Datasets:

krvhrv

/

crawl-books

like 0

coracobrachialis muscle coracobrachialis muscle the coracobrachialis muscle is a muscle in the upper medial part of the arm. it is located within the anterior compartment of the arm. it originates from the coracoid process of the scapula; it inserts onto the middle of the medial aspect of the body of the humerus. it is innervated by the musculocutaneous nerve. it acts to adduct and flex the arm. coracobrachialis muscledeep muscles of the chest and front of the arm, with the boundaries of the axilla. coracobrachialis is shown in blue.position of coracobrachialis muscle (shown in red)detailsorigincoracoid process of scapulainsertionanteromedial surface of humerus distal to crest of lesser tuberclearterybrachial arterynervemusculocutaneous nerve (c5, c6, and c7)actionsadducts humerus, flexes the arm at glenohumeral jointidentifierslatinmusculus coracobrachialista98a04.6.02.017ta22468fma37664anatomical terms of muscle structure origin coracobrachialis muscle arises from the (deep surface of the) apex of the coracoid process of the scapula (a common origin with the short head of the biceps brachii). it additionally also arises from the proximal portion of tendon of origin of the biceps brachii muscle. insertion it is inserted (by means of a flat tendon) into an impression at the middle of the medial border of the body of the humerus (shaft of the humerus) between the attachments of the medial head of the triceps brachii and the brachialis. innervation coracobrachialis muscle is perforated by and innervated by the musculocutaneous nerve, which arises from the anterior division of the upper trunk (c5, c6) and middle trunk (c7) of the brachial plexus. variation the coracobrachialis muscle has been classified into distinct superficial and deep layers. in 16% of japanese individuals the muscle is fully divided into these layers. in 8% of individuals, there is incomplete seperation. in the remaining 76%, individuals show no discernible signs of separation between the layers. function the action of the coracobrachialis is to flex and adduct the arm at the glenohumeral joint (shoulder joint). also, the coracobrachialis resists deviation of the arm from the frontal plane during abduction. therefore, the contraction of the coracobrachialis leads to two distinct movements at the shoulder joint. it both draws the humerus forward, causing flexion of the arm, and draws the humerus toward the torso, causing adduction of the arm. to a smaller extent, it also turns the humerus inwards, causing internal rotation. another important function of the coracobrachialis is the stabilization of the humeral head within the shoulder joint, especially when the arm is hanging freely at a person's side. clinical significance the overuse of the coracobrachialis can lead to stiffening of the muscle. common causes of injury include chest workouts or activities that require one to press the arm very tight towards the body, e.g. work on the rings in gymnastics. symptoms of overuse or injury are pain in the arm and shoulder, radiating down to the back of the hand. in more severe cases, the musculocutaneous nerve can get trapped, causing disturbances in sensation to the skin on the radial part of the forearm and weakened flexion of the elbow, as the nerve also supplies the biceps brachii and brachialis muscles. actual rupture to the coracobrachialis muscle is extremely rare. very few case reports exist in the literature, and it is reported to be caused by direct trauma to the contracted muscle. avulsion of the muscle's origin from the coracoid as a result of indirect forces is even more unusual.

choking game choking game the choking game or blackout challenge is the act of intentionally cutting off oxygen to the brain with the goal of inducing temporary loss of consciousness and euphoria. reasons for practice limited research has been conducted regarding motivations for practicing the fainting game, although thrill seeking has been identified as a risk factor, as has the perception that it is a low-risk activity. anecdotal reasons stated include: peer pressure, a challenge or dare, a rite of passage into a social group or amusement over erratic behavior. curiosity in experiencing an altered state of consciousness, the experience of a greyout, or an imagined approximation to a near-death experience. a belief that it can induce a brief sense of euphoria (a rushing sensation or high). the prospect of intoxication, albeit brief, at no financial cost. reasons for practice are distinct from erotic asphyxiation. steve field, chairman of the royal college of general practitioners in london, claims that the fainting game is pursued primarily by children and teens "to get a high without taking drugs." children "aren't playing this game for sexual gratification." it is frequently confused with erotic asphyxiation, which is oxygen deprivation for sexual arousal. unlike erotic asphyxiation, practice of the fainting game appears to be uncommon in adulthood. mechanisms of effect the vulnerable carotid artery, (large, red tube), and the vagus nerve running parallel on its left there are two main mechanisms behind many variations of this practice, both resulting in cerebral hypoxia (oxygen deprivation to the brain). the two mechanisms tend to be confused with each other or treated as one but are quite dissimilar although both have the potential to cause permanent brain damage or death. the two mechanisms are strangulation and self-induced hypocapnia and work as follows: strangulation a ligature such as a belt or rope around the neck, or hands or arm pressure on the neck compresses the internal carotid artery. apart from the direct restriction of blood to the brain there are two other significant responses produced by pressing on the neck: pressing on the carotid arteries also presses on baroreceptors. these bodies then cause vasodilatation in the brain leading to insufficient blood to perfuse the brain with oxygen and maintain consciousness. a message is also sent via the vagus nerve to the main pacemaker of the heart to decrease the rate and volume of the heartbeat, typically by a third. in some cases there is evidence that this may escalate into asystole, a form of cardiac arrest that is difficult to treat. there is a dissenting view on the full extent how and when a person reaches a stage of permanent injury, but it is agreed that pressure on the vagus nerve causes changes to pulse rate and blood pressure and is dangerous in cases of carotid sinus hypersensitivity. increased breathing the second mechanism requires hyperventilation (forced overbreathing) until symptoms of hypocapnia such as tingling, light-headedness or dizziness are felt, followed by a breath-hold. this alone is enough to cause a blackout, but it is widely believed that the effect is enhanced if lung air pressure is increased by holding the breath "hard" or "bearing down" (tightening the diaphragm as in a forced exhalation while allowing no air to escape or having an assistant apply a bear-hug). these latter actions may augment the effects of hypoxia by approximating the valsalva maneuver, causing vagal stimulation. the hyperventilation leads to an excessive elimination of carbon dioxide (co2) whereas no significant additional amounts of oxygen can be stocked in the body. as only carbon dioxide is responsible for the breathing stimulus, after hyperventilation, breath can be held longer until cerebral hypoxia occurs. the blood also becomes abnormally alkaline as a result of the excessive elimination of carbon dioxide; this subsequent rise in blood ph is termed alkalosis. alkalosis interferes with normal oxygen utilization by the brain. the symptoms of alkalosis are neuromuscular irritability, muscular spasms, tingling and numbness of the extremities and around the mouth, and a dizziness, or giddiness, often interpreted as a sense of euphoria. in the body alkalosis generally induces vasodilation (widening of the blood vessels) but in the brain alone it causes vasoconstriction (narrowing of the blood vessels). this vasoconstriction appears to be made even worse by a sudden increase in blood pressure caused by squeezing or holding the breath "hard". the alkalosis-induced euphoria can be followed rapidly by hypoxia-induced unconsciousness. the sequence of events leading to unconsciousness from hyperventilation is as follows: decrease in partial pressure of alveolar co2. decrease in partial pressure of arterial co2. increase in blood ph, (respiratory alkalosis). vasoconstriction of blood vessels supplying brain. pooling of the blood present in the brain at the time. brain rapidly uses up oxygen (o2) available in the pooled blood. o2 concentration in the brain drops. unconsciousness from hypoxia of cerebral tissue. because the brain cannot store reserves of oxygen and, unlike other organs, has an exceedingly low tolerance of oxygen deprivation, it is highly vulnerable if vasoconstriction is not reversed. normally, if the brain is hypoxic, autonomous systems in the body divert blood to the brain at the expense of other organs; because the brain is vasoconstricted this mechanism is not available. vasoconstriction is only reversed by the build-up of carbon dioxide in the blood through suspension of breathing. in some versions the bear-hug is replaced by pressure on the neck in which case blackout is a hybrid of strangulation and self-induced hypocapnia. other mechanisms unconsciousness may be induced by other methods although these are controversial: pressure over the carotid sinus may induce syncope (fainting) without any other action at all but this is difficult to reproduce and is not the basis of the game. for those susceptible to carotid sinus syncope, of which most people would be unaware until it occurred, this can be an exceedingly dangerous game. in both strangulation and self-induced hypocapnia blackouts the victim may experience dreaming or hallucinations, though fleetingly, and regains consciousness with short-term memory loss and involuntary movement of their hands or feet. full recovery is usually made within seconds if the strangulation stops. prevalence a 2008 centre for addiction and mental health study found that at least 79,000 students in the canadian province of ontario participated in this act. the 2006 youth health risk behavioral survey in williams county, ohio found that 11% of youths aged 12–18 years and 19% of youths aged 17–18 reported ever having practiced it. a challenge, named the "blackout challenge", became widespread on tiktok in 2021, resulting in multiple fatalities of children. injuries and fatalities age distribution of youths aged 6–19 years whose deaths were attributed to the "choking game" (n=82) during 1995–2007, compared with youths whose deaths were attributed to suicide by hanging/suffocation (n=5,101) during 1999–2005 any activity that deprives the brain of oxygen has the potential to cause moderate to severe brain cell death leading to permanent loss of neurological function ranging from difficulty in concentration or loss of short-term memory capacity through severe, lifelong mental disability to death. statistics on fatalities and neurological damage are controversial; no definitive, empirical study exists although the indications are that the practice is a significant contributor to death and disability, particularly among male juveniles in most developed countries. many believe that deaths are significantly underreported because of false attributions to suicide. one study by the u.s. centers for disease control and prevention (cdc) found sufficient evidence to indicate that since 1995 at least 82 youths between the age of 6 and 19 have died in the united states as a result of the game (roughly 1% of the deaths attributed to suicide by suffocation in the same age group), see chart. of these 86.6% were male, and the mean age was 13.3. 95.7% of these deaths occurred while the youth was alone; parents of the decedents were unaware of the game in 92.9% of cases. deaths were recorded in 31 states and were not clustered by location, season or day of week. neurological damage is harder to attribute accurately because of the difficulty of linking generalised, acquired neurological disability to a specific past event. incidental, or indirect, injuries may arise from falling or uncontrolled movements and crushing by a ligature or an assistant. such injuries may include concussion, bone fractures, tongue biting and hemorrhaging of the eyes. the cdc encourages parents, educators and health-care providers to familiarize themselves with the signs of the game. these include discussion of the game, bloodshot eyes, marks on the neck, severe headaches, disorientation after spending time alone, ropes, scarves, and belts tied to bedroom furniture or doorknobs or found knotted on the floor, and unexplained presence of things like dog leashes, choke collars and bungee cords. in popular culture the choking game phenomenon was the subject of the 2014 television film the choking game, based on the novel choke by diana lopez.

potexvirus potexvirus potexvirus is a genus of pathogenic viruses in the order tymovirales, in the family alphaflexiviridae. plants serve as natural hosts. there are 48 species in this genus, three of which are assigned to a subgenus. diseases associated with this genus include: mosaic and ringspot symptoms. the genus name comes from potato virus x). potexvirus color break symptoms caused by narcissus mosaic virus (nmv) in daffodils (a, b) and normal flower (c) virus classification (unranked): virus realm: riboviria kingdom: orthornavirae phylum: kitrinoviricota class: alsuviricetes order: tymovirales family: alphaflexiviridae genus: potexvirus taxonomy potexvirus contains one subgenus that has three species and 45 additional species unassigned to a subgenus. the following 48 species are assigned to the genus: subgenus: mandarivirus citrus yellow mottle-associated virus citrus yellow vein clearing virus indian citrus ringspot virus the following species are unassigned to a subgenus: allium virus x alstroemeria virus x alternanthera mosaic virus ambrosia asymptomatic virus 1 asparagus virus 3 babaco mosaic virus bamboo mosaic virus cactus virus x cassava colombian symptomless virus cassava common mosaic virus cassava virus x clover yellow mosaic virus cnidium virus x cymbidium mosaic virus euonymus yellow mottle associated virus euonymus yellow vein virus foxtail mosaic virus hosta virus x hydrangea ringspot virus lagenaria mild mosaic virus lettuce virus x lily virus x malva mosaic virus mint virus x narcissus mosaic virus nerine virus x opuntia virus x papaya mosaic virus pepino mosaic virus phaius virus x pitaya virus x plantago asiatica mosaic virus plantain virus x potato aucuba mosaic virus potato virus x schlumbergera virus x senna mosaic virus strawberry mild yellow edge virus tamus red mosaic virus tulip virus x turtle grass virus x vanilla virus x white clover mosaic virus yam virus x zygocactus virus x virology the virion length may vary considerably (between 470-1000 nanometers or more) and is 12-13 nm in diameter. the pitch of the helix is of the basic helix 3.3-3.7 nm (8-9 copies of the coat protein per turn). it is non-enveloped, flexuous and filamentous. the coat itself is composed of 1000-1500 copies of the coat protein. the genome is linear, 5.9-7 kilobases in length with a capped 5' end and a polyadenylated 3' end. the genome encodes 5 proteins. from left to right these proteins are: the viral replication protein that consists of a capping enzyme domain, a helicase-like domain, the rna dependent rna polymerase, three proteins - the triple gene block (tgb) 1, 2 and 3 - and the coat protein. genusstructuresymmetrycapsidgenomic arrangementgenomic segmentation potexvirusfilamentousnon-envelopedlinearmonopartite the rna is translated giving rise to the viral rna polymerase. this in turn produces a negative stranded template from which a series of subgenomic rnas are generated. these subgenomic rnas are then translated into the viral proteins. the 5' end is about 80 nucleotides in length and typically begins with the sequence gaaaa. in addition to its rna polymerase activity, the viral rna polymerase (molecular weight ~150 kilodaltons) also has methyltransferase and rna helicase activities. the tgb proteins are conserved among the allexivirus, carlavirus, foveavirus, furovirus, hordeivirus, pecluvirus, pomovirus and potexvirus genera. their functions are a matter of active research. tgb 1 (molecular weight 23 kda) is a multifunctional protein. it has rna helicase activity and seems to be involved in cell to cell movement. the tgb 2 (molecular weight 11 kda) and tgb 3 (molecular weight 10 kda) proteins associate with the endoplasmic reticulum. the coat protein has a molecular weight of ~25kda. the 3' untranslated region is ~100 nucleotides in length. life cycle viral replication is cytoplasmic. entry into the host cell is achieved by penetration into the host cell. replication follows the positive stranded rna virus replication model. positive stranded rna virus transcription is the method of transcription. translation takes place by leaky scanning. the virus exits the host cell by tripartite non-tubule guided viral movement. the virus is transmitted via a vector (insects). transmission routes are vector and mechanical. genushost detailstissue tropismentry detailsrelease detailsreplication siteassembly sitetransmission potexvirusplantsnoneviral movement; mechanical inoculationviral movementcytoplasmcytoplasminsects hosts known hosts are various flowering plants. distribution these viruses appear to occur worldwide.

3,4-methylenedioxy-n-propargylamphetamine 3,4-methylenedioxy-n-propargylamphetamine 3,4-methylenedioxy-n-propargylamphetamine (mdpl) is a lesser-known psychedelic drug and a substituted amphetamine. mdpl was first synthesized by alexander shulgin. in his book pihkal (phenethylamines i have known and loved), the minimum dosage is listed as 150 mg, and the duration unknown. mdpl causes few to no effects. very little data exists about the pharmacological properties, metabolism, and toxicity of mdpl. 3,4-methylenedioxy-n-propargylamphetamine names preferred iupac name n-prop-2-yn-1-amine identifiers cas number 74698-46-7 3d model (jsmol) interactive image chemspider 21106336 pubchem cid 44719587 unii tk2wh78t88 comptox dashboard (epa) dtxsid70660372 inchi inchi=1s/c13h15no2/c1-3-6-14-10(2)7-11-4-5-12-13(8-11)16-9-15-12/h1,4-5,8,10,14h,6-7,9h2,2h3key: lryutpibtledjj-uhfffaoysa-n smiles cc(ncc#c)cc1ccc2ococ2c1 properties chemical formula c13h15no2 molar mass 217.268 g·mol−1 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). infobox references legality united kingdom this substance is a class a drug in the drugs controlled by the uk misuse of drugs act.

thermal trauma thermal trauma thermal trauma is any burn-related injury that can potentially lead to serious outcomes. there are various causes of thermal trauma, including fire, radiant heat, radiation, chemical, or electrical contact, that can affect a person in many ways based on factors from anatomical and physiological factors. depending on the severity of the burns, quick management and transport to an appropriate burn facility may be necessary to prevent loss of life. various classification scales exist for use with thermal trauma to determine the severity of the burns, which is used to determine the resources used and for statistical collection. the initial assessment is critical in determining the extent of injuries and what will be needed to manage an injury, and treating immediate life threats. thermal traumaspecialtyemergency medicine classification burn injuries are generally classified by either severity, the location of damage, or a combination of both. various scales exist to provide a quantifiable metric to measure the severity of burn-related injuries. the value can be used for triaging a patient or for statistical analysis. burn injury scales measure damage to anatomical parts, physiological values (blood pressure etc.), comorbidities or a combination of those.

specific language impairment specific language impairment specific language impairment (sli) (the term developmental language disorder is preferred by some) is diagnosed when a child's language does not develop normally and the difficulties cannot be accounted for by generally slow development, physical abnormality of the speech apparatus, autism spectrum disorder, apraxia, acquired brain damage or hearing loss. twin studies have shown that it is under genetic influence. although language impairment can result from a single-gene mutation, this is unusual. more commonly sli results from the combined influence of multiple genetic variants, each of which is found in the general population, as well as environmental influences. specific language impairmentspecialtyneurologytreatmentspeech-language pathology classification specific language impairment (sli) is diagnosed when a child has delayed or disordered language development for no apparent reason. usually the first indication of sli is that the child is later than usual in starting to speak and subsequently is delayed in putting words together to form sentences. spoken language may be immature. in many children with sli, understanding of language, or receptive language, is also impaired, though this may not be obvious unless the child is given a formal assessment. although difficulties with use and understanding of complex sentences are a common feature of sli, the diagnostic criteria encompass a wide range of problems, and for some children other aspects of language are problematic (see below). in general, the term sli is reserved for children whose language difficulties persist into school age, and so it would not be applied to toddlers who are late to start talking, most of whom catch up with their peer group after a late start. terminology the terminology for children's language disorders is extremely wide-ranging and confusing, with many labels that have overlapping but not necessarily identical meanings. in part this confusion reflects uncertainty about the boundaries of sli, and the existence of different subtypes. historically, the terms "developmental dysphasia" or "developmental aphasia" were used to describe children with the clinical picture of sli. these terms have, however, largely been abandoned, as they suggest parallels with adult acquired aphasia. this is misleading, as sli is not caused by brain damage. some synonyms currently in use for specific language impairment are language impairment, developmental language delay (dld), language disorder, and language-learning disability. researcher bonnie brinton argues that the term "specific language impairment" is misleading because the disorder does not only affect language, but also affects reading, writing, and social/pragmatics. in medical circles, terms such as specific developmental language disorder are often used, but this has the disadvantage of being wordy, and is also rejected by some people who think sli should not be seen as a "disorder". in the uk educational system, speech, language and communication needs (slcn) is currently the term of choice, but this is far broader than sli, and includes children with speech and language difficulties arising from a wide range of causes. subtypes (rapin and allen 1987) although most experts agree that children with sli are quite variable, there is little agreement on how best to subtype them. there is no widely accepted classification system. in 1983 rapin and allen proposed a classification of developmental language disorders based on the linguistic features of language impairment, which was subsequently updated by rapin. note that rapin is a child neurologist, and she refers to different subtypes as "syndromes"; many of those coming from the perspective of education or speech-language therapy reject this kind of medical label, and argue that there is not a clear dividing line between sli and normal variation. also, although most experts would agree that children with characteristics of the rapin subtypes can be identified, there are many cases who are less easy to categorise, and there is also evidence that categorisation can change over time. rapin's subgroups fall into three broad categories: receptive/expressive developmental language disorder receptive/expressive phonologic/syntactic deficit syndrome is the most common form of sli, in which the child's most obvious problems are a tendency to speak in short, simplified sentences, with omission of some grammatical features, such as past tense -ed. it is common also to see simplified speech production when the child is young. for instance, clusters of consonants may be reduced, so that "string" is pronounced as "ting". vocabulary is often limited, with a tendency to use "general all-purpose" terms, rather than more specific words. verbal auditory agnosia is a very rare form of language impairment, in which the child appears unable to make sense of speech sounds. it typically occurs as a symptom of landau-kleffner syndrome, in which case a diagnosis of sli would not be appropriate, as there is a known neurological origin of the language difficulties. expressive developmental language disorder syndromes developmental verbal dyspraxia (dvd) – in the child with dvd, comprehension is adequate; the onset of speech is very delayed and extremely limited with impaired production of speech sounds and short utterances. the poor speech production cannot be explained in terms of structural or neurological damage of the articulators. there is much disagreement about diagnostic criteria, but the label most often used for children whose intelligibility declines markedly when they attempt complex utterances, compared to when they are producing individual sounds or syllables. another key feature is inconsistency of speech sound production from one occasion to another. although the term "dyspraxia" suggests a pure output disorder, many – perhaps all – of these children have difficulty in doing tasks that involve mentally manipulating speech sounds, such as phonological awareness tasks. children with dvd also typically have major literacy problems, and receptive language levels may be poor on tests of vocabulary and grammar. phonologic programming deficit syndrome – the child speaks in long but poorly intelligible utterances, producing what sounds like jargon. outside rapin's group, little has been written about this subtype, which is not generally recognised in diagnostic frameworks. higher order processing disorders lexical deficit disorder – the child has word finding problems and difficulty putting ideas into words. there is poor comprehension for connected speech. again, there is little research on this subtype, which is not widely recognised. pragmatic language impairment – the child speaks in fluent and well-formed utterances with adequate articulation; content of language is unusual; comprehension may be over-literal and language use is odd. the child may chatter incessantly and be poor at turn-taking in conversation and maintaining a topic. there has been a great deal of controversy about this category, which is termed pragmatic language impairment (pli) in the uk. debate has centred over the question of whether it is a subtype of sli, part of the autistic spectrum, or a separate condition. in dsm-5, the term social communication disorder has been introduced; this is equivalent to pli. relationship with other neurodevelopmental disorders although textbooks draw clear boundaries between different neurodevelopmental disorders, there is much debate about overlaps between them. many children with sli meet diagnostic criteria for developmental dyslexia, and others have features of autism. presentation associated factors males are more affected by sli than females. in clinical samples, the sex ratio of affected males: females is around 3 or 4:1. the reason for this association is not known: no linkage has been found to genes on the sex chromosomes. poor motor skills are commonly found in children with sli. brain scans do not usually reveal any obvious abnormalities in children with sli, although quantitative comparisons have found differences in brain size or relative proportions of white or grey matter in specific regions. in some cases, unusual brain gyri are found. to date, no consistent "neural signature" for sli has been found. differences in the brains of children with sli vs typically developing children are subtle and may overlap with atypical patterns seen in other neurodevelopmental disorders. genetic it is now generally accepted that sli is a strongly genetic disorder. the best evidence comes from studies of twins. two twins growing up together are exposed to the same home environment, yet may differ radically in their language skills. such different outcomes are, however, seen almost exclusively in fraternal (non-identical) twins, who are genetically different. identical twins share the same genes and tend to be much more similar in language ability. there can be some variation in the severity and persistence of sli in identical twins, indicating that environmental factors affect the course of disorder, but it is unusual to find a child with sli who has an identical twin with normal language. sli is not usually caused by a mutation in a single gene. current evidence suggests that there are many different genes that can influence language learning, and sli results when a child inherits a particularly detrimental combination of risk factors, each of which may have only a small effect. it has been hypothesized, however, that a mutation of the foxp2 gene may have an influence on the development on sli to a certain degree, as it regulates genes pertinent to neural pathways related to language. only a handful of non-genetic factors have been found selectively to impact on language development in children. later-born children in large families are at greater risk than earlier born. overall, genetic mutation, hereditary influences, and environmental factors may all have a role in the development and manifestation of sli. it is important, therefore, to not associate the development to a single factor, but recognize that it is oftentimes the result of complex interactions between any or all of these factors. diagnosis sli is defined purely in behavioural terms: there is no biological test for sli. there are three points that need to be met for a diagnosis of sli: the child has language difficulties that interfere with daily life or academic progress other causes are excluded: the problems cannot be explained in terms of hearing loss, general developmental delay, autism, or physical difficulty in speaking performance on a standardized language test (see assessment, below) is significantly below age level there is considerable variation in how this last criterion is implemented. tombin et al. (1996) proposed the episli criterion, based on five composite scores representing performance in three domains of language (vocabulary, grammar, and narration) and two modalities (comprehension and production). children scoring in the lowest 10% on two or more composite scores are identified as having language disorder. assessment assessment will usually include an interview with the child's caregiver, observation of the child in an unstructured setting, a hearing test, and standardized tests of language and nonverbal ability. there is a wide range of language assessments in english. some are restricted for use by speech and language professionals (therapists or salts in the uk, speech-language pathologists, slps, in the us and australia). a commonly used test battery for diagnosis of sli is the clinical evaluation of language fundamentals (celf). assessments that can be completed by a parent or teacher can be useful to identify children who may require more in-depth evaluation. the grammar and phonology screening (gaps) test is a quick (ten minute) simple and accurate screening test developed and standardized in the uk. it is suitable for children from 3;4 to 6;8 years;months and can be administered by professionals and non-professionals (including parents) alike, and has been demonstrated to be highly accurate (98% accuracy) in identifying impaired children who need specialist help vs non-impaired children. this makes it potentially a feasible test for widespread screening. the children's communication checklist (ccc–2) is a parent questionnaire suitable for testing language skills in school-aged children. informal assessments, such as language samples, may also be used. this procedure is useful when the normative sample of a given test is inappropriate for a given child, for instance, if the child is bilingual and the sample was of monolingual children. it is also an ecologically valid measure of all aspects of language (e.g. semantics, syntax, pragmatics, etc.). to complete a language sample, the slp will spend about 15 minutes talking with the child. the sample may be of a conversation (hadley, 1998), or narrative retell. in a narrative language sample, the slp will tell the child a story using a wordless picture book (e.g. frog where are you?, mayer, 1969), then ask the child to use the pictures and tell the story back. language samples are typically transcribed using computer software such as the systematic analysis of language software (salt, miller et al. 2012), and then analyzed. for example, the slp

might look for whether the child introduces characters to their story or jumps right in, whether the events follow a logical order, and whether the narrative includes a main idea or theme and supporting details. intervention intervention is usually carried out by speech and language therapists, who use a wide range of techniques to stimulate language learning. in the past, there was a vogue for drilling children in grammatical exercises, using imitation and elicitation methods, but such methods fell into disuse when it became apparent that there was little generalisation to everyday situations. contemporary approaches to enhancing development of language structure are more likely to adopt 'milieu' methods, in which the intervention is interwoven into natural episodes of communication, and the therapist builds on the child's utterances, rather than dictating what will be talked about. in addition, there has been a move away from a focus solely on grammar and phonology toward interventions that develop children's social use of language, often working in small groups that may include typically developing as well as language-impaired peers. another way in which modern approaches to remediation differ from the past is that parents are more likely to be directly involved, particularly with preschool children. a radically different approach has been developed by tallal and colleagues, who have devised a computer-based intervention, fast forword, that involves prolonged and intensive training on specific components of language and auditory processing. the theory underlying this approach maintains that language difficulties are caused by a failure to make fine-grained auditory discriminations in the temporal dimension, and the computerised training materials are designed to sharpen perceptual acuity. for all these types of intervention, there are few adequately controlled trials that allow one to assess clinical efficacy. in general, where studies have been done, results have been disappointing, though some more positive outcomes have been reported. in 2010, a systematic review of clinical trials assessing the fastforword approach was published, and reported no significant gains relative to a control group. outcome longitudinal studies indicate that problems are largely resolved by five years in around 40% of 4-year-olds with sli. however, for children who still have significant language difficulties at school entry low levels of literacy are common, even for children who receive specialist help, and educational attainments are typically poor. poor outcomes are most common in cases where comprehension as well as expressive language is affected. there is also evidence that the nonverbal iq of children with sli decreases over the course of development. sli is associated with a high rate of psychiatric disorder. for instance, conti-ramsden and botting (2004) found that 64% of a sample of 11-year-olds with sli scored above a clinical threshold on a questionnaire for psychiatric difficulties, and 36% were regularly bullied, compared with 12% of comparison children. in the longer-term, studies of adult outcomes of children with sli find elevated rates of unemployment, social isolation and psychiatric disorder. however, most studies focused on children with severe problems, where comprehension as well as expressive language was affected. better outcomes are found for children who have milder difficulties and do not require special educational provision. prevalence epidemiological surveys, in the us and canada, estimated the prevalence of sli in five-year-olds at around 7%. however, neither study adopted the stringent "discrepancy" criteria of the diagnostic and statistical manual of mental disorders or icd-10; sli was diagnosed if the child scored below cut-off on standardized language tests, but had a nonverbal iq of 90 or above and no other exclusionary criteria. research much research has focused on trying to identify what makes language learning so hard for some children. a major divide is between theories that attribute the difficulties to a low-level problem with auditory temporal processing, and those that propose there is a deficit in a specialised language-learning system. other accounts emphasise deficits in specific aspects of memory. it can be difficult to choose between theories because they do not always make distinctive predictions, and there is considerable heterogeneity among children with sli. it has also been suggested that sli may only arise when more than one underlying deficit is present.

apicoectomy apicoectomy a root end surgery, also known as apicoectomy (apico- + -ectomy), apicectomy (apic- + -ectomy), retrograde root canal treatment (c.f. orthograde root canal treatment) or root-end filling, is an endodontic surgical procedure whereby a tooth's root tip is removed and a root end cavity is prepared and filled with a biocompatible material. it is an example of a periradicular surgery. apicoectomyx-ray of a tooth after root end surgeryicd-9-cm23.7meshd001047 an apicoectomy is necessary when conventional root canal therapy has failed and a re-treatment was already unsuccessful or is not advised. removal of the root tip is indicated to remove the entire apical delta ensuring no uncleaned missed anatomy. the only alternative may be extraction followed by prosthetic replacement with a denture, dental bridge or dental implant. state-of-the-art procedures make use of microsurgical endodontic techniques, such as a dental operating microscope, micro instruments, ultrasonic preparation tips and calcium-silicate based filling materials. in an apicoectomy, only the tip of the root is removed. this is in contrast to root resection, where an entire root is removed, and hemisection, where a root together with its overlying portion of the crown are separated the rest of the tooth and optionally removed. materials the primary aim of any endodontic treatment is to disinfect the root canal system in order to reduce the bacterial load as much as possible, and to seal the system to prevent ingress or egress of bacteria or their byproducts. failure is often due to leakage, and therefore any materials used to seal the end of the root must provide a good seal. it is also important that they are biocompatible; that is, that they are non-carcinogenic and non-toxic to the surrounding tissues or the body as a whole. they must also be stable in moisture and at body temperature. it is beneficial if they are easy to handle, as they are placed in small amounts under technically demanding conditions, and if they are easily identified on radiographs (i.e. radio-opaque). below is a list of some of the commonly used root-end filling materials. this list is by no means exhaustive. amalgam is widely used as a root-end filling, and meets many of the desired criteria. it is easy to handle, easy to see on radiographs, not sensitive to moisture, and stable at body temperature. amalgam provides a relatively good seal if placed correctly. there have been some concerns about toxicity, as amalgam contains mercury as an ingredient, but there is very little evidence to support these. composite resin is commonly used as a filling material due to its aesthetic qualities and ability to effectively bond to tooth structure, especially enamel. it is less commonly used as a root-end filling material, as its placement is technique sensitive, particularly to moisture. moisture contamination will result in a weakened bond that is very susceptible to leakage and subsequent failure. there is some evidence that, when placed correctly, composite resin can produce high success rates. mineral trioxide aggregate (mta) is a cement containing mineral oxides which absorb water to form a colloidal gel, which solidifies over a period of approximately 4 hours. it has proven very popular as a root-end filling material and has shown generally high success rates. mta produces a high ph environment, which is bactericidal, and may stimulate osteoblasts to produce bone to fill in any defects caused by infection. modified versions of zinc oxide eugenol cement (zoe) cement, such as irm or super eba, have high compressive strength, high tensile strength, neutral ph, and low solubility. success rates reported success rates for apicoectomy vary widely. studies generally focus on one material or method of treatment compared to another, so it can be difficult to obtain any good evidence on the overall success rate. a meta-analysis published in 2010 indicated an overall success rate of 85-95% for surgical endodontic treatment using a modern technique, with the evidence level rated high. a similar systematic review published in 2009 suggested an overall success rate of 77.8% for surgical endodontic treatment at 2–4 years, falling to 71.8% at 4–6 years, and 62.9% at 6+ years. there are many factors which will affect the likelihood of success of apicoectomy. if performed correctly, it can be highly successful in preventing loss of teeth which would otherwise be extracted.

phytohabitans phytohabitans phytohabitans is a gram-positive, aerobic, mesophilic and non-motile genus of bacteria from the family of micromonosporaceae. phytohabitans scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: micromonosporales family: micromonosporaceae genus: phytohabitansinahashi et al. 2010 type species phytohabitans suffuscusinahashi et al. 2010 species p. flavus inahashi et al. 2012 p. houttuyneae inahashi et al. 2012 p. kaempferiae niemhom et al. 2016 p. rumicis inahashi et al. 2012 p. suffuscus inahashi et al. 2010

lacteal lacteal a lacteal is a lymphatic capillary that absorbs dietary fats in the villi of the small intestine. lactealtransverse section of a villus, from the human intestine. x 350.a. basement membrane, here somewhat shrunken away from the epithelium.b. lacteal.c. columnar epithelium.d. its striated border.e. goblet cells.f. leucocytes in epithelium.f’. leucocytes below epithelium.g. bloodvessels.h. muscle cells cut across.villi of small intestine, showing bloodvessels and lymphatic vessels.anatomical terminology triglycerides are emulsified by bile and hydrolyzed by the enzyme lipase, resulting in a mixture of fatty acids, di- and monoglycerides. these then pass from the intestinal lumen into the enterocyte, where they are re-esterified to form triglyceride. the triglyceride is then combined with phospholipids, cholesterol ester, and apolipoprotein b48 to form chylomicrons. these chylomicrons then pass into the lacteals, forming a milky substance known as chyle. the lacteals merge to form larger lymphatic vessels that transport the chyle to the thoracic duct where it is emptied into the bloodstream at the subclavian vein. at this point, the fats are in the bloodstream in the form of chylomicrons. once in the blood, chylomicrons are subject to delipidation by lipoprotein lipase. eventually, enough lipid has been lost and additional apolipoproteins gained, that the resulting particle (now referred to as a chylomicron remnant) can be taken up by the liver. from the liver, the fat released from chylomicron remnants can be re-exported to the blood as the triglyceride component of very low-density lipoproteins. very low-density lipoproteins are also subject to delipidation by vascular lipoprotein lipase, and deliver fats to tissues throughout the body. in particular, the released fatty acids can be stored in adipose cells as triglycerides. as triglycerides are lost from very low-density lipoproteins, the lipoprotein particles become smaller and denser (since protein is denser than lipid) and ultimately become low-density lipoproteins. ldl particles are highly atherogenic. note that in contrast to any other route of absorption from the small intestine, the lymphatic system avoids first pass metabolism. notes and references young, barbara; wheater, paul, eds. (2006). wheater's functional histology: a text and colour atlas. elsevier health sciences. p. 279. isbn 978-0-443-06850-8. newsholme, eric; leech, anthony (2009). functional biochemistry in health and disease. john wiley & sons. p. 79. isbn 978-0-471-98820-5. montague, susan e.; et al., eds. (2005). physiology for nursing practice. elsevier. p. 502. isbn 978-0-7020-2676-8. carmena, rafael; duriez, patrick; fruchart, jean-charles (2004-06-15). "atherogenic lipoprotein particles in atherosclerosis". circulation. 109 (23_suppl_1): iii–2. doi:10.1161/01.cir.0000131511.50734.44. pmid 15198959. s2cid 15994547.

cepp cepp cepp is a chemotherapy regimen that is intended for treatment of aggressive non-hodgkin lymphomas. it consists of cyclophosphamide, etoposide, procarbazine, and prednisone. unlike chop, this chemotherapy regimen does not contain doxorubicin or any other anthracycline. thus, it can be used in patients with severe cardiovascular diseases and contraindications for doxorubicin-containing regimens. this regimen also does not contain vincristine and can be used in patients with neuropathy. there are several modifications of cepp. in combination with bleomycin, this regimen is called cepp (b). with the further addition of the anti-cd20 monoclonal antibody rituximab, it is called r-cepp(b). r-cepp(b) regimen consists of: rituximab - a monoclonal antibody that is able to kill cd20-positive b cells, either normal or malignant cyclophosphamide - an alkylating antineoplastic agent etoposide- a topoisomerase inhibitor from the epipodophyllotoxin group procarbazine - an alkylating antineoplastic agent prednisone or prednisolone - a glucocorticoid hormone that has the ability to cause apoptosis and lysis of lymphocytes, either normal or malignant bleomycin - an antitumor antibiotic r-cepp(b) dosing regimen drugdosemodedays rituximab375 mg/m2iv infusionday 1 cyclophosphamid600 mg/m2iv infusiondays 1 and 8 etoposide70 mg/m2iv infusiondays 1-3 procarbazine60 mg/m2po qddays 1-10 prednisone or prednisolone60 mg/m2po qddays 1-10 bleomycin10 iu/m2iv bolusday 1

globicatella sulfidifaciens globicatella sulfidifaciens globicatella sulfidifaciens is a gram-positive bacteria from the family of globicatella which has been isolated from the lungs of cattle and lambs in belgium. it is associated with purulent infections of domestic mammals and urinary tracts of swine. unlike other globicatella species and species of related genera, g. sulfidifaciens is pyr negative. globicatella sulfidifaciens bacteria are resistant against the antibiotics neomycin, erythromycin and clindamycin. globicatella sulfidifaciens scientific classification domain: bacteria phylum: bacillota class: bacilli order: lactobacillales family: aerococcaceae genus: globicatella species: g. sulfidifaciens binomial name globicatella sulfidifaciensvandamme et al. 2001 type strain ccug 44365, cip 107175, dsm 15739, lmg 18844, gem 604 synonyms globicatella sulfidofaciens

multicenter aids cohort study multicenter aids cohort study the multicenter aids cohort study (macs) is an ongoing cohort study involving over 6,000 men, including both those infected with hiv, as well as hiv-negative men. the macs has four main sites: baltimore, pittsburgh, los angeles, and chicago. the los angeles component of the macs is called the los angeles mens study or lams. lams affiliated with ucla and is supervised by dr roger detels, md & john oishi. the study, a program of the division of acquired immunodeficiency syndrome, has been ongoing since 1984 and has resulted in over 1,000 scientific publications. it helped to establish that aids was the result of a viral illness and how hiv was spread. participants were quizzed in detail about their sexual behavior. "they ask you for numbers, how many times did you do what." some participants who had many sexual partners were not infected, and this led to the realization that some people had genetic resistance to the virus.

ukrainian medical and dental academy ukrainian medical and dental academy poltava ukrainian medical & stomatological academy as poltava state medical and dental academy in english is a tertiary education institution in poltava, ukraine which was founded in 1921. it is a part of the poltava state medical and dental university (umsa). the academy offers courses in english medicine(mb/bs), dentistry and nursing. ukrainian medical and dental academyукраїнська медична стоматологічна академіяlatin: ukrayinska medychna stomatologichna akademiyamottone discere cessaestablished1921rectorvyacheslav zhdanstudents3627locationpoltava, ukrainewebsite history umsa was founded in ukraine 1921 as poltava state medical and dental university by the odontologic faculty of the kharkiv medical academy. in 1967, the academy moved and was given its current name. in 1994, it was granted the sixth highest accreditation level in ukraine, as well as the status of a poltava state medical university (psmu), because of its low surgical death rate. as of 2004, psmu had reached a confirmed level iv accreditation. campuses and buildings the academy occupies sixteen buildings, including five academic buildings, four dormitories, household enclosures, a vivarium, hangars, a library, reading rooms, sports complex, dining room, cafe, and health and sports camp. the student population is over 3,500 including international students. activities psmu (poltava stomotological & medical university) has six faculties and a preparatory department for international students. psmu conducts courses varying from two to six years in the subjects of medicine, pediatrics, oral surgery, maxillofacial surgery, pharmacy and medical nursing. students range from graduate to masters levels. clinical and consulting work is carried out at thirty-five clinical chairs located in regional and city medical institutions. research is also conducted. academics psmu trains specialists in six faculties and a preparatory department. psmu specialists are trained with junior specialists, specialists, and masters levels for the following specialties: medicine (mbbs/md) (6 years) pediatrics (6 years) stomatology (surgery) (5 years) pharmacy (5 years) medical nursing (2–3 years) orthopedic stomatology (2 years) psmu has an annual enrollment of over 3,500 students, including 729 international students from thirty-nine countries. the faculties are general medicine, pediatrics, pharmacy and stomatological (dentistry) faculties, preparatory (for training international students), postgraduate and the preparatory training course department. a medical college that provides training for bachelors and junior specialists was founded based on the psmu. the pumsa has fifty-six chairs, including nine leading chairs. clinical and consulting work is carried out by thirty-five clinical chairs of the psmu, located at the best regional and city medical establishments of poltava. its scientific potential is represented by eighty-two doctors of medical science, 316 candidates of science, seventy-five professors, 174 assistant professors, two winners of the ukrainian state prize, eight honoured science and technology workers of ukraine, and six honoured physicians of ukraine. recognition the ukrainian medical stomatological academy participated in both the "modern education in ukraine" and "education and career" exhibitions, where they presented various achievements in the organization of educational processes, such as scientific and methodological innovations, modern information and telecommunications, multimedia learning systems, etc. for these accomplishments, the academy was awarded gold, silver, and bronze medals and diplomas. at the third international exhibition and presentation, "innovative learning technology", the academy won a prize for the contest "innovation in the learning process". the academy was awarded "leader of modern education" for its innovative teaching. while a member of the ukrainian project "best institutions of medical education in ukraine - medical olympus", the academy was awarded a diploma from the ministry of health of ukraine and the ministry of education and science of ukraine, for its significant contribution to the development of medical education. the academy team was also awarded the certificate of merit by the cabinet of ministers of ukraine for their significant contribution to the development of medical education and science. according to the "top 200 ukraine," a ranking of higher educational institutions in ukraine, the hseiu "umsa" is ranked forty-first.

