<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Experimental autoimmune encephalomyelitis and can you explain it in depth? [/INST] Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.EAE was motivated by observations during the convalescence from viral diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primates was published in the Journal of Experimental Medicine.  An acute monophasic illness, it has been suggested that EAE is far more similar to ADEM than MS.

Types of EAE
EAE can be induced in a number of species, including mice, rats, guinea pigs, rabbits and primates.
The most commonly used antigens in rodents are spinal cord homogenate (SCH), purified myelin, myelin protein such as MBP, PLP, and MOG, or peptides of these proteins, all resulting in distinct models with different disease characteristics regarding both immunology and pathology. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens.Depending on the antigen used and the genetic make-up of the animal, rodents can display a monophasic bout of EAE, a relapsing-remitting form, or chronic EAE. The typical susceptible rodent will debut with clinical symptoms around two weeks after immunization and present with a relapsing-remitting disease.  The archetypical first clinical symptom is weakness of tail tonus that progresses to paralysis of the tail, followed by a progression up the body to affect the hind limbs and finally the forelimbs.However, similar to MS, the disease symptoms reflect the anatomical location of the inflammatory lesions, and may also include emotional lability, sensory loss, optic neuritis, difficulties with coordination and balance (ataxia), and muscle weakness and spasms. Recovery from symptoms can be complete or partial and the time varies with symptoms and disease severity. Depending on the relapse-remission intervals, rats can have up to three bouts of disease within an experimental period.

In mice
Demyelination is produced by injection of brain extracts, CNS proteins (such as myelin basic protein), or peptides from such protein emulsified in an adjuvant such as complete Freunds adjuvant.  The presence of the adjuvant allows the generation of inflammatory responses to the protein/peptides.  In many protocols, mice are coinjected with pertussis toxin to break down the blood-brain barrier and allow immune cells access to the CNS tissue.  This immunisation leads to multiple small disseminated lesions of demyelination (as well as micro-necroses) in the brain and spinal cord and the onset of clinical symptoms.Although sharing some features, mostly demyelination, this model, first introduced in the 1930s, differs from human MS in several ways. EAE either kills animals or leaves them with permanent disabilities; animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different from MS, being the main antigen (MBP) in charge. Some key differences between EAE in mice, and MS in humans include:

B-cells: Some research points to anti-CD20 B-cells being the basis of the autoimmune attacks. This has been shown to be completely different in EAE and MS.
oxidative injury: Mitochondrial injury is seen in EAE and MS, but mitochondrial gene deletions have so far only been detected in MS lesions.
microglia behaviour: In contrast to experimental models of inflammatory demyelination, lesion formation in multiple sclerosis occurs on a background of pro-inflammatory microglia activation, which is seen already in the normal white matter of age-matched controls, and this may contribute to neurodegeneration in the disease.
pathological patterns: EAE is unable to reproduce MS pathological patterns III and IV.

Secondary damage
Given that some conditions as MS show cortical damage together with the WM damage, there has been interest if this can appear as a secondary damage of the WM.

Human Anti-MOG in mice
Anti-MOG associated encephalomyelitis can be passed from humans to mice, inducing MS type II demyelination (pattern II)

Immunogenetic interactions
Deficiency of TBX21 or STAT4 provides resistance against EAE, while interferon-γ-, interferon-γ-receptor-, interleukin-12 subunit α-, interleukin 12 receptor, β 2 subunit-, and interleukin 18-deficiency exacerbated disease.

In humans
Sometimes the human equivalent to EAE has been triggered in humans by accident or medical mistake </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Connective tissue nevus and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Escherichia coli and can you explain it in depth? [/INST] Escherichia coli (), also known as E. coli (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes (EPEC, ETEC etc.) can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. The harmless strains are part of the normal microbiota of the gut, and can benefit their hosts by producing vitamin K2, and preventing colonisation of the intestine with pathogenic bacteria, having a mutualistic relationship. E. coli is expelled into the environment within faecal matter.  The bacterium grows massively in fresh faecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.E. coli and other facultative anaerobes constitute about 0.1% of gut microbiota, and fecal–oral transmission is the major route through which pathogenic strains of the bacterium cause disease. Cells are able to survive outside the body for a limited amount of time, which makes them potential indicator organisms to test environmental samples for fecal contamination. A growing body of research, though, has examined environmentally persistent E. coli which can survive for many days and grow outside a host.The bacterium can be grown and cultured easily and inexpensively in a laboratory setting, and has been intensively investigated for over 60 years. E. coli is a chemoheterotroph whose chemically defined medium must include a source of carbon and energy. E. coli is the most widely studied prokaryotic model organism, and an important species in the fields of biotechnology and microbiology, where it has served as the host organism for the majority of work with recombinant DNA. Under favourable conditions, it takes as little as 20 minutes to reproduce.

Biology and biochemistry
Type and morphology
E. coli is a Gram-negative, facultative anaerobe, nonsporulating coliform bacterium.  Cells are typically rod-shaped, and are about 2.0 μm long and 0.25–1.0 μm in diameter, with a cell volume of 0.6–0.7 μm3.  Antibiotics can effectively treat E. coli infections outside the digestive tract and most intestinal infections but are not used to treat intestinal infections by one strain of these bacteria. The flagella which allow the bacteria to swim have a peritrichous arrangement. It also attaches and effaces to the microvilli of the intestines via an adhesion molecule known as intimin.

Metabolism
E. coli can live on a wide variety of substrates and uses mixed acid fermentation in anaerobic conditions, producing lactate, succinate, ethanol, acetate, and carbon dioxide. Since many pathways in mixed-acid fermentation produce hydrogen gas, these pathways require the levels of hydrogen to be low, as is the case when E. coli lives together with hydrogen-consuming organisms, such as methanogens or sulphate-reducing bacteria.In addition, E. colis metabolism can be rewired to solely use CO2 as the source of carbon for biomass production. In other words, this obligate heterotrophs metabolism can be altered to display autotrophic capabilities by heterologously expressing carbon fixation genes as well as formate dehydrogenase and conducting laboratory evolution experiments. This may be done by using formate to reduce electron carriers and supply the ATP required in anabolic pathways inside of these synthetic autotrophs.E. coli have three native glycolytic pathways: EMPP, EDP, and OPPP. The EMPP employs ten enzymatic steps to yield two pyruvates, two ATP, and two NADH per glucose molecule  while OPPP serves as an oxidation route for NADPH synthesis. Although the EDP is the more thermodynamically favourable of the three pathways, E. coli do not use the EDP for glucose metabolism, relying mainly on the EMPP and the OPPP. The EDP mainly remains inactive except for during growth with gluconate.

Catabolite repression
When growing in the presence of a mixture of sugars, bacteria will often consume the sugars sequentially through a process known as catabolite repression. By repressing the expression of the genes involved in metabolizing the less preferred sugars, cells will usually first consume the sugar yielding the highest growth rate, followed by the sugar yielding the next highest growth rate, and so on. In doing so the cells ensure that their limited metabolic resources are being used to maximize the rate of growth. The well-used example of this with E. coli involves the growth of the bacterium on glucose and lactose, where E. coli will consume glucose before lactose. Catabolite repression has also been observed in E. coli in the presence of other non-glucose sugars, such as arabinose and xylose, sorbitol, rhamnose, and ribose. In E. coli, glucose catabolite repression is regulated by the phosphotransferase system, a multi-protein phosphorylation cascade that couples glucose uptake and metabolism.

Culture growth
Optimum growth of E. coli occurs at 37 °C (99 °F), but some laboratory strains can multiply at temperatures up to 49 °C (120 °F). E. coli grows in a variety of defined laboratory media, such as lysogeny broth, or any medium that contains glucose, ammonium phosphate monobasic, sodium chloride, magnesium sulfate, potassium phosphate dibasic, and water. Growth can be driven by aerobic or anaerobic respiration, using a large variety of redox pairs, including the oxidation of pyruvic acid, formic acid, hydrogen, and amino acids, and the reduction of substrates such as oxygen, nitrate, fumarate, dimethyl sulfoxide, and trimethylamine N-oxide. E. coli is classified as a facultative anaerobe. It uses oxygen when it is present and available. It can, however, continue to grow in the absence of oxygen using fermentation or anaerobic respiration. The ability to continue growing in the absence of oxygen is an advantage to bacteria because their survival is increased in environments where water predominates.

