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metiapine metiapine metiapine is a typical antipsychotic medication of the dibenzothiazepine group. there is scarce research on the safety and efficacy of metiapine in humans, though limited human trials exist. metiapineclinical datadrug classtypical antipsychoticidentifiers iupac name 8-methyl-6-(4-methylpiperazin-1-yl)benzobenzothiazepine cas number5800-19-1pubchem cid22047chemspider20718unii775d6d91j8keggd02672chemblchembl2106892comptox dashboard (epa)dtxsid7020891 chemical and physical dataformulac19h21n3smolar mass323.46 g·mol−13d model (jsmol)interactive image smiles cc1=cc2=c(c=c1)sc3=cc=cc=c3n=c2n4ccn(cc4)c inchi inchi=1s/c19h21n3s/c1-14-7-8-17-15(13-14)19(22-11-9-21(2)10-12-22)20-16-5-3-4-6-18(16)23-17/h3-8,13h,9-12h2,1-2h3key:ioepxyjohizygq-uhfffaoysa-n medical uses metiapine has been investigated for the treatment of schizophrenia. side effects like other typical antipsychotics, it has a high rate of extrapyramidal side effects. pharmacology metiapine has strong antidopaminergic effects and is classified as a typical (i.e., first-generation) antipsychotic. chemistry metiapine is a dibenzothiazepine derivative. like clothiapine, metiapine has a sulfur atom replacing the nitrogen atom found in dibenzapine derivative antipsychotics like clozapine. synthesis metiapine can be synthesized through the following mechanism: history metiapine was first discovered in the 1970s by marion merrell dow (now a part of sanofi). research a 2017 cochrane review provided guidance for a double-blind, randomized controlled trial of metiapine versus chlorpromazine for the treatment of schizophrenia, though the authors acknowledged that it is unlikely that any future trials will investigate the use of metiapine in humans. the available evidence for the use of metiapine is very limited.

agoraphobia agoraphobia agoraphobia is a mental and behavioral disorder, specifically an anxiety disorder characterized by symptoms of anxiety in situations where the person perceives their environment to be unsafe with no easy way to escape. these situations can include open spaces, public transit, shopping centers, crowds and queues, or simply being outside their home on their own. being in these situations may result in a panic attack. those affected will go to great lengths to avoid these situations. in severe cases, people may become completely unable to leave their homes. agoraphobiaan ancient agora in delos, greece—one of the public spaces after which the condition is named.pronunciation/ˌæɡərəˈfoʊbiəˌ əˌɡɔːrə-/ specialtypsychiatry, clinical psychologysymptomsanxiety in situations perceived to be unsafe, panic attackscomplicationsdepression, substance use disorderduration> 6 monthscausesgenetic and environmental factorsrisk factorsfamily history, stressful eventdifferential diagnosisseparation anxiety, post-traumatic stress disorder, major depressive disordertreatmentcognitive behavioral therapyprognosisresolution in half with treatmentfrequency1.9% of adults agoraphobia is believed to be due to a combination of genetic and environmental factors. the condition often runs in families, and stressful or traumatic events such as the death of a parent or being attacked may be a trigger. in the dsm-5 agoraphobia is classified as a phobia along with specific phobias and social phobia. other conditions that can produce similar symptoms include separation anxiety, post-traumatic stress disorder, and major depressive disorder. the diagnosis of agoraphobia has been shown to be comorbid with depression, substance abuse, and suicide ideation. without treatment it is uncommon for agoraphobia to resolve. treatment is typically with a type of counselling called cognitive behavioral therapy (cbt). cbt results in resolution for about half of people. in some instances, those with a diagnosis of agoraphobia have reported taking benzodiazepines and antipsychotics augmentation. agoraphobia affects about 1.7% of adults. women are affected about twice as often as men. the condition is rare in children, often begins in early adulthood, and becomes less common in old age. etymology the term "agoraphobia" was coined in german in 1871 by pioneering german psychologist karl friedrich otto westphal (1833–1890), in his article "die agoraphobie, eine neuropathische erscheinung." archiv für psychiatrie und nervenkrankheiten, berlin, 1871–72; 3: 138–161. it is derived from greek ἀγορά, agorā́, meaning a "place of assembly" or "market-place" and -φοβία, -phobía, meaning "fear". signs and symptoms agoraphobia is a condition where individuals become anxious in unfamiliar environments or where they perceive that they have little control. triggers for this anxiety may include wide-open spaces, crowds (social anxiety), or traveling (even short distances). agoraphobia is often, but not always, compounded by a fear of social embarrassment, as the agoraphobic fears the onset of a panic attack and appearing distraught in public. most of the time they avoid these areas and stay in the comfort of their haven, usually their home. agoraphobia is also defined as "a fear, sometimes terrifying, by those who have experienced one or more panic attacks". in these cases, the patient is fearful of a particular place because they have experienced a panic attack at the same location at a previous time. fearing the onset of another panic attack, the patient is fearful or even avoids a location. some refuse to leave their homes even in medical emergencies because the fear of being outside of their comfort areas is too great. the person with this condition can sometimes go to great lengths to avoid the locations where they have experienced the onset of a panic attack. agoraphobia, as described in this manner, is actually a symptom professionals check when making a diagnosis of panic disorder. other syndromes like obsessive compulsive disorder or post-traumatic stress disorder can also cause agoraphobia. essentially, any irrational fear that keeps one from going outside can cause the syndrome. people with agoraphobia may experience temporary separation anxiety disorder when certain other individuals of the household depart from the residence temporarily, such as a parent or spouse, or when they are left home alone. such temporary conditions can result in an increase in anxiety or a panic attack or feeling the need to separate themselves from family or maybe friends. people with agoraphobia sometimes fear waiting outside for long periods of time; that symptom can be called "macrophobia". panic attacks agoraphobia patients can experience sudden panic attacks when traveling to places where they fear they are out of control, help would be difficult to obtain, or they could be embarrassed. during a panic attack, epinephrine is released in large amounts, triggering the body's natural fight-or-flight response. a panic attack typically has an abrupt onset, building to maximum intensity within 10 to 15 minutes, and rarely lasts longer than 30 minutes. symptoms of a panic attack include palpitations, rapid heartbeat, sweating, trembling, nausea, vomiting, dizziness, tightness in the throat, and shortness of breath. many patients report a fear of dying, fear of losing control of emotions, or fear of losing control of behaviors. causes agoraphobia is believed to be due to a combination of genetic and environmental factors. the condition often runs in families, and stressful or traumatic events such as the death of a parent or being attacked may be a trigger. research has uncovered a link between agoraphobia and difficulties with spatial orientation. individuals without agoraphobia are able to maintain balance by combining information from their vestibular system, their visual system, and their proprioceptive sense. a disproportionate number of agoraphobics have weak vestibular function and consequently rely more on visual or tactile signals. they may become disoriented when visual cues are sparse (as in wide-open spaces) or overwhelming (as in crowds). likewise, they may be confused by sloping or irregular surfaces. in a virtual reality study, agoraphobics showed impaired processing of changing audiovisual data in comparison with subjects without agoraphobia. substance-induced chronic use of tranquilizers and sleeping pills such as benzodiazepines has been linked to onset of agoraphobia. in 10 patients who had developed agoraphobia during benzodiazepine dependence, symptoms abated within the first year of assisted withdrawal. similarly, alcohol use disorders are associated with panic with or without agoraphobia; this association may be due to the long-term effects of alcohol consumption causing a distortion in brain chemistry. tobacco smoking has also been associated with the development and emergence of agoraphobia, often with panic disorder; it is uncertain how tobacco smoking results in anxiety-panic with or without agoraphobia symptoms, but the direct effects of nicotine dependence or the effects of tobacco smoke on breathing have been suggested as possible causes. self-medication or a combination of factors may also explain the association between tobacco smoking and agoraphobia and panic. attachment theory some scholars have explained agoraphobia as an attachment deficit, i.e., the temporary loss of the ability to tolerate spatial separations from a secure base. recent empirical research has also linked attachment and spatial theories of agoraphobia. spatial theory in the social sciences, a perceived clinical bias exists in agoraphobia research. branches of the social sciences, especially geography, have increasingly become interested in what may be thought of as a spatial phenomenon. one such approach links the development of agoraphobia with modernity. factors considered contributing to agoraphobia within modernity are the ubiquity of cars and urbanization. these have helped develop the expansion of public space and the contraction of private space, thus creating in the minds of agoraphobia-prone people a tense, unbridgeable divide between the two. evolutionary psychology an evolutionary psychology view is that the more unusual primary agoraphobia without panic attacks may be due to a different mechanism from agoraphobia with panic attacks. primary agoraphobia without panic attacks may be a specific phobia explained by it once having been evolutionarily advantageous to avoid exposed, large, open spaces without cover or concealment. agoraphobia with panic attacks may be an avoidance response secondary to the panic attacks, due to fear of the situations in which the panic attacks occurred. diagnosis most people who present to mental health specialists develop agoraphobia after the onset of panic disorder. agoraphobia is best understood as an adverse behavioral outcome of repeated panic attacks and subsequent anxiety and preoccupation with these attacks that leads to an avoidance of situations where a panic attack could occur. early treatment of panic disorder can often prevent agoraphobia. agoraphobia is typically determined when symptoms are worse than panic disorder, but also do not meet the criteria for other anxiety disorders such as depression. agoraphobia without history of panic disorder agoraphobia without a history of panic disorder (also called primary agoraphobia) is an anxiety disorder where the individual with the diagnosis does not meet the dsm-5 criteria for panic disorder. agoraphobia typically develops as a result of having panic disorder. in a small minority of cases, however, agoraphobia can develop by itself without being triggered by the onset of panic attacks. agoraphobia can be caused by traumatic experiences, such as bullying or abuse. historically, there has been debate over whether agoraphobia without panic genuinely existed, or whether it was simply a manifestation of other disorders such as panic disorder, general anxiety disorder, avoidant personality disorder and social phobia. one researcher said: "out of 41 agoraphobics seen (at a clinic) during a period of 1 year, only 1 fit the diagnosis of agoraphobia without panic attacks, and even this particular classification was questionable...do not expect to see too many agoraphobics without panic". in spite of this earlier skepticism, current thinking is that agoraphobia without panic disorder is indeed a valid, unique illness which has gone largely unnoticed, since those with the condition are far less likely to seek clinical treatment. according to the dsm-iv-tr, a widely used manual for diagnosing mental disorders, the condition is diagnosed when agoraphobia is present without panic disorder where symptoms are not caused by or are unreasonable to an underlying medical problem or pharmacological influence. treatments therapy systematic desensitization can provide lasting relief to the majority of patients with panic disorder and agoraphobia. the disappearance of residual and sub-clinical agoraphobic avoidance, and not simply of panic attacks, should be the aim of exposure therapy. many patients can deal with exposure easier if they are in the company of a friend on whom they can rely. patients must remain in the situation until anxiety has abated because if they leave the situation, the phobic response will not decrease and it may even rise. a related exposure treatment is in vivo exposure, a cognitive behavioral therapy method, that gradually exposes patients to the feared situations or objects. this treatment was largely effective with an effect size from d = 0.78 to d = 1.34, and these effects were shown to increase over time, proving that the treatment had long-term efficacy (up to 12 months after treatment). psychological interventions in combination with pharmaceutical treatments were overall more effective than treatments simply involving either cbt or pharmaceuticals. further research showed there was no significant effect between using group cbt versus individual cbt. cognitive restructuring has also proved useful in treating agoraphobia. this treatment involves coaching a participant through a dianoetic discussion, with the intent of replacing irrational, counterproductive beliefs with more factual and beneficial ones. relaxation techniques are often useful skills for the agoraphobic to develop, as they can be used to stop or prevent symptoms of anxiety and panic. videoconferencing psychotherapy (vcp) is an emerging modality used to treat various disorders in a remote method. similar to traditional face-to-face interventions, vcp can be used to administer cbt. the use of vcp has been shown to be equally effective as face-to-face interventions at treating panic disorder and agoraphobia (pda) and motivating the client to continue treatment. medications antidepressant medications most commonly used to treat anxiety disorders are mainly selective serotonin reuptake inhibitors. benzodiazepines, monoamine oxidase inhibitor, and tricyclic antidepressants are also sometimes prescribed for treatment of agoraphobia. antidepressants are important because some have anxiolytic effects. antidepressants should be used in conjunction with exposure as a form of self-help or with cognitive behaviour therapy. a combination of medication and cognitive behaviour therapy is sometimes the most effective treatment for agoraphobia. benzodiazepines and other anxiolytic medications such as alprazolam and clonazepam are used to treat anxiety and can also help control the symptoms of a panic attack. alternative medicine eye movement desensitization and reprocessing (emdr) has been studied as a possible treatment for agoraphobia, with poor results. as such, emdr is only recommended in cases where cognitive-behavioral approaches have proven ineffective or in cases where agoraphobia has developed following trauma.

many people with anxiety disorders benefit from joining a self-help or support group (telephone conference-call support groups or online support groups being of particular help for completely housebound individuals). sharing problems and achievements with others, as well as sharing various self-help tools, are common activities in these groups. in particular, stress management techniques and various kinds of meditation practices and visualization techniques can help people with anxiety disorders calm themselves and may enhance the effects of therapy, as can service to others, which can distract from the self-absorption that tends to go with anxiety problems. also, preliminary evidence suggests aerobic exercise may have a calming effect. since caffeine, certain illicit drugs, and even some over-the-counter cold medications can aggravate the symptoms of anxiety disorders, they should be avoided. epidemiology agoraphobia occurs about twice as commonly among women as it does in men. panic disorder with or without agoraphobia affects roughly 5.1% of americans, and about 1/3 of this population with panic disorder have co-morbid agoraphobia. it is uncommon to have agoraphobia without panic attacks, with only 0.17% of people with agoraphobia not presenting panic disorders as well. society and culture notable cases woody allen (b. 1935), american actor, director, musician kim basinger (b. 1953), american actress earl campbell (b. 1955), american pro football player macaulay culkin (b. 1980), american actor, known for his portrayal of kevin mccallister in home alone and home alone 2: lost in new york, said he had "self-diagnosed" agoraphobia. paula deen (b. 1947), american chef, author, and television personality h.l. gold (1914–1996), science fiction editor – as a result of trauma during his wartime experiences, his agoraphobia became so severe that for more than two decades he was unable to leave his apartment. towards the end of his life, he acquired some control over the condition. daryl hannah (b. 1960), american actress howard hughes (1905–1976), american aviator, industrialist, film producer and philanthropist olivia hussey (b. 1951), anglo-argentine actress shirley jackson (1916–1965), american writer – her agoraphobia is considered to be a primary inspiration for the novel we have always lived in the castle. elfriede jelinek (b. 1946), austrian writer, nobel prize laureate in literature in 2004 mike patton (b. 1968), american musician. bolesław prus (1847–1912), polish journalist and novelist peter robinson (b. 1962), british musician known as marilyn brian wilson (b. 1942), american singer and songwriter, primary songwriter of the beach boys, a former recluse and agoraphobic who has schizophrenia ben weasel, singer and songwriter

börjeson–forssman–lehmann syndrome börjeson–forssman–lehmann syndrome börjeson-forssman-lehmann syndrome (bfls) is a rare genetic disease that causes intellectual disability, obesity, and growth defects. börjeson–forssman–lehmann syndromeother namesintellectual disability-epilepsy-endocrine disorders syndromeaffected males with bflsspecialtymedical genetics signs and symptoms some symptoms of bfls are discernible at birth, but they develop over time. babies with bfls are born at normal weight but have muscle hypotonia and difficulty feeding. as development progresses, moderate to severe intellectual disability and developmental delays become evident. beyond intellectual disability, the central nervous system of affected people shows other symptoms, including impaired vision (cataracts and hyperopia, particularly) and nystagmus. vision impairments can develop before age 30. the peripheral nervous system may also be affected by polyneuropathy. some individuals may have psychiatric problems, most commonly anxiety disorders, depression, behavioral disorders, and hypersexuality. the appearance of affected individuals is characteristic, featuring ptosis, large ears, supraorbital ridge, short stature (in approximately half of affected individuals), gynecomastia, deposits of abdominal fat, swollen cheeks and eyelids, short toes, and tapered fingers. kyphosis or scoliosis may also be present. the genitourinary system is also affected by bfls; the testes of affected children often show hypogonadism and cryptorchidism. diabetes has co-occurred in several cases. hearing loss, epilepsy, cleft lip and palate, acute precursor t-cell acute lymphoblastic leukemia, legg-calvé-perthes disease, and hypopituitarism are uncommon. people with xx chromosomes are usually carriers of the disease and show few, if any symptoms. if affected, they may have obesity, polyneuropathy, or mild intellectual disability. pathophysiology bfls is an x-linked recessive genetic disease caused by mutations in phf6, a gene that encodes a zinc finger protein involved in cell growth. point mutations lead to less severe forms of the disease than loss of function mutations or deletions. it is highly expressed during development in the pituitary gland, face, and brain. it occurs primarily in people with xy chromosomes because there is only one copy of the x chromosome present and therefore the only copy of phf6 is the mutated copy. diagnosis definitive diagnosis of bfls is made with a genetic test, though it can be suspected where there are several people in a family showing the characteristic symptoms. magnetic resonance imaging, electroencephalography, and electroneuronography can be used to assess the severity of the disease. mutations in the phf6 gene have been shown to be the cause of this condition. other diseases that may need to be distinguished from bfls include prader–willi syndrome, coffin–lowry syndrome, klinefelter syndrome, wilson–turner syndrome, bardet–biedl syndrome, smith–fineman–myers syndrome (chudley-lowry syndrome), and coffin–siris syndrome. treatment there is no cure for bfls, but its symptoms can be managed with surgery and medication. surgery is used to treat cryptorchidism and cleft palate, whereas medication is used to treat epilepsy that may result from the condition. prognosis though affected children can have severe developmental delays, they typically learn to walk between 4 and 6 years old. intellectual disability in affected individuals does not worsen over time; some affected individuals see their symptoms become less severe. epidemiology bfls is extremely rare, with less than 100 cases reported in the literature since its discovery. as with other x-linked diseases, it mostly occurs in males, however females can be affected, particularly if they have skewed x-inactivation. as of 2022, a patient advocate group bfls inc is forming a patient registry. history bfls was described in 1962 by the physicians for whom it is named.

pseudobutyrivibrio pseudobutyrivibrio pseudobutyrivibrio is a gram-negative, anaerobic and non-spore-forming bacterial genus from the family of lachnospiraceae. pseudobutyrivibrio scientific classification domain: bacteria phylum: bacillota class: clostridia order: eubacteriales family: lachnospiraceae genus: pseudobutyrivibriovan gylswyk et al. 1996 type species pseudobutyrivibrio ruminis species p. ruminis p. xylanivorans pseudobutyrivibrio as gram-negative, is in contrast to butyrivibrio, which is gram-positive, as is typical of most bacillota phylum bacteria.

asprobacter asprobacter asprobacter is a gram-negative and aerobic genus of bacteria from the family of hyphomonadaceae with one known species (asprobacter aquaticus). asprobacter aquaticus has been isolated from fresh water. asprobacter scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: caulobacterales family: hyphomonadaceae genus: asprobacterjin et al. 2017 species a. aquaticus

nuclear pharmacy nuclear pharmacy nuclear pharmacy, also known as radiopharmacy, involves preparation of radioactive materials for patient administration that will be used to diagnose and treat specific diseases in nuclear medicine. it generally involves the practice of combining a radionuclide tracer with a pharmaceutical component that determines the biological localization in the patient. radiopharmaceuticals are generally not designed to have a therapeutic effect themselves, but there is a risk to staff from radiation exposure and to patients from possible contamination in production. due to these intersecting risks, nuclear pharmacy is a heavily regulated field. the majority of diagnostic nuclear medicine investigations are performed using technetium-99m. pharmaceutical drug which emits radiation, used as a diagnostic or therapeutic agent history the concept of nuclear pharmacy was first described in 1960 by captain william h. briner while at the national institutes of health (nih) in bethesda, maryland. along with mr. briner, john e. christian, who was a professor in the school of pharmacy at purdue university, had written articles and contributed in other ways to set the stage of nuclear pharmacy. william briner started the nih radiopharmacy in 1958. john christian and william briner were both active on key national committees responsible for the development, regulation and utilization of radiopharmaceuticals. a technetium-99m generator was commercially available, followed by the availability of a number of tc-99m based radiopharmaceuticals. in the united states nuclear pharmacy was the first pharmacy specialty established in 1978 by the board of pharmacy specialties. various models of production exist internationally. institutional nuclear pharmacy is typically operated through large medical centers or hospitals while commercial centralized nuclear pharmacies provide their services to subscriber hospitals. they prepare and dispense radiopharmaceuticals as unit doses that are then delivered to the subscriber hospital by nuclear pharmacy personnel. operation a few basic steps are typically involved in technetium based preparations. first the active technetium is obtained from a radionuclide generator on site, which is then added to a non-radioactive kit containing the pharmaceutical component. further steps may be required depending on the materials in question to ensure full binding of the two components. these procedures are usually carried out in a clean room or isolator to provide radiation shielding and sterile conditions. for positron emission tomography (pet), fludeoxyglucose (18f) is the most common radiopharmaceutical, with the radioactive component usually obtained from a cyclotron. the short half life of fluorine-18 and many other pet isotopes necessitates rapid production. pet radiopharmaceuticals are now often produced by automated computer controlled systems to reduce complexity and radiation doses to staff. training and regulation radiopharmacy is a heavily regulated field, as it combines several practices and fields which may come under the purview of multiple regulators and legislation. these include occupational exposure of staff to ionising radiation, preparation of medicines, patient exposure to ionising radiation, transport of radioactive materials, and environmental exposure to ionising radiation. different regulations may cover the various stages involved in radiopharmacies, ranging from production of "cold" (non-radioactive) kits, to the marketing and distribution of final products. staff working in nuclear pharmacies require extensive training on aspects of good manufacturing practice, radiation safety concerns and aseptic dispensing. in the united states an authorised nuclear pharmacist must be a fully qualified pharmacist with evidence of additional training and qualification in nuclear pharmacy practice. several european union directives cover radiopharmaceuticals as a special group of medicines, reflecting the wide range of types of producers and staff groups that may be involved. in the uk qualified pharmacists may be involved along with clinical scientists or technologists, with relevant training.

thymidylate synthase inhibitor thymidylate synthase inhibitor thymidylate synthase inhibitors are chemical agents which inhibit the enzyme thymidylate synthase and have potential as an anticancer chemotherapy. this inhibition prevents the methylation of c5 of deoxyuridine monophosphate (dump) thereby inhibiting the synthesis of deoxythymidine monophosphate (dtmp). the downstream effect is promotion of cell death because cells would not be able to properly undergo dna synthesis if they are lacking dtmp, a necessary precursor to dttp. five agents were in clinical trials in 2002: raltitrexed, pemetrexed, nolatrexed, zd9331, and gs7904l. examples include raltitrexed, used for colorectal cancer since 1998 fluorouracil, used for colorectal cancer bgc 945 osi-7904l

coxalgia coxalgia coxalgia (/kok sáljə/), also known as coxodynia (/koks'ō-din'ē-ă/, from latin coxa 'hip', and algia/odyne 'pain'), is defined as pain in the hip or disease-related pain of the hip. coxalgia refers to general sensation of pain in the hip area, including the muscles surrounding the hip – sartorius, tensor fasciae latae, ilio-tibial banding and the sensation of the tissue surrounding bones. coxalgia will have an underlying cause- in adults this is most commonly osteoarthritis, degeneration of hip joints or bursitis (inflammation of the bursae-fluid sacs) of the joints. coxalgia may precede diagnosis or identification of other diseases by some considerable time as indicated for monitoring and review. coxalgia is a symptom of underlying hip joint pathology and must be examined and referred as the symptoms of pain and reduced mobility will increase and worsen, leading to chronic pain states. coxalgia may be due to trauma, dysplasia and abnormal growth, degeneration, osteo-deficiencies of b12 or folate or metastasising cancer. pain management should include robust use of pharmacological and non-pharmacological interventions. diagnosis coxalgia may be identified by a physician through a hip joint exam, by observing antalgic gait and stance, reduced mobility and reduced tone, power and co-ordination through the normal expected range of hip joint motion. treatment coxalgia may be treated in the short-term by over-the-counter pain relief such as paracetamol, aspirin or ibuprofen. further pain management must be sought in co-ordination with a gp or healthcare specialist. diagnostic tools such as ultrasound, ct imaging and mri to identify the extent of the underlying disease at which point referral to specialist general practitioner or orthopaedic surgeon should follow. complementary adjunct therapies such as physiotherapy, tens trans-cutaneous electro-neuro- stimulation and bio-mechanical therapies may be useful in managing the reduced mobility and alleviating the pain. various aids are available for minimising the angles and strains of the hip joint and enabling peri-operative recovery. these include, modified toilet seats, cushions for optimum 'sitting angle' and aids for reaching and manoeuvring through the symptoms without causing harm.

virgibacillus marismortui virgibacillus marismortui virgibacillus marismortui is a gram-positive, moderately halophilic and rod-shaped bacterium from the genus of virgibacillus which has been isolated from water from the dead sea. virgibacillus marismortui scientific classification domain: bacteria phylum: bacillota class: bacilli order: bacillales family: bacillaceae genus: virgibacillus species: v. marismortui binomial name virgibacillus marismortui(arahal et al. 1999) heyrman et al. 2003 type strain atcc 700626, cect 5066, cip 105609, dsm 12325, lmg 18992, ny-13, strain 123 synonyms bacillus marismortui salibacillus marismortui

roseomonas cervicalis roseomonas cervicalis roseomonas cervicalis is a species of gram negative, strictly aerobic, coccobacilli-shaped, pink-pigmented bacterium. it was first isolated from the cervix of a woman in new jersey in 1980. the new species was among the first roseomonas species proposed in 1993, and the name derives from the fact that it was first isolated from a cervix. r. cervicalis is pathogenic for humans and can cause urogenital or eye infections, among others. roseomonas cervicalis scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: rhodospirillales family: acetobacteraceae genus: roseomonas species: r. cervicalis binomial name roseomonas cervicalisrhis 1993

mucilaginibacter gracilis mucilaginibacter gracilis mucilaginibacter gracilis is a gram-negative, facultatively aerobic, heterotrophic and non-motile bacterium from the genus of mucilaginibacter which has been isolated from sphagnum peat bog in the tomsk region in russia. mucilaginibacter gracilis scientific classification domain: bacteria phylum: bacteroidota class: sphingobacteriia order: sphingobacteriales family: sphingobacteriaceae genus: mucilaginibacter species: m. gracilis binomial name mucilaginibacter gracilispankratov et al. 2007 type strain atcc baa-1391, dsm 18602, tpt18, vkm b-2447

biopharmaceutics classification system biopharmaceutics classification system the biopharmaceutics classification system is a system to differentiate the drugs on the basis of their solubility and permeability. this system restricts the prediction using the parameters solubility and intestinal permeability. the solubility classification is based on a united states pharmacopoeia (usp) aperture. the intestinal permeability classification is based on a comparison to the intravenous injection. all those factors are highly important because 85% of the most sold drugs in the united states and europe are orally administered . bcs classes bcs classes according to the biopharmaceutical classification system (bcs) drug substances are classified to four classes upon their solubility and permeability: class i - high permeability, high solubility example: metoprolol, paracetamol those compounds are well absorbed and their absorption rate is usually higher than excretion. class ii - high permeability, low solubility example: glibenclamide, bicalutamide, ezetimibe, aceclofenac the bioavailability of those products is limited by their solvation rate. a correlation between the in vivo bioavailability and the in vitro solvation can be found. class iii - low permeability, high solubility example: cimetidine the absorption is limited by the permeation rate but the drug is solvated very fast. if the formulation does not change the permeability or gastro-intestinal duration time, then class i criteria can be applied. class iv - low permeability, low solubility example: bifonazole those compounds have a poor bioavailability. usually they are not well absorbed over the intestinal mucosa and a high variability is expected. definitions the drugs are classified in bcs on the basis of solubility, permeability, and dissolution. solubility class boundaries are based on the highest dose strength of an immediate release product. a drug is considered highly soluble when the highest dose strength is soluble in 250 ml or less of aqueous media over the ph range of 1 to 7.5. the volume estimate of 250 ml is derived from typical bioequivalence study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water. permeability class boundaries are based indirectly on the extent of absorption of a drug substance in humans and directly on the measurement of rates of mass transfer across human intestinal membrane. alternatively non-human systems capable of predicting drug absorption in humans can be used (such as in-vitro culture methods). a drug substance is considered highly permeable when the extent of absorption in humans is determined to be 90% or more of the administered dose based on a mass-balance determination or in comparison to an intravenous dose. for dissolution class boundaries, an immediate release product is considered rapidly dissolving when no less than 85% of the labeled amount of the drug substance dissolves within 15 minutes using usp dissolution apparatus 1 at 100 rpm or apparatus 2 at 50 rpm in a volume of 900 ml or less in the following media: 0.1 m hcl or simulated gastric fluid or ph 4.5 buffer and ph 6.8 buffer or simulated intestinal fluid.

apusozoa apusozoa the apusozoa are an obazoa phylum comprising several genera of flagellate eukaryotes. they are usually around 5–20 μm in size, and occur in soils and aquatic habitats, where they feed on bacteria. they are grouped together based on the presence of an organic shell or theca under the dorsal surface of the cell. for an explanation of very similar terms, see obazoa. apusozoa apusomonas sp. scientific classification clade: obazoa phylum: apusozoacavalier-smith 1997 em. orders apusomonadida breviata the name derives from the ancient greek words for footless (ἄπους) and animal (ζῷον). this phylum is currently defined as containing the breviata and the apusomonadida. however, it currently usually is viewed as paraphyletic, with the breviata as more basal. the opisthokonts appear to have emerged as sister of the apusomonadida. it has been suggested that the mantamonadida be classified in apusozoa. the ancyromonadida appear to be varisulca, planomonadida, shifting them possibly more basal than the amoebozoa, or less basal. while some classification systems have placed hemimastigida in apusozoa, 2018 research indicated that hemimastigotes (hemimastix kukwesjijk/hemimastix/spironemidae) are their own supra-kingdom. characteristics the apusomonads have two flagella inserted at right angles, near the anterior of the cell. they move by gliding, with one flagellum trailing along the side and one directed to the anterior. the form of the mitochondria varies between the different orders. among the apusomonads they have tubular cristae, the ancyromonads flat cristae, and the hemimastigids ambiguous or sacculate cristae. this characteristic was originally considered a good indicator of relationships, but is now known to vary even among close relatives. eukaryotes diphoda diaphoretickes cryptista archaeplastida rhodophyta (red algae) picozoa glaucophyta viridiplantae (plants) 1600 mya haptista tsar telonemia sar halvaria stramenopiles alveolata rhizaria provora hemimastigophora discoba ? metamonada bikonts ancyromonadida malawimonada crums amorphea amoebozoa obazoa breviatea apusomonadida opisthokonta holomycota (inc. fungi) holozoa (inc. animals) 1300 mya 1500 mya 2200 mya one view of the great kingdoms and their stem groups.

nirogacestat nirogacestat nirogacestat (pf-03084014) is a selective gamma secretase inhibitor developed by springworks therapeutics that has potential anti-tumor activity. it was granted fda breakthrough drug designation in september 2019 for adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. nirogacestatclinical dataother namespf-03084014atc codenoneidentifiers iupac name (s)-2-((s)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-3-ylamino)-n-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1h-imidazol-4-yl)pentanamide cas number1290543-63-3pubchem cid46224413drugbankdb12005chemspider26232306uniiqz62892ofjkeggd10960comptox dashboard (epa)dtxsid60235679 chemical and physical dataformulac27h41f2n5omolar mass489.656 g·mol−13d model (jsmol)interactive image smiles ccc(n1()ccc2=cc(f)=cc(f)=c2c1)()/c(o)=n/c3=cn(c(c)(cncc(c)(c)c)c)c=n3 inchi inchi=1s/c27h41f2n5o/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4/h11-12,14,17,20,23,30,32h,7-10,13,15-16h2,1-6h3,(h,33,35)/t20-,23-/m0/s1key:vfcrklwbymdaed-rewpjtcusa-n medical uses nirogacestat is currently in phase 2 clinical trials for unresectable desmoid tumors. in addition, a phase 3 clinical trial, defi, is currently in progress for nirogacestat for adults with desmoid tumors and aggressive fibromatosis. in addition, three trials are presently recruiting patients that include nirogacestat with other anticancer therapies in multiple myeloma, including the universal study for nirogacestat with the allogeneic car-t therapy allo-715.

museum of the history of lithuanian medicine and pharmacy museum of the history of lithuanian medicine and pharmacy the museum of the history of lithuanian medicine and pharmacy (lithuanian: lietuvos medicinos ir farmacijos istorijos muziejus) is located in a restored 16th-century building at the town hall square in the old town of kaunas, lithuania. museum interior it moved to its current location in 1987, although its history dates to 1936. alfonsas kaikaris (1922–1997), a professor of pharmacy, is credited as the founder of the museum; his personal collection formed the basis of its holdings. the lithuanian pharmacists' union worked to collect materials as well. it is sponsored by kaunas university of medicine. the museum's permanent collection consists of the belongings of lithuanian doctors, pharmacists and hospitals, along with medical and pharmaceutical implements and documents. temporary exhibitions commemorate prominent doctors' and pharmacists' anniversaries. the exhibits include dental equipment along with displays of archaic medications such as erektosan (a herbal version of viagra), love potions, venus hair potion, and caput mortuum (a medieval male vitality booster and epilepsy treatment composed of dead heads). there one can enjoy the scenes of pre-history of medicine and pharmacy – watching exhibition stands arranged with great inventiveness and authenticity: presenting a shaman curing a baby as well as a lithuanian sorceress.

