompatible variables always involve important intervention by the experimenter, as described quantitatively by the observer effect. In classical thermodynamics, processes are initiated by interventions called thermodynamic operations. In other branches of science, for example astronomy, the experimenter can often observe with negligible intervention. The theory of "causal calculus" (also known as do-calculus, Judea Pearls Causal Calculus, Calculus of Actions) permits one to infer interventional probabilities from conditional probabilities in causal Bayesian networks with unmeasured variables. One very practical result of this theory is the characterization of confounding variables, namely, a sufficient set of variables that, if adjusted for, would yield the correct causal effect between variables of interest. It can be shown that a sufficient set for estimating the causal effect of X {\displaystyle X} on Y {\displaystyle Y} is any set of non-descendants of X {\displaystyle X} that d {\displaystyle d} -separate X {\displaystyle X} from Y {\displaystyle Y} after removing all arrows emanating from X {\displaystyle X} . This criterion, called "backdoor", provides a mathematical definition of "confounding" and helps researchers identify accessible sets of variables worthy of measurement. Structure learning While derivations in causal calculus rely on the structure of the causal graph, parts of the causal structure can, under certain assumptions, be learned from statistical data. The basic idea goes back to Sewall Wrights 1921 work on path analysis. A "recovery" algorithm was developed by Rebane and Pearl (1987) which rests on Wrights distinction between the three possible types of causal substructures allowed in a directed acyclic graph (DAG): X → Y → Z {\displaystyle X\rightarrow Y\rightarrow Z} X ← Y → Z {\displaystyle X\leftarrow Y\rightarrow Z} X → Y ← Z {\displaystyle X\rightarrow Y\leftarrow Z} Type 1 and type 2 represent the same statistical dependencies (i.e., X {\displaystyle X} and Z {\displaystyle Z} are independent given Y {\displaystyle Y} ) and are, therefore, indistinguishable within purely cross-sectional data. Type 3, however, can be uniquely identified, since X {\displaystyle X} and Z {\displaystyle Z} are marginally independent and all other pairs are dependent. Thus, while the skeletons (the graphs stripped of arrows) of these three triplets are identical, the directionality of the arrows is partially identifiable. The same distinction applies when X {\displaystyle X} and Z {\displaystyle Z} have common ancestors, except that one must first condition on those ancestors. Algorithms have been developed to systematically determine the skeleton of the underlying graph and, then, orient all arrows whose directionality is dictated by the conditional independencies observed.Alternative methods of structure learning search through the many possible causal structures among the variables, and remove ones which are strongly incompatible with the observed correlations. In general this leaves a set of possible causal relations, which should then be tested by analyzing time series data or, preferably, designing appropriately controlled experiments. In contrast with Bayesian Networks, path analysis (and its generalization, structural equation modeling), serve better to estimate a known causal effect or to test a causal model than to generate causal hypotheses. For nonexperimental data, causal direction can often be inferred if information about time is available. This is because (according to many, though not all, theories) causes must precede their effects temporally. This can be determined by statistical time series models, for instance, or with a statistical test based on the idea of Granger causality, or by direct experimental manipulation. The use of temporal data can permit statistical tests of a pre-existing theory of causal direction. For instance, our degree of confidence in the direction and nature of causality is much greater when supported by cross-correlations, ARIMA models, or cross-spectral analysis using vector time series data than by cross-sectional data. Derivation theories Nobel laureate Herbert A. Simon and philosopher Nicholas Rescher claim that the asymmetry of the causal relation is unrelated to the asymmetry of any mode of implication that contraposes. Rather, a causal relation is not a relation between values of variables, but a function of one variable (the cause) on to another (the effect). So, given a system of equations, and a set of variables appearing in these equations, we can introduce an asymmetric relation among individual equations and variables that corresponds perfectly to our commonsense notion of a causal ordering. The system of equations must have certain properties, most importantly, if some values are chosen arbitrarily, the remaining values will be determined uniquely through a path of serial discovery that is perfectly causal. They postulate the inherent serialization of such a system of equations may correctly capture causation in all empirical fields, including physics and economics. Manipulation theories Some theorists have equated causality with manipulability. Under these theories, x causes y only in the case that one can change x in order to change y. This coincides with commonsense notions of causations, since often we ask causal questions in order to change some feature of the world. For instance, we are interested in knowing the causes of crime so that we might find ways of reducing it. These theories have been criticized on two primary grounds. First, theorists complain that these accounts are circular. Attempting to reduce causal claims to manipulation requires that manipulation is more basic than causal interaction. But describing manipulations in non-causal terms has provided a substantial difficulty. The second criticism centers around concerns of anthropocentrism. It seems to many people that causality is some existing relationship in the world that we can harness for our desires. If causality is identified with our manipulation, then this intuition is lost. In this sense, it makes humans overly central to interactions in the world. Some attempts to defend manipulability theories are recent accounts that do not claim to reduce causality to manipulation. These accounts use manipulation as a sign or feature in causation without claiming that manipulation is more fundamental than causation. Process theories Some theorists are interested in distinguishing between causal processes and non-causal processes (Russell 1948; Salmon 1984). These theorists often want to distinguish between a process and a pseudo-process. As an example, a ball moving through the air (a process) is contrasted with the motion of a shadow (a pseudo-process). The former is causal in nature while the latter is not. Salmon (1984) claims that causal processes can be identified by their ability to transmit an alteration over space and time. An alteration of the ball (a mark by a pen, perhaps) is carried with it as the ball goes through the air. On the other hand, an alteration of the shadow (insofar as it is possible) will not be transmitted by the shadow as it moves along. These theorists claim that the important concept for understanding causality is not causal relationships or causal interactions, but rather identifying causal processes. The former notions can then be defined in terms of causal processes. A subgroup of the process theories is the mechanistic view on causality. It states that that causal relations supervene on mechanisms. While the notion of mechanism is understood differently, the definition put forward by the group of philosophers referred to as the New Mechanists dominate the literature. Fields Science For the scientific investigation of efficient causality, the cause and effect are each best conceived of as temporally transient processes. Within the conceptual frame of the scientific method, an investigator sets up several distinct and contrasting temporally transient material processes that have the structure of experiments, and records candidate material responses, normally intending to determine causality in the physical world. For instance, one may want to know whether a high intake of carrots causes humans to develop the bubonic plague. The quantity of carrot intake is a process that is varied from occasion to occasion. The occurrence or non-occurrence of subsequent bubonic plague is recorded. To establish causality, the experiment must fulfill certain criteria, only one example of which is mentioned here. For example, instances of the hypothesized cause must be set up to occur at a time when the hypothesized effect is relatively unlikely in the absence of the hypothesized cause; such unlikelihood is to be established by empirical evidence. A mere observation of a correlation is not nearly adequate to establish causality. In nearly all cases, establishment of causality relies on repetition of experiments and probabilistic reasoning. Hardly ever is causality established more firmly than as more or less probable. It is most convenient for establishment of causality if the contrasting material states of affairs are precisely matched, except for only one variable factor, perhaps measured by a real number. Physics One has to be careful in the use of the word cause in physics. Properly speaking, the hypothesized cause and the hypothesized effect are each temporally transient processes. For example, force is a useful concept for the explanation of acceleration, but force is not by itself a cause. More is needed. For example, a temporally transient process might be characterized by a definite change of force at a definite time. Such a process can be regarded as a cause. Causality is not inherently implied in equations of motion, but postulated as an additional constraint that needs to be satisfied (i.e. a cause always precedes its effect). This constraint has mathematical implications such as the Kramers-Kronig relations. Causality is one of the most fundamental and essential notions of physics. Causal efficacy cannot propagate faster than light. Otherwise, reference coordinate systems could be constructed (using the Lorentz transform of special relativity) in which an observer would see an effect precede its cause (i.e. the postulate of causality would be violated). Causal notions appear in the context of the flow of mass-energy. Any actual process has causal efficacy that can propagate no faster than light. In contrast, an abstraction has no causal efficacy. Its mathematical expression does not propagate in the ordinary sense of the word, though it may refer to virtual or nominal velocities with magnitudes greater than that of light. For example, wave packets are mathematical objects that have group velocity and phase velocity. The energy of a wave packet travels at the group velocity (under normal circumstances); since energy has causal efficacy, the group velocity cannot be faster than the speed of light. The phase of a wave packet travels at the phase velocity; since phase is not causal, the phase velocity of a wave packet can be faster than light.Causal notions are important in general relativity to the extent that the existence of an arrow of time demands that the universes semi-Riemannian manifold be orientable, so that "future" and "past" are globally definable quantities. Engineering A causal system is a system with output and internal states that depends only on the current and previous input values. A system that has some dependence on input values from the future (in addition to possible past or current input values) is termed an acausal system, and a system that depends solely on future input values is an anticausal system. Acausal filters, for example, can only exist as postprocessing filters, because these filters can extract future values from a memory buffer or a file. Biology, medicine and epidemiology Austin Bradford Hill built upon the work of Hume and Popper and suggested in his paper "The Environment and Disease: Association or Causation?" that aspects of an association such as strength, consistency, specificity, and temporality be considered in attempting to distinguish causal from noncausal associations in the epidemiological situation. (See Bradford-Hill criteria.) He did not note however, that temporality is the only necessary criterion among those aspects. Directed acyclic graphs (DAGs) are increasingly used in epidemiology to help enlighten causal thinking. Psychology Psychologists take an empirical approach to causality, investigating how people and non-human animals detect or infer causation from sensory information, prior experience and innate knowledge. AttributionAttribution theory is the theory concerning how people explain individual occurrences of causation. Attribution can be external (assigning causality to an outside agent or force—claiming that some outside thing motivated the event) or internal (assigning causality to factors within the person—taking personal responsibility or accountability for ones actions and claiming that the person was directly responsible for the event). Taking causation one step further, the type of attribution a person provides influences their future behavior. The intention behind the cause or the effect can be covered by the subject of action. See also accident; blame; intent; and responsibility. Causal powersWhereas David Hume argued that causes are inferred from non-causal observations, Immanuel Kant claimed that people have innate assumptions about causes. Within psychology, Patricia Cheng attempted to reconcile the Humean and Kantian views. According to her power PC theory, people filter observations of events through an intuition that causes have the power to generate (or prevent) their effects, thereby inferring specific cause-effect relations. Causation and salienceOur view of causation depends on what we consider to be the relevant events. Another way to view the statement, "Lightning causes thunder" is to see both lightning and thunder as two perceptions of the same event, viz., an electric discharge that we perceive first visually and then aurally. Naming and causalityDavid Sobel and Alison Gopnik from the Psychology Department of UC Berkeley designed a device known as the blicket detector which would turn on when an object was placed on it. Their research suggests that "even young children will easily and swiftly learn about a new causal power of an object and spontaneously use that information in classifying and naming the object." Perception of launching eventsSome researchers such as Anjan Chatterjee at the University of Pennsylvania and Jonathan Fugelsang at the University of Waterloo are using neuroscience techniques to investigate the neural and psychological underpinnings of causal launching events in which one object causes another object to move. Both temporal and spatial factors can be manipulated.See Causal Reasoning (Psychology) for more information. Statistics and economics Statistics and economics usually employ pre-existing data or experimental data to infer causality by regression methods. The body of statistical techniques involves substantial use of regression analysis. Typically a linear relationship such as y i = a 0 + a 1 x 1 , i + a 2 x 2 , i + ⋯ + a k x k , i + e i {\displaystyle y_{i}=a_{0}+a_{1}x_{1,i}+a_{2}x_{2,i}+\dots +a_{k}x_{k,i}+e_{i}} is postulated, in which y i {\displaystyle y_{i}} is the ith observation of the dependent variable (hypothesized to be the caused variable), x j , i {\displaystyle x_{j,i}} for j=1,...,k is the ith observation on the jth independent variable (hypothesized to be a causative variable), and e i {\displaystyle e_{i}} is the error term for the ith observation (containing the combined effects of all other causative variables, which must be uncorrelated with the included independent variables). If there is reason to believe that none of the x j {\displaystyle x_{j}} s is caused by y, then estimates of the coefficients a j {\displaystyle a_{j}} are obtained. If the null hypothesis that a j = 0 {\displaystyle a_{j}=0} is rejected, then the alternative hypothesis that a j ≠ 0 {\displaystyle a_{j}\neq 0} and equivalently that x j {\displaystyle x_{j}} causes y cannot be rejected. On the other hand, if the null hypothesis that a j = 0 {\displaystyle a_{j}=0} cannot be rejected, then equivalently the hypothesis of no causal effect of x j {\displaystyle x_{j}} on y cannot be rejected. Here the notion of causality is one of contributory causality as discussed above: If the true value a j ≠ 0 {\displaystyle a_{j}\neq 0} , then a change in x j {\displaystyle x_{j}} will result in a change in y unless some other causative variable(s), either included in the regression or implicit in the error term, change in such a way as to exactly offset its effect; thus a change in x j {\displaystyle x_{j}} is not sufficient to change y. Likewise, a change in x j {\displaystyle x_{j}} is not necessary to change y, because a change in y could be caused by something implicit in the error term (or by some other causative explanatory variable included in the model). The above way of testing for causality requires belief that there is no reverse causation, in which y would cause x j {\displaystyle x_{j}} . This belief can be established in one of several ways. First, the variable x j {\displaystyle x_{j}} may be a non-economic variable: for example, if rainfall amount x j {\displaystyle x_{j}} is hypothesized to affect the futures price y of some agricultural commodity, it is impossible that in fact the futures price affects rainfall amount (provided that cloud seeding is never attempted). Second, the instrumental variables technique may be employed to remove any reverse causation by introducing a role for other variables (instruments) that are known to be unaffected by the dependent variable. Third, the principle that effects cannot precede causes can be invoked, by including on the right side of the regression only variables that precede in time the dependent variable; this principle is invoked, for example, in testing for Granger causality and in its multivariate analog, vector autoregression, both of which control for lagged values of the dependent variable while testing for causal effects of lagged independent variables. Regression analysis controls for other relevant variables by including them as regressors (explanatory variables). This helps to avoid false inferences of causality due to the presence of a third, underlying, variable that influences both the potentially causative variable and the potentially caused variable: its effect on the potentially caused variable is captured by directly including it in the regression, so that effect will not be picked up as an indirect effect through the potentially causative variable of interest. Given the above procedures, coincidental (as opposed to causal) correlation can be probabilistically rejected if data samples are large and if regression results pass