Cell cycle
The bacterial cell cycle is divided into three stages.  The B period occurs between the completion of cell division and the beginning of DNA replication.  The C period encompasses the time it takes to replicate the chromosomal DNA.  The D period refers to the stage between the conclusion of DNA replication and the end of cell division.  The doubling rate of E. coli is higher when more nutrients are available.  However, the length of the C and D periods do not change, even when the doubling time becomes less than the sum of the C and D periods.  At the fastest growth rates, replication begins before the previous round of replication has completed, resulting in multiple replication forks along the DNA and overlapping cell cycles.The number of replication forks in fast growing E. coli typically follows 2n (n = 1, 2 or 3). This only happens if replication is initiated simultaneously from all origins of replications, and is referred to as synchronous replication. However, not all cells in a culture replicate synchronously. In this case cells do not have multiples of two replication forks. Replication initiation is then referred to being asynchronous. However, asynchrony can be caused by mutations to for instance DnaA or DnaA initiator-associating protein DiaA.

Genetic adaptation
E. coli and related bacteria possess the ability to transfer DNA via bacterial conjugation or transduction, which allows genetic material to spread horizontally through an existing population. The process of transduction, which uses the bacterial virus called a bacteriophage, is where the spread of the gene encoding for the Shiga toxin from the Shigella bacteria to E. coli helped produce E. coli O157:H7, the Shiga toxin-producing strain of E. coli.

Diversity
E. coli encompasses an enormous population of bacteria that exhibit a very high degree of both genetic and phenotypic diversity. Genome sequencing of many isolates of E. coli and related bacteria shows that a taxonomic reclassification would be desirable. However, this has not been done, largely due to its medical importance, and E. coli remains one of the most diverse bacterial species: only 20% of the genes in a typical E. coli genome is shared among all strains.In fact, from the more constructive point of view, the members of genus Shigella (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei) should be classified as E. coli strains, a phenomenon termed taxa in disguise. Similarly, other strains of E. coli (e.g. the K-12 strain commonly used in recombinant DNA work) are sufficiently different that they would merit reclassification.

A strain is a subgroup within the species that has unique characteristics that distinguish it from other strains. These differences are often detectable only at the molecular level; however, they may result in changes to the physiology or lifecycle of the bacterium. For example, a strain may gain pathogenic capacity, the ability to use a unique carbon source, the ability to take upon a particular ecological niche, or the ability to resist antimicrobial agents. Different strains of E. coli are often host-specific, making it possible to determine the source of fecal contamination in environmental samples. For example, knowing which E. coli strains are present in a water sample allows researchers to make assumptions about whether the contamination originated from a human, another mammal, or a bird.

Serotypes
A common subdivision system of E. coli, but not based on evolutionary relatedness, is by serotype, which is based on major surface antigens (O antigen: part of lipopolysaccharide layer; H: flagellin; K antigen: capsule), e.g. O157:H7). It is, however, common to cite only the serogroup, i.e. the O-antigen. At present, about 190 serogroups are known. The common laboratory strain has a mutation that prevents the formation of an O-antigen and is thus not typeable.

Genome plasticity and evolution
Like all lifeforms, new strains of E. coli evolve through the natural biological processes of mutation, gene duplication, and horizontal gene transfer; in particular, 18% of the genome of the laboratory strain MG1655 was horizontally acquired since the divergence from Salmonella. E. coli K-12 and E. coli B strains are the most frequently used varieties for laboratory purposes. Some strains develop traits that can be harmful to a host animal. These virulent strains typically cause a bout of diarrhea that is often self-limiting in healthy adults but is frequently lethal to children in the developing world. More virulent strains, such as O157:H7, cause serious illness or death in the elderly, the very young, or the immunocompromised.The genera Escherichia and Salmonella diverged around 102 million years ago (credibility interval: 57–176 mya), an event unrelated to the much earlier (see Synapsid) divergence of their hosts: the former being found in mammals and the latter in birds and reptiles. This was followed by a split of an Escherichia ancestor into five species (E. albertii, E. coli, E. fergusonii, E. hermannii, and E. vulneris). The last E. coli ancestor split between 20 and 30 million years ago.
The long-term evolution experiments using E. coli, begun by Richard Lenski in 1988, have allowed direct observation of genome evolution over more than 65,000 generations in the laboratory. For instance, E. coli typically do not have the ability to grow aerobically with citrate as a carbon source, which is used as a diagnostic criterion with which to differentiate E. coli from other, closely, related bacteria such as Salmonella. In this experiment, one population of E. coli unexpectedly evolved the ability to aerobically metabolize citrate, a major evolutionary shift with some hallmarks of microbial speciation.
In the microbial world, a relationship of predation can be established similar to that observed in the animal world. Considered, it has been seen that E. coli is the prey of multiple generalist predators, such as Myxococcus xanthus. In this predator-prey relationship, a parallel evolution of both species is observed through genomic and phenotypic modifications, in the case of E. coli the modifications are modified in two aspects involved in their virulence such as mucoid production (excessive production of exoplasmic acid alginate ) and the suppression of the OmpT gene, producing in future generations a better adaptation of one of the species that is counteracted by the evolution of the other, following a co-evolutionary model demonstrated by the Red Queen hypothesis.

Neotype strain
E. coli is the type species of the genus (Escherichia) and in turn Escherichia is the type genus of the family Enterobacteriaceae, where the family name does not stem from the genus Enterobacter + "i" (sic.) + "aceae", but from "enterobacterium" + "aceae" (enterobacterium being not a genus, but an alternative trivial name to enteric bacterium).The original strain described by Escherich is believed to be lost, consequently a new type strain (neotype) was chosen as a representative: the neotype strain is U5/41T, also known under the deposit names DSM 30083, ATCC 11775, and NCTC 9001, which is pathogenic to chickens and has an O1:K1:H7 serotype. However, in most studies, either O157:H7, K-12 MG1655, or K-12 W3110 were used as a representative E. coli. The genome of the type strain has only lately been sequenced.

Phylogeny of E. coli strains
Many strains belonging to this species have been isolated and characterised. In addition to serotype (vide supra), they can be classified according to their phylogeny, i.e. the inferred evolutionary history, as shown below where the species is divided into six groups. Particularly the use of whole genome sequences yields highly supported phylogenies. Based on such data, five subspecies of E. coli were distinguished.The link between phylogenetic distance ("relatedness") and pathology is small, e.g. the O157:H7 serotype strains, which form a clade ("an exclusive group")—group E below—are all enterohaemorragic strains (EHEC), but not all EHEC strains are closely related. In fact, four different species of Shigella are nested among E. coli strains (vide supra), while E. albertii and E. fergusonii are outside this group.
Indeed, all Shigella species were placed within a single subspecies of E. coli in a phylogenomic study that included the type strain, and for this reason an according reclassification is difficult.
All commonly used research strains of E. coli belong to group A and are derived mainly from Cliftons K-12 strain (λ+ F+; O16) and to a lesser degree from dHerelles Bacillus coli strain (B strain) (O7).

Genomics
The first complete DNA sequence of an E. coli genome (laboratory strain K-12 derivative MG1655) was published in 1997. It is a circular DNA molecule 4.6 million base pairs in length, containing 4288 annotated protein-coding genes (organized into 2584 operons), seven ribosomal RNA (rRNA) operons, and 86 transfer RNA (tRNA) genes. Despite having been the subject of intensive genetic analysis for about 40 years, many of these genes were previously unknown. The coding density was found to be very high, with a mean distance between genes of only 118 base pairs. The genome was observed to contain a significant number of transposable genetic elements, repeat elements, cryptic prophages, and bacteriophage remnants.More than three hundred complete genomic sequences of Escherichia and Shigella species are known. The genome sequence of the type strain of E. coli was added to this collection before 2014. Comparison of these sequences shows a remarkable amount of diversity; only about 20% of each genome represents sequences present in every one of the isolates, while around 80% of each genome can vary among isolates. Each individual genome contains between 4,000 and 5,500 genes, but the total number of different genes among all of the sequenced E. coli strains (the pangenome) exceeds 16,000. This very large variety of component genes has been interpreted to mean that two-thirds of the E. coli pangenome originated in other species and arrived through the process of horizontal gene transfer.