karen (orangutan) karen (orangutan) karen (born 11 june 1992), is a sumatran orangutan (pongo abelii), who on 27 august 1994 at san diego zoo was the first orangutan to have open heart surgery and in 2021 was among the first non-humans to receive a vaccine for covid-19. karenother name(s)kare-bearspeciessumatran orangutansexfemaleborn (1992-06-11) june 11, 1992san diego zooknown forfirst orangutan to have open heart surgery (1994) & first non-human to get vaccinated for covid-19 (2021)residencesan diego zooparent(s)karta (mother) otis (father) concerns for the endangered species of sumatran orangutan at a time when routine open heart surgery was being performed in human babies, combined with a collaboration between san diego zoo and the uc san diego health, led to the planning of repairing the large hole in the heart in two-year-old karen. the operation and after-care required the co-operation of more than 100 volunteers and the resulting procedure was successful and widely publicised. karen became a favorite with zoo visitors, surviving more than 25 years. karen is the subject of a book by georgeanne irvine titled karen’s heart: the true story of a brave baby orangutan, published by blue sneaker press in 2018. background wild sumatran orangutans are critically endangered. in the 1970s, uc san diego health (ucsd) pathologist kurt benirschke, persuaded zoo trustees to establish a research department, at the zoo's center for the reproduction of endangered species, which he subsequently led, providing the collaboration between the university and the zoo. orangutan and human hearts have much similarity, and open heart surgery had become routine in human babies. early life and family karen, also known as "kare-bear", a sumatran orangutan, was born at san diego zoo on 11 june 1992 to nine-year-old mother karta and father otis. after 1995, karta lost six infants over the course of 15 years. observations eventually led to the discovery of karta's difficulties in breastfeeding due to her small nipples. her babies were either stillborn or could not latch on and therefore failed to thrive. the zookeepers observed that karen was not being nursed in the first few days of life and she was therefore removed from karta. on reintroducing her back to karta, no change was seen and karen was removed again to be handraised. karta was subsequently sent to adelaide zoo in november 1992 and karen was adopted by orangutan josephine. karen was found to have a heart murmur at a health check-up at the age of two, after it was noted that she was not growing at the appropriate speed. tests then confirmed a penny-size hole in the heart. at the time, karen weighed 22 pounds (10.0 kg) and her condition was considered fatal without surgical correction. heart surgery a surgical team led by cardiothoracic surgeon stuart w. jamieson from ucsd repaired the defect by opening karen's chest and heart and stitching the hole to close it. despite some structural variation between karen's chest wall and that of a human, once inside the chest cavity, the surgeons felt familiar with the heart surgery. the whole procedure required the co-operation of a number of surgeons, nurses, anaesthetists, medical technicians, veterinarians and animal keepers and lasted seven hours. jamieson reported that "if karen were human, i'd tell her parents that everything went fine, and her prognosis is excellent". she became the first orangutan to have open heart surgery. following the operation, karen required carefully co-ordinated care, which involved more than 100 volunteers. although she suffered a lung complication, it was managed successfully and she survived to make headlines, receiving get-well cards from all over the world. life after surgery karen subsequently became a favorite with zoo visitors. she has been described as "stubborn and willful, just like her mum", and is said to have a signature move, where she rolls rather than walks. although not usually housed together, karen, like some other orangutans is found to get along well with siamang gibbons. a book about karen was published in 2018, titled karen’s heart: the true story of a brave baby orangutan. covid-19 vaccination karen was one of the first non-humans to receive a covid-19 vaccine.

sodium hypochlorite sodium hypochlorite sodium hypochlorite names iupac name sodium hypochlorite other names antiforminbleachchloride of sodain dilution:carrel-dakin solutionmodified dakin's solutionsurgical chlorinated soda solution identifiers cas number 7681-52-9 (anhydrous) y10022-70-5 (pentahydrate) y 3d model (jsmol) interactive image chebi chebi:32146 y chemspider 22756 y drugbank dbsalt001517 echa infocard 100.028.790 ec number 231-668-3 kegg d01711 y pubchem cid 23665760 rtecs number nh3486300 unii dy38vhm5od y un number 1791 comptox dashboard (epa) dtxsid8021276 inchi inchi=1s/clo.na/c1-2;/q-1;+1 ykey: sukjfigyrhowbl-uhfffaoysa-n yinchi=1/clo.na/c1-2;/q-1;+1key: sukjfigyrhowbl-uhfffaoyad smiles .cl properties chemical formula naocl molar mass 74.442 g/mol appearance greenish-yellow solid (pentahydrate) odor chlorine-like and sweetish density 1.11 g/cm3 melting point 18 °c (64 °f; 291 k) pentahydrate boiling point 101 °c (214 °f; 374 k) (decomposes) solubility in water 29.3 g/100ml (0 °c) acidity (pka) 7.5185 basicity (pkb) 6.4815 thermochemistry std enthalpy offormation (δfh⦵298) -347.1 kj/mol pharmacology atc code d08ax07 (who) hazards occupational safety and health (ohs/osh): main hazards oxidizer, corrosive ghs labelling: pictograms signal word danger hazard statements h302, h314, h410 precautionary statements p260, p264, p273, p280, p301+p330+p331, p303+p361+p353, p304+p340, p305+p351+p338, p310, p321, p363, p391, p405, p501 nfpa 704 (fire diamond) 2 0 1ox safety data sheet (sds) icsc 1119 (solution, >10% active chlorine)icsc 0482 (solution, <10% active chlorine) related compounds other anions sodium chloridesodium chloritesodium chloratesodium perchlorate other cations lithium hypochloritecalcium hypochloritepotassium hypochlorite related compounds hypochlorous acid except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). n verify (what is yn ?) infobox references sodium hypochlorite, commonly known in a dilute solution as (chlorine) bleach, is an inorganic chemical compound with the formula naocl (or naclo), comprising a sodium cation (na+) and a hypochlorite anion (ocl−or clo−). it may also be viewed as the sodium salt of hypochlorous acid. the anhydrous compound is unstable and may decompose explosively. it can be crystallized as a pentahydrate naocl·5h2o, a pale greenish-yellow solid which is not explosive and is stable if kept refrigerated. sodium hypochlorite is most often encountered as a pale greenish-yellow dilute solution referred to as liquid bleach, which is a household chemical widely used (since the 18th century) as a disinfectant or a bleaching agent. in solution, the compound is unstable and easily decomposes, liberating chlorine, which is the active principle of such products. sodium hypochlorite is the oldest and still most important chlorine-based bleach. its corrosive properties, common availability, and reaction products make it a significant safety risk. in particular, mixing liquid bleach with other cleaning products, such as acids found in limescale-removing products, will produce chlorine gas, which was used as a chemical weapon in world war i. a common urban legend states that mixing bleach with ammonia also releases chlorine, but in reality the two chemicals react differently, producing chloramines and/or nitrogen trichloride. with excess ammonia and sodium hydroxide, hydrazine may be generated. chemistry stability of the solid anhydrous sodium hypochlorite can be prepared but, like many hypochlorites, it is highly unstable and decomposes explosively on heating or friction. the decomposition is accelerated by carbon dioxide at atmospheric levels. it is a white solid with the orthorhombic crystal structure. sodium hypochlorite can also be obtained as a crystalline pentahydrate naocl·5h2o, which is not explosive and is much more stable than the anhydrous compound. the formula is sometimes given as 2naocl·10h2o.. the cl–o bond length in the pentahydrate is 1.686 å. the transparent, light greenish-yellow, orthorhombic crystals contain 44% naocl by weight and melt at 25–27 °c. the compound decomposes rapidly at room temperature, so it must be kept under refrigeration. at lower temperatures, however, it is quite stable: reportedly only 1% decomposition after 360 days at 7 °c. a 1966 us patent claims that stable solid sodium hypochlorite dihydrate naocl·2h2o can be obtained by carefully excluding chloride ions (cl−), which are present in the output of common manufacturing processes and are said to catalyze the decomposition of hypochlorite into chlorate (clo−3) and chloride. in one test, the dihydrate was claimed to show only 6% decomposition after 13.5 months storage at −25 °c. the patent also claims that the dihydrate can be reduced to the anhydrous form by vacuum drying at about 50 °c, yielding a solid that showed no decomposition after 64 hours at −25 °c. equilibria and stability of solutions at typical ambient temperatures, sodium hypochlorite is more stable in dilute solutions that contain solvated na+ and ocl− ions. the density of the solution is 1.093 g/ml at 5% concentration, and 1.21 g/ml at 14%, 20 °c. stoichiometric solutions are fairly alkaline, with ph 11 or higher since hypochlorous acid is a weak acid: ocl− + h2o ⇌ hocl + oh− the following species and equilibria are present in naocl/nacl solutions: hocl (aq) ⇌ h+ + ocl− hocl (aq) + cl− + h+ ⇌ cl2 (aq) + h2o cl2 (aq) + cl− ⇌ cl−3 cl2 (aq) ⇌ cl2 (g) the second equilibrium equation above will be shifted to the right if the chlorine cl2 is allowed to escape as gas. the ratios of cl2, hocl, and ocl− in solution are also ph dependent. at ph below 2, the majority of the chlorine in the solution is in the form of dissolved elemental cl2. at ph greater than 7.4, the majority is in the form of hypochlorite clo−. the equilibrium can be shifted by adding acids (such as hydrochloric acid) or bases (such as sodium hydroxide) to the solution: clo− (aq) + 2 hcl (aq) → cl2 (g) + h2o (aq) + cl− (aq) cl2 (g) + 2 oh− → clo− (aq) + cl− (aq) + h2o (aq) at a ph of about 4, such as obtained by the addition of strong acids like hydrochloric acid, the amount of undissociated (nonionized) hocl is highest. the reaction can be written as: clo− + h+ ⇌ hclo sodium hypochlorite solutions combined with acid evolve chlorine gas, particularly strongly at ph < 2, by the reactions: hocl (aq) + cl− + h+ ⇌ cl2 (aq) + h2o cl2 (aq) ⇌ cl2 (g) at ph > 8, the chlorine is practically all in the form of hypochlorite anions (ocl−). the solutions are fairly stable at ph 11–12. even so, one report claims that a conventional 13.6% naocl reagent solution lost 17% of its strength after being stored for 360 days at 7 °c. for this reason, in some applications one may use more stable chlorine-releasing compounds, such as calcium hypochlorite ca(clo)2 or trichloroisocyanuric acid (cnclo)3. anhydrous sodium hypochlorite is soluble in methanol, and solutions are stable. decomposition to chlorate or oxygen in solution, under certain conditions, the hypochlorite anion may also disproportionate (autoxidize) to chloride and chlorate: 3 clo− + h+ → hclo3 + 2 cl− in particular, this reaction occurs in sodium hypochlorite solutions at high temperatures, forming sodium chlorate and sodium chloride: 3 naocl (aq) → 2 nacl (aq) + naclo3 (aq) this reaction is exploited in the industrial production of sodium chlorate. an alternative decomposition of hypochlorite produces oxygen instead: 2 ocl− → 2 cl− + o2 in hot sodium hypochlorite solutions, this reaction competes with chlorate formation, yielding sodium chloride and oxygen gas: 2 naocl (aq) → 2 nacl (aq) + o2 (g) these two decomposition reactions of naclo solutions are maximized at ph around 6. the chlorate-producing reaction predominates at ph above 6, while the oxygen one becomes significant below that. for example, at 80 °c, with naocl and nacl concentrations of 80 mm, and ph 6–6.5, the chlorate is produced with ∼95% efficiency. the oxygen pathway predominates at ph 10. this decomposition is affected by light and metal ion catalysts such as copper, nickel, cobalt, and iridium. catalysts like sodium dichromate na2cr2o7 and sodium molybdate na2moo4 may be added industrially to reduce the oxygen pathway, but a report claims that only the latter is effective. titration titration of hypochlorite solutions is often done by adding a measured sample to an excess amount of acidified solution of potassium iodide (ki) and then titrating the liberated iodine (i2) with a standard solution of sodium thiosulfate or phenylarsine oxide, using starch as indicator, until the blue color disappears. according to one us patent, the stability of sodium hypochlorite content of solids or solutions can be determined by monitoring the infrared absorption due to the o–cl bond. the characteristic wavelength is given as 140.25 μm for water solutions, 140.05 μm for the solid dihydrate naocl·2h2o, and 139.08 μm for the anhydrous mixed salt na2(ocl)(oh). oxidation of organic compounds oxidation of starch by sodium hypochlorite, that adds carbonyl and carboxyl groups, is relevant to the production of modified starch products. in the presence of a phase-transfer catalyst, alcohols are oxidized to the corresponding carbonyl compound (aldehyde or ketone). sodium hypochlorite can also oxidize organic sulfides to sulfoxides or sulfones, disulfides or thiols to sulfonyl halides, imines to oxaziridines. it can also de-aromatize phenols. oxidation of metals and complexes heterogeneous reactions of sodium hypochlorite and metals such as zinc proceed slowly to give the metal oxide or hydroxide: naocl + zn → zno + nacl homogeneous reactions with metal coordination complexes proceed somewhat faster. this has been exploited in the jacobsen epoxidation. other reactions if not properly stored in airtight containers, sodium hypochlorite reacts with carbon dioxide to form sodium carbonate: 2 naocl + co2 + h2o → na2co3 + 2 hocl sodium hypochlorite reacts with most nitrogen compounds to form volatile monochloramine, dichloramines, and nitrogen trichloride: nh3 + naocl → nh2cl + naoh nh2cl + naocl → nhcl2 + naoh nhcl2 + naocl → ncl3 + naoh neutralization sodium thiosulfate is an effective chlorine neutralizer. rinsing with a 5 mg/l solution, followed by washing with soap and water, will remove chlorine odor from the hands. production chlorination of soda potassium hypochlorite was first produced in 1789 by claude louis berthollet in his laboratory on the quai de javel in paris, france, by passing chlorine gas through a solution of potash lye. the resulting liquid, known as "eau de javel" ("javel water"), was a weak solution of potassium hypochlorite. antoine labarraque replaced potash lye by the cheaper soda lye, thus obtaining sodium hypochlorite (eau de labarraque). cl2 (g) + 2 naoh (aq) → nacl (aq) + naclo (aq) + h2o (aq) hence, chlorine is simultaneously reduced and oxidized; this process is known as disproportionation. the process is also used to prepare the pentahydrate naocl·5h2o for industrial and laboratory use. in a typical process, chlorine gas is added to a 45–48% naoh solution. some of the sodium chloride precipitates and is removed by filtration, and the pentahydrate is then obtained by cooling the filtrate to 12 °c . from calcium hypochlorite another method involved the reaction of sodium carbonate ("washing soda") with chlorinated lime ("bleaching powder"), a mixture of calcium hypochlorite ca(ocl)2, calcium chloride cacl2, and calcium hydroxide ca(oh)2: na2co3 (aq) + ca(ocl)2 (aq) → caco3 (s) + 2 naocl (aq) na2co3 (aq) + cacl2 (aq) → caco3 (s) + 2 nacl (aq) na2co3 (aq) + ca(oh)2 (s) → caco3 (s) + 2 naoh (aq) this method was commonly used to produce hypochlorite solutions for use as a hospital antiseptic that was sold after world war i under the names "eusol", an abbreviation for edinburgh university solution of (chlorinated) lime – a reference to the university's pathology department, where it was developed. electrolysis of brine near the end of the nineteenth century, e. s. smith patented the chloralkali process: a method of producing sodium hypochlorite involving the electrolysis of brine to produce sodium hydroxide and chlorine gas, which then mixed to form sodium hypochlorite. the key reactions are: 2 cl− → cl2 + 2 e− (at the anode) 2 h2o + 2 e− → h2 + 2 ho− (at the cathode) both electric power and brine solution were in cheap supply at the time, and various enterprising marketers took advantage of the situation to satisfy the market's demand for sodium hypochlorite. bottled solutions of sodium hypochlorite were sold under numerous trade names. today, an improved version of this method, known as the hooker process (named after hooker chemicals, acquired by occidental petroleum), is the only large-scale industrial method of sodium hypochlorite production. in the process, sodium hypochlorite (naclo) and sodium chloride (nacl) are formed when chlorine is passed into cold dilute sodium hydroxide solution. the chlorine is prepared industrially by electrolysis with minimal separation between the anode and the cathode.

the solution must be kept below 40 °c (by cooling coils) to prevent the undesired formation of sodium chlorate. commercial solutions always contain significant amounts of sodium chloride (common salt) as the main by-product, as seen in the equation above. from hypochlorous acid and soda a 1966 patent describes the production of solid stable dihydrate naocl·2h2o by reacting a chloride-free solution of hypochlorous acid hclo (such as prepared from chlorine monoxide clo and water), with a concentrated solution of sodium hydroxide. in a typical preparation, 255 ml of a solution with 118 g/l hclo is slowly added with stirring to a solution of 40 g of naoh in water 0 °c. some sodium chloride precipitates and is removed by filtration. the solution is vacuum evaporated at 40–50 °c and 1–2 mmhg until the dihydrate crystallizes out. the crystals are vacuum-dried to produce a free-flowing crystalline powder. the same principle was used in a 1993 patent to produce concentrated slurries of the pentahydrate naclo·5h2o. typically, a 35% solution (by weight) of hclo is combined with sodium hydroxide at about or below 25 °c. the resulting slurry contains about 35% naclo, and are relatively stable due to the low concentration of chloride. from ozone and salt sodium hypochlorite can be easily produced for research purposes by reacting ozone with salt. nacl + o3 → naclo + o2 this reaction happens at room temperature and can be helpful for oxidizing alcohols. packaging and sale bleach packaged for household use, with 2.6% sodium hypochlorite household bleach sold for use in laundering clothes is a 3–8% solution of sodium hypochlorite at the time of manufacture. strength varies from one formulation to another and gradually decreases with long storage. sodium hydroxide is usually added in small amounts to household bleach to slow down the decomposition of naclo. domestic use patio blackspot remover products are ~10% solutions of sodium hypochlorite. a 10–25% solution of sodium hypochlorite is, according to univar's safety sheet, supplied with synonyms or trade names bleach, hypo, everchlor, chloros, hispec, bridos, bleacol, or vo-redox 9110. a 12% solution is widely used in waterworks for the chlorination of water, and a 15% solution is more commonly used for disinfection of waste water in treatment plants. sodium hypochlorite can also be used for point-of-use disinfection of drinking water, taking 0.2-2 mg of sodium hypochlorite per liter of water. dilute solutions (50 ppm to 1.5%) are found in disinfecting sprays and wipes used on hard surfaces. uses bleaching household bleach is, in general, a solution containing 3–8% sodium hypochlorite, by weight, and 0.01–0.05% sodium hydroxide; the sodium hydroxide is used to slow the decomposition of sodium hypochlorite into sodium chloride and sodium chlorate. cleaning sodium hypochlorite has destaining properties. among other applications, it can be used to remove mold stains, dental stains caused by fluorosis, and stains on crockery, especially those caused by the tannins in tea. it has also been used in laundry detergents and as a surface cleaner. it is also used in sodium hypochlorite washes. its bleaching, cleaning, deodorizing and caustic effects are due to oxidation and hydrolysis (saponification). organic dirt exposed to hypochlorite becomes water-soluble and non-volatile, which reduces its odor and facilitates its removal. disinfection sodium hypochlorite in solution exhibits broad spectrum anti-microbial activity and is widely used in healthcare facilities in a variety of settings. it is usually diluted in water depending on its intended use. "strong chlorine solution" is a 0.5% solution of hypochlorite (containing approximately 5000 ppm free chlorine) used for disinfecting areas contaminated with body fluids, including large blood spills (the area is first cleaned with detergent before being disinfected). it may be made by diluting household bleach as appropriate (normally 1 part bleach to 9 parts water). such solutions have been demonstrated to inactivate both c. difficile and hpv. "weak chlorine solution" is a 0.05% solution of hypochlorite used for washing hands, but is normally prepared with calcium hypochlorite granules. "dakin's solution" is a disinfectant solution containing low concentration of sodium hypochlorite and some boric acid or sodium bicarbonate to stabilize the ph. it has been found to be effective with naocl concentrations as low as 0.025%. us government regulations allow food processing equipment and food contact surfaces to be sanitized with solutions containing bleach, provided that the solution is allowed to drain adequately before contact with food, and that the solutions do not exceed 200 parts per million (ppm) available chlorine (for example, one tablespoon of typical household bleach containing 5.25% sodium hypochlorite, per gallon of water). if higher concentrations are used, the surface must be rinsed with potable water after sanitizing. a similar concentration of bleach in warm water is used to sanitize surfaces prior to brewing of beer or wine. surfaces must be rinsed with sterilized (boiled) water to avoid imparting flavors to the brew; the chlorinated byproducts of sanitizing surfaces are also harmful. the mode of disinfectant action of sodium hypochlorite is similar to that of hypochlorous acid. solutions containing more than 500 ppm available chlorine are corrosive to some metals, alloys and many thermoplastics (such as acetal resin) and need to be thoroughly removed afterwards, so the bleach disinfection is sometimes followed by an ethanol disinfection. liquids containing sodium hypochlorite as the main active component are also used for household cleaning and disinfection, for example toilet cleaners. some cleaners are formulated to be viscous so as not to drain quickly from vertical surfaces, such as the inside of a toilet bowl. the undissociated (nonionized) hypochlorous acid is believed to react with and inactivate bacterial and viral enzymes. neutrophils of the human immune system produce small amounts of hypochlorite inside phagosomes, which digest bacteria and viruses. deodorizing sodium hypochlorite has deodorizing properties, which go hand in hand with its cleaning properties. waste water treatment sodium hypochlorite solutions have been used to treat dilute cyanide waste water, such as electroplating wastes. in batch treatment operations, sodium hypochlorite has been used to treat more concentrated cyanide wastes, such as silver cyanide plating solutions. toxic cyanide is oxidized to cyanate (ocn−) that is not toxic, idealized as follows: cn− + ocl− → ocn− + cl− sodium hypochlorite is commonly used as a biocide in industrial applications to control slime and bacteria formation in water systems used at power plants, pulp and paper mills, etc., in solutions typically of 10–15% by weight. endodontics sodium hypochlorite is the medicament of choice due to its efficacy against pathogenic organisms and pulp digestion in endodontic therapy. its concentration for use varies from 0.5% to 5.25%. at low concentrations it dissolves mainly necrotic tissue; at higher concentrations it also dissolves vital tissue and additional bacterial species. one study has shown that enterococcus faecalis was still present in the dentin after 40 minutes of exposure of 1.3% and 2.5% sodium hypochlorite, whereas 40 minutes at a concentration of 5.25% was effective in e. faecalis removal. in addition to higher concentrations of sodium hypochlorite, longer time exposure and warming the solution (60 °c) also increases its effectiveness in removing soft tissue and bacteria within the root canal chamber. 2% is a common concentration as there is less risk of an iatrogenic hypochlorite incident. a hypochlorite incident is an immediate reaction of severe pain, followed by edema, haematoma, and ecchymosis as a consequence of the solution escaping the confines of the tooth and entering the periapical space. this may be caused by binding or excessive pressure on the irrigant syringe, or it may occur if the tooth has an unusually large apical foramen. nerve agent neutralization at the various nerve agent (chemical warfare nerve gas) destruction facilities throughout the united states, 50% sodium hypochlorite is used to remove all traces of nerve agent or blister agent from personal protection equipment after an entry is made by personnel into toxic areas. 50% sodium hypochlorite is also used to neutralize any accidental releases of the nerve agent in the toxic areas. lesser concentrations of sodium hypochlorite are used in a similar fashion in the pollution abatement system to ensure that no nerve agent is released into the furnace flue gas. reduction of skin damage dilute bleach baths have been used for decades to treat moderate to severe eczema in humans, but it has not been clear why they work. one of the reasons why bleach helps is that eczema can frequently result in secondary infections, especially from bacteria like staphylococcus aureus, which makes managing it difficult. staphylococcus aureus infection is related to the pathogenesis of eczema and ad. bleach baths are one method for lowering the risk of staph infections in people with eczema.the antibacterial and anti-inflammatory properties of sodium hypochlorite contribute to the reduction of harmful bacteria on the skin and the reduction of inflammation, respectively. according to work published by researchers at the stanford university school of medicine in november 2013, a very dilute (0.005%) solution of sodium hypochlorite in water was successful in treating skin damage with an inflammatory component caused by radiation therapy, excess sun exposure or aging in laboratory mice. mice with radiation dermatitis given daily 30-minute baths in bleach solution experienced less severe skin damage and better healing and hair regrowth than animals bathed in water. a molecule called nuclear factor kappa-light-chain-enhancer of activated b cells (nf-κb) is known to play a critical role in inflammation, aging, and response to radiation. the researchers found that if nf-κb activity was blocked in elderly mice by bathing them in bleach solution, the animals' skin began to look younger, going from old and fragile to thicker, with increased cell proliferation. the effect diminished after the baths were stopped, indicating that regular exposure was necessary to maintain skin thickness. safety it is estimated that there are about 3,300 accidents needing hospital treatment caused by sodium hypochlorite solutions each year in british homes (rospa, 2002). oxidation and corrosion sodium hypochlorite is a strong oxidizer. oxidation reactions are corrosive. solutions burn the skin and cause eye damage, especially when used in concentrated forms. as recognized by the nfpa, however, only solutions containing more than 40% sodium hypochlorite by weight are considered hazardous oxidizers. solutions less than 40% are classified as a moderate oxidizing hazard (nfpa 430, 2000). household bleach and pool chlorinator solutions are typically stabilized by a significant concentration of lye (caustic soda, naoh) as part of the manufacturing reaction. this additive will by itself cause caustic irritation or burns due to defatting and saponification of skin oils and destruction of tissue. the slippery feel of bleach on skin is due to this process. storage hazards contact of sodium hypochlorite solutions with metals may evolve flammable hydrogen gas. containers may explode when heated due to release of chlorine gas. hypochlorite solutions are corrosive to common container materials such as stainless steel and aluminium. the few compatible metals include titanium (which however is not compatible with dry chlorine) and tantalum. glass containers are safe. some plastics and rubbers are affected too; safe choices include polyethylene (pe), high density polyethylene (hdpe, pe-hd), polypropylene (pp), some chlorinated and fluorinated polymers such as polyvinyl chloride (pvc), polytetrafluoroethylene (ptfe), and polyvinylidene fluoride (pvdf); as well as ethylene propylene rubber, and viton. containers must allow venting of oxygen produced by decomposition over time, otherwise they may burst. reactions with other common products mixing bleach with some household cleaners can be hazardous. sodium hypochlorite solutions, such as liquid bleach, will release toxic chlorine gas when mixed with an acid, such as hydrochloric acid or vinegar. a 2008 study indicated that sodium hypochlorite and organic chemicals (e.g., surfactants, fragrances) contained in several household cleaning products can react to generate chlorinated volatile organic compounds (vocs). these chlorinated compounds are emitted during cleaning applications, some of which are toxic and probable human carcinogens. the study showed that indoor air concentrations significantly increase (8–52 times for chloroform and 1–1170 times for carbon tetrachloride, respectively, above baseline quantities in the household) during the use of bleach containing products. the increase in chlorinated volatile organic compound concentrations was the lowest for plain bleach and the highest for the products in the form of "thick liquid and gel." the significant increases observed in indoor air concentrations of several chlorinated vocs (especially carbon tetrachloride and chloroform) indicate that the bleach use may be a source that could be important in terms of inhalation exposure to these compounds. the

authors suggested that using these cleaning products may significantly increase the cancer risk. in particular, mixing hypochlorite bleaches with amines (for example, cleaning products that contain or release ammonia, ammonium salts, urea, or related compounds and biological materials such as urine) produces chloramines. these gaseous products can cause acute lung injury. chronic exposure, for example, from the air at swimming pools where chlorine is used as the disinfectant, can lead to the development of atopic asthma. bleach can react violently with hydrogen peroxide and produce oxygen gas: h2o2 (aq) + naocl (aq) → nacl (aq) + h2o (aq) + o2 (g) explosive reactions or byproducts can also occur in industrial and laboratory settings when sodium hypochlorite is mixed with diverse organic compounds. limitations in health care the uk's national institute for health and care excellence in october 2008 recommended that dakin's solution should not be used in routine wound care. environmental impact in spite of its strong biocidal action, sodium hypochlorite per se has limited environmental impact, since the hypochlorite ion rapidly degrades before it can be absorbed by living beings. however, one major concern arising from sodium hypochlorite use is that it tends to form persistent chlorinated organic compounds, including known carcinogens, that can be absorbed by organisms and enter the food chain. these compounds may be formed during household storage and use as well during industrial use. for example, when household bleach and wastewater were mixed, 1–2% of the available chlorine was observed to form organic compounds. as of 1994, not all the byproducts had been identified, but identified compounds include chloroform and carbon tetrachloride. the exposure to these chemicals from use is estimated to be within occupational exposure limits.

nc ratio nc ratio the nuclear-cytoplasmic ratio (also variously known as the nucleus:cytoplasm ratio, nucleus-cytoplasm ratio, n:c ratio, or n/c) is a measurement used in cell biology. it is a ratio of the size (i.e., volume) of the nucleus of a cell to the size of the cytoplasm of that cell. nuclear-cytoplasmic ratios. the n:c ratio indicates the maturity of a cell, because as a cell matures the size of its nucleus generally decreases. for example, "blast" forms of erythrocytes, leukocytes, and megakaryocytes start with an n:c ratio of 4:1, which decreases as they mature to 2:1 or even 1:1 (with exceptions for mature thrombocytes and erythrocytes, which are anuclear cells, and mature lymphocytes, which only decrease to a 3:1 ratio and often retain the original 4:1 ratio). an increased n:c ratio is commonly associated with precancerous dysplasia as well as with malignant cells.

splanchnopleuric mesenchyme splanchnopleuric mesenchyme in the anatomy of an embryo, the splanchnopleuric mesenchyme is a structure created during embryogenesis when the lateral mesodermal germ layer splits into two layers. the inner (or splanchnic) layer adheres to the endoderm, and with it forms the splanchnopleure (mesoderm external to the coelom plus the endoderm). splanchnopleuric mesenchymea series of transverse sections through an embryo of the dog. (after bonnet.) section i is the most anterior. in v the neural plate is spread out nearly flat. the series shows the uprising of the neural folds to form the neural canal. a. aortæ. c. intermediate cell mass. ect. ectoderm. ent. entoderm. h, h. rudiments of endothelial heart tubes. in iii, iv, and v the scattered cells represented between the endoderm and splanchnic layer of mesoderm are the vasoformative cells which give origin in front, according to bonnet, to the heart tubes, h; l.p. lateral plate still undivided in i, ii, and iii; in iv and v split into somatic (sm) and splanchnic (sp) layers of mesoderm. mes. mesoderm. p. pericardium. so. primitive segment.transverse section through the region of the heart in a rabbit embryo of nine days. x 80. (kölliker.) j, j. jugular veins. ao. aorta. ph. pharynx. som. somatopleure. bl. proamnion. ect. ectoderm. ent. entoderm. p. pericardium. spl. splanchnopleure. ah. outer wall of heart. ih. endothelial lining of heart. é. septum between heart tubes.detailscarnegie stage9precursorlateral plate mesoderm, endodermgives rise tomesenchymeidentifierslatinmesenchyma splanchnopleuraletemesenchyme_by_e4.0.4.1.0.0.4 e4.0.4.1.0.0.4 anatomical terminology

university of occupational and environmental health japan university of occupational and environmental health japan university of occupational and environmental health japan (産業医科大学, sangyō ika daigaku) is a private university in kitakyushu city, fukuoka prefecture, japan, established in 1978.

tsukamurella sinensis tsukamurella sinensis tsukamurella sinensis is a bacterium from the genus of tsukamurella which has been isolated from a patient from the queen mary hospital in hong kong. tsukamurella sinensis scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: mycobacteriales family: tsukamurellaceae genus: tsukamurella species: t. sinensis binomial name tsukamurella sinensisteng et al. 2016 type strain dsm 100207, jcm 30714, hku51

modicisalibacter modicisalibacter modicisalibacter is a gram-negative, non-spore-forming, aerobic, moderately halophilic and motile genus from the family of halomonadaceae, with one known species (modicisalibacter tunisiensis). modicisalibacter scientific classification domain: bacteria phylum: pseudomonadota class: gammaproteobacteria order: oceanospirillales family: halomonadaceae genus: modicisalibacterben ali gam et al. 2007 species m. tunisiensis

propionivibrio pelophilus propionivibrio pelophilus propionivibrio pelophilus is a bacterium from the genus of propionivibrio. propionibacter pelophilus has been reclassified to propionivibrio pelophilus. propionivibrio pelophilus scientific classification domain: bacteria phylum: pseudomonadota class: betaproteobacteria order: rhodocyclales family: rhodocyclaceae genus: propionivibrio species: p. pelophilus binomial name propionivibrio pelophilusbrune et al. 2002 type strain asp66, cip 106101, dsm 12018 synonyms propionibacter pelophilus

suicide methods suicide methods a suicide method is any means by which a person may choose to end their lives. suicide attempts do not always result in death, and a non-fatal suicide attempt can leave the person with serious physical injuries, long-term health problems, and brain damage. for information on methods of suicide intervention, see suicide prevention. le suicidé (the suicide) by édouard manet, depicting suicide by gunshot suicide social aspects altruistic copycat epidemic legislation philosophy religious views right to die voluntary euthanasia crisis assessment of risk crisis hotline (list) intervention prevention suicide watch types assisted bullying and suicide (list) copycat familicide forced honor jauhar mass murder–suicide prisoner suicide pact internet prayopavesa sallekhana sati self-sacrifice senicide seppuku sokushinbutsu suicide attack vatakkiruttal epidemiology gender differences methods rate by country youth suicide among lgbt youth history list of suicides suicide in antiquity list of suicides in the 21st century in warfare banzai charge kamikaze suicide mission related phenomena suicide attempt locations ideation major depressive disorder non-suicidal self-injury suicide note suicide terminology by country rate by country australia bangladesh cameroon canada china france greenland india iran ireland japan lithuania nepal pakistan romania russia singapore south korea spain sri lanka sweden switzerland ukraine united kingdom united states organizations compassion & choices death with dignity national center dignitas exit international final exit network hemlock society worldwide, three suicide methods predominate with the pattern varying in different countries. these are hanging, poisoning by pesticides, and firearms. some suicides are impulse decisions that may be preventable by removing the means. making common suicide methods less accessible leads to an overall reduction in the number of suicides. some ways to do this include restricting access to pesticides, firearms, and known-used drugs. other important measures are the introduction of policies that address the misuse of alcohol and the treatment of mental disorders. gun-control measures in a number of countries have seen a reduction in suicides and other gun-related deaths. purpose of study the study of suicide methods aims to identify those commonly used, and the groups at risk of suicide; making methods less accessible may be useful in suicide prevention. limiting the availability of means such as pesticides and firearms is recommended by a world health report on suicide and its prevention. the early identification of mental disorders and substance abuse disorders, follow-up care for those who have attempted suicide, and responsible reporting by the media are all seen to be key in reducing the number of deaths by suicide. national suicide prevention strategies are also advocated using a comprehensive and coordinated response to suicide prevention. this needs to include the registration and monitoring of suicides and attempted suicide, breaking figures down by age, sex, and method. such information allows public health resources to focus on the problems that are relevant in a particular place, or for a given population or subpopulation. for instance, if firearms are used in a significant number of suicides in one place, then public health policies there could focus on gun safety, such as keeping guns locked away, and the key inaccessible to at-risk family members. if young people are found to be at increased risk of suicide by overdosing on particular medications, then an alternative class of medication may be prescribed instead, a safety plan and monitoring of medication can be put in place, and parents can be educated about how to prevent the hoarding of medication for a future suicide attempt. media reporting media reporting of the methods used in suicides is "strongly discouraged" by the world health organization, government health agencies, universities, and the associated press among others. detailed descriptions of suicides or the personal characteristics of the person who died contribute to copycat suicides (suicide contagion). dramatic or inappropriate descriptions of individual suicides by mass media has been linked specifically to copycat suicides among teenagers. writing for the new yorker about celebrity suicides, andrew solomon wrote that "you who are reading this are at statistically increased risk of suicide right now." in one study, changes in how news outlets reported suicide reduced suicides by a particular method. media reporting guidelines also apply to "online content including citizen-generated media coverage". the recommendations for reporting on suicide, created by journalists, suicide prevention groups, and internet safety non-profit organizations, encourage linking to resources such as a list of suicide crisis lines and information about risk factors for suicide, and reporting on suicide as a multi-faceted, treatable health issue. method restriction

octosporella (apicomplexa) octosporella (apicomplexa) octosporella is a genus in the phylum apicomplexa. this genus has been poorly studied and little is known about it. species in this genus infect fish, lizards and echidnas. octosporella scientific classification domain: eukaryota (unranked): sar (unranked): alveolata phylum: apicomplexa class: conoidasida subclass: coccidiasina order: eucoccidiorida suborder: eimeriorina family: eimeriidae genus: octosporella species octosporella hystrix octosporella mabuiae octosporella notropis octosporella opeongoensis octosporella sanguinolentae octosporella sasajewunensis history this genus was created in 1942 by ray and raghavachari. taxonomy the type species is octosporella mabuiae. six species are currently recognised. description the oocysts each have 8 sporocysts. each sporocyst has 2 sporozoites.