aquabacterium limnoticum aquabacterium limnoticum aquabacterium limnoticum is a gram-negative, facultatively anaerobic, short-rod-shaped, non-spore-forming and non-motile bacterium of the genus aquabacterium which has been isolated from a freshwater spring in taiwan. aquabacterium limnoticum scientific classification domain: bacteria phylum: pseudomonadota class: betaproteobacteria order: burkholderiales family: comamonadaceae genus: aquabacterium species: a. limnoticum binomial name aquabacterium limnoticumchen et al. 2012 type strain abp-4, bcrc 80167, kctc 23306

adrenocortical hormone adrenocortical hormone in humans and other animals, the adrenocortical hormones are hormones produced by the adrenal cortex, the outer region of the adrenal gland. these polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to stress (for example, the fight-or-flight response), and they also regulate other functions in the body. threats to homeostasis, such as injury, chemical imbalances, infection, or psychological stress, can initiate a stress response. examples of adrenocortical hormones that are involved in the stress response are aldosterone and cortisol. these hormones also function in regulating the conservation of water by the kidneys and glucose metabolism, respectively. classes adrenocortical hormones are divided into three classes by function: mineralocorticoids, glucocorticoids, and androgens. mineralocorticoid hormones are synthesized in the outermost layer of the adrenal cortex known as the zona glomerulosa. their function is to regulate the concentration of electrolytes circulating in the blood. for example, aldosterone functions to raise blood sodium levels and lower blood potassium levels by targeting the kidneys. specifically, it binds receptors of cells that comprise the distal tubules of the kidneys which then stimulate ion channels to conserve sodium and excrete potassium. additionally, the ion gradient initiates conservation of water. the glucocorticoid family of hormones is synthesized in the middle layer of the adrenal cortex known as the zona fasciculata. these hormones regulate the processing of proteins, fats, and carbohydrates by the human body. they also play a role in maintaining a normal stress response cycle. androgens, or sex hormones, are synthesized in the innermost layer of the adrenal cortex known as the zona reticularis. these hormones, such as estrogen in females and testosterone in males, are commonly known for promoting sexual characteristics and the maturation of reproductive organs of the respective gender. structure adrenocortical hormones are considered steroid hormones because of the shared characteristic of a cholesterol backbone. the structures of different steroids differ by the types and locations of additional atoms on a cholesterol backbone. the cholesterol backbone consists of four hydrocarbon rings, three cyclohexane rings and one cyclopentane, that contribute to its insolubility in aqueous environments. however, the hydrophobic nature allows them to readily diffuse through the plasma membrane of cells. this is important to the function of steroid hormones as they rely on cellular response pathways to restore the homeostatic imbalance that initiated the hormone release. synthesis the synthesis of adrenocortical steroid hormones involves a chain of oxidation-reduction reactions catalyzed by a series of enzymes. synthesis begins with a molecule of cholesterol. through shared intermediates and pathways branching off those shared intermediates, the different classes of steroids are synthesized. steroids are synthesized from cholesterol in their respective regions of the adrenal cortex. the process is controlled by steroidogenic acute regulatory protein (star) which sits in the mitochondrial membrane and regulates the passage of cholesterol. this is the rate-limiting step of steroid biosynthesis. once star has transported cholesterol into the mitochondria, the cholesterol molecule undergoes a string of oxidation-reduction reactions catalyzed by a series of enzymes from the family of cytochrome p450 enzymes. a coenzyme system called adrenodoxin reductase transfers electrons to the p450 enzyme which initiates the oxidation-reduction reactions that transform cholesterol into the steroid hormones. though synthesis is initiated inside mitochondria, precursors are shuttled to the endoplasmic reticulum for processing by enzymes present in the endoplasmic reticulum. the precursors are shuttled back to the mitochondria in the region of the adrenal cortex within which synthesis initially began and it is there that synthesis is completed. pathology cushing's syndrome cushing’s syndrome arises from the repeated hypersecretion of glucocorticoids. it can be caused by either an adrenal tumor or by hypersecretion of adrenocorticotropic hormone (acth) from the anterior pituitary gland. it is predominantly due to an excess of the glucocorticoid cortisol. secretion is typically regulated by the hypothalamus which secretes corticotropin-releasing hormone (crh) to the pituitary gland, stimulating the pituitary to secrete adrenocorticotropic hormone (acth). acth then travels to the adrenal glands and induces the release of cortisol into the bloodstream. in cushing’s syndrome, this process occurs in excess. some symptoms of an individual with cushing’s syndrome include low tissue protein levels, due to muscle and bone atrophy, and high blood glucose levels. sodium levels also see an increase which results in fluid retention in tissues and elevated blood pressure. in addition to hypersecretion of cortisol, excess androgens are secreted. in females, increased secretion of androgens, such as testosterone, results in masculinization which may present as facial hair growth and a deepened voice. treatment for cushing’s syndrome aims to reduce the high levels of cortisol circulating through the human body. the course of action ultimately depends on the cause of the hypersecretion. cushing’s can be induced by repeated synthetic steroid use to treat inflammatory diseases, or it can also be caused by a tumor in the pituitary gland or adrenal gland. in either case, treatment may rely on removal of the tumor or of the adrenal glands. without the adrenal glands, the human body is unable to supply the hormones it produces and therefore requires hormone replacement therapy. addison's disease addison’s disease is an autoimmune disorder that affects the adrenal cortex such that it is unable to efficiently secrete hormones. the immune system specifically targets the cells of the adrenal cortex and destroys them, but addison’s disease can also be caused by a severe infection such as tuberculosis. some symptoms include hypoglycemia and decreased blood sodium levels and increased blood potassium levels caused by a deficiency of aldosterone. these electrolyte imbalances induce nerve and muscle issues. other symptoms include fatigue, salt cravings, weight loss, and increased skin pigmentation. increased skin pigmentation is caused by a deficiency of the adrenocortical hormone hydrocortisone. its normal behavior would be as negative feedback at the pituitary gland, stimulating the pituitary gland to decrease secretion of corticotropin. because hydrocortisone is not able to be produced in addison’s disease, the pituitary gland continues to secrete corticotropin which binds to the receptor for melanocyte-stimulating hormone. it then causes melanocytes to produce more pigment, thus darkening the skin tone. the standard treatment for addison’s disease is hormone replacement therapy for the mineralocorticoids and glucocorticoids that are no longer able to be synthesized. former u.s. president john f. kennedy is a well-known individual who suffered from addison’s disease throughout his presidency. due to the availability of hormone replacement therapy, he and his staff were able to cover up his condition. stress and immunity recent studies have discovered a pathway that links stress to the onset of disease through the activation of certain genes. the experience of psychological stress activates transcription factors that activate genes. in a study by cole et al., it was concluded that gaba-1 transcription factor activates the interleukin-6-gene. this gene codes for a protein that activates the inflammatory response which directs an immune response to the site of the inflammation. chronic inflammation makes an individual more susceptible to diseases such as cancer, heart disease, and diabetes. another study found that physical stress caused increased cortisol:dheas (dehydroepiandrosterone sulphate) molar ratios which may contribute to reduced immunity, especially in the elderly for whom cortisol:dheas ratios are already increased. this is because dheas levels decrease with age while cortisol levels do not. this high ratio was found to suppress the activity of neutrophils and raise susceptibility for infection.

dental technician dental technician a dental technician is a member of the dental team who, upon prescription from a dental clinician, constructs custom-made restorative and dental appliances. dental technician building porcelain dental bridge. there are four major disciplines within dental technology. these are fixed prosthesis including crowns, bridges and implants; removable prosthesis, including dentures and removable partial dentures; maxillofacial prosthesis, including ocular prosthesis and craniofacial prosthesis; and orthodontics and auxiliaries, including orthodontic appliances and mouthguards. the dentist communicates with the dental technician with prescriptions, drawings, and measurements taken from the patient. the most important aspect of this is a dental impression into which the technician flows a gypsum dental stone to create a replica of the patient's anatomy known as a dental cast. a technician can then use this cast for the construction of custom appliances. fixed restorations a fixed dental restoration is an appliance designed to replace a tooth or teeth that may have been lost or damaged by injury, caries or other oral diseases. these restorations are distinguished from other restorations by the fact that once they have been placed by a dentist the patient can not remove them. such restorations include crowns, bridges, veneers, fixed implant restorations, inlays and onlays. removable restorations removable restorations are dental appliances to replace one or more teeth that have been completely lost. these restorations ideally remain stable in normal function but can be removed by the patient for cleaning and at night. removable restorations are either retained by the patients soft tissue as in full dentures, anchored and stabilized by other teeth as with partial dentures and overdentures or on implant attachments as with implant-retained overdentures and partial dentures. orthodontics orthodontic technicians make removable orthodontic appliances with wires, springs, and screws on prescription from an orthodontist to either move teeth to form a more harmonious occlusion and aesthetic appearance of teeth or to maintain the position of previously moved teeth. specialization training to become a dental technician requires a combination of academic study as well as experience gained from working on the job. therefore, regardless of the country that they are from, after becoming a qualified technician (so long as the title of “dental technician” exists there) one has finished their studies, but not their training since these crafts take years of experience to master. depending on the position held by the dental technician, their specific title could differ as well (“ceramicist”, “polisher”, “orthodontist”, etc.). in fact, due to the complexity of the work that is carried out by dental technicians, a professional generally specializes in one field of dental prosthesis. since the range of devices to design and create is extremely varied, it would be impossible to make all of them with the same set of skills, further, to completely master any technique may require years of experience. in general, the first step a dental technician makes is to “master the plaster”, meaning that they first start in the part of the lab where dental impressions are made, cutting models, and mounting articulators. the dental technician may acquire the ability to carry out various and disparate tasks in the lab, being able to even execute most steps in the production of various prosthetics, such as removable partial dentures, complete and partially made of resin, and orthodontic devices (including braces and retainers). nevertheless, as mentioned previously, dental technicians need to specialize; in fact, there are many specific dental labs that exist for each and every type of prosthesis. the distinct specialties are described below: polisher a polisher is a dental technician who dedicates themselves to the setup of teeth, either in making removable prosthetics made of resin or metal, molding the neck of the tooth, or loading the resin. within their profession, they can also be referred to as a waxer. metalworker a metalworker is a dental technician who is in charge of casting dental rods, which means they mold the metal and obtain the metallic frames for fixed prostheses, similar to the removable prosthetics made of resin. they are also in charge of processing and reworking said metal. these professionals can also be in charge of designing the wax patterns of removable metallic prostheses, such as the copings of crowns and fixed bridges. among other things, this depends on the dental technician and the lab in which they work. prosthetic orthodontists it is very common to differentiate a prosthetist who works with removable orthodontics, as it is normal to find professionals who specialize in this field. removable equipment consists of a variety of different devices, each with specific naming and characteristics. prosthetic orthodontists should be both agile and precise when handling different pliers and manipulating wires. ceramicist a ceramicist is a dental physician who has specialized in the final stage of making fixed prosthetics, which consists of the assembly of ceramic on different prosthetic structures such as: bridges, crowns, prosthetic implants or prosthetic attachments. this technique is complex and requires artistic talent, so much so that dental technicians can achieve different levels of ability, developing their creativity to a greater or lesser extent to give your teeth the most natural look possible. as such, ceramicists are often considered valued professionals. products dental technicians predominantly make dentures, or similarly, create artificial parts that are intended to basically replace the natural, missing teeth of the patient. therefore, dental technicians make complete resin prosthetics (commonly called dentures), partial prosthetics (being metallic or made of resin), bridges and crowns of any type (fixed prosthetics, also called dental implants), and mixed prosthetic devices. further, dental technicians also make all removable orthodontic devices (removable orthodontics), dental splints, individual compression trays, temporary resin prosthetics, bite plates, as well as study models. dental technicians are also in charge of making composites (the repairing of prosthetics in case they break) and relining (the readjustment of prosthetics when they are too big or become flimsy in the mouth due to the reabsorption of alveolar bone over time). all of these, concerning the plaster models or instructor models, being a crime that acts on the patient's mouth. in every country that legally regulates the profession of dental technicians, the prosthetist is the only professional trained and authorized by law to make the previously mentioned products. by law, dental technicians can never, even if there is a medical prescription, take impressions- the client of the prosthetists is legally the dentist, and it is considered an intrusive crime by the penal code if a prosthetist touches the mouth of the patient. objectives the goal of a dental technician can be summarized as restoring functionality, health, and aesthetic of the mouth. the only goal of a prosthetist is not just to create a prosthetic, but rather to restore the loss of functionality of a patient’s mouth, from mastication and swallowing to speaking and correct phonetics. through the work of a prosthetist, a patient’s oral health, mechanical function, hygiene, and comfort are revamped, including the aesthetic of the mouth and face. this objective is a combined effort between clinical and lab members, an effort that is, in part, coordinated and achieved by the dentist and the prosthetist. that said, the only one in charge of the creation of prosthetics is the prosthetist, being a handcrafted, personalized, unique item designed in the dental lab.

nomurabacteria nomurabacteria nomurabacteria is a candidate phylum of bacteria belonging to the cpr group so they are ultra-small bacteria. they have been found in a wide variety of environments, mainly in sediments under anaerobic conditions. nomurabacteria scientific classification domain: bacteria (unranked): cpr group phylum: nomurabacteria bacteria of this phylum share several of their characteristics with other ultra-small bacteria: such as nanometric size, small genomes, reduced metabolism, low capacity to synthesize nucleotides and aminoacids, they lack respiratory chains and the krebs cycle. in addition, many can be endosymbionts of larger bacteria. phylogenetic analyzes have suggested that nomurabacteria and the other ultra-small bacteria make up the most basal clade of all bacteria. the archaea of the dpann group are ultra-small archaea that share the same characteristics with these bacteria and are the most basal group of the archaeo-eukaryotic clade, although it can also be paraphyletic of eukaryotes and the other archaea as will be seen below. in some phylogenetic analyzes of the proteome, ultra-small bacteria emerge outside the traditional bacterial domain and emerge as a paraphyletic group of traditional bacteria and the clade composed of archaea and eukaryotes. in these analyzes nomurabacteria turns out to be the most basal clade of all cellular organisms. phylogeny proteome analyzes have shown that nomurabacteria can be the most basal clade of cellular organisms and that the other cpr bacteria are a paraphyletic group as can be seen in the cladogram that shows the phylogenetic relationships between multiple bacterial, archaean and eukaryotes. a 2016 metagenomic representation of the tree of life using ribosomal protein sequences

porion porion for people with the surname, see porion (surname). porionside view of head, showing surface relations of bones. (porion is visible at the superior margin of the external acoustic meatus.)identifiersta2423fma264711anatomical terminology the porion is the point on the human skull located at the upper margin of each ear canal (external auditory meatus, external acoustic meatus). it lies on the superior margin of the tragus. it is a cephalometric landmark with significance in biological anthropology and in clinical applications such as oral and maxillofacial surgery. anatomical significance the porion is one of the three anatomical points used to determine the frankfurt plane. the frankfurt plane (also called the auriculo-orbital plane) was established at the world congress on anthropology in frankfurt, germany in 1884, and decreed as the anatomical position of the human skull for comparative craniometric measurements. it was decided that a plane passing through the inferior margin of the left orbit (the point called the left orbitale) and the upper margin of each ear canal or external auditory meatus, a point called the porion, was most nearly parallel to the surface of the earth at the position the head is normally carried in the living subject. in normal subjects, both orbitales and both porions lie in a single plane. however, due to pathology, this is not always the case. the formal definition specifies only the three points listed above, sufficient to describe a plane in three-dimensional space. the mastoid index (a craniometric measurement) is the distance from the porion to the asterion. the determination of the frankfort plane differs between skeletal and soft tissues, soft tissue using the tragus as the landmark in place of the porion. additional images the porion.human skull.

monteggia fracture monteggia fracture the monteggia fracture is a fracture of the proximal third of the ulna with dislocation of the proximal head of the radius. it is named after giovanni battista monteggia. monteggia fracture-dislocationx-ray of monteggia fracture of right forearmspecialtyorthopedic surgery, orthopedic surgery causes mechanisms include: fall outstretched hand with the forearm in excessive pronation (hyper-pronation injury). the ulna fractures in the proximal one-third of the shaft due to extreme dislocation. depending on the impact and forces applied in each direction, degree of energy absorption determines pattern, involvement of the radial head and whether or not open soft tissue occurs. direct blow on back of upper forearm would be a very uncommon cause. in this context, isolated ulnar shaft fractures are most commonly seen in defence against blunt trauma (e.g. nightstick injury). such an isolated ulnar shaft fracture is not a monteggia fracture. it is called a 'nightstick fracture'. diagnosis classification there are four types (depending upon displacement of the radial head): bado classification - monteggia fractures i - extension type (60%) - ulna shaft angulates anteriorly (extends) and radial head dislocates anteriorly. ii - flexion type (15%) - ulna shaft angulates posteriorly (flexes) and radial head dislocates posteriorly. iii - lateral type (20%) - ulna shaft angulates laterally (bent to outside) and radial head dislocates to the side. iv - combined type (5%) - ulna shaft and radial shaft are both fractured and radial head is dislocated, typically anteriorly. these are known as the bado types. management monteggia fractures may be managed conservatively in children with closed reduction (resetting and casting), but due to high risk of displacement causing malunion, open reduction internal fixation is typically performed. osteosynthesis (open reduction and internal fixation) of the ulnar shaft is considered the standard of care in adults. it promotes stability of the radial head dislocation and allows very early mobilisation to prevent stiffness. the elbow joint is particularly susceptible to loss of motion. prognosis in children, the results of early treatment are always good, typically normal or nearly so. if diagnosis is delayed, reconstructive surgery is needed and complications are much more common and results poorer. in adults, the healing is slower and results usually not as good. complications of orif surgery for monteggia fractures can include non-union, malunion, nerve palsy and damage, muscle damage, arthritis, tendonitis, infection, stiffness and loss of range of motion, compartment syndrome, audible popping or snapping, deformity, and chronic pain associated with surgical hardware such as pins, screws, and plates. several surgeries may be needed to correct this type of fracture as it is almost always a very complex fracture that requires a skilled orthopedic surgeon, usually a specialist familiar with this type of injury.

sphingomonas oligophenolica sphingomonas oligophenolica sphingomonas oligophenolica is a gram-negative, strictly aerobic and non-motile bacteria from the genus of sphingomonas which has been isolated from paddy field soil in japan. sphingomonas oligophenolica has the ability to degrade phenolic acids. sphingomonas oligophenolica scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: sphingomonadales family: sphingomonadaceae genus: sphingomonas binomial name sphingomonas oligophenolicaohta et al. 2004 type strain ccug 56448, cip 107926, dsm 17107, jcm 12082, s213

experimental models of alzheimer's disease experimental models of alzheimer's disease experimental models of alzheimer's disease are organism or cellular models used in research to investigate biological questions about alzheimer's disease as well as develop and test novel therapeutic treatments. alzheimer's disease is a progressive neurodegenerative disorder associated with aging, which occurs both sporadically (the most common form of diagnosis) or due to familial passed mutations in genes associated with alzheimer's pathology. common symptoms associated with alzheimer's disease include: memory loss, confusion, and mood changes. experimental methods used to study alzheimer's disease as alzheimer's disease affects around 55 million patients globally and accounts for approximately 60-70% of all dementia cases, billions of dollars are spent yearly towards research to better understand the biological mechanisms of the disease as well as develop effective therapeutic treatments for it. researchers commonly use post-mortem human tissue or experimental models to conduct experiments relating to alzheimer's disease. experimental models of alzheimer's disease are particularly useful as they allow complex manipulation of biological systems to elucidate questions about alzheimer's disease without the risk of harming humans. these models often have genetic modifications that enable them to be more representative of human alzheimer's disease and its associated pathology: extracellular amyloid-beta (aβ) plaques and intracellular neurofibrillary tangles (nfts). current methods used by researchers are: traditional 2d cell culture, 3d cell culture, microphysiological systems, and animal models. cell culture models cortical neuron culture 2d cell culture traditional two dimensional cell culture is a useful experimental model of alzheimer's disease to conduct experiments in a high throughput manner. these cultures occur on a dish or flask in a monolayer and can be made up of a single cell type or multiple cell types. 2d cultures often have difficulties producing insoluble amyloid-β plaques even when they are able to secrete the amyloid-β peptide. common types of 2d cell culture used to model alzheimer's disease are immortalized cell lines, primary neuron cultures, and patient derived induced pluripotent stem cells (ipsc). immortalized cell lines immortalized cell lines are cells from an organism which have been genetically manipulated to be able to proliferate in vitro, making them a useful tool for researchers as they can do so quickly allowing for high-throughput experimentation. these mutations can occur from a natural caused mutation, like those found in cancer cells, or from being introduced by researchers. common immortalized cell lines used to study alzheimer's disease include: human embryonic kidney 293 (hek293), human neuroblastoma (sh-sy5y), human neuroglioma (h4), human embryonic mesencephalic (luhmes), human neural progenitor (ren), and pheochromocytoma (pc12) cells. these types of cells are commercially available, relatively inexpensive, and easy to culture and maintain. pro-death compounds can be used in these models to induce alzheimer's disease related cell death. these compounds include: amyloid-β 42, tau protein, glutamic acid, and oxidative/pro-inflammatory compounds. primary neuron culture primary neuron cultures are generated from embryonic or postnatal rodent brain tissue and cultured on plates. common brain regions used for cultures to study alzheimer's disease include the hippocampus, cortex, and amygdala; however any brain region is suitable for cultures. this method requires dissection of the desired brain region from rodent tissue followed by digestion, dissociation, and plating steps. as these cultures are derived directly from rodent brain tissue, they morphologically and physiologically resemble human brain cells, contain multiple neuronal cell types, and do not proliferate. when initially cultured, these cells are spherical and over time begin to form axons, dendrites, and eventually develop synaptic connections. induced pluripotent stem cells ipsc methods used in alzheimer's disease research patient-derived induced pluripotent stem cell (ipsc) lines are unique in which differentiated somatic cells are taken from alzheimer's disease patients and reverted into pluripotent stem cells via an ectopic transcriptional "tamanaka" factor cocktail. these stem cells can then be directed to differentiate into many cell types, including neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells. this allows these models to be generated from both early-onset familial alzheimer's disease (fad) patients with mutations in app, psen1, or psen2 genes as well as late-onset/sporadic alzheimer's disease (sad) patients, a population which is not wholly replicated in animal models. as sad is the most commonly diagnosed form of ad, this highlights ipscs as key tools for understanding this form of the disease. these cells can also be purchased commercially. crispr-cas9 technology can be used alongside ipsc cells to generate neurons carrying multiple fad mutations. one major downfall of these models are that they can inadequately resemble mature neurons as well as being more expensive and difficult to maintain. ipscs have also been shown to exhibit genomic instability and develop additional mutations when passaged (harvested and reseeded into daughter cultures) numerous times, posing both safety concerns for patient use as well as potential reproducibility problems in experimental studies. due to the nature of reprogramming procedures, ipsc cells lose cellular and epigenetic signatures acquired by aging and environmental factors, limiting ipscs ability to recapitulate diseases associated with aging, like alzheimer's disease. while these cultures have some limitations, many fundamental discoveries about alzheimer's disease biology have been elucidated using this model system. important alzheimer's disease findings using ipscs cell type mutation(s) importance astrocytes isogenic psen1δe9 isogenic apoe3 and apoe4 psen1 astrocytes lacking exon 9 displayed increased amyloid-β production and oxidative stress, decreased neuronal support functionality, and changed calcium homeostasis as well as cytokine release apoe4 astrocytes showed an increase in cholesterol and reduced amyloid-β clearance microglia isogenic apoe3 and apoe4 apoe4 microglia showed decreased morphological complexity and reduced uptake of amyloid-β from culture media neurons sad, appdp down syndrome isogenic apoe3, apoe4, apoe null ad neurons from early ipsc experiments showed increased amyloid-β, phosphorylated-tau, and endoscope accumulation neurons from down syndrome patients (containing triplication of chromosome 21 containing the app gene) displayed increased amyloid-β secretion and aggregation as well as tau phosphorylation apoe4 neurons showed increased amounts of amyloid-β and phosphorylated-tau and degeneration of gabaergic neurons 3d cultures overexpression appk670n/m671l, appv717i, psen1δe9 overexpression appk670n/m671l, appv717i, psen1δe9 accumulation of amyloid-β from these cells caused filamentous tau deposition neurons, astrocytes, and human microglia co-cultured together replicated ad phenotypes, neuroinflammation, and microglial recruitment 3d organoid culture three dimensional organoid culture methods have become a popular way of recapitulating ad pathology in a more "brain-like" environment than traditional 2d culture as they create a organized structure similar to that of the human cortex. this has proven effective specifically for modeling alzheimer's disease as 2d cultures tend to fail at producing insoluble amyloid-β while 3d culture models are able. these models consist of multiple neuronal cell types co-cultured together in artificial matrices allowing for the understanding of how non-neuronal cells and neuroinflammation influence alzheimer's disease pathogenesis. the neuronal cell types expressed in these models often include neurons, astrocytes, microglia, oligodendrocytes, epithelial, and endothelial cells. these organoids develop over many months in order to display alzheimer's pathology and can be maintained for long periods of time. they can be derived from both ipscs or immortalized undifferentiated cells and typically reach a diameter of several millimeters. 3d cultures can either be allowed to self-organize or be placed under guided formation in which exogenous factors influence the differentiation pattern of the organoid. 3d culture methods have shown more robust amyloid-β aggregation, phosphorylated-tau accumulation, and endosome abnormalities than 2d culture methods of the same cell lines, indicating accelerated pathology. brain-on-a-chip common issues arising from the use of 3d cultures is the lack of vasculature within the organoid, leading to cell death and dysfunction at inner layers. current efforts are focusing on introducing endothelial cells into guided formation cultures in order to create vascular systems and provide nutrient distribution to deep layers. self-organizing organoids also vary in terms in proportion and location of expressed cells causing challenges in reproducibility of experiments. more effort has been placed on guided formation organoids to account for this problem, however this method is more time consuming and difficult to optimize. 3d organoid culture's ability to resemble aging phenotypes is also limited as many organoid methods rely on ipscs which are more similar to prenatal brain cells due to reprograming protocols. researchers are currently investigating common transcriptional profiles associated with alzheimer's disease and aging in order to reintroduce these lanscapes into ipscs for future biomedical research and therapeutic development. microphysiological systems neuronal microphysiological systems, also referred to as a "brain-on-a-chip," are a combination of 3d cultures and a microfluidics platform, which circulates the media provided to the cultured cells. these devices are beneficial as they improve cell viability and better model physiological conditions as they improve oxygen availability and nutrient delivery to inner layers of 3d cultures. these systems additionally introduce physiological cues such as fluid sheer stress, tension, and compression which allows these in vitro conditions to better resemble the in vivo environment. microphysiological systems were shown to replicate amyloid-β aggregation, hyperphosphorylated tau, and neuroinflamation as well as display microglial recruitment, release of cytokines and chemokines, and microglial neurotoxic activation as a response of more physiologically relevant cell-cell interactions. these systems can also be developed incorporating brain endothelial cells to mimic the blood–brain barrier, making this an extremely useful model for bbb dysfunction in alzheimer's disease, screening novel therapeutics potential to pass from the blood into the brain, therapeutic pharmacokinetics, as well as drug adsorption, distribution, metabolism, elimination, and toxicity (admet) tendencies. animal models rodents familial alzheimer's disease mutations commonly used in animal models rodent animal models of alzheimer's disease are commonly used in research as rodents and humans have many of the same major brain regions and neurotransmitter systems. these models are small, easy to house, as well as breed very well. mice and rats on average tend to live for 2 years, a much shorter lifespan than humans, presenting both limitations as well as benefits for more rapid experiment completion. in order to recapitulate and accelerate human alzheimer's disease pathology, scientists commonly introduce fad associated mutations. common genes targeted for genetic engineering in animal models are app, mapt, psen1, psen2, and apoe. this results in the animal models having a higher tendency to form amyloid-β plaques and/or neurofibrillary tangles, the two pathological hallmarks of alzheimer's disease. these mutated genes can either be over-expressed (first generation models) or expressed at endogenous levels (second generation models) as a way of further replicating disease pathology. scientists also over-express non-mutated human genes in the hope of seeing similar alzheimer's disease pathology. these introduced mutations or over-expression of human alzheimer's associated genes, can lead these animals to additionally display cognitive impairment, deficits in long-term potentiation (ltp), synaptic loss, gliosis, and neuronal loss. as current models are highly reliant on fad mutations to induce alzheimer's like pathology, there is still no ideal model that fully replicates sad (sporadic alzheimer's disease), which is the most common type of diagnosis in patients. common methods used to generate these lines are the use of transgenes controlled by a specific promoter, cre-lox recombination, and the crispr-cas9 system. scientists can also use injection methods such as intracerebroventricular injection, intravenous injection, or intrahippocampal injection to modify wild type rodents into displaying alzheimer's disease pathology. these rodent models are often used to test and develop drugs treating alzheimer's disease before progressing to clinical trials in humans. mouse models name genes modification information promoter known pathology (age of onset in months) app models appswe tgc3-3 app express both murine and human app carrying the swedish mutation murine prp aβ plaques (24-26 mo) tg2576 app over-expresses human app with the swedish mutation hamster prp synaptic loss (4-6 mo), ltp deficits (4-6 mo), cognitive impairment (4-6 mo), gliosis (10-16 mo), aβ plaques (11-13 mo) app23 app display a 7-fold over-expression of human app carrying the swedish mutation murine thy1 cognitive impairment (3 mo), aβ plaques (6 mo), gliosis (6 mo), neuronal loss (14-18 mo) pdapp app over-express human app carrying the indiana mutation pdgfβ cognitive impairment (3 mo), ltp deficits (4-5 mo), aβ plaques (6 mo), gliosis (6 mo), synaptic loss (8 mo) tgcrnd8 app display 5-fold over-expression of human app carrying the swedish and indiana mutations syrian hamster prp cognitive impairment (3 mo), aβ plaques (3 mo), gliosis (3 mo), ltp deficit (6 mo), synaptic loss (6 mo), neuronal loss (6 mo) appnl-f app express humanized app with the swedish and iberian mutations n/a aβ plaques (6 mo), gliosis (6 mo), synaptic loss (9-12 mo), cognitive impairment (18 mo) appnl-g-f app express endogenous levels of humanized app carrying

the swedish, iberian, and arctic mutations n/a aβ plaques (2 mo), gliosis (2 mo), synaptic loss (4 mo), cognitive impairment (6 mo) tau models jnpl3 mapt express 4 repeat human tau carrying the p301l mutation murine prp neurofibrillary tangles (4.5 mo), neuronal loss (10 mo), gliosis (10 mo) pr5 mapt over-express 4 repeat human tau carrying the p301l mutation murine thy1 cognitive impairment (5 mo), ltp deficits (6 mo), gliosis (7 mo), neurofibrillary tangles (8 mo) tau p301s mapt over-express human tau carrying the p301s mutation murine prp gliosis (3 mo), synaptic loss (3 mo), neurofibrillary tangles (6 mo), ltp defects (6 mo), cognitive impairment (6 mo), neuronal loss (9-12 mo) psen models ps1 m146v psen1 over-express psen1 with the m146v mutation rat pdgfβ neuropathology is absent in these mice. cognitive ability has not been observed. other models tapp app, mapt over-expression of human app carrying the swedish mutation and 4 repeat human tau with the p301l mutation. hamster prp, murine prp neurofibrillary tangles (3 mo), gliosis (3 mo), aβ plaques (9 mo) 3xtg-ad app, psen1, mapt express human app with the swedish mutation, mapt with the p301l mutation, and psen1 with the m146v mutation murine thy1 (ps1 knockin) cognitive impairment (4 mo), aβ plaques (6 mo), ltp deficits (6 mo), gliosis (7 mo), neurofibrillary tangles (12 mo) psapp app, psen1 over-express human app with the swedish mutation and psen1 with the m146l mutation hamster prp, pdgfβ cognitive impairment (3 mo), aβ plaques (6 mo), gliosis (6 mo), neuronal loss (22 mo) 5xfad (b6sjl) app, psen1 over-express human app with the swedish, florida, and london mutations and psen1 with the m146l and l286v mutations murine thy1 aβ plaques (2 mo), gliosis (2 mo), synaptic loss (4 mo), cognitive impairment (4-5 mo), ltp deficit (4-6 mo), neuronal loss (4-6 mo) 5xfad (c57bl6) app, psen1 over-express human app with the swedish, florida, and london mutations and psen1 with the m146l and l286v mutations murine thy1 ltp defecits (2 mo), aβ plaques (2 mo), gliosis (2 mo), cognitive impairment (3-6 mo), synaptic loss (3-6 mo), neuronal loss (12 mo) huapoe ki apoe2, apoe3, apoe4 express humanized apoe2, apoe3, or apoe4 n/a no data rat models name genes modification information promoter known pathology (age of onset in months) mcgill-r-thy1-app app express human app with the swedish and indiana mutations murine thy1.2 cognitive impairment (3 mo), ltp deficits (3 mo), aβ plaques (6 mo), gliosis (6 mo), neuronal loss (18 mo), synaptic loss (20 mo) appnl-g-fki app express humanized aβ with the swedish, arctic, and iberian mutations n/a aβ plaques (1 mo), cognitive impairment (5-7 mo), gliosis (6 mo), synaptic loss (6 mo), neuronal loss (12 mo) app+ps1 app, psen1 express human app with the swedish and indiana mutations and human psen1 with the l166p mutation ubc cognitive impairment (10 mo); aβ plaques (19 mo), neuronal loss (19 mo) tgf344-ad app, psen1 express human app with the swedish mutation and human psen1 with the δexon9 mutation murine prp gliosis (6 mo), cognitive impairment (6 mo), aβ plaques (6 mo), neurofibrillary tangles (16 mo), neuronal loss (16 mo) non-human primates non-human primates can be used by researchers to study mechanisms of alzheimer's disease as well as develop therapeutics. non-human primates are useful as they have a more similar aging pattern to humans compared to rodent models. during non-human primate aging, they can display neuropathy, cognitive changes, and amyloid-β deposits, similar to that of alzheimer's disease. while these models are useful in studying the process of aging, they are not always exact models of alzheimer's disease. common non-human primates used in ad research include: rhesus monkeys (macaca mulattas), stump-tailed macaques (macaca arctoides), mouse lemurs (microcebus murinus), the common marmoset (callithrix jacchus), and crab-eating macaques (macaca fascicularis). these models can be studied both spontaneously or through artificial induction of alzheimer's disease responses. common techniques used to induce these models include: cholinergic nervous system injury, amyloid-β injection, intrinsic formaldehyde, and streptozotocin (a methyl nitrosourea sugar compound which induces diabetes). alternative organisms zebrafish drosophila caenorhabditis elegans

ingression (biology) ingression (biology) ingression is one of the many changes in the location or relative position of cells that takes place during the gastrulation stage of embryonic development. it produces an animal's mesenchymal cells at the onset of gastrulation. during the epithelial–mesenchymal transition (emt), the primary mesenchyme cells (pmcs) detach from the epithelium and become internalized mesenchyme cells that can migrate freely. while the mechanisms of ingression are not fully understood, studies using the sea urchin as a model organism have begun to shed light on this developmental process, and will be the focus here. there are three main changes that must occur within a cell to enable the process of ingression. the ingressing pmcs must first alter their affinity for the neighboring epithelial cells that will remain in the vegetal pole (vertebrate pmcs ingress from the primitive streak). during this time, these cells must lose their affinity for the hyaline layer to which their apical surface is attached. the ingressing cells will then apically constrict and alter their cellular architecture through a dramatic reorganization of their cytoskeleton. lastly, these cells will modify their mode of motility and presumably gain affinity for the basal lamina which composes the lining of the blastocoel, the future migration substrate of the pmcs. changes in the adhesion properties of these cells are the best characterized and understood mechanism of ingression. in sea urchins, epithelial cells adhere to one another as well as the hyaline layer through classic cadherins and adherens junctions. ingression is a very dynamic process however, and the first sign of an ingressing cell is seen when a future pmc loses its adhesion to hyaline, and cadherin, and increases its adhesion to a basal laminal substrate. these processes occur rapidly, over approximately 30 minutes. it is not understood how the pmcs penetrate the basal lamina. the basal lamina is a loose matrix, therefore it is possible that the ingressing cells squeeze through the matrix. it is also hypothesized that the pmcs use a protease. emt is determined by a dynamic gene regulatory network (grn). snail and twist are two key transcription factors that makes up the grn. within an hour of ingression, numerous transcript factors are activated. it is known that beta-catenin (β-catenin) plays a key role in emt. when β-catenin function is blocked, no emt results. if β-catenin is over-expressed, too many cells undergo emt. the vascular endothelial growth factor receptor is also necessary for the pmcs to function as mesenchymal cells. lastly, it is thought that the ingression of pmcs is further facilitated simply through the simultaneous ingression neighboring cells. within birds and mammals, epiblast cells converge at the midline and ingress at the primitive streak. ingression of these cells results in formation of the mesoderm. the use of ingression to internalize presumptive mesoderm is considered a major evolutionary change in mesoderm morphogenesis within chordates. within chordate embryos, there is an evolutionary trend exhibited in the mechanisms used to internalize presumptive mesoderm. basal chordates rely predominantly on invagination, anamniote vertebrates and reptiles on a varying combination of involution and ingression, and birds and mammals primarily on ingression. besides ingression, two other types of internalizing cell movements may occur during gastrulation: invagination and involution.

juvenile active ossifying fibroma juvenile active ossifying fibroma a juvenile active ossifying fibroma is a benign fibro-osseous neoplasm composed of mixture of stroma and bone characterized by rapid and destructive growth. classification this tumor has gone by several names in the past, but active ossifying fibroma is similar to juvenile active ossifying fibroma, except it does not develop in young patients. aggressive psammomatoid ossifying fibroma is still employed by some, but is to be discouraged. signs and symptoms most patients are asymptomatic, and come to clinical attention when a mass is discovered incidentally on routine dental x-rays. when patients are symptomatic, they present with non-specific symptoms, such as chronic sinusitis, rhinorrhea, obstruction, pain, facial enlargement and possibly visual changes. imaging findings a computed tomography sagittal view of a front sinus active ossifying fibroma when performing imaging studies, bone windows in computed tomography studies are the best. the lesion is usually identified as a well demarcated, expansile mass with an ossified rim at the periphery. calcifications are noted throughout. mri shows a variable finding depending on t1 or t2 weighted images, dependent on the amount of bone to fibrous connective tissue ratio. pathology findings the tumors are described as "shelling out" by the surgeon, which gives a well-circumscribed, smooth surface of tan, white, firm-gritty material. the tumors range in size from a few millimeters up to 10 cm. a hematoxylin and eosin stained slide show a cellular stroma with an innumerable psammoatoid calcifications by microscopic evaluation, the tumors are composed of a variably cellular stroma make up of spindled to stellate fibroblast-like cells. within this stroma, are numerous small, rounded, mineralized collagenous ossicles and immature osteoid. many times the curved-shaped bone fragments have a collagenous rim around them. ossicles may fuse to form much large mineralizations. cementum-like psammomatous bodies (cementicles) may also be present. osteoblastic rimming is not uncommon. occasionally, giant cells and even mitoses are seen. differential diagnoses active ossifying fibroma must be separated from fibrous dysplasia, cementoblastoma, and meningioma. this type of separation must be made with the aid of imaging studies, and should not be done by histology examination only. management it is important to get complete excision as early in the disease process as possible. once the lesion is removed, the prognosis is excellent. however, if the lesion is incompletely excised, recurrences may be seen in up to 60% of patients. the recurrences are highest in sinus tumors. epidemiology this tumor is far less common than conventional ossifying fibroma, and is considered a rare tumor. patients usually come to clinical attention when <15 years of age, but a wide age range (3 months to 70 years) can be affected. both genders are affected equally, with the paranasal sinuses most commonly affected. specifically, the ethmoid sinus is affected most often, followed by frontal sinus, maxillary sinus and sphenoid sinus. the maxilla is the second most common location after the paranasal sinuses, while the mandible and temporal bone are infrequently affected. this tumor does not frequently extracranial sites nor soft tissues sites.

allopathic medicine allopathic medicine allopathic medicine, or allopathy, is an archaic and derogatory label originally used by 19th-century homeopaths to describe heroic medicine, the precursor of modern evidence-based medicine . there are regional variations in usage of the term. in the united states, the term is sometimes used to contrast with osteopathic medicine, especially in the field of medical education. in india, the term is used to distinguish conventional modern medicine from ayurveda, homeopathy, unani and other alternative and traditional medicine traditions, especially when comparing treatments and drugs. homeopathy looks at the horrors of allopathy, by alexander beideman (1857) the terms were coined in 1810 by the creator of homeopathy, samuel hahnemann. heroic medicine was the conventional european medicine of the time and did not rely on evidence of effectiveness. it was based on the belief that disease is caused by an imbalance of the four "humours" (blood, phlegm, yellow bile, and black bile) and sought to treat disease symptoms by correcting that imbalance, using "harsh and abusive" methods to induce symptoms seen as opposite to those of diseases rather than treating their underlying causes: disease was caused by an excess of one humour and thus would be treated with its "opposite". a study released by the world health organization (who) in 2001 defined allopathic medicine as "the broad category of medical practice that is sometimes called western medicine, biomedicine, evidence-based medicine, or modern medicine." the who used the term in a global study in order to differentiate western medicine from traditional and alternative medicine, noting that in certain areas of the world "the legal standing of practitioners is equivalent to that of allopathic medicine" where practitioners can be separately certified in complementary/alternative medicine and western medicine. the term allopathy was also used to describe anything that was not homeopathy. kimball atwood, an american medical researcher and alternative medicine critic, said the meaning implied by the label of allopathy has never been accepted by conventional medicine and is still considered pejorative. american health advocate and sceptic william t. jarvis, stated that "although many modern therapies can be construed to conform to an allopathic rationale (e.g., using a laxative to relieve constipation), standard medicine has never paid allegiance to an allopathic principle" and that the label "allopath" was "considered highly derisive by regular medicine." most modern science-based medical treatments (antibiotics, vaccines, and chemotherapeutics, for example) do not fit hahnemann's definition of allopathy, as they seek to prevent illness or to alleviate an illness by eliminating its cause. etymology the terms "allopathic medicine" and "allopathy" are drawn from the greek prefix ἄλλος (állos), "other," "different" + the suffix πάθος (páthos), "suffering". history the practice of medicine in both europe and north america during the early 19th century is sometimes referred to as heroic medicine because of the extreme measures (such as bloodletting) sometimes employed in an effort to treat diseases. the term allopath was used by hahnemann and other early homeopaths to highlight the difference they perceived between homeopathy and the "conventional" heroic medicine of their time. with the term allopathy (meaning "other than the disease"), hahnemann intended to point out how physicians with conventional training employed therapeutic approaches that, in his view, merely treated symptoms and failed to address the disharmony produced by underlying disease. homeopaths saw such symptomatic treatments as "opposites treating opposites" and believed these methods were harmful to patients. practitioners of alternative medicine have used the term "allopathic medicine" to refer to the practice of conventional medicine in both europe and the united states since the 19th century. in that century, the term allopath was used most often as a derogatory name for the practitioners of heroic medicine, a precursor to modern medicine that itself did not rely on evidence of effectiveness. james whorton discusses this historical pejorative usage: one form of verbal warfare used in retaliation by irregulars was the word "allopathy". ..."allopathy" and "allopathic" were liberally employed as pejoratives by all irregular physicians of the nineteenth century, and the terms were considered highly offensive by those at whom they were directed. the generally uncomplaining acceptance of "allopathic medicine" by today's physicians is an indication of both a lack of awareness of the term's historical use and the recent thawing of relations between irregulars and allopaths. the controversy surrounding the term can be traced to its original usage during a heated 19th-century debate between practitioners of homeopathy and those they derisively referred to as "allopaths." hahnemann used "allopathy" to refer to what he saw as a system of medicine that combats disease by using remedies that produce effects in a healthy subject that are different (hence the greek root allo- "different") from the effects produced by the disease to be treated. the distinction comes from the use in homeopathy of substances that are meant to cause similar effects as the symptoms of a disease to treat patients (homeo - meaning "similar"). as used by homeopaths, the term allopathy has always referred to the principle of treating disease by administering substances that produce other symptoms (when given to a healthy human) than the symptoms produced by a disease. for example, part of an allopathic treatment for fever may include the use of a drug which reduces the fever, while also including a drug (such as an antibiotic) that attacks the cause of the fever (such as a bacterial infection). a homeopathic treatment for fever, by contrast, is one that uses a diluted dosage of a substance that in an undiluted form would induce fever in a healthy person. these preparations are typically diluted so heavily that they no longer contain any actual molecules of the original substance. hahnemann used this term to distinguish medicine as practiced in his time from his use of infinitesimally small (or nonexistent) doses of substances to treat the spiritual causes of illness. the companion encyclopedia of the history of medicine states that " gave an all-embracing name to regular practice, calling it 'allopathy'. this term, however imprecise, was employed by his followers and other unorthodox movements to identify the prevailing methods as constituting nothing more than a competing 'school' of medicine, however dominant in terms of number of practitioner proponents and patients". contrary to the present usage, hahnemann reserved the term "allopathic medicine" to the practice of treating diseases by means of drugs inducing symptoms unrelated (i.e., neither similar nor opposite) to those of the disease. he called the practice of treating diseases by means of drugs producing symptoms opposite to those of the patient "enantiopathic" (from the greek ἐνάντιος (enántios), meaning "opposite") or "antipathic medicine". current usage in the united states, the term is used in the modern era to differentiate between two types of us medical schools (both of which teach aspects of science-based medicine and neither of which teach homeopathy): allopathic (granting the md degree) and osteopathic (granting the do degree). in india the term is used principally to distinguish "western medicine" from ayurveda, especially when comparing treatments and drugs. a study released by the world health organization (who) in 2001 defined "allopathic medicine" as "the broad category of medical practice that is sometimes called western medicine, biomedicine, evidence-based medicine, or modern medicine." the who used the term in a global study in order to differentiate western medicine from traditional medicine, and from complementary/alternative medicine, noting that in certain areas of the world “the legal standing of practitioners is equivalent to that of allopathic medicine” where practitioners are certified in both complementary/alternative medicine and western medicine. as of 2004, use of the term remained common among homeopaths and had spread to other alternative medicine practices. kimball atwood, an american medical researcher and alternative medicine critic, said the meaning implied by the label of allopathy has never been accepted by conventional medicine and is still considered pejorative by some. american health educator and skeptic william t. jarvis, stated in 2008 that "although many modern therapies can be construed to conform to an allopathic rationale (e.g., using a laxative to relieve constipation), standard medicine has never paid allegiance to an allopathic principle" and that the label "allopath" was "considered highly derisive by regular medicine". most modern science-based medical treatments (antibiotics, vaccines, and chemotherapeutics, for example) do not fit samuel hahnemann's definition of allopathy, as they seek to prevent illness, or remove the cause of an illness by acting on the cause of disease.