Gene nomenclature
Genes in E. coli are usually named in accordance with the uniform nomenclature proposed by Demerec et al. Gene names are 3-letter acronyms that derive from their function (when known) or mutant phenotype and are italicized. When multiple genes have the same acronym, the different genes are designated by a capital later that follows the acronym and is also italicized. For instance, recA is named after its role in homologous recombination plus the letter A. Functionally related genes are named recB, recC, recD etc. The proteins are named by uppercase acronyms, e.g. RecA, RecB, etc. When the genome of E. coli strain K-12 substr. MG1655 was sequenced, all known or predicted protein-coding genes were numbered (more or less) in their order on the genome and abbreviated by b numbers, such as b2819 (= recD). The "b" names were created after Fred Blattner, who led the genome sequence effort. Another numbering system was introduced with the sequence of another E. coli K-12 substrain, W3110, which was sequenced in Japan and hence uses numbers starting by JW... (Japanese W3110), e.g. JW2787 (= recD).  Hence, recD = b2819 = JW2787. Note, however, that most databases have their own numbering system, e.g. the EcoGene database  uses EG10826 for recD. Finally, ECK numbers are specifically used for alleles in the MG1655 strain of E. coli K-12. Complete lists of genes and their synonyms can be obtained from databases such as EcoGene or Uniprot.

Proteomics
Proteome
The genome sequence of E. coli predicts 4288 protein-coding genes, of which 38 percent initially had no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.Several studies have experimentally investigated the proteome of E. coli. By 2006, 1,627 (38%) of the predicted proteins (open reading frames, ORFs) had been identified experimentally. Mateus et al. 2020 detected 2,586 proteins with at least 2 peptides (60% of all proteins).

Post-translational modifications (PTMs)
Although much fewer bacterial proteins seem to have post-translational modifications (PTMs) compared to eukaryotic proteins, a substantial number of proteins are modified in E. coli. For instance, Potel et al. (2018) found 227 phosphoproteins of which 173 were phosphorylated on histidine. Interestingly, the majority of phosphorylated amino acids were serine (1,220 sites) with only 246 sites on histidine and 501 phosphorylated theronines and 162 tyrosines.

Interactome
The interactome of E. coli has been studied by affinity purification and mass spectrometry (AP/MS) and by analyzing the binary interactions among its proteins.
Protein complexes. A 2006 study purified 4,339 proteins from cultures of strain K-12 and found interacting partners for 2,667 proteins, many of which had unknown functions at the time. A 2009 study found 5,993 interactions between proteins of the same E. coli strain, though these data showed little overlap with those of the 2006 publication.Binary interactions. Rajagopala et al. (2014) have carried out systematic yeast two-hybrid screens with most E. coli proteins, and found a total of 2,234 protein-protein interactions. This study also integrated genetic interactions and protein structures and mapped 458 interactions within 227 protein complexes.

Normal microbiota
E. coli belongs to a group of bacteria informally known as coliforms that are found in the gastrointestinal tract of warm-blooded animals. E. coli normally colonizes an infants gastrointestinal tract within 40 hours of birth, arriving with food or water or from the individuals handling the child.  In the bowel, E. coli adheres to the mucus of the large intestine. It is the primary facultative anaerobe of the human gastrointestinal tract. (Facultative anaerobes are organisms that can grow in either the presence or absence of oxygen.) As long as these bacteria do not acquire genetic elements encoding for virulence factors, they remain benign commensals.

Therapeutic use
Due to the low cost and speed with which it can be grown and modified in laboratory settings, E. coli is a popular expression platform for the production of recombinant proteins used in therapeutics. One advantage to using E. coli over another expression platform is that E. coli naturally does not export many proteins into the periplasm, making it easier to recover a protein of interest without cross-contamination. The E. coli K-12 strains and their derivatives (DH1, DH5α, MG1655, RV308 and W3110) are the strains most widely used by the biotechnology industry. Nonpathogenic E. coli strain Nissle 1917 (EcN), (Mutaflor) and E. coli O83:K24:H31 (Colinfant)) are used as probiotic agents in medicine, mainly for the treatment of various gastrointestinal diseases, including inflammatory bowel disease. It is thought that the EcN strain might impede the growth of opportunistic pathogens, including Salmonella and other coliform enteropathogens, through the production of microcin proteins the production of siderophores.

Role in disease
Most E. coli strains do not cause disease, naturally living in the gut, but virulent strains can cause gastroenteritis, urinary tract infections, neonatal meningitis, hemorrhagic colitis, and Crohns disease. Common signs and symptoms include severe abdominal cramps, diarrhea, hemorrhagic colitis, vomiting, and sometimes fever. In rarer cases, virulent strains are also responsible for bowel necrosis (tissue death) and perforation without progressing to hemolytic-uremic syndrome, peritonitis, mastitis, sepsis, and Gram-negative pneumonia. Very young children are more susceptible to develop severe illness, such as hemolytic uremic syndrome; however, healthy individuals of all ages are at risk to the severe consequences that may arise as a result of being infected with E. coli.Some strains of E. coli, for example O157:H7, can produce Shiga toxin (classified as a bioterrorism agent). The Shiga toxin causes inflammatory responses in target cells of the gut, leaving behind lesions which result in the bloody diarrhea that is a symptom of a Shiga toxin-producing E. coli (STEC) infection. This toxin further causes premature destruction of the red blood cells, which then clog the bodys filtering system, the kidneys, in some rare cases (usually in children and the elderly) causing hemolytic-uremic syndrome (HUS), which may lead to kidney failure and even death. Signs of hemolytic uremic syndrome include decreased frequency of urination, lethargy, and paleness of cheeks and inside the lower eyelids. In 25% of HUS patients, complications of nervous system occur, which in turn causes strokes.  In addition, this strain causes the buildup of fluid (since the kidneys do not work), leading to edema around the lungs, legs, and arms.  This increase in fluid buildup especially around the lungs impedes the functioning of the heart, causing an increase in blood pressure.Uropathogenic E. coli (UPEC) is one of the main causes of urinary tract infections. It is part of the normal microbiota in the gut and can be introduced in many ways. In particular for females, the direction of wiping after defecation (wiping back to front) can lead to fecal contamination of the urogenital orifices. Anal intercourse can also introduce this bacterium into the male urethra, and in switching from anal to vaginal intercourse, the male can also introduce UPEC to the female urogenital system.
Enterotoxigenic E. coli (ETEC) is the most common cause of travelers diarrhea, with as many as 840 million cases worldwide in developing countries each year. The bacteria, typically transmitted through contaminated food or drinking water, adheres to the intestinal lining, where it secretes either of two types of enterotoxins, leading to watery diarrhea. The rate and severity of infections are higher among children under the age of five, including as many as 380,000 deaths annually.In May 2011, one E. coli strain, O104:H4, was the subject of a bacterial outbreak that began in Germany. Certain strains of E. coli are a major cause of foodborne illness. The outbreak started when several people in Germany were infected with enterohemorrhagic E. coli (EHEC) bacteria, leading to hemolytic-uremic syndrome (HUS), a medical emergency that requires urgent treatment. The outbreak did not only concern Germany, but also 15 other countries, including regions in North America. On 30 June 2011, the German Bundesinstitut für Risikobewertung (BfR) (Federal Institute for Risk Assessment, a federal institute within the German Federal Ministry of Food, Agriculture and Consumer Protection) announced that seeds of fenugreek from Egypt were likely the cause of the EHEC outbreak.Some studies have demonstrated an absence of E. coli in the gut flora of subjects with the metabolic disorder Phenylketonuria. It is hypothesized that the absence of these normal bacterium impairs the production of the key vitamins B2 (riboflavin) and K2 (menaquinone) - vitamins which are implicated in many physiological roles in humans such as cellular and bone metabolism - and so contributes to the disorder.Carbapenem-resistant E. coli (carbapenemase-producing E. coli) that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule.

Incubation period
The time between ingesting the STEC bacteria and feeling sick is called the "incubation period". The incubation period is usually 3–4 days after the exposure, but may be as short as 1 day or as long as 10 days. The symptoms often begin slowly with mild belly pain or non-bloody diarrhea that worsens over several days. HUS, if it occurs, develops an average 7 days after the first symptoms, when the diarrhea is improving.