subdural space subdural space the subdural space (or subdural cavity) is a potential space that can be opened by the separation of the arachnoid mater from the dura mater as the result of trauma, pathologic process, or the absence of cerebrospinal fluid as seen in a cadaver. in the cadaver, due to the absence of cerebrospinal fluid in the subarachnoid space, the arachnoid mater falls away from the dura mater. it may also be the site of trauma, such as a subdural hematoma, causing abnormal separation of dura and arachnoid mater. hence, the subdural space is referred to as "potential" or "artificial" space. subdural spacediagrammatic representation of a section across the top of the skull, showing the membranes of the brain, etc. ("subdural cavity" visible at left.)diagrammatic transverse section of the medulla spinalis and its membranes. (subdural cavity is colored green, labeled at bottom and top right.)detailsidentifierslatinspatium subdurale, cavum subduralemeshd013355ta98a14.1.01.109ta25380fma83803anatomical terminology

teflurane teflurane teflurane (inn, usan, code name abbott 16900) is a halocarbon drug which was investigated as an inhalational anesthetic but was never marketed. its clinical development was terminated due to a high incidence of cardiac arrhythmias in patients, similarly to the cases of halopropane and norflurane. tefluraneclinical dataatc codenoneidentifiers iupac name 2-bromo-1,1,1,2-tetrafluoroethane cas number124-72-1pubchem cid31300chemspider29040unii6492u1o9v8comptox dashboard (epa)dtxsid10861765 chemical and physical dataformulac2hbrf4molar mass180.928 g·mol−13d model (jsmol)interactive image smiles c(c(f)(f)f)(f)br inchi inchi=1s/c2hbrf4/c3-1(4)2(5,6)7/h1hkey:rzxzizdrfqfcta-uhfffaoysa-n chemistry teflurane is 2-bromo-1,1,1,2-tetrafluoroethane, a haloalkane. it is a gas at standard conditions. the compound is chiral.

inferior ganglion inferior ganglion inferior ganglion may refer to: inferior cervical ganglion inferior cervical sympathetic ganglion inferior ganglion of vagus nerve inferior ganglion of glossopharyngeal nerve inferior mesenteric ganglion this article is issued from wikipedia. the text is licensed under creative commons - attribution - sharealike. additional terms may apply for the media files.

brachyspira brachyspira brachyspira is a genus of bacteria classified within the phylum spirochaetota. brachyspira scientific classification domain: bacteria phylum: spirochaetota class: spirochaetia order: brachyspirales family: brachyspiraceae genus: brachyspirahovind-hougen et al. 1983 non foliella non pfeiffer 1855 type species brachyspira aalborgihovind-hougen et al. 1983 species b. aalborgi b. alvinipulli "b. canis" (duhamel et al. 1998) oxberry & hampson 2003 "b. corvi" jansson et al. 2008 b. hampsonii b. hyodysenteriae "b. ibaraki" tachibana et al. 2003 (presumably an 16s-rdna variant of b. aalborgi) b. innocens b. intermedia b. murdochii "b. muridarum" backhans et al. 2010 "b. muris" backhans et al. 2010 b. pilosicoli "b. pulli" stephens and hampson 2001 "b. rattus" backhans et al. 2010 b. suanatina synonyms "anguillina" lee et al. 1993 serpula stanton et al. 1991 non (persson 1801) gray 1821 non linnaeus 1758 serpulina stanton 1992 non zborzevski 1834 brachyspira species include pathogens in pigs, birds, dogs, and humans. b. pilosicoli colonizes millions of humans worldwide, leading to human intestinal spirochaetosis, a chronic, intermittent watery diarrhea vastly underdiagnosed because of the lack of a simple diagnostic tool for clinicians. multiplex qpcrs are promising diagnostic tools, as brachyspira do not grow on conventional media. b. pilosicoli also cause avian spirochetosis: birds might be considered as the natural reservoir. b. hyodysenteriae leads to diarrheal disease in growing pigs worldwide, causing the so-called swine dysentery, typhlocolitis or porcine intestinal spirochaetosis, which contributes to major "production losses" in agrobusiness. some species like b. innocens or b. intermedia seem to be less virulent. phylogeny the currently accepted taxonomy is based on the list of prokaryotic names with standing in nomenclature (lpsn) and national center for biotechnology information (ncbi). 16s rrna based ltp_12_2021 gtdb 07-rs207 by genome taxonomy database brachyspira b. aalborgi b. pilosicoli b. alvinipulli b. hampsonii b. intermedia b. suanatina b. hyodysenteriae b. innocens b. murdochii brachyspira b. aalborgi hovind-hougen et al. 1983 (type sp.) "b. catarrhinii" phillips, la & hampson 2019 b. pilosicoli (trott et al. 1996) ochiai et al. 1998 b. alvinipulli stanton et al. 1998 b. innocens (kinyon and harris 1979) ochiai et al. 1998 b. murdochii (stanton et al. 1997) hampson and la 2006 b. hampsonii mirajkar et al. 2017 b. hyodysenteriae (harris et al. 1972) ochiai et al. 1998 b. intermedia (stanton et al. 1997) hampson and la 2006 b. suanatina mushtaq et al. 2016 evolutionary hypothesis it is interesting to consider that brachyspira could be the missing link between independent gram-negatives and eventually internalized organisms like mitochondria. one could imagine the following phylogenetic pathway: gram-negative free dwellers -> spirochetes attached to cell cytoskeleton and expressing porins creating cytoplasmic bridges and genome complementarity between parasite and mother cell -> rickettsia with full internalization --> permanent intracellular host = mitochondrion pathogenesis of human intestinal spirochetosis (his) brachyspira bacteria have evolved a parasitic lifestyle through genomic reduction (~2.5 to 3.3 mb) compared to other gram negative bacteria (~5 mb). humans become infected through dirty water ingestion, possibly by swimming in waters containing the bacteria or by direct oral exposure to contaminated feces (outdoor tribes, raw egg eaters, slum inhabitants with no sanitation, msm). genome homologies between borellia, treponema and brachyspira imply that brachyspira is expected to: import carbohydrates and short fatty acids (6->3 carbons) for its energetic needs from the colon lumen, swim to and through (viscotaxis) mucin layers thanks to its spiroid shape and flagellum (see film ), attach to colonocytes apically and to each other laterally, thereby creating a continuous layer of bacterial cells which can withstand feces movement in vivo: this is the pathognomonic brush border seen in histology on colonic biopsies it is still to be elucidated if brachyspira is, as borrelia, able to attach to decorin and progress in loose connective tissue and invade other tissues, as for borrelia and syphilis, brachyspira may be able to translocate to seminal vesicles where it would find another niche "outside" the body with mucins to invade, epithelia to attach and glucose available. brachyspira may be a sexually transmittable disease in msm communities via ano-oral route but also penetrative route. once attached apically to the enterocyte, hidden to the natural and acquired immunity by the mucous layer and occupying a niche that other bacteria cannot use, brachyspira most likely expresses at its apex porins allowing it to import from the colonocyte's cytoplasm the amino acids and nucleic acids necessary to replicate. it has also been demonstrated that brachyspira creates an environment which is favorable to its locomotion by upregulating mucin expression: it creates its own niche. clinical manifestations in human medicine publications now tend to point out that brachyspira colonization should not be considered harmless commensalism: chronic diarrhea irritable bowel syndrome acute intestinal pain ulcerative colitis post translocation spirochetemia and cardiogenic shock antibiotic treatment and resistances in human medicine treament with 10 days co-amoxicilline 1g bid + metronidazole 500 tid seems to have very good results on abdominal symptoms. it is advised to administer saccharomyces boulardii once a day during this course of antibiotherapy. doxycycline resistance has been documented and should be avoided. antibiotic treatment and resistance in veterinary medicine veterinary antibiotics used to treat pigs with dysentery due to brachyspira species include the lincosamide lincomycin, the ionophore salinomycin, the quinoxaline carbadox, the pleuromodulins tiamulin and valnemulin, as well as the aminoglycoside gentamicin, an important antibiotic used in humans. brachyspira resistance to the above antibiotics has been increasingly reported. while no clinical and laboratory standards institute (clsi) antimicrobial breakpoints for brachyspira have been established, resistance to the pleuromodulins tiamulin and valnemulin is considered at mic ≥ 2 µg/ml. resistance to pleuromodulins is important, because they are antibiotics of "last resort"; as of 2001, they were the only antibiotics with sufficient minimum inhibitory concentration (mic) values left to treat swine dysentery in sweden, per the national veterinary institute in uppsala. antibiotic resistance varies by geographic region and is not developing as rapidly in u.s. isolates as has been seen in isolates from other countries. tiamulin resistance was first described in 1996 in hungary, and subsequently reported from other countries in europe and asia,. in spain, 7.4% of brachyspira isolates were reported to be venamulin-resistant and 17.6% were tiamulin-resistant in 2009. in sweden, 10-15% of b. pilosicoli isolates between 2002 and 2010 were resistant to tiamulin (mics >4 μg/ml), and a gradual increase in tiamulin mics was seen in b. hyodysenteriae between 1990 and 2003, which has since plateaued. decreased susceptibility to lincomycin, but not to tiamulin was found among polish isolates. in the us, resistance of brachyspira species collected 2008–2010 was common only against lincomycin (80% had mic of 32 or 64), mic's were moderately high against gentamicin, while resistance to valnemulin(4.7%) and tiamulin (3.2% of isolates) was yet uncommon, as reported in the only u.s. study to date, from iowa. the use of pleuromodulins in u.s. food animals is not separately reported in the u.s. food and drug administration's annual animal drug user fee act (adufa) report, "antimicrobials sold or distributed for use in food-producing animals". however, the amount of 190 tonnes of lincosamides used is substantial per adufa; antibiotics used in the u.s. in food animals in 2011 was: ionophores 4,123,259 kg, aminoglycosides 214,895 kg, and lincosamides 190,101 kg. microbiologic identification brachyspira are capable of hemolysis, the degree of which has been used to characterize them, with b. hyodysenteriae showing strong beta hemolysis while b. pilosicoli, b. intermedia, b. murdochii, and b. innocens have been described as weakly hemolytic. however, in a recent study from iowa state university, all (10/10) b. intermedia isolates, 91% (9/11) of brachyspira spp. isolates, and 20% (2/6) of b. pilosicoli isolates from farms in north carolina (36), iowa (23), minnesota (9), nebraska (3), michigan (2), illinois (2), missouri (1), north dakota (1), south dakota (1), and ohio (1), demonstrated strong beta-hemolysis. recently quantitative pcr seems to be a more sensitive way to identify brachyspira, which is globally a very fastidious bacterium to grow. change in ecology in the u.s.a. brachyspira-associated pig disease and isolation of brachyspira species from swine with diarrheal disease largely disappeared from swine herds in the late 1990s and early 2000s, but returned in the mid-2000s for unknown reasons. a 2011 study of isolates from midwestern swine herds described major changes in brachyspira spp frequency and hemolysis, i.e. pathogenicity: the majority of isolated brachyspira species were previously considered minimally pathogenic or commensal, like brachyspira murdochi (27%)or novel/unclassifiable brachyspira species (25%), while only 40.5% of 79 isolates from diseased pigs could be confirmed as the classic pathogens b. hyodysenteriae or brachyspira pilosicoli by pcr. brachyspira species previously capable of weak hemolysis only, like b. intermedia and b. pilosicoli were found to produce strong hemolysis. they were also frequently identified from diseased swine which suggests they are emerging pathogens. a compelling explanation for this change in epidemiology and ecology is selection by the increasing use of antibiotics in pigs (e.g. as growth promoters), since b. murdochii and unclassifiable brachyspira spp. are less susceptible to antimicrobials than the previously established brachyspira pathogens.

2x2 project 2x2 project the 2x2 project is a collaboration of epidemiologists, health science communicators and writers that publishes public health news and analysis. the project is sponsored by the columbia university's department of epidemiology at the mailman school of public health. the 2x2 projectformation2012typepublic health news and analysislegal statusactivepurposehealth news and information that is accessible, accurate and engages the general public.headquartersnew york city, new yorklocationdepartment of epidemiology, mailman school of public health, columbia universityregion served united statesofficial language englisheditor in chiefdr. dana marchparent organizationdepartment of epidemiology at the mailman school of public healthaffiliationscolumbia universitystaff 12websitethe2x2project.org background the 2x2 project went live on september 10, 2012, using the slogan, "health beyond the headlines." the principle behind the 2x2 project's creation is that public health information should be accessible to everyone, not just researchers who read scientific literature. its goal is to share health news and information in clear, compelling language that engages the public. contributors and fellows write stories discussing issues varying from aids activism to brain trauma in professional football players. the project also publishes a weekly roundup of the "best and worst" health news from around the web, ranking reports on a scale from 'fail' to 'ftw' (for the win). the editor in chief is dana march, an assistant professor of epidemiology at columbia's mailman school of public health. according to their website, the 2x2 project wants to bring epidemiology, the science of public health focused on the promotion of population health through disease prevention, out of the ivory tower: "our goal through the 2×2 project is to engage a broader audience—including thought leaders and policy makers from outside the discipline—who can help translate scientific findings into practice." media one of the website's editors, social epidemiologist abdul el-sayed, received media attention from abc news radio when he wrote an open letter to nba player lebron james saying his promotion of coca-cola and mcdonald's in commercials that were targeted largely toward his young fans was contributing to the problem of childhood obesity. el-sayed calculated that james was responsible for selling more than a billion spoons of sugar and illustrated his point using a digitally altered image of the athlete as an obese man. "what if lebron james drank all of the sprite (soft drink) he wants our kids to drink?" the caption read. el-sayed also told abc news at the time that beyoncé should reconsider her deal to become a spokesperson for pepsi. the 2x2 project also contributes regularly to other online media, including huffington post, sense and sustainability, a website on sustainable development, and other non-profit and online media. a weekly feature of the project includes a series on the relationship of pop culture and public health. through a crowd sourced selection of music, the 2x2 project examines the impact of both intentional and unintentional public health messaging found in our favourite pop songs. fellowships the 2x2 project offers fellowships to students interested in hands-on communication of health information. the annual communication in health and epidemiology fellowship (chef) provides education in both theory and practice through formal training in health communication in the form of didactic lectures, workshops, and networking events along with formal work experience.

caldisphaera caldisphaera in taxonomy, caldisphaera is a genus of the caldisphaeraceae. caldisphaera scientific classification domain: archaea kingdom: proteoarchaeota superphylum: tack group phylum: thermoproteota class: thermoprotei order: sulfolobales family: acidilobaceae genus: caldisphaeraitoh, suzuki, sanchez & nakase 2003 type species caldisphaera lagunensisitoh et al. 2003 species "c. dracosis" boyd et al. 2007 c. lagunensis itoh et al. 2003

cross syndrome cross syndrome cross–mckusick–breen syndrome (also known as "cross syndrome", "hypopigmentation and microphthalmia", and "oculocerebral-hypopigmentation syndrome") is an extremely rare disorder characterized by white skin, blond hair with yellow-gray metallic sheen, small eyes with cloudy corneas, jerky nystagmus, gingival fibromatosis and severe intellectual disability and physical retardation.: 867–8 cross syndromeother namesoculocerebral hypopigmentation syndrome, cross typecross syndrome is inherited in an autosomal recessive mannerspecialtyendocrinology it was characterized in 1967.

carditis carditis carditis (pl. carditides) is the inflammation of the heart. carditisspecialtycardiology immunologysymptomsanginacomplicationsdeathcausesbacteria virus 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

tpa-023 tpa-023 tpa-023 (mk-0777) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. it has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. it is a subtype-selective, mixed allosteric modular at the benzodiazepine location on gabaa receptors, where it acts as a partial agonist at the α2 and α3 subtypes, but as a silent antagonist at α1 and α5 subtypes. it has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose. tpa-023clinical dataother namesmk-0777routes ofadministrationby mouthpharmacokinetic datametabolismliverelimination half-life6.7 hoursidentifiers iupac name 7-(1,1-dimethylethyl)-6-(2-ethyl-2h-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolopyridazine cas number252977-51-8 ypubchem cid9908684chemspider8084336unii1fi3ktc550comptox dashboard (epa)dtxsid10179938 chemical and physical dataformulac20h22fn7omolar mass395.442 g·mol−13d model (jsmol)interactive image smiles cc(c)(c)c2=cc3nnc(-c1ccccc1f)n3n=c2occ4ncnn4cc inchi inchi=1s/c20h22fn7o/c1-5-27-17(22-12-23-27)11-29-19-14(20(2,3)4)10-16-24-25-18(28(16)26-19)13-8-6-7-9-15(13)21/h6-10,12h,5,11h2,1-4h3key:qkiwqblntsqoly-uhfffaoysa-n (verify) in human trials on healthy volunteers, tpa-023 was comparable to lorazepam, but had much less side effects on cognition, memory, alertness or coordination. in phase ii trials, the compound was significantly superior to placebo without inducing sedation. the clinical development was halted due to preclinical toxicity (cataract) in long term dosing studies. tpa-023 is well absorbed following oral administration and extensively metabolised by the liver, with a half-life of 6.7 hours. the main enzyme involved in its metabolism is cyp3a4, with some contribution by cyp3a5.

cassidulina (foraminifera) cassidulina (foraminifera) cassidulina is a genus of foraminifera described in the treatise part c. (loeblich & tappan, 1964), as having a free, lenticular test, with central boss of clear calcite on either side. chambers are biserially arranged, enrolled planispirally with a subangular to keeled periphery. the wall is calcareous, hyaline (glassy), optically granular, perforate. the surface is smooth with a polished appearance. sutures are radial to oblique, straight or curved. the aperture is a narrow arched slip at the base of the apertural face, partly closed by an apertural place. (loeblich and tappan 1988) cassidulinatemporal range: u eocene to recent scientific classification domain: eukaryota (unranked): sar (unranked): rhizaria superphylum: retaria phylum: foraminifera order: rotaliida superfamily: cassidulinacea family: cassidulinidae subfamily: cassidulininae genus: cassidulinad'orbigny, 1826 species see text the taxonomy of cassidulina is rather stable, and is included in the cassidulinidae at least as far back as cushman, 1950. related genera include cassidulinella, favocassidulina, globocassidulina, and buriela. cassidulina, itself, is cosmopolitan, with a stratigraphic range extending from the upper eocene to recent. species cassidulina albemariensis mcculloch, 1977 cassidulina alternans yabe & hanzawa, 1925 cassidulina asanoi uchio, 1950 cassidulina bradshawi uchio, 1960 cassidulina braziliensis cushman, 1922 cassidulina caledoniana mcculloch, 1981 cassidulina carapitana hedberg, 1937 † cassidulina carinata silvestri, 1896 cassidulina costatula cushman, 1933 cassidulina cretacea cushman, 1931 cassidulina crustosa saidova, 1975 cassidulina curvata phleger & parker, 1951 cassidulina curvatiformis mcculloch, 1977 cassidulina cushmani r.e. & k.c. stewart, 1930 cassidulina deafueraensis mcculloch, 1977 cassidulina delicatiformis (mcculloch, 1977) cassidulina detierraensis mcculloch, 1977 cassidulina differens mcculloch, 1977 cassidulina elegantissima cushman, 1925 cassidulina globosa hantken, 1865 cassidulina hoodensis mcculloch, 1977 cassidulina inflatiformis mcculloch, 1977 cassidulina insueta cushman, 1947 cassidulina izuensis aoki, 1967 cassidulina kasiwazakiensis husezima & maruhasi, 1944 cassidulina laevigata d'orbigny, 1826 cassidulina limbata cushman & hughes, 1925 cassidulina lineocorrugata mcculloch, 1977 cassidulina lobulata mcculloch, 1977 cassidulina lomitensis galloway & wissler, 1927 cassidulina margareta karrer, 1877 † cassidulina marshallana todd, 1954 cassidulina moluccensis germeraad, 1946 cassidulina monicaniformis mcculloch, 1977 cassidulina monstruosa voloshinova, 1952 † cassidulina neoteretis seidenkrantz, 1995 cassidulina norvangi thalmann, 1952 cassidulina obtusa williamson, 1858 cassidulina oshimai aoki, 1967 cassidulina palmerae bermúdez & acosta, 1940 cassidulina patula cushman, 1933 cassidulina penangensis mcculloch, 1977 cassidulina perumbonata keyzer, 1953 cassidulina pilasensis mcculloch, 1977 cassidulina planata saidova, 1975 cassidulina planulata mcculloch, 1977 cassidulina pulchella d'orbigny, 1839 cassidulina quadrata cushman & hughes, 1925 cassidulina radiata chave, 1987 cassidulina rarilocula cushman, 1933 cassidulina reniforme nørvangi, 1945 cassidulina seca mcculloch, 1977 cassidulina simpsonsbayensis mcculloch, 1977 cassidulina spiniferiformis mcculloch, 1977 cassidulina spiralis natland, 1938 cassidulina striatostoma zheng, 1979 cassidulina subcalifornica drooger, 1953 cassidulina subcarinata uchio, 1960 cassidulina sublaevigata hofker, 1956 cassidulina sublimbata asano & nakamura, 1937 cassidulina subtumida cushman, 1933 cassidulina teretis tappan, 1951 cassidulina tortuosa cushman & hughes, 1925 cassidulina translucens cushman & hughes, 1925 cassidulina tumida natland, 1938 cassidulina velaensis mcculloch, 1981 cassidulina victoriensis collins, 1974 cassidulina vulgata mcculloch, 1977 cassidulina wakasaensis asano & nakamura, 1937 cassidulina weinmanensis mcculloch, 1977 cassidulina wordeni mcculloch, 1977 cassidulina wrangellensis mcculloch, 1977 cassidulina yabei asano & nakamura, 1937

antihistamine antihistamine antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. antihistamines are usually for short-term treatment. chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use. antihistaminedrug classhistamine structureclass identifierspronunciation/ˌæntiˈhɪstəmiːn/ atc coder06mechanism of action • receptor antagonist • inverse agonistbiological targethistamine receptors • hrh1 • hrh2 • hrh3 • hrh4

folliculogenesis folliculogenesis in biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an immature oocyte. folliculogenesis describes the progression of a number of small primordial follicles into large preovulatory follicles that occurs in part during the menstrual cycle. although the process is similar in many animals, this article will deal exclusively with human folliculogenesis. order of changes in ovary.1 - menstruation2 - developing follicle3 - mature follicle4 - ovulation5 - corpus luteum6 - deterioration of corpus luteum contrary to male spermatogenesis, which can last indefinitely, folliculogenesis ends when the remaining follicles in the ovaries are incapable of responding to the hormonal cues that previously recruited some follicles to mature. this depletion in follicle supply signals the beginning of menopause. overview the primary role of the follicle is oocyte support. from the whole pool of follicles a woman is born with, only 0.1% of them will rise ovulation, whereas 99.9% will break down (in a process called follicular atresia). from birth, the ovaries of the human female contain a number of immature, primordial follicles. these follicles each contain a similarly immature primary oocyte. at puberty, clutches of follicles begin folliculogenesis, entering a growth pattern that ends in ovulation (the process where the oocyte leaves the follicle) or in atresia (death of the follicle's granulosa cells). during follicular development, primordial follicles undergo a series of critical changes in character, both histologically and hormonally. first they change into primary follicles and later into secondary follicles. the follicles then transition to tertiary, or antral, follicles. at this stage in development, they become dependent on hormones, particularly fsh which causes a substantial increase in their growth rate. the late tertiary or pre-ovulatory follicle ruptures and discharges the oocyte (that has become a secondary oocyte), ending folliculogenesis. follicle ‘selection’ is the process by which a single ‘dominant’ follicle is chosen from the recruited cohort or wave for preferential growth. it has generally been documented to occur once in the early- to mid- follicular phase of the menstrual cycle, leading to ovulation. diagram of folliculogenesis, starting from pre-antral (late secondary), courtesy ncbi phases of development folliculogenesis is continuous, meaning that at any time the ovary contains follicles in many stages of development. the majority of follicles die and never complete development. a few develop fully to produce a secondary oocyte which is released by rupture of the follicle in a process called ovulation. the growing follicle passes through the following distinct stages that are defined by certain structural characteristics: in a larger perspective, the whole folliculogenesis, from primordial to preovulatory follicle, belongs to the stage of ootidogenesis of oogenesis. stagedescriptionsize primordialdormant, small, only one layer of flat granulosa cellsprimordial follicles are about 0.03–0.05 mm in diameter. primarymitotic cells, cuboidal granulosa cellsalmost 0.1 mm in diameter secondarypresence of theca cells, multiple layers of granulosa cellsthe follicle is now 0.2 mm in diameter early tertiarythe early tertiary follicle is arbitrarily divided into five classes. class 1 follicles are 0.2 mm in diameter, class 2 about 0.4 mm, class 3 about 0.9 mm, class 4 about 2 mm, and class 5 about 5 mm. late tertiaryfully formed antrum, no further cytodifferentiation, no novel progressclass 6 follicles are about 10 mm in diameter, class 7 about 16 mm, and class 8 about 20 mm. it is common for non-dominant follicles to grow beyond class 5, but rarely is there more than one class 8 follicle. preovulatorybuilding growth in estrogen concentration, all other follicles atretic or dead in addition, follicles that have formed an antrum are called antral follicles or graafian follicles. definitions differ in where this shift occurs in the staging given above, with some stating that it occurs when entering the secondary stage, and others stating that it occurs when entering the tertiary stage. until the preovulatory stage, the follicle contains a primary oocyte that is arrested in prophase of meiosis i. during the late preovulatory stage, the oocyte continues meiosis and becomes a secondary oocyte, arrested in metaphase ii. (a) the maturation of a follicle is shown in a clockwise direction proceeding from the primordial follicles. fsh stimulates the growth of a tertiary follicle, and lh stimulates the production of estrogen by granulosa and theca cells. once the follicle is mature, it ruptures and releases the oocyte. cells remaining in the follicle then develop into the corpus luteum. (b) in this electron micrograph of a secondary follicle, the oocyte, theca cells (thecae folliculi), and developing antrum are clearly visible. electron microscopy images primordial at 18–22 weeks post-conception, the cortex of the female ovary (foetal female ovary) contains its peak number of follicles (about 4 to 5 million in the average case, but individual peak populations range from 6 to 7 million). these primordial follicles contain immature oocytes surrounded by flat, squamous granulosa cells (support cells) that are segregated from the oocyte's environment by the basal lamina. they are quiescent, showing little to no biological activity. because primordial follicles can be dormant for up to 50 years in humans, the length of the ovarian cycle does not include this time. the supply of follicles decreases slightly before birth, and to 500,000 by puberty for the average case (populations at puberty range from 25,000 to 1.5 million). by virtue of the "inefficient" nature of folliculogenesis (discussed later), only 400–500 of these follicles will ever reach the preovulatory stage. at menopause, only 1,000 follicles remain. it seems likely that early menopause occurs for women with low populations at birth, and late menopause occurs for women with high populations at birth, but there is as yet no clinical evidence for this. the process by which primordial cells 'wake up' is known as initial recruitment. research has shown that initial recruitment is mediated by the counterbalance of various stimulatory and inhibitory hormones and locally produced growth factors. primary during ovarian follicle activation, the granulosa cells of the primordial follicles change from a flat to a cuboidal structure, marking the beginning of the primary follicle. the oocyte genome is activated and genes become transcribed. rudimentary paracrine signaling pathways that are vital for communication between the follicle and oocyte are formed. both the oocyte and the follicle grow dramatically, increasing to almost 0.1 mm in diameter. primary follicles develop receptors to follicle stimulating hormone (fsh) at this time, but they are gonadotropin-independent until the antral stage. research has shown, however, that the presence of fsh accelerates follicle growth in vitro. a glycoprotein polymer capsule called the zona pellucida forms around the oocyte, separating it from the surrounding granulosa cells.the zona pellucida, which remains with the oocyte after ovulation, contains enzymes that catalyze with sperm to allow penetration. secondary stroma-like theca cells are recruited by oocyte-secreted signals. they surround the follicle's outermost layer, the basal lamina, and undergo cytodifferentiation to become the theca externa and theca interna. an intricate network of capillary vessels forms between these two thecal layers and begins to circulate blood to and from the follicle. the late-term secondary follicle is marked histologically and structurally by a fully grown oocyte surrounded by a zona pellucida, approximately nine layers of granulosa cells, a basal lamina, a theca interna, a capillary net, and a theca externa. the development of the antrum also starts taking place in secondary follicle stage antrum formation the formation of a fluid-filled cavity adjacent to the oocyte called the antrum designates the follicle as an antral follicle, in contrast to a so-called preantral follicle that still lacks an antrum. an antral follicle is also called a graafian follicle. definitions differ as to which stage this shift occurs in, with some designating follicles in the secondary stage as antral, and others designating them as preantral. early tertiary in the tertiary follicle, the basic structure of the mature follicle has formed and no novel cells are detectable. granulosa and theca cells continue to undergo mitotis concomitant with an increase in antrum volume. tertiary follicles can attain a tremendous size that is hampered only by the availability of fsh, which it is now dependent on. under action of an oocyte-secreted morphogenic gradient, the granulosa cells of the tertiary follicle undergo differentiation into four distinct subtypes: corona radiata, surrounding the zona pellucida; membrana, interior to the basal lamina; periantral, adjacent to the antrum and cumulus oophorus, which connects the membrana and corona radiata granulosa cells together. each type of cell behaves differently in response to fsh. theca interna cells express receptors for luteinizing hormone (lh). lh induces the production of androgens by the theca cells, most notably androstendione, which are aromatized by granulosa cells to produce estrogens, primarily estradiol. consequently, estrogen levels begin to rise. late tertiary and preovulatory (the follicular phase of the menstrual cycle) at this point, the majority of the group of follicles that started growth have died. this process of follicle death is known as atresia, and it is characterized by radical apoptosis of all constituent cells and the oocyte. although it is not known what causes atresia, the presence of high concentrations of fsh has been shown to prevent it. a rise in pituitary fsh caused by the disintegration of the corpus luteum at the conclusion of a menstrual cycle precipitates the recruitment of five to seven class 5 follicles to participate in the next cycle. these follicles enter the end of the prior menstrual cycle and transition into the follicular phase of the next one. the selected follicles, called antral follicles, compete with each other for growth-inducing fsh. the pattern of this emergence of a cohort of five to seven antral follicles is debated. there are theories of continuous recruitment of antral follicles, theories of a single recruitment episode at the end of the luteal phase, and more recently there has been evidence for a recruitment model marked by 2 - 3 waves of follicle recruitment and development during the menstrual cycle (only one of which is actually an ovulatory wave). in response to the rise of fsh, the antral follicles begin to secrete estrogen and inhibin, which have a negative feedback effect on fsh. follicles that have fewer fsh-receptors will not be able to develop further; they will show retardation of their growth rate and become atretic. eventually, only one follicle will be viable. this remaining follicle, called the dominant follicle, will grow quickly and dramatically—up to 20 mm in diameter—to become the preovulatory follicle. note: many sources misrepresent the pace of follicle growth, some even suggesting that it takes only fourteen days for a primordial follicle to become preovulatory. actually, the follicular phase of the menstrual cycle means the time between selection of a tertiary follicle and its subsequent growth into a preovulatory follicle. the actual time for development of a follicle varies. the growth of the dominant follicle during the follicular phase is about 1.5 mm per day (±0.1 mm), both in natural cycles and for any dominant follicle developing while taking combined oral contraceptive pill. performing controlled ovarian hyperstimulation leads to a greater recruitment of follicles, growing at about 1.6 mm per day. ovulation and the corpus luteum by the end of the follicular (or proliferative) phase of the thirteenth day of the menstrual cycle, the cumulus oophorus layer of the preovulatory follicle will develop an opening, or stigma, and excrete the oocyte with a complement of cumulus cells in a process called ovulation. in natural cycles, ovulation may occur in follicles that are at least 14 mm. the oocyte is technically still a secondary oocyte, suspended in the metaphase ii of meiosis. it will develop into an ootid, and rapidly thereafter into an ovum (via completion of meiosis ii) only upon fertilization. the oocyte will now travel down one of the fallopian tubes to eventually be discharged through menstruation in the case that it is unfertilized or if it is not successfully implanted in the uterus (if previously fertilized). the ruptured follicle will undergo a dramatic transformation into the corpus luteum, a steroidiogenic cluster of cells that maintains the endometrium of the uterus by the secretion of large amounts of progesterone and minor amounts of estrogen. these two steps, while not part of folliculogenesis, are included for completeness. they are discussed in their entirety by their respective articles, and placed into perspective by the menstrual cycle article. it is recommended that these three topics

be reviewed. hormone function as with most things related to the reproductive system, folliculogenesis is controlled by the endocrine system. five hormones participate in an intricate process of positive and negative feedback to regulate folliculogenesis. they are: gonadotropin-releasing hormone (gnrh) secreted by the hypothalamus two gonadotropins: follicle-stimulating hormone (fsh) luteinizing hormone (lh) estrogen progesterone gnrh stimulates the release of fsh and lh from the anterior pituitary gland that will later have a stimulatory effect on follicle growth (not immediately, however, because only antral follicles are dependent on fsh and lh). when theca cells form in the tertiary follicle the amount of estrogen increases sharply (theca-derived androgen is aromatized into estrogen by the granulosa cells). at low concentration, estrogen inhibits gonadotropins, but high concentration of estrogen stimulates them. in addition, as more estrogen is secreted, more lh receptors are made by the theca cells, inciting theca cells to create more androgen that will become estrogen downstream. this positive feedback loop causes lh to spike sharply, and it is this spike that causes ovulation. following ovulation, lh stimulates the formation of the corpus luteum. estrogen has since dropped to negative stimulatory levels after ovulation and therefore serves to maintain the concentration of fsh and lh. inhibin, which is also secreted by the corpus luteum, contributes to fsh inhibition. progesterone, secreted by the corpus luteum, inhibits the follicular growth and maintains the pregnancy. the endocrine system coincides with the menstrual cycle and goes through thirteen cycles (and thus thirteen lh spikes) during the course of normal folliculogenesis. however, coordinated enzyme signalling and the time-specific expression of hormonal receptors ensures that follicle growth does not become disregulated during these premature spikes. number of follicles "percentage of ovarian reserve related to increasing age. the curve describes the percentage of ovarian reserve remaining at ages from birth to 55 years, based on the adc model. 100% is taken to be the maximum ovarian reserve, occurring at 18–22 weeks post-conception. the percentages apply to all women whose ovarian reserve declines in line with our model (i.e. late and early menopause are associated with high and low peak ngf populations, respectively). we estimate that for 95% of women by the age of 30 years only 12% of their maximum pre-birth ngf population is present and by the age of 40 years only 3% remains. doi:10.1371/journal.pone.0008772.g005"recently, two publications have challenged the idea that a finite number of follicles are set around the time of birth. renewal of ovarian follicles from germline stem cells (originating from bone marrow and peripheral blood) was reported in the postnatal mouse ovary. studies attempting to replicate these results are underway, but a study of populations in 325 human ovaries found no supporting evidence for follicular replenishment. in 2010, researchers at the university of edinburgh determined that by the time women are 30 years old, only 10% of their non-growing follicles (ngfs) remain. at birth, women have all their follicles for folliculogenesis, and they steadily decline until menopause. depletion of the ovarian reserve as women (and mice) age, double-strand breaks accumulate in their primordial follicle reserve. these follicles contain primary oocytes that are arrested in prophase of the first cell division of meiosis. double-strand breaks are accurately repaired during meiosis by searching for, and building off of, the matching strand (termed “homologous recombinational repair”). titus et al. (2013) found that, as humans (and mice) age, expression of four key dna repair genes necessary for homologous recombinational repair declines in oocytes. they hypothesized that dna double-strand break repair is vital for the maintenance of oocyte reserve, and that a decline in efficiency of repair with age plays a key role in the depletion of the ovarian reserve (ovarian aging).

