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Ann J. Johanson (1934 – 2020) was an American pediatric endocrinologist. She was a professor at the University of Virginia School of Medicine . At UVA, she was the founding director of the Division of Pediatric Endocrinology. In 1971, she and her colleague Robert M. Blizzard first described Johanson-Blizzard Syndrome . [ 1 ] [ 2 ]
Johanson was born in St. Louis, Missouri , and was a graduate of Webster Groves High School . [ 2 ]
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Anna L Gloyn FMedSci is a geneticist , who is Professor of Pediatrics (Endocrinology) and Genetics at Stanford University . She was the recipient of the Minkowski Prize in 2014 for her research into causal mechanisms of diabetes pathogenesis. Her work has contributed to improved treatment options for people with rare forms of diabetes and helped advance our understanding of type 2 diabetes. [ 1 ] [ 2 ]
Gloyn studied for a BSc in Medical Biochemistry at the University of Surrey . [ 3 ] This was followed by a DPhil on the Molecular Genetics of Type 2 Diabetes at Green College at the University of Oxford , supervised by Professor Robert Turner . She worked at the University of Exeter for her post-doctoral training, supervised by Professors Andrew Hattersley & Sian Ellard , as well as Professor Franz M. Matschinsky at the University of Pennsylvania . [ 4 ]
In 2004 Gloyn returned to the University of Oxford funded by a Diabetes UK RD Lawrence Career Development Fellowship to establish a research group to examine "beta-cell function through the investigation of genetic variants causally implicated in monogenic diabetes". [ 5 ] In 2011 she was awarded a Wellcome Senior Fellowship in Basic Biomedical Science to continue her research. This was renewed in 2016. [ 5 ] Her research has focused on how human genetic variants can be used as tools to examine how insulin secretion and action are regulated. [ 6 ] In 2014 she was awarded the Minkowski Prize . [ 7 ] The same year she was promoted to Professor of Molecular Genetics & Metabolism. [ 8 ]
In 2020 Gloyn was appointed Professor of Pediatrics (Endocrinology) and, by courtesy, of Genetics, at Stanford University . [ 5 ] This appointment enabled the movement of her research group to Stanford where it now runs as the Translational Genomics of Diabetes Lab. [ 9 ]
Gloyn is a founding member of the International Common Disease Alliance (ICDA). [ 10 ] She is also a member of the executive committee of the Atlas of Variant Effects Alliance . [ 11 ]
16. Academy announces new fellows Retrieved 2025-05-22.
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The Annals of Oncology is a peer-reviewed medical journal of oncology . It was launched in 1990 with Kluwer Academic Publishers and is currently published by Elsevier . It is the official journal of the European Society for Medical Oncology . The editor-in-chief is Fabrice André ( Villejuif, France ). Previous editors were Jean-Charles Soria , Jan Vermorken , David J. Kerr and Franco Cavalli . [ 1 ]
Some articles are available for free public access. [ 2 ]
Before coming to Elsevier the journal was published by Oxford University Press, and Springer.
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The Annals of Pediatric Surgery is a quarterly peer-reviewed medical journal covering research on pediatric surgery . It was established in October 2005 and is the official journal of the Egyptian Pediatric Surgical Association . [ 1 ] The editor-in-chief is Essam A. Elhalaby Tanta University ).
The journal is abstracted and indexed in Scopus . [ 2 ]
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Annals of Plastic Surgery is a monthly peer-reviewed medical journal covering all aspects of plastic and reconstructive surgery . It is published by Lippincott Williams & Wilkins and the editor-in-chief is William C. Lineaweaver (Joseph M. Still Burn and Reconstructive Center, Brandon, Mississippi , United States). [ 1 ]
The journal is abstracted and indexed in CAB Abstracts , [ 2 ] Current Contents /Clinical Medicine, [ 3 ] Embase , [ 4 ] Index Medicus / MEDLINE / PubMed , [ 5 ] Science Citation Index Expanded , [ 3 ] and Scopus . [ 6 ] According to the Journal Citation Reports , the journal has a 2022 impact factor of 1.5. [ 7 ]
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The Annals of Surgery is a monthly peer-reviewed medical journal of surgical science and practice. It was started in 1885 by Lippincott Williams & Wilkins (United States, United Kingdom). [ 1 ]
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Annals of Surgical Oncology is a peer-reviewed medical journal published by Springer International Publishing on behalf of the Society of Surgical Oncology . It is an official journal of the Society of Surgical Oncology, and the American Society of Breast Surgeons . [ 1 ] The editor-in-chief is Kelly M. McMasters ( University of Louisville School of Medicine ).
The journal is abstracted and indexed in Index Medicus / MEDLINE / PubMed , [ 2 ] Current Contents /Clinical Medicine, [ 3 ] Excerpta Medica , and the Science Citation Index . [ 3 ] According to the Journal Citation Reports , the journal has a 2020 impact factor of 5.344. [ 4 ]
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Annals of the Royal College of Surgeons of England is a medical journal published eight times a year by the College , in January, March, April, May, July, September, October and November. The sister journal of the Annals is the Bulletin of the Royal College of Surgeons of England .
The Annals publishes peer reviewed papers on all branches of surgery, with emphasis on clinical research. [ 1 ] [ 2 ] It also includes: letters and comments, a technical section, news from NICE , discussion of controversial topics, CORESS [ 3 ] feedback, and book reviews. There is in addition a selection of trainee presentations from England and Wales. The editorial board consists of members of the College Council and experts from surgical specialties. [ 4 ]
The current Editor-in-Chief of the Annals is Professor Benedict Rogers. [ 5 ] Back issues from one year ago or more are archived on PubMed Central and thus may be accessed free of charge. [ 6 ] Current and recent issues can be accessed online via Ingenta Connect. [ 7 ]
As of 2019 [update] , the impact factor for the Annals is 1.220. [ 8 ]
The journal is indexed in PubMed and Science Citation Index. [ 6 ]
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Anne Fausto-Sterling ( née Sterling ; born July 30, 1944) is an American sexologist who has written extensively on the social construction of gender , sexual identity , gender identity , gender roles , and intersexuality . She is the Nancy Duke Lewis Professor Emerita of Biology and Gender Studies at Brown University . [ 1 ]
Fausto-Sterling's mother, Dorothy Sterling , was a noted writer and historian while her father was also a published writer. [ 2 ] Fausto-Sterling received her Bachelor of Arts degree in zoology from the University of Wisconsin in 1965 and her Ph.D. in developmental genetics from Brown University in 1970. After earning her Ph.D. she joined the faculty of Brown, where she was appointed Nancy Duke Lewis Professor of Biology and Gender Studies.
In a 1993 paper titled " The Five Sexes ", Fausto-Sterling laid out a thought experiment considering an alternative model of gender containing five sexes: male , female , merm, ferm, and herm . [ 3 ] She later said that the paper "had intended to be provocative, but I had also written with tongue firmly in cheek". [ 4 ]
Fausto-Sterling has written two books intended for a general audience. The first of those books, Myths of Gender , was first published in 1985. [ 5 ] Her second book for the general public is Sexing the Body: Gender Politics and the Construction of Sexuality , published in 2000. [ 6 ] [ 7 ] In the book she sets out to "convince readers of the need for theories that allow for a good deal of human variation and that integrate the analytical powers of the biological and the social into the systematic analysis of human development." [ 8 ]
Fausto-Sterling married Paula Vogel , a Yale professor and Pulitzer-winning playwright , in 2004. [ 2 ] She has served on the editorial board of the journal Perspectives in Biology and Medicine and on the advisory board of the feminist academic journal Signs . [ 9 ] [ 10 ] She retired from Brown University in 2014, after 44 years on the faculty. [ 11 ]
Historian of science Evelynn M. Hammonds describes Fausto-Sterling as one of the most influential feminist scientists of her generation. [ 12 ] Reviewing Myths of Gender in the Los Angeles Times , Elaine Kendall writes that "Her most dramatic and valuable chapters concentrate upon the lingering educational misapprehensions operating to keep women away from the 'hard' sciences and out of such lucrative fields as engineering, sidetracking them instead into lower-paying careers in the humanities or the 'nurturant' professions." [ 13 ] Publishers Weekly describes Fausto-Sterling's work as "insightful", stating that Sexing the Body "offers profound challenges to scientific research, the creation of social policy and the future of feminist and gender theory." [ 14 ]
Fausto-Sterling's sexual continuum argument has not gained the same prominence in the biological sciences as it has in gender studies . [ 15 ] French anthropologist Priscille Touraille called Fausto-Sterling an isolated case which has failed to create a consensus or controversy among biologists. [ 16 ] Physician and psychologist Leonard Sax criticized Fausto-Sterling's theory of a sexual continuum. He also argued that her claim that around 1.7% of births are intersex is incorrect, because most of the conditions she considered intersex are not considered intersex from a clinical perspective. [ 17 ] Philosopher of science David N. Stamos argued that Fausto-Sterling's theory of a sexual continuum is problematic because sex , for Stamos, is defined by gamete type. [ 18 ] [ 19 ] Notably, Fausto-Sterling pre-empts these objections, describing these modern definitions of intersexuality as a historically recent innovation aimed at defining intersexuality out of existence. [ 8 ]
The psychologist Suzanne Kessler , in her book Lessons from the Intersexed , criticized Fausto-Sterling's analysis in "The Five Sexes" because it "still gives genitals...primary signifying status and ignores the fact that in the everyday world gender attributions are made without access to genital inspection." Kessler further commented that "What has primacy in everyday life is the gender that is performed, regardless of the flesh's configuration under the clothes." [ 20 ] In a later paper titled "The Five Sexes, Revisited", Fausto-Sterling wrote that she now agreed with Kessler's objections to the five-sex theory, and believed that sexual diversity might instead fit into a broader picture of possibilities for each social gender. [ 8 ]
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The Annual Review of Cancer Biology is a peer-reviewed academic journal that publishes review articles about oncology . It published its first volume in 2017, making it the 47th journal published by the nonprofit Annual Reviews . Founded by Tyler Jacks and Charles L. Sawyers , it is currently edited by Laura Attardi and Scott A. Armstrong . [ 3 ] It is content is broadly focused on cancer cell biology, tumorigenesis and cancer progression, and translational cancer science . As of 2020, Annual Review of Cancer Biology has been published open access under the Subscribe to Open (S2O) publishing model. [ 1 ] [ 4 ]
The Annual Review of Cancer Biology was first published in 2017, making it the 47th journal title published by Annual Reviews . [ 5 ] The stated goals of the journal were to cover the biology of tumor cells, the interaction between the tumor cells and host cells, cancer genomes , drugs for treating cancer , and the resistance of cancer to certain drugs. [ 6 ] Each volume has three broad themes: cancer cell biology, tumorigenesis and cancer progression, and translational cancer science . [ 7 ] Tyler Jacks and Charles L. Sawyers were the founding editors in 2017. [ 6 ] They were succeeded in 2022 by Laura Attardi and Scott A. Armstrong . [ 3 ]
As of 2024, Journal Citation Reports lists the journal's impact factor as 4.7, ranking it 73rd of 322 journal titles in the category "Oncology". [ 2 ] The journal is not published in print, and is only available electronically. [ 8 ] Under Annual Reviews's Subscribe to Open publishing model, the 2020 volume of Annual Review of Cancer Biology was published open access , a first for the journal. [ 9 ] [ 10 ]
The Annual Review of Cancer Biology is helmed by the editors . The editors are assisted by the editorial committee, which includes associate editors, regular members, and occasionally guest editors. Guest members participate at the invitation of the editors, and serve terms of one year. All other members of the editorial committee are appointed by the Annual Reviews board of directors and serve five-year terms. The editorial committee determines which topics should be included in each volume and solicits reviews from qualified authors. [ 11 ] Unsolicited manuscripts are not accepted. Peer review of accepted manuscripts is undertaken by the editorial committee. [ 12 ]
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The Annual Review of Pathology: Mechanisms of Disease is a peer-reviewed academic journal that publishes an annual volume of review articles relevant to pathology . It was established in 2006 and is published by Annual Reviews . Its co- editors have been Jon C. Aster , Mel B. Feany , and Jayanta Debnath since 2021. As of 2023, Annual Review of Pathology: Mechanisms of Disease is being published as open access , under the Subscribe to Open model. [ 1 ] As of 2024, Journal Citation Reports gives the journal a 2023 impact factor of 28.4, ranking it first of 88 journal titles in the category "Pathology". [ 2 ]
The Annual Review of Pathology: Mechanisms of Disease was first published in 2006 by the nonprofit publisher Annual Reviews . [ 3 ] The editorial goals for the journal were to cover recent advancements in the study of disease mechanism and present new analytical methodologies for pathology. [ 4 ] Its first co- editors were Abul K. Abbas , James R. Downing , and Vinay Kumar . [ 5 ] Though it was initially in publication with a print volume, it is now only published electronically. [ 6 ]
The Annual Review of Pathology: Mechanisms of Disease defines its scope as covering significant developments in research on the initiation and progression of human disease . [ 7 ] It is abstracted and indexed in Scopus , Science Citation Index Expanded , EMBASE , MEDLINE , and Academic Search , among others. [ 8 ]
The Annual Review of Pathology: Mechanisms of Disease is helmed by the editor or the co-editors. The editor is assisted by the editorial committee, which includes associate editors, regular members, and occasionally guest editors. Guest members participate at the invitation of the editor, and serve terms of one year. All other members of the editorial committee are appointed by the Annual Reviews board of directors and serve five-year terms. The editorial committee determines which topics should be included in each volume and solicits reviews from qualified authors. [ 9 ] Unsolicited manuscripts are not accepted. Peer review of accepted manuscripts is undertaken by the editorial committee. [ 10 ]
Dates indicate publication years in which someone was credited as a lead editor or co-editor of a journal volume. The planning process for a volume begins well before the volume appears, so appointment to the position of lead editor generally occurred prior to the first year shown here. An editor who has retired or died may be credited as a lead editor of a volume that they helped to plan, even if it is published after their retirement or death.
As of 2022, the editorial committee consists of the three co-editors and the following members: [ 18 ]
As of 2022, the committee's members were:
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The Annual Review of Phytopathology is a peer-reviewed academic journal that publishes review articles about phytopathology , the study of diseases that affect plants . It was first published in 1963 as the result of a collaboration between the American Phytopathological Society and the nonprofit publisher Annual Reviews . As of 2024, Journal Citation Reports lists the journal's 2023 impact factor as 9.1, ranking it tenth of 265 journal titles in the category "Plant Sciences". [ 1 ] As of 2023, it is being published as open access , under the Subscribe to Open model. [ 2 ] Its current editors are John M. McDowell and Gwyn A. Beattie . [ 3 ]
In the 1950s, the American Phytopathological Society had intended to publish its own journal to cover significant developments in the field of phytopathology , or plant diseases. However, the nonprofit publisher Annual Reviews offered to publish the journal for them, and they agreed due to their publishing experience. In 1961, the American Phytopathological Society compiled the editorial board of the journal at their annual meeting. The first volume was published in 1963. [ 4 ] It was the twelfth journal title published by Annual Reviews. In its first ten volumes, it published a total of 188 reviews from authors from twenty-one countries. [ 5 ]
It defines its scope as covering significant developments related to plant pathology , including diagnosis, plant pathogens , host–pathogen interactions , epidemiology of plant disease, breeding plants for disease resistance , and plant disease management. [ 6 ] It is abstracted and indexed in Scopus , Science Citation Index Expanded , Civil Engineering Abstracts , Inspec , and Academic Search , among others. [ 7 ]
The Annual Review of Phytopathology is helmed by the editor or the co-editors. The editor is assisted by the editorial committee, which includes associate editors, regular members, and occasionally guest editors. Guest members participate at the invitation of the editor, and serve terms of one year. All other members of the editorial committee are appointed by the Annual Reviews board of directors and serve five-year terms. The editorial committee determines which topics should be included in each volume and solicits reviews from qualified authors. [ 8 ] Unsolicited manuscripts are not accepted. Peer review of accepted manuscripts is undertaken by the editorial committee. [ 9 ]
Dates indicate publication years in which someone was credited as a lead editor or co-editor of a journal volume. The planning process for a volume begins well before the volume appears, so appointment to the position of lead editor generally occurred prior to the first year shown here. An editor who has retired or died may be credited as a lead editor of a volume that they helped to plan, even if it is published after their retirement or death.
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Anomic aphasia , also known as dysnomia , nominal aphasia , and amnesic aphasia , is a mild, fluent type of aphasia where individuals have word retrieval failures and cannot express the words they want to say (particularly nouns and verbs ). [ 1 ] By contrast, anomia is a deficit of expressive language , and a symptom of all forms of aphasia, but patients whose primary deficit is word retrieval are diagnosed with anomic aphasia. [ 2 ] Individuals with aphasia who display anomia can often describe an object in detail and maybe even use hand gestures to demonstrate how the object is used, but cannot find the appropriate word to name the object. [ 3 ] Patients with anomic aphasia have relatively preserved speech fluency , repetition , comprehension , and grammatical speech.
Anomic aphasia occurring by itself may be caused by damage to almost anywhere in the left hemisphere and in some cases can be seen in instances of right hemisphere damage. [ 7 ] Anomia can be genetic or caused by damage to various parts of the parietal lobe or the temporal lobe of the brain due to traumatic injury, stroke , or a brain tumor . [ 8 ] While anomic aphasia is primarily caused by structural lesions, they may also originate in Alzheimer's disease (anomia may be the earliest language deficit in posterior cortical atrophy variant of Alzheimer's) or other neurodegenerative diseases . [ 7 ]
Although the main causes are not specifically known, many researchers have found other factors contributing to anomic aphasia. People with damage to the left hemisphere of the brain are more likely to have anomic aphasia. Broca's area , the speech production center in the brain, was linked to being the source for speech execution problems, with the use of functional magnetic resonance imaging (fMRI), now commonly used to study anomic patients. [ 9 ] Other experts believe that damage to Wernicke's area , which is the speech comprehension area of the brain, is connected to anomia because the patients cannot comprehend the words that they are hearing. [ 10 ]
Although many experts have believed that damage to Broca's area or Wernicke's area are the main causes of anomia, current studies have shown that damage in the left parietal lobe is the cause of anomic aphasia. [ 11 ] One study was conducted using a word repetition test as well as fMRI in order to see the highest level of activity as well as where the lesions are in the brain tissue. [ 11 ] Fridrikkson, et al. saw that damage to neither Broca's area nor Wernicke's area were the sole sources of anomia in the subjects. Therefore, the original anomia model, which theorized that damage occurred on the surface of the brain in the grey matter was debunked, and it was found that the damage was in the white matter deeper in the brain, on the left hemisphere. [ 11 ] More specifically, the damage was in a part of the nerve tract called the arcuate fasciculus , for which the mechanism of action is unknown, though it is known to connect the posterior (back) of the brain to the anterior (front) and vice versa. [ 12 ]
While anomic aphasia is associated with lesions throughout the left hemisphere, severe and isolated anomia has been considered a sign of deep temporal lobe or lateral temporo-occipital damage. Damage to these areas is seen in patients showing infarction limited to regions supplied by the dominant posterior cerebral artery (PCA) and is referred to as posterior cerebral artery syndrome . [ 13 ]
The best way to see if anomic aphasia has developed is by using verbal and imaging tests. The combination seems to be most effective, since either test done alone may give false positives or false negatives. For example, the verbal test is used to see if a speech disorder presents, and whether the problem is in speech production or comprehension. Patients with Alzheimer's disease have speech problems linked to dementia or progressive aphasias , which can include anomia. [ 14 ] [ 15 ] The imaging test, mostly done using MRI scans, is ideal for lesion mapping or viewing deterioration in the brain. However, imaging cannot diagnose anomia on its own because the lesions may not be located deep enough to damage the white matter or the arcuate fasciculus. However, anomic aphasia is very difficult to associate with a specific lesion location in the brain. Therefore, the combination of speech tests and imaging tests has the highest sensitivity and specificity . [ 16 ]
Picture-naming tests, such as the Philadelphia Naming Test (PNT), are also utilized in diagnosing aphasias. Analysis of picture-naming is compared with reading, picture categorizing, and word categorizing. There is a considerable similarity among aphasia syndromes in terms of picture-naming behavior, however anomic aphasiacs produced the fewest phonemic errors and the most multiword circumlocutions. These results suggest minimal word-production difficulty in anomic aphasia relative to other aphasia syndromes. [ 17 ]
Anomic aphasia has been diagnosed in some studies using the Aachen Aphasia Test (AAT), which tests language functioning after brain injury. This test aims to: identify the presence of aphasia; provide a profile of the speaker's language functioning according to different language modalities (speaking, listening, reading, writing) and different levels of linguistic description (phonology, morphology, semantics, and syntax); give a measure of severity of any breakdown. [ 18 ] This test was administered to patients participating in a study in 2012, and researchers found that on the naming subtest of the AAT patients showed relevant naming difficulties and tended to substitute the words they could not produce with circumlocutions. [ 19 ]
The Western Aphasia Battery is another test that is conducted with the goal of classifying aphasia subtypes and rating the severity of the aphasiac impairment. The test is composed of four language and three performance domains. Syndrome classification is determined by the pattern of performance on the four language subtests, which assess spontaneous speech, comprehension, repetition, and naming. [ 20 ]
Doing a hearing test first is important, in case the patient cannot clearly hear the words or sentences needed in the speech repetition test. [ 21 ] In the speech tests, the person is asked to repeat a sentence with common words; if the person cannot identify the word, but he or she can describe it, then the person is highly likely to have anomic aphasia. However, to be completely sure, the test is given while a test subject is in an fMRI scanner, and the exact location of the lesions and areas activated by speech are pinpointed. [ 11 ] Few simpler or cheaper options are available, so lesion mapping and speech repetition tests are the main ways of diagnosing anomic aphasia. [ citation needed ]
Anomic aphasia (anomia) is a type of aphasia characterized by problems recalling words, names, and numbers. Speech is fluent and receptive language is not impaired in someone with anomic aphasia. [ 22 ] Subjects often use circumlocutions (speaking in a roundabout way) to avoid a name they cannot recall or to express a certain word they cannot remember. Sometimes, the subject can recall the name when given clues. Additionally, patients are able to speak with correct grammar; the main problem is finding the appropriate word to identify an object or person. [ citation needed ]
Sometimes, subjects may know what to do with an object, but still not be able to give a name to the object. For example, if a subject is shown an orange and asked what it is called, the subject may be well aware that the object can be peeled and eaten, and may even be able to demonstrate this by actions or even verbal responses; however, they cannot recall that the object is called an "orange". Sometimes, when a person with this condition is multilingual , they might confuse the language they are speaking in trying to find the right word (inadvertent code-switching ). [ citation needed ]
No method is available to completely cure anomic aphasia. However, treatments can help improve word-finding skills.
Although a person with anomia may find recalling many types of words to be difficult, such as common nouns , proper nouns , verbs , etc., many studies have shown that treatment for object words, or nouns, has shown promise in rehabilitation research. [ 21 ] The treatment includes visual aids, such as pictures, and the patient is asked to identify the object or activity. However, if that is not possible, then the patient is shown the same picture surrounded by words associated with the object or activity. [ 23 ] [ 24 ] Throughout the process, positive encouragement is provided. The treatment shows an increase in word finding during treatment; however, word identifying decreased two weeks after the rehabilitation period. [ 21 ] Therefore, it shows that rehabilitation effort needs to be continuous for word-finding abilities to improve from the baseline. The studies show that verbs are harder to recall or repeat, even with rehabilitation. [ 21 ] [ 25 ]
Other methods in treating anomic aphasia include circumlocution-induced naming therapy (CIN), wherein the patient uses circumlocution to assist with his or her naming rather than just being told to name the item pictured after given some sort of cue. Results suggest that the patient does better in properly naming objects when undergoing this therapy because CIN strengthens the weakened link between semantics and phonology for patients with anomia, since they often know what an object is used for, but cannot verbally name it. [ 26 ]
Anomia is often challenging for the families and friends of those affected by it. One way to overcome this is computer-based treatment models, effective especially when used with clinical therapy. Leemann et al. provided anomic patients with computerized-assisted therapy (CAT) sessions, along with traditional therapy sessions using treatment lists of words. Some of the patients received a drug known to help relieve symptoms of anomia ( levodopa ), while others received a placebo . The researchers found that the drug had no significant effects on improvement with the treatment lists, but almost all of the patients improved after the CAT sessions. They concluded that this form of computerized treatment is effective in increasing naming abilities in anomic patients. [ 27 ]
Additionally, one study researched the effects of using "excitatory (anodal) transcranial direct current stimulation " over the right temporoparietal cortex, a brain area that seems to correlate to language. The electrical stimulation seemed to enhance language training outcome in patients with chronic aphasia. [ 28 ]
Contextual repetition priming treatment is a technique which involves repeated repetition of names of pictures that are related semantically, phonologically, or are unrelated. Patients with impaired access to lexical-semantic representations show no long-term improvement in naming, but patients with good access to semantics show long-term benefits. [ 29 ]
Development of self-cueing strategies can also facilitate word retrieval. Patients identify core words that can be retrieved without struggle, and establish a relationship between cue words and words that begin with the same sound but cannot be retrieved. Patients then learn to use the cue word to facilitate word retrieval for the target object. [ 30 ]
Many different populations can and do have anomia. For instance, deaf patients who have had a stroke can demonstrate semantic and phonological errors, much like hearing anomic patients. Researchers have called this subtype sign anomia . [ 31 ]
Multilingual patients typically experience anomia to a greater degree in just one of their fluent languages. However, evidence conflicts as to which language – first or second – is impacted more. [ 32 ] [ 33 ]
Research on children with anomia has indicated that children who undergo treatment are, for the most part, able to gain back normal language abilities, aided by brain plasticity . However, longitudinal research on children with anomic aphasia due to head injury shows that even several years after the injury, some signs of deficient word retrieval are still observed. These remaining symptoms can sometimes cause academic difficulties later on. [ 34 ]
This disorder may be extremely frustrating for people with and without the disorder. Although the persons with anomic aphasia may know the specific word, they may not be able to recall it and this can be very difficult for everyone in the conversation. Positive reinforcements are helpful. [ 21 ]
Although not many literary cases mention anomic aphasia, many nonfiction books have been written about living with aphasia . One of them is The Man Who Lost His Language by Sheila Hale. It is the story of Hale's husband, John Hale , a scholar who had had a stroke and lost speech formation abilities. In her book, Hale also explains the symptoms and mechanics behind aphasia and speech formation. She adds the emotional components of dealing with a person with aphasia and how to be patient with the speech and communication. [ 35 ] [ 36 ]
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Anophthalmia (Greek: ἀνόφθαλμος, "without eye") is the medical term for the absence of one or both eyes . Both the globe and the ocular tissue are missing from the orbit. [ 1 ] The absence of the eye will cause a small bony orbit, a constricted mucosal socket , short eyelids , reduced palpebral fissure and malar prominence . [ 2 ] Genetic mutations , chromosomal abnormalities , and prenatal environment can all cause anophthalmia. Anophthalmia is an extremely rare disease and is mostly rooted in genetic abnormalities. It can also be associated with other syndromes.
The most common genetic cause for anophthalmia is mutated SOX2 gene. Sox2 anophthalmia syndrome is caused by a mutation in the Sox2 gene that does not allow it to produce the Sox2 protein that regulates the activity of other genes by binding to certain regions of DNA. Without this Sox2 protein, the activity of genes that is important for the development of the eye is disrupted. Sox2 anophthalmia syndrome is an autosomal dominant inheritance, but the majority of patients who have Sox2 anophthalmia are the first in their family history to have this mutation. In certain cases, one parent will possess the mutated gene only in their egg or sperm cell and the offspring will inherit it through that. This is called germline mosaicism . [ 3 ] There are at least 33 mutations in the Sox2 gene that have been known to cause anophthalmia. Some of these gene mutations will cause the Sox2 protein not to be formed, while other mutations will yield a non-functional version of this protein.
RBP4 has recently been linked to autosomal dominant form of anophthalmia. [ 4 ] This form of anophthalmia has variable penetrance and a unique maternal inheritance effect that is rooted in pregnancy. Specifically, the disease only occurs when a mother and fetus both carry a RBP4 mutation which predisposes the fetus to vitamin A deficiency (a known environmental risk factor for anophthalmia) during pregnancy. If Vitamin A deficiency occurs during the first several months when the eye is developing, it may lead to anophthalmia. This form of anophthalmia is the first that may be intervened upon with vitamin A supplementation of retinyl esters during the first several months of pregnancy. This strategy exploits an RBP-independent pathway. Clinical research is underway. See RBP4 for more information.
SOX2 and RBP4 are not the only genes that can cause anophthalmia. Other important genes include OTX2 , CHX10 and RAX . Each of these genes are an important in retinal expression. Mutations in these genes can cause a failure of retinal differentiation . [ 5 ] OTX2 is dominantly inherited. Mutation effects vary in severity, and can include microphthalmia. BMP4 is also linked to anophthalmia, as well as causing myopia and microphthalmia. It is dominantly inherited. BMP4 interacts with the Sonic hedgehog (SHH) pathway and can cause anophthalmia. [ 6 ] Haploinsufficiency of PRR12 is also known to result in anophthalmia among other abnormalities. [ 7 ] [ 8 ]
Many environmental conditions have also been known to cause anophthalmia. The strongest support for environmental causes has been studies where children have had gestational-acquired infections . These infections are typically viral. A few known pathogens that can cause anophthalmia are Toxoplasma , rubella , and certain strains of the influenza virus . [ 9 ] Other known environmental conditions that have led to anophthalmia are maternal vitamin A deficiency , exposure to X-rays during gestation, solvent abuse , and exposure to thalidomide . [ 5 ]
An interstitial deletion of chromosome 14 has been known to occasionally be the source of anophthalmia. The deletion of this region of chromosome has also been associated with patients having a small tongue, and high arched palate, developmental and growth retardation , undescended testes with a micropenis , and hypothyroidism . The region that has been deleted is region q22.1-q22.3. This confirms that region 22 on chromosome 14 influences the development of the eye. [ 10 ]
There are three classifications for this condition:
Ultrasounds can be used to diagnose anophthalmia during gestation. Due to the resolution of the ultrasound, it is difficult to diagnose it until the second trimester . The earliest time to detect anophthalmia this way is approximately 20 weeks. [ 11 ]
It is possible to diagnose prenatally with amniocentesis , but it may not show a correct negative result. Amniocentesis can only diagnose anophthalmia when there is a chromosomal abnormality. Chromosomal abnormalities are only a minority of cases of anophthalmia. [ 11 ]
MRIs and CTs can be used to scan the brain and orbits. Radiologists use this to assess the internal structures of the globe, the optic nerve and extraocular muscles , and brain anatomy.
Physicians, specifically ophthalmologists , can examine the child and give a correct diagnosis. Some will do molecular genetics tests to see if the cause is linked with gene mutations.
Genetic testing can include chromosomal microarray analysis, single-gene testing, or multigene-panel testing. Genomic testing including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing or use of a multigene panel fails to confirm a molecular diagnosis.
There are a few conditions that are associated with anophthalmia. These include: [ 12 ]
Aside from these associative conditions, anophthalmia in only one eye tends to be associated with complications in the other eye. These risks include a higher chance of having glaucoma or a detached retina .
Currently, there is not a treatment option for regaining vision by developing a new eye. There are, however, cosmetic options so the absence of the eye is not as noticeable. Typically, the child will need to go to an ocularist to have conformers fitted into the eye. Conformers are made of clear plastic and are fitted into the socket to promote socket growth and expansion. As the child's face grows and develops, the conformer will need to be changed. An expander may also be needed in anophthalmia to expand the socket that is present. The conformer is changed every few weeks the first two years of life. After that, a painted prosthetic eye can be fitted for the child's socket. [ 13 ] The prosthetic eye can be cleaned with mild baby soap and water. Rubbing alcohol should be avoided because it may damage the prosthetic eye. Children need to be checked regularly to ensure the fit and size is appropriate. [ 14 ]
A Cochrane Review published in 2016 asked whether the type of material used to make the prosthetic eye affects the success of the operation. [ 15 ] Prosthetic eyes can be made from two types of material; porous or non-porous material. "If the material is porous then the artificial eye can become integrated into the body because new blood vessels can grow into the material. If the material is non-porous, then the artificial eye remains separate from the rest of the body's tissue." After assessing three studies, the review concluded that there wasn't enough evidence to conclude which material was better.
If the proper actions are not taken to expand the orbit, many physical deformities can appear. It is important that if these deformities do appear, that surgery is not done until at least the first two years of life. Many people get eye surgery, such as upper eyelid ptosis surgery and lower eyelid tightening. These surgeries can restore the function of the surrounding structures like the eyelid in order to create the best appearance possible. This is more common with people who have degenerative anophthalmia. [ 16 ]
Anophthalmia has been reported to be present in 3 out of every 100,000 births. [ 5 ] Many instances of anophthalmia also occur with microphthalmia . A recent study in the UK indicated that anophthalmia and microphthalmia had a combined average of 1 in every 10,000 births. [ 1 ] The annual rate of occurrence of anophthalmia/microphthalmia in the United States is about 780 children born/year. [ 17 ] The most extensive epidemiological survey on this congenital malformation has been carried out by Dharmasena et al. [ 18 ] and using English National Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the incidence of congenital anophthalmia ranged from 2.4 (95% CI 1.3 to 4.0) per 100 000 infants in 1999 to 0.4 (0 to 1.3) in 2011. Parents that already have a child who has anophthalmia have a 1 in 8 chance of having another child with anophthalmia. [ 19 ] Approximately 2/3 of all cases of anophthalmia are determined to be of genetic basis. Anophthalmia is one of the leading causes of congenital blindness and accounts for 3-11% of blindness in children. [ 20 ] Anophthalmia and microphthalmia together make up 1.7-1.8% of reconstructive surgical cases in laboratory of plastic surgery and ocular prostheses . [ 21 ]
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Anosmia , also known as smell blindness , is the lack of ability to detect one or more smells . [ 1 ] [ 2 ] Anosmia may be temporary or permanent. [ 3 ] It differs from hyposmia , which is a decreased sensitivity to some or all smells. [ 2 ]
Anosmia can be categorized into acquired anosmia and congenital anosmia . Acquired anosmia develops later in life due to various causes, such as upper respiratory infections, head trauma , or neurodegenerative diseases . [ 4 ] In contrast, congenital anosmia is present from birth and is typically caused by genetic factors or developmental abnormalities of the olfactory system. [ 5 ] While acquired anosmia may have potential treatments depending on the underlying cause, such as medications or surgery, congenital anosmia currently has no known cure, and management focuses on safety precautions and coping strategies. [ 6 ]
Anosmia can be due to a number of factors, including inflammation of the nasal mucosa , blockage of nasal passages , or destruction of temporal lobular tissue. [ 7 ] Anosmia stemming from sinus inflammation is due to chronic mucosal changes in the lining of the paranasal sinus and in the middle and superior turbinates . [ 8 ] [ 9 ]
When anosmia is caused by inflammatory changes in the nasal passageways, it is treated simply by reducing inflammation. [ 10 ] [ 11 ] It can be caused by chronic meningitis and neurosyphilis that would increase intracranial pressure over a long period of time, [ 12 ] and, in some cases, by ciliopathy , [ 13 ] including ciliopathy due to primary ciliary dyskinesia . [ 14 ]
The term derives from the Neo-Latin anosmia , based on Ancient Greek ἀν- ( an -) + ὀσμή ( osmḗ 'smell'; another related term, hyperosmia , refers to an increased ability to smell). Some people may be anosmic for one particular odor, a condition known as "specific anosmia". The absence of the sense of smell from birth is known as congenital anosmia . [ 15 ]
In the United States, 3% of people aged over 40 are affected by anosmia. [ 3 ]
Anosmia is a common symptom of COVID-19 and can persist as long COVID . [ 16 ]
Anosmia is the inability to smell . [ 1 ] It may be partial or total, and can be specific to certain smells. [ 2 ] Reduced sensitivity to some or all smells is hyposmia . [ 2 ]
Anosmia can have a number of harmful effects. [ 17 ] People with sudden onset anosmia may find food less appetizing, though congenital anosmics rarely complain about this, and none report a loss in weight. Loss of smell can also be dangerous because it hinders the detection of gas leaks , fire, and spoiled food. Misconceptions of anosmia as trivial can make it more difficult for a patient to receive the same types of medical aid as someone who has lost other senses, such as hearing or sight. [ citation needed ]
Many experience one sided loss of smell, often as a result of minor head trauma. This type of anosmia is normally only detected if both of the nostrils are tested separately. Using this method of testing each nostril separately will often show a reduced or even completely absent sense of smell in either one nostril or both, something which is often not revealed if both nostrils are simultaneously tested. [ 18 ]
Losing an established and sentimental smell memory (e.g. the smell of grass , of the grandparents' attic, of a particular book, of loved ones, or of oneself) has been known to cause feelings of depression . [ 19 ] [ better source needed ]
Loss of the ability to smell may lead to the loss of libido , but this usually does not apply to those with olfactory dysfunction at birth. [ 19 ] [ 20 ]
Often people who have loss of smell at birth report that they pretended to be able to smell as children because they thought that smelling was something that older/mature people could do, or did not understand the concept of smelling but did not want to appear different from others. When children get older, they often realize and report to their parents that they do not actually possess a sense of smell, often to the surprise of their parents. [ citation needed ]
A temporary loss of smell can be caused by a blocked nose or infection. In contrast, a permanent loss of smell may be caused by death of olfactory receptor neurons in the nose or by brain injury in which there is damage to the olfactory nerve or damage to brain areas that process smell (see olfactory system ). The lack of the sense of smell at birth, usually due to genetic factors, is referred to as congenital anosmia . Family members of the patient with congenital anosmia are often found with similar histories; this suggests that the anosmia may follow an autosomal dominant pattern. [ 21 ] Anosmia may very occasionally be an early sign of a degenerative brain disease such as Parkinson's disease and Alzheimer's disease . [ 22 ]
Another specific cause of permanent loss could be from damage to olfactory receptor neurons because of use of certain types of nasal spray ; i.e., those that cause vasoconstriction of the nasal microcirculation. To avoid such damage and the subsequent risk of loss of smell, vasoconstricting nasal sprays should be used only when absolutely necessary and then for only a short amount of time. Non-vasoconstricting sprays, such as those used to treat allergy-related congestion, are safe to use for prescribed periods of time. [ 23 ] Anosmia can also be caused by nasal polyps. These polyps are found in people with allergies, histories of sinusitis, and family history. Individuals with cystic fibrosis often develop nasal polyps. [ citation needed ]
Amiodarone is a drug used in the treatment of arrhythmias of the heart. A clinical study demonstrated that the use of this drug induced anosmia in some patients. Although rare, there was a case in which a 66-year-old male was treated with amiodarone for ventricular tachycardia . After the use of the drug he began experiencing olfactory disturbance, however after decreasing the dosage of amiodarone, the severity of the anosmia decreased accordingly, suggesting a relationship between use of amiodarone to the development of anosmia. [ 24 ]
Chemosensory disturbances, including loss of smell or taste, are the predominant neurological symptom of COVID-19 . [ 25 ] [ 26 ] As many as 80% of COVID-19 patients exhibit some change in chemesthesis , including smell. Loss of smell has also been found to be more predictive of COVID-19 than all other symptoms, including fever, cough, or fatigue, based on a survey of 2 million participants in the UK and US. [ 27 ] Google searches for "smell", "loss of smell", "anosmia", and other similar terms increased since the early months of the pandemic, and strongly correlated with increases in daily cases and deaths. [ 28 ] Research into the mechanisms underlying these symptoms is currently ongoing. [ 29 ] [ 30 ]
Many countries list anosmia as an official COVID-19 symptom, and some have developed "smell tests" as potential screening tools. [ 31 ] [ 32 ]
In 2020, the Global Consortium for Chemosensory Research, a collaborative research organization of international smell and taste researchers, formed to investigate loss of smell and related chemosensory symptoms. [ 33 ]
Studies have indicated that patients who presented with anosmia during the acute phase of COVID-19 are more likely to develop changes in decision-making, exhibiting more impulsive responses, which are associated with functional and structural brain changes. [ 34 ]
Diagnosis begins with a detailed history, including possible related injuries, such as upper respiratory infections or head injury. The examination may involve nasal endoscopy for obstructive factors such as polyps or swelling. [ 7 ] A nervous system examination is performed to see if the cranial nerves are affected. [ 7 ] On occasion, after head traumas, there are people who have unilateral anosmia. The sense of smell should be tested individually in each nostril. [ 18 ]
Many cases of congenital anosmia remain unreported and undiagnosed. Since the disorder is present from birth the individual may have little or no understanding of the sense of smell, hence is unaware of the deficit. [ 56 ] It may also lead to reduction of appetite. [ 57 ]
Though anosmia caused by brain damage cannot be treated, anosmia caused by inflammatory changes in the mucosa may be treated with glucocorticoids . Reduction of inflammation through the use of oral glucocorticoids such as prednisone, followed by long term topical glucocorticoid nasal spray, would easily and safely treat the anosmia. A prednisone regimen is adjusted based on the degree of the thickness of mucosa, the discharge of oedema and the presence or absence of nasal polyps. [ 10 ] However, the treatment is not permanent and may have to be repeated after a short while. [ 10 ] Together with medication, pressure of the upper area of the nose must be mitigated through aeration and drainage. [ 58 ]
Anosmia caused by a nasal polyp may be treated by steroidal treatment or removal of the polyp. [ 59 ]
Although very early in development, gene therapy has restored a sense of smell in mice with congenital anosmia when caused by ciliopathy . In this case, a genetic condition had affected cilia in their bodies which normally enabled them to detect air-borne chemicals, and an adenovirus was used to implant a working version of the IFT88 gene into defective cells in the nose, which restored the cilia and allowed a sense of smell. [ 60 ] [ 61 ]
In the United States, 3% of people aged over 40 are affected by anosmia. [ 3 ]
In 2012, smell was assessed in persons aged 40 years and older with rates of anosmia/severe hyposmia of 0.3% at age 40–49 rising to 14.1% at age 80+. Rates of hyposmia were much higher: 3.7% at age 40–49 and 25.9% at 80+. [ 62 ]
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Anosodiaphoria is the inability to recognize the full importance of a neurological disability brought on by a brain lesion. [ 1 ] It might be specifically associated with defective functioning of the frontal lobe of the right hemisphere. [ 2 ]
Joseph Babinski first used the term anosodiaphoria in 1914 to describe a disorder of the body schema in which patients verbally acknowledge a clinical problem (such as hemiparesis ) but fail to be concerned about it. [ 3 ] Anosodiaphoria follows a stage of anosognosia , in which there may be verbal, explicit denial of the illness, and after several days to weeks, develop the lack of emotional response. [ 4 ]
A few possible explanations for anosodiaphoria exist:
Other explanations include reduced emotional experience, impaired emotional communication, alexithymia , behavioral abnormalities , dysexecutive syndrome , and the frontal lobes . [ 4 ]
Anosodiaphoria occurs after stroke of the brain. 27% of patients with an acute hemispheric stroke had the stroke in the right hemisphere, while 2% have it in their left. [ 5 ]
The frontal lobe is thought to be the primary area for the lack of emotional insight seen in anosodiaphoria, such as in frontotemporal dementia . A recent 2011 study done by Mendez and Shapira found that people with frontotemporal dementia also had a loss of insight more properly described at "frontal anosodiaphoria", a lack of concern for proper self-appraisal. Patients were found to have a lack of emotional updating, or concern for having an illness; an absence of an emotional self-referent tagging of information on their disorder, which they think is possibly from disease in the ventromedial prefrontal cortex , anterior cingulate -anterior insula area, especially on the right. [ 6 ]
Indifference to illness may have an adverse impact on a patient's engagement in neurological rehabilitation , cognitive rehabilitation and physical rehabilitation . Patients are not likely to implement rehabilitation for a condition about which they are indifferent. Although anosognosia often resolves in days to weeks after stroke, anosodiaphoria often persists. [ 7 ]
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The Anrep effect describes the rapid increase in myocardial contractility in response to the sudden rise in afterload , the pressure the heart must work against to eject blood. [ 1 ] [ 2 ] This adaptive mechanism allows the heart to sustain stroke volume and cardiac output despite increased resistance. It operates through homeometric autoregulation , meaning that contractility adjustments occur independently of preload (the initial stretch of the heart muscle) or heart rate . [ 1 ] [ 2 ] [ 3 ]
The Anrep effect is characterized by a two-step elevation in myocardial contractility, in response to elevated afterload, involving two distinct mechanistic phases: a primary, rapid rise in contractility driven by sarcomeric strain sensing, and a secondary, sustained phase of contraction mediated by post-translational modifications of contractile proteins . [ 3 ] [ 4 ] First described by Gleb von Anrep in 1912 [ 5 ] and further elaborated in the 1960s by Sarnoff et al., [ 1 ] [ 2 ] the Anrep effect represents a distinct cardiac regulation mechanism, differing fundamentally from the Frank-Starling mechanism , [ 6 ] the slow force response, [ 7 ] [ 8 ] and the Gregg effect. [ 9 ]
While traditionally considered a short-term adaptation, recent studies suggest that the Anrep effect may also occur in chronic conditions involving persistent afterload elevation, such as hypertrophic obstructive cardiomyopathy . [ 4 ]
The heart adjusts its pumping efficiency through changes in muscle length and load. When the cardiac muscle is stretched, it triggers a biphasic rise in force generation. The initial phase, governed by the Frank-Starling law (heterometric autoregulation), results in an immediate increase in contractile strength due to increased end-diastolic volume . This adjustment helps balance cardiac output with changes in filling pressure. The second phase, termed the slow force response, unfolds over several minutes, reflecting a sustained increase in contractility when preload remains constant following the initial stretch. In contrast, the Anrep effect (homeometric autoregulation) enhances ventricular contractility in response to acute afterload elevation, independent of preload or heart rate variations. The Anrep effect is often confused with other regulatory processes (e.g., the slow force response, the Gregg phenomenon) but has unique, very distinct, characteristics:
The Frank-Starling mechanism describes how increased preload (ventricular filling) stretches cardiac muscle fibers, enhancing stroke work through length-dependent activation of the myofilaments . This process aligns actin and myosin filaments for efficient cross-bridge formation while also recruiting myosin heads from dormant states into contraction-ready configurations. [ 6 ] [ 10 ] Additionally, stretching the sarcomeres sensitizes the thin (actin) filaments to calcium, promoting stronger and more sustained contractions. [ 6 ] By contrast, the Anrep effect occurs at constant preload, triggered solely by afterload. [ 1 ] [ 2 ] [ 3 ] It is characterized by increased contractility (steeper end-systolic pressure-volume relationship) and higher stroke work, without changes in stroke volume or end-diastolic volume. [ 3 ] [ 4 ]
This stretch-related (preload) response involves a gradual rise in contractility over several minutes (from 2 to 15 minutes, depending on species and experimental conditions) [ 7 ] [ 8 ] [ 11 ] due to stretch-activated ion channels and G-protein-coupled receptors . [ 7 ] [ 12 ] It is mediated by angiotensin II and endothelin-1 , which increase intracellular sodium and calcium concentrations through sodium-calcium exchangers . In contrast, the afterload-dependent response of the Anrep effect is initiated in milliseconds and concludes within 10 seconds, bypassing extracellular calcium regulation through the slow force response. [ 3 ] Additionally, streptomycin , an inhibitor of stretch-activated ion channels, blocks the slow force response but does not affect the Anrep effect, reinforcing that the two mechanisms operate through distinct pathways. [ 3 ]
This effect describes increased contractility due to improved coronary perfusion . [ 9 ] It originates from changes in microvascular volume that trigger stretch-activated ion channels, resulting in increased intracellular calcium transient. [ 13 ] The Gregg phenomenon generally begins to affect contractility approximately 5 seconds after onset, reaching peak force development within 40 seconds of sustained perfusion. [ 3 ] However, the Anrep effect persists even in denervated, isolated hearts with constant coronary flow, eliminating perfusion-based explanations. [ 3 ] Like the slow force response, the Gregg effect is sensitive to streptomycin, while the Anrep effect remains unaffected. [ 3 ]
The activation of the Anrep effect involves recruiting a significant portion of dormant myosin motors within cardiomyocytes , as most myosin heads in each heart cell remain in a resting state. [ 4 ] This recruitment transitions myosin from its inactive configuration to a contraction-ready state through a biphasic activation process that increases contractility in response to the afterload, and consequently elevates energy consumption:
The Anrep effect can be understood in terms of its hemodynamic impact on the heart during afterload increases: [ 3 ] [ 4 ]
These responses ensure the heart maintains stroke volume and cardiac output, despite increased afterload, at the cost of higher energy consumption. [ 4 ]
The Anrep effect was first described by Gleb von Anrep in 1912 [ 5 ] during experiments involving splanchnic nerve stimulation in dogs. He observed that stimulating the splanchnic nerve caused peripheral vasoconstriction, which increased blood pressure and afterload. In response, cardiac contractility increased, a phenomenon Anrep attributed to the release of adrenaline from the suprarenal glands, independent of preload changes. Later, Ernest Starling suggested that enhanced coronary flow, improving myocardial nourishment (a concept later termed the Gregg effect [ 9 ] ), might explain the increase in contractility observed by von Anrep. [ 15 ] However, both historical and recent research has demonstrated that the Anrep effect arises from an intrinsic property of the myocardium, independent of adrenaline release or coronary flow. [ 1 ] [ 2 ] [ 3 ] In the mid-20th century, Sarnoff et al. [ 1 ] [ 2 ] introduced the term homeometric autoregulation to describe the heart’s ability to augment contractility in response to elevated afterload, independent of preload or hormonal stimulation. This concept distinguished the Anrep effect from the Frank-Starling law, which involves heterometric autoregulation, where increased preload enhances contractility by stretching myocardial fibers. Despite Sarnoff’s clarification, some of his experiments reported a brief, transient increase in preload following afterload elevation. He dismissed this effect as non-essential for triggering the Anrep effect, yet this observation led to persistent confusion. To this day, some studies mistakenly associate the Anrep effect with the slow force response, despite clear differences in their underlying physiology.
Although originally considered an acute and transient response, recent research suggests that the Anrep effect may persist in chronic conditions involving sustained afterload increases. One example is hypertrophic obstructive cardiomyopathy, where left ventricular outflow tract obstruction results in persistent afterload elevation, potentially activating the Anrep effect chronically. [ 4 ] Understanding this mechanism has important implications for cardiac physiology, heart failure management, and therapeutic interventions targeting afterload reduction.
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Antagonism (in phytopathology ) occurs when one organism inhibits or slows down the growth of a plant disease-causing organism, such as harmful bacteria or fungi . [ 1 ] Most plants can host a variety of pathogens and are often infected by multiple species simultaneously. [ 2 ] In ecology , species competing for the same resource can influence each other in two ways: antagonism, where one pathogen harms another, and synergism, where one pathogen supports the growth of another. [ 3 ]
Antagonism is often employed as a natural method to protect plants from diseases. This can occur through mechanism such as competition for space and nutrients, the production of toxins or siderophores by one pathogen to suppress another, [ 4 ] induction of host resistance, or other processes that inhibit the growth or reproduction of pathogens, as demonstrated in the Ascochyta blight complex on peas . [ 5 ]
The mechanism of antibiosis involves an interaction between two organisms, where one organism produces substances such as toxins, enzymes, or antibiotics that harm another organism, particularly pathogens. [ 6 ] These interactions reduce pathogen viability of pathogens, limit the spread of disease, and enhance plant protection. For instance, antagonistic microbes can produce lytic enzymes, such as chitinases , which break down the cell walls of fungal pathogens, effectively inhibiting their growth. [ 7 ] [ 8 ] Another example is Pseudomonas aeruginosa , [ 9 ] which shows antagonism against Cladosporium . S uch organisms are of great practical importance as they often produce antibiotics that modify normal growth processes.
The mechasism of hyperparasitism involves a parasitic relationship where one organism, typically a fungus, directly attacks another pathogenic fungus. [ 7 ] The hyperparasite physically interacts with the host, penetrates its cell wall, and extract nutrients. An example is the hyperparasitic fungus, Cladosporium cladosporioides , which parasitizes Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust . [ 10 ]
Induction of resistance in antagonism refers to the ability of an antagonistic bacterium to activate a host's defense mechanisms through biochemical changes, such as the production of pathogenesis-related proteins or antimicrobial compounds, thereby enhancing the plant's immunity locally or systemically against pathogens. [ 11 ] For example, Bacillus subtilis induces systemic resistance in plants by triggering the production of pathogenesis-related proteins and antimicrobial compounds, offering protection against fungal pathogens such as Botrytis cinerea . [ 12 ]
Competition for resources occurs as antagonistic bacteria colonize the host and outcompete phytopathogens for essential nutrients, such as carbon sources like sucrose , fructose , and glucose , thereby reducing spore germination and the pathogen's ability to invade the host. [ 13 ] For example, the yeast antagonist Rhodotorula glutinis deprives pathogens of critical micronutrients, such as iron, by producing siderophores . [ 14 ]
Plant diseases are typically managed using synthetic pesticides , however, their use can lead to environmental contamination, reduced biological diversity, the development of resistance in pathogens, and risks to human and animal health. [ 15 ] Antagonism plays a critical role in agriculture, particularly in the development of biological control agent (BCAs) to manage phytopathogens and reduce reliance on synthetic pesticides. [ 16 ] Numerous microbial antagonists, including yeasts and bacteria , are isolated from diverse environments such as soil, plants, compost, and oceans for their potential to control plant diseases. For example, endophyte microorganisms found inside guarana seeds and rhizospheric soil have shown their ability to fight harmful pathogens, making them promising candidates for BCAs.
BCAs are applied during both preharvest and postharvest stages to protect crops like citrus, bananas, peaches, and strawberries. [ 17 ] [ 18 ] Preharvest applications of antagonistic microbes, such as Burkholderia spinosa on bananas and Pantoea agglomerans on citrus, have successfully reduced diseases caused by pathogens such as Penicillium digitatum and Colletotrichum acutatum . [ 19 ] [ 20 ] Additionally, combining BCAs with antimicrobial compounds like chitosan or bicarbonates , has been shown to enhance their effectiveness and increase crop yield. [ 21 ]
In postharvest stages, microbial antagonists are applied directly to fruits through spraying or immersion in solutions. [ 22 ] Several bacterial strains, including Bacillus subtilis , Pantoea agglomerans , and Serratia plymuthica , have been used successfully to suppress fungal growth and control diseases during storage. [ 23 ]
Overall, BCAs provide a sustainable alternative to synthetic pesticides, offering effective plant protection. [ 24 ] However, continued research and development are essential to enhance their efficacy and addressing challenges such as high costs and limited commercial viability.
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In dentistry , Ante's law is a postulate about crown-to-root ratio put forth by Irwin H. Ante [ 1 ] in a thesis paper he wrote in 1926. [ 2 ]
Ante's law states that "the total periodontal membrane area of the abutment teeth must equal or exceed that of the teeth to be replaced."
Later claims were made that "the length of the periodontal membrane attachment of the abutment tooth should be at least one half to two thirds of that of its normal root attachment". [ 3 ]
Because of these unsubstantiated, empirical concepts, many teeth were subsequently excluded from suitability as an abutment for fixed partial dentures and double abutments became a popular means of complying with Ante's law.
Ante's law has not been confirmed by long-term clinical trials. [ 4 ] [ 5 ]
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Anterior interosseous syndrome is a medical condition in which damage to the anterior interosseous nerve (AIN), a distal motor and sensory branch of the median nerve , classically with severe weakness of the pincer movement of the thumb and index finger , and can cause transient pain in the wrist (the terminal, sensory branch of the AIN innervates the bones of the carpal tunnel ).
Most cases of AIN syndrome are now thought to be due to a transient neuritis , although compression of the AIN in the forearm is a risk, such as pressure on the forearm from immobilization after shoulder surgery. Trauma to the median nerve or around the proximal median nerve have also been reported as causes of AIN syndrome.
Studies are limited, and no randomized controlled trials have been performed regarding the treatment of AIN syndrome. While the natural history of AIN syndrome is not fully understood, studies following patients who have been treated without surgery show that symptoms can resolve starting as late as one year after onset. Other retrospective studies have concluded that there is no difference in outcome in surgically versus nonsurgically treated patients. The role of surgery in AIN syndrome remains controversial. Indications for considering surgery include a known space-occupying lesion that is compressing the nerve (a mass) or fascial compression, and persistent symptoms beyond 1 year of conservative treatment.
The findings are weakness in bending (flexion) the tips of the thumb and index finger. [ 1 ]
In a pure lesion of the anterior interosseous nerve there is weakness of the long flexor muscle of the thumb ( Flexor pollicis longus ), the deep flexor muscles of the index and middle fingers ( Flexor digitorum profundus I & II).
Injuries of the forearm with compression of the nerve from swelling is the most common cause: examples include supracondylar fractures , often associated with haemorrhage into the deep musculature; injury secondary to open reduction of a forearm fracture; or dislocation of the elbow. [ 2 ] [ 3 ]
Direct trauma from a penetrating injury such as a stab wound is a possible cause for the syndrome. [ citation needed ]
Fibrous bands or Arcuate ligament~arcuate (curved) ligaments may entrap the median as well as the anterior interosseous nerve, in which case a patient may experience hand numbness as well as wrist pain. [ 4 ] [ 5 ]
Very similar syndromes can be caused by more proximal lesions, such as brachial plexus neuritis . [ 6 ]
Anterior interosseous nerve entrapment or compression injury remains a difficult clinical diagnosis because it is mainly a motor nerve problem, and the syndrome is often mistaken for index finger and/or thumb tendon injury. [ 7 ]
Although there is still controversy among upper extremity surgeons, AIN syndrome is now regarded as a neuritis (inflammation of the nerve) in most cases; this is similar to Parsonage–Turner syndrome . Although the exact etiology is unknown, there is evidence that it is caused by an immune-mediated response that can follow other illnesses, such as pneumonia or severe viral illness . [ citation needed ]
The anterior interosseous nerve is a branch of the median nerve, with a large sensory branch to the wrist bones, which arises just below the elbow. It passes distally, anteriorly along the interosseous membrane and innervates flexor pollicis longus , flexor digitorum profundus to index and middle finger as well as pronator quadratus , and supplies sensory feedback from the wrist bones, i.e. the carpal tunnel, not skin. [ citation needed ]
Electrophysiologic testing is an essential part of the evaluation of anterior interosseous nerve syndrome. Nerve conduction studies may be normal or show pronator quadratus latency. [ 7 ] Electromyography (EMG) is generally most useful and will reveal abnormalities in the flexor pollicis longus, flexor digitorum profundus I and II and pronator quadratus muscles. [ 8 ] [ 7 ]
The role or MRI and ultrasound imaging in the diagnosis of Kiloh-Nevin syndrome is unclear. [ 9 ] [ 10 ]
If asked to make the "OK" sign, patients will make a triangle sign instead. This 'pinch-test' exposes the weakness of the flexor pollicis longus muscle and the flexor digitorum profundus I leading to weakness of the flexion of the distal phalanges of the thumb and index finger. This results in impairment of the pincer movement and the patient will have difficulty picking up a small item, such as a coin, from a flat surface. [ 3 ] [ 11 ]
Surgical decompression can give excellent results if the clinical picture and the EMG suggest a compression neuropathy . [ 12 ] [ 13 ] [ 14 ] In brachial plexus neuritis, conservative management may be more appropriate. [ 6 ] Spontaneous recovery has been reported, but is said to be delayed and incomplete. [ 3 ] [ 15 ]
There may be a role for physiotherapy in some cases, and this should be directed specifically towards the pattern of pain and symptoms. Soft tissue massage, stretches and exercises to directly mobilise the nerve tissue may be used. [ 16 ]
Studies following patients who have been treated without surgery show that symptoms can resolve starting as late as one year after onset. Other retrospective studies have concluded that there is no difference in outcome in surgically versus nonsurgically treated patients. The role of surgery in AIN syndrome remains controversial. Indications for considering surgery include a known space-occupying lesion that is compressing the nerve (a mass) or fascial compression and persistent symptoms beyond 1 year of conservative treatment.