Diagnosis
Diagnosis of infectious diarrhea and identification of antimicrobial resistance is performed using a stool culture with subsequent antibiotic sensitivity testing. It requires a minimum of 2 days and maximum of several weeks to culture gastrointestinal pathogens.  The sensitivity (true positive) and specificity (true negative) rates for stool culture vary by pathogen, although a number of human pathogens can not be cultured. For culture-positive samples, antimicrobial resistance testing takes an additional 12–24 hours to perform.
Current point of care molecular diagnostic tests can identify E. coli and antimicrobial resistance in the identified strains much faster than culture and sensitivity testing. Microarray-based platforms can identify specific pathogenic strains of E. coli and E. coli-specific AMR genes in two hours or less with high sensitivity and specificity, but the size of the test panel (i.e., total pathogens and antimicrobial resistance genes) is limited. Newer metagenomics-based infectious disease diagnostic platforms are currently being developed to overcome the various limitations of culture and all currently available molecular diagnostic technologies.

Treatment
The mainstay of treatment is the assessment of dehydration and replacement of fluid and electrolytes. Administration of antibiotics has been shown to shorten the course of illness and duration of excretion of enterotoxigenic E. coli (ETEC) in adults in endemic areas and in travellers diarrhea, though the rate of resistance to commonly used antibiotics is increasing and they are generally not recommended. The antibiotic used depends upon susceptibility patterns in the particular geographical region. Currently, the antibiotics of choice are fluoroquinolones or azithromycin, with an emerging role for rifaximin. Oral rifaximin, a semisynthetic rifamycin derivative, is an effective and well-tolerated antibacterial for the management of adults with non-invasive travellers diarrhea. Rifaximin was significantly more effective than placebo and no less effective than ciprofloxacin in reducing the duration of diarrhea. While rifaximin is effective in patients with E. coli-predominant travellers diarrhea, it appears ineffective in patients infected with inflammatory or invasive enteropathogens.

Prevention
ETEC is the type of E. coli that most vaccine development efforts are focused on. Antibodies against the LT and major CFs of ETEC provide protection against LT-producing, ETEC-expressing homologous CFs. Oral inactivated vaccines consisting of toxin antigen and whole cells, i.e. the licensed recombinant cholera B subunit (rCTB)-WC cholera vaccine Dukoral, have been developed. There are currently no licensed vaccines for ETEC, though several are in various stages of development. In different trials, the rCTB-WC cholera vaccine provided high (85–100%) short-term protection. An oral ETEC vaccine candidate consisting of rCTB and formalin inactivated E. coli bacteria expressing major CFs has been shown in clinical trials to be safe, immunogenic, and effective against severe diarrhoea in American travelers but not against ETEC diarrhoea in young children in Egypt. A modified ETEC vaccine consisting of recombinant E. coli strains over-expressing the major CFs and a more LT-like hybrid toxoid called LCTBA, are undergoing clinical testing.Other proven prevention methods for E. coli transmission include handwashing and improved sanitation and drinking water, as transmission occurs through fecal contamination of food and water supplies. Additionally, thoroughly cooking meat and avoiding consumption of raw, unpasteurized beverages, such as juices and milk are other proven methods for preventing E. coli. Lastly, cross-contamination of utensils and work spaces should be avoided when preparing food.

Model organism in life science research
Because of its long history of laboratory culture and ease of manipulation, E. coli plays an important role in modern biological engineering and industrial microbiology. The work of Stanley Norman Cohen and Herbert Boyer in E. coli, using plasmids and restriction enzymes to create recombinant DNA, became a foundation of biotechnology.E. coli is a very versatile host for the production of heterologous proteins, and various protein expression systems have been developed which allow the production of recombinant proteins in E. coli. Researchers can introduce genes into the microbes using plasmids which permit high level expression of protein, and such protein may be mass-produced in industrial fermentation processes. One of the first useful applications of recombinant DNA technology was the manipulation of E. coli to produce human insulin.Many proteins previously thought difficult or impossible to be expressed in E. coli in folded form have been successfully expressed in E. coli. For example, proteins with multiple disulphide bonds may be produced in the periplasmic space or in the cytoplasm of mutants rendered sufficiently oxidizing to allow disulphide-bonds to form, while proteins requiring post-translational modification such as glycosylation for stability or function have been expressed using the N-linked glycosylation system of Campylobacter jejuni engineered into E. coli.Modified E. coli cells have been used in vaccine development, bioremediation, production of biofuels, lighting, and production of immobilised enzymes.Strain K-12 is a mutant form of E. coli that over-expresses the enzyme Alkaline Phosphatase (ALP). The mutation arises due to a defect in the gene that constantly codes for the enzyme. A gene that is producing a product without any inhibition is said to have constitutive activity. This particular mutant form is used to isolate and purify the aforementioned enzyme.Strain OP50 of Escherichia coli is used for maintenance of Caenorhabditis elegans cultures.
Strain JM109 is a mutant form of E. coli that is recA and endA deficient. The strain can be utilized for blue/white screening when the cells carry the fertility factor episome. Lack of recA decreases the possibility of unwanted restriction of the DNA of interest and lack of endA inhibit plasmid DNA decomposition. Thus, JM109 is useful for cloning and expression systems.

Model organism
E. coli is frequently used as a model organism in microbiology studies. Cultivated strains (e.g. E. coli K12) are well-adapted to the laboratory environment, and, unlike wild-type strains, have lost their ability to thrive in the intestine. Many laboratory strains lose their ability to form biofilms. These features protect wild-type strains from antibodies and other chemical attacks, but require a large expenditure of energy and material resources. E. coli is often used as a representative microorganism in the research of novel water treatment and sterilisation methods, including photocatalysis. By standard plate count methods, following sequential dilutions, and growth on agar gel plates, the concentration of viable organisms or CFUs (Colony Forming Units), in a known volume of treated water can be evaluated, allowing the comparative assessment of materials performance.In 1946, Joshua Lederberg and Edward Tatum first described the phenomenon known as bacterial conjugation using E. coli as a model bacterium, and it remains the primary model to study conjugation. E. coli was an integral part of the first experiments to understand phage genetics, and early researchers, such as Seymour Benzer, used E. coli and phage T4 to understand the topography of gene structure. Prior to Benzers research, it was not known whether the gene was a linear structure, or if it had a branching pattern.E. coli was one of the first organisms to have its genome sequenced; the complete genome of E. coli K12 was published by Science in 1997From 2002 to 2010, a team at the Hungarian Academy of Science created a strain of Escherichia coli called MDS42, which is now sold by Scarab Genomics of Madison, WI under the name of "Clean Genome E. coli", where 15% of the genome of the parental strain (E. coli K-12 MG1655) were removed to aid in molecular biology efficiency, removing IS elements, pseudogenes and phages, resulting in better maintenance of plasmid-encoded toxic genes, which are often inactivated by transposons. Biochemistry and replication machinery were not altered.
By evaluating the possible combination of nanotechnologies with landscape ecology, complex habitat landscapes can be generated with details at the nanoscale. On such synthetic ecosystems, evolutionary experiments with E. coli have been performed to study the spatial biophysics of adaptation in an island biogeography on-chip.
In other studies, non-pathogenic E. coli has been used as a model microorganism towards understanding the effects of simulated microgravity (on Earth) on the same.

Uses in biological computing
Since 1961, scientists proposed the idea of genetic circuits used for computational tasks.  Collaboration between biologists and computing scientists has allowed designing digital logic gates on the metabolism of E. coli. As Lac operon is a two-stage process, genetic regulation in the bacteria is used to realize computing functions. The process is controlled at the transcription stage of DNA into messenger RNA.Studies are being performed attempting to program E. coli to solve complicated mathematics problems, such as the Hamiltonian path problem.A computer to control protein production of E. coli within yeast cells has been developed. A method has also been developed to use bacteria to behave as an LCD screen.In July 2017, separate experiments with E. coli published on Nature showed the potential of using living cells for computing tasks and storing information. A team formed with collaborators of the Biodesign Institute at Arizona State University and Harvard’s Wyss Institute for Biologically Inspired Engineering developed a biological computer inside E. coli that responded to a dozen inputs. The team called the computer "ribocomputer", as it was composed of ribonucleic acid. Meanwhile, Harvard researchers probed that is possible to store information in bacteria after successfully archiving images and movies in the DNA of living E. coli cells.  In 2021, a team led by biophysicist Sangram Bagh realized a study with E. coli to solve 2 × 2 maze problems to probe the principle for distributed computing among cells.