rosoxacin rosoxacin rosoxacin (also known as acrosoxacin, tradename eradacil) is a quinolone antibiotic indicated for the treatment of urinary tract infections and certain sexually transmitted diseases. rosoxacin is not available in the united states. rosoxacinclinical datatrade nameseradacilahfs/drugs.cominternational drug namesatc codej01mb01 (who) identifiers iupac name 1-ethyl-4-oxo-7-pyridin-4-ylquinoline-3-carboxylic acid cas number40034-42-2 ypubchem cid287180drugbankdb00817 nchemspider253208 nunii3y1ot3j4nwkeggd02305 nchebichebi:131715 nchemblchembl291157 ncomptox dashboard (epa)dtxsid90193091 echa infocard100.049.763 chemical and physical dataformulac17h14n2o3molar mass294.310 g·mol−13d model (jsmol)interactive imagemelting point290 °c (554 °f) smiles ccn1cc(c(=o)o)c(=o)c2ccc(-c3ccncc3)cc21 inchi inchi=1s/c17h14n2o3/c1-2-19-10-14(17(21)22)16(20)13-4-3-12(9-15(13)19)11-5-7-18-8-6-11/h3-10h,2h2,1h3,(h,21,22) ykey:xbpzxdszhpdxqu-uhfffaoysa-n y ny (what is this?) (verify) it was developed in 1978 by george lesher and his colleagues at winthrop-stearns (now part of sanofi-aventis), as an extension of the work that originally led to nalidixic acid. it is classified as a first generation quinolone. synthesis rosoxacin synthesis: the synthesis of rosoxacin begins with a modified hantzsch pyridine synthesis employing as component parts ammonium acetate, two equivalents of methyl propiolate, and one of 3-nitrobenzaldehyde. oxidation of the resulting dihydropyridine (2) with nitric acid followed by saponification, decarboxylation, and reduction of the nitro group with iron and hcl acid gives aniline 3. this undergoes the classic sequence of gould-jacobs reaction with methoxymethylenemalonate ester to form the 4-hydroxyquinoline ring, and then alkylation with ethyl iodide and saponification of the ester to complete the synthesis of the antibacterial agent rosoxacin (4).

spinocerebellar tract spinocerebellar tract the spinocerebellar tract is a nerve tract originating in the spinal cord and terminating in the same side (ipsilateral) of the cerebellum. spinocerebellar tractspinocerebellar tracts are labeled in blue at right.detailsidentifierslatintractus spinocerebellarismeshd020824neuronames1978anatomical terms of neuroanatomy origins of proprioceptive information proprioceptive information is obtained by golgi tendon organs and muscle spindles. golgi tendon organs consist of a fibrous capsule enclosing tendon fascicles and bare nerve endings that respond to tension in the tendon by causing action potentials in type ib afferents. these fibers are relatively large, myelinated, and quickly conducting. muscle spindles monitor the length within muscles and send information via faster ia afferents. these axons are larger and faster than type ib (from both nuclear bag fibers and nuclear chain fibers) and type ii afferents (solely from nuclear chain fibers). all of these neurons are sensory (first order, or primary) and have their cell bodies in the dorsal root ganglia. they pass through rexed laminae layers i-vi of the posterior grey column (dorsal horn) to form synapses with second order or secondary neurons in layer vii just beneath the dorsal horn. subdivisions of the tract the tract is divided into: division peripheral process of first order the neuron region of innervation dorsal (posterior) spinocerebellar tractfrom muscle spindle (primarily) and golgi tendon organsipsilateral caudal aspect of the body and legs ventral (anterior) spinocerebellar tractfrom golgi tendon organsipsilateral caudal aspect of the body and legs cuneocerebellar tractfrom muscle spindle (primarily) and golgi tendon organsipsilateral arm rostral spinocerebellar tractfrom golgi tendon organsipsilateral arm dorsal spinocerebellar tract the dorsal spinocerebellar tract (posterior spinocerebellar tract, flechsig's fasciculus, flechsig's tract) conveys proprioceptive information from proprioceptors in the skeletal muscles and joints to the cerebellum. it is part of the somatosensory system and runs in parallel with the ventral spinocerebellar tract. it carries proprioceptive information from muscle spindles and golgi tendon organs of ipsilateral part of trunk and lower limb. proprioceptive information is taken to the spinal cord via central processes of dorsal root ganglia (first order neurons). these central processes travel through the dorsal horn where they synapse with second order neurons of clarke's nucleus. axon fibers from clarke's nucleus convey this proprioceptive information in the spinal cord in the peripheral region of the funiculus lateralis ipsilaterally. the fibers continue to course through the medulla oblongata of the brainstem, at which point they pass through the inferior cerebellar peduncle and into the cerebellum, where unconscious proprioceptive information is processed. this tract involves two neurons and ends up on the same side of the body. the terms flechsig's fasciculus and flechsig's tract are named after german neuroanatomist, psychiatrist and neuropathologist paul flechsig. ventral spinocerebellar tract the ventral spinocerebellar tract (or anterior spinocerebellar tract) conveys proprioceptive information from the body to the cerebellum. historically, it has also been known as gowers' column (or fasciculus or tract), after sir william richard gowers. it is part of the somatosensory system and runs in parallel with the dorsal spinocerebellar tract. both these tracts involve two neurons. the ventral spinocerebellar tract will cross to the opposite side of the body first in the spinal cord as part of the anterior white commissure and then cross again to end in the cerebellum (referred to as a "double cross"), as compared to the dorsal spinocerebellar tract, which does not decussate, or cross sides, at all through its path. the ventral tract (under l2/l3) gets its proprioceptive/fine touch/vibration information from a first order neuron, with its cell body in a dorsal ganglion. the axon runs via the fila radicularia to the dorsal horn of the grey matter. there it makes a synapse with the dendrites of two neurons: they send their axons bilaterally to the ventral border of the lateral funiculi. the fibers of the ventral spinocerebellar tract then enters the cerebellum via the superior cerebellar peduncle. this is in contrast with the dorsal spinocerebellar tract (c8 - l2/l3), which only has 1 unilateral axon that has its cell body in clarke's column (only at the level of c8 - l2/l3). originates from ventral horn at lumbosacral spinal levels. axons first cross midline in the spinal cord and run in the ventral border of the lateral funiculi. these axons ascend to the pons where they join the superior cerebellar peduncle to enter the cerebellum. once in the deep white matter of the cerebellum, the axons recross the midline, give off collaterals to the globose and emboliform nuclei, and terminate in the cortex of the anterior lobe and vermis of the posterior lobe. comparison with dorsal spinocerebellar tract when the dorsal roots are cut in a cat performing a step cycle, peripheral excitation is lost, and the dorsal spinocerebellar tract has no activity; the ventral spinocerebellar tract continues to show activity. this suggests that the dorsal spinocerebellar tract carries sensory information to the spinocerebellum through the inferior cerebellar peduncle during movement (since the inferior peduncle is known to contain fibres from the dorsal tract), and that the ventral spinocerebellar tract carries internally generated motor information about the movement through the superior cerebellar peduncle. posterior external arcuate fibers the posterior external arcuate fibers (dorsal external arcuate fibers or cuneocerebellar tract) take origin in the accessory cuneate nucleus; they pass to the inferior cerebellar peduncle of the same side. the term "cuneocerebellar tract" is also used to describe an exteroceptive and proprioceptive components that take origin in the gracile and cuneate nuclei; they pass to the inferior cerebellar peduncle of the same side. the posterior external arcuate fibers carry proprioceptive information from the upper limbs and neck. it is an analogue to the dorsal spinocerebellar tract for the upper limbs. in this context, the "cuneo-" derives from the accessory cuneate nucleus, not the cuneate nucleus. (the two nuclei are related in space, but not in function.) it is uncertain whether fibers are continued directly from the gracile and cuneate fasciculi into the inferior peduncle. rostral spinocerebellar tract the rostral spinocerebellar tract is a tract which transmits information from the golgi tendon organs of the cranial half of the body to the cerebellum. it terminates bilaterally in the anterior lobe of the cerebellum (lower cerebellar peduncle) after travelling ipsilaterally from its origin in the cervical portion of the spinal cord. it reaches the cerebellum partly through the brachium conjunctivum (superior cerebellar peduncle) and partly through the restiform body (inferior cerebellar peduncle). pathway for dorsal and spinocuneocerebellar tracts the sensory neurons synapse in an area known as clarke's nucleus or "clarke's column". this is a column of relay neuron cell bodies within the medial gray matter within the spinal cord in layer vii (just beneath the dorsal horn), specifically between t1-l3. these neurons then send axons up the spinal cord, and project ipsilaterally to medial zones of the cerebellum through the inferior cerebellar peduncle. below l3, relevant neurons pass into the fasciculus gracilis (usually associated with the dorsal column-medial lemniscal system) until l3 where they synapse with clarke's nucleus (leading to considerable caudal enlargement). the neurons in the accessory cuneate nucleus have axons leading to the ipsilateral cerebellum via the inferior cerebellar peduncle. pathway for ventral and rostral spinocerebellar tracts some neurons of the ventral spinocerebellar tract instead form synapses with neurons in layer vii of l4-s3. most of these fibers cross over to the contralateral lateral funiculus via the anterior white commissure and through the superior cerebellar peduncle. the fibers then often cross over again within the cerebellum to end on the ipsilateral side. for this reason the tract is sometimes termed the "double-crosser." the rostral tract synapses at the dorsal horn lamina (intermediate gray zone) of the spinal cord and ascends ipsilaterally to the cerebellum through the inferior cerebellar peduncle additional images decussation of pyramids. superficial dissection of brain-stem. lateral view. deep dissection of brain-stem. lateral view. dissection of brain-stem. lateral view. dissection of brain-stem. dorsal view.

nocardia transvalensis nocardia transvalensis nocardia transvalensis is a species of bacteria from the genus nocardia that is known to cause nocardiosis. nocardia transvalensis scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: mycobacteriales family: nocardiaceae genus: nocardia species: n. transvalensis binomial name nocardia transvalensispijper and pullinger 1927 (approved lists 1980) type strain atcc 6865ccug 45937cip 104841dsm 43405dsm 43582ifo 15921jcm 9099nbrc 15921nrrl b-16037vkm ac-867

haloechinothrix haloechinothrix haloechinothrix is a genus from the family pseudonocardiaceae. haloechinothrix scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: pseudonocardiales family: pseudonocardiaceae genus: haloechinothrixtang et al. 2010 type species haloechinothrix albatang et al. 2010 species "h. aidingensis" yang et al. 2021 h. alba tang et al. 2010 h. halophila (tang et al. 2010) nouioui et al. 2018 h. salitolerans (guan et al. 2012) nouioui et al. 2018

ralstonia solanacearum ralstonia solanacearum ralstonia solanacearum is an aerobic non-spore-forming, gram-negative, plant pathogenic bacterium. r. solanacearum is soil-borne and motile with a polar flagellar tuft. it colonises the xylem, causing bacterial wilt in a very wide range of potential host plants. it is known as granville wilt when it occurs in tobacco. bacterial wilts of tomato, pepper, eggplant, and irish potato caused by r. solanacearum were among the first diseases that erwin frink smith proved to be caused by a bacterial pathogen. because of its devastating lethality, r. solanacearum is now one of the more intensively studied phytopathogenic bacteria, and bacterial wilt of tomato is a model system for investigating mechanisms of pathogenesis. ralstonia was until recently classified as pseudomonas, with similarity in most aspects, except that it does not produce fluorescent pigment like pseudomonas. the genomes from different strains vary from 5.5 mb up to 6 mb, roughly being 3.5 mb of a chromosome and 2 mb of a megaplasmid. while the strain gmi1000 was one of the first phytopathogenic bacteria to have its genome completed, the strain uy031 was the first r. solanacearum to have its methylome reported. within the r. solanacearum species complex, the four major monophyletic clusters of strains are termed phylotypes, that are geographically distinct: phylotypes i-iv are found in asia, the americas, africa, and oceania, respectively. ralstonia solanacearum damage caused by ralstonia solanacearum on tomato stem scientific classification domain: bacteria phylum: pseudomonadota class: betaproteobacteria order: burkholderiales family: burkholderiaceae genus: ralstonia species: r. solanacearum binomial name ralstonia solanacearum(smith 1896) yabuuchi et al 1995 type strain atcc 11696 ccug 14272 cfbp 2047 dsm 9544 icmp 5712 jcm 10489 lmg 2299 ncaim b.01459 ncppb 325 nrrl b-3212 synonyms burkholderia solanacearum (smith 1896) yabuuchi et al. 1993 bacillus solanacearum smith 1896 pseudomonas solanacearum (smith 1896) smith 1914 pseudomonas batatae cheng and faan 1962 pseudomonas ricini (archibald) robbs 1954 ralstonia solanacearum was once considered as a possible biological control agent for kahili ginger (hedychium gardnerianum), a highly invasive species. however, r. solanacearum is no longer used as a biological control for kahili ginger in hawaiian forests because of its wide host range. the ginger-parasitizing strain will infect numerous ginger species, including edible ginger (zingiber officinale), shampoo ginger (z. zerumbet), and pink and red ginger (alpinia purpurata). hosts and symptoms photograph of tomato plant with ralstonia wilt symptoms, clemson university - usda cooperative extension slide series hosts plant hosts that r. solanacearum infects include: crops potato (solanum tuberosum); tomato (lycopersicum esculentum); soybean (glycine max); eggplant/aubergine (solanum melongena); banana, (musa spp); geranium (pelargonium spp.); ginger (zingiber officinale); tobacco (nicotiana tabacum); bell pepper/sweet pepper (capsicum spp.); olive (olea europea); rose (rosa). wild hosts woody nightshade (solanum dulcamara) symptoms geranium: wilting begins with lower leaves and petioles and works its way up the plant. wilted leaves have chlorotic, wedge-shaped areas or chlorotic and/or necrotic leaf margins. no leaf spots are evident. eventually, the entire plant collapses on the medium. white runny material oozes from cut stems. potato: wilting of the leaves occurs at the end of the day with recovery at night. plants eventually fail to recover and die. brown staining of vascular ring happens and pus may exude from the ring when the tuber is squeezed. pale ooze may exude from eyes and heel end of potato. soil will adhere to the oozing eyes. cross-section of a stem placed in water will exude milky white strands. unlike the fungal wilts, the leaves remains green in bacterial wilt. disease cycle survival ralstonia solanacearum can overwinter in plant debris or diseased plants, wild hosts, seeds, or vegetative propagative organs (other germplasm) like tubers. the bacteria can survive for a long time in water (up to 40 years at 20–25 °c (68–77 °f) in pure water), and the bacterial population is reduced in extreme conditions (temperature, ph, salts, e.g.). infected land sometimes cannot be used again for susceptible crops for several years. r. solanacearum can also survive in cool weather and enter a state of being viable but not culturable. in most cases, this stage is not an agricultural threat because the bacteria usually become avirulent after recovering. dispersal ralstonia solanacearum causes wilting at high populations (108 – 1010 cfu/g tissue) and disperses in several routes. the large number of r. solanacearum can shed from roots of symptomatic and nonsymptomatic plants. besides that, bacterial ooze (which is usually used as a sign for detection) on plant surfaces) can enter the surrounding soil or water, contaminating farming equipment or may be acquired by insect vectors. in addition, this pathogen can be spread by contaminated flood water, irrigation, contaminated tools, or infected seeds. in northern europe, the pathogen has become established in solanaceous weeds which grow in slow-moving rivers. when such contaminated water is used to irrigate potatoes, the pathogen enters the potato production system. the race 3 biovar 2 strain can survive in perennial nightshades which act as secondary hosts, and can also cause bacterial wilt of tomato. some eu states and middle eastern countries have not yet been able to eradicate this pathogen. infection ralstonia solanacearum usually enters the plant by a wound. natural wounds (created by abscission of flowers, genesis of lateral roots) and unnatural ones (by agricultural practices or nematodes and xylem-feeding insects) could become entry sites for r. solanacearum. the bacteria get access to the wounds partially by flagellar-mediated swimming motility and chemotaxic attraction toward root exudates. unlike many phytopathogenic bacteria, r. solanacearum potentially requires only one entry site to establish a systemic infection that results in bacterial wilt. after invading a susceptible host, r. solanacearum multiplies and moves systemically within the plant before bacterial wilt symptoms occur. wilting should be considered as the most visible side effect that usually occurs after extensive colonization of the pathogen. when the pathogen gets into the xylem through natural openings or wounds, tyloses may form to block the axial migration of bacteria within the plant. in susceptible plants, this sometimes happens slowly and infrequently to prevent pathogen migration, and may instead lead to vascular dysfunction by unspecifically obstructing uncolonized vessels. wilting occurs at high bacterial populations in the xylem and is partially due to vascular dysfunction in which sufficient water cannot reach the leaves. at this time, extracellular polysaccharide (eps1) content is about 10 μg/g tissue in the taproot, hypocotyl, and midstem; eps1 concentration is higher later on at more than 100 μg/g tissue in fully wilted plant. ralstonia's systemic toxin also causes loss of stomatal control, but no evidence shows excessive transpiration as its consequence. the primary factor contributing to wilting is probably blocking of pit membranes in the petioles and leaves by the high molecular weight eps1. high bacterial densities are byproducts of plant cell wall degradation; tyloses and gums produced by the plant itself are other contributing factors to wilting. natural genetic transformation most strains of r. solanacearum are competent for genetic transformation. natural genetic transformation is a sexual process involving dna transfer from one bacterial cell to another through the intervening medium, and the integration of the donor sequence into the recipient genome by homologous recombination. r. solanacearum is able to exchange large dna fragments ranging from 30 to 90 thousand bases. virulence mechanisms ralstonia solanacearum possesses genes for all six protein secretion pathways that have been characterized in gram-negative bacteria. perhaps the best-studied of these is the type iii secretion system (t3ss or ttss), which secretes infection-promoting effector proteins (t3es) into host cells. around 74 suspected or confirmed t3es have been identified in r. solanacearum to date, although the functions of very few are currently known. despite being just one of several protein secretion systems, t3ss is necessary for r. solanacearum to cause disease. no single effector protein has been found to significantly alter pathogenicity of r. solanacearum, but simultaneous disruption of certain subsets of effectors (such as the set of seven gala effectors in strain gmi1000) strongly affects virulence of the pathogen. for example, gala 7 is necessary for virulence on medicago truncatula, hinting that t3e diversity may play a role in determining the broad host range of the r. solanacearum species complex. the type iii secretion system is not unique to r. solanacearum, and is, in fact, very ancient. the evolutionary history of the t3ss is contested; a high degree of similarity to the flagellum has sparked debate over the relationship between these two structures. about half of t3ss proteins are highly conserved in r. solanacearum and likely constitute a very old and stabilized group of effectors in the core genome of the species complex.​​ among the other half showing variation among different strains of r. solanacearum, only a third show evidence of lateral gene transfer. the origins of the remaining effectors are unknown, although some researchers hypothesize that gene-for-gene interactions may play a significant role in shaping virulence genes in r. solanacearum. some of these effector proteins are homologous to transcription activator-like effectors (tal effectors) from xanthomonas and could possibly have a similar function of activating specific genes in the host plant cells during r. solanacearum pathogenesis. environment the environment in which r. solanacearum is commonly found is affected by the particular race (a genetically diverse population within a species), and the particular biovar (a strain that differs physiologically or biochemically from other strains.) race 1, race 2 biovar 1, and race 3, biovar 2 are three of the most common and important strains. race 1 strains have a broad host range including tobacco and bananas, and are usually found in tropical and subtropical environments, as they have trouble surviving cooler temperatures, and are endemic to the southeastern united states. race 2 strains have a more limited host range than race 1, and are mostly restricted to tropical environments. race 3 strains are more cold tolerant than the other two and are found in tropical highlands and temperate areas. the host range for race 3 biovar 2 includes potatoes, tomatoes, and geraniums. race 3 biovar 2 is very common throughout the world, but is not generally reported in north america, so is the focus of many sanitation and quarantine management practices to prevent the introduction or spread of the pathogen. although it is not there yet, researchers at the university of guam are concerned about the possible spread of r. solanacearum to guam. management general management commercial chemicals have generally proven to be ineffective in controlling the pathogen and are not recommended as a means of control. in regions where the pathogen is established, a strategy of integrated disease management is the best method to reduce any impact of the pathogen. using pathogen-free planting materials is a necessity. planting resistant cultivars minimizes the ill effects of the pathogen, although no completely immune cultivars are now available. finally, a good rotation system that follows susceptible crops with resistant or nonhost crops can assist in diminishing the pathogen. the pathogen is listed as a select agent in the united states; if the pathogen is detected by a proper authority, a number of management protocols may be implemented. these can range from surveys to quarantines of infected and potentially infected plant material, which in turn may lead to larger eradication and sanitation programs. potato wilting and yellowing of the leaves, as well as overall stunting of the plant, are typical symptoms. the leaves may also take on a bronze cast along with stems becoming streaked and tuber eyes becoming discolored. tubers also start to rot if left in the ground. a milky-white sticky exudate or ooze, consisting of bacterial cells and their extracellular polysaccharide, is usually noticeable in freshly cut-sections of infected tubers. control of r. solanacearum is difficult because it is a soil borne pathogen, has wide host range, long survival in the soil, and has wide biological variation. no single control method has been found to be 100% effective, although in locations where the pathogen is established, some level of bacterial wilt control has been possible through use of a combination of diverse methods. these methods include phytosanitation and cultural practices, chemical control, biological control, and host resistance. general sanitation practices are recommended to prevent spread of the disease, as chemical control is ineffective. crop rotation with resistant crops is useful, as is altering the ph of the soil to keep it low in the summer (4-5), and higher in the fall (6.) tomato younger leaves

of the plant will become flaccid, and adventitious roots may appear on the stem of the plant. the vascular system exhibits a progressively darker brown color as the disease progresses, in addition to possible lesions on the stem. management practices are similar to those of potato. banana ralstonia solanacearum on an overripe banana commonly known as moko disease, after a banana variety from trinidad that went extinct in the 1890s. typically, yellowing and wilting of older leaves occurs, as well as reduced fruit size and eventual rotting of the fruit. in addition, flowers can become blackened and shriveled, and the vascular tissue discolored. exclusion of the disease where it is not present is the only effective means of control. if an area does become infected, all of the infected plants must be eliminated, which is why strong sanitation practices must be used to reduce the spread of disease. importance ralstonia solanacearum is classified as one of the world's most important phytopathogenic bacteria due to its lethality, persistence, wide host range, and broad geographic distribution. although the pathogen causes major yield losses in the tropics and subtropics, it is currently a continuing threat in temperate climates. ralstonia solanacearum is a high-profile alien plant pathogen of a2 quarantine status affecting a very wide range of crops. this means that it is present in parts of europe, but is under statutory control. worldwide, the most important crops affected are: potato, tomato, tobacco, banana, and geranium. in the uk and the rest of the eu, the most important crops affected are potato and tomato. it would cause serious economic damage were it to become more established than it currently is. losses are due to actual yield reduction and also due to statutory measures taken to eliminate the disease. bacterial wilt caused by r. solanacearum is of economic importance because it infects over 250 plant species in over 50 families. as of 2007, this pathogen has affected over 450 host species representing 54 plant families due to its broad host range around the world. the disease is known as southern wilt, bacterial wilt, and brown rot of potato. many more dicots suffer from the disease than do monocots. among the monocot hosts, the order zingiberales dominates, with five of nine families being infected by this bacterium. the reason why some families are more susceptible to bacterial wilt is still unknown. originally, r. solanacearum is found in tropical, subtropical, and warm, temperate climates, but is not believed to survive cold temperatures. however, this pathogen has recently been detected in geraniums (pelargonium spp.) in wisconsin, usa and was traced back to the import of geranium cuttings to north america and europe from the highland tropics where race 3 biovar 2 is endemic brown rot of potato caused by r. solanacearum race 3 biovar 2 is among the most serious disease of potato worldwide, and is responsible for an estimated $950 million in losses each year. race 3 biovar 2 is cold tolerant and classified as a quarantine pathogen. in addition, this race/biovar has been listed as a select agent in the agricultural bioterrorism act of 2002, and is considered to have potential to be developed as a bioterror weapon.

glesatinib glesatinib glesatinib (mgcd265) is an experimental anti-cancer drug. glesatinibclinical dataroutes ofadministrationby mouthatc codenonelegal statuslegal status investigational identifiers iupac name n-methyl}-2-pyridinyl)thienopyridin-7-yl]oxy}phenyl)carbamothioyl]-2-(4-fluorophenyl)acetamide cas number936694-12-1pubchem cid25181472chemspider52084900unii7q29oxd98nkeggd11136chemical and physical dataformulac31h27f2n5o3s2molar mass619.71 g·mol−13d model (jsmol)interactive image smiles coccncc1ccc(nc1)c2cc3c(s2)c(ccn3)oc4ccc(cc4f)nc(=s)nc(=o)cc5ccc(cc5)f inchi inchi=1s/c31h27f2n5o3s2/c1-40-13-12-34-17-20-4-8-24(36-18-20)28-16-25-30(43-28)27(10-11-35-25)41-26-9-7-22(15-23(26)33)37-31(42)38-29(39)14-19-2-5-21(32)6-3-19/h2-11,15-16,18,34h,12-14,17h2,1h3,(h2,37,38,39,42)key:yrchyhrcbxnynu-uhfffaoysa-n it is in phase 2 clinical trials for non-small cell lung cancer (nsclc). it is a spectrum selective tyrosine kinase inhibitor "for the treatment of non-small cell lung cancer (nsclc) patients with genetic alterations of met".

arcuate nucleus (medulla) arcuate nucleus (medulla) in the medulla oblongata, the arcuate nucleus is a group of neurons located on the anterior surface of the medullary pyramids. these nuclei are the extension of the pontine nuclei. they receive fibers from the corticospinal tract and send their axons through the anterior external arcuate fibers and medullary striae to the cerebellum via the inferior cerebellar peduncle. this article is about the structure in the medulla oblongata. for the hypothalamic structure, see arcuate nucleus. arcuate nucleus (medulla)transverse section of medulla oblongata below the middle of the olive. ("nucleus arcuatus" visible near bottom right.)dissection of brain-stem. lateral view. (labels for "external arcuate fibers" and "dorsal external arcuate fibers" visible at lower right.)detailsidentifierslatinnucleus arcuatus medullae oblongataeneuronames775neurolex idbirnlex_2635ta98a14.1.04.256ta26016fma72609anatomical terms of neuroanatomy arcuate nuclei are capable of chemosensitivity and have a proven role in the respiratory center controlling the breathing rate. additional images diagram showing the course of the arcuate fibers. the formatio reticularis of the medulla oblongata, shown by a transverse section passing through the middle of the olive.

termination of pregnancy act (zimbabwe) termination of pregnancy act (zimbabwe) the termination of pregnancy act is a law in zimbabwe governing abortion. enacted in 1977 by the parliament of rhodesia and effective starting 1 january 1978, it was retained after zimbabwe's independence in 1980. the law expanded abortion access, permitting it under three circumstances: if the pregnancy endangers the life of the woman or threatens to permanently impair her physical health, if the child may be born with serious physical or mental defects, or if the fetus was conceived as a result of rape or incest. termination of pregnancy actcoat of arms of rhodesiaparliament of rhodesiaparliament of zimbabwe long title termination of pregnancy act, 1977 citationno. 29 of 1977territorial extentrhodesia (today zimbabwe)enacted bythe parliament of rhodesiaenacted1977effective1 january 1978summaryexpanded legal abortion access in rhodesia (today zimbabwe)status: in force background before 1977, abortion in zimbabwe (then rhodesia) was governed by the british 1861 offences against the person act and roman-dutch common law, which permitted abortion only to save the life of the pregnant woman. at the time, bulawayo was the "abortion centre" of rhodesia, with most abortion procedures being performed by gynaecologists at bulawayo central hospital. with the advent of the women's liberation movement in rhodesia in the early 1970s, debate over the country's abortion law increased. in july 1976, the government's commission of inquiry into the termination of pregnancy in rhodesia published its recommendations that some restrictions on abortion be loosened. in the report, the commission acknowledged that "perhaps the majority of younger rhodesians wish to see abortion laws liberalized." the commission's report, and the proposed legislation in parliament that followed, sparked public debate on what it described as "a key social issue in rhodesian society." in december 1976, acting on the commission's findings, the parliament introduced legislation addressing abortion, in what would become the termination of pregnancy act. provisions the termination of pregnancy act (no. 29 of 1977), which took effect on 1 january 1978, was similar to south africa's now-repealed abortion and sterilization act of 1975. it expanded abortion access, allowing the procedure to be performed under three conditions: if the pregnancy seriously endangers the mother's life or threatens to permanently impair her physical health, if there is a significant risk that the child would be born with serious physical or mental defects, or if the fetus was conceived as a result unlawful intercourse, defined as rape, incest, or intercourse with a mentally handicapped woman (other sexual offenses, like statutory rape, are not legal grounds for an abortion). an abortion may only be performed by a medical practitioner in an institution designated by the ministry of health and child care, with the written permission of the hospital superintendent or administrator. in order for the abortion procedure to be performed, two medical practitioners who are not from the same medical partnership or institution must certify that the requisite conditions indeed exist. in cases of unlawful intercourse, (rape, incest, or intercourse with a mentally handicapped woman), a court magistrate of the jurisdiction in which the abortion would take place must issue a certificate certifying that the pregnancy was probably that the result of unlawful intercourse as defined in the act. abortion services are provided by the ministry of health and child care, and are free to low-income and unemployed women. illegal abortion carries a penalty of imprisonment up to five years and/or a fine. the termination of pregnancy act set the fine at z$5,000. however, zimbabwe no longer uses the zimbabwean dollar. under section 60 of the criminal law and codification reform act, illegal abortion is punishable by up to five years in prison and/or a fine not exceeding level 10. impact and reception at the time of its passage, although the new law expanded abortion access, it did not go far enough for some: jacquie stafford, president of the national organisation for women, wrote in a letter to the rhodesia herald that the law "showed nothing but contempt for the women of this country, and makes me wonder at the sanity of our parliamentary representatives." while it expanded the circumstances under which legal abortion could be obtained, it also made it difficult to access abortion services by requiring physician's, and in some cases, a magistrate's, approval for the procedure to go forward. in recent years, there has been growing vocal support to amend the law and expand legal abortion access. many support expanded legal abortion access in order to end unsafe illegal abortions which often threatens the health of the mother, or results in maternal death. zimbabwean women are 200 times more likely to die from an abortion procedure than women in south africa, where obtaining an abortion is easier. and zimbabwe's maternal mortality rate is three times higher than south africa. one abortion-rights group active in zimbabwe is right here right now (rhrn), which advocates for a review of the termination of pregnancy act, which they consider "archaic". other calls to amend the law came from the organization zimbabwe doctors for human rights, as well as former minister of finance tendai biti.

butyrivibrio proteoclasticus butyrivibrio proteoclasticus butyrivibrio proteoclasticus is a bacterium from the family lachnospiraceae originally described in the genus clostridium. butyrivibrio proteoclasticus scientific classification domain: bacteria phylum: bacillota class: clostridia order: eubacteriales family: lachnospiraceae genus: butyrivibrio species: b. proteoclasticus binomial name butyrivibrio proteoclasticus(attwood et al. 1996) moon et al. 2008 synonyms clostridium proteoclasticum attwood et al. 1996 butyrivibrio proteoclasticus b316t butyrivibrio proteoclasticus b316t was the first butyrivibrio species to have its genome sequenced. it was first isolated and described by attwood et al. (1996), and was originally assigned to the genus clostridium based on its similarity to clostridium aminophilum, a member of the clostridium sub-cluster xiva. further analysis has shown that it is more appropriately placed within the genus butyrivibrio and the organism was given its current name. within this genus its 16s rdna sequence is most similar to, but distinct from, that of b. hungateii. b. proteoclasticus is found in rumen contents at significant concentrations of from 2.01 x 106/ml to 3.12 x 107/ml as estimated by competitive pcr or 2.2% to 9.4% of the total eubacterial dna within the rumen, as estimated by real time pcr. b. proteoclasticus cells are anaerobic, slightly curved rods, commonly found singly or in short chains, but it is not unusual for them to form long chains. they possess a single sub-terminal flagellum, but unlike other butyrivibrio species, they are not motile. they are ultrastructurally gram-positive, although as with all butyrivibrio species, they stain gram-negative b. proteoclasticus has been shown to have an important role in biohydrogenation, converting linoleic acid to stearic acid.

covid-19 vaccination in the united states covid-19 vaccination in the united states the covid-19 vaccination campaign in the united states is an ongoing mass immunization campaign for the covid-19 pandemic in the united states. the food and drug administration (fda) first granted emergency use authorization to the pfizer–biontech vaccine on december 10, 2020, and mass vaccinations began four days later. the moderna vaccine was granted emergency use authorization on december 17, 2020, and the janssen (johnson & johnson) vaccine was granted emergency use authorization on february 27, 2021. by april 19, 2021, all u.s. states had opened vaccine eligibility to residents aged 16 and over. on may 10, 2021, the fda approved the pfizer-biontech vaccine for adolescents aged 12 to 15. on august 23, 2021, the fda granted full approval to the pfizer–biontech vaccine for individuals aged 16 and over. covid-19 vaccination in the united statesunited states. percentage with at least one vaccination dose. see commons source for date of last upload. us territories: gu = guam. as = american samoa. mp = northern mariana islands. vi = virgin islands. associated states: pw = republic of palau. fm = federated states of micronesia. mh = marshall islands.datedecember 14, 2020 (2020-12-14) – presentlocation united statescompact of free association: palau marshall islands micronesiacausecovid-19 pandemic in the united statesorganized bycenters for disease control and preventionparticipants262,323,837 people have received at least one dose administered of pfizer–biontech, moderna or janssen(august 17, 2022)223,684,995 people have been fully vaccinated (both doses of pfizer–biontech or moderna, or one dose of janssen)outcome79% of the united states population has received at least one dose of a vaccine 67% of the united states population is fully vaccinatedwebsitecdc weekly confirmed covid-19 deaths map of cumulative covid-19 death rates by us state. the u.s. government first began the campaign under the presidency of donald trump with operation warp speed, a public–private partnership to expedite the development and manufacturing of covid-19 vaccines. joe biden became the new president of the united states on january 20, 2021. biden began his term with an immediate goal of administering 100 million vaccine doses within his first hundred days in office, signing an executive order which included increasing supplies for vaccination. this goal was met on march 19, 2021. on march 25, 2021, he announced he would increase the goal to 200 million within his first 100 days in office. this goal was eventually reached on april 21, 2021. by july 4, 2021, 67% of the united states' adult population had received at least one dose, just short of a goal of 70%. this goal was eventually met on august 2, 2021. while vaccines have helped significantly reduce the number of new covid-19 infections nationwide, states with below-average vaccination rates began to see increasing numbers of cases credited to the highly infectious delta variant by july 2021, which led to an increased push by organizations and companies to begin imposing de facto mandates for their employees be vaccinated for covid-19. on september 9, 2021, president biden announced plans by the federal government to use executive orders and emergency temporary standards enforced by osha to mandate the vaccination of all federal branch employees, and require that all companies with more than 100 employees regularly test all employees who are not yet fully vaccinated for covid-19. on january 26, 2022, osha completely withdrew the vaccine mandate for companies with more than 100 employees due to a ruling from the supreme court of the united states that blocked the mandate. as of march 2022, according to the commonwealth fund, covid-19 vaccination in the united states has prevented an additional 2.3 million deaths, an additional 17 million hospitalizations, and an additional 66.2 million infections from covid-19. vaccination has also prevented an additional $899.4 billion in healthcare costs. according to a june 2022 study published in the lancet, covid-19 vaccination in the united states prevented an additional 1.9 million deaths from december 8, 2020, to december 8, 2021. according to a july 2022 study published in jama network open, covid-19 vaccination in the united states prevented an additional 235,000 deaths, an additional 1.6 million hospitalizations, and an additional 27 million infections from december 1, 2020, to september 30, 2021. vaccination program the us map below is for the percent of people of all ages who received all doses prescribed by the initial covid-19 vaccination protocol. two of the three covid-19 vaccines used in the u.s. require two shots to be fully vaccinated. the other vaccine requires only one shot. booster doses are recommended too. percent of people fully vaccinated. see commons source for date of last upload. vaccine united states timeline of daily covid-19 vaccine doses administered in the us. see the latest date on the timeline at the bottom. total number of people who have received vaccinations in the united states as of october 12, 2022 unvaccinated population: ~66.8 million people (20.14%) population who have received only one dose of a two-dose vaccine: 38,910,734 (11.72%) population who are fully vaccinated, but haven't received an additional booster shot: 115,364,980 (34.75%) population who are fully vaccinated and received an additional booster shot: 85,212,292 (25.67%) population who are fully vaccinated and received two additional booster shots: 25,623,483 (7.72%) vaccines administered per pharmaceutical company as of october 19, 2022 pfizer–biontech (381,978,824) (59.43%) moderna (241,011,491) (37.50%) johnson & johnson (18,916,447) (2.94%) novavax (35,302) (0.006%) not identified (690,663) (0.107%) vaccines were distributed to states on a population basis, with the vaccine rollouts being administered by each individual u.s. state. the centers for disease control and prevention suggested that hospital workers and nursing home personnel be the first individuals vaccinated. the subsequent phases of the rollout are determined by each individual state agency. the cdc has issued cards that can be used to track vaccine progress and serve as a proof of vaccination when requested (such as during international travel). states such as california and new york have offered a digital immunity passport accessible via a mobile app. eligibility of non-citizens on february 1, 2021, the department of homeland security said it "fully support equal access to the covid-19 vaccines and vaccine distribution sites for undocumented immigrants" and that related federal agencies "will not conduct enforcement operations at or near vaccine distribution sites or clinics". states may have intended that vaccines be prioritized for their residents ahead of tourists, but there was some difficulty communicating and enforcing this. some american adults have no driver's license, and the united states does not automatically provide each citizen with identity documentation in a centralized system. furthermore, when people did not show up for their vaccine appointments, many clinics vaccinated anyone else who happened to show up so that the doses would not be wasted. as a result, some tourists as well as undocumented immigrants were vaccinated. as of early february 2021, states including florida, california, new york, and texas were specifically trying to restrict "vaccine tourism": brief visits to the u.s. with the primary intention of obtaining a vaccine. however, contrary to rumors that spread on social media, the united states did not have a policy of cancelling visas or imposing fines on tourists who sought vaccination. diplomats pointed out that the b1/b2 tourist visa allows people to seek medical treatment while within the united states, even if they do not turn out to be eligible for the covid-19 vaccine. as of may 13, 2021, according to the colombian newspaper el tiempo, the following u.s. states were not requiring foreigners to present proof of residency to receive the vaccine: alabama, arizona, california, colorado, florida, iowa, louisiana, maryland, michigan, minnesota, missouri, montana, nevada, new hampshire, new mexico, new york, north carolina, north dakota, ohio, oklahoma, pennsylvania, south carolina, tennessee, texas, virginia, and wyoming. thousands of latin americans were booking travel to the united states and being vaccinated in the country. vaccination centers in some u.s. states were accepting foreign passports as valid identification. travel agencies were advertising "vaccination tourism," and the u.s. embassy in peru, for example, advised that travelers to the united states could seek vaccination. the governor of alaska announced that, as of june 1, any international visitor over age 12 could be vaccinated in alaska and vaccines would be available at airports for convenience. background from early 2020, more than seventy companies worldwide (with five or six operating primarily in the u.s.) began vaccine research. 28 different vaccines are being worked on and developed using the research provided by those companies. the global competition had national security implications for various countries. in preparation for large-scale production, congress set aside more than $3.5 billion for this purpose as part of the cares act. among the labs working on a vaccine is the walter reed army institute of research, which has previously studied other infectious diseases, such as hiv/aids, ebola, and mers. by march 18, tests had begun with dozens of volunteers in seattle, sponsored by the u.s. government, and similar safety trials were planned for other potential vaccines. bill gates, whose foundation shifted its focus nearly entirely to the pandemic, anticipated in early 2020 that a vaccine could be ready by early 2021. on august 5, 2020, the united states agreed to pay johnson & johnson more than $1 billion to create a hundred million doses of covid-19 vaccine. the deal gave the u.s. an option to order an additional two hundred million. the doses were supposed to be provided for free to americans if they are used in a covid-19 vaccination campaign. on august 31, 2020, the centers for disease control and prevention (cdc) released their outline for how the covid-19 vaccine would be administered and distributed across the entire country. senior citizens await covid-19 vaccine at a maryland pharmacy in january 2021. bio, a trade group of all covid-19 vaccine makers except astrazeneca, tried to persuade secretary azar to publish strict fda guidelines that would help ensure the safety and public uptake of the vaccine. politics impacted scientific practice, however, when chief of staff mark meadows blocked the fda when it was realized that the timing of the provisions would make it impossible for a vaccine to be authorized before the november election. ultimately, the guidelines emerged from the office of management and budget and were published on the fda website. as of october 2020, 44 were in clinical trials on humans, and 91 pre-clinical vaccines were being tested on animals. most of these trials were underway. on november 20, 2020, the pfizer–biontech partnership submitted a request for emergency use authorization (eua) to the food and drug administration (fda), and the fda announced that its vaccines and related biological products advisory committee (vrbpac) would review the request. an eua is a mechanism under the pandemic and all-hazards preparedness reauthorization act of 2013 that permits products not yet fully approved by the fda to be used as part of an existing state of emergency. on december 11, the fda granted emergency use authorization for the pfizer–biontech vaccine. an initial shipment of 2.9 million doses were scheduled to be distributed rapidly, and pfizer promised to continue supplying the rest of the hundred million doses through march 2021. pfizer had adequate stocks available and began this distribution on december 17, 2020, but the federal government reduced the amount pfizer was allowed to distribute. on december 18, 2020, the fda granted the moderna vaccine emergency use authorization, which moderna had requested on november 30, 2020. the u.s. planned to rapidly distribute 5.9 million doses with more to come later. despite his involvement in spurring their development via operation warp speed, trump largely downplayed vaccines during his final months in office, and both trump and first lady melania trump received the vaccine in private before joe biden took office as the new president in january 2021. on february 27, 2021, the janssen covid-19 vaccine was granted emergency use authorization by the fda for use. however, this vaccine has faced backlash from some government officials, believing it to be not as effective as pfizer or moderna. on march 5, the mayor of detroit, mike duggan, rejected a shipment of the janssen vaccine, saying, "moderna and pfizer are the best. and i am going to do everything i can to make sure the residents of the city of detroit get the best." after backlash, duggan declared he would no longer decline the vaccine. on