The syndrome was first described by Parsonage and Turner in 1948 [ 17 ] and further defined as isolated lesion of the anterior interosseous nerve by Leslie Gordon Kiloh and Samuel Nevin in 1952. [ 18 ]
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Anterior urethral cancer is a disease in which malignant cancer cells are found in the part of the urethra that is closest to the outside of the body. [ 1 ]
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Anterior vertebral body tethering (AVBT) is a relatively new surgery for the treatment of scoliosis [ 1 ] in pediatric patients. [ 2 ] Left untreated, severe scoliosis can worsen and eventually affect a person's lungs and heart . [ 3 ] [ 4 ] [ 5 ]
In the 1950s and 1960s, doctors began experimenting with a technique called spinal fusion to straighten the spine and prevent long-term health consequences of curvatures . Fusion surgery in children employs pedicle screws [ 6 ] and metal rods to correct the curve. Improvements to fusion techniques have been made over the years, and it remains the standard of care today. [ 7 ] However, fusion has drawbacks, [ 8 ] and pioneers in the field of pediatric orthopedics and neurosurgery have introduced AVBT as a minimally invasive alternative. [ 9 ]
The US Food and Drug Administration (FDA) approved the compassionate use of AVBT in August 2019 [ citation needed ] for a small population of patients. [ 10 ] VBT uses a strong, flexible tether that is attached to screws embedded in the spine. It is important to have the surgery while the child or teen is still growing because the tether is meant to gradually change the severity of the curve as growth occurs. In addition to realigning the spine , the main benefit of VBT is that flexibility is maintained. The word " anterior " is connected with this technique because it can be done through the front or side of the chest wall (rather than the back) [ 2 ] via a number of small incisions that typically heal quickly with proper post-surgical care . The ideal candidate has a severe curve that cannot be corrected with bracing and a Sanders Score (which measures skeletal maturity ) of 3-4. [ 11 ]
This procedure is considered an in-patient surgery under general anesthesia with hospital stays that typically last several days. [ 11 ] AVBT may not be covered by health care insurance ; [ 12 ] nevertheless several state-of-the-art US health systems ( Cincinnati Children's Hospital , Mayo Clinic , Shriners Hospitals for Children , Texas Children's Hospital and University of Missouri Health Care ) offer it as an alternative to fusion for a small number of patients through the FDA's humanitarian device exemption (HDE) pathway. [ 13 ] [ failed verification ] Most patients are eventually able to return to sports and other physical activities that require spinal flexibility. [ 14 ]
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According to the International Federation of Kinesiology , anthropomaximology is the study of the anatomy , physiology , and mechanics of body movement, especially in humans, and its application to the evaluation and treatment of muscular imbalance or derangement. [ 1 ] The concept was developed in the USSR during the 1970s–1980s as a result of numerous Olympic victories. The Soviets utilized anthropomaximology in their athletic training , combining rigorous physical exercise with mental training techniques which allowed the competitors to tap into "hidden reserves" and surpass other athletes' endurance. [ 2 ] [ 3 ]
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Anti-Cancer Drugs is an international medical journal , which aims to promote and encourage research on anti-cancer agents . It was first published in 1990 and it includes reports on clinical and experimental research results, from conventional cytotoxic chemotherapy to hormonal or biological response modalities. [ 1 ] The journal has 10 issues per year and the current editor in chief is Mels Sluyser. According to the 2014 Journal Citation Reports , the journal has an impact factor of 1.784, ranking it 164th out of 211 in the category Oncology and 162nd out of 254 in the category Pharmacology & Pharmacy.
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Anti-neurofascin demyelinating diseases (anti-NF diseases) refers to health conditions engendered by auto-antibodies against neurofascins , which can produce both central and peripheral demyelination . Some cases of combined central and peripheral demyelination (CCPD) could be produced by them. [ 1 ] [ non-primary source needed ]
Whether ANFAs are part of a unique and emerging disease entity, disease modifiers, or inconsequential remains to be elucidated with time. [ 8 ] [ 9 ] Anti-neurofascin antibodies are found in multiple sclerosis, and chronic inflammatory demyelinating polyradiculoneuropathy. [ 10 ]
The first report about a subgroup of MS patients with anti-NF and contactin 2 auto-antibodies was published in 2011 [ 11 ]
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Anti-psychiatry , sometimes spelled antipsychiatry , is a movement based on the view that psychiatric treatment can often be more damaging than helpful to patients. [ 1 ] [ 2 ] The term anti-psychiatry was coined in 1912, and the movement emerged in the 1960s, highlighting controversies about psychiatry . [ 3 ] Objections include the reliability of psychiatric diagnosis, the questionable effectiveness and harm associated with psychiatric medications, the failure of psychiatry to demonstrate any disease treatment mechanism for psychiatric medication effects, and legal concerns about equal human rights and civil freedom being nullified by the presence of diagnosis. Historical critiques of psychiatry came to light after focus on the extreme harms associated with electroconvulsive therapy and insulin shock therapy . [ 4 ] The term "anti-psychiatry" is in dispute and often used to dismiss all critics of psychiatry, many of whom agree that a specialized role of helper for people in emotional distress may at times be appropriate, and allow for individual choice around treatment decisions.
Beyond concerns about effectiveness, anti-psychiatry might question the philosophical and ethical underpinnings of psychotherapy and psychoactive medication , seeing them as shaped by social and political concerns rather than the autonomy and integrity of the individual mind. They may believe that "judgements on matters of sanity should be the prerogative of the philosophical mind", and that the mind should not be a medical concern. Some activists reject the psychiatric notion of mental illness . [ 5 ] Anti-psychiatry considers psychiatry a coercive instrument of oppression due to an unequal power relationship between doctor, therapist, and patient or client, and a highly subjective diagnostic process. Involuntary commitment , which can be enforced legally through sectioning , is an important issue in the movement. When sectioned, involuntary treatment may also be legally enforced by the medical profession against the patient's will.
The decentralized movement has been active in various forms for two centuries. [ 6 ] [ 4 ] In the 1960s, there were many challenges to psychoanalysis and mainstream psychiatry, in which the very basis of psychiatric practice was characterized as repressive and controlling. [ 7 ] Psychiatrists identified with the anti-psychiatry movement included Timothy Leary , R. D. Laing , Franco Basaglia , Theodore Lidz , Silvano Arieti , and David Cooper . Others involved were Michel Foucault , Gilles Deleuze , Félix Guattari , and Erving Goffman . Cooper used the term "anti-psychiatry" in 1967, and wrote the book Psychiatry and Anti-psychiatry in 1971. [ 6 ] [ 4 ] [ 5 ] The word Antipsychiatrie was already used in Germany in 1904. [ 8 ] Thomas Szasz introduced the idea of mental illness being a myth in the book The Myth of Mental Illness (1961). However his literature actually very clearly states that he was directly undermined by the movement led by David Cooper (1931–1986) and that Cooper sought to replace psychiatry with his own brand of it. Giorgio Antonucci , who advocated a non-psychiatric approach to psychological suffering, did not consider himself to be part of the antipsychiatric movement. His position is represented by "the non-psychiatric thinking, which considers psychiatry an ideology devoid of scientific content, a non-knowledge, whose aim is to annihilate people instead of trying to understand the difficulties of life, both individual and social, and then to defend people, change society, and create a truly new culture". [ 9 ] Antonucci introduced the definition of psychiatry as a prejudice in the book I pregiudizi e la conoscenza critica alla psichiatria (1986).
The movement continues to influence thinking about psychiatry and psychology, both within and outside of those fields, particularly in terms of the relationship between providers of treatment and those receiving it. [ 5 ] [ 4 ] Contemporary issues include freedom versus coercion, nature versus nurture, and the right to be different. [ 10 ]
Critics of antipsychiatry from within psychiatry itself object to the underlying principle that psychiatry is harmful, although they usually accept that there are issues that need addressing. [ 11 ] Medical professionals often consider anti-psychiatry movements to be promoting mental illness denial , and some consider their claims to be comparable to conspiracy theories . [ 12 ]
The first widespread challenge to the prevailing medical approach in Western countries occurred in the late 18th century. [ 13 ] Part of the progressive Age of Enlightenment , a " moral treatment " movement challenged the harsh, pessimistic, somatic (body-based) and restraint-based approaches that prevailed in the system of hospitals and "madhouses" for people considered mentally disturbed, who were generally seen as wild animals without reason. [ 13 ] Alternatives were developed, led in different regions by ex-patient staff, physicians themselves in some cases, and religious and lay philanthropists. [ 13 ] This "moral treatment" was seen as pioneering more humane psychological and social approaches, whether or not in medical settings; however, it also involved some use of physical restraints, threats of punishment, and personal and social methods of control. [ 13 ] As it became the establishment approach in the 19th century, opposition to its negative aspects also grew. [ 13 ]
According to Michel Foucault , there was a shift in the perception of madness, whereby it came to be seen as less about delusion , i.e. disturbed judgment about the truth, than about a disorder of regular, normal behavior or will. [ 14 ] Foucault argued that, prior to this, doctors could often prescribe travel, rest, walking, retirement and generally engaging with nature, seen as the visible form of truth, as a means to break with artificialities of the world (and therefore delusions). [ 15 ] Another form of treatment involved nature's opposite, the theater, where the patient's madness was acted out for him or her in such a way that the delusion would reveal itself to the patient.
Thus the most prominent therapeutic technique became to confront patients with a healthy sound will and orthodox passions, ideally embodied by the physician. [ citation needed ] The "cure" involved a process of opposition, of struggle and domination, of the patient's troubled will by the healthy will of the physician. It was thought the confrontation would lead not only to bring the illness into broad daylight by its resistance, but also to the victory of the sound will and the renunciation of the disturbed will. We must apply a perturbing method, to break the spasm by means of the spasm.... We must subjugate the whole character of some patients, subdue their transports, break their pride, while we must stimulate and encourage the others ( Esquirol, J. E. D. , 1816 [ 16 ] ). Foucault also argued that the increasing internment of the "mentally ill" (the development of more and bigger asylums) had become necessary not just for diagnosis and classification but because an enclosed place became a requirement for a treatment that was now understood as primarily the contest of wills, a question of submission and victory.
The techniques and procedures of the asylums at this time included "isolation, private or public interrogations, punishment techniques such as cold showers, moral talks (encouragements or reprimands), strict discipline, compulsory work, rewards, preferential relations between the physician and his patients, relations of vassalage, of possession, of domesticity, even of servitude between patient and physician at times". [ 16 ] Foucault summarized these as "designed to make the medical personage the 'master of madness'" [ 16 ] through the power the physician's will exerts on the patient. The effect of this shift then served to inflate the power of the physician relative to the patient, correlated with the rapid rise of internment (asylums and forced detention). [ 17 ]
Other analyses suggest that the rise of asylums was primarily driven by industrialization and capitalism , including the breakdown of traditional family structures. By the end of the 19th century, psychiatrists often had little power in the overcrowded asylum system, acting mainly as administrators who rarely attended to patients in a system where therapeutic ideals had turned into institutional routines. [ 18 ] In general, critics point to negative aspects of the shift toward so-called "moral treatments", and the concurrent widespread expansion of asylums, medical power and involuntary hospitalization laws, that played an important part in the development of the anti-psychiatry movement. [ 19 ]
Various 19th-century critiques of the newly emerging field of psychiatry overlap thematically with 20th-century anti-psychiatry, for example in their questioning of the medicalization of "madness". Those critiques occurred at a time when physicians had not yet achieved hegemony through psychiatry, however, so there was no single, unified force to oppose. [ 19 ] Nevertheless, there was increasing concern at the ease with which people could be confined, with frequent reports of abuse and illegal confinement. For example, Daniel Defoe , the author of Robinson Crusoe , had previously argued for more government oversight of "madhouses" and for due process prior to involuntary internment. [ 20 ] He later argued that husbands used asylum hospitals to incarcerate their disobedient wives, [ 21 ] and in a subsequent pamphlet that wives even did the same to their husbands. [ 22 ] It was also proposed that the role of asylum keeper be separated from doctor, to discourage exploitation of patients. [ 23 ] There was general concern that physicians were undermining personhood by medicalizing problems, by claiming they alone had the expertise to judge, and by arguing that mental disorder was physical and hereditary. The Alleged Lunatics' Friend Society arose in England in the mid-19th century to challenge the system and campaign for rights and reforms. [ 24 ] In the United States, Elizabeth Packard published a series of books and pamphlets describing her experiences in the Illinois insane asylum, to which she had been committed at the request of her husband.
Throughout, the class nature of mental hospitals and their role as agencies of control were well recognized. The new psychiatry was partially challenged by two powerful social institutions – the church and the legal system. These trends have been thematically linked to the later 20th century anti-psychiatry movement. [ 25 ]
As psychiatry became more professionally established during the nineteenth century (the term itself was coined in 1808 in Germany by Johann Christian Reil , as "Psychiaterie") and developed allegedly more invasive treatments, opposition increased. [ 26 ] In the Southern US, black slaves and abolitionists encountered drapetomania , a pseudo-scientific diagnosis that presented the desire of slaves to run away from their masters as a symptom of pathology. [ 27 ]
There was some organized challenge to psychiatry in the late 1870s from the new speciality of neurology , largely centered around control of state insane asylums in New York. [ 28 ] Practitioners criticized mental hospitals for failure to conduct scientific research and adopt the modern therapeutic methods such as nonrestraint. Together with lay reformers and social workers, neurologists formed the National Association for the Protection of the Insane and the Prevention of Insanity. However, when the lay members questioned the competence of asylum physicians to even provide proper care at all, the neurologists withdrew their support and the association floundered. [ 25 ]
It has been noted that "the most persistent critics of psychiatry have always been former mental hospital patients", but that very few were able to tell their stories publicly or to confront the psychiatric establishment openly, and those who did so were commonly considered so extreme in their charges that they could seldom gain credibility. [ 25 ] In the early 20th century, ex-patient Clifford W. Beers campaigned to improve the plight of individuals receiving public psychiatric care, particularly those committed to state institutions, publicizing the issues in his book, A Mind that Found Itself (1908). [ 29 ] While Beers initially condemned psychiatrists for tolerating mistreatment of patients, and envisioned more ex-patient involvement in the movement, he was influenced by Adolf Meyer and the psychiatric establishment, and toned down his hostility since he needed their support for reforms. In Germany during this time were similar efforts which used the term "Antipsychiatrie". [ 30 ]
Beers' reliance on rich donors and his need for approval from experts led him to hand over to psychiatrists the organization he helped found, the National Committee for Mental Hygiene, which eventually became the National Mental Health Association . [ 25 ] In the UK, the National Society for Lunacy Law Reform was established in 1920 by angry ex-patients who sought justice for abuses committed in psychiatric custody, and were aggrieved that their complaints were patronizingly discounted by the authorities, who were seen to value the availability of medicalized internment as a 'whitewashed' extrajudicial custodial and punitive process. [ 31 ] In 1922, ex-patient Rachel Grant-Smith added to calls for reform of the system of neglect and abuse she had suffered by publishing "The Experiences of an Asylum Patient". [ 32 ] In the US, We Are Not Alone (WANA) was founded by a group of patients at Rockland State Hospital in New York, and continued to meet as an ex-patient group. [ 33 ]
French surrealist Antonin Artaud would also openly criticize that no patient should be labeled as "mentally ill" as an exterior identification, as he notes in his 1925 L'Ombilic des limbes , as well as arguing against narcotic's restriction laws in France. Much influenced by the Dada and surrealist enthusiasms of the day, he considered dreams , thoughts and visions no less real than the "outside" world. [ 34 ] In this era before penicillin was discovered, eugenics was popular. People believed diseases of the mind could be passed on so compulsory sterilization of the mentally ill was enacted in many countries . [ 35 ]
In the 1930s several controversial medical practices were introduced and framed as "treatments" for mental disorders, including inducing seizures (by electroshock , insulin or other drugs) or psychosurgery ( lobotomy ). In the US, beginning in 1939 through 1951, over 50,000 lobotomy operations were performed in mental hospitals, a procedure ultimately seen as inhumane. [ 36 ]
Holocaust historians argued that the medicalization of social programs and systematic euthanasia of people in German mental institutions in the 1930s provided the institutional, procedural, and doctrinal origins of the mass murder of the 1940s. The Nazi programs were called Action T4 and Action 14f13 . [ 37 ] [ 38 ] [ 39 ] The Nuremberg Trials convicted a number of psychiatrists who held key positions in Nazi regimes. As one Swiss psychiatrist stated: "A not so easy question to be answered is whether it should be allowed to destroy lives objectively 'unworthy of living' without the expressed request of its bearers. (...) Even in incurable mentally ill ones suffering seriously from hallucinations and melancholic depressions and not being able to act, to a medical colleague I would ascript the right and in serious cases the duty to shorten — often for many years — the suffering" (Bleuler, Eugen, 1936: "Die naturwissenschaftliche Grundlage der Ethik". Schweizer Archiv Neurologie und Psychiatrie, Band 38, Nr.2, S. 206).
The post-World War II decades saw an enormous growth in psychiatry; many Americans were persuaded that psychiatry and psychology, particularly psychoanalysis , were a key to happiness. Meanwhile, most hospitalized mental patients received at best decent custodial care, and at worst, abuse and neglect.
The psychoanalyst Jacques Lacan has been identified as an influence on later anti-psychiatry theory in the UK, and as being the first, in the 1940s and 50s, to professionally challenge psychoanalysis to reexamine its concepts and to appreciate psychosis as understandable. Other influences on Lacan included poetry and the surrealist movement, including the poetic power of patients' experiences. Critics disputed this and questioned how his descriptions linked to his practical work. The names that came to be associated with the anti-psychiatry movement knew of Lacan and acknowledged his contribution even if they did not entirely agree. [ 40 ] The psychoanalyst Erich Fromm is also said to have articulated, in the 1950s, the secular humanistic concern of the coming anti-psychiatry movement. In The Sane Society (1955), Fromm wrote "An unhealthy society is one which creates mutual hostility [and] distrust, which transforms man into an instrument of use and exploitation for others, which deprives him of a sense of self, except inasmuch as he submits to others or becomes an automaton"..."Yet many psychiatrists and psychologists refuse to entertain the idea that society as a whole may be lacking in sanity. They hold that the problem of mental health in a society is only that of the number of 'unadjusted' individuals, and not of a possible unadjustment of the culture itself". [ 41 ]
In the 1950s new psychiatric drugs, notably the antipsychotic chlorpromazine , slowly came into use. Although often accepted as an advance in some ways, there was opposition, partly due to serious adverse effects such as tardive dyskinesia , and partly due their "chemical straitjacket" effect and their alleged use to control and intimidate patients. [ 36 ] Patients often opposed psychiatry and refused or stopped taking the drugs when not subject to psychiatric control. [ 36 ] There was also increasing opposition to the large-scale use of psychiatric hospitals and institutions, and attempts were made to develop services in the community . [ citation needed ]
According to the Encyclopedia of Theory and Practice in Psychotherapy and Counseling, "In the 1950s in the United States, a right-wing anti-mental health movement opposed psychiatry, seeing it as liberal , left-wing , subversive and anti-American or pro-Communist. There were widespread fears that it threatened individual rights and undermined moral responsibility. An early skirmish was over the Alaska Mental Health Bill , where the right wing protestors were joined by the emerging Scientology movement." [ 42 ] [ 43 ]
The field of psychology sometimes came into opposition with psychiatry. Behaviorists argued that mental disorder was a matter of learning not medicine; for example, Hans Eysenck argued that psychiatry "really has no role to play". The developing field of clinical psychology in particular came into close contact with psychiatry, often in opposition to its methods, theories and territories. [ 44 ]
Coming to the fore in the 1960s, "anti-psychiatry" (a term first used by David Cooper in 1967) defined a movement that vocally challenged the fundamental claims and practices of mainstream psychiatry. While most of its elements had precedents in earlier decades and centuries, in the 1960s it took on a national and international character, with access to the mass media and incorporating a wide mixture of grassroots activist organizations and prestigious professional bodies. [ 44 ]
Cooper was a South African psychiatrist working in Britain. A trained Marxist revolutionary, he argued that the political context of psychiatry and its patients had to be highlighted and radically challenged, and warned that the fog of individualized therapeutic language could take away people's ability to see and challenge the bigger social picture. He spoke of having a goal of "non-psychiatry" as well as anti-psychiatry. [ 44 ]
The psychiatrists R D Laing (from Scotland), Theodore Lidz (from America), Silvano Arieti (from Italy) and others, argued that "schizophrenia" and psychosis were understandable, and resulted from injuries to the inner-self-inflicted by psychologically invasive "schizophrenogenic" parents or others. It was sometimes seen as a transformative state involving an attempt to cope with a sick society. Laing, however, partially dissociated himself from his colleague Cooper's term "anti-psychiatry". Laing had already become a media icon through bestselling books (such as The Divided Self and The Politics of Experience ) discussing mental distress in an interpersonal existential context; Laing was somewhat less focused than his colleague Cooper on wider social structures and radical left wing politics, and went on to develop more romanticized or mystical views (as well as equivocating over the use of diagnosis, drugs and commitment). Although the movement originally described as anti-psychiatry became associated with the general counter-culture movement of the 1960s, Lidz and Arieti never became involved in the latter. Franco Basaglia promoted anti-psychiatry in Italy and secured reforms to mental health law there.
Laing, through the Philadelphia Association founded with Cooper in 1965, set up over 20 therapeutic communities including Kingsley Hall , where staff and residents theoretically assumed equal status and any medication used was voluntary. Non-psychiatric Soteria houses, starting in the United States, were also developed [ 46 ] as were various ex-patient-led services.
Psychiatrist Thomas Szasz argued that " mental illness " is an inherently incoherent combination of a medical and a psychological concept. He opposed the use of psychiatry to forcibly detain, treat, or excuse what he saw as mere deviance from societal norms or moral conduct. As a libertarian , Szasz was concerned that such usage undermined personal rights and moral responsibility. Adherents of his views referred to "the myth of mental illness", after Szasz's controversial 1961 book of that name (based on a paper of the same name that Szasz had written in 1957 that, following repeated rejections from psychiatric journals, had been published in the American Psychologist in 1960 [ 47 ] ). Although widely described as part of the main anti-psychiatry movement, Szasz actively rejected the term and its adherents; instead, in 1969, he collaborated with Scientology to form the Citizens Commission on Human Rights . [ 11 ] It was later noted that the view that insanity was not in most or even in any instances a "medical" entity, but a moral issue, was also held by Christian Scientists and certain Protestant fundamentalists , as well as Szasz. [ 25 ] Szasz was not a Scientologist himself and was non-religious; he commented frequently on the parallels between religion and psychiatry.
Erving Goffman , Gilles Deleuze , Félix Guattari and others criticized the power and role of psychiatry in society, including the use of " total institutions " and the use of models and terms that were seen as stigmatizing . [ 48 ] The French sociologist and philosopher Foucault, in his 1961 publication Madness and Civilization : A History of Insanity in the Age of Reason , analyzed how attitudes towards those deemed "insane" had changed as a result of changes in social values. He argued that psychiatry was primarily a tool of social control, based historically on a "great confinement" of the insane and physical punishment and chains, later exchanged in the moral treatment era for psychological oppression and internalized restraint. American sociologist Thomas Scheff applied labeling theory to psychiatry in 1966 in "Being Mentally Ill". Scheff argued that society views certain actions as deviant and, in order to come to terms with and understand these actions, often places the label of mental illness on those who exhibit them. Certain expectations are then placed on these individuals and, over time, they unconsciously change their behavior to fulfill them. [ citation needed ]
Observation of the abuses of psychiatry in the Soviet Union in the so-called Psikhushka hospitals also led to questioning the validity of the practice of psychiatry in the West. [ 49 ] In particular, the diagnosis of many political dissidents with schizophrenia led some to question the general diagnosis and punitive usage of the label schizophrenia . This raised questions as to whether the schizophrenia label and resulting involuntary psychiatric treatment could not have been similarly used in the West to subdue rebellious young people during family conflicts. [ 50 ] [ unreliable source? ]
New professional approaches were developed as an alternative or reformist complement to psychiatry. The Radical Therapist , a journal begun in 1971 in North Dakota by Michael Glenn, David Bryan, Linda Bryan, Michael Galan and Sara Glenn, challenged the psychotherapy establishment in a number of ways, raising the slogan "Therapy means change, not adjustment." It contained articles that challenged the professional mediator approach, advocating instead revolutionary politics and authentic community making. Social work , humanistic or existentialist therapies, family therapy , counseling and self-help and clinical psychology developed and sometimes opposed psychiatry.
The psychoanalytically trained psychiatrist Szasz , although professing fundamental opposition to what he perceives as medicalization and oppressive or excuse-giving "diagnosis" and forced "treatment", was not opposed to other aspects of psychiatry (for example attempts to "cure-heal souls", although he also characterizes this as non-medical). Although generally considered anti-psychiatry by others, he sought to dissociate himself politically from a movement and term associated with the radical left-wing. In a 1976 publication "Anti-psychiatry: The paradigm of a plundered mind", which has been described as an overtly political condemnation of a wide sweep of people, Szasz claimed Laing, Cooper and all of anti-psychiatry consisted of "self-declared socialists , communists , anarchists or at least anti- capitalists and collectivists ". [ need quotation to verify ] While saying he shared some of their critique of the psychiatric system, Szasz compared their views on the social causes of distress/deviance to those of anti-capitalist anti- colonialists who claimed that Chilean poverty was due to plundering by American companies, a comment Szasz made not long after a CIA -backed coup had deposed the democratically elected Chilean president and replaced him with Pinochet . Szasz argued instead that distress/deviance is due to the flaws or failures of individuals in their struggles in life. [ 51 ]
The anti-psychiatry movement was also being driven by individuals with adverse experiences of psychiatric services. This included those who felt they had been harmed by psychiatry or who felt that they could have been helped more by other approaches, including those compulsorily (including via physical force) admitted to psychiatric institutions and subjected to compulsory medication or procedures. During the 1970s, the anti-psychiatry movement was involved in promoting restraint from many practices seen as psychiatric abuses.
The gay rights movement continued to challenge the classification of homosexuality as a mental illness and in 1974, in a climate of controversy and activism, the American Psychiatric Association membership (following a unanimous vote by the trustees in 1973) voted by a small majority (58%) to remove it as an illness category from the DSM , replacing it with a category of "sexual orientation disturbance" and then "ego-dystonic homosexuality," which was deleted in 1986, although a wide variety of " paraphilias " remain.
The diagnostic label gender identity disorder (GID) was used by the DSM until its reclassification as gender dysphoria in 2013, with the release of the DSM-5 . The diagnosis was reclassified to better align it with medical understanding of the condition and to remove the stigma associated with the term disorder . [ 52 ] [ 53 ] The American Psychiatric Association, publisher of the DSM-5, stated that gender nonconformity is not the same thing as gender dysphoria, [ 54 ] and that "gender nonconformity is not in itself a mental disorder. The critical element of gender dysphoria is the presence of clinically significant distress associated with the condition." [ 55 ] Some transgender people and researchers support declassification of the condition because they say the diagnosis pathologizes gender variance and reinforces the binary model of gender . [ 52 ] [ 56 ] [ 57 ] Szasz also publicly endorsed the transmisogynist work of Janice Raymond . In a 1979 New York Times book review of Raymond's The Transsexual Empire , Szasz drew connections between his ongoing critique of psychiatric diagnosis and Raymond's feminist critique of trans women. [ 58 ]
Increased legal and professional protections, and a merging with human rights and disability rights movements, added to anti-psychiatry theory and action.
Anti-psychiatry came to challenge a " biomedical " focus of psychiatry (defined to mean genetics , neurochemicals and pharmaceutic drugs). There was also opposition to the increasing links between psychiatry and pharmaceutical companies , which were becoming more powerful and were increasingly claimed to have excessive, unjustified and underhand influence on psychiatric research and practice. There was also opposition to the codification of, and alleged misuse of, psychiatric diagnoses into manuals, in particular the American Psychiatric Association, which publishes the Diagnostic and Statistical Manual of Mental Disorders .
Anti-psychiatry increasingly challenged alleged psychiatric pessimism and institutionalized alienation regarding those categorized as mentally ill. An emerging consumer/survivor movement often argues for full recovery , empowerment , self-management and even full liberation. Schemes were developed to challenge stigma and discrimination, often based on a social model of disability ; to assist or encourage people with mental health issues to engage more fully in work and society (for example through social firms ), and to involve service users in the delivery and evaluation of mental health services. However, those actively and openly challenging the fundamental ethics and efficacy of mainstream psychiatric practice remained marginalized within psychiatry, and to a lesser extent within the wider mental health community.
Three authors came to personify the movement against psychiatry, and two of these were practicing psychiatrists. The initial and most influential of these was Thomas Szasz who rose to fame with his book The Myth of Mental Illness , although Szasz himself did not identify as an anti-psychiatrist. The well-respected R D Laing wrote a series of best-selling books, including The Divided Self . Intellectual philosopher Michel Foucault challenged the very basis of psychiatric practice and cast it as repressive and controlling. The term "anti-psychiatry" was coined by David Cooper in 1967. [ 6 ] [ 4 ] In parallel with the theoretical production of the mentioned authors, the Italian physician Giorgio Antonucci questioned the basis themselves of psychiatry through the dismantling of the psychiatric hospitals Osservanza and Luigi Lolli and the liberation – and restitution to life – of the people there secluded. [ 59 ]
In recent years, psychotherapists David Smail and Bruce E. Levine , considered part of the anti-psychiatry movement, have written widely on how society, culture, politics and psychology intersect. They have written extensively of the "embodied nature" of the individual in society, and the unwillingness of even therapists to acknowledge the obvious part played by power and financial interest in modern Western society. They argue that feelings and emotions are not, as is commonly supposed, features of the individual, but rather responses of the individual to their situation in society. Even psychotherapy, they suggest, can only change feelings in as much as it helps a person to change the "proximal" and "distal" influences on their life, which range from family and friends, to the workplace, socio-economics, politics and culture. [ 60 ] [ 61 ]
R. D. Laing emphasized family nexus as a mechanism by which individuals become victimized by those around them, and spoke about a dysfunctional society. [ 62 ] [ 63 ] [ 64 ]
Psychiatrists have been trying to differentiate mental disorders based on clinical interviews since the era of Kraepelin, but now realize that their diagnostic criteria are imperfect. Tadafumi Kato writes, "We psychiatrists should be aware that we cannot identify 'diseases' only by interviews. What we are doing now is just like trying to diagnose diabetes mellitus without measuring blood sugar." [ 65 ]
In 2013, psychiatrist Allen Frances said that "psychiatric diagnosis still relies exclusively on fallible subjective judgments rather than objective biological tests". [ 66 ]
Reasons have been put forward to doubt the ontic status of mental disorders. [ 67 ] : 13 Mental disorders engender ontological skepticism on three levels:
In the scientific and academic literature on the definition or classification of mental disorder, one extreme argues that it is entirely a matter of value judgements (including of what is normal ) while another proposes that it is or could be entirely objective and scientific (including by reference to statistical norms). [ 68 ] Common hybrid views argue that the concept of mental disorder is objective but a "fuzzy prototype " that can never be precisely defined, or alternatively that it inevitably involves a mix of scientific facts and subjective value judgments. [ 69 ]
One remarkable example of psychiatric diagnosis being used to reinforce cultural bias and oppress dissidence is the diagnosis of drapetomania . In the US prior to the American Civil War, physicians such as Samuel A. Cartwright diagnosed some slaves with drapetomania, a mental illness in which the slave possessed an irrational desire for freedom and a tendency to try to escape. [ 70 ] By classifying such a dissident mental trait as abnormal and a disease, psychiatry promoted cultural bias about normality, abnormality, health, and unhealth. This example indicates the probability for not only cultural bias but also confirmation bias and bias blind spot in psychiatric diagnosis and psychiatric beliefs. [ 71 ]
It has been argued by philosophers like Foucault that characterizations of "mental illness" are indeterminate and reflect the hierarchical structures of the societies from which they emerge rather than any precisely defined qualities that distinguish a "healthy" mind from a "sick" one. Furthermore, if a tendency toward self-harm is taken as an elementary symptom of mental illness, then humans, as a species , are arguably insane in that they have tended throughout recorded history to destroy their own environments, to make war with one another, etc. [ 72 ]
Mental disorders were first included in the sixth revision of the International Classification of Diseases (ICD-6) in 1949. [ 73 ] Three years later, the American Psychiatric Association created its own classification system, DSM-I. [ 73 ] The definitions of most psychiatric diagnoses consist of combinations of phenomenological criteria, such as symptoms and signs and their course over time. [ 73 ] Expert committees combined them in variable ways into categories of mental disorders, defined and redefined them again and again over the last half century. [ 73 ]
The majority of these diagnostic categories are called disorders and are not validated by biological criteria, as most medical diseases are; although they purport to represent medical diseases and take the form of medical diagnoses. [ 73 ] These diagnostic categories are actually embedded in top-down classifications, similar to the early botanic classifications of plants in the 17th and 18th centuries, when experts decided a priori about which classification criterion to use, for instance, whether the shape of leaves or fruiting bodies were the main criterion for classifying plants. [ 73 ] Since the era of Kraepelin, psychiatrists have been trying to differentiate mental disorders by using clinical interviews. [ 65 ]
In 1972, psychologist David Rosenhan published the Rosenhan experiment , a study questioning the validity of psychiatric diagnoses. [ 74 ] The study arranged for eight individuals with no history of psychopathology to attempt admission into psychiatric hospitals. The individuals included a graduate student, psychologists, an artist, a housewife, and two physicians, including one psychiatrist. All eight individuals were admitted with a diagnosis of schizophrenia or bipolar disorder. Psychiatrists then attempted to treat the individuals using psychiatric medication. All eight were discharged within 7 to 52 days. In a later part of the study , psychiatric staff were warned that pseudo-patients might be sent to their institutions, but none were actually sent. Nevertheless, a total of 83 patients out of 193 were believed by at least one staff member to be actors. The study concluded that individuals without mental disorders were indistinguishable from those with mental disorders. [ 74 ]
Critics such as Robert Spitzer cast doubt on the validity and credibility of the study, but did concede that the consistency of psychiatric diagnoses needed improvement. [ 75 ] The challenge of the validity versus the reliability of diagnostic categories continues to plague diagnostic systems. Neuroscientist Tadafumi Kato advocates for a new classification of diseases based on the neurobiological features of each mental disorder. [ 65 ] while Austrian psychiatrist Heinz Katsching advises psychiatrists to replace the term "mental illness" by "brain illness." [ 73 ]
There are recognized problems regarding the diagnostic reliability and validity of mainstream psychiatric diagnoses, both in ideal and controlled circumstances [ 76 ] and even more so in routine clinical practice (McGorry et al. . 1995). [ 77 ] Criteria in the principal diagnostic manuals, the DSM and ICD , are not consistent between the two manuals. [ 78 ] Some psychiatrists in critiquing diagnostic criteria point out that comorbidity , when an individual meets criteria for two or more disorders, is the rule rather than the exception, casting doubt on the distinctness of the categories, with overlap and vaguely defined or changeable boundaries between what are asserted to be distinct disorders. [ 79 ]
Other concerns raised include using standard diagnostic criteria in different countries, cultures, genders or ethnic groups. Critics contend that Westernized, white, male-dominated psychiatric practices and diagnoses disadvantage and misunderstand those from other groups. For example, several studies have shown that African Americans are more often diagnosed with schizophrenia than white people, [ 80 ] and men more than women. Some within the anti-psychiatry movement are critical of the use of diagnosis at all as it conforms with the biomedical model , seen as illegitimate.
According to Franco Basaglia, Giorgio Antonucci , and Bruce E. Levine , whose approach pointed out the role of psychiatric institutions in the control and medicalization of deviant behaviors and social problems, psychiatry is used as the provider of scientific support for social control to the existing establishment, and the ensuing standards of deviance and normality brought about repressive views of discrete social groups. [ 61 ] [ 81 ] [ 82 ] : 70 According to Mike Fitzpatrick, resistance to medicalization was a common theme of the gay liberation, anti-psychiatry, and feminist movements of the 1970s, but now there is actually no resistance to the advance of government intrusion in lifestyle if it is thought to be justified in terms of public health. [ 83 ]
In the opinion of Mike Fitzpatrick, the pressure for medicalization also comes from society itself. As one example, Fitzpatrick claims that feminists who once opposed state intervention as oppressive and patriarchal, now demand more coercive and intrusive measures to deal with child abuse and domestic violence. [ 83 ] According to Richard Gosden, the use of psychiatry as a tool of social control is becoming obvious in preventive medicine programs for various mental diseases. [ 84 ] : 14 These programs are intended to identify children and young people with divergent behavioral patterns and thinking and send them to treatment before their supposed mental diseases develop. [ 84 ] : 14 Clinical guidelines for best practice in Australia [ citation needed ] include the risk factors and signs which can be used to detect young people who are in need of prophylactic drug treatment to prevent the development of schizophrenia and other psychotic conditions. [ 84 ] : 14
Critics of psychiatry commonly express a concern that the path of diagnosis and treatment in contemporary society is primarily or overwhelmingly shaped by profit prerogatives, echoing a common criticism of general medical practice in the United States, where many of the largest psychopharmaceutical producers are based. [ 61 ] [ 85 ]
Psychiatric research has demonstrated varying degrees of efficacy for improving or managing a number of mental health disorders through either medications, psychotherapy, or a combination of the two. Typical psychiatric medications include stimulants , antidepressants , anxiolytics , and antipsychotics (neuroleptics).
On the other hand, organizations such as MindFreedom International and World Network of Users and Survivors of Psychiatry maintain that psychiatrists exaggerate the evidence of medication and minimize the evidence of adverse drug reaction . They and other activists believe individuals are not given balanced information, and that current psychiatric medications do not appear to be specific to particular disorders in the way mainstream psychiatry asserts; [ 86 ] and psychiatric drugs not only fail to correct measurable chemical imbalances in the brain, but rather induce undesirable side effects. For example, though children on Ritalin and other psycho-stimulants become more obedient to parents and teachers, [ 87 ] critics have noted that they can also develop abnormal movements such as tics, spasms and other involuntary movements. [ 88 ] This has not been shown to be directly related to the therapeutic use of stimulants, but to neuroleptics. [ 89 ] [ 90 ] The diagnosis of attention deficit hyperactivity disorder on the basis of inattention to compulsory schooling also raises critics' concerns regarding the use of psychoactive drugs as a means of unjust social control of children. [ 87 ]
The influence of pharmaceutical companies is another major issue for the anti-psychiatry movement. As many critics from within and outside of psychiatry have argued, there are many financial and professional links between psychiatry, regulators, and pharmaceutical companies. Drug companies routinely fund much of the research conducted by psychiatrists, advertise medication in psychiatric journals and conferences, fund psychiatric and healthcare organizations and health promotion campaigns, and send representatives to lobby general physicians and politicians. Peter Breggin , Sharkey, and other investigators of the psycho-pharmaceutical industry maintain that many psychiatrists are members, shareholders or special advisors to pharmaceutical or associated regulatory organizations. [ 91 ] [ 92 ]
There is evidence that research findings and the prescribing of drugs are influenced as a result. A United Kingdom cross-party parliamentary inquiry into the influence of the pharmaceutical industry in 2005 concludes: "The influence of the pharmaceutical industry is such that it dominates clinical practice" [ 93 ] and that there are serious regulatory failings resulting in "the unsafe use of drugs; and the increasing medicalization of society". [ 94 ] The campaign organization No Free Lunch details the prevalent acceptance by medical professionals of free gifts from pharmaceutical companies and the effect on psychiatric practice. [ 95 ] The ghostwriting of articles by pharmaceutical company officials, which are then presented by esteemed psychiatrists, has also been highlighted. [ 96 ] Systematic reviews have found that trials of psychiatric drugs that are conducted with pharmaceutical funding are several times more likely to report positive findings than studies without such funding. [ 97 ]
The number of psychiatric drug prescriptions have been increasing at an extremely high rate since the 1950s and show no sign of abating. [ 36 ] In the United States antidepressants and tranquilizers are now the top selling class of prescription drugs, and neuroleptics and other psychiatric drugs also rank near the top, all with expanding sales. [ 97 ] As a solution to the apparent conflict of interests, critics propose legislation to separate the pharmaceutical industry from the psychiatric profession.
John Read and Bruce E. Levine have advanced the idea of socioeconomic status as a significant factor in the development and prevention of mental disorders such as schizophrenia and have noted the reach of pharmaceutical companies through industry sponsored websites as promoting a more biological approach to mental disorders, rather than a comprehensive biological, psychological and social model. [ 61 ] [ 98 ]
Psychiatrists may advocate psychiatric drugs, psychotherapy or more controversial interventions such as electroshock or psychosurgery to treat mental illness. Electroconvulsive therapy (ECT) is administered worldwide typically for severe mental disorders. Across the globe it has been estimated that approximately 1 million patients receive ECT per year. [ 99 ] Exact numbers of how many persons per year have ECT in the United States are unknown due to the variability of settings and treatment. Researchers' estimates generally range from 100,000 to 200,000 persons per year. [ 100 ] [ self-published source ]
Some persons receiving ECT die during the procedure (ECT is performed under a general anesthetic, which always carries a risk). Leonard Roy Frank writes that estimates of ECT-related death rates vary widely. The lower estimates include:
Higher estimates include:
Psychiatrists around the world have been involved in the suppression of individual rights by states in which the definitions of mental disease have been expanded to include political disobedience. [ 103 ] : 6 Nowadays, in many countries, political prisoners are sometimes confined and abused in mental institutions. [ 104 ] : 3 Psychiatry possesses a built-in capacity for abuse which is greater than in other areas of medicine. [ 105 ] : 65 The diagnosis of mental disease can serve as proxy for the designation of social dissidents, allowing the state to hold persons against their will and to insist upon therapies that work in favor of ideological conformity and in the broader interests of society. [ 105 ] : 65 In a monolithic state, psychiatry can be used to bypass standard legal procedures for establishing guilt or innocence and allow political incarceration without the ordinary odium attaching to such political trials. [ 105 ] : 65
Under the Nazi regime in the 1940s, the "duty to care" was violated on an enormous scale. [ 39 ] In Germany alone 300,000 individuals that had been deemed mentally ill, work-shy or feeble-minded were sterilized . An additional 200,000 were euthanized. [ 106 ] These practices continued in territories occupied by the Nazis further afield (mainly in eastern Europe ), affecting thousands more. [ 107 ] From the 1960s up to 1986, political abuse of psychiatry was reported to be systematic in the Soviet Union, and to surface on occasion in other Eastern European countries such as Romania , Hungary , Czechoslovakia , and Yugoslavia , [ 105 ] : 66 as well as in Western European countries, such as Italy. An example of the use of psychiatry in the political field is the "case Sabattini", described by Giorgio Antonucci in his book Il pregiudizio psichiatrico . [ 108 ] A "mental health genocide" reminiscent of the Nazi aberrations has been located in the history of South African oppression during the apartheid era. [ 109 ] A continued misappropriation of the discipline was later attributed to the People's Republic of China. [ 110 ]
K. Fulford, A. Smirnov, and E. Snow state: "An important vulnerability factor, therefore, for the abuse of psychiatry, is the subjective nature of the observations on which psychiatric diagnosis currently depends." [ 111 ] In an article published in 1994 by the Journal of Medical Ethics , American psychiatrist Thomas Szasz stated that "the classification by slave owners and slave traders of certain individuals as Negroes was scientific, in the sense that whites were rarely classified as blacks. But that did not prevent the 'abuse' of such racial classification, because (what we call) its abuse was, in fact, its use." [ 112 ] Szasz argued that the spectacle of the Western psychiatrists loudly condemning Soviet colleagues for their abuse of professional standards was largely an exercise in hypocrisy. [ 84 ] : 220 [ 112 ] Szasz states that K. Fulford, A. Smirnov, and E. Snow, who correctly emphasize the value-laden nature of psychiatric diagnoses and the subjective character of psychiatric classifications, fail to accept the role of psychiatric power. [ 112 ] He stated that psychiatric abuse, such as people usually associated with practices in the former USSR, was connected not with the misuse of psychiatric diagnoses, but with the political power built into the social role of the psychiatrist in democratic and totalitarian societies alike. [ 84 ] : 220 [ 112 ] Musicologists, drama critics, art historians, and many other scholars also create their own subjective classifications; however, lacking state-legitimated power over persons, their classifications do not lead to anyone's being deprived of property, liberty, or life. [ 112 ] For instance, a plastic surgeon's classification of beauty is subjective, but the plastic surgeon cannot treat his or her patient without the patient's consent, so there cannot be any political abuse of plastic surgery. [ 112 ]
The bedrock of political medicine is coercion masquerading as medical treatment. [ 113 ] : 497 In this process, physicians diagnose a disapproved condition as an "illness" and declare the intervention they impose on the victim a "treatment," and legislators and judges legitimate these categorizations. [ 113 ] : 497 In the same way, physician- eugenicists advocated killing certain disabled or ill persons as a form of treatment for both society and patient long before the Nazis came to power. [ 113 ] : 497 [ 114 ]
From the commencement of his political career, Hitler put his struggle against "enemies of the state" in medical rhetoric. [ 113 ] : 502 In 1934, addressing the Reichstag, he declared, "I gave the order… to burn out down to the raw flesh the ulcers of our internal well-poisoning." [ 113 ] : 502 [ 115 ] : 494 The entire German nation and its National Socialist politicians learned to think and speak in such terms. [ 113 ] : 502 Werner Best , Reinhard Heydrich 's deputy, stated that the task of the police was "to root out all symptoms of disease and germs of destruction that threatened the political health of the nation… [In addition to Jews,] most [of the germs] were weak, unpopular and marginalized groups, such as gypsies, homosexuals, beggars, 'antisocials', 'work-shy', and 'habitual criminals'." [ 113 ] : 502 [ 115 ] : 541
In spite of all the evidence, people ignore or underappreciate the political implications of the pseudotherapeutic character of Nazism and of the use of medical metaphors in modern democracies. [ 113 ] : 503 Dismissed as an " abuse of psychiatry ", this practice is a controversial subject not because the story makes psychiatrists in Nazi Germany look bad, but because it highlights the dramatic similarities between pharmacratic controls in Germany under Nazism and those that have emerged in the US under the free market economy. [ 113 ] : 503 [ 116 ] [ page needed ]
The "therapeutic state" is a phrase coined by Szasz in 1963. [ 117 ] The collaboration between psychiatry and government leads to what Szasz calls the "therapeutic state", a system in which disapproved actions, thoughts, and emotions are repressed ("cured") through pseudomedical interventions. [ 118 ] [ 119 ] : 17 Thus suicide, unconventional religious beliefs, racial bigotry, unhappiness, anxiety, shyness, sexual promiscuity, shoplifting, gambling, overeating, smoking, and illegal drug use are all considered symptoms or illnesses that need to be cured. [ 119 ] : 17 When faced with demands for measures to curtail smoking in public, binge-drinking, gambling or obesity, ministers say that "we must guard against charges of nanny statism". [ 83 ] The "nanny state" has turned into the "therapeutic state" where nanny has given way to counselor. [ 83 ] Nanny just told people what to do; counselors also tell them what to think and what to feel. [ 83 ] The "nanny state" was punitive, austere, and authoritarian, the therapeutic state is touchy-feely, supportive—and even more authoritarian. [ 83 ] According to Szasz, "the therapeutic state swallows up everything human on the seemingly rational ground that nothing falls outside the province of health and medicine, just as the theological state had swallowed up everything human on the perfectly rational ground that nothing falls outside the province of God and religion". [ 113 ] : 515
Faced with the problem of "madness", Western individualism proved to be ill-prepared to defend the rights of the individual: modern man has no more right to be a madman than medieval man had a right to be a heretic because if once people agree that they have identified the one true God, or Good, it brings about that they have to guard members and nonmembers of the group from the temptation to worship false gods or goods. [ 113 ] : 496 A secularization of God and the medicalization of good resulted in the post-Enlightenment version of this view: once people agree that they have identified the one true reason, it brings about that they have to guard against the temptation to worship unreason—that is, madness. [ 113 ] : 496
Civil libertarians warn that the marriage of the State with psychiatry could have catastrophic consequences for civilization . [ 120 ] In the same vein as the separation of church and state , Szasz believes that a solid wall must exist between psychiatry and the State. [ 113 ]
In his book Asylums , Erving Goffman coined the term ' total institution ' for mental hospitals and similar places which took over and confined a person's whole life. [ 121 ] : 150 [ 122 ] : 9 Goffman placed psychiatric hospitals in the same category as concentration camps, prisons, military organizations, orphanages, and monasteries. [ 123 ] In Asylums Goffman describes how the institutionalization process socializes people into the role of a good patient, someone 'dull, harmless and inconspicuous'; it in turn reinforces notions of chronicity in severe mental illness. [ 124 ]
In the US, critics of psychiatry contend that the intersection of the law and psychiatry create extra-legal entities. For example, the insanity defense , leading to detainment in a psychiatric institution versus a prison, can be worse than criminal imprisonment according to some critics, as it involves the risk of compulsory medication with neuroleptics or the use of electroshock treatment. [ 125 ] [ 126 ] [ unreliable source? ] While a criminal imprisonment has a predetermined and known time of duration, patients are typically committed to psychiatric hospitals for indefinite durations, an arguably outrageous imposition of fundamental uncertainty. [ 127 ] It has been argued that such uncertainty risks aggravating mental instability, and that it substantially encourages a lapse into hopelessness and acceptance that precludes recovery. [ citation needed ]
Critics see the use of legally sanctioned force in involuntary commitment as a violation of the fundamental principles of free or open societies. The political philosopher John Stuart Mill and others have argued that society has no right to use coercion to subdue an individual as long as they do not harm others. Research evidence regarding violent behavior by people with mental illness does not support a direct connection in most studies. [ 128 ] [ 129 ] The growing practice, in the United Kingdom and elsewhere, of Care in the Community was instituted partly in response to such concerns. Alternatives to involuntary hospitalization include the development of non-medical crisis care in the community.
The American Soteria project was developed by psychiatrist Loren Mosher as an alternative model of care in a residential setting to support those experiencing psychiatric symptoms or extreme states. The Soteria houses closed in 1983 in the United States due to lack of financial support. [ 130 ] Similar programs were established in Europe, including in Sweden and other North European countries. [ 131 ] In 2015, a Soteria House opened in Vermont, US. [ 132 ]
The physician Giorgio Antonucci , during his activity as a director of the Ospedale Psichiatrico Osservanza of Imola in Italy from 1979 to 1996, refused any form of coercion and any violation of the fundamental principles of freedom, questioning the basis of psychiatry itself. [ 81 ] [ 133 ]
Many of the above issues lead to the claim that psychiatry is a pseudoscience . [ 134 ] According to some philosophers of science, for a theory to qualify as science it needs to exhibit the following characteristics:
Psychiatrists Colin A. Ross and Alvin Pam maintain that biopsychiatry does not qualify as a science on many counts. [ 135 ]
Psychiatric researchers have been criticized on the basis of the replication crisis [ 136 ] and textbook errors. [ 137 ] Questionable research practices are known to bias key sources of evidence. [ 138 ]
Stuart A. Kirk has argued that psychiatry is a failed enterprise, as mental illness has grown, not shrunk, with about 20% of American adults diagnosable as mentally ill in 2013. [ 139 ]
According to a 2014 meta-analysis, psychiatric treatment is no less effective for psychiatric illnesses in terms of treatment effects than treatments by practitioners of other medical specialties for physical health conditions. The analysis found that the effect sizes for psychiatric interventions are, on average, on par with other fields of medicine. [ 140 ]
Szasz has since (2008) re-emphasized his disdain for the term anti-psychiatry, arguing that its legacy has simply been a "catchall term used to delegitimize and dismiss critics of psychiatric fraud and force by labeling them antipsychiatrists ". He points out that the term originated in a meeting of four psychiatrists (Cooper, Laing, Berke and Redler ) who never defined it yet "counter-label[ed] their discipline as anti-psychiatry", and that he considers Laing most responsible for popularizing it despite also personally distancing himself. Szasz describes the deceased (1989) Laing in vitriolic terms, accusing him of being irresponsible and equivocal on psychiatric diagnosis and use of force, and detailing his past "public behavior" as "a fit subject for moral judgment" which he gives as "a bad person and a fraud as a professional". [ 141 ]
Daniel Burston, however, has argued that overall the published works of Szasz and Laing demonstrate far more points of convergence and intellectual kinship than Szasz admits, despite the divergence on a number of issues related to Szasz being a libertarian and Laing an existentialist; that Szasz employs a good deal of exaggeration and distortion in his criticism of Laing's personal character, and unfairly uses Laing's personal failings and family woes to discredit his work and ideas; and that Szasz's "clear-cut, crystalline ethical principles are designed to spare us the agonizing and often inconclusive reflections that many clinicians face frequently in the course of their work". [ 142 ] Szasz has indicated that his own views came from libertarian politics held since his teens , rather than through experience in psychiatry; that in his "rare" contacts with involuntary mental patients in the past he either sought to discharge them (if they were not charged with a crime) or "assisted the prosecution in securing [their] conviction" (if they were charged with a crime and appeared to be prima facie guilty); that he is not opposed to consensual psychiatry and "does not interfere with the practice of the conventional psychiatrist", and that he provided "listening-and-talking ("psychotherapy")" for voluntary fee-paying clients from 1948 until 1996, a practice he characterizes as non-medical and not associated with his being a psychoanalytically trained psychiatrist. [ 141 ]
The gay rights or gay liberation movement is often thought to have been part of anti-psychiatry in its efforts to challenge oppression and stigma and, specifically, to get homosexuality removed from the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders. However, a psychiatric member of APA's Gay, Lesbian, and Bisexual Issues Committee has recently sought to distance the two, arguing that they were separate in the early 70s protests at APA conventions and that APA's decision to remove homosexuality was scientific and happened to coincide with the political pressure. Reviewers have responded, however, that the founders and movements were closely aligned; that they shared core texts, proponents and slogans; and that others have stated that, for example, the gay liberation critique was "made possible by (and indeed often explicitly grounded in) traditions of antipsychiatry". [ 143 ] [ 144 ]
In the clinical setting, the two strands of anti-psychiatry—criticism of psychiatric knowledge and reform of its practices—were never entirely distinct. In addition, in a sense, anti-psychiatry was not so much a demand for the end of psychiatry, as it was an often self-directed demand for psychiatrists and allied professionals to question their own judgments, assumptions and practices. In some cases, the suspicion of non-psychiatric medical professionals towards the validity of psychiatry was described as anti-psychiatry, as well the criticism of "hard-headed" psychiatrists towards "soft-headed" psychiatrists. Most leading figures of anti-psychiatry were themselves psychiatrists, and equivocated over whether they were really "against psychiatry", or parts thereof. Outside the field of psychiatry, however—e.g. for activists and non-medical mental health professionals such as social workers and psychologists—'anti-psychiatry' tended to mean something more radical. The ambiguous term "anti-psychiatry" came to be associated with these more radical trends, but there was debate over whether it was a new phenomenon, whom it best described, and whether it constituted a genuinely singular movement. [ 145 ] In order to avoid any ambiguity intrinsic to the term anti-psychiatry, a current of thought that can be defined as critique of the basis of psychiatry, radical and unambiguous, aims for the complete elimination of psychiatry. The main representative of the critique of the basis of psychiatry is an Italian physician, Giorgio Antonucci , the founder of the non-psychiatric approach to psychological suffering, who posited that the "essence of psychiatry lies in an ideology of discrimination". [ 146 ]
In the 1990s, a tendency was noted among psychiatrists to characterize and to regard the anti-psychiatric movement as part of the past, and to view its ideological history as flirtation with the polemics of radical politics at the expense of scientific thought and enquiry. It was also argued, however, that the movement contributed towards generating demand for grassroots involvement in guidelines and advocacy groups, and to the shift from large mental institutions to community services. Additionally, community centers have tended in practice to distance themselves from the psychiatric/medical model and have continued to see themselves as representing a culture of resistance or opposition to psychiatry's authority. Overall, while antipsychiatry as a movement may have become an anachronism by this period and was no longer led by eminent psychiatrists, it has been argued that it became incorporated into the mainstream practice of mental health disciplines. [ 40 ] On the other hand, mainstream psychiatry became more biomedical, increasing the gap between professionals.
Henry Nasrallah claims that while he believes anti-psychiatry consists of many historical exaggerations based on events and primitive conditions from a century ago, "antipsychiatry helps keep us honest and rigorous about what we do, motivating us to relentlessly seek better diagnostic models and treatment paradigms. Psychiatry is far more scientific today than it was a century ago, but misperceptions about psychiatry continue to be driven by abuses of the past. The best antidote for antipsychiatry allegations is a combination of personal integrity, scientific progress, and sound evidence-based clinical care". [ 4 ]
A criticism was made in the 1990s that three decades of anti-psychiatry had produced a large literature critical of psychiatry, but little discussion of the deteriorating situation of the mentally troubled in American society. Anti-psychiatry crusades have thus been charged with failing to put suffering individuals first, and therefore being similarly guilty of what they blame psychiatrists for. The rise of anti-psychiatry in Italy was described by one observer as simply "a transfer of psychiatric control from those with medical knowledge to those who possessed socio-political power". [ 44 ]
Critics of this view, however, from an anti-psychiatry perspective, are quick to point to the industrial aspects of psychiatric treatment itself as a primary causal factor in this situation that is described as "deteriorating". The numbers of people labeled "mentally ill", and in treatment, together with the severity of their conditions, have been going up primarily due to the direct efforts of the mental health movement, and mental health professionals, including psychiatrists, and not their detractors. Envisioning "mental health treatment" as violence prevention has been a big part of the problem, especially as you are dealing with a population that is not significantly more violent than any other group. [ citation needed ]
On October 7, 2016, the Ontario Institute for Studies in Education (OISE) at the University of Toronto announced that they had established a scholarship for students doing theses in the area of antipsychiatry. Called "The Bonnie Burstow Scholarship in Antipsychiatry", it is to be awarded annually to an OISE thesis student. An unprecedented step, the scholarship should further the cause of freedom of thought and the exchange of ideas in academia. The scholarship is named in honor of Bonnie Burstow, a faculty member at the University of Toronto, a radical feminist, and an antipsychiatry activist. She is also the author of Psychiatry and the Business of Madness (2015).