History
In 1885, the German-Austrian pediatrician Theodor Escherich discovered this organism in the feces of healthy individuals. He called it Bacterium coli commune because it is found in the colon. Early classifications of prokaryotes placed these in a handful of genera based on their shape and motility (at that time Ernst Haeckels classification of bacteria in the kingdom Monera was in place).Bacterium coli was the type species of the now invalid genus Bacterium when it was revealed that the former type species ("Bacterium triloculare") was missing. Following a revision of Bacterium, it was reclassified as Bacillus coli by Migula in 1895 and later reclassified in the newly created genus Escherichia, named after its original discoverer, by Aldo Castellani and Albert John Chalmers.In 1996, the worlds worst to date outbreak of E. coli food poisoning occurred in Wishaw, Scotland, killing 21 people. This death toll was exceeded in 2011, when the 2011 Germany E. coli O104:H4 outbreak, linked to organic fenugreek sprouts, killed 53 people.

Uses
E. coli has several practical uses besides its use as a vector for genetic experiments and processes. For example, E. coli can be used to generate synthetic propane and recombinant human growth hormone.

See also
References
Databases and external links

EcoCyc – literature-based curation of the entire genome, and of transcriptional regulation, transporters, and metabolic pathways
Membranome database provides information about single-pass transmembrane proteins from E </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Toxic encephalopathy and can you explain it in depth? [/INST] Toxic encephalopathy is a neurologic disorder caused by exposure to neurotoxic organic solvents such as toluene, following exposure to heavy metals such as manganese, as a side effect of melarsoprol treatment for African trypanosomiasis, adverse effects to prescription drugs, or exposure to extreme concentrations of any natural toxin such as cyanotoxins found in shellfish or freshwater cyanobacteria crusts.  Toxic encephalopathy can occur following acute or chronic exposure to neurotoxicants, which includes all natural toxins.  Exposure to toxic substances can lead to a variety of symptoms, characterized by an altered mental status, memory loss, and visual problems. Toxic encephalopathy can be caused by various chemicals, some of which are commonly used in everyday life, or cyanotoxins which are bio-accumulated from harmful algal blooms (HABs) which have settled on the benthic layer of a waterbody. Toxic encephalopathy can permanently damage the brain and currently treatment is mainly just for the symptoms.

Signs and symptoms
"Encephalopathy" is a general term describing brain malfunctions and "toxic" asserts that the malfunction is caused by toxins on the brain. The most prominent characteristic of toxic encephalopathy is an altered mental status.  Acute intoxication is a reversible symptom of exposure to many synthetic chemical neurotoxicants.  Acute intoxication symptoms include lightheadedness, dizziness, headache and nausea, and regular cumulative exposure to these neurotoxicants over a number of years puts the individual at high risk for developing toxic encephalopathy.  Chronic exposure to low levels of neurotoxic chemicals can also cause reversible changes in mood and affect which resolve with cessation of exposure.  Acute and chronic toxic encephalopathy on the other hand, are persistent changes in neurological function that typically occur with exposure to higher concentrations and longer durations respectively.  The symptoms of acute and chronic toxic encephalopathy do not resolve with cessation of exposure and can include memory loss, dementia, small personality changes/increased irritability, insidious onset of concentration difficulties, headache, lightheadedness, ataxia, involuntary movements (parkinsonism), fatigue, seizures, arm strength problems, and depression.  A paper by Feldman and colleagues described neurobehavioral effects in a 57-year-old house painter with regular exposure to large amounts of solvents.Magnetic Resonance Imaging (MRI) analyses have also demonstrated increased rates of dopamine synthesis in the putamen, reduced  anterior and total corpus callosum volume, demyelination in the parietal white matter, basal ganglia, and thalamus, as well as atypical activation of frontal areas of the brain due to neural compensation.The regions of interest on SPECT brain imaging include a majority of all cortical regions, and the globus pallidus in Carbon monoxide poisoning. Based on medical literature on SPECT brain imaging, signature patterns for toxic encephalopathy is a nonspecific patchy, diffuse pattern on the cortex, and sometimes is shown in subcortical regions, if exposure was severe.A thorough and standard diagnostic process is paramount with toxic encephalopathy, including a careful occupational, medication and medical history, standardized imaging and neuropsychological testing.

Causes
In addition, chemicals, such as lead, that could instigate toxic encephalopathy are sometimes found in everyday products such as prescription drugs, cleaning products, building materials, pesticides, air fresheners, and even perfumes. These harmful chemicals can be inhaled (in the case of air fresheners) or applied (in the case of perfumes). The substances diffuse into the brain rapidly, as they are lipophilic and readily transported across the blood–brain barrier. This is a result of increased membrane solubility and local blood flow, with central nervous system (CNS) solvent uptake being further increased with high levels of physical activity. When they are not detoxified immediately, the symptoms of toxic encephalopathy begin to emerge. However, in chronic situations, these effects may not become severe enough to be noticed until much later. Increased exposure time and increased concentration of the chemicals will worsen the effects of toxic encephalopathy, due to the associated structural CNS damage and direct functional impairment consequences.Subacute toxic encephalopathies are challenging to identify due to their often insidious tempo of evolution, nonspecific manifestations, relative infrequency as individual entities, and frequent lack of specific diagnostic testing. Yet they are crucial to recognize in aggregate, subacute toxic encephalopathies are a common problem that can lead to severe, irreversible harm if not diagnosed and treated efficiently. This article reviews the clinically relevant aspects of some of the more important subacute toxic encephalopathy syndromes caused by inorganic toxins, carbon monoxide (CO), anti- biotics, antineoplastic agents, and psychiatric medications.All therapeutic interventions are double-edged swords with benefits and adverse effects, and pharmacotherapy is not an exception. Shortly after the introduction of conventional antipsychotic drugs into clinical practice, relatively rare but serious complications with hyperthermia, muscle rigidity, autonomic instability, and disturbed mental status were recognized to develop in some patients treated with antipsychotics. This type of encephalopathy induced by the use of antipsychotics was referred to as neuroleptic malignant syndrome (NMS), and almost all physicians prescribing antipsychotics are nowadays aware of this adverse phenomenon. Another well-known type of encephalopathy associated with psychotropic drug therapy is serotonin toxicity (ST) or serotonin syndrome (SS), which is characterized by autonomic and neuromuscular symptoms and altered mental status. In contrast with the idiosyncratic nature of NMS, ST is a spectrum pathophysiological state assumed to derive from excess serotonergic neural transmission caused by serotonin-related psychotropic agents. In these two decades, pharmacotherapy with psychotropic drugs for patients with mental illness has been dramatically changed, and classical prototypal antipsychotics and antidepressants have been replaced with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs), respectively. These newly developed psychotropic drugs are generally safer and more tolerable than older drugs. However, atypical antipsychotics are not free of the risk of development of NMS, and the explosive prevalence of SSRIs prescribed not only for depression but also for a number of psychiatric diagnoses such as anxiety, eating, impulse-control, and personality disorders may increase the incidence of ST. Therefore, these two pathological states still remain as major adverse effects of psychotropic drugs involving altered functioning of the central nervous system (CNS), to which all clinicians prescribing psychoactive drugs should pay attention. The popularity of SSRIs also increased the case reports of patients with discontinuation syndrome, which sometimes includes CNS symptoms like anxiety and irritability. In this chapter, the author provides a comprehensive overview of the above- mentioned adverse effects affecting the CNS function associated with psychotropic pharmacotherapy. In addition, several other pathological conditions potentially causing encephalopathic symptoms in psychiatric patients treated with psychotropic drugs, e.g., hyponatremia, valproate-induced hyperammonemia, transient splenial lesion of the corpus callosum, and so on, are also described.Fume events on aircraft have been linked to cases of toxic encephalopathy, for example in the case of JetBlue Captain Andrew Myers, who as a result of exposure needed a cane to walk, experienced tremors and struggled to speak. In the following year, the Federal Aviation Administration revoked Myers medical certificate; the workers compensation board agreed that Myers experienced brain damage as a result of the event.

Diagnosis
Rapid diagnosis is important to attempt to prevent further damage to the brain and further neurologic deficits. It is a diagnosis of exclusion, so a full work up for other possible etiologies (hepatic, uremic, infectious, oncologic) should be performed. In addition to  the neurological examination, diagnostic testing could include MRI, PET or SPECT brain imaging, EEG, QEEG and most importantly, neuropsychological testing. Screening for heavy metals, as well as other toxins, should be done immediately as those are some of the most common causes and the patient can then remove themselves from the dangerous environment. In addition, a full examination of blood (CBC) and metabolites (CMP) should be done.