march 11, 2021, president biden announced that he would direct all states to make vaccines available to all adults no later than may 1. on april 6 he said he would direct states to make all adults eligible for vaccination by april 19. this deadline was met after several states opened up vaccination to everyone 16 and above the same day. on march 26, 2021, ocugen submitted its master file for covaxin a conventional inactivated vaccine to the fda. in june the fda suggested that the company go the longer route to gain full fda approval instead of emergency use authorization. as of may 2021, most experts thought the united states would be unable to achieve herd immunity, at least in the near term, given insufficient demand for the vaccines. on that note, many sources are saying the new variants last longer than 14 days, such as those found at home and abroad. on july 6, biden announced plans for more targeted outreach in order to reach under-vaccinated populations, such as shifting from larger mass clinics to having wider availability at community locations and events, and going "neighborhood by neighborhood, and oftentimes, door to door—literally knocking on doors—to get help to the remaining people protected from the virus" on july 16, the fda approved a request by pfizer to give its vaccine a priority review designation, meaning that final approval of the vaccine would be pursued on an expedited timetable. while priority review processes usually take up to six months, it was expected that the pfizer vaccine may be approved within weeks. on august 23, the fda announced that it had formally approved the pfizer vaccine for individuals 16 and over. it remains subject to eua for individuals aged 12 to 15. incentives efforts have been made by private businesses to help encourage vaccination, including ridesharing services offering free transport to vaccine clinic sites, and promotional incentives and discounts being offered to those who present proof of a recent vaccination. free items included beer, pizza, crawfish, donuts, and french fries. some sports teams established partnerships to offer vaccine clinics at their venues on game days, with free tickets to games offered to those who use the clinics. free cannabis was available in washington state when getting a vaccine at a dispensary. massachusetts ran a free lottery for fully vaccinated people, and gave out $6.5 million to ten people in the form of cash and scholarships. ohio ran a similar lottery, maine gave away hunting licenses, and west virginia gave away $100 savings bonds. vaccines in order vaccine submitted (eua) emergency use authorization deployment submitted (full) full approval pfizer–biontech november 20, 2020 december 11, 2020 december 14, 2020 may 7, 2021 august 23, 2021 moderna november 30, 2020 december 17, 2020 december 21, 2020 june 1, 2021 january 31, 2022 janssen february 4, 2021 february 27, 2021 march 1, 2021 no no novavax january 31, 2022 july 19, 2022 (ages 18+) august 1, 2022 no no covaxin march 26, 2021 (ages 18+)november 5, 2021 (ages 2–18) pending no no no astrazeneca — — no no no sanofi–gsk no no no no no vaccine administration listed in millions, as of april 14, 2023 100 200 300 400 500 pfizer–biontech moderna janssen novavax pfizer-biontech bivalent booster moderna bivalent booster not identified vaccine deliveries listed in millions, as of april 14, 2023 100 200 300 400 500 600 pfizer–biontech moderna janssen novavax pfizer-biontech bivalent booster moderna bivalent booster booster doses on august 12, 2021, the fda amended the eua for the moderna and pfizer vaccines in order to allow a third, booster dose for patients who are immunocompromised or have received organ transplants. director of the cdc rochelle walensky stated in a press briefing that "certain people who are immune compromised, such as people who have had an organ transplant and some cancer patients, may not have had an adequate immune response to just two doses of the ." in an interview with today, director of the national institute of allergy and infectious diseases (niaid) anthony fauci stated that "inevitably, there will be a time when we'll have to give boosts . what we're doing literally on a weekly and monthly basis is following cohorts of patients to determine if, when and whom should get it. but right now at this moment, other than the immune compromised, we're not going to be giving boosters to people." the world health organization (who) discourages the use of booster shots for covid-19 in developed countries, as they would divert supplies away from the unvaccinated. on august 18, 2021, walensky and acting commissioner of the fda janet woodcock released a joint statement indicating that, pending fda approval, booster doses for the moderna and pfizer vaccines could become generally available by the week of september 20, for those who had received their second dose at least eight months prior. they stated that that protection against severe outcomes or death "could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout", such as health care workers and seniors. on september 17, 2021, the fda vaccines and related biological products advisory committee voted unanimously against recommending that booster doses of the pfizer vaccine be distributed to the general public, citing the lack of evidence that a third dose is safe for younger populations. on september 23, walensky officially approved the distribution of pfizer booster doses to certain populations six months after their second dose, including those who are 65 and over, those with underlying conditions, and those who work in high-risk settings. on october 14, 2021, the committee recommended a half-dose booster for the moderna vaccine among the same populations. the next day, the committee also recommended that a second dose be generally distributed for the janssen vaccine, at least two months after the first. an fda analysis cited that a single dose of the vaccine had a consistently lower efficacy in comparison to the mrna vaccines. timeline vice president elect kamala harris, like many other public officials, was vaccinated on-camera. drive-through vaccination site at the larkspur ferry terminal in larkspur, california december 2020 on december 10, 2020, the fda granted emergency use to the pfizer vaccine. on december 14, 2020, the first vaccine doses were administered. sandra lindsay of queens, new york city, was the first american to be administered an fda-authorized covid-19 vaccine. the moderna vaccine was granted emergency use authorization three days later, on december 17. on december 21, president-elect joe biden publicly received his first dose of the pfizer vaccine during a media event at christiana hospital in delaware. the event was intended as a means by the incoming biden administration to boost public confidence in the vaccines. biden stated that trump "deserve some credit getting this off the ground with operation warp speed", and told the press "it's going to take time, and in the meantime—i don't want to sound a sour note here—but i hope people listen to all the experts." vice president-elect kamala harris received her first dose of the moderna vaccine on december 29, also in public. march 2021 on march 12, 2021, the united states surpassed 100 million doses administered. over the course of the month, seven states (arkansas, mississippi, ohio, connecticut, arizona, texas, and georgia) made the vaccine available to all adults, following a period of selective vaccination for elderly and other vulnerable populations. california and washington announced that all adults would be eligible for a vaccine starting april 15. indiana announced that it would make vaccines available to university students and would specifically facilitate the transfer of vaccines to university-based vaccine clinics, including one such clinic at the university of notre dame. on day 58 (march 19) of the biden administration, it achieved its goal of administering 100 million doses within its first 100 days. on march 25, the administration set a new goal of administering 200 million doses in its first 100 days. april 2021 on april 3, more than four million doses of the covid-19 vaccine were reported administered in the past 24 hours, setting a new record and bringing the seven-day average to more than three million a day. as of april 11, more than 187 million vaccine doses have been administered. on april 13, the cdc and fda issued a statement recommending a pause in the use of the johnson & johnson vaccine "out of an abundance of caution" after six women aged 18 through 48 developed a rare and severe type of blood clot called cerebral venous sinus thrombosis; on april 23, the recommended pause was lifted. by april 19, all u.s. states had made americans aged 16 and older eligible for vaccination. on april 22, the biden administration announced that it had achieved its new goal of 200 million vaccine doses administered within its first 100 days. as of april 28, the cdc reported an average of 2.7 million daily vaccinations over the past week. may 2021 on may 4, 2021, biden announced a new target of having at least 70% of u.s. adults receive one vaccine dose by july 4. on may 10, 2021, the fda granted emergency use authorization for the pfizer vaccine for use on adolescents aged 12–15, making the united states the second country in the world, after canada, to do so. on may 12, director of the cdc rochelle walensky approved the recommendation. on may 25, the biden administration announced that 50% of adults had been fully vaccinated. june 2021 by june 2021, the pace of vaccination had begun to decrease, amid increasing spread of the highly-infectious delta variant across the country. on june 3, the white house announced additional private-sector partnerships in order to expand targeted outreach and vaccine availability, including an initiative to promote and offer vaccines through black-owned barber shops throughout june, and a partnership with brewery anheuser-busch—who pledged in a promotional campaign to offer a "free beer" to all adults over 21 if the country met biden's 70% goal. the united states passed 600,000 covid deaths on tuesday, june 15, more than 200 times higher than the number of lives lost during the attacks of september 11, 2001. by late-june, one-quarter of covid-19 cases in the u.s. were attributable to the delta variant. dr. fauci warned that vaccination disparities could lead to "two americas" where less vaccinated u.s. populations were at much higher risk of covid-19. july 2021 the u.s. missed biden's 70% goal by approximately three million residents, or 3%. only 18 states reached the 70% goal among their local population. generally, the goal was met for adults 27 and over, but not for younger populations. by early-july 2021, the number of daily covid-19 cases in the u.s. had declined by around 90% since the peak in january. however, cases had also begun to increase in parts of the country with below-average vaccination rates, and hesitancy towards the vaccine had become a partisan issue: a poll by the washington post and abc news found that 86% of self-identified democrats surveyed had received at least one dose, as opposed to 45% of self-identified republicans, the 18 states that did reach 70% of first doses by july 4 were all won by biden during the 2020 election, and a july 8 report by kff found that the average vaccination rate in counties that voted for biden was growing in comparison to those that voted for trump. anti-vaccination rhetoric increased among conservatives, including republican politicians and right-wing media outlets (such as fox news and newsmax) promoting misinformation and conspiracy theories (such as falsely claiming that the biden administration would impose mandatory door-to-door vaccination—an exaggeration of biden's recently announced plans for targeted outreach), republican lawmakers attempting to inhibit vaccine outreach, and state laws to prohibit "discrimination" against the unvaccinated (which effectively ban vaccine mandates). on july 15, surgeon general vivek murthy warned that health-related misinformation was a public health threat. the next day, president biden accused social networking service facebook of "killing people" by enabling the spread of vaccine misinformation. on july 19, after criticism from facebook over the comments, biden stated that they were based on a report suggesting that approximately 12 social media users were responsible for at least 60% of vaccine misinformation, and clarified that "facebook isn't killing people,

these 12 people are out there giving misinformation. anyone listening to it is getting hurt by it. it's killing people. it's bad information". he went on to explain that "my hope is that facebook, instead of taking it personally that somehow i'm saying facebook is killing people, that they would do something about the misinformation, the outrageous misinformation about the vaccine". in late-july, amid increasing covid-19 hospitalizations in a number of republican-led states, some republican politicians became more vocal in promoting vaccination, including senate minority leader mitch mcconnell, senator of texas john cornyn, and former surgeon general jerome adams. governor of florida ron desantis—who has been critical of fauci and covid-19 restrictions—stated in a press appearance that vaccines were "saving lives" and "reducing mortality" (citing the majority of hospitalizations being unvaccinated individuals), while criticizing mask mandates as displaying a lack of confidence in the efficacy of vaccines. mcconnell used campaign funds to purchase radio advertisements in his home state of kentucky to promote vaccination; the ad features mcconnell discussing his childhood battle with polio, and stating that the development of multiple safe and effective covid-19 vaccines in such a short time was "nothing short of a modern medical miracle", in comparison to the "decades" it took to develop a polio vaccine. a number of conservative commentators also abruptly made statements in support of vaccination, including fox news hosts steve doocy and sean hannity during broadcasts of fox & friends and hannity respectively, newsmax ceo and trump confidant christopher ruddy (who praised biden in an op-ed for "making a huge dent" in the pandemic by embracing and prioritizing the rollout of the "effective vaccine" inherited from the trump presidency), and conservative commentator ben shapiro. however, hannity subsequently walked back his remarks on his radio show and hannity, arguing that he never urged his viewers to get the vaccine, and adding the caveat that they should get the vaccine "if it's right for you", after doing "all of your research" and speaking with medical professionals that they trust. on july 26, 2021, a number of organizations announced that they would mandate the vaccination of their employees, including the american medical association and american nurses association, and frontline health care workers of the department of veterans affairs. california and new york city announced that all government employees would be subject to weekly testing if they are not vaccinated. on july 29, president biden similarly announced that unvaccinated federal employees and on-site contractors will be subject to mandatory social distancing, masks, weekly or bi-weekly covid-19 testing, and limitations on work travel. biden cited delta variant and a "pandemic of the unvaccinated" as justification for the measures. he also announced that the federal government planned to use funds from the american rescue plan to reimburse small and medium-sized businesses for paid time off for employee vaccine appointments (similar to paid time off provided for voting in elections), and called for states to offer $100 payments to the newly vaccinated using american rescue plan funding as an "extra incentive to boost vaccination rates, protect communities, and save lives." biden stated that "i know that paying people to get vaccinated might sound unfair to folks that have gotten vaccinated already but here's the deal: if incentives help us beat this virus, i believe we should use them." august 2021 on august 1, the cdc reported that there had been a 24% week-over-week increase in the number of first doses administered, especially in states with lower vaccination rates. as of august 2, at least 70% of u.s. adults had received at least one vaccine dose. on august 6, the cdc reported that half of the u.s. population has been fully vaccinated. several major cities announced or approved plans to restrict access to non-essential indoor locations such as cinemas, restaurants, and other entertainment venues, to those who are vaccinated. the fda gave full approval to the pfizer-biontech vaccine on august 23 for patients 16 and older, prompting president biden to encourage those who had been waiting for full approval to get vaccinated. anthony fauci projected that at least 20% of unvaccinated americans "will now step forward and get vaccinated" due to the approval. with the approval, it was also announced that the department of defense was preparing guidance requiring the vaccination of military members for covid-19, with press secretary john kirby stating that this would "ensure the safety of our service members and promote the readiness of our force, not to mention the health and safety of the communities around the country in which we live." october 2021 a poster on a massachusetts train station offering covid-19 vaccines for children 5 through 11 years of age. on october 20, the white house said it had enough pfizer-biontech pediatric vaccine for every child in the country aged 5–11 and that it expected federal health officials to approve the vaccine within weeks, upon which approval the white house planned to begin distributing the doses. dr. fauci said on october 24 that it seemed likely that the fda might approve the vaccine for distribution in early november. on october 29, 2021, the u.s. food and drug administration authorized the emergency use of the pfizer-biontech covid-19 vaccine for children 5 through 11 years of age. vice president harris received her booster shot of the moderna vaccine on october 30. june 2022 on june 18, the cdc recommended vaccines for children as young as 6 months, with a rollout of these vaccines beginning the week after. vaccination mandates main article: covid-19 vaccination mandates in the united states these paragraphs are an excerpt from covid-19 vaccination mandates in the united states. over the course of the covid-19 pandemic, covid-19 vaccine mandates have been enacted by numerous states and municipalities in the united states, and also by private entities. in september 2021, president joe biden announced that the federal government would take steps to mandate covid-19 vaccination for certain entities under the authority of the federal government or federal agencies. most federal mandates thus imposed were either overturned through litigation, or withdrawn by the administration, although a mandate on health care workers has remained in place. a small number of states have gone in the opposite direction, through executive orders or legislation designed to limit vaccination mandates. vaccinations by state and territory number of people who have received at least one dose of a covid-19 vaccine. also, the percentage by state or territory. as of june 3, 2022. state/territory vaccinated % of pop. alabama 3,090,117 63% alaska 512,683 70.1% arizona 5,361,796 73.7% arkansas 2,024,120 67.1% california 32,605,347 82.5% colorado 4,593,119 79.8% connecticut 3,433,007 95% delaware 815,451 83.7% florida 17,138,353 79.8% georgia 6,980,368 65.7% hawaii 1,243,635 87.8% idaho 1,107,825 62% illinois 9,708,189 76.6% indiana 4,157,548 61.8% iowa 2,151,825 68.2% kansas 2,181,870 74.9% kentucky 2,968,456 66.4% louisiana 2,848,292 61.3% maine 1,226,747 91.3% maryland 5,260,427 87% massachusetts 6,829,570 95% michigan 6,717,817 67.3% minnesota 4,253,011 75.4% mississippi 1,782,209 59.9% missouri 4,081,989 66.5% montana 700,374 65.5% nebraska 1,364,224 70.5% nevada 2,332,395 75.7% new hampshire 1,210,143 89% new jersey 8,079,293 91% new mexico 1,853,965 88.4% new york 17,636,744 90.7% north carolina 8,925,348 85.1% north dakota 502,017 65.9% ohio 7,466,872 63.9% oklahoma 2,829,476 71.5% oregon 3,301,377 78.3% pennsylvania 10,953,487 85.6% rhode island 1,054,432 95% south carolina 3,504,526 68.1% south dakota 683,077 77.2% tennessee 4,266,051 62.5% texas 21,403,595 73.8% utah 2,321,276 72.4% vermont 587,103 94.1% virginia 7,361,040 86.2% washington 6,183,446 81.2% west virginia 1,170,466 65.3% wisconsin 4,200,761 72.1% wyoming 337,550 58.3% 50 states 253,302,809 ?% american samoa 45,415 95% district of columbia 722,457 95% guam 154,504 91.7% northern mariana islands 45,593 87.9% puerto rico 3,044,677 95% us virgin islands 70,350 66.2% u.s. territories 4,082,996 ?% united states 257,385,805 ?% marshall islands 36,481 46.9% micronesia 69,545 68% palau 20,439 94.9% compact of free association 126,465 ?% usa + cofa 257,512,270 ?% vaccinations in the u.s. military on august 9, 2021, all servicemembers received a memo explaining that, under a plan endorsed by president biden and by military leadership, covid-19 vaccination would become mandatory within about a month. about a third of active u.s. military service members had already been vaccinated as of late april; and about two-thirds (73% of all service members) had already been vaccinated by the time the memo was sent. the u.s. navy had been the fastest to begin vaccination in early 2021. as of april 22, 2021, considering active military personnel who had received at least one dose, the u.s. navy had the highest percentage at 51%, the marines at 36%, the air force/space force at 34%, and the army at 27%. by late may 2021, at least 58% of active military personnel had received at least one dose of the covid-19 vaccine. as of april 9, 2021, 39% of u.s. marines to whom the military offered the vaccine had refused it. the highest rate of refusal was at camp lejeune in north carolina, where 57% of marines had refused the vaccine. on august 23, 2021, the pfizer-biotech vaccine got its full fda approval, prompting vaccinations to be required for all active duty, reserve, and national guard troops starting august 25. by the time the vaccination requirement order was sent out, only 68% of active-duty troops were fully vaccinated. on september 1, 2021, the u.s. navy mandated vaccination of all active-duty navy sailors and u.s. marines by november 28 and of reservists by december 28. on september 3, 2021, the u.s. air force mandated vaccination of all active-duty airmen and u.s. space force guardians by november 2, while air force reservists had until december 2. on september 14, 2021, the u.s. army mandated vaccination of all active duty soldiers by december 15 and of reservists by june 30, 2022. vaccine certificates the u.s. does not issue a federally mandated covid-19 certificate nor a digital proof that would allow venues to check the vaccine status of participants consistently. cdc vaccine cards that contain personal information including patient numbers and place of vaccinations are accepted in those european countries where american military personnel are stationed. however, those cards are not immediately transferrable to eu digital covid certificates since cdc cards are not digitally validated and do not contain a counterfeit-proof or unique identifier. asian countries have similar health certificate requirements for entering their territories. the lack of a federal system for checking covid-19 status has put the united states in a disadvantage compared to nations in europe and asia. public opinion the kaiser family foundation conducts ongoing polling and analysis in a project called the kff covid-19 vaccine monitor. it considers demographics including age, race, political party, education, and insurance status when examining vaccine hesitancy. a kff study in december 2020 showed that 27% of the general public, and 29% of health careworkers, were hesitant to be vaccinated. in december 2020 a gallup poll found that 63% of americans were willing to receive the covid-19 vaccine. safety concerns about the currently available vaccines are a primary factor in vaccine hesitancy and refusal. most unvaccinated adults are not confident in the safety of the available vaccines and while 63% of parents are confident the vaccines are safe for adults only about half of those who are confident in safety for adults are confident they are safe for ages 12–17 and it is further reduced for even younger age groups. the need for more research for the vaccines is the most stated reason given by parents for not wanting to have their child vaccinated. political leanings are reflected in vaccine hesitancy. early in the pandemic, before vaccines were available, a poll conducted may 20–21, 2020, found that 44% of republicans and 19% of democrats believed a debunked conspiracy theory that bill gates was plotting to use a covid-19 vaccine to inject microchips into the population. months after vaccination began, a monmouth poll conducted april 8–12, 2021, found that two-thirds of democratic voters had already been vaccinated but only one-third of republican voters had done so. a quinnipiac poll conducted on the same dates found that 45% of republicans said they did not plan to be vaccinated. the new york times wrote that the vaccination program was "hitting what appears to be a soft ceiling" as it moved to dealing with the demographic groups where vaccine hesitancy was stronger. in january 2021, approximately one third of the population was concerned the vaccine might be

made mandatory. a frank luntz poll in mid-april 2021 found a rise in vaccine confidence from the previous month, despite the pause of the johnson and johnson vaccine. a later poll by the washington post and abc news found that 86% of self-identified democrats surveyed had received at least one dose, as opposed to 45% of self-identified republicans. in july 2021, the new york times noted that there were two groups of americans who remained hesitant to get the vaccine, the first group being "a mix of people but tend to be disproportionately white, rural, evangelical christian and politically conservative" and the second group being "a broad range of people, but tend to be a more diverse and urban group, including many younger people, black and latino americans, and democrats." at the end of november 2022, "only about 13% of those eligible ha received an updated booster dose."

neotenic complex syndrome neotenic complex syndrome neotenic complex syndrome (ncs) is a syndrome that presents as an extreme form of developmental delay, with the defining characteristic being neoteny of the patient. it was named in 2017 by dr. richard f. walker, who discovered several genes implicated in the syndrome. neotenic complex syndromeother namessyndrome xusual onsetusually detected at or after age 3, but likely present at birthcausespossibly genetic (de novo mutations)frequencyextremely rare: less than 100 confirmed cases worldwide prior to 2015, when whole genome sequencing was used to identify some genes involved in ncs, the condition was labelled "syndrome x" when it was first discovered in brooke greenberg. thereafter, others with the developmental symptoms were sought out in order to find common genetic aberrations that could provide clues as to cause. to date, seven human females have been diagnosed with ncs. in five patients, coding de novo mutations were found in five different genes which fall into similar functional categories of transcription regulation and chromatin modification. genetics in most of the patients analyzed, researchers identified missense de novo mutations in a set of genes. mutations in three of these genes (ddx3x, tlk2 and hdac8) were shared with those found in databases of individuals with developmental delay or autism spectrum disorder. a mutation in one gene (tmem63b) was identified in a large knockout mouse study as likely to result in disease in humans. in two patients, a small (~150 kb) non-coding region of chromosome x was discovered to have a rare haplotype. this region appears to have regulatory functions (histone acetylation and dnase i hypersensitivity) and is in close proximity to several genes (ap1s2, mrx59, mrxsf, mrxs21, mrxs5 and pgs) involved in mental retardation. the fact that ncs has so far only been found in females may be by chance or may be due to the x linkage of some of the genes and regions potentially responsible for ncs, in which the lack of a healthy copy on a second x chromosome could render the disease lethal in males. whether or not these mutations contribute to ncs is unclear. not enough research has been conducted, complicated by the rarity of the syndrome. many genetic differences were noted to be insignificant, and the effects of mutations in some genes are currently beyond scientific understanding. history an 1888 article in the newspaper the diamond drill of crystal falls, michigan, describes a 17-year-old girl from stockeran, vienna, named maria schumann. due to her condition (identified at the time as "microcephaly"), she had never outgrown the mental state or size of an infant, but was of "sound composition". she could not speak or masticate, consumed only liquids and pulpy foods despite having all of her teeth, and often slept for 2 days and 2 nights at a time. prominent cases brooke greenberg

rule of six (viruses) rule of six (viruses) the rule of six is a feature of some paramyxovirus genomes. these rna viruses have genes made from rna and not dna, and their whole genome – that is the number of nucleotides – is always a multiple of six. this is because during their replication, these viruses are dependent on nucleoprotein molecules that each bind to six nucleotides. electron micrograph of the ribonucleoprotein of mumps virus, which has a herring-bone like structure

mecp2 duplication syndrome mecp2 duplication syndrome mecp2 duplication syndrome (m2ds) is a rare disease that is characterized by severe intellectual disability and impaired motor function. it is an x-linked genetic disorder caused by the overexpression of mecp2 protein. mecp2 duplication syndromeother namesx-linked intellectual disability-hypotonia-recurrent infections syndromethis condition is due to mecp2 overexpressionspecialtymedical genetics signs and symptoms symptoms of m2ds include infantile hypotonia and failure to thrive, delayed psychomotor development, impaired speech, abnormal or absent gait, epilepsy, spasticity, gastrointestinal motility problems, recurrent infections, and genitourinary abnormalities. many of those affected by m2ds also fit diagnostic criteria for autism. m2ds can be associated with syndromic facies, namely an abnormally flat back of the head, underdevelopment of the midface, ear anomalies, deep-set eyes, prominent chin, pointed nose, and a flat nasal bridge. cause m2ds is one of the several types of x-linked intellectual disability. the cause of m2ds is a duplication of the mecp2 or methyl cpg binding protein 2 gene located on the x chromosome (xq28). the mecp2 protein plays a pivotal role in regulating brain function. increased levels of mecp2 protein results in abnormal neural function and impaired immune system. mutations in the mecp2 gene are also commonly associated with rett syndrome in females. advances in genetic testing and more widespread use of array comparative genomic hybridization has led to increased diagnosis of mecp2 duplication syndrome. it is thought to represent ~1% of x-linked male mental disability cases. females affected by this condition often do not show symptoms. diagnosis diagnosis is made based on genetic testing. management treatment is supportive and based on symptoms. epidemiology the syndrome primarily affects young males. preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of those affected do not live beyond 25 years of age, with deaths attributed to the impaired immune function. history m2ds was first described in 1999. in a nature article published on november 25, 2015, it was revealed that researchers at the baylor college of medicine, led by dr. huda y. zoghbi, have reversed mecp2 duplication syndrome in adult symptomatic mice using antisense therapy. mice treated with an experimental aso administered through the central nervous system had a reduction of mecp2 protein to normal levels and symptoms of hypoactivity, anxiety, and abnormal social behavior were resolved. additionally, the seizure activity of the mice and abnormal eeg discharges were abolished. initial studies demonstrated that reducing the mecp2 protein levels to the correct amount also normalized the expression of the other genes controlled by the mecp2 protein.

nocardiopsis ganjiahuensis nocardiopsis ganjiahuensis nocardiopsis ganjiahuensis is a bacterium from the genus of nocardiopsis which has been isolated from soil from the ganjiahu natural reserve from the xinjiang province in china. nocardiopsis ganjiahuensis scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: streptosporangiales family: nocardiopsaceae genus: nocardiopsis species: n. ganjiahuensiszhang et al. 2008 binomial name nocardiopsis ganjiahuensis type strain cgmcc 4.3500, dsm 45031, hbum 20038, jcm 15475

shoulder pad sign shoulder pad sign the shoulder pad sign is an enlargement of the anterior shoulder due to amyloid deposition in periarticular soft tissue. this type of infiltration is not common, but it is pathognomonic for al amyloidosis. shoulder pad signshoulder pad signdifferential diagnosisal amyloidosis analysis of the amyloid protein has demonstrated that it has a kappa iii ig light chain structure. the variable region of kappa iii amyloid proteins may show an increased likelihood of depositing in soft tissue.

raghib syndrome raghib syndrome raghib syndrome is rare a congenital heart defect where the left superior vena cava (lsvc) is draining into the left atrium in addition to an absent coronary sinus and an atrial septal defect. this can be considered a dangerous heart condition because it puts the individual at a high risk of stroke. other defects that are often associated with raghib syndrome can include ventricular septal defects, enlargement of the tricuspid annulus, and pulmonary stenosis. while this is considered an extremely rare developmental complex, cases regarding a persistent left superior vena cava (plsvc) are relatively common among congenital heart defects. it is also important to note that the plsvc often drains into the right atrium, and only drains into the left atrium in approximately 10 to 20% of individuals with the defect. in an individual with no underlying heart condition, the superior vena cava delivers blood returning from the body to the right atrium. due to oxygen being used by various biological processes throughout the body, this blood has extremely low blood oxygenation levels. therefore, the right side of the heart pumps this blood to the lungs where gas exchange takes place in the capillaries. the oxygenated blood is then transported back to the left side of the heart through pulmonary veins. the left atrium and left ventricle work to push the now oxygen saturated blood up through the aorta and out to the body. as stated earlier, individuals with raghib syndrome experience drainage from the left superior vena cava into the left atrium. this means that the deoxygenated blood returning from the body is directly bypassing the lungs and entering the left atrium where it will be pumped back into the body causing cyanosis. the result of this can have major implications on several biological processes, often requiring surgical intervention. the coronary sinus is a vein continuing off of the great cardiac vein. it collects blood from the ventricular veins of the heart muscle during ventricle contraction and moves this blood into the right atrium. essentially, this coronary sinus takes de-oxygenated blood from veins in the heart muscle (epicardial ventricular veins) and delivers it to the right side of the heart so it can be transported to the lungs and oxygenated again. it is extremely rare for an individual to be lacking this component of the heart. lastly, a common aspect of raghib syndrome is an atrial septal defect. this is when there is a hole in the septum dividing the right and left atriums of the heart. the size of this hole may vary significantly from individual to individual some may not even notice the symptoms of this defect until they are well into adulthood, if at all. the main concern with an atrial septal defect, is it can cause the right side of the heart to become overworked. this is because the amount of blood being pumped to the lungs increases significantly as blood from the left atrium leaks back into the right atrium. thus leading to damaged blood vessels, increased blood pressure, and can even increase the right side of the heart. causes raghib syndrome being classified as a congenital heart defect, means that this defect was present at birth. the anterior and posterior cardinal veins are a part of the embryonic venous system. during the eighth week of fetal development these cardinal veins will slowly shrink and disappear into other structures. the left anterior cardinal vein eventually transforms into the ligament of marshall. if this vein fails to disappear, the persistent left superior vena cava will form. this anomaly is present in between 0.3% and 0.5% of the population and roughly 2.1% to 4.3% of those with congenital heart disease. usually babies who experience the persistence of a left superior vena cava display other heart anomalies as well. in raghib syndrome these additional defects include an absent coronary sinus along with an atrial septal defect. the persistent left super vena cava can interfere with rotation of the sinoatrial region, which thus causes the right and left cardinal veins of the heart to lie at the same level preventing the formation of a coronary sinus. signs and symptoms symptoms of raghib syndrome include: heart palpitation bluish discoloration of the skin (cyanosis) left-handed clumsiness hypertension facial edema (facial swelling) swelling of extremities difficulty with fine motor tasks slurred speech left-sided facial numbness fatigue irregular heartbeats (arrhythmias) the bluish discoloration of the skin, otherwise characterized as cyanosis, is a result of inadequate oxygenation of red blood cells. this presents mainly in the skin, nails, lips, or surrounding the eyes of individuals. this lack of oxygenation in the bloodstream can also be the cause of symptoms regarding issues with fine motor tasks or cognitive issues. other symptoms of raghib syndrome are usually classified as a cryptogenic stroke, otherwise known a stroke resulting from an unknown origin. these symptoms can include slurred speech, left-sided facial numbness, and left-handed clumsiness. while some of the symptoms of raghib syndrome can be intense, other individuals might be asymptomatic and unaware they have this congenital heart defect. diagnosis can often be difficult since anomalies may not be noticed until a postmortem evaluation is done. thus, in some instances it may be considered a benign anomaly. impact of cyanosis on a cellular level essentially, the main symptoms making this disease dangerous are a result of a lack of oxygen reaching vital tissues, muscles, and organs. cyanosis is typically classified as having 85% or less oxygen saturation in your bloodstream. typically your blood oxygen saturation levels should fall around 95% or higher. oxygen is used in a number of biological processes throughout your body. perhaps the most vital of these processes is cellular respiration. cells take molecules of glucose and convert them to chemical energy in the form of adenosine triphosphate (atp). during glycolysis, a single molecule of glucose is broken down into two molecules of pyruvate. pyruvate is then converted into to acetyl-coenzyme a (acetyl-coa). the citric acid cycle then takes acetyl-coa and through a series of reactions generates molecules of nadh and fadh2 that are used in the electron transport chain. the electron transport chain uses nadh and fadh2 to form a proton gradient in the mitochondria that will be used generate atp. oxygen comes into play in complex iv of the electron transport chain. oxygen is considered the final electron acceptor in this process. essentially, complex iv accepts electrons from cytochrome c, one at a time, and then donates them to oxygen in order to form water. during this process, two hydrogen protons are transported into the inter-membrane space of the mitochondria. therefore, oxygen is a vital part of generating energy for cells. diagnosis in some cases, raghib syndrome is not diagnosed until there is a postmortem evaluation of an individual. however, if symptoms are present or an individual has an evaluation of their heart conducted this can lead to early detection. diagnosis typically involves the use of cardiac magnetic resonance imaging (cmri). magnetic resonance imagining is a medical imagine technique where the use of a magnetic field and computer-generated radio waves are able to construct 3d images of organs or tissues in your body. often times this is accompanied by a cardiac computed tomography (cct) scan which creates 3d images of the heart and its blood vessels. unlike the cmri, this is done by directing x-rays at various angles in order to form a detailed and high-resolution scan of the heart. thus, leading to the diagnosis of issues regarding the structure of the heart, valves, arteries, aorta, veins, and more. a cct scan does involve the intravenous injection of contrast media that is used to not only define tissues, but differentiate between them. the use of an mri and a cct scan can also aid doctors in determining a surgical intervention plan. another possible way to diagnose this heart condition is using an electrocardiogram (ecg or ekg). an individual will have electrodes placed on their chest that measure the electrical signal from the heart as it beats. there are several things tracked during an ekg. first is the "p wave" which takes place as the electrical impulse travels to the left and right atria causing them to contract and pump blood into the ventricles. these ventricles then make the "qrs" complex as they contract and push blood up and out of the heart muscle. the heart then fully relaxes and the "t wave" is the re-polarization of the ventricles. ekgs of individuals with raghib syndrome could show t wave inversions in leads v2-v4, and left ventricular hypertrophy. an echocardiogram, on the other hand, uses sound waves in order to create 3d images of the heart while it is in motion. this allows doctors to visualize how well blood is being pumped throughout the heart. cardiac catheterization is another way to understand the blood flow through the heart. during cardiac catheterization a long thin tube, otherwise known as a catheter, is inserted into a blood vessel to examine the heart valves, take blood or heart samples, and even can place dye into the bloodstream for better visualization. this catheter can be placed into a blood vessel in the groin, upper thigh, arm, or neck. lastly, patients may also display a significant reduction in arterial blood oxygen saturation. but depending on the size and impact of these heart defects, certain patients with raghib syndrome could maintain oxygen saturation levels of over 90%. treatment usually, treatment involves surgical intervention in order to repair the persistent left superior vena cava (plsvc) from draining into the left atrium. several surgical options can be used based on the individual. the main goal of these surgical interventions is to re-establish intracardiac flow of blood through the heart. atrial patches can be applied to areas of concern such as the roof of the left atrium or where the coronary sinus should be. this helps to form a tunnel aiding blood flow. often a surgical correction can be done to divert blood flow from the plsvc into the right atrium, rather than the left atrium. some sources indicate this is the main surgical solution. this can be done by attaching the pslvc directly to the right atrium using a graft, attaching the pslvc to the left pulmonary artery with an intra-atrial baffle, or performing a litigation of the pslvc in general. however, surgically attaching the plsvc to the left pulmonary artery can increase the risk of thrombosis. some sources indicated that re-roofing the coronary sinus is important during this procedure to yield optimum results. another source indicates simple monitoring of an individual and placing them on medications can be used in less extreme cases. it is important to seek medical advice from a professional, as symptoms and degrees of this defect can very immensely individual to individual. case studies in one case study a 40-year-old female was given a pericardial patch to close the atrial septal defect and then anastomosed the pslvc directly to the left pulmonary artery. thus, getting rid of the leakage of blood to the left atrium and ensuring the blood from the pslvc is directed into the right side of the heart and pumped to the lungs. a follow-up several years later indicated the surgery was successful and she had no symptoms of a cryptogenic stroke. another case study was done with an 18-month-old infant diagnosed with raghib syndrome after an mri was done on his heart. an extracardiac intervention method was applied where the plsvc was directly connected to the right atrial appendage. this was seen as the best intervention method since it decreased the risk of obstructing pulmonary vein blood flow, reduced tension on the left atrium, and hopefully prevented future arrhythmias. a 31-year-old female showing left-handed clumsiness, hypertension, and stroke-like symptoms such as facial numbness and slurred speech was brought in for diagnosis. an in-depth analysis on her brain and heart showed signs of raghib syndrome. unlike other individuals here, she was discharged with several medications (aspirin and metoprolol), as well as a holter monitor to keep track of her symptoms. lastly, a 25-year-old female had experienced several years of cyanosis and heart palpitations. the individual underwent surgical intervention after being diagnose with raghib syndrome using a chest x-ray and ecg. during surgery doctors found her coronary sinus was

completely unroofed and the plsvc was draining directly into the left atrium. surgeons reroofed the coronary sinus, reconstructed the atrial septum to prevent drainage, and redirected the plsvc to the right atrium. prognosis with surgical intervention, many individuals suffering from this defect are able to go on and lead fully functional lives. issues may arise if the heart condition goes undiagnosed, thus putting an individual at an increased risk of stroke. however, it could remain a benign anomaly in other individuals and never result in symptoms or a diagnosis. related syndromes persistent left superior vena cava (plsvc) atrial septal defect (asd) ventricular septal defect (vsd) atrioventricular septal defect (avsd) patent ductus arteriosus (pda) acyanotic heart defect

vinylbital vinylbital vinylbital, also known as butylvinal, is a sedative hypnotic drug which is a barbiturate derivative. it was developed by aktiebolaget pharmacia in the 1950s. vinylbitalclinical dataroutes ofadministrationoralatc coden05ca08 (who) legal statuslegal status ca: schedule iv de: anlage ii (authorized trade only, not prescriptible) us: schedule iv pharmacokinetic datametabolismhepaticexcretionrenalidentifiers iupac name 5-(1-methylbutyl)-5-vinylpyrimidine-2,4,6(1h,3h,5h)-trione cas number2430-49-1 npubchem cid72135chemspider65109 yunii3w58itx06qkeggd07321 yecha infocard100.017.633 chemical and physical dataformulac11h16n2o3molar mass224.260 g·mol−13d model (jsmol)interactive image smiles o=c1nc(=o)nc(=o)c1(\c=c)c(c)ccc inchi inchi=1s/c11h16n2o3/c1-4-6-7(3)11(5-2)8(14)12-10(16)13-9(11)15/h5,7h,2,4,6h2,1,3h3,(h2,12,13,14,15,16) ykey:kgkjzekqjqqotd-uhfffaoysa-n y ny (what is this?) (verify)

musée des lunettes et lorgnettes pierre marly musée des lunettes et lorgnettes pierre marly the musée de la lunette is a museum of eyeglasses located in morez (jura - franche-comté), france. it was formerly located in paris, with the name musée pierre marly - lunettes et lorgnettes. the eyewear museummusée de la lunettelocationplace jean jaurès, 39400 morez, francecoordinatestypehistory of eyeglasses and lensesfounderpierre marlywebsitehttp://www.musee-lunette.fr/en the museum was created by pierre marly, optician to crowned heads, public figures and celebrities. it contains almost 3,000 objects, ranging from spectacles dating from the 13th century to wooden inuit snow goggles, with a permanent exhibition of lorgnettes, glasses, telescopes, and binoculars of all shapes and sizes. items of interest include glasses made for cats and dogs, maria callas' contact lens, and glasses belonging to princess victoire of france (daughter of louis xv), the dalai lama, marlene dietrich, sammy davis, jr., elton john, and lorgnettes belonging to sarah bernhardt.