cross-validation tests showing that the correlations hold even for data that were not used in the regression. Asserting with certitude that a common-cause is absent and the regression represents the true causal structure is in principle impossible.Apart from constructing statistical models of observational and experimental data, economists use axiomatic (mathematical) models to infer and represent causal mechanisms. Highly abstract theoretical models that isolate and idealize one mechanism dominate microeconomics. In macroeconomics, economists use broad mathematical models that are calibrated on historical data. A subgroup of calibrated models, dynamic stochastic general equilibrium (DSGE) models are employed to represent (in a simplified way) the whole economy and simulate changes in fiscal and monetary policy. Management For quality control in manufacturing in the 1960s, Kaoru Ishikawa developed a cause and effect diagram, known as an Ishikawa diagram or fishbone diagram. The diagram categorizes causes, such as into the six main categories shown here. These categories are then sub-divided. Ishikawas method identifies "causes" in brainstorming sessions conducted among various groups involved in the manufacturing process. These groups can then be labeled as categories in the diagrams. The use of these diagrams has now spread beyond quality control, and they are used in other areas of management and in design and engineering. Ishikawa diagrams have been criticized for failing to make the distinction between necessary conditions and sufficient conditions. It seems that Ishikawa was not even aware of this distinction. Humanities History In the discussion of history, events are sometimes considered as if in some way being agents that can then bring about other historical events. Thus, the combination of poor harvests, the hardships of the peasants, high taxes, lack of representation of the people, and kingly ineptitude are among the causes of the French Revolution. This is a somewhat Platonic and Hegelian view that reifies causes as ontological entities. In Aristotelian terminology, this use approximates to the case of the efficient cause. Some philosophers of history such as Arthur Danto have claimed that "explanations in history and elsewhere" describe "not simply an event—something that happens—but a change". Like many practicing historians, they treat causes as intersecting actions and sets of actions which bring about "larger changes", in Dantos words: to decide "what are the elements which persist through a change" is "rather simple" when treating an individuals "shift in attitude", but "it is considerably more complex and metaphysically challenging when we are interested in such a change as, say, the break-up of feudalism or the emergence of nationalism".Much of the historical debate about causes has focused on the relationship between communicative and other actions, between singular and repeated ones, and between actions, structures of action or group and institutional contexts and wider sets of conditions. John Gaddis has distinguished between exceptional and general causes (following Marc Bloch) and between "routine" and "distinctive links" in causal relationships: "in accounting for what happened at Hiroshima on August 6, 1945, we attach greater importance to the fact that President Truman ordered the dropping of an atomic bomb than to the decision of the Army Air Force to carry out his orders." He has also pointed to the difference between immediate, intermediate and distant causes. For his part, Christopher Lloyd puts forward four "general concepts of causation" used in history: the "metaphysical idealist concept, which asserts that the phenomena of the universe are products of or emanations from an omnipotent being or such final cause"; "the empiricist (or Humean) regularity concept, which is based on the idea of causation being a matter of constant conjunctions of events"; "the functional/teleological/consequential concept", which is "goal-directed, so that goals are causes"; and the "realist, structurist and dispositional approach, which sees relational structures and internal dispositions as the causes of phenomena". Law According to law and jurisprudence, legal cause must be demonstrated to hold a defendant liable for a crime or a tort (i.e. a civil wrong such as negligence or trespass). It must be proven that causality, or a "sufficient causal link" relates the defendants actions to the criminal event or damage in question. Causation is also an essential legal element that must be proven to qualify for remedy measures under international trade law. History Hindu philosophy Vedic period (c. 1750–500 BCE) literature has karmas Eastern origins. Karma is the belief held by Sanatana Dharma and major religions that a persons actions cause certain effects in the current life and/or in future life, positively or negatively. The various philosophical schools (darshanas) provide different accounts of the subject. The doctrine of satkaryavada affirms that the effect inheres in the cause in some way. The effect is thus either a real or apparent modification of the cause. The doctrine of asatkaryavada affirms that the effect does not inhere in the cause, but is a new arising. See Nyaya for some details of the theory of causation in the Nyaya school. In Brahma Samhita, Brahma describes Krishna as the prime cause of all causes.Bhagavad-gītā 18.14 identifies five causes for any action (knowing which it can be perfected): the body, the individual soul, the senses, the efforts and the supersoul. According to Monier-Williams, in the Nyāya causation theory from Sutra I.2.I,2 in the Vaisheshika philosophy, from causal non-existence is effectual non-existence; but, not effectual non-existence from causal non-existence. A cause precedes an effect. With a threads and cloth metaphors, three causes are: Co-inherence cause: resulting from substantial contact, substantial causes, threads are substantial to cloth, corresponding to Aristotles material cause. Non-substantial cause: Methods putting threads into cloth, corresponding to Aristotles formal cause. Instrumental cause: Tools to make the cloth, corresponding to Aristotles efficient cause.Monier-Williams also proposed that Aristotles and the Nyayas causality are considered conditional aggregates necessary to mans productive work. Buddhist philosophy Karma is the causality principle focusing on 1) causes, 2) actions, 3) effects, where it is the minds phenomena that guide the actions that the actor performs. Buddhism trains the actors actions for continued and uncontrived virtuous outcomes aimed at reducing suffering. This follows the Subject–verb–object structure.The general or universal definition of pratityasamutpada (or "dependent origination" or "dependent arising" or "interdependent co-arising") is that everything arises in dependence upon multiple causes and conditions; nothing exists as a singular, independent entity. A traditional example in Buddhist texts is of three sticks standing upright and leaning against each other and supporting each other. If one stick is taken away, the other two will fall to the ground.Causality in the Chittamatrin Buddhist school approach, Asangas (c. 400 CE) mind-only Buddhist school, asserts that objects cause consciousness in the minds image. Because causes precede effects, which must be different entities, then subject and object are different. For this school, there are no objects which are entities external to a perceiving consciousness. The Chittamatrin and the Yogachara Svatantrika schools accept that there are no objects external to the observers causality. This largely follows the Nikayas approach.The Vaibhashika (c. 500 CE) is an early Buddhist school which favors direct object contact and accepts simultaneous cause and effects. This is based in the consciousness example which says, intentions and feelings are mutually accompanying mental factors that support each other like poles in tripod. In contrast, simultaneous cause and effect rejectors say that if the effect already exists, then it cannot effect the same way again. How past, present and future are accepted is a basis for various Buddhist schools causality viewpoints.All the classic Buddhist schools teach karma. "The law of karma is a special instance of the law of cause and effect, according to which all our actions of body, speech, and mind are causes and all our experiences are their effects." Western philosophy Aristotelian Aristotle identified four kinds of answer or explanatory mode to various "Why?" questions. He thought that, for any given topic, all four kinds of explanatory mode were important, each in its own right. As a result of traditional specialized philosophical peculiarities of language, with translations between ancient Greek, Latin, and English, the word cause is nowadays in specialized philosophical writings used to label Aristotles four kinds. In ordinary language, the word cause has a variety of meanings, the most common of which refers to efficient causation, which is the topic of the present article. Material cause, the material whence a thing has come or that which persists while it changes, as for example, ones mother or the bronze of a statue (see also substance theory). Formal cause, whereby a things dynamic form or static shape determines the things properties and function, as a human differs from a statue of a human or as a statue differs from a lump of bronze. Efficient cause, which imparts the first relevant movement, as a human lifts a rock or raises a statue. This is the main topic of the present article. Final cause, the criterion of completion, or the end; it may refer to an action or to an inanimate process. Examples: Socrates takes a walk after dinner for the sake of his health; earth falls to the lowest level because that is its nature.Of Aristotles four kinds or explanatory modes, only one, the efficient cause is a cause as defined in the leading paragraph of this present article. The other three explanatory modes might be rendered material composition, structure and dynamics, and, again, criterion of completion. The word that Aristotle used was αἰτία. For the present purpose, that Greek word would be better translated as "explanation" than as "cause" as those words are most often used in current English. Another translation of Aristotle is that he meant "the four Becauses" as four kinds of answer to "why" questions.Aristotle assumed efficient causality as referring to a basic fact of experience, not explicable by, or reducible to, anything more fundamental or basic. In some works of Aristotle, the four causes are listed as (1) the essential cause, (2) the logical ground, (3) the moving cause, and (4) the final cause. In this listing, a statement of essential cause is a demonstration that an indicated object conforms to a definition of the word that refers to it. A statement of logical ground is an argument as to why an object statement is true. These are further examples of the idea that a "cause" in general in the context of Aristotles usage is an "explanation".The word "efficient" used here can also be translated from Aristotle as "moving" or "initiating".Efficient causation was connected with Aristotelian physics, which recognized the four elements (earth, air, fire, water), and added the fifth element (aether). Water and earth by their intrinsic property gravitas or heaviness intrinsically fall toward, whereas air and fire by their intrinsic property levitas or lightness intrinsically rise away from, Earths center—the motionless center of the universe—in a straight line while accelerating during the substances approach to its natural place. As air remained on Earth, however, and did not escape Earth while eventually achieving infinite speed—an absurdity—Aristotle inferred that the universe is finite in size and contains an invisible substance that held planet Earth and its atmosphere, the sublunary sphere, centered in the universe. And since celestial bodies exhibit perpetual, unaccelerated motion orbiting planet Earth in unchanging relations, Aristotle inferred that the fifth element, aither, that fills space and composes celestial bodies intrinsically moves in perpetual circles, the only constant motion between two points. (An object traveling a straight line from point A to B and back must stop at either point before returning to the other.) Left to itself, a thing exhibits natural motion, but can—according to Aristotelian metaphysics—exhibit enforced motion imparted by an efficient cause. The form of plants endows plants with the processes nutrition and reproduction, the form of animals adds locomotion, and the form of humankind adds reason atop these. A rock normally exhibits natural motion—explained by the rocks material cause of being composed of the element earth—but a living thing can lift the rock, an enforced motion diverting the rock from its natural place and natural motion. As a further kind of explanation, Aristotle identified the final cause, specifying a purpose or criterion of completion in light of which something should be understood. Aristotle himself explained, Cause means (a) in one sense, that as the result of whose presence something comes into being—e.g., the bronze of a statue and the silver of a cup, and the classes which contain these [i.e., the material cause]; (b) in another sense, the form or pattern; that is, the essential formula and the classes which contain it—e.g. the ratio 2:1 and number in general is the cause of the octave—and the parts of the formula [i.e., the formal cause]. (c) The source of the first beginning of change or rest; e.g. the man who plans is a cause, and the father is the cause of the child, and in general that which produces is the cause of that which is produced, and that which changes of that which is changed [i.e., the efficient cause]. (d) The same as "end"; i.e. the final cause; e.g., as the "end" of walking is health. For why does a man walk? "To be healthy", we say, and by saying this we consider that we have supplied the cause [the final cause]. (e) All those means towards the end which arise at the instigation of something else, as, e.g., fat-reducing, purging, drugs, and instruments are causes of health; for they all have the end as their object, although they differ from each other as being some instruments, others actions [i.e., necessary conditions]. Aristotle further discerned two modes of causation: proper (prior) causation and accidental (chance) causation. All causes, proper and accidental, can be spoken as potential or as actual, particular or generic. The same language refers to the effects of causes, so that generic effects are assigned to generic causes, particular effects to particular causes, and actual effects to operating causes. Averting infinite regress, Aristotle inferred the first mover—an unmoved mover. The first movers motion, too, must have been caused, but, being an unmoved mover, must have moved only toward a particular goal or desire. Pyrrhonism While the plausibility of causality was accepted in Pyrrhonism, it was equally accepted that it was plausible that nothing was the cause of anything. Middle Ages In line with Aristotelian cosmology, Thomas Aquinas posed a hierarchy prioritizing Aristotles four causes: "final > efficient > material > formal". Aquinas sought to identify the first efficient cause—now simply first cause—as everyone would agree, said Aquinas, to call it God. Later in the Middle Ages, many scholars conceded that the first cause was God, but explained that many earthly events occur within Gods design or plan, and thereby scholars sought freedom to investigate the numerous secondary causes. After the Middle Ages For Aristotelian philosophy before Aquinas, the word cause had a broad meaning. It meant answer to a why question or explanation, and Aristotelian scholars recognized four kinds of such answers. With the end of the Middle Ages, in many philosophical usages, the meaning of the word cause narrowed. It often lost that broad meaning, and was restricted to just one of the four kinds. For authors such as Niccolò Machiavelli, in the field of political thinking, and Francis Bacon, concerning science more generally, Aristotles moving cause was the focus of their interest. A widely used modern definition of causality in this newly narrowed sense was assumed by David Hume. He undertook an epistemological and metaphysical investigation of the notion of moving cause. He denied that we can ever perceive cause and effect, except by developing a habit or custom of mind where we come to associate two types of object or event, always contiguous and occurring one after the other. In Part III, section XV of his book A Treatise of Human Nature, Hume expanded this to a list of eight ways of judging whether two things might be cause and effect. The first three: "The cause and effect must be contiguous in space and time." "The cause must be prior to the effect." "There must be a constant union betwixt the cause and effect. Tis chiefly this quality, that constitutes the relation." And then additionally there are three connected criteria which come from our experience and which are "the source of most of our philosophical reasonings": And then two more: In 1949, physicist Max Born distinguished determination from causality. For him, determination meant that actual events are so linked by laws of nature that certainly reliable predictions and retrodictions can be made from sufficient present data about them. He describes two kinds of causation: nomic or generic causation and singular causation. Nomic causality means that cause and effect are linked by more or less certain or probabilistic general laws covering many possible or potential instances; this can be recognized as a probabilized version of Humes criterion 3. An occasion of singular causation is a particular occurrence of a definite complex of events that are physically linked by antecedence and contiguity, which may be recognized as criteria 1 and 2. See also References Further reading Spirtes, Peter, Clark Glymour and Richard Scheines Causation, Prediction, and Search, MIT Press, ISBN 0-262-19440-6 University of California journal articles, including Judea Pearls articles between 1984 and 1998 Search Results - Technical Reports. Miguel Espinoza, Théorie du déterminisme causal, LHarmattan, Paris, 2006. ISBN 2-296-01198-5. External links Causality at PhilPapers Causality at the Indiana Philosophy Ontology Project Causation – Internet Encyclopedia of Philosophy Metaphysics of Science – Internet Encyclopedia of Philosophy Causal Processes at the Stanford Encyclopedia of Philosophy The Art and Science of Cause and Effect – A slide show and tutorial lecture by Judea Pearl Donald Davidson: Causal Explanation of Action – The Internet Encyclopedia of Philosophy Causal inference in statistics: An overview – By Judea Pearl (September 2009) An R implementation of causal calculus TimeSleuth - A tool for discovering causality