Some components of antipsychiatric theory have in recent decades been reformulated into a critique of "corporate psychiatry", heavily influenced by the pharmaceutical industry . A recent editorial about this was published in the British Journal of Psychiatry by Moncrieff, arguing that modern psychiatry has become a handmaiden to conservative political commitments. David Healy is a psychiatrist and professor in psychological medicine at Cardiff University School of Medicine , Wales . He has a special interest in the influence of the pharmaceutical industry on medicine and academia . [ 147 ]
In the meantime, members of the psychiatric consumer/survivor movement continued to campaign for reform, empowerment and alternatives, with an increasingly diverse representation of views. Groups often have been opposed and undermined, especially when they proclaim to be, or when they are labeled as being, "anti-psychiatry". [ 149 ] However, as of the 1990s, more than 60 percent of ex-patient groups reportedly support anti-psychiatry beliefs and consider themselves to be "psychiatric survivors". [ 150 ] Although anti-psychiatry is often attributed to a few famous figures in psychiatry or academia, it has been pointed out that consumer/survivor/ex-patient individuals and groups preceded it, drove it and carried on through it. [ 151 ]
A schism exists among those critical of conventional psychiatry between radical abolitionists and more moderate reformists. Laing, Cooper and others associated with the initial anti-psychiatry movement stopped short of actually advocating for the abolition of coercive psychiatry. Thomas Szasz, from near the beginning of his career, crusaded for the abolition of forced psychiatry. Today, believing that coercive psychiatry marginalizes and oppresses people with its harmful, controlling, and abusive practices, many who identify as anti-psychiatry activists are proponents of the complete abolition of non-consensual and coercive psychiatry.
Critics of antipsychiatry from within psychiatry itself object to the underlying principle that psychiatry is by definition harmful. Most psychiatrists accept that issues exist that need addressing, but that the abolition of psychiatry is harmful. Nimesh Desai concludes: "To be a believer and a practitioner of multidisciplinary mental health, it is not necessary to reject the medical model as one of the basics of psychiatry." and admits "Some of the challenges and dangers to psychiatry are not so much from the avowed antipsychiatrists, but from the misplaced and misguided individuals and groups in related fields." [ 11 ]
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Anti-vaccine activism , which collectively constitutes the " anti-vax " movement , [ 1 ] is a set of organized activities expressing opposition to vaccination , and these collaborating networks have often sought to increase vaccine hesitancy by disseminating vaccine misinformation and/or forms of active disinformation . As a social movement , it has utilized multiple tools both within traditional news media and also through various forms of online communication . Activists have primarily (though far from entirely) focused on issues surrounding children , with vaccination of the young receiving pushback, and they have sought to expand beyond niche subgroups into national political debates . [ 2 ]
Ideas that would eventually coalesce into anti-vaccine activism have existed for longer than vaccines themselves. [ 3 ] Various myths and conspiracy theories (alongside outright disinformation and misinformation) have been spread by the anti-vaccination movement and fringe doctors. These have been spread in a way that has significantly increased vaccine hesitancy (and altered public policy around ethical , legal, and medical matters related to vaccines). However, no serious sense of hesitancy or of debate (in the broad sense) exists within mainstream medical circles about the benefits of vaccination. The scientific consensus in favor of vaccines is "clear and unambiguous". [ 4 ] At the same time, however, the anti-vax movement has partially succeeded in distorting common understandings of science in popular culture . [ 2 ]
In a 2002 paper in the British Medical Journal , two medical historians suggested that the arguments made against the safety and effectiveness of vaccines in the late 20th century are similar to those of the early anti-vaccinationists. Both the 19th and 20th century arguments included "vaccine safety issues, vaccine failures, infringement of personal liberty, and an unholy alliance between the medical establishment and the government to reap huge profits for the medical establishment at the expense of the public." [ 5 ] However, the authors only considered the use of "newspaper articles and letters, books, journals, and pamphlets to warn against the dangers of vaccination", and did not address the impact of the internet. [ 5 ] Comments on YouTube videos during the COVID-19 pandemic clustered similarly around "concerns about side-effects, effectiveness, and lack of trust in corporations and government". [ 6 ]
In some instances, anti-vaccine organizations have used names intended to sound non-partisan on the issue: e.g. National Vaccine Information Center (USA), Vaccination Risk Awareness Network (Canada), Australian Vaccination Network. [ 7 ] In November 2013 the Australian Vaccination Network was ordered by the New South Wales Administrative Decisions Tribunal to change their name so that consumers are aware of the anti-vaccination nature of the group. Lateline reported that former AVN president Meryl Dorey "claimed she was a victim of hate groups and vested interests" in response to the ruling. [ 8 ]
Although physicians and nurses are still rated as the most trusted source for vaccine information, some vaccine-hesitant individuals report being more comfortable discussing vaccines with providers of complementary and alternative medical (CAM) treatments. [ 4 ] With the rise of the internet, many people have turned online for medical information. [ 9 ] In some instances, anti-vaccine activists seek to steer people away from vaccination and health-care providers and towards alternative medicines sold by certain activists. [ 10 ]
Anti-vaccination writings on the internet have been argued to be characterized by a number of differences from medical and scientific literature. These include:
For example, a 2020 study examined Instagram posts related to the HPV vaccine , which can prevent some types of cancer. Anti-vaccine posts were more likely than pro-vaccine posts to be sent by non-healthcare individuals, to include personal narratives, and to reference other Instagram users, links, or reposts. Anti-vaccine posts were also more likely to involve concealment or distortion, particularly conspiracy theories and unsubstantiated claims. In total, 72.3% of antivaccine posts made inaccurate claims, including exaggerating the risks of vaccines and minimizing risks of disease. [ 17 ]
A number of specific disinformation tactics have been noted in anti-vaccination messaging, including: [ 7 ] [ 18 ]
Information is more likely to be believed after repeated exposure. Disinformers use this illusory truth effect as a tactic, repeating false information to make it feel familiar and influence belief. [ 23 ] Anti-vaccine activists have leveraged social media to develop interconnected networks of influencers that shape people's opinion, recruit allies, impact policy [ 2 ] and monetize vaccine-related disinformation. [ 24 ] In 2022, the Journal of Communication published a study of the political economy underlying vaccine disinformation. Researchers identified 59 English-language "actors" that provided "almost exclusively anti-vaccination publications". Their websites monetized disinformation through appeals for donations, sales of content-based media and other merchandise, third-party advertising, and membership fees. Some maintained a group of linked websites, attracting visitors with one site and appealing for money and selling merchandise on others. Their activities to gain attention and obtain funding displayed a "hybrid monetization strategy". They attracted attention by combining eye-catching aspects of "junk news" and online celebrity promotion. At the same time, they developed campaign-specific communities to publicize and legitimize their position, similar to radical social movements. [ 24 ]
In the United States, the Vaccine Adverse Event Reporting System (VAERS) is used to gather information on potential vaccine adverse reactions, but is susceptible to unverified reports, misattribution, underreporting , and inconsistent data quality . [ 25 ] Raw, unverified data from VAERS has often been used by the anti-vaccine community to justify misinformation regarding the safety of vaccines; it is generally not possible to find out from VAERS data if a vaccine caused an adverse event, or how common the event might be. [ 26 ]
After Republicans gained a majority in the U.S. House of Representatives in January 2023, the House Judiciary Committee used legal action to oppose both disinformation research and government involvement in fighting disinformation. One of the projects targeted was the Virality Project, which has examined the spread of false claims about vaccines. The House Judiciary Committee sent letters, subpoenas, and threats of legal action to researchers, demanding notes, emails and other records from researchers and even student interns, dating back to 2015. Institutions subjected to such inquiries included the Stanford Internet Observatory at Stanford University , the University of Washington , the Atlantic Council 's Digital Forensic Research Lab and the social media analytics firm Graphika. Researchers emphasized that they have academic freedom to study disinformation as well as freedom of speech to report their results. [ 27 ] [ 28 ] [ 29 ]
Despite conservative claims that the government acted to censor speech online, "no evidence has emerged that government officials coerced the companies to take action against accounts". [ 27 ] The actions of the House Judiciary Committee have been described as an "attempt to chill research,” [ 27 ] creating a "chilling effect" [ 28 ] through increased time demands, legal costs and online harassment of researchers. [ 28 ] [ 27 ]
Persons undertaking efforts to counter vaccine misinformation, including public health experts who use social media, have been targeted for harassment by anti-vaccine activists such as blogger Paul Thacker . [ 2 ] [ 14 ] [ 30 ]
For example, Slovakian physician Vladimír Krčméry was a prominent member of the government advisory team during the COVID-19 pandemic in Slovakia , and was the first person in that country to receive a COVID-19 vaccine . Due to his prominent role in the vaccination campaign, Krčméry and his family became a target of anti-vaccine activists, who physically threatened him and his family. [ 31 ]
In June 2023, Texas-based physician and researcher Peter Hotez tweeted his concerns about Robert F. Kennedy Jr. sharing misinformation about vaccines on Joe Rogan 's podcast. Rogan, Kennedy, and Twitter owner Elon Musk asked Hotez to participate in a debate on the podcast. Upon declining the invitation, Hotez was harassed by their fans, with anti-vaccine activist Alex Rosen confronting him at his home. [ 14 ] [ 32 ] [ 33 ]
In his book The Deadly Rise of Anti-science: A Scientist's Warning , Hotez describes how he and other scientists who publicly defend vaccines have been attacked on social media, harassed with threatening emails, intimidated, and confronted physically by opponents of vaccination. He attributes the increase in aggressiveness of the anti-vaccination movement to the influence of the extreme wing of the Republican Party. [ 34 ] [ 35 ] Hotez estimates that roughly 200,000 preventable deaths from COVID-19, mainly among Republicans, occurred in the US because of refusal to be vaccinated. [ 36 ] [ 37 ]
At the extreme end, opposition to vaccination has resulted in substantial violence against vaccinators. In Pakistan, "more than 200 polio team workers have lost their lives" (team members include not only vaccinators but police and security personnel) from "targeted killing and terrorism" while working on polio vaccination campaigns. [ 38 ]
Various efforts have been suggested and undertaken to address concerns about vaccines and counter anti-vaccine disinformation. Efforts include social media advertising campaigns, by public health organizations, in support of public health goals. [ 39 ] [ 6 ]
Best practices for combating vaccine mis- and disinformation include addressing issues openly, clearly identifying areas of scientific consensus and areas of uncertainty, and being sensitive to the cultural and religious values of communities. [ 40 ] [ 41 ] [ 42 ] In countering anti-vaccine disinformation, both factual and emotional aspects need to be addressed. [ 43 ]
Whether people will update a mistaken belief is complicated and involves psychological factors and social goals as well as accuracy of information. [ 44 ] [ 23 ] [ 20 ] There is some evidence that both debunking and " pre-bunking " of disinformation can be effective, at least in the short term. [ 23 ] [ 20 ] [ 45 ] [ 46 ] Elements that may help to correct inaccurate information include: warning people before they are exposed to misinformation; high perceived credibility of message sources, affirmations of identity and social norms; graphical presentation; and focusing attention on clear core messages. [ 47 ] Alternative explanations of a situation need to fit plausibly into the original scenario and ideally indicate why the incorrect explanation was previously thought to be correct. [ 44 ]
The cultivation of critical thinking, health and science awareness, and media literacy skills are all recommended to help people more critically assess the credibility of the information they see. [ 42 ] People who seek out multiple reputable news sources at local and national levels are more likely to detect disinformation than those who rely on few sources from a particular viewpoint. [ 48 ] Particularly on social media, beware of sensational headlines that appeal to emotion, fact-check information broadly (not just through your usual sources), and consider possible agendas or conflicts of interest of those relaying information. [ 49 ] [ 50 ]
Other suggestions for countering anti-vaccine activism focus on changing the operation of social media platforms. Interventions such as accuracy nudges and source labeling change the context in which information is presented. [ 51 ] For example, correct information can be directly presented to counter disinformation. [ 52 ] [ 53 ] Other possibilities include flagging or removing misleading information on social media platforms. [ 54 ] [ 55 ] [ 56 ] Research suggests that a majority of individuals in the United States would support the removal of harmful misinformation posts and the suspension of accounts. This position is less popular with Republicans than Democrats. [ 57 ]
While private entities like Facebook, Twitter and Telegram could legally establish guidelines for moderation of information and disinformation on their platforms (subject to local and international laws) [ 58 ] [ 50 ] [ 59 ] such companies do not have strong incentives to control disinformation or to self-regulate. Algorithms that are used to maximize user engagement and profits can lead to unbalanced, poorly sourced, and actively misleading information. [ 60 ] [ 61 ] [ 62 ]
Criticized for its role in vaccine hesitancy , Facebook announced in March 2019 that it would provide users with "authoritative information" on the topic of vaccines. [ 63 ] Facebook introduced several policies chosen to reduce the impact of anti-vaccine content, without actually removing it. These included reducing the ranking of anti-vaccine sources in searches and not recommending them; rejecting ads and targeted advertising that contained vaccine misinformation; and using banners to present vaccine information from authoritative sources. A study examined the six months before and after the policy changes. It found a moderate but significant decrease in the number of likes for anti-vaccine posts following the policy changes. Likes of pro-vaccine posts were unchanged. [ 64 ] Facebook has been criticized for not being more aggressive in countering disinformation. [ 65 ] In response to efforts to police misinformation, anti-vaccine communities on social media have adopted coded language to refer to vaccinated persons and the vaccines themselves. [ 66 ]
Supply-side interventions reduce circulation of misinformation directly at their sources through actions such as application of social media policies, regulation, and legislation. [ 51 ] A study published in the journal Vaccine examined advertisements posted in the three months prior to the Facebook's 2019 policy changes. It found that 54% of the anti-vaccine advertisements on Facebook were placed by just two organizations, funded by well-known anti-vaccination activists. [ 67 ] [ 68 ] The Children's Health Defense / World Mercury Project chaired by Robert F. Kennedy Jr. and Stop Mandatory Vaccination , run by campaigner Larry Cook, posted 54% of the advertisements. The ads often linked to commercial products, such as natural remedies and books. [ 69 ] Kennedy was suspended from Facebook in August 2022, [ 70 ] but reinstated in June 2023. [ 71 ]
In 2023, however, state governments that were politically aligned with anti-vaccine activists successfully sought a preliminary injunction to prevent the Biden Administration from seeking to pressure social media companies into fighting misinformation. The order issued by United States Court of Appeals for the Fifth Circuit "severely limits the ability of the White House, the surgeon general, [and] the Centers for Disease Control and Prevention... to communicate with social media companies about content related to Covid-19... that the government views as misinformation". [ 72 ] In October 2023, this injunction was paused by the Supreme Court of the United States , pending further litigation. [ 73 ]
Algorithms and user data can be used to identify selected subgroups who can then be provided with specialized content. This type of approach has been used both by anti-vaccine activists [ 42 ] [ 2 ] and by health providers who hope to counter vaccine-related disinformation. [ 74 ] [ 75 ] [ 76 ] For example, in the United States, the CDC's Social Vulnerability Index (SVI) has been used to identify communities that have traditionally been under-served or are at elevated risk for infection, morbidity, and mortality. [ 74 ] Programs have been developed in such communities to address disinformation and vaccine hesitancy. [ 77 ]
Steps have been taken to counter anti-vaccine messaging by directly engaging with communities. Outreach efforts include call centers and texting campaigns, partnering with local community leaders, and holding community-based vaccine clinics. [ 77 ] [ 75 ] [ 78 ] Creating digital and science literacy resources and distributing them via schools, libraries, municipal offices, churches and other community groups can help to counter misinformation in under-resourced communities. [ 79 ]
The Black Doctors COVID-19 Consortium in Philadelphia is one example of a successful direct outreach initiative. [ 80 ] Another is the New York State Vaccine Equity Task Force. [ 77 ] In line with the Strategic Advisory Group of Experts (SAGE)'s 3C's model, outreach to communities has focused on addressing mistrust and increasing Confidence, providing information to improve risk assessment (Complacency), and improving access to COVID-19 vaccines (Convenience). It has been necessary to counter disinformation in all three areas. [ 76 ] [ 77 ]
Recommendations for combating vaccine disinformation include increasing the presence of trusted health agencies and credible information on social media, partnering with social media platforms to promote evidence-based public health information, and identifying and responding to emerging concerns and disinformation campaigns. [ 76 ] Networked communities of public health officials and other stakeholders, connecting with the public through a variety of credible and trusted messengers, are recommended. Sharing of messages through such networks could help to debunk and counter highly networked and coordinated disinformation attacks. [ 2 ]
A networked community approach would differ from the current model of US public health communication, which tends to rely on a single credible messenger (e.g. Anthony Fauci ) and is susceptible to disinformation attacks. To deal with disinformation, community networks would need to address issues of liberty and human rights as well as vaccine safety, effectiveness and access. Networks could also help to show support for those attacked by anti-vaccine activists. [ 2 ]
Ideas that would eventually coalesce into anti-vaccine activism have existed for longer than vaccines themselves. [ 3 ] Some philosophical approaches (e.g. homeopathy , vitalism ) are incompatible with the microbiological paradigm that explains how the immune system and vaccines work. Vaccine hesitancy and anti-vaccine activism exist within a broader context that involves cultural tradition, religious belief, approaches to health and disease, and political affiliation. [ 4 ]
Opposition to variolation for smallpox (a predecessor to vaccination) was organized as early as the 1720s around the premise that vaccination was unnatural and an attempt to thwart divine judgment. [ 81 ] Religious arguments against inoculation , the earliest arguments against vaccination, were soon advanced. [ 82 ] For example, in a 1722 sermon entitled "The Dangerous and Sinful Practice of Inoculation", the English theologian Reverend Edmund Massey argued that diseases are sent by God to punish sin and that any attempt to prevent smallpox via inoculation is a "diabolical operation". [ 83 ] It was customary at the time for popular preachers to publish sermons, which reached a wide audience. This was the case with Massey, whose sermon reached North America, where there was early religious opposition, particularly by John Williams . A greater source of opposition there was William Douglass , a medical graduate of Edinburgh University and a Fellow of the Royal Society , who had settled in Boston. [ 84 ] : 114–22
Vaccination itself was invented by British physician Edward Jenner , who published his findings on the efficacy of the practice for smallpox in 1798. By 1801, the practice had been widely endorsed in the scientific community, and by several world leaders. Philadelphia physician John Redman Coxe , noting that even then false accounts were circulated of negative effects of vaccination, wrote,
"Such are the falsehoods which impede the progress of the brightest discovery which has ever been made! But the contest is in vain! Time has drawn aside the veil which obstructed our knowledge of this invaluable blessing; and in the examples of the Emperor of Constantinople, of the Dowager Empress of Russia, and the King of Spain, we may date the downfall of further opposition." [ 85 ]
Coxe's expectation of an end to opposition to vaccination proved premature, and through much of the nineteenth century, the principles, practices and impact of vaccination were matters of active scientific debate. The principles behind vaccination were not clearly understood until the end of the nineteenth century. The importance of hygiene in the preparation, storage, and administration of vaccines was not always understood or practiced. Reliable statistics on vaccine efficacy and side effects were difficult to obtain before the 1930s. [ 4 ]
In the United Kingdom , the Vaccination Act 1853 ( 16 & 17 Vict. c. 100) required that every child be vaccinated within three or four months of birth. [ 86 ] It set a precedent for the state regulation of physical bodies, and was fiercely resisted. [ 87 ] The following year, in 1854, John Gibbs published the first anti-compulsory-vaccination pamphlet, Our Medical Liberties . [ 88 ] By the 1860s, anti-vaccinationism in Britain was active in the working class, labor aristocracy, and lower middle class. It had become associated with alternative medicine and was part of a larger culture of social and political dissent that included both labor unions and religious dissenters. [ 87 ] [ 89 ]
In June 1867, the publication "Human Nature" campaigned in the United Kingdom against "The Vaccination Humbug", [ 90 ] reporting that many petitions had been presented to Parliament against Compulsory Vaccination for smallpox , including from parents who alleged that their children had died through the procedure, and complaining that these petitions had not been made public. The journal reported the formation of the Anti-Compulsory Vaccination League "To overthrow this huge piece of physiological absurdity and medical tyranny", and quoted Richard Gibbs (a cousin of John Gibbs) who ran the Free Hospital at the same address as stating "I believe we have hundreds of cases here, from being poisoned with vaccination, I deem incurable. One member of a family dating syphilitic symptoms from the time of vaccination, when all the other members of the family have been clear. We strongly advise parents to go to prison, rather than submit to have their helpless offspring inoculated with scrofula, syphilis, and mania". [ 90 ]
Notable members of the Anti-Compulsory Vaccination League included James Burns , George Dornbusch and Charles Thomas Pearce . [ 91 ] After the death of Richard B. Gibbs in 1871, the Anti-Compulsory Vaccination League "languished" [ 86 ] until 1876 when it was revived under the leadership of Mary Hume-Rothery and the Rev. W. Hume-Rothery. [ 92 ] The Anti-Compulsory Vaccination League published the Occasional Circular which later merged into the National Anti-Compulsory Vaccination Reporter . [ 93 ]
In the United States, many states and local school boards established immunization requirements, beginning with a compulsory school vaccination law in Massachusetts in 1855. [ 88 ] The Anti-Vaccination Society of America was founded in 1879, after a visit to the United States by British anti-vaccine activist William Tebb , [ 94 ] and opposed compulsory smallpox vaccination for smallpox from the final decades of the 19th century through the 1910s. [ 95 ] During this period, smallpox vaccination was the only form of vaccination that was widely practiced, and the society published a periodical opposing it, called Vaccination . [ 96 ]
A series of American legal cases, beginning in various states and culminating with that of Henning Jacobson of Massachusetts in 1905, upheld the mandating of compulsory smallpox vaccination for the good of the public. The court ruled in Jacobson v. Massachusetts that "the liberty secured by the Constitution of the United States to every person within its jurisdiction does not import an absolute right in each person to be, at all times and in all circumstances, wholly freed from restraint. There are manifold restraints to which every person is necessarily subject for the common good". [ 88 ]
In 1880, William Tebb enlarged and reorganized the Anti-Compulsory Vaccination League in the UK with the formation of the London Society for the Abolition of Compulsory Vaccination, with William Young as secretary. [ 93 ] The Vaccination Inquirer , established by Tebb in 1879, was adopted as the official organ of the Society. [ 93 ] A series of fourteen "Vaccination Tracts" was begun by Young in 1877 and completed by Garth Wilkinson in 1879. William White was the first editor of the Vaccination Inquirer and after his death in 1885, he was succeeded by Alfred Milnes. [ 93 ] Frances Hoggan and her husband authored an article for the Vaccination Inquirer in September 1883 which argued against compulsory vaccination. [ 97 ] The London Society focused on lobbying parliamentary support in the 1880s and early 1890s. [ 93 ] They gained support from several members of the House of Commons of which the most prominent was Peter Alfred Taylor , the member for Leicester , which was described as the "Mecca of antivaccination". [ 98 ]
The UK movement grew, and as the influence of the London Society overshadowed the Hume-Rotherys and it took the national lead, [ 92 ] it was decided in February 1896 to re-form the Society as The National Anti-Vaccination League . [ 93 ] Arthur Phelps was elected as president. [ 93 ] In 1898, the league took on a school leaver named Lily Loat , who was elected as the league's Secretary by 1909. [ 99 ] In 1906, George Bernard Shaw wrote a supportive letter to the National Anti-Vaccination League, equating methods of vaccination with "rubbing the contents of the dustpan into the wound". [ 100 ]
In 1908, the Anti-Vaccination League of America was created by Charles M. Higgins and industrialist John Pitcairn Jr. , [ 101 ] with anti-vaccination campaigns focused on New York and Pennsylvania . [ 101 ] Members were opposed to compulsory vaccination laws. [ 102 ] Higgins was the League's chief spokesman and pamphleteer. [ 103 ] Historian James Colgrove noted that Higgins "attempted to overturn the New York State's law mandating vaccination of students in public schools". [ 102 ] The League should not be confused with the Anti-Vaccination Society of America , that was formed in 1879. [ 101 ] Higgins was criticized by medical experts for spreading misinformation and ignoring facts as to the efficacy of vaccination. [ 104 ] [ 105 ] The League dissolved after the death of Higgins in 1929. [ 106 ]
Anti-vaccine activism ebbed for much of the twentieth century, but never completely vanished. In the UK, the National Anti-Vaccination League continued to publish new issues of its journal until 1972, [ 99 ] by which time the global campaign for smallpox eradication through vaccination had made the disease so uncommon that compulsory vaccination for smallpox was no longer required in the United Kingdom. [ 107 ]
New vaccines were developed and used against diseases such as diphtheria and whooping cough . In the UK, these were often introduced on a voluntary basis, without arousing the same kind of anti-vaccination response that had accompanied compulsory smallpox vaccination. [ 107 ]
In the United States, numerous measles outbreaks occurred in the 1960s and 1970s, and were shown to be more frequent in states that lacked mandatory vaccination requirements. This led to calls in the 1970s for a national level vaccination requirement for children entering schools. Joseph A. Califano Jr. appealed to state governors, and by 1980, all 50 states legally required vaccination for school entrance. Many of these laws allowed exemptions in response to lobbyists. In New York State, a 1967 law allowed exemptions from receiving polio vaccine for members of religious organizations such as Christian Scientists . [ 88 ]
Anti-vaccine activism in the 2000s regained prominence through exploratory research by Andrew Wakefield based on 12 selected cases. He then made claims about a link between the MMR vaccine and autism . [ 42 ] These claims were subsequently extensively investigated and found to be false, and the original study turned out to be based on faked data. The scientific consensus is that there is no link between the MMR vaccine and autism , and that the MMR vaccine's benefits in preventing measles , mumps , and rubella greatly outweigh its potential risks. [ 108 ]
The idea of an autism link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud, which Dennis K Flaherty at the University of Charleston characterized as "perhaps the most damaging medical hoax of the last 100 years". [ 109 ] The fraudulent research paper authored by Wakefield and published in The Lancet falsely claimed the vaccine was linked to colitis and autism spectrum disorders. The paper was retracted by Lancet in 2010 [ 110 ] but is still cited by anti-vaccine activists. [ 111 ]
The claims in the paper were widely reported, [ 112 ] leading to a sharp drop in vaccination rates in the UK and Ireland. Promotion of the claimed link, which continued in anti-vaccination propaganda for the next three decades despite being refuted, [ 113 ] [ 114 ] was estimated to have led to an increase in the incidence of measles and mumps , resulting in deaths and serious permanent injuries. [ 115 ] [ 116 ] Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention , [ 117 ] the American Academy of Pediatrics , the Institute of Medicine of the US National Academy of Sciences , [ 118 ] the UK National Health Service , [ 119 ] and the Cochrane Library [ 108 ] [ 120 ] all found no link between the MMR vaccine and autism. [ 121 ] Physicians, medical journals, and editors [ 122 ] [ 123 ] [ 124 ] [ 125 ] [ 126 ] have described Wakefield's actions as fraudulent and tied them to epidemics and deaths. [ 127 ] [ 128 ]
An investigation by journalist Brian Deer found that Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest , [ 129 ] [ 130 ] had manipulated evidence, [ 131 ] and had broken other ethical codes. After a subsequent 2.5-year investigation, the General Medical Council ruled that Wakefield had acted "dishonestly and irresponsibly" in doing his research, carrying out unauthorized procedures for which he was not qualified, and acting with "callous disregard" for the children involved. [ 132 ] Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010, and was struck off the Medical Register , meaning he could no longer practise as a physician in the UK. [ 133 ]
The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet ' s editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. [ 134 ] In January 2011, Deer published a series of reports in the British Medical Journal , [ 135 ] [ 136 ] [ 137 ] in which a signed editorial stated of the journalist, "It has taken the diligent scepticism of one man, standing outside medicine and science, to show that the paper was in fact an elaborate fraud." [ 138 ] [ 139 ] A 2011 journal article described the vaccine-autism connection as "the most damaging medical hoax of the last 100 years". [ 121 ]
Wakefield continues to promote anti-vaccine beliefs and conspiracy theories in the United States. [ 140 ] In February 2015, Wakefield denied that he bore any responsibility for the measles epidemic that started at Disneyland among unvaccinated children that year. He also reaffirmed his discredited belief that "MMR contributes to the current autism epidemic". [ 141 ] By that time, at least 166 measles cases had been reported. Paul Offit disagreed, saying that the outbreak was "directly related to Dr. Wakefield's theory". [ 142 ] Wakefield and other anti-vaccine activists were active in the American-Somali community in Minnesota, where a drop in vaccination rates was followed by the largest measles outbreak in the state in nearly 30 years in 2017. [ 143 ] [ 144 ] [ 145 ]
The anti-vaccination movement was historically apolitical, but in the 2010s and 2020s the movement in the United States has increasingly targeted conservatives. [ 2 ] As measles outbreaks increased, so did calls to eliminate exemptions from vaccine administration. As of 2015, 19 American states had suggested legislation to eliminate or increase the difficulty of exemptions, including California. [ 88 ] Concurrently, American anti-vaccine activists reached out to libertarian and right-leaning groups such as the Tea Party movement to broaden their base. While earlier anti-vaccination activists focused on health impacts and safety of vaccines, recent themes increasingly involve philosophical arguments about liberty, medical freedom and parental rights. [ 2 ]
With the growing anti-vaccine movement from the 2010s onwards, the United States has seen a resurgence of certain vaccine-preventable diseases . The measles virus lost its elimination status in the US as the number of measles cases continued to rise in the late 2010s with a total of 17 outbreaks in 2018 and 465 outbreaks in 2019 (as of April 4, 2019). [ 146 ]
Vaccine hesitancy led to declining rates of vaccination for measles, culminating in the 2019–2020 measles outbreaks . The most significant of these in proportion to national population was the 2019 Samoa measles outbreak . [ 147 ]
In July 2018, two 12-month-old children died in Samoa after receiving incorrectly prepared MMR vaccinations. [ 148 ] These two deaths were picked up by anti-vaccine groups and used to incite fear towards vaccination on social media, causing the government to suspend its measles vaccination programme for ten months, despite advice from the WHO. [ 149 ] [ 150 ] The incident caused many Samoan residents to lose trust in the healthcare system. [ 151 ] UNICEF and the World Health Organization estimate that the measles vaccination rate in Samoa fell from 74% in 2017 to 34% in 2018, [ 152 ] [ 153 ] similar to some of the poorest countries in Africa. [ 154 ]
In August 2019, an infected passenger on one of the more than 8,000 annual flights between New Zealand and Samoa probably brought the disease from Auckland to Upolu . [ 148 ] A full outbreak of measles began on the island in October 2019 and continued for the next four months. As of January 6, 2020, there were over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,874. [ 155 ] [ 156 ] Over three percent of the population were infected. [ 157 ] The cause of the outbreak was attributed to decreased vaccination rates, from 74% in 2017 to 31–34% in 2018, even though nearby islands had rates near 99%. [ 157 ] [ 156 ] a rate of 14.3 deaths per 1000 infected) and 5,520 cases (2.75% of the population) of measles in Samoa. [ 158 ] [ 157 ] [ 156 ] Sixty-one out of the first 70 deaths were four years old and under, and all but seven were under 15. [ 159 ] [ 160 ] After the outbreak, anti-vaxxers employed racist tropes and misinformation to credit the scores of measles deaths to poverty and poor nutrition or even to the vaccine itself, but this has been discounted by the international emergency medical support that arrived in November and December. [ 148 ] There was no evidence of acute malnutrition, clinical vitamin A deficiency, or immune deficiency as claimed by various anti-vaxxers. [ 148 ]
During the COVID-19 pandemic , anti-vaccine activists undertook various efforts to hinder people who wanted to receive the vaccines, with such activities occurring in countries including Australia, [ 161 ] Israel, [ 162 ] the United Kingdom, [ 163 ] and the United States. [ 164 ] These included attempts to physically blockade vaccination sites, and making false reservations for vaccination appointments to clog up vaccination booking systems. Protests were also organized by the activists to raise awareness for their cause. [ 165 ]
In some instances, anti-vaccine rhetoric has been traced to state-sponsored internet troll activities designed to create social dissension. [ 166 ] [ 167 ] Worldwide, foreign disinformation campaigns have been associated with declining vaccination rates in target countries. [ 168 ] Anti-vaccine activism online both before and during the pandemic has been linked to extreme levels of falsehoods, rumors, hoaxes, and conspiracy theories. [ 2 ] [ 169 ] [ 7 ]
Anti-vaccine activists have falsely claimed in social media posts that numerous deaths or injuries had to do with reactions to vaccines. In one highly publicized instance in early 2023, after Buffalo Bills football player Damar Hamlin experienced an in-game episode of commotio cordis , there was an increase in rhetoric and disinformation from figures such as Charlie Kirk and Drew Pinsky making unfounded claims about Hamlin's cardiac arrest and COVID-19 vaccines . [ 170 ] [ 171 ] [ 172 ] In another 2023 incident, college basketball player Bronny James experienced cardiac arrest at the Galen Center at the University of Southern California , leading to assertions that this was a result of receiving a COVID-19 vaccine ; it was later revealed that the episode had been caused by a congenital heart defect . [ 173 ] Also, anti-vaccine activists believed Foo Fighters drummer Taylor Hawkins died in 2022 from the COVID-19 vaccine, while in actuality it was a drug overdose. [ 174 ] In December 2023, The New York Times published a detailed investigation of the distortion and misrepresentation of the circumstances surrounding the death of 24-year-old George Watts Jr. by Robert F. Kennedy Jr. and other anti-vaccine activists. [ 175 ] Some unvaccinated persons opposed to COVID-19 vaccination began referring to themselves in social media groups as "purebloods", a term historically connoting racial purity. [ 176 ] [ 177 ] [ 178 ]
Prominent biomedical researcher Peter Hotez , asserted that he and other American scientists who publicly defend vaccines have been attacked on social media, harassed with threatening emails, intimidated, and confronted physically by opponents of vaccination. He further attributes the increase in aggressiveness of the anti-vaccination movement to the influence of the extreme wing of the Republican Party. Hotez estimates that roughly 200,000 preventable deaths from COVID-19, mainly among Republicans, occurred in the US because of refusal to be vaccinated. [ 179 ] A 2023 study published in the Journal of the American Medical Association found "evidence of higher excess mortality for Republican voters compared with Democratic voters in Florida and Ohio after, but not before, COVID-19 vaccines were available to all adults in the US". [ 180 ]
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https://en.wikipedia.org/wiki/Anti-vaccine_activism
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Antiarrhythmic agents , also known as cardiac dysrhythmia medications , are a class of drugs that are used to suppress abnormally fast rhythms ( tachycardias ), such as atrial fibrillation , supraventricular tachycardia and ventricular tachycardia .
Many attempts have been made to classify antiarrhythmic agents. Many of the antiarrhythmic agents have multiple modes of action, which makes any classification imprecise.
The cardiac myocyte has two general types of action potentials: conduction system and working myocardium. The action potential is divided into 5 phases and shown in the diagram. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing efflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage-sensitive calcium channels . Each phase utilizes different channels and it is useful to compare these phases to the most common classification system — Vaughan Williams — described below.
The Vaughan Williams classification [ 1 ] was introduced in 1970 by Miles Vaughan Williams . [ 2 ]
Vaughan Williams was a pharmacology tutor at Hertford College , Oxford. One of his students, Bramah N. Singh , [ 3 ] contributed to the development of the classification system. The system is therefore sometimes known as the Singh-Vaughan Williams classification .
The five main classes in the Vaughan Williams classification of antiarrhythmic agents are:
With regard to management of atrial fibrillation, classes I and III are used in rhythm control as medical cardioversion agents, while classes II and IV are used as rate-control agents.
Class Ia drugs prolong the action potential and has an intermediate effect on the 0 phase of depolarization.
Class Ib drugs shorten the action potential of myocardial cell and has a weak effect on the initiation of phase 0 of depolarization
Class Ic drugs do not affect action potential duration and have the strongest effect on the initiation phase 0 of depolarization
Sotalol is also a beta blocker [ 5 ] Amiodarone has mostly Class III activity, but also I, II, & IV activity [ 6 ]
The class I antiarrhythmic agents interfere with the sodium channel .
Class I agents are grouped by what effect they have on the Na + channel, and what effect they have on cardiac action potentials .
Class I agents are called membrane-stabilizing agents, "stabilizing" referring to the decrease of excitogenicity of the plasma membrane which is brought about by these agents. (Also noteworthy is that a few class II agents like propranolol also have a membrane stabilizing effect .)
Class I agents are divided into three groups (Ia, Ib, and Ic) based upon their effect on the length of the action potential. [ 10 ] [ 11 ]
Class II agents are conventional beta blockers . They act by blocking the effects of catecholamines at the β 1 -adrenergic receptors , thereby decreasing sympathetic activity on the heart, which reduces intracellular cAMP levels and hence reduces Ca 2+ influx. These agents are particularly useful in the treatment of supraventricular tachycardias . They decrease conduction through the AV node .
Class II agents include atenolol , esmolol , propranolol , and metoprolol .
Class III agents predominantly block the potassium channels , thereby prolonging repolarization. [ 12 ] Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become refractory). The class III agents exhibit reverse-use dependence (their potency increases with slower heart rates, and therefore improves maintenance of sinus rhythm). Inhibiting potassium channels results in slowed atrial-ventricular myocyte repolarization. Class III agents have the potential to prolong the QT interval of the EKG, and may be proarrhythmic (more associated with development of polymorphic VT).
Class III agents include: bretylium , amiodarone , ibutilide , sotalol , dofetilide , vernakalant , and dronedarone .
Class IV agents are slow non-dihydropyridine calcium channel blockers . They decrease conduction through the AV node , and shorten phase two (the plateau) of the cardiac action potential . They thus reduce the contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility. [ citation needed ]
Class IV agents include verapamil and diltiazem .
Since the development of the original Vaughan Williams classification system, additional agents have been used that do not fit cleanly into categories I through IV. Such agents include:
The initial classification system had 4 classes, although their definitions different from the modern classification. Those proposed in 1970 were: [ 2 ]
Another approach, known as the "Sicilian gambit", placed a greater approach on the underlying mechanism. [ 20 ] [ 21 ] [ 22 ]
It presents the drugs on two axes, instead of one, and is presented in tabular form. On the Y axis, each drug is listed, in roughly the Singh-Vaughan Williams order. On the X axis, the channels, receptors, pumps, and clinical effects are listed for each drug, with the results listed in a grid. It is, therefore, not a true classification in that it does not aggregate drugs into categories. [ 23 ]
A recent publication (2018) has now emerged with a fully modernised drug classification. [ 24 ] This preserves the simplicity of the original Vaughan Williams framework while capturing subsequent discoveries of sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules. The result is an expanded but pragmatic classification that encompasses approved and potential anti-arrhythmic drugs. This will aid our understanding and clinical management of cardiac arrhythmias and facilitate future therapeutic developments. It starts by considering the range of pharmacological targets, and tracks these to their particular cellular electrophysiological effects. It retains but expands the original Vaughan Williams classes I to IV, respectively covering actions on Na+ current components, autonomic signalling, K + channel subspecies, and molecular targets related to Ca 2+ homeostasis . It now introduces new classes incorporating additional targets, including:
It also allows for multiple drug targets/actions and adverse pro-arrhythmic effects. The new scheme will additionally aid development of novel drugs under development and is illustrated here.
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Antibiotic misuse , sometimes called antibiotic abuse or antibiotic overuse , refers to the misuse or overuse of antibiotics , with potentially serious effects on health. It is a contributing factor to the development of antibiotic resistance , including the creation of multidrug-resistant bacteria , informally called "super bugs": relatively harmless bacteria (such as Staphylococcus , Enterococcus and Acinetobacter ) can develop resistance to multiple antibiotics and cause life-threatening infections. [ 1 ]
Antibiotics have been around since 1928 when penicillin was discovered by Alexander Fleming . In the 1980s, antibiotics that were determined medically important for treatment of animals could be approved under veterinary oversight. In 1996, the National Antimicrobial Resistance Monitoring System (NARMS) was established. [ 2 ] Starting in 2010, publications regarding antimicrobial drugs in food became an annual report. Starting in 2012, there was publicly solicited input on how data is to be collected and reported for matters relating to the use of antimicrobials for food-producing animals. Resulting from this, the FDA revised its sampling structure within NARMS with the goal of obtaining more representative livestock data for the key organisms under surveillance. [ 2 ] "NARMS partners at CDC and USDA have published over 150 peer-reviewed research articles examining the nature and magnitude of antimicrobial resistance hazards associated with antibiotic use in food-producing animals." In 2014, the FDA began working with the United States Department of Agriculture (USDA) and the Centers of Disease Control and Prevention (CDC) to explore additional mechanisms to obtain data that is representative of antibiotic use in food-producing animals. In 2015, the FDA issued the Veterinary Feed Directive (VFD) final rule, under which veterinarians must authorize the use of antimicrobials within feed for the animals they serve. [ 2 ]
In addition to antibiotic regulation in food production, there have been numerous policies put in place to regulate antibiotic distribution in healthcare, specifically in hospital settings. In 2014, the CDC officially recognized the need for antimicrobial stewardship within all U.S. hospitals in their publication of the Core Elements of Hospital Antibiotic Stewardship Programs. These programs outline opportunities for reducing unnecessary antibiotic usage, and provide guidelines for antibiotic prescription for common infections. The CDC highlighted post-prescription tactics for antibiotic regulation, such as reassessing dosages and the class or type of antibiotic used, in order to optimally treat each infection. [ 3 ] The CDC also emphasized the need for evidence-based prescribing, a practice that focuses on the utilization of evidence and research to make informed medical decisions; [ 4 ] these sentiments were echoed by the American Dental Association (ADA) which works to provide detailed guidelines for dentists considering prescribing their patients antibiotics. [ 5 ] In 2019, the CDC published a report concerning the issue and updating the public on the effectiveness of past policy. This report, titled Antibiotic Resistance Threats in the United States, 2019 , indicated which pathogens posed the greatest threat of resistance, and highlighted the importance of infection prevention, providing recommendations for prevention strategies. [ 6 ]
There has also been a substantial effort to educate not only prescribers, but patients too on the issue of antibiotic misuse. The World Health Organization (WHO) has designated a "World Antimicrobial Awareness Week" in November. In 2021, the week's theme was "Spread Awareness, Stop Resistance" and the organization published many different forms of media including podcasts, articles, and infographics to raise awareness for the issue. [ 7 ] In the United States, the CDC has published posters and other materials for the purpose of educating the public on antibiotic resistance. [ 8 ] State health departments, such as Colorado's Department of Public Health & Environment, have partnered with the CDC to distribute these materials to healthcare providers. [ 9 ]
Antibiotics treats bacterial infections rather than viral infections.
Common situations in which antibiotics are overused include the following: [ 10 ]
Antibiotics can cause severe reactions and add significantly to the cost of care. [ 21 ] In the United States, antibiotics and anti-infectives are the leading cause of adverse effect from drugs. In a study of 32 States in 2011, antibiotics and anti-infectives accounted for nearly 24 percent of ADEs that were present on admission, and 28 percent of those that occurred during a hospital stay. [ 22 ]
If antimicrobial resistance continues to increase from current levels, it is estimated that by 2050 ten million people would die every year due to lack of available treatment [ 23 ] and the world's GDP would be 2 – 3.5% lower in 2050. [ 24 ] If worldwide action is not taken to combat antibiotic misuse and the development of antimicrobial resistance, from 2014 – 2050 it is estimated that 300 million people could die prematurely due to drug resistance and $60 – 100 trillion of economic output would be lost. [ 24 ] If the current worldwide development of antimicrobial resistance is delayed by just 10 years, $65 trillion of the world's GDP output can be saved from 2014 to 2050. [ 24 ]
Prescribing by an infectious disease specialist compared with prescribing by a non-infectious disease specialist decreases antibiotic consumption and reduces costs. [ 25 ]
Though antibiotics are required to treat severe bacterial infections, misuse has contributed to a rise in bacterial resistance. [ 26 ] The overuse of fluoroquinolone and other antibiotics fuels antibiotic resistance in bacteria, which can inhibit the treatment of antibiotic-resistant infections. [ 27 ] [ 28 ] [ 29 ] Their excessive use in children with otitis media has given rise to a breed of bacteria resistant to antibiotics entirely. [ 30 ] Additionally, the use of antimicrobial substances in building materials and personal care products has contributed to a higher percentage of antibiotic resistant bacteria in the indoor environment, where humans spend a large majority of their lives. [ 31 ]
Widespread use of fluoroquinolones as a first-line antibiotic has led to decreased antibiotic sensitivity , with negative implications for serious bacterial infections such as those associated with cystic fibrosis , where quinolones are among the few viable antibiotics. [ 32 ] [ 33 ] [ 34 ]
Antibiotics have no effect on viral infections such as the common cold. They are also ineffective against sore throats, which are usually viral and self-resolving. [ 35 ] Most cases of bronchitis (90–95%) are viral as well, passing after a few weeks—the use of antibiotics against bronchitis is superfluous and can put the patient at risk of developing adverse reactions. [ 36 ] Antibiotic misuse can lead to resistance in harmless bacteria that can be shared with other bacteria, or create an opportunity for potentially harmful bacteria to replace the harmless ones. [ 37 ]
Official guidelines by the American Heart Association for dental antibiotic prophylaxis call for the administration of antibiotics to prevent infective endocarditis . Though the current (2007) guidelines dictate more restricted antibiotic use, many dentists [ 38 ] and dental patients [ 39 ] follow the 1997 guidelines instead, leading to overuse of antibiotics. [ 40 ]
A study by Imperial College London in February 2017 found that of 20 online websites, 9 would provide antibiotics (illegally) without a prescription to UK residents. [ 41 ]
Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse. [ 42 ] [ 43 ] Antibiotics should also be used at the lowest dose for the shortest course. For example, research in the UK has shown that a 3-day course of antibiotics ( amoxicillin ) was as effective as 7-day course for treating children with pneumonia . [ 44 ] [ 45 ]
There has been significant use of antibiotics in animal husbandry . The most abundant use of antimicrobials worldwide is in livestock; they are typically distributed in animal feed or water for purposes such as disease prevention and growth promotion. [ 46 ] Debates have arisen surrounding the extent of the impact of these antibiotics, particularly antimicrobial growth promoters, on human antibiotic resistance. Although some sources assert that there remains a lack of knowledge on which antibiotic use generates the most risk to humans, [ 47 ] policies and regulations have been placed to limit any harmful effects, such as the potential of bacteria developing antibiotic resistance within livestock, and that bacteria transferring resistance genes to human pathogens [ 48 ] Many countries already ban growth promotion, and the European Union has banned the use of antibiotics for growth promotion since 2006. [ 49 ] On 1 January 2017, the FDA enacted legislation to require that all human medically important feed-grade antibiotics (many prior over-the-counter-drugs) become classified as Veterinary Feed Directive drugs (VFD). This action requires that farmers establish and work with veterinaries to receive a written VFD order. [ 50 ] The effect of this act places a requirement on an established veterinarian-client-patient relationship (VCPR). Through this relationship, farmers will receive an increased education in the form of advice and guidance from their veterinarian. Resistant bacteria in food can cause infections in humans. Similar to humans, giving antibiotics to food animals will kill most bacteria, but resistant bacteria can survive. When food animals are slaughtered and processed, resistant germs in the animal gut can contaminate the meat or other animal products.
Resistant germs from the animal gut can also get into the environment, like water and soil, from animal manure. If animal manure or water containing resistant germs are used on fruits, vegetables, or other produce as fertilizer or irrigation, then this can spread resistant germs. [ 51 ]
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Antibiotic prophylaxis refers to, for humans, the prevention of infection complications using antimicrobial therapy (most commonly antibiotics). Antibiotic prophylaxis in domestic animal feed mixes has been employed in America since at least 1970. [ 1 ]
Antibiotic prophylaxis is most commonly used prior to dental surgery , [ 2 ] but may be used in other cases, such as prior to sexual intercourse for patients who suffer from recurrent urinary tract infections . [ 3 ]
Even when sterile techniques are adhered to, surgical procedures can introduce bacteria and other microbes in the blood (causing bacteremia ), which can colonize and infect different parts of the body. An estimated 5 to 10 percent of hospitalized patients undergoing otolaryngology ("head and neck") surgery acquire a nosocomial ("hospital") infection, which adds a substantial cost and an average of 4 extra days to the hospital stay. [ citation needed ]
Antibiotics can be effective in reducing the occurrence of such infections. Patients should be selected for prophylaxis if the medical condition or the surgical procedure is associated with a considerable risk of infection or if a postoperative infection would pose a serious hazard to the patient's recovery and well-being. [ 4 ]
Antibiotic prophylaxis is also commonly used to prevent respiratory tract infections in antibody deficient patients. [ 5 ]
Local wound infections (superficial or deep-sided), urinary tract infections (caused by a bladder catheter inserted for surgery), and pneumonia (due to impaired breathing/coughing, caused by sedation and analgesics during the first few hours of recovery) may endanger the health of patients after surgery. Visibly worse are postoperative bacterial infections at the site of implanted foreign bodies ( sutures , osteosynthetic material, joint replacements, pacemaker implants, etc.) Often, the outcome of the procedure may be put into question and the life of the patient may even be put at risk. [ citation needed ]
Worldwide experience with antimicrobial prophylaxis in surgery has proven to be effective and cost-efficient, both avoiding severe patient suffering while saving lives (provided the appropriate antibiotics have been carefully chosen and used to the best of current medical knowledge). [ citation needed ]
A proper regimen of antibiotics for perioperative prophylaxis of septic complications decreases the total amount of antimicrobials needed and eases the burden on hospitals. The choice of antibiotics should be made according to data on pharmacology , microbiology , clinical experience and economy. Drugs should be selected with a reasonable spectrum of activity against pathogens likely to be encountered, and antibiotics should be chosen with kinetics that will ensure adequate serum and tissue levels throughout the risk period. Depending on the type of surgery and anticipated contamination associated with it, combinations of different agents or different routes of administration (e.g. intravenous and oral antibiotics) might be beneficial in reducing perioperative adverse events. [ 6 ] [ 7 ]
For prophylaxis in surgery, only antibiotics with good tolerability should be used. Cephalosporins remain the preferred drugs for perioperative prophylaxis due to their low toxicity . Parenteral systemic antibiotics seem to be more appropriate than oral or topical antibiotics because the chosen antibiotics must reach high concentrations at all sites of danger. It is well recognized that broad- spectrum antibiotics are more likely to prevent gram-negative sepsis . New data demonstrate that third generation cephalosporins are more effective than first and second generation cephalosporins if all perioperative infectious complications are taken into consideration. Dermatologic surgeons commonly use antibiotic prophylaxis to prevent bacterial endocarditis. Based on previous studies, though, the risk of endocarditis following cutaneous surgery is low and thus the use of antibiotic prophylaxis is controversial. Although this practice is appropriate for high-risk patients when skin is contaminated, it is not recommended for noneroded, noninfected skin. [ 8 ]
There are many factors that affect physicians' compliance with guideline recommendations, including cultural factors, educational background, training, nurse and pharmacist influences, medication supply, and logistics. [ citation needed ]
The American Dental Association (ADA) recommends antibiotic prophylaxis for few people since only a small number of cases of endocarditis might be caused by dental procedures. [ 9 ]
Long-acting, broad-spectrum antibiotics offer the following advantages by comparison to short-acting antimicrobials in perioperative prophylaxis: [ citation needed ]
There are many factors that affect physicians' compliance with guideline recommendations, including cultural factors, educational background, training, nurse and pharmacist influences, medication supply, and logistics. [ citation needed ]
The American Heart Association (AHA) now recommends antibiotic prophylaxis for very few patients since only a small number of cases of endocarditis might be prevented by this procedure. [ 10 ]
Antibiotic prophylaxis in domestic animal feed mixes has been employed in America since at least 1970. [ 1 ] Over time, the use of antibiotics for growth promotion purposes in livestock was discovered.
In 1986, some European countries banned the use of antibiotics because of research they found that linked antibiotic use in livestock and drug resistant bacteria in humans. [ 11 ] The European Union regulated in 2006 against antibiotics for growth promotion purposes. [ 12 ]
It was estimated in 2014 that over 80% of the world's antibiotic use was on farms. [ 13 ] [ 12 ] Coccidiosis in fowl had evolved increased tolerance to the antibiotic feed. [ 12 ] The WHO warned in April 2014 that farm use was a contributor to superbugs in humans. [ 13 ] The Auditor General of Canada found lack of progress in 2014 on antimicrobial resistance despite three years of government funds that should have been used to implement a reduction programme. [ 12 ] A CBC writer was concerned that there was in Canada "no coordinated national system to control antibiotics in agriculture." [ 13 ]
Due to the serious problem of superbugs (which are bred in antibiotic-rich environments) the Food and Drug Administration issued a guidance document in December 2013. The chief public health officer of Canada said four months later that "antibiotics should only be used in animals to treat infection rather than guard against disease or promote growth." The Canadian guidance document calls for "the prudent use of antibiotics in animal agriculture and a gradual phasing out of growth promoting drugs in feed and water over the three years" ending in 2017. [ 14 ] Producers will no longer be allowed to continuously feed animals doses of antibiotics as a way to promote growth. [ 15 ] A veterinarian said that ""If you don't put (antibiotics) in the feed, and you wait until you get an outbreak of necrotic enteritis , you've got a lot of dead birds and you've lost a lot of money." [ 15 ] The Beef Cattle Research Council were irritated by the change, while the Chicken Farmers of Canada had pre-empted it by teamwork four years earlier. [ 14 ] However, concerns were raised by the Chief Veterinarian of Ontario that "In other jurisdictions, they've found that, the drugs are not used for growth promotion, wink, wink, they're used for disease prevention." [ 13 ]
As of 2016, Health Canada had approved for employment in cattle three natural hormones and three synthetic hormones. [ 11 ]
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There are many circumstances during dental treatment where antibiotics are prescribed by dentists to prevent further infection (e.g. post-operative infection). The most common antibiotic prescribed by dental practitioners is penicillin in the form of amoxicillin , however many patients are hypersensitive to this particular antibiotic. Therefore, in the cases of allergies , erythromycin is used instead.
Antibiotics should only be used for oral infections where there is evidence of spreading infection ( cellulitis , lymph node involvement, swelling) or systemic involvement (fever, malaise), and where drainage or debridement is impossible. [ 1 ] There are a limited number of localized oral lesions that are indicated for antibiotic use and these include periodontal abscess , acute necrotizing ulcerative gingivitis , and pericoronitis . [ 1 ] A periapical abscess responds well to antibiotics if chewing gum is used during the first two half-lives of each dose (caution: overzealous mastication may result in muscle pain).
Another condition in which antibiotics are indicated is staphylococcal mucositis and it is mostly found in immunocompromised patients and the elderly. [ 2 ] Patients will experience oral discomfort, mucosal inflammation and mucosal bleeding. The common treatment for this type of infection is oral lavages and flucloxacillin. [ 2 ]
Bacteraemia is a condition in which bacteria are present in the blood and may cause disease, including systemic disease such as infective endocarditis . [ 3 ] Some dental treatments may cause bacteraemia, such as tooth extractions , subgingival scaling or even simple aggressive tooth brushing by patients. [ 4 ]
If the bacteria involved in the bacteraemia reach the cardiac tissue, infective (or bacterial) endocarditis can develop, with fatal outcomes. Infective endocarditis is an infection of the endothelium lining of the heart. [ 5 ] Infective endocarditis is known to dentists as a post-operative infection and is very serious and life-threatening, especially to patients at high risk of developing the disease, due to a weakened heart. This may be through having congenital heart defect, rheumatic or acquired valvular heart disease and prosthetic heart valves or vessels. [ 4 ] The most common bacteria associated with infective endocarditis are streptococcus sanguinis . [ 4 ]
Historically, the use of antibiotic prophylaxis to prevent post-operative infections, resulting from bacteraemia, and infective endocarditis was practiced by dentists, especially in patients at high risk (i.e. with heart problems). However, according to new recommendations from the National Institution for Health and Care Excellence (NICE), antibiotic prophylaxis should not be offered for all patients at risk of infective endocarditis. [ 6 ] This is due to the ever-increasing antibiotic resistance and there is no or very little evidence to show whether antibiotic prophylaxis is effective or ineffective against post-operative infections. [ 7 ] Moreover, it is yet to be established whether the benefits of administering antibiotics prophylactically outweighs the inherent risks, such as anaphylactic reaction related deaths. [ 7 ] Ethically, there is still a need to discuss with patients, the benefits and disadvantages of antibiotic prophylaxis before they make a decision on whether they will go through with it or not. [ citation needed ]
An abscess is a painful collection of pus usually caused by bacterial infections. Abscesses are usually the secondary stage of infection. The initial stage of infection is the bacterial infection called cellulitis and is caused by facultative anaerobe bacteria such as Streptococci (e.g. streptococcus pyogenes ). This occurs when bacteria gain access into the underlying tissues through odontogenic sources. Pus is usually not produced during this infection. [ 4 ] Antibiotic treatment (usually penicillin ) is used to prevent progression to a second stage of cellulitis – abscess . [ 4 ]
These abscesses are formed from a blockage in a periodontal pocket and have a vital pulp associated with the tooth. [ 5 ] Usually treatment involves the drainage and irrigation of the abscess with antiseptic mouthwash (0.2% Chlorhexidine ) and antibiotic therapy is rarely required. [ 8 ]
These abscesses are the most commonly occurring orofacial bacterial infection. [ 5 ] They are often the result of an inflamed or necrotic dental pulp or an infection of pulpless root canals. [ 9 ] [ needs update ] This pulp death is often due to the invasion of bacteria from advanced caries . [ 5 ] The first line of treatment is the removal of the source of inflammation or infection by local operative measures. [ 9 ] Generally, the abscess can be eradicated through surgical drainage alone; however this is sometimes inadequate. Therefore, systemic antibiotic treatment may be required, but only if there is evidence of spreading infection. [ 9 ] As the bacteria involved are known, antibiotic therapy selection can be specific, based on published susceptibilities. [ 9 ] Penicillin in the form of amoxicillin is the most common antibiotic to use. [ 4 ] However, 3% of the patient population is allergic to penicillin, so erythromycin is often used in cases of hypersensitivity.