aniseikonia aniseikonia aniseikonia is an ocular condition where there is a significant difference in the perceived size of images. it can occur as an overall difference between the two eyes, or as a difference in a particular meridian. if the ocular image size in both eyes are equal, the condition is known as iseikonia. aniseikoniaspecialtyophthalmology symptomsobjects different sizes in each eyecausescataract surgery, refractive surgery symptoms and signs up to 7% difference in image size is well tolerated. if magnification difference becomes excessive the effect can cause diplopia, suppression, disorientation, eyestrain, headache, and dizziness and balance disorders. asthenopic symptoms alone may occur even if image size difference is less than 7%. causes retinal image size is determined by many factors. the size and position of the object being viewed affects the characteristics of the light entering the system. corrective lenses affect these characteristics and are used commonly to correct refractive error. the optics of the eye including its refractive power and axial length also play a major role in retinal image size. aniseikonia can occur naturally or be induced by the correction of a refractive error, usually anisometropia (having significantly different refractive errors between each eye) or antimetropia (being myopic (nearsighted) in one eye and hyperopic (farsighted) in the other.) meridional aniseikonia occurs when these refractive differences only occur in one meridian (see astigmatism). one cause of significant anisometropia and subsequent aniseikonia has been aphakia. aphakic patients do not have a crystalline lens. the crystalline lens is often removed because of opacities called cataracts. the absence of this lens left the patient highly hyperopic (farsighted) in that eye. for some patients the removal was only performed on one eye, resulting in the anisometropia / aniseikonia. today, this is rarely a problem because when the lens is removed in cataract surgery, an intraocular lens, or iol is left in its place. retinal aniseikonia occur due to forward displacement, stretching or edema of retina. diagnosis a way to demonstrate aniseikonia is to hold a near target (e.g., a pen or a finger) approximately 6 inches directly in front of one eye. the person then closes one eye, and then the other. the person should notice that the target appears larger to the eye that it is directly in front of. when this object is viewed with both eyes, it is seen with a small amount of aniseikonia. the principles behind this demonstration are relative distance magnification (closer objects appear larger) and asymmetrical convergence (the target is not an equal distance from each eye). treatment optical aniseikonia due to anisometropia can be corrected by spectacles, contact lenses or refractive corneal surgeries. spectacle correction is done by changing the optical magnification properties of the auxiliary optics (corrective lenses). the optical magnification properties of spectacle lenses can be adjusted by changing parameters like the base curve, vertex distance, and center thickness. magnification size matched lenses that are used to correct aniseikonia are known as iseikonic lenses. contact lenses may also provide less difference in retinal image size. wider and better field of vision is another benefit of contact lens use. the difference in magnification can also be eliminated by a combination of contact lenses and glasses (creating a weak telescope system). the optimum design solution will depend on different parameters like cost, cosmetic implications, and if the patient can tolerate wearing a contact lens. for reducing aniseikonia, similar to contact lens correction, optical image size difference will be reduced in refractive surgeries also. aniseikonia due to uniocular aphakia is best corrected surgically by intraocular lens implantation. similarly retinal aniseikonia is corrected by treating causative retinal disease. note however that before the optics can be designed, first the aniseikonia should be measured. when the image disparity is astigmatic (cylindrical) and not uniform, images can appear wider, taller, or diagonally different. when the disparity appears to vary across the visual field (field-dependent aniseikonia), as may be the case with an epiretinal membrane or retinal detachment, the aniseikonia cannot fully be corrected with traditional optical techniques like standard corrective lenses. however, partial correction often improves the patient's vision comfort significantly. etymology the word "aniseikonia" is derived from the following greek morphemes: "an" = "not" (as in "anæmia"); "is(o)" = "equal" (as in "isobar"); "eikōn" = "image" (as in "icon").

glutamatergic glutamatergic glutamatergic means "related to glutamate". a glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. examples include excitatory amino acid receptor agonists, excitatory amino acid receptor antagonists, and excitatory amino acid reuptake inhibitors. main article: glutamate

lumbar lumbar in tetrapod anatomy, lumbar is an adjective that means of or pertaining to the abdominal segment of the torso, between the diaphragm and the sacrum. the lumbar region is sometimes referred to as the lower spine, or as an area of the back in its proximity. in human anatomy the five lumbar vertebrae (vertebrae in the lumbar region of the back) are the largest and strongest in the movable part of the spinal column, and can be distinguished by the absence of a foramen in the transverse process, and by the absence of facets on the sides of the body. in most mammals, the lumbar region of the spine curves outward. the actual spinal cord terminates between vertebrae one and two of this series, called l1 and l2. the nervous tissue that extends below this point are individual strands that collectively form the cauda equina. in between each lumbar vertebra a nerve root exits, and these nerve roots come together again to form the largest single nerve in the human body, the sciatic nerve. the sciatic nerve runs through the back of each leg and into the feet. this is why a disorder of the low back that affects a nerve root, such as a spinal disc herniation, can cause pain that radiates along the sciatic nerve (sciatica) down into the foot. there are several muscles in the low back that assist with rotation, flexibility and strength. these muscles are susceptible to injury, especially while lifting heavy objects, or lifting while twisting. a low back muscle strain can be extremely painful but will usually heal within a few days or weeks. the lumbar portion of the spine bears the most body weight and also provides the most flexibility, a combination that makes it susceptible to injury and wear and tear over time. this is why low back pain is so prevalent.

lymphangioleiomyomatosis lymphangioleiomyomatosis lymphangioleiomyomatosis (lam) is a rare, progressive and systemic disease that typically results in cystic lung destruction. it predominantly affects women, especially during childbearing years. the term sporadic lam is used for patients with lam not associated with tuberous sclerosis complex (tsc), while tsc-lam refers to lam that is associated with tsc. lymphangioleiomyomatosis (lam)other nameslymphangiomyomatosis, lamfigure a shows the location of the lungs and airways in the body. the inset image shows a cross-section of a healthy lung. figure b shows a view of the lungs with lam and a collapsed lung (pneumothorax). the inset image shows a cross-section of a lung with lam.specialtypulmonology signs and symptoms the average age of onset is the early-to-mid-30s. exertional dyspnea (shortness of breath) and spontaneous pneumothorax (lung collapse) have been reported as the initial presentation of the disease in 49% and 46% of patients, respectively. diagnosis is typically delayed 5 to 6 years. the condition is often misdiagnosed as asthma or chronic obstructive pulmonary disease. the first pneumothorax, or lung collapse, precedes the diagnosis of lam in 82% of patients. the consensus clinical definition of lam includes multiple symptoms: fatigue cough coughing up blood (rarely massive) chest pain chylous complications arising from lymphatic obstruction, including chylothorax chylous ascites chylopericardium chyloptysis chyluria chyle in vaginal discharge chyle in stool angiomyolipomas (fatty kidney tumors) are present in about 30% of patients with sporadic lam and up to 90% of patients with tsc-lam. angiomyolipomas can sometimes spontaneously bleed, causing pain or low blood pressure. cystic lymphangiomas or lymph nodes with hypodense centers, which mimic necrotizing lymphomas, ovarian or renal cancers, or other malignancies can occur in the retroperitoneum, pelvis or mediastinum. lung destruction in lam is a consequence of diffuse infiltration by neoplastic smooth muscle-like cells that invade all lung structures including the lymphatics, airway walls, blood vessels and interstitial spaces. the consequences of vessel and airway obstruction include chylous fluid accumulations, hemoptysis, airflow obstruction and pneumothorax. the typical disease course displays progressive dyspnea on exertion, spaced by recurrent pneumothoraces and in some patients, chylous pleural effusions or ascites. most people have dyspnea on exertion with daily activities by 10 years after symptom onset. many patients require supplemental oxygen over that interval. genetics lam occurs in two settings: in the disease tuberous sclerosis complex (tsc-lam) and in a sporadic form, in women who do not have tsc (sporadic lam). in both settings, genetic evidence indicates that lam is caused by inactivating or “loss of function” mutations in the tsc1 or tsc2 genes, which were cloned in 1997 and 1993, respectively. the tsc1 gene is located on the long arm of chromosome 9 (9q34) and the tsc2 gene is located on the short arm of chromosome 16 (16p13). tsc-lam occurs in women who have germline mutations in either the tsc1 or the tsc2 gene. sporadic lam is primarily associated with somatic tsc2 gene mutations. germline and somatic mutations in lam include many types of mutations spread across the genes, with no clear “hot spots,” including missense changes, in-frame deletions and nonsense mutations. because of the large size of the genes (together they have more than 60 exons) and because mutations can be located virtually anywhere within the genes, mutation detection is often challenging. on a cellular basis, lam cells carry bi-allelic inactivation of the tsc2 genes, consistent with the “two-hit” tumor suppressor gene model. the second hit event in lam cells is often loss of the chromosomal region containing the wild-type copy of the tsc2 gene; this is referred to as loss of heterozygosity or loh. loh can be detected in microdissected lam cells, in angiomyolipomas and lymph nodes from women with lam, and in circulating lam cells (cells in blood and urine). angiomyolipomas and pulmonary lam cells from women with the sporadic form of lam carry identical mutations in tsc2. this, together with the fact that recurrent lam after lung transplantation carries the same tsc2 mutations as the original lam, has led to the "benign metastasis" hypothesis that lam cells can migrate or metastasize from one site to another. pathophysiology a variable percentage of cells within the lam lesion contain mutational inactivation of the tuberous sclerosis complex (tsc1 or tsc2) tumor suppressor genes. tsc1 mutations cause a less severe clinical phenotype than tsc2 mutations. the discovery of tsc1/2 gene function as negative regulator of the mammalian target of rapamycin complex 1 (mtorc1) led to successful use of rapamycin analog sirolimus in clinical trials and fda approval of sirolimus for treatment of lam. tsc1 and tsc2 form a tumor suppressor complex that regulates mammalian target of rapamycin (mtor) signaling complex by directly controlling the activity of the small gtpase rheb via the gtpase activating protein (gap) domain of tsc2. rheb binds to raptor and controls the activity of mtor complex 1 (mtorc1) that directly phosphorylates p70 s6 kinase (s6k1) and 4e-bp1. mtor forms two physically and functionally distinct multiprotein complexes: the rapamycin-sensitive mtorc1 and the rapamycin-insensitive mtorc2. mtorc1 consists of five proteins including raptor that positively regulate mtor activity. mtorc2 consists of six proteins including mtor and rictor, which defines the activation level of mtorc2 and modulates the assembly of the actin cytoskeleton through rho gtpases, and rac1 is required for mtor activation. in tsc2-null and human lam cells, rho gtpase activity is required for cell adhesion, motility, proliferation and survival. loss of tsc1/tsc2 in lam induces uncontrolled lam cell growth and increases lam cell viability. upregulation of stat1 and stat3 and autophagy are known mediators of lam cell viability and survival. lam cells behave, in many ways, like metastatic tumor cells. lam cells appear to arise from an extrapulmonary source and migrate to the lung. increased lam cell migration and invasiveness is rescued by tsc2 re-expression. the cellular and molecular mechanisms of neoplastic transformation and lung parenchymal destruction by lam cells remain unknown. lung remodeling may be mediated by an imbalance between matrix degrading metalloproteinases (mmps) and their endogenous inhibitors timps. the invasive cell phenotype in lam is associated with timp-3 downregulation and tsc2-dependent upregulation of mmps. clinical and histopathological evidence demonstrate the lymphatic involvement in lam. the prevailing hypothesis is that lam lesions secrete the lymphangiogenic factor vegf-d, recruit lymphatic endothelial cells (lecs) that form lymphatic vessels and induce lung cysts. vegf-d serum levels are increased in lam compared to other cystic lung diseases, including pulmonary langerhans cell histiocytosis, emphysema, sjögren's syndrome, or birt–hogg–dubé syndrome. vegf-d levels correlate with the severity of lam, evaluated as a measure of ct grade (the abundance of chylous effusions and lymphatic involvement). vegf-d is a secreted homodimeric glycoprotein and a member of the vegf family of growth factors, is known for its role in cancer lymphangiogenesis and metastasis. proteolytic processing of vegf-d affects cognate binding to vegfr3. histopathologically, lam lesions are surrounded by cells that stain for vegfr3, the lymphatic vessel endothelial hyaluronan receptor 1 (lyve-1) and podoplanin. vegf-d binds to the receptor protein tyrosine kinases vegfr-2 and vegfr-349 in humans, and to vegfr3 in mice. surprisingly, knock-out of vegf-d in mice has little effect on lymphatic system development. nevertheless, during tumorigenesis vegf-d promotes formation of tumor lymphatic vessels and facilitates metastatic spread of cancer cells. however, little is known about a role of abnormal lymphatics and vegf-d in lam pathogenesis. diagnosis micrograph of lymphangioleiomyomatosis. h&e stain ct scan of the lungs in a patient with lymphangioleiomyomatosis showing numerous thin walled cysts within the lungs lam can come to medical attention in several ways, most of which trigger a chest ct. thin-walled cystic change in the lungs may be found incidentally on ct scans of the heart, chest or abdomen (on the cuts that include lung bases) obtained for other purposes. hrcts of tsc patients reveals that about 20% of women have cystic change by age 20 and about 80% of women have cystic changes after age 40. lam is sometimes revealed by chest ct in patients who present with an apparent primary spontaneous pneumothorax, but more often ct scanning is not ordered (in the united states) until recurrences occur. progressive dyspnea on exertion without the exacerbations and remissions that are characteristic of asthma or copd sometimes prompt a chest ct. a review of the ct by an expert familiar with lam may increase diagnostic accuracy. chylothorax can also bring lam to attention. in some cases, a lam diagnosis can be made with confidence on clinical grounds (without biopsy) in patients with typical cystic changes on high resolution ct scanning of the lung and findings of tuberous sclerosis, angiomyolipoma, lymphangioleiomyoma, chylothorax or serum vegf-d > 800 pg/ml. if none of these clinical features are present, a biopsy may be necessary to make the diagnosis. video-assisted thoracoscopic lung biopsy is the most definitive technique, but transbronchial biopsy has a yield of over 50% and can also be effective. the safety of the latter procedure in patients with diffuse cystic disease and the profusion of cystic change that predicts an informative biopsy are incompletely understood, however. cytology of chylous fluids, aspirated abdominal nodes or lymphatic masses can also be diagnostic. diagram 1 outlines a proposed algorithm for the diagnosis of lam.diagram 1. outlines a proposed algorithm for the diagnosis of lam. ct: computed tomography; tsc: tuberous sclerosis complex; aml: angiomyolipoma; vegf-d: vascular endothelial growth factor d; tbbx: transbronchial biopsy; vats: video-assisted thoracoscopic surgery chest radiograph the chest radiograph may appear relatively normal, even late in the disease, or may suggest hyperinflation only. as the disease progresses, the chest radiograph often demonstrates diffuse, bilateral and symmetric reticulonodular opacities, cysts, bullae or a "honeycomb" (i.e., pseudo fibrotic) appearance. pleural effusion and pneumothorax may be apparent. preservation of lung volumes in the presence of increased interstitial markings is a radiographic hallmark of lam that helps distinguish it from most other interstitial lung diseases, in which alveolar septal and interstitial expansion tend to increase the lung's elastic recoil properties and decreased lung volumes. computed tomography the high-resolution computed tomography (hrct) chest scan is better than the chest radiograph to detect cystic parenchymal disease and is almost always abnormal at the time of diagnosis, even when the chest radiograph and pulmonary function assessments are normal. the typical ct shows diffuse round, bilateral, thin-walled cysts of varying sizes ranging from 1 to 45 mm in diameter. the numbers of cysts varies in lam from a few to almost complete replacement of normal lung tissue. the profusion of cysts tends to be milder in patients with tsc-lam than s-lam, perhaps explained in part because tsc-lam patients typically receive earlier screening. pleural effusions are seen on ct in 12% of patients with s-lam and 6% of patients with tsc-lam. other ct features include linear densities (29%), hilar or mediastinal lymphadenopathy (9%), pneumothorax, lymphangiomyoma, and thoracic duct dilation. ground-glass opacities (12%) suggest the presence of interstitial edema due to lymphatic congestion. in patients with tsc, nodular densities on hrct may represent multifocal micronodular pneumocyte hyperplasia (mmph) made up of clusters of hyperplastic type ii pneumocytes. mmph may be present in males or females with tsc in the presence or absence of lam, but not in patients with s-lam. mmph is not typically associated with physiologic or prognostic consequences, but one case of respiratory failure due to mmph has been reported. ventilation-perfusion scans in one study ventilation-perfusion scans were abnormal in 34 of 35 lam patients. the most common abnormality was nonspecific diffuse heterogeneity, usually grossly matched. these authors also described an “unusual,” “speckling pattern” on the perfusion images in 74% of patients, consisting of “small, often peripheral collections of radioisotope.” positron emission tomography lam and aml lesions do not typically exhibit increased uptake of 18f-fluorodeoxyglucose on positron emission tomography (pet) scanning. other neoplasms (or sources of inflammation) should therefore be considered in known or suspected lam cases in which fdg-pet results are positive. abdominal imaging abnormalities on abdominal imaging, such as renal aml and enlarged lymphatic structures, are also common in lam. fat density within a renal mass is pathognomonic of amls. amls are more prevalent and more frequently bilateral and large in patients with tsc-lam than in patients with s-lam. aml size correlates with the prevalence of pulmonary cysts in patients with tsc. one study ct imaged 256 patients with s-lam and 67 with tsc-lam. renal amls were present in 32% of patients with s-lam and 93% of patients with tsc-lam. hepatic amls were present in

2% of patients with s-lam and 33% of patients with tsc-lam. ascites was uncommon, seen in fewer than 10% of patients with lam. abdominal lymphangiomatosis, often containing both cystic and solid components, were seen in 29% of patients with s-lam and 9% of patients with tsc-lam. central nervous system imaging central nervous system abnormalities, such as cortical or subependymal tubers and astrocytomas, are common in patients with tsc, including those with tsc-lam, but are not found in women with s-lam. moss and associates reported that women with s-lam and tsc-lam may have an increased incidence of meningioma, but the significance of that finding has been challenged. pulmonary function studies pulmonary function testing in patients with lam may be normal or may reveal obstructive, restrictive or mixed patterns. obstructive physiology is the most common abnormality. quality-controlled lung function data were collected prospectively by the nhlbi registry, a five-year study of patients with lam in centers around the united states. spirometry revealed obstructive changes in about 57% of patients and normal results in 34%. restriction, defined as a total lung capacity less than the lower limit of normal, was seen in 11%. hyperinflation was present in about 6%. the average residual volume was 125% of predicted when measured by plethysmography, but was only 103% of predicted determined with gas dilution methods, suggesting significant air trapping in noncommunicating airspaces. approximately 25% of patients with obstructive physiology may demonstrate bronchodilator responsiveness but may be less in more severe obstruction. the obstructive physiologic defect in lam is primarily attributable to airflow obstruction. the earliest change in initial pulmonary function testing in various case series was abnormal gas transfer, as assessed by the diffusing capacity for carbon monoxide (dlco), described in 82% to 97% of patients. it is not unusual for dlco to be reduced out of proportion to forced expiratory volume in 1 second (fev1). reduction in dlco and increase in residual volume are generally considered to be lam's earliest physiologic manifestations. cardiopulmonary exercise testing in a much larger cohort of patients with lam revealed a reduced maximal oxygen consumption (vo2 max) and anaerobic threshold in 217 patients. exercise-induced hypoxemia was found even in patients who did not have resting abnormalities in fev1 and dlco. in most patients, exercise was thought to be ventilation limited, owing to airflow obstruction and increased dead-space ventilation. disease progression is usually accompanied by a progressive obstructive ventilatory defect. decline in fev1 is the most commonly used parameter to monitor disease progression. although resting pulmonary hypertension appears to be unusual in lam, pulmonary arterial pressure often rises with low levels of exercise, related in part to hypoxemia. one study reported an increase in intraparenchymal shunts in dyspneic patients with lam, which may contribute to resting and exercise hypoxemia. pathology grossly, lam lungs are enlarged and diffusely cystic, with dilated air spaces as large as several centimeters in diameter. microscopic examination of the lung reveals foci of smooth muscle-like cell infiltration of the lung parenchyma, airways, lymphatics, and blood vessels associated with areas of thin-walled cystic change. lam lesions often contain an abundance of lymphatic channels, forming an anastomosing meshwork of slit-like spaces lined by endothelial cells. lam cells generally expand interstitial spaces without violating tissue planes but have been observed to invade the airways, the pulmonary artery, the diaphragm, aorta, and retroperitoneal fat, to destroy bronchial cartilage and arteriolar walls, and to occlude the lumen of pulmonary arterioles. there are two major cell morphologies in the lam lesion: small spindle-shaped cells and cuboidal epithelioid cells. lam cells stain positively for smooth muscle actin, vimentin, desmin, and, often, estrogen and progesterone receptors. the cuboidal cells within lam lesions also react with a monoclonal antibody called hmb-45, developed against the premelanosomal protein gp100, an enzyme in the melanogenesis pathway. this immunohistochemical marker is very useful diagnostically, because other smooth muscle-predominant lesions in the lung do not react with the antibody. the spindle-shaped cells of the lam lesion are more frequently proliferating cell nuclear antigen positive than the cuboidal cells, consistent with a proliferative phenotype. compared with cigar-shaped normal smooth muscle cells, spindle-shaped lam cells contain less abundant cytoplasm and are less eosinophilic. estrogen and progesterone receptors are also present in lam lesions, but not in adjacent normal lung tissue. lam lesions express lymphatic markers lyve-1, prox1, podoplanin and vegfr-3. the smooth muscle-like cells of amls are morphologically and immunohistochemically similar to lam cells, including reactivity with antibodies directed against actin, desmin, vimentin, and hmb-45 as well as estrogen and progesterone receptors. unlike the dilated airspaces in emphysema, the cystic spaces found in lam may be partially lined with hyperplastic type ii cells. treatment an fda-approved drug for treatment of lam, the mtor inhibitor sirolimus, is available for stabilization of lung function decline. lung transplant remains the last resort for patients with advanced disease. pneumothorax pneumothoraces in lam patients tend to recur, especially after conservative management such as observation, aspiration or simple tube thoracostomy. over 65% of lam patients develop pneumothorax during the course of their illness, averaging 3.5 pneumothoraces in those who have at least one pneumothorax. the lam foundation pleural consensus group advocated the use of a pleural symphysis procedure with the first pneumothorax, given the greater than 70% chance of recurrence. chemical sclerosis, mechanical abrasion, talc poudrage and pleurectomy have been effective in patients with lam, but mechanical abrasion is preferred for those who may require pulmonary transplantation in the future. about half of lam patients who have undergone transplant have had a prior pleurodesis procedure, and more than 75% of those had had prior bilateral pleurodesis. although pleurodesis is not a contraindication to transplantation, it can result in increased perioperative bleeding. chylothorax chyle does not generally cause pleural inflammation or fibrosis. small stable chylous effusions rarely require intervention once the lam diagnosis is made. shortness of breath may mandate possibly repeated drainage. sirolimus is effective for chylous effusions and most experts believe it should be used as the first line of therapy. imaging the source of the leak with heavy t2-weighted mri or contrast lymphangiography is an advised for refractory effusions. some leaks are amenable to embolization through catheters threaded from groin lymph nodes into the thoracic duct. thoracic duct ligation can be considered, but since thoracic effusions sometimes originate from ascites that are siphoned into the chest by the bellows action of the thorax, it is important to rule out an abdominal source before considering this option. pleural symphysis may be required to prevent nutritional and lymphocyte deficiencies that can result from repeated taps or persistent drainage. chemical pleurodesis is generally an effective therapy for chylothorax, as is mechanical abrasion and talc poudrage. angiomyolipoma renal angiomyolipomas (amls) may require embolization or cauterization for control of bleeding, a complication that is thought to be more common when tumor diameter exceeds 4 cm. the extent of aneurysmal change may determine bleeding risk. serial abdominal imaging should be performed to assess aml size at 6- to 12-month intervals, at least until trends in growth are clear. nephron sparing partial resections may be considered for very large tumors. nephrectomy is sometimes required for tumors with intravascular extension or other reasons, but is rarely the approach of choice for amls that can be managed by less invasive means. everolimus is approved by the us food and drug administration (fda) for aml treatment. lymphangioleiomyoma lymphangioleiomyomatoses are fluid-filled hypodense structures present in the retroperitoneal regions of the abdomen and pelvis in about 30% of lam patients. they generally do not require intervention. biopsy or resection can lead to prolonged leakage. mtor inhibitors are effective at shrinking the size of lymphangioleiomyomatosis, and can lead to total resolution. management-other estrogen-containing medications can exacerbate lam and are contraindicated. agents that antagonize the effects of estrogen have not been proven to be effective for treatment, but no proper trials have been done. a trial of bronchodilators should be considered in lam patients, because up to 17–25% have bronchodilator-responsive airflow obstruction. oxygen should be administered to maintain oxyhemoglobin saturations of greater than 90% with rest, exercise and sleep. bone densitometry should be considered in all patients who are immobilized and/or on antiestrogen therapies, and appropriate therapy instituted for osteoporotic patients. proper attention should be paid to cardiovascular health following natural or induced menopause. immunizations for pneumococcus and influenza should be kept up to date. pulmonary rehabilitation seems to be particularly rewarding in young, motivated patients with obstructive lung disease, but studies to assess this intervention's effect on exercise tolerance, conditioning and quality of life have not been done. medication sirolimus is an mtor inhibitor that stabilizes lung function and improves some measures of life in lam patients. it is approved by the fda for use in lam, based on the results of the multicenter international lam efficacy and safety of sirolimus (miles) trial. miles data supports the use of sirolimus in patients who have abnormal lung function (i.e. fev1<70% predicted). whether the benefits of treatment outweigh the risks for asymptomatic lam patients with normal lung function is not clear, but some physicians consider treatment for declining patients who are approaching the abnormal range for fev1. sirolimus also appears to be effective for the treatment chylous effusions and lymphangioleiomyomatosis. the benefits of sirolimus only persist while treatment continues. the safety of long term therapy has not been studied. potential side effects from mtor inhibitors include swelling in the ankles, acne, oral ulcers, dyspepsia, diarrhea, elevation of cholesterol and triglycerides, hypertension and headache. sirolimus pneumonitis and latent malignancy are more serious concerns, but occur infrequently. sirolimus inhibits wound healing. it is important to stop therapy with the drug for 1–2 weeks before and after elective procedures that require optimal wound healing. precautions must be taken to avoid prolonged sun exposure due to increased skin cancer risk. treatment with another mtor inhibitor, everolimus, was reported in a small, open-label trial to be associated with improvement in fev1 and six-minute walking distance. serum levels of vegf-d and collagen iv were reduced by treatment. adverse events were generally consistent with those known to be associated with mtor inhibitors, although some were serious and included peripheral edema, pneumonia, cardiac failure and pneumocystis jirovecii infection. escalating doses of everolimus were used, up to 10 mg per day; higher than what is typically used clinically for lam. serum vegf-d concentration is useful, predictive and prognostic biomarker. higher baseline vegf-d levels predicts more rapid disease progression and a more robust treatment response. hormonal approaches to treatment have never been tested in proper trials. in the absence of proven benefit, therapy with progesterone, gnrh agonists (e.g., leuprorelin, goserelin) and tamoxifen are not routinely recommended. doxycycline had no effect on the rate of lung function decline in a double blind trial. sirolimus is often effective as first-line management for chylothorax. if chylous leakage or accumulations persist despite treatment, imaging with heavy t2 weighted mri, mri lymphangiography or thoracic duct lymphangiography can be considered. pleural fusion procedures can be considered in refractory cases. prognosis survival estimates vary, dependent on mode of presentation or ascertainment, and have generally trended upward, probably due to earlier recognition through more widespread use of ct scanning. in a recent population-based cohort survey, median survival was found to be 29 years. data from earlier, large case series indicated that 38% to 78% of patients were alive at 8.5 years from the time of disease onset. patients typically develop progressive airflow obstruction. in a cohort of patients in the united kingdom, 10 years after symptom onset, 55% of 77 patients were breathless walking on flat ground and 10% were housebound. the average annual rate of decline in fev1 and dlco in 275 patients studied in a single pulmonary function laboratory at the nhlbi was 75 ± 9 ml, and 0.69 ± 0.07 ml/min/mm hg, respectively. in other series from europe, the rate of decline in fev1 was considerably higher, estimated at approximately 100 to 120 ml/yr. in the miles trial, patients in the placebo group lost 134 cc/yr. there was some evidence in these studies that rate of decline in lung function correlates with initial dlco, with menopausal status and high baseline vegf-d. estimates of median survival vary from 10 to 30 years, depending on whether hospital-based or population-based cohorts are studied. epidemiology lam is almost completely restricted to women. while lung cysts consistent with lam are

reported in some men with tuberous sclerosis, very few of these men develop symptoms. the prevalence of lam is estimated using data from registries and patient groups and is between 3.4 and 7.8/million women. the number of new cases each year is between 0.23 and 0.31/million women/year in the us, uk and switzerland. the variation between countries and between adjacent states in the us, suggest that a significant number of women with lam remain either undiagnosed or their symptoms are attributed to other diseases. adult women with tuberous sclerosis are more likely to develop lam than women without tuberous sclerosis. cohorts of patients with tuberous sclerosis have been screened for lam using ct scanning. in a retrospective study of adults with tuberous sclerosis, ct demonstrated lung cysts in 42% of 95 women and 13% of 91 men. in general, lung cysts were larger and more numerous in women than in men. in a further retrospective study of women with tsc who underwent ct scanning to detect lam, 25% of those in their 20s had lung cysts whereas 80% of women in their 40s were affected, suggesting that the development of lam is age dependent at least in tuberous sclerosis-related lam. although the prevalence of tuberous sclerosis at 1 in 6,000 births is much greater than that of lam, most pulmonary clinics see more cases of sporadic than tuberous sclerosis–lam: probably due to a combination of low levels of screening for lam in tuberous sclerosis and in many, the absence of symptoms. female sex and tuberous sclerosis are the only known risk factors. although use of supplemental estrogen is not associated with development of lam, one study suggested that use of estrogen-containing contraceptive pills was associated with earlier onset. it occurs in more than 30% of women with tuberous sclerosis complex (tsc-lam), a heritable syndrome that is associated with seizures, cognitive impairment and benign tumors in multiple tissues. most lam patients who present for medical evaluation have the sporadic form of the disease (s-lam), however, which is not associated with other manifestations of tuberous sclerosis complex. mild cystic changes consistent with lam have been described in 10–15% of men with tsc, but symptomatic lam in males is rare. sporadic lam occurs exclusively in women, with one published exception to date. both tsc-lam and s-lam are associated with mutations in tuberous sclerosis genes. pregnancy pregnancy has been reported to exacerbate lam in some cases. however, the risk has not been rigorously studied. in a survey of 318 patients who indicated that they had had at least one pregnancy, 163 responded to a second survey focusing on lung collapse. a total of 38 patients reported a pneumothorax with pregnancy, consistent with an incidence of pneumothorax in pregnancy of at least 10% (38 of 318). in one third of patients, the pneumothorax during pregnancy led to the lam diagnosis. pneumothoraces were almost twice as frequent on the right as on the left, and four women presented with bilateral spontaneous pneumothorax. most pneumothoraces took place during the second and third trimesters. this study and others suggest that pregnancy is associated with pleural complications in lam patients. few women with a known lam diagnosis choose to become pregnant and patients in whom lam is diagnosed during pregnancy rarely have baseline pulmonary function tests available, complicating resolution of this question. society the lam foundation was founded in 1995 as a grassroots organization to provide patient advocacy and research funding. today, the lam foundation provides support and education for women with lam and their families, engages doctors and scientists to continue to learn more about the disease, and raises funds for the continued study of lam. it seeks safe and effective treatments, and ultimately a cure, for lymphangioleiomyomatosis. it is headquartered in cincinnati, ohio. in popular culture in "lucky thirteen", the fifth episode of the fifth season of house, spencer (angela gots) was diagnosed with lam, though later it was found to be a case of sjögren's syndrome.