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

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

Bad breath, also known as halitosis, is a symptom in which a noticeably unpleasant breath odour is present. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder.The concerns of bad breath may be divided into genuine and non-genuine cases. Of those who have genuine bad breath, about 85% of cases come from inside the mouth. The remaining cases are believed to be due to disorders in the nose, sinuses, throat, lungs, esophagus, or stomach. Rarely, bad breath can be due to an underlying medical condition such as liver failure or ketoacidosis. Non-genuine cases occur when someone complains of having bad breath but other people cannot detect it. This is estimated to make up between 5% and 72% of cases.The treatment depends on the underlying cause. Initial efforts may include tongue cleaning, mouthwash, and flossing. Tentative evidence supports the use of mouthwash containing chlorhexidine or cetylpyridinium chloride. While there is tentative evidence of benefit from the use of a tongue cleaner it is insufficient to draw clear conclusions. Treating underlying disease such as gum disease, tooth decay, tonsil stones, or gastroesophageal reflux disease may help. Counselling may be useful in those who falsely believe that they have bad breath.Estimated rates of bad breath vary from 6% to 50% of the population. Concern about bad breath is the third most common reason people seek dental care, after tooth decay and gum disease. It is believed to become more common as people age. Bad breath is viewed as a social taboo and those affected may be stigmatized. People in the United States spend more than $1 billion per year on mouthwash to treat it. Signs and symptoms Bad breath is when a noticeably unpleasant odour is believed to be present on the breath. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder. Causes Mouth In about 90% of genuine halitosis cases, the origin of the odour is in the mouth itself. This is known as intra-oral halitosis, oral malodour or oral halitosis. The most common causes are odour producing biofilm on the back of the tongue or other areas of the mouth due to poor oral hygiene. This biofilm results in the production of high levels of foul odours. The odours are produced mainly due to the breakdown of proteins into individual amino acids, followed by the further breakdown of certain amino acids to produce detectable foul gases. Volatile sulfur compounds are associated with oral malodour levels, and usually decrease following successful treatment. Other parts of the mouth may also contribute to the overall odour, but are not as common as the back of the tongue. These locations are, in order of descending prevalence, inter-dental and sub-gingival niches, faulty dental work, food-impaction areas in between the teeth, abscesses, and unclean dentures. Oral based lesions caused by viral infections like herpes simplex and HPV may also contribute to bad breath. The intensity of bad breath may differ during the day, due to eating certain foods (such as garlic, onions, meat, fish, and cheese), smoking, and alcohol consumption. Since the mouth is exposed to less oxygen and is inactive during the night, the odour is usually worse upon awakening ("morning breath"). Bad breath may be transient, often disappearing following eating, drinking, tooth brushing, flossing, or rinsing with specialized mouthwash. Bad breath may also be persistent (chronic bad breath), which affects some 25% of the population in varying degrees. Tongue The most common location for mouth-related halitosis is the tongue. Tongue bacteria produce malodourous compounds and fatty acids, and account for 80 to 90% of all cases of mouth-related bad breath. Large quantities of naturally occurring bacteria are often found on the posterior dorsum of the tongue, where they are relatively undisturbed by normal activity. This part of the tongue is relatively dry and poorly cleansed, and the convoluted microbial structure of the tongue dorsum provides an ideal habitat for anaerobic bacteria, which flourish under a continually-forming tongue coating of food debris, dead epithelial cells, postnasal drip and overlying bacteria, living and dead. When left on the tongue, the anaerobic respiration of such bacteria can yield either the putrescent smell of indole, skatole, polyamines, or the "rotten egg" smell of volatile sulfur compounds (VSCs) such as hydrogen sulfide, methyl mercaptan, allyl methyl sulfide, and dimethyl sulfide. The presence of halitosis-producing bacteria on the back of the tongue is not to be confused with tongue coating. Bacteria are invisible to the naked eye, and degrees of white tongue coating are present in most people with and without halitosis. A visible white tongue coating does not always equal the back of the tongue as an origin of halitosis, however a "white tongue" is thought to be a sign of halitosis. In oral medicine generally, a white tongue is considered a sign of several medical conditions. Patients with periodontal disease were shown to have sixfold prevalence of tongue coating compared with normal subjects. Halitosis patients were also shown to have significantly higher bacterial loads in this region compared to individuals without halitosis. Gums Gingival crevices are the small grooves between teeth and gums, and they are present in health, although they may become inflamed when gingivitis is present. The difference between a gingival crevice and periodontal pocket is that former is <3mm in depth and the latter is >3mm. Periodontal pockets usually accompany periodontal disease (gum disease). There is some controversy over the role of periodontal diseases in causing bad breath. However, advanced periodontal disease is a common cause of severe halitosis. People with uncontrolled diabetes are more prone to have multiple gingival and periodontal abscess. Their gums are evident with large pockets, where pus accumulation occurs. This nidus of infection can be a potential source for bad breath. Removal of the subgingival calculus (i.e. tartar or hard plaque) and friable tissue has been shown to improve mouth odour considerably. This is accomplished by subgingival scaling and root planing and irrigation with an antibiotic mouth rinse. The bacteria that cause gingivitis and periodontal disease (periodontopathogens) are invariably gram negative and capable of producing VSC. Methyl mercaptan is known to be the greatest contributing VSC in halitosis that is caused by periodontal disease and gingivitis. The level of VSC on breath has been shown to positively correlate with the depth of periodontal pocketing, the number of pockets, and whether the pockets bleed when examined with a dental probe. Indeed, VSC may themselves have been shown to contribute to the inflammation and tissue damage that is characteristic of periodontal disease. However, not all patients with periodontal disease have halitosis, and not all patients with halitosis have periodontal disease. Although patients with periodontal disease are more likely to develop halitosis than the general population, the halitosis symptom was shown to be more strongly associated with degree of tongue coating than with the severity of periodontal disease. Another possible symptom of periodontal disease is a bad taste, which does not necessarily accompany a malodour that is detectable by others. Other causes Other less common reported causes from within the mouth include: Deep carious lesions (dental decay) – which cause localized food impaction and stagnation Recent dental extraction sockets – fill with blood clot, and provide an ideal habitat for bacterial proliferation Interdental food packing – (food getting pushed down between teeth) - this can be caused by missing teeth, tilted, spaced or crowded teeth, or poorly contoured approximal dental fillings. Food debris becomes trapped, undergoes slow bacterial putrefaction and release of malodourous volatiles. Food packing can also cause a localized periodontal reaction, characterized by dental pain that is relieved by cleaning the area of food packing with interdental brush or floss. Acrylic dentures (plastic false teeth) – inadequate denture hygiene practises such as failing to clean and remove the prosthesis each night, may cause a malodour from the plastic itself or from the mouth as microbiota responds to the altered environment. The plastic is actually porous, and the fitting surface is usually irregular, sculpted to fit the edentulous oral anatomy. These factors predispose to bacterial and yeast retention, which is accompanied by a typical smell. Oral infections Oral ulceration Fasting Stress/anxiety Menstrual cycle – at mid cycle and during menstruation, increased breath VSC were reported in women. Smoking – Smoking is linked with periodontal disease, which is the second most common cause of oral maloduor. Smoking also has many other negative effects on the mouth, from increased rates of dental decay to premalignant lesions and even oral cancer. Alcohol Volatile foods – e.g. onion, garlic, durian, cabbage, cauliflower and radish. Volatile foodstuffs may leave malodourous residues in the mouth, which are the subject to bacterial putrefaction and VSC release. However, volatile foodstuffs may also cause halitoisis via the blood borne halitosis mechanism. Medication – often medications can cause xerostomia (dry mouth) which results in increased microbial growth in the mouth. Nose and sinuses In this occurrence, the air exiting the nostrils has a pungent odour that differs from the oral odour. Nasal odour may be due to sinus infections or foreign bodies.Halitosis is often stated to be a symptom of chronic rhinosinusitis, however gold standard breath analysis techniques have not been applied. Theoretically, there are several possible mechanisms of both objective and subjective halitosis that may be involved. Tonsils There is disagreement as to the proportion of halitosis cases which are caused by conditions of the tonsils. Some claim that the tonsils are the most significant cause of halitosis after the mouth. According to one report, approximately 3% of halitosis cases were related to the tonsils. Conditions of the tonsils which may be associated with halitosis include chronic caseous tonsillitis (cheese-like material can be exuded from the tonsillar crypt orifi), tonsillolithiasis (tonsil stones), and less commonly peritonsillar abscess, actinomycosis, fungating malignancies, chondroid choristoma and inflammatory myofibroblastic tumor. Esophagus The lower esophageal sphincter, which is the valve between the stomach and the esophagus, may not close properly due to a hiatal hernia or GERD, allowing acid to enter the esophagus and gases to escape to the mouth. A Zenkers diverticulum may also result in halitosis due to aging food retained in the esophagus. Stomach The stomach is considered by most researchers as a very uncommon source of bad breath. The esophagus is a closed and collapsed tube, and continuous flow of gas or putrid substances from the stomach indicates a health problem—such as reflux serious enough to be bringing up stomach contents or a fistula between the stomach and the esophagus—which will demonstrate more serious manifestations than just foul odour.In the case of allyl methyl sulfide (the byproduct of garlics digestion), odour does not come from the stomach, since it does not get metabolized there. Systemic diseases There are a few systemic (non-oral) medical conditions that may cause foul breath odour, but these are infrequent in the general population. Such conditions are: Fetor hepaticus: an example of a rare type of bad breath caused by chronic liver failure. Lower respiratory tract infections (bronchial and lung infections). Kidney infections and kidney failure. Carcinoma. Trimethylaminuria ("fish odour syndrome"). Diabetes mellitus. Metabolic conditions, e.g. resulting in elevated blood dimethyl sulfide.Individuals affected by the above conditions often show additional, more diagnostically conclusive symptoms than bad breath alone. Delusional halitosis One quarter of the people seeking professional advice on bad breath have an exaggerated concern of having bad breath, known as halitophobia, delusional halitosis, or as a manifestation of olfactory reference syndrome. They are sure that they have bad breath, although many have not asked anyone for an objective opinion. Bad breath may severely affect the lives of some 0.5–1.0% of the adult population. Diagnosis Self diagnosis Scientists have long thought that smelling ones own breath odour is often difficult due to acclimatization, although many people with bad breath are able to detect it in others. Research has suggested that self-evaluation of halitosis is not easy because of preconceived notions of how bad we think it should be. Some people assume that they have bad breath because of bad taste (metallic, sour, fecal, etc.), however bad taste is considered a poor indicator. Patients often self-diagnose by asking a close friend.One popular home method to determine the presence of bad breath is to lick the back of the wrist, let the saliva dry for a minute or two, and smell the result. This test results in overestimation, as concluded from research, and should be avoided. A better way would be to lightly scrape the posterior back of the tongue with a plastic disposable spoon and to smell the drying residue. Home tests that use a chemical reaction to test for the presence of polyamines and sulfur compounds on tongue swabs are now available, but there are few studies showing how well they actually detect the odour. Furthermore, since breath odour changes in intensity throughout the day depending on many factors, multiple testing sessions may be necessary. Testing If bad breath is persistent, and all other medical and dental factors have been ruled out, specialized testing and treatment is required. Hundreds of dental offices and commercial breath clinics now claim to diagnose and treat bad breath. They often use some of several laboratory methods for diagnosis of bad breath: Halimeter: a portable sulfide monitor used to test for levels of sulfur emissions (to be specific, hydrogen sulfide) in the mouth air. When used properly, this device can be very effective at determining levels of certain VSC-producing bacteria. However, it has drawbacks in clinical applications. For example, other common sulfides (such as mercaptan) are not recorded as easily and can be misrepresented in test results. Certain foods such as garlic and onions produce sulfur in the breath for as long as 48 hours and can result in false readings. The Halimeter is also very sensitive to alcohol, so one should avoid drinking alcohol or using alcohol-containing mouthwashes for at least 12 hours prior to being tested. This analog machine loses sensitivity over time and requires periodic recalibration to remain accurate. Gas chromatography: portable machines are being studied. This technology is designed to digitally measure molecular levels of major VSCs in a sample of mouth air (such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide). It is accurate in measuring the sulfur components of the breath and produces visual results in graph form via computer interface. BANA test: this test is directed to find the salivary levels of an enzyme indicating the presence of certain halitosis-related bacteria. β-galactosidase test: salivary levels of this enzyme were found to be correlated with oral malodour.Although such instrumentation and examinations are widely used in breath clinics, the most important measurement of bad breath (the gold standard) is the actual sniffing and scoring of the level and type of the odour carried out by trained experts ("organoleptic measurements"). The level of odour is usually assessed on a six-point intensity scale. Classification Two main classification schemes exist for bad breath, although neither are universally accepted.The Miyazaki et al. classification was originally described in 1999 in a Japanese scientific publication, and has since been adapted to reflect North American society, especially with regards halitophobia. The classification assumes three primary divisions of the halitosis symptom, namely genuine halitosis, pseudohalitosis and halitophobia. This classification has been suggested to be most widely used, but it has been criticized because it is overly simplistic and is largely of use only to dentists rather than other specialties. Genuine halitosis A. Physiologic halitosis B. Pathologic halitosis (i) Oral (ii) Extra-oral Pseudohalitosis HalitophobiaThe Tangerman and Winkel classification was suggested in Europe in 2002. This classification focuses only on those cases where there is genuine halitosis, and has therefore been criticized for being less clinically useful for dentistry when compared to the Miyazaki et al. classification. Intra-oral halitosis Extra-oral halitosis A. Blood borne halitosis (i) Systemic diseases (ii) Metabolic diseases (iii) Food (iv) Medication B. Non-blood borne halitosis (i) Upper respiratory tract (ii) Lower respiratory tractThe same authors also suggested that halitosis can be divided according to the character of the odour into 3 groups: "Sulfurous or fecal" caused by volatile sulfur compounds (VSC), most notably methyl mercaptan, hydrogen sulfide and dimethyl sulfide. "Fruity" caused by acetone, present in diabetes. "Urine-like or ammoniacal" caused by ammonia, dimethyl amine and trimethylamine (TMA), present in trimethylaminuria and uremia.Based on the strengths and weaknesses of previous attempts at classification, a cause based classification has been proposed: Type 0 (physiologic) Type 1 (oral) Type 2 (airway) Type 3 (gastroesophageal) Type 4 (blood-borne) Type 5 (subjective)Any halitosis symptom is potentially the sum of these types in any combination, superimposed on the physiologic odour present in all healthy individuals. Management Approaches to improve bad breath may include physical or chemical means to decrease bacteria in the mouth, products to mask the smell, or chemicals to alter the odour creating molecules. Many different interventions have been suggested and trialed such as toothpastes, mouthwashes, lasers, tongue scraping, and mouth rinses. There is no strong evidence to indicate which interventions work and which are more effective. It is recommended that in those who use tobacco products stop. Evidence does not support the benefit of dietary changes or chewing gum. Mechanical measures Brushing the teeth may help. While there is evidence of tentative benefit from tongue cleaning it is insufficient to draw clear conclusions. A 2006 Cochrane review found tentative evidence that it might decrease levels of odour molecules. Flossing may be useful. Mouthwashes A 2008 systematic review found that antibacterial mouthrinses may help. Mouthwashes often contain antibacterial agents including cetylpyridinium chloride, chlorhexidine, zinc gluconate, zinc chloride, zinc lactate, hydrogen peroxide, chlorine dioxide, amine fluorides, stannous fluoride, hinokitiol, and essential oils. Listerine is one of the well-known mouthwash products composed of different essential oils. Other formulations containing herbal products and probiotics have also been proposed. Cetylpyridinium chloride and chlorhexidine can temporarily stain teeth. Underlying disease If gum disease and cavities are present, it is recommended that these be treated.If diseases outside of the mouth are believed to be contributing to the problem, treatment may result in improvements.Counselling may be useful in those who falsely believe that they have bad breath. Epidemiology It is difficult for researchers to make estimates of the prevalence of halitosis in the general population for several reasons. Firstly, halitosis is subject to societal taboo and stigma, which may impact individuals willingness to take part in such studies or to report accurately their experience of the condition. Secondly, there is no universal agreement about what diagnostic criteria and what detection methods should be used to define which individuals have halitosis and which do not. Some studies rely on self reported estimation of halitosis, and there is contention as to whether this is a reliable predictor of actual halitosis or not. In reflection of these problems, reported epidemiological data are widely variable. History, society and culture The earliest known mention of bad breath occurs in ancient Egypt, where detailed recipes for toothpaste are made before the Pyramids are built. The 1550 BC Ebers Papyrus describes tablets to cure bad breath based on incense, cinnamon, myrrh and honey. Hippocratic medicine advocated a mouthwash of red wine and spices to cure bad breath. Alcohol-containing mouthwashes are now thought to exacerbate bad breath as they dry the mouth, leading to increased microbial growth. The Hippocratic Corpus also describes a recipe based on marble powder for females with bad breath. The Ancient Roman physician Pliny wrote about methods to sweeten the breath.Ancient Chinese emperors required visitors to chew clove before an audience. The Talmud describes bad breath as a disability, which could be grounds for legal breaking of a marriage license. Early Islamic theology stressed that the teeth and tongue should be cleaned with a siwak, a stick from the plant Salvadora persica tree. This traditional chewing stick is also called a Miswak, especially used in Saudi Arabia, an essentially is like a natural toothbrush made from twigs. During the Renaissance era, Laurent Joubert, doctor to King Henry III of France states bad breath is "caused by dangerous miasma that falls into the lungs and through the heart, causing severe damages".In B. G. Jefferis and J. L. Nichols "Searchlights on Health" (1919), the following recipe is offered: "[One] teaspoonful of the following mixture after each meal: One ounce chloride of soda, one ounce liquor of potassa, one and one-half ounces phosphate of soda, and three ounces of water." In the present day, bad breath is one of the biggest social taboos. The general population places great importance on the avoidance of bad breath, illustrated by the annual $1 billion that consumers in the United States spend on deodorant-type mouth (oral) rinses, mints, and related over-the-counter products. Many of these practices are merely short term attempts at masking the odour. Some authors have suggested that there is an evolutionary basis to concern over bad breath. An instinctive aversion to unpleasant odours may function to detect spoiled food sources and other potentially invective or harmful substances. Body odours in general are thought to play an important role in mate selection in humans, and unpleasant odour may signal disease, and hence a potentially unwise choice of mate. Although reports of bad breath are found in the earliest medical writings known, the social stigma has likely changed over time, possibly partly due to sociocultural factors involving advertising pressures. As a result, the negative psychosocial aspects of halitosis may have worsened, and psychiatric conditions such as halitophobia are probably more common than historically. There have been rare reports of people committing suicide because of halitosis, whether there is genuine halitosis or not. Etymology The word halitosis is derived from the Latin word halitus, meaning breath, and the Greek suffix -osis meaning diseased or a condition of. With modern consumerism, there has been a complex interplay of advertising pressures and the existing evolutionary aversion to malodour. Contrary to the popular belief that Listerine coined the term halitosis, its origins date to before the products existence, being coined by physician Joseph William Howe in his 1874 book The Breath, and the Diseases Which Give It a Fetid Odor, although it only became commonly used in the 1920s when a marketing campaign promoted Listerine as a solution for "chronic halitosis". The company was the first to manufacture mouth washes in the United States. According to Freakonomics: Listerine "...was invented in the nineteenth century as powerful surgical antiseptic. It was later sold, in distilled form, as both a floor cleaner and a cure for gonorrhea. But it wasnt a runaway success until the 1920s, when it was pitched as a solution for "chronic halitosis"— a then obscure medical term for bad breath. Listerines new ads featured forlorn young women and men, eager for marriage but turned off by their mates rotten breath. "Can I be happy with him in spite of that?" one maiden asked herself. Until that time, bad breath was not conventionally considered such a catastrophe, but Listerine changed that. As the advertising scholar James B. Twitchell writes, "Listerine did not make mouthwash as much as it made halitosis." In just seven years, the companys revenues rose from $115,000 to more than $8 million." Alternative medicine According to traditional Ayurvedic medicine, chewing areca nut and betel leaf is a remedy for bad breath. In South Asia, it was a custom to chew areca or betel nut and betel leaf among lovers because of the breath-freshening and stimulant drug properties of the mixture. Both the nut and the leaf are mild stimulants and can be addictive with repeated use. The betel nut will also cause dental decay and red or black staining of teeth when chewed. Both areca nut and betel leaf chewing, however, can cause premalignant lesions such as leukoplakia and submucous fibrosis, and are recognized risk factors for oral and oropharyngeal squamous cell carcinoma (oral cancer).Practitioners and purveyors of alternative medicine sell a vast range of products that claim to be beneficial in treating halitosis, including dietary supplements, vitamins, and oral probiotics. Halitosis is often claimed to be a symptom of "candida hypersensitivity syndrome" or related diseases, and is claimed to be treatable with antifungal medications or alternative medications to treat fungal infections. Research In 1996, the International Society for Breath Odor Research (ISBOR) was formed to promote multidisciplinary research on all aspects of breath odours. References == External links ==