harvard step test harvard step test the harvard step test, in scientific literature sometimes referred to as the brouha test, is a type of cardiac stress test for detecting and diagnosing cardiovascular disease. it is also a good measurement of fitness and a person's ability to recover after a strenuous exercise by checking the recovery rate. the test was developed by lucien brouha and his associates in 1942. harvard step testpurposecardiac stress test procedure the test subject repeatedly steps onto and off of a platform in a cycle of two seconds. the height of the platform is 20 inches or 51 centimetres for men and 16 inches or 41 centimetres for women. the rate of 30 steps per minute must be sustained for five minutes or until exhaustion. to ensure the right speed, a metronome is used. exhaustion is the point at which the subject cannot maintain the stepping rate for 15 seconds. the subject immediately sits down on completion of the test, and the heartbeats are counted for 1 to 1.5, 2 to 2.5, and 3 to 3.5 minutes. the results are written down as time until exhaustion in seconds ( t e ) and total heartbeats counted ( h b ). it is plotted into a simple fitness index equation: t e ∗ 100 h b ∗ 2 *100}*2}}} the outcome of the equation is rated as follows: ratingfitness index excellent> 96 good83–96 average68–82 low average54–67 poor< 54 modified versions the test was developed at harvard university in 1942. several modified versions of the original harvard step test exist; examples include the tecumseh step test and the kasch step test. another modified version, the sharkey step test, was developed in the 1970s for use by the united states forest service at the university of montana in missoula.

microstomia microstomia microstomia is a small mouth (micro- a combining form meaning small + -stomia a combining form meaning mouth = (abnormally) "small mouth" in greek.) microstomiaacquired microstomia from congenital syphilisspecialtymedical genetics congenital it is a feature of many craniofacial syndromes, including freeman–sheldon syndrome and sheldon-hall syndromes (or distal arthrogryposis multiplex congenita). it may present with whistling-face feature, as well, as in freeman-sheldon syndrome. in this syndrome, it impairs alimentation and may require repeated oral surgeries (called commissurotomy) to improve function. acquired microstomia can occur as a result of scarring due to many conditions. it is seen as complication of facial burns. it can also be a feature of systemic scleroderma.

adequate stimulus adequate stimulus the adequate stimulus is a property of a sensory receptor that determines the type of energy to which a sensory receptor responds with the initiation of sensory transduction. sensory receptor are specialized to respond to certain types of stimuli. the adequate stimulus is the amount and type of energy required to stimulate a specific sensory organ. many of the sensory stimuli are categorized by the mechanics by which they are able to function and their purpose. sensory receptors that are present within the body typically are made to respond to a single stimulus. sensory receptors are present all throughout the body, and they take a certain amount of a stimulus to trigger these receptors. the use of these sensory receptors allows the brain to interpret the signals to the body which allow a person to respond to the stimulus if the stimulus reaches a minimum threshold to signal the brain. the sensory receptors will activate the sensory transduction system which will in turn send an electrical or chemical stimulus to a cell, and the cell will then respond with electrical signals to the brain which were produced from action potentials. the minuscule signals, which result from the stimuli, enter the cells must be amplified and turned into an sufficient signal that will be sent to the brain. a sensory receptor's adequate stimulus is determined by the signal transduction mechanisms and ion channels incorporated in the sensory receptor's plasma membrane. adequate stimulus are often used in relation with sensory thresholds and absolute thresholds to describe the smallest amount of a stimulus needed to activate a feeling within the sensory organ. categorizations of receptors they are categorized through the stimuli to which they respond. adequate stimulus are also often categorized based on their purpose and locations within the body. the following are the categorizations of receptors within the body: visual – these are found in the visual organs of species and are responsive to stimuli such as light and often consist of light sensitive molecules that enable certain species to have the ability to see the world in with they live. olfaction – these types of receptor sense are activated in order to sense the external molecules that enter the nasal organ and attach to the receptors which will interpret the stimuli and send the signal containing information about the stimuli to the brain. auditory – these types of receptors are often found within the organs used to hear and are responsive to vibrations within the surrounding areas, and they often allow their owners to understand information about sound waves traveling through the aid. vestibular – these types of receptors are usually found within organs used to hear, and they aid in the detection of movement that surrounds the creature using it. gustatory – these sensory receptors are present within the mouth and are responsive to the molecular stimuli that enter the mouth. the receptors in the mouth typically fall into two of the following categories: receptors that are responsive to specific chemicals and receptors that are responsive to particles such as hydrogen ions, which are charged. tactile – these types of receptors are normally present within the skin and are able to respond to stimulation such as heat, pressure, and movement classes there are several different types of stimuli to which adequate stimuli respond. the following are examples of stimuli to which receptors may: light – when the adequate stimulus of a sensory receptor is light, the sensory receptors contain pigment molecules whose shape is transformed by light, and the changes in these molecules activate ion channels which initiate sensory transduction. sound – when the adequate stimulus of a sensory receptor is sound, the sensory receptors are hair cells (mechanoreceptors). these hair cells contain stereocilia, which when bent, trigger the opening of ion channels. thus hair cells transform the pressure waves of the sound into receptor potentials to initiate sensory transduction. sensory receptors sensory receptors are the ends of nerves within the body that respond to stimuli. there are many different types of sensory receptors that each respond to stimuli that they are uniquely fitted to res types of sensory receptors include the following: nociceptor – these are stimulus that are responsive to the stimuli that signal potential damage to the body. photoreceptors – these are receptors that are responsive to light that enters the eye and produces the visual stimuli that many animals use to function. mechanoreceptors – these are receptors that are responsive to physical stimulation such as movement, vibration, and stress. thermoreceptors – these are types of receptors that are present within the skin and monitor any changes in the skins temperature classic examples of absolute threshold in 1962, eugene galanter, a psychologist, tested stimuli till people were able to feel them approximately 50% of the time, then used the following as examples of absolute threshold: visual – on a clear, dark night a candle can be seen from approximately 30 miles away. olfactory – a person can smell a single drop of perfume after it has diffused into 3 rooms. auditory – in a silent area, a person can hear a watch tick from approximately 20 feet. vestibular – a person is able to tell of a tilt that when on a clock face is seen to be less than half a minute. gustatory – a person can taste a single teaspoon of sugar which is diluted in 2 gallons of water. tactile – a person can feel a fly's wing dropped from 3 feet above them falling onto their cheek. through these conditions, galanter was able to show that human's sensory organs are often more sensitive than originally thought. notes frings, stephan (2012-01-01). "sensory cells and sensory organs". in barth, friedrich g.; giampieri-deutsch, patrizia; klein, hans-dieter (eds.). sensory perception. springer vienna. pp. 5–21. doi:10.1007/978-3-211-99751-2_1. isbn 9783211997505. frings, stephan (2012-01-01). "sensory cells and sensory organs". in barth, friedrich g.; giampieri-deutsch, patrizia; klein, hans-dieter (eds.). sensory perception. springer vienna. pp. 5–21. doi:10.1007/978-3-211-99751-2_1. isbn 9783211997505. frings, stephan (2012-01-01). "sensory cells and sensory organs". in barth, friedrich g.; giampieri-deutsch, patrizia; klein, hans-dieter (eds.). sensory perception. springer vienna. pp. 5–21. doi:10.1007/978-3-211-99751-2_1. isbn 9783211997505. wolfe, jermy m.; kluender, keith r.; levi, dennis m. (2015). sensation and perception (fourth ed.). sunderland, massachusetts u.s.a.: sinauer associates, inc. pp. 427–429. isbn 978-1605352114. frings, stephan (2012-01-01). "sensory cells and sensory organs". in barth, friedrich g.; giampieri-deutsch, patrizia; klein, hans-dieter (eds.). sensory perception. springer vienna. pp. 10–11. doi:10.1007/978-3-211-99751-2_1. isbn 9783211997505. wolfe, jermy m.; kluender, keith r.; levi, dennis m. (2015). sensation and perception (fourth ed.). sunderland, massachusetts u.s.a.: sinauer associates, inc. p. 471. isbn 978-1605352114. wolfe, jermy m.; kluender, keith r.; levi, dennis m. (2015). sensation and perception (fourth ed.). sunderland, massachusetts u.s.a.: sinauer associates, inc. p. 392. isbn 978-1605352114. walker, richard (2008). firefly guide to the human body (rev. ed.). buffalo, ny: firefly books. p. 46. isbn 978-1552978795. frings, stephan (2012-01-01). "sensory cells and sensory organs". in barth, friedrich g.; giampieri-deutsch, patrizia; klein, hans-dieter (eds.). sensory perception. springer vienna. pp. 5–21. doi:10.1007/978-3-211-99751-2_1. isbn 9783211997505. frings, stephan (2012-01-01). "sensory cells and sensory organs". in barth, friedrich g.; giampieri-deutsch, patrizia; klein, hans-dieter (eds.). sensory perception. springer vienna. pp. 5–21. doi:10.1007/978-3-211-99751-2_1. isbn 9783211997505. walker, richard (2008). firefly guide to the human body (rev. ed.). buffalo, ny: firefly books. p. 47. isbn 978-1552978795. wolfe, jermy m.; kluender, keith r.; levi, dennis m. (2015). sensation and perception (fourth ed.). sunderland, massachusetts u.s.a.: sinauer associates, inc. p. 394. isbn 978-1605352114. hockenbury, don h; hockenbury, sandra e. (2010). psychology (5th ed.). new york, ny: worth publishers. pp. 92. isbn 978-1429201438. wolfe, jermy m.; kluender, keith r.; levi, dennis m. (2015). sensation and perception (fourth ed.). sunderland, massachusetts u.s.a.: sinauer associates, inc. p. 7. isbn 978-1605352114.

tumor alopecia tumor alopecia tumor alopecia is the hair loss in the immediate vicinity of either benign or malignant tumors of the scalp.: 762

meningohydroencephalocoele meningohydroencephalocoele meningohydroencephalocoele (ame: meningohydroencephalocele) is a form of meningocele (ame) - a developmental abnormality of the central nervous system. meningohydroencephalocoelespecialtyneurology like meningocoele, meningohydroencephalocoele is caused by defects in bone ossification; in particular, the intramembranous ossification related to the closure of infantile fontanelles. it refers to the protrusion of the meninges between the un-fused bones, to lie subcutaneously. meningocoele - refers to herniation of meninges. meningoencephalocoele refers to the condition if brain tissue is included with the meninges in the herniation. meningohydroencephalocoele refers to the condition including meninges, brain tissue and part of the ventricular system in the herniation. encephalocoele defects occur in approximately 1 in 2000 live births.

history of chronic fatigue syndrome history of chronic fatigue syndrome the history of chronic fatigue syndrome (cfs; also known as myalgic encephalomyelitis (me) and by several other names) is thought to date back to the 19th century and before. royal free hospital in london, where myalgic encephalomyelitis came to prominent attention in 1955 timeline several descriptions of illness resembling those of chronic fatigue syndrome have been reported for at least 200 years. in the 19th century, neurologist george miller beard popularised the concept of neurasthenia, with symptoms including fatigue, anxiety, headache, impotence, neuralgia and depression. this concept remained popular well into the 20th century, eventually coming to be seen as a behavioural rather than physical condition, with a diagnosis that excluded postviral syndromes. neurasthenia has largely been abandoned as a medical diagnosis. the icd-10 system of the world health organization categorized neurasthenia under (f48 other neurotic disorders) which specifically excluded chronic fatigue syndrome. the current version of icd, icd-11, does not include neurasthenia and “deprecates” its use. a united states public health service (usphs) official, alexander gilliam, described an illness that resembled poliomyelitis, after interviewing patients and reviewing records of one of several clusters which had occurred in los angeles, during 1934. the los angeles county hospital outbreak included all or most of its nurses and doctors. gilliam called the outbreak "atypical poliomyelitis" and described the symptoms as: rapid muscle weakness, vasomotor instability, clonic twitches and cramps, ataxia, severe pain (usually aggravated by exercise), neck and back stiffness, menstrual disturbance and dominant sensory involvement. there was a cluster of "encephalitis" cases in 1936, at a convent in wisconsin, amongst novices and convent candidates. the following year two towns in switzerland had outbreaks of "abortive poliomyelitis" , and 73 swiss soldiers were given the same diagnosis in 1939. outbreaks in iceland were called "akureyri disease" or "simulating poliomyelitis" and were later called "iceland disease." 800 people in adelaide, australia became ill during 1949–1951 with a disease "resembling poliomyelitis." two smaller clusters in the united states during 1950 were diagnosed as "epidemic neuromyasthenia" and "resembling iceland disease simulating acute anterior poliomyelitis." additional outbreaks of poliomyelitis-like "mystery diseases" occurred from the 1950s through the 1980s, in denmark, the united states, south africa, and australia, among others. several outbreaks of a polio-resembling illness occurred in britain in the 1950s. a 1955 outbreak at the royal free hospital group was later called "royal free disease" or "benign myalgic encephalomyelitis". after the royal free hospital outbreak, a disorder with similar symptoms was found among the general population and the epidemic form came to be considered the exception. pathology findings, both in monkeys and in rare human casualties, led to the conclusion that the disorder was caused by inflammation of the brain and the spinal cord, particularly the afferent nerve roots, perhaps with neuroimmune etiology. in the 1960s and 1970s, chronic fatigue symptoms were often attributed to chronic brucellosis, but typically people were seen as having psychiatric disorders, in particular depression. epidemic cases of benign myalgic encephalomyelitis were called mass hysteria by psychiatrists mcevedy and beard in 1970, provoking criticism in letters to the editor of the british medical journal by outbreak researchers, attending physicians, and physicians who fell ill. the psychiatrists were faulted for not adequately investigating the patients they described, and their conclusions have been refuted. in 1978 a symposium held at the royal society of medicine (rsm) concluded that "epidemic myalgic encephalomyelitis" was a distinct disease entity with a clear organic basis. the illness gained national attention in the united states when the popular magazine hippocrates ran a cover story of an epidemic at lake tahoe, nevada, in the mid-1980s. the designation chronic epstein-barr virus was in use in the u.s., but the magazine used the term "raggedy ann syndrome" to note the fatigue and loss of muscle power patients felt. researchers investigating the lake tahoe cluster did not find evidence that ebv was involved, and they proposed the name "chronic fatigue syndrome", describing the main symptom of the illness. they published the first working case definition for cfs in 1988. research increased considerably, and more so after the criteria were relaxed in 1994. in 1990, researchers presented evidence they found dna sequences very similar to the human htlv-ii retrovirus in some cfs patients, at a conference in kyoto, japan. their study was later published in the proceedings of the national academy of sciences. a reporter on prime time live stated the announcement made headlines all over the world. the cdc first ignored their findings, then later conducted a study and published a paper that refuted the hypothesis. in the united kingdom, the chief medical officer kenneth calman requested a report from the medical royal colleges in 1996. this led to the publication of a joint report in which the term "chronic fatigue syndrome" was found to be most representative. this was followed in 2002 by a further report by the new cmo, liam donaldson. the u.s. centers for disease control & prevention (cdc) recognize cfs as a serious illness, and launched a campaign in june 2006 to raise public and medical awareness about it. a 2009 study published in the journal science reported an association between a retrovirus xenotropic murine leukemia virus-related virus (xmrv) and cfs. the editors of science subsequently attached an "editorial expression of concern" to the report, to the effect that the validity of the study "is now seriously in question". and in september 2011, the authors published a "partial retraction" of their 2009 findings; this was followed by a full retraction by the magazine's editor in chief, after the authors failed to agree on a full retraction statement. also in september 2011, the blood xmrv scientific research working group published a report, which concluded "that currently available xmrv/p-mlv assays, including the assays employed by the three participating laboratories that previously reported positive results on samples from cfs patients and controls (2, 4), cannot reproducibly detect direct virus markers (rna, dna, or culture) or specific antibodies in blood samples from subjects previously characterized as xmrv/p-mlv positive (all but one with a diagnosis of cfs) or healthy blood donors." in december 2011, the proceedings of the national academy of sciences published a similar retraction for an august 2010 paper. some members of the patient community, who had viewed the xmrv findings as a source of hope for a possible cure, initially reacted negatively when the papers were called into question. one uk researcher reported verbal abuse after publishing an early paper indicating that the xmrv studies were flawed. international classifications the world health organization's (who) international classification of diseases (icd), mandates the international classifications of diseases to allow comparison of health and health fields across countries and throughout the world. not all terms appear in the tabular list (volume 1), and many more terms are listed in the alphabetic index (volume 3) of the icd. icd-8 since its introduction into the eighth edition of the who icd-8 in 1969 (code 323), (benign) myalgic encephalomyelitis has been classified as a disease of the central nervous system. icd-9 the term "benign myalgic encephalomyelitis" appears in the 1975 icd-9 alphabetic index, and references code 323.9, encephalitis of unspecified cause. the code 323.9 did not include reference to postviral syndrome. the term “postviral syndrome” was classified to code 780.7, malaise and fatigue, in chapter 16, symptoms, signs and ill-defined conditions. the name chronic fatigue syndrome has been attributed to the us centers for disease control 1988 research case definition for the illness, "chronic fatigue syndrome: a working case definition". chronic fatigue syndrome (cfs) was added to icd-9 after 1988 and listed under code 780.71, symptoms signs and ill-defined conditions. icd-9-cm since 1979 the u.s. has used a clinical modification of who's icd 9th revision (icd-9-cm), and me is under index: "encephalomyelitis (chronic) (granulomatous) (hemorrhagic necrotizing, acute) (myalgic, benign) (see also encephalitis) 323.9." for cfs, a modification to the alphabetic index was made, effective on october 1, 1991, to direct users to code 780.7, malaise and fatigue, the same code used to identify cases of postviral syndrome. in 1998, a new five-digit code included 780.71, chronic fatigue syndrome, consistent with the who version of icd-9. chronic fatigue syndrome is classified in tabular list: "symptoms, signs and ill-defined conditions," under the sub-heading of "general symptoms". icd-10 cfs is not included as a coded term in the 1992 icd-10, who created a new category g93, other disorders of brain, in chapter vi, diseases of the nervous system, and created a new code g93.3, post-viral fatigue syndrome (pvfs), a condition which was previously in the symptom chapter of icd-9. who also moved benign myalgic encephalomyelitis to g93.3, subordinate to pvfs. the alphabetic index contains other terms, such as chronic fatigue syndrome, to which who assigned the same code. icd-10-cm the 2010 version of the icd-10-cm separates cfs and postviral fatigue syndrome into mutually exclusive categories. "chronic fatigue, unspecified | chronic fatigue syndrome not otherwise specified" appears in chapter xviii under r53.82. "postviral fatigue syndrome | benign myalgic encephalomyelitis" appears in chapter vi under g93.3. the chronic fatigue syndrome advisory committee (cfsac) had previously recommended cfs to be placed under the same neurological code as me and pvfs, g93.3. the 2023 update to the icd-10-cm added a specific code for me/cfs, g93.32, giving cfs a code separate from unspecified chronic fatigue.

agromyces binzhouensis agromyces binzhouensis agromyces binzhouensis is a gram-positive, heterotrophic, non-spore-forming and rod-shaped bacterium from the genus of agromyces which has been isolated from soil from the yellow river delta from binzhou in china. agromyces binzhouensis scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: micrococcales family: microbacteriaceae genus: agromyces species: a. binzhouensis binomial name agromyces binzhouensischen et al. 2016

primary urethral groove primary urethral groove the primary urethral groove or urethral groove is a temporary linear indentation on the underside (ventral side) of the male penis during embryonic development. primary urethral groovedetailsprecursorurogenital foldsgives rise tourethraidentifierslatinsulcus urethralis primariusteurethral groove_by_e5.6.4.2.1.7.3 e5.6.4.2.1.7.3 anatomical terminology in humans, it typically appears around 8 weeks of gestation and becomes closed into a normal male urethra by the 12th week. clinical significance failure of complete closure can be associated with hypospadias.

polish medical association polish medical association polish medical association (polish: polskie towarzystwo lekarskie) is a scientific society created in 1951, bringing together physicians of various specialties. the society refers to the tradition of medical societies in vilnius (towarzystwo lekarskie wileńskie, from 1805) and warsaw (towarzystwo lekarskie warszawskie, from 1820). polish medical associationformation1951headquarterswarsaw, polandlocationul. aleje ujazdowskie 22, 00-478 warszawamembership 25,000websitewww.ptl.medserwis.pl the president of polish medical association is professor waldemar kostewicz. in the structure of the society there are branches, circles and sections and the main seat is in warsaw. polish medical association publishes three scientific journals "przegląd lekarski", "wiadomości lekarskie" and "polski merkuriusz lekarski" and organizes several cyclic conferences, e.g. the world congresses of medical polonia and the international conference "human ecology".

pseudophenmetrazine pseudophenmetrazine pseudophenmetrazine is a psychostimulant compound of the morpholine class. it is the n-demethylated and cis-configured analogue of phendimetrazine as well as the cis-configured stereoisomer of phenmetrazine. in addition, along with phenmetrazine, it is believed to be one of the active metabolites of phendimetrazine, which itself is inactive and behaves merely as a prodrug. relative to phenmetrazine, pseudophenmetrazine is of fairly low potency, acting as a modest releasing agent of norepinephrine (ec50 = 514 nm), while its (+)-enantiomer is a weak releaser of dopamine (ec50 = 1,457 nm) whereas its (−)-enantiomer is a weak reuptake inhibitor of dopamine (ki = 2,691 nm); together as a racemic mixture with the two enantiomers combined, pseudophenmetrazine behaves overall more as a dopamine reuptake inhibitor (ki = 2,630 nm), possibly due to the (+)-enantiomer blocking the uptake of the (−)-enantiomer into dopaminergic neurons and thus preventing it from inducing dopamine release. neither enantiomer has any significant effect on serotonin reuptake or release (both ki = >10,000 nm and ec50 = >10,000 nm, respectively). pseudophenmetrazineclinical dataatc codenoneidentifiers iupac name (±)-cis-3-methyl-2-phenylmorpholineor(±)-(2rs,3sr)-3-methyl-2-phenylmorpholine cas number13580-23-9 yunii5bxe22z857chemical and physical dataformulac11h15nomolar mass177.247 g·mol−1

degeneration (medicine) degeneration (medicine) degeneration is deterioration in the medical sense. generally, it is the change from a higher to a lower form. more specifically, it is the change of tissue to a lower or less functionally active form. true degeneration: when there is actual chemical change of the tissue itself. infiltration: when the change consists of the deposit of abnormal matter in the tissues degenerative disease

pentasomy x pentasomy x pentasomy x, also known as 49,xxxxx, is a chromosomal disorder in which a female has five, rather than two, copies of the x chromosome. pentasomy x is associated with short stature, intellectual disability, characteristic facial features, heart defects, skeletal anomalies, and pubertal and reproductive abnormalities. the condition is exceptionally rare, with an estimated prevalence between 1 in 85,000 and 1 in 250,000. pentasomy xother names49,xxxxxkaryotype of pentasomy xspecialtymedical genetics symptomsintellectual disability, facial dysmorphisms, heart defectsusual onsetconceptiondurationlifelongcausesnondisjunctiondiagnostic methodkaryotype the condition has a large variety of symptoms, and it is difficult to paint a conclusive portrait of its phenotypes. though significant disability is characteristic, there are so few diagnosed cases that confident conclusions about the presentation and prognosis remain impossible. pentasomy x may be mistaken for more common chromosomal disorders, such as down syndrome or turner syndrome, before a conclusive diagnosis is reached. pentasomy x is not inherited, but rather occurs via nondisjunction, a random event in gamete development. in rare cases, it may be related to a parent's chromosomal mosaicism. the karyotype observed in pentasomy x is formally known as 49,xxxxx, which represents the 49 chromosomes observed in the disorder as compared to the 46 in normal human development. presentation the major clinical features of pentasomy x are intellectual disability, short stature, facial and musculoskeletal abnormalities, and congenital heart defects. although one recorded case has been of low average intelligence, all other known cases have been intellectually disabled, with an average iq of 50. the overall portrait is one of moderate intellectual disability, defined by an adult cognitive capacity similar to that of a six- to eight-year-old and the ability to acquire basic living and employment skills with support. some girls with pentasomy x attend special education in mainstream schools through mainstreaming or inclusion, while some attend special schools. a 15-year-old girl with pentasomy x, demonstrating facial, limb, and skeletal features pentasomy x is associated with a number of physical anomalies, including short stature, clinodactyly (incurved pinky fingers), and distinctive facial features. common findings include microcephaly, low-set ears, hypertelorism (wide-spaced eyes), and epicanthic folds. the characteristic facies have been described as "coarse", much like those of the related disorder tetrasomy x. pentasomy x is unique amongst x-chromosome polysomies for its association with short stature, when most related disorders are associated with tall stature; the average height in pentasomy x is one standard deviation below the norm. hypotonia, often severe, is a frequent finding, as are related musculoskeletal issues such as hip dysplasia. the severity of repeated joint dislocations may lead to a differential diagnosis of larsen syndrome, as suggested in one reported case. bone maturation may be delayed. another skeletal finding is taurodontism, where the pulp of the teeth is enlarged into the roots; other dental abnormalities, such as missing teeth and severe tooth decay, have also been reported. these findings are not specific to pentasomy x, but rather common to sex chromosome aneuploidies in general and in particular show a strong resemblance to the male counterpart 49,xxxxy. epicanthic folds and hypertelorism are also observed in tetrasomy and trisomy x, while clinodactyly and radioulnar synostosis are seen in all sex chromosome aneuploidies and taurodontism is specifically common to x-chromosome polysomies. heart defects are associated with the syndrome. pentasomy x has one of the highest rates of congenital heart defects of any chromosomal disorder, with 56.5% of recorded patients having a heart defect of some kind. patent ductus arteriosus is particularly frequent. the majority of such conditions resolve without surgical treatment, although a minority require it. ventricular septal defects are also frequent. other internal medical issues frequently recorded include kidney and urinary defects. epilepsy has been associated with the condition, though seems to be rare. in sex chromosome aneuploidies as a whole, epilepsy is usually mild and amenable to treatment, and reports of epilepsy in pentasomy x have described it resolving with treatment and allowing antiepileptic drugs to eventually be stopped. puberty is altered in pentasomy x, although as few adults with the condition have been reported, the full scope of such alterations is unclear. in the sister condition of tetrasomy x, half of all women undergo puberty normally, while half have no or incomplete puberty. some adolescents and adults with pentasomy x have been prepubertal, while some have had premature ovarian failure (early menopause) and some have had apparently non-noteworthy pubertal development. though external genitalia is generally normal, underlying gonadal dysfunction is frequent, including ovarian dysfunction or an unusually small uterus. no cases are known of women with pentasomy x having children, but although fertility is likely reduced, some may be able to. little is understood about the psychological and behavioural phenotype of pentasomy x. girls and women with the disorder are frequently described as shy and cooperative. such traits are common to other conditions involving extra copies of the x chromosome. developmental delays can cause difficulty communicating, resulting in frustration and tantrums. overall, the syndrome is not associated with severe behavioural issues. a number of disorders have been reported as comorbid with sex chromosome aneuploidies, including pentasomy x. in one case report, pentasomy x occurred alongside the similarly rare hyperimmunoglobulin e syndrome. other possibly coincidental associations have included cerebral palsy and dandy–walker malformation. causes maternal age in 21 cases of pentasomy x, showing the unclear relationship pentasomy x is caused by nondisjunction, a process through which gametes (eggs or sperm) with too many or too few chromosomes are produced. in nondisjunction, homologous chromosomes or sister chromatids fail to separate properly when producing gametes. in sex chromosome tetrasomy and pentasomy, the extra chromosomes are consistently inherited from one parent. in the specific case of pentasomy x, all known cases have inherited the additional chromosomes from the mother. this has been suggested to relate to genomic imprinting; specifically, it is hypothesized that specific loci on the sex chromosomes are affected by imprinting such that only maternal overimprinting is survivable, and cases of pentasomy x where the additional chromosomes were inherited from the father would be incompatible with life. as well as during gamete development, nondisjunction can occur after conception, resulting in a mosaic karyotype. nondisjunction is related to advanced maternal age, although due to its rarity, the maternal age effect in pentasomy x is unclear. more common aneuploidy syndromes, such as down syndrome and klinefelter's syndrome, have strong relationships with maternal age. pentasomy x is not inherited and is not caused by the actions of the parents. however, in rare cases, pentasomy x may be related to chromosomal mosaicism in a parent. x inactivation is a major factor in pentasomy x. x inactivation is the process through which genes in second (or higher) copies of the x chromosome are turned off, such that any cell has only one active copy of the chromosome. however, x inactivation appears to be disrupted in pentasomy x, allowing up to half of the supposedly inactive genetic material to actually work. this is assumed to contribute to the severe phenotype of the condition compared to other sex chromosome aneuploidies. diagnosis chromosome aneuploidies such as pentasomy x are diagnosed through the process of karyotyping, or chromosome testing. diagnosis cannot be made on the basis of phenotype alone, as multiple other conditions present similarly. the phenotype of pentasomy x is not specific to the disorder, and many other conditions can be differential diagnoses. one is tetrasomy x, a related disorder in which a girl or woman has four copies of the x chromosome. the general profiles of the conditions are similar, with developmental delays, mild dysmorphic features, and shared congenital anomalies such as clinodactyly and radioulnar synostosis. however, the phenotype of pentasomy x is more severe than that of tetrasomy x, with lower iq and more severe dysmorphism. pentasomy x also has additional characteristics uncommon in the tetrasomy, such as short stature. mosaic karyotypes, with both 48,xxxx and 49,xxxxx cells, are also possible. though very few mosaic cases have been reported, the phenotype appears intermediate in severity between tetrasomy and pentasomy x. another potential differential diagnosis is down syndrome. the features of the two conditions overlap, and some girls with pentasomy x may be assumed to have down's before genetic ascertainment. some cases of pentasomy x have had family histories of down syndrome, inciting speculation that the conditions may tend to recur in the same family lines; alternatively, it may suggest that some patients diagnosed with down syndrome on the basis of phenotype may actually have pentasomy x. the phenotype of pentasomy x has also been compared to that of turner syndrome, characterised by a female having one copy of the x chromosome. both turner's and pentasomy x are female-only disorders characterised by short stature, heart defects, and abnormal pubertal development. however, the intellectual disabilities observed in pentasomy x are rare in turner syndrome. prognosis the long-term prognosis of pentasomy x is unclear, due to its low prevalence. though some reviews claim a poor prognosis due to the congenital defects observed in severe cases, support groups report milder abnormalities than common in the medical literature, including adults with pentasomy x in fair health. the spectrum of severity varies; long-term support is consistent, though some women have been reported as being able to work part-time and manage some of their affairs. for sex chromosome tetrasomy and pentasomy disorders as a whole, good prognosis is linked to strong parental and personal support. girls and women with pentasomy x whose caregivers have acted as advocates for their success have been reported as achieving at higher personal and social levels than the general portrait of the medical literature. epidemiology pentasomy x is exceptionally rare. the disorder is estimated to occur in approximately 1 in 250,000 females. some higher estimates posit the condition may be as frequent as 1 in 85,000, as observed in the related 49,xxxxy syndrome. fewer than thirty cases of the disorder have been reported in the medical literature, although it is speculated that many more cases have gone undiagnosed. pentasomy x only occurs in females, as the y chromosome is in most cases necessary for male sexual development. history pentasomy x was first diagnosed in 1963, in a two-year-old girl karyotyped for severe intellectual disability. at the time, four cases of xxxxy syndrome had already been recorded. pentasomy x was one of the later sex chromosome aneuploidies to be discovered, being preceded by turner, klinefelter, and trisomy x in 1959, xxyy syndrome in 1960, and xyy and tetrasomy x in 1961. by the time of linden, bender, and robinson's seminal review of sex chromosome tetrasomy and pentasomy in 1995, only 25 cases had been recorded, the eldest in a girl of 16. as late as 2011, reviews claimed no adult women with pentasomy x had been ascertained, though chromosomal disorder organization unique noted in 2005 its oldest member with pentasomy x was 29 years old.

growth hormone therapy growth hormone therapy growth hormone therapy refers to the use of growth hormone (gh) as a prescription medication—it is one form of hormone therapy. growth hormone is a peptide hormone secreted by the pituitary gland that stimulates growth and cell reproduction. in the past, growth hormone was extracted from human pituitary glands. growth hormone is now produced by recombinant dna technology and is prescribed for a variety of reasons. gh therapy has been a focus of social and ethical controversies for 50 years. growth hormone therapyspecialtyendocrinologist this article describes the history of gh treatment and the current uses and risks arising from gh use. other articles describe gh physiology, diseases of gh excess (acromegaly and pituitary gigantism), deficiency, the recent phenomenon of hgh controversies, growth hormone in sports, and growth hormone for cows. medical uses hgh deficiency in children growth hormone deficiency is treated by replacing growth hormone. lonapegsomatropin was approved for medical use in the united states in august 2021. hgh deficiency in adults the endocrine society has recommended that adult patients diagnosed with growth hormone deficiency (ghd) be administered an individualized gh treatment regimen. with respect to diagnosis, their guidelines state that "adults patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies be considered for evaluation for acquired ghd" and that "idiopathic ghd in adults is very rare, and stringent criteria are necessary to make this diagnosis. because in the absence of suggestive clinical circumstances there is a significant false-positive error rate in the response to a single gh stimulation test, we suggest the use of two tests before making this diagnosis." gh replacement therapy can provide a number of measurable benefits to gh-deficient adults. these include improved bone density, increased muscle mass, decrease of adipose tissue, faster hair and nail growth, strengthened immune system, increased circulatory system, and improved blood lipid levels, but long term mortality benefit has not yet been demonstrated. a peer-reviewed article published in 2010 indicates that "growth hormone (gh) replacement unequivocally benefits growth, body composition, cardiovascular risk factors and quality of life. less is known about the effects of gh on learning and memory." other as of 2004, gh has been approved by the u.s. food and drug administration for treatment of other conditions such as: in adults, wasting (or cachexia) caused by aids. turner syndrome epitomizes the response of non-deficient shortness. at doses 20% higher than those used in gh deficiency, growth accelerates. with several years of treatment the median gain in adult height is about 2–3 in (5.1–7.6 cm) on this dose. the gains appear to be dose-dependent. it has been used successfully in toddlers with turner syndrome, as well as in older girls. short-stature homeobox gene deficiency chronic kidney failure results in many problems, including growth failure. gh treatment for several years both before and after transplantation may prevent further deceleration of growth and may narrow the height deficit, though even with treatment net adult height loss may be about 4 in (10 cm) prader–willi syndrome, a generally non-hereditary genetic condition, is a case where gh is prescribed for benefits in addition to height. gh is one of the treatment options an experienced endocrinologist may use when treating a child with pws. gh can help children with pws in height, weight, body mass, strength, and agility. . reports have indicated increase of growth rate (especially in the first year of treatment) and a variety of other positive effects, including improved body composition (higher muscle mass, lower fat mass); improved weight management; increased energy and physical activity; improved strength, agility, and endurance; and improved respiratory function. the prader-willi syndrome association (usa) recommends that a sleep study be conducted before initiating gh treatment in a child with pws. at this time there is no direct evidence of a causative link between growth hormone and the respiratory problems seen in pws (among both those receiving and those not receiving gh treatment), including sudden death. a follow-up sleep study after one year of gh treatment may also be indicated. gh (specifically pfizer's version, genotropin) is the only treatment that has received an fda indication for children with pws. the fda indication only applies to children. children short because of intrauterine growth retardation are small for gestational age at birth for a variety of reasons. if early catch-up growth does not occur and their heights remain below the third percentile by 2 or 3 years of age, adult height is likely to be similarly low. high-dose gh treatment has been shown to accelerate growth, but data on long term benefits and risks are limited. idiopathic short stature (iss) is one of the most controversial indications for gh as pediatric endocrinologists do not agree on its definition, diagnostic criteria, or limits. the term has been applied to children with severe unexplained shortness that will result in an adult height below the 3rd percentile. in the late 1990s, the pharmaceutical manufacturer eli lilly and company sponsored trials of their brand of rhgh (humatrope) in children with extreme iss, those at least 2.25 standard deviations below mean (in the lowest 1.2 percent of the population). these boys and girls appeared to be headed toward heights of less than 63" (160 cm) and 59" (150 cm) respectively. they were treated for about 4 years and gained 1.5–3 in (3.8–7.6 cm) in adult height. controversy has arisen as to whether all of these children were truly "short normal" children, since the average igf1 was low. approval of hgh for the treatment of this extreme degree of shortness led to an increase in the number of parents seeking its use to make otherwise normal children a little taller. adverse effects the new england journal of medicine published two editorials in 2003 expressing concern about off-label uses of hgh and the proliferation of advertisements for "hgh-releasing" dietary supplements, and emphasized that there is no evidence that use of hgh in healthy adults or in geriatric patients is safe and effective – and especially emphasized that risks of long-term hgh treatment are unknown. one editorial was by jeffrey m. drazen, m.d., the editor-in-chief of the journal; the other one was by mary lee vance, who provided the nejm's editorial original, cautious comment on a much cited 1990 study on the use of hgh in geriatric patients with low growth hormone levels. a small but controlled study of gh given to severely ill adults in an intensive care unit setting for the purpose of increasing strength and reducing the muscle wasting of critical illness showed a higher mortality rate for the patients having received gh. the reason is unknown, but gh is now rarely used in icu patients unless they have severe growth hormone deficiency. gh treatment usually decreases insulin sensitivity, but some studies showed no evidence for increased diabetes incidence in gh-treated adult hypopituitary patients. in past it was believed that gh treatment could increase the cancer risk; a large study recently concluded that "with relatively short follow-up, the overall primary cancer risk in 6840 patients receiving gh as adults was not increased. elevated sirs (which is risk of getting cancer) were found for subgroups in the usa cohort defined by age <35 years or childhood onset gh deficiency." the fda issued a safety communication in august 2011, stating that the evidence regarding recombinant human growth hormone and increased risk of death is inconclusive after reviewing sources including a french study which compared persons with certain kinds of short stature (idiopathic growth hormone deficiency and idiopathic or gestational short stature) treated with recombinant human growth hormone during childhood and who were followed over a long period of time, with individuals in the general population of france. history perhaps the most famous person who exemplified the appearance of untreated congenital growth hormone deficiency was charles sherwood stratton (1838–1883), who was exhibited by p. t. barnum as general tom thumb, and married lavinia warren. pictures of the couple show the typical adult features of untreated severe growth hormone deficiency. despite the severe shortness, limbs and trunks are proportional. by the middle of the twentieth century, endocrinologists understood the clinical features of growth hormone deficiency. gh is a protein hormone, like insulin, which had been purified from pig and cow pancreases for treatment of type 1 diabetes since the 1920s. however, pig and cow gh did not work at all in humans, due to greater species-to-species variation of molecular structure (i.e., insulin is considered more "evolutionarily conserved" than gh). extraction for treatment extracted growth hormone was used since the late 1950s until the late 1980s when its use was replaced by recombinant gh. in the late 1950s, maurice raben purified enough gh from human pituitary glands to successfully treat a gh-deficient boy. a few endocrinologists began to help parents of severely gh-deficient children to make arrangements with local pathologists to collect human pituitary glands after removal at autopsy. parents would then contract with a biochemist to purify enough growth hormone to treat their child. few families could manage such a complicated undertaking. in 1960, the national pituitary agency was formed as a branch of the u.s. national institutes of health. the purpose of this agency was to supervise the collection of human pituitary glands when autopsies were performed, arrange for large-scale extraction and purification of gh, and distribute it to a limited number of pediatric endocrinologists for treating gh-deficient children under research protocols. canada, uk, australia, new zealand, france, israel, and other countries establish similar government-sponsored agencies to collect pituitaries, purify gh, and distribute it for treatment of severely gh-deficient children. supplies of this “cadaver growth hormone” were limited, and only the most severely deficient children were treated. from 1963 to 1985 about 7700 children in the u.s. and 27,000 children worldwide were given gh extracted from human pituitary glands to treat severe gh deficiency. physicians trained in the relatively new specialty of pediatric endocrinology provided most of this care, but in the late 1960s there were only a hundred of these physicians in a few dozen of the largest university medical centers around the world. in 1977, the npa gh extraction and purification procedure was refined and improved. a shortage of available cadaver gh worsened in the late 1970s as the autopsy rate in the u.s. declined, while the number of pediatric endocrinologists able to diagnose and treat gh deficiency increased. gh was "rationed." often, treatment would be stopped when a child reached an arbitrary minimal height, such as 5 ft 0 in (1.52 m). children who were short for reasons other than severe gh deficiency were lied to and told that they would not benefit from treatment. only those pediatric endocrinologists that remained at university medical centers with departments able to support a research program had access to npa growth hormone. in the late 1970s, a swedish pharmaceutical company, kabi, contracted with a number of hospitals in europe to buy pituitary glands for the first commercial gh product, crescormon. although an additional source of gh was welcomed, crescormon was greeted with ambivalence by pediatric endocrinologists in the united states. the first concern was that kabi would begin to purchase pituitaries in the u.s., which would quickly undermine the npa, which relied on a donation system like blood transfusion. as the number of autopsies continued to shrink, would pathologists sell pituitaries to a higher bidder? the second offense was kabi-pharmacia's marketing campaign, which was directed at primary care physicians under the slogan, “now, you determine the need,” implying that the services of a specialist were not needed for growth hormone treatment anymore and that any short child might be a candidate for treatment. although the crescormon controversy in the u.s. is long forgotten, kabi's pituitary purchase program continued to generate scandal in europe as recently as 2000. recombinant human growth hormone (rhgh) in 1981, the new american corporation genentech, after collaboration with kabi, developed and started trials of recombinant human growth hormone (rhgh) made by a new technology (recombinant dna) in which human genes were inserted into bacteria so that they could produce unlimited amounts of the protein. because this was new technology, approval was deferred as lengthy safety trials continued over the next four years. in 1985, four young adults in the u.s. having received npa growth hormone

in the 1960s developed cjd (creutzfeldt–jakob disease). the connection was recognized within a few months, and use of human pituitary gh rapidly ceased. between 1985 and 2003, a total of 26 cases of cjd occurred in adults having received npa gh before 1977 (out of 7700), comparable numbers of cases occurred around the world. by 2003 there had been no cases in people who received only gh purified by the improved 1977 methods. discontinuation of human cadaver growth hormone led to rapid food and drug administration approval of genentech's recombinant human growth hormone, which was introduced in 1985 as protropin in the united states. although this previously scarce commodity was suddenly available in "bucketfuls", the price of treatment (us$10,000–30,000 per year) was the highest at the time. genentech justified it by the prolonged research and development investment, orphan drug status, and a pioneering post-marketing surveillance registry for tracking safety and effectiveness (national cooperative growth study). within a few years, gh treatment had become more common and competitors entered the market. eli lilly launched a competing natural sequence growth hormone (humatrope). pharmacia (formerly kabi, now pfizer) introduced genotropin. novo nordisk introduced norditropin. serono (now emd serono) introduced saizen and serostim. ferring has introduced zomacton. genentech eventually introduced another hgh product, nutropin, and stopped making protropin in 2004. price competition had begun. teva, which is primarily a generics company, has introduced tev-tropin. chinese companies have entered the market as well and have introduced more pricing competition: neogenica bioscience ltd. introduced hypertropin, genescience introduced jintropin, anhui anke biotechnology introduced ansomone, shanghai united kefei biotechnology introduced kefei hgh, and hygene biopharm introduced hygetropin. these are all recombinant human growth hormone products and they have competed with various marketing strategies. most children with severe deficiency in the developed world are now likely to have access to a pediatric endocrinologist and be diagnosed and offered treatment. pediatric endocrinology became a recognizable specialty in the 1950s, but did not reach board status in the u.s. until the late 1970s. even 10 years later, as a cognitive, procedureless specialty dealing with mostly rare diseases, it was one of the smallest, lowest-paid, and more obscure of the medical specialities. pediatric endocrinologists were the only physicians interested in the arcana of gh metabolism and children's growth , but their previously academic arguments took on new practical significance with major financial implications. the major scientific arguments dated back to the days of gh scarcity: everyone agrees on the nature and diagnosis of severe gh deficiency, but what are the edges and variations? how should marked constitutional delay be distinguished from partial gh deficiency? to what extent is "normal shortness" a matter of short children naturally making less growth hormone? can a child make gh in response to a stimulation test but fail to make enough in "daily life" to grow normally? if a stimulation test is used to define deficiency, what gh cutoff should be used to define normal? it was the ethical questions that were new. is gh not a wise use of finite healthcare resources, or is the physician's primary responsibility to the patient? if gh is given to most extremely short children to make them taller, will the definition of “extremely short” simply rise, negating the expected social benefit? if gh is given to short children whose parents can afford it, will shortness become a permanent mark of lower social origins? more of these issues are outlined in the ethics section. whole meetings were devoted to these questions; pediatric endocrinology had become a specialty with its own bioethics issues. despite the price, the 1990s became an era of experimentation to see what else growth hormone could help. the medical literature of the decade contains hundreds of reports of small trials of gh use in nearly every type of growth failure and shortness imaginable. in most cases, the growth responses were modest. for conditions with a large enough potential market, more rigorous trials were sponsored by pharmaceutical companies that were making growth hormone to achieve approval to market for those specific indications. turner syndrome and chronic kidney failure were the first of these “nongh-deficient causes of shortness” to receive fda approval for gh treatment, and prader-willi syndrome and intrauterine growth retardation followed. similar expansion of use occurred in europe. one obvious potential market was adult gh deficiency. by the mid-1990s, several gh companies had sponsored or publicized research into the quality of life of adults with severe gh deficiency. most were people having been treated with gh in childhood for severe deficiency. although the injections are painless, many of them had been happy to leave injections behind as they reached final heights in the low-normal range. however, as adults in their 30s and 40s, these people, who had been children with growth hormone deficiency, were now adults with growth hormone deficiency and had more than their share of common adult problems: reduced physical, mental, and social energy, excess adipose and diminished muscle, diminished libido, poor bone density, higher cholesterol levels, and higher rates of cardiovascular disease. research trials soon confirmed that a few months of gh could improve nearly all of these parameters. however, despite marketing efforts, most gh-deficient adults remain untreated. though gh use was slow to be accepted among adults with gh deficiency, similar research to see if gh treatment could slow or reverse some of the similar effects of aging attracted much public interest. the most publicized trial was reported by daniel rudman in 1990. as with other types of hormone supplementation for aging (testosterone, estrogen, dhea), confirmation of benefit and accurate understanding of risks has been only slowly evolving. in 1997, ronald klatz of the american academy of anti-aging medicine published grow young with hgh: the amazing medically proven plan to reverse the effects of aging, an uncritical touting of gh as the answer to aging. this time, the internet amplified the proposition and spawned a hundred frauds and scams. however, their adoption of the "hgh" term has provided an easy way to distinguish the hype from the evidence. in 2003, growth hormone hit the news again, when the us fda granted eli lilly approval to market humatrope for the treatment of idiopathic short stature. the indication was controversial for several reasons, the primary one being the difficulty in defining extreme shortness with normal test results as a disease rather than the extreme end of the normal height range recombinant growth hormone available in the u.s. (and their manufacturers) include nutropin (genentech), humatrope (eli lilly and company), genotropin (pfizer), norditropin (novo nordisk), tev-tropin (teva) and saizen (merck serono). the products are nearly identical in composition, efficacy, and cost, varying primarily in the formulations and delivery devices. somapacitan-beco (sogroya) is first once-per week subcutaneous human growth hormone (hgh) therapy that was approved in the united states. it was approved for medical use in the united states in august 2020. terminology growth hormone (gh l) is also called somatotropin (british: somatotrophin). the human form of growth hormone is known as human growth hormone, or hgh (ovine growth hormone, or sheep growth hormone, is abbreviated ogh). gh can refer either to the natural hormone produced by the pituitary (somatotropin), or biosynthetic gh for therapy. cadaver growth hormone is the term for gh extracted from the pituitary glands of human cadavers between 1960 and 1985 for therapy of deficient children. in the u.s., cadaver gh, also referred to as npa growth hormone, was provided by the national pituitary agency, and by other national programs and commercial firms as well. in 1985 it was associated with the development of creutzfeldt–jakob disease, and was withdrawn from use. rhgh (rhgh, rhgh) refers to recombinant human growth hormone, that is, somatropin (inn). its amino acid sequence is identical with that of endogenous human gh. it is coincidental that rhgh also refers to rhesus monkey gh (rhgh), using the accepted naming convention of rh for rhesus. rhesus growth hormone was never used by physicians to treat human patients, but rhesus gh was part of the lore of the underground anabolic steroid community in those years, and fraudulent versions may have been bought and sold in gyms. met-gh refers to methionyl–growth hormone, that is, somatrem (inn). this was the first recombinant gh product marketed (trade name protropin by genentech). it had the same amino acid sequence as human gh with an extra methionine at the end of the chain to facilitate the manufacturing process. it was discontinued in 2004. rbst refers to recombinant bovine somatotropin (cow growth hormone), or recombinant bovine gh (rbgh, rbgh).