Studies conducted to investigate the effects of antibiotics on patients with acute periapical periodontitis and acute apical abscess showed that patients receiving antibiotics in addition to root canal treatment did not have a reduced level of inflammation as compared to the patients not receiving antibiotics. However the available research on this topic is not of optimal quality therefore the results are not entirely reliable. [ 10 ]
Phenoxymethyl Penicillin : Penicillin-based antibiotics are used commonly against a broad range of bacterial infections within the body, primarily due to non-toxic effects and minor side effects. In dentistry, phenoxymethyl penicillin is used as it is acid-resistant and can be administered orally. Its common uses include treatment against acute oral infections such as dental abscesses, [ 5 ] pericoronitis , salivary gland infections and post-extraction infection. The main disadvantage however, is that patients can be allergic to penicillin based materials with a severe anaphylactic reaction occurring. Despite this, it is still commonly used due to it being highly cost effective and relatively safe. Alternative antibiotics include Erythromycin, cephalosporin and several others. [ 11 ]
Tetracycline : A wide spectrum antibiotic used to treat multiple bacterial infections. If prescribed during permanent tooth eruption in the mouth, grey staining can occur on the erupting teeth, presenting as a grey band at the point of eruption . The severity of the stain can vary depending on the level of intake of tetracycline. [ 12 ] In the UK, there are restrictions on when tetracycline can be prescribed as this staining can be quite severe. [ 12 ] [ 13 ] [ 14 ] Due to the side effect of deposition of tetracycline within developing teeth, it should not be prescribed to children up to 8 years of age as well as pregnant or lactating women. [ 11 ] [ 15 ]
Tetracycline has been used with some success in the treatment of localised juvenile periodontitis and this has proven to be particularly effective with in vitro studies of organisms associated with chronic and juvenile periodontitis. [ 11 ]
Ampicillin and amoxicillin : These antibiotics are a part of the penicillin group of antibiotics but are effective against a broader range of organisms. [ 15 ] Amoxicillin is a derivative of ampicillin. In Dentistry, Ampicillin is sometimes used when dealing with dentoalveolar infections, when the antibiotic sensitivity patterns of the causative organisms are unknown. Antibiotics are no longer used as prophylactic treatment of infective endocarditis in the UK, however, Amoxicillin was once used for prophylaxis of infective endocarditis in patients who have undergone oral surgery or deep scaling. [ 4 ]
While effective, ampicillin is associated with a higher incidence of drug rashes than penicillin and thus, should not be prescribed to patients with Infectious mononucleosis or lymphocytic leukaemia as there is a higher risk of developing a drug rash. [ 11 ]
Erythromycin : This is a wide spectrum antibiotic that has a similar range on the antibacterial spectrum to penicillin, making it the ideal first choice if patients are allergic to penicillin. It is also useful for treatment against B-lactamase-producing bacteria although it is not particularly as effective against oral and dental infections, due to such infections usually being caused by obligate anaerobes. [ 15 ]
Cephalosporin : This is an example of a wide spectrum antibiotic that is relatively stable to staphylococcal penicillinase although this stability varies with different cephalosporins. Certain cephalosporins in dentistry can be administered orally while others can be given by injections. In the case of an allergy to penicillin, cephalosporins may be a suitable alternative. [ 11 ] [ 15 ]
Metronidazole : This is an antimicrobial effective against some protozoa and strict anaerobes . In the UK, it has effective use in dentistry as it is the primary drug prescribed for acute ulcerative gingivitis . It is also sometimes used either alongside penicillin or alone against dentoalveolar infections with the advantage of having a low allergenicity. Mild side effects of metronidazole include transient rashes, furred tongue, an unpleasant taste in the mouth alongside several other side effects not restricted to the oral cavity. [ 4 ] [ 15 ]
Sulphonamides : This a group of drugs which is used in dentistry as they have a major advantage of being able to penetrate cerebrospinal fluid and this is particularly relevant when prescribing antibiotics, prophylactically against bacterial meningitis in patients who have had severe maxillofacial injuries, where the risk of infection is high. There are various other uses for sulphonamides as treatment with other parts of the body. [ citation needed ]
Cotrimoxazole : This is an antibiotic which incorporates sulphonamides and trimethoprim . It covers a broad spectrum of activity and in dentistry, is often used where there are clear signs and indications of bacterial infection that is sensitive to cotrimoxazole. This is determined by bacteriological sensitivity tests. [ 11 ]
Hypersensitive reactions are a major problem associated with the use of penicillin. A true allergy to penicillin is rare with an estimated frequency of anaphylaxis at 1-5 per 10 000 cases of penicillin therapy. Many adverse reactions will result in anaphylaxis , nausea , wheezing and laryngeal oedema . [ 16 ]
Some antibiotics are actively eliminated through the kidneys. Impaired renal function will require reduction of the drug dose to avoid excessively elevated plasma drug concentrations that could lead to toxicity. [ 17 ] Dose adjustment can be done by reducing the amount administered in each dose or by increasing the interval between doses. [ 17 ]
Many antibiotics are metabolized in the liver. In patients with liver failure, the use of such antibiotics should be restricted in order to avoid toxicity and subsequent overdose. [ 17 ] Erythromycin, clindamycin and metronidazole are antibiotics that would require dose adjustments when administered to patients with liver failure. Tetracyclines should also be avoided as they are potentially hepatotoxic . [ 17 ]
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Antibiotics and Chemotherapy was a peer-reviewed medical journal covering antimicrobial and cancer chemotherapy published by Karger Publishers . It was established in 1954 as Antibiotica et Chemotherapia: Fortschritte. Advances. Progrès , obtaining its current name in 1971. [ 1 ] It ceased publication in 2000.
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Antibody barcoding is a protein profiling technique that has been used to analyze hundreds of proteins from small tissue samples, such as minimally invasive fine-needle aspirates from cancer tissue. [ 1 ] Although promising, the technique has not yet been extensively proven or developed. [ 2 ]
The method involves optical mapping of DNA sequences that are added as "barcodes" to antibodies attached to the cells in the sample. The method showed high reproducibility and achieved single-cell sensitivity. [ 1 ] In addition to profiling cancer cells, the method shows promise as a clinical tool to identify pathway responses to molecularly targeted drugs and to predict drug response in patient samples. [ 1 ]
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Anticancer Research is an independent international peer-reviewed medical journal published by the International Institute of Anticancer Research , addressing experimental and clinical topics in oncology .
Issues are released monthly print and online (by Highwire Press ), and an annual Index is also published. Anticancer Research was established in 1981 by John G. Delinassios.
According to the Journal Citation Reports , the journal had a 2020 impact factor of 2.480 and 25,656 total cites. The 2020 rejection rate was 68%.
According to Scimago , the journal belongs to the second quartile (Q2) in the "Medicine" category.
Articles in Anticancer Research are abstracted and/or indexed by:
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Anticancer genes have a special ability to target and kill cancer cells without harming healthy ones. They do this through processes like programmed cell death, known as apoptosis , and other mechanisms like necrosis and autophagy . In the late 1990s, researchers discovered these genes while studying cancer cells. Sometimes, mutations or changes in these genes can occur, which might lead to cancer. These changes can include small alterations in the DNA sequence or larger rearrangements that affect the gene's function. When these anticancer genes are lost or altered, it can disrupt their ability to control cell growth, potentially leading to the development of cancer.
Cancer is a group of diseases where cells multiply uncontrollably. [ 1 ] Normally, cells have a built-in process called apoptosis that triggers cell death to prevent excessive growth. However, when these processes are disrupted, cancer can develop. Studies show that cancer is one of the leading causes of death worldwide. [ 1 ] Despite this, recent advancements in treatment have significantly increased survival rates for many patients.
The treatment for cancer varies depending on its type and how advanced it is. Chemotherapy is a common treatment that uses drugs to kill cancer cells. It works by damaging the DNA of cancer cells or stopping them from dividing. This process can also impact genes that control cell growth, affecting both cancer-causing and anticancer genes.
[ 2 ]
Apoptin was the first anticancer gene to be identified. [ 3 ] It originates from the Chicken Anemia Virus (CAV), which has circular DNA. [ 4 ] This virus belongs to the Gyrovirus family and is being researched for its potential in cancer treatment and diagnosis. [ 5 ] The apoptin protein, also known as viral protein 3 (VP3), was first isolated from chickens and has been found to cause programmed cell death in human cancer cells. [ 6 ]
Apoptin induces apoptosis, or cell death, in deformed or cancerous cells independently of a protein called p53 , meaning it is active in cells deficient of p53, as well as those with mutated or wild-type p53 expression. [ 7 ] In cancer cells, apoptin is mostly found in the nucleus and is activated, while in normal cells, it remains inactive in the cytoplasm . This difference allows apoptin to selectively target cancer cells.
Research has shown that apoptin can detect early changes that lead to cancer and can convert survival signals in cancer cells into signals for cell death. It interacts with various proteins, such as DEDAF, Nur77, Nmi, Hippi, and APC1. Studies using animal models and genetically modified mice have demonstrated that apoptin is a safe and effective anticancer agent, capable of significantly reducing tumor size. It holds promise for future cancer therapies as a treatment target and an early indicator of tumor-specific processes.
Apoptin is unique in its ability to attack deformed and cancerous cells while sparing healthy ones. It induces apoptosis through a pathway that involves mitochondria but does not rely on the p53 protein or death receptors typically involved in cell death. [ 8 ] In healthy cells, apoptin stays in the cytoplasm, but in cancer cells, it moves to the nucleus after being activated by a process called phosphorylation . This movement is triggered by the enzyme CDK2 at a specific site on the protein. [ citation needed ] [ 9 ]
For apoptin to function fully, it requires interactions with other molecules such as DNA, cyclinA-CDK2 , and FADD . [ citation needed ] Current therapeutic agents using apoptin have shown effectiveness in treating types of cancer like Lewis lung carcinomas and osteosarcomas , with potential applications in liver cancer treatment. [ 4 ]
Brevinin 2R:
Skin from the frog Rana brevipoda porsa (now known as Pelophylax porosus ) was used to isolate the unique non-hemolytic defensin known as brevinin-2R. [ 10 ] Malignant cells such as T-cell leukemia Jurkat, B-cell lymphoma BJAB, colon cancers HT29/219, SW742, fibrosarcoma L929, breast cancer MCF-7, and A549 (lung carcinoma) exhibit preferential cytotoxicity towards it in comparison to primary cells such T cells, human lung fibroblasts, and peripheral blood mononuclear cells (PBMC). Jurkat, MCF-7, and L929 overexpressing cells as well as MCF-7 cells overexpressing a dominant-negative mutant of a pro-apoptotic BNIP3 (TM-BNIP3) were largely resistant to Brevinin-2R treatment. [ 10 ]
These 25 amino acid peptides, in contrast to the majority of peptides within the Brevinine family, have low hemolytic action. [ 11 ] Not only does the peptide have a reduced hemolytic action, it also is semi-selective towards cancer cells and leaves non-cancerous cells largely unharmed. This peptide works to prevent the progression of cancer by arresting the cell cycle at the G2/M phase, resulting in an induction of apoptosis.
This defensin traditionally works as a part of the innate immune system, working as an antimicrobial defense. [ 10 ] However, this peptide is currently being studied as an anticancer peptide. Brevinin-2R works to trigger cell death by reducing the mitochondrial membrane potential resulting in lower cellular ATP levels while simultaneously increasing the concentration of reactive oxygen species. [ 10 ] Currently and somewhat unrelated, Brevinin-2R is being considered for diabetic treatments. In treating type II diabetes, or diabetes mellitus, Brevinins have been shown to promote insulin release. Finally, these peptides even have the capability to increase the rate of tissue regeneration, as seen with the frog in which Brevinin-2R was isolated from. [ 10 ]
Early region 4 open-reading-frame 4 (E4orf4) is an adenovirus protein of 14kDa which regulates growth in all stages of the adenovirus (Ad) infection. E4orf4 partners mainly with protein phosphatase 2A (PP2A) and Src kinases to induce cell death. Modeling of this protein reveals that it is likely made up of 3 α-helices with N- and C-terminal loops. It has a small stretch of amino acids in positions 66–75, which are highly basic, and likely are a place of nuclear and nucleolar targeting, as well as a place for Src kinases to bind. [ 12 ]
E4orf4 is an important regulator of adenoviruses. Additionally, outside of the context of the virus, it causes programmed cell death both in the context of a healthy cellular environment, and cancer. E4orf4 is a key regulator of Ad by down-regulating both viral and cellular genes, which plays an important role in regulating the proliferation of the virus. In turn, the down-regulation also impacts the alternative splicing of the viral RNA and protein translation. In the absence of a viral infection, E4orf4 induces apoptosis in a p53 and caspase -independent manner; however, there is still communication between this pathway and the caspase-dependent apoptosis pathway. In the context of cancer, E4orf4 is even more efficient at inducing cell death than in healthy cells, which could be an important finding for potential cancer therapies. It has been discovered that the mechanisms behind the function of E4orf4 are closely associated with several other proteins including the B55 subunit of PP2A. E4orf4 binds to PP2A to reduce the phosphorylation of the DNA damage response (DDR) proteins. Consequently, this reduces the function of DDR and limits DNA repair. Many cancer cells have defects in the DDR pathways and targeting these cells with E4orf4 can potentially destroy the remaining DDR pathways, resulting in cancer cell death. [ 13 ]
The main mechanism behind the specificity of cancer cell targeting by E4orf4 is unknown but there are multiple hypotheses that scientists are considering: 1) The activation of the oncogenic state causes dormant apoptotic signals to be initiated and cause cell death to be more easily achieved by different signals. 2) There has been some indication that cancer cells become addicted to oncogenic pathways. E4orf4 may inhibit these pathways, causing cell death in cancer cells, but not normal cells. 3) E4orf4 may use oncogenes that have been activated in cancer cells, including Src, to cause cell death. 4) Cancer cells have disrupted cell cycle checkpoints and E4orf4 can take advantage of this by disrupting checkpoints in mitosis. 5) A Drosophila model demonstrated that E4orf4 can inhibit classical apoptosis in healthy tissues. It has been considered that this function of E4orf4 is lost in cancer cells causing a more effective killing of cells. 6) E4orf4 has been shown to cause structural changes in mitochondria , which could impact metabolic reprogramming and may affect cancer and healthy cells differently. [ 12 ]
HAMLET is known as an anticancer protein complex found in breast milk. One of the two molecules of this complex is multimeric alpha lactalbumin (MAL), which was first discovered during a study in 1995 that investigated how breast milk affects bacteria transformed with lung cancer . This study found that transformed cells were selected for apoptosis at a much higher rate than the untransformed, healthy cells. [ 14 ] A later study in 2000, ascertained that oleic acid , a C18:1 fatty acid, is a cofactor that binds to MAL forming HAMLET. This complex, in a partially unfolded state, then displays apoptotic activity in cancer cells. [ 15 ]
Apoptosis, or programmed cell death, can occur through activation of three different pathways, intrinsic , extrinsic, or tumor necrosis factor . HAMLET proceeds by both a multifaceted intrinsic pathway and the caspase cascade , a subsection of the TNF pathway, through targeting many different cell components. [ 16 ] First, after uptake by the cell, HAMLET proceeds to the mitochondria and depolarize the membranes at cytochrome c . Consequently, mitochondria-dependent apoptosis factors are released as well as the caspase cascade is activated. [ 17 ] Second, proteasomes are targeted by HAMLET through a mechanism that is less understood. Research does suggest that HAMLET directly binds to the proteasome leading to its inhibition. [ 18 ] Third, HAMLET has been found to target the nucleus, specifically histones . HAMLET irreversibly binds to histones leading to the inactivation of transcription and chromatin condensation, which inevitably causes apoptosis. [ 19 ] Lastly, studies show that cells treated by HAMLET exhibit behaviors common to macroautophagy . This includes the presence of cytoplasmic vacuoles , double-membrane vesicles, and a dose-dependent decrease in ATP levels. [ 16 ]
Melanoma differentiation associated gene-7 ( mda-7 ), and also known as IL-24 , was discovered in the mid-1900s using subtraction hybridization . mda-7 is classified in the interleukin IL-10 family because of similar structure and amino acid sequence to other interleukins in that class, the chromosomal location ( human chromosome 1q32-33 ), [ 20 ] and the shared properties it has with cytokines . Protein structural studies reveal that it is a dimer and glycosylated . It has been found that its expression is either not present or present at very low levels in tumor cells, including advanced stage melanoma and metastatic disease , compared to normal non- transformed cells . Multiple studies within the past 15 years have demonstrated that increasing mda-7 expression in tumor cells results in growth arrest and cell death in many different cell lines. When mda-7 is over-expressed in normal cells, no change in growth or cell viability is detected. mda-7 is also considered a radio-sensitizing cytokine because it generates a reactive oxygen species and causes stress in endoplasmic reticulum . [ 21 ] mda-7 has been used in several clinical trials because of its ability to induce apoptosis, prevent tumor angiogenesis , cause immune-regulation, and increase radiation lethality. It was seen in one Phase I clinical trial that injecting mda-7 via an adenovirus directly into a tumor resulted in safe tumor regulation and immune activation. [ 21 ]
mda-7 interacts with two of the type II cytokine hetero-dymeric receptor complexes IL-20R1/IL-20R2 and IL-22R1/IL-20R2. It has been seen that in some contexts, mda-7 activates STAT transcription factors. However, the STAT pathway is not always activated and is not required for mda-7 cell growth arrest and cell death. mda-7 can be placed into tumor cell lines via transfection or adenovirus- transduction ; it has been seen that following this, apoptosis is induced only in the tumor cells and results in no toxicity in the healthy cells. [ 20 ] Its function as a tumor suppressor is not fully understood, but it has been observed that in the context of melanoma , mda-7 expression is drastically decreased. While there are no official studies published backing this claim, it is thought that mda-7 could potentially act as a paracrine factor , be involved in signaling short-range, and immune function in skin. mda-7 is also thought to have a pro-inflammatory purpose. It is also possible that mda-7 induces cytokine secretion, which causes antigen-presenting cells to present tumor antigens, resulting in an immune response against tumors. It has also been discovered that mda-7, and its translated protein MDA-7, interacts with kinases including serine/threonine protein kinase (PKR). [ 20 ] Further studies will need to be performed to better understand the mechanisms of mda-7 action.
Noxa, isolated from mice, is a member of the Bcl-2 family and is able to regulate cell death through a variety of intracellular stress signals. [ 22 ] Having been discovered nearly three decades ago in 1990 by Hijikata et al., this gene product was isolated this protein from an adult T-cell leukemia (ATL) library [ 23 ] This gene, and its protein in which it encodes for, has been studied as a potential therapeutic in chronic lymphocytic leukemia (CLL), the most common leukemia found in adults in the Western world . [ 22 ] In humans, the Noxa homologue is known as APR/PMAIP1. [ 23 ]
Upon receiving intrinsic death signals, the gene NOXA encodes for the protein Noxa through a three-exon transcript. [ 23 ] This protein binds to anti-apoptotic proteins resulting in these proteins' inhibition. [ 22 ] As a p53 inducible gene, NOXA is transcribed and translated to Noxa in response to DNA damage and hypoxia induced apoptosis. [ 22 ] A constitutive gene found in the brain , thymus , spleen , and several other organs, it initiates apoptosis through Bax-mediated mitochondrial-dysfunction through the inhibition of the Bcl2 family's antiapoptotic members. [ 23 ] Through gene knockout studies, it was shown that double deficient Noxa there was no spontaneous tumor development as commonly observed with knockout of p53. [ 23 ] Noxa has been shown to be involved in the maintenance of memory CD4+ T Th1/Th2 cell homeostasis where in the absence of Noxa, Th2 memory T-cell death results. [ 23 ]
In the 1960s rodent parvovirus was discovered by Dr. Helene Toolan to have an oncosuppressive activity. [ 24 ] [ 25 ] [ 26 ] [ 27 ] [ 28 ] However, the specific gene found in the parvovirus genome, which is called NS1, that causes the oncosuppressive activity was not characterized until later. NS1 is a small protein (only 672 amino acids) with 5 distinct domains that exert different functions that inevitably lead to apoptosis and cell death. NS1 activates cell death through two different pathways, apoptosis/lysosomal-like programmed cell death and necrosis/ cytolysis . [ 29 ]
NS1 is considered a regulatory protein due to its activity in transcription, translation, and protein-protein interactions, which allows the parvovirus to replicate unhindered. However, scientists are primarily interested in utilizing its cytolytic activity since this has been proven to be active in cancerous cells. The first way NS1 propagates cell death through cytolysis is by interrupting the cell cycle at the S / G2 junction, causing a stress response in the cell. Specifically, NS1 interacts with many molecules and compounds important in the transition and inhibits their activity. When NS1 expression reaches a certain threshold, the triggered stress response finally causes caspase 3/9-mediated programmed cell death . [ 29 ] Another way that NS1 causes cytolysis is through degradation of the cytoskeleton of the cell. NS1 specifically targets and degrades the microfilament tropomyosin using casein kinase II , actin filaments through activation of actin-severing protein gelsolin , and vimentin through an unknown mechanism. [ 30 ] [ 31 ] [ 32 ] The last NS1-mediated mechanism of cytolysis involves the depolarization of the mitochondria. This results in the release of many reactive oxygen species , causing DNA damage. When DNA is damaged, a DNA damage response occurs, which in this case results in cell death. [ 33 ]
Organic Cation Transporter Like-3 (ORCTL3) was first discovered as a result of a large-scale DNA sequencing project in search of genes with a tumor-specific apoptosis activity. [ 34 ] The name ORCTL3 was decided upon because of its structural homology to proteins belonging to the family of organic cation transporters . [ 35 ] However, the name is a misnomer as after examining the properties of ORCTL3, it was revealed that ORCTL3 is a transporter for urate . The ORCTL3 gene spans around 12 kb of genomic DNA and consists of ten exons. It was shown that the 2.4 kb transcript of this gene is universally expressed in all human tissues. Additionally, ORCTL3 transfection into numerous tumorigenic cells induced apoptosis, while normal and primary cells remained healthy. [ 36 ]
ORCTL3 is a 90 kDa protein composed of 351 amino acids. [ 37 ] [ 38 ] It is suggested that the protein spans the cell membrane several times, based on computational methods. [ 39 ] Overexpressed ORCTL3 is localized to the endoplasmic reticulum (ER), Golgi and the plasma membrane but not to mitochondria. [ 36 ] ORCTL3 was identified as the first high-affinity nicotinate exchanger in kidneys and intestine. Nicotinate is an essential vitamin ( Vitamin B3 ) that is involved in NAD+ synthesis, which in turn is important for energetic processes, signal transduction pathways, and the activation of the NAD+ -dependent histone deacetylase SIRT1 . ORCTL3 has been shown to be activated for apoptosis induction in renal cells in vitro , in vivo and ex vivo . For its apoptosis effect ORCTL3 targets stearoyl-CoA desaturase (SCD), an enzyme that introduces a double bond in the fatty acid stearic acid . [ 40 ] The fact that SCD is commonly overexpressed in cancer and oncogene transformed cells might explain the tumor-specificity of ORCTL3 to some extent, however, the existence of other additional targets of ORCTL3 cannot formally be ruled out.
Prostate apoptosis response-4 ( Par-4 ) is a tumor suppressor protein with a pro-apoptotic function. Par-4 was first discovered in rat prostate cancer cells as part of an effort determined in discovering genes that were induced in response to increased Ca 2+ in cells, although it is now known to be ubiquitously expressed in a wide variety of tissues across many different species. [ 41 ] The Par-4 gene is located on the minus strand of chromosome 12q21.2 , spanning 99.06 kb of DNA and containing seven exons and six introns. Par-4 is known to be downregulated in certain terminally differentiated cells such as neurons , specific retinal cells, and smooth muscle cells as well as in certain cancer cells such as renal cancers , neuroblastoma , and leukemia . [ 42 ] [ 43 ] Par-4 has also been shown to be generally higher in dying cells, consistent with its pro-apoptotic functions.
Par-4 is a 38 kDa multi-domain protein composed of about 340 amino acids. Conserved domains among human, mouse, and rat homologs include the leucine zipper (LZ) domain at the C-terminal region, two nuclear localization sequences, NLS1 and NLS2, in the N-terminal region, and a nuclear export sequence within the LZ domain. [ 44 ] Although Par-4 mutations are rare, it was identified that an A to T point mutation affecting residue 189 localized in exon 3 causes premature termination of Par-4 in human endometrial carcinoma. [ 45 ] Knockout of Par-4 in mice leads to the development of spontaneous tumors in various tissues revealed by increased proliferative response of peripheral T cells , inhibition of apoptosis, increased NF-κB activity, and decreased JNK activity. [ 46 ] Par-4 overexpression is sufficient to induce apoptosis in most cancer cells in the absence of a second apoptotic signal, but does not induce apoptosis in normal or immortalized cells. [ 44 ] [ 47 ] [ 48 ]
The anticancer function of Par-4 is achieved by two distinct means: activating the molecular components of the cell-death machinery and inhibiting pro-survival factors. One essential apoptotic function of Par-4 is inhibiting the NF-κB pathway, which is a key contributing factor in many tumors and prevents cell death by activating the expression of pro-survival genes. Par-4 also assists in PCD by enabling the trafficking of specific ligands such and cell surface death receptors, such as FasL and Fas , respectively, to the plasma membrane thus activating the extrinsic death pathway. Overexpression of Par-4 selectively induces apoptosis in cancer cells, attributed to the selective activation via phosphorylation of the T155 residue by protein kinase A (PKA). [ 49 ] It has been shown that two events are required for Par-4 activation: nuclear entry and phosphorylation by PKA.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family that also includes Fas ligands , TNFα , and TL1A . It was discovered in 1995 by Wiley et al. and then further characterized in 1996 by Pitti et al. The former study discovered that TRAIL is localized to surfaces of cells in most human tissues, excluding the brain, liver, and testes, [ 50 ] while the latter study was able to elicit that the protein is a type II membrane protein that can also be cleaved into a soluble form. [ 51 ]
The intrigue surrounding TRAIL is all due to this protein's ability both in vivo and in vitro to specifically target tumor cells for apoptosis while leaving healthy cells intact. This activity proceeds by both the intrinsic and extrinsic pathway. First, the homotrimer of TRAIL binds three molecules of either TRAIL-receptor 1 or 2, which are transmembrane proteins that contain a cytoplasmic death domain. Once TRAIL is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming death-inducing signaling complex (DISC) that proceeds through two different mechanisms depending on the cell type. In one cell type, DISC can directly activate the effector caspase leading to apoptosis, while in the other the complex activates a bcl-2-mediated pathway in a similar fashion as HAMLET that results in the release of cytochrome c from the mitochondria, which then causes the activation of effector caspase. The latter mechanism is the focus of many oncogenic therapies because p53, the tumor suppressor gene, activates the same pathway. Since cancer is commonly caused by the inactivation of p53, TRAIL could mediate this effect by still activating the apoptotic pathway. [ 52 ]
TP-53 is a gene that encodes for the protein p53 ; this protein is a tumor suppressor. p53 was discovered in 1979 stemming from a study involving cancer immunology and the role of viruses in some cancers. The protein was so named because it was measured to have a weight of 53 kDa. This study was conducted by David Philip Lane and technician Alan K. Roberts, in Lionel V. Crawford's lab in London. It was seen in this study that p53 could bind to viral tumor antigens . This information was corroborated during the same year when a separate study found that p53 had immunoreactivity with serum from tumors containing antibodies . This later study was run by Daniel I. H. Linzer and Arnold J. Levine out of Princeton University. Further papers came out around the same time all mentioning the discovery of a tumor-suppressing protein. While p53 was first officially identified in 1979, many labs in previous years had come across the same protein, without knowing what it was. In the mid-1970s, a scientist by the name of Peter Tegtmeyer happened upon a protein with an approximate size of 50 kDa. However, because he was focusing his studies on SV40 , a tumor-causing virus affecting monkeys and humans, he did not pay much attention to this protein. [ 53 ]
The p53 protein is a tumor-suppressing transcription factor (TF), which can recognize when there is an alteration in a cell's DNA caused by factors including chemical toxins, radiation, ultraviolet (UV) rays, and other damaging agents. [ 54 ] Crucially, p53 plays a role in determining whether the damaged genetic material in the cell can be repaired, or if the cell should be destroyed through apoptosis. [ 55 ] [ 56 ] The individual topologically associating domains (TADs) target different genes and unique effector pathways. It has been observed that inactivating both of the TADs detrimentally affects the ability of p53 to suppress tumor growth and interact with target genes. When only one TAD is inactivated, p53 can still suppress specific tumors; however, it can no longer successfully engage in transactivation. The C-terminal domain (CTD) is an intrinsically disordered domain (IDD), which can take on different conformations depending on what it is binding with and is a location of many post-translational modifications , resulting in its ability to regulate p53 function depending on what it is bound to and what modifications are linked with the CTD. This domain also aids in the binding of the central DNA-binding domain (DBD) to specific DNA sequences; the CTD is a positive regulator of DNA binding and stabilizes the interaction of the DNA with the DBD. [ 54 ] p53 is unique as a transcription factor in that it can recognize and bind response elements (RE) in many different environments and doesn't need other transcription factors to cooperatively bind with it like many other TFs. [ 54 ]
Mutations in the p53 pathway have been observed in almost all cancer types including breast cancer , bladder cancer , lung cancer , ovarian cancer , cholangiocarcinoma , head and neck squamous cell carcinoma , melanoma , wilms tumor , and other cancers often due to a single point mutation in p53. [ 55 ] [ 56 ] Li-Fraumeni Syndrome is a condition linked to inherited mutations, at least 140 mutations, in the TP-53 gene. This condition largely increases the risk of developing cancers like breast cancer, bone cancer, and soft tissue sarcomas . Specifically, this impacts children and young adults. A majority of these mutations in the TP-53 gene are single amino acid changes, but other mutations cause a small portion of the DNA to be absent. This leads to a faulty p53 protein that fails to recognize DNA damage in cells, control cell growth, and initiate apoptosis in cells with damaged DNA. Consequently, cells containing erroneous DNA can uncontrollably divide. [ 55 ]
BRCA gene mutations:
The tumor suppressing BRCA genes frequently help in cancer prevention. They control how cells divide and develop and help repair DNA damage BRCA gene abnormalities, however, can the likelihood of having specific cancers is raised. Cancers BRCA1 and BRCA2 are the two BRCA recognized cancer-causing gene alterations. The likelihood that a woman may develop ovarian and breast cancer is increased by certain gene abnormalities. Male breast cancer and prostate cancer risk are both increased by BRCA2 gene mutations Men and women with BRCA2 gene mutations have a marginally increased chance of acquiring pancreatic cancer. (53)
Often, genes are confused with the proteins they code for. Genes are composed of nucleotides , while proteins are composed of amino acids . The genes serve as codes and blueprints to create either proteins of interest, or various non-coding ribonucleic acids ( ncRNAs ), which exhibit various effects, such as working to prevent cancer within cells.
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https://en.wikipedia.org/wiki/Anticancer_gene
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The antiestrogen withdrawal response is a paradoxical improvement in breast cancer caused by discontinuation of antiestrogen therapy for breast cancer. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] It has been documented rarely with the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] The phenomenon indicates that these agents can somehow result in stimulation of breast cancer tumor progression under certain circumstances. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] One proposed theory for the mechanism is that the sensitivity of breast cells to estrogens shifts with estrogen deprivation, and upon antiestrogen withdrawal, endogenous estrogen acts in the manner of high-dose estrogen therapy in the breast to inhibit breast cancer growth and induce breast cancer cell death . [ 1 ] The antiestrogen withdrawal syndrome is analogous to but less common and well-known than the antiandrogen withdrawal syndrome , a phenomenon in which paradoxical improvement in prostate cancer occurs upon discontinuation of antiandrogen therapy. [ 4 ]
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https://en.wikipedia.org/wiki/Antiestrogen_withdrawal_response
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Antihormone therapy is a type of hormone therapy that suppresses selected hormones or their effects, in contrast with hormone replacement therapy , which encourages hormone activity.
The suppression of certain hormones can benefit patients with certain cancers because certain hormones prompt or help the growth of a tumor . [ 1 ] This is especially true in cancers relating to the sex organs . [ 2 ]
Hormones are made by glands and circulated through the bloodstream. [ 3 ] Hormones may act as a signal to cells to grow by attaching to them. [ 3 ] Antihormone therapy blocks hormones from sending these messages to cells. If a diagnostic test shows cancer in places with hormones attached, drugs may be prescribed to the patient to block the receptors and inhibit the growth of cancer cells. [ 3 ] Most antihormone therapies are administered by pill for 5 to 10 years after surgery. [ 4 ]
Hormone replacement therapy began in the 1960s but gained traction in the late 1990s. [ 5 ] Therapy methods have been developed rapidly since the 1970s, and survivorship of individuals with hormone receptor-positive cancer has skyrocketed. [ 6 ] In more recent years, since the 1990s, new classes of drugs have been released and greatly changed the way hormonal cancers, like prostate and breast cancer, are treated. [ 7 ] Research to understand how hormones influence the growth of cancer cells has prompted researchers to find new ways to use drugs to prevent and treat hormone receptor-positive cancer cells by limiting the production of sex hormones. [ 7 ] These methods of hormone suppression have opened the door for pioneering new cancer chemoprevention drugs. [ 7 ]
Tamoxifen is a SERM and is one of the most common and oldest forms of hormone therapy. [ 8 ] When breast cancer is found at an early stage or found to be Metastatic breast cancer , tamoxifen can be prescribed to selectively block estrogen 's effect on certain cells. SERMs like tamoxifen attach to receptors on the cancer cells which blocks estrogen from attaching to the receptors. Tamoxifen is successful in lowering breast cancer reoccurrence rates, breast cancer occurrence in the opposite breast, and death from breast cancer in cases of hormone receptor-positive and hormone-sensitive cancer . [ 9 ] Tamoxifen is also thought to lower the risk of breast cancer in those who have a predisposition or at risk. [ 9 ] Tamoxifen may be used in pre and postmenopausal women. [ 10 ] Toremifene is a similar SERM drug to tamoxifen, but is less common and only approved for treatment of metastatic cancer. Toremifene is generally prescribed once tamoxifen is no longer effective. [ 11 ]
Fulvestrant is a SERD drug that acts by damaging and blocking estrogen receptors. [ 11 ] Fulvestrant is currently only approved by the FDA to treat cancer in postmenopausal women, but it is often prescribed off-label in combination with and LHRH agonist in premenopausal women to halt the functionality of the ovaries. [ 11 ] Fulvestrant is administered via injection in the buttocks . [ 11 ]
A group of drugs called aromatase inhibitors are commonly prescribed to postmenopausal women who test positive for hormone receptor-positive cancer. Aromatase in fat and muscle can circulate estrogen in postmenopausal women. [ 12 ] Aromatase in highly estrogen-sensitive tissues, such as the breast, uterus, vagina, bone, and blood vessels, provides estrogen locally, so aromatase inhibitors work by reducing this estrogen production. [ 12 ]
Ovarian suppression is known to slow the growth of hormone receptor-positive breast cancer in premenopausal women [ 13 ] and can also help preserve fertility during chemotherapy. [ 14 ] Ovarian suppression through drugs temporarily shuts down the ovaries preventing the production of oestrogen , thus slowing the rate of growth of hormone receptor-positive tumors. [ 14 ] Ovary suppression may also be achieved through surgical intervention known as an oophorectomy , which removes one or both ovaries sometimes in combination with the fallopian tubes . [ 15 ]
LHRH (luteinising hormone-releasing hormone) agonists block the production of sex hormones in both men and women. [ 16 ] In men, LHRH agonists seize testosterone production in the testicles , and in women it blocks the ovaries from producing estrogen and progesterone. [ 16 ] These drugs are most commonly used in treatments for prostate cancer. [ 16 ]
Side effects of antihormone therapy are generally minimal, but can produce similar feelings to menopause in women. [ 4 ] Common symptoms of all antihormone therapies include irregular menstrual cycles, hot flashes, weight gain, vaginal dryness, headaches, mood swings and hair thinning. [ 4 ] Less common but more serious drug-specific side effects include: [ 11 ]
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https://en.wikipedia.org/wiki/Antihormone_therapy
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The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial , also known as ALLHAT , was a randomized, double-blind , active-controlled study comparing at the same time, four different classes of antihypertensive drugs with the rate of coronary heart disease (CHD) events in ‘high-risk’ people with hypertension . [ 1 ] Participants were initially randomised to chlorthalidone ( diuretic ) versus doxazosin ( alpha-adrenergic blocker ), lisinopril ( ACE-inhibitor ), and amlodipine ( calcium channel blocker ). [ 2 ] [ 3 ]
The doxazosin arm was discontinued early on in the trial because of a higher rate of combined cardiovascular events and admissions for heart failure compared with chlorthalidone. The study concluded that major CHD events did not differ between initial use of chlorthalidone versus lisinopril or amlodipine. As a result, the Joint National Committee (7) guidelines of 2003, recommended the cheaper but equally effective diuretics as a first line treatment for hypertension. The study also confirmed the previously held views that ACE inhibitors were less effective in blood pressure control and stroke prevention in men of African and Caribbean descent. [ 3 ] [ 4 ]
By the mid-1990s, there was increasing awareness of the relative reduction of risks for stroke and CHD with lowering blood pressure, and the main drugs in use were initially diuretics and beta-blockers . [ 5 ] Shortly after, other newer classes of blood pressure lowering drugs were developed and the ALLHAT study aimed to clarify their relative values with the aim to also answer which one to use first. [ 3 ]
The trial was supported mainly by the National Heart, Lung and Blood Institute , part of the National Institutes of Health (NIH), and received some support from Pfizer . [ 6 ]
Since 1971, the Coordinating Center for Clinical Trials ( [1] ) at The University of Texas School of Public Health has played a leading role in cardiovascular disease and vision research by serving as a coordinating center for 25 nationwide multicenter clinical trials . The CCCT's primary function is to provide and coordinate all operations, procedures, and activities of a large-scale randomized controlled clinical trial. The CCCT serves as the Clinical Trials Center (Data and Clinical Coordinating Centers) for the ALLHAT. The CTC was led by C. Morton Hawkins (1993-2000) and Barry R. Davis (2000-2016).
In February 1994, initially 42,418 people, age over 55 years, with stage I or II hypertension or who were taking medication for high blood pressure were recruited across 623 centres in Canada, Puerto Rico, the US, and the US Virgin Islands. All had at least one other CHD risk factor including previous heart attack or stroke , electrocardiogram or echocardiogram verified left ventricular hypertrophy (LVH), a history of type II diabetes mellitus , current cigarette smoking , and low high-density lipoprotein cholesterol levels. [ 7 ] 35% were African American. [ 5 ] The doxazosin arm was discontinued in January 2000 because of a higher rate of combined cardiovascular events and admissions for heart failure compared with chlorthalidone. Follow-up of the remaining 33,357 participants was completed in 2002. [ 7 ]
ALLHAT showed that major CHD events did not differ between initial use of chlorthalidone versus lisinopril or amlodipine. As diuretics proved equally effective and were cheaper, the Joint National Committee 7 guidelines of 2003, recommended diuretics as a first line treatment for hypertension. The study confirmed the previously held views that ACE inhibitors were less effective in blood pressure control and stroke prevention in men of African and Caribbean descent. The study also revealed that calcium channel blockers did not cause higher rates of gastrointestinal bleeding or cancers and they were not less effective than other antihypertensives. [ 3 ]
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https://en.wikipedia.org/wiki/Antihypertensive_and_Lipid_Lowering_Treatment_to_Prevent_Heart_Attack_Trial
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Antineoplastic resistance , often used interchangeably with chemotherapy resistance, is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies. [ 1 ] In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance .
There are two general causes of antineoplastic therapy failure: Inherent genetic characteristics, giving cancer cells their resistance and acquired resistance after drug exposure, which is rooted in the concept of cancer cell heterogeneity . [ 1 ] Characteristics of resistant cells include altered membrane transport , enhanced DNA repair , apoptotic pathway defects, alteration of target molecules, protein and pathway mechanisms, such as enzymatic deactivation. [ 1 ] Since cancer is a genetic disease, two genomic events underlie acquired drug resistance: Genome alterations (e.g. gene amplification and deletion) and epigenetic modifications .
Cancer cells are constantly using a variety of tools, involving genes, proteins, and altered pathways, to ensure their survival against antineoplastic drugs.
Antineoplastic resistance, synonymous with chemotherapy resistance, is the ability of cancer cells to survive and grow despite different anti-cancer therapies, i.e. their multiple drug resistance . There are two general causes of antineoplastic therapy failure: [ 2 ] Inherent resistance, such as genetic characteristics, giving cancer cells their resistance from the beginning, which is rooted in the concept of cancer cell heterogeneity and acquired resistance after drug exposure. [ 2 ]
Cancer cell heterogeneity, or tumour heterogeneity , is the idea that tumours are made up of different populations of cancer cells that are morphologically, phenotypically and functionally different. [ 3 ]
Cancer cell heterogeneity can cause disease progression when molecularly targeted therapy , fails to kill those tumor cells which do not express the marker, then divide and mutate further, creating a new heterogeneous tumour. In breast cancer models of the mouse the immune microenvironment affects susceptibility to neoadjuvant chemotherapy . In breast cancer, particularly in the triple-negative subtype, immune checkpoint blockade has been used successfully in metastatic cases and neoadjuvant therapy. [ 4 ]
Since cancer is a genetic disease, [ 5 ] two genomic events underlie these mechanisms of acquired drug resistance: Genome alterations (e.g. gene amplification and deletion) and epigenetic modifications .
Chromosomal rearrangement due to genome instability can cause gene amplification and deletion. Gene amplification is the increase in copy number of a region of a chromosome. [ 6 ] which occur frequently in solid tumors, and can contribute to tumor evolution through altered gene expression. [ 6 ]
Hamster cell research in 1993 showed that amplifications in the DHFR gene involved in DNA synthesis began with chromosome break in below the gene, and subsequent cycles of bridge-breakage-fusion formations result in large intrachromosomal repeats. [ 7 ] The over amplification of oncogenes can occur in response to chemotherapy, thought to be the underlying mechanism in several classes of resistance. [ 6 ] For example, DHFR amplification occurs in response to methotrexate , [ 8 ] TYMS (involved in DNA synthesis) amplification occurs in response to 5-fluorouracil , [ 9 ] and BCR-ABL amplification occurs in response to imatinib mesylate . [ 10 ] Determining areas of gene amplification in cells from cancer patients has huge clinical implications. Gene deletion is the opposite of gene amplification, where a region of a chromosome is lost and drug resistance occurs by losing tumor suppressor genes such as TP53 . [ 2 ]
Genomic instability can occur when the replication fork is disturbed or stalled in its migration. This can occur with replication fork barriers, proteins such as PTIP , CHD4 and PARP1 , which are normally cleared by the cell's DNA damage sensors, surveyors, and responders BRCA1 and BRCA2. [ 11 ]
Epigenetic modifications in antineoplastic drug resistance play a major role in cancer development and drug resistance as they contribute to the regulation of gene expression. [ 12 ] Two main types of epigenetic control are DNA methylation and histone methylation/acetylation. DNA methylation is the process of adding methyl groups to DNA, usually in the upstream promoter regions, which stops DNA transcription at the region and effectively silences individual genes. Histone modifications , such as deacetylation , alters chromatin formation and silence large chromosomal regions. In cancer cells, where normal regulation of gene expression breaks down, the oncogenes are activated via hypomethylation and tumor suppressors are silenced via hypermethylation. Similarly, in drug resistance development, it has been suggested that epigenetic modifications can result in the activation and overexpression of pro-drug resistance genes. [ 12 ]
Studies on cancer cell lines have shown that hypomethylation (loss of methylation) of the MDR1 gene promoter caused overexpression and the multidrug resistance. [ 13 ]
In a methotrexate resistant breast cancer cell lines without drug uptake and folate carrier expression, giving DAC , a DNA methylation inhibitor, improved drug uptake and folate carrier expression. [ 14 ]
Acquired resistance to the alkylating drug fotemustine in melanoma cell showed high MGMT activity related to the hypermethylation of the MGMT gene exons. [ 15 ]
In Imatinib resistant cell lines, silencing of the SOCS-3 gene via methylation has been shown to cause STAT3 protein activation, which caused uncontrolled proliferation. [ 16 ]
Cancer cells can become resistant to multiple drugs by altered membrane transport , enhanced DNA repair , apoptotic pathway defects, alteration of target molecules, protein and pathway mechanisms, such as enzymatic deactivation. [ 12 ]
Many classes of antineoplastic drugs act on intracellular components and pathways, like DNA, nuclear components, meaning that they need to enter the cancer cells. The p-glycoprotein (P-gp), or the multiple drug resistance protein, is a phosphorylated and glycosylated membrane transporter that can shuttle drugs out of the cell, thereby decreasing or ablating drug efficacy. This transporter protein is encoded by the MDR1 gene and is also called the ATP-binding cassette (ABC) protein . MDR1 has promiscuous substrate specificity, allowing it to transport many structurally diverse compounds across the cell membrane, mainly hydrophobic compounds. Studies have found that the MDR1 gene can be activated and overexpressed in response to pharmaceutical drugs, thus forming the basis for resistance to many drugs. [ 2 ]
For example, the antibiotic rifampicin has been found to induce MDR1 expression. Experiments in different drug resistant cell lines and patient DNA revealed gene rearrangements which had initiated the activation or overexpression of MDR1. [ 17 ] A C3435T polymorphism in exon 226 of MDR1 has also been strongly correlated with p-glycoprotein activities. [ 18 ]
MDR1 is activated through NF-κB , a protein complex which acts as a transcription factor. [ 19 ] [ 20 ] [ 21 ] [ 22 ] In the rat, an NF-κB binding site is adjacent to the mdr1b gene, [ 23 ] NF-κB can be active in tumour cells because its mutated NF-κB gene or its inhibitory IκB gene mutated under chemotherapy. In colorectal cancer cells, inhibition of NF-κB or MDR1 caused increased apoptosis in response to a chemotherapeutic agent. [ 19 ]
Enhanced DNA repair plays an important role in the ability for cancer cells to overcome drug-induced DNA damages.
Platinum-based chemotherapies, such as cisplatin , target tumour cells by cross-linking their DNA strands, causing mutation and damage. [ 2 ] Such damage will trigger programmed cell death (e.g. apoptosis ) in cancer cells. Cisplatin resistance occurs when cancer cells develop an enhanced ability to reverse such damage by removing the cisplatin from DNA and repairing any damage done. [ 2 ] [ 12 ] The cisplatin-resistant cells upregulate expression of the excision repair cross-complementing (ERCC1) gene and protein. [ 2 ]
Some chemotherapies are alkylating agents meaning they attach an alkyl group to DNA to stop it from being read. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme which removes alkyl groups from DNA. MGMT expression is upregulated in many cancer cells, which protects them from alkylating agents. [ 12 ] Increased MGMT expression has been found in colon cancer, lung cancer, non-Hodgkin's lymphoma, breast cancer, gliomas, myeloma and pancreatic cancer. [ 24 ]
TP53 is a tumor suppressor gene encoding the p53 protein, which responds to DNA damage either by DNA repair , cell cycle arrest, or apoptosis . Losing TP53 via gene deletion can allow cells to continuously replicate despite DNA damage. The tolerance of DNA damage can grant cancer cells a method of resistance to those drugs which normally induce apoptosis through DNA damage. [ 2 ] [ 12 ]
Other genes involved in the apoptotic pathway related drug resistance include h-ras and bcl-2 /bax. [ 25 ] Oncogenic h-ras has been found to increase expression of ERCC1, resulting in enhanced DNA repair (see above). [ 26 ] Inhibition of h-ras was found to increase cisplatin sensitivity in glioblastoma cells. [ 27 ] Upregulated expression of Bcl-2 in leukemic cells ( non-Hodgkin's lymphoma ) resulted in decreased levels of apoptosis in response to chemotherapeutic agents, as Bcl-2 is a pro-survival oncogene . [ 28 ]
During targeted therapy , oftentimes the target has modified itself and decreased its expression to the point that therapy is no longer effective. One example of this is the loss of estrogen receptor (ER) and progesterone receptor (PR) upon anti-estrogen treatment of breast cancer. [ 29 ] Tumors with loss of ER and PR no longer respond to tamoxifen or other anti-estrogen treatments, and while cancer cells remain somewhat responsive to estrogen synthesis inhibitors, they eventually become unresponsive to endocrine manipulation and no longer dependent on estrogen for growth. [ 29 ]
Another line of therapeutics used for treating breast cancer is targeting of kinases like human epidermal growth factor receptor 2 (HER2) from the EGFR family . Mutations often occur in the HER2 gene upon treatment with an inhibitor, with about 50% of patients with lung cancer found to have an EGFR-T790M gatekeeper mutation. [ 12 ]
Treatment of chronic myeloid leukemia (CML) involves a tyrosine kinase inhibitor that targets the BCR/ABL fusion gene called imatinib . In some people resistant to Imatinib, the BCR/ABL gene is reactivated or amplified, or a single point mutation has occurred on the gene. These point mutations enhance autophosphorylation of the BCR-ABL protein, resulting in the stabilization of the ATP-binding site into its active form, which cannot be bound by imatinib for proper drug activation. [ 30 ]
Topoisomerase is a lucrative target for cancer therapy due to its critical role as an enzyme in DNA replication , and many topoisomerase inhibitors have been made. [ 31 ] Resistance can occur when topoisomerase levels are decreased, or when different isoforms of topoisomerase are differentially distributed within the cell. Mutant enzymes have also been reported in patient leukemic cells, as well as mutations in other cancers that confer resistance to topoisomerase inhibitors. [ 31 ]
One of the mechanisms of antineoplastic resistance is over-expression of drug-metabolizing enzymes or carrier molecules. [ 2 ] By increasing expression of metabolic enzymes, drugs are more rapidly converted to drug conjugates or inactive forms that can then be excreted. For example, increased expression of glutathione promotes drug resistance, as the electrophilic properties of glutathione allow it to react with cytotoxic agents, inactivating them. [ 32 ] In some cases, decreased expression or loss of expression of drug-metabolising enzymes confers resistance, as the enzymes are needed to process a drug from an inactive form to an active form. Arabinoside , a commonly used chemotherapy for leukemia and lymphomas, is converted into cytosine arabinoside triphosphate by deoxycytidine kinase. Mutation of deoxycytidine kinase or loss of expression results in resistance to arabinoside. [ 2 ]
Growth factor expression levels can also promote resistance to antineoplastic therapies. [ 2 ] In breast cancer, drug resistant cells were found to express high levels of IL-6, while sensitive cells did not express significant levels of the growth factor. IL-6 activates the CCAAT enhancer-binding protein transcription factors which activate MDR1 gene expression (see Alteration of Membrane Transport). [ 33 ]
Pharmacogenetics play an increasingly important role in antineoplastic treatment. [ 34 ] Rapid sequencing technologies can identify genetic markers for treatment sensitivity and potential resistance. Certain markers are more representative and more likely to be used clinically. [ 34 ]
When BRCA1 and BRCA2 are missing, as in 5 percent to 10 percent of all breast cancers, a stalled fork remains destabilized and its newly synthesized DNA is degraded. This genomic instability means the cancer cell is actually more sensitive to DNA-damaging chemotherapy drugs. [ 35 ]
MDR proteins are known to be drug-resistance genes, and are highly expressed in various cancers. Inhibition of the MDR genes could result in sensitization of cells to therapeutics and a decrease in antineoplastic resistance. Reversin 121 (R121) is a high-affinity peptide for MDR, and use of R121 as a treatment for pancreatic cancer cells results in increased chemosensitivity and decreased proliferation. [ 36 ]
Aberrant NF-κB expression is found in many cancers, and NF-κB has been found to be involved in resistance to platinum-based chemotherapies, such as cisplatin. NF-κB inhibition by genistein in various cancer cell lines (prostate, breast, lung and pancreas) showed increased growth inhibition and an increase in chemosensitivity, seen as an increase in apoptosis induced by therapeutic agents. [ 37 ] However, targeting the NF-κB pathway can be difficult, as there can be many off-target and non-specific effects.
Expression of mutated TP53 causes defects in the apoptotic pathway, allowing cancerous cells to avoid death. Re-expression of the wild-type gene in cancer cells in vitro has been shown to inhibit cell proliferation, induce cell cycle arrest and apoptosis. [ 38 ]
In ovarian cancer , the ATP7B gene encodes for a copper efflux transporter, found to be upregulated in cisplatin-resistant cell lines and tumors. Development of antisense deoxynucleotides against ATP7B mRNA and treatment of an ovarian cancer cell line shows that inhibition of ATP7B increases sensitivity of the cells to cisplatin. [ 39 ]
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Antiphospholipid syndrome , or antiphospholipid antibody syndrome ( APS or APLS ), is an autoimmune , hypercoagulable state caused by antiphospholipid antibodies . APS can lead to blood clots ( thrombosis ) in both arteries and veins , pregnancy-related complications , and other symptoms like low platelets, kidney disease , heart disease , and rash . Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. [ 3 ]
Diagnosis is made based on symptoms and testing, but sometimes research criteria are used to aid in diagnosis. The research criteria for definite APS requires one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect lupus anticoagulant , anti-apolipoprotein antibodies , and/or anti-cardiolipin antibodies . [ 4 ]
Antiphospholipid syndrome can be primary or secondary.
• Primary antiphospholipid syndrome occurs in the absence of any other related disease.
• Secondary antiphospholipid syndrome occurs with other autoimmune diseases , such as systemic lupus erythematosus .
In rare cases, APS leads to rapid organ failure due to generalized thrombosis; this is termed " catastrophic antiphospholipid syndrome " (CAPS or Asherson syndrome) and is associated with a high risk of death. [ 5 ]
Antiphospholipid syndrome often requires treatment with anticoagulant medication to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. The anticoagulant medication used for treatment may differ depending on the circumstance, such as pregnancy.
Antiphospholipid syndrome is known for causing arterial or venous blood clots , in any organ system, and pregnancy -related complications. While blood clots and pregnancy complications are the most common and diagnostic symptoms associated with APS, other organs and body parts may be affected like platelet levels, heart, kidneys, brain, and skin. [ 4 ] [ 6 ] Also, people with APS may have symptoms associated with other autoimmune diseases like lupus erythematosus that are not caused by APS because APS can occur at the same time as other autoimmune diseases.
In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke . [ 7 ] People with a blood clot in their extremities may experience swelling, pain, or redness in the affected area. [ 8 ] People experiencing a stroke can experience a variety of symptoms depending on what blood vessel in the brain is affected. Symptoms include but are not limited to trouble speaking, loss of sensation, or weakness in one side of the face or body. [ 9 ] Blood clots can also occur in the lungs , which may cause trouble breathing or chest pain, and they can occur in the heart, which could lead to a heart attack. [ 6 ]
Blood clots in patients with APS are often considered unprovoked, which means they occur in the absence of conditions that typically cause blood clots (i.e. prolonged sedentary behavior, immoblization, infection, cancer). However, a person can develop a provoked blood clot while having APS due to APS causing an increased risk of blood clot development. [ 6 ] Exogenous estrogen therapies, such as estrogen-based contraceptives, significantly increase the risk of developing blood clots for patients with APS. [ 10 ]
In pregnant people affected by APS, there is an increased risk of recurrent miscarriage , preterm birth , intrauterine growth restriction , pre-eclampsia , eclampsia . [ 11 ] [ 12 ] Recurrent miscarriages associated with APS typically occur prior to 10th week of gestation, but miscarriage associated with APS can also occur after the 10th week of gestation. [ 12 ] Certain causes must be excluded prior to attributing these complications to APS. Also, in pregnant individuals with lupus and antiphospholipid syndrome, antiphospholipid syndrome is responsible for most of the miscarriages in later trimesters. [ 13 ]
Other common findings that suggest APS are low platelet count , heart valve disease , high blood pressure in the lungs, kidney disease, and a rash called livedo reticularis . [ 6 ] There are also associations between antiphospholipid antibodies and different neurologic manifestations [ 14 ] including headache , [ 15 ] migraine , [ 16 ] epilepsy , [ 17 ] and dementia [ 18 ] although more research is needed to prove that these symptoms are indicative of APS. Cancer is also observed to occur at the same time in some patients with APS. [ 19 ]
Antiphospholipid syndrome is an autoimmune disease , in which "antiphospholipid antibodies" react against proteins that bind to anionic phospholipids on plasma membranes . Anticardiolipin antibodies, β2glycoprotein 1, and lupus anticoagulant are antiphospholipid antibodies that are thought to clinically cause disease. These antibodies lead to blood clots and vascular disease in the presence (secondary APS) or absence (primary APS) of other diseases. [ 20 ] While the exact functions of the antibodies are not known, the activation of the coagulation system is evident.
Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH. ApoH inhibits protein C , a glycoprotein with important regulatory function of coagulation (inactivates Factor Va and Factor VIIIa ). Lupus anticoagulant antibodies bind to prothrombin , thus increasing its cleavage to thrombin , its active form. [ citation needed ]
Other antibodies associated with APS include antibodies against protein S and annexin A5. Protein S is a co-factor of protein C, which is one of the body's own anti-clotting factors. Annexin A5 forms a shield around negatively charged phospholipid molecules, which reduces the membrane's ability to participate in clotting. Thus, antibodies against protein S and anti-annexin A5 decrease protein C efficiency and increase phospholipid-dependent coagulation steps respectively, which leads to increased clotting potential. [ 21 ] [ 22 ]
The lupus anticoagulant antibodies are those that show the closest association with thrombosis; those that target β 2 glycoprotein 1 have a greater association with thrombosis than those that target prothrombin.
Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (over 40 GPLU or MPLU).
Patients with both lupus anticoagulant antibodies and moderate or high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone. [ citation needed ]
The increased risks of recurrent miscarriage , intrauterine growth restriction and preterm birth by antiphospholipid antibodies, as supported by in vitro studies, include decreased trophoblast viability, syncytialization and invasion, deranged production of hormones and signalling molecules by trophoblasts, as well as activation of coagulation and complement pathways . [ 11 ]
Diagnosis of antiphospholipid syndrome is often made through the combination of symptoms and testing. Repeat antibody testing 12 weeks after discovering the presence of antiphospholipid antibodies (aPL) is needed to establish a diagnosis because false positives can occur. [ 4 ] [ 23 ] [ 24 ]
While APS was previously categorized into primary and secondary APS based on the absence or presence of concurrent autoimmune disease respectively, the 16th International Congress on Antiphospholipid Antibodies Task Force categorizes APS into 6 categories: [ 6 ]
In their report, they acknowledge that some individuals may qualify for more than one category based on symptoms. [ 6 ]
Because there are no agreed upon diagnostic criteria for APS, research classification criteria are sometimes used to aid in diagnosis. [ 6 ] The Sapporo APS classification criteria (1998, published in 1999) [ 25 ] were replaced by the Sydney criteria in 2006. [ 12 ] The Sydney criteria requires one clinical (thrombosis or pregnancy related) manifestation and persistent presence of one or more APS antibody. [ 12 ] In the 2023 American College of Rheumatology and European League Against Rheumatism joint criteria they added heart related symptoms and low platelet levels as clinical criteria and changed some thresholds and specifics for antibody testing. [ 4 ] However, all previously proposed research criteria are meant to create a standardized group of individuals with APS in order to increase accuracy in statistical analysis, so the criteria are not be representative of all individuals with APS. [ 4 ] [ 6 ] Thus, people who do not meet all of the criteria could still have APS.