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

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

Boniva may refer to: Boniva, a company acquired by software company SSA Global Technologies in August 2005 Ibandronic acid (marketed as Boniva), a potent bisphosphonate drug used in the prevention and treatment of osteoporosis

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

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

Radiation proctitis or radiation proctopathy is condition characterized by damage to the rectum after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctopathy may occur as acute inflammation called "acute radiation proctitis" (and the related radiation colitis) or with chronic changes characterized by radiation associated vascular ectasiae (RAVE) and chronic radiation proctopathy. Radiation proctitis most commonly occurs after pelvic radiation treatment for cancers such as cervical cancer, prostate cancer, bladder cancer, and rectal cancer. RAVE and chronic radiation proctopathy involves the lower intestine, primarily the sigmoid colon and the rectum, and was previously called chronic radiation proctitis, pelvic radiation disease and radiation enteropathy. Signs and symptoms Acute radiation proctopathy often causes pelvic pain, diarrhea, urgency, and the urge to defecate despite having an empty colon (tenesmus). Hematochezia and fecal incontinence may occur, but are less common. Chronic radiation damage to the rectum (>3 months) may cause rectal bleeding, incontinence, or a change in bowel habits secondary. Severe cases may lead to with strictures or fistulae formation. Chronic radiation proctopathy can present at a median time of 8-12 months following radiation therapy. Histopathology Acute radiation proctopathy occurs due to direct damage of the lining (epithelium) of the colon. Rectal biopsies of acute radiation proctopathy show superficial depletion of epithelial cells and acute inflammatory cells located in the lamina propria. By contrast, rectal biopsies of RAVE and chronic radiation proctopathy demonstrates ischemic endarteritis of the submucosal arterioles, submucosal fibrosis, and neovascularization. Diagnosis Where chronic radiation proctopathy or RAVE is suspected, a thorough evaluation of symptoms is essential. Evaluation should include an assessment of risk factors for alternate causes of proctitis, such as C. difficile colitis, NSAID use, and travel history. Symptoms such as diarrhea and painful defecation need to be systematically investigated and the underlying causes each carefully treated. Testing for parasitic infections (amebiasis, giardiasis) and sexually transmitted infections (Neisseria gonorrhoeae and herpes simplex virus) should be considered. The location of radiation treatment is important, as radiation directed at regions of the body other than the pelvis (eg brain, chest, etc) should not prompt consideration of radiation proctopathy.Endoscopy is the mainstay of diagnosis for radiation damage to the rectum, with either colonoscopy or flexible sigmoidoscopy. RAVE is usually recognized by the macroscopic appearances on endoscopy characterized by vascular ectasias. Mucosal biopsy may aid in ruling out alternate causes of proctitis, but is not routinely necessary and may increase the risk of fistulae development. Telangiectasias are characteristic and prone to bleeding. Additional endoscopic findings may include pallor (pale appearance), edema, and friability of the mucosa. Classification Radiation proctitis can occur a few weeks after treatment, or after several months or years: Acute radiation proctitis — symptoms occur in the first 3 months after therapy. These symptoms include diarrhea and the urgent need to defecate. Radiation associated vascular ectasias (RAVE) and Chronic radiation proctopathy — previously known as "chronic radiation proctitis" occur 3-6 months after the initial exposure. RAVE is characterized by rectal bleeding, chronic blood loss and anemia. Chronic radiation proctopathy is characterized by urgency, change in stool caliber and consistency and increased mucus. Severe cases may present with fistulas and strictures which are rare. Treatment Several methods have been studied in attempts to lessen the effects of radiation proctitis. Acute radiation proctitis usually resolves without treatment after several months. When treatment is necessary, symptoms often improve with hydration, anti-diarrheal agents, and discontinuation of radiation. Butyrate enemas may also be effective.In contrast, RAVE and chronic radiation proctopathy usually is not self-limited and often requires additional therapies. These include sucralfate, hyperbaric oxygen therapy, corticosteroids, metronidazole, argon plasma coagulation, radiofrequency ablation and formalin irrigation. The average number of treatment sessions with argon plasma coagulation to achieve control of bleeding ranges from 1 to 2.7 sessions.In rare cases that do not respond to medical therapy and endoscopic treatment, surgery may be required. Overall, less than 10 percent of individuals with radiation proctopathy require surgery. In addition, complications such as obstruction and fistulae may require surgery. Epidemiology Up to 30 percent of individuals who receive pelvic radiation therapy for cancer may develop radiation proctopathy. See also Radiation enteropathy References == External links ==

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I'm looking for a concise explanation of the medical term 'Erythema toxicum neonatorum.'