flammeovirga kamogawensis flammeovirga kamogawensis flammeovirga kamogawensis is a bacterium from the genus of flammeovirga which has been isolated from coastal seawater from kamogawa in japan. flammeovirga kamogawensis scientific classification kingdom: bacteria phylum: bacteroidota class: cytophagia order: cytophagales family: flammeovirgaceae genus: flammeovirga species: f. kamogawensis binomial name flammeovirga kamogawensishosoya and yokota 2007 type strain iam 15451, jcm 23196, ncimb 14281, ys10 synonyms flammeovirga bosoensis

2014 democratic republic of the congo ebola virus outbreak 2014 democratic republic of the congo ebola virus outbreak in 2014, an outbreak of ebola virus disease in the democratic republic of the congo (drc) occurred. genome sequencing has shown that this outbreak was not related to the 2014–15 west africa ebola virus epidemic, but was of the same ebov species. it began in august 2014 and was declared over in november of that year, after 42 days without any new cases. this is the 7th outbreak there, three of which occurred during the period of zaire. 2014 democratic republic of the congo ebola outbreakdemocratic republic of the congo (orthographic projection)dateaugust – november 2014casualties cases / deaths (as at end of outbreak) dr congo: 66 / 49 epidemiology articles related to thewestern africanebola virus epidemic overview ebola virus disease timeline of the epidemic responses to the epidemic timeline, tables and graphs ebola virus disease treatment research post-ebola virus syndrome ebola vaccine nations with widespread cases guinea liberia sierra leone other affected nations mali nigeria senegal spain united states united kingdom italy other outbreaks list of ebola outbreaks 1976 zaire ebola virus outbreak 2014 dr congo outbreak kivu ebola epidemic list of epidemics and pandemics index patient the outbreak was traced to a woman living in ikanamongo village in the remote northern équateur province who fell ill after handling bushmeat. despite treatment in a local clinic, the woman died on 11 august 2014. at the time of her death, her diagnosis was hemorrhagic fever of unknown etiology. subsequent laboratory studies confirmed she had died of ebola virus disease. response medecins sans frontieres/doctors without borders (msf) deployed a team of 50 staff to the area and opened two evd treatment centers with a combined capacity of 50 beds. msf, together with the country's ministry of health and the world health organization (who) worked to heighten public awareness and ensure that surveillance, contact tracing, and follow-up activities were carried out in order to limit the spread of the disease. there are no roads to the affected area, which made working conditions difficult. subsequent cases by 18 august, 13 people, including three health care workers, were reported to have died of ebola-like symptoms in équateur province, a province that lies about 1,200 km (750 mi) north of the capital kinshasa. on 26 august, the équateur province ministry of health confirmed an outbreak of ebola to the who. on 2 september, the who said that there were currently 31 deaths in the northern boende area in the province of équateur and 53 confirmed, suspected or likely cases. on 9 september, the who raised the number of cases to 62 and the death toll to 35 from possible or confirmed ebola cases. included in this number were 9 health-care workers with 7 deaths among them. in total, 386 contacts were listed and 239 contacts were being followed. the outbreak was still contained in jeera county in the boende region. as of 28 october, there had been 66 cases reported. in total, 49 deaths had been reported, including eight among health care workers. no new reported contacts were being followed and twenty days had passed since the last reported case tested negative for the second time and was discharged. it was stated that the drc would therefore be declared free of ebola disease 42 days after the date of the second negative test if no new cases were reported. the outbreak was declared over on 15 november 2014. subsequent findings in october 2014, it was reported that more recent findings suggested that there may have been several previous cases. the husband of the woman that was believed to have been the index case told an investigation team that shortly before she became ill she had visited two women who later died from ebola-like symptoms. other village residents also told the team that all the pigs in the village had died just before the illness hit the village and they had eaten the pigs. according to the research team, "it was the third time, after 2007 and 2012, that widespread pig deaths had preceded ebola outbreaks in humans in the dr congo...and it has been established that the pigs that died in 2012 carried the ebola virus." pig to human transmission has never been proven in previous outbreaks, but villagers have been told to avoid eating them and the investigation is ongoing. virology ebola virions further information: ebola virus disease results from virus sequencing of samples from the ebola outbreak in the democratic republic of congo have shown that the virus is the zaire species in a lineage most closely related to a virus from the 1995 ebola outbreak in kikwit. the zaire species of the virus is indigenous to the area. when the outbreak was first reported there were fears that an ongoing epidemic in west africa may have spread to the drc, however results from virus characterization, together with findings from the epidemiological investigation, showed that the outbreak in drc is a distinct and independent event, with no relationship to the outbreak in west africa. history of ebola outbreaks in the drc further information: list of ebola outbreaks scientists wearing personal protective equipment (ppe) testing samples for the ebola virus from animals collected in zaire ~ 1995 multiple documented outbreaks of ebola virus disease have occurred in the drc since 1976, which are summarised in the table below. the first case of ebola disease ever recorded occurred in august 1976 in yambuku, a small village in mongala district in northern democratic republic of the congo (then known as zaire). the first victim of the disease was the village school headmaster, who had toured an area near the central african republic border along the ebola river in mid-august. on 8 september, he died of what would become known as ebola virus disease. subsequently, a number of other cases were reported, almost all centered on the yambuku mission hospital or having close contact with other cases. a total of 318 cases and 280 deaths (an 88% fatality rate) resulted from this outbreak, which, along with an outbreak in sudan that had begun a few weeks previously, were the first outbreaks of ebola ever recorded. the virus responsible for the initial outbreak, named after the nearby ebola river, was first thought to be marburg virus but was later identified as a new type of virus related to marburg. timeline of ebola outbreaks in the democratic republic of the congo (formerly zaire) since 1976 v・tdatecountrymajor locationoutbreak informationsource straincasesdeathscfr aug 1976zaireyambukuebov31828088% jun 1977zairetandalaebov11100% may–jul 1995zairekikwitebov31525481% aug–nov 2007democratic republic of the congokasai-occidentalebov26418771% dec 2008–feb 2009democratic republic of the congokasai-occidentalebov321445% jun–nov 2012democratic republic of the congoorientalebdbv773647% aug–nov 2014democratic republic of the congotshuapaebov664974% may–jul 2017democratic republic of the congolikatiebov8450% apr–jul 2018democratic republic of the congoéquateur provinceebov543361% aug 2018–june 2020democratic republic of the congokivuebov3,4702,28066% june–nov 2020democratic republic of the congoéquateur provinceebov1305542% feb 2021–may 2021democratic republic of the congonorth kivuebov12650% april 2022democratic republic of the congoéquateur provinceebov55100% august 2022democratic republic of the congonorth kivuebov11100%

falsirhodobacter deserti falsirhodobacter deserti falsirhodobacter deserti is a gram-negative, aerobic, halotolerant, heterotrophic and non-motile bacteria bacterium from the genus of falsirhodobacter which has been isolated from the desert of xinjiang in china. falsirhodobacter deserti scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: rhodobacterales family: rhodobacteraceae genus: falsirhodobacter species: f. deserti binomial name falsirhodobacter desertiwang et al. 2015 type strain accc 05851, w402, kctc 32408 synonyms falsirhodobacter taklimaensis

parapontixanthobacter aurantiacus parapontixanthobacter aurantiacus parapontixanthobacter aurantiacus is a gram-negative and aerobic bacterium from the genus of parapontixanthobacter which has been isolated from deep-sea sediments from the pacific ocean. parapontixanthobacter aurantiacus scientific classification domain: bacteria phylum: pseudomonadota class: alphaproteobacteria order: sphingomonadales family: erythrobacteraceae genus: parapontixanthobacterxu et al. 2020 species: p. aurantiacus binomial name parapontixanthobacter aurantiacus(zhang et al. 2016) xu et al. 2020 type strain cgmcc 1.12762, jcm 19853, lmg 28110, mccc 1a09962, strain o30 synonyms altererythrobacter aurantiacus zhang et al. 2016

air filtration in operating rooms air filtration in operating rooms air filtration guidelines for operating rooms are determined by the american society of heating, refrigerating and air-conditioning engineers (ashrae) using a standard known as minimum efficiency reporting value (merv). merv is determined based on the size of particles successfully removed from the air and is used to classify the efficiency of hepa filters. ratings range from 1-16 and efficiency increases as the rating increases. ashrae groups surgeries into three categories: minor surgical procedures (a); minor or major surgical procedures performed with minor sedation (b); and major surgical procedures performed with general anesthesia or regional block anesthesia (c). each surgical category is given a minimum merv rating it must comply with. hepa filter high-efficiency particulate air (hepa) filter is at least 99.97% effective in removing particles ≥0.3 μm in diameter (as a reference, aspergillus spores are 2.5–3.0 μm in diameter). high-level hepa filtration and increasing air changes per hour (ach) can reduce particulate matter (pm) and bacterial concentrations in the operating room. the facility guidelines institute recommends using sequential hepa filters for ors with a merv rating of 7 (i.e., captures particle 10 to 3 μm in size) and 14 (i.e., captures particles from 1 to 0.3 μm in size). one mechanism by which hepa filters capture particles is electrostatic charge. negatively charged particles are attracted to and get trapped by positively charged fibers in the filter. standards air filtration standards differ between the u.s. and other countries. the american ashrae rating system does not account for changes in filtration efficiency due to electrostatic charge. these merv ratings do not account for a decrease in efficiency over the first few weeks of use due to a drop in static charge. the air filtration rating system from the international standardization organization (iso) does account for this loss in filtration efficiency. iso standards are widely used in europe and other countries. laminar airflow ventilation laminar airflow ventilation consists of air flowing a single direction, as opposed to turbulent ventilation. current research shows mixed results as whether laminar airflow in an operating room decreases surgical site infections. laminar airflow ventilation is more frequently used in operating rooms in europe and is considered best practice for operating rooms to prevent surgical site infections. the centers for disease control and prevention (cdc) in the united states does not find the use of laminar airflow in operating rooms beneficial.

fudania jinshanensis fudania jinshanensis fudania jinshanensis is a gram-positive species of bacteria from the family actinomycetaceae which has been isolated from the faeces of an antelope (pantholops hodgsonii). fudania jinshanensis scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: actinomycetales family: actinomycetaceae genus: fudaniazhu et al. 2019 species: f. jinshanensis binomial name fudania jinshanensiszhu et al. 2019 type strain 313cgmcc 4.7453dsm 106216

european federation for immunogenetics european federation for immunogenetics the european federation for immunogenetics (efi) is the european association of people with interests in the field of immunogenetics. history of the efi during the early 1980s, members of the committee created a more formal organisation and the organisation was made official in the mid-1980s. it was initiated to give scientists an opportunity to collaborate with one another, and to ensure that their findings were accurate and of high quality. efi sets a series of standards for laboratories to adhere to and works to create relationships with other organisations worldwide that carry out similar work. accreditation there are now over 200 laboratories accredited by the efi. these laboratories are found not only in europe, but also in israel, south africa and mexico and have met the criteria that have been set out by efi. the laboratories undergo regular inspections to ensure that they are continuing to follow the standards and that they are producing the high-quality work expected. committees there are various committees within the efi, including a standards and quality assurance, accreditation, education and scientific. these ensure that the high standards set out by the federation are adhered to. president the current president of the efi is ann-margaret little. information there are other immunogenetic societies worldwide. these include aseatta, ashi, bshi, and dgi.

proteus ox19 proteus ox19 proteus ox19 is a strain of the proteus vulgaris bacterium. proteus ox19 scientific classification domain: bacteria phylum: pseudomonadota class: gammaproteobacteria order: enterobacterales family: enterobacteriaceae genus: proteus species: p. vulgaris binomial name proteus vulgarishauser, 1885 history in 1915, arthur felix and edward weil discovered that proteus ox19 reacted to the same human immune antibodies as typhus. other proteus strains were similarly used to create reagents for other rickettsiae diseases, thus resulting in the commercial weil-felix antibody-agglutination test. use in fake epidemic in poland drs. eugeniusz lazowski and his medical-school friend stanisław matulewicz were practicing in the small town of rozwadów in poland during world war ii. dr. matulewicz realized that since proteus vulgaris strain ox19 was used to manufacture the then-common weil-felix antibody-agglutination test for typhus, inoculating villagers with dead proteus would cause a false positive result without causing any disease. when the blood samples of the townspeople were sent to the german authorities for testing, authorities were convinced a typhus epidemic was raging in rozwadów, and the area was avoided by the germans, saving thousands of poles. in fiction the novel 1979 night trains, by barbara wood and gareth wootton, is a fictionalized account of the proteus story, with details altered.

styloglossus styloglossus the styloglossus muscle is a bilaterally paired muscle of the tongue. it originates at the styloid process of the temporal bone. it inserts onto the side of the tongue. it acts to elevate and retract the tongue. it is innervated by the hypoglossal nerve (cranial nerve xii). styloglossusextrinsic muscles of the tongue. left side. (styloglossus xii visible at center top.)coronal section of tongue, showing intrinsic muscles. (styloglossus labeled at center left.)detailsoriginstyloid process of temporal boneinsertiontip and sides of tonguearterysublingual branch of the lingual artery.nervehypoglossal nerve (cn xii)actionsretraction and elevation of tongueidentifierslatinmusculus styloglossusta98a05.1.04.105ta22121fma46692anatomical terms of muscle anatomy the styloglossus muscle is the shortest and smallest of the three styloid muscles. origin it arises from (the anterior and lateral surfaces of) the styloid process of the temporal bone near its apex, and from the stylomandibular ligament. course and relations it passes anterioinferiorly from its origin to its insertion between the internal carotid artery and the external carotid artery, and between the superior pharyngeal constrictor muscle and the middle pharyngeal constrictor muscle. insertion it divides upon the side of the tongue near the dorsal surface of the tongue, blending with the fibers of the longitudinalis inferior muscle anterior to the hyoglossus muscle. innervation the styloglossus is innervated by the hypoglossal nerve (cn xii) (like all muscles of the tongue except palatoglossus which is innervated by the pharyngeal plexus of vagus nerve (cn x)). function the styloglossus draws up the sides of the tongue to create a trough for swallowing. acting bilaterally (both styloglossus muscles contracting simultaneously) they also aid in retracting the tongue. additional images left temporal bone. outer surface. muscles of the neck. anterior view. the internal carotid and vertebral arteries. right side. course and distribution of the glossopharyngeal, vagus, and accessory nerves. hypoglossal nerve, cervical plexus, and their branches. styloglossus muscle styloglossus muscle styloglossus muscle styloglossus muscle

retinoblastoma retinoblastoma retinoblastoma (rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. it is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children. this article is about the disease. for the protein, see retinoblastoma protein. retinoblastomaa pathology specimen of a retinoblastoma tumor from an enucleated eye of a 3-year-old femalespecialtyneuro-oncologysymptomsleukocoria seen in patient's pupil in photospoor visionone or both eyes turning inward or outwardeye painusual onsetunder 3 years oldtreatmentsurgery (including eye removal in advanced cases)chemotherapy (after surgery in cases of metastasis)focal therapyfrequency~250–300 children diagnosed annually (united states) though most children in high income countries survive this cancer, they may lose their vision in the affected eye(s) or need to have the eye removed. almost half of children with retinoblastoma have a hereditary genetic defect associated with retinoblastoma. in other cases, it is caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein). signs and symptoms leukocoria in a child with retinoblastoma crossed eyes in a child with retinoblastoma retinoblastoma is universally known as the most intrusive intraocular cancer among children. the chance of survival and preservation of the eye depends fully on the severity. retinoblastoma is extremely rare as there are only about 200 to 300 cases every year in the united states. looking at retinoblastoma globally, only 1 in about 15,000 children have this malignancy but these numbers continuously increase. intraocular malignancies are more curable rather than extraocular malignancies due to early diagnosis and an early treatment prognosis. during infant screenings, if they incorporate an eye screening like they do a hearing screening, it can be detected at an earlier age, therefore, preventing its spread. leucocoria is the primary indication of retinoblastoma and is when the cancer is still intraocular, meaning inside the eye. when light is reflected by the white tumor, the view of the red retina is blocked. retinoblastoma can be curable after the initial sign and up to six months, if the tumor is intraocular. if you do not visit an ophthalmologist with signs of leucocoria within a reasonable amount of time, the delay in the diagnosis could lead to a more severe prognosis. due to a delay in the diagnosis, it could result in proptosis which is then considered extraocular, the most severe. the most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cat's eye reflex. other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding. depending on the position of the tumors, they may be visible during a simple eye examination using an ophthalmoscope to look through the pupil. a positive diagnosis is usually made only with an examination under anesthetic (eua). a white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as coats' disease. the presence of the photographic fault red eye in only one eye and not in the other may be a sign of retinoblastoma. a clearer sign is "white eye" or "cat's eye" (leukocoria). cause mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body. alterations in rb1 or mycn can give rise to retinoblastoma. rb1 in children with the heritable genetic form of retinoblastoma, a mutation occurs in the rb1 gene on chromosome 13. rb1 was the first tumor suppressor gene cloned. although rb1 interacts with over 100 cell proteins, its negative regulator effect on the cell cycle principally arises from binding and inactivation of the transcription factor e2f, thus repressing the transcription of genes which are required for the s phase. the defective rb1 gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. the expression of the rb1 allele is autosomal dominant with 90% penetrance. inherited forms of retinoblastomas are more likely to be bilateral. in addition, inherited uni- or bilateral retinoblastomas may be associated with pineoblastoma and other malignant midline supratentorial primitive neuroectodermal tumors (pnets) with a dismal outcome; retinoblastoma concurrent with a pnet is known as trilateral retinoblastoma. a 2014 meta-analysis showed that 5-year survival of trilateral retinoblastoma increased from 6% before 1995 to 57% by 2014, attributed to early detection and improved chemotherapy. the development of retinoblastoma can be explained by the two-hit model. according to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors. the first mutational event can be inherited (germline or constitutional), which will then be present in all cells in the body. the second “hit” results in the loss of the remaining normal allele (gene) and occurs within a particular retinal cell. in the sporadic, nonheritable form of retinoblastoma, both mutational events occur within a single retinal cell after fertilization (somatic events); sporadic retinoblastoma tends to be unilateral. several methods have been developed to detect the rb1 gene mutations. attempts to correlate gene mutations to the stage at presentation have not shown convincing evidence of a correlation. mycn not all retinoblastoma cases are with rb1 inactivation. there are cases reported with only one rb1 mutation or even two functional rb1 alleles, which indicates other oncogenic lesions of retinoblastoma. somatic amplification of the mycn oncogene is responsible for some cases of nonhereditary, early-onset, aggressive, unilateral retinoblastoma. mycn can act as a transcription factor and promotes proliferation by regulating the expression of cell cycle genes. although mycn amplification accounted for only 1.4% of retinoblastoma cases, researchers identified it in 18% of infants diagnosed at less than 6 months of age. median age at diagnosis for mycn retinoblastoma was 4.5 months, compared with 24 months for those who had nonfamilial unilateral disease with two rb1 gene mutations. diagnosis rb tumors taken with a retinoscan before and during chemotherapy screening for retinoblastoma should be part of a "well baby" screening for newborns during the first 3 months of life, to include: the red reflex: checking for a normal reddish-orange reflection from the eye's retina with an ophthalmoscope or retinoscope from about 30 cm or 1 foot, usually done in a dimly lit or dark room the corneal light reflex or hirschberg test: checking for symmetrical reflection of beam of light in the same spot on each eye when a light is shined into each cornea, to help determine whether the eyes are crossed eye examination: checking for any structural abnormalities classification the two forms of the disease are a heritable form and nonheritable form (all cancers are considered genetic in that mutations of the genome are required for their development, but this does not imply that they are heritable, or transmitted to offspring). approximately 40% of patients have a heritable form of retinoblastoma, carrying a mutation in the rb1 gene. if no history of the disease exists within the family, the disease is labeled "sporadic", but this does not necessarily indicate that it is the nonheritable form. bilateral retinoblastomas are commonly heritable, while unilateral retinoblastomas are commonly nonheritable. in about two-thirds of cases, only one eye is affected (unilateral retinoblastoma); in the other third, tumors develop in both eyes (bilateral retinoblastoma). the number and size of tumors on each eye may vary. in certain cases, the pineal gland or the suprasellar or parasellar region (or in very rare cases other midline intracranial locations) is also affected (trilateral retinoblastoma). the position, size, and quantity of tumors are considered when choosing the type of treatment for the disease. differential diagnosis mri pattern of retinoblastoma with optic nerve involvement (sagittal enhanced t1-weighted sequence) 1. persistent hyperplastic primary vitreous is a congenital developmental anomaly of the eye resulting from failure of the embryological, primary vitreous, and hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and may present with whitening of the pupil. 2. coats disease is a typically unilateral disease characterised by abnormal development of blood vessels behind the retina, leading to blood vessel abnormalities in the retina and retinal detachment to mimic retinoblastoma. 3. toxocariasis is a parasitic disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment. 4. retinopathy of prematurity is associated with low-birth-weight infants who receive supplemental oxygen in the period immediately after birth, and it involves damage to the retinal tissue and may lead to retinal detachment. 5. congenital cataract 6. norrie disease if the eye examination is abnormal, further testing may include imaging studies, such as computerized tomography (ct), magnetic resonance imaging (mri), and ultrasound. ct and mri can help define the structure abnormalities and reveal any calcium depositions. ultrasound can help define the height and thickness of the tumor. bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain. morphology gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. microscopically, both undifferentiated and differentiated elements may be present. undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include flexner-wintersteiner rosettes, homer wright rosettes, and fleurettes from photoreceptor differentiation. drawing of a large retinoblastoma aspect of trilateral retinoblastoma on mri an ocular ultrasound of a large retinoblastoma tumor within the eye of a 3-year-old boy funduscopic finding of a retinoblastoma ocular fundus aspect of retinoblastoma large exophytic white tumor with foci of calcification producing total exudative retinal detachment flexner-wintersteiner rosettes in retinoblastoma retinoblastoma, 400 x magnification crystal structure of the retinoblastoma tumor suppressor protein bound to e2f peptide polymer genetic testing identifying the rb1 gene mutation that led to a child's retinoblastoma can be important in the clinical care of the affected individual and in the care of (future) siblings and offspring. it may run in the family. bilaterally affected individuals and 13-15% of unilaterally affected individuals, are expected to show an rb1 mutation in blood. by identifying the rb1 mutation in the affected individual, (future) siblings, children, and other relatives can be tested for the mutation; if they do not carry the mutation, child relatives are not at risk of retinoblastoma, so need not undergo the trauma and expense of examinations under anaesthetic. for the 85% of unilaterally affected patients found not to carry either of their eye tumor rb1 mutations in blood, neither molecular testing nor clinical surveillance of siblings is required. if the rb1 mutation of an affected individual is identified, amniotic cells in an at-risk pregnancy can be tested for the family mutation; any fetus that carries the mutation can be delivered early, allowing early treatment of any eye tumors, leading to better visual outcomes. for cases of unilateral retinoblastoma where no eye tumor is available for testing, if no rb1 mutation is detected in blood after high-sensitivity molecular testing (i.e. >93% rb1 mutation detection sensitivity), the risk of a germline rb1 mutation is reduced to less than 1%, a level at which only clinic examination (and not examinations under anaesthetic) is recommended for the affected individual and their future offspring (national retinoblastoma strategy, canadian guidelines for care). imaging traditional ultrasound b scan can detect calcifications in the tumour while high-frequency ultrasound b scan is able to provide higher resolution than the traditional ultrasound and determine the proximity of the tumour with front portion of the eye. mri scan can detect high-risk features such as optic nerve invasion; choroidal invasion, scleral invasion, and intracranial invasion. ct scan is generally avoided because radiation can stimulate the formation of more eye tumours in those with rb1 genetic mutation. staging in order to properly diagnose retinoblastoma, there must be guidelines to follow to properly classify the risk of the tumor. the reese ellsworth classification system, by dr. algernon reese and dr. robert ellsworth, is universally used to determine

the size, location, and multi-focality of the tumor. the system was originally used to decide the best treatment result by using external beam radiotherapy, as well as, the likeliness of salvaging the globe of the eye. due to chemotherapy not being part of the reese ellsworth classification system, there needed to be an updated classification system to foresee the treatment outcomes of chemotherapy. the international classification for intraocular retinoblastoma is now the current system being used, and it was created by murphree and associates. according to reese and ellsworth, there were different groups that had various features in order to classify the globe salvage as very favorable to the category of very unfavorable. in order to salvage the affected eye, the disc diameter had to be around 4dd and behind the equator to have higher favorability. if the tumor was around ten in disc diameter and involved roughly 50% of the retina, it was considered unfavorable to salvage the globe which could result in enucleation. according to murphree, the different groups were classified from very low risk to very high risk which was determined by features of the given tumor. very low risk means that the tumor has to be less than 3mm and there must be no seeding of the vitreous or sub-retinal area. when a patient is very high risk, the tumor presents itself with multiple features and is going to have to be treated with conservative treatment modalities or enucleation. group clinical features a very low risk all tumors are 3mm or smaller, confined to the retina, and located at least 3mm from the foveola and 1.5mm from the optic nerve. no vitreous or subretinal seeding b low risk retinal tumors may be any size or location not in group a, no vitreous or subretinal seeding allowed. a small cuff of subretinal fluid extending no more than 5mm from the base of the tumor is allowed c moderate risk eyes with only focal vitreous or subretinal seeding and discrete retinal tumors of any size and location. vitreous or subretinal seeding may extend no more than 3mm from the tumor. up to one quadrant of subretinal fluid may be present d high risk eyes with diffuse vitreous or subretinal seeding and/or massive, nondiscrete endophytic or exophytic disease. more than one quadrant of retinal detachment e very high risk eyes eyes with one or more of the following: irreversible neovascular glaucoma massive intraocular hemorrhage aseptic orbital cellulitis phthisis or pre-phthisis tumor anterior to anterior vitreous face tumor touching the lens diffuse infiltrating retinoblastoma international classification for intraocular retinoblastoma treatment historical image showing gordon isaacs, the first patient treated with the linear accelerator (external beam radiation therapy) for retinoblastoma, in 1957. gordon's right eye was removed january 11, 1957 because the cancer had spread. his left eye, however, had only a localized tumor that prompted henry kaplan to try to treat it with the electron beam. the priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. the exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist. correct treatment also depends on the mutation type, whether it is a germline rb1 mutation, a sporadic rb1 mutation or mycn amplification with functional rb1. children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies). the various treatment modalities for retinoblastoma includes: enucleation of the eye – most patients with unilateral disease present with advanced intraocular disease, so usually undergo enucleation, which results in a cure rate of 95%. in bilateral rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision. external beam radiotherapy (ebrt) – the most common indication for ebrt is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. however, patients with hereditary disease who received ebrt therapy are reported to have a 35% risk of second cancers. brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. it used as the primary treatment, or more frequently, in patients with small tumors or in those who had failed initial therapy including previous ebrt therapy. thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. it is also used for small tumors. laser photocoagulation is recommended only for small posterior tumors. an argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor. cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. it may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods. systemic chemotherapy has become forefront of treatment in the past decade, in the search for globe-preserving measures and to avoid the adverse effects of ebrt therapy. the common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. it is also used in patients with unilateral disease when the tumors are small, but cannot be controlled with local therapies alone. intra-arterial chemotherapy – chemotherapeutic drugs are administered locally by a thin catheter threaded through the groin, through the aorta, and the neck, directly into the optic vessels. nanoparticulate chemotherapy – to reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed, which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects. chemoreduction is a combined approach using chemotherapy to initially reduce the size of the tumor, and adjuvant focal treatments, such as transpupillary thermotherapy, to control the tumor. prognosis in the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with more than 90% of sufferers surviving into adulthood. in the uk, around 40 to 50 new cases are diagnosed each year. good prognosis depends upon early presentation of the child in health facility. late presentation is associated with a poor prognosis. survivors of hereditary retinoblastoma have a higher risk of developing other cancers later in life. epidemiology retinoblastoma presents with cumulative lifetime incidence rate of one case of retinoblastoma per 18000 to 30000 live births worldwide. a higher incidence is noted in developing countries, which has been attributed to lower socioeconomic status and the presence of human papilloma virus sequences in the retinoblastoma tissue. almost 80% of children with retinoblastoma are diagnosed before three years of age and diagnosis in children above six years of age is extremely rare. in the uk, bilateral cases usually present within 14 to 16 months, while diagnosis of unilateral cases peaks between 24 and 30 months.

pseudonocardia mongoliensis pseudonocardia mongoliensis pseudonocardia mongoliensis is a bacterium from the genus of pseudonocardia which has been isolated from soil near the khuvsgul lake in khuvsgul in the mongolia. pseudonocardia mongoliensis scientific classification domain: bacteria phylum: actinomycetota class: actinomycetia order: pseudonocardiales family: pseudonocardiaceae genus: pseudonocardia species: p. mongoliensis binomial name pseudonocardia mongoliensisara et al. 2011 type strain atcc 51535, dsm 43089, ifo 15048, imru 1300, imsnu 21327

history of pharmacy in the united states history of pharmacy in the united states the history of pharmacy in the united states is the story of a melting pot of new pharmaceutical ideas and innovations drawn from advancements that europeans shared, native american medicine and newly discovered medicinal plants in the new world. american pharmacy grew from this fertile mixture, and has impacted u.s. history, and the global course of pharmacy. cooley pharmacy, toledo, ohio c. 1900 this article is about the history of pharmacy in the united states. for the development of pharmacy globally, see history of pharmacy. apothecary—an ancient title that, especially in pre-modern or early modern contexts, indicates a broader set of skills and duties than the core role of dispensing medications, like prescribing remedies and even giving some treatments difficult to self-administer, e.g. enemas—have largely been within the "pharmacist" umbrella in the u.s. since the mid-19th century, when edward parrish of the american pharmaceutical association successfully proposed that the apha "consider all the varied pharmaceutical practitioners 'pharmacists'” to better "standardize the field." unlike in the uk, where pharmacists were separated from apothecaries by parliament and the pharmacist had effectively eclipsed the ancient apothecary, appellations and professions have been far more fluid and overlapping in the u.s., especially prior to the regulatory schemes widely adopted in the late 19th century. "apothecary" still crops up as synonym for pharmacist, along with "druggist," and has yet to fall entirely out of use, with some in the u.s. still calling themselves apothecaries. as the pharmacist increasingly became the distinct discipline and tightly defined profession it is today, american pharmacists added their own discoveries and innovations, and played a prominent role in the revolution in medical knowledge in the 19th and 20th centuries and the subsequent development of modern medicine. the history of pharmacy has lagged behind other fields in the history of science and medicine, perhaps because primary sources in the field are sparse. historical inquiries in this area have been few, and unlike the growing number of programs in the history of medicine, history of pharmacy programs remain few in number in the united states. colonial period early developments alongside colonization as soon as columbus started his explorations of the americas in the late 15th century, a european effort to find valuable medicinal plants among the flora of the new world to add to the medical canon got underway. early new world medicines uncovered included guaiacum from the west indies (for coughs, rheumatism and a wide variety of other uses), sassafras from florida, copaiba from brazil, peru balsam and, most famously, cinchona bark from peru, also called "jesuit's bark" in honor of its discoverer, which became the first effective treatment for malaria. the active ingredient of this cinchona bark, quinine, was the primary treatment for malaria well into the 1940s. "about 170 drugs used by the indians of british north america, and perhaps 50 used by the indigenous people of the caribbean, mexico, central and south america" became important enough in the u.s. (as the practitioners of chemistry and pharmacy eventually catalogued, analyzed and understood them) to merit listing in the united states pharmacopoeia (est. 1820) or the national formulary. a living historian interprets a 19th-century apothecary shop for visitors, old salem, north carolina. in the early 1700s, james oglethorpe, founder of the georgia colony, with the financial backing of the worshipful society of apothecaries of london and others, launched an effort to identify and transplant beneficial plant species from the tropical colonies to savannah, georgia. unfortunately for oglethorpe (and all the southern colonists) the expedition that marked this first attempt by an organized group of old world apothecaries to benefit from british north america's potential as a medicine farm never bore fruit. the caribbean expedition's lead investigator, botanist robert miller, was hampered by illness and uncooperative spanish colonials, and all support from london ceased when miller died without much success. pharmacy in eighteenth-century north america the first "drugstores" in north america "appeared in bethlehem, pennsylvania, boston, new york, and philadelphia," with likely proto-drugstores—for example gysbert van imbroch ran a "general store" that sold drugs from 1663 to 1665 in wildwyck, new netherland, today's kingston, new york—preceding the dedicated apothecary shops of the 1700s, and providing a model. because of that model, and customs that stretch back to the first apothecary shops in the medieval arab world most drugstores continued selling more general goods, perfumes, cosmetics, and drinks of all sorts alongside medicines, and still do. non-british influences that the spanish colonials, not the british, were the first in north america to license a pharmacist (in 1769 in new orleans) and were also the first to regulate pharmacy as a separate profession, points to the importance of non-british colonial governments and, indeed, settlers from mainland europe throughout north america, in importing and translating the more modern pharmacy methods, standards and ways of organization and regulation—developing in europe since at least the 1600s—for application in the infant united states. "franco-spanish" louisiana "more clearly reflected development in continental europe." influential milestones achieved in 18th-century louisiana included the february 12th, 1770 edict from the governor in new orleans, don alexandre o'reilly, delineating the responsibilities and boundaries of medicine, surgery and pharmacy and marking the first legal recognition of pharmacy as a distinct discipline in the territories that would become the united states. though the number of pharmacists licensed under this system in spanish louisiana never surpassed the single-digits, o'reilly's decree and its ethical code for pharmacists set an important precedent future developments would build upon. it also brought on-line an important independent pipeline of licensed druggists, albeit a small pipeline, to add to the scant supply of old world apothecaries who had immigrated to set up shop in the colonies. of the few apothecaries imported from europe, those of jesuit training had a long-felt impact in both new spain and new france; so great was jesuit involvement in "care of the sick" in their foreign missions, in fact, they sought and received a papal exemption from the ban on clerics serving in medical roles. two dedicated "pharmacopoles or apothecary brethren" jesuits are listed under the heading "missions of north america in new france" in society of jesus personnel records for the "province of france at the end of the year 1749." jesuit contributions, especially in translating native american ethnobotany into medicines for european use, were highly influential as pharmacy developed in north america. in british north america pharmacist ambrose hunsberger, in his sweeping introduction covering pharmacy's development in the united states prior to the events discussed in his 1923 article on prohibition's impact, "the practice of pharmacy under the volstead act," described pharmacy before its organization (which he places around 1821) in terms that evoke the snake oil salesmen and medicine shows that hit every town, hamlet and village in the country: "...the disorganized system of hawking medicinal remedies which prevailed throughout our thinly populated country. there was no method of protecting the public from fraud through control or regulation of the sale of adulterated and harmful medicinal products, and the credulous citizenry of the young nation was beguiled by every description of fakir and charlatan into buying their fantastic panaceas." hunsberger puts the practice of "more or less methodical" pharmacy in europe "two or three centuries" back, as early as the 16th or 17th century, whereas he places the start of organized pharmacy in the united states with the founding of america's first formal college of pharmacy, the philadelphia college of pharmacy (pcp), in 1821. prior to this, however, the original british colonies retained a much more ad hoc, improvisational approach to pharmacy, and "there were, as was to be expected in a land so vast and so sparsely settled, virtually no limitations as to where or by whom pharmacy could be practiced." lines between the professions of pharmacist, wholesale druggist and physician did not yet exist in the way they would later; "their provinces overlapped, and appellations, which often meant little, frequently changed." dicey and co.'s true daffy's elixir, its 18th century-type embossed medicine bottle seen here (center), was one of the more popular examples of the patent medicines americans imported from across the atlantic in the 18th and 19th centuries.in the colonial and early independence years, necessity demanded a do-it-yourself approach to pharmacy. "most, if not all, american medical men prepared and dispensed their own medications, since fee bills and custom usually provided fees for the medication and not the visit, unless surgery or delivery was involved." thus, oftentimes the doctor was the apothecary and the apothecary the doctor, especially among rural "country doctors" who predominated in this era of farmers with "freeholds" thinly dotting the colonies. "even in the 1760s, when a younger and largely native born cohort of physicians returned from europe, most of the reputable and even famous among the american medici ran their own pharmaceutical business," which, for most doctors for the bulk of the 18th century included mostly medications mixed and dispensed by hand, sometimes augmented with a supply of patent medicines imported from the uk or mainland europe. in the cities, the foundations of commercial pharmacy were slowly building. by 1721 there were "14 apothecary shops in boston," and the first "commissioned pharmaceutical officer in an american army" was the boston apothecary, andrew craigie. a sort of warrior-apothecary, he took part in the battle of bunker hill, june 17, 1775. and "when congress reorganized the medical department of the army in 1777, craigie became the first apothecary general." an engraving depicting an 18th-century chemical laboratory, from william lewis' later work commercium philosophico-technicum (mid-1760s) important early american "apothecary shops" include the one in colonial fredericksburg run by later-brigadier general in the continental army, hugh mercer, (the building is now a museum, and has been "scientifically dated" to 1771 or 1772). and the marshall apothecary (established 1729, open for 96 years) in philadelphia, which was a manufacturer of medicines as well as a retailer, and served as an important supplier throughout the revolutionary war. advertisements from the period indicate "that there were drugstores in virtually all american cities by the end of the eighteenth century." economic historian bernice hamilton describes the 1700s as having "completely transformed" all "the medical professions," explaining that "advances in medical education and science," the emergence of a robust middle class, "as well as the growth of 'a professional feeling'" had greatly changed the socio-economic order by the end of the 18th century. thanks to the ruling in the rose case back in london, apothecaries began 1705 as fully accredited medical professionals who could write prescriptions. hamilton notes "…the apothecaries, once mere tradesmen and the 'servants of the physician,' had become practicing doctors," treating patients directly. these trends spread to the colonies, and though apothecaries never organized into a legally distinct and guilded profession in north america, the rural hinterlands mirrored the prevalence of the apothecary in britain, where "in more remote locales, the apothecary 'was usually the only doctor.'" the pharmacopoeia, which simply lists useful drugs—or sometimes more importantly, drops questionable substances from the canon—"came fully into its own in the early modern age", encompassing roughly the span of history covering the 1500s up until the french revolutions in the late 1700s. but pharmacopoeias mainly offered some basics and compounding instructions. not until the first dispensatories were there books disseminating more comprehensive information on pharmaceuticals: guidance on uses for drugs, how and in what situations to employ them, experience with best practices, etc. "this kind of book, the dispensatory, became something of a british specialty in the late seventeenth and eighteenth century." these dispensatories, chief among them william lewis' the new dispensatory, which debuted in 1753 and was regarded as "the first truly scientific work on pharmacy in the english language," along with a later (1786) book intended as "'an improvement' on lewis," the edinburgh new dispensatory, were undoubtedly formative for pharmacy in british north america. the new dispensatory and edinburgh new dispensatory were printed in many editions and numerous languages within their lifespans (1753-1830) including six printings for american use between them.' the 19th century: american pharmacy emerges the 19th century (1800s) birthed "pharmacy as we know it." and again, pharmacy's development in mainland europe continued to fuel its growth in the young american republic. the philadelphia