health in ivory coast health in ivory coast the human rights measurement initiative finds that the ivory coast is fulfilling 55.8% of what it should be fulfilling for the right to health based on its level of income. when looking at the right to health with respect to children, the ivory coast achieves 78.5% of what is expected based on its current income. in regards to the right to health amongst the adult population, the country achieves only 62.1% of what is expected based on the nation's level of income. the ivory coast falls into the "very bad" category when evaluating the right to reproductive health because the nation is fulfilling only 26.7% of what the nation is expected to achieve based on the resources (income) it has available. health status historical development of life expectancy in ivory coast malaria in ivory coast, malaria is the leading cause of mortality among children and continues to be the top reason for medical consultations and hospitalizations. there were approximately 2.3 million presumed and confirmed malaria cases in 2015 in children under five years of age reported from health facilities. malaria is endemic throughout ivory coast the entire year, with peaks during the rainy season. the current malaria control strategy in ivory coast aims to reduce malaria morbidity and mortality by increasing the proportion of the population sleeping under an insecticide-treated mosquito net, of pregnant women taking sulfadoxine/pyrimethamine, and of malaria cases which are confirmed and treated in accordance with national guidelines. the strategy includes an emphasis on introducing an integrated approach to community interventions (malaria, pneumonia, and diarrhea) and a more participative and inclusive role for the private sector in combating malaria. hiv/aids according to the cia world factbook, in ivory there are a total of 460,100 people who live with hiv/aids as of 2014. maternal and child health care the 2010 maternal mortality rate per 100,000 births for ivory coast is 470. this is compared with 944.1 in 2008 and 580.3 in 1990. the under 5 mortality rate, per 1,000 births is 121 and the neonatal mortality as a percentage of under 5's mortality is 33. in ivory coast the number of midwives per 1,000 live births is 4 and the lifetime risk of death for pregnant women 1 in 44. about 36% of women have undergone female genital mutilation (as of 2006). diseases and illness caused by hunger there are a lot of disease and illness caused by hunger. ivory coast decided to contain some diseases or illness in their national development plan. these were all problems relating to hunger. whether it is not being able to access the right food or starving from hunger. diseases or illnesses that ivory coast wants to reduce: anemia in women stunting under the age of 5 low birth weight under 5 wasting (deaths) hospitals there were 1,792 medical facilities in the ivory coast in 2019.

pyridostigmine pyridostigmine pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. it is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. it is typically given by mouth but can also be used by injection. the effects generally begin within 45 minutes and last up to 6 hours. not to be confused with physostigmine. pyridostigmineclinical datatrade namesmestinon, othersahfs/drugs.commonographmedlineplusa682229pregnancycategory au: c routes ofadministrationby mouth, intravenousatc coden07aa02 (who) legal statuslegal status uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability7.6 +/- 2.4%elimination half-life1.78 +/- 0.24hrsexcretionkidneyidentifiers iupac name 3--1-methylpyridinium cas number155-97-5 ypubchem cid4991drugbankdb00545 ychemspider4817 yunii19qm69hh21keggd00487 ychemblchembl1115 ycomptox dashboard (epa)dtxsid20165786 chemical and physical dataformulac9h13n2o2molar mass181.215 g·mol−13d model (jsmol)interactive image smiles o=c(oc1ccc(c1)c)n(c)c inchi inchi=1s/c9h13n2o2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7h,1-3h3/q+1 ykey:rvollaqwkvftge-uhfffaoysa-n y (verify) common side effects include nausea, diarrhea, frequent urination, and abdominal pain. more severe side effects include low blood pressure, weakness, and allergic reactions. it is unclear if use in pregnancy is safe for the fetus. pyridostigmine is an acetylcholinesterase inhibitor in the cholinergic family of medications. it works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine. pyridostigmine was patented in 1945 and came into medical use in 1955. it is on the world health organization's list of essential medicines. pyridostigmine is available as a generic medication. medical uses pyridostigmine is used to treat muscle weakness in people with myasthenia gravis or forms of congenital myasthenic syndrome and to combat the effects of curariform drug toxicity. pyridostigmine bromide has been fda approved for military use during combat situations as an agent to be given prior to exposure to the nerve agent soman in order to increase survival. used in particular during the first gulf war, pyridostigmine bromide has been implicated as a causal factor in gulf war syndrome. with pyridostigmine classified as a type of parasympathomimetic, it can be used to treat underactive bladder. pyridostigmine sometimes is used to treat orthostatic hypotension. it may also be of benefit in chronic axonal polyneuropathy. it is also being prescribed 'off-label' for postural tachycardia syndrome as well as complications resulting from ehlers–danlos syndrome. contraindications pyridostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma. side effects common side effects include: sweating diarrhea nausea vomiting abdominal cramps increased salivation tearing increased bronchial secretions constricted pupils facial flushing due to vasodilation erectile dysfunction additional side effects include: muscle twitching muscle cramps and weakness mechanism of action pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the hydrolysis of acetylcholine. like its predecessor neostigmine, it is a quaternary carbamate inhibitor of cholinesterase that does not cross the blood–brain barrier. it carbamylates about 30% of peripheral cholinesterase enzyme, and the carbamylated enzyme eventually regenerates by natural hydrolysis and excess acetylcholine (ach) levels revert to normal. the ach diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing an influx of sodium (na+,) resulting in depolarization. if large enough, this depolarization results in an action potential. to prevent constant stimulation once the ach is released, an enzyme called acetylcholinesterase is present in the endplate membrane close to the receptors on the post synaptic membrane, and quickly hydrolyses ach. names pyridostigmine bromide is available under the trade names mestinon (valeant pharmaceuticals), regonol and gravitor (sun pharma).

national swedish board of health national swedish board of health the national swedish board of health (swedish: medicinalstyrelsen) was a swedish government agency between 1878 and 1968, with responsibility for the health and medical services and the pharmacy services. all the activities in the field of public health in sweden (including medical care) are either operated or controlled by public authorities. public health is under the ministry of health and social affairs, the chief of which is a member of the cabinet. the national swedish board of health was the principal instrument of the state for governing, superintending and promoting the activities and the work of the institutions pertaining to this field. the board supervised the medical personnel, the hospitals and the pharmacies and had the direct control of the state pharmaceutical laboratory, the state institutions for forensic medicine, a unit for mass radiofluorography etc. the national swedish board of health was dissolved in 1968 and became the national board of health and welfare. history the national swedish board of health originated from a corporation association of physicians in stockholm, who first received certain privileges on 16 may 1663 under the name of collegium medicorum (later collegium medicum), which was confirmed and extended in particular by the so-called medical schemes of 30 october 1688. by letters patent on 27 january 1813, the collegium changed to a real administrative government agency under the name of the sundhetskollegium ("health collegium") and initially consisted of 1 chairman, 1 vice chairman, 2 medical councillors (head of divisions) and 6 assessors, and the senior physicians and professors, who then held membership in the collegium medicum for life. according to the instruction issued on 6 december 1815, the sundhetskollegium received the oversight and the board over all that related to the state of health as well as the medical care and the sick care of both the country's inhabitants in general and in the armed forces on land and sea in peace and wartime. as early as 1821, two assessors' offices were abolished, and in 1841 all the other assessors and the vice-chairman, whereas the medical councillors was increased to four. the sundhetskollegium received a far broader activity than collegium medicum. among other things, the obligation to give a statement in forensic purposes, to have control over the veterinary system, the dental and fältskär system, variolation and more, was allowed. however, only in 1876 did the board of directors of the hospital and mental health services (from the serafimerordensgillet, "seraphim order guild") be transferred to the sundhetskollegium. from 1878, the agency name change to the national swedish board of health. the state for the new agency was established on 1 june 1877, and instruction for the same was issued 2 november the same year. minor changes were done over time, the most important of which occurred on 31 december 1900. the national swedish board of health now consists of 1 chairman referred to as director general and 5 medical councillors. the director general and 4 of the medical councillors should be licensed physicians, the fifth medical councillor should be a licensed veterinarian. the staff of the chancellery consisted of 1 secretary, 1 registrar and 3 notaries, and at the accounting office of 2 accountants and 1 treasurer. in addition, the board was assisted by 1 ombudsman and 1 procurator fiscal, 1 chief inspector for mental health care, 1 hospital inspector and 1 architect, and by the necessary number of assistants and temporary officials. for the execution of bacteriological and forensic investigations, the board had at its disposal a state medical institution, the statsmedicinska anstalten, with a bacteriological and a chemical chemistry department. the national swedish board of health exercised the highest oversight of the general health care system in sweden and dealt with matters concerning the state's medical health. the board had insight into everyone who was occupied with the expansion of the medical or pharmaceutical sciences, with the exception of university teachers as such, and acted as the national board of sweden's hospitals and supervised the mental health of the insane in general. in addition, the board had oversight over the hospitals and the cottage hospitals, swimming facilities and other such health centers, as well as the pharmacy system, the midwifery and the fältskär system, as well as the practitioners of the dentistry and physiotherapy activities. the national swedish board of health also had to provide the courts, public and municipal authorities and officials with the information that they wanted and which lie within the area of the board's activities, as well as investigating the forensic issues that arise. finally, the board had to watch over the epidemic care operations and to exercise the highest level of insight into the variolation and the institutions established for it. from 1 july 1963, the national swedish board of health was organized under the ministry of health and social affairs, which was the country's highest administrative body in the field. its task was then to exercise the oversight over the work of the medical staff, the healthcare agencies and the pharmacy and to have the highest management of the state mental hospitals and other institutions. it was organized in nine bureaus. at its side, the national swedish board of health had various advisory councils and committees taking independent decisions. in addition to the national swedish board of health, some other central institutions operated in the area of general health care. the national institute of public health (statens institut för folkhälsan) with the main task of conducting scientific-practical investigations and conducting research activities in the areas of general hygiene, food hygiene and occupational hygiene, and thereby constituting a central investigative body for the food control according to the food charter. the institute also had to conduct some teaching. questions about occupational hygiene were dealt with by the institute of occupational health (arbetsmedicinska institutet). the central board of hospital planning and equipment (centrala sjukvårdsberedningen) had the task to advise on the planning of hospital buildings and their equipment and to work for standardization and rationalization of the hospitals' utensils and operations and the national bacteriological laboratory (statens bakteriologiska laboratorium) with the task of investigating, researching, producing serum, inoculants etc. in the bacteriological, virological and epidemiological fields of human medicine. as of 1 january 1968, the highest administrative body for health and medical care is the national board of health and welfare, which was formed through a merger of the national swedish board of health and the old national board of health and welfare. chairman of the sundhetskollegium 1813–1822: david von schulzenheim 1822–1841: christian ehrenfried von weigel 1841–1849: erik af edholm 1849–1860: carl johan ekströmer 1860–1864: magnus huss 1864–1873: nils johan berlin (acting) 1873–1877: nils johan berlin directors general of the national swedish board of health bror rexed, the last director-general of the national swedish board of health. 1877–1883: nils johan berlin 1883–1898: august almén 1898–1913: klas linroth 1913–1928: bertil buhre 1928–1935: nils hellström 1935–1952: axel höjer 1952–1967: arthur engel 1967–1968: bror rexed

human alphaherpesvirus 2 human alphaherpesvirus 2 human alphaherpesvirus 2 (hhv-2) is a species of virus in the genus simplexvirus, subfamily alphaherpesvirinae, family herpesviridae, and order herpesvirales. human alphaherpesvirus 2 transmission electron micrograph of herpes simplex virus virus classification (unranked): virus realm: duplodnaviria kingdom: heunggongvirae phylum: peploviricota class: herviviricetes order: herpesvirales family: herpesviridae genus: simplexvirus species: human alphaherpesvirus 2 synonyms herpes simplex virus evolution human alphaherpesvirus 2 can be divided into two clades: one is globally distributed and the other is mostly limited to sub saharan africa. pathology

whole health action management whole health action management whole health action management (wham) is a peer-led intervention to facilitate self-management to reach whole health goals through peer coaching and support groups. it is a method of utilizing the power of peer support to support healthcare delivery, and to counter high rates of chronic physical health conditions such as diabetes, heart disease and obesity among those with behavioral health diagnoses. the samhsa-hrsa center for integrated health solutions (cihs) developed the wham program to "encourage increased resiliency, wellness, and self-management of health and behavioral health among people with mental illnesses, substance use disorders, and chronic physical health conditions." wham is based on a collaboration between peers and health professionals. peers encourage clients to get routine health exams and comply with physician recommendations. they frequently discuss common health behaviors such as smoking cessation, physical exercise, stress reduction, and healthy food choices. wham is very similar to peer support whole health and resiliency wham facilitators participate in a 2-day training, which then enables them to train others in wham. participants receive six hours of instruction spread over up to three weeks, followed by an 8-week wham-focused support group as they work toward, achieve, and maintain whole health goals. history the wham model is based on a pilot program led by larry fricks when in 2013 georgia received federal approval to bill medicaid for peer support specialists to provide health coaching., as well as the earlier the chronic disease self-management health and recovery peer (harp) program. since then, fricks and his colleagues have trained peers across the country on the model under the name whole health action management. in 2014, spanish-language resources were produced to implement the program in the latino community. presbyterian healthcare services in new mexico has trained over 600 of their staff in wham. between 2012 and 2016, over 3000 people have been trained in the wham model. content wham facilitators are trained in teaching skills to promote health factors utilizing a "whole health perspective". these skills target the following health factors: stress management healthy eating physical activity restful sleep service to others support network optimism based on positive expectations cognitive skills to avoid negative thinking spiritual beliefs and practices a sense of meaning and purpose peer specialists are trained to help clients: elicit the relaxation response to manage stress engage in cognitive skills to avoid negative thinking identify strengths and supports in 10 science-based whole health and resiliency factors know basic whole health screenings and prepare for them participate in peer support to create new health behavior write a concise and achievable whole health goal and weekly action plans as part of a person-centered planning process use shared decision-making skills and tools for engaging with doctors

ileum ileum the ileum (/ˈɪliəm/) is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. in fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum. its main function is to absorb vitamin b12, bile salts, and whatever products of digestion that were not absorbed by the jejunum. ileumsmall intestinethe cecal fossa. the ileum and cecum are drawn backward and upward.detailsprecursormidgutarteryileal arteriesveinileal veinsnerveceliac ganglia, vagusidentifierslatinileummeshd007082ta98a05.6.04.001ta22959fma7208anatomical terminology major parts of thegastrointestinal tract upper gastrointestinal tract mouth esophagus stomach duodenum lower gastrointestinal tract small intestine jejunum ileum large intestine sigmoid colon rectum anus

bigeminy bigeminy bigeminy is a cardiac arrhythmia in which there is a single ectopic beat, or irregular heartbeat, following each regular heartbeat. most often this is due to ectopic beats occurring so frequently that there is one after each sinus beat, or normal heartbeat. the two beats are figuratively similar to two twins (hence bi- + gemini). for example, in ventricular bigeminy, a sinus beat is shortly followed by a premature ventricular contraction (pvc), a pause, another normal beat, and then another pvc. in atrial bigeminy, the other "twin" is a premature atrial contraction (pac). bigeminyother namesbigeminibigeminy as seen on a 12 lead ecgpronunciationbigeminy /baɪˈdʒɛmɪni/ or bigemini /baɪˈdʒɛmɪˌnaɪ/ cause after any pvc there is a pause that can lead to the development of bigeminy. a pvc wavefront often encounters a refractory av node that does not conduct the wavefront retrograde. thus the atrium is not depolarized and the sinus node is not reset. since the sinus p wave to pvc interval is less than the normal p–p interval, the interval between the pvc and the next p wave is prolonged to equal the normal time elapsed during two p–p intervals. this is called a "compensatory" pause. the pause after the pvc leads to a longer recovery time, which is associated with a higher likelihood of myocardium being in different stages of repolarization. this then allows for re-entrant circuits and sets up the ventricle for another pvc after the next sinus beat. the constant interval between the sinus beat and pvc suggests a reentrant etiology rather than spontaneous automaticity of the ventricle. premature atrial contractions by contrast do not have a compensatory pause, since they reset the sinus node, but atrial or supraventricular bigeminy can occur. if the pacs are very premature, the wavefront can encounter a refractory av node and not be conducted. this can be mistaken for sinus bradycardia if the pac is buried in the t wave since the pac will reset the sa node and lead to a long p–p interval. diagnosis a rhythm strip demonstrating bigeminy simple ecg of a supraventricular bigeminy rule of bigeminy when the atrial rhythm is irregular (as in atrial fibrillation or sinus arrythmia) the presence of bigeminy depends on the length of the p–p interval and happens more frequently with a longer interval. as with post pvc pauses, a longer p–p interval leads to a higher chance of re-entrant circuits and thus pvcs. the term "rule of bigeminy" is used to refer to the dependence of bigeminy on the ventricular cycle length in irregular rhythms. classification there can be similar patterns depending on the frequency of abnormal beats. if every other beat is abnormal, it is described as bigeminal. if every third beat is aberrant, it is trigeminal; every fourth would be quadrigeminal. typically, if every fifth or more beat is abnormal, the aberrant beat would be termed occasional. bigeminy is contrasted with couplets, which are paired abnormal beats. groups of three abnormal beats are called triplets and are considered a brief run of non-sustained ventricular tachycardia (nsvt), and if the grouping lasts for more than 30 seconds, it is ventricular tachycardia (vt). treatment in people without underlying heart disease and who do not have any symptoms, bigeminy in itself does not require any treatment. if it does become symptomatic, beta-blockers can be used to try and suppress ventricular ectopy. class i and iii agents are generally avoided as they can provoke more serious arrhythmias.

glutamate hypothesis of schizophrenia glutamate hypothesis of schizophrenia the glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms of schizophrenia linked to glutamatergic signaling. the hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via nmda receptors. while thought to be more proximal to the root causes of schizophrenia, it does not negate the dopamine hypothesis, and the two may be ultimately brought together by circuit-based models. the development of the hypothesis allowed for the integration of the gabaergic and oscillatory abnormalities into the converging disease model and made it possible to discover the causes of some disruptions. like the dopamine hypothesis, the development of the glutamate hypothesis developed from the observed effects of mind-altering drugs. however, where dopamine agonists can mimic positive symptoms with significant risks to brain structures during and after use, nmda antagonists mimic some positive and negative symptoms with less brain harm, when combined with a gabaa activating drug. likely, both dopaminergic and glutaminergic abnormalities are implicated in schizophrenia, from a profound alteration in the function of the chemical synapses, as well as electrical synaptic irregularities. these form a portion of the complex constellation of factors, neurochemically, psychologically, psychosocially, and structurally, which result in schizophrenia. the role of heteromer formation alteration in the expression, distribution, autoregulation, and prevalence of specific glutamate heterodimers alters relative levels of paired g proteins to the heterodimer-forming glutamate receptor in question. namely: 5ht2a and mglu2 form a dimer which mediates psychotomimetic and entheogenic effects of psychedelics; as such this receptor is of interest in schizophrenia. agonists at either constituent receptor may modulate the other receptor allosterically; e.g. glutamate-dependent signaling via mglu2 may modulate 5ht2a-ergic activity. equilibrium between mglu2/5ht2a is altered against tendency towards of psychosis by neuroleptic-pattern 5ht2a antagonists and mglu2 agonists; both display antipsychotic activity. ampa, the most widely distributed receptor in the brain, is a tetrameric ionotropic receptor; alterations in equilibrium between constituent subunits are seen in mglu2/5ht2a antagonist (antipsychotic) administration- glur2 is seen to be upregulated in the pfc while glur1 downregulates in response to antipsychotic administration. reelin abnormalities may also be involved in the pathogenesis of schizophrenia via a glutamate-dependent mechanism. reelin expression deficits are seen in schizophrenia, and reelin enhances expression of ampa and nmda alike. as such deficits in these two ionotropic glutamate receptors may be partially explained by altered reelin cascades. neuregulin 1 deficits may also be involved in glutaminergic hypofunction as nrg1 hypofunction leads to schizophrenia-pattern behavior in mice; likely due in part to reduced nmda signaling via src suppression. the role of synaptic pruning various neurotrophic factors dysregulate in schizophrenia and other mental illnesses, namely bdnf; expression of which is lowered in schizophrenia as well as in major depression and bipolar disorder. bdnf regulates in an ampa-dependent mechanism - ampa and bdnf alike are critical mediators of growth cone survival. ngf, another neurotrophin involved in maintenance of synaptic plasticity is similarly seen in deficit. dopaminergic excess, classically understood to result in schizophrenia, puts oxidative load on neurons; leading to inflammatory response and microglia activation. similarly, toxoplasmosis infection in the cns (positively correlated to schizophrenia) activates inflammatory cascades, also leading to microglion activation. the lipoxygenase-5 inhibitor minocycline has been seen to be marginally effective in halting schizophrenia progression. one of such inflammatory cascades' downstream transcriptional target, nf-κb, is observed to have altered expression in schizophrenia. in addition, cb2 is one of the most widely distributed glial cell-expressed receptors, downregulation of this inhibitory receptor may increase global synaptic pruning activity. while difference in expression or distribution is observed, when the cb2 receptor is knocked out in mice, schizophreniform behaviors manifest. this may deregulate synaptic pruning processes in a tachyphlaxis mechanism wherein immediate excess cb2 activity leads to phosphorylation of the receptor via girk, resultant in b-arrestin-dependent internalization and subsequent trafficking to the proteasome for degradation. the role of endogenous antagonists alterations in production of endogenous nmda antagonists such as agmatine and kynurenic acid have been shown in schizophrenia. deficit in nmda activity produces psychotomimetic effects, though it remains to be seen if the blockade of nmda via these agents is causative or actually mimetic of patterns resultant from monoaminergic disruption. ampa, the most widely distributed receptor in the brain, mediates long term potentiation via activity-dependent modulation of ampa density. glur1 subunit-containing ampa receptors are ca2+ permeable while glur2/3 subunit-positive receptors are nearly impermeable to calcium ions. in the regulated pathway, glur1 dimers populate the synapse at a rate proportional to nmda-ergic ca2+ influx. in the constitutative pathway, glur2/3 dimers populate the synapse at a steady state. this forms a positive feedback loop, where a small trigger impulse degating nmda from mg2+ pore blockade results in calcium influx, this calcium influx then triggers trafficking of glur1-containing(ca2+ permeable) subunits to the psd, such trafficking of glur1-positive ampa to the postsynaptic neuron allows for upmodulation of the postsynaptic neuron's calcium influx in response to presynaptic calcium influx. robust negative feedback at nmda from kynurenic acid, magnesium, zinc, and agmatine prevents runaway feedback. misregulation of this pathway would sympathetically dysregulate ltp via disruption of nmda. such alteration in ltp may play a role, specifically in negative symptoms of schizophrenia, in creation of more broad disruptions such as loss of brain volume; an effect of the disease which antidopaminergics actually worsen, rather than treat. the role of a7 nicotinic anandamide, an endocannabinoid, is an a7 nicotinic antagonist. cigarettes, consumed far out of proportion by schizophrenics, contain nornitrosonicotine; a potent a7 antagonist. this may indicate a7 pentameter excess as a causative factor, or possibly as a method of self-medication to combat antipsychotic side effects. cannabidiol, a faah inhibitor, increases levels in anandamide and may have antipsychotic effect; though results are mixed here as anandamide also is a cannabinoid and as such displays some psychotomimetic effect. however, a7 nicotinic agonists have been indicated as potential treatments for schizophrenia, though evidence is somewhat contradictory there is indication a7 nachr is somehow involved in the pathogenesis of schizophrenia. the role of 5-ht this deficit in activation also results in a decrease in activity of 5-ht1a receptors in the raphe nucleus. this serves to increase global serotonin levels, as 5-ht1a serves as an autoreceptor. the 5-ht1b receptor, also acting as an autoreceptor, specifically within the striatum, but also parts of basal ganglia then will inhibit serotonin release. this disinhibits frontal dopamine release. the local deficit of 5-ht within the striatum, basal ganglia, and prefrontal cortex causes a deficit of excitatory 5-ht6 signalling. this could possibly be the reason antipsychotics sometimes are reported to aggravate negative symptoms as antipsychotics are 5ht6 antagonists this receptor is primarily gabaergic, as such, it causes an excess of glutamatergic, noradrenergic, dopaminergic, and cholinergic activity within the prefrontal cortex and the striatum. an excess of 5-ht7 signaling within the thalamus also creates too much excitatory transmission to the prefrontal cortex. combined with another critical abnormality observed in those with schizophrenia: 5-ht2a dysfunction, this altered signalling cascade creates cortical, thus cognitive abnormalities. 5-ht2a allows a link between cortical, thus conscious, and the basal ganglia, unconscious. axons from 5-ht2a neurons in layer v of the cerebral cortex reach the basal ganglia, forming a feedback loop. signalling from layer v of the cerebral cortex to the basal ganglia alters 5-ht2c signalling. this feedback loop with 5-ht2a/5-ht2c is how the outer cortex layers can exert some control over our neuropeptides, specifically opioid peptides, oxytocin and vasopressin. this alteration in this limbic-layer v axis may create the profound change in social cognition (and sometimes cognition as a whole) that is observed in schizophrenia. however, genesis of the actual alterations is a much more complex phenomena. the role of inhibitory transmission the cortico-basal ganglia-thalamo-cortical loop is the source of the ordered input necessary for a higher level upper cortical loop. feedback is controlled by the inhibitory potential of the cortices via the striatum. through 5-ht2a efferents from layer v of the cortex transmission proceeds through the striatum into the globulus pallidus internal and substantia nigra pars compacta. this core input to the basal ganglia is combined with input from the subthalamic nucleus. the only primarily dopaminergic pathway in this loop is a reciprocal connection from the substantia nigra pars reticulata to the striatum. dopaminergic drugs such as dopamine releasing agents and direct dopamine receptor agonists create alterations in this primarily gabaergic pathway via increased dopaminergic feedback from the substantia nigra pars compacta to the striatum. however, dopamine also modulates other cortical areas, namely the vta; with efferents to the amygdala and locus coeruleus, likely modulating anxiety and paranoid aspects of psychotic experience. as such, the glutamate hypothesis is probably not an explanation of primary causative factors in positive psychosis, but rather might possibly be an explanation for negative symptoms. dopamine hypothesis of schizophrenia elaborates upon the nature of abnormal lateral structures found in someone with a high risk for psychosis. altered signalling cascades again, thalamic input from layer v is a crucial factor in the functionality of the human brain. it allows the two sides to receive similar inputs, thus be able to perceive the same world. in psychosis, thalamic input loses much of its integrated character: hyperactive core feedback loops overwhelm the ordered output. this is due to excessive d2 and 5-ht2a activity. this alteration in input to the top and bottom of the cortex. the altered 5-ht signal cascade enhances the strength of excitatory thalamic input from layer v. this abnormality, enhancing the thalamic-cortical transmission cascade versus the corticostriatal control, creates a feedback loop, resulting in abnormally strong basal ganglia output. the root of psychosis (experiences that cannot be explained, even within their own mind) is when basal ganglia input to layer v overwhelms the inhibitory potential of the higher cortexies resulting from striatal transmission. when combined with the excess prefrontal, specifically orbitofrontal transmission, from the hippocampus, this creates a brain prone to falling into self reinforcing belief. however, given a specific environment, a person with this kind of brain (a human) can create a self-reinforcing pattern of maladaptive behavior, from the altered the layer ii/iii and iii/i axises, from the disinhibited thalamic output. rationality is impaired, primarily as response to the deficit of oxytocin and excess of vasopressin from the abnormal 5ht2c activity. frontal cortex activity will be impaired, when combined with excess da activity: the basis for the advancement of schizophrenia, but it is also the neurologic mechanism behind many other psychotic diseases as well.. heredation of schizophrenia may even be a result of conspecific "refrigerator parenting" techniques passed on though generations. however, the genetic component is the primary source of the neurological abnormalities which leave one prone to psychological disorders. specifically, there is much overlap between bipolar disorder and schizophrenia, and other psychotic disorders. psychotic disorder is linked to excessive drug use, specifically dissociatives, psychedelics, stimulants, and marijuana. treatment alterations in serine racemase indicate that the endogenous nmda agonist d-serine may be produced abnormally in schizophrenia and that d-serine may be an effective treatment for schizophrenia. schizophrenia is now treated by medications known as antipsychotics (or neuroleptics) that typically reduce dopaminergic activity because too much activity has been most strongly linked to positive symptoms, specifically persecutory delusions. dopaminergic drugs do not induce the characteristic auditory hallucinations of schizophrenia. dopaminergic drug abuse such as abuse of methamphetamine may result in a short lasting psychosis or provocation of a longer psychotic episode that may include symptoms of auditory hallucinations. the typical antipsychotics are known to have significant risks of side effects that can increase over time, and only show clinical effectiveness in reducing positive symptoms. additionally, although newer atypical antipsychotics can have less affinity for dopamine receptors and still reduce positive symptoms, do not significantly reduce negative symptoms. a 2006 systematic review investigated the efficacy of glutamatergic drugs as add-on: outcome findings in words findings in numbers quality of evidence global outcome relapse(add-on glycine)at present it is not possible to be confident about the effect of adding the glutamatergic drug to standard antipsychotic treatment. data supporting this finding are very limited.rr 0.39 (0.02 to 8.73)very low service outcome hospital admission(add-on glycine)there is no clarity about the benefits or otherwise of adding a glutamatergic drug to antipsychotics for outcomes about how much hospital/community care is used. data supporting this finding are based on low quality evidence. rr 2.63 (0.12

to 59.40)low mental state no clinically significant improvement(add-on glycine)there is no evidence of clear advantage of using add-on glutamatergic to standard antipsychotic medication. these findings are based on data of low quality.rr 0.92 (0.79 to 1.08)low adverse effects constipation(add-on glycine or d-serine)there is no clarity from very limited data. additional glutamatergic could cause constipation or help avoid it. data are very limited. rr 0.61 (0.06 to 6.02)very low insomnia(add-on glycine or d-serine)additional glutamatergic may help or cause insomnia - it is not clear from the very limited data.rr 0.61 (0.13 to 2.84)very low missing outcomes quality of lifethis outcome was not reported in any studies psychotomimetic glutamate antagonists ketamine and pcp were observed to produce significant similarities to schizophrenia. ketamine produces more similar symptoms (hallucinations, withdrawal) without observed permanent effects (other than ketamine tolerance). both arylcyclohexamines have some(um) affinity to d2 and as triple reuptake inhibitors. pcp is representative symptomatically, but does appear to cause brain structure changes seen in schizophrenia. although unconfirmed, dizocilpine discovered by a team at merck seems to model both the positive and negative effects in a manner very similar to schizophreniform disorders. possible glutamate based treatment an early clinical trial by eli lilly of the drug ly2140023 has shown potential for treating schizophrenia without the weight gain and other side-effects associated with conventional anti-psychotics. a trial in 2009 failed to prove superiority over placebo or olanzapine, but lilly explained this as being due to an exceptionally high placebo response. however, eli lilly terminated further development of the compound in 2012 after it failed in phase iii clinical trials. this drug acts as a selective agonist at metabotropic mglur2 and mglur3 glutamate receptors (the mglur3 gene has previously been associated with schizophrenia). studies of glycine (and related co-agonists at the nmda receptor) added to conventional anti-psychotics have also found some evidence that these may improve symptoms in schizophrenia. animal models research done on mice in early 2009 has shown that when the neuregulin-1\erbb post-synaptic receptor genes are deleted, the dendritic spines of glutamate neurons initially grow, but break down during later development. this led to symptoms (such as disturbed social function, inability to adapt to predictable future stressors) that overlap with schizophrenia. this parallels the time delay for symptoms setting in with schizophrenic humans who usually appear to show normal development until early adulthood. disrupted in schizophrenia 1 is a gene that is disrupted in schizophrenia. notes and references lisman je, coyle jt, green rw, et al. 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dorsal nucleus of vagus nerve dorsal nucleus of vagus nerve the dorsal nucleus of vagus nerve (or posterior nucleus of vagus nerve or dorsal vagal nucleus or nucleus dorsalis nervi vagi or nucleus posterior nervi vagi) is a cranial nerve nucleus for the vagus nerve in the medulla that lies ventral to the floor of the fourth ventricle. it mostly serves parasympathetic vagal functions in the gastrointestinal tract, lungs, and other thoracic and abdominal vagal innervations. these functions include, among others, bronchoconstriction and gland secretion. the cell bodies for the preganglionic parasympathetic vagal neurons that innervate the heart reside in the nucleus ambiguus. dorsal nucleus of vagus nervenuclei of origin of cranial motor nerves schematically represented; lateral view. ("x" visible at bottom center.)#9 is vagus nerve and nucleusdetailsidentifierslatinnucleus posterior nervi vagi, nucleus dorsalis nervi vagineuronames755neurolex idbirnlex_2642ta98a14.1.04.229ta26013fma54585anatomical terms of neuroanatomy additional cell bodies are found in the nucleus ambiguus, which give rise to the branchial efferent motor fibers of the vagus nerve (cn x) terminating in the laryngeal, pharyngeal muscles, and musculus uvulae. additional images section of the medulla oblongata at about the middle of the olive. the cranial nerve nuclei schematically represented; dorsal view. motor nuclei in red; sensory in blue. dorsal motor nucleus of vagus with lewy body pathology

european bank for induced pluripotent stem cells european bank for induced pluripotent stem cells the european bank for induced pluripotent stem cells (ebisc) is a non-profit induced pluripotent stem cell (ipsc) biorepository and service provider with central facilities in germany and the united kingdom. ebisc was set up between 2014 and 2017 by a consortium that represented researchers, clinicians and industry stakeholders. a second phase of the project runs between 2019 and 2022 with the aim of consolidating ebisc as a not-for-profit, self-sustainable ipsc bank and service provider. the initiative is funded by the european commission and the european federation of pharmaceutical industries and associations under the innovative medicines initiative. the european bank for induced pluripotent stem cells performs collection, banking, quality control and distribution of ipsc lines for research purposes. ebisc’s stated goal is to supply academic, non-profit and commercial researchers with quality-controlled, disease-relevant ipsc lines, data and other services. it also seeks to promote the international standardisation of ipsc banking practices and to act as a central hub that ensures the sustainability and accessibility of ipsc lines generated by different research organisations. ipsc lines generated externally can be deposited into ebisc for storage, banking, quality control and distribution. catalogue and facilities in february 2020, the ebisc catalogue contained ipsc lines representing diseases and conditions such as alzheimer’s disease, frontotemporal dementia, parkinson's disease, huntington’s disease, dravet syndrome, bardet-biedl syndrome, depression and pain, diabetes mellitus, eye diseases and heart disease. these ipsc lines have been deposited into ebisc by academic institutions and non-profit and commercial organisations internationally. this includes lines generated within research projects such as stembancc, hipsci, imi-adapted, crack it badips and crack it untangle. the ebisc bank is run by two central facilities: the main distributor of ebisc cell lines, the european collection of authenticated cell cultures in the uk, and the ‘mirror bank’ storing duplicates of all deposited lines long-term, established by the fraunhofer institute for biomedical engineering (ibmt) in germany. all ebisc lines are distributed by the european collection of authenticated cell cultures operated by public health england.