Treatment
Treatment is mainly for the symptoms that toxic encephalopathy causes, and vary depending on how severe the case is. Diet changes and nutritional supplements may help some patients. To reduce or halt seizures, anticonvulsants may be prescribed. Dialysis or organ replacement surgery may be needed in some severe cases.Lifelong abstinence from alcohol, a well-established neurotoxin and cause of the condition, is encouraged to prevent further loss of neurocognitive function.Management of affected individuals consists of immediate removal from exposure to the toxic substance(s), treatment of the common clinical manifestation of depression if present, and counselling for the provision of life strategies to help cope with the potentially debilitating condition.

Prognosis
Toxic encephalopathy is often irreversible. If the source of the problem is treated by removing the toxic chemical from the system, further damage can be prevented, but prolonged exposure to toxic chemicals can quickly destroy the brain. Long-term studies have demonstrated residual cognitive impairment (primarily attention and information-processing impairment resulting in dysfunction in working memory) up to 10 years following cessation of exposure. Severe cases of toxic encephalopathy can be life-threatening.

Research
Research is being done by organizations such as NINDS (National Institute of Neurological Disorders and Stroke) on what substances can cause encephalopathy, why they do this, and eventually how to protect, treat, and cure the brain from this condition.

See also
Brain damage
Chronic solvent-induced encephalopathy
Encephalopathy
Neurology

Notes
References
Lerner, David P.; Tadevosyan, Aleksey; Burns, Joseph D. (November 2020). "Toxin-Induced Subacute Encephalopathy". Neurologic Clinics. 38 (4): 799–824. doi:10.1016/j.ncl.2020.07.006. PMID 33040862. S2CID 222301922.
Bradley, Walter (2004). Neurology in Clinical Practice (4 ed.). Taylor & Francis. ISBN 9997625897.
Baker, Edward L. (May 2008). "Chronic toxic encephalopathy caused by occupational solvent exposure". Annals of Neurology </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Delusional disorder and can you explain it in depth? [/INST] Delusional disorder is a mental illness in which a person has delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect. Delusions are a specific symptom of psychosis. Delusions can be bizarre or non-bizarre in content; non-bizarre delusions are fixed false beliefs that involve situations that could occur in real life, such as being harmed or poisoned. Apart from their delusion or delusions, people with delusional disorder may continue to socialize and function in a normal manner and their behavior does not necessarily generally seem odd. However, the preoccupation with delusional ideas can be disruptive to their overall lives.For the diagnosis to be made, auditory and visual hallucinations cannot be prominent, though olfactory or tactile hallucinations related to the content of the delusion may be present. The delusions cannot be due to the effects of a drug, medication, or general medical condition, and delusional disorder cannot be diagnosed in an individual previously properly diagnosed with schizophrenia. A person with delusional disorder may be high functioning in daily life. Recent and comprehensive meta-analyses of scientific studies point to an association between a deterioration in aspects of IQ in psychotic patients, in particular perceptual reasoning.According to German psychiatrist Emil Kraepelin, patients with delusional disorder remain coherent, sensible and reasonable. The Diagnostic and Statistical Manual of Mental Disorders (DSM) defines six subtypes of the disorder characterized as erotomanic (belief that someone is in love with one), grandiose (belief that one is the greatest, strongest, fastest, richest, or most intelligent person ever), jealous (belief that one is being cheated on), persecutory (delusions that the person or someone to whom the person is close is being malevolently treated in some way), somatic (belief that one has a disease or medical condition), and mixed, i.e., having features of more than one subtype.Delusions also occur as symptoms of many other mental disorders, especially the other psychotic disorders.
The DSM-IV and psychologists agree that personal beliefs should be evaluated with great respect to cultural and religious differences, since some cultures have widely accepted beliefs that may be considered delusional in other cultures.An earlier, now obsolete, nosological name for delusional disorder was "paranoia".

Classification
The International Classification of Diseases classifies delusional disorder as a mental and behavioural disorder.
Diagnosis of a specific type of delusional disorder can sometimes be made based on the content of the delusions, to wit,  the Diagnostic and Statistical Manual of Mental Disorders (DSM) enumerates seven types:

Erotomanic type (erotomania): delusion that another person, often a prominent figure, is in love with the individual. The individual may breach the law as they try to obsessively make contact with the desired person.
Grandiose type (megalomania): delusion of inflated worth, power, knowledge, identity or believing oneself to be a famous person, claiming the actual person is an impostor or an impersonator.
Jealous type: delusion that the individuals sexual partner is unfaithful when it is untrue. The patient may follow the partner, check text messages, emails, phone calls etc. in an attempt to find "evidence" of the infidelity.
Persecutory type: This delusion is a common subtype. It includes the belief that the person (or someone to whom the person is close) is being malevolently treated in some way. The patient may believe that they have been drugged, spied upon, harmed, harassed and so on and may seek "justice" by making reports, taking  action or even acting violently.
Somatic type: delusions that the person has some physical defect or general medical condition
Mixed type: delusions with characteristics of more than one of the above types but with no one theme predominating.
Unspecified type: delusions that cannot be clearly determined or characterized in any of the categories in the specific types.

Signs and symptoms
The following can indicate a delusion:
An individual expresses an idea or belief with unusual persistence or force, even when evidence suggests the contrary.
That idea appears to have an undue influence on the persons life, and the way of life is often altered to an inexplicable extent.
Despite their profound conviction, there is often a quality of secretiveness or suspicion when the person is questioned about it.
The individual tends to be humorless and oversensitive, especially about the belief.
There is a quality of centrality: no matter how unlikely it is that these strange things are happening to the person, he or she accepts them relatively unquestioningly.
An attempt to contradict the belief is likely to arouse an inappropriately strong emotional reaction, often with irritability and hostility. They will not accept any other opinions.
The belief is, at the least, unlikely, and out of keeping with the individuals social, cultural, and religious background.
The person is emotionally over-invested in the idea and it overwhelms other elements of his or her psyche.
The delusion, if acted out, often leads to behaviors which are abnormal, and out of character, although perhaps understandable in light of the delusional beliefs.
Other people who know the individual observe that the belief and behavior are uncharacteristic and alien.Additional features of delusional disorder include the following:
It is a primary disorder.
It is a stable disorder characterized by the presence of delusions to which the patient clings with extraordinary tenacity.
The illness is chronic and frequently lifelong.
The delusions are logically constructed and internally consistent.
The delusions do not interfere with general logical reasoning (although within the delusional system the logic is perverted) and there is usually no general disturbance of behavior. If disturbed behavior does occur, it is directly related to the delusional beliefs.
The individual experiences a heightened sense of self-reference.  Events which, to others, are nonsignificant are of enormous significance to him or her, and the atmosphere surrounding the delusions is highly charged.However this should not be confused with gaslighting, where a person denies the truth, and causes the one being gaslit to think that they are being delusional.

Causes
The cause of delusional disorder is unknown, but genetic, biochemical, and environmental factors may play a significant role in its development. Some people with delusional disorders may have an imbalance in neurotransmitters, the chemicals that send and receive messages to the brain. There does seem to be some familial component, and immigration (generally for persecutory reasons), drug abuse, excessive stress, being married, being employed, low socioeconomic status, celibacy among men, and widowhood among women may also be risk factors. Delusional disorder is currently thought to be on the same spectrum or dimension as schizophrenia, but people with delusional disorder, in general, may have less symptomatology and functional disability.

Diagnosis
Differential diagnosis includes ruling out other causes such as drug-induced conditions, dementia, infections, metabolic disorders, and endocrine disorders. Other psychiatric disorders must then be ruled out. In delusional disorder, mood symptoms tend to be brief or absent, and unlike schizophrenia, delusions are non-bizarre and hallucinations are minimal or absent.Interviews are important tools to obtain information about the patients life situation and history to help make a diagnosis. Clinicians generally review earlier medical records to gather a full history. Clinicians also try to interview the patients immediate family, as this can be helpful in determining the presence of delusions. The mental status examination is used to assess the patients current mental condition.
A psychological questionnaire used in the diagnosis of the delusional disorder is the Peters Delusion Inventory (PDI) which focuses on identifying and understanding delusional thinking. However, this questionnaire is more likely used in research than in clinical practice.
In terms of diagnosing a non-bizarre delusion as a delusion, ample support should be provided through fact checking. In case of non-bizarre delusions,  Psych Central notes, "All of these situations could be true or possible, but the person suffering from this disorder knows them not to be (e.g., through fact-checking, third-person confirmation, etc.)."