college of pharmacy and the birth of organized american pharmacy the philadelphia college of pharmacy (pcp), modeled—at least in concept—after the collége de pharmacie in paris, was aided by european talent in its early, formative years. elias durand, who had served as "pharmacien of the grand army of napoleon i," set up shop in philadelphia in 1825, and "...in connection with the philadelphia college of pharmacy, immediately exerted a strong foreign influence on american pharmacy." according to william procter, jr., durand "directly and indirectly had much to do with the introduction of scientific pharmacy into philadelphia." without teaching at the college, durand still had a big impact by spreading new findings about medicinal plants, making "medicinal chemicals" never before created in the u.s., by training apprentices, like augustine duhamel, who went on to make important contributions and publish in the college journal, and by serving as a role model for foundational figures like procter. hunsberger cites the founding of the philadelphia college of pharmacy (pcp) as "the first step forward in the development of a system of pharmaceutical practice in the united states," with the 1821 "meeting of apothecaries...held in carpenters' hall" (where the continental association had been signed) to set up the first formal college of pharmacy and first pharmacists' association (the philadelphia college of pharmacy) in north america the seminal founding event. on march 13, 1821, "sixty-eight pharmacists signed the constitution of the first pharmaceutical association in the united states," with the symbolism of the carpenters' hall backdrop undeniable: american pharmacy would have a constitution, following in the footsteps of the founding fathers and their constitutional framework. the pcp constitution included a strict code of ethics that would expel anyone from the college who "adulterated" medications or knowingly sold "articles of that character," and provided for a "committee of inspection" to verify the purity, safety and effectiveness of medicines, and a "committee of equity" to arbitrate disputes between member pharmacists. the college, which was founded as an association to advance the discipline of pharmacy not just a university, quickly became a game-changer: in 1824 they published "carefully determined formulas" for the fabrication of (formerly) "secret-formula" patent medicines previously imported from the uk, an essential step toward self-sufficient pharmaceutical manufacturing in the u.s. the philadelphia college of pharmacy also aided the rise of the american pharmaceutical association (apha), which formed at a founding convention congregated in the hall of the college, october 6 to 8, 1852. daniel b. smith, who had long been the pcp's president—ultimately from 1829 to 1854—was elected the apha's first president at the founding convention, and william procter, jr. the first secretary. the "father of american pharmacy" william procter, jr., who graduated from, then taught at the philadelphia college of pharmacy for 20 years, went on to exert so much influence over the formative years of professional pharmacy that he's now widely considered the "father of american pharmacy." procter successfully argued for the establishment of a chair of pharmacy for pharmacist-professors at the pcp in 1844, then wrote "the first american pharmacy textbook," which came to be known as mohr, redwood, and procter's practical pharmacy (1849). the book was not commercially successful, but became a model for subsequent "works of long-lived popularity: edward parrish's an introduction to practical pharmacy (1855-1884), and joseph p. remington's practice of pharmacy (1888-1995 )". procter also led the american journal of pharmacy for 22 years, served 30 years on the u.s.p. revision committee, where he did much to improve the u.s. pharmacopeia, and following five years as the american pharmaceutical association's corresponding secretary, he became the apha's president, leading delegations of american pharmacists in conferences with their counterparts offshore. at the second international congress of pharmacy in paris, france, august 21 to 24, 1867, procter argued forcefully against the "compulsory limitation of pharmacies" (capping their number in a given city or province) under consideration, telling the assembled delegates that, in the u.s., "there is not the slightest obstacle toward a multiplication of drug stores save that a lack of success" and that the american public is "a forceful agent of reform" to keep unscrupulous operators in check. procter's declaration was later seen as a defining statement of "the american way of pharmacy." pharmacy schools and professional organizations spread other major cities on the eastern seaboard followed philadelphia's lead, establishing university training programs, professional associations and colleges of pharmacy that acted as professional associations like the pcp. new york city was among the quickest to follow suit with the new york college of pharmacy, established 1829. as this 1851 notice from the new york daily times exemplifies, pharmacy schools (here the new york college of pharmacy) often were acting as professional associations, or at least promoted pharmacist education and the distinct profession of pharmacist with a guild-like zeal, with this article advertising training for "those who desire to qualify themselves thoroughly as apothecaries" while calling out "inferior druggists" and cautioning that "community ought not to be indifferent" to the character and motives of druggists who "stand aloof from the college." note the use of the term "druggists" to denote medication providers who are not trained pharmacists, while the term "apothecary" is still used as positive synonym. 1860 the first pharmacists arrive on the west coast of america in the newly formed state of california the dr. wilson foskett home and drugstore, opened c. 1897 and now a registered national historic place in idaho county, idaho, shows how pharmaceutical businesses run by a doctor in conjunction with their medical practice, a ubiquitous feature of medicine in 1700s north america, persisted in more rural areas during the 19th century, sometimes even into the 20th century. although the "modern" form of pharmacy was well into its development by the beginning of the 1800s on the east coast and other areas to the west of america, it would take several decades until 1847 before america would finally have control over the furthest south-western continental territories. although there were several legitimate american doctors in los angeles by 1850, none of whom had studied or held degrees in the pharmaceutical sciences, in particular (pharmaceutical formulation) but nonetheless subsequently functioned as "druggist" and as an interesting side note, almost all of whom were not primarily doctors as a main occupation but had other main forms of livelihoods. in ca. 1854 one such case, and also one of the first doctors in l.a., dr. william b. osborn (sometimes spelled as osburn, osbourne, or osbourn), also credited as being the first "drug-store" establisher in los angeles, had turned his business over (to pursue other non-medical endeavors) to dr. james p. mcfarland and john gately downey. the store then under the control of the partnership between mcfarland and downey was then actually run by a dr. alexander hope also a "druggist" as more of an employee of the two men. downey had previously only apprenticed at an apothecary in washington, d.c., until 1846 and later worked as an independent "druggist" in cincinnati, ohio, before finally arriving in california in 1849. once in los angeles, downey's main focus and foremost career ambition was mainly that of a politician rather than that of a schooled, professional apothecary or pharmacist. in 1856 dr. mcfarland had also left the business partnership and california to return home to tennessee. downey eventually sold the "drug-store" to dr. henry m. myles and c.m. small (in order to further pursue his true vocation in politics and go on to become the seventh governor of california from 1860 to 1862) and shortly thereafter dr. myles died and a german immigrant, pharmacist had taken the business over. it was not until c. 1860, which saw the first of two european, immigrant, career pharmacists / apothecaries (both of german descent) who arrived in the newly founded american frontier town of los angeles, california. the first was the pharmacist theodore wollweber (main st. / hall at 59) and in 1861 his only competitor at the time, the second pharmacist adolph junge, who also established his "drug store" in the same temple block (temple street) area on 99 main-st. north of commercial st. and was in operation for about 20 years thereafter until ca. 1880. the future medical pioneer dr. joseph kurtz (german) arrived in l.a. in 1868 at the encouragement and recommendation of close associate adolph junge and would go on to be the first los angeles county medical examiner - coroner from 1870 to 1873 and again from 1876 to 1877 in addition to being one of the founders of the los angeles county medical association in 1871 and the professor of surgery at usc school of medicine (founded in 1885 and in 1999 renamed as keck school of medicine of usc) for 25 years, from 1885 to 1910. also, the later locally well-known (german) pharmacist f.j. gieze came to work as a clerk and colleague following in 1874 for a time thereafter with junge, and would later gain recognition as a trusted pharmacist. around this same time period a dr. j.m. jansco (who specialized in "diseases of children") pediatrician had his practice located at junge's drug-store as well as dr. osborn who had also maintained his office at junge's drug-store from 1865 until his death in 1867. the original prescription book of pharmacist adolph junge bears historical witness to his activity and can still be viewed / researched today in the natural history museum of los angeles county (as part of the "prudhomme papers" archives). the usc college of pharmacy was established in 1905. since the arrival of the first two european-schooled pharmacists in 1860, wollweber and junge, it would then take some 60+ years longer for the retail pharmacy industry as a whole to further develop, "when in 1919 brothers harry and robert borun, along with brother-in-law norman levin, founded borun brothers, a los angeles drug wholesaler". following 10 years later, in 1929, the brothers opened their own los angeles retail outlets under the name thrifty cut rate, which would shortly thereafter be renamed to thrifty drug store and in turn would usher in the age of the modern "drug, sundries & household wares" chain-store model with hired/contracted professional in-house pharmacists. the first store was located at 412 s. broadway in downtown los angeles, just across the street from the original broadway department store. by 1942, they operated 58 chain stores in and around the greater los angeles area, which also served as a business model that most all other large corporate drug store chains would follow. pharmacy and the industrial revolution with the rise of mechanization and mass production, new modes of medication-delivery, among them the tablet (1884), the enteric-coated pill (1884) and the gelatin capsule (first produced on a large scale in 1875 by parke, davis & company, detroit) became practicable. by 1900, most pharmacies stocked the shelves, partially or predominantly, with medicines prefabricated en masse by the growing pharmaceutical industry instead of custom-produced by individual pharmacisti, and the traditional role of the scientifically trained pharmacist to produce medicines increasingly eroded. this shift worried many, raising concerns of quality control, professional irrelevance and more. william procter lamented that, "if the pharmacist becomes a mere dispenser of medicines, 'he relapses into a simple shopkeeper.'” at the "london chemists" drugstore at eighth avenue and 23rd street in manhattan, many foods and medicines are advertised, including ex-lax. photo taken following the gangland killing of mad dog coll, who was using the drugstore phone booth, february 8th, 1932. "soda jerks" dispensing coca-cola at fleeman's pharmacy, atlanta, georgia, circa 1948. this photo documents the first-ever installation of this model of "boat motor"-styled coca-cola dispenser. 20th century 21st century developments background by the turn of the 21st century, several factors gave rise to concerns about a shortage of primary care in the united states . from an aging generation of baby boomers to increasing numbers of physician retirees, it was projected that the united states would be short about 40,000-52,000 physicians by the 2020s. furthermore, "implementation of the affordable care act identifies millions of newly insured patients needing primary care." this shortage was viewed by many as an opportunity to expand the scope of practice of existing healthcare professionals, such as pharmacists. provider status on the federal level, legislation regarding pharmacists' provider status was first introduced to the u.s. house of representatives

in 2014 by representative brett guthrie (r-ky) in the 113th congress. the purpose of the pharmacy and medically underserved areas enhancement act (hr 592) was to amend the social security act to recognize pharmacists as healthcare providers and cover their services in medically underserved communities under medicare part b. this bill failed to pass and was reintroduced in 2015 by representatives brett guthrie (r-ky), g.k. butterfield (d-nc), and todd young (r-in). unfortunately, this bill expired once more at the end of the 114th congress. it was reintroduced for the third time on jan 12, 2017 during the 115th congress by representatives sherrod brown (d-oh), bob casey (d-pa), and chuck grassley (r-ia). the bill was referred to the committee on finance but was not enacted. a number of states are expanding the pharmacist's scope of practice through the implementation of advanced practice pharmacy. in addition to the advanced practice designation, pharmacists in certain practice settings have been granted the ability to perform certain tasks under a collaborative practice agreement (cpa) with a physician. these tasks include the following: assess the patient by gathering subjective and objective information prescribe medications to manage disease states (starting, stopping, or adjusting treatment) order lab tests and interpret the results coordinate patient care with other healthcare professionals develop relationships with patient to allow for ongoing care under this movement for expansion of pharmacists' scope of practice, the state of california instated senate bill 493 in 2014, written by senator ed hernandez, authorizing pharmacists to furnish self-administered hormonal contraceptives, nicotine replacement products, and prescription medications recommended for international travelers not requiring a diagnosis, among other functions. the bill also authorized california-licensed pharmacists to order tests pertaining to the efficacy and safety of patient drug therapies as well as performing patient assessments. this bill was followed by assembly bill 1535 in 2014, granting california pharmacists the authority to furnish naloxone. as an adjunct to sb493 and ab1535, assembly bill 1114 was approved in california in 2016 to establish a fee schedule for pharmacist services under the medi-cal program, allowing for proper reimbursement of the following provided or furnished services: furnishing naloxone hydrochloride for opioid overdose initiating and administering immunizations furnishing self-administered hormonal contraception providing tobacco cessation counseling and furnishing nicotine replacement therapy furnishing travel medications to individuals not requiring a diagnosis in 2019, the california department of health care services (dhcs) established the fee schedule for ab1114, issuing the billing codes needed to implement the pharmacy services outlined by the bill. under ab 1114, pharmacists may bill for services using cpt code 99201 for new patients, cpt code 99212 for established patients, or cpt code 90471 for immunization administration. women in pharmacy in the united states elizabeth gooking greenleaf was the first female apothecary in the thirteen colonies. she is considered to be the first female pharmacist in the united states. mary corinna putnam jacobi graduated from the new york college of pharmacy in 1863, which made her the first woman to graduate from a united states school of pharmacy. susan hayhurst was the first woman to receive a pharmacy degree in the united states, which occurred in 1883. cora dow (1868–1915), a pharmacist in cincinnati, ohio, was the leading female pharmacist of her time, with eleven stores under her name when she died. julia pearl hughes (1873-1950) was the first african-american female pharmacist to own and operate her own drug store. anna louise james (1886-1977) was the first african-american female pharmacist in connecticut.

william b. coley award william b. coley award the william b. coley award for distinguished research in basic and tumor immunology is presented annually by the cancer research institute, to scientists who have made outstanding achievements in the fields of basic and tumor immunology and whose work has deepened our understanding of the immune system's response to disease, including cancer. the first awards were made in 1975 to a group of 16 scientists called the "founders of cancer immunology." in 1993, the award was renamed after william b. coley, a late-nineteenth century surgeon who made the first attempts at the non-surgical treatment of cancer through stimulation of the immune system. for this reason, coley has become known as the "father of cancer immunotherapy." recipients source: 1975: garry abelev000 –edward a. boyse000 –edgar j. foley000 –robert a. good000 –peter a. gorer, frs000 –ludwik gross000 –gertrude henle & werner henle000 –robert j. huebner000 –edmund klein000 –eva klein & george klein000 –donald l. morton000 –lloyd j. old000 –richmond t. prehn000 –hans o. sjögren 1978: howard b. andervont000 –jacob furth000 –earl l. green & margaret c. green000 –walter e. heston000 –clarence c. little000 –george d. snell000 –leonell c. strong 1979: yuang-yun chu000 –zongtang sun000 –zhao-you tang 1983: richard k. gershon 1987: thierry boon000 –rolf m. zinkernagel 1989: howard grey000 –alain townsend000 –emil unanue 1993: pamela bjorkman000 –john kappler000 –philippa marrack000 –alvaro morales000 –jack strominger000 –don wiley 1995: ferdy j. lejeune000 –malcolm a. s. moore000 –timothy springer 1996: giorgio trinchieri 1997: robert l. coffman000 –tim r. mosmann000 –stuart f. schlossman 1998: klas kärre000 –lorenzo moretta000 –ralph m. steinman 1999: james e. darnell, jr.000 –ian m. kerr000 –richard a. lerner000 –george robert stark, frs000 –greg winter 2000: mark m. davis000 –michael pfreundschuh 2001: robert d. schreiber 2002: lewis lanier000 –david h. raulet000 –mark j. smyth 2003: jules a. hoffmann000 –charles janeway000 –bruno lemaitre000 –ruslan medzhitov 2004: shimon sakaguchi000 –ethan m. shevach 2005: for distinguished research in basic and tumor immunology000 –james p. allison 2006: for distinguished research in basic immunology000 –shizuo akira000 –bruce a. beutler000 –for distinguished research in tumor immunology000 –ian h. frazer000 –harald zur hausen 2007: for distinguished research in basic and tumor immunology000 –jeffrey v. ravetch 2008: for distinguished research in basic and tumor immunology000 –michael john bevan, frs 2009: for distinguished research in tumor immunology000 –cornelis j. m. melief000 –for distinguished research in basic immunology (joint prize)000 –frederick w. alt000 –klaus rajewsky 2010: for distinguished research in tumor immunology000 –haruo ohtani000 –wolf herve fridman000 –jérôme galon 2011: for distinguished research in tumor immunology (joint prize)000 –philip d. greenberg000 –steven a. rosenberg 2012: for distinguished research in basic immunology (joint prize)000 –richard a. flavell, frs.000 –laurie h. glimcher000 –kenneth m. murphy000 –for distinguished research in tumor immunology (joint prize)000 –carl h. june000 –michel sadelain 2013: for distinguished research in basic immunology000 –michael b. karin 2014: for distinguished research in tumor immunology (joint prize)000 –tasuku honjo000 – lieping chen000 – arlene sharpe000 – gordon j. freeman000 – 2015: glenn dranoff, for distinguished research in tumor immunology000 –alexander y. rudensky, for distinguished research in basic immunology 2016: ton n. schumacher, for distinguished research in tumor immunology000 –dan r. littman, for distinguished research in basic immunology 2017: thomas f. gajewski, for distinguished research in tumor immunology000 –rafi ahmed, for distinguished research in basic immunology 2018: miriam merad, for distinguished research in basic immunology000 –padmanee sharma, for distinguished research in tumor immunology 2019:for distinguished research in basic immunology000 –zelig eshhar 000 –lawrence e. samelson000 –brian seed000 –arthur weiss000 –for distinguished research in tumor immunology000 –elizabeth m. jaffee 000 –antoni ribas 2020:for distinguished research in basic immunology and tumor immunology000 –andrea ablasser 000 –glen n. barber000 –zhijian j. chen000 –veit hornung000 –russell e. vance000 –

ball and chain inactivation ball and chain inactivation in neuroscience, ball and chain inactivation is a model to explain the fast inactivation mechanism of voltage-gated ion channels. the process is also called hinged-lid inactivation or n-type inactivation. a voltage-gated ion channel can be in three states: open, closed, or inactivated. the inactivated state is mainly achieved through fast inactivation, by which a channel transitions rapidly from an open to an inactivated state. the model proposes that the inactivated state, which is stable and non-conducting, is caused by the physical blockage of the pore. the blockage is caused by a "ball" of amino acids connected to the main protein by a string of residues on the cytoplasmic side of the membrane. the ball enters the open channel and binds to the hydrophobic inner vestibule within the channel. this blockage causes inactivation of the channel by stopping the flow of ions. this phenomenon has mainly been studied in potassium channels and sodium channels. diagram of a voltage-gated ion channel, showing the three states: closed, open, and inactivated. ball and chain inactivation can only happen if the channel is open. discovery electrophysiological evidence the initial evidence for a ball and chain inactivation came in 1977 with clay armstrong and francisco bezanilla's work. the suggestion of a physical basis for non-conductance came from experiments in squid giant axons, showing that internal treatment with pronase disrupted the inactivation phenomenon. this suggested a physical, tethered mechanism for inactivation as the pronase was inferred to degrade the channel blocker and abolish the inactivation process. these experiments also showed that inactivation can only occur after the opening of the channel. this was done by hyperpolarising the membrane, causing the channel to open, and observing a delay in inactivation. inactivation was not observed when the membrane was depolarised (closed). introducing tetraethylammonium (tea) on the intracellular side of the channel was found to mimic inactivation in non-inactivating channels. blockage of the channel by tea is mutually exclusive with peptide-mediate blockage, suggesting that tea competes for an inactivation binding site. molecular evidence mutagenesis experiments have identified an intracellular string of amino acids as prime candidates for the pore blocker. the precise sequence of amino acids that makes up the channel-blocking ball in potassium channels was identified through the creation a synthetic peptide. the peptide was built based on the sequence of a 20 amino acid residue from the drosophila melanogaster's shaker shb protein and applied on the intracellular side of a non-inactivating channel in xenopus oocytes. the peptide restored inactivation to the channel, giving further support to the ball and chain model. in β2 proteins, the first three residues after the initial methionine have been identified as essential for inactivation. the initial residues have a sequence motif of phenylalanine, isoleucine and tryptophan without which inactivation does not occur. modifying the subsequent residues alters the speed and efficacy of inactivation without abolishing it. structural evidence more recently, nuclear magnetic resonance studies in xenopus oocyte bk channels have shed further light on the structural properties of the ball and chain domain. the introduction of the kcnmb2 β subunit to the cytoplasmic side of a non-inactivating channel restored inactivation, conforming to the expected behaviour of a ball and chain-type protein. nmr analysis showed that the ball domain is composed of residues 1–17 and the chain region of residues 20–45. the three amino acids in the middle constitute a flexible linker region between the two functional regions. the ball is at the n-terminus of the β subunit and consists of a disordered part (residues 1–10) and a loop-helix motif formed by a block of amino acids spanning from serine at position 11 to aspartate at position 16. the structure of the chain domain is 4-turn alpha helix structure. structure the ball and chain domains are on the cytoplasmic side of the channel. the most precise structural studies have been carried out in shaker potassium channels, in which the precise residues involved in the process have been identified. the first 19 amino acids of the n-terminus constitute the ball domain. this is made up of 11 hydrophobic amino acids, 8 hydrophilic ones and 4 positively charged ones. the following 60 amino acids constitute the chain domain. modifying the amino acids of the ball while preserving their chemical properties does not disrupt the inactivation mechanism. this suggests that the ball occludes the channel by binding electrostatically rather than covalently. structural studies have shown that the inner pore of the potassium channel is accessible only through side slits between the cytoplasmic domains of the four α-subunits, rather than from a central route as previously thought. the ball domain enters the channel through the side slits and attaches to a binding site deep in the central cavity. this process involves a conformational change, which allows the ball and chain blocker to elongate and reach the inner center of the channel. diagram of a voltage-gated sodium channel, showing the important residues for inactivation in red. the domain structure (i – iv) is further subdivided into segments (s1 – 6). the s4 segment is the voltage sensor, which moves out during depolarisation of the cell membrane. this frees up the alanine and asparagine residues with which the ifmt residues in the ball domain bind to. adapted from goldin, 2003. a positively charged region between the iii and iv domains of sodium channels is thought to act in a similar way. the essential region for inactivation in sodium channels is four amino acid sequence made up of isoleucine, phenylalanine, methionine and threonine (ifmt). the t and f interact directly with the docking site in the channel pore. when voltage-gated sodium channels open, the s4 segment moves outwards from the channel and into the extracellular side. this exposes hydrophobic residues in the s4 and s5 segments which interact with the inactivation ball. the phenylalanine of the ball interacts with the alanine in domain iii's s4-s5 segments and the asparagine in domain iv's s4-s5 segments. this explains why inactivation can only occur once the channel is open. lateral slits are also present in sodium channels, suggesting that the access route for the ball domain may be similar. there is a distinction between direct inactivation and two-step inactivation. direct inactivation, which occurs in shaker potassium channels results from the direct blockage of the channel by the ball protein, while two-step inactivation, thought to occur in bk channels, requires an intermediate binding step. the mechanism of ball-and-chain inactivation is also distinct from that of voltage-dependent blockade by intracellular molecules or peptide regions of beta4 subunits in sodium channels. when these blocks contribute to sodium channel inactivation after channel opening, repolarization of the membrane reverses the block and can causes a resurgent current: a flow of ions between unblocking and closure of the channel. inactivation prevention domain potassium channels have an additional feature in the n-terminus which makes the channels unable to inactivate. the n-type inactivation-prevention (nip) domain counteracts the effect of the peptide ball. channels containing the nip domain behave as mutated non-inactivating channels, as they have no inactivation activity. the effect is thought be stoichiometric, as the gradual introduction of un-tethered synthetic balls to the cytoplasm eventually restores inactivation. effects on neuronal firing the interplay between opening and inactivation controls the firing pattern of a neuron by changing the rate and amount of ion flow through the channels. voltage-gated ion channels open upon depolarization of the cell membrane. this creates a current caused by the flow of ions through the channel. shortly after opening, the channel is blocked by the peptide ball. the β1 subunit aids recovery from inactivation, while β2 accelerates inactivation. the β subunits can also interfere with ball and chain domains by blocking their entry into the channel. this leads to persistent currents, caused by the continued influx of ions. the β3 subunit can increase persistent current in certain sodium channels. implications for disease differences in persistent and resurgent currents have been implicated in certain human neurological and neuromuscular disorders. in epilepsy, mutations in sodium channels genes delay inactivation. this leads to the channel staying open for longer and thus longer-lasting neuronal firing. higher levels of persistent current are observed in epilepsy. this constant, low-level neuronal stimulation has been linked to the seizures typical of this disorder. inactivation anomalies have also been linked to brugada syndrome. mutations in genes encoding the α subunit in cardiac sodium channels affect inactivation. these increase persistent current by interfering with inactivation, though different mutations have opposite effects in inactivation speed. mutations in the α subunit of skeletal muscles are also associated with myotonia. the characteristic muscular hyperexcitation of myotonia is mainly caused by the presence sodium channels which do not inactivate, causing high levels of persistent current in the muscles.

deep branch of ulnar nerve deep branch of ulnar nerve the deep branch of the ulnar nerve is a terminal, primarily motor branch of the ulnar nerve. it is accompanied by the deep palmar branch of ulnar artery. deep branch of ulnar nervesuperficial palmar nerves. (deep branch of ulnar labeled at center right.)detailsfrompalmar branch of ulnar nerveinnervatesdorsal interossei, palmar interossei, lumbricals #3 and 4, adductor pollicis, hypothenar eminenceidentifierslatinramus profundus nervi ulnarista98a14.2.03.048ta26457fma44877anatomical terms of neuroanatomy structure it passes between the abductor digiti minimi and the flexor digiti minimi brevis. it then perforates the opponens digiti minimi and follows the course of the deep palmar arch beneath the flexor tendons. as the deep ulnar nerve passes across the palm, it lies in a fibrous tunnel formed between the hook of the hamate and the pisiform (guyon's canal). function at its origin it innervates the hypothenar muscles. as it crosses the deep part of the hand, it innervates all the interosseous muscles and the third and fourth lumbricals. it ends by innervating the adductor pollicis and the medial (deep) head of the flexor pollicis brevis. it also sends articular filaments to the wrist-joint (following hilton's law)

h4k8ac h4k8ac h4k8ac, representing an epigenetic modification to the dna packaging protein histone h4, is a mark indicating the acetylation at the 8th lysine residue of the histone h4 protein. it has been implicated in the prevalence of malaria. nomenclature h4k8ac indicates acetylation of lysine 8 on histone h4 protein subunit: abbr. meaning h4 h4 family of histones k standard abbreviation for lysine 8 position of amino acid residue (counting from n-terminus) ac acetyl group histone modifications the genomic dna of eukaryotic cells is wrapped around special protein molecules known as histones. the complexes formed by the looping of the dna are known as chromatin. the basic structural unit of chromatin is the nucleosome: this consists of the core octamer of histones (h2a, h2b, h3 and h4) as well as a linker histone and about 180 base pairs of dna. these core histones are rich in lysine and arginine residues. the carboxyl (c) terminal end of these histones contribute to histone-histone interactions, as well as histone-dna interactions. the amino (n) terminal charged tails are the site of the post-translational modifications, such as the one seen in h3k36me3. h4 histone h4 modifications are not as well known as h3's and h4 have fewer variations which might explain their important function. h4k8ac h4k8ac is part of 17 modifications of a group of active promoters. h4k8ac is found more often in active promoters and transcribed regions than other marks. h4k8ac is modified by a different group of enzymes than other h4 lysines. lysine acetylation and deacetylation lysine acetylation proteins are typically acetylated on lysine residues and this reaction relies on acetyl-coenzyme a as the acetyl group donor. in histone acetylation and deacetylation, histone proteins are acetylated and deacetylated on lysine residues in the n-terminal tail as part of gene regulation. typically, these reactions are catalyzed by enzymes with histone acetyltransferase (hat) or histone deacetylase (hdac) activity, although hats and hdacs can modify the acetylation status of non-histone proteins as well. the regulation of transcription factors, effector proteins, molecular chaperones, and cytoskeletal proteins by acetylation and deacetylation is a significant post-translational regulatory mechanism these regulatory mechanisms are analogous to phosphorylation and dephosphorylation by the action of kinases and phosphatases. not only can the acetylation state of a protein modify its activity, but this post-translational modification may also crosstalk with phosphorylation, methylation, ubiquitination, sumoylation, and others for dynamic control of cellular signaling. epigenetic implications the post-translational modification of histone tails by either histone modifying complexes or chromatin remodeling complexes are interpreted by the cell and lead to complex, combinatorial transcriptional output. it is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a particular region. the current understanding and interpretation of histones comes from two large scale projects: encode and the epigenomic roadmap. the purpose of the epigenomic study was to investigate epigenetic changes across the entire genome. this led to chromatin states which define genomic regions by grouping the interactions of different proteins and/or histone modifications together. chromatin states were investigated in drosophila cells by looking at the binding location of proteins in the genome. use of chip-sequencing revealed regions in the genome characterised by different banding. different developmental stages were profiled in drosophila as well, an emphasis was placed on histone modification relevance. a look in to the data obtained led to the definition of chromatin states based on histone modifications. the human genome was annotated with chromatin states. these annotated states can be used as new ways to annotate a genome independently of the underlying genome sequence. this independence from the dna sequence enforces the epigenetic nature of histone modifications. chromatin states are also useful in identifying regulatory elements that have no defined sequence, such as enhancers. this additional level of annotation allows for a deeper understanding of cell specific gene regulation. methods the histone mark acetylation can be detected in a variety of ways: 1. chromatin immunoprecipitation sequencing (chip-sequencing) measures the amount of dna enrichment once bound to a targeted protein and immunoprecipitated. it results in good optimization and is used in vivo to reveal dna-protein binding occurring in cells. chip-seq can be used to identify and quantify various dna fragments for different histone modifications along a genomic region. 2. micrococcal nuclease sequencing (mnase-seq) is used to investigate regions that are bound by well positioned nucleosomes. use of the micrococcal nuclease enzyme is employed to identify nucleosome positioning. well positioned nucleosomes are seen to have enrichment of sequences. 3. assay for transposase accessible chromatin sequencing (atac-seq) is used to look in to regions that are nucleosome free (open chromatin). it uses hyperactive tn5 transposon to highlight nucleosome localisation. clinical significance this mark has been implicated in the prevalence of malaria.

polymorphic toxins polymorphic toxins polymorphic toxins (pts) are multi-domain proteins primarily involved in competition between bacteria but also involved in pathogenesis when injected in eukaryotic cells. they are found in all major bacterial clades. bacteria live in complex multispecies communities such as biofilms and human-associated microbiotas. the dynamics and structure of these communities are greatly influenced by interbacterial competition through the secretion of toxic effectors. bacteria have evolved several systems to outcompete their neighbors by poisoning them through a contact-dependent killing (including effectors of type v and vi secretion systems) or the release of soluble toxins (including colicins) in the environment. definition polymorphic toxins are bacterial exotoxins which share common features regarding their domain architecture. each family of pts is defined by a conserved n-terminal region associated with diverse c-terminal (ct) toxic domains, which can be found in several other pt families. the fact that toxic domains are shared between several families of pts is a hallmark of this category of toxins. a pool of more than 150 distinct toxic domains have been predicted by an in silico study. the most frequent toxic activities found among pts are rnases, dnases, peptidases and protein-modifying activities. pts are involved in killing or inhibiting the growth of bacterial competitors lacking the adequate immunity protein. indeed, in pt systems, a gene encoding a protective immunity protein is always located immediately downstream of the toxin gene. the immunity protein is present in the cytoplasm to protect the toxin producing-cell both from auto-intoxication and from toxin produced by other strains. polymorphic toxin families the most studied pt families encompass colicins, toxic effectors of type v secretion systems, some toxic effectors of type vi secretion systems and mafb toxins. colicins contact-dependent growth inhibition (cdi) systems: cdia toxins rhs toxins "extended" vgrg toxins "extended" hcp toxins mafb toxins

list of orthodontic functional appliances list of orthodontic functional appliances this is a comprehensive list of functional appliances that are used in the field of orthodontics. the functional appliances can be divided into fixed and removable. the fixed functional appliances have to be bonded to the teeth by an orthodontist. a removable functional appliance does not need to be bonded on the teeth and can be removed by the patient. a removable appliance is usually used by patients who have high degree of compliance with their orthodontic treatment. fixed appliances are able to produce very accurate movement in the teeth upper and lower jaw functional expanders both fixed and removable functional appliances can be used to correct a malocclusion in three planes: anterior-posterior, vertical and transverse. in the anterior-posterior dimension, appliances such as class ii and class iii are used. appliances used in transverse dimension are utilized to expand either the maxillary or the mandibular arch. appliances used in the vertical dimension are used to correct open or deep bite. history it is important to note that initially dento-facial orthopaedics was mainly done in europe. the united states was introduced to fixed orthodontics by edward angle. norman william kingsley was the first person to show "jumping the bite" by using an anterior bite plate. hotz then developed the vorbissplate which was a modification of kingsley's plate. wilhelm roux is credited with being the first person who studied the effects of functional forces on orthodontics in 1883. his workings were then used by other dentists studying dental orthopaedics. his teachings became known as roux hypothesis, which karl haupl later expanded upon. the monobloc was developed by pierre robin (surgeon) in 1902 and is considered to be one of the first functional appliances in orthodontics. the monobloc was a modification of ottolengui's removable plate. in 1908, viggo andersen developed the activator appliance. this was the first functional appliance to be widely accepted, especially in europe. this appliance became the "norwegian" system of treatment in orthodontics in the early 1900s. in addition, in 1905 the herbst appliance was introduced by emil herbst. this appliance did not go through much evolution until the 1970s when hans pancherz revived interest in it. in the 1950s, wilhem balters modified andersen's activator appliance and gave the new appliance the name bionator appliance, which was designed to produce forward positioning of the mandible. the positioner appliance was developed by harold kesling in 1944 in order to aid the orthodontic treatment during the finishing stage. the frankel appliance were developed by rolf frankel in 1957 for treatment of class i, ii, iii malocclusions . william clark also developed twin block appliance in 1978 which resembled artur martin schwarz double plates that he developed in the 1950s. fixed appliances distalization appliances "new" distalizer pasin-pin-system barrel fixed 3-way beneslider cd distalizer nance appliance with coil springs carriere motion 3d crickett appliance crozat appliance distal jet fast back appliance first class appliance greenfield molar distalizer (piston appliance) intraoral body molar distalizer (ibmd) jones jig keles slider korn lip bumper k loop appliance lokar appliance mandibular anterior repositioning appliance (mara) molar distalization bow multi-distalizing arch pendulum appliance p-rax molar distalizer simplified molar distalizer (frog) t-rex veltri's distalizer vertical holding appliance wilson's bimetric distalizing arch class ii appliances amoric torsion coil herbst appliance miniscopetm telescoping herbst malu herbst appliance mara appliance jasper jumper eureka spring carriere motion 3d appliance twin force bite corrector churro jumper klapper super spring scandee tubular jumper magnetic telescopic device bionator appliance higgins xbow powerscope 2 forsus appliance ventral telescope ist appliance biopedic appliance lm-activator biobitecorrector fixed lingual mandibular growth modificator (flmgm) class iii appliances quick fix modified tandem appliances (mta) class iii tandem bow carriere® motion™ appliance for class iii correction face mask intrusion appliances rapid molar intruder mesialization appliances mesial jet t bar appliance vertical dimension appliances thurow appliance modified thurow appliance removable appliances components some of the components of removal appliances are retentive in nature. they are usually connecting by an acrylic component known as baseplate. the majority of the appliances include components such as labial bow and adams clasp, both of these components are passive in nature. labial bow is a wire attached to the baseplate which goes around the incisor teeth to provide retention of those teeth. labial bow usually have u-loops at the end to allow it to activate more. adams clasps are used for retention of these removable appliances and are usually fabricated in the molar areas. they are usually manufactured from 0.7mm hard stainless steel wire (hssw), or 0.6mm hssw when planned for deciduous teeth. removal of the appliance is usually performed by holding the bridge of this clasp. other clasps that are usually used are c clasps on canines, southend clasp (on anteriors), ball-ended clasp (primarily for use with the twin block system in the lower anteriors) and plint clasp. active components of removable appliances include springs which provides light forces on a tooth to move it orthodontically. components such as palatal finger springs, buccal canine retractor, z-spring, t-spring, coffin spring, active labial bows (mill's bow or roberts retractor), screws and elastics are all considered to be active components of the removable functional appliances. if a spring is moving one tooth it is made of 0.5mm thick stainless steel wire. the thickness increases to 0.6 or 0.7mm wire if it is to move more teeth or a larger/multi rooted tooth. palatal finger spring - these springs are used to move teeth buccally or lingually. buccal canine retractor - these springs are used to bring a buccally placed canine more lingual. z-spring - this spring is used to move one or two teeth labially t-spring - this spring is used to move teeth labially. coffin spring - this spring is used for expansion and can be substituted instead of a screw in an expansion device. they apply heavy forces and is activated by flattening the spring. class ii appliances twin-block appliance frankel ii mono-bloc appliance rickonator dynamax appliance r-appliance anterior inclined bite plate (aibp) schwarz double plate activator appliance split activator (bow activator) eschler's modification harvold - woodside activator herren's activator (1953) occlus-o-guide®, nite-guide®, and ortho-t® preformed activators/positioners h-activator klammt activator lm-activator lsu activator v-activator schwarz activator medium opening activator expansion and labial segment alignment appliance (elsaa) pam - guias póstero-anterior marinho (brasil) propulsor de rossi (brasil) simões network - sn (brasil) class iii appliances eganhouse class iii appliance frankel iii pam - guias póstero-anterior marinho (brasil) simões network - sn (brasil) transverse appliances frankel i, ii, iv pam - guias póstero-anterior marinho (brasil) simões network - sn (brasil) distalization appliances acrylic cervical occipital anchorage appliance (acco) removable molar distalization splint orthodontic/deprogramming splints dorsal splint superior repositioning splint farrar splint maxillary anterior deprogrammer maxillary flat plane stack bionator luco splint gelb splint/mora modified gelb splint tanner repositioning splint pull forward splint flat occlusal plane splint mini deprogrammer "b" splint (wilkerson style) cranham deprogrammer kois deprogrammer full contact splint with anterior guidance pankey style brucia/face style dawson style spear style

non-insured health benefits non-insured health benefits the non-insured health benefits (nihb) program provides medically necessary coverage for eligible first nations and inuit in canada. it is administered by health canada and covers benefit claims for certain drugs, dental care, vision care, medical supplies and equipment, short-term crisis intervention mental health counselling, and medical transportation. in canada, provinces and territories deliver health care services, which can be accessed by first nations people and inuit. the nihb program provides health-related goods and services not insured by provinces and territories or other private insurance plans. part of a series onhealthcare in canada health canada minister of health health act medicare health transfer non-insured health benefits controlled drugs and substances act history of medicine physicians nursing father of medicare comparison with the us indian hospital hids act topics abortion drug policy euthanasia refugees hiv/aids smoking suicide obesity canada portal health care providers must submit cases to health canada for review to access all vision care, transportation, and counselling, most dental, medical supplies and equipment benefits, and for some drug benefits. coverage of benefits benefits are considered for coverage when: listed on an nihb benefit list or schedule intended for home or other ambulatory care settings prior approval or predetermination is obtained (if required) unavailable through other health or social programs prescribed by a licensed health professional provided by a recognized provider. eligibility non-insured health benefits are available for eligible first nations people and inuit in canada, as well as infants under one year whose parent is eligible. inuit inuit must be canadian residents and must be beneficiaries of the nunavut land claims agreement or beneficiaries of the inuvialuit final agreement. inuit living in nunavut or the northwest territories are automatically registered for the program when they receive their territorial health care card. if they live outside the land claim settlement area they must register with the land claim organization and provide documentation to the government to receive an 'n' number, a personal identification number. first nations first nations people must be canadian residents and a registered indian according to the indian act in order to access nihb programs. controversy health canada asserts the program exists to support first nations people and inuit in reaching an overall health status that is comparable with other canadians. many first nations groups assert that health benefits are an inherent aboriginal and treaty right and are constitutionally protected. only treaty 6 specifically mentions health care, which includes a clause for a medicine chest to be held at the indian agent's home and a clause for emergency help. other treaty negotiations included a discussion about medical services, and doctors were often in attendance when treaty annuities were paid out. the medicine chest clause and historical documentation of treaty discussions have been interpreted by first nations groups to signal a responsibility for the government to provide ongoing healthcare. from the government of canada's perspective, there were no statutory or treaty obligations for providing health care to indigenous people, though health services would be provided when medically necessary. though they recognized that medical care had been written into treaty 6, the government provided health services on humanitarian rather than on legal grounds. drug benefit list the drug benefit list (dbl) is a list of drugs that are covered by the nihb program. updates are issued quarterly and drugs are frequently added or removed from the list. the dbl also provides a tool for doctors and pharmacists to encourage the use of generic drugs.