francisella tularensis francisella tularensis francisella tularensis is a pathogenic species of gram-negative coccobacillus, an aerobic bacterium. it is nonspore-forming, nonmotile, and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. it is a fastidious, facultative intracellular bacterium, which requires cysteine for growth. due to its low infectious dose, ease of spread by aerosol, and high virulence, f. tularensis is classified as a tier 1 select agent by the u.s. government, along with other potential agents of bioterrorism such as yersinia pestis, bacillus anthracis, and ebola virus. when found in nature, francisella tularensis can survive for several weeks at low temperatures in animal carcasses, soil, and water. in the laboratory, f. tularensis appears as small rods (0.2 by 0.2 µm), and is grown best at 35–37 °c. francisella tularensis francisella tularensis bacteria (blue) infecting a macrophage (yellow) scientific classification domain: bacteria phylum: pseudomonadota class: gammaproteobacteria order: thiotrichales family: francisellaceae genus: francisella species: f. tularensis binomial name francisella tularensis(mccoy and chapin 1912)dorofe'ev 1947 history this species was discovered in ground squirrels in tulare county, california in 1911. bacterium tularense was soon isolated by george walter mccoy (1876–1952) of the us plague lab in san francisco and reported in 1912. in 1922, edward francis (1872–1957), a physician and medical researcher from ohio, discovered that bacterium tularense was the causative agent of tularemia, after studying several cases with symptoms of the disease. later, it became known as francisella tularensis, in honor of the discovery by francis. the disease was also described in the fukushima region of japan by hachiro ohara in the 1920s, where it was associated with hunting rabbits. in 1938, soviet bacteriologist vladimir dorofeev (1911–1988) and his team recreated the infectious cycle of the pathogen in humans, and his team was the first to create protection measures. in 1947, dorofeev independently isolated the pathogen that francis discovered in 1922. hence it is commonly known as francisella dorofeev in former soviet countries. classification three subspecies (biovars) of f. tularensis are recognised (as of 2020): f. t. tularensis (or type a), found predominantly in north america, is the most virulent of the four known subspecies, and is associated with lethal pulmonary infections. this includes the primary type a laboratory strain, schus4. f. t. holarctica (also known as biovar f. t. palearctica or type b) is found predominantly in europe and asia, but rarely leads to fatal disease. an attenuated live vaccine strain of subspecies f. t. holarctica has been described, though it is not yet fully licensed by the food and drug administration as a vaccine. this subspecies lacks the citrulline ureidase activity and ability to produce acid from glucose of biovar f. t. palearctica. f. t. mediasiatica, is found primarily in central asia; little is currently known about this subspecies or its ability to infect humans. additionally, f. novicida has sometimes previously been classified as f. t. novicida. it was characterized as a relatively nonvirulent francisella; only two tularemia cases in north america have been attributed to the organism, and these were only in severely immunocompromised individuals. pathogenesis f. tularensis has been reported in invertebrates including insects and ticks, and vertebrates such as birds, amphibians, reptiles, fish and mammals, including humans. human infection is often caused by vectors, particularly ticks but also mosquitos, deer flies and horse-flies. direct contact with infected animals or carcasses is another source. important reservoir hosts include lagomorphs (e.g. rabbits), rodents, galliform birds and deer. infection via fomites (objects) is also important. human-to-human transmission has not been demonstrated. f. tularensis can survive for weeks outside a mammalian host and has been found in water, grassland, and haystacks. aerosols containing the bacteria may be generated by disturbing carcasses due to brush cutting or lawn mowing; as a result, tularemia has been referred to as "lawnmower disease". epidemiological studies have shown a positive correlation between occupations involving the above activities and infection with f. tularensis. human infection with f. tularensis can occur by several routes. portals of entry are through blood and the respiratory system. the most common occurs via skin contact, yielding an ulceroglandular form of the disease. inhalation of bacteria, particularly biovar f. t. tularensis, leads to the potentially lethal pneumonic tularemia. while the pulmonary and ulceroglandular forms of tularemia are more common, other routes of inoculation have been described and include oropharyngeal infection due to consumption of contaminated food or water, and conjunctival infection due to inoculation at the eye. lifecycle f. tularensis is a facultative intracellular bacterium that is capable of infecting most cell types, but primarily infects macrophages in the host organism. entry into the macrophage occurs by phagocytosis and the bacterium is sequestered from the interior of the infected cell by a phagosome. f. tularensis then breaks out of this phagosome into the cytosol and rapidly proliferates. eventually, the infected cell undergoes apoptosis, and the progeny bacteria are released in a single "burst" event to initiate new rounds of infection. virulence factors a tularemia lesion on the dorsal skin of a hand the virulence mechanisms for f. tularensis have not been well characterized. like other intracellular bacteria that break out of phagosomal compartments to replicate in the cytosol, f. tularensis strains produce different hemolytic agents, which may facilitate degradation of the phagosome. a hemolysin activity, named nlya, with immunological reactivity to escherichia coli anti-hlya antibody, was identified in biovar f. t. novicida. acid phosphatase acpa has been found in other bacteria to act as a hemolysin, whereas in francisella, its role as a virulence factor is under vigorous debate. f. tularensis contains type vi secretion system (t6ss), also present in some other pathogenic bacteria. it also contains a number of atp-binding cassette (abc) proteins that may be linked to the secretion of virulence factors. f. tularensis uses type iv pili to bind to the exterior of a host cell and thus become phagocytosed. mutant strains lacking pili show severely attenuated pathogenicity. the expression of a 23-kd protein known as iglc is required for f. tularensis phagosomal breakout and intracellular replication; in its absence, mutant f. tularensis cells die and are degraded by the macrophage. this protein is located in a putative pathogenicity island regulated by the transcription factor mgla. f. tularensis, in vitro, downregulates the immune response of infected cells, a tactic used by a significant number of pathogenic organisms to ensure their replication is (albeit briefly) unhindered by the host immune system by blocking the warning signals from the infected cells. this downmodulation of the immune response requires the iglc protein, though again the contributions of iglc and other genes are unclear. several other putative virulence genes exist, but have yet to be characterized for function in f. tularensis pathogenicity. genetics like many other bacteria, f. tularensis undergoes asexual replication. bacteria divide into two daughter cells, each of which contains identical genetic information. genetic variation may be introduced by mutation or horizontal gene transfer. the genome of f. t. tularensis strain schu4 has been sequenced. the studies resulting from the sequencing suggest a number of gene-coding regions in the f. tularensis genome are disrupted by mutations, thus create blocks in a number of metabolic and synthetic pathways required for survival. this indicates f. tularensis has evolved to depend on the host organism for certain nutrients and other processes ordinarily taken care of by these disrupted genes. the f. tularensis genome contains unusual transposon-like elements resembling counterparts that normally are found in eukaryotic organisms. phylogenetics much of the known global genetic diversity of f. t. holarctica is present in sweden. this suggests this subspecies originated in scandinavia and spread from there to the rest of eurosiberia. use as a biological weapon

bentracimab bentracimab bentracimab is a monoclonal antibody medication which has been shown in phase one and two clinical trials to function as a reversal agent for the anti–blood clotting drug ticagrelor (which acts as a p2y12 inhibitor and is sold under the brand name brilinta among others). it is under investigation for use in major, life-threatening bleeding in patients being treated with ticagrelor. it is not commercially available. bentracimabmonoclonal antibodytypefab fragmentsourcehumantargetticagrelor, ar-c124910xx (the active metabolite)clinical dataother namespb2452, medi2452routes ofadministrationintravenous infusionatc codenonelegal statuslegal status investigational identifierscas number2260568-31-6pubchem sid405226665drugbankdb16659unii1tbm83qr9skeggd11799chemical and physical dataformulac2095h3240n560o674s12molar mass47440.93 g·mol−1

alaskapox virus alaskapox virus alaskapox virus is a species of the orthopoxvirus genus, first documented in 2015 in the united states state of alaska. as of 2022, there are four known cases of illness caused by the virus, all of which occurred in fairbanks north star borough, with none resulting in hospitalization or death. alaskapox virus virus classification (unranked): virus realm: varidnaviria kingdom: bamfordvirae phylum: nucleocytoviricota class: pokkesviricetes order: chitovirales family: poxviridae genus: orthopoxvirus species: alaskapox virus discovery in july 2015, a woman visited a clinic in fairbanks, alaska, with lesions that were confirmed to contain an orthopox virus but did not match any known members of the genus. subsequent genetic analysis established that the woman, who recovered, had been infected with a novel orthopox virus. the name alaskapox virus was proposed after full analysis of its genome was published in 2019. subsequent cases in 2020, the alaska department of health and social services announced the second known infection of alaskapox in another fairbanks woman. two additional cases were identified in the fairbanks area in the summer of 2021. all four known cases were mild, not requiring hospitalization. all known cases have occurred in fairbanks north star borough, but it is possible that other infections have occurred elsewhere. signs and symptoms in the identified cases, alaskapox virus causes small lesions on the skin that heal after a few weeks, according to the alaska department of health and social services, but the first known patient indicated the lesion took six months to fully resolve. other reported symptoms include joint or muscle pain and swollen lymph nodes. transmission transmission of the virus to humans is hypothesized to be via small animals, though it is not yet clear specifically how this occurs. as of 2021, there was not established evidence of transmission among humans.

heritability of autism heritability of autism the heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic. autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether autism spectrum disorder (asd) is explained more by multigene interactions or by rare mutations with major effects. early studies of twins estimated the heritability of autism to be more than 90%; in other words, that 90% of the differences between autistic and non-autistic individuals are due to genetic effects. this however may be an overestimate: new twin data and models with structural genetic variation are needed. when only one identical twin is autistic, the other often has learning or social disabilities. for adult siblings, the likelihood of having one or more features of the broader autism phenotype might be as high as 30%, much higher than the likelihood in controls. genetic linkage analysis has been inconclusive; many association analyses have had inadequate power. for each autistic individual, mutations in more than one gene may be implicated. mutations in different sets of genes may be involved in different autistic individuals. there may be significant interactions among mutations in several genes, or between the environment and mutated genes. by identifying genetic markers inherited with autism in family studies, numerous candidate genes have been located, most of which encode proteins involved in neural development and function. however, for most of the candidate genes, the actual mutations that increase the likelihood for autism have not been identified. typically, autism cannot be traced to a mendelian (single-gene) mutation or to single chromosome abnormalities such as fragile x syndrome or 22q13 deletion syndrome. deletion (1), duplication (2) and inversion (3) are all chromosome abnormalities that have been implicated in autism. the large number of autistic individuals with unaffected family members may result from copy number variations (cnvs)—spontaneous alterations in the genetic material during meiosis that delete or duplicate genetic material. sporadic (non-inherited) cases have been examined to identify candidate genetic loci involved in autism. a substantial fraction of autism may be highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome. although the fraction of autism traceable to a genetic cause may grow to 30–40% as the resolution of array cgh improves, several results in this area have been described incautiously, possibly misleading the public into thinking that a large proportion of autism is caused by cnvs and is detectable via array cgh, or that detecting cnvs is tantamount to a genetic diagnosis. the autism genome project database contains genetic linkage and cnv data that connect autism to genetic loci and suggest that every human chromosome may be involved. it may be that using autism-related subphenotypes instead of the diagnosis of autism per se may be more useful in identifying susceptible loci. twin studies twin studies are a helpful tool in determining the heritability of disorders and human traits in general. they involve determining concordance of characteristics between identical (monozygotic or mz) twins and between fraternal (dizygotic or dz) twins. possible problems of twin studies are: (1) errors in diagnosis of monozygocity, and (2) the assumption that social environment sharing by dz twins is equivalent to that of mz twins. a condition that is environmentally caused without genetic involvement would yield a concordance for mz twins equal to the concordance found for dz twins. in contrast, a condition that is completely genetic in origin would theoretically yield a concordance of 100% for mz pairs and usually much less for dz pairs depending on factors such as the number of genes involved and assortative mating. an example of a condition that appears to have very little if any genetic influence is irritable bowel syndrome (ibs), with a concordance of 28% vs. 27% for mz and dz pairs respectively. an example of a human characteristics that is extremely heritable is eye color, with a concordance of 98% for mz pairs and 7–49% for dz pairs depending on age. identical twin studies put autism's heritability in a range between 36% and 95.7%, with concordance for a broader phenotype usually found at the higher end of the range. autism concordance in siblings and fraternal twins is anywhere between 0 and 23.5%. this is more likely 2–4% for classic autism and 10–20% for a broader spectrum. assuming a general-population prevalence of 0.1%, the risk of classic autism in siblings is 20- to 40-fold that of the general population. notable twin studies have attempted to shed light on the heritability of autism. a small scale study in 1977 was the first of its kind to look into the heritability of autism. it involved 10 dz twins and 11 mz twins in which at least one twin in each pair showed infantile autism. it found a concordance of 36% in mz twins compared to 0% for dz twins. concordance of "cognitive abnormalities" was 82% in mz pairs and 10% for dz pairs. in 12 of the 17 pairs discordant for autism, a biological hazard was believed to be associated with the condition. a 1979 case report discussed a pair of identical twins concordant for autism. the twins developed similarly until the age of 4, when one of them spontaneously improved. the other twin, who had had infrequent seizures, remained autistic. the report noted that genetic factors were not "all important" in the development of twins. in 1985, a study of twins enrolled with the ucla registry for genetic studies found a concordance of 95.7% for autism in 23 pairs of mz twins, and 23.5% for 17 dz twins. in a 1989 study, nordic countries were screened for cases of autism. eleven pairs of mz twins and 10 of dz twins were examined. concordance of autism was found to be 91% in mz and 0% in dz pairs. the concordances for "cognitive disorder" were 91% and 30% respectively. in most of the pairs discordant for autism, the autistic twin had more perinatal stress. a british twin sample was reexamined in 1995 and a 60% concordance was found for autism in mz twins vs. 0% concordance for dz. it also found 92% concordance for a broader spectrum in mz vs. 10% for dz. the study concluded that "obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors." a 1999 study looked at social cognitive skills in the general-population of children and adolescents. it found "poorer social cognition in males", and a heritability of 0.68 with higher genetic influence in younger twins. in 2000, a study looked at reciprocal social behavior in general-population identical twins. it found a concordance of 73% for mz, i.e. "highly heritable", and 37% for dz pairs. a 2004 study looked at 16 mz twins and found a concordance of 43.75% for "strictly defined autism". neuroanatomical differences (discordant cerebellar white and grey matter volumes) between discordant twins were found. the abstract notes that in previous studies 75% of the non-autistic twins displayed the broader phenotype. another 2004 study examined whether the characteristic symptoms of autism (impaired social interaction, communication deficits, and repetitive behaviors) show decreased variance of symptoms among monozygotic twins compared to siblings in a sample of 16 families. the study demonstrated significant aggregation of symptoms in twins. it also concluded that "the levels of clinical features seen in autism may be a result of mainly independent genetic traits." an english twin study in 2006 found high heritability for autistic traits in a large group of 3,400 pairs of twins. one critic of the pre-2006 twin studies said that they were too small and their results can be plausibly explained on non-genetic grounds. sibling studies a study of 99 autistic probands which found a 2.9% concordance for autism in siblings, and between 12.4% and 20.4% concordance for a "lesser variant" of autism. a study of 31 siblings of autistic children, 32 siblings of children with developmental delay, and 32 controls. it found that the siblings of autistic children, as a group, "showed superior spatial and verbal span, but a greater than expected number performed poorly on the set-shifting, planning, and verbal fluency tasks." a 2005 danish study looked at "data from the danish psychiatric central register and the danish civil registration system to study some risk factors of autism, including place of birth, parental place of birth, parental age, family history of psychiatric disorders, and paternal identity." it found an overall prevalence rate of roughly 0.08%. prevalence of autism in siblings of autistic children was found to be 1.76%. prevalence of autism among siblings of children with asperger syndrome or pdd was found to be 1.04%. the risk was twice as high if the mother had been diagnosed with a psychiatric disorder. the study also found that "the risk of autism was associated with increasing degree of urbanisation of the child's place of birth and with increasing paternal, but not maternal, age." a study in 2007 looked at a database containing pedigrees of 86 families with two or more autistic children and found that 42 of the third-born male children showed autistic symptoms, suggesting that parents had a 50% chance of passing on a mutation to their offspring. the mathematical models suggest that about 50% of autistic cases are caused by spontaneous mutations. the simplest model was to divide parents into two risk classes depending on whether the parent carries a pre-existing mutation that causes autism; it suggested that about a quarter of autistic children have inherited a copy number variation from their parents. other family studies a 1994 study looked at the personalities of parents of autistic children, using parents of children with down syndrome as controls. using standardized tests it was found that parents of autistic children were "more aloof, untactful and unresponsive" compared to parents whose children did not have autism. a 1997 study found higher rates of social and communication deficits and stereotyped behaviors in families with multiple-incidence autism. autism was found to occur more often in families of physicists, engineers and scientists. 12.5% of the fathers and 21.2% of the grandfathers (both paternal and maternal) of children with autism were engineers, compared to 5% of the fathers and 2.5% of the grandfathers of children with other syndromes. other studies have yielded similar results. findings of this nature have led to the coinage of the term "geek syndrome". a 2001 study of brothers and parents of autistic boys looked into the phenotype in terms of one current cognitive theory of autism. the study raised the possibility that the broader autism phenotype may include a "cognitive style" (weak central coherence) that can confer information-processing advantages. a study in 2005 showed a positive correlation between repetitive behaviors in autistic individuals and obsessive-compulsive behaviors in parents. another 2005 study focused on sub-threshold autistic traits in the general population. it found that correlation for social impairment or competence between parents and their children and between spouses is about 0.4. a 2005 report examined the family psychiatric history of 58 subjects with asperger syndrome (as) diagnosed according to dsm-iv criteria. three (5%) had first-degree relatives with as. nine (19%) had a family history of schizophrenia. thirty five (60%) had a family history of depression. out of 64 siblings, 4 (6.25%) were diagnosed with as. according to a 2022 study held on 86 mother-child dyads across 18 months, "prior maternal depression didn’t predict child behavior problems later." twinning risk it has been suggested that the twinning process itself is a risk factor in the development of autism, presumably due to perinatal factors. however, three large-scale epidemiological studies have refuted this idea. these studies took place in california, sweden, and australia. one study done in western australia, utilized the maternal and child health research database that houses birth records for all infants born, including infants and later children diagnosed with autism spectrum disorder. during this study, the population analyzed for the incidence of autism spectrum disorder was restricted to those children with birth years between 1980 and 1995. the focus was on the incidence of autism spectrum disorder in the twin population in comparison to the non twin population. the following two studies, explored

the risk of autism spectrum disorder in the twin population. the conclusion that the twinning process alone is not a risk factor was drawn. in these studies the data exemplified that both mz twins will have autism spectrum disorder, but only one of the dz twins will have autism spectrum disorder with an incidence rate of 90% in mz twins compared to 0% in dz twins. the high symmetry in mz twins can explain the high symmetry of autism spectrum disorder in mz twins outcome compared to dz twins and non twin siblings. proposed models

palaeococcus ferrophilus palaeococcus ferrophilus palaeococcus ferrophilus is a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney. it cells are irregular cocci and motile with multiple polar flagella. palaeococcus ferrophilus scientific classification domain: archaea kingdom: euryarchaeota phylum: euryarchaeota class: thermococci order: thermococcales family: thermococcaceae genus: palaeococcus species: p. ferrophilus binomial name palaeococcus ferrophilustakai et al. 2000 paleococcus was the third genus within euryarchaeota to be described in the literature. these organisms prefer to use elemental sulfur as an electron acceptor, but they can also use ferrous oxide.

ventrolateral preoptic nucleus ventrolateral preoptic nucleus the ventrolateral preoptic nucleus (vlpo), also known as the intermediate nucleus of the preoptic area (ipa), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animals. the brain's sleep-promoting nuclei (e.g., the vlpo, parafacial zone, nucleus accumbens core, and lateral hypothalamic mch neurons), together with the ascending arousal system which includes components in the brainstem, hypothalamus and basal forebrain, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states. the vlpo is active during sleep, particularly during non-rapid eye movement sleep (nrem sleep), and releases inhibitory neurotransmitters, mainly gaba and galanin, which inhibit neurons of the ascending arousal system that are involved in wakefulness and arousal. the vlpo is in turn innervated by neurons from several components of the ascending arousal system. the vlpo is activated by the endogenous sleep-promoting substances adenosine and prostaglandin d2. the vlpo is inhibited during wakefulness by the arousal-inducing neurotransmitters norepinephrine and acetylcholine. the role of the vlpo in sleep and wakefulness, and its association with sleep disorders – particularly insomnia and narcolepsy – is a growing area of neuroscience research. ventrolateral preoptic nucleusthe vlpo is located at the anterior of the hypothalamus. it is also called the intermediate nucleus of the preoptic areadetailspart ofpreoptic nucleusidentifiersacronym(s)vlpo or ipaneuronames3122anatomical terms of neuroanatomy structure at least 80% of neurons in the vlpo that project to the ascending arousal system are gabaergic (neurons that produce gaba). in vitro studies in rats have shown that many neurons in the vlpo that are inhibited by norepinephrine or acetylcholine are multipolar triangular shaped cells with low threshold spikes. these triangular multipolar neurons exist in two sub-populations in the vlpo: type 1 – inhibited by serotonin. type 2 – excited by serotonin and adenosine. as adenosine accumulates during wakefulness it is likely that type 2 cells play a role in sleep induction. the remaining third of neurons in the vlpo are excited by norepinephrine. their role is unclear. function sleep/wakefulness schematic representation of the flip-flop switch hypothesis in the early 20th century, constantin von economo noted that humans who had encephalitis with lesions in the anterior hypothalamus had insomnia, and proposed a sleep-promoting influence from that area. animal studies in the mid-20th century in rats and cats confirmed that very large lesions in the preoptic area and basal forebrain resulted in insomnia but did not identify the cell group that was responsible. in 1996, sherin and colleagues reported the presence of a cell group in the vlpo that expresses cfos (a protein often found in neurons that have recently been active) during sleep, and that these neurons contain the inhibitory neurotransmitters gaba and galanin. these same neurons were found to innervate components of the ascending arousal system, including the tuberomammillary nucleus (tmn) and other components of the lateral hypothalamus; the raphe nuclei; the locus coeruleus (lc); the pedunculopontine (ppt) and laterodorsal tegmental nuclei (ldt); and the parabrachial nucleus (pb). more recent studies using opto- or chemogenetic activation of vlpo neurons have confirmed that they promote sleep. the sleep-promoting effects of the vlpo neurons is thought to be due to release of gaba and possibly galanin that suppresses firing of arousal system neurons. as the vlpo is also inhibited by neurotransmitters released by components of the arousal systems, such as acetylcholine and norepinephrine, a current theory has proposed that the vlpo and the arousal system form a "flip-flop" circuit. this term from electrical engineering denotes a circuit in which mutual inhibition means that each component of the circuit, as it turns on, turns the other off, resulting in rapid transitions from one state (wake or sleep) to the other, with minimal time in transition states. this theory has been used to create mathematical models that explain much of the wake-sleep behavior in animals, including in pathological states and responses to drugs. orexin neurons in the posterior lateral hypothalamus potentiate neurons in the ascending arousal system and help stabilize the brain in the waking state (and consolidated wakefulness, which builds up homeostatic sleep drive, helps stabilize the brain during later sleep). the loss of orexin neurons in the disorder narcolepsy destabilizes the wake-sleep switch, resulting in overwhelming sleep episodes during the waking day, as well as more frequent awakenings from sleep at night. circadian rhythm there is a strong circadian rhythm of sleep in mammals. the “master clock” for circadian rhythms in mammals is the suprachiasmatic nucleus (scn). the scn has little if any projection directly to the vlpo neurons. instead, they project strongly to the adjacent subparaventricular zone, which in turn contains inhibitory gabaergic neurons that innervate the dorsomedial nucleus of the hypothalamus. lesions of the dorsomedial nucleus almost completely eliminate the circadian rhythm of sleep. gabaergic neurons in the dorsomedial nucleus innervate the vlpo, and glutamatergic neurons innervate the lateral hypothalamus, suggesting that the dorsomedial nucleus mainly promotes wakefulness during the active period (daytime for humans). clinical significance insomnia elderly human patients with more galanin neurons in their intermediate nucleus (the human equivalent of the vlpo galanin neurons in rodents) have better, more continuous sleep. a reduced number of vlpo neurons is associated with more fragmented sleep (more awakenings throughout the night). lesions in the vlpo in rats results in 50-60% decrease in nrem sleep time and prolonged insomnia. more recent research suggests that stress-induced insomnia could be due to an imbalance of input to arousal system and vlpo neurons. sedative/hypnotic drugs many sedative/hypnotic drugs act by binding to and potentiating gaba-a receptors. these include older drugs such as ethanol, chloral hydrate and barbiturates, as well as newer benzodiazepines and "non-benzodiazepine" drugs (such as zolpidem, which bind to the same receptor but have a different chemical configuration), and even anesthetics such as propofol and isoflurane. as the vlpo inputs to the arousal system use this same receptor, these drugs at low doses essentially act by potentiating the vlpo, producing a sleepy state. animal studies show that vlpo neurons show cfos activation after sedative doses of these drugs, and that vlpo lesions produce resistance to their sedative effects. however, at high doses that produce a surgical plane of anesthesia, these drugs have much more widespread inhibitory effects, that do not depend upon the vlpo. studies have shown that multiple sedative/hypnotic drugs that act by potentiating gaba-a receptors, including ethanol, chloral hydrate, propofol and gas anesthetics such as isoflurane, at sedative doses increase the activity of the vlpo neurons in mice. this finding suggests that at relatively low sedative doses, these medications may have a common mechanism of action, which includes potentiating the firing of vlpo neurons. high doses used in surgical anesthesia, however, reduce activity of neurons throughout the nervous system.

jannaschia donghaensis jannaschia donghaensis jannaschia donghaensis is a gram-negative and non-motile bacterium from the genus of jannaschia which has been isolated from seawater from the sea of japan from the liancourt rocks. jannaschia donghaensis scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: rhodobacterales family: rhodobacteraceae genus: jannaschia species: j. donghaensis binomial name jannaschia donghaensisyoon et al. 2007 type strain jcm 14563, kctc 12862, strain dsw-17

rotalidia rotalidia rotalidia comprises a class of foraminifera where foraminifera is regarded as a phylum, (kingdom protista or rhizaria, not chromista) that unites foraminifera that have tests composed of secreted lamellar calcium carbonate, optically radial or granular calcite, or aragonite; separating them from those with porcelaneous, agglutinated, or microgranular, tests, or tests composed of organic compounds. seven orders are included, the: rotaliida delage & hérouard, 1896 carterinida loeblich & tappan, 1981 globigerinida delage & hérouard, 1896 involutinida hohenegger & piller, 1977 lagenida delage & hérouard, 1896 silicoloculinida resig et al. 1980 spirillinida hohenegger & piller, 1975. rotalidia ammonia beccarii (rotaliidae) scientific classification domain: eukaryota (unranked): sar (unranked): rhizaria superphylum: retaria phylum: foraminifera class: rotalidia orders see text

substance abuse and mental health services administration substance abuse and mental health services administration the substance abuse and mental health services administration (samhsa; pronounced /ˈsæmsə/) is a branch of the u.s. department of health and human services. samhsa is charged with improving the quality and availability of treatment and rehabilitative services in order to reduce illness, death, disability, and the cost to society resulting from substance abuse and mental illnesses. the administrator of samhsa reports directly to the secretary of the u.s. department of health and human services. samhsa's headquarters building is located outside of rockville, maryland. united states substance abuse and mental health services administrationagency overviewformedjuly 1992 (1992-07)jurisdictionfederal government of the united statesheadquartersnorth bethesda, maryland (rockville mailing address)agency executivemiriam delphin-rittmon, administratorparent departmentdepartment of health and human serviceswebsitewww.samhsa.gov history the front of the samhsa building outside of rockville, md samhsa was established in 1992 by congress as part of a reorganization stemming from the abolition of alcohol, drug abuse, and mental health administration (adamha). adamha had been established in 1973, combining the national institute on alcohol abuse and alcoholism (niaaa), national institute on drug abuse (nida), national institute of mental health (nimh). the 1992 adamha reorganization act consolidated the treatment functions that were previously scattered amongst the nimh, niaaa, and nida into samhsa, established as an agency of the public health service (phs). nimh, niaaa, and nida continued with their research functions as agencies within the national institutes of health. congress directed samhsa to target effectively substance abuse and mental health services to the people most in need and to translate research in these areas more effectively and rapidly into the general health care system. charles curie was samhsa's director until his resignation in may 2006. in december 2006 terry cline was appointed as samhsa's director. dr. cline served through august 2008. rear admiral eric broderick served as the acting director upon dr. cline's departure, until the arrival of the succeeding administrator, pamela s. hyde, j.d. in november 2009. she resigned in august 2015 and kana enomoto, m.a. served as acting director of samhsa until dr. elinore f. mccance-katz was appointed as the inaugural assistant secretary for mental health and substance abuse. the title was changed by section 6001 of the 21st century cures act. organization samhsa headquarters at 5600 fishers lane in rockville, maryland samhsa's mission is to reduce the impact of substance abuse and mental illness on american's communities. four samhsa offices, called centers, administer competitive, formula, and block grant programs and data collection activities: the center for mental health services (cmhs) focuses on prevention and treatment of mental disorders. the center for substance abuse prevention (csap) seeks to reduce the abuse of illegal drugs, alcohol, and tobacco. the center for substance abuse treatment (csat) supports effective substance abuse treatment and recovery services. the center for behavioral health statistics and quality (cbhsq) collects, analyzes, and publishes behavior health data. the centers give grant and contracts to u.s. states, territories, tribes, communities, and local organizations. they support the provision of quality behavioral-health services such as addiction-prevention, treatment, and recovery-support services through competitive programs of regional and national significance grants. several staff offices support the centers: office of the administrator office of policy, planning, and innovation office of behavioral health equity office of financial resources office of management, technology, and operations office of communications office of tribal affairs and policy center for mental health services the center for mental health services (cmhs) is a unit of the substance abuse and mental health services administration (samhsa) within the u.s. department of health and human services. this u.s. government agency describes its role as: the center for mental health services leads federal efforts to promote the prevention and treatment of mental disorders. congress created cmhs to bring new hope to adults who have serious mental illness and children with emotional disorders. as of march 2016, the director of cmhs is paolo del vecchio. cmhs is the driving force behind the largest us children's mental health initiative to date, which is focused on creating and sustaining systems of care. this initiative provides grants (now cooperative agreements) to states, political subdivisions of states, territories, indian tribes and tribal organizations to improve and expand their systems of care to meet the needs of the focus population—children and adolescents with serious emotional, behavioral, or mental disorders. the children's mental health initiative is the largest federal commitment to children’s mental health to date, and through fy 2006, it has provided over $950 million to support soc development in 126 communities. center for substance abuse prevention the center for substance abuse prevention (csap) aims to reduce the use of illegal substances and the abuse of legal ones. csap promotes self-esteem and cultural pride as a way to reduce the attractiveness of drugs, advocates raising taxes as a way to discourage drinking alcohol by young people, develops alcohol and drug curricula, and funds research on alcohol and drug abuse prevention. csap encourages the use of "evidence-based programs" for drug and alcohol prevention. evidence-based programs are programs that have been rigorously and scientifically evaluated to show effectiveness in reducing or preventing drug use. the current director of csap is frances harding. history and legal definition csap was established in 1992 from the previous office of substance abuse prevention by the law called the adamha reorganization act. defining regulations include those of title 42. center for substance abuse treatment the center for substance abuse treatment (csat) was established in october 1992 with a congressional mandate to expand the availability of effective treatment and recovery services for alcohol and drug problems. csat supports a variety of activities aimed at fulfilling its mission: to improve the lives of individuals and families affected by alcohol and drug abuse by ensuring access to clinically sound, cost-effective addiction treatment that reduces the health and social costs to our communities and the nation. csat works with states and community-based groups to improve and expand existing substance abuse treatment services under the substance abuse prevention and treatment block grant program. csat also supports samhsa’s free treatment referral service to link people with the community-based substance abuse services they need. because no single treatment approach is effective for all persons, csat supports the nation's effort to provide multiple treatment modalities, evaluate treatment effectiveness, and use evaluation results to enhance treatment and recovery approaches. the current director of csat is louis a. trevisan, md center for behavioral health statistics and quality the center for behavioral health statistics and quality (cbhsq) conducts data collection and research on "behavioral health statistics" relating to mental health, addiction, substance use, and related epidemiology. cbhsq is headed by a director. subunits of cbhsq include: office of program analysis and coordination division of surveillance and data collection division of evaluation, analysis and quality the center's headquarters are outside of rockville, maryland. regional offices cms has its headquarters outside of rockville, maryland with 10 regional offices located throughout the united states: region i – boston, massachusetts connecticut, massachusetts, maine, new hampshire, rhode island and vermont. region ii – new york, new york new york state, new jersey, u.s. virgin islands and puerto rico. region iii – philadelphia, pennsylvania delaware, maryland, pennsylvania, virginia, west virginia and the district of columbia. region iv – atlanta, georgia alabama, florida, georgia, kentucky, mississippi, north carolina, south carolina and tennessee. region v – chicago, illinois illinois, indiana, michigan, minnesota, ohio and wisconsin. region vi – dallas, texas arkansas, louisiana, new mexico, oklahoma and texas. region vii – kansas city, missouri iowa, kansas, missouri, and nebraska. region viii – denver, colorado colorado, montana, north dakota, south dakota, utah, and wyoming. region ix – san francisco, california arizona, california, hawaii, nevada, american samoa, guam, and the northern marina islands. region x – seattle, washington alaska, idaho, oregon, and washington strategic direction in 2010, samhsa identified 8 strategic initiatives to focus the agency's work. below are the 8 areas and goals associated with each category: prevention of substance abuse and mental illness – create prevention-prepared communities in which individuals, families, schools, workplaces, and communities take action to promote emotional health; and, to prevent and reduce mental illness, substance (including tobacco) abuse, and, suicide, across the lifespan trauma and justice – reduce the pervasive, harmful, and costly public-health impacts of violence and trauma by integrating trauma-informed approaches throughout health and behavioral healthcare systems; also, to divert people with substance-abuse and mental disorders away from criminal-/juvenile-justice systems, and into trauma-informed treatment and recovery. military families – active, guard, reserve, and veteran – support of our service men & women, and their families and communities, by leading efforts to ensure needed behavioral health services are accessible to them, and successful outcomes. health reform – broaden health coverage and the use of evidence-based practices to increase access to appropriate and high quality care; also, to reduce existing disparities between: the availability of substance abuse and mental disorders; and, those for other medical conditions. housing and homelessness – to provide housing for, and to reduce the barriers to accessing recovery-sustaining programs for, homeless persons with mental and substance abuse disorders (and their families) health information technology for behavioral health providers – to ensure that the behavioral-health provider network—including prevention specialists and consumer providers—fully participate with the general healthcare delivery system, in the adoption of health information technology. data, outcomes, and quality – demonstrating results – realize an integrated data strategy that informs policy, measures program impact, and results in improved quality of services and outcomes for individuals, families, and communities. public awareness and support – increase understanding of mental and substance abuse prevention & treatment services, to achieve the full potential of prevention, and, to help people recognize and seek assistance for these health conditions with the same urgency as any other health condition. their budget for the fiscal year 2010 was about $3.6 billion. it was re-authorized for fy2011. most recently, the fy 2016 budget requests $3.7 billion for samhsa, an increase of $45 million above fy 2015. controversy in february 2004, the administration was accused of requiring the name change of an oregon mental health conference from "suicide prevention among gay/lesbian/bisexual/transgender individuals" to "suicide prevention in vulnerable populations." in 2002, then-president george w. bush established the new freedom commission on mental health. the resulting report was intended to provide the foundation for the federal government's mental health services programs. however, many experts and advocates were highly critical of its report, achieving the promise: transforming mental health care in america.