Erythema toxicum neonatorum is a common, non-threatening rash in newborns. It appears in 4-70% of newborns within the first week of life, and it typically improves within 1–2 weeks. It only occurs during the newborn period, but may appear slightly later in premature babies. The rash has a variable appearance. It typically includes blotchy red spots, often with overlying firm, yellow-white bumps or pus-filled boils. There may be only a few or many lesions. The lesions can appear almost anywhere on the body, and individual lesions may appear and disappear within hours. There are no other symptoms associated with erythema toxicum neonatorum, and the rash does not have any long-term effects on the skin. Erythema toxicum neonatorum is not harmful and does not require any treatment. Epidemiology The exact prevalence of erythema toxicum neonatorum is unknown, and studies estimate prevalence as low as 3.7 percent to as high as 72 percent. It is one of the most commonly diagnosed rashes in healthy babies. It is more common among infants born at higher gestational age and is rare among premature infants. Erythema toxicum neonatorum is more likely to develop in infants delivered vaginally. Higher birth weight is an additional risk factor. There may be a slightly increased risk in males, but this association is unclear. There are no known associations with race or ethnicity. Presentation Erythema toxicum neonatorum usually appears during the first week of life, most often on day two. It may develop several days or weeks later in premature babies.The rash has a variable appearance, ranging from a few blotchy red spots to many yellow-white bumps and boils. The classic presentation is 1–3 mm, firm, yellow-white bumps with a surrounding red halo. The rash is often described as "flea-bitten." There may be only a few or many lesions, and they may be clustered or widespread. The rash often appears on the cheeks first and may later spread throughout the face, trunk, arms, and legs. Lesions most often appear on the thighs, buttocks, and trunk. The palms and soles are not affected, likely because the skin in these areas does not have hair follicles.Individual lesions may grow and shrink over hours or days. They usually fade within a week or two. The rash may recur within the next few weeks, but this is rare. Cause Erythema toxicum neonatorum is related to activation of the immune system, but its exact cause is unknown. Many inflammatory factors have been detected in erythema toxicum neonatorum lesions, including IL-1alpha, IL-1beta, IL-8, and eotaxin. These molecules cause redness and swelling in the skin and attract immune cells.Eosinophils and other immune cells are found in the upper layer of the skin in erythema toxicum neonatorum lesions. Immune cells tend to cluster around hair follicles in particular. The leading hypothesis about the cause of erythema toxicum neonatorum is that bacteria activate the immune system when they enter hair follicles for the first time. This is part of a normal process in which bacteria from the environment start to grow on a babys skin. It is unknown whether the immune response that causes erythema toxicum neonatorum is helpful to the baby. Recent research indicates an association with Demodex mites infestation (demodicosis). Diagnosis Health professionals can diagnose erythema toxicum neonatorum with a skin exam. Most cases of erythema toxicum neonatorum can be diagnosed without further testing. If more testing is needed to make a diagnosis, the contents of a lesion can be examined under a microscope. A health professional may make a small cut into a pus-filled lesion and collect a swab of pus for testing. Lesions caused by erythema toxicum neonatorum contain eosinophils and other immune cells. These cells can be seen under a microscope when a special stain is applied to the sample.Since the appearance of erythema toxicum neonatorum varies, it may be confused with other newborn rashes. Some newborn infections cause bumps or boils, which may look like erythema toxicum neonatorum. Bacterial infections, including Staphylococcus and Streptococcus infections, almost always cause additional symptoms. These symptoms may be severe, and they are usually not limited to rash. Bacterial rashes can be diagnosed by testing pus from a lesion along with a blood sample. Bacteria can be seen under a microscope with a special stain or may be found on a culture. Fungal infection with Candida may also cause a similar rash in newborns, but it usually causes additional symptoms like thrush. Similarly, fungus can be seen under a microscope or found on a culture. Some viral infections may cause a rash with boils on a reddish base. Rashes caused by herpes simplex virus and varicella zoster virus in particular may be confused with erythema toxicum neonatorum. These viruses are diagnosed by scraping the base of a lesion. Multinucleated giant cells can be seen under a microscope. Some of these tests may be ordered if the diagnosis is unclear. Treatment Erythema toxicum neonatorum resolves without treatment, typically within one or two weeks. There are no associated systemic symptoms or long-term consequences of the rash. History The rash of erythema toxicum neonatorum has been described by doctors for centuries. Ancient Mesopotamians believed that it represented a cleansing mechanism against the mothers blood. Later physicians believed that it was caused by the skins response to meconium. The name erythema toxicum neonatorum was first used by Dr. Karl Leiner in 1912 because he believed that the rash was caused by enterotoxins. Although Leiners hypothesis was incorrect and the rash is not actually caused by toxins, the medical community continues to call the rash erythema toxicum neonatorum. References == External links ==

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Can you demystify the medical term 'Blastic plasmacytoid dendritic cell neoplasm' for me?

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy. It was initially regarded as a form of lymphocyte-derived cutaneous lymphoma and alternatively named CD4+CD56+ hematodermic tumor, blastic NK cell lymphoma, and agranular CD4+ NK cell leukemia. Later, however, the disease was determined to be a malignancy of plasmacytoid dendritic cells rather than lymphocytes and therefore termed blastic plasmacytoid dendritic cell neoplasm. In 2016, the World Health Organization designated BPDCN to be in its own separate category within the myeloid class of neoplasms. It is estimated that BPDCN constitutes 0.44% of all hematological malignancies.Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy with features of cutaneous lymphoma (e.g. malignant plasmacytoid dendritic cell infiltrations into the skin to form single or multiple lesions) and/or leukemia (i.e. malignant plasmacytoid dendritic cells in blood and bone marrow). While commonly presenting with these clinical features, BPDCN, particularly in its more advanced stages, may also involve malignant plasmacytoid dendritic cell infiltrations in and thereby injury to the liver, spleen, lymph nodes, central nervous system, or other tissues. The neoplasm occurs in individuals of all ages but predominates in the elderly; in children, it afflicts males and females equally but in adults is far more common (~75% of cases) in males.Blastic plasmacytoid dendritic cell neoplasm typically responds to chemotherapy regimens used to treat hematological malignancies. All too often, however, the disease rapidly recurs and does so in a more drug-resistant form. Furthermore, the disease may occur in association with the myelodysplastic syndrome or transform to acute myeloid leukemia. Consequently, BPDCN has a very low 5 year survival rate. Current translational research studies on treating BPDCN have therefore focused on non-chemotherapeutic regimens that target the molecular pathways which may promote the disease. Presentation Blastic plasmacytoid dendritic cell neoplasm occurs in children, including neonates, but is more common in adults, particularly those between the ages 60–80. BPDCN usually (i.e. 61% to 90% of cases) presents with skin lesions, i.e. nodules, tumors, red or purple papules, bruise-like patches, and/or ulcers that most often occur on the head, face, and upper torso. The lesions are due to diffuse infiltrations of the skin by malignant pDC. In one large study, this presentation was accompanied by swollen lymph nodes, usually in the neck, due to malignant pDC infiltrations (~50% of cases); enlarged liver (~16% of cases) and/or spleen (26% of cases), also due to malignant pDC infiltrations; increased levels of malignant pDC in blood (i.e. >2% of nucleated cells) (~40% of cases), bone marrow (~65% of cases) and cerebrospinal fluid (47% of childhood cases but less often detected in adult cases). More advanced or severe cases may present with extreme organ and/or lymph node enlargements, skin lesions in virtually any site, and clinical evidence of malignant pDC infiltrations in the breasts, eyes, kidneys, lungs, gastrointestinal tract, bone, sinuses, ears, or testes. About 10% of individuals with BPDCN present with a leukemia-like disease, i.e. they exhibit circulating malignant pDC, anemia, thrombocytopenia, and/or leukopenia due to extensive malignant pDC infiltrations in the bone marrow. A leukemic phase of the disease is a common feature of end stage and post-therapy relapsing BPDCN. Pathophysiology There are three types of dendritic cells, plasmacytic dendritic cells (pDC) and two types of conventional dendritic cells (cDC), myeloid cDC1 and myeloid cDC2. pDC circulate in the blood, representing <0.4% of all nucleated blood cells, and are present in various hematological tissues such as lymph nodes and spleen. Their major function is to detect and then initiate immune responses to intracellular pathogens, particularly viruses such as the cold sore-causing Herpes simplex viruses, HIV, and hepatitis viruses but also bacteria such as the tuberculosis-causing Mycobacterium tuberculosis, fungi such as the aspergillosis-causing Aspergillus fumigatus and parasites such as malaria-causing Plasmodium falciparum. Following detection of these intracellular pathogens, pCD initiate immune responses by producing massive amounts of type I and type III interferons as well as by differentiating (i.e. maturing) into conventional dendritic cells that further promote immune responses by, e.g. functioning as antigen-presenting cells. The malignant pDC in BPDCN have the appearance of immature plasmacytoid dendritic cells. They are distinguished from other dendritic, myeloid, lymphoid and NK cell types by exhibiting at least several of the following properties: 1) plasmacytoid morphology; 2) production of large amounts of type I interferons when properly stimulated; 3) ability to differentiate into conventional dendritic cells when properly stimulated; 4) the expression of key marker proteins such as granzyme B, TCF4, interleukin-3 receptor (i.e. CD123), CLEC4C, and Neuropilin, and 5) failure to express certain marker proteins that are commonly expressed by myeloid, lymphoid, and NK cell lineages.Blastic plasmacytoid dendritic cell neoplasm typically arises after the serial acquisition of multiple genetic abnormalities in pDC or their precursor cells. Inactivating mutations (i.e. mutations which cause the gene to make no or a less active product) in the TET2 gene are the most common genetic abnormality in the disease, occurring in 32–67% of all BPDCN cases and often accompanied by mutations in either the NPM1 or SRSF2 gene. Numerous other genetic abnormalities are associated with the disease: 1) mutations in NRAS, ASXL1, and TP53; 2) deletions of the CDKN2A-ARF-CDKN2B locus on the short arm of chromosome 9, CDKN1B locus on the short arm of chromosome 12, RB1 locus on the long arm of chromosome 13, or NRC1 locus on the long arm of chromosome 5; 3) fusions of KMT2A on the long arm of chromosome 11 with MLLT1 on the short arm of chromosome 10, SUPT3H on the short arm of chromosome with MYC on the long arm of chromosome 8, or KMT2A on the long arm of chromosome 11 with MLLT1 on the long arm of chromosome 19; and 4) duplication or loss of entire chromosomes, particularly chromosomes 9, 13, or 15. Laboratory studies indicate that malignant pDC have a pathologically overactive NF-κB pathway that promotes their survival and production of various cytokines) that stimulate their own proliferation. Presumably, these genetic abnormalities lead to the activation of the NF-κB pathway and/or other cellular activation pathways which promote the survival, proliferation, and/or other malignant phenotypic traits in pDC and thereby cause BPDCN. Diagnosis BPDCN is suggested by a biopsy of skin lesions which reveals the infiltration by medium-sized blast (i.e. immature) cells into the dermis while sparing the epidermis. These cells exhibit irregular nuclei, fine chromatin, and at least one small nucleolus. Such blast cells may also be observed in the circulation, bone marrow, or other tissues and suggest BPDCN. However, the diagnosis of this disease requires determination that these cells are pDC blast cells rather than AML, T-cell lymphoblastic lymphoma (TCLL), or aggressive NK-cell leukemia (NKL) blast cells. Various studies have offered similar but not identical criteria to make this determination. All studies agree that pDC should have a typical plasmacytoid morphology and express a particular profile of marker proteins as detected by immunoassay and/or flow cytometry. However, the studies disagree on which marker proteins to profile. One studys profile assayed 1) CD4, CD56, CD123 (i.e. Interleukin-3 receptor, and TLC1, which are expressed on 80–100% of pDC but uncommon on AML, TCLL, or NKL blasts); 2) CD2AP and CLEC4C which are unique to pDC; and 3) myeloperoxidase, lysozyme, CD34, CD14, CD11c, and CD163 which are unique to AML, TCLL, or NKL blasts. Two other studies recommended assaying somewhat different sets of marker proteins. Treatment There have been no controlled studies to define the optimal treatment for BPDCN. Studies on small numbers of individuals with the disease have found that the standard chemotherapy regimens used for the initial induction treatments of AML, acute lymphoblastic leukemia, and high-grade lymphoma give complete remission rates of 77%, 93%, and 80%, respectively, in childhood PBDN and 47%, 77%, and 53%, respectively, in adult PBDN. However, these remissions were short-lived: post-treatment mean times to relapse or death were 12 months for children and 6.8 months for adults. Given these poor remission and survival rates, other treatments have been added to the initial treatment regimens. Studies have shown that the addition of intrathecally administered drugs (administered directly into the spinal canal) as prophylaxis prolongs the period of CNS-free disease and increases overall survival. Hematopoietic stem cell transplantation following initial chemotherapy-induced remission also prolongs these remissions and, it is suggested, offers potential for curing the disease. (A graft-versus-leukemia effect may have contributed to the benefits seen after transplantation.) Studies have not yet determined whether allogenic (i.e. taken from others) or autologous (i.e. taken from self) stem cells achieve better results, although one retrospective study in Japan found that autologous stem cells gave significantly better overall and progression-free survival rates. A phase I clinical research study to test the safety and efficacy of a combination chemotherapy regimen consisting of methotrexate, L-asparaginase, idarubicin, and dexamethasone followed by allogenic or autologous bone marrow transplantation in 26 participants newly diagnosed with BPDCN is planned but not yet in its recruiting phase.While few studies have reported on the treatment of BPDCN that has recurred following initial therapy, donor lymphocyte infusions coupled with alternative chemotherapy treatments have induced second complete or partial remissions in a few patients. Tagraxofusp-erzs Tagraxofusp-erzs (trade name Elzonris; formerly SL-401 and DT388-IL3) was approved in the United States in December 2018 for the treatment of BPDCN. Tagraxofusp-erzs is a fusion protein consisting of interleukin 3 (i.e. IL-3) fused to diphtheria toxin. The fusion protein readily kills cultured pDC by binding to their IL-3 receptors to thereby gain entrance to the cells and then blocking these cells protein synthesis (due to diphtheria toxin-mediated inhibition of eukaryotic elongation factor 2). Prognosis Due to the high rates of recurrence following initial therapy and the short overall survival times of individuals with BPDCN, prognosis of the disease is poor. However, further study of treatment regimens that include intrathecal chemotherapy and hematological stem cell transplantation in initial treatment regimens (see previous section) and newer non-chemotherapeutic drug treatments (see next section) may improve this situation. Research UCART123 UCART123 are chimeric T cell receptor-bearing cells, i.e. T lymphocytes engineered to bear a monoclonal antibody that directs them to attack and kill BPDCN cells. The intravenous infusion of these cells in patients with BPDCN is in phase 1 clinical trials but in September 2017, the Federal Drug Administration suspended these because one patient developed a Grade 5 (i.e. lethal) cytokine release syndrome (see UCART123#CAR-T cancer treatment). The suspension was lifted in November 2017 after the trial used reduced amounts of the cells and with additional conditions were applied. A new phase 1 clinical trial is now recruiting 76 new patients to study the safety and efficacy of UCAR123 in treating BPDCN. The study began in June 2017 and is scheduled to end in December 2021. Venetoclax BCL-2 is a cellular protein that can act to inhibit cell death due to apoptosis. The BCL-2 gene appears to be one of the most up-regulated (i.e. overactive) genes in BPDCN. Venetoclax inhibits the apoptosis-inhibiting action of BCL-2 and proved active in treating two patients with relapsed or refractory BPDCN. A phase I clinical trial testing the safety and efficacy of the drug in BPDCN is planned but not yet in its recruiting phase. == References ==

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Small fiber peripheral neuropathy'?

Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, peripheral nerves, and organs. The role of these nerves is to innervate the skin (somatic fibers) and help control autonomic function (autonomic fibers). It is estimated that 15–20 million people in the United States have some form of peripheral neuropathy. Signs and symptoms Small fiber neuropathy is a condition characterized by severe pain. Symptoms typically begin in the feet or hands but can start in other parts of the body. Some people initially experience a more generalized, whole-body pain. The pain is often described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy can occur at any point in life depending on the underlying cause. Individuals with small fiber neuropathy often cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (allodynia). People affected with this condition may also have a reduced ability to differentiate between hot and cold. Sudomotor dysfunction is one of the most common and earliest neurophysiological manifestations of small fiber neuropathies.In some instances, the small fibers of the autonomic nervous system can be affected, leading to urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. Insensitivity to pain can be particularly problematic. One may be bleeding or have a skin injury without even knowing it. Topographic pattern Like many polyneuropathies, the symptoms are typically length-dependent, starting in the longer nerves and progressively attacking shorter nerves. This means that symptoms often start in the hands and feet before progressing upwards, and that symptoms are usually more severe in the extremities. Some patients have a widespread, non-length dependent, or "patchy", presentation which is sporadic and can affect many nerves. Patients with Fabry disease have isolated small fiber engagement, and can have a more widespread small fiber disruption. Causes Mutations in the SCN9A or SCN10A gene can cause small fiber neuropathy. These genes provide instructions for making pieces (the alpha subunits) of sodium channels. The SCN9A gene instructs the production of the alpha subunit for the NaV1.7 sodium channel and the SCN10A gene instructs the production of the alpha subunit for the NaV1.8 sodium channel. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cells ability to generate and transmit electrical signals. The NaV1.7 and NaV1.8 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The SCN9A gene mutations that cause small fiber neuropathy result in NaV1.7 sodium channels that do not close completely when the channel is turned off. Many SCN10A gene mutations result in NaV1.8 sodium channels that open more easily than usual. The altered channels allow sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, causing individuals to be more sensitive to stimulation that might otherwise not cause pain. In this condition, the small fibers that extend from the nociceptors through which pain signals are transmitted (axons) degenerate over time. The cause of this degeneration is unknown, but it likely accounts for signs and symptoms such as the loss of temperature differentiation and pinprick sensation. The combination of increased pain signaling and degeneration of pain-transmitting fibers leads to a variable condition with signs and symptoms that can change over time. SCN9A gene mutations have been found in approximately 30 percent of individuals with small fiber neuropathy; SCN10A gene mutations are responsible for about 5 percent of cases. In some instances, other health conditions cause this disorder. Diabetes mellitus and impaired glucose tolerance are the most common diseases that lead to this disorder, with 6 to 50 percent of diabetics or pre-diabetics developing small fiber neuropathy. Other causes of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection.Recently several studies have suggested an association between autonomic small fiber neuropathy and postural orthostatic tachycardia syndrome. Other notable studies have shown a link between erythromelalgia, fibromyalgia, and Ehlers–Danlos Syndrome. Diagnosis The diagnosis of small fiber neuropathy often requires ancillary testing. Nerve conduction studies and electromyography are commonly used to evaluate large myelinated sensory and motor nerve fibers, but are ineffective in diagnosing small fiber neuropathies.Quantitative sensory testing (QST) assesses small fiber function by measuring temperature and vibratory sensation. Abnormal QST results can be attributed to dysfunction in the central nervous system. Furthermore, QST is limited by a patients subjective experience of pain sensation. Electrochemical skin conductance and quantitative sudomotor axon reflex testing (QSART) measures sweating response at local body sites to evaluate the small nerve fibers that innervate sweat glands.Electrochemical skin conductance has been evaluated for both early diagnosis of small fiber neuropathy and follow-up of treatment efficacy. Skin biopsy A skin biopsy for the measurement of epidermal nerve fiber density is an increasingly common technique for the diagnosis of small fiber peripheral neuropathy. Physicians can biopsy the skin with a 3-mm circular punch tool and immediately fix the specimen in 2% paraformaldehyde lysine-periodate or Zambonis fixative. Specimens are sent to a specialized laboratory for processing and analysis where the small nerve fibers are quantified by a neuropathologist to obtain a diagnostic result.This skin punch biopsy measurement technique is called intraepidermal nerve fiber density (IENFD). The following table describes the IENFD values in males and females of a 3 mm biopsy 10 cm above the lateral malleolus (above ankle outer side of leg). Any value measured below the 0.05 Quantile IENFD values per age span, is considered a reliable positive diagnosis for small fiber peripheral neuropathy. Treatment Treatment is based on the underlying cause, if any. Where the likely underlying condition is known, treatment of this condition is indicated to reduce progression of the disease and symptoms. For cases without those conditions, there is only symptomatic treatment. See also Neuropathy Polyneuropathy Wartenbergs migratory sensory neuropathy Burning feet syndrome Electrochemical skin conductance References External links Peripheral Neuropathy Fact Sheet – NINDS [1]

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

Glycosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reabsorb all of the filtered glucose from the tubular fluid back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to untreated diabetes mellitus. Rarely, glycosuria is due to an intrinsic problem with glucose reabsorption within the kidneys (such as Fanconi syndrome), producing a condition termed renal glycosuria. Glycosuria leads to excessive water loss into the urine with resultant dehydration, a process called osmotic diuresis. Alimentary glycosuria is a temporary condition, when a high amount of carbohydrate is taken, it is rapidly absorbed in some cases where a part of the stomach is surgically removed, the excessive glucose appears in urine producing glycosuria. Follow-up In a patient with glucosuria, diabetes is confirmed by measuring fasting or random plasma glucose and glycated hemoglobin(HbA1c). Pathophysiology Blood is filtered by millions of nephrons, the functional units that comprise the kidneys. In each nephron, blood flows from the arteriole into the glomerulus, a tuft of leaky capillaries. The Bowmans capsule surrounds each glomerulus, and collects the filtrate that the glomerulus forms. The filtrate contains waste products (e.g. urea), electrolytes (e.g. sodium, potassium, chloride), amino acids, and glucose. The filtrate passes into the renal tubules of the kidney. In the first part of the renal tubule, the proximal tubule, glucose is reabsorbed from the filtrate, across the tubular epithelium and into the bloodstream. The proximal tubule can only reabsorb a limited amount of glucose (~375 mg/min), known as the transport maximum. When the blood glucose level exceeds about 160–180 mg/dL (8.9-10 mmol/L), the proximal tubule becomes overwhelmed and begins to excrete glucose in the urine. This point is called the renal threshold for glucose (RTG). Some people, especially children and pregnant women, may have a low RTG (less than ~7 mmol/L glucose in blood to have glucosuria). If the RTG is so low that even normal blood glucose levels produce the condition, it is referred to as renal glycosuria. Glucose in urine can be identified by Benedicts qualitative test. If yeast is present in the bladder, the sugar in the urine may begin to ferment, producing a rare condition known as urinary auto-brewery 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.

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

Gnathostomiasis (also known as larva migrans profundus: 436 ) is the human infection caused by the nematode (roundworm) Gnathostoma spinigerum and/or Gnathostoma hispidum, which infects vertebrates. Symptoms and signs A few days after ingestion epigastric pain, fever, vomiting, and loss of appetite resulting from migration of larvae through intestinal wall to the abdominal cavity will appear in the patient. Migration in the subcutaneous tissues (under the skin) causes intermittent, migratory, painful, pruritic swellings (cutaneous larva migrans). Patches of edema appear after the above symptoms clear and are usually found on the abdomen. These lesions vary in size and can be accompanied by pruritus (itchy anus), rash, and stabbing pain. Swellings may last for 1 to 4 weeks in a given area and then reappear in a different location. Migration to other tissues (visceral larva migrans), can result in cough, hematuria (blood in urine), ocular (eye) involvement, meningitis, encephalitis and eosinophilia. Eosinophilic myeloencephalitis may also result from invasion of the central nervous system by the larvae. Causes Human gnathostomiasis is infection by the migrating third-stage larvae of any of five species of Gnathostoma, which is type of worm (more specifically a type of nematode). The most common cause in Asia is G. spinigerum, and the most common cause in the Americas is G. binucleatum. G. hispidium and G. doloresi occur in East and Southeast Asia; the former has also been found in Eastern Europe. G. nipponicum occurs only in Japan and China. There is one unconfirmed report of G. malaysiae causing disease in humans. Transmission Gnathostomiasis is transmitted by the ingestion of raw or insufficiently cooked definitive hosts such as fresh water fish, poultry, or frogs.In Thailand and Vietnam, the most common cause appears to be consumption of undercooked Asian swamp eels (Monopterus albus, also called Fluta alba) which transmit G. spinigerum. Monopterus albus is an invasive species in North America, but no Gnathostoma infections in humans have yet been conclusively identified in the US. Hosts Intermediate host The primary intermediate host is the minute crustaceans of the genus Cyclops. These crustaceans are then ingested by a second intermediate host, such as frogs. Definitive host The definitive hosts for gnathostomiasis include cats, dogs, tigers, leopards, lions, mink, opossums, raccoons, poultry, frogs, freshwater fish, snakes or birds. Incubation period The incubation period for gnathostomiasis is 3–4 weeks when the larvae begin to migrate through the subcutaneous tissue of the body. Morphology The adult parasite is reddish-brown in color and has a globular cephalic dome that is separated from the rest of the body by constriction. The posterior portion of the nematode is smooth while the anterior half is covered with fine leaf-like spines. The head is round and contains 4 to 8 transverse rows of hooklets that are protected by a pair of fleshy lips . The males are shorter than the females, 11–25 mm (0.43–0.98 in) compared to 25–54 mm (0.98–2.13 in) respectively. Eggs are oval and have a mucoid plug at one end. Life cycle Life cycle in definitive hosts Adult worms are found in a tumor located in the gastric wall of the definitive hosts and release eggs into the hosts digestive tract. The eggs are then released with feces and in about a week hatch in water to develop into first stage larva. Larvae are then ingested by minute copepods of the genus Cyclops. Once entering the copepod, the larvae penetrate the gastric wall of their intermediate host and begin to develop into second-stage and even early third-stage larvae. The copepods are then ingested by a second intermediate host such as fish, frogs, or snakes. Within this second intermediate or definitive host the larva repeat a similar pattern of penetrating the gastric wall, but then continue to migrate to muscular tissue and develop into advanced third-stage larvae. These larvae then encyst within the musculature of the new host. If the cyst containing flesh of these hosts is ingested by a definitive host, such as dogs, and cats, the cysts are ingested and the larvae escape the cysts and penetrate the gastric wall. These released larvae travel to the connective tissue and muscle as observed before and after 4 weeks they return to the gastric wall as adults. Here they form a tumor and continue to mature into adults for the next 6–8 months. Worms mate and females begin to excrete fertilized eggs with feces 8–12 months after ingestion of cysts. They are passed out in the feces and eaten by another fish. Life cycle in humans Infection of humans by gnathostomiasis is accidental because humans are not one of the definitive hosts of the parasite and do not allow the parasite to complete its life cycle. Infection in humans follows ingestion of raw or insufficiently cooked infected intermediate hosts. The ingested third stage larva migrates from the gastric wall and its migration results in the symptoms associated with infection by gnathostomiasis. The third stage larvae dont return to the gastric wall preventing it from maturing into adult worms, leaving the life cycle incomplete. Instead the larvae continue to migrate unpredictably unable to develop into adults, so eggs are seldom found in diagnostic tests. This also means the number of worms present in humans is a reflection of the number of third stage larvae ingested. Diagnosis Diagnosis of gnathostomiasis is possible (with microscopy) after removal of the worm. The primary form of diagnosis of gnathostomiasis is the identification of larva in the tissue. Serological testing such as enzyme-linked immunosorbent assay (ELISA) or the Western blot are also reliable but may not be easily accessible in endemic areas.CT scanning or MRI can be used to help identify a soft tissue worm and when looking at CNS disease it can be used to reveal the presence of the worm. The presence of haemorrhagic tracks on gradient-echo T2-weighted MRI is characteristic and possibly diagnostic. Prevention The best strategies for preventing accidental infection of humans is to educate those living in endemic areas to only consume fully cooked meat. The inability of the parasite to complete its life cycle within humans means that transmission can easily be contained by adequate preparation of meat from intermediate hosts. This is especially useful because of the difficulty and lack of feasibility inherent in eliminating all intermediate hosts of gnathostomiasis. So instead, individuals in endemic areas should avoid eating raw and undercooked meat in endemic areas, but this may be difficult in these areas. The dish ceviche is native to Peru and a favorite of Mexico. It consists of onion, cubed fish, lime or lemon juice and Andean spices including salt and chili. The ingredients are mixed together and they are allowed to marinate several hours before being served at room temperature. Then in endemic areas in Southeast Asia there are traditional dishes associated with these areas that also include raw uncooked fish, such as koipla in Thailand, goi ca song in Vietnam, sashimi and sushi in Japan.Acknowledging these cultural traditions, individuals in these cultural can be educated on methods of adapting their food preparation activities in order to remove the larvae without greatly altering these traditional dishes. For instance, meat should be marinated in vinegar for six hours or in soy sauce for 12 hours in order to successfully kill the larvae. In areas with reliable electricity, meat can be frozen at -20 degrees Celsius for 3–5 days to achieve the same results of killing the larvae present. Treatment Surgical removal or treatment with albendazole or ivermectin is recommended. The most prescribed treatment for gnathostomiasis is surgical removal of the larvae but this is only effective when the worms are located in an accessible location. In addition to surgical excision, albendazole and ivermectin have been noted in their ability to eliminate the parasite. Albendazole is recommended to be administered at 400 mg daily for 21 days as an adjunct to surgical excision, while ivermectin is better tolerated as a single dose. Ivermectin can also serve as a replacement for those that cant handle albendazole 200 ug/kg p.o. as a single dose. However, ivermectin has been shown to be less effective than albendazole. Epidemiology Endemic areas include Asia, Mexico, India and parts of South Africa. Originally believed to be confined to Asia, in the 1970s gnathostomiasis was discovered in Mexico, and found in Australia in 2011. Even though it is endemic in areas of Southeast Asia and Latin America, it is an uncommon disease. However, researchers have noticed recently an increase in incidence. This disease is most common in both Thailand and Japan, but in Thailand it is responsible for most of the observed parasitic CNS infection. It has long been recognised in China, but reports have only recently appeared in the English literature. History The first case of Gnathostoma infection was identified by Sir Richard Owen when inspecting the stomach of a young tiger that had died at London Zoo from a ruptured aorta. However it was not until 1889 that the first human case was described by Levinson when he found the Gnathostoma larva in an infested Thai woman. The lifecycle of G. spinigerum was described by Svasti Daengsvang and Chalerm Prommas from Thailand in 1933 and 1936. This delay in identification of the parasite in humans is due to the fact that humans are not a definitive host for this parasite making infection from this parasite rare. Gnathostomiasis infection is rare because the parasite must be digested when it has reached its third larvae stage, providing only a short time frame in which the parasite is capable of infecting humans. It is uncommon for the larvae to penetrate the skin of individuals exposed to contaminated food or water without ingestion. See also List of parasites (human) List of migrating cutaneous conditions References External links Gnathostomiasis Archived 2013-02-15 at the Wayback Machine at CDC Gnathostomiasis at eMedicine