Treatment
A challenge in the treatment of delusional disorders is that most patients have limited insight, and do not acknowledge that there is a problem.  Most patients are treated as out-patients, although hospitalization may be required in some cases if there is a risk of harm to self or others. Individual psychotherapy is recommended rather than group psychotherapy, as patients are often quite suspicious and sensitive.  Antipsychotics are not well tested in delusional disorder, but they do not seem to work very well, and often have no effect on the core delusional belief. Antipsychotics may be more useful in managing agitation that can accompany delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders.Psychotherapy for patients with delusional disorder can include cognitive therapy which is conducted with the use of empathy. During the process, the therapist can ask hypothetical questions in a form of therapeutic Socratic questioning. This therapy has been mostly studied in patients with the persecutory type. The combination of pharmacotherapy with cognitive therapy integrates treating the possible underlying biological problems and decreasing the symptoms with psychotherapy as well. Psychotherapy has been said to be the most useful form of treatment because of the trust formed in a patient and therapist relationship.Supportive therapy has also been shown to be helpful. Its goal is to facilitate treatment adherence and provide education about the illness and its treatment.
Furthermore, providing social skills training has been found to be helpful for many people. It can promote interpersonal competence as well as confidence and comfort when interacting with those individuals perceived as a threat.Insight-oriented therapy is rarely indicated or contraindicated; yet there are reports of successful treatment. Its goals are to develop therapeutic alliance, containment of projected feelings of hatred, powerlessness, and badness; measured interpretation as well as the development of a sense of creative doubt in the internal perception of the world. The latter requires empathy with the patients defensive position.

Epidemiology
Delusional disorders are uncommon in psychiatric practice, though this may be an underestimation due to the fact that those with the condition lack insight and thus avoid psychiatric assessment. The prevalence of this condition stands at about 24 to 30 cases per 100,000 people while 0.7 to 3.0 new cases per 100,000 people are reported every year. Delusional disorder accounts for 1–2% of admissions to inpatient mental health facilities. The incidence of first admissions for delusional disorder is lower, from 0.001 to 0.003%.Delusional disorder tends to appear in middle to late adult life, and for the most part first admissions to hospital for delusional disorder occur between age 33 and 55. It is more common in women than men, and immigrants seem to be at higher risk.

Criticism
In some situations the delusion may turn out to be true belief. For example, in delusional jealousy, where a person believes that the partner is being unfaithful (in extreme cases perhaps going so far as to follow the partner into the bathroom, believing the other to be seeing a lover even during the briefest of separations), it may actually be true that the partner is having sexual relations with another person. In this case, the delusion does not cease to be a delusion because the content later turns out to be verified as true or the partner actually chose to engage in the behavior of which they were being accused.
In other cases, the delusion may be mistakenly assumed to be false by a doctor or psychiatrist assessing the belief, just because it seems to be unlikely, bizarre or held with excessive conviction. Psychiatrists rarely have the time or resources to check the validity of a persons claims leading to some true beliefs to be erroneously classified as delusional. This is known as the Martha Mitchell effect, after the wife of the attorney general who alleged that illegal activity was taking place in the White House. At the time, her claims were thought to be signs of mental illness, and only after the Watergate scandal broke was she proved right (and hence sane).
Similar factors have led to criticisms of Jaspers definition of true delusions as being ultimately un-understandable. Critics (such as R. D. Laing) have argued that this leads to the diagnosis of delusions being based on the subjective understanding of a particular psychiatrist, who may not have access to all the information that might make a belief otherwise interpretable.
Another difficulty with the diagnosis of delusions is that almost all of these features can be found in "normal" beliefs. Many religious beliefs hold exactly the same features, yet are not universally considered delusional. For instance, if a person was holding a true belief then they will of course persist with it. This can cause the disorder to be misdiagnosed by psychiatrists. These factors have led the psychiatrist Anthony David to write that "there is no acceptable (rather than accepted) definition of a delusion."

In popular culture
In the 2010 psychological thriller Shutter Island, directed by Martin Scorsese and starring Leonardo DiCaprio, delusional disorder is portrayed along with other disorders. An Indian movie Anantaram (Thereafter) directed by Adoor Gopalakrishnan also portrays the complex nature of delusions. The plot of the French movie He Loves Me... He Loves Me Not revolves around a case of erotomania, as does the plot of the Ian McEwan novel, Enduring Love.

See also
Delusional parasitosis
Monothematic delusions
Morgellons
Paranoia
Shared delusional disorder

References
Further reading
Arnold, K.; Vakhrusheva, J. (2015). "Resist the negation reflex: Minimizing reactance in psychotherapy of delusions" (PDF). Psychosis </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Botryoid odontogenic cyst and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Posterior ischemic optic neuropathy and can you explain it in depth? [/INST] Posterior ischemic optic neuropathy (PION) is a medical condition characterized by damage to the retrobulbar portion of the optic nerve due to inadequate blood flow (ischemia) to the optic nerve. Despite the term posterior, this form of damage to the eyes optic nerve due to poor blood flow also includes cases where the cause of inadequate blood flow to the nerve is anterior, as the condition describes a particular mechanism of visual loss as much as the location of damage in the optic nerve. In contrast, anterior ischemic optic neuropathy (AION) is distinguished from PION by the fact that AION occurs spontaneously and on one side in affected individuals with predisposing anatomic or cardiovascular risk factors.

Signs and symptoms
PION is characterized by moderate to severe painless vision loss of abrupt onset. One or both eyes may be affected and color vision is typically impaired.

Ophthalmoscopic exam
Looking inside the persons eyes at the time of onset, ophthalmoscope exam reveals no visible changes to the optic nerve head. Weeks after ischemic insult, nerve atrophy originating from the damaged posterior optic nerve progresses to involve the anterior optic nerve head. Four to eight weeks after onset, atrophy of the optic nerve head is observable upon ophthalmoscope exam.

Pupils
If both eyes are affected by PION, the pupils may look symmetrical. However, if the eyes are asymmetrically affected, i.e. one eyes optic nerve is more damaged than the other, it will produce an important sign called an afferent pupillary defect.Defective light perception in one eye causes an asymmetrical pupillary constriction reflex called the afferent pupillary defect (APD).

Arteritic PION
A-PION most commonly affects Caucasian women, with an average age of 73. At onset vision loss is unilateral, but without treatment it rapidly progresses to involve both eyes. Vision loss is usually severe, ranging from counting fingers to no light perception. Associated symptoms are jaw pain exacerbated by chewing, scalp tenderness, shoulder and hip pain, headache and fatigue.

Perioperative PION
Vision loss is usually apparent upon waking from general anesthesia. Signs observable to a bystander include long surgery duration and facial swelling. Vision loss is usually bilateral and severe, ranging from counting fingers to no light perception.

Cause
PION is a watershed infarction of the optic nerve that may cause either unilateral or, more often, bilateral blindness. PION typically occurs in two categories of people:
People who have undergone non-ocular surgery that is particularly prolonged or is associated with a significant blood loss.
People who have experienced significant bleeding from an accident or ruptured blood vessels.  In these cases, the person may develop anemia (too few oxygen-delivering red blood cells in the bloodstream) and often have low blood pressure as well. This combination can produce circulatory shock, and PION has sometimes been called shock-induced optic neuropathy.The combination of anemia and low blood pressure means that the blood is carrying less oxygen to the tissues. The optic nerve can be at very high risk for damage from insufficient blood supply due to swelling (from lack of oxygen) in a confined bony space resulting in a compartment syndrome. Restricted blood flow can lead to permanent damage to the optic nerve and result in blindness (often in both eyes). For technical reasons this occurs more frequently with spinal surgeries.

Cardiovascular risk factors
Perioperative PION patients have a higher prevalence of cardiovascular risk factors than in the general population. Documented cardiovascular risks in people affected by perioperative PION include high blood pressure, diabetes mellitus, high levels of cholesterol in the blood, tobacco use, abnormal heart rhythms, stroke, and obesity. Men are also noted to be at higher risk, which is in accordance with the trend, as men are at higher risk of cardiovascular disease. These cardiovascular risks all interfere with adequate blood flow, and also may suggest a contributory role of defective vascular autoregulation.