In terms of catastropic APS, the International Consensus Statement is commonly used for diagnosis. Based on this statement, Definite CAPS diagnosis requires: [ 26 ]
Antiphospholipid antibody tests are either liquid-phase coagulation assays to detect lupus anticoagulant or solid phase ELISA (enzyme-linked immunosorbent assay) to detect anti-cardiolipin antibodies and β 2 glycoprotein 1 . [ 24 ] The use of testing for antibodies specific for individual targets of aPL such as phosphatidylserine is currently under debate. [ citation needed ]
This is tested for by using two coagulation tests that are phospholipid-sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. A patient with lupus anticoagulant antibodies on initial screening will typically have been found to have a prolonged partial thromboplastin time (PTT) that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The PTT (plus 80:20 mix), dilute Russell's viper venom time , silica clotting time and prothrombin time (using a lupus-sensitive thromboplastin ) are the principal tests used for the detection of lupus anticoagulant . The Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis no longer recommends the kaolin clotting time , dilute thromboplastin time, and Taipan/Ecarin snake venom based assays due to implementation issues from a variety of factors. [ 23 ]
Distinguishing a lupus anticoagulant antibody from a specific coagulation factor inhibitor (e.g.: factor VIII ) is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors ( factor VIII , factor IX , factor XI and factor XII ). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%). Monitoring IV anticoagulant therapy by the PTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by antithrombin in the presence of heparin . [ citation needed ]
Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test , which screens for the presence of β 2 glycoprotein 1 dependent anticardiolipin antibodies. A low platelet count and positivity for antibodies against phosphatidylserine may also be observed in a positive diagnosis. [ citation needed ]
The presence of antiphospholipid antibodies may not indicate APS, which is why considering the symptoms present and retesting antibody levels is essential. People may be transiently positive, incorrectly positive, or incorrectly negative if they are tested when the following is occurring: [ 23 ]
It is recommended to generally re-test people 12 weeks after the first positive test to confirm that it was correct, except for those who test positive during pregnancy. [ 23 ] For that group, it is recommend to wait 3 months to re-test if possible. Re-testing is more nuanced if the person is taking an anticoagulant, which may require not taking the medication for a certain period of time or specifically timing the test. [ 23 ]
Also, patients who have certain antiphospholipid antibodies may have false positive VDRL test, which aims to detect a syphilis infection. This occurs because the aPL bind to the lipids in the test and make it come out positive. A more specific test for syphilis, FTA-Abs , will not have a false-positive result in the presence of aPL. [ citation needed ]
For people with blood clot related APS, other conditions that can cause blood clots should be considered including but not limited to acquired blood clots , genetic thrombophilia , and paroxysmal nocturnal hemoglobinuria . Genetic thrombophilia can coexist in some patients with APS. [ citation needed] For people with pregnancy related APS, other causes of recurrent miscarriage should be considered before the diagnosis of APS, such as genetic, structural, or immune abnormalities.
Treatment depends on a person's APS symptoms. [ 27 ] Typically a medication that decreases the body's ability to form blood clots is given to prevent future clots. Low dose aspirin can be given to people who have APS antibodies but no symptoms, high risk individuals with lupus erythematosus and APS antibodies but no symptoms of APS, and non-pregnant people who had APS during pregnancy. [ 27 ] [ 28 ] For those people with APS who have had a blood clot (venous or arterial), anticoagulants such as warfarin are used to prevent future clots. [ 27 ] [ 28 ] If warfarin is used, the INR is kept between 2.0 and 3.0. [ 28 ] Direct-acting oral anticoagulants may be used as an alternative to warfarin, but not in people with APS who had a previous arterial blood clot [ 29 ] [ 30 ] or are "triple positive" with all types of antiphospholipid antibody (lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein I antibody). [ 27 ] [ 28 ] [ 31 ] [ 32 ] In people with arterial blood clot related APS, using direct-acting oral anticoagulants has shown to increase the risk of future arterial blood clots and should not be used. [ 29 ] [ 30 ]
In pregnant women with only pregnancy related APS or only past blood clot related APS, low molecular weight heparin and low-dose aspirin are used instead of warfarin because of warfarin's ability to cause birth defects . [ 27 ] [ 28 ] Heparin and aspirin together appears to make miscarriage less likely in pregnant women with APS. [ 28 ] Women with recurrent miscarriages are often advised to take aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle . [ citation needed ] In refractory cases plasmapheresis may be used. [ citation needed ]
Factors that increase likelihood of developing APS related future blood clots and pregnancy complications include:
Also, a history of previous blood clots in someone with APS increases the risk for certain pregnancy complications, such as death of the child, smaller sized baby, and blood clots during and after pregnancy. [ 33 ] Outside of people with APS having an increased risk of blood clots and pregnancy complications, people with APS generally have increased risk of atherosclerotic disease. [ 7 ] [ 34 ]
Other risk stratification criteria for predicting blood clots and pregnancy complications have been proposed, such as the aPL Score and the Global APS score, but further data is needed to validate these tools. [ 6 ]
Factors associated with developing antiphospholipid syndrome include:
In a study of 1000 patients, only 12.7% were diagnosed after the age of 50. [ 37 ]
Antiphospholipid syndrome was described in full in the 1980s, by E. Nigel Harris and Aziz Gharavi. They published the first papers in 1983. [ 38 ] [ 39 ] The syndrome was referred to as "Hughes syndrome" among colleagues after the rheumatologist Graham R.V. Hughes ( St. Thomas' Hospital , London , UK ), who brought together the team. [ citation needed ]
According to a 2006 Sydney consensus statement, [ 12 ] it is advisable to classify APS into one of the following categories for research purposes:
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" Antiseptic Principle of the Practice of Surgery " is a paper regarding antiseptics written by Joseph Lister in 1867.
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Antivirulence is the concept of blocking virulence factors . [ 1 ] In regards to bacteria , the idea is to design agents that block virulence rather than kill bacteria en masse, as the current regime results in much more selective pressure (on antibiotic resistance ).
From the early 1950s onwards, a large number of antibiotics , due to the emergence of multidrug-resistant common pathogen strains (both gram-negative and gram-positive ), became scarcely effective and not-useful. This scenario has stimulated the research for an alternative strategy focused on agents ( antivirulence or antipathogenic agents ) aimed to disarm microorganisms cause of infectious disease , without killing or inhibiting the growth of microorganisms themselves and therefore with limited selective pressure to promote the antibiotic resistance phenomenon.
The antivirulence strategy needs the knowledge of the pathogenic mechanisms and of the virulence factors that underlie them. Virulence factors are the weapons possessed by pathogens to cause damage to the host, hence they are molecules or bacterial cell structures involved in the various stages of pathogenesis such as adhesion , invasion and colonization and also in the ability to escape host defenses and to injury the host tissues by producing toxic molecules (bacterial endotoxins and exotoxins ).
The bacterial adhesion to the host tissues, involving a direct and a specific interaction between bacterial surface molecules and host ligands, is a fundamental step for microbial colonization and infection of both Gram-positive and Gram-negative pathogens. Interfere with adhesion, the first step of pathogenesis, could be an efficient way to prevent or treat infections. [ 2 ] Gram-positive and Gram-negative pathogens adhere to the host tissues through filamentous organelles known as pili. [ 3 ] The pili function on initial bacterial adhesion, invasion and biofilm formation, has been mainly studied for Gram-negative bacteria. There are some works on the synthesis of pilicides, chemical agents synthesized to target the chaperone–subunit interaction and the chaperone interaction with a protein involved in the biogenesis of the pili in Gram-negative known as fimbrial usher protein. [ 4 ] Uropathogenic Escherichia coli (UPEC) is the major aetiological agent of Urinary Tract Infections (UTIs) and is often studied as a model of Gram-negative pathogen for the development of pilicides compounds.
Similar structural motifs of pilin components has been found in an important family of Gram-positive surface proteins linked to peptidoglycan , the Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs), able to recognize extracellular matrix proteins of host, such as fibrinogen, fibronectin, and collagen. If we consider the important part played by MSCRAMMs in the first step of Gram-positive pathogenesis and of biofilm formation, new antivirulence agents could be developed by using as a target the enzyme responsible of linking such proteins to cell wall, that is the Sortase A (SrtA), rather than any single surface protein involved in the mechanism of virulence. [ 5 ] The SrtA is a membrane-bound cysteine transpeptidase that is responsible, in Gram-positive bacteria, for the covalent anchoring of surface proteins to bacterial cell wall. 3,6-Disubstituted triazolo-thiadiazole compounds are under preclinical evaluation (including animal models) as antivirulence drugs against Staphylococcus aureus . [ 6 ] Other cell surface molecules in Gram-positive bacteria, involved in the adhesion process, without cell wall anchorage, are non proteinaceous adhesins like Wall Teichoic acids (WTAs) and lipoteichoic acids. Since WTAs are required for host infection and play important role in biofilm formation, it has been suggested that they are important virulence factors required for the establishment and spread of infection in a host. Therefore, the enzymes involved in WTAs biosynthesis can be considered as good targets for novel antivirulence agents that interfere with Gram-positive pathogenic process. One possible target is the WTA biosynthetic pathway because strains of S.aureus and Bacillus subtilis mutants in WTAs are not able to colonize the host tissue and show a greatly diminished ability to establish infection in animal models. [ 7 ]
Early examples of the antivirulence approach include mainly the inactivation of bacterial toxins with anti-toxin antibodies administered to post-exposure patients (serological therapy that induces artificially acquired passive immunization). Since inactivation of toxin during infection has proven to be an effective way to prevent or alleviate the symptoms of acute disease, significant progress has been made in the development of novel anti-toxic monoclonal antibodies. Therefore, in October 2016 the US Food and Drug Administration (FDA) and in July 2018 the Italian Drug Agency (AIFA) approved the therapeutic use of a monoclonal antibody called bezlotoxumab (Zinplava) as a treatment aimed at reducing the recurrence of Clostridioides difficile infection in patients at high risk of recurrence. [ 8 ]
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Antonio Mano Azul is a Portuguese physician specialising in stomatology . [ 1 ] He was president of the European Association of Oral Medicine in 2000–02. [ 2 ] He was professor of microbiology and oral surgery at the Faculty of Medicine of Lisbon. [ 3 ]
He was the director of the Revista Portuguesa de Estomatologia e Cirurgia Maxilo-facial ( Portuguese Journal of Stomatology and Maxillofacial Surgery ).
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Aortic valve replacement is a cardiac surgery procedure whereby a failing aortic valve is replaced with an artificial heart valve . The aortic valve may need to be replaced because of aortic regurgitation (back flow), or if the valve is narrowed by stenosis .
Current methods for aortic valve replacement include open-heart surgery , minimally invasive cardiac surgery (MICS) , surgical aortic valve replacement (SAVR), percutaneous or transcatheter aortic valve replacement (TAVR; also PAVR, PAVI, TAVI), [ citation needed ] and robotic aortic valve replacement (RAVR). [ 1 ]
A cardiologist can evaluate whether a heart valve repair or valve replacement would be of benefit. [ 2 ]
During the late 1940s and early 1950s, the first surgical approaches towards treating aortic valve stenosis had limited success. The first attempts were valvotomies, (i.e. cutting the valve while the heart is pumping). A ball valve prosthesis placed on the descending thoracic aorta (heterotopically) was developed by Hufnagel, Harvey and others to address aortic stenosis, but had disastrous complications. Later, with the innovation of cardiopulmonary bypass, the ball valve prosthesis was placed orthotopically (i.e. in same place as the original aortic valve). This first generation of prosthetic valves was durable, but needed intense anti-coagulation, and cardiac hemodynamics were compromised. During the mid-1950s, a single-leaflet prosthesis was developed by Bahnson, et al . In early 1960, Ross and Barratt-Boyes used allografts. Tissue prosthetic valves were introduced in 1965 by Binet in Paris, but they degenerated quickly because the tissue was insufficiently preserved. Carpentier solved this problem by introducing glutaraldehyde-preserved stent-mounted porcine valves. [ 3 ] [ 4 ] The first combined robotic aortic valve replacement (RAVR) and coronary artery bypass grafting (CABG) was performed on October 31, 2024. Cardiothoracic surgeon Vinay Badhwar of West Virginia University Heart and Vascular Institute succeeded through a single small incision, using a da Vinci Xi robot . [ 5 ] [ 6 ]
The aortic valve is one of the two semilunar valves of the heart with three cusps, or leaflets. It separates the heart from the aorta . Each cusp is attached to the aortic wall creating a sinus called an aortic sinus . The origins of the two coronary arteries are sited in two aortic sinuses. Cusps also known as leaflets are separated by commissures . The posterior leaflet is in continuation with the anterior leaflet of the mitral valve (the tissue is called the aorto-mitral curtain). [ 7 ] The aortic valve is opened during systole, the driving force for it to open is the difference in pressure between the contracting left ventricle of the heart and the aorta. During cardiac diastole (when the heart chamber gets bigger) the aortic valve closes. [ 8 ]
Aortic stenosis most commonly is the result of calcification of the cusps. Other reasons for stenosis are the bicuspid valve (some patients have only two cusps at the aortic valve instead of the usual three) and rheumatic aortic stenosis (now rare in the West). Obstruction at the level of the aortic valve causes increased pressure within the heart's left ventricle. This can lead to hypertrophy and ultimately dysfunction of the heart. While x-ray and ECG might indicate aortic stenosis, echocardiography is the diagnostic procedure of choice. US findings also help in grading the severity of the disease. In cases of symptomatic severe aortic stenosis, AVR is warranted. In cases of asymptomatic but severe aortic stenosis, more factors should be taken into consideration. [ 9 ]
Aortic regurgitation, on the other hand, has many causes: degeneration of the cusps, endocarditis, bicuspid aortic valve, aortic root dilatation, trauma, connective tissue disorders such as Marfan syndrome or Ehlers-Danlos lead to imperfect closure of the valve during diastole, hence the blood is returning from the aorta towards the left ventricle of the heart. Acute aortic regurgitation (caused by endocarditis, aortic dissection or trauma) ends up in pulmonary edema, because of the acute increase in left ventricle (LVEDP) that does not have time to adjust to the regurgitation. Chronic regurgitation, by contrast, gives the heart time to change shape, resulting in eccentric hypertrophy , which has disastrous effects on the myocardium. Ultrasound is here also the best diagnostic mobility, either it is transthoracic or transesophageal. [ 10 ]
As long-term data on the survival and quality of life of people following valve replacement have become available, evidence-based guidelines for aortic valve replacement have been developed. These help healthcare professionals decide when aortic valve replacement is the best option for a patient. Two widely accepted sets of guidelines used by surgeons and cardiologists are the American Heart Association and American College of Cardiology Guidelines for the Management of Patients with Valvular Heart Disease, [ 11 ] and the European Society of Cardiology and the European Association for Cardio‑Thoracic Surgery Guidelines for the management of valvular heart disease. [ 12 ]
Aortic stenosis is treated with aortic valve replacement in order to avoid angina , syncope , or congestive heart failure . Individuals with severe aortic stenosis are candidates for aortic valve replacement once they develop symptoms or when their heart function is impacted. Some people with asymptomatic aortic stenosis may also be candidates for aortic valve replacement, especially if symptoms appear during exercise testing . [ 12 ] Patients with moderate aortic valve stenosis who need another type of cardiac surgery (i.e. coronary artery bypass surgery ) should also have their valve addressed by the surgical team if echocardiography unveils significant heart problems. [ 13 ]
Low gradient aortic stenosis with concomitant left ventricular dysfunction poses a significant question to the anesthesiologist and the patient. Stress echocardiography (i.e. with dobutamine infusion) can help determine if the ventricle is dysfunctional because of aortic stenosis, or because the myocardium lost its ability to contract. [ 14 ]
Many people with aortic insufficiency often do not develop symptoms until they have had the condition for many years. [ 15 ] Aortic valve replacement is indicated for symptoms such as shortness of breath , and in cases where the heart has begun to enlarge (dilate) from pumping the increased volume of blood that leaks back through the valve. [ 12 ]
There are two basic types of replacement heart valve: tissue (bioprosthetic) valves and mechanical valves. [ 16 ]
Tissue heart valves are usually made from animal tissue (heterografts) mounted on a metal or polymer support. [ 17 ] Bovine (cow) tissue is most commonly used, but some are made from porcine (pig) tissue. [ 18 ] The tissue is treated to prevent rejection and calcification (where calcium builds up on the replacement valve and stops it working properly). [ 19 ]
Occasionally, alternatives to animal tissue valves are used: aortic homografts and pulmonary autografts . An aortic homograft is an aortic valve from a human donor, retrieved either after their death or from their heart if they are undergoing a heart transplant. [ 20 ] A pulmonary autograft, also known as the Ross procedure is where the aortic valve is removed and replaced with the patient's own pulmonary valve (the valve between the right ventricle and the pulmonary artery). A pulmonary homograft (a pulmonary valve taken from a cadaver) is then used to replace the patient's own pulmonary valve. This procedure was first performed in 1967 and is used primarily in children, as it allows the patient's own pulmonary valve (now in the aortic position) to grow with the child. [ 20 ]
Tissue valves can last 10–20 years. [ 21 ] However, they tend to deteriorate more quickly in younger patients. [ 22 ] New ways of preserving the tissue for longer are being investigated. One such preservation treatment is now being used in a commercially available tissue heart valve. In sheep and rabbit studies, the tissue (called RESILIA tissue) had less calcification than control tissue. Mid-term data on the safety and haemodynamic performance of the Inspiris RESILIA aortic bioprosthesis are encouraging. [ 23 ] [ 24 ]
Stented and stentless tissue valves are available. Stented valves come in sizes from 19 mm to 29 mm. [ 25 ] Stentless valves are directly sutured at the aortic root. The major advantage of stentless valves is that they limit patient–prosthesis mismatch (when the area of the prosthetic valve is too small in relation to the size of the patient, increasing the pressure inside the valve [ 26 ] ) and can be helpful when dealing with small aortic root. However, stentless valves take more time than stented valves to implant. [ 27 ]
Mechanical valves are made from synthetic materials, such as titanium or pyrolytic carbon . [ 28 ] Their durability is long life, while tissue valves can last for up to 15–20 years. [ 29 ] [ 30 ] [ 16 ] Since the risk of blood clots forming is higher with mechanical valves than with tissue valves, patients with mechanical heart valves are required to take anticoagulant (blood-thinning) drugs, such as warfarin , long-life, making them more prone to bleeding (1% per year). [ 16 ] The sound of the valve can be heard very rarely, often as clicks, and might be disturbing. [ 31 ] The choice of prosthetic valve should be individualized, carefully considering each patient's unique circumstances. In that context, the new generation aortic mechanical valve (On-X) offers a potential lifetime solution without need for a repeat operation, while minimizing the risks of long-term anticoagulation due to reduced anticoagulation target INR of 1.5 to 2.0. [ 32 ]
Valve choice is a balance between the lower durability of tissue valves and the increased risk of blood clots and bleeding with mechanical valves. Guidelines suggest that patient age, lifestyle and medical history should all be considered when choosing a valve. Tissue valves deteriorate more rapidly in young patients and during pregnancy, but they are preferable for women who wish to have children because pregnancy increases the risk of blood clots. Typically, a mechanical valve is considered for patients under 60 years old, while a tissue valve is considered for patients over the age of 65 years. [ 16 ]
Surgical aortic valve replacement is conventionally done through a median sternotomy , meaning the incision is made by cutting through the breastbone ( sternum ). Once the protective membrane around the heart ( pericardium ) has been opened, the patient is cannulated (aortic cannulation by a cannula placed on the aorta and a venous canulation by a single atrial venous cannula inserted through the right atrium). The patient is put on a cardiopulmonary bypass machine, also known as the heart–lung machine. This machine breathes for the patient and pumps their blood around their body while the surgeon replaces the heart valve. [ citation needed ]
Once on cardiopulmonary bypass, the patient's heart is stopped ( cardioplegia ). This can be done with a Y-type cardioplegic infusion catheter placed on the aorta, de-aired and connected to the cardiopulmonary bypass machine. Alternatively, a retrograde cardioplegic cannula can be inserted at the coronary sinus. Some surgeons also opt to place a vent in the left ventricle through the right superior pulmonary vein, because this helps to prevent left ventricular distention before and after cardiac arrest. When the set-up is ready, the aorta is clamped shut with a cross-clamp to stop blood pumping through the heart and cardioplegia is infused. The surgeon incises the aorta a few milometers above the sinotubular junction (just above the coronary ostia, where the coronary arteries join the aorta) – a process known as aortotomy. After this, cardioplegia is delivered directly through the ostia. [ 33 ] [ 34 ]
The heart is now still and the surgeon removes the patient's diseased aortic valve. The cusps of the aortic valve are excised, and calcium is removed (debrided) from the aortic annulus. The surgeon measures the size of the aortic annulus and fits a mechanical or tissue valve of the appropriate size. Usually the valve is fixed in place with sutures, although some sutureless valves are available. If the patient's aortic root is very small, the sutures are placed outside of the aortic root instead of at the annulus, to gain some extra space. [ citation needed ]
Once the valve is in place and the aorta has been closed, patient is placed in a Trendelenburg position and the heart is de-aired and restarted. The patient is taken off the cardiopulmonary bypass machine. Transesophageal echocardiogram (an ultrasound of the heart done through the esophagus) can be used to verify that the new valve is functioning properly. Pacing wires are usually put in place, so that the heart can be manually controlled should any complications arise after surgery. Drainage tubes are also inserted, to drain fluids from the chest. These are usually removed within 36 hours, while the pacing wires are generally left in place until right before the patient is discharged from the hospital. [ 33 ] [ 34 ]
After surgical aortic valve replacement, the patient will usually stay in an intensive care unit for 12–36 hours. Unless complications arise, the patient is then able to go home after approximately four to seven days. [ 35 ] Common complications include disturbances to the heart's rhythm ( heart block ), which typically require the permanent insertion of a cardiac pacemaker . [ 36 ]
Recovery from aortic valve replacement takes about three months if the patient is in good health. Patients are advised not to lift anything heavier than 10 lbs for several weeks, and not to do any heavy lifting for 4–6 months after surgery to avoid damaging their breastbone. Often patients will be referred to participate in cardiopulmonary rehabilitation , which optimizes recovery and physical function in patients with recent cardiac surgeries. This can be done in an outpatient setting. [ 37 ]
Surgery usually relieves the aortic disease symptoms that led the patient to the operating room. The survival curve of patients who undergo aortic valve replacements is slightly inferior to the curve of their corresponding healthy same-aged same sex population. [ 38 ] Pre-operative severe left ventricular hypertrophy is a contributing factor to morbidity. [ 38 ]
The risk of dying as a result of aortic valve replacement is estimated at 1–3%. [ 39 ] [ 40 ] [ 41 ] Combining aortic valve replacement with coronary artery bypass grafting increases the risk of mortality. [ 39 ] Older patients, as well as those who are frail and/or have other health problems ( comorbidities ), have a higher risk of experiencing complications. [ 40 ] Possible problems include cardiac infarction or failure, arrhythmia or heart block typically requiring the permanent insertion of a cardiac pacemaker , mediastinal bleeding, stroke and infection. Late complications include endocarditis , thromboembolic events ( blood clots ), prosthetic valve dysfunction and paravalvular leak (blood flowing between the edge of the prosthetic valve and the cardiac tissue). [ 38 ]
When dealing with a small aortic annulus, the surgeon might have to insert a prosthetic aortic valve of small size, with an orifice too small in relation to the size of the patient (patient–prosthesis mismatch). This increases the pressure of the blood flowing through the valve, and can lead to worse outcomes. [ 26 ] Various techniques, including stentless valves, have been utilized to avoid this problem. [ 42 ]
Since the late 1990s, some cardiac surgeons have been performing aortic valve replacement using an approach referred to as minimally invasive cardiac surgery (MICS). [ 43 ] Using this approach, the surgeon replaces the valve through a smaller chest incision (6–10 cm) than that for a median sternotomy. MICS typically requires shorter recovery times, and produces less visible scarring. [ 44 ] Alternatively, aortic valve replacement can be performed with right minithoracotomy approach via the 2nd or 3rd intercostal space. There is growing evidence that this approach can reduce postoperative morbidity allowing less blood loss, less pain,
faster recovery, and a shorter hospital stay with no difference in mortality. [ 45 ] This approach can be particularly valuable in higher risk and elderly patients. [ 46 ]
Another alternative for many high-risk or elderly patients is transcatheter aortic valve replacement (TAVR, also known as TAVI, transcatheter aortic valve implantation). Rather than removing the existing valve, the new valve is pushed through it in a collapsed state. It is delivered to the site of the existing valve through a tube called a catheter, which may be inserted through the femoral artery in the thigh (transfemoral approach), or using a small incision in the chest and then through a large artery or the tip of the left ventricle (transapical approach). [ 47 ] Fluoroscopy and transthoracic echocardiogram (TTE) are visual aids used to guide the process. [ 47 ] Once the collapsed replacement valve is in place it is expanded, pushing the old valve's leaflets out of the way. [ 48 ]
Guidelines suggest TAVR for most patients aged 75 years and older, and surgical aortic valve replacement for most younger patients. [ 49 ] Ultimately, the choice of treatment is based on many factors. [ 50 ] [ 49 ]
Systematic reviews have addressed this comparison: [ 51 ] [ 52 ]
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Aortocaval compression syndrome , also known as supine hypotensive syndrome , is compression of the abdominal aorta and inferior vena cava by the gravid uterus when a pregnant woman lies on her back, i.e. in the supine position . It is a frequent cause of low maternal blood pressure ( hypotension ), which can result in loss of consciousness [ 1 ] and in extreme circumstances fetal demise. [ 2 ] [ 3 ]
Aortocaval compression syndrome may cause syncope, restlessness, dizziness, headache, tinnitus, visual disturbances, numbness or paresthesia of the limbs, abdominal/chest discomfort or pain, nausea, and vomiting. [ 4 ] Some patients may be asymptomatic. [ 5 ]
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Aortopexy is a surgical procedure in which the aortic arch is fixated to the sternum . It results in the tracheal lumen being pulled open. It is used to treat severe tracheomalacia or tracheal compression.
The procedure was originally proposed as a treatment for tracheomalacia Filler et al. [ 1 ] in 1976.
This surgery article is a stub . You can help Wikipedia by expanding it .
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The apex beat (lat. ictus cordis ), also called the apical impulse , [ 1 ] is the pulse felt at the point of maximum impulse ( PMI ), which is the point on the precordium farthest outwards (laterally) and downwards (inferiorly) from the sternum at which the cardiac impulse can be felt. The cardiac impulse is the vibration resulting from the heart rotating, moving forward, and striking against the chest wall during systole . The PMI is not the apex of the heart but is on the precordium not far from it. Another theory for the occurrence of the PMI is the early systolic contraction of the longitudinal fibers of the left ventricle located on the endocardial surface of this chamber. This period of the cardiac cycle is called isovolumic contraction. Because the contraction starts near the base of the left ventricle and spreads toward the apex most of the longitudinal fibers of the left ventricle have shortened before the apex. The rapidly increasing pressure developed by the shortening of these fibers causes the aortic valve to open and the apex to move outward causing the PMI. Anatomical dissection of the musculature of the apex reveals that muscle fibers are no longer longitudinal oriented but form a spiral mass of muscular tissues which may also have an effect on the ability of the apex to contract longitudinally. After the longitudinal fibers contract, the ejection of blood out of the left ventricle is accomplished by the torsional (as one would wring out a face cloth) action of the circumferential muscle fibers of the left ventricle that are in the mid-portion of the ventricle and contract after the longitudinal fibers. During the longitudinal fiber contraction, the volume of the left ventricle has not changed keeping the apex in intimate contact with the chest wall allowing the ability to feel the apex move outward before the heart empties greater than 55% of its volume and the apex falling away from the chest wall. [ 2 ]
The normal apex beat can be palpated in the precordium left 5th intercostal space, half-inch medial to the left midclavicular line and 3–4 inches left of left border of sternum.
In children the apex beat occurs in the fourth rib interspace medial to the nipple. The apex beat may also be found at abnormal locations; in many cases of dextrocardia , the apex beat may be felt on the right side.
Lateral and/or inferior displacement of the apex beat usually indicates enlargement of the heart, called cardiomegaly . The apex beat may also be displaced by other conditions:
Sometimes, the apex beat may not be palpable, either due to a thick chest wall, or conditions where the stroke volume is reduced; such as during ventricular tachycardia or shock .
The character of the apex beat may provide vital diagnostic clues:
Sustained apex beat, namely prolonged upward cardiac force during systole in a physical exam , can be seen in some chronic conditions such as hypertension and aortic stenosis , especially in elderly and females. [ 3 ]
An algorithm for the classification of some common apex beat characteristics is shown in the image
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Apex location is a method of determining the length of the root canal of a tooth - manually or with a mechanical canal instrument that passes a low intensity electric current through the tooth. [ citation needed ]
The electrical characteristics of the tooth structure are measured and the exact position of the instrument in the tooth is determined. When the tool tip touches the top of the tooth, the instrument signals that the apical foramen is reached. [ citation needed ] Whenever the channel instrument is pulled out its length can be measured to determine the depth of the root canal and all other dental tools can be adjusted to this length. [ citation needed ]
The apex is the tip of the tooth’s root. On the apex, there is an opening called Apical foramen . That is the place where all the blood vessels and nerves come inside the tooth. The apex is located on the tip of the root, or on the pointed end of it. Different teeth have a different number of roots. For example, the incisors have only one root and one apex. Teeth that have two roots have two apexes and so on. [ citation needed ]
The method of Sonada measures the canal's impedance using one or more electric frequencies. The method tracks the penetration of the instrument in the canal. [ citation needed ] It is unreliable though in the presence of fluid in the canal which requires additional drying. [ citation needed ]
The method of Kobayashi performs a calculation of the ratio of the measured impedance of two or more electric frequencies. The method is highly accurate in the presence of fluid in the root canal. The method does not provide good monitoring of the penetration before reaching the apex. This method faces difficulties when working in a dry canal. Therefore the canal should be moistened. After measurement the canal should be dried. [ citation needed ]
The Adaptive method of measurement is implemented by the so-called electronic apex locator . [ citation needed ] In the process of penetrating the instrument makes continuous measurements and selects a suitable method of measurement. In case of dry canal the device uses the method of Sonada. In case of wet canal the device automatically adjusts the measurement method of Kobayashi. The adaptive method is highly accurate and does not require moistening or drying the canal. [ citation needed ]
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Apexification is a method of dental treatment to induce a calcific barrier in a root with incomplete formation or open apex of a tooth with necrotic pulp . [ 1 ] Pulpal involvement usually occurs as a consequence of trauma or caries involvement of young or immature permanent teeth. As a sequelae of untreated pulp involvement, loss of pulp vitality or necrotic pulp took place for the involved teeth.
The main purpose of apexification includes restoring the original physiologic structures and functions of the pulp- dentin complex of the teeth. [ 1 ] In addition to that, the elimination of the pulp tissue within a tooth, the disinfection of root canal system by using irrigants such as sodium hypochlorite and ethylenediaminetetraacetic acid are the necessary steps to ensure that the purpose of apexification is being met. [ 2 ]
The apexification procedure will normally requires several monthly appointments or follow-ups to observe any calcific changes induced at the apex of tooth concerned. In these visits, a material known as calcium hydroxide ( Ca(OH) 2 ) will be placed inside the root canal systems to eliminate intracanal infection , stimulates calcification and achieves apical barrier seal at the apex of tooth root. The success rate of applying the traditionally used calcium hydroxide to induce calcific barrier is between 74%-100%. Nowadays, a newer material known as mineral trioxide aggregate (MTA) is widely used as well. [ 1 ]
Some difficulties are said to be a major clinical challenge when carrying out apexification, including difficulty in achieving appropriate apical seal with an open apex. Besides that, the termination of development of dentinal walls after pulpal pathologies occur will result in roots with thin dentinal wall and thus, producing a higher risk of tooth fracture. [ 2 ]
Apexification is indicated for immature permanent teeth that are non-vital with incompletely formed roots. [ 3 ] The objective of this procedure is to induce root end closure (apexification) at the apices of immature roots through the formation of mineralized tissue. Apical closure can take various forms but in most cases, it appears to be irregular and aberrant. Along with apical closure, root development may or may not continue. [ 4 ]
There are different materials to be used in apexification such as Mineral trioxide aggregate (MTA), Bioceramics and Biodentine.
Mineral trioxide aggregate (MTA) is composed primarily of tricalcium silicate , tricalcium aluminate , tricalcium oxide , and silicate oxide . It has been used in endodontics as a root-end filling material, and sets in the presence of moisture. [ 5 ] It presents in either grey or white form, the difference between the two being that white MTA lacks iron. [ 6 ]
After numerous testing and analysis, MTA showed superior properties from its physical properties and biocompatibility . It is shown to have less marginal gap formation, less leakage and better adaptation than other filling materials. Besides, root ends filled with MTA showed good healing with absence of periradicular inflammation over the root-end filling material, as compared to amalgam . [ 5 ] The use of MTA as endodontic repair material stimulates bone formation as well as inhibits bone resorption . [ 6 ]
Due to its physical properties and biocompatibility, MTA has been used in numerous clinical situations other than as a root-end filling. It is widely used to repair perforations, to close open apices in apexification, as a direct pulp capping material for deep carious tooth, and to cover pulp stumps for apexogenesis . This material possesses great sealing ability, good antimicrobial activity, great biocompatibility, and enhances dentin biomineralization. [ 5 ] However, there is some known drawbacks to the use of MTA such as the potential release of hazardous substances, potential for discoloration , and inconvenience of handling. [ 6 ]
In order to overcome the limitations of MTA, recent advance in dental materials has introduced bioceramics as a new root canal obturation and repair material. Its composition mainly includes zirconium oxide, calcium silicates, calcium phosphate monobasic, calcium hydroxide, filler, and thickening agents. [ 6 ]
As a pre-mixed form, it is easy to use and is applied in root canal therapy. Biodentin has similar to or better than those of MTA, from biocompatibility, antimicrobial activity, sealing ability and ability to enhance dentin biomineralization. The bonding ability in a high-humidity environment and color stability of biodentine were significantly better than those of MTA. [ 6 ]
Biodentine is a tricalcium silicate-based material, as an alternative to permanent dentin. It is biocompatible and is a new bioactive dentin substitute cement, which is composed of powder that consists of tricalcium silicate , dicalcium silicate , calcium carbonate , calcium oxide , zirconium oxide , and calcium hydroxide . It allows good marginal sealing, thus preventing marginal leakage as well as protecting the underlying pulp by inducing the formation of tertiary dentin . [ 7 ]
Unlike other dentin substitutes, biodentine application does not require any conditioning of the dentin surface in providing good sealing property. This is because tag like structures are formed after the penetration of biodentine material into the dentin tubules. Besides, it can also be bonded with different types of adhesives before finishing the final restoration with composite resin. [ 7 ]
The setting time of biodentine is shorter as compared with that of MTA, In conclusion, this material is clinically indicated for permanent dentin substitute, direct and indirect pulp capping, pulpotomy , repair of furcation and root perforations, retrograde root-end filling, and apexification. [ 7 ]
Proper assessment of the tooth is important in determining an accurate diagnosis in order to formulate an appropriate treatment plan. Clinical evaluation of pulpal status includes a comprehensive history and diagnostic tests. Radiographic examination is used to determine the maturity of the developing root. However, immature teeth are commonly associated with young patients and pulp testing in children is complex and subjective to nature. [ 8 ] [ 9 ]
The following steps are included in this procedure: [ 10 ]
Apexification procedure can be completed in one or two appointments depending on the initial clinical sign and symptoms. The procedure may also vary depending on the materials or medication used. Generally, the treatment paste is allowed to remain for six months before the evaluation for an apical closure. [ 10 ]
If apical closure has not occurred within six months, the root canal is retreated again with the material of choice. Ideally, the tooth should demonstrate continued apical growth and closure or an apical stop. When closure is observed, the canal is filled with a root canal filling material known as gutta-percha . [ 10 ]
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Apicoaortic Conduit (AAC) , also known as Aortic Valve Bypass (AVB) , is a cardiothoracic surgical procedure that alleviates symptoms caused by blood flow obstruction from the left ventricle of the heart. Left ventricular outflow tract obstruction (LVOTO) is caused by narrowing of the aortic valve ( aortic stenosis ) and other valve disorders. AAC, or AVB, relieves the obstruction to blood flow by adding a bioprosthetic valve to the circulatory system to decrease the load on the aortic valve. When an apicoaortic conduit is implanted, blood continues to flow from the heart through the aortic valve. In addition, blood flow bypasses the native valve and exits the heart through the implanted valved conduit. The procedure is effective at relieving excessive pressure gradient across the natural valve. High pressure gradient across the aortic valve can be congenital or acquired. A reduction in pressure gradient results in relief of symptoms.
The figure depicts a typical apicoaortic configuration with a left ventricle connector sutured to the apex of the heart , and a conduit containing a bioprosthetic valve anastomosed to the descending thoracic aorta . Blood exits the left ventricle either through the natural valve or the bypass conduit. [ citation needed ]
The concept of an apicoaortic conduit to bypass valvular aortic stenosis (AS) was conceived by Carrel [ 1 ] in 1910, and performed experimentally by Sarnoff and colleagues on dogs in 1955. [ 2 ] In 1962-63, Templeton implanted prostheses similar to those originally described by Sarnoff in five patients with severe aortic valve stenosis; one patient survived more than 10 years. In 1975, Bernhard and coworkers reported a reoperation in which a conduit was implanted between the left ventricle and the thoracic aorta. [ 3 ] The procedure was also developed in the late 1970s as a way to treat complex left ventricular outflow tract obstructions (LVOTO) in children and young adults. [ 4 ] [ 5 ] AAC is no longer performed on children as the Ross procedure has superseded it. [ 6 ]
Today, AAC is performed clinically on elderly aortic stenosis patients, and has gained in popularity in recent years. In the past 25 years, a number of case series on adults have been published. [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] As of 2010, the estimated total number of AAC cases performed worldwide in the last 30 years is greater than 1500. The procedure has not been adopted widely because it is technically challenging and blood loss can be significant. The most difficult part of the procedure is the insertion of a left ventricle connector into the apex of the heart . [ citation needed ]
AAC requires specialized implants and installation tools. Hancock Laboratories, now part of Medtronic (Minneapolis, MN), developed and released a set of left ventricle connectors, valved conduits, and installation trocars in the 1970s. The Hancock left ventricle connectors, with inner diameters of 12 to 22 mm, have been used clinically for the vast majority of AAC procedures reported in the literature. For the valved conduit, surgeons have used the Medtronic Hancock Model 105 or 150 valved conduits which contain a complete porcine aortic valve. Other surgeons have constructed valved conduits on the back table using a variety of bioprosthetic valves such as the Medtronic Freestyle valve. The Hancock trocars for creating a hole in the left ventricle are rarely used clinically. Surgeons typically assemble their own tools to core and remove a plug of muscle from the left ventricular wall.
In 2011, Correx (Waltham, MA) [ 16 ] released a complete kit for AVB with an installation tool that enables coring and insertion of a left ventricle connector on a beating heart while maintaining hemostasis . Cardiopulmonary bypass (CPB) is not required. The kit is CE Marked and available in Europe. Several cases have been done in Canada under the Special Access Programme. [ 17 ] This kit is not currently available for use or sale in the United States.
The general procedure has evolved over the years as surgeons gained experience and improved techniques. [ 18 ] A video of an AVB procedure performed by Dr. Jim Gammie of the University of Maryland Medical Center can be found here. [ 19 ]
The patient is placed on the table in the supine position. Anesthesia is induced, and the patient is intubated with a double-lumen endotracheal tube, which facilitates one-lung ventilation and allows the surgeon to work within the left chest. The patient is positioned with his or her left side up (see figure). A left anterior-lateral thoracotomy is performed between the fifth and sixth ribs to expose the heart and provide access to the descending aorta . A portion of a rib may be removed to enable easier access and to minimize the chance of a rib fracture. The left lung is deflated and retracted. [ citation needed ]
With the descending aorta exposed, the surgeon applies a side clamp to the aorta, effectively pinching and isolating one side of the great vessel. Blood continues to flow to the body's lower half through the unisolated remainder of the aorta. A lengthwise slit is made through the pinched face, and the open end of the valved conduit is carefully sutured to the slit. Once the suture line is checked for leaks, the aortic partial side clamp is removed and the valved conduit fills with blood up to the bioprosthetic valve. The valve acts as a check valve, thereby maintaining hemostasis.
The surgeon next opens the pericardium and exposes the apex of the heart . The surgeon closely examines the surface of the heart and chooses and marks an insertion site near the apex. A ring of sutures reinforced with pledgets is installed around the insertion site. The free ends of the sutures are looped through a sewing ring on the left ventricle connector. At this point, CPB is typically initiated, although a few surgeons are able to complete the left ventricle installation off-pump (without CPB).
A circular core of myocardium is cut and removed using specialized coring tools. Care must be taken to avoid damaging structures inside the left ventricle such as the interventricular septum , and the chordae tendineae . The left ventricle connector is filled with sterile saline to displace any air and then inserted into the hole. The sutures are sequentially tightened and tied off to permanently secure the left ventricle connector to the apex. CPB is terminated. [ citation needed ]
With blood now flowing through the bypass conduit, the left ventricular outflow tract obstruction (LVOTO) is effectively relieved. 60% to 70% of the heart's output flows through the bypass to the aorta. The load on the heart is markedly reduced, and symptoms such as dyspnea , syncope , and chest pain disappear.
Patients historically referred for apicoaortic conduit surgery have been considered high risk or ineligible for conventional aortic valve replacement . The literature reports generally favorable outcomes for apicoaortic surgery given the age, frailty, and comorbidities of the patient population. Patients typically improve from New York Heart Association Functional Classification III or IV to Class I or II. AVB effectively relieves the LVOTO caused by aortic stenosis .
There is long-term stability of the left ventricular hemodynamics after AVB, with no further biologic progression of native aortic valve stenosis. Once the pressure gradient across the native valve is substantially reduced, the narrowing and calcification of the native valve halts. In one study of 47 patients whose average age was 82 years, the mean gradient across the native valve was reduced from 46 +/- 14 mm HG to 17 +/- 7 mm HG. [ 20 ]
Throughout the published literature, perioperative stroke is uncommon. This is because the native valve and ascending aorta are not manipulated in any way. Calcified layers and other debris do not break free and migrate to the brain. [ citation needed ]
The literature also reports that postoperative stroke is rare. Whenever a prosthetic device such as a valve is introduced into the bloodstream, there is an ongoing risk of thrombus formation which can lead to an embolism should the thrombus become mobile. Computational flow studies [ 21 ] conclude that the presence of an aortic valve bypass conduit has no effect on cerebral blood flow. All blood flow to the brain continues to flow across the native valve. Should a thrombus form on the bioprosthetic valve in the bypass conduit, it will likely migrate to the lower half of the body and not to the brain. This fact is believed to reduce the long-term risk of cerebral thromboembolism (stroke) with AAC.
The published literature reports that the need for pacemaker after AAC is very rare as the (electrical) conduction center of the heart near the aortic valve is not disturbed in any way.
AAC avoids the risk of leakage around a replacement heart valve ( aortic insufficiency ), a serious complication of alternate treatments such as aortic valve replacement (AVR) and percutaneous aortic valve replacement (PAVR or TAVI). With AAC, the native aortic valve is left completely undisturbed. [ citation needed ]
With aortic valve replacement (AVR) as the accepted standard of care for critical AS, patients receiving apicoaortic conduits have often been refused AVR and as such are considered "no option" patients. AAC is also sometimes chosen by surgeons and cardiologists over other treatments, such as AVR and percutaneous aortic valve replacement (PAVR or TAVI), to treat critical AS. Patients who could benefit from AAC or AVB include those who: [ citation needed ]
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Apparent infection rate is an estimate of the rate of progress of a disease, based on proportional measures of the extent of infection at different times.
Firstly, a proportional measure of the extent of infection is chosen as the disease extent metric. For example, the metric might be the proportion of leaf area affected by mildew or the proportion of plants in a population showing dieback lesions. Measures of disease extent are then taken over time, and a mathematical model is fitted. The model is based on two assumptions:
There is a single model parameter r , which is the apparent infection rate. It can be calculated analytically using the formula
where
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Apple cider vinegar , or cider vinegar , is a vinegar made from cider , [ 3 ] and used in salad dressings, marinades , vinaigrettes , food preservatives , and chutneys . [ 4 ] It is made by crushing apples , then squeezing out the juice. The apple juice is then fermented by yeast which converts the sugars in the juice to ethanol . In a second fermentation step, the ethanol is converted into acetic acid by acetic acid-forming bacteria ( Acetobacter species), yielding cider vinegar. [ 4 ] The acetic acid, together with the malic acid naturally present in apple juice, contribute to the sour taste of this vinegar. [ 3 ]
There is no high-quality clinical evidence that regular consumption of apple cider vinegar helps to maintain or lose body weight , [ 5 ] or is effective to manage blood glucose and lipid levels. [ 4 ]
Apples are loaded onto a processing belt where they are washed, crushed, pressed, and the juice separated. [ 4 ] [ 6 ] Autochthonous or inoculated yeasts , mainly Saccharomyces cerevisiae , initiate alcoholic fermentation , converting the sugars in the juice into ethanol and producing apple cider . The apple cider is then inoculated with either a pure culture of acetic acid bacteria or a proportion of 'mother vinegar' , resulting in a secondary acetic fermentation which then converts the ethanol in the cider to acetic acid , yielding apple cider vinegar. [ 3 ] [ 4 ] [ 6 ] The "mother" is an undefined microbial culture left in the vinegar prior to distilling and pasteurization . [ 7 ]
Apple cider vinegar is 94% water and 5% acetic acid with 1% carbohydrates and no fat or protein (table). In a 100 gram reference amount, it provides 90 kilojoules (22 kcal) of energy, with negligible content of micronutrients . [ 8 ]
Despite its history of use in traditional medicine , [ 4 ] due to inadequate research of high quality, the evidence for the health effects of apple cider vinegar is insufficient to support any health claims – such as for weight loss , glycemic control [ 9 ] or skin infections [ 3 ] – in humans, and its use is not recommended for any indication in medical guidelines of major public health organizations or regulatory agencies . [ 10 ]
Moderate consumption of apple cider vinegar is safe, particularly if it is diluted, and the chance of side effects when it is consumed as directed and in the recommended amounts appears to be low. [ 9 ] Reported adverse effects include esophageal damage due to incomplete swallowing of apple cider vinegar tablets, tooth enamel damage due to swallowing excessive quantities of apple cider vinegar, and increased frequency of burping , flatulence , and bowel movements . Consumption of vinegar can increase dentin hypersensitivity . [ 9 ] Irritation and redness are common when the eyes come into contact with vinegar, and corneal injury can occur. [ 10 ] Using vinegar as a topical medication , ear cleaning solution, or eye wash is hazardous. [ 10 ] Although small amounts of apple cider vinegar may be used as a food flavoring , [ 10 ] it may be unsafe for use by pregnant and breastfeeding women and by children. [ 3 ] Different commercial brands of apple cider vinegar were found to have inconsistent acid levels, with some contaminated by molds and yeast . [ 4 ]
If used as a homemade cleaning agent , apple cider vinegar, like any kind of vinegar, should not be mixed with chlorine bleach , the combination of which may release chlorine gas and irritate airways, eyes, nose and throat. [ 10 ]
People with allergies to apples may experience allergic reactions to apple cider vinegar. [ 4 ] Topical use of apple cider vinegar to treat skin diseases may cause burns. [ 4 ] The use of apple cider vinegar may cause untoward interactions with prescription drugs , such as insulin or diuretics . [ 5 ]
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Appropriate use criteria ( AUC ), sometimes referred to as appropriateness criteria ( AC ), specify when it is appropriate to perform a medical procedure or service. An "appropriate" procedure is one for which the expected health benefits exceed the expected health risks by a wide margin. Ideally, AUC are evidence-based, but in the absence of sufficient evidence, may be derived from a consensus of expert opinion. AUC are typically classified in terms of the quality of the evidence on which they are based. In general, AUC are promulgated by medical specialty organizations (professional societies). [ citation needed ] The definition of "appropriate" is subject to interpretation. For example, a key issue is whether or not a procedure or investigation can be deemed appropriate if it does not result in a change in management. [ 1 ]
Relative costs of alternative appropriate procedures may or may not be considered in selecting a procedure for an individual patient, but in there is evidence that performing only appropriate procedures reduces volume [ 2 ] and cost. [ 3 ] To reduce the cost of (advanced) diagnostic imaging tests, a requirement for the use of clinical decision support for was included in the Protecting Access to Medicare Act of 2014 , though it does not apply to emergency or inpatient services.
AUC are not always consistent between sources, or with other guidelines, or with reimbursement decisions. [ 4 ] [ 5 ] Additionally, AUC have not shown an impact in physician's behaviour. [ 6 ] AUC may be promulgated in human-readable form, or converted into an electronic structured form for use in a clinical decision support system , such as a computerized physician order entry system.
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This dentistry article is a stub . You can help Wikipedia by expanding it .
In dentistry, the approximal surfaces are those surfaces which form points of contact between adjacent teeth. However, in diastematic individuals these surfaces may not make contact but are still considered approximal. Due to the topography of approximal sites the removal of plaque by brushing may be difficult and hence a significant build-up may occur increasing the risk of plaque-related diseases such as dental caries or gingivitis , [ 1 ] [ page needed ] therefore dental flossing is recommended. [ by whom? ]
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Aprosodia is a neurological condition characterized by the inability of a person to properly convey or interpret emotional prosody . Prosody in language refers to the ranges of rhythm, pitch, stress, intonation, etc. These neurological deficits can be the result of damage of some form to the non-dominant hemisphere areas of language production. The prevalence of aprosodias in individuals is currently unknown, as testing for aprosodia secondary to other brain injury is only a recent occurrence.
Receptive aprosodia can result from impairment at one or more sensory and/or cognitive levels ranging from hearing (signal acquisition) to auditory processing (signal isolation) to emotional comprehension (signal interpretation). For example, the first two difficulties impair an individual's ability to observe and discern changes in stress and intonation, whereas the third impairs an individual's ability to assess the significance of those stress and intonation changes that he or she correctly observes and discerns; impairment of the third type correlates significantly with expressive aprosodia. [ 3 ]
One cause of aprosodia is trauma to one of several specific areas of the brain, resulting in the inability to properly process or convey
emotional cues. This brain damage can occur in the form of ischemic damage from stroke. [ 4 ]
An inability to process or exhibit emotions in a proper manner has been shown to exist in people who consume excessive amounts of alcohol and those who were exposed to alcohol while fetuses (FAexp). Initially, when people with an alcohol use disorder are detoxified and FAexp individuals were tested for impairment in cognitive function, it was limited to testing the non-affective aspects of language, as those were the more easily recognized by a physician not trained in analyzing affective prosody. When tested using the aprosodia battery, it was found that those with alcohol use disorder who detoxified and FAexp individuals demonstrated significant impairment in their ability to detect affective prosody when used by others. The major factors which influence affective prosody in those impacted by alcohol use, from greatest to least impact, are: alcohol use by mother, age at onset of chronic abuse of alcohol, age at initial abuse, how chronic the abuse is, and the age when a person first becomes drunk. [ 5 ]
Aprosodia has also been shown to appear secondary to several diseases such as multiple sclerosis or post traumatic stress disorder . [ 6 ] It is likely that as time passes more diseases will be shown to exhibit aprosodia as a symptom. Aprosodia is a condition that was not often tested for in the presence of neurological deficits; however, as more becomes known about it, the aprosodia battery will likely be administered more frequently. For example, the first study testing for aprosodia in MS did not occur until 2009. [ 7 ]
Emotional batteries consist of asking patients to read various sentences with specific emotional indicators. Their performance is subjectively analyzed by an expert to determine if they are aprosodic. The analysis is often performed by two experts independently, with one of the judges not being present during the interview in case the patient was still able to use facial cues. [ 8 ]
Another method implemented to test for aprosodia involves having questionnaires filled out by those close to the patient. The doctors and nurses taking care of a patient are also requested to fill out a questionnaire if aprosodia is suspected. This diagnosis method occurs more as an indicator that the aprosodia battery should be administered rather than being used as a singular diagnosis tool. Implementation of the questionnaire is expected to become more widespread as aprosodia is revealed to be a side-effect of more diseases. [ 8 ]
Brain imaging studies related to speech functions have yielded insights into the subtle difference between aprosodia and dysprosody . The major differences in these result from functions which are characterized as belonging mainly to the left or right hemisphere. Several of the functions have been described as dominant and lateralized functions of the corresponding hemispheres, while some have been found to arise from communication between the two hemispheres. [ 1 ]
The two main forms of treatment are cognition based and imitation based. Cognitive treatments attempt to rebuild the "emotional toolbox" of those with aprosodia. The basis for this treatment is the belief that there exists a defined set of emotional responses that can be chosen for a given scenario. Choosing the proper emotional response can very much be likened to choosing the proper word when describing an object, and this deficiency can be likened to Broca's Aphasia but for emotions. Imitative treatments attempt to help "kickstart" the motor systems involved in the production of both vocal and facial emotive gestures. The basis for this treatment is the belief that the pathways responsible for the motor elements of expressive prosody were damaged. It is hypothesized that the motor damage occurs at the level of planning as well as the level of execution. [ 9 ]
The methods of treatment are being evaluated and changed through several iterations to reach the most beneficial treatment for those with aprosodia. Although the biggest limitation on progress of aprosodia treatment is sample size, some significant data has been found to influence each subsequent phase of study. The Rosenbek lab at the University of Florida is currently in a new phase of treatment study based on combinations of the cognitive-linguistic and imitative therapies delivered in a randomized fashion in an effort to gain more insight into what most prominently affects aprosodia treatment. [ 8 ]
Research into the perisylvan region of the right hemisphere has shown that there are similarly mapped analogues to the speech center in the left hemisphere. This is especially evident in those areas resembling Broca's area and Wernicke's area . [ 10 ]
Additionally, in studying the brain regions associated with aprosodia, brain imaging tests were performed to determine if aprosodia is both a lateralized and dominant function of the right hemisphere areas of language production. Aprosodia can be considered a dominant function of the right hemisphere because strong correlation was found between deficits in affective prosody and distribution of lesions in the cortices of those with right brain damage. No correlation was found between the distribution of cortical lesions in patients with left brain damage and the types of aphasic deficits pronounced in those patients. Aprosodia can be considered a lateralized function of the right hemisphere because of the differences in the ability of a patient to respond to affective prosodic information in those with left brain damage when compared to those with right brain damage. Patients with affective-prosodic deficits in the left hemisphere (dysprosodic patients) showed improvement in understanding and repeating prosodic information when other conveyed linguistic information was simplified, i.e. requiring the patient to mainly determine prosodic information contained in an interaction. This improvement in processing affective prosodic information under reduced linguistic processing demands did not occur for patients with right brain damage. [ 1 ]
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In pathology , an apudoma is an endocrine tumour that arises from an APUD cell [ 1 ] [ 2 ] from structures such as the ampulla of Vater . [ 3 ] They were historically thought to be derived from neural crest cells , [ 4 ] but this has since been shown to be untrue (see neuroendocrine tumor ).The term dates back to at least 1975. [ 5 ] Because the label "apudoma" is very general, it is preferred to use a more specific term when possible. [ citation needed ]
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Aquafresh (originally spelt "Aqua-Fresh") is a brand of toothpaste and toothbrushes that has been on sale since 1973. It is produced by the health products manufacturer Haleon . One of its characteristics is its striped pattern. Today, the stripes are red, white, and blue (aqua), although initially there were only blue and white stripes. [ 1 ]
In 2013 Aquafresh launched the Better Brushing Programme to help promote good oral care habits from an early age including new packaging designs and age appropriate toothpaste formulations. [ 2 ]
In May 2025, Aquafresh launched a new range of toothpaste named White Renew . [ 3 ]
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The OIE Aquatic Animal Health Code (AAHC) implements improvement standards of worldwide aquatic animal health and welfare and public health from a scientific point of view. The AAHC "compiles information on diseases of fish , molluscs and crustaceans , and on methods used to control these diseases". [ 1 ]
The AAHC includes standards international trade in welfare of farmed fish and utilisation of antimicrobial agents in aquatic animals and their merchandise. [ 2 ] All members of the World Trade Organization (WTO) must have an aquatic animal health program that meets the OIE standards. [ 3 ] National veterinary authorities use it to provide for early detection of pathogens and to prevent the transfer of same by international trade in animals and animal merchandise, while skirting "unjustified sanitary barriers to trade". [ 2 ]
The standards in the AAHC have been adopted by the World Assembly of the OIE. [ 2 ] The WTO Agreement on the Application of Sanitary and Phytosanitary Measures "recognises the OIE as the international standard setting organisation for animal health and zoonotic diseases and specifically encourages the Members of the WTO to base their" legislation and regulations "on international standards, guidelines and recommendations, where they exist." [ 2 ]
The AAHC had been through 21 editions as of August 2019. [ 2 ]
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https://en.wikipedia.org/wiki/Aquatic_Animal_Health_Code
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WHX Dubai , formerly Arab Health is a healthcare conference and trade show in the Middle East . [ 2 ] It first took place in Dubai , United Arab Emirates in 1975. [ 3 ] Healthcare industry representatives attend from the Middle East, Asia, Europe and the United States. [ citation needed ]
The congress is one of the world's largest medical conferences. [ 4 ]
WHX Dubai is supported by the UAE Ministry of Health , the Abu Dhabi Health Authority , the Dubai Health Authority and the Dubai Healthcare City Authority . [ 5 ]
Awards are given for innovation and achievement in the industry. [ 6 ] They include awards for radiology , surgery , laboratory work, patient-centred care, and clinicians.
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https://en.wikipedia.org/wiki/Arab_Health
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The Archives of Pathology & Laboratory Medicine (Arch Pathol Lab Med) is a core clinical medical journal published by the College of American Pathologists and the American Medical Association . It continues in series publications entitled the Archives of Pathology and Laboratory Medicine (1926–28), the Archives of Pathology (1928–50), the A.M.A. Archives of Pathology (1950–60), and the Archives of Pathology (1960–75).