clavulinopsis (foram) clavulinopsis (foram) clavulinopsis is a genus of foraminifera from the upper cretaceous of the united states (texas, arkansas), included in the textulariida. the type species is clavulinopsis hofkeri banner and desai, 1985. clavulinopsistemporal range: late cret (camp - maastr) scientific classification domain: eukaryota (unranked): sar (unranked): rhizaria superphylum: retaria phylum: foraminifera class: globothalamea order: textulariida superfamily: textulariacea family: pseudogaudryinidae genus: clavulinopsisbanner and desai, 1985 clavulinopsis has a free aggulinated test with a considerable calcareous groundmass. the early stage is triserial, later abruptly becoming uniserial; cross section triangular. sutures are slightly depressed, horizontal to slightly arched at the center of the flattened sides. lateral walls are filled with fine micro-tubular cavities (term: canaliculate) that open into the chamber interiors, but are sealed externally by a finely agglutinated outer layer. septa are solid, without micro-tubular cavities. the aperture is cribrate, with irregular pores at the end of a slightly produced neck.

parvularculaceae parvularculaceae the "parvularculaceae" are a family of marine bacteria. "parvularculaceae" scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: "parvularculales"garrity et al. 2003 family: "parvularculaceae"garrity et al. 2003 genera amphiplicatus zhang et al. 2014 aquisalinus zhong et al. 2016 hyphococcus sun et al. 2017 marinicaulis yu et al. 2018 parvularcula cho and giovannoni 2003

eicar (antiviral) eicar (antiviral) eicar is a drug which acts as an inhibitor of the enzyme imp dehydrogenase. it is a nucleoside derivative which has both anti-cancer and antiviral effects, and was originally developed for the treatment of leukemia, but was unsuccessful in human clinical trials. it has broad spectrum antiviral effects with activity against pox viruses, semliki forest virus, junin virus, reovirus, influenza, measles virus and respiratory syncytial virus among others, although it is not active against coronaviridae such as sars-cov-1. this useful spectrum of activity means that eicar and related derivatives continue to be investigated for the treatment of viral diseases. eicarclinical dataother names5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamidelegal statuslegal status us: investigational new drug identifiers iupac name 1--5-ethynylimidazole-4-carboxamide cas number118908-07-9pubchem cid21120184chemspider399153comptox dashboard (epa)dtxsid50922809 chemical and physical dataformulac11h13n3o5molar mass267.24 g·mol−13d model (jsmol)interactive image smiles nc(=o)c1ncn(c1c#c)c2(o)(o)(o2)co inchi inchi=1s/c11h13n3o5/c1-2-5-7(10(12)18)13-4-14(5)11-9(17)8(16)6(3-15)19-11/h1,4,6,8-9,11,15-17h,3h2,(h2,12,18)/t6-,8-,9-,11?/m1/s1key:swqqelwgjdxcft-abhrneansa-n

night doctors night doctors night doctors (also known as night riders, night witches, ku klux doctors and student doctors) are bogeymen of african american folklore, with some factual basis. body snatching from graves and enforced medical experimentation led to the development of african american folklore stories that told of doctors who would abduct, kill, and dissect bodies. the goal of these "night doctors" was to further prevent slaves, freedmen, and black workers from leaving for the northern united states. the term night doctors is often broadly used, referring to those who steal, buy, or practice on african american corpses to further their medical knowledge. at this time, the cadaver shortage among medical schools in the south led to people digging up their graves in the night to steal bodies, and slave owners selling their deceased to make some extra money. grave robbing often happened in poor communities where they had no means to have or fund any deterrence of grave robbing or protection of their cemeteries. night doctors preying on these marginalized communities were often overlooked by wealthier, more powerful people in the communities, and led to the fleeing of african americans in the early to mid 20th century, now known as the great migration. the african american community's distrust of the medical occupation and doctors predates the tuskegee syphilis study, where doctors unethically withheld treatment from african americans with the disease to use them as an experimental basis for untreated syphilis. when night doctors started emerging, the bodies of southern blacks were a valuable resource for dissection and autopsy studies in medical colleges. the horrors night doctors caused continued even after the american civil war as they kept stealing african american bodies for dissection. unethical practices against african americans led to fear and distrust in the medical community. body snatching throughout the late 18th and early 19th centuries in the united states, the demand for cadavers exceeded the supply when hands-on dissection became popular in medical schools. the importance of human bodies in explaining general anatomy and fundamental methods like amputation has existed since ancient times. however, the need was intensified in the 19th century by the increased acceptability of dissecting human bodies. the necessity for dead bodies was met by grave-robbing and using slave bodies. the government put into place various countermeasures to deter grave robbers. however, these measures took time and money. therefore, african american bodies were the most common ones to be robbed since they were legally, economically, and socially disadvantaged. hence, the most frequent targets of grave robbers were african americans, immigrants, and the impoverished. grave robbers avoided stealing white american bodies because the dissection of white cadavers carried far greater risks for physicians. the bodies of african americans were often sold to chattel for dissection by slave owners after their death. there is an overwhelming amount of evidence suggesting that the bodies of impoverished people, african americans, and underprivileged individuals were used to improve the medical training of white elites. grave robbers and their crimes were frequently overlooked by white americans since grave robbing had no direct impact on them. the tales of night doctors, who bought and stole bodies, became part of african american history and traditions. body snatching increased during the post-revolutionary period because medical students started to perform dissections rather than simply observing professors. in the early 19th century, most states legislated against grave robbery. even though grave robbing was formally prohibited, the penalty was comparatively light since grave robbing was considered misconduct rather than a felony. the punishment for grave robbing was a possible fine and a short period of imprisonment. due to these permissive attitudes, relatives of the lately departed had to take it upon themselves to watch their loved ones' graves. following this, grave robbery was very frequent even though there were laws prohibiting it in some states. because of grave robbing, several riots took place between 1765 and 1852, the most well-known of which was new york doctors' riot of 1788. in the new york doctors' riot of 1788, the unauthorized acquisition of bodies from the graves of the recently departed sparked a massive outburst of anger and dissatisfaction among impoverished people, specifically aimed at doctors and medical trainees. in january 1789, a year after the riot, a law was successfully passed that regulated the appropriate treatment of dead bodies, with heavy penalties inflicted on anyone who disobeyed the law. the warburton anatomy act of 1832, which handed unclaimed remains to scientists and eventually ended grave robbery in britain, was instrumental in enacting legislation in the united states that curtailed grave robbing. massachusetts passed an identical, albeit less harshly worded, anatomy act of 1831, which legalized the use of dead bodies for dissection and anatomical studies. most states soon passed similar legislation, and by the turn of the century, cadavers were almost entirely sourced from unclaimed remains. an example of a medical college that used the bodies of african americans, immigrants, and impoverished people is the medical college of georgia. excavations at the medical college of georgia in 1989 yielded more than 9,000 bones. no records exist, and none of the remains have been identified, but it fits the inflammatory story to claim that they were mainly from working-class individuals and approximately 80% of those were african americans. in addition to being the majority of cadavers, many teaching hospitals would only perform new live surgical techniques and demonstrations on african american patients. the consequences of employing the majority of african american bodies led to the dehumanization of african american people in the medical system, a lack of confidence between african american people and medical experts, and a reluctance among african american people to donate their bodies for medical purposes. the inordinate use of african american bodies for autopsy and medical studies unwittingly formed a view of black people as nothing more than medical experimentation material. the usage of african american bodies as experimental subjects has a long history in the united states, dating back to the use of henrietta lacks' cancer cells for research purposes without her proper consent to the tuskegee syphilis study. in both of these instances, patients did not give consent to the medical projects and research being done on them. they were not informed and were blatantly misled. medical injustice to people of color still remains, leaving a mistrust of the medical system throughout the country. needle men and the black bottle men in new orleans, charity hospitall (now the medical center of louisiana at new orleans) was a teaching hospital that needed cadavers for their students which is why they had a variation of night doctors called the "needle men." this hospital was known for many different racist incidents. in 1926, a sign prohibited black people to enter through the front door and forced these individuals to use the back door. the eponymous needle men would poke unsuspecting individuals in the arm, resulting in death. several other explanations for these deaths were suggested, such as epilepsy. in 1924, there was a case where a man would poke women with a bayonet which resulted in their deaths. ultimately, the substance in the needles caused people to die. from a quote taken from the collection of louisiana folk tales, it's apparent that people were aware of what was going on at the time and feared being victim to the needle men."i sure don't go out much at this time of year. you take a chance just walkin' on the streets. them needle men's is everywhere. they always come 'round in the fall, and they're 'round to about march. you see, them needle mens is medical students from the charity hospital tryin' to git your body to work on. that's 'cause stiffs are very scarce at this time of the year,"there were also students at charity hospital that were referred to as "black bottle men." the black bottle would be a poison given upon entrance to charity hospital, and the patient would die shortly after drinking the black bottle. it is now thought that the black bottle is referred to as cascara (rhamnus purshiana) mixed with milk of magnesia, a laxative is commonly given to admitted patients of the era. it is unclear how a mild laxative could kill, but the myth continues that these bodies were used by medical students as cadavers for dissections. charity hospital did not have sole responsibility for "needle men" or "black bottle men." johns hopkins hospital (the teaching hospital of johns hopkins university) was believed to be another source. from 1898 to 1904, the cadavers used by johns hopkins university were 2⁄3 african american which is highly disproportional to the surrounding population at the time. personal anecdotes about these "needle men" or "black bottle men" show their impact on the black community. a woman from the book the immortal life of henrietta lacks states, "you'd be surprised how many people disappeared in east baltimore when i was a girl. i'm telling you, i lived here in the fifties when they got henrietta, and we weren't allowed to go anywhere near hopkins. when it got dark and we were young, we had to be on the steps, or hopkins might get us." even though needle men and black bottle men are no longer around, they have had a lasting impact on the black communities surrounding the hospitals. there are still feelings of fear and distrust for medical professionals which can be detrimental to someone's health. modern day consequences since african americans arrived in the united states, they were marginalized and forced to be test subjects in various ways. many white people believe that they still had a right to their bodies even after death. for many slaves, death was thought of as the one time their body may rest and they will suffer no more. with the night doctors digging up bodies that were already laid to rest, a great fear swept across the african american community. the studies that were done on african americans in american history were often done without any consent. today, this plays a great role because it has left african americans distrusting and wary of the medical system which has wronged them in the past. it has exaggerated the racial divides between blacks and whites. even today, neighborhoods between white people and african americans are often separated, leading to separations in their access to medical care as well. the information gathered from the studies on black cadavers benefits people who have easy access to health care, such as wealthy, white communities, rather than the communities of marginalized people who were unethically used to obtain the information. african american communities tend to be underfunded, with less access to health care, education, insurance, and resources. african americans are also less likely to seek out medical care for fear of what may be done to them against their will. there have been instances that african americans are denied pain medication because they are perceived to be in less pain or faking it since they are taken less seriously among medical professionals. night doctors left many modern-day repercussions on black communities in search of medical care.

brevinema andersonii brevinema andersonii brevinema andersonii (brev. i. ne' ma. l. adj. brevis, short; gr. n. nema, thread; n.l. neut. n. brevinema, a short thread.) (an.derso'ni.i. n.l. gen. n. andersonii, of anderson), named for john f. anderson, who first described the organism. this organism is a gram-negative, microaerophilic, helical shaped, chemoorganotrophic organism from the genus brevinema. brevinema andersonii is host associated, strains have been isolated from blood and other tissues of short-tailed shrews (blarina brevicauda) and white-footed mice (peromyscus zeucopus) and are infectious for laboratory mice and syrian hamsters.b. andersonii is readily identified by restriction enzyme analysis, and sds-page, or fatty acid composition data. another identifier for b. andersonii is the sheathed periplasmic flagella in the 1-2-1 configuration. while cells are visible by dark-field or phase-contrast microscopy, they cannot be seen when bright-field microscopy is used. brevinema andersonii scientific classification domain: bacteria phylum: spirochaetota class: spirochaetia order: brevinematalesgupta et al. 2014 family: brevinemataceaepaster 2012 genus: brevinemadefosse et al. 1995 species: b. andersonii binomial name brevinema andersoniidefosse et al. 1995 history brevinema andersonii was first identified in 1987 by anderson f. john, russell c. johnson, louis a.magnarell, fred w. hyde, and theodore g andreadis in blood and tissues from blarina brevicauda (short-tailed shrew) and peromyscus leucopus (white-footed mouse). initially thought to be associated with borrelia burgdorferi this organism was finally brought to light with more advanced growth mediums. upon electron microscopy of cultures from this medium, a distinct morphology stood out from the rest. it was not until 1995 that a push for this organism to be found as a new species. this push came as an article from the journal of systematic bacteriology that exclaimed data supports this organism to be its own genus species was broadcast. written by d.l. defosse, r. c. johnson, b. j. paster, f. e. dewhirst, they found genomic evidence to support their claim that brevienma andersonii was its own deep rooted spirochete. their findings showed that this organism was around 75% similar in genome to other known spirochetes, this showed that b. andersonii was in a taxon of its own. biology and biochemistry type and morphology brevinema andersonii stains as g- due to the peptidoglycan in the triple-layered outer membrane. its metabolism is chemoorganotrophic. the organism exists in microaerophilic environments. b. andersonii is a motile and flexible helical shaped spiral bacteria that possess a triple-layered outer envelope. between the outer membrane and the peptidoglycan layer there is a single sheathed flagella in the 1-2-1 configuration, as well as a protoplasmic cylinder. the cells are usually 0.2–0.3μm in diameter and 4-5μm in length. 1–2 waves occur along the cell with wavelengths of 2-3μm. the typical final density of the cells are around 4x10−7 cells per milliliter. biochemistry brevinema andersonii can be readily identified by enzyme analysis and sds-page, or fatty acid composition data. an enzyme analysis of b. andersonii showed activity with butyrate, valerate, caproate, caprylate, nonanoate, caprate, esterase lipase, alkaline phosphatase, acid phosphatase, and β-glucuronidase. the fatty acid composition mainly consists of myristic acid (14:0), palmitic acid (16:0), and oleic acid (18:l), and smaller amounts of stearic acid (18:1) and linoleic acid (18:2). there were low levels, less than 1%, of other fatty acids detected. b. andersonii was found to be catalase negative. growth brevenima andersonii was found to be grown successfully on a modified bsk medium, referred to as shrew-mouse spirochete medium. the optimum temperature range that b. andersonii grows at is between 30 °c to 34 °c, but b. andersonii cannot grow below 25 °c. the ideal ph for b. andersonii is neutral with an optimum ph of 7.4. it takes 11 to 14 hours per generation time at optimum conditions. genome the type strain of brevinema andersonii was designated as atcc 43811. the g+c content of this organism was fount t be 34 mol%. unique single-base nucleotide signatures at positions 52•359 (g•c) and 783•799 (u•a) differentiate b. andersonii from other major spirochete groups. there is also a distinguishing 16s rrna sequence that corresponds to position 724 to 750 in e. coli (5'-ggcagcuaccuaugcuaagauugacgc-3'). the 16s rrna genome is extracted was a partial genome with 1490 bp, the 16s rrna partial genome reads as:

cirmtuzumab cirmtuzumab cirmtuzumab (also uc-961) is an anti-ror1 humanised monoclonal antibody. cirmtuzumabmonoclonal antibodytype?sourcehumanizedtargetror1clinical dataother namesuc-961legal statuslegal status investigational identifierscas number1643432-38-5 yuniifeh7rq7b3j it is an experimental drug in early-stage clinical trials for various cancers including chronic lymphocytic leukemia (cll).

binswanger's disease binswanger's disease binswanger's disease, also known as subcortical leukoencephalopathy and subcortical arteriosclerotic encephalopathy, is a form of small-vessel vascular dementia caused by damage to the white brain matter. white matter atrophy can be caused by many circumstances including chronic hypertension as well as old age. this disease is characterized by loss of memory and intellectual function and by changes in mood. these changes encompass what are known as executive functions of the brain. it usually presents between 54 and 66 years of age, and the first symptoms are usually mental deterioration or stroke. binswanger's diseaseother namessubcortical arteriosclerotic encephalopathyspecialtyneurology it was described by otto binswanger in 1894, and alois alzheimer first used the phrase "binswanger's disease" in 1902. however, jerzy olszewski is credited with much of the modern-day investigation of this disease which began in 1962. signs and symptoms symptoms include mental deterioration, language disorder, transient ischemic attack, muscle ataxia, and impaired movements including change of walk, slowness of movements, and change in posture. these symptoms usually coincide with multiple falls, epilepsy, fainting, and uncontrollable bladder. because binswanger's disease affects flow processing speed and causes impaired concentration, the ability to do everyday tasks such as managing finances, preparing a meal and driving may become very difficult. neurological presentation binswanger's disease is a type of subcortical vascular dementia caused by white matter atrophy to the brain. however, white matter atrophy alone is not sufficient for this disease; evidence of subcortical dementia is also necessary. the histologic findings are diffuse, irregular loss of axons and myelin accompanied by widespread gliosis, tissue death due to an infarction or loss of blood supply to the brain, and changes in the plasticity of the arteries. the pathologic mechanism may be damage caused by severe atherosclerosis. the onset of this disease is typically between 54 – 66 years of age and the first symptoms are usually mental deterioration or stroke. the vessels that supply the subcortical white matter come from the vessels that support basal ganglia, internal capsule, and thalamus. it is described as its own zone by and susceptible to injury. chronic hypertension is known to cause changes in the tension of the smooth wall vessels and changes in the vessel diameter. arterioles can become permeable resulting in compromise of the blood brain barrier. it has been shown that binswanger's disease targets the vessels in this zone of the subcortex, but spares the microcirculation's vessels and capillaries which may be attributed to a difference between alzheimer's and binswanger's disease. psychiatric presentation there is a difference between cortical and subcortical dementia. cortical dementia is atrophy of the cortex which affects ‘higher’ functions such as memory, language, and semantic knowledge whereas subcortical dementia affects mental manipulation, forgetfulness, and personality/emotional changes. binswanger's disease has shown correlations with impairment in executive functions, but have normal episodic or declarative memory. executive functions are brain processes that are responsible for planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting relevant sensory information. there have been many studies done comparing the mental deterioration of binswanger patients and alzheimer patients. it has been found in the graphical sequence test that binswanger patients have hyperkinetic perseveration errors which cause the patients to repeat motion even when not asked whereas alzheimer patients have semantic perseveration because when asked to write a word they will instead draw an image depicting the word. diagnosis binswanger's disease can usually be diagnosed with a ct scan, magnetic resonance imaging, and proton magnetic resonance spectrography in addition to clinical examination. indications include infarctions, lesions, or loss of intensity of central white matter and enlargement of ventricles, and leukoaraiosis. a mini–mental state examination has been created to quickly assess cognitive impairment and serves as a screening test for dementia across different cultures. imaging leukoaraiosis refers to the imaging finding of white matter changes that are common in binswanger disease. however, leukoaraiosis can be found in many different diseases and even in normal patients, especially in people older than 65 years of age. there is controversy whether leukoaraiosis and mental deterioration actually have a cause and effect relationship. research has shown that different types of leukoaraiosis can affect the brain differently, and that proton magnetic resonance spectroscopy would be able to distinguish the different types more effectively and better diagnose and treat the issue. because of this information, white matter changes indicated by magnetic resonance imaging or computerized tomography cannot alone diagnose binswanger disease, but can aid to a bigger picture in the diagnostic process. there are many diseases similar to binswanger's disease including cadasil syndrome and alzheimer's disease, which makes this specific type of white matter damage hard to diagnose. binswanger disease may be diagnosed by a team of experts including a neurologist and psychiatrist to rule out other psychological or neurological problems. because doctors must successfully detect enough white matter alterations to accompany dementia as well as an appropriate level of dementia, two separate technological systems are needed in the diagnosing process. much of the major research today is done on finding better and more efficient ways to diagnose this disease. many researchers have divided the magnetic resonance imaging of the brain into different sections or quadrants. a score is given to each section depending on how severe the white matter atrophy or leukoaraiosis is. research has shown that the higher these scores, the more of a decrease in processing speed, executive functions, and motor learning tasks. other researchers have begun using computers to calculate the percentage of white matter atrophy by counting the hyper-intense pixels of the magnetic resonance images. these and similar reports show a correlation between the amount of white matter alterations and the decline of psychomotor functions, reduced performance on attention and executive control. one type of technology is called susceptibility weighted imaging (swi) which is a magnetic resonance technique which has an unusually high degree of sensitivity and can better detect white matter alterations. management binswanger's disease has no cure and has been shown to be the most severe impairment of all of the vascular dementias. the successful management of vascular risk factors that contribute to poor perfusion in the brain is to treat the cause, such as chronic hypertension or diabetes. history binswanger in 1894 was the first to claim that white matter atrophy caused by 'vascular insufficiency' can result in dementia. he described a patient who had slow progression of dementia as well as subcortical white matter atrophy, ventricle enlargement, aphasia, hemianopsia, and hemiparesis. he named this disease 'encenphailitis subcorticalis chronica progressive.' binswanger did not conduct any microscopic investigations so many did not believe his findings and attributed the neural damage to neural syphilis. alzheimer in 1902 studied binswanger's work with pathological evidence that concluded and supported binswanger's ideas and hypotheses. alzheimer renamed this disease binswanger's disease. in the late 19th century vascular dementia was heavily studied, however by 1910 scientists were lumping binswanger's disease with all other subcortical and cortical dementia and labeling everything senile dementia despite all previous research and efforts to distinguish this disease from the rest. in 1962 j. olszewski published an extensive review of all literature about binswanger's disease so far. he discovered that some of the information in the original reports was incorrect and that at least some of the patients studied in these cases probably had neurosyphilis or other types of dementia. even with these errors, olszewski concluded that binswanger disease did exist as a subset of cerebral arteriosclerosis. yet again, in 1974 the term multi-infarct dementia was coined and all vascular dementia was grouped into one category. because of this, the specific names of these types of this dementia, including binswanger's disease were lost. this was until 1992 when alzheimer's diagnostic centers created specific criteria known as the hachinski ischemic scale (after dr. vladimir hachinski) which became the standard for diagnosing mid or vascular dementia. the complicated history of binswanger's disease and the fact that it was overlooked as a disease for many years means some patients may have been misdiagnosed with alzheimer's disease.

dactinomycin dactinomycin dactinomycin, also known as actinomycin d, is a chemotherapy medication used to treat a number of types of cancer. this includes wilms tumor, rhabdomyosarcoma, ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. it is given by injection into a vein. dactinomycinclinical datatrade namescosmegenother namesactinomycin d2-amino- 4,6-dimethyl- 3-oxo- 3h-phenoxazine- 1,9-dicarboxylic acid bis- ahfs/drugs.commonographmedlineplusa682224pregnancycategory au: d routes ofadministrationivatc codel01da01 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic dataprotein binding5%elimination half-life36 hoursidentifiers iupac name 2-amino-n,n′- bisoxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-3h-phenoxazine-1,9-dicarboxamide cas number50-76-0 ypubchem cid2019drugbankdb00970 nchemspider10482167 yunii1cc1jfe158keggc06770 nchebichebi:27666 ychemblchembl1554 yniaid chemdb009885comptox dashboard (epa)dtxsid9020031 echa infocard100.000.058 chemical and physical dataformulac62h86n12o16molar mass1255.438 g·mol−13d model (jsmol)interactive image smiles cc1c2oc3c(c)ccc(c(o)=n4c(o)=n(c(c)c)c(=o)n5ccc5c(=o)n(c)cc(=o)n(c)(c(c)c)c(=o)o4c)c3nc-2c(c(o)=n2c(o)=n(c(c)c)c(=o)n3ccc3c(=o)n(c)cc(=o)n(c)(c(c)c)c(=o)o2c)c(n)c1=o inchi inchi=1s/c62h86n12o16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49h,17-20,23-26,63h2,1-16h3,(h,65,80)(h,66,81)(h,67,78)(h,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1 ykey:rjurfgzvjuqbhk-iixsonldsa-n y ny (what is this?) (verify) most people develop side effects. common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains. other serious side effects include future cancers, allergic reactions, and tissue death at the site of injection. use in pregnancy may harm the baby. dactinomycin is in the cytotoxic antibiotic family of medications. it is believed to work by blocking the creation of rna. dactinomycin was approved for medical use in the united states in 1964. it is on the world health organization's list of essential medicines. medical use actinomycin is a clear, yellowish liquid administered intravenously and most commonly used in treatment of a variety of cancers, including: gestational trophoblastic neoplasia wilms' tumor rhabdomyosarcoma ewing's sarcoma malignant hydatidiform mole sometimes it will be combined with other drugs in chemotherapy regimens, like the vac regimen (with vincristine and cyclophosphamide) for treating rhabdomyosarcoma and ewing's sarcoma. it is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation. side effects common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. actinomycin is a vesicant, if extravasation occurs. mechanism in cell biology, actinomycin d is shown to have the ability to inhibit transcription. actinomycin d does this by binding dna at the transcription initiation complex and preventing elongation of rna chain by rna polymerase. history actinomycin d was the first antibiotic shown to have anti-cancer activity. it was first isolated by selman waksman and his co-worker h. boyd woodruff in 1940. it was approved by the u.s. food and drug administration (fda) on december 10, 1964, and launched by merck sharp and dohme under the trade name cosmegen. research use because actinomycin can bind dna duplexes, it can also interfere with dna replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of dna synthesis. actinomycin d and its fluorescent derivative, 7-aminoactinomycin d (7-aad), are used as stains in microscopy and flow cytometry applications. the affinity of these stains/compounds for gc-rich regions of dna strands makes them excellent markers for dna. 7-aad binds to single stranded dna; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones.

footwell intrusion footwell intrusion in the field of automotive engineering, footwell intrusion describes a situation in which an automobile engine or other vehicle component penetrates the space normally allocated for the feet of the front seat occupants. automotive crash testing agencies such as euro ncap and iihs consider levels of footwell intrusion when conducting assessments. vehicles that display excessive deformation of the footwell are noted.aftermath of nhtsa crash test of a 2004 ford escape showing healthy footwell intrusion. more of the physical property is conducive to greater crash injuries to driver's and passengers' lower legs and feet. the interaction between feet, pedals and (on crash) invading vehicle parts is directly linked with damage to the ankles, tibia and adjoining cartilage.