Perioperative PION
As illustrated by the risk factors above, perioperative hypoxia is a multifactorial problem. Amidst these risk factors it may be difficult to pinpoint the optic nerves threshold for cell death, and the exact contribution of each factor.Low blood pressure and anemia are cited as perioperative complications in nearly all reports of PION, which suggests a causal relationship. However, while low blood pressure and anemia are relatively common in the perioperative setting, PION is exceedingly rare. Spine and cardiac bypass surgeries have the highest estimated incidences of PION, 0.028% and 0.018% respectively, and this is still extremely low. This evidence suggests that optic nerve injury in PION patients is caused by more than just anemia and low blood pressure.Evidence suggests that the multifactorial origin of perioperative PION involves the risks discussed above and perhaps other unknown factors. Current review articles of PION propose that vascular autoregulatory dysfunction and anatomic variation are under-investigated subjects that may contribute to patient-specific susceptibility.

Pathogenesis
PION
In both types of PION, decreased blood flow leads to the death of optic nerve cells. Ischemic injury to the optic nerve causes inflammation and swelling. Because the posterior optic nerve passes through the optic canal, a bony tunnel leading to the brain, swelling in this rigid space causes compression of the optic nerve. This compression worsens ischemia and perpetuates the cycle of injury, and swelling, and compression.

A-PION
A-PION is caused by an inflammatory disease called giant cell arteritis (GCA). GCA is an inflammatory disease of blood vessels. It is believed to be an autoimmune disease caused by inappropriate T-cell activity. When T-cells damage arteries supplying the optic nerve, a blood clot forms and stops blood flow. When blood flow stops, oxygen delivery stops and optic nerve fibers die.

Perioperative PION
The exact cause of perioperative PION is unknown. Many risk factors have been identified, all of which contribute to inadequate delivery of oxygen to optic nerve cells. Alone, none of these risk factors is enough to cause PION. However, in susceptible individuals, a combination of these risk factors produces devastating blindness. This evidence suggests that PION is a disease of multifactorial origin.Risks of perioperative PION can be divided into two categories, intraoperative ischemic pressures, and cardiovascular risk factors.

Intraoperative ischemic pressures
Many causes of decreased blood flow during surgery are systemic, i.e. they decrease blood flow throughout the body. Studies have shown that nearly all perioperative PION patients had prolonged periods of low blood pressure during the operation and postoperative anemia. The average perioperative PION patient loses 4 liters of blood during surgery, and the majority receive blood transfusions. Massive blood loss is just one cause of low blood pressure. Medications used for general anesthesia can also lower blood pressure. The average surgery duration in PION cases is 7 to 9 hours, which increases the risk of prolonged low blood pressure.Other intraoperative ischemic pressures are local, i.e. they decrease blood flow to the affected area, the optic nerve. Facial swelling, periorbital swelling, direct orbital compression, facedown position during surgery, and a tilted operating table in feet-above-head position, have all been reported to be associated with perioperative PION. All of these factors are believed to increase tissue pressure and venous pressure around the optic nerve, thereby decreasing local blood flow and oxygen delivery.Surgeries with the highest estimated incidence of PION are surgeries with a higher risk of the aforementioned conditions. In spine surgery, patients are susceptible to significant blood loss, and they are positioned face down for long periods of time, which increases venous pressure, decreases arterial perfusion pressure, and often causes facial swelling (increased tissue pressure). Spine surgery is estimated to have the highest incidence of PION, 0.028%. Long duration of feet-above-head position in prostate surgery has also been suggested to increase risk of PION.

Diagnosis
The diagnosis of PION is often difficult since the optic nerves initially appear normal.  The injury occurs posterior to that portion of the nerve visible during ophthalmoscopic examination.  There may be an abnormal relative pupillary response (APD) if the injury is confined to one optic nerve, but often it is bilateral and the symmetry of pupillary responses is maintained.  Furthermore, MRI scanning may not be helpful.  It is not uncommon for the erroneous diagnoses of malingering or cortical blindness to be made. If possible, an urgent neuro-ophthalmology consult is most likely to lead to the correct diagnosis.There is no confirmatory test for PION. PION is a diagnosis of exclusion. To prevent impending blindness, it is urgent to rule out giant cell arteritis when a patient over 50 presents with sudden vision loss.

Differential diagnosis
In the postoperative setting, without gross eye injury, visual loss requires an assessment of the whole visual system for ischemic damage. The optic nerve is not the only tissue of the visual pathway susceptible to decreased blood flow. Decreased oxygenation of the retina or brain could also impair vision.

Anterior ischemic optic neuropathy
PION is less common than Anterior Ischemic Optic Neuropathy (AION). Blood supply and surrounding anatomy make the anterior and posterior portions of the optic nerve susceptible to different ischemic pressures.The posterior optic nerve receives blood primarily from the pial branches of the ophthalmic artery. The optic canal, a boney tunnel leading to the brain, surrounds the most posterior part of this optic nerve segment.The anterior optic nerve receives blood primarily from the posterior ciliary arteries. The anterior optic nerve, a.k.a. the optic nerve head, is surrounded by the scleral canal, and is vulnerable to crowding of nerve fibers. The portion of the optic nerve head that is visible by looking into the eye with an ophthalmoscope is called the optic disc.

PION versus AION
At the onset of symptoms, ophthalmoscope examination can differentiate AION from PION. If optic nerve head involvement is observed, it is AION. PION does not produce optic atrophy that is observable via ophthalmoscope until four to eight weeks after onset. In addition, AION often shows a characteristic altitudinal defect on a Humphrey Visual Field test.

GCA
The American College of Rheumatology has defined a combination of physical symptoms and inflammatory changes to diagnose giant cell arteritis.

Prevention
Individuals with a history of high blood pressure, diabetes, and smoking are most susceptible to PION as they have a compromised system of blood vessel autoregulation.  Hence, extra efforts may need to be taken for them in the form of careful or staged surgery or the controlling the anemia from blood loss (by administration of blood transfusions), and the careful maintenance of their blood pressure.

Treatment
Once visual loss has occurred, it becomes more problematic, but there are reports of recovered vision if blood transfusions and agents that raise blood pressure are administered within hours.

A-PION
If a diagnosis of GCA is suspected, treatment with steroids should begin immediately. A sample (biopsy) of the temporal artery should be obtained to confirm the diagnosis and guide future management, but should not delay initiation of treatment. Treatment does not recover lost vision, but prevents further progression and second eye involvement. High dose corticosteroids may be tapered down to low doses over approximately one year.

Perioperative
Rapid blood transfusions, to correct anemia and raise blood pressure, may improve PION outcomes. In one report of a related disease, hypotension-induced AION, 3 out of 3 patients who received rapid transfusions reported partial recovery of vision. While rapid transfusions offer some hope, the prognosis for perioperative PION remains poor. Prevention remains the best way to reduce PION.
One retrospective report proposes that incidence of PION could be reduced in high-risk cases by altering surgical management. For example, for patients undergoing spine surgery, measures could be taken to minimize intraoperative hypotension, to accelerate the process of blood replacement, and to aggressively treat facial swelling.

Epidemiology
PION most commonly affects the elderly. The mean patient age was 62 years in one series (range 18 to 90 years).The mean age varies by etiology category; patients with giant cell arteritis (GCA) are older (mean 78 years, range 50 to 82 years), while those with PION in the setting of spine surgery are younger on average.There is a higher than expected prevalence of atherosclerotic risk factors and comorbid vascular disease, especially in patients with nonarteritic (idiopathic) PION, with 87 percent of patients having at least one risk factor for, or one other manifestation of, atherosclerotic vascular disease.
While anterior ischemic optic neuropathy (AION) appears to be more common than PION after cardiac surgery, PION is relatively more common in cases of spine surgery.

References
Further reading
Luneau K, Newman NJ, Biousse V (November 2008). "Ischemic optic neuropathies". The Neurologist. 14 (6): 341–54. doi:10.1097/NRL.0b013e318177394b. PMID 19008740. S2CID 8445417.
Remigio D, Wertenbaker C (2000) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Athletic heart syndrome and can you explain it in depth? [/INST] Athletic heart syndrome (AHS) is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal.
The athletes heart is associated with physiological cardiac remodeling as a consequence of repetitive cardiac loading. Athletes heart is common in athletes who routinely exercise more than an hour a day, and occurs primarily in endurance athletes, though it can occasionally arise in heavy weight trainers. The condition is generally considered benign, but may occasionally hide a serious medical condition, or may even be mistaken for one.

Signs and symptoms
Athletes heart most often does not have any physical symptoms, although an indicator would be a consistently low resting heart rate. Athletes with AHS often do not realize they have the condition unless they undergo specific medical tests, because athletes heart is a normal, physiological adaptation of the