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The arcuate nucleus of the hypothalamus ( ARH ), [ 1 ] or ARC , [ 2 ] is also known as the infundibular nucleus to distinguish it from the arcuate nucleus of the medulla oblongata in the brainstem . [ 1 ] The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus , adjacent to the third ventricle and the median eminence . The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons , centrally projecting neurons, and astrocytes . The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. [ 3 ] [ 2 ] [ 4 ] The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis . The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation. [ 3 ] [ 2 ] [ 4 ] [ 5 ]
Different groups of arcuate nucleus neuroendocrine neurons secrete various types or combinations of neurotransmitters and neuropeptides , such as neuropeptide Y (NPY), gonadotropin-releasing hormone (GnRH), agouti-related peptide (AgRP), cocaine- and amphetamine-regulated transcript (CART), kisspeptin , dopamine , substance P , growth hormone–releasing hormone (GHRH), neurokinin B (NKB), β-endorphin , melanocyte-stimulating hormone (MSH), and somatostatin . Proopiomelanocortin (POMC) is a precursor polypeptide that is cleaved into MSH, ACTH, and β-endorphin and expressed in the arcuate nucleus. [ 3 ]
Groups of neuroendocrine neurons include:
Other types of neurons have projection pathways from the arcuate nucleus to mediate different regions of the hypothalamus or to other regions outside of the hypothalamus. [ 2 ] [ 4 ] Projections of these neurons extend a long distance from the arcuate nucleus to the median eminence to influence the release of hormones from the pituitary gland. [ 3 ] [ 2 ] Neurons of the arcuate nucleus have intrahypothalamic projections for neuroendocrine circuitry. [ 3 ] such as neural projections that influence feeding behavior project to the paraventricular nucleus of the hypothalamus (PVH), the dorsomedial hypothalamic nucleus (DMH), and the lateral hypothalamic area (LHA). [ 3 ] Populations of neurons connect to the intermediate lobes of the pituitary gland, from the lateral division of the ARH to the neural and intermediate parts of the pituitary gland, and the caudal division of ARH to the median eminence. [ 2 ]
Groups of neurons that project elsewhere within the central nervous system include:
Other cell populations include:
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The arcuate uterus is a form of a uterine anomaly or variation where the uterine cavity displays a concave contour towards the fundus . Normally the uterine cavity is straight or convex towards the fundus on anterior-posterior imaging, but in the arcuate uterus the myometrium of the fundus dips into the cavity and may form a small septation . The distinction between an arcuate uterus and a septate uterus is not standardized.
The condition may not be known to the affected individual and not result in any reproductive problems; thus normal pregnancies occur. [ 1 ] Indeed, there is no consensus on the relationship of the arcuate uterus and recurrent pregnancy loss . [ 2 ] Accordingly, the condition may be a variation or a pathology. [ citation needed ]
One view maintains that the condition is associated with a higher risk for miscarriage , premature birth , and malpresentation . Thus a study that evaluated women with uterine bleeding by hysteroscopy found that 6.5% of subjects displayed the arcuate uterus and had evidence of reproductive impairments. [ 3 ] A study based on hysterosalpingraphic detected arcuate lesions documented increased fetal loss and obstetrical complications as a risk for affected women. [ 4 ] Woelfer found that the miscarriage risk is more pronounced in the second trimester. [ 5 ] In contrast, a study utilizing 3-D ultrasonography to document the prevalence of the arcuate uterus in a gynecological population found no evidence of increased risk of reproductive loss; in this study 3.1% of women had an arcuate uterus making it the most common uterine anomaly; this prevalence was similar than in women undergoing sterilization and lower than in women with recurrent pregnancy loss. [ 6 ]
The uterus is formed during embryogenesis by the fusion of the two Müllerian ducts . During this fusion a resorption process eliminates the partition between the two ducts to create a single cavity. This process begins caudally and advances cranially, thus an arcuate uterus represents an incomplete absorption process in the final stage. [ citation needed ]
A transvaginal ultrasound can reveal the condition.
Helpful techniques to investigate the uterine structure are transvaginal ultrasonography and sonohysterography , hysterosalpingography , MRI , and hysteroscopy . More recently 3-D ultrasonography has been advocated as an excellent non-invasive method to delineate the condition. [ 5 ]
The major differential diagnosis is the uterine septum. The lack of agreement to separate these two entities makes it difficult to assess the results in the literature. [ citation needed ]
Many patients with an arcuate uterus will not experience any reproductive problems and do not require any surgery. In patients with recurrent pregnancy loss thought to be caused by an arcuate uterus hysteroscopic resection can be performed. [ citation needed ]
Most studies of uterine malformations are based on populations of women who have experienced a miscarriage and thus do not address the issue of the prevalence in the general population. A screening study by Woelfer et al. of women without a history of reproductive problems found that about 5% of women had an arcuate uterus when they defined an arcuate uterus any fundal protrusion into the cavity that had an apical angle of more than 90 degrees. Accordingly, it was the most common uterine anomaly, followed by septate uterus (3%) and bicornuate uterus (0.5%). [ 5 ]
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The Armed Forces Institute of Pathology is a medical research laboratory and premier diagnostic institution of the Bangladesh Armed Forces . It is situated in Dhaka Cantonment . Major General Nishat Jubaida is the current commandant and Brigadier General Abdullah-Al-Baki (LPR) is the current consultant of this institution.
The Army Pathological Laboratory (APL) was established as a small laboratory in 1951 as part of the Pakistan Army . [ 1 ] After the independence of Bangladesh it became part of the Bangladesh Army . In 1974, APL was restructured and re-equipped with modern equipment. [ 2 ] [ 3 ] [ 4 ] In 1987, the institute was awarded the Independence Day Award . In 1991, APL was renamed to Armed Forces Institute of Pathology. [ 5 ] This institute is recognized by the Bangladesh College of Physicians and Surgeons (BCPS), University of Dhaka, Bangabandhu Sheikh Mujib Medical University (BSMMU) and also by Bangladesh University of Professionals (BUP) for postgraduate studies and training. [ citation needed ]
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Armin Abron (born October 24, 1975, in Frankfurt , Germany ) [ citation needed ] is a periodontist , who practices in Washington, D.C. He is also an adjunct assistant professor of periodontology at UNC School of Dentistry in Chapel Hill. [ 1 ]
Abron earned his Bachelor of Science degree (B.S.) and Doctor of Dental Surgery degree (D.D.S.) from the University of North Carolina at Chapel Hill , and his Master of Science degree (M.S.) in periodontology at Columbia University School of Dental and Oral Surgery in New York City . [ 2 ]
He is the recipient of the Mel Morris Award for Clinical and Academic Excellence in Periodontics . [ citation needed ]
Abron has been involved in many research projects related to implants and periodontology. [ 3 ] His work has been published in national and international journals, including the European Journal of Oral Science, Journal of Prosthetic Dentistry , and Journal of Clinical Periodontology . [ 4 ] [ 5 ]
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The Armitage–Doll model is a statistical model of carcinogenesis , proposed in 1954 by Peter Armitage and Richard Doll , in which a series of discrete mutations result in cancer . [ 1 ] The original paper has recently been reprinted with a set of commentary articles.
The rate of incidence and mortality from a wide variety of common cancers follows a power law : someone's risk of developing a cancer increases with a power of their age. [ 2 ]
The model is very simple, and reads
r a t e = N p 1 p 2 p 3 ⋯ p r ( r − 1 ) ! t r − 1 {\displaystyle \mathrm {rate} ={\frac {Np_{1}p_{2}p_{3}\cdots p_{r}}{(r-1)!}}t^{r-1}}
in Ashley's notation. [ 3 ]
Their interpretation was that a series of r {\displaystyle r} mutations were required to initiate a tumour. [ 1 ] This is now widely accepted, and part of the mainstream view of carcinogenesis . In their original paper, they found that r {\displaystyle r} was typically between 5 and 7. Other cancers were later discovered to require fewer mutations: retinoblastoma , typically emerging in early childhood, can emerge from as few as 1 or 2, depending on pre-existing genetic factors.
This was some of the earliest strong evidence that cancer was the result of an accumulation of mutations. With their 1954 paper, Armitage and Doll began a line of research that led to Knudson's two-hit hypothesis and thus the discovery of tumour suppressor genes . [ 3 ] [ 4 ]
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Erik Arne Björk (22 December 1911 – 5 February 1996) [ 1 ] was a Swedish dentist famous for his The Face in Profile Analysis which he published in 1947. He is also known to develop the implant radiography. [ 2 ]
Björk was born in Ludvika , Sweden. [ 1 ] He received his dental training in Stockholm . He practiced dentistry from 1937 to 1951. He served as chairman of orthodontics in Malmö , Sweden from 1940 to 1950. He then served as Professor of Orthodontics in Royal Dental College , Denmark. During his studying, he published his thesis called "Face in the Profile" which made him famous in the orthodontic circles. [ 3 ] Eventually, he became the head of Department of Orthodontics and head of Craniofacial Growth Center at the Royal Dental College for next 30 years. He was nominated as member of World Federation of Orthodontists in 1995. [ 4 ]
Björk was one of the first people to work on Implant Radiography . [ 5 ] He, along with his coworkers, placed metal pins in bones of jaws and other parts of the skeleton. They then looked at these pins in a Cephalometric Analysis to assess the growth pattern of a growing individual. This technique was instrumental in providing a way to study the grown pattern of a human mandible. [ 6 ] Previously to his work, the information about how rotation of jaws playing a role in growth of maxilla and mandible was under-appreciated. Björk, through his research, defined concepts of Forward Rotation and Backward Rotation of jaws. [ 6 ] He defined Forward Rotation of jaw where the posterior growth of maxilla and mandible is greater than the anterior and Backward Rotation as where the anterior growth of jaws is greater than the posterior areas.
Björk also developed seven structural signs that helped find the direction of the growth of the mandible, also known as Bjork Analysis . [ 5 ]
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Aromatherapy is a practice based on the use of aromatic materials , including essential oils and other aroma compounds , with claims for improving psychological well-being . [ 1 ] [ 2 ] [ 3 ] It is used as a complementary therapy or as a form of alternative medicine , and typically is used via inhalation and not by ingestion. [ 2 ]
Fragrances used in aromatherapy are not approved as prescription drugs in the United States. [ 3 ] Although there is insufficient medical evidence that aromatherapy can prevent, treat or cure any disease, [ 1 ] [ 2 ] [ 4 ] aromatherapy is used by some people with diseases, such as cancer, to provide general well-being and relief from pain, nausea or stress. [ 1 ] [ 2 ] People may use blends of essential oils as a topical application , massage, inhalation, or water immersion. [ 1 ] [ 2 ] [ 5 ] Due to the low quality of research evidence, it is uncertain if aromatherapy provides any benefit to people experiencing nausea after surgery. [ 6 ]
Essential oils comprise hundreds to thousands of aromatic constituents, like terpinoids and phenylpropanoids , and to sufficiently research the pharmacological effects of essential oil constituents, each isolated constituent in the selected essential oil would have to be studied. [ 2 ] [ 3 ]
Oils and the belief that they had healing properties, along with other beliefs of the time, are described by Dioscorides in his De Materia Medica , written in the 1st century A.D. [ 7 ] Distilled cedarwood oil was used by the ancient Egyptians, and the process of distilling essential oils like rose essence was refined by the 11th century Persian scholar Ibn Sina . Hildegard of Bingen used distilled lavender oil for medicinal treatments in the 12th century, and by the 15th century, oils were commonly distilled from various plant sources. [ 8 ]
In the era of modern medicine, the name "aromatherapy" first appeared in print in 1937 in a French book on the subject: Aromathérapie: Les Huiles Essentielles, Hormones Végétales by René-Maurice Gattefossé, a chemist. An English version was published in 1993. [ 9 ]
Jean Valnet, a French surgeon, pioneered the supposed medicinal uses of essential oils, which he used as antiseptics in the treatment of wounded soldiers during World War II . [ 10 ]
Aromatherapy products, and essential oils in particular, may be regulated differently depending on their intended use. [ 3 ] Products that are marketed with a therapeutic use in the US are regulated by the US Food and Drug Administration (FDA) ; products with a cosmetic use must meet safety requirements, regardless of their source. [ 3 ] The US Federal Trade Commission (FTC) regulates any aromatherapy advertising claims. [ 3 ]
There are no standards for determining the quality of essential oils in the United States; while the term "therapeutic grade" is in use, it does not have a regulatory meaning. [ 3 ] [ 11 ]
Analysis using gas chromatography and mass spectrometry has been used to identify bioactive compounds in essential oils. [ 12 ] These techniques are able to measure the levels of components to a few parts per billion. [ 13 ] This does not make it possible to determine whether each component is natural or whether a poor oil has been "improved" by the addition of synthetic aromachemicals , but the latter is often signalled by the minor impurities present.
There is no clinical evidence that aromatherapy can prevent or cure any disease, [ 1 ] [ 6 ] [ 14 ] although it may be useful for managing symptoms. [ 2 ] [ 15 ]
Evidence for the efficacy of aromatherapy in treating medical conditions is poor, with a particular lack of studies employing rigorous methodology. [ 1 ] [ 2 ] [ 6 ] In 2015, the Australian Government's Department of Health published the results of a review of alternative therapies that sought to determine if any were suitable for being covered by health insurance ; aromatherapy was one of 17 therapies evaluated for which no clear evidence of effectiveness was found. [ 16 ]
Several systematic reviews have studied the clinical effectiveness of aromatherapy in respect to pain management in labor, [ 17 ] the treatment of post-operative nausea and vomiting , [ 6 ] managing challenging behaviors in people suffering from dementia , [ 18 ] and symptom relief in cancer . [ 19 ]
According to the US National Cancer Institute , no studies of aromatherapy in cancer treatment have been published in a peer-reviewed scientific journal. Results are mixed for other studies. Some showed improved sleep, [ 20 ] anxiety, mood, nausea, and pain, [ 15 ] while others showed no change in symptoms. [ 21 ]
Aromatherapy carries several risks of adverse effects ; combined with the lack of evidence of its therapeutic benefit, the practice is of questionable worth. [ 22 ]
Many studies have explored the concerns that essential oils are highly concentrated and can irritate the skin when used in undiluted form, often referred to as neat application. [ 3 ] [ 23 ] [ 24 ] Therefore, they are normally diluted with a carrier oil for topical application such as jojoba oil , olive oil , sweet almond oil or coconut oil . Phototoxic reactions may occur with many cold-pressed citrus peel oils such as lemon or lime . [ 25 ]
Many essential oils have chemical components that are sensitisers (meaning that they will, after several uses, cause reactions on the skin and more so in the rest of the body). [ 3 ] All cosmetic products and ingredients must meet the same safety requirements, regardless of their source. Chemical composition of essential oils could be affected by herbicides if the original plants are cultivated versus wild-harvested. [ 26 ] [ 27 ] Some oils can be toxic to some domestic animals, with cats being particularly prone. [ 28 ]
Most oils can be toxic to humans as well. [ 29 ] A report on three different cases documented gynecomastia in prepubertal boys who were exposed to topical lavender and tea tree oils . [ 30 ] The Aromatherapy Trade Council of the UK issued a rebuttal. [ 31 ]
Another article published by a different research group also documented three cases of gynecomastia in prepubertal boys who were exposed to topical lavender oil. [ 32 ] Persistent exposure to lavender products may be associated with premature breast development in girls and "that chemicals in lavender oil and tea tree oil are potential endocrine disruptors with varying effects on receptors for two hormones – estrogen and androgen ". [ 33 ]
Essential oils can be toxic when ingested or absorbed internally. Doses as low as 2 ml have been reported to cause clinically significant symptoms and severe poisoning can occur after ingestion of as little as 4 ml. [ 34 ] A few reported cases of toxic reactions like liver damage and seizures have occurred after ingestion of sage, hyssop, thuja and cedar oils. [ 35 ] Accidental ingestion may happen when oils are not kept out of reach of children. As with any bioactive substance, an essential oil that may be safe for the general public could still pose hazards for pregnant and lactating people. [ 36 ]
Oils both ingested and applied to the skin can potentially have negative interactions with conventional medicine. For example, the topical use of methyl salicylate –heavy oils like wintergreen may cause bleeding in users taking the anticoagulant warfarin .
In late 2021, an aromatherapy spray was recalled after it was found to be contaminated with Burkholderia pseudomallei , the bacterial agent that causes melioidosis , which led to four cases of the disease and two deaths. [ 37 ]
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The Aronson Prize ( German : Aronson-Preis ) is a prize awarded for achievements in microbiology and immunology . It was established by the will of the pediatrician and bacteriologist Hans Aronson and has been awarded since 1921. Aronson bequeathed a large part of his estate to the establishment of the prize. The prize is awarded biannually on 8 March, the date of Aronson's death.
In 1969, the foundation that awarded the prize was dissolved on the initiative of its last chairman Georg Henneberg , and the responsibility for the prize and the remaining capital was transferred to the (West) Berlin government, in order to safeguard the existence of the prize. Since 1970, the prize has been awarded by the Senate of Berlin .
The first laureate was August von Wassermann . Among the Aronson laureates are several scientists who later were awarded the Nobel Prize in Physiology or Medicine , such as Karl Landsteiner and Gerhard Domagk . [ 1 ]
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The term " arrested development " has had multiple meanings for over 200 years. In the field of medicine, the term "arrested development" was first used, circa 1835–1836, to mean a stoppage of physical development; the term continues to be used in the same way. [ 1 ] In literature, Ernest Hemingway used the term in The Sun Also Rises , published in 1926: On page 51, Harvey tells Cohn, "I misjudged you [...] You're not a moron. You're only a case of arrested development." [ 2 ]
In contrast, the UK's Mental Health Act 1983 used the term "arrested development" to characterize a form of mental disorder comprising severe mental impairment , resulting in a lack of intelligence. However, some researchers have objected to the notion that mental development can be "arrested" or stopped, preferring to consider mental status as continuing to develop in other ways. Consequently, the term "arrested development" is no longer used when referring to a developmental disorder in mental health. [ 3 ]
In anthropology and archaeology , the term "arrested development" means that a plateau of development in some sphere has been reached. Often it is a technological plateau such as the development of high temperature ceramics without glaze because of a lack of materials, or copper smelting without the development of bronze, because of a lack of tin. [ 4 ] Arrested development is key in the insight of self-domestication in the evolution of hominidae where it involves being in an environment that favors reduction in aggression, including interspecific and intraspecific antagonism , for survival, in favor of attitudes that favor living together in a group, social behavior, traits that favor the group as a whole to come to the front stage, elimination of bullies - individuals with an antisocial personality disorder . [ 5 ]
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The Arris and Gale Lecture , named for Edward Arris and John Gale, is an awarded lectureship of the Royal College of Surgeons . The first lecture was delivered by Sir William Blizard in 1810. [ 1 ] [ 2 ]
In 1646 Edward Arris , an Alderman of the City of London , established a lecture on muscle anatomy. [ 3 ] John Gale, a surgeon, later made a donation for a lecture (Gale anatomy lecture) on the anatomy of bones, the first of which was delivered by Clopton Havers in 1694. [ 3 ] The two lectures were combined in 1810, to form the Arris and Gale Lecture, encompassing all human anatomy and physiology. [ 3 ] The first lecture was delivered by Sir William Blizard in 1810. [ 4 ]
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Arriscope is a fully digital operating microscope delivering high-definition output streams in 3D and is developed and manufactured by Arri . [ 1 ] The Arriscope has been presented to the public in a prototype version in May 2013 on the 84th Annual Meeting of the German Society
of Oto-Rhino-Laryngology, Head and Neck Surgery. [ 2 ] A release date was not published yet.
The microscope is based on the famous Arri Alexa camera system [ 1 ] and
its stereoscopic optics and the led illumination are specially designed to match the camera sensor specifications.
The camera system is carried by a balanced 6-axis stand with pneumatic-driven breaks.
The camera itself produces two full-HD streams that can be displayed on electronic binoculars
and also on a 3D monitor with polarization glasses.
Further specifications have not been released yet as they might change in the final product.
In contrast to conventional optical microscopes it enables patients, students and staff
to see precisely the same view as the surgeon.
Moreover, the same quality images can be recorded for documentation and educative purposes.
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Arteriotomy (or arterotomy ) is a medical term for an opening or cut of an artery wall. [ 1 ] It is a common step in many vascular surgical procedures and operations. The corresponding term for an incision into a vein is a venotomy .
Either a transverse or a longitudinal incision can be made (with respect to the direction of the artery), depending on the situation. The incision is typically made with a scalpel and extended with surgical scissors . [ 2 ]
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The arteriovenous oxygen difference , or a-vO 2 diff , is the difference in the oxygen content of the blood between the arterial blood and the venous blood . It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body. The a-vO 2 diff and cardiac output are the main factors that allow variation in the body's total oxygen consumption, and are important in measuring VO 2 . The a-vO 2 diff is usually measured in millilitres of oxygen per 100 millilitres of blood (mL/100 mL). [ 1 ]
The arteriovenous oxygen difference is usually taken by comparing the difference in the oxygen concentration of oxygenated blood in the femoral , brachial , or radial artery and the oxygen concentration in the deoxygenated blood from the mixed supply found in the pulmonary artery (as an indicator of the typical mixed venous supply). [ citation needed ]
Put in simple terms:
The usual unit for a-vO 2 diff is millilitres of oxygen per 100 millilitres of blood (mL/100 mL), [ 1 ] however, particularly in medical uses, other units may be used, such as micro moles per millilitre (μmol/mL). [ 2 ]
In practice, a-vO 2 diff may be determined using the Fick Principle rather than by taking direct blood samples. In order to do so oxygen consumption (VO 2 ) may be measured using a spirometer to detect gaseous concentrations in exhaled air compared to inhaled air, while cardiac output can be determined using a Doppler ultrasound . [ 3 ]
Arterial blood will generally contain an oxygen concentration of around 20 mL/100 mL. [ 1 ] Venous blood with an oxygen concentration of 15 mL/100 mL would therefore lead to typical values of the a-vO 2 diff at rest of around 5 mL/100 mL. During intense exercise, however, the a-vO 2 diff can increase to as much as 16 mL/100 mL due to the working muscles extracting far more oxygen from the blood than they do at rest. [ citation needed ]
Alternatively, in order to find the efficiency of the lungs in replenishing blood oxygen levels, the a-vO 2 diff may instead be taken by comparing blood from the pulmonary artery and the pulmonary vein ; in this case a negative value for a-vO 2 diff would be obtained as the oxygen content of the blood would have increased. [ citation needed ]
Physical exercise leads to an increase in the arteriovenous oxygen difference in all individuals. As exercise intensities increase, the muscles increase the amount of oxygen they extract from the blood, and this therefore results in further increases in a-vO 2 diff. [ 4 ]
The maximum a-vO 2 diff is also usually greater in trained athletes than in untrained individuals. [ citation needed ] This is a result of aerobic exercise leading to hypertrophy of the slow twitch muscle fibres mainly due to increased capillarisation. The increase in capillary beds in the muscle means that blood supply to that muscle can be greater and diffusion of oxygen, carbon dioxide , and other metabolites increases. [ 5 ] With training the muscles also improve in their ability to extract oxygen from the blood and process the oxygen, [ 5 ] possibly due to adaptations of the mitochondria and an increase in the muscle's myoglobin content. [ citation needed ]
Research has shown that following the commencement of exercise there is a delay in the increase of the a-vO 2 diff, and that a-vO 2 diff only has a marginal impact in the total change in VO 2 in the early stages of exercise. The bulk of the early increase in oxygen consumption after a sudden change in exercise levels results from increased cardiac output. [ 3 ] However it has also been found that the increase in the maximal a-vO 2 diff resulting from adaptations to a physical training program can account for most of the difference in VO 2 max in subjects participating in sub-maximal exercise. [ 6 ]
Arteriovenous oxygen difference is also used in other areas of study such as medicine and medical research . For example, the a-vO 2 diff has been used to measure cerebral blood flow in comatose patients, assisting with their diagnosis and treatment . [ 2 ] The a-vO 2 diff has also been used to determine the effects of physical training in coronary patients . [ 6 ]
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Many species of arthropods (insects, arachnids, millipedes and centipedes) can bite or sting human beings. These bites and stings generally occur as a defense mechanism or during normal arthropod feeding. While most cases cause self-limited irritation, medically relevant complications include envenomation , allergic reactions , and transmission of vector-borne diseases . [ 1 ]
Most arthropod bites and stings cause self-limited redness, itchiness and/or pain around the site. Less commonly (around 10% of Hymenoptera sting reactions), a large local reaction occurs when the area of swelling is greater than 10 centimetres (4 in). Rarely (1-3% of Hymenoptera sting reactions), systemic reactions can affect multiple organs and pose a medical emergency, as in the case of anaphylactic shock . [ 2 ] [ 3 ]
Many arthropods bite or sting in order to immobilize their prey or deter potential predators as a defense mechanism. Stings containing venom are more likely to be painful. Less frequently, venomous spider bites are also associated with morbidity and mortality in humans.
Most arthropod stings involve Hymenoptera (ants, wasps, and bees). While the majority of Hymenoptera stings are locally painful, their associated venom rarely cause toxic reactions unless victims receive many stings at once. The low mortality (around 60 deaths per year in the US out of unreported millions of stings nationwide) associated with Hymenoptera is mostly due to anaphylaxis from venom hypersensitivity . [ 4 ]
Most scorpion stings also cause self-limited pain or paresthesias . Only certain species (from family Buthidae ) inject neurotoxic venom, responsible for most morbidity and mortality. Severe toxic reactions can occur resulting in progressive hemodynamic instability, neuromuscular dysfunction, cardiogenic shock , pulmonary edema , multi-organ failure, and death. Although robust epidemiological data is unavailable, global estimates of scorpion stings exceed 1.2 million resulting in more than 3000 deaths annually. [ 5 ]
Spider bites most often cause minor symptoms and resolve without intervention. Medically significant spider bites involve substantial envenomation from only certain species such as widow spiders and recluse spiders . Symptoms of latrodectism (from widow spiders) may include pain at the bite or involve the chest and abdomen, sweating, muscle cramps and vomiting among others. By comparison, loxoscelism (from recluse spiders) can present with local necrosis of the surrounding skin and widespread breakdown of red blood cells . Headaches, vomiting and a mild fever may also occur. [ 6 ]
Feeding bites have characteristic patterns and symptoms that reflect feeding habits of the offending pest and the chemistry of its saliva. Feeding bites are less likely to be felt at the time of the bite, although there are some exceptions. Since feeding requires longer attachment to prey than envenomation, feeding bites are more often associated with vector transmission of disease. [ 7 ]
In addition to stings and bites causing discomfort in of themselves, bites can also spread secondary infections if the arthropod is carrying a virus, bacteria, or parasite. [ 8 ] The World Health Organization (WHO) estimates that 17% of all infectious diseases worldwide were transmitted by arthropod vectors, resulting in over 700,000 deaths annually. [ 9 ] The table below lists common arthropod vectors and their associated diseases. The figure below represents endemic areas of common vector-borne diseases .
( Culicidae )
Protozoa ( Plasmodia )
Nematode ( Wuchereria bancrofti )
Malaria
Lymphatic filariasis
( Simuliidae )
( Reduviidae )
( Phlebotominae )
( Ixodidae )
Bacteria ( Rickettsia , Anaplasma , Ehrlichia , Borrelia burgdorferi , Coxiella burnetti )
Protozoa ( Babesia )
Rocky Mountain spotted fever , anaplasmosis , ehrlichiosis , Lyme disease , Q fever
Babesiosis
( Glossinidae )
( Tabanidae )
( Siphonaptera , Pulicidae )
( Phthiraptera , Pediculidae )
* Estimated global number of cases annually according to WHO in 2017. [ 9 ] If a vector transmits multiple diseases, aggregate case numbers are listed. Rough estimates are only meant to provide a sense of scale. Unknown disease burden is listed as NA for not available.
Most arthropod bites and stings do not require a specific diagnosis since they typically improve with supportive management alone. Certain bites and stings present with characteristic appearances and distributions. In general, however, dermoscopic findings of bitten or stung skin rarely aid in diagnosis. [ 11 ] Rather, patient history (recent travel to endemic areas, outdoor activities, and other risk factors) primarily guides the diagnostic approach, which can raise clinical suspicion for more serious complications like vector-borne diseases.
Skin biopsies are not indicated for bites or stings, since the histomorphologic appearance is non-specific . Bites and stings as well as other conditions (e.g. drug reactions, urticarial reactions , and early bullous pemphigoid ) can cause microscopic changes such as a wedge -shaped superficial dermal perivascular infiltrate consisting of abundant lymphocytes and scattered eosinophils , as shown in the adjacent figure: [ 12 ]
Prevention strategies against arthropod bites and stings comprise measures for personal protection, travel advisories, public health and environmental concerns.
Travelers should seek to minimize outdoor activity during peak activity times and avoid high risk areas such as regions with known outbreaks or epidemics . Standing water and dense vegetation also commonly attract arthropods. Clothes covering most exposed skin can also provide a measure of physical protection, which may be augmented when the fabric is treated with pesticides such as Permethrin . Topical repellants such as N,N-diethyl-m-toluamide ( DEET ) is supported by a large body of evidence. [ 7 ]
Vaccines may also help prevent vector-borne diseases for eligible patients. For example, Japanese encephalitis , Yellow fever , and Dengue fever have FDA-approved vaccines available. Since they are relatively new vaccines, however, they are not standard of care as of 2023. Additionally, patients traveling to Malaria endemic regions are routinely prescribed Malaria chemoprophylaxis . [ 13 ]
Patients with a history of venom hypersensitivity may benefit from venom immunotherapy (VIT). Patients eligibile for VIT include those with a prior anaphylactic reaction to a venomous sting and who have IgE to venom allergens. VIT can help prevent future severe systemic reactions in select patients. [ 2 ]
International organizations such as WHO aim to reduce disease burdens of neglected tropical diseases, many of which are vector borne. [ 14 ] Such campaigns must incorporate multipronged approaches to consider global inequality, access to resources, and climate change . [ citation needed ]
Most arthropod bites and stings require only supportive care. However, complications such as envenomation and severe allergic reactions can present as medical emergencies.
Local reactions to bites and stings are treated symptomatically. If a stinger is still embedded, manual removal can reduce further irritation. Washing the affected area with soap and water can help reduce risk of contamination. Oral antihistamines , calamine lotion, topical corticosteroids and cold compresses are common over the counter remedies to reduce itchiness and local inflammation. In more severe cases, such as large local reactions, systemic glucocorticoids are sometimes prescribed, although limited evidence supports their effectiveness. There are limited data to support one treatment over another. [ 15 ]
Systemic reactions from venom hypersensitivity can rapidly progress to a medical emergency. The mainstay of anaphylactic shock management is intramuscularly injected epinephrine . The patient should be stabilized and transferred to an intensive care unit. [ 2 ]
Toxic reactions to envenomation are similarly managed with medical stabilization and symptomatic treatment. Tetanus prophylaxis should be up to date but antibiotics are typically unnecessary unless a bacterial superinfection is suspected. Antivenom drugs have been created for certain species such as Centruroides scorpion stings, but these drugs are not yet widely available and so typically reserved for severe systemic toxicity. [ 15 ]
Several vector-borne diseases can present emergently.
After confirmation of diagnosis, antimicrobials are prescribed according to standard of care.
A bite is defined as coming from the mouthparts of the arthropod . The bite consists of both the bite wound and the saliva . The saliva of the arthropod may contain anticoagulants , as in insects and arachnids which feed from blood. Feeding bites may also contain anaesthetic , to prevent the bite from being felt. Feeding bites may also contain digestive enzymes , as in spiders ; spider bites have primarily evolved to paralyse and then digest prey. A sting comes from the abdomen; in most insects (which are all largely hymenopterans ), the stinger is a modified ovipositor , [ 16 ] which protrudes from the abdomen. The sting consists of an insertion wound, and venom. The venom is evolved to cause pain to a predator, paralyse a prey item, or both. Because insect stingers evolved from ovipositors, in most hymenopterans only the female can sting. However, there are a few orders of wasp where the male has evolved a "pseudo sting" - the male genitalia has evolved two sharp protrusions which can deliver an insertion wound. However, they do not contain venom, so they are not considered a true sting. [ 17 ] In ants that bite instead of sting, such as the Formicinae , the bite causes the wound, but during the bite the abdomen bends forward to spray formic acid into the wound, causing additional pain. In arachnids that sting (all largely scorpions ), the stinger is not a modified ovipositor, but instead a metasoma that bears a telson. [ 18 ] (Scorpions lack an ovipositor entirely and give birth to live young .)
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Arthroscopy: The Journal of Arthroscopic and Related Surgery is a peer-reviewed medical journal that was established in 1985 and covers research on the clinical practice of arthroscopic and minimally invasive surgery , a subspecialty of orthopedic surgery . It is the official journal of the Arthroscopy Association of North America . The initiative in establishing the journal was taken by Imran sheikh and the first editor-in-chief was S. Ward Casscells, who was succeeded in 1992 by Gary G. Poehling. In 2014 James H. Lubowitz succeeded the retiring Dr. Poehling. [ 1 ] [ 2 ] Arthroscopy Techniques is an open access online companion journal publishing peer-reviewed techniques videos.
The journal is abstracted and indexed by MEDLINE , Web of Science , and Scopus .
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See tips for writing articles about academic journals . Further suggestions might be found on the article's talk page .
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In surgery , an arthrotomy is the creation of an opening in a joint that may be used in drainage . [ 1 ]
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Arthur DeBoer , (July 2, 1917-July 31, 2007), was an American cardiologist specializing in cardiac surgery at Northwestern University 's Feinberg School of Medicine . DeBoer was one of the pioneer cardiac surgeons in Chicago and was on staff at Wesley Memorial Hospital (later called Northwestern University Hospital ). DeBoer was the hospital's first chief of cardiothoracic surgery, and performed the first open heart operation at Wesley Memorial Hospital in 1958. [ citation needed ] He served as Chair of Northwestern's Department of Cardiovascular Surgery until 1975. [ 1 ] He was also a pioneer in research on congenital heart defects .
He was born to John and Lucy DeBoer in Gallatin County, Montana , and was a graduate of Montana Normal School (now University of Montana Western ) earning his B.E. Degree in 1938. He earned a B.S. Degree from University of Montana while teaching school. He graduated from Northwestern University Medical School in 1946 and after serving his internship at Wesley Hospital he served in the U.S. Army Medical Corps in Asia. [ 1 ]
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The Articella ('little art') or Ars medicinae ('art of medicine') is a Latin collection of medical treatises bound together in one volume that was used mainly as a textbook and reference manual between the 13th and the 16th centuries. In medieval times , several versions of this anthology circulated in manuscript form among medical students. Between 1476 and 1534, printed editions of the Articella were also published in several European cities.
The earliest surviving manuscript of the collection was copied just after 1100. The original five texts, in their standard order, are the Isagoge Ioannitii ad Tegni Galieni by Hunayn ibn Ishaq ; the Hippocratic Aphorisms and Prognostics ; the De urinis of Theophilus Protospatharius ; and the De pulsibus of Philaretus . The collection is usually supposed to have grown around Hunayn's Isagoge , an abridged introduction to Galen 's classical Greek treatise Ars medica ( Techne iatrike ) translated from Arabic into Latin by Constantine the African in the 11th century. It circulated independently of the Articella . In the late 12th century, Galen's Ars was added to the Articella as a sixth text under the title Tegni . It was later moved into second place. [ 1 ]
In the mid-13th century, the emergence of formal medical education in several European universities fueled a demand for comprehensive textbooks. Instructors from the influential Salernitan medical school in southern Italy popularized the practice of binding other treatises together with their manuscript copies of the Isagoge .
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Articulating paper is a diagnostic tool used in dentistry to highlight occlusal contacts and the distribution of occlusal forces. That is, it marks those points on the teeth where the teeth contact during biting and grinding. [ 1 ] Articulating paper is made of a thin, non-adhesive paper strip covered in fluorescent ink or dye-containing wax. [ 2 ] A strip of articulating paper is placed between the teeth while the desired mandibular movements are performed. Articulating paper is manufactured as "books" of many leaves which are torn out and used when required. These can be rectangular or dental-arch (horse shoe) shaped .
Example uses of articulating paper include:
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In audiology , the Articulation Index (AI) is a tool used to predict the amount of speech that is audible to a patient with a specific hearing loss . The AI figure for a given patient can range from zero to one, representing the proportion of the average speech signal that is audible. The closer the AI is to one, or 100 percent , the better the person should be able to hear speech. The calculation is also used in industrial settings for the design of safety devices, such as flight helmets , where audio signals are required to be clearly heard.
The AI is often used as a counseling tool since it presents an individual's hearing loss in terms of percentage of speech that is audible during a typical one-on-one conversation. The AI can also be used to measure the effectiveness of hearing aids and other forms of amplification devices.
Since the creation of the AI, there have been several proposed ways to simplify and increase its use. In 1990, Gustav Mueller and Mead Killion proposed an AI calculation involving one hundred dots on an audiogram , each of which represented an important speech frequency ; the proportion of dots audible to the listener estimates the patient's AI. Unfortunately, not all areas on the audiogram (taking into account frequencies and intensity levels) are equally weighted. According to this procedure, the highest density of the audiogram dots is concentrated in the frequency region of 1-3 kHz , since this is the region containing the most speech information.
In many industrial settings noise exposure metrics have been established to quantify human exposure to sound. In aerospace settings the Speech Intelligibility Index (SII), published in 1986 by the American National Standards Institute , is a major revision of the AI standard and defines computational methods "that produce results highly correlated with the intelligibility of speech under a variety of adverse listening conditions, such as noise masking, filtering and reverberation". [ 1 ]
Amlani, A., Punch, J., and Ching, T. (2002), "Methods and Applications of the Audibility Index in Hearing Aid Selection and Fitting" in Trends in Amplification , 6(3), pp. 81–129: [1]
Mueller, G. and Killion, M. (1990), "An Easy Method for Calculating the Articulation Index" in The Hearing Journal , 43(9), pp. 14–17: [2]
French, N.R. and Steinberg, J.C. (1947), "Factors governing the intelligibility of speech sounds" in J Acoust Soc Am , 19, p. 90: [3]
Kryter, K.D. (1962), "Methods for the calculation and use of the Articulation Index" in J Acoust Soc Am , 34(11): pp. 1689–1697.
Kryter, K.D. (1962), "Validation of the Articulation Index" in J Acoust Soc Am , 34(11): pp. 1668: [4] .
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An artificial facet replacement is a joint prosthesis intended to replace the natural facets and other posterior elements of the spine, restoring normal (or near-normal) motion while providing stabilization of spinal segments. It is typically used as an adjunct to laminectomy , laminotomy , neural decompression , and facetectomy , in lieu of standard lumbar fusion . [ 1 ] The prosthesis is indicated for back and leg pain caused by central or lateral spinal stenosis , degenerative disease of the facets with instability, and grade 1 degenerative spondylolisthesis with objective evidence of neurological impairment. [ 1 ]
Patents related to facet replacement have been around since the 1980s; more intense research into artificial facet replacement as an effective and marketable prosthesis has been ongoing since the mid-2000s. [ 2 ] Prominent researched options include:
In 2011, in a retrospective and future analysis of the technology in the International Journal of Spine Surgery , Serhan et al. opined that artificial facet replacement still had much to prove:
In the future, facet replacement devices will require a substantial amount of validation testing and numerous clinical studies before they can be considered a viable treatment option for the treatment of spinal disorders. To date, most pathophysiologic research and thus surgical treatments have been focused on the disc as a pain generator. A more comprehensive focus on re-establishing the structure and function of the human functional spinal unit may include facet replacement. A better understanding of facet function and facet-mediated pain, possibly through classification of facet degeneration, may be needed to support the use of such devices. [ 2 ]
More recently, an August 2014 critique in the journal Neurosurgery has suggested that research aside, at least in the United States the regulatory process has led to "time lag inherent in the design, development and implementation of new technologies" such as artificial facet replacement, noting that both ACADIA and TOPS were still not FDA -approved within the U.S. [ 1 ]
In the short-term, study literature has provided "insufficient support" for the prosthesis, with pessimal results for the procedure. [ 9 ] : 168 [ 10 ] However, more long-term results (such as those from the seven-year follow-up on TOPS implants) have been encouraging, albeit limited by patient sample size. [ 5 ]
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An artificial heart valve is a one-way valve implanted into a person's heart to replace a heart valve that is not functioning properly ( valvular heart disease ). Artificial heart valves can be separated into three broad classes: mechanical heart valves, bioprosthetic tissue valves and engineered tissue valves.
The human heart contains four valves: tricuspid valve , pulmonary valve , mitral valve and aortic valve . Their main purpose is to keep blood flowing in the proper direction through the heart, and from the heart into the major blood vessels connected to it (the pulmonary artery and the aorta ). Heart valves can malfunction for a variety of reasons, which can impede the flow of blood through the valve ( stenosis ) and/or let blood flow backwards through the valve ( regurgitation ). Both processes put strain on the heart and may lead to serious problems, including heart failure . While some dysfunctional valves can be treated with drugs or repaired, others need to be replaced with an artificial valve. [ 2 ]
A heart contains four valves (tricuspid, pulmonary, mitral and aortic valves) which open and close as blood passes through the heart. [ 3 ] Blood enters the heart in the right atrium and passes through the tricuspid valve to the right ventricle. From there, blood is pumped through the pulmonary valve to enter the lungs. After being oxygenated, blood passes to the left atrium, where is it pumped through the mitral valve to the left ventricle. The left ventricle pumps blood to the aorta through the aortic valve .
There are many potential causes of heart valve damage, such as birth defects, age related changes, and effects from other disorders, such as rheumatic fever and infections causing endocarditis . High blood pressure and heart failure which can enlarge the heart and arteries, and scar tissue can form after a heart attack or injury. [ 4 ]
The three main types of artificial heart valves are mechanical, biological (bioprosthetic/tissue), and tissue-engineered valves. In the US, UK and the European Union, the most common type of artificial heart valve is the bioprosthetic valve. Mechanical valves are more commonly used in Asia and Latin America. [ citation needed ] Companies that manufacture heart valves include Edwards Lifesciences, [ 5 ] Medtronic, [ 6 ] Abbott (St. Jude Medical), [ 7 ] CryoLife, [ 8 ] and LifeNet Health. [ 9 ]
Mechanical valves come in three main types – caged ball, tilting-disc and bileaflet – with various modifications on these designs. [ 10 ] Caged ball valves are no longer implanted. [ 11 ] Bileaflet valves are the most common type of mechanical valve implanted in patients today. [ 12 ]
The first artificial heart valve was the caged ball valve, a type of ball check valve , in which a ball is housed inside a cage. When the heart contracts and the blood pressure in the chamber of the heart exceeds the pressure on the outside of the chamber, the ball is pushed against the cage and allows blood to flow. When the heart finishes contracting, the pressure inside the chamber drops and the ball moves back against the base of the valve forming a seal.
In 1952, Charles A. Hufnagel implanted caged ball heart valves into ten patients (six of whom survived the operation), marking the first success in prosthetic heart valves. [ citation needed ] A similar valve was invented by Miles 'Lowell' Edwards and surgically implanted for the first time by surgeon Albert Starr in 1960. Today, the early version is known as the Starr-Edwards silastic ball valve. [ 13 ] This consisted of a silicone ball enclosed in a methyl metacrylate cage welded to a ring. The Starr-Edwards valve was first implanted in a human on August 25, 1960, and was discontinued by Edwards Lifesciences in 2007. [ 13 ]
Caged ball valves are strongly associated with blood clot formation, so people who have one required a high degree of anticoagulation , usually with a target INR of 3.0–4.5. [ 14 ]
Introduced in 1969, the first clinically available tilting-disc valve was the Bjork-Shiley valve . [ 15 ] Tilting‑disc valves, a type of swing check valve , are made of a metal ring covered by an ePTFE fabric. The metal ring holds, by means of two metal supports, a disc that opens when the heart beats to let blood flow through, then closes again to prevent blood flowing backwards. The disc is usually made of an extremely hard carbon material ( pyrolytic carbon ), enabling the valve to function for years without wearing out. [ citation needed ]
Introduced in 1979, bileaflet valves are made of two semicircular leaflets that revolve around struts attached to the valve housing. With a larger opening than caged ball or tilting-disc valves, they carry a lower risk of blood clots. They are, however, vulnerable to blood backflow. [ citation needed ]
The major advantage of mechanical valves over bioprosthetic valves is their greater durability. [ 16 ] Made from metal and/or pyrolytic carbon , [ 10 ] they can last 20–30 years. [ 16 ]
One of the major drawbacks of mechanical heart valves is that they are associated with an increased risk of blood clots . Clots formed by red blood cell and platelet damage can block blood vessels leading to stroke . People with mechanical valves need to take anticoagulants (blood thinners), such as warfarin , for the rest of their life. [ 16 ] Mechanical heart valves can also cause mechanical hemolytic anemia , a condition where the red blood cells are damaged as they pass through the valve. [ citation needed ] Cavitation , the rapid formation of microbubbles in a fluid such as blood due to a localized drop of pressure, can lead to mechanical heart valve failure, [ 17 ] so cavitation testing is an essential part of the valve design verification process.
Many of the complications associated with mechanical heart valves can be explained through fluid mechanics . For example, blood clot formation is a side effect of high shear stresses created by the design of the valves. From an engineering perspective, an ideal heart valve would produce minimal pressure drops, have small regurgitation volumes, minimize turbulence, reduce prevalence of high stresses, and not create flow separations in the vicinity of the valve. [ citation needed ]
Implanted mechanical valves can cause foreign body rejection. The blood may coagulate and eventually result in a hemostasis. The usage of anticoagulation drugs will be interminable to prevent thrombosis. [ 18 ] [ non-primary source needed ]
Bioprosthetic valves are usually made from animal tissue (heterograft/ xenograft ) attached to a metal or polymer support. [ 11 ] Bovine (cow) tissue is most commonly used, but some are made from porcine (pig) tissue. [ 19 ] [ non-primary source needed ] The tissue is treated to prevent rejection and calcification . [ citation needed ]
Alternatives to animal tissue valves are sometimes used, where valves are used from human donors, as in aortic homografts and pulmonary autografts . An aortic homograft is an aortic valve from a human donor, retrieved either after their death or from a heart that is removed to be replaced during a heart transplant. [ 12 ] A pulmonary autograft, also known as the Ross procedure , is where the aortic valve is removed and replaced with the patient's own pulmonary valve (the valve between the right ventricle and the pulmonary artery). A pulmonary homograft (a pulmonary valve taken from a cadaver) is then used to replace the patient's own pulmonary valve. This procedure was first performed in 1967 and is used primarily in children, as it allows the patient's own pulmonary valve (now in the aortic position) to grow with the child. [ 12 ]
Bioprosthetic valves are less likely than mechanical valves to cause blood clots, so do not require lifelong anticoagulation. As a result, people with bioprosthetic valves have a lower risk of bleeding than those with mechanical valves. [ 16 ]
Tissue valves are less durable than mechanical valves, typically lasting 10–20 years. [ 20 ] This means that people with bioprosthetic valves have a higher incidence of requiring another aortic valve replacement in their lifetime. [ 16 ] Bioprosthetic valves tend to deteriorate more quickly in younger patients. [ 21 ]
In recent years, scientists have developed a new tissue preservation technology, with the aim of improving the durability of bioprosthetic valves. In sheep and rabbit studies, tissue preserved using this new technology had less calcification than control tissue. [ 22 ] A valve containing this tissue is now marketed, but long-term durability data in patients are not yet available. [ 23 ] [ non-primary source needed ]
Current bioprosthetic valves lack longevity, and will calcify over time. [ 24 ] When a valve calcifies, the valve cusps become stiff and thick and cannot close completely. [ 24 ] Moreover, bioprosthetic valves can't grow with or adapt to the patient: if a child has bioprosthetic valves they will need to get the valves replaced several times to fit their physical growth. [ 24 ]
For over 30 years researchers have been trying to grow heart valves in vitro . [ 25 ] These tissue‑engineered valves involve seeding human cells on to a scaffold. [ 25 ] The two main types of scaffold are natural scaffolds, such as decellularized tissue, or scaffolds made from degradable polymers. [ 26 ] The scaffold acts as an extracellular matrix , guiding tissue growth into the correct 3D structure of the heart valve. [ 26 ] [ 25 ] Some tissue-engineered heart valves have been tested in clinical trials, [ 26 ] but none are commercially available.
Tissue engineered heart valves can be person-specific and 3D modeled to fit an individual recipient [ 27 ] 3D printing is used because of its high accuracy and precision of dealing with different biomaterials. [ 27 ] Cells that are used for tissue engineered heart valves are expected to secrete the extracellular matrix (ECM). [ 24 ] Extracellular matrix provides support to maintain the shape of the valves and determines the cell activities. [ 28 ]
Scientists can follow the structure of heart valves to produce something that looks similar to them, but since tissue engineered valves lack the natural cellular basis, they either fail to perform their functions like natural heart valves, or function when they are implanted but gradually degrade over time. [ citation needed ] An ideal tissue engineered heart valve would be non-thrombogenic, biocompatible, durable, resistant to calcification, grow with the surrounding heart, and exhibit a physiological hemodynamic profile. [ 29 ] To achieve these goals, the scaffold should be carefully chosen—there are three main candidates: decellularized ECM (xenografts or homografts), natural polymers, and synthetic polymers. [ 29 ]
Mechanical and tissue valves are made of different materials. Mechanical valves are generally made of titanium and carbon. [ 30 ] Tissue valves are made up of human or animal tissue. The valves composed of human tissue, known as allografts or homografts, are from donors' human hearts. [ 30 ]
Mechanical valves can be a better choice for younger people and people at risk of valve deterioration due to its durability. It is also preferable for people who are already taking blood thinners and people who would be unlikely to tolerate another valve replacement operation. [ citation needed ]
Tissue valves are better for older age groups as another valve replacement operation may not be needed in their lifetime. Due to the risk of forming blood clots for mechanical valves and severe bleeding as a major side effect of taking blood-thinning medications, people who have a risk of blood bleeding and are not willing to take warfarin may also consider tissue valves. Other patients who may be more suitable for tissue valves are people who have other planned surgeries and unable to take blood-thinning medications. People who plan to become pregnant may also consider tissue valves as warfarin causes risks in pregnancy. [ citation needed ]
An artificial heart valve should ideally function like a natural heart valve. [ 11 ] The functioning of natural heart valves is characterized by many advantages:
The performance of an artificial heart valve can be tested in vitro before clinical use by means of a pulse duplicator . [ 32 ]
Artificial heart valves are expected to last from 10 to 30 years. [ 16 ]
The most common problems with artificial heart valves are various forms of degeneration, including gross billowing of leaflets, ischemic mitral valve pathology, and minor chordal lengthening. [ 24 ] The repairing process of the artificial heart valve regurgitation and stenosis usually requires an open-heart surgery, and a repair or partial replacement of regurgitant valves is usually preferred. [ 24 ]
Researchers are investigating catheter-based surgery that allows repair of an artificial heart valve without large incisions. [ 33 ]
Researchers are investigating Interchangeable Prosthetic Heart Valve that allows redo and fast-track repair of an artificial heart valve. [ 34 ]
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An artificial hymen is a type of prosthetic created for the purpose of simulating an idealized human hymen , usually to fake virginity, [ 1 ] [ 2 ] which some wrongly believe can be identified by the appearance, tightness, or bleeding of the hymen during vaginal penetration. [ 3 ] [ 4 ]
Artificial hymens are made of a material which, when properly inserted, adhere to the inside of the vagina , temporarily giving the appearance of an idealized "intact" hymen and releasing a red liquid that looks like blood when subjected to pressure. [ 5 ]
Artificial hymens do not mimic real hymens, but an false idealized popular image of hymens. While there is a popular misconception that hymens are either "intact" or "broken", there is no such distinction, and there is no medical or scientific way to prove or disprove virginity by the state of the hymen. Real hymens do not in fact "break", and more often than not do not tear or alter during vaginal intercourse, being quite elastic after puberty. Hymens have few blood vessels and may not bleed significantly even if torn. Vaginal walls are more likely to bleed, due to lack of lubrication or forced penetration. [ 3 ] [ 4 ]
There are various opinions on artificial hymen treatments and related "hymen reconstruction" surgeries . These arguments may range from the perspectives and experiences of medical professionals performing the procedures to the women who are directly involved in seeking them out. These outlooks are founded on discussing what the role of the prosthetic is on society's adherence to the concept of virginity, specifically the virginity of women. In addition to medical professionals arguing against these procedures, there have also been feminist writers and other individuals who have argued against the use of artificial hymen for differing reasons. Alternatively, there are other accounts from feminist writers and different women who argue for the existence of these procedures for various reasons. [ citation needed ]
The majority of the retaliation for artificial hymen stems from different individuals finding it either oppressive to women or deceitful towards others. Many scholars find the artificial hymen and related procedures to be degrading of women. They specifically argue that these procedures act in parallel with other forms of patriarchal control over women's bodies. [ 6 ] [ 7 ] The medical community has also established how it is typical for many women to not bleed during their first intercourse, [ 8 ] [ 9 ] and that hymen "restoration" procedures further glorify myths surrounding hymens alongside patriarchal ideals surrounding female virginity. [ 10 ] In continuation, other scholars argue that by obtaining these procedures women are giving up bodily autonomy and complying with societal expectations of the concept of virginity. Alternatively, more conservative-leaning individuals argue that these procedures should be banned because they are morally wrong and deceitful towards others. More specifically, Egyptian lawmakers have argued for the banning of artificial hymen products because they believed they encouraged women to participate in pre-marital sex by allowing them to fake their virginity, which goes against the standards set in place through their religious beliefs. [ 11 ] [ 12 ]
The existence of the artificial hymen has also been supported by medical professionals, feminist scholars, and women seeking out the procedures. In overview, these individuals generally argue that these procedures further degrade the patriarchy while providing women with bodily autonomy and a means to cope with trauma. Feminist scholars and professors who have written on this subject have held a controversial opinion in stating that hymen "reconstruction" procedures exist as a manner for which women could further weaken the control that the patriarchy holds over them. They see the choice to obtain an artificial hymen and related procedures as empowering by allowing women to obtain control over their sexuality. [ 13 ] Research on hymen "reconstruction" focused on interviewing the women obtaining these procedures has further revealed their personal experiences. Some of these studies have highlighted how women that have suffered sexual trauma find these procedures as a form of coping. [ 14 ] [ 15 ]
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An artificial iris is an intraocular implant (implant inside the eye) that is used as both a cosmetic and to treat those with aniridia (missing or damaged irises ) or other eye trauma. [ 1 ] People with this condition experience photophobia , or increased sensitivity to light. [ 2 ] The artificial iris, made from silicone , acts as a replacement iris. The artificial iris is implanted in the eye using different surgery techniques depending on the patient's eye trauma. Most of the major artificial iris manufacturers are European and the treatment is used sparingly in the United States because of limited FDA approval, in part due to possibility of vision loss and other risks. [ 3 ]
The iris controls how much light enters the eye, so if a person has a damaged iris or lacks an iris ( aniridia ), they can experience large amounts of glare from normal daylight. [ 4 ] They may also have other visual disturbances such as seeing arcs or halos. Implanting an artificial iris allows the patient's eye to regulate light. After implantation, patients saw an improvement in overall visual acuity , contrast sensitivity , depth of focus , and a decrease in perceived glare. [ 5 ]
The artificial iris treats those who were born with aniridia or who have experienced eye trauma that lead to a damaged iris, such as a complication from eye surgeries like ruptured globe repair. It is only recommended to get surgical implants if the patient has aphakic (absence of lens) or pseudophakic (artificial lens) eyes. The artificial iris is an alternative to eyepatches, sunglasses, or blackout contact lenses. [ 6 ]
Artificial irises may be implanted into people with healthy eyes to change their eye color. These cosmetic irises are marketed as an alternative to cosmetic contact lenses . Cosmetic implants are criticized by ophthalmologists as they can lead to vision loss in healthy eyes. [ 3 ]
Each artificial iris is custom-made for the patient's eye, using an image of their undamaged iris, or any other iris as reference. [ 7 ] [ 6 ] Artificial irises are made from silicone or other polymer matrix composites into a disk shape with a hole in the middle. Encased inside, is the color design. Before implantation, the iris' size is adjusted to fit the eye. The implants can be made with a tough fiber mesh so that they can be sewn onto a damaged iris. When there is no iris to attach to, the implants are made without the mesh to be more flexible to adapt to the eye's shape. [ 6 ] [ 7 ]
The artificial iris is implanted in the area of the eye behind the iris and in front of the ciliary body (what focuses your eye) in an area called the ciliary sulcus. Multiple techniques can be used to implant artificial irises that involve the use of forceps , injector systems, and suturing . [ 2 ] The artificial iris is folded and placed in a cartridge on the side of the injector that is then injected into the ciliary sulcus like a syringe . [ 8 ] All operations are performed with the patient under general anesthesia . [ 2 ]
When only part of the iris is damaged, surgeons cut the artificial iris into a segment that covers the damaged area. The segment is folded and inserted into a clear corneal incision using an injector or forceps. That segment is then unfolded and sutured to the damaged iris. [ 2 ] [ 9 ]
When the patient has complete aniridia, the artificial iris can be folded and inserted through a corneal or scleral incision via an injector system or forceps. After the iris is unfolded, it does not need to be sutured. This version of the artificial iris is more flexible and will adapt to the shape of the eye. [ 9 ]
To prevent hemorrhaging of the eye, ophthalmologists use silicone oil as a tamponade (block bleeding). The oil surrounds the eye and it is viscous enough to prevent bleeding. [ 11 ] Some patients who have eye trauma require a long-term silicone oil tamponade. To prevent the silicone oil from touching the cornea and causing corneal dystrophy, a diaphragm made of polymethylacrylate (PMMA) is installed to seal the area around the cornea. [ 12 ] For patients needing a long-term silicone oil tamponade, it is possible to implant an artificial iris that will act as this diaphragm while also appearing as a natural iris. [ 7 ] However, if the patient's eyes are hypotonic (have low pressure), there is still a chance of silicone oil breaching the diaphragm. [ 5 ]
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An artificial urinary sphincter ( AUS ) is an implanted device to treat moderate to severe stress urinary incontinence , most commonly in men. The AUS is designed to supplement the function of the natural urinary sphincter that restricts urine flow out of the bladder .
There are two types of artificial urinary sphincters:
The common theme among currently available designs is a mechanical constriction mechanism – an inflatable cuff filled with sterile saline solution and placed around the urethra which keeps the urethral lumen closed; this is due to the pressure produced inside the device and an externally accessible control pump mechanism placed between two skin layers of the scrotum (subdartos pouch) which allows the user to manually relieve the constriction to allow urination.