american association for pediatric ophthalmology and strabismus american association for pediatric ophthalmology and strabismus the american association for pediatric ophthalmology and strabismus (aapos) is an academic association of pediatric ophthalmologists and strabismus surgeons. the pediatric ophthalmology fellowships in the united states are accredited by the aapos. international members are also allowed based on evident valuable contributions and dedication to the field of pediatric ophthalmology. the association also publishes the journal of aapos as its official publication. past presidents president annual meeting year r. michael siatkowski, md san diego, ca 2018-2019 derek t. sprunger, md washington dc 2017-2018 robert e. wiggins, jr, md, mha nashville, tn 2016-2017 m. edward wilson, jr, md vancouver, bc, canada 2015-2016 sherwin j. isenberg, md new orleans, la 2014-2015 sharon f. freedman, md palm springs, ca 2013-2014 k. david epley, md boston, ma 2012-2013 steven e. rubin, md san antonio, tx 2011-2012 david a. plager, md san diego, ca 2010-2011 c. gail summers, md orlando, fl 2009-2010 bradley c. black, md san francisco, ca 2008-2009 edward g. buckley, md seattle, wa 2007-2008 christie l. morse, md seattle, wa 2006-2007 michael x. repka, md keystone, co 2005-2006 susan h. day, md orlando, fl 2004-2005 george s. ellis, jr, md washington, dc 2003-2004 joseph h. calhoun, md waikoloa, hi 2002-2003 jane d. kivlin, md seattle, wa 2001-2002 albert w. biglan, md orlando, fl 2000-2001 maynard b. wheeler, md san diego, ca 1999-2000 marilyn t. miller, md toronto, canada 1998-1999 john w. simon, md palm springs, ca 1997-1998 earl a. palmer, md charleston, sc 1996-1997 john d. baker, md snowbird, ut 1995-1996 malcolm l. mazow, md orlando, fl 1994-1995 david l. guyton, md vancouver, bc, canada 1993-1994 forrest d. ellis, md palm springs, ca 1992-1993 john t. flynn, md maui, hi 1991-1992 henry s. metz, md montreal, qc, canada 1990-1991 eugene m. helveston, md lake george, ny 1989-1990 william e. scott, md kiawah, hi 1988-1989 arthur l. rosenbaum, md boston, ma 1987-1988 gunter k. von noorden, md scottsdale, az 1986-1987 thomas d. france, md maui, hi 1985-1986 eugene r. folk, md puerto rico 1984-1985 john a. pratt-johnson, md vail, co 1983-1984 alfred g. smith, md vancouver, bc, canada 1982-1983 arthur jampolsky, md monterey, ca 1981-1982 webb chamberlain, md orlando, fl 1980-1981 phillip knapp, md san diego, ca 1979-1980 david s. friendly, md toronto, on, canada 1978-1980 robison d. harley, md williamsburg, va 1977-1978 jack c. crawford, md san francisco, ca 1876-1977 robert d. reinecke, md bermuda 1975-1976 marshall m. parks, md lake tahoe, nv 1974-1975

biomedical model biomedical model the biomedical model of medicine is the current dominating model of illness used in most western healthcare settings, and is built from the perception that a state of health is defined purely in the absence of illness.: 24, 26 the biomedical model contrasts with sociological theories of care,: 1 and has generally been associated with huge improvement in medical care. forms of the biomedical model have existed since before 400 bc, with hippocrates, the "father of medicine" advocating for physical aetiologies of illness. despite this, the model did not form the dominant view of health until the 1800s during the scientific revolution.: 25 criticism of the model generally surrounds its perception that health is independent of the sociocultural setting in which it occurs, and can be defined one way, across all populations. similarly, the model is also criticised for its view of the health system as socially and politically neutral, and not as a source of social or cultural power or embedded into the structure of society. features of the biomedical model in their book society, culture and health: an introduction to sociology for nurses, health sociologists dr karen willis and dr shandell elmer outline eight 'features' of the biomedical model's approach to illness and health.: 27–29 they are: doctrine of specific aetiology: that all illness and disease is attributable to a specific, physiological dysfunction body as a machine: that the body is formed of machinery to be fixed by medical doctors mind-body distinction: that the mind and body are separate entities that do not interrelate reductionism narrow definition of health: a state of health is always the absence of a definable illness individualistic: that sources of ill-health are always in the individual, and not the environment which health occurs treatment versus prevention: that the focus of health is on diagnosis and treatment of illness, not prevention treatment imperative: that medicine can 'fix the broken machinery' of ill-health neutral scientific process: that health care systems and agents of health are socially and culturally detached and irrelevant

ortervirales ortervirales ortervirales is an order that contains all accepted species of single-stranded rna viruses that replicate through a dna intermediate (group vi) and all accepted species of double-stranded dna viruses (except hepadnaviridae) that replicate through an rna intermediate (group vii). the name is derived from the reverse of retro. ortervirales hi-virión virus classification (unranked): virus realm: riboviria kingdom: pararnavirae phylum: artverviricota class: revtraviricetes order: ortervirales families belpaoviridae caulimoviridae metaviridae pseudoviridae retroviridae all reverse-transcribing viruses possess significant similarities to each other. their reverse transcriptase proteins share a common origin. moreover, belpaoviruses, metaviruses, pseudoviruses, and retroviruses have other features in common. their polymerase proteins are similar in structure and include aspartic protease (retroviral aspartyl protease) and an integrase belonging to the dde recombinase superfamily (see recombination-activating gene ). they also share similar capsid and nucleocapsid proteins/domains. caulimoviruses also share some features with belpaoviruses, metaviruses, pseudoviruses, and retroviruses such as a homologous aspartate protease. on the other hand, hepadnaviridae family appears to be more distantly related to the above-mentioned families. taxonomy there are five families in this order: family belpaoviridae – ltr retrotransposon, bel/pao family family metaviridae – ltr retrotransposon, ty3/gypsy family family pseudoviridae – ltr retrotransposon, ty1/copia family family retroviridae – retroviruses, e.g. hiv family caulimoviridae – dsdna-rt viruses infecting plants

salibacterium halochares salibacterium halochares salibacterium halochares is a gram-positive, aerobic and halophilic bacterium from the genus of salibacterium which has been isolated from a saltern from mesolongi in greece. salibacterium halochares scientific classification domain: bacteria phylum: bacillota class: bacilli order: bacillales family: bacillaceae genus: salibacterium species: s. halochares binomial name salibacterium halochares(pappa et al. 2010) vishnuvardhan et al. 2015 type strain dsm 21373, lmg 24571, mss4 synonyms bacillus halochares

pipobroman pipobroman pipobroman (trade names vercite, vercyte) is an anti-cancer drug that probably acts as an alkylating agent. it is marketed in france and italy. pipobromanclinical datatrade namesvercite, vercyteahfs/drugs.cominternational drug namesatc codel01ax02 (who) identifiers iupac name 3-bromo-1--propan-1-one cas number54-91-1 ypubchem cid4842iuphar/bps7271drugbankdb00236 ychemspider4676 yunii6q99rdt97rkeggd00467 ychebichebi:8242chemblchembl1585 ycomptox dashboard (epa)dtxsid7023485 chemical and physical dataformulac10h16br2n2o2molar mass356.058 g·mol−13d model (jsmol)interactive image smiles o=c(n1ccn(c(=o)ccbr)cc1)ccbr inchi inchi=1s/c10h16br2n2o2/c11-3-1-9(15)13-5-7-14(8-6-13)10(16)2-4-12/h1-8h2 ykey:njbfooclydnzjn-uhfffaoysa-n y (verify)

clofazimine clofazimine clofazimine, sold under the brand name lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. it is specifically used for multibacillary (mb) leprosy and erythema nodosum leprosum. evidence is insufficient to support its use in other conditions though a retrospective study found it 95% effective in the treatment of mycobacterium avium complex (mac) when administered with a macrolide and ethambutol, as well as the drugs amikacin and clarithromycin. however, in the united states, clofazimine is considered an orphan drug, is unavailable in pharmacies, and its use in the treatment of mac is overseen by the food and drug administration. it is taken orally. clofazimineclinical datatrade nameslampreneother namesn,5-bis(4-chlorophenyl)-3-(1-methylethylimino)-5h-phenazin-2-amine ahfs/drugs.commonographmedlineplusa682128routes ofadministrationby mouthatc codej04ba01 (who) legal statuslegal status us: ℞-only pharmacokinetic dataelimination half-life70 daysidentifiers iupac name n,5-bis(4-chlorophenyl)-3-(propan-2-ylimino)-3,5-dihydrophenazin-2-amine cas number2030-63-9 ypubchem cid2794drugbankdb00845 ychemspider21159573 nuniid959ae5usfkeggd00278 ychemblchembl1292 ycomptox dashboard (epa)dtxsid7022839 echa infocard100.016.347 chemical and physical dataformulac27h22cl2n4molar mass473.396 g·mol−13d model (jsmol)interactive imagemelting point210 to 212 °c (410 to 414 °f) smiles cc(c)/n=c/1\cc-2n(c3ccccc3nc2cc1nc4ccc(cc4)cl)c5ccc(cc5)cl inchi inchi=1s/c27h22cl2n4/c1-17(2)30-24-16-27-25(15-23(24)31-20-11-7-18(28)8-12-20)32-22-5-3-4-6-26(22)33(27)21-13-9-19(29)10-14-21/h3-17,31h,1-2h3 nkey:wdqpamhffcxsnu-uhfffaoysa-n n ny (what is this?) (verify) common side effects include abdominal pain, diarrhea, itchiness, dry skin, and change in skin color. it can also cause swelling of the lining of the gastrointestinal tract, increased blood sugar, and sensitivity to the sun. it is unclear if use during pregnancy is safe. clofazimine is a phenazine dye and is believed to work by interfering with dna. clofazimine was discovered in the 1950s at trinity college, dublin, and approved for medical use in the united states in 1986. it is on the world health organization's list of essential medicines. in the united states it is not available commercially but can be obtained from the us department of health and human services. medical uses the primary use of clofazimine is for the treatment of leprosy. other uses have not been proven to be safe or effective. it has been studied in combination with other antimycobacterial drugs to treat mycobacterium avium infections in people with hiv/aids and mycobacterium avium paratuberculosis. clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum (enl). (from ama drug evaluations annual, 1993, p1619). the drug is given as an alternative to people who can not tolerate the effects of dapsone for leprosy. early research suggested clofazimine inhibits the replication of sars-cov-2 in vitro and reduce viral load and inflammation in the lung in animal models side effects clofazimine produces pink to brownish skin pigmentation in 75-100% of patients within a few weeks, as well as similar discoloration of most bodily fluids and secretions. these discolorations are reversible but may take months to years to disappear. there is evidence in medical literature that as a result of clofazimine administration, several patients have developed depression which in some cases resulted in suicide. it has been hypothesized that the depression was a result of this chronic skin discoloration. cases of icthyosis and skin dryness are also reported in response to this drug (8%-28%), as well as rash and itchiness (1-5%). 40-50% of patients develop gastrointestinal intolerance. rarely, patients have died from bowel obstructions and intestinal bleeding, or required abdominal surgery to correct the same problem. mechanism clofazimine works by binding to the guanine bases of bacterial dna, thereby blocking the template function of the dna and inhibiting bacterial proliferation. it also increases activity of bacterial phospholipase a2, leading to release and accumulation of lysophospholipids, which are toxic and inhibit bacterial proliferation. clofazimine is also a fiasma (functional inhibitor of acid sphingomyelinase). metabolism clofazimine has a biological half life of about 70 days. autopsies performed on those who have died while on clofazimine show crystal-like aggregates in the intestinal mucosa, liver, spleen, and lymph nodes. history clofazimine, initially known as b663, was first synthesised in 1954 by a team of scientists at trinity college, dublin: frank winder, j.g. belton, stanley mcelhinney, m.l. conalty, seán o'sullivan, and dermot twomey, led by vincent barry. clofazimine was originally intended as an anti-tuberculosis drug but proved ineffective. in 1959, a researcher named y. t. chang identified its effectiveness against leprosy. after clinical trials in nigeria and elsewhere during the 1960s, swiss pharmaceutical company novartis launched the product in 1969 under the brand name lamprene. novartis was granted fda approval of clofazimine in december 1986 as an orphan drug. the drug is currently no longer commercially available in the united states. society and culture clofazimine is marketed under the trade name lamprene by novartis. one producer of the clofazimine molecule is sangrose laboratories, located in mavelikara, india. research the immunosuppressive effects of clofazimine were immediately noticed when applied in animal model. macrophages were first reported to be inhibited due to the stabilization of lysosomal membrane by clofazimine. clofazimine also showed a dosage-dependent inhibition of neutrophil motility, lymphocyte transformation, mitogen-induced pbmc proliferation and complement-mediated solubilization of pre-formed immune complexes in vitro. a mechanistic studying of clofazimine in human t cells revealed that this drug is a kv1.3 (kcna3) channel blocker. this indicates that clofazimine will be potentially used for treatment of multiple sclerosis, rheumatoid arthritis and type 1 diabetes. because the kv1.3-high effector memory t cells (tem) are actively involved in the development of these diseases, and kv1.3 activity is essential for stimulation and proliferation of tem by regulating calcium influx in the t cells. several clinical trials were also conducted looking for its immunosuppressive activity even before it was approved for leprosy by fda. it was first reported to be effective in treating chronic discoid lupus erythematosus with 17 out of 26 patients got remission. but later another group found it was ineffective in treating diffuse, photosensitive, systemic lupus erythematosus. clofazimine also has been sporadically reported with some success in other autoimmune diseases such as psoriasis, miescher's granulomatous cheilitis.

health geography health geography health geography is the application of geographical information, perspectives, and methods to the study of health, disease, and health care. medical geography, a sub-discipline of or sister field of health geography, focuses on understanding spatial patterns of health and disease as related to the natural and social environment. conventionally, there are two primary areas of research within medical geography: the first deals with the spatial distribution and determinants of morbidity and mortality, while the second deals with health planning, help-seeking behavior, and the provision of health services. hepatitis a prevalence worldwide, 2005. overview medical geography the first area of study within medical geography has been described as geographical epidemiology or disease geography and is focused on the spatial patterns and processes of health and disease outcomes. this area of inquiry can be differentiated from the closely related discipline of epidemiology in that it uses concepts and methods from geography, allowing an ecologic perspective on health that considers how interactions between humans and the environment result in observed health outcomes. the second area of study focused on the planning and provision of health services, often with a focus on the spatial organization of health systems and exploration of how this arrangement affects accessibility of care. health geography the study of health geography has been influenced by repositioning medical geography within the field of social geography due to a shift towards a social model in health care, rather than a medical model. this advocates for the redefinition of health and health care away from prevention and treatment of illness only to one of promoting well-being in general. under this model, some previous illnesses (e.g., mental ill health) are recognized as behavior disturbances only, and other types of medicine (e.g., complementary or alternative medicine and traditional medicine) are studied by the medicine researchers, sometimes with the aid of health geographers without medical education. this shift changes the definition of care, no longer limiting it to spaces such as hospitals or doctor's offices. also, the social model gives priority to the intimate encounters performed at non-traditional spaces of medicine and healthcare as well as to the individuals as health consumers. this alternative methodological approach means that medical geography is broadened to incorporate philosophies such as marxian political economy, structuralism, social interactionism, humanism, feminism and queer theory. history john snow's cholera map of the 1854 broad street cholera outbreak. relationships between place and health have long been recognized throughout human history, predating modern health delivery systems and providing insights into the transmission of infectious agents, well before the germ theory paradigm shift in the late 1800s. throughout history there have been many examples of place and location playing major roles in shaping perceptions of health and risk. the associations between geographical characteristics and health outcomes, which essentially form the foundation of modern medical geography, were recognized more than 2,000 years ago by hippocrates in his treatise ’’on airs, waters, and places’’ (ca. 400 bc). the industrial revolution in the 1700s brought with it a plethora of novel public health issues stemming from rapid urban development and poor sanitation, conditions which fueled the development of disease mapping, or medical cartography. a precursor to medical geography, medical cartography arose from the need to communicate spatial discrepancies in risk for diseases of unknown cause, particularly urban outbreaks of cholera and yellow fever. one of the most prominent figures in both epidemiology and medical geography is john snow, the physician who correctly identified the source of exposure during the 1854 broad street cholera outbreak. snow's famous 1854 map of the cholera outbreak graphically demonstrates that cases were clustered around the broad street pump, the source of contaminated water that fueled the epidemic. this map led snow to identify the contaminated pump and conclude that cholera was a waterborne illness, a remarkable feat given that bacteria were unknown to science at the time. while snow's contributions to medical geography and epidemiology are irrefutable, the role of the map in this particular investigation is somewhat overstated. dot maps of cases produced during the industrial period were powerful tools in communicating the findings of traditional epidemiological measures of association, but their role as analytic tools were restricted due to technological limitations. modern medical geography arose in the united states in the 1950s with the pioneering work of jacques may, who worked as a surgeon in thailand and vietnam and noticed differences between the health experiences of his patients in these locations and in europe. although the notion that the environment could influence human health has been understood since hippocrates, medical geography as envisioned by may built on this idea, describing medical geography as working to understand the nature of the relationships between pathogen transmission and geographical factors. may soon began mapping global distributions of disease and exploring the cultural and environmental factors that influenced these distributions. areas of study health geography is considered to be divided into two distinct elements. the first of which is focused on geographies of disease and ill health, involving descriptive research quantifying disease frequencies and distributions, and analytic research concerned with finding what characteristics make an individual or population susceptible to disease. this requires an understanding of epidemiology. the second component of health geography is the geography of health care, primarily facility location, accessibility, and utilization. this requires the use of spatial analysis and often borrows from behavioral economics. geographies of disease and ill health health geographers are concerned with the prevalence of different diseases along a range of spatial scales from a local to global view, and inspects the natural world, in all of its complexity, for correlations between diseases and locations. this situates health geography alongside other geographical sub-disciplines that trace human-environment relations. health geographers use modern spatial analysis tools to map the dispersion of health, including various diseases, as individuals spread them amongst themselves, and across wider spaces as they migrate. health geographers also consider all types of spaces as presenting health risks, from natural disasters, to interpersonal violence, stress, and other potential dangers. health insurance coverage geography of health care provision although healthcare is a public good, it is not equally available to all individuals. demand for public services is continuously increasing. people need advance knowledge and the latest prediction technology, that health geography offers. the latest example of such technology is telemedicine. many people in the united states are not able to access proper healthcare because of inequality in health insurance and the means to afford medical care. mobility and disease tracking: with the advent of mobile technology and its spread, it is now possible to track individual mobility. by correlating the movement of individuals through tracking the devices using access towers or other tracking systems, it is now possible to determine and even control disease spread. while privacy laws question the legality of tracking individuals, the commercial mobile service providers are using covert techniques or obtaining government waivers to allow permission to track people. methods geographic information systems (gis) are used extensively in medical geography to visualize and analyze georeferenced health-related data. these spatial data can be vector (point, line, or polygon) or raster (continuous grid) format and are often presented in quantitative thematic maps. disease outcomes and sociodemographic characteristics collected through surveillance systems and population censuses are frequently used as data sources in medical geography studies. in disease ecology studies, interpolated climate data, gridded land surveys, and remote sensing imagery are examples of data used to quantify the environmental characteristics of disease systems. spatial statistics or analysis are applied to test hypotheses regarding patterns or relationships within these data, such as the property of spatial dependency (spatially closer entities are more similar or related than spatially distant entities) or spatial heterogeneity (locations are unique relative to other locations). some examples of the spatial analyses used in medical geography include point pattern analysis, tests for spatial autocorrelation, geographically weighted regression (gwr), ecological niche modeling, spatial scan statistics, and network analysis. health geographers notable health geographers include: sarah curtis william c. gorgas kelvyn jones john snow

ve (nerve agent) ve (nerve agent) ve (s-(diethylamino)ethyl o-ethyl ethylphosphonothioate) is a "v-series" nerve agent closely related to the better-known vx nerve agent. it was first reported in 1958 as a pesticide. ve names iupac name (s)-(ethyl (ethyl)phosphinate) identifiers cas number 21738-25-0 3d model (jsmol) interactive image chemspider 59011 y pubchem cid 65568 comptox dashboard (epa) dtxsid00893813 inchi inchi=1s/c10h24no2ps/c1-5-11(6-2)9-10-15-14(12,8-4)13-7-3/h5-10h2,1-4h3 ykey: qxrunsumqbtcqs-uhfffaoysa-n yinchi=1/c10h24no2ps/c1-5-11(6-2)9-10-15-14(12,8-4)13-7-3/h5-10h2,1-4h3key: qxrunsumqbtcqs-uhfffaoyay smiles o=p(occ)(sccn(cc)cc)cc properties chemical formula c10h24no2ps molar mass 253.34 g·mol−1 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). y verify (what is yn ?) infobox references like most of the agents in the v-series (with the exception of vx), ve has not been extensively studied outside of military science. it is commonly theorized that the so-called "second-generation" v series agents came from a cold war era russian chemical weapons development program. they may have been developed sometime between 1950 and 1990. they have similar lethal dose levels to vx (between 10–50 mg) and have similar symptoms and method of action to other nerve agents that act on cholinesterase, and treatment remains the same, but the window for effectively treating second generation v series seizures is shorter. in addition to the standard seizures, some of the second generation v series agents are known to cause comas.

vaginal artery vaginal artery the vaginal artery is an artery in females that supplies blood to the vagina and the base of the bladder. vaginal arteryarteries of the female reproductive tract (posterior view): uterine artery, ovarian artery and vaginal arteries.vessels of the uterus and its appendages, rear view.detailssourceinternal iliac arteryuterine arteryveinvaginal venous plexussuppliesurinary bladder, ureter, vaginaidentifierslatinarteria vaginalista98a12.2.15.035fta24336fma18832anatomical terminology structure vaginal artery the vaginal artery is usually a branch of the internal iliac artery. some sources say that the vaginal artery can arise from the uterine artery, but the phrase vaginal branches of uterine artery is the term for blood supply to the vagina coming from the uterine artery. the vaginal artery is frequently represented by two or three branches. these descend to the vagina, supplying its mucous membrane. they anastomose with branches from the uterine artery. it can send branches to the bulb of the vestibule, the fundus of the bladder, and the contiguous part of the rectum. function the vaginal artery supplies oxygenated blood to the muscular wall of the vagina, along with the uterine artery and the internal pudendal artery. it also supplies the cervix, along with the uterine artery. other animals in horses, the vaginal artery may haemorrhage after birth, which can cause death.

merosome merosome a merosome is a life stage of malaria parasites of the genus plasmodium. after injection by mosquitoes into the human host, malaria parasites first migrate to liver cells (hepatocytes), where they replicate asexually inside the host cell. afterwards, they go on to infect red blood cells. this transition is characterised by the 'budding off' of membrane-bound structures called merosomes, first characterised by sturm and amino et al. in 2006. it is thought that these structures, that are derived from hepatocytes including their membranes, aid in the parasites' evasion of immune cells known as kupffer cells that are located in the liver.

anterior inferior anterior inferior anterior inferior may refer to: anterior inferior cerebellar artery anterior inferior iliac spine anterior tibiofibular ligament anterior inferior pancreaticoduodenal artery this article is issued from wikipedia. the text is licensed under creative commons - attribution - sharealike. additional terms may apply for the media files.

drug-induced urticaria drug-induced urticaria drug-induced urticaria occurs by immunologic and nonimmunologic mechanisms, urticaria most commonly caused by aspirin and nsaids.: 120 drug-induced urticariaspecialtydermatology

catagmatic catagmatic in pre-modern medicine, the term catagmatic generally referred to any treatment purported to heal bone fractures, by promoting the formation of a callus. the principal catagmatics were armenian bole, tragacanth, osteocolla, cyprus nuts, frankincense, aloes, and acacia. the word comes from the greek καταγμα, "fracture".

plasmodium venkataramiahii plasmodium venkataramiahii plasmodium venkataramiahii is a parasite of the genus plasmodium. plasmodium venkataramiahii scientific classification kingdom: protista phylum: apicomplexa class: aconoidasida order: haemosporida family: plasmodiidae genus: plasmodium species: p. venkataramiahii binomial name plasmodium venkataramiahii like all plasmodium species p. achromaticum has both vertebrate and insect hosts. the vertebrate hosts for this parasite are birds. clinical features and host pathology this species infects crows (corvus splendens).

cd4 cd4 in molecular biology, cd4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the t-cell receptor (tcr). cd4 is found on the surface of immune cells such as t helper cells, monocytes, macrophages, and dendritic cells. it was discovered in the late 1970s and was originally known as leu-3 and t4 (after the okt4 monoclonal antibody that reacted with it) before being named cd4 in 1984. in humans, the cd4 protein is encoded by the cd4 gene. cd4available structurespdbortholog search: pdbe rcsb list of pdb id codes1cdh, 1cdi, 1cdj, 1cdu, 1cdy, 1g9m, 1g9n, 1gc1, 1jl4, 1q68, 1rzj, 1rzk, 1wio, 1wip, 1wiq, 2b4c, 2jkr, 2jkt, 2klu, 2nxy, 2nxz, 2ny0, 2ny1, 2ny2, 2ny3, 2ny4, 2ny5, 2ny6, 2qad, 3b71, 3cd4, 3jwd, 3jwo, 3lqa, 3o2d, 3s5l, 3t0e, 4jm2, 1wbr, 3s4s, 4h8w, 4p9h, 4q6i, 4r2g, 4r4h, 4rqs, 3j70, 5a7x, 5a8h, 5cayidentifiersaliasescd4, cd4mut, cd4 molecule, okt4d, imd79external idsomim: 186940 mgi: 88335 homologene: 513 genecards: cd4 gene location (human)chr.chromosome 12 (human)band12p13.31start6,786,858 bpend6,820,799 bpgene location (mouse)chr.chromosome 6 (mouse)band6 f2|6 59.17 cmstart124,841,655 bpend124,865,184 bprna expression patternbgeehumanmouse (ortholog)top expressed inmonocytelymph nodespleenappendixgallbladderthymusupper lobe of left lungright lungright lobe of liverbloodtop expressed inthymuslymph nodebloodspleenexternal carotid arteryinternal carotid arterysuperior frontal gyrusmolarsecondary oocyteglobus pallidusmore reference expression databiogpsn/agene ontologymolecular function transmembrane signaling receptor activity virus receptor activity protein homodimerization activity zinc ion binding extracellular matrix structural constituent enzyme binding immunoglobulin binding protein binding coreceptor activity interleukin-16 binding interleukin-16 receptor activity mhc class ii protein binding identical protein binding protein tyrosine kinase binding signaling receptor activity protein kinase binding signaling receptor binding cellular component endoplasmic reticulum lumen integral component of membrane early endosome membrane cell surface endoplasmic reticulum membrane membrane raft t cell receptor complex external side of plasma membrane plasma membrane clathrin-coated vesicle membrane integral component of plasma membrane biological process transmembrane receptor protein tyrosine kinase signaling pathway defense response to gram-negative bacterium positive regulation of protein kinase activity mitigation of host defenses by virus positive regulation of calcium-mediated signaling signal transduction helper t cell enhancement of adaptive immune response t cell selection response to estradiol induction by virus of host cell-cell fusion adaptive immune response response to vitamin d t cell differentiation cell surface receptor signaling pathway positive regulation of t cell proliferation positive regulation of peptidyl-tyrosine phosphorylation enzyme linked receptor protein signaling pathway t cell activation positive regulation of t cell activation maintenance of protein location in cell cytokine production t cell receptor signaling pathway immune system process positive regulation of calcium ion transport into cytosol regulation of t cell activation immune response cell adhesion viral process fusion of virus membrane with host plasma membrane membrane organization positive regulation of protein phosphorylation positive regulation of kinase activity interleukin-15-mediated signaling pathway positive regulation of i-kappab kinase/nf-kappab signaling positive regulation of mapk cascade positive regulation of monocyte differentiation positive regulation of transcription, dna-templated positive regulation of viral entry into host cell regulation of calcium ion transport positive regulation of erk1 and erk2 cascade cellular response to granulocyte macrophage colony-stimulating factor stimulus cytokine-mediated signaling pathway macrophage differentiation sources:amigo / quickgoorthologsspecieshumanmouseentrez92012504ensemblensg00000010610ensmusg00000023274uniprotp01730p06332refseq (mrna)nm_000616nm_001195014nm_001195015nm_001195016nm_001195017nm_001382705nm_001382706nm_001382707nm_001382714nm_013488refseq (protein)np_000607np_001181943np_001181944np_001181945np_001181946np_001369634np_001369635np_001369636np_001369643np_038516location (ucsc)chr 12: 6.79 – 6.82 mbchr 6: 124.84 – 124.87 mbpubmed searchwikidataview/edit humanview/edit mouse cd4, cluster of differentiation 4, extracellularstructure of t-cell surface glycoprotein cd4, monoclinic crystal formidentifierssymbolcd4-extrcelpfampf09191interproipr015274scop21cid / scope / supfamopm superfamily193opm protein2klucddcd07695membranome27available protein structures:pfam structures / ecod pdbrcsb pdb; pdbe; pdbjpdbsumstructure summary image of cd4 co-receptor binding to mhc (major histocompatibility complex) non-polymorphic region. cd4+ t helper cells are white blood cells that are an essential part of the human immune system. they are often referred to as cd4 cells, t-helper cells or t4 cells. they are called helper cells because one of their main roles is to send signals to other types of immune cells, including cd8 killer cells, which then destroy the infectious particle. if cd4 cells become depleted, for example in untreated hiv infection, or following immune suppression prior to a transplant, the body is left vulnerable to a wide range of infections that it would otherwise have been able to fight. structure schematic representation of cd4 receptor. like many cell surface receptors/markers, cd4 is a member of the immunoglobulin superfamily. it has four immunoglobulin domains (d1 to d4) that are exposed on the extracellular surface of the cell: d1 and d3 resemble immunoglobulin variable (igv) domains. d2 and d4 resemble immunoglobulin constant (igc) domains. the immunoglobulin variable (igv) domain of d1 adopts an immunoglobulin-like β-sandwich fold with seven β-strands in 2 β-sheets, in a greek key topology. cd4 interacts with the β2-domain of mhc class ii molecules through its d1 domain. t cells displaying cd4 molecules (and not cd8) on their surface, therefore, are specific for antigens presented by mhc ii and not by mhc class i (they are mhc class ii-restricted). mhc class i contains beta-2 microglobulin. the short cytoplasmic/intracellular tail (c) of cd4 contains a special sequence of amino acids that allow it to recruit and interact with the tyrosine kinase lck. function cd4 is a co-receptor of the t cell receptor (tcr) and assists the latter in communicating with antigen-presenting cells. the tcr complex and cd4 bind to distinct regions of the antigen-presenting mhc class ii molecule. the extracellular d1 domain of cd4 binds to the β2 region of mhc class ii. the resulting close proximity between the tcr complex and cd4 allows the tyrosine kinase lck bound to the cytoplasmic tail of cd4 to phosphorylate tyrosine residues of immunoreceptor tyrosine activation motifs (itams) on the cytoplasmic domains of cd3 to amplify the signal generated by the tcr. phosphorylated itams on cd3 recruit and activate sh2 domain-containing protein tyrosine kinases (ptk), such as zap70, to further mediate downstream signalling through tyrosine phosphorylation. these signals lead to the activation of transcription factors, including nf-κb, nfat, ap-1, to promote t cell activation. other interactions cd4 has also been shown to interact with spg21, and uncoordinated-119 (unc-119). disease hiv infection hiv-1 uses cd4 to gain entry into host t-cells and achieves this through its viral envelope protein known as gp120. the binding to cd4 creates a shift in the conformation of gp120 allowing hiv-1 to bind to a co-receptor expressed on the host cell. these co-receptors are chemokine receptors ccr5 or cxcr4. following a structural change in another viral protein (gp41), hiv inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane. hiv pathology hiv infection leads to a progressive reduction in the number of t cells expressing cd4. medical professionals refer to the cd4 count to decide when to begin treatment during hiv infection, although recent medical guidelines have changed to recommend treatment at all cd4 counts as soon as hiv is diagnosed. a cd4 count measures the number of t cells expressing cd4. while cd4 counts are not a direct hiv test—e.g. they do not check the presence of viral dna, or specific antibodies against hiv—they are used to assess the immune system of a patient. national institutes of health guidelines recommend treatment of any hiv-positive individuals, regardless of cd4 count normal blood values are usually expressed as the number of cells per microliter (μl, or equivalently, cubic millimeter, mm3) of blood, with normal values for cd4 cells being 500–1200 cells/mm3. patients often undergo treatments when the cd4 counts reach a level of 350 cells per microliter in europe but usually around 500/μl in the us; people with less than 200 cells per microliter are at high risk of contracting aids defined illnesses. medical professionals also refer to cd4 tests to determine efficacy of treatment. viral load testing provides more information about the efficacy for therapy than cd4 counts. for the first 2 years of hiv therapy, cd4 counts may be done every 3–6 months. if a patient's viral load becomes undetectable after 2 years then cd4 counts might not be needed if they are consistently above 500/mm3. if the count remains at 300–500/mm3, then the tests can be done annually. it is not necessary to schedule cd4 counts with viral load tests and the two should be done independently when each is indicated. reference ranges for blood tests of white blood cells, comparing cd4+ cell amount (shown in green-yellow) with other cells. other diseases cd4 continues to be expressed in most neoplasms derived from t helper cells. it is therefore possible to use cd4 immunohistochemistry on tissue biopsy samples to identify most forms of peripheral t cell lymphoma and related malignant conditions. the antigen has also been associated with a number of autoimmune diseases such as vitiligo and type i diabetes mellitus. t-cells play a large part in autoinflammatory diseases. when testing a drug's efficacy or studying diseases, it is helpful to quantify the amount of t-cells on fresh-frozen tissue with cd4+, cd8+, and cd3+ t-cell markers (which stain different markers on a t-cell - giving different results).

black death in norway black death in norway the black death was present in norway between 1349 and 1350. the black death in norway is more documented than any other nordic country, but the information is unbalanced and mainly focused on western norway. 1346–1353 spread of the black death in europe map mother there comes an old woman (mor der kommer en kjerring). an illustration of the black death. in traditional norwegian history, the black death is given major importance, as an explanation for the deterioration of norway from an independent nation in the early 14th century, to its loss of political independence in the kalmar union in the late century, which caused norway to lose political and economic independence and become a danish province for centuries onward. while the exact number of deaths from the black death is unknown, it is clear that the plague caused a demographic shock, and that the population did not recover to pre-pandemic levels until the 17th century. background norway in the mid-14th century at this point in time, norway was in a personal union with sweden under the same monarch, magnus iv of sweden. the black death since the outbreak of the black death at the crimea, it had reached sicily by an italian ship from the crimea. after having spread across the italian states, and from italy to france, spain and england, the plague reached norway by a plague ship from england in the summer of 1349. plague migration western norway the bubonic plague pandemic known as the black death reached bergen in norway by ship from england in late summer (probably august) of 1349, and spread from bergen north to trondheim in the autumn of 1349. the black death in norway is famously described in the unique contemporary icelandic sources gotskalks annal and lögmanns-annál by einar haflidason, which describes the migration of the black death in detail in western norway. the lögmanns-annál contains the witness statements of the icelandic bishops orm of hólar and gyrd ivarsson of skalholt, who visited norway when the plague arrived from england and returned to iceland when it had left norway again in 1351. in this testimony, it is described how the infamous "plague ship" arrived to bergen in norway from england. when the cargo was unloaded from the ship, the ship crew started to die. shortly after, the inhabitants of bergen started to die, and from bergen it continued all over norway, ultimately killing a third of the population. the ship from england reportedly was sunk, but several plague ships were to have stranded along the beaches in the same fashion. the gotskalks annal also gives a detailed account of the same event. it also names a number of the victims of the plague, among whom were several members of the clergy, an account that can be verified by other sources. it also states that the plague migrated from bergen north to nidaros in 1349. additional information is found from wills, contracts, and other documents from the period of the plague. because of this, the plague in western norway is better documented than in sweden, denmark and finland (the plague did not reach iceland until 1402). eastern norway in contrast to the famous and documented plague migration in western norway, the migration of the plague in eastern norway is only indirectly documented, as there are no direct references to it or testimonies similar to the one in western norway. because of the great focus on western norway, it was long believed that the plague migrated only from bergen to the rest of the country. by the data from the plague deaths in oslo, it appears that oslo was in fact reached by the plague before bergen: already in may or june 1349, with the difference that there are no witness accounts from its progress in contrast to western norway. the plague is likely to have reached oslo by sea in the spring or early summer of 1349, presumably by ship. from oslo, it migrated north toward hamar, west toward valdres in central norway, south west toward stavanger, and to the east toward sweden. the black death appear not to have reached stavanger in the south from bergen, because the first plague deaths are not noted there until 1350, and it likely migrated to it from oslo. northern norway it is unknown whether the black death reached northern norway. however, the fact that the church in trondenes was built in the late 14th century or early 15th century, when the rest of norway rather abandoned churches because of the population loss than built new ones, indicate that the plague did not reach this part of the nation. consequences in traditional history, the black death has played a major role as the explanation to why norway lost its position as a major kingdom in the early 14th century, and entered a many centuries-long period of stagnation as the most neglected of the kingdoms of the kalmar union under denmark in the late 14th century. norway entered the kalmar union in 1380, initially as an equal kingdom under a personal union but from 1536 as a danish province: it was transferred to a personal union under sweden in 1814, and was not to regain its status as an independent nation until 1905. this period was a traumatic period of stagnation, exploitation and lack of development under foreign power, and a major contributing factor to this has been attributed to the black death, and the population loss caused by it. that norway did experience a demographic shock is clearly documented. of the 36.500 farms and 60.000 households that existed around the year 1300, 16.000 farms and 23.000 households existed in 1520, and the population in 15th-century norway is estimated to have been less than half of what it had been in 1300. between 60 and 65 percent of the population are estimated to have died during the black death, and norway was not to recover until the 17th century. however, this is not enough to attribute the political decline of norway: england also lost about 60 or 65 percent of its population to the black death, and sweden also did not recover until the 17th century. what may however support the traditional explanation that the black death caused the political decline of norway was the fact that the death toll among the social elite classes appears to have been much higher in norway than in both sweden and england, contributing to a smaller class which could protect norway's role and independence toward the dominance of foreign elites during the kalmar union. it appears that the death toll was big in all the elite classes in norwegian society, contributing to the norwegian loss of independence under the kalmar union in several areas. this is clear when the comparison is made to sweden, which also became a part of the kalmar union under denmark, but who unlike norway managed to protect their rights much better toward denmark because of the strong swedish nobility. while all bishops survived the black death in sweden, all bishops in norway died in the plague with the exception of the bishop of oslo: in 1371, it was noted that of the 300 priests in norway prior to the plague, only 40 was left. the norwegian class of officials appear to have experienced heavy losses, as the king was forced to concentrate those left to the southern provinces to restore order while leaving the northern provinces to themselves, and in 1351–52, a report stated that the tax to the pope was impossible to collect in norway because the administration had broken down and a great lack organization existed there because of the plague. the diminished norwegian nobility was not able to protect the political rights of norway in the kalmar union and the military power was lost to denmark who used mercenaries from germany; the norwegian merchant class lost their power of the norwegian economy to the german merchants of the hanseatic league who established themselves in bergen; and the dead norwegian officials were replaced by german and danish officials appointed to administer norway for denmark; all of which has been described as the decline of norway under the danish dominance of the kalmar union.