radalbuvir radalbuvir radalbuvir (inn, also known as gs-9669) is an experimental antiviral drug for the treatment of hepatitis c virus (hcv) infection developed by gilead sciences. radalbuvir acts as an ns5b inhibitor. it is currently in clinical trials. it targets ns5b polymerase. radalbuvirclinical dataother namesgs-9669legal statuslegal status us: investigational new drug identifiers iupac name 5-(3,3-dimethylbut-1-yn-1-yl)-3-methyl)cyclohexyl]-4-methylcyclohex-3-ene-1-carboxamido}thiophene-2-carboxylic acid cas number1314795-11-3pubchem cid53259022chemspider31140180unii273k4v0spcchemical and physical dataformulac30h41no6smolar mass543.72 g·mol−13d model (jsmol)interactive image smiles cc1=cc(cc1)c(=o)n(2cc(cc2)(o)co3cocc3)c4c(sc(c4)c#cc(c)(c)c)c(=o)o inchi inchi=1s/c30h41no6s/c1-20-5-7-21(8-6-20)27(32)31(25-17-24(11-13-29(2,3)4)38-26(25)28(33)34)22-9-14-30(35,15-10-22)19-37-23-12-16-36-18-23/h5,17,21-23,35h,6-10,12,14-16,18-19h2,1-4h3,(h,33,34)/t21-,22-,23-,30+/m0/s1key:muicupwicxunrs-gdccixdysa-n

genodermatosis genodermatosis genodermatosis is a hereditary skin disease with three inherited modes including single gene inheritance, multiple gene inheritance and chromosome inheritance. there are many different types of genodermatosis, the prevalence of genodermatosis ranges from 1 per 6000 people to 1 per 500,000 people. genodermatosis has influence on the texture, color and structure of skin cuticle and connective tissue, specific lesion site and clinical manifestations on the body vary depending on the type. in the spite of the variety and complexity of genodermatosis, there are still some common methods that can help people diagnose. after diagnosis, different types of genodermatosis require different levels of therapy including interventions, nursing interventions and treatments. among that, research of therapy for some new, complex and rare types are still in the developing stage. the impact of genodermatosis not only can be seen in body but also can be seen in all aspects of patients' life, including but not limited to psychological, family life, economic conditions and social activities. accordingly, the patients need treatment, support and help in these areas. genodermatosisother namesgenodermatosesa patient with clouston's hidrotic ectodermal dysplasia, one of the rare genodermatosis.specialtydermatology, medical geneticscausesfamily history; gene mutation; chromosome abnormality hereditary modes genodermatosis is inherited in three modes: single gene inheritance, multiple gene inheritance and chromosome inheritance. single gene (monogenic) single-gene inheritance of genodermatosis refers to the inheritance of a skin disease caused by one genetic abnormality and single gene heredity is divided into four kinds mainly. autosomal dominant inheritance the first kind is autosomal dominant inheritance, in this kind of inheritance, patients can be of any sex and their genodermatosis are often inherited from one of the parents. cases of skin disease that may be inherited in this kind of mode include epidermolysis bullosa simplex (ebs), acute intermittent porphyria, white sponge nevus, ichthyosis, epidermolytic palmoplantar keratoderma, hereditary benign intraepithelial dyskeratosis and so on. autosomal recessive inheritance the second kind is autosomal recessive inheritance, in this kind of inheritance, patients can be of any sex and inbreeding tends to lead to this inheritance. cases of skin disease that may be inherited in this kind of mode include epidermolysis bullosa, xeroderma pigmentosum, acrodermatitis enteropathica, ichthyosis and so on. x-linked dominant inheritance the third kind is x-linked dominant inheritance, in this kind of inheritance, patients can be of any sex. male patients can pass the disease on to their sons and the chances of female patients passing it to their daughters or sons are almost equal. cases of skin disease that may be inherited in this kind of mode include incontinentia pigmenti, focal dermal hypoplasia and so on. x-linked recessive inheritance the last kind is x-linked recessive inheritance, in this kind of inheritance, patients can be of any sex and the prevalence in men is higher than that in women. male patients cannot pass the disease on to their sons. cases of skin disease that may be inherited in this kind of mode include fabry disease, anhidrotic ectodermal dysplasia, dyskeratosis congenita and so on. multiple gene (polygenic) multiple-gene inheritance of genodermatosis refers to the inheritance of a skin disease caused by multiple genetic abnormalities. cases of skin disease that may be inherited in this mode include vitiligo, psoriasis, pemphigus vulgaris, systemic lupus erythematosus and so on. chromosome chromosome inheritance of genodermatosis refers to the inheritance of a skin disease caused by chromosome abnormality. the same disease can be inherited in different modes. for instance, epidermolysis bullosa can be inherited in the mode of autosomal dominant or in the mode of autosomal recessive. types ichthyosis harlequin ichthyosisepidermolysis bullosa simplex genodermatosis has many types, many of which are rare. ichthyosis ichthyosis refers mainly to ichthyosis vulgaris, a common genodermatosis, people with this disease have a fishy, dry skin, which usually appears in early childhood and may disappear in adulthood. the prevalence of ichthyosis vulgaris is high, affecting almost 1 per 250 people. there are also rare types of ichthyosis, such as epidermolytic hyperkeratosis, harlequin ichthyosis and so on. michelin tyre baby syndrome michelin tyre baby syndrome is a rare genodermatosis that occurs at birth, the skin of the patients is stacked symmetrically in layers like the image of the michelin tyre's mascot, which is also how this disease got its name. epidermolysis bullosa epidermolysis bullosa is a rare type of genodermatosis, people with this disease have blisters on their skin and this disease is never completely cured for a lifetime. epidermolysis bullosa is mainly subdivided into four types: dystrophic epidermolysis bullosa, epidermolysis bullosa simplex, junctional epidermolysis bullosa and kindler syndrome. almost 1 in 50,000 people has epidermolysis bullosa. pachyonychia congenita dystrophic epidermolysis bullosaepidermolytic hyperkeratosishidrotic ectodermal dysplasia pachyonychia congenita is a rare type of genodermatosis, its clinical manifestations are abnormal enlargement of fingernails or toenails, excessive or poor palmoplantar keratinization, excessive sweating in the palmar or the plantar. between 5000 and 10000 people in the world have pachyonychia congenita. epidermolytic palmoplantar keratoderma epidermolytic palmoplantar keratoderma often appears at birth and it is almost impossible to be cured completely. the clinical manifestations of this disease include excessive palmoplantar keratinization, the palmar or plantar become yellow divergently with around the edges or abnormally excessive sweating and clinical manifestation appear in a symmetrical form on the body. hereditary benign intraepithelial dyskeratosis hereditary benign intraepithelial dyskeratosis is a rare type of genodermatosis that may occur in infancy and early childhood, its symptoms often appear in the patients' eyes and mouths. the patients' eyes appear red due to the dilatation of superficial vessels and appearance of conjunctival plaques in their eyes, patients may have variable-size, thick, soft and white plaques in their mouth. spring is an acute episode of symptoms, such as itching, erythema, photophobia and so on. epidermolytic hyperkeratosis epidermolytic hyperkeratosis is a rare genodermatosis which is also referred to as disorder of cornification type 3 and bullous congenital ichthyosiform erthroderma, affecting almost 1 per 200,000 - 300,000 people. they also stated that its clinical manifestations often begin at birth with large rashes all over the body, and the patients' skin will be so sensitive that even mild wounds can cause blisters and peeling. potential complications of this disease include electrolyte disturbances, sepsis and so on. hidrotic ectodermal dysplasia hidrotic ectodermal dysplasia is a rare genodermatosis which is also known as clouston syndrome. the patients' nails may be too thick, too brittle, too bent or have different colors, their hair also appear mottled, sparse and other abnormalities. these symptoms often begin when the patient is an infant. diagnostic methods genodermatosis is often rare and varied, but diagnostic methods have some commonalities, the diagnosis of rare genodermatosis is basically divided into six steps: 1. each genodermatosis has different clinical manifestations. people can observe the special features and changes of the skin to judge whether they are sick or not. features will be different in different age groups, so it is necessary to observe and record the special features of the skin in each age group; 2. genodermatosis is a hereditary disease, knowing as much as possible about a detailed and complete family history helps in screening and diagnosis; 3. people can do a detailed physical examination to observe the special features and manifestations of other organs besides skin. it can help to narrow down the disease and make a definitive diagnosis; 4. people can carry out laboratory tests such as skin biopsies with high-tech and precise scientific instruments to have further results; 5. different genodermatosis and their clinical manifestations may be caused by abnormalities in the same gene, and abnormalities in different genes may also lead to the same clinical manifestations. in order to have a definitive diagnosis or identify complex and specific types of genodermatosis, genotype–phenotype correlation needs attention; 6. if the above five steps fails to help people who suspected of having a genodermatosis to obtain the diagnosis result, they should keep all their information such as the diagnosis record and the clinical manifestations at different stages, and continue to record the changes of the body, waiting with a positive attitude, the future medicine may give the answer. therapy the therapy of genodermatosis not only needs to take care of patients' skin, reduce their pain and prevent complications, but also needs to carry out mental support for patients and their families. prevention and care different types of genodermatosis require different kinds of prevention and care. ichthyosis there is no radical therapeutic method for ichthyosis, but some care can ease the symptoms. to prevent skin thickening and hydrate skin, patients can apply a cream containing alpha hydroxy acids and patients can also be treated with antibiotics for subsequent infections. epidermolysis bullosa for epidermolysis bullosa, daily care is important. when treating a wound, keep it clean and reduce friction, the bandages and dressing used must be non-sticky and gentle, and the patient should wear loose clothing to avoid damaging the wound. epidermolytic hyperkeratosis the treatment of epidermolytic hyperkeratosis is mainly control and alleviate symptoms, and good nursing can reduce the incidence of complications like electrolyte disturbances and sepsis. to improve the look and feeling of the skin, patients can apply a cream containing alpha hydroxy acids, glycerol and urea, and if necessary, patients can use antibiotics to control secondary infections. pachyonychia congenita there is no radical therapeutic method for pachyonychia congenita, but some care can ease the symptoms. patients can polish and trim thickened nails, some of them can use retinoids to relieve symptoms but it may increase pain. neurofibromatosis type i selumetinib and trametinib have been shown to reduce and control tumor growth in people with neurofibromatosis type i, reducing the likelihood of malignant lesions. therapeutic methods there are some new and developing genetic therapies available in genodermatosis. in the case of x-linked hypohidrotic ectodermal dysplasia, unborn babies diagnosed with this disease can be treated in their mothers' womb. providing regulatory proteins in the womb during a critical period of infant growth may help correct the development of babies' sweat glands. ustekinumab is a biologic therapy that can be used in a variety of genodermatosis such as congenital ichthyosis, psoriasis, deficiency of interleukin-36 receptor antagonist (ditra) and so on. a new topical method could treat skin abnormalities in rare inherited lipid metabolic diseases. this method obstructs abnormal mevalonate by topical application of lovastatin so that the production and cumulation of poisonous metabolic intermediates can be inhibited as much as possible and takes the place of the lacking lipid in the skin by topical application of cholesterol. the idea that similar treatments could be developed for other genodermatosis was also pointed out at the annual conference of the european society of dermatology and venereology. for epidermolysis bullosa, a method called crispr can be used to treat this disease by gene analysis, modification and substitution, but the method is ethically controversial because it consents to editing genes highly. treatments for some rare diseases are still being studied. the therapy of genodermatosis requires the updating of technology, and the development of technology depends on the continuous understanding of the mechanism of the disease. research on the treatment of genodermatosis is at a positive stage of development. effects genodermatosis affects patients in many ways. genodermatosis is a kind of skin disease, it affects the texture, color and structure of the cuticle and connective tissue of the skin, some of which can cause abnormalities in other organs. on the social side, because the genodermatosis makes the patients' skin and appearance different from the ordinary people and makes them have limitations in some activities, they more or less encounter obstacles in the process of making friends, seeking a mate, going to school and entering the workplace. difficulties in communicating with others as well as worldly prejudice may affect their mental health. patients are also affected by genodermatosis in terms of family life. because of the behavioral disorders and treatment of certain genodermatosis, families need to spend more time caring for the patient, and the patient may have more concerns and considerations about procreating children due to the disease. in terms of economy, the treatment of genodermatosis is not a simple and short process, which will generate additional family expenses and increase economic pressure on patients and their families.

mucilaginibacter gossypii mucilaginibacter gossypii mucilaginibacter gossypii is a gram-negative, non-motile and plant-growth-promoting bacterium from the genus of mucilaginibacter which has been isolated from rhizosphere soil from cotton plants. mucilaginibacter gossypii scientific classification domain: bacteria phylum: bacteroidota class: sphingobacteriia order: sphingobacteriales family: sphingobacteriaceae genus: mucilaginibacter species: m. gossypii binomial name mucilaginibacter gossypiimadhaiyan et al. 2010 type strain kctc 22380, ncimb 14470, gh-67

spurling's test spurling's test the spurling test is a medical maneuver used to assess nerve root pain (also known as radicular pain). the patient rotates their head to the affected side and extends their neck, while the examiners applies downward pressure to the top of the patient's head. a positive spurling's sign is when the pain arising in the neck radiates in the direction of the corresponding dermatome ipsilaterally. it is a type of cervical compression test. spurling's testpurposeassess nerve root pain patients with a positive spurling's sign can present with a variety of symptoms, including pain, numbness and weakness. in addition to the clinical history, the neurological examination may show signs suggesting a cervical radiculopathy. indications the spurling test is used during a spinal or neck examination to aid in the diagnosis and assessment of cervical radiculopathy. it should be used to assess patients with radicular symptoms. the results of this test can guide a clinician when considering further imaging and necessary steps needed to make a proper diagnosis. however, caution should be used when assessing patients with acute cervical injuries, critically ill patients, and those with other neoplastic or infectious processes. cervical instability is also a reason to avoid performing this medical maneuver. accuracy spurling's test is somewhat specific when used for individuals with an abnormal electromyogram study and is a relatively sensitive physical examination maneuver in diagnosing cervical spondylosis or acute cervical radiculopathy. it is not a very sensitive test when used for individuals without classic radicular signs suggestive of cervical radiculopathy. in 2011, one study evaluated 257 patients with clinical cervical radiculopathy and correlated ct scan findings with clinical exam findings using the spurling's test. the spurling's test was 95% sensitive and 94% specific for diagnosing nerve root pathology. in another study done in the late 1900s, 255 patients were examined using a spurling test and afterwards received an electrodiagnostic examination. the study results showed the spurling test was 30% sensitive, and 93% specific for finding cervical radiculopathy diagnosed by electrodiagnostic examination. the conclusions drawn from this study demonstrate clinical utility of the spurling test to confirm cervical radiculopathy rather than for screening purposes. overall, there continues to be limited data on the specificity and sensitivity of the spurling test.

spike: the virus vs. the people - the inside story spike: the virus vs. the people - the inside story spike: the virus vs. the people - the inside story is a 2021 book by british medical researcher jeremy farrar and british indian science journalist anjana ahuja. the book gives farrar's account of the covid-19 pandemic, his view of government policy as a member of britain's scientific advisory group for emergencies, and his fears about the virus's origins. first edition

racal suit racal suit a racal suit (also known as a racal space suit) is a protective suit with a powered air-purifying respirator (papr). it consists of a plastic suit and a battery-operated blower with hepa filters that supplies filtered air to a positive-pressure hood (also known as a racal hood). racal suits were among the protective suits used by the aeromedical isolation team (ait) of the united states army medical research institute of infectious diseases to evacuate patients with highly infectious diseases for treatment. racal suits used at the united states army medical research institute of infectious diseases originally, the hood was manufactured by racal health & safety, a subsidiary of racal electronics located in frederick, maryland, the same city where ait was based. the division of racal responsible for the suit's manufacture later became part of 3m, and the respirator product line was branded as 3m/racal. components details of the suit componentsthe main body of the protective suit consists of a lightweight coverall made of polyvinyl chloride (pvc), rubber gloves, and rubber boots. originally, the coverall was in a bright orange color, and the racal suit was known as an orange suit. the hood is a separate component from the protective suit. the racal hood is a type of papr consisting of a transparent hood connected to a respirator, which is powered by a rechargeable battery. the respirator has three hepa filters that are certified to remove 99.7% of particles of 0.03 to 3.0 microns in diameter. the filtered air is supplied at the rate of 170 l/min to the top of the hood under positive pressure for breathing and cooling. the air is forced out through an air exhaust valve at the base of the hood. a two-way radio system is installed inside the hood for communication. the ait later switched from using transparent bubble hoods to butyl rubber hoods. procedures the main purpose of the ait was to evacuate a patient from the field to a specialized isolation unit. as part of their procedures, ait members wore racal suits while transporting the patients. they were trained to take a bathroom break before suiting up, since the time they would be in the suits could be 1 hour and 45 minutes for a training session and 4 to 6 hours for an actual mission. the patient was placed in a mobile stretcher isolator during transit. after the patient was delivered to the isolation unit, the members would leave the unit and enter into an anteroom with an airlock. they were then sprayed with glutaraldehyde solution to disinfect before the suit was cut away and sent to an on-site incinerator for complete destruction. similar suits the racal suit is similar to other positive pressure personnel suits such as the chemturion, in that there is an air supply to provide positive pressure to reduce the chance of airborne agents entering the suit. however, several components are different. the positive pressure section for the racal suit is only available at the hood. the air supply for racal suits comes from a battery-operated blower that makes the suit portable, whereas other suits must be connected to an air hose that is part of the building, such as in biosafety level 4 laboratories. the main body part of the racal suit is also more lightweight and can be disposed of by burning after use. in popular culture racal suits were used in films such as outbreak in 1995. the term is also used in literature related to situations with infectious diseases, such as in the hot zone: a terrifying true story, infected, and executive orders.

anterior chamber of eyeball anterior chamber of eyeball the anterior chamber (ac) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. hyphema, anterior uveitis and glaucoma are three main pathologies in this area. in hyphema, blood fills the anterior chamber as a result of a hemorrhage, most commonly after a blunt eye injury. anterior uveitis is an inflammatory process affecting the iris and ciliary body, with resulting inflammatory signs in the anterior chamber. in glaucoma, blockage of the trabecular meshwork prevents the normal outflow of aqueous humour, resulting in increased intraocular pressure, progressive damage to the optic nerve head, and eventually blindness. anterior chamber of eyeballanterior part of human eye, with anterior chamber at right.schematic diagram of the human eye.detailsidentifierslatincamera anterior bulbi oculiacronym(s)acmeshd000867ta98a15.2.06.003ta26792fma58078anatomical terminology the depth of the anterior chamber of the eye varies between 1.5 and 4.0 mm, averaging 3.0 mm. it tends to become shallower at older age and in eyes with hypermetropia (far sightedness). as depth decreases below 2.5 mm, the risk for angle closure glaucoma increases. clinical significance depth measurement determining the anterior chamber depth (acd) is important in estimating the risk of angle closure glaucoma. there are various method of measuring acd, including examination through a slit lamp, ultrasound and scheimpflug photography. these methods require sophisticated examination equipment and expertise. a simpler clinical method of quantitatively estimating acd using smartphone photography (ez ratio) was developed by dr ehud zamir from the centre for eye research australia, the university of melbourne, and published in 2016. ez ratio method the ez ratio method is one way to calculate the estimated anterior chamber depth. to start, the patient looks at a target in the distance with one eye covered. the examiner takes a digital photograph of the open, examined eye, from the side, perpendicular to the visual axis (a profile photograph). the following parameters then need to be measured in the photograph, using a personal computer or a smartphone (figures 1,2): 1. the pixel distance between the limbus (the junction between clear cornea and white sclera) and the front of the cornea. this distance is referred to as z. 2. the pixel distance between the limbus and the centre of the pupil. this distance is referred to as e. e:z ratio is the arithmetic ratio between e and z. this ratio is linearly correlated with the depth of the anterior chamber with the following equation: anterior chamber depth (expressed in millimetres) = -3.3 x ez ratio + 4.2 this estimate has been shown to be accurate with a 95% confidence interval of +/– 0.33 mm error, when compared to measurements of the anterior chamber depth by scheimpflug photography. figure 1. calculating ez ratio. figure 2. different anterior chamber depths as seen from the lateral perpendicular (profile) view. the more forward the pupil is, the shallower the anterior chamber. in the leftmost photo, the pupil is relatively posterior (set back), indicating an ez ratio of < 0.5 and an anterior chamber deeper than 2.5 mm. in the middle photo, the pupil is midway between the sclera posteriorly and the cornea anteriorly, indicating an ez ratio of 0.5, and a medium chamber depth of about 2.5 mm. in the rightmost photo, the pupil is very anterior (forward), indicating an ez ratio of more than 0.5 and a shallow anterior chamber of less than 2.5 mm. associated immune deviation one peculiar feature of the anterior chamber is dampened immune response to allogenic grafts. this is called anterior chamber associated immune deviation (acaid), a term introduced in 1981 by streilein et al. this phenomenon is relevant to the fact that the eye is considered an "immune privileged site", like the brain and the testis. pathology glaucoma hyphema hypopyon intraocular pressure ocular hypertension additional images anterior chamber angle cross-section imaged by an sd-oct. gonioscopy of the anterior chamber angle gonioscopy of the anterior chamber angle. labeled structures: 1. schwalbe's line, 2. trabecular meshwork (tm), 3. scleral spur, 4. ciliary body, 5. iris anterior chamber iol structures of the eye labeled this image shows another labeled view of the structures of the eye

simtuzumab simtuzumab simtuzumab (inn; formerly gs 6624) is a humanized monoclonal antibody designed for the treatment of fibrosis. it binds to loxl2 and acts as an immunomodulator. in january 2016, gilead sciences terminated its phase 2 clinical study in patients with idiopathic pulmonary fibrosis (ipf) due to lack of efficacy. simtuzumabmonoclonal antibodytypewhole antibodysourcehumanizedtargetloxl2clinical dataatc codenoneidentifierscas number1318075-13-6iuphar/bps8412chemspidernoneunii11z5aiu653chemical and physical dataformulac6558h10134n1736o2037s50molar mass147492.33 g·mol−1

waldmann disease waldmann disease waldmann disease is a rare disease characterized by enlargement of the lymph vessels supplying the lamina propria of the small intestine. although its prevalence is unknown, it being classified as a "rare disease" means that less than 200,000 of the population of the united states are affected by this condition and its subtypes. waldmann diseaseother nameswaldmann's disease, primary intestinal lymphangiectasia signs and symptoms signs and symptoms of the disease include diarrhea, nausea, swelling of the legs, protein-losing enteropathy, immunodeficiency and loss of lymphatic fluid into the intestines. it is usually diagnosed before the patient is 3 years old, but it is sometimes diagnosed in adults. pathophysiology the illness is usually caused by lymphatic vessels that were misshaped at birth, causing obstruction and subsequent enlargement. the condition can also be a result of other illnesses such as constrictive pericarditis and pancreatitis. diagnosis the disease is diagnosed by doing a biopsy of the affected area. severity of the disease is then determined by measuring alpha1-antitrypsin proteins in a stool sample. management once the main cause of the disease is treated, a diet of low-fat and high-protein aliments, supplemental calcium and certain vitamins has been shown to reduce symptom effects. this diet, however, is not a cure. if the diet is stopped, the symptoms will eventually reappear. history the disease was first reported in 1961 by t.a. waldmann. he described 18 cases of patients having a low level 131i-albumin. biopsies of the small intestine were examined under the microscope and found various levels of dilatation of the lymph vessels.

ectodermal dysplasia ectodermal dysplasia ectodermal dysplasia (ed) is a group of genetic syndromes all deriving from abnormalities of the ectodermal structures.: 570 more than 150 different syndromes have been identified. ectodermal dysplasiaectodermal dysplasia. this image shows peg-shaped teeth and sparse hair.specialtymedical genetics despite some of the syndromes having different genetic causes, the symptoms are sometimes very similar. diagnosis is usually by clinical observation, often with the assistance of family medical histories so that it can be determined whether transmission is autosomal dominant or recessive. ectodermal dysplasias are described as "heritable conditions in which there are abnormalities of two or more ectodermal structures such as the hair, teeth, nails, sweat glands, salivary glands, cranial-facial structure, digits and other parts of the body." presentation hair individuals affected by an ed syndrome frequently have abnormalities of the hair follicles. scalp and body hair may be thin, sparse, and very light in color, even though beard growth in affected males may be normal. the hair may grow very slowly or sporadically and it may be excessively fragile, curly, or even twisted. kinky hair is also a possibility. nails fingernails and toenails may be thick, abnormally shaped, discolored, ridged, slow-growing, or brittle. the cuticles may be prone to infections. skin the skin may be lightly pigmented. skin sustaining injury may grow back permanently hypo-pigmented. in some cases, red or brown pigmentation may be present. skin can be prone to rashes or infections and can be thick over the palms and soles. care must be taken to prevent cracking, bleeding, and infection. sweat glands individuals affected by certain ed syndromes cannot perspire. their sweat glands may function abnormally or may not have developed at all because of inactive proteins in the sweat glands. without normal sweat production, the body cannot regulate temperature properly. therefore, overheating is a common problem, especially during hot weather. access to cool environments is important. dental abnormalities in a 5-year-old girl from north sweden family who had various symptoms of autosomal dominant hypohidrotic ectodermal dysplasia (hed): a) intraoral view. note that the upper incisors have been restored with composite material to disguise their original conical shape. b) orthopantomogram showing absence of ten primary and eleven permanent teeth in the jaws of the same individual. salivary glands several studies have examined salivary flow rate in individuals and found parotid and submandibular salivary flow ranging from 5 to 15 times lower than average. this is consistent with the salivary glands being of ectodermal origin, although some findings have suggested that there is also mesodermal input. teeth the development of tooth buds frequently results in congenitally absent teeth (in many cases a lack of a permanent set) and/or in the growth of teeth that are peg-shaped or pointed. the enamel may also be defective. cosmetic dental treatment is almost always necessary and children may need dentures as early as two years of age. multiple denture replacements are often needed as the child grows, and dental implants may be an option in adolescence, once the jaw is fully grown. nowadays the option of extracting the teeth and substituting them with dental implants is quite common. in other cases, teeth can be crowned. orthodontic treatment also may be necessary. because dental treatment is complex, a multi-disciplinary approach is best. other features people with ed often have certain cranial-facial features which can be distinctive: frontal bossing is common, longer or more pronounced chins are frequent, broader noses are also very common. sunken cheeks, wrinkled hyper pigmented periorbital skin , thick everted protuberant lips are also seen in ed cases .in some types of ed, abnormal development of parts of the eye can result in dryness of the eye, cataracts, and vision defects. professional eye care can help minimize the effects of ed on vision. similarly, abnormalities in the development of the ear may cause hearing problems. respiratory infections can be more common because the normal protective secretions of the mouth and nose are not present. precautions must be taken to limit infections.. genetics ed can be classified by inheritance (autosomal dominant, autosomal recessive and x-linked) or by which structures are involved (hair, teeth, nails and/or sweat glands). there are several different types with distinct genetic causes: hay–wells syndrome (rapp–hodgkin syndrome) and eec syndrome are all associated with tp63. hypohidrotic ectodermal dysplasia can be associated with eda, edar and edaradd. margarita island ectodermal dysplasia is associated with pvrl1. ectodermal dysplasia with skin fragility is associated with pkp1. clouston's hidrotic ectodermal dysplasia is associated with gjb6. naegeli syndrome/dermatopathia pigmentosa reticulariss is associated with krt14. pachyonychia congenita is caused by multiple keratins. focal dermal hypoplasia is associated with porcn. ellis–van creveld syndrome is associated with evc. palmoplantar ectodermal dysplasia refers to several different conditions selectively affecting the hands and feet. cortes lacassie syndrome is characterized by seizures, abnormalities in nails, hair and teeth, and malformed hands and feet. diagnosis in terms of the clinical evaluation, clinical features are the classification method treatment management for this condition is symptom specific society and culture notable cases michael berryman, american actor with hypohidrotic ectodermal dysplasia melanie gaydos, american model levi hawken, new zealand skateboarder and artist who became well known in 2011 in new zealand for the "nek minnit" viral video on youtube cory devante williams, more commonly known as coryxkenshin on youtube, american youtuber.

nerve of latarjet nerve of latarjet the nerve of latarjet or the posterior nerve of the lesser curvature is a branch of the posterior vagal trunk which supplies the pylorus. it is cut in selective vagotomy and preserved in highly selective vagotomy. it functions by increasing peristalsis and relaxing the sphincter, thus draining the contents of the stomach into the first part of duodenum. if damage occurs to this nerve, it can cause retention syndrome.

healthcare in wiltshire healthcare in wiltshire healthcare in wiltshire, england, is the responsibility of the integrated care board (icb) for bath and north east somerset, swindon and wiltshire. history prior to 2022 victoria hospital in swindon was established in 1887, at first with 12 beds, increasing to 22 by 1904; it finally closed in 2007. from 1947 to 1974, nhs services in wiltshire were managed by the south-west metropolitan regional hospital board (covering new sarum, wilton, and the rural districts of amesbury, mere and tisbury, and salisbury and wilton), by the south-western board (responsible for the lyme regis area) and by oxford regional hospital board (marlborough and swindon). in 1965 a new board was formed for wessex which covered the boroughs of new sarum and wilton and the rural districts of amesbury, mere and tisbury, and salisbury and wilton. in 1974 the boards were abolished and replaced by regional health authorities, with the whole of wiltshire coming under the wessex rha. regions were reorganised in 1996 and dorset came under the south and west regional health authority. wiltshire had three area health authorities: wiltshire, salisbury and swindon, from 1974 until 1994 when it was united into one authority for bath and wiltshire. regional health authorities were reorganised and renamed strategic health authorities in 2002; wiltshire was part of avon, gloucestershire and wiltshire sha. in 2006 regions were again reorganised and wiltshire came under nhs south west until that was abolished in 2013. there was one primary care trust for the county. bath, swindon and wiltshire formed a sustainability and transformation plan area in march 2016, chaired from december 2019 by stephanie elsy, a former leader of southwark council. commissioning prior to 2022 bath and north east somerset, swindon and wiltshire clinical commissioning group (ccg) was formed in april 2020 by merging three ccgs which covered bath and north east somerset, swindon and wiltshire. at that time the combined ccg had an annual budget of £1.3 billion and served a population of 934,000 across an area of 1,511 square miles (3,910 km2). the ccg's headquarters were in chippenham and it had offices in bath, devizes and swindon. its chief executive was tracey cox, formerly a manager at bath and north east somerset primary care trust and then the corresponding ccg. swindon ccg agreed in june 2015 to fund a community therapy team at the prospect hospice, providing occupational and physiotherapy at home, in order to reduce pressure on hospital beds. wiltshire ccg expected a £23 million funding gap in 2016/17 and to miss its financial target by £4.8m in 2015/6. consequently it capped the amount of planned care delivered in hospitals, limited the number of funded procedures, and recovered money from drug companies. since 2022 in july 2022, integrated care boards (icbs) were established throughout nhs england to plan and deliver health and care services, replacing ccgs. wiltshire is covered by the board for bath and north east somerset, swindon and wiltshire, which is branded as bsw together. stephanie elsy continued in the new role of icb chair, and sue harriman – formerly a nurse and chief executive of solent nhs trust – was appointed as the first chief executive of the icb. the icb is required to work with local authorities to create an integrated care partnership (icp) committee, to include local organisations such as the voluntary sector and social enterprises. the icp works on prevention, wider social and economic factors affecting health, and reducing health inequalities. the first icp chair is richard clewer, leader of wiltshire council. primary care as of april 2020, there were 22 gp practices in swindon and 49 in wiltshire; the ccg's 94 practices are grouped into 23 primary care networks. out-of-hours services are provided by medvivo. community care community child health services, including children’s specialist community nursing, health visiting and speech and language therapy, have been run by virgin care since april 2016. they were formerly run by five separate nhs organisations. swindon council and swindon clinical commissioning group set up a contract with seqol, a newly formed community interest company, to provide a variety of adult social care services in 2011. the council paid £9.4 million and the ccg £17 million a year. in march 2016, they decided not to renew the contract because of performance problems: in 2014-15 the average daily rate, per 100,000 population, of delayed hospital discharges from hospital attributable to social care was 6.9 in swindon, compared to a national average of 3.7. seqol requested to end their involvement without completing the 12 months' notice provided in the contract, and from october 2016, great western hospitals nhs foundation trust were responsible for these services. seqol's staff returned to employment by the hospital or the council, and the company intended to cease trading. from april 2022, community cardiology services in wiltshire are provided by wiltshire health and care llp, who already ran community hospitals in the county. these services include diagnostics, assessment and advice, and rehabilitation of heart failure patients. mental health avon and wiltshire mental health partnership nhs trust (awp) provides adult mental health and related services in wiltshire and the former county of avon, an area centered on bristol. from april 2010, oxford health nhs foundation trust has provided tiers 3 and 4 of child and adolescent mental health services (camhs) in wiltshire and bath and north east somerset following a competitive tender. previously this service had been operated by three providers, though primarily awp. the service is jointly funded by the nhs and local authorities. hospital provision great western hospitals nhs foundation trust and salisbury nhs foundation trust are the main acute providers in the county. in june 2018 they agreed to form an alliance with royal united hospitals bath nhs foundation trust, as they provide most of the hospital services in the bath, north east somerset, swindon and wiltshire sustainability and transformation plan area. community hospitals at chippenham, devizes, melksham, marlborough (savernake), trowbridge and warminster are run since 2016 by wiltshire health and care llp. the chippenham and trowbridge hospitals have minor injuries units.

ximelagatran ximelagatran ximelagatran (exanta or exarta, h 376/95) is an anticoagulant that has been investigated extensively as a replacement for warfarin that would overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy. in 2006, its manufacturer astrazeneca announced that it would withdraw pending applications for marketing approval after reports of hepatotoxicity (liver damage) during trials, and discontinue its distribution in countries where the drug had been approved (germany, portugal, sweden, finland, norway, iceland, austria, denmark, france, switzerland, argentina and brazil). ximelagatranclinical datatrade namesexantapregnancycategory uncategorized routes ofadministrationoral (tablets)atc codeb01ae05 (who) legal statuslegal status withdrawn from market pharmacokinetic databioavailability20%metabolismto melagatranelimination half-life3–5 hoursexcretionrenal (80%)identifiers iupac name ethyl 2-methylcarbamoyl]azetidin-1-yl]-2-oxo-ethyl]amino]acetate cas number192939-46-1 npubchem cid9574101iuphar/bps6381drugbankdb04898 ychemspider7848559 yunii49hfb70472keggd01981 ychemblchembl522038 ycomptox dashboard (epa)dtxsid5049075 chemical and physical dataformulac24h35n5o5molar mass473.574 g·mol−1 (429 g/mol after conversion)3d model (jsmol)interactive image smiles o=c(ncc1ccc(c(=n\o)\n)cc1)3n(c(=o)(ncc(=o)occ)c2ccccc2)cc3 inchi inchi=1s/c24h35n5o5/c1-2-34-20(30)15-26-21(17-6-4-3-5-7-17)24(32)29-13-12-19(29)23(31)27-14-16-8-10-18(11-9-16)22(25)28-33/h8-11,17,19,21,26,33h,2-7,12-15h2,1h3,(h2,25,28)(h,27,31)/t19-,21+/m0/s1 ykey:zxibcjhyvwyiki-pzjwppbqsa-n y ny (what is this?) (verify) method of action ximelagatran, a direct thrombin inhibitor, was the first member of this class that can be taken orally. it acts solely by inhibiting the actions of thrombin. it is taken orally twice daily, and rapidly absorbed by the small intestine. ximelagatran is a prodrug, being converted in vivo to the active agent melagatran. this conversion takes place in the liver and many other tissues through hydrolysis and dehydroxylation (replacing the ethyl and hydroxyl groups with hydrogen). the conversion of ximelagatran to melagatran. this conversion includes dealkylation and dehydroxylation. uses ximelagatran was expected to replace warfarin and sometimes aspirin and heparin in many therapeutic settings, including deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke. the efficacy of ximelagatran for these indications had been well documented, except for non valvular atrial fibrillation. an advantage, according to early reports by its manufacturer, was that it could be taken orally without any monitoring of its anticoagulant properties. this would have set it apart from warfarin and heparin, which require monitoring of the international normalized ratio (inr) and the partial thromboplastin time (ptt), respectively. a disadvantage recognised early was the absence of an antidote in case acute bleeding develops, while warfarin can be antagonised by prothrombin complex concentrate and/or vitamin k and heparin by protamine sulfate. side effects ximelagatran was generally well tolerated in the trial populations, but a small proportion (5–6%) developed elevated liver enzyme levels, which prompted the fda to reject an initial application for approval in 2004. the further development was discontinued in 2006 following reports of hepatotoxicity. subsequent analysis of phase 2 clinical study data using extreme value modelling showed that the elevated liver enzyme levels observed in phase 3 clinical studies could have been predicted; if this had been known at the time, it might have affected decisions on future development of the compound. a chemically different but pharmacologically similar substance, azd-0837, was developed by aztrazeneca for similar indications. it is a prodrug of a potent, competitive, reversible inhibitor of free and fibrin-bound thrombin called arh0637. the development of azd-0837 has been discontinued. due to a limitation identified in long-term stability of the extended-release azd-0837 drug product, a follow-up study from assure on stroke prevention in patients with non-valvular atrial fibrillation, was prematurely closed in 2010 after 2 years. there was also a numerically higher mortality against warfarin. in a phase 2 trial for af the mean serum creatinine concentration increased by about 10% from baseline in patients treated with azd-0837, which returned to baseline after cessation of therapy.

cabinet secretary for nhs recovery, health and social care cabinet secretary for nhs recovery, health and social care the cabinet secretary for nhs recovery, health and social care (scottish gaelic: rùnaire a’ chaibineit airson slànachadh sns, slàinte agus cùram sòisealta), commonly referred to as the health secretary (scottish gaelic: rùnaire na slàinte), is a cabinet position in the scottish government. the cabinet secretary is responsible for the health and social care directorates and nhs scotland. cabinet secretary for nhs recovery, health and social carescottish gaelic: rùnaire a’ chaibineit airson slànachadh sns, slàinte agus cùram sòisealtaincumbentmichael mathesonsince 29 march 2023health and social care directoratesnhs scotlandscottish governmentscottish cabinetstylecabinet secretary (formal) health secretary (informal)member ofscottish parliamentscottish cabinetreports tothe first minister of scotland and the scottish parliamentseatedinburghappointerfirst ministerterm lengthnone the cabinet secretary is appointed by the first minister following a resignation or cabinet reshuffle.inaugural holdersusan deacon minister for health and community careformationmay 1999deputymaree todd (minister for public health, women's health and sport) kevin stewart (minister for mental wellbeing and social care)salary£118,511 per annum (2023)(including £67,662 msp salary)websitewww.gov.scot the cabinet secretary is assisted by the minister for public health, women's health and sport, maree todd and minister for mental wellbeing and social care, kevin stewart. the current cabinet secretary is michael matheson. this article is part of a series within thepolitics of the united kingdom on thepolitics of scotland the crown the monarch charles iii heir apparent william, duke of rothesay prerogative royal family succession privy council union of the crowns balmoral castle holyrood palace scottish republicanism executive scottish government yousaf government first minister the rt hon humza yousaf msp deputy first minister shona robison msp cabinet secretaries junior ministers directorates scottish budget taxation executive agencies public bodies bute house st andrew's house legislature scottish parliament sixth session presiding officer alison johnstone msp primary legislation statutory instrument committees first minister's questions scotland act 1998 (2012 act · 2016 act) eu continuity act 2020 law and justice justice secretary keith brown msp lord advocate dorothy bain kc lord president the rt hon lord carloway kc pc scots law udal law courts judiciary scottish courts and tribunals service crown office and procurator fiscal service police scotland scottish prison service advocate general solicitor general elections and referendumsscottish parliament elections 1999 · 2003 · 2007 · 2011 · 2016 · 2021 · next united kingdom parliament elections 1801 co-option 1802 1806 1807 1812 1818 1820 1826 1830 1831 1832 1835 1837 1841 1847 1852 1857 1859 1865 1868 1874 1880 1885 1886 1892 1895 1900 1906 1910 (jan) 1910 (dec) 1918 1922 1923 1924 1929 1931 1935 1945 1950 1951 1955 1959 1964 1966 1970 1974 (feb) 1974 (oct) 1979 1983 1987 1992 1997 2001 2005 2010 2015 2017 2019 european parliament elections 1979 1984 1989 1994 1999 2004 2009 2014 2019 local elections 1967 1968 1969 1970 1971 1972 1973 1974 1977 1980 1982 1984 1986 1988 1990 1992 1994 1995 1999 2003 2007 2012 2017 2022 referendums 1975 1979 1994 1997 2005 2011 2014 2016 scottish parliament constituencies scottish parliament electoral regions scottish westminster constituencies proposed second independence referendum electoral system political parties scotland and the united kingdom united kingdom government sunak ministry prime minister the rt hon rishi sunak mp secretary of state for scotland the rt hon alister jack mp scottish devolution treaty of union house of commons house of lords scotland office scottish affairs committee scottish grand committee interministerial standing committee barnett formula reserved matters sewel motion administration council areas history sheriffdoms community councils lieutenancy areas convention of scottish local authorities category · scotland portal other countries history the position was created in 1999 as the minister for health and community care, with the advent of devolution and the institution of the scottish parliament, taking over some of the roles and functions of the former scottish office that existed prior to 1999. after the 2007 election the ministerial position was renamed to the cabinet secretary for health and wellbeing. after the 2011 election the full ministerial title was cabinet secretary for health, wellbeing and cities strategy with the portfolio being expanded to include cities strategy which was part of the snp manifesto to have a dedicated "minister for cities"; at the same time the responsibility for housing was removed and transferred to the new cabinet secretary for infrastructure and capital investment. responsibilities for the cities strategy and the delivery of the 2014 commonwealth games in glasgow were later transferred to other members of the cabinet. after the 2016 election, the name of the post was changed to simply cabinet secretary for health and sport. in the 2021 cabinet reshuffle, the post was retitled to cabinet secretary for health and social care. overview responsibilities the responsibilities of the cabinet secretary for health and social care include: nhs scotland and its performance, staff and pay health care and social integration patient services and patient safety primary care allied healthcare services carers, adult care and support child and maternal health medical records, health improvement and protection public bodies the following public bodies report to the cabinet secretary for health and social care: nhs scotland care inspectorate mental welfare commission for scotland scottish social services council sportscotland list of office holders minister for health and community care name portrait entered office left office party first minister susan deacon: 2–4 19 may 1999 28 november 2001 labour party donald dewar malcolm chisholm: 5–7 : 2–4 28 november 2001 6 october 2004 labour party henry mcleish jack mcconnell andy kerr: 3–8 6 october 2004 17 may 2007 labour party jack mcconnell cabinet secretary for health and wellbeing nicola sturgeon 17 may 2007 19 may 2011 scottish national party alex salmond cabinet secretary for health, wellbeing and cities strategy nicola sturgeon 19 may 2011 5 september 2012 scottish national party alex salmond cabinet secretary for health and wellbeing alex neil 5 september 2012 21 november 2014 scottish national party alex salmond cabinet secretary for health, wellbeing and sport shona robison 21 november 2014 18 may 2016 scottish national party nicola sturgeon cabinet secretary for health and sport shona robison 18 may 2016 26 june 2018 scottish national party nicola sturgeon jeane freeman 26 june 2018 19 may 2021 scottish national party nicola sturgeon cabinet secretary for health and social care humza yousaf 20 may 2021 28 march 2023 scottish national party nicola sturgeon cabinet secretary for nhs recovery, health and social care michael matheson 29 march 2023 incumbent scottish national party humza yousaf

hellenic centre for diseases control and prevention hellenic centre for diseases control and prevention the hellenic centre for diseases control and prevention, hcdcp (greek: κέντρο ελέγχου και πρόληψης νοσημάτων, κεελπνο) was greece's public health organization until 2019. it was based in athens, greece, and was named "hcidc" (hellenic centre for infectious diseases control) up to 2005. hcdcp was replaced in 2019 and its full successor is the national public health organization.