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

A sneeze (also known as sternutation) is a semi-autonomous, convulsive expulsion of air from the lungs through the nose and mouth, usually caused by foreign particles irritating the nasal mucosa. A sneeze expels air forcibly from the mouth and nose in an explosive, spasmodic involuntary action. This action allows for mucus to escape through the nasal cavity. Sneezing is possibly linked to sudden exposure to bright light, sudden change (fall) in temperature, breeze of cold air, a particularly full stomach, exposure to allergens, or viral infection. Because sneezes can spread disease through infectious aerosol droplets, it is recommended to cover ones mouth and nose with the forearm, the inside of the elbow, a tissue or a handkerchief while sneezing. In addition to covering the mouth, looking down is also recommended in order to change the direction of the droplets spread and avoid high concentration in the human breathing heights. The function of sneezing is to expel mucus containing foreign particles or irritants and cleanse the nasal cavity. During a sneeze, the soft palate and palatine uvula depress while the back of the tongue elevates to partially close the passage to the mouth, creating a venturi (similar to a carburetor) due to Bernoullis principle so that air ejected from the lungs is accelerated through the mouth and thus creating a low pressure point at the back of the nose. This way air is forced in through the front of the nose and the expelled mucus and contaminants are launched out the mouth. Sneezing with the mouth closed does expel mucus through the nose but is not recommended because it creates a very high pressure in the head and is potentially harmful. Sneezing cannot occur during sleep due to REM atonia – a bodily state where motor neurons are not stimulated and reflex signals are not relayed to the brain. Sufficient external stimulants, however, may cause a person to wake from sleep to sneeze, but any sneezing occurring afterwards would take place with a partially awake status at minimum. Description Sneezing typically occurs when foreign particles or sufficient external stimulants pass through the nasal hairs to reach the nasal mucosa. This triggers the release of histamines, which irritate the nerve cells in the nose, resulting in signals being sent to the brain to initiate the sneeze through the trigeminal nerve network. The brain then relates this initial signal, activates the pharyngeal and tracheal muscles and creates a large opening of the nasal and oral cavities, resulting in a powerful release of air and bioparticles. The powerful nature of a sneeze is attributed to its involvement of numerous organs of the upper body – it is a reflexive response involving the face, throat, and chest muscles. Sneezing is also triggered by sinus nerve stimulation caused by nasal congestion and allergies. The neural regions involved in the sneeze reflex are located in the brainstem along the ventromedial part of the spinal trigeminal nucleus and the adjacent pontine-medullary lateral reticular formation. This region appears to control the epipharyngeal, intrinsic laryngeal and respiratory muscles, and the combined activity of these muscles serve as the basis for the generation of a sneeze.The sneeze reflex involves contraction of a number of different muscles and muscle groups throughout the body, typically including the eyelids. The common suggestion that it is impossible to sneeze with ones eyes open is, however, inaccurate. Other than irritating foreign particles, allergies or possible illness, another stimulus is sudden exposure to bright light – a condition known as photic sneeze reflex (PSR). Walking out of a dark building into sunshine may trigger PSR, or the ACHOO (autosomal dominant compulsive helio-ophthalmic outbursts of sneezing) syndrome as its also called. The tendency to sneeze upon exposure to bright light is an autosomal dominant trait and affects 18-35% of the human population. A rarer trigger, observed in some individuals, is the fullness of the stomach immediately after a large meal. This is known as snatiation and is regarded as a medical disorder passed along genetically as an autosomal dominant trait. Epidemiology While generally harmless in healthy individuals, sneezes spread disease through the infectious aerosol droplets, commonly ranging from 0.5 to 5 µm. A sneeze can produce 40,000 droplets. To reduce the possibility of thus spreading disease (such as the flu), one holds the forearm, the inside of the elbow, a tissue or a handkerchief in front of ones mouth and nose when sneezing. Using ones hand for that purpose has recently fallen into disuse as it is considered inappropriate, since it promotes spreading germs through human contact (such as handshaking) or by commonly touched objects (most notably doorknobs). Until recently, the maximum visible distance over which the sneeze plumes (or puffs) travel was observed at 0.6 metres (2.0 ft), and the maximum sneeze velocity derived was 4.5 m/s (about 10 mph). In 2020, sneezes were recorded generating plumes of up to 8 meters (26 ft). Prevention Proven methods to reduce sneezing generally advocate reducing interaction with irritants, such as keeping pets out of the house to avoid animal dander; ensuring the timely and continuous removal of dirt and dust particles through proper housekeeping; replacing filters for furnaces and air-handling units; air filtration devices and humidifiers; and staying away from industrial and agricultural zones. Tickling the roof of the mouth with the tongue can stop a sneeze. Some people, however, find sneezes to be pleasurable and would not want to prevent them.Holding in sneezes, such as by pinching the nose or holding ones breath, is not recommended as the air pressure places undue stress on the lungs and airways. One computer simulation suggests holding in a sneeze results in a burst of air pressure of 39 kPa, approximately 24 times that of a normal sneeze. History In Ancient Greece, sneezes were believed to be prophetic signs from the gods. In 401 BC, for instance, the Athenian general Xenophon gave a speech exhorting his fellow soldiers to fight against the Persians. A soldier underscored his conclusion with a sneeze. Thinking that this sneeze was a favorable sign from the gods, the soldiers were impressed. Another divine moment of sneezing for the Greeks occurs in the story of Odysseus. His waiting wife Penelope, hearing Odysseus may be alive, says that he and his son would take revenge on the suitors if he were to return. At that moment, their son sneezes loudly and Penelope laughs with joy, reassured that it is a sign from the gods (Odyssey 17: 541-550). It may be because this belief survived through the centuries, that in certain parts of Greece today, when someone is asserting something and the listener sneezes promptly at the end of the assertion, the former responds "bless you and I am speaking the truth", or "bless you and here is the truth" ("γεια σου κι αλήθεια λέω", ya sou ki alithia leo, or "γεια σου και να κι η αλήθεια", ya sou ke na ki i alithia). A similar practice is also followed in India. If either the person just having made a not most obvious statement in Flemish, or some listener sneezes, often one of the listeneners will say "It is beniesd", literally "Its sneezed upon", as if a proof of truth – usually self-ironically recalling this old superstitious habit, without either suggesting doubt or intending an actual confirmation, but making any apology by the sneezer for the interruption superfluous as the remark is received by smiles.In Europe, principally around the early Middle Ages, it was believed that ones life was in fact tied to ones breath – a belief reflected in the word "expire" (originally meaning "to exhale") gaining the additional meaning of "to come to an end" or "to die". This connection, coupled with the significant amount of breath expelled from the body during a sneeze, had likely led people to believe that sneezing could easily be fatal. Such a theory could explain the reasoning behind the traditional English phrase, "God bless you", in response to a sneeze, the origins of which are not entirely clear (see "Traditional Responses To A Sneeze" below for alternative explanations). Sir Raymond Henry Payne Crawfurd, for instance, the registrar of the Royal College of Physicians, in his 1909 book, "The Last Days of Charles II", states that, when the controversial monarch was on his deathbed, his medical attendants administered a concoction of cowslips and extract of ammonia to promote sneezing. However, it is not known if this promotion of sneezing was done to hasten his death (as coup de grâce) or as an ultimate attempt at treatment. In certain parts of Eastern Asia, particularly in Chinese culture, Korean culture, Japanese culture and Vietnamese culture, a sneeze without an obvious cause was generally perceived as a sign that someone was talking about the sneezer at that very moment. This can be seen in the Book of Songs (a collection of Chinese poems) in ancient China as early as 1000 BC, and in Japan this belief is still depicted in present-day manga and anime. In China, Vietnam, South Korea, and Japan, for instance, there is a superstition that if talking behind someones back causes the person being talked about to sneeze; as such, the sneezer can tell if something good is being said (one sneeze), someone is thinking about you (two sneezes in a row), even if someone is in love with you (three sneezes in a row) or if this is a sign that they are about to catch a cold (multiple sneezes).Parallel beliefs are known to exist around the world, particularly in contemporary Greek, Slavic, Celtic, English, French, and Indian cultures. Similarly, in Nepal, sneezers are believed to be remembered by someone at that particular moment.In English, the onomatopoeia for sneezes is usually spelled achoo and it is similar to that of different cultures. Culture In Indian culture, especially in northern parts of India, Bengali (Bangladesh and Bengal of India) culture and also in Iran, it has been a common superstition that a sneeze taking place before the start of any work was a sign of impending bad interruption. It was thus customary to pause in order to drink water or break any work rhythm before resuming the job at hand in order to prevent any misfortune from occurring. Contrarily, in Polish culture, especially in the Kresy Wschodnie borderlands, a popular belief persists that sneezes may be an inauspicious sign that, depending on the local version, either someone unspecified or ones mother-in-law speaks ill of the person sneezing at that moment. In other regions, however, this superstition concerns hiccups rather than sneezing. As with other Catholic countries, such as Mexico, Italy, or Ireland, the remnants of pagan culture are fostered in Polish peasant idiosyncratic superstitions. The practice among Islamic culture, in turn, has largely been based on various prophetic traditions and the teachings of the prophet Muhammad. An example of this is Al-Bukhaaris narrations from Abu Hurayrah that Muhammad once said: When one of you sneezes, let him say, "Al-hamdu-Lillah" (Praise be to God), and let his brother or companion say to him, "Yarhamuk Allah" (May God have mercy on you). If he says, "Yarhamuk-Allah", then let [the sneezer] say, "Yahdeekum Allah wa yuslihu baalakum" (May God guide you and rectify your condition). Verbal responses In English-speaking countries, one common verbal response to another persons sneeze is "[May God] bless you". Another less common verbal response in the United States and Canada to anothers sneeze is "Gesundheit", which is a German word that means, appropriately, "good health". Several hypotheses exist for why the custom arose of saying "bless you" or "God bless you" in the context of sneezing: Some say it came into use during the plague pandemics of the 14th century. Blessing the individual after showing such a symptom was thought to prevent possible impending death due to the lethal disease. In Renaissance times, a superstition was formed claiming ones heart stopped for a very brief moment during the sneeze; saying bless you was a sign of prayer that the heart would not fail. It has also been stated that one says "(God) bless you" so that one does not catch the flu, cold, or any other forms of sickness.Other cultures have similar traditions: In China, after a person sneezes they often say "百岁!" which translates to "may you live one hundred years!" the pronunciation is similar to "bless you" in English. pronunciation: [Bai Sui] In Iran, it is common to respond to sneezing with the Persian phrase عافیت باشه âfiyat bâše, which translates to "health", similar to common European expressions. Indian culture is to respond with Krishna, similar to a blessing in western cultures. In Italy after a person sneezes the people present respond with the word "salute" (meaning: health). The louder the sneeze the more emphatic the response. In Slovakia, after a person sneezes, it is proper to say "Na zdravie!" which means "For health!"; a proper response should be "Ďakujem" which means "Thanks". This is also the case in Finland where "terveydeksi" means "for health". Likewise in Russian or Ukrainian, "будь здоров" (bud zdorov), translates as "be healthy". In Tamil, a reciprocation to someones sneeze is "ஆயுசு நூறு" (aa-yu-su noo-ru) or "ஆயுள் நூறு" (aa-yul noo-ru) which, in direct translation, means "100 years-long life". It is a particularly endearing expression often used by elderly when a young child sneezes, wishing upon them good health, as a sort of blessing. Some may say "Dheergaiyish", meaning "may you live long", but that is more closely related to Sanskrit. In Turkey, after a person sneezes, it is proper to say "Çok yaşa" which means "Live long"; a proper response should be "Sen de gör" which means "May you see too [that I lived long enough]". In Telugu, a reciprocation to someones sneeze is "chiranjeeva sataish" (చిర౦జీవ) which means "may you live long" (from Sanskrit). In Japanese and Chinese entertainment, such as anime or dramas, a characters sneeze usually means that someone is talking about the character. In the Netherlands and Flanders, the usual verbal response is "Gezondheid!" which has the same meaning as the also occasionally used German word "Gesundheit!". This is usually met with a "Dankjewel" as a response, which means "Thank you". In Sweden, Norway and Denmark after a person sneezes, it is proper to say "Prosit", which has latin roots, and loosely translates to "Be well" or "May it do you good". Sexuality Some people may sneeze during the initial phases of sexual arousal. Doctors suspect that the phenomenon might arise from a case of crossed wires in the autonomic nervous system, which regulates a number of functions in the body, including "waking up" the genitals during sexual arousal. The nose, like the genitals, contains erectile tissue. This phenomenon may prepare the vomeronasal organ for increased detection of pheromones.A sneeze has been compared to an orgasm, since both orgasms and sneeze reflexes involve tingling, bodily stretching, tension and release. On this subject, sexologist Vanessa Thompson from the University of Sydney states, "Sneezing and orgasms both produce feel-good chemicals called endorphins but the amount produced by a sneeze is far less than an orgasm."According to Dr. Holly Boyer from the University of Minnesota, there is a pleasurable effect during a sneeze, where she states, "the muscle tension that builds up in your chest causes pressure, and when you sneeze and the muscles relax, it releases pressure. Anytime you release pressure, it feels good...Theres also some evidence that endorphins are released, which causes your body to feel good". Endorphins induce the brains reward system, and because sneezes occur in a quick burst, so does the pleasure. In non-humans Sneezing is not confined to humans or even mammals. Many animals including cats, dogs, chickens and iguanas sneeze. African wild dogs use sneezing as a form of communication, especially when considering a consensus in a pack on whether or not to hunt. Some breeds of dog are predisposed to reverse sneezing. See also Cough Rhinitis Seizure Snatiation Sniffle References Further reading External links The dictionary definition of sneeze at Wiktionary Media related to Sneezing at Wikimedia Commons

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 seeking clarification on the medical term 'Metamucil.' Could you explain it?