Frederic Foley was the first to describe an externally worn artificial urinary sphincter to treat urinary incontinence, published in 1947. [ 5 ] In 1972, F. Brantley Scott and colleagues from Baylor College of Medicine designed the first precursor of contemporary artificial urinary sphincter. [ 6 ] [ 7 ] The first AUS model on the market was the AMS 800 ( Boston Scientific , Marlborough , MA ), developed 50 years ago. [ 8 ] [ 9 ] It is a 3-component device with a cuff placed around the urethra, a pump inserted in the scrotum and a pressure generating reservoir placed in the pelvis, which comes as a kit to prepare and to fill up before implantation. [ 10 ]
Another AUS model is the ZSI 375 ( Zephyr Surgical Implants , Geneva , Switzerland ), introduced in 2008. [ 11 ] It is a one-piece two-part device with a cuff and a pump unit with an integrated spring; it comes in one piece, pre-connected and pre-filled. [ 1 ] [ 12 ] There is no abdominal component in the ZSI 375, which along with its ready-to-implant configuration reduces the operating time. [ 13 ] Furthermore, because there is no abdominal component, surgical interventions in the retroperitoneal space are not required. Previous surgeries, such as radical prostatectomy, may lead to post-operative scarring and fibrosis in the retroperitoneal space. Thus, avoiding dissection of retroperitoneal tissues avoids risks of surgical complications. [ 14 ] [ 15 ] Another advantage of the ZSI 375 model is the possibility to increase or decrease the pressure inside the device after implantation to meet the desired continence rate and satisfaction of the patient. These adjustments particularly help to control continence in cases of post-implantation urethral atrophy or urinary retention (poor urine flow). [ 16 ] [ 17 ] [ 13 ] Adjustment of the pressure can be done in an outpatient setting by adding or removing sterile saline solution via a syringe through the scrotum . [ 12 ] By 2019, more than 4,500 ZSI 375 artificial urinary sphincters have been implanted worldwide. [ 11 ] In addition to the devices mentioned above, new devices are being brought to market, such as the Rigicon ContiClassic and ContiReflex Artificial Urinary Sphincter systems. [ 18 ] [ 19 ]
In both models, sterile saline solution inside the system is used to generate pressure and compress the urethra (to prevent urine from leaking). The urethral cuff is deflated manually by pressing the control pump that is placed in the scrotum, allowing the patient to empty the bladder. The urethral cuff then re-inflates automatically to refill the urethral cuff and once again prevent urine from leaking. [ 20 ] [ 21 ]
The list includes AUS models available in 2023:
The intrinsic sphincter deficiency leading to stress incontinence is the most common indication for AUS implantation. [ 9 ] The European Association of Urology recommends AUS implantation for moderate-to-severe stress incontinence in men. [ 22 ] Additionally, despite the novel treatment options ( slings , urethral bulking injections , stem-cell therapy ), AUS is considered to be the gold standard surgical management both for stress incontinence in men and for urinary incontinence developed as a complication of surgery, such as prostatectomy , cystectomy and TURP . [ 8 ] [ 4 ] [ 3 ]
There are several case reports published in the literature of AUS implantation in children for secondary incontinence resulting from traumatic urethral injury . [ 23 ] [ 24 ]
There is limited data on AUS use in women, and not every product available in the market is designed for use in women. [ 25 ] [ 26 ] The European Association of Urology provides limited recommendation on AUS use in women, stating that although cure is possible the risk of complication is high. [ 22 ] Nonetheless, AUS has been used as a last resort for treating urinary incontinence in women due to congenital causes and secondary to neurological diseases. [ 25 ]
Numerous studies have been published regarding the outcomes of patients that have undergone artificial urinary sphincter implantation. The success rate, generally defined as achieving total (no pad use) or social continence (use of ≤1 pad/day) with the implanted device, ranges from 61% to 100% in the literature. [ 4 ] Improvement in quality of life has also been considered as success even if more than 1 pad/day was needed. The success rate was reported at 78% with a 3-year follow-up, [ 27 ] and over 72% with 5 to 7 years of follow-up. [ 28 ] In a recent systematic review, the success rate was reported to be 79% with follow-up period ranging from 5 months to 16 years. [ 29 ] A comparative study among patients implanted with different models of artificial urinary sphincter and achieved social continence showed no difference between two groups in regards of urodynamic tests , such as flow rate , urethral pressure , etc. [ 2 ] A randomised controlled trial found that the artificial urinary sphincter was non-inferior to the male or synthetic sling with respect to improving incontinence. The male sling was more cost-effective. [ 30 ] [ 31 ]
In different studies with a mean follow-up of more than 6 years, [ 32 ] [ 33 ] at least 73% of men with an implanted artificial urinary sphincter were satisfied or very satisfied with the device, and 10-23% reported dissatisfaction. At shorter periods of follow-up (2–4 years) the satisfaction rates achieved over 90%. [ 29 ] [ 32 ] [ 4 ] In another study with mean follow-up of over 7 years, the overall satisfaction rate measured 3.9 on a scale from 0 to 5. [ 32 ] The satisfaction rate in patients after radiotherapy does not seem to be unfavorably affected. [ 34 ] The initial satisfaction with the continence rate is reported to be improved by adjusting the pressure inside the implant with the ZSI 375 model. [ 26 ]
Surveys of patients that underwent the procedure have found that over 90% would recommend the procedure to a friend or relative with the same problem, and over 90% would undergo the implantation again. [ 35 ] [ 36 ] Along with this, 14% of patients reported improvement in sexual activity. [ 36 ]
The quality of life after AUS implantation has been shown to be significantly improved in numerous studies using various scaling tools. [ 29 ] [ 7 ] And the quality of life appears not to be adversely affected by reinterventions, providing that the device continues to function after the revision. [ citation needed ]
In the largest available series evaluating 1082 patients that underwent primary AUS placement, the 5-year device survival rate was 74% which is consistent with the reported outcomes in the literature, ranging from 59% to 79%. [ 37 ] Notably, in all series, over time some patients needed to undergo a repeat surgery for recurrent urinary incontinence or infection of the device. In a pooled analysis of the available studies the reintervention rate (for any cause) was roughly 26%. [ 29 ] Significantly, some studies have demonstrated that surgeons who perform this procedure more frequently (high-volume surgeons) have improved outcomes compared to those who do them less frequently. [ 26 ] In fact, in this series the reoperative rates decreased by approximately 50% as surgeons reached their 200th case emphasizing the need for potential patients to seek high volume surgeons to improve their chance of success. [ 26 ]
Possible risks arising from the implantation of the AUS include: [ 1 ]
The overall reported complication rate in males is 37%. [ 38 ] The most common postoperative complications are:
Other less frequent complications are hematoma , urethral stenosis , urinary fistula . [ 39 ] Mechanical failures and non-mechanical complications may lead to surgical revision in 8-45% and 7-17% of cases, respectively. The overall device explantation rates in males is reported to be 16-20%. [ 40 ]
One of the causes of mechanical failure are the complications related to the balloon reservoir. It has been reported that 26% of men with an implanted AUS required reoperation at the 10-year follow-up, in order to regulate the pressure inside the device.
Sexual intercourse should be avoided for the first 6 weeks after the procedure to allow the wound to heal properly. [ 41 ] Physical activities that put direct pressure on the wound, such as horseback and bike riding, should also be avoided for at least 6 weeks. Patients may be prescribed with a scrotal support to be worn for 1 week after the procedure. [ 42 ]
To minimize the risk of damage to their AUS or urethra , it is vital that the patient informs their health care provider they have an AUS fitted before any urinary catheter placement , cystoscopy or any other medical intervention on the urinary tract. [ 43 ] Deactivating the device at nights may be recommended to patients, especially those who report being dry at night, to minimize the risks of urethral atrophy. [ 44 ] [ 41 ]
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The Artois-Baillet Latour Foundation is a Belgian non-profit organization which was founded on 1 March 1974.
The foundation was born by the initiative of Count Alfred de Baillet Latour , who was the Director of the Artois Breweries in Leuven , Belgium . He was the last male heir of the old House of Baillet , and was through his mother related to the House of Spoelberch , who own the Artois Company. In 1995 the name was changed to Interbrew-Baillet Latour Foundation and again in 2005 to InBev-Baillet Latour Fund .
The Foundation wants to encourage and reward achievements of outstanding human value in the Arts and Sciences. It can do this by means of Prizes, or by any other means that the Foundation might deem appropriate.
The Artois-Baillet Latour Health Prize was established in 1977 to be awarded periodically to recognize the merits of a person whose work has contributed prominently to the improvement of human health in the fields of metabolic disorders, infectious diseases, neurological diseases, cancer and cardiovascular disease. Since 2000 the prize has been awarded annually. Worth 250,000 euros, it is Belgium's major scientific prize. Since 2005, it has been known as the InBev-Baillet Latour Health Prize.
Source: [ 1 ]
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Arts syndrome is a rare metabolic disorder that causes serious neurological problems in males due to a malfunction of the PRPP synthetase 1 enzyme. Arts Syndrome is part of a spectrum of PRPS-1 related disorders with reduced activity of the enzyme that includes Charcot–Marie–Tooth disease and X-linked non-syndromic sensorineural deafness. [ 1 ]
Males show more serious symptoms than females affected by this disorder. [ 2 ] The symptoms for males are:
Symptoms for females:
Very rarely seen hearing loss that begins in adulthood (age > 20 years) combined with ataxia and neuropathy. Optic atrophy and retinitis pigmentosa [ 5 ] observed in some cases too. [ 6 ]
Arts syndrome is caused by a loss of function mutation in the PRPS1 gene. [ 6 ] The PRPS1 gene codes for the enzyme phosphoribosyl pyrophosphate synthetase 1 or PRPP synthetase 1. This enzyme is involved in producing purines and pyrimidines which are the building blocks of DNA, RNA, ATP and other molecules. The mutations that cause Arts syndrome replace single amino acids the PRPP synthetase 1 enzyme. [ 7 ] The resulting enzyme is unstable. Disruption of purine and pyrimidine production may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome. The reason for the increased risk of respiratory infections in Arts syndrome is unclear. [ citation needed ]
Novel missense mutation - c.367C>G (p.His123Asp) [ 3 ]
c.455T→C (p. L152P), c.398A→C (p.Q133P) [ 8 ]
p. Ile275Thr and p.Gly306Glu [ 9 ]
Arts syndrome follows an X-linked inheritance. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes features of the disorder; in other cases, these females do not experience any symptoms. In the small number of Arts syndrome cases that have been identified, affected individuals have inherited the mutation from a mother who carries an altered copy of the PRPS1 gene. If the mother is a carrier, the chance of transmitting the PRPS1 mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may or may not be mildly affected. Males with Arts syndrome do not reproduce. [ 10 ]
Charcot-Marie-Tooth disease-5, Arts syndrome and X-linked nonsyndromic sensorineural deafness present three clinically distinct but genetically allelic disorders, caused by reduced phosphoribosylpyrophosphate synthetase 1 (PRS1) activity due to PRPS1 mutations. Only three families with CMTX5 and two families Arts syndrome, respectively, have been reported worldwide so far. Thus, evidence is still rare whether these two disorders are separate entities, or rather clusters on a phenotypic continuum of PRPS1-related disease. [ citation needed ]
Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date. Arts syndrome patients were also found to have reduced levels of hypoxanthine levels in urine and uric acid levels in the serum. [ 8 ] In vitro, PRS-1 activity was reduced in erythrocytes and fibroblasts. [ citation needed ]
Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides [ 4 ] and open new avenues of therapeutic intervention. [ 8 ] [ 11 ] Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring. [ citation needed ]
Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended. [ citation needed ] Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known. [ 5 ] [ 10 ]
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Arturo Jiménez Borja (1908–2000) was a Peruvian physician, ethnologist, painter and writer. He was born in Tacna on July 21, 1908, and died in Lima on January 13, 2000. He was a first order descendant of the last indigenous curaca in Tacna, Toribio Ara.
Jiménez attained the title of doctor-surgeon in 1943 at the Universidad Nacional Mayor de San Marcos , heading the departments of Therapeutics and Endocrinology at the Faculty of Medicine, San Fernando .
He devoted his studies to indigenous clothing, masks and musical instruments. He achieved the restoration of ancient monuments in areas such as Puruchuco, Pachacamac and Paramonga , building a museum in each of them. He was director of the museum site of Pachacamac (1956) and Director of the National Museum.
He donated his collection of musical instruments from Peru to the Universidad Nacional Mayor de San Marcos . His collection of masks from all over Peru , the most comprehensive and most valuable, admired by friends and strangers, can now be seen very well maintained, in the Museum of Arts and Traditions of the Riva Aguero Institute at the Catholic Pontifical University in Peru.
He was murdered on January 13, 2000, in Lima.
Jiménez published many works on ethnology, plus his work recounting Peruvian stories and legends.
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Arytenoid adduction is a surgical procedure used to treat vocal cord paralysis . A suture is used to emulate the action of the lateral cricoarytenoid muscle and position the paralyzed vocal cord closer to the midline. This allows the two vocal cords to meet and can improve speaking and swallowing ability for affected patients. Arytenoid adduction is often performed in conjunction with medialization thyroplasty .
One of the key functions of the larynx is phonation , the production of sound. Phonation requires the vocal cords to be adducted (positioned towards the midline) so that they can meet and vibrate together as air is expelled between them. Physiologically, the glottis is closed by intrinsic laryngeal muscles such as the lateral cricoarytenoid , thyroarytenoid , and interarytenoid muscles. [ 1 ] These muscles act on the arytenoid cartilages at the posterior ends of the vocal cords and are innervated by the left and right recurrent laryngeal nerves . Damage to these nerves results in vocal cord paralysis - the reduced mobility and inability to adduct one or both vocal cords. Many cases of vocal cord paralysis result from trauma during surgery. [ 2 ] Symptoms include hoarseness of voice, difficulty projecting, difficulty swallowing, and throat pain. [ citation needed ]
The arytenoid adduction procedure alleviates these symptoms by manually positioning the paralyzed vocal cord towards the midline. This is accomplished by passing a suture between the muscular process of the arytenoid cartilage and the thyroid cartilage . [ 3 ] This rotates the arytenoid cartilage and adducts the vocal cord.
[ 3 ]
Options for surgical treatment of vocal cord paralysis include vocal cord injection, medialization thyroplasty, and arytenoid adduction. [ 4 ] Each of these techniques results in medialization of the paralyzed vocal cord. However, arytenoid adduction is preferred in cases where there is a large posterior glottal gap or vertical misalignment between the vocal folds. Arytenoid adduction is often performed at the same time as a medialization thyroplasty. Animal model studies suggest that combining the two procedures produces better outcomes than when performing either alone. [ 5 ]
The paralyzed vocal cord may rest close to or far from the midline. An extremely laterally positioned vocal cord can result in a large posterior glottal gap - an opening between the two vocal cords even when the functioning vocal cord is fully medialized. Vocal cord injection is ineffective for closing a large glottal gap. [ 6 ] Arytenoid adduction is more effective than medialization thyroplasty for closing a posterior gap. It has been suggested that this is because arytenoid adduction directly rotates the arytenoid cartilage and thus more actively medializes the posterior aspect of the vocal cord. [ 7 ]
The paralyzed vocal cord may rest on a different plane than the opposite vocal cord. This results in a vertical gap between the two vocal cords that cannot be resolved using vocal cord injection or medialization thryoplasty. The suture placed in the arytenoid adduction procedure mimics the action of the lateral cricoarytenoid muscle and pulls the vocal process of the arytenoid cartilage medially and inferiorly. [ 8 ] Thus arytenoid adduction can correct the vertical position of an elevated vocal cord.
Arytenoid adduction with or without medialization thyroplasty significantly improves quality of life for patients with vocal cord paralysis. Subjective outcome measures of voice quality include the Grade, Roughness, Breathiness, Asthenia, Strain (GBRAS) voice scale, Voice Handicap Index, and closure of the glottic gap. Objective outcome measures include mean and maximum phonation time, phonatory airflow, and signal-to-noise ratio. [ 9 ] Arytenoid adduction produces improvements in all of these parameters. [ 10 ] [ 11 ] [ 12 ] [ 13 ]
Arytenoid adduction is more technically challenging than either vocal cord injection or medialization thyroplasty and has a high learning curve. [ 12 ] Increased incidence of complications have been reported for arytenoid adduction compared to medialization thyroplasty. [ 14 ]
Potential complications include: [ citation needed ]
Intubation and/or tracheotomy may be required as a result of these complications. [ citation needed ]
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Arytenoidectomy is a surgical procedure performed on the arytenoid cartilage, which is located in the larynx or voice box. This surgery is typically used to treat conditions such as severe laryngeal stenosis, where the airway becomes narrowed due to scarring or other factors. [ 1 ]
During an arytenoidectomy, the surgeon removes the arytenoid cartilage. The arytenoid cartilages are a pair of pyramid-shaped structures in the larynx (voice box) that play an essential role in vocal sound production. Various techniques, such as laser surgery or conventional surgical instruments, may be employed based on the severity of the stenosis and the patient's specific requirements. Typically performed under general anesthesia, arytenoidectomy necessitates hospitalization for postoperative observation and recovery. Patients might experience temporary hoarseness or swallowing difficulties as the area heals. [ 2 ]
This surgery article is a stub . You can help Wikipedia by expanding it .
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The mineral asbestos is subject to a wide range of laws and regulations that relate to its production and use, including mining, manufacturing, use and disposal. [ 1 ] [ 2 ] [ 3 ] Injuries attributed to asbestos have resulted in both workers' compensation claims and injury litigation. [ 4 ] [ 5 ] Health problems attributed to asbestos include asbestosis , mesothelioma , lung cancer , and diffuse pleural thickening. [ 6 ] [ 7 ]
One of the major issues relating to asbestos in civil proceedings is the latency of asbestos-related diseases. Most countries have limitation periods to bar actions that are taken long after the cause of action has lapsed. For example, in Malaysia the time period to file a tort action is six years from the time the tort occurred. Due to several asbestos-related actions, countries such as Australia have amended their laws relating to limitations to accumulate starting from time of discovery rather than time when the cause of action accrued. The first employee claims for injury from exposure to asbestos in the workplace were made in 1927, and the first lawsuit against an asbestos manufacturer was filed in 1929. Since then, many lawsuits have been filed. As a result of the litigation, manufacturers sold off subsidiaries, diversified, produced asbestos substitutes, and started asbestos removal businesses.
Worldwide, 67 countries and territories (including those in the European Union ) have banned the use of asbestos. [ 8 ] [ 9 ] It is listed as a category of controlled waste under Annex I of the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and their Disposal [1992]. This means that parties to the convention are required to prohibit the export of hazardous wastes to parties which have prohibited the import of such wastes via the notification procedure in Article 13 of the convention. In places such as India , however, there continues to be a high use of friable or dust-based asbestos in compressed asbestos fiber (CAF) gaskets, ropes, cloth, gland packings, millboards, insulation, brake liners, and other products which are being exported without adequate knowledge and information to the other countries. Asbestos use is prevalent in India because there is no effective enforcement of the rules.
In the late 19th century and early 20th century, asbestos was considered an ideal material for use in the construction industry. It was known to be an excellent fire retardant, to have high electrical resistance, and was inexpensive and easy to use.
The dangers related to asbestos arise mainly when the fibers become airborne and are inhaled. Because of the size of the fibers, the lungs cannot expel them. [ 10 ] These fibers are also sharp and penetrate internal tissues.
Health problems attributed to asbestos include: [ 6 ]
Considerable international controversy exists regarding the perceived rights and wrongs associated with litigation on compensation claims related to asbestos exposure and alleged subsequent medical consequences. Some measure of the vast range of views expressed in legal and political circles can perhaps be exemplified by the two quotes below, the first [ 17 ] from Prof. Lester Brickman , an American legal ethicist writing in the Pepperdine Law Review , and second, Michael Wills , a British Member of Parliament , speaking in the House of Commons on July 13. 2006:
"A review of the scholarly literature indicates a substantial degree of indifference to the causes of this civil justice system failure. Many of the published articles on asbestos litigation focus on transactional costs and ways in which the flow of money from defendants to plaintiffs and their lawyers can be expeditiously and efficiently prioritized and routed. The failure to acknowledge, let alone analyze, the overriding reality of specious claiming and meritless claims demonstrates a disconnect between the scholarship and the reality of the litigation that is nearly as wide as the disconnect between rates of disease claiming and actual disease manifestation".
"Many of those who I see in my surgeries have worked in a number of workplaces and they could have been exposed to asbestos in each of them, but medical science is such that no one can identify which of them it is. As a result, there has been a long and complex history of legal discussion on how to apportion liability . The lawyers and the judiciary have wrestled, rightly and valiantly, with complex and difficult law, but it has created despair for the families whom we represent. Many of my constituents ' families have been riven by the consequences of litigation in trying to get some compensation for a disease that has been contracted through no fault of theirs. That is cruel and unacceptable." [ 18 ]
Worldwide, 68 countries and territories (including those in the European Union ) have banned the use of asbestos. Exemptions for minor uses are permitted in some countries listed; however, all countries listed must have banned the use of all types of asbestos. [ 8 ] [ 9 ]
Asbestos is listed as a category of controlled waste under Annex I of the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and their Disposal [1992]. Specifically, any waste streams having asbestos (dust and fibers) as constituents are controlled (Item Y36). In general terms, Parties to the convention are required to prohibit and not permit the export of hazardous wastes to the Parties which have prohibited the import of such wastes via the notification procedure in Article 13 of the convention.
A nationwide ban on importing and using all forms asbestos took effect on 31 December 2003. Reflecting the ban, the National Occupational Health and Safety Commission (NOHSC) revised asbestos-related material to promote a consistent approach to controlling exposure to workplace asbestos and to introduce best-practice health and safety measures for asbestos management, control and removal. The ban does not cover asbestos materials or products already in use at the time the ban was implemented. [ 21 ]
Although Australia has only a third of the UK's population, its asbestos disease fatalities approximate Britain's of more than 3,000 people per year. [ 22 ]
Western Australia' center of blue asbestos mining was Wittenoom . The mine was run by CSR Limited (a company that had been the Colonial Sugar Refinery). The main manufacturer of asbestos products was James Hardie , which set up a minor fund for its workers, then transferred operations to the Netherlands where it would be out of reach of the workers when the fund expired.
The São Paulo State law 12.684/07 prohibits the use of any product which utilizes asbestos. This legislation has been formally upheld by the Brazilian Supremo Tribunal Federal . [ 23 ]
Since the 1980s, Canada has not permitted crocidolite asbestos to be used and has had limitations on certain uses of other types of asbestos, notably in some construction materials and textiles.
In late 2011, Canada's remaining two asbestos mines, both located in the Province of Quebec , halted operations. [ 24 ] The following year, Quebec's government announced a halt to asbestos mining [ 25 ] and the federal government announced that it would end its opposition to adding chrysotile asbestos to the list of hazardous substances under the international Rotterdam Convention. [ 26 ]
In 2018, the Canadian federal government posted proposed regulations planned for implementation later that year, which would prohibit use, sale, import, and export of all forms of asbestos. [ 27 ] Since 30 December 2018, the import, sale, and use of raw asbestos have been formally prohibited, and products containing asbestos are also banned except for certain specialized uses, such as in nuclear facilities. [ 28 ]
France banned the use of asbestos in 1997, and the World Trade Organization (WTO) upheld France's right to the ban in 2000. In addition, France has called for a worldwide ban. [ 29 ]
The import, shipment, supply of, and use of all forms of asbestos is banned in Hong Kong under the Air Pollution Control Ordinance (Cap. 311). [ 30 ]
Before the 1980s, use of the material was common in construction, manufacturing, and shipping. The government banned the use of most asbestos products in public areas in 1978. [ 31 ] The Factories and Industrial Undertakings (Asbestos) Special Regulation (Cap. 59X), which came into force in 1986, and the subsequent Factories and Industrial Undertakings (Asbestos) Regulation (Cap. 59AD) implemented controls on the use of asbestos in the workplace and banned the use of amphibole asbestos completely. [ 32 ] [ 33 ]
The import of amosite or crocidolite to Hong Kong was banned in 1996 by the Air Pollution Control Ordinance (Cap. 311). [ 33 ] On 4 April 2014, the Air Pollution Control (Amendment) Ordinance 2014 came into force, completely banning the import, transshipment, supply and installation of all forms of asbestos and asbestos-containing materials in Hong Kong by amending the existing Air Pollution Control Ordinance. Buildings built before the mid-1980s may continue the use of asbestos-containing materials. [ 34 ]
The Vision Statement on Environment and Human Health of the Government of India states " Alternatives to asbestos may be used to the extent possible and use of asbestos may be phased out. " [ 35 ]
In Case No.693/30/97-98, National Human Rights Commission (NHRC) has clearly directed to " Replace all asbestos sheets roofing with roofing made up of some other material that would not be harmful to inmates ."
The Secretary of the Post Graduate Institute of Medical Education & Research (PGIMER, Chandigarh also voiced its opinion " Asbestos is definitely a harmful material, it causes cancer and other related diseases ." In their complete statement and recommendation to NHRC they have clearly expressed their concern: " White asbestos (chrysotile asbestos) is implicated in so many studies with the following diseases: Mesothelioma (cancer of pleura), Lung Cancer, Peritoneal Cancer, Asbestosis, and is also considered as a cause for Ovarian Cancer, Laryngeal Cancer, Other Cancererous Diseases are produced in the person involved in Asbestos Industry ." It concludes its position by specifying, " Hence, Use of White Asbestos should be completely banned in India and the same may be replaced by some safer alternative material ."
The Joint Secretary, Government of Uttarakhand in Case No.2951/30/0/2011, submitted to the NHRC that "There is no cure for Asbestos Diseases. Stopping all exposure to Asbestos is only essential."
The Union Ministry of Labour's concept paper declared, " The Government of India is considering the ban on use of chrysotile asbestos in India to protect the workers and the general population against primary and secondary exposure to Chrysotile form of Asbestos." The Concept paper further notes, " Asbestosis is yet another occupational disease of the Lungs which is on an increase under similar circumstances warranting concentrated efforts of all stake holders to evolve strategies to curb this menace ".
The Indian Factory Act and Bureau of Indian Standard already have rules and regulations for safe usage of asbestos contaminated products such as:
However, there is no enforcement of the rules at ground level, hence asbestos usage is prevalent without following even the simplest basic safety rules.
The Centre for Pollution Control Board struggles to enforce their own guidelines for asbestos as hazardous waste and relies on industries and companies to volunteer themselves to follow Safety Regulations.
There continues to be a high usage of friable or dust based asbestos in compressed asbestos fiber (CAF) gaskets, ropes, cloth, gland packings, millboards, insulation and brake liners in factories and industries within India as well as inadvertently exported by equipment manufacturers without adequate knowledge and information to the other countries.
On 21 January 2011, the Supreme Court of India reiterated the guidelines laid down by it in the 1995 judgement regarding asbestos. [ 36 ]
In spite of the health hazards, asbestos is widely used in India without any restriction. [ 37 ] Activists in India and abroad have tried to persuade the governments of Canada and Quebec to stop asbestos mining in Quebec and exporting to India. The Canadian government has repeatedly blocked asbestos being listed as a hazardous chemical by the UN even though it spends massive amounts of money to remove it from Canadian homes and offices. [ 38 ] While India recognizes it as a hazardous substance and has banned asbestos mining and its waste trade , it keeps its price low through patronage. [ 38 ]
On 15 August 2016, in the strongest statement till date, the Anil Madhav Dave , Union Minister of Environment, Forest & Climate Change categorically specified " Since the use of asbestos is affecting human health, its usage should gradually be minimised and ended. As far as I know, its use is declining, but it must end " [ 39 ]
The Ban Asbestos Network of India (BANI) has been working towards an asbestos free India to safeguard the health of the present and future generations amidst the misinformation campaign of the White Chrysotile Industry.
On 5 May 2017, India opposed listing of asbestos under the Prior Informed Consent (PIC) list of hazardous substances during the 2017 United Nations Rotterdam Convention. [ 40 ] As such, India is the second democracy (after Russia) to have such a stance, globally. Besides India, Russia, Kazakhstan, Kyrgyzstan, Syria, and Zimbabwe also opposed the listing. While, all the other countries opposing are producers of asbestos; India ( where mining is banned ) is the sole ( and largest ) consumer and importer of asbestos still opposing its inclusion on the PIC List.
The National Asbestos Profile of India made in cooperation by Peoples Training and Research Centre, Vadodara, Occupational & Environmental Health Network of India, New Delhi and Asia Monitor Resource Centre, Hong Kong is the first such attempt and resource for identifying total asbestos usage in India. [ 41 ] This extensive profile documents the manufacturers, consumers, health and disease statistics of asbestos use in India.
Italy fully banned the use of asbestos in 1992 with law 257/92 art. 1 and set up a comprehensive plan for asbestos decontamination in industry and housing. [ 42 ]
Japan did not fully ban asbestos until 2004. Its government has been held responsible for related diseases. [ 43 ]
The Philippines has a limited ban on asbestos. While the use of amphibole asbestos is banned as early as 2000 through Administrative
Order for the Chemical Control Order of Asbestos issued by the Department of Environment and Natural Resources , chrysotile asbestos is allowed for use in specific high density products. [ 44 ]
Poland fully banned asbestos in 1997. [ 45 ] Since then the import of asbestos and products containing it, production of anything containing asbestos and circulation of asbestos and products which have it is prohibited.
Asbestos was banned in South Africa in 2008. [ 46 ] Prior to this, the country was one of the global leaders in asbestos production, and consequently had one of the highest rates of mesothelioma. [ 47 ] Regulations to ban asbestos in South Africa occurred in March 2008 under the leadership of Environmental Affairs and Tourism Minister Marthinus van Schalkwyk . The first draft regulations were announced in November 2005 for public comment and again in September 2007. The regulations prohibited the use, processing, manufacturing, and import and export of any asbestos or asbestos-containing materials (ACMs). A grace period of 120 days was allowed to give people or traders currently dealing in asbestos or ACMs to clear their stock. Exemptions would be granted under strict control. The regulations did not prohibit the continued use of asbestos-containing materials that were already in place such as asbestos-cement roof sheets or ceilings, the department was satisfied that there was "no undue risk" and they would be replaced in due time. Penalties for the continued use of asbestos include a fine which would not exceed R100 000 and/or imprisonment of less than ten years. Prior to the regulations' implementation, asbestos had been in the process of being phased out from as early as 2003. Requests from Zimbabwe and Canada to be excepted from the prohibition were denied. South Africa also terminated all import of asbestos or ACMs from Zimbabwe. South Africa would allow products to pass through its borders while in transit under strict conditions and if registered with the department of Environmental Affairs and Tourism. Everite, a building company, supported the government's ban on imports from Zimbabwe [ 48 ] [ 49 ] It became an offence to acquire, process, package or repackage, manufacture or distribute these products from after July 28, 2008. Kgalagadi Relief Trust (KRT) chair Brian Gibson stated that asbestos may still be imported into South Africa for research or analysis. Asbestos may also be imported into the country for disposal from Southern African Development Community (SADC) countries that were unable to dispose of the waste themselves. [ 50 ]
In May 1997, the manufacture and use of crocidolite and amosite , commonly known as blue and brown asbestos, were fully banned in South Korea . In January 2009, a full-fledged ban on all types of asbestos occurred when the government banned the manufacture, import, sale, storage, transport or use of asbestos or any substance containing more than 0.1% of asbestos. [ 51 ] In 2011, South Korea became the world's sixth country to enact an asbestos harm aid act, which entitles any Korean citizen to free lifetime medical care as well as monthly income from the government if they are diagnosed with an asbestos-related disease. [ 52 ]
In 1984, the import of raw amphibole (blue and brown) asbestos into New Zealand was banned. In 2002, the import of chrysotile (white) asbestos was banned. [ 53 ]
The British Government 's Health and Safety Executive (HSE) has promoted rigorous controls on asbestos handling, based on reports linking exposure to asbestos dust or fibres with thousands of annual deaths from mesothelioma and asbestos-related lung cancer.
The HSE does not assume that there is any minimum threshold for exposure to asbestos below which a person is at zero risk of developing mesothelioma, since they consider that it cannot currently be quantified for practical purposes; they cite evidence from epidemiological studies of asbestos-exposed groups to argue that even if there is any such threshold for mesothelioma, it must be at a very low level. [ 56 ] Previously it was possible to claim compensation for pleural plaques caused by negligent exposure to asbestos, on the grounds that although it is in itself asymptomatic, it is linked to development of diffuse pleural thickening, which causes lung impairment. It has been highly contentious, however, as to the probability of pleural plaques developing into pleural thickening or other asbestos-related illnesses. On October 17, 2007, this point was clarified by the Law Lords ' ruling that workers who have pleural plaques as a result of asbestos exposure will no longer be able to seek compensation as it does not in itself constitute a disease. [ 57 ] This ruling was, however, superseded, so far as sufferers of pleural plaques in Scotland are concerned, by the passing of the Damages (Asbestos-related Conditions)(Scotland) Act 2009, which provides that in Scots law pleural plaques are to be considered an actionable type of personal injury.
The Control of Asbestos Regulations were introduced in the UK in November 2006 and were an amalgamation of three previous sets of legislation (Asbestos Prohibition, Asbestos Licensing and the Control of Asbestos at Work Regulations) aimed at minimising the use and disturbance of asbestos containing materials within British workplaces. Essentially this legislation bans the import and use of most asbestos products and sets out guidelines on how best to manage those currently in situ. [ 58 ]
The Control of Asbestos Regulations were amended and the revised regulations came into force on 6 April 2012 to take account of the European Commission's view that the UK had not fully implemented the EU Directive on exposure to asbestos (Directive 2009/148/EC). These changes were relatively minor and included additional requirements for non-licensed asbestos work. These changes mean that some non-licensed asbestos work now requires notification, and has additional requirements for managing this work (e.g. record keeping and health surveillance). [ 59 ]
Dutyholders of all non-domestic properties within the UK must establish an asbestos register and a management plan. The definition of "non-domestic" is "a property or structure (commercial, domestic or residential) where work is carried out" and the obligation of a "dutyholder" is to ensure that people are not exposed to any asbestos-based materials during the course of their work. The Asbestos Register states the presence or non-presence of asbestos related to the inside and outside of the structure. The exception is where the property age (post-1999 when chrysotile asbestos was banned) would indicate that such products will not have been used during the construction of the building. [ 59 ]
Regulation 4 prescribes that each non-domestic building's "dutyholder", as defined in law, has a duty to manage the risk from asbestos and mandates that "a suitable and sufficient assessment is carried out". Risk assessment involves a combination of factors relating to the type and condition of the asbestos-containing materials and the likelihood of disturbance and exposure. Human exposure potential depends on the number of occupants in a building and the frequency and duration of use, and the nature of any disturbance: for example, intrusive maintenance activity within the building increases the risk of exposure - removing a number of asbestos-containing ceiling tiles to undertake works above the ceiling level would raise greater risks than changing a light bulb. Buildings may be ranked according to whether disturbance activity is undertaken:
The HSE uses a priority scoring tool which combines assessment of the material containing asbestos and the disturbance risk. [ 60 ]
The outcome of the risk assessment will identify priorities for management of the locations and materials containing asbestos, for example areas which require urgent attention, materials which are not suited to any form of containment may need to be removed or encased, minor repairs may be needed, or labelling and provision of information may be sufficient to ensure that significant health risks can be avoided, e.g. for a little-used store room it may be sufficient to keep the door locked and attach a warning notice to the door.
The HSE points out that "Regulation 4 is a duty to manage, not [just] a duty to survey". [ 61 ]
The removal of high-risk asbestos products from non-domestic properties is tightly controlled by the HSE and high-risk products such as thermal insulation must be removed under controlled conditions by licensed contractors. Further guidance on which products this applies to can be found on the HSE website along with a list of licensees.
The current regulations show that it is a legal requirement that all who may come across asbestos in their day-to-day work have been provided with the relevant asbestos training.
The manufacture and import of Blue and Brown Asbestos were banned in the United Kingdom in 1985 by The asbestos (Prohibitions) Regulations 1985. [ 62 ] The use of White Asbestos was banned in England, Scotland and Wales in 1999 by The Asbestos (Prohibitions) (Amendment) Regulations 1999. [ 63 ] Asbestos was banned in Northern Ireland in 2000 by the Asbestos (Prohibitions) (Amendment) Regulations (Northern Ireland) 2000. [ 64 ]
The Environmental Protection Agency ( EPA ) has no general ban on the use of asbestos. However, asbestos was one of the first hazardous air pollutants regulated under Section 112 of the Clean Air Act of 1970 , and many applications have been forbidden by the Toxic Substances Control Act (TSCA). The United States has extensive laws regulating the use of asbestos at the federal, state, and local level. [ 65 ]
One of the major issues relating to asbestos in civil procedure is the latency of asbestos-related diseases. Most countries have limitation periods to bar actions that are taken long after the cause of action has lapsed. For example, in Malaysia the time period to file a tort action is six years from the time the tort occurred. Due to several asbestos-related actions, countries such as Australia have amended their laws relating to limitations to accumulate starting from time of discovery rather than time when the cause of action accrued.
The first employee claims for injury from exposure to asbestos in the workplace were made in 1927, [ 66 ] and the first lawsuit against an asbestos manufacturer was filed in 1929. [ 67 ] Since then, many lawsuits have been filed. As a result of the litigation, manufacturers sold off subsidiaries, diversified, produced asbestos substitutes, and started asbestos removal businesses. [ 68 ]
In June 2008, the Brazilian Supreme Federal Court (STF) voted to maintain the law (12.684/07) which prohibits the use of any product which utilizes asbestos in São Paulo State. [ 23 ] It was expected then the decision would be extended to include the whole country. [ 69 ]
In August 2017, in what is known in Brazil as a "direct action for the declaration of unconstitutionality", an instrument to declare the unconstitutionality of law or federal norms, with respect to the current Constitution (the equivalent in the U.S. as a "judicial review"), the constitutionality of the prohibitive law of São Paulo was questioned. The Supreme Federal Court considered it constitutional and even incidentally declared the unconstitutionality of Art. 2 of Federal Law nº 9.055/95, that authorized the use of chrysotile asbestos in a controlled manner. [ 70 ] [ 71 ]
On November 29, 2017, the Supreme Federal Court prohibited the extraction, industrialization and commercialization of asbestos throughout the country. Despite this, asbestos has continued to be extracted in Goiás under claims that the state's asbestos is "the only one recognized worldwide as not causing any ill effects to the population". [ 72 ] As of January 2025, the Supreme Federal Court has yet to rule on the constitutionality of the state law that allows for the extraction. [ 72 ]
The Lubbe v Cape Plc case [2000] UKHL 41 is a conflict of laws case, which is also significant for the question of " lifting the corporate veil " in relation to tort victims. [ 73 ] Mrs Lubbe was exposed to asbestos while working for a South African subsidiary company of the UK parent company, Cape plc .
The Richard Meeran-run Cape Plc case was settled in 2003.
The Richard Spoor-run Gencor case was settled in 2003. [ 74 ] [ 75 ]
400 Swaziland ARD victims from the Havelock mine
The Havelock chrysotile mine cases were suspended in 2003 because Turner and Newall, the company that owned the mine, had filed for bankruptcy in 2001. [ 76 ]
Swiss Eternit Group
This was a voluntary agreement which was reached in 2006. The agreement enabled ex-miners of the Kuruman and Danielskuil Cape Blue Asbestos (KCBA and DCBA) mines in the Northern Cape province to apply under similar conditions as the open settlement of the ART. The Kgalagadi Relief Trust (KRT) was
thus created. The terms of the trust are not clarified however in practice R136 million was paid over for compensation purposes, for payouts until 2026. The trustees of the KRT requested the ART to administer the KRT settlement as the two trusts were very similarly structured. [ 77 ] [ 78 ]
Seventy-five percent of the claimants in the Cape Plc case came from Limpopo province and the remaining twenty-five percent from the Prieska Koegas area in the Northern Cape province. [ 79 ] The majority of the claimants in the ART settlement (around 78%) were exposed in the Kuruman area in the Northern Cape province, with the balance exposed at Penge in Limpopo province and Msauli in Mpumalanga province, which were equally proportioned. [ 80 ]
Statistically, mesothelioma and asbestos related lung cancer sufferers receiving the highest payments of R71,500 each. [ 76 ] Due to Gencor's significant contribution settlements, it was prohibited for those who had received compensation under the Cape agreement to later be paid by the ART, even if the worker had worked on the Kuruman or Penge mines when under Gencor control. [ 81 ]
In 2006, Cape plc started a trust to compensate those who have suffered from asbestos related diseases as a result of Cape's historical activities. To date, this Trust has paid out over £30m to those who have become sick or to their dependents. The Scheme of Arrangement was approved by the High Court and is separately funded. Its funds being administered by two independent trustees. [ 82 ]
Asbestos Relief Trust (ART) is regarded as a model of efficient occupational disease compensation in South Africa. Gencor was a major contributor to the Richard Meeran-run Cape Plc case and the Richard Spoor-run Gencor case. Glencor provided 29% of the R138 million that went to the Cape Plc's set of claimants, and 96% of the R381 million that formed the ART. An additional sum of R35 million went to environmental rehabilitation, and about R20 million was added to the ART to contribute to supplementary and additional payments. After some time and publicity claims against The Cape Plc list had grown from 2 000 in January 1999 and to 7 500 in August 2001. The ART settlement was open, and made provision for compensation to any person who met the compensation criteria set out in the Trust deed, until the year 2028. [ 83 ] [ 74 ] [ 84 ] Many companies agreed to compensate the workers which were exposed to asbestos in addition to the compensation payable under the Occupational Diseases in Mines and Works Act (ODMWA) [ 85 ] The settlement included environmentally expose victims of ARDS. This settlement model was achieved by personal communication, Georgina Jephson, attorney at Richard Spoor Inc. Attorneys. [ 84 ]
The Trust provides compensation for people in these four categories related to Acute respiratory distress syndrome (ARD) namely:
A model by the ART estimated that about 16 800 individuals would submit claims to the Trust, of which approximately 5 036 (30%) would be successful. This was subsequently revised to 5 162. Of these, 219 (4.2%) would be environmental claimants, 150 (2.9%) would have lung cancer and 556 (10.8%) would have mesothelioma; the balance would have asbestosis and/or pleural thickening. No definitive figures were provided for the expected ARD1/
ARD2 ratio. [ 87 ] The amounts payable for compensation vary, but the average amount of compensation since 2003 has been about R40 000, R80 000, R170 000 and R350 000 for each of the categories ARD 1-4 described above. These amounts are paid over and above any compensation that the claimants might receive under the ODMWA. In order for a case to be compensable, a victim needs to show that he/she was both exposed to asbestos from one of the operations run by the funders of the ART, and has a compensable disease. [ 86 ]
A lack of facilities for terminally ill mesothelioma sufferers results in a larger burden of service, according to Sister Phemelo Magabanyane, a palliative care nurse who has cared for over 100 mesothelioma and lung cancer sufferers in the greater Kuruman district in the Northern Cape . Mesothelioma is a life-threatening cancer of the pleura or peritoneum which can be diagnosed up to 40 years after exposure to asbestos. [ 88 ]
South Africa has the highest prevalence of mesothelioma in the world. [ 89 ] Richard Spoor, a lawyer who represented the claimants against Gencor says: "The environmental scale of the disaster we are seeing unfold in the Northern Cape is on a level with the nuclear disaster at Chernobyl, in terms of impact, spread and longevity," he also says that children are particularly vulnerable to mesothelioma. Since September 2016, five of the 1 600 claimants he represents in the Northern Cape have died. Internationally renowned photographer David Goldblatt started photographing victims after a friend died of mesothelioma despite never being in close proximity to a mine. It has been reported that she picked up the disease from rubbing a blue asbestos rock ornament that she kept in her home. [ 90 ]
Guardian Unlimited reported a test-case ruling in 2005, that allowed thousands of workers to be compensated for pleural plaques. Diffuse or localised fibrosis of the pleura, or pleural plaques, is less serious than asbestosis or mesothelioma, but is also considered a disease closely linked to the inhalation of asbestos. [ 91 ] However, insurers claimed the plaques are "simply a marker for asbestos exposure rather than an injury." Mr Justice Holland rejected the insurers' arguments, and counsel for workers hailed the decision as a "victory that puts people before profits." [ 92 ] However this decision was reversed by the Court of Appeal. On 17 October 2007, the House of Lords confirmed the Court of Appeal's decision. Pleural plaques no longer constitute actionable injury in England, Wales and Northern Ireland. The Scottish government introduced legislation in 2009 to preserve the status of pleural plaques as an actionable injury in Scotland [ 93 ] and there are proposals to introduce similar legislation in Northern Ireland. [ 94 ]
Insurance companies allege that asbestos litigation has taken too heavy a toll on insurance and industry. A 2002 article in the British The Daily Telegraph ' s associate quoted Equitas, the reinsurance vehicle which assumed Lloyd's of London 's liabilities, which argued that asbestos claims were the "greatest single threat" to Lloyd's of London's existence. [ 95 ] Of note is that Lloyd's of London had been sued for fraud by its investors, who claimed Lloyd's misrepresented pending losses from asbestos claims. [ 96 ]
In May 2006, the House of Lords ruled that compensation for asbestos injuries should be reduced where responsibility could not be attached to a single employer. [ 97 ] Critics, including trade unions, asbestos groups and Jim Wallace, former justice minister, have condemned the ruling. They said it overturned the traditional Scottish law to such cases, and was a breach of natural justice. As a result of this outcry, the ruling has been overturned by section three of the Compensation Act 2006 .
In February 2010 a court ruling set a new precedent for asbestosis claims. [ 98 ] The case, in which widow Della Sabin attempted to claim compensation following her husband's death from asbestosis, hinged on the issue of how many asbestos fibers must be present in the lungs for a claim to be valid. A research team based at Llandough Hospital initially reported that the minimum amount of fibers that needed to be present for a claim to be valid was 20 million (only 7 million were found in the sample taken from Mrs Sabin's husband Leslie). However, a subsequent US study suggested that, due to the fact that Leslie had lived for more than forty years after his exposure, a large number of fibers would have cleared from his body naturally; had he died twenty years earlier the asbestos count in his lungs would have been about 35 million fibers per gram. The judge preferred this evidence, and ruled in favor of Mrs Sabin. [ 99 ]
Litigation related to asbestos injuries and property damages has been claimed to be the longest-running mass tort in U.S. history, involving more than 8,000 defendants and 700,000 claimants. [ 100 ] [ 101 ] Since asbestos-related disease has been identified by the medical profession in the late 1920s, workers' compensation cases were filed and resolved in secrecy, with a flood of litigation starting in the United States in the 1970s, and culminating in the 1980s and 1990s. Current trends indicate that the rate at which people are diagnosed with asbsestos-related disease will likely increase through the next decade. Analysts have estimated that the total costs of asbestos litigation in the USA alone will eventually reach $200 to $275 billion. The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.
A multi-district litigation (MDL) complex filing has remained pending in the Eastern District of Pennsylvania for over 20 years. As many of the scarring-related injury cases have been resolved, asbestos litigation continues to be hard-fought among the litigants, mainly in individually brought cases for terminal cases of asbestosis, mesothelioma, and other cancers.
In June 1982, a retired boilermaker, James Cavett, won an award of $2.3 million compensatory and $1.5 million in punitive damages against Johns-Manville. [ 68 ] The Manville Corporation, formerly the Johns-Manville Corporation, filed for reorganization and protection under the United States Bankruptcy Code in August 1982. At the time, it was the largest company ever to file bankruptcy, and was one of the richest. Manville was then 181st on the Fortune 500 , but was the defendant of 16,500 lawsuits related to the health effects of asbestos. [ 68 ] The company was described by Ron Motley , a South Carolina attorney, as "the greatest corporate mass murderer in history." Court documents show that the corporation had a long history of hiding evidence of the ill effects of asbestos from its workers and the public.
By the early 1990s, "more than half of the 25 largest asbestos manufacturers in the US, including Amatex, Carey-Canada, Celotex, Eagle-Picher , Forty-Eight Insulations, Manville Corporation, National Gypsum , Standard Insulation, Unarco, and UNR Industries had declared bankruptcy. Filing for bankruptcy protects a company from its creditors." [ 68 ]
Asbestos-related cases increased on the U.S. Supreme Court docket after 1980 and the court has dealt with several asbestos-related cases since 1986. Two large class action settlements, designed to limit liability, came before the court in 1997 and 1999. Both settlements were ultimately rejected by the court because they would exclude future claimants, or those who later developed asbestos-related illnesses. [ 102 ] [ 103 ] These rulings addressed the 20-50 year latency period of serious asbestos-related illnesses.
In 1988, the United States Environmental Protection Agency (USEPA) issued regulations requiring certain U.S. companies to report the asbestos used in their products. [ 104 ]
Several legislative remedies have been considered by the U.S. Congress but each time rejected for a variety of reasons. In 2005, Congress considered but did not pass legislation entitled the "Fairness in Asbestos Injury Resolution Act of 2005". The act would have established a $140 billion trust fund in lieu of litigation, but as it would have proactively taken funds held in reserve by bankruptcy trusts, manufacturers and insurance companies, it was not widely supported either by victims or corporations.
On April 26, 2005, Dr. Philip J. Landrigan , professor and chair of the Department of Community and Preventive Medicine at Mount Sinai Medical Center in New York City, testified before the US Senate Committee on the Judiciary against this proposed legislation. [ 105 ] He testified that many of the bill's provisions were unsupported by medicine and would unfairly exclude a large number of people who had become ill or died from asbestos: "The approach to the diagnosis of disease caused by asbestos that is set forth in this bill is not consistent with the diagnostic criteria established by the American Thoracic Society. If the bill is to deliver on its promise of fairness, these criteria will need to be revised." Also opposing the bill were the American Public Health Association and the Asbestos Workers' Union. [ 106 ]
On June 14, 2006, the Senate Judiciary Committee approved an amendment to the act which would have allowed victims of mesothelioma $1.1M within 30 days of their claim's approval. [ 106 ] This version would have also expanded eligible claimants to people exposed to asbestos from the September 11 attacks on the World Trade Center, and to construction debris in hurricanes Katrina and Rita . [ 107 ] Ultimately, the bill's reliance on funding from private entities large and small, as well as debate over a sunset provision and the impact on the U.S. budgetary process caused the bill to fail to leave committee.
Since the bankruptcy filing of Johns-Manville in 1984, many U.S. and U.K. asbestos manufacturers have escaped litigation by filing bankruptcy. Once in bankruptcy, these companies typically are required to fund special "bankruptcy trusts" that pay pennies on the dollar to injured parties. However, these trusts do permit larger numbers of claimants to receive some kind of compensation, even if greatly reduced from potential recoveries in the tort system.
Since 2002, asbestos lawsuits in the U.S. have included the following as defendants:
Defendants in the first category have contested liability on the grounds that nearly all of them either did not ship asbestos-containing parts with their products at all (that is, asbestos was installed only by end users) or did not sell replacement parts for their own products (in cases where the plaintiff was allegedly exposed well after any factory-original asbestos-containing parts would have been replaced), and either way cannot be responsible for toxic third-party parts that they did not manufacture, distribute, or sell. In 2008, the Washington Supreme Court , the first to reach the issue, decided in favor of the defense. [ 108 ] On January 12, 2012, the Supreme Court of California also decided in favor of the defense in O'Neil v. Crane Co. [ 109 ] This is significant as a 2007 study found that California and Washington were the two most influential state supreme courts in the United States in the period from 1940 to 2005. [ 110 ]
In a decision from January 2014, Gray v. Garlock Sealing Technologies had entered into bankruptcy proceedings, and discovery in the case uncovered evidence of fraud [ 111 ] that led to a reduction in estimated future liability to a tenth of what was estimated.
Some defendants raise what is sometimes called the chrysotile -defense, under which manufacturers of some products containing only chrysotile fibers claim that these are not as harmful as amphibole -containing products. As 95% of the products used in the United States historically were mostly chrysotile, this claim is widely disputed by health officials and medical professionals. [ 112 ] The World Health Organization recognizes that exposure to all types of asbestos fibers, including chrysotile, can cause cancer of the lung, larynx, and ovary, mesothelioma, and asbestosis. [ 113 ]
On February 20, 1973, a federal grand jury in Detroit, Michigan , indicted Adamo Wrecking Company for violating provisions of the Clean Air Act by knowingly causing the emission of asbestos by failure to wet and remove friable asbestos materials from demolitions. [ 114 ]
Adamo was one of a number of demolition contractors indicted throughout the country for the alleged violation of the Clean Air Act. The United States District Court for the Eastern District of Michigan dismissed the criminal indictment on the ground that it was not an "emission standard," but a "work practice standard," which under the terms of the statute, did not carry criminal liability. [ 115 ]
The government appealed and the Sixth Circuit Court of Appeals reversed the decision of the trial court, stating that it erred in determining that it had jurisdiction to review the validity of the standard in a criminal proceeding. [ 116 ] Adamo's attorneys appealed to the Supreme Court . [ 117 ]
On January 10, 1978, the Supreme Court ruled in favor of Adamo when it held that the trial court did have jurisdiction to review the standard in a criminal proceeding and also agreed with the trial court that the requirements in the act were "not standards" but "procedures" and therefore the proceedings were properly dismissed. [ 118 ] [ 119 ]
A federal grand jury indicted W. R. Grace and Company and seven top executives on February 5, 2005, for its operations of a vermiculite mine in Libby, Montana . The indictment accused Grace of wire fraud , knowing endangerment of residents by concealing air monitoring results, obstruction of justice by interfering with an Environmental Protection Agency (EPA) investigation, violation of the Clean Air Act, providing asbestos materials to schools and local residents, and conspiracy to release asbestos and cover up health problems from asbestos contamination. According to the Baltimore Sun the Department of Justice said 1,200 residents had developed asbestos-related diseases and some had died, and there could be many more injuries and deaths. [ 120 ]
According to the Baltimore Sun W. R. Grace and Company faced fines of up to $280 million for polluting the town of Libby, Montana . Libby was declared a Superfund disaster area in 2002, and the EPA has spent $54 million in cleanup. Grace was ordered by a court to reimburse the EPA for cleanup costs, but the bankruptcy court must approve any payments [ citation needed ] .
On June 8, 2006, a federal judge dismissed the conspiracy charge of "knowing endangerment" because some of the defendant officials had left the company before the five-year statute of limitations had begun to run. The wire fraud charge was dropped by prosecutors in March. [ when? ]
Asbestos abatement (removal of asbestos) has become a thriving industry in the United States. Strict removal and disposal laws have been enacted to protect the public from airborne asbestos. The Clean Air Act requires that asbestos be wetted during removal and strictly contained, and that workers wear safety gear and masks. The federal government has prosecuted dozens of violations of the act and violations of Racketeer Influenced and Corrupt Organizations Act (RICO) related to the operations. Often these involve contractors who hire undocumented workers without proper training or protection to illegally remove asbestos. [ 121 ]
On April 2, 1998, three men were indicted in a conspiracy to use homeless men for illegal asbestos removal from an aging Wisconsin manufacturing plant. Then-US Attorney General Janet Reno said, "Knowingly removing asbestos improperly is criminal. Exploiting the homeless to do this work is cruel." [ 122 ]
On December 12, 2004, owners of New York asbestos abatement companies were sentenced to the longest federal jail sentences for environmental crimes in U.S. history, after they were convicted on 18 counts of conspiracy to violate the Clean Air Act and the Toxic Substances Control Act , and actual violations of the Clean Air Act and Racketeer-Influenced and Corrupt Organizations Act. The crimes involved a 10-year scheme to illegally remove asbestos. The RICO counts included obstruction of justice, money laundering, mail fraud and bid rigging, all related to the asbestos cleanup. [ 123 ]
On January 11, 2006, San Diego Gas & Electric Co., two of its employees, and a contractor were indicted by a federal grand jury on charges that they violated safety standards while removing asbestos from pipes in Lemon Grove, California . The defendants were charged with five counts of conspiracy, violating asbestos work practice standards and making false statements . [ citation needed ]
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Within the United States, the use of asbestos is limited by state and federal regulations and legislation. Improper use of asbestos and injury from exposure is addressed through administrative action, litigation, and criminal prosecution. Injury claims arising from asbestos exposure may be tried as mass torts .
Asbestos litigation is the longest, most expensive mass tort in U.S. history, involving more than 8,000 defendants and 700,000 claimants. [ 1 ] By the early 1990s, "more than half of the 25 largest asbestos manufacturers in the US, including Amatex, Carey-Canada, Celotex, Eagle-Picher , Forty-Eight Insulations, Manville Corporation, National Gypsum , Standard Insulation, Unarco, and UNR Industries had declared bankruptcy . Analysts have estimated that the total costs of asbestos litigation in the U.S. alone will eventually reach $200 to $275 billion." [ 1 ] The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.
Claims made against employers by injured workers will typically be in the form of a workers compensation claim, although the long onset for diseases such as mesothelioma may make it impossible for a worker to pursue workers' compensation benefits. [ 2 ] However, it is possible for an injured worker to also bring a product liability claim against a third party that is responsible for introducing asbestos into the workplace. Plaintiffs' attorneys have attempted to offer "every exposure" or "substantial factor" liability theories under which they do not need to prove defendants were the proximate cause of plaintiffs' injuries because no level of asbestos exposure is safe. [ 3 ] This approach has been rejected by U.S. District Judge David C. Norton . [ 3 ]
Asbestos lawsuits in the U.S. have included the following as defendants:
Manufacturers of machinery in which asbestos-containing parts were used have contested liability on the grounds that nearly all of them either did not ship asbestos-containing parts with their products at all (that is, asbestos was installed only by end users) or did not sell replacement parts for their own products (in cases where the plaintiff was allegedly exposed well after any factory-original asbestos-containing parts would have been replaced), and either way cannot be responsible for toxic third-party parts that they did not manufacture, distribute, or sell. In 2008, the Washington Supreme Court , the first state supreme court to reach the issue, decided in favor of the defense. [ 11 ] On January 12, 2012, the Supreme Court of California also decided in favor of the defense in O'Neil v. Crane Co. [ 12 ]
Another area of dispute remains the so-called chrysotile -defense. Manufacturers of some products containing only chrysotile fibers claim that these are not as harmful as amphibole -containing products. As 95% of the products used in the United States historically were mostly chrysotile, this claim is widely disputed by health officials and medical professionals. [ 13 ] The World Health Organization recognizes that exposure to all types of asbestos fibers, including chrysotile, can cause cancer of the lung, larynx, and ovary, mesothelioma , and asbestosis . [ 14 ]
As of March 2024, the U.S. Environmental Protection Agency finalized regulations banning imports of chrysotile asbestos (effective immediately) due to its link to lung cancer and mesothelioma . However, the new rules can allow up to a dozen years to phase out the use of chrysotile asbestos in some manufacturing facilities. [ 15 ] The long phase-out period was a result of a strong lobby by Olin Corporation , a major chemical manufacturer, as well as trade groups like the U.S. Chamber of Commerce and the American Chemistry Council . Chrysotile asbestos is now banned in more than 50 other countries.
Defendants in asbestos litigation have accused the lawyers who represent plaintiffs of unethical conduct, but those allegations have not been successful in stopping the litigation, nor have courts been sufficiently convinced by the allegations to sanction the law firms against whom the allegations have been raised. [ 16 ]
Since the bankruptcy filing of Johns-Manville in 1984, many U.S. and U.K. asbestos manufacturers have avoided litigation by filing bankruptcy. Asbestos bankruptcy trusts are personal injury trusts established by firms that have filed for reorganization under Chapter 11 of the United States Bankruptcy Code to pay personal injury claims caused by exposure to asbestos. At least fifty-six trusts were established from the mid-1970s through 2011. [ 19 ] The largest 26 of these trusts paid about 2.4 million claims totaling about $10.9 billion up to 2008. [ 19 ] The trusts are governed by trust advisory committees that are generally controlled by lawyers from a few prominent law firms such as Baron & Budd, P.C. and Weitz & Luxenberg P.C. [ 20 ]
Bankruptcy trusts may pay pennies on the dollar to people injured as a result of asbestos exposure. [ 21 ] At the same time, these trusts may permit larger numbers of claimants to receive some kind of compensation, even if greatly reduced from potential recoveries in the tort system.
The federal Medicare Secondary Payer law imposes penalties for paying settlements directly to claimants without repaying the government for medical costs covered under the same programs under the legal doctrine of subrogation . [ 20 ] In late 2016, attorneys general from 13 states sent demand letters to bankruptcy trusts for Armstrong World Industries , Babcock & Wilcox , DII, and Owens Corning . The purpose of the demand letters was to determine if the funds are reimbursing states for medical treatment received under Medicaid and Medicare . [ 22 ]
The pursuit of compensation for asbestos injuries often involves both litigation against solvent defendants and filing claims against asbestos bankruptcy trusts. [ 23 ]
The amount of compensation recovered by an injured plaintiff may depend on whether evidence of exposure to products from bankrupt firms is introduced at trial. If no evidence of exposure from bankrupt firms is presented then increased financial responsibility is likely to be assigned to solvent defendants. [ 23 ] Researchers from RAND Corporation found that if a company filed for bankruptcy plaintiffs claimed exposure to their products in interrogatories and depositions at significantly reduced rates. [ 23 ]
When a plaintiff claiming an asbestos injury has filed a claim against a solvent defendant, courts may extend or reopen discovery when it is discovered that the plaintiff failed to disclose a trust claims. For example, in the 2008 case of Edwards v. John Crane-Houdaille, Inc production of claim forms was delayed until two weeks before trial. [ 24 ] In the 2004 case of Stoeckler v. American Oil Co. [ 25 ] the defendants discovered that the plaintiff did not disclose trust claims only three days after the start of the trial, resulting in the re-opening of discovery. [ 26 ] To help avoid this type of issue, Judges will often adopt mandatory disclosure obligations for bankruptcy trust claims. [ 26 ]
According to a September 2004 of the American Journal of Respiratory and Critical Care Medicine , asbestos is still a hazard for 1.3 million US workers in the construction industry and for workers involved in the maintenance of buildings and equipment. [ 27 ]
Asbestos is not part of an ASTM (American Society for Testing and Materials) E 1527-05 Phase I Environmental Site Assessment (ESA) [ citation needed ] . A building survey for asbestos is considered an out-of-scope consideration under the industry standard ASTM 1527-05 Phase I ESA (see ASTM E 1527-05). ASTM Standard E 2356-04 should be consulted by the owner or owner's agent to determine which type of asbestos building survey is appropriate, typically either a baseline survey or a design survey of functional areas. Both types of surveys are explained in detail under ASTM Standard E 2356-04. Typically, a baseline survey is performed by an EPA (or state) licensed asbestos inspector. The baseline survey provides the buyer with sufficient information on presumed asbestos at the facility, often which leads to reduction in the assessed value of the building (due primarily to forthcoming abatement costs). Note: EPA NESHAP (National Emissions Standards for Hazardous Air Pollutants) and OSHA (Occupational Safety and Health Administration) Regulations must be consulted in addition to ASTM Standard E 2356-04 to ensure all statutory requirements are satisfied, ex. notification requirements for renovation/demolition. Asbestos is not a material covered under CERCLA (Comprehensive Environmental Response, Compensation, and Liability Act ) innocent purchaser defense. In some instances, the U.S. EPA includes asbestos contaminated facilities on the NPL (Superfund). Buyers should be careful not to purchase facilities, even with an ASTM E 1527-05 Phase I ESA completed, without a full understanding of all the hazards in a building or at a property, without evaluating non-scope ASTM E 1527-05 materials, such as asbestos, lead, PCBs, mercury, radon, et al. A standard ASTM E 1527-05 does not include asbestos surveys as standard practice.
In 1988, the United States Environmental Protection Agency (USEPA) issued regulations requiring certain U.S. companies to report the asbestos used in their products. [ 28 ]
A Senate subcommittee of the Health Education Labor and Pensions Committee heard testimony on July 31, 2001, regarding the health effects of asbestos. Members of the public, doctors, and scientists called for the United States to join other countries in a ban on the product. [ 29 ]
Several legislative remedies have been considered by the U.S. Congress but each time rejected for a variety of reasons. In 2005, Congress considered but did not pass legislation entitled the "Fairness in Asbestos Injury Resolution Act of 2005". The act would have established a $140 billion trust fund in lieu of litigation, but as it would have proactively taken funds held in reserve by bankruptcy trusts, manufacturers and insurance companies, it was not widely supported either by victims or corporations.
On April 26, 2005, Philip J. Landrigan , professor and chair of the Department of Community and Preventive Medicine at Mount Sinai Medical Center in New York City, [ 30 ] testified before the US Senate Committee on the Judiciary against this proposed legislation. He testified that many of the bill's provisions were unsupported by medicine and would unfairly exclude a large number of people who had become ill or died from asbestos: "The approach to the diagnosis of disease caused by asbestos that is set forth in this bill is not consistent with the diagnostic criteria established by the American Thoracic Society. If the bill is to deliver on its promise of fairness, these criteria will need to be revised." Also opposing the bill were the American Public Health Association and the Asbestos Workers' Union. [ 31 ]
On June 14, 2006, the Senate Judiciary Committee approved an amendment to the act which would have allowed victims of mesothelioma $1.1M within 30 days of their claim's approval. [ 31 ] This version would have also expanded eligible claimants to people exposed to asbestos from the September 11, 2001 attacks on the World Trade Center, and to construction debris in hurricanes Katrina and Rita . [ 32 ] Ultimately, the bill's reliance on funding from private entities large and small, as well as debate over a sunset provision and the impact on the U.S. budgetary process caused the bill to fail to leave committee. The Environmental Protection Agency ( EPA ) has no general ban on the use of asbestos. However, asbestos was one of the first hazardous air pollutants regulated under Section 112 of the Clean Air Act of 1970, and many applications have been forbidden by the Toxic Substances Control Act (TSCA).
In 2010, Washington passed a ban on hazardous materials in automotive brakes, phasing out asbestos in vehicle brakes, starting in 2014. [ 33 ]
In 2013, Ohio passed became the first state to pass a law requiring transparency in asbestos bankruptcy trust claims. [ 34 ] The same year Oklahoma passed a similar law called The Personal Injury Trust Fund Transparency Act. This law applies to all personal injury trusts. It requires plaintiffs to disclose all previously filed and anticipated trust claims for personal injuries within 90 days of filing a personal injury tort but not until at least 180 days before the assigned court date. If the plaintiff anticipates filing a trust claim all proceedings are stayed until their filing is complete. Filing new claims or amending claims after the initial disclosure triggers a new disclosure requirement. The law also allows defendants to stay proceedings by showing that the plaintiff could make a good faith filing with a trust. The law gives plaintiffs ten days to either file such a claim or show that it would probably be unsuccessful. [ 26 ]
In South Carolina in 2015, State Senator Shane Massey introduced Senate Bill 281, "The Court Transparency Act." S.281 would prohibit the state of South Carolina from hiring outside lawyers. Similar bills have been passed into law by 18 states. The bill would also prevent juries from awarding damages that exceed actual out of pocket costs incurred by plaintiffs. [ 35 ] [ 36 ] [ 37 ]
In June 2015, Texas Governor Greg Abbott signed Texas House Bill 1492 into law. The law was written to end so-called asbestos "double dipping" in Texas. [ 38 ] This law requires asbestos victims to perform more actions before proceeding to trial, and lowers the standard of proof of asbestos exposure for manufacturers to shift the blame onto other bankrupt companies. [ 39 ] A year earlier, Wisconsin Governor Scott Walker signed a similar bill into law.
In June 2016, President Obama signed into law the Frank R. Lautenburg Chemical Safety for the 21st Century Act (H.R. 2576). It serves to reform the TSCA of 1976 and aims to make federal safety regulations on toxic substances and chemicals effective. [ 40 ]
In 2017, Iowa , Mississippi , North Dakota , and South Dakota all passed asbestos trust claims transparency laws. [ 34 ]
Asbestos abatement (removal of asbestos) has become a thriving industry in the United States. Strict removal and disposal laws have been enacted to protect the public from airborne asbestos. [ 41 ] The Clean Air Act requires that asbestos be wetted during removal and strictly contained, and that workers wear safety gear and masks. The federal government has prosecuted dozens of violations of the act and violations of Racketeer Influenced and Corrupt Organizations Act (RICO) related to the operations. Often these involve contractors who hire undocumented workers without proper training or protection to illegally remove asbestos. [ 42 ]
W. R. Grace and Company faces fines of up to $280 million for polluting the town of Libby , Montana . Libby was declared a Superfund disaster area in 2002, and the EPA has spent $54 million in cleanup. Grace was ordered by a court to reimburse the EPA for cleanup costs, but the bankruptcy court must approve any payments. [ 43 ]
The U.S. Supreme Court has dealt with several asbestos-related cases since 1986. Two large class action settlements, designed to limit liability, came before the court in 1997 and 1999. Both settlements were ultimately rejected by the court because they would exclude future claimants, or those who later developed asbestos-related illnesses. [ 44 ] [ 45 ] These rulings addressed the 20-50 year latency period of serious asbestos-related illnesses.
In this case a federal appeals court ruled that an insulation installer from Texas could sue asbestos manufactures for failure to warn. Borel's lawyers argued that had warning labels been affixed to Fiberboard's products he would have been able to protect himself more effectively. [ 46 ]
The Manville Corporation, formerly the Johns-Manville Corporation, filed for reorganization and protection under the United States Bankruptcy Code in August 1982. At the time, it was the largest company ever to file bankruptcy, and was one of the richest. Manville was then 181st on the Fortune 500 , but was the defendant of 16,500 lawsuits related to the health effects of asbestos. The company was described by Ron Motley , a South Carolina attorney, as "the greatest corporate mass murderer in history." Court documents show that the corporation had a long history of hiding evidence of the ill effects of asbestos from its workers and the public.
In a decision from January 2014, Gray v. Garlock Sealing Technologies had entered into bankruptcy proceedings, and discovery in the case uncovered evidence of fraud [ 47 ] that led to a reduction in estimated future liability to a tenth of what was estimated.
A number of lawsuits have been filed under the Racketeer Influenced and Corrupt Organizations Act (RICO) in response to what defendants claim to be fraudulent asbestos-related lawsuits. RICO suits are civil in nature and brought by private parties. They typically allege that the suits themselves are forms of racketeering or that lawyers and experts had to engage in racketeering activities in order to bring them. [ 48 ]
For example,
Some companies and their executives have faced criminal prosecution for their actions in exposing workers to the dangers of asbestos, or their improper handling of asbestos waste.
On February 20, 1973 a federal grand jury in Detroit, Michigan indicted Adamo Wrecking Company ("Adamo") for violating provisions of the Clean Air Act by knowingly causing the emission of asbestos by failure to wet and remove friable asbestos materials from demolitions. [ 55 ]
Adamo was one of a number of demolition contractors indicted throughout the country for the alleged violation of the Clean Air Act. The United States District Court for the Eastern District of Michigan dismissed the criminal indictment on the ground that it was not an "emission standard," but a "work practice standard," which under the terms of the statute, did not carry criminal liability. [ 56 ]
The government appealed and the Sixth Circuit Court of Appeals reversed the decision of the trial court, stating that it erred in determining that it had jurisdiction to review the validity of the standard in a criminal proceeding. [ 57 ] Adamo's attorneys appealed to the Supreme Court . [ 58 ]
On January 10, 1978, the Supreme Court ruled in favor of Adamo when it held that the trial court did have jurisdiction to review the standard in a criminal proceeding and also agreed with the trial court that the requirements in the act were "not standards" but "procedures" and therefore the proceedings were properly dismissed. [ 59 ] [ 60 ]
A federal grand jury indicted W. R. Grace and Company and seven top executives on February 5, 2005, for its operations of a vermiculite mine in Libby, Montana . The indictment accused Grace of wire fraud , knowing endangerment of residents by concealing air monitoring results, obstruction of justice by interfering with an Environmental Protection Agency (EPA) investigation, violation of the Clean Air Act, providing asbestos materials to schools and local residents, and conspiracy to release asbestos and cover up health problems from asbestos contamination. The Department of Justice said 1,200 residents had developed asbestos-related diseases and some had died, and there could be many more injuries and deaths. [ 43 ] [ 61 ]
On June 8, 2006, a federal judge dismissed the conspiracy charge of "knowing endangerment" because some of the defendant officials had left the company before the five-year statute of limitations [ clarification needed ] had begun to run. The wire fraud charge was dropped by prosecutors in March.
On April 2, 1998, three men were indicted in a conspiracy to use homeless men for illegal asbestos removal from an aging Wisconsin manufacturing plant. Then-US Attorney General Janet Reno said, "Knowingly removing asbestos improperly is criminal. Exploiting the homeless to do this work is cruel." [ 62 ]
On December 12, 2004, owners of New York asbestos abatement companies were sentenced to the longest federal jail sentences for environmental crimes in U.S. history, after they were convicted on 18 counts of conspiracy to violate the Clean Air Act and the Toxic Substances Control Act , and actual violations of the Clean Air Act and Racketeer-Influenced and Corrupt Organizations Act. The crimes involved a 10-year scheme to illegally remove asbestos. The RICO counts included obstruction of justice, money laundering, mail fraud and bid rigging, all related to the asbestos cleanup. [ 63 ]
On January 11, 2006, San Diego Gas & Electric Co., two of its employees, and a contractor were indicted by a federal grand jury on charges that they violated safety standards while removing asbestos from pipes in Lemon Grove, California . The defendants were charged with five counts of conspiracy, violating asbestos work practice standards and making false statements . [ citation needed ]
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Mira Ashby , CM (1922 – July 16, 2005 [ 1 ] ) was the founder of Ashby House, which opened in 1978 in Toronto. [ 2 ] Ashby House was the first community-based brain injury rehabilitation program in North America. The first transitional living program for adults with acquired brain injury , it became the model for many other programs across Canada, the US and many other parts of the world. Ashby House has changed its name to Community Head Injury Resource Services of Toronto (CHIRS) where there is still the Ashby Community Support Services. Mira Ashby received the Order of Canada in 1984 for her work on brain injury rehabilitation. [ citation needed ]
Ashby was also doctor in the Red Cross during World War II and spoke more than eight languages fluently. She died in Toronto on July 16, 2005, when she was 84 years old.
This biography related to medicine in Canada is a stub . You can help Wikipedia by expanding it .
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The Ashley Treatment refers to a controversial set of medical procedures performed on an American child, " Ashley X ". Ashley, born in 1997, has severe developmental disabilities due to static encephalopathy ; she is assumed to be at an infant level mentally, but continues to grow physically. The treatment included growth attenuation via high-dose estrogens , hysterectomy , bilateral breast bud removal, and appendectomy . [ 1 ] In June 2016, after 18 years of searching, Ashley's condition was determined to be the result of a de novo (not inherited, i.e. a mutation ) and non-mosaic single-nucleotide polymorphism in the GRIN1 gene, [ 2 ] which is implicated in neurotransmission .
The principal purpose of the treatment was to improve Ashley's quality of life by limiting her growth in size, eliminating menstrual cramps and bleeding, and preventing discomfort from large breasts. The combination of the surgery and the estrogen therapy attracted much public comment and ethical analysis in early 2007, both supportive and condemning. [ 3 ] [ 4 ]
Ashley's parents granted their first written interview to CNN Health in March 2008, [ 5 ] and their second to The Guardian in March 2012. [ 6 ] In addition, The Guardian published two interviews with mothers of a girl [ 7 ] and a boy [ 8 ] who had completed the treatment. A 2014 TV program and article tell the similar story of a girl in New Zealand . [ 9 ] [ 10 ] A survey on growth attenuation among pediatric endocrinologists was published in July 2015. [ 11 ] [ 12 ]
Ashley was born with a severe brain impairment of genetic cause, [ 2 ] termed a "static encephalopathy " because it does not improve. Although she sleeps and awakens, and breathes on her own, she is unable to raise her head, sit up, hold an object, walk, or talk, and must be tube-fed. Nonetheless, she is alert and responsive to her environment, particularly enjoying the music of Andrea Bocelli . Her parents have nicknamed Ashley "Pillow Angel", because she always remains where she is placed, which is usually on a pillow. [ 2 ]
In 2004 when Ashley was six and a half years old, she began to show signs of puberty [ 2 ] and her parents and doctors began to anticipate a variety of issues common in children with severe neurological impairments. As these children grow larger, it takes more strength to move them and provide basic bodily care, raising the risk of pressure sores from immobility. Precocious puberty is common in children with various forms of severe brain damage. The early appearance of secondary sexual characteristics is often distressing to parents and caretakers. Many parents of severely disabled children explore possible ways to avoid having to deal with menstruation and fertility in a diapered child. [ citation needed ] A variety of treatments have been used over the last several decades to deal with these issues.
In July 2004, Ashley had a hysterectomy (to prevent menstruation ) and surgical removal of her nascent breast buds (to prevent development). She also underwent an appendectomy (because Ashley would not be able to vocalize symptoms). The surgery was performed at Seattle 's Children's Hospital and Regional Medical Center . In addition, in December 2006 she completed estrogen therapy through dermal patches, which sped up the natural closure of her growth plates .
Ashley's story first broke in October 2006, in the Archives of Pediatrics & Adolescent Medicine . In January 2007, her parents, who wish to remain anonymous, set up a blog to explain their reasoning for their decision and to share their story with families of other children who might benefit. [ 2 ]
The parents state that they sought such treatment for the best interests of their daughter, namely, to enable them to personally continue constant care for her at home; to maximize her inclusion in family activities; to avoid the cramps and discomfort associated with menstruation; and to avoid the discomfort from large breasts (which runs in Ashley's family) while lying down or strapped in the chest area while in her wheelchair. Furthermore, they cited additional side benefits: to reduce the risk of bedsores; to prevent breast cancer and fibrocystic growth (both of which have occurred in her family); to prevent pregnancy ; and to prevent appendicitis , which occurs in 5% of the population and which would be difficult to diagnose in Ashley as she would be unable to communicate the symptoms. They also believe that without secondary sexual characteristics , Ashley will be less vulnerable to sexual abuse [ 2 ] by future caregivers when her parents will no longer be able to care for her.
In an article published in June 2009 on Growth Attenuation, two pediatric endocrinologists and two bioethicists concluded as follows:
Our analysis suggests that growth attenuation is an innovative and sufficiently safe therapy that offers the possibility of an improved quality of life for nonambulatory children with profound cognitive disability and their families. Pediatricians and other care providers should include discussion of these options as part of anticipatory guidance around the age of 3 years so that, if elected, potential clinically meaningful benefits of growth-attenuation therapy can be realized. [ 13 ]
The two bioethicists from the previous article also published an article in January 2010 cataloging and countering the criticisms that targeted the Ashley Treatment, and concluded as follows:
The purpose of this paper is to provide a brief review of the [Ashley Treatment] case and the issues it raised, then address 25 distinct substantive arguments that have been proposed as reasons that Ashley's treatment might be unethical. We conclude that while some important concerns have been raised, the weight of these concerns is not sufficient to consider the interventions used in Ashley's case to be contrary to her best interests, nor are they sufficient to preclude similar use of these interventions in the future for carefully selected patients who might also benefit from them. [ 14 ]
After a year, Ashley's parents considered her treatment a success: She will never experience menstrual discomfort and cramps, she will always be flat chested and avoid breast related discomfort and other issues, and with her growth plates closed, she has reached her adult height of 53 inches (135 cm, or 4 ft 5 in) and weight of 63 pounds (29 kg), an estimated reduction of her potential height and weight of 20% and 40%, respectively. [ tone ] [ 15 ]
In the United States, Arthur Caplan , of the University of Pennsylvania's Center for Bioethics , has criticized the Ashley Treatment in an MSNBC editorial, arguing that it is "a pharmacological solution for a social failure—the fact that American society does not do what it should to help severely disabled children and their families." [ 16 ] Three renowned bioethicists spoke in support of the treatment and discussed different aspects of it in opinion statements presented by Scientific American. [ 17 ]
Disability rights advocates, including Not Dead Yet [ 18 ] and Feminist Response in Disability Activism (FRIDA), called the treatment "invasive medical experimentation", "mutilation", "desexualization", and a violation of Ashley's human rights . FRIDA called on the American Medical Association to condemn the Ashley Treatment. [ 19 ] The Disability Rights Education and Defense Fund (DREDF) declared, "we hold as non-negotiable the principle that personal and physical autonomy of all people with disabilities be regarded as sacrosanct". [ 20 ]
Ashley's parents reported that 95% of the 5,000 emails they received were in support of the treatment, many of these testimonies and support emails are posted on Ashley's blog. [ 2 ] The parents indicated that there was especially strong support among parents and caregivers of children with similar conditions to Ashley's, those who have the direct experience. They cite several ethicists in support of the treatment, including George Dvorsky , [ 21 ] Peter Singer , [ 22 ] Norm Fost, [ 23 ] and
Doug Diekema. [ 24 ]
In the United Kingdom, the British Medical Association stated, "If a similar case occurred in the UK, we believe it would go to court and whatever decision was ruled would be in the best interests of the child." Dr. Peter Hindmarsh, Professor of Paediatric Endocrinology at Great Ormond Street Hospital was troubled by the treatment decision being taken by a hospital ethics committee . " 'I am not sure the ethics committee was the right place to decide,' he said, adding that it was not clear who represented the child's interests when it went before the committee." [ 25 ]
In Canada , ethicist Arthur Schafer 's nationwide opinion piece [ 26 ] defending the operation as justifiable considering Ashley's comfort engendered criticism from disability rights activists such as Dave Hingsburger [ 27 ] of the York Central Hospital and Keenan Wellar from the LiveWorkPlay self-advocacy organization. In a rebuttal, [ 28 ] Wellar attacked the notion that Ashley's limited mental abilities justified the decisions made on her behalf: "Infants have human rights even though they can't speak for themselves. Why should Ashley have received any less consideration?"
On May 8, 2007, an investigative report done by Disability Rights Washington (formerly The Washington Protection and Advocacy System) in conjunction with The Utah Disability Law Center criticized the hospital that performed this controversial procedure for violating Washington State law, [ 29 ] which is disputed by the family's attorney.
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The Asian Pacific Journal of Cancer Prevention is a biweekly peer-reviewed open access medical journal covering oncology . It was established in 2000 and is published by the Asian Pacific Organization for Cancer Prevention , of which it is the official journal. It is also the official journal of the International Association of Cancer Registries . [ 1 ] The editor-in-chief is Alireza Mosavi Jarrahi ( Shahid Beheshti University of Medical Sciences Tehran, Iran).
The journal is abstracted and indexed in Index Medicus / MEDLINE / PubMed , [ 1 ] and Scopus . [ 2 ] According to the Journal Citation Reports , the journal has a 2014 impact factor of 2.514 but has not had an impact factor recorded since then. [ 3 ]
This article about an oncology journal is a stub . You can help Wikipedia by expanding it .
See tips for writing articles about academic journals . Further suggestions might be found on the article's talk page .
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Askin's tumor is a rare, primitive neuroectodermal tumor which arises from the soft tissues of the chest wall , particularly of the paravertebral region. [ 1 ] [ 2 ] It was first described by Askin et al. in 1979. [ 3 ] Askin's tumor is now recognized as part of the Ewing's sarcoma family of tumors . [ 4 ] This neoplasm tended to recur locally, but did not seem to disseminate as widely as some of the other small cell tumors of childhood such as rhabdomyosarcoma or neuroblastoma .
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Asomatognosia (also Somatoagnosia ) is a neurological disorder characterized as loss of recognition or awareness of part of the body. [ 1 ] [ 2 ] The failure to acknowledge, for example, a limb, may be expressed verbally or as a pattern of neglect. The limb may also be attributed to another person, a delusion known as somatoparaphrenia . However, they can be shown their limb and this error is temporarily corrected. [ 3 ] [ 4 ] Some authors have focused on the prevalence of hemispatial neglect in such patients. [ 5 ]
Asomatognosia is the inability to feel, recognize, or be conscious of one's own specific body parts or bodily conditions (Whishaw, 2015). Generally, asomatognosia often arises from damage to the right parietal lobe (Whishaw, 2015). Evidence indicates that damage to the right hemisphere often results from a stroke or pre-existing hemispatial neglect , or inattention to the left visual field (Antoniello, 2016) (Keenan, 2004). Individuals who suffer from somatoparaphrenia, a specific form of asomatognosia, ignore or deny ownership of a body part contralateral to the brain lesion (Feinberg, 1990). Although this condition can affect one or both sides of the body, most patients exhibit the inability to recognize limbs/body parts (i.e., arm, leg, head, breast) on the left side of their body as their own (Keenan, 2004). While individuals with asomatognosia typically suffer large lesions across several temporoparietal sectors, those with somatoparaphrenia also suffer lesions in the right medial and orbitofrontal regions of the brain (Feinberg 2010).
In 20th century literature, asomatognosia was often distinguished from the closely related somatoparaphrenia . According to Gerstmann 's (1942) definition, asomatognosia was described as the "imperception of the affected limbs or body half, in various degrees from simple forgetting to obstinate denial of their existence." Critchley (1953) [ 6 ] numbered various deficits of body image, including somatoparaphrenia and the rare loss of awareness of one body half corresponding to asomatognosia or hemi depersonalization . He stated that these (as well as other bodily) phenomena are not "sharply demarcated" and that it is not uncommon for one condition to merge into another. In Hécaen (1972) hemiasomatognosia and disownership were also distinguished but closely linked. Feinberg and colleagues (1990, 2010) forwarded a different definition, according to which verbal asomatognosia was defined as the denial of ownership, while somatoparaphrenia as a subtype of asomatognosia where patients also display delusional misidentification and complex confabulation . [ 7 ]
The term asomatognosia was coined from the Greek : a (without), soma ( stem somat– body or bodily), and gnosis (knowledge), thus defined as the "lack of awareness [of ownership] of one's body parts". [ 8 ] The word Somatoagnosia (constructed from the same roots) is sometimes also used instead. [ 9 ] [ 10 ] [ 11 ]
In most commonly observed instances, individuals with this condition fail to recognize and sense their left arm after suffering lesions to the right hemisphere (Keenan, 2004). In one specific instance, a patient suffering from asomatognosia tried to throw her own left arm into a garbage can because she believed it was her husband's arm repeatedly falling on her and disrupting her sleep (Keenan, 2004). Even when patients are told that the body part belongs to them, many will deny the reality and remain firm in their belief that it is not a part of them. There is a case in which a patient with severe asomatognosia had the ability to use his right hand to trace his paralyzed left arm to his own left shoulder, but still failed to acknowledge that the left arm belonged to him (Keenan, 2004). Overall, there is an interesting phenomenon in which individuals will claim that the body part belongs to someone of the opposite gender within their family. For example, women with asomatognosia tend to claim that their left arm belongs to a man (i.e., their husband) while men claim their arm belongs to a woman, such as his daughter or wife. There also exist patients that treat the arm as a child or small animal. (Keenan, 2004)
In addition to instances of asomatognosia in which patients deny ownership of a specific part, this condition is also associated with the following: anosognosia (unawareness or denial of illness), anosodiaphoria (indifference to illness), autopagnosia (inability to localize and name body parts), and asymbolia for pain (absence of typical reactions to pain). Out of these varieties of asomatognosia, autopagnosia is the only one in which an individual struggles to recognize the right side of their body due to lesions in the left parietal cortex (Whishaw, 2015).
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The assault on T. J. Joseph occurred on 4 July 2010. T. J. Joseph, a professor of Malayalam at Newman College, Thodupuzha , a Christian minority institution affiliated with Mahatma Gandhi University [ 3 ] had his wrist disarticulated on allegation of blasphemy , by members of Popular Front of India , an Islamic organisation in India. [ 4 ] The then Minister of Home Affairs of Kerala, Kodiyeri Balakrishnan , made a statement that while government is aware that there is a local Dar-ul Khada set up by All India Muslim Personal Law Board , functioning to resolve civil disputes, there were no complaints received that it was passing "Taliban-model" orders. [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ]
T. J. Joseph , a professor of Malayalam language at Newman College , Thodupuzha , set a question in the Malayalam internal examination paper for second-year BCom students in March 2010. In the examination, question number 11 asked students to punctuate a dialogue between a character and God, given below: [ 10 ]
The passage was adapted from a lecture by Malayalam film director P. T. Kunju Muhammed that was in his book, Thirakathayude Reethisasthram (Methodology of Screenplay), published by Kerala State Institute of Languages . [ 12 ] [ 13 ] In the original text, Kunju Muhammed explains a scene in his 1999 film Garshom , in which the character Nasarudheen, an NRI who has returned to India, is madly talking to himself. Kunju Muhammed based the character Nasarudheen on a person with schizophrenia he had met near the road who was talking to God.
T.J. Joseph named the character 'Muhammed' in the question paper, which was a reference to the author P.T. Kunju Muhammed , but it also made the text open to misinterpretation as a dialogue between God and the Islamic Prophet Muhammad .
The local edition of the Madhyamam newspaper reported the incident, [ 14 ] sparking off the controversy alleging blasphemy. Several Muslim organisations protested the alleged defamation of Muhammed. [ 15 ] The Campus Front, the Popular Front of India 's student wing, launched an agitation against the professor. [ 14 ] Student groups affiliated to the Indian National Congress and the Indian Union Muslim League also marched towards the college in protest. [ 16 ] Copies of the question paper were circulated in sensitive areas by various Muslim organisations. [ 17 ]
An all-party meeting called by the District Collector decided to recommend action against the professor responsible for incorporating the question that reportedly hurt the religious sentiments of the community. [ 18 ]
The state police registered a case under Section 295 of the Indian Penal Code (for causing communal hatred) against the professor who subsequently absconded. The police then issued a lookout notice for him and arrested him a week later. He was then released on bail in April. The Newman College authorities also suspended him from the college and apologised for the mistake. [ 19 ] [ 20 ] [ 21 ] [ 22 ] His son was taken to hospital after being beaten up in police custody. [ 23 ]
On 4 July 2010, a group of eight people in a Maruti Omni waylaid the professor near his home at Muvattupuzha . According to Joseph's sister, Stella Joseph, around eight people armed with swords and knives came in a van and waylaid their vehicle. They pulled out the lecturer after smashing the windscreen. They then chopped off his right hand and stabbed him in the left thigh. When they tried to stop the assault, she and her mother were attacked by the assailants who then detonated bombs and fled the scene. [ 24 ] [ 1 ] [ 25 ] [ 26 ] According to police, the attack was carried out by an eight-member team consisting of Savad of Asamannoor , Pareeth of North Vazhakkulam, Shobin of Kothamangalam , Nazar of Aluva , Shajil of Muvattupuzha , Shamsuddin of Perumbavoor , Shanvas and Jamal. [ 27 ]
A neighbour rushed Joseph to Nirmala Hospital where first aid was administered, while the severed hand was collected and packed in ice. Joseph was taken to the Specialists Hospital in Kochi where he underwent an operation that lasted 16 hours.
Joseph gave a media interview from his hospital bed, where he stated that he had used an extract from a university-approved book on the Malayalam language, and that his opponents did not give him an opportunity to explain the situation. He said that the naming of the village madcap as Muhammad had been done as a tribute to the original author, P. T. Kunju Muhammed . Joseph's family made a statement that they forgive the attackers. [ 28 ]
On 24 July 2010, his suspension from the college was revoked by the Mahatma Gandhi University which described the issue as an "unintentional error". The attack on the teacher and his financial conditions were also considered. [ 29 ]
On 4 September 2010, the management of college terminated Professor Joseph from service with effect from September for hurting the religious sentiments of a community. [ 30 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ] Joseph, who expressed grief over the management decision, said that he never expected the same. He said that management has given the highest punishment for him and his family. [ 35 ] Terming the action of management as irrational, pro-Left writers, cultural forums and teachers unions came in support of the Professor. [ 36 ] [ 37 ] [ 38 ] [ 39 ]
PFI leader Anas won the Vanchinad division of Vazhakkulam block in Ernakulam district in the civic body elections, while he was in judicial custody and lodged in the Viyyur central jail in connection with the case. [ 40 ]
On 19 March 2014, Joseph's wife Salomi (48), was found dead, having hanged herself at her residence. She had resorted to the extreme measure due to mental pressure over her husband not having been reinstated into the college. The family had been failing to make both ends meet with no regular income for a lengthy period of time. [ 41 ]
The state police arrested two activists of the Popular Front of India , Asharaf and Jaffer, on the same day. According to the police, Asharaf had been privy to the entire operation, and had arranged the vehicle used by the assailants. The vehicle was then reportedly handed over to Jaffer for dismantling.
On the night of 4 July, Aluva ASP J. Jayanath conducted a raid at the house of Mansoor, Eranakulam District Secretary of the Popular Front of India at Kunnathery , Aluva and seized documents and CDs which revealed the connection of PFI activists with the attack. [ 42 ] [ 43 ] The State police was criticised when some of the officers of Ernakulam range made a deal with the Popular Front of India for ending investigation in the case. The move was reported to be thwarted by the involvement of state internal affairs minister. According to DGP Jacob Punnoose a new investigation team under Thrissur Crime Branch SP P.N. Unniraja was made in charge of investigation [ 44 ] Punnoose also informed that the crime was well-organised with pumping in money. [ 45 ]
The Kerala State Police on 9 July 2010 issued 'look out notices' for three accused who absconded after the attack.
On 8 July 2010, a team led by Aluva ASP J Jayanath unearthed a gun from the house of Ayoob, a leader of the Popular Front of India. [ 46 ]
The state police also raided the houses and offices of Popular Front of India and its political arm Social Democratic Party of India (SDPI) [ 47 ] [ 48 ] at Muvattupuzha , Kothamangalam Perumbavoor , Chalakudy , Thrishur , Angamaly , Aluva , Cochin and Ernakulam . [ 47 ] [ 48 ] [ 49 ]
The Kerala state police seized explosives, country-made bombs, weapons and incriminating materials. [ 47 ] [ 50 ] [ 51 ] [ 52 ] A CD linked to al-Qaeda has also been seized from a PFI activist Kunjumon. [ 53 ] [ 54 ] The police eventually booked him under anti-terrorism laws. [ 55 ] It is reported to be a propaganda CD with brutal killing and torture of westerners. [ 56 ] [ 57 ] [ 58 ] According to Police, the CDs have been in used condition and were used to train PFI activists to commit the crime. It also showed that the organisation had contact with international bodies. [ 59 ] The CDs have been reported to be brought from either Afghanistan, Pakistan or the Gulf countries. [ 60 ]
Judicial First Class Magistrate Court, Muvattupuza, declared the absconding Popular Front of India leaders, K K Ali and Nazar as proclaimed offenders. [ 61 ]
A dentist, an active PFI worker, had been arrested on charges of sedition. Dr Raneef, a native of Aluva near Kochi , had given first aid to one of the assailants who was injured during the attack. Two books that speak against democracy have been recovered from the doctor, who had been associated with extremist activities since 2002. Copies of one of the seized books, Islam and Democracy , had been recovered from a Students Islamic Movement of India (SIMI) camp held in 2006 at Aluva. [ 62 ]
On 21 July 2010, the Kerala police arrested the Popular Front of India leader, who was suspected to be one of the conspirators behind the attack on the professor. Yunus, 33, a divisional leader of the PFI, was arraigned as the fourth accused in the case. [ 62 ]
Based on the confessions of Yunus, cases of conspiracy have been registered against Shiyas, divisional secretary of PFI 's Nellimattam unit in Ernakulam district and Mohammed Ali of Muvattupuzha , while a case has been registered against Latheef of Aluva and MoideenKutty of Valancherry in Malappuram district for harbouring some of the accused involved in the attack on Joseph. [ 63 ]
On 13 August 2010, The Aluva police led by ASP J. Jayanath arrested six activists of the Popular Front of India while they were holding a meeting and attempting to distribute propaganda booklets. 320 copies of the book "Asavarnarkku Nallathu Islam", which contained material tarnishing Hindu and Christian religions, were seized from the hall where the meeting was being held. [ 64 ] [ 65 ]
On 15 August, police arrested Niyaz against whom a lookout notice had been issued in the case relating to the attack as he was travelling in a train from Tamil Nadu to Kerala. He was arrested when the train reached Shoranur. [ 66 ] Niyas reportedly owned the Lancer car recovered by Aluva police from Kunjunnikkara on 29 July. [ 67 ]
On 17 August, a police team led by Debesh Kumar Behera, ACP (South) raided Nanma books in Court Road, Kozhikode and a huge cache of books and compact discs containing incriminating and anti-national content were seized at the publishing firm. [ 68 ]
P Abdul Hameed, Kerala state general secretary of the Popular Front of India , was questioned by the Special Investigation Team probing the hand-chopping case in Ernakulam on 17 August. Earlier on 16 August, Prof P Koya, chief editor of Thejas daily and member of PFI supreme council, was questioned at the Aluva police club by the SIT. [ 69 ]
On 19 August Special Investigation Team (SIT) officials questioned Nazeruddin Elamaram, President of the Popular Front of India at Muvattupuzha . [ 70 ]
Shamsuddin, one of the attackers in the team, who hails from Perumbavoor was arrested from Palakkad by the police on 20 August. [ 71 ] Based on the information provided by him police arrested Jamal from the Beemapally area in Thiruvananthapuram on 28 August. [ 72 ] [ 73 ] Announcing Jamal's arrest, SP P N Unnirajan, heading the SIT informed the newsmen that the trial of the case would be conducted in the special court in Ernakulam where the NIA cases were also handled. [ 74 ]
On 26 August the National Investigation Agency (NIA) informed the Kerala High Court that they are not planning to investigate the case as charges framed by the police does not cover anti-national terrorist activities. [ 75 ] On the same day SIT questioned M Usman, managing director of Thejas daily. [ 76 ]
KK Ali, who purchased the van which was used by the attackers, from Lawrance of Thrissur, two weeks prior to the attack was arrested by SIT from Pollachi on 30 August. [ 77 ]
Police arrested Shobin, a B-Tech graduate of Kothamangalam , and Shanavaz alias Shemy of Valluvalli near North Paravur, from the Coimbatore railway station on 6 September.
On 6 September 2010, the Kerala Government informed the state high court that investigators found no evidence of a connection between the Popular Front of India with Hizbul Mujahideen, Lashkar-e Taiba (Let) or al-Qaeda. [ 78 ] [ 79 ]
On 8 September the Kerala High Court dismissed the bail applications of seven activists of Popular Front of India - Siyad, Sikander, Kamarudeen, Abdul Lateef, Moideen Kutty, Shiyas and Mohammed Ali. Turning down their bail pleas, Justice V Ramkumar said the objective of the activity was to disturb harmony and tranquility of the society and to create fear. It would be held to be a terror activity. [ 80 ] [ 81 ]
On 15 September the Kerala government transferred four cases registered against PFI activists to the Internal Security Investigation Team (ISIT) which probes terrorism-related incidents. [ 82 ]
On 17 September the Kerala High Court gave bail to Dr. Raneef. The complaint of Dr Raneef that the police conducted a raid at his residence and hospital to come out with allegedly incriminating CDs, leaflets etc. as he refused to oblige the Aluva ASP J. Jayanath to become an approver by confessing that he was a conspirator in the hand chopping case, was accepted by the court while considering his bail application. [ 83 ]
On 7 October police arrested Pareeth of Vazhakkulam, who was directly involved in the attack from Mangalore in Karnataka. [ 84 ] Some reports suggest that Pareeth, who was hiding in Mumbai actually surrendered before the police in a deal with PFI . [ 85 ]
On 3 January 2011 the Ernakulam Additional Sessions Court Judge V Shersy granted bail for the two main accused. Prime accused Jaffar (29) and second accused Ashraf (37) were granted bail on strict conditions. On the same day the Supreme Court bench comprising Js Markandey Katju and Dhyansudha Misra upheld the bail granted to Dr Raneef (ninth accused) by the Kerala High Court. [ 86 ] [ 87 ]
On 14 January police filed a charge sheet against 27 activists of the PFI accusing them of attempt to murder and other offences like IPC Sections 201 (causing disappearance of evidence), 202 (intentional omission to give information of offence), 212 (harbouring offender), 143 (unlawful assembly), 148 (rioting armed with deadly weapon), 120(B) (Criminal conspiracy) and 323 (causing hurt). [ 88 ]
On 10 January 2024, after 13 years of absconding, one of the main accused Savad was arrested from a rented house in Kannur. He was produced before the NIA Special Court in Kochi on 11 January 2024. [ 89 ]
The Kerala State Assembly raised its voice in unison to strongly condemn the hacking of T. J. Joseph, by fundamentalist elements on the following day. [ 90 ]
Various Muslim organisations including the Indian Union Muslim League (IUML) condemned the attacks as "against the tenets of Islam". [ 91 ] [ 92 ] A rally under the banner of Muslim Aiykyavedi (Muslim United Front) was organised the next day in Muvattupuzha and Perumbavoor . They also blocked the local police station at Perumbavoor demanding the release of arrested Popular Front of India leaders. The protest though was dismissed by other Muslim organisations as a ploy by the Popular Front of India and challenged it to name any other organisation involved in the protest. [ 93 ] [ 94 ] A meeting of all the major Muslim organisations in Kerala proclaimed that the hand chopping incident has been a shame to the Muslim community in Kerala. They have also decided to isolate radical outfit like Popular Front of India . [ 95 ]
The Kothamangalam diocese demanded National Investigation Agency inquiry into the entire incident. The Bishop of Kothamangalam diocese, Mar George Punnakottil issued pastoral letters condemning the attack on Professor and demanding nabbing of culprits. The pastoral letter also defended the dismissal of the professor from the college. Prayer meetings and silent protest marches were also organised in various churches and locations. [ 96 ] Christian organisations like Global Council of Indian Christians and Catholic Bishops' Conference of India (CBCI) condemned the act and demanded that the attackers be brought to justice soon and be exemplarily punished. [ 97 ] [ 98 ] The Newman fraternity made a public appeal to extend a helping hand to Prof. T. J. Joseph. [ 99 ] However, the Catholic authorities of the college dismissed him from the job and defend their action. [ 100 ]
The Bharatiya Janata Party set up a four-member panel headed by Mr Harin Pathak (senior Supreme Court lawyer), Pinky Anand, Wilfred Misquita (Goa BJP vice-president) Advocate Balasubramanium Kamarasu. The Committee met with the members of family of Prof. Joseph to get a first-hand report on the sequence of events during the attack. They demanded a probe by the National Investigation Agency (NIA) into the incident. Mr Harin Pathak alleged that the Kerala Government had failed miserably in combating terror and the State was becoming a breeding ground for terrorist activities. Pathak also demanded that outfits like the NDF and Popular Front of India should be banned and the State Government produce a white paper on the investigation into terror activities in the state. He also noted that his party would highlight the gruesome attack on Prof. Joseph in the upcoming session of the Indian Parliament . [ 101 ] [ 102 ]
The Hindu in its editorial said "Freedom of expression has increasingly come under attack from religious fanatics in democratic and secular India and it is the duty of society and the political system to intervene more effectively to defend those who are targeted even if they express unpopular views". The Hindu also noted in its editorial that "The act of a gang that cut off the hand of a college teacher, by wielding an axe on a thoroughfare in Kerala in broad daylight, had Talibanism writ all over it. This act of barbarism, however, points to the rise of bloodthirst driven by religious fundamentalism that certain fringe elements may be seeking to impose on the State. That it was a planned operation carried out with brutal intent adds to the shock.". [ 103 ]
Littérateur M.N. Karasseri, himself a retired professor and someone who keeps tabs on Muslim politics, noted in an Outlook article, "The Muslim youth today are looking for idealism and adventure. They are being misguided by the proponents of Maududism that espouses a do-or-die battle for ensuring hukumathe ilahi (the rule of Allah). The SDPI ( Socialist Democratic Party of India ), Jamaat ( Jamaat e Islami Hind ) and several other outfits subscribe to this philosophy. If the rest of society does not realise the inherent danger, more Taliban-model reprisals will follow". [ 14 ]
Progressive Muslim writer Hameed Chennamangaloor says in an article in The Economic Times , "the circumstances are ideal for fanatics to convince their community members here that the problems their community faces in Iraq or Afghanistan are their own problems. The fact is that the problems of even the Muslims in Kerala are quite different from their community members in northern states. Some of these groups have more funds than even mainline political parties like the Congress or the CPM, and can hire any number of hands". [ 104 ]
Speaking of the extremists, at a press conference in Delhi, Kerala Chief Minister V.S. Achuthanandan controversially said: "They want to turn Kerala into a Muslim-majority state in 20 years. They are using money and other inducements to convert people to Islam. They even marry women from outside their community in order to increase the Muslim population." [ 105 ] [ 106 ]
Syed Hyderali Shihab Thangal , president, Muslim League said that the extremists have done considerable damage to the community and that they have to be isolated. [ 105 ]
Autobiography of Prof. T J Joseph titled Attupokatha Ormakal was published by DC Books in January 2020 [ 107 ] [ 108 ]
On 15 November 2013 Joseph was acquitted of all charges by a court in Kerala. [ 109 ]
In July 2013, criminal charges were brought against 37 people, of which 31 subsequently underwent trial in a special National Investigation Agency court, with the remaining 6 absconding. [ 110 ] [ 111 ]
On 8 May 2015, the court convicted 13 of the defendants, all activists of PFI , [ 112 ] 10 of whom were sentenced to 8 years in jail, and 3 of whom were sentenced to 2 years in jail. A fine of ₹ 8 lakh was imposed on the convicted, to be paid to Joseph as compensation. The court acquitted the remaining 18 defendants due to insufficient evidence. [ 110 ] [ 111 ]
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https://en.wikipedia.org/wiki/Assault_on_T._J._Joseph
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Assertive community treatment ( ACT ) is an intensive and highly integrated approach for community mental health service delivery. [ 1 ] ACT teams serve individuals who have been diagnosed with serious and persistent forms of mental illness, predominantly but not exclusively the schizophrenia spectrum disorders. ACT service recipients may also have diagnostic profiles that include features typically found in other DSM-5 categories (for example, bipolar, depressive, anxiety, and personality disorders, among others). Many have histories of frequent psychiatric hospitalization, substance abuse, victimization and trauma, arrests and incarceration, homelessness, and additional significant challenges. The symptoms and complications of their mental illnesses have led to serious functioning difficulties in several areas of life, often including work, social relationships, residential independence, money management, and physical health and wellness. By the time they start receiving ACT services, they are likely to have experienced failure, discrimination, and stigmatization, and their hope for the future is likely to be quite low.
The defining characteristics of ACT include:
In the array of standard mental health service types, ACT is considered a "medically monitored non-residential service" (Level 4), making it more intensive than "high-intensity community-based services" (Level 3) but less intensive than "medically monitored residential services" (Level 5), as measured by the widely accepted LOCUS utilization management tool. [ 10 ] While ACT is more staff-intensive than most other forms of community treatment, it is viewed as a less restrictive option for carefully selected service recipients, compared to custodial or more heavily supervised alternatives; see Olmstead v. L.C. In general, appropriate candidates are those for whom less intensive approaches have proven unsuccessful or insufficient.
ACT was first developed during the early 1970s, the heyday of deinstitutionalization , when large numbers of patients were being discharged from state-operated psychiatric hospitals to an underdeveloped, poorly integrated "nonsystem" of community services characterized (in the words of one of the model's founders) by serious "gaps" and "cracks." [ 11 ] [ 12 ] The founders were Leonard I. Stein, [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] Mary Ann Test, [ 2 ] [ 11 ] [ 20 ] [ 21 ] [ 22 ] [ 23 ] [ 24 ] [ 25 ] Arnold J. Marx, [ 26 ] Deborah J. Allness, [ 6 ] [ 27 ] William H. Knoedler, [ 6 ] [ 28 ] [ 29 ] and their colleagues [ 30 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ] at the Mendota Mental Health Institute , a state operated psychiatric hospital in Madison, Wisconsin. Also known in the professional literature as the Training in Community Living project, the Program of Assertive Community Treatment (PACT), or simply the "Madison model," this innovation seemed radical at the time but has since evolved into one of the most influential service delivery approaches in the history of community mental health. The original Madison project received the American Psychiatric Association 's prestigious Gold Award in 1974. [ 35 ] After conceiving the model as a strategy to prevent hospitalization in a relatively heterogeneous sample of prospective state hospital patients, the PACT team turned its attention in the early 1980s to a more narrowly defined target group of young adults with early-stage schizophrenia. [ 36 ]
Since the late 1970s, the ACT approach has been replicated or adapted widely. [ 37 ] The Harbinger program in Grand Rapids, Michigan, is generally recognized as the first replication, [ 38 ] [ 39 ] and a family-initiated early adaptation in Minnesota, known as Sharing Life in the Community when it was founded in 1976, also traces its origins to the Madison model. [ 40 ]
Starting in 1978, Jerry Dincin, Thomas F. Witheridge, and their colleagues [ 41 ] developed the Bridge assertive outreach program [ 7 ] [ 42 ] [ 43 ] [ 44 ] [ 45 ] at the Thresholds [ 46 ] psychiatric rehabilitation center in Chicago, Illinois—the first big-city adaptation of ACT [ 47 ] and the first such program to focus on the most frequently hospitalized segment of the mental health consumer population. [ 48 ] [ 49 ] In the 1980s and '90s, Thresholds further adapted the approach to serve deaf people with mental illness, [ 50 ] homeless people with mental illness , [ 51 ] people experiencing psychiatric crises, [ 52 ] and people with mental illness who are caught up in the criminal justice system. [ 53 ]
In British Columbia, an experimental assertive outreach program based on the Thresholds model was established in 1988 [ 54 ] and later expanded to additional sites. Outside of North America, one of the first research-based adaptations was an assertive outreach program in Australia. [ 55 ] [ 56 ] [ 57 ] Other replications or adaptations of the ACT approach can be found throughout the English-speaking world and elsewhere. In Wisconsin, the original Madison model was adapted by its founders for the realities of a sparsely populated rural environment. [ 58 ] [ 59 ] The Veterans Health Administration has adapted the ACT model for use at multiple sites throughout the United States. [ 60 ] There are also major program concentrations in Delaware, Florida, Georgia, Idaho, Illinois, [ 43 ] [ 46 ] Indiana (home of numerous research-based ACT programs [ 61 ] [ 62 ] and the Indiana ACT Center [ 63 ] ), Michigan, [ 64 ] [ 65 ] Minnesota, [ 66 ] Missouri, [ 67 ] [ 68 ] [ 69 ] New Jersey, New Mexico, New York, [ 70 ] North Carolina (home to the UNC Institute for Best Practices ), Ohio, Rhode Island, South Carolina, [ 71 ] [ 72 ] South Dakota, Texas, Virginia, Australia, [ 55 ] [ 56 ] Canada, [ 73 ] [ 74 ] [ 75 ] and the United Kingdom, [ 76 ] [ 77 ] [ 78 ] among many other places.
In 1998, the National Alliance on Mental Illness (NAMI) published the first manualization of the ACT model, written by two of its original developers, Allness and Knoedler. [ 79 ] From 1998 to 2004, NAMI operated an ACT technical assistance center, dedicated to advocacy and training to make the model more widely available, with funding from the U.S. federal government's Substance Abuse and Mental Health Services Administration (SAMHSA), an agency within the Department of Health and Human Services. [ 80 ]
Although most of the early PACT replicates and adaptations were funded by grants from federal, state/provincial, or local mental health authorities, there has been a growing tendency to fund these services through Medicaid [ 72 ] and other publicly supported health insurance plans. Medicaid funding has been used for ACT services throughout the United States, starting in the late 1980s, when Allness left PACT to head Wisconsin's state mental health agency and led the development of ACT operational standards. Since then, U.S. and Canadian standards have been developed, and many states and provinces have used them in the development of ACT services for individuals with psychiatric disabilities who would otherwise be dependent on more costly, less effective alternatives. [ 81 ] Even though Medicaid has turned out to be a mixed blessing — it can be difficult to demonstrate a person's eligibility for this insurance program, to meet its documentation and claim requirements, or to find supplemental funding for necessary services it will not cover — Medicaid reimbursement has led to a long-overdue expansion of ACT in previously unserved or underserved jurisdictions. [ 66 ]
Public mental health system planners have attempted to resolve the implementation problems associated with replicating the original Madison approach in sparsely populated rural areas or with low-incidence special populations in urban areas. [ 82 ] A related issue for planners is to determine the number of ACT or "ACT-like" programs a particular geographical area needs and can support. [ 83 ] Some promising areas for further development are identified below in the section on the future of ACT.
ACT and its variations are among the most widely and intensively studied intervention approaches in community mental health. [ 84 ] The original Madison studies by Stein and Test and their colleagues are classics in the field. [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 26 ] [ 85 ] [ 86 ] Another major contributor to the ACT literature is Gary Bond, who completed several studies at Thresholds in Chicago [ 52 ] [ 87 ] [ 88 ] [ 89 ] [ 90 ] and later developed a major psychiatric rehabilitation research and training program at Indiana University-Purdue University at Indianapolis . Bond has been particularly influential in the development of fidelity measurement scales for ACT [ 91 ] [ 92 ] [ 93 ] [ 94 ] [ 95 ] and other evidence-based practices . [ 96 ] [ 97 ] [ 98 ] He and his colleagues (especially Robert E. Drake [ 99 ] [ 100 ] [ 101 ] at Dartmouth Medical School ) have attempted to consolidate and harmonize several major currents in this continuously developing area of practice, including:
An evidence review conducted by the AcademyHealth [ 111 ] policy center in July 2016, examining the impact of housing-related services and supports on the health outcomes of homeless people enrolled in Medicaid, concluded that ACT reduces self-reported psychiatric symptoms, psychiatric hospital stays, and hospital emergency department visits among people with mental illness and substance use diagnoses. [ 112 ]
Because of its long track record of success with high-priority service recipients in a wide variety of geographical and organizational settings — as demonstrated by a large and growing body of rigorous outcome evaluation studies [ 113 ] [ 114 ] — ACT has been recognized by SAMHSA, [ 115 ] [ 116 ] NAMI, [ 117 ] and the Commission on Accreditation of Rehabilitation Facilities , [ 118 ] among other recognized arbiters, as an evidence-based practice [ 119 ] [ 120 ] worthy of widespread dissemination.
However, the acclaim for assertive community treatment and related service approaches is not universal. For example, Patricia Spindel and Jo Anne Nugent [ 121 ] have argued that the main difficulty with the Program of Assertive Community Treatment (PACT) model and some other case management approaches is that there has been no critical analysis of how personally empowering (as opposed to socially controlling) such programs are. These authors have argued that PACT does not meet the criteria for being an empowerment approach for "working with disadvantaged, labelled, and stigmatized people." Furthermore, they assert, PACT does not have a philosophical base that stresses true individual empowerment. There is much literature, they say, questioning the way in which human services are delivered, but this literature is not considered in evaluations of the PACT approach. Spindle and Nugent conclude that "PACT may be little more than a means of transporting the social control and biomedical functions of the hospital or the institution to the community. For a community mental health system which says that it wants a more progressive approach, PACT simply does not fit the bill." Other concerns have arisen out of the harm reduction/Housing First version of the model, as implemented in the late 2010s. Some clinicians and dual diagnosis specialists have voiced concerns that the model creates a safe environment for increased drug use, resulting in more instances of overdose and even death; they are awaiting an empirical study to confirm these suspicions.
Tomi Gomory [ 122 ] [ 123 ] [ 124 ] at Florida State University has also been critical of PACT. He has written: "Advocates of Programs of Assertive Community Treatment (PACT) make numerous claims for this intensive intervention program, including reduced hospitalization, overall cost, and clinical symptomatology, and increased client satisfaction, and vocational and social functioning. However, a reanalysis of the controlled experimental research finds no empirical support for any of these claims." [ 125 ] Gomory has asserted that the chief characteristics of PACT are "intensity, assertiveness, or aggressiveness, which may better be identified as coercion. For example, reduced hospitalization in ACT is simply accomplished by having an administrative decision rule not to admit ACT patients into the hospital regardless of symptomatic behavior (the patients are kept and treated in the community) while patients in routine treatment are hospitalized regularly. When this rule is not present the research shows no reduced hospitalization by ACT compared to routine treatment." [ 125 ] Madison psychiatrist Ronald J. Diamond has provided support for that position: "The development of Programs for Assertive Community Treatment (PACT), assertive community treatment (ACT) teams and a variety of similar mobile, continuous treatment programs has made it possible to coerce a wide range of behaviors in the community." [ 126 ] Gomory has also argued that professional enthusiasm for the medical model is the main driver of PACT expansion, rather than any clear benefit to clients who receive the service. [ 125 ]
In the professional journal Psychiatric Services , Test and Stein have replied to Gomory's assertions that PACT is inherently coercive and that the research claiming to support it is scientifically invalid, [ 127 ] and Gomory, in turn, has answered their reply. [ 128 ] Moser and Bond address coercion and the broader concept of "agency control" (practices in which the treatment team maintains supervisory responsibility over consumers) in a discussion of data from 23 ACT programs. Their review shows that "agency control" varies greatly among different programs; it may be particularly high with patients diagnosed in the schizophrenia spectrum who also have active substance use issues. [ 129 ] A widely distributed book co-authored by Gomory [ 130 ] has called the public's attention to various treatment failures allegedly caused by therapies described in the book as "coercive," including PACT.
The cost-effectiveness of ACT was relatively easy to demonstrate in the early days, when psychiatric hospital beds were more heavily used than they are now. [ 131 ] In the years to come, program planners will have to justify the comparatively high cost of ACT through the continued use of careful admission criteria and rigorous program evaluation. To ensure the best possible service quality on a routine basis, public regulators and payers would also benefit from having fidelity and outcome monitoring tools more easily administered than those currently available.
The defining characteristics of the ACT approach will remain an attractive framework for services to meet the needs of special populations, such as individuals whose psychiatric symptoms get them into trouble with the criminal justice system, [ 132 ] [ 133 ] [ 134 ] [ 135 ] [ 136 ] [ 137 ] [ 138 ] [ 139 ] refugees from foreign countries who struggle with the added burden of mental illness, [ 140 ] and children and adolescents with serious emotional disturbances. [ 141 ] One major piece of unfinished business in the mental health field is the discovery that people with serious mental illnesses die an average of 25 years earlier than the general public, often from disorders that are inherently preventable or treatable; this public health disaster is a critical issue for ACT providers and the people they serve. [ 142 ] [ 143 ] [ 144 ]
Another important area for future program design and evaluation is the use of ACT in combination with other established interventions, such as integrated dual disorder treatment for people with co-occurring mental health and substance use diagnoses, [ 104 ] supported employment programs, [ 72 ] [ 105 ] education for concerned family members, [ 145 ] [ 146 ] and dialectical behavior therapy for individuals diagnosed with borderline personality disorder . [ 147 ] [ 148 ] [ 149 ]
Ironically, the dissemination of separate evidence-based practices, not all of which are easily integrated with each other, has once again made service coordination a pivotal issue in community mental health — as it was during the latter decades of the 20th century, when ACT was created as an antidote to the "nonsystem" of care. [ 11 ]
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https://en.wikipedia.org/wiki/Assertive_community_treatment
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The assessment and plan (abbreviated A/P" [ 1 ] or A&P ) is a component of an admission note .
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https://en.wikipedia.org/wiki/Assessment_and_plan
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