Metamucil is a fiber supplement. Introduced in 1934 by G. D. Searle & Company, Metamucil was acquired by Procter & Gamble in 1985. The name is a combination of the Greek word for change (meta) and the class of fiber that it utilizes (mucilage). In its early years, Metamucil achieved sporadic drug-store distribution as a "behind the counter" brand. Since 1974, the brand was also marketed to consumers by print and TV advertising and became available in food outlets. Flavored versions were added in 1979. Products The brand is sold as powdered drink mixes, capsules and wafers in a variety of flavors. Metamucil contains psyllium seed husks as the active ingredient. It is manufactured in Phoenix, Arizona, by Procter & Gamble. When first marketed to consumers in 1974, Metamucil was marketed as a laxative. The advertising slogan at that time was "If not nature, then Metamucil". Procter & Gamble sought to make Metamucil a household name by advertising in magazines and on television, using the claim "All fiber is not created equal".The target group was older people who are more likely to suffer from constipation. On October 4, 2013, Procter & Gamble partnered with Tony Danza to organize the “Do More Than You Think” contest to promote and fund health and wellness charities. The main prize was the chance to select the charity that would receive a $100,000 donation from Procter & Gamble. == References ==

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

Acephalgic migraine (also called migraine aura without headache, amigrainous migraine, isolated visual migraine, and optical migraine) is a neurological syndrome. It is a relatively uncommon variant of migraine in which the patient may experience some migraine symptoms such as aura, nausea, photophobia, and hemiparesis, but does not experience headache. It is generally classified as an event fulfilling the conditions of migraine with aura with no (or minimal) headache. It is sometimes distinguished from visual-only migraine aura without headache, also called ocular migraine. Symptoms and misdiagnosis Acephalgic migraines can occur in individuals of any age. Some individuals, more commonly male, only experience acephalgic migraine, but frequently patients also experience migraine with headache. Generally, the condition is more than twice as likely to occur in females than males. Pediatric acephalgic migraines are listed along with other childhood periodic syndromes by W.A. Al-Twaijri and M.I. Shevell as "migraine equivalents" (although not listed as such in the International Classification of Headache Disorders), which can be good predictors of the future development of typical migraines. Individuals who experience acephalgic migraines in childhood are highly likely to develop typical migraines as they grow older. Among women, incidents of acephalgic migraine increase during perimenopause.Scintillating scotoma is the most common symptom which usually happens concurrently with Expanding Fortification Spectra. Also frequently reported is monocular blindness. Acephalgic migraines typically do not persist more than a few hours and may last for as little as 15 seconds. On rare occasions, they may continue for up to two days.Acephalgic migraines may resemble transient ischemic attacks or, when longer in duration, stroke. The concurrence of other symptoms such as photophobia and nausea can help in determining the proper diagnosis. Occasionally, patients with acephalgic migraine are misdiagnosed as having epilepsy with visual seizures, but the reverse misdiagnosis is more common. Treatment The prevention and treatment of acephalgic migraine is broadly the same as for classical migraine, but the symptoms are usually less severe than those of classic migraine, so treatment is less likely to be required. See also ICHD classification and diagnosis of migraine == References ==

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

Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord, can cause the myelin and axon to be damaged resulting in symptoms such as paralysis and sensory loss. Myelitis is classified to several categories depending on the area or the cause of the lesion; however, any inflammatory attack on the spinal cord is often referred to as transverse myelitis. Types of myelitis Myelitis lesions usually occur in a narrow region but can be spread and affect many areas. Acute flaccid myelitis: a polio-like syndrome that causes muscle weakness and paralysis. Poliomyelitis: disease caused by viral infection in the gray matter with symptoms of muscle paralysis or weakness Transverse myelitis: caused by axonal demyelination encompassing both sides of the spinal cord Leukomyelitis: lesions in the white matter Meningococcal myelitis (or meningomyelitis): lesions occurring in the region of meninges and the spinal cordOsteomyelitis of the vertebral bone surrounding the spinal cord (that is, vertebral osteomyelitis) is a separate condition, although some infections (for example, Staphylococcus aureus infection) can occasionally cause both at once. The similarity of the words reflects that the combining form myel(o)- has multiple (homonymous) senses referring to bone marrow or the spinal cord. Symptoms Depending on the cause of the disease, such clinical conditions manifest different speed in progression of symptoms in a matter of hours to days. Most myelitis manifests fast progression in muscle weakness or paralysis starting with the legs and then arms with varying degrees of severity. Sometimes the dysfunction of arms or legs cause instability of posture and difficulty in walking or any movement. Also symptoms generally include paresthesia which is a sensation of tickling, tingling, burning, pricking, or numbness of a persons skin with no apparent long-term physical effect. Adult patients often report pain in the back, extremities, or abdomen. Patients also present increased urinary urgency, bowel or bladder dysfunctions such as bladder incontinence, difficulty or inability to void, and incomplete evacuation of bowel or constipation. Others also report fever, respiratory problems and intractable vomiting. Diseases associated with myelitis Conditions associated with myelitis include: Acute disseminated encephalomyelitis: autoimmune demyelination of the brain causing severe neurological signs and symptoms Multiple sclerosis: demyelination of the brain and spinal cord Neuromyelitis optica or Devics disease: immune attack on optic nerve and spinal cord Sjögrens syndrome: destruction of the exocrine system of the body Systemic lupus erythematosus: a systemic autoimmune disease featuring a wide variety of neurological signs and symptoms Sarcoidosis: chronic inflammatory cells form as nodules in multiple organs Atopy: an immune disorder of children manifesting as eczema or other allergic conditions. It can include atopic myelitis, which causes weakness. Immune-mediated myelopathies, heterogeneous group of inflammatory spinal cord disorders including autoimmune disorders with known antibodies Cause Myelitis occurs due to various reasons such as infections. Direct infection by viruses, bacteria, mold, or parasites such as human immunodeficiency virus (HIV), human T-lymphotropic virus types I and II (HTLV-I/II), syphilis, lyme disease, and tuberculosis can cause myelitis but it can also be caused due to non-infectious or inflammatory pathway. Myelitis often follows after the infections or after vaccination. These phenomena can be explained by a theory of autoimmune attack which states that the autoimmune bodies attack its spinal cord in response to immune reaction. Mechanism of myelitis The theory of autoimmune attack claims that a person with neuroimmunologic disorders have genetic predisposition to auto-immune disorder, and the environmental factors would trigger the disease. The specific genetics in myelitis is not completely understood. It is believed that the immune system response could be to viral, bacterial, fungal, or parasitic infection; however, it is not known why the immune system attacks itself. Especially, for the immune system to cause inflammatory response anywhere in the central nervous system, the cells from the immune system must pass through the blood brain barrier. In the case of myelitis, not only is the immune system dysfunctional, but the dysfunction also crosses this protective blood brain barrier to affect the spinal cord. Infectious myelitis Viral myelitisMost viral myelitis is acute, but the retroviruses (such as HIV and HTLV) can cause chronic myelitis. Poliomyelitis, or gray matter myelitis, is usually caused by infection of anterior horn of the spinal cord by the enteroviruses (polioviruses, enteroviruses (EV) 70 and 71, echoviruses, coxsackieviruses A and B) and the flaviviruses (West Nile, Japanese encephalitis, tick-borne encephalitis). On the other hand, transverse myelitis or leukomyelitis, or white matter myelitis, are often caused by the herpesviruses and influenza virus. It can be due to direct viral invasion or via immune mediated mechanisms. Bacterial myelitisBacterial myelitis includes Mycoplasma pneumoniae, which is a common agent for respiratory tract. Studies have shown respiratory tract infections within 4–39 days prior to the onset of transverse myelitis. Or, tuberculosis, syphilis, and brucellosis are also known to cause myelitis in immune-compromised individuals. Myelitis is a rare manifestation of bacterial infection. Fungal myelitisFungi have been reported to cause spinal cord disease either by forming abscesses inside the bone or by granuloma. In general, there are two groups of fungi that may infect the CNS and cause myelitis - primary and secondary pathogens. Primary pathogens include the following: Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitides, and Hystoplasma capsulatum. Secondary pathogens are opportunistic agents that primarily infect immunocompromised hosts such as Candida species, Aspergillus species, and zygomycetes. Parasitic myelitisParasitic species infect human hosts through larvae that penetrate the skin. Then they enter the lymphatic and circulatory system, and migrate to liver and lung. Some reach the spinal cord. Parasitic infections have been reported with Schistosoma species, Toxocara canis, Echinococcus species, Taenia solium, Trichinella spiralis, and Plasmodium species. Autoimmune myelitis In 2016, it was identified in Mayo clinic an autoimmune form of myelitis due to the presence of anti-GFAP autoantibodies. Immunoglobulins directed against the α-isoform of glial fibrillary acidic protein (GFAP-IgG) predicted a special meningoencephalomyelitis termed autoimmune GFAP Astrocytopathy that later was found also to be able to appear as a myelitis. Diagnosis Myelitis has an extensive differential diagnosis. The type of onset (acute versus subacute/chronic) along with associated symptoms such as the presence of pain, constitutional symptoms that encompass fever, malaise, weight loss or a cutaneous rash may help identify the cause of myelitis. In order to establish a diagnosis of myelitis, one has to localize the spinal cord level, and exclude cerebral and neuromuscular diseases. Also a detailed medical history, a careful neurologic examination, and imaging studies using magnetic resonance imaging (MRI) are needed. In respect to the cause of the process, further work-up would help identify the cause and guide treatment. Full spine MRI is warranted, especially with acute onset myelitis, to evaluate for structural lesions that may require surgical intervention, or disseminated disease. Adding gadolinium further increases diagnostic sensitivity. A brain MRI may be needed to identify the extent of central nervous system (CNS) involvement. Lumbar puncture is important for the diagnosis of acute myelitis when a tumoral process, inflammatory or infectious cause are suspected, or the MRI is normal or non-specific. Complementary blood tests are also of value in establishing a firm diagnosis. Rarely, a biopsy of a mass lesion may become necessary when the cause is uncertain. However, in 15–30% of people with subacute or chronic myelitis, a clear cause is never uncovered. Treatment Since each case is different, the following are possible treatments that patients might receive in the management of myelitis. Intravenous steroidsHigh-dose intravenous methyl-prednisolone for 3–5 days is considered as a standard of care for patients suspected to have acute myelitis, unless there are compelling reasons otherwise. The decision to offer continued steroids or add a new treatment is often based on the clinical course and MRI appearance at the end of five days of steroids. Plasma exchange (PLEX)Patients with moderate to aggressive forms of disease who do not show much improvement after being treated with intravenous and oral steroids will be treated with PLEX. Retrospective studies of patients with TM treated with IV steroids followed by PLEX showed a positive outcome. It also has been shown to be effective with other autoimmune or inflammatory central nervous system disorders. Particular benefit has been shown with patients who are in the acute or subacute stage of the myelitis showing active inflammation on MRI. However, because of the risks implied by the lumbar puncture procedure, this intervention is determined by the treating physician on a case-by-case basis. Immunosuppressants/Immunomodulatory agentsMyelitis with no definite cause seldom recurs, but for others, myelitis may be a manifestation of other diseases that are mentioned above. In these cases, ongoing treatment with medications that modulate or suppress the immune system may be necessary. Sometimes there is no specific treatment. Either way, aggressive rehabilitation and long-term symptom management are an integral part of the healthcare plan. Prospective research direction Central nervous system nerve regeneration would be able to repair or regenerate the damage caused to the spinal cord. It would restore functions lost due to the disease. Engineering endogenous repairCurrently, there exists a hydrogel based scaffold which acts as a channel to deliver nerve growth-enhancing substrates while providing structural support. These factors would promote nerve repairs to the target area. Hydrogels macroporous properties would enable attachment of cells and enhance ion and nutrient exchange. In addition, hydrogels biodegradability or bioresolvability would prevent the need for surgical removal of the hydrogel after drug delivery. It means that it would be dissolved naturally by the bodys enzymatic reaction. Biochemical repairNeurotropic factor therapy and gene therapy Neurotropic growth factors regulate growth, survival, and plasticity of the axon. They benefit nerve regeneration after injury to the nervous system. They are a potent initiator of sensory axon growth and are up-regulated at the lesion site. The continuous delivery of neurotropic growth factor (NGF) would increase the nerve regeneration in the spinal cord. However, the excessive dosing of NGF often leads to undesired plasticity and sprouting of uninjured sensory nerves. Gene therapy would be able to increase the NGF efficacy by the controlled and sustained delivery in a site-specific manner.Stem cell-based therapiesThe possibility for nerve regeneration after injury to the spinal cord was considered to be limited because of the absence of major neurogenesis. However, Joseph Altman showed that cell division does occur in the brain which allowed potential for stem cell therapy for nerve regeneration. The stem cell-based therapies are used in order to replace cells lost and injured due to inflammation, to modulate the immune system, and to enhance regeneration and remyelination of axons. Neural stem cells (NSC) have the potential to integrate with the spinal cord because in the recent past investigations have demonstrated their potential for differentiation into multiple cell types that are crucial to the spinal cord. Studies show that NSCs that were transplanted into a demyelinating spinal cord lesion were found to regenerate oligodendrocytes and Schwann cells, and completely remyelinated axons. See also Encephalomyelitis Myalgic encephalomyelitis – also known as chronic fatigue syndrome Transverse myelitis References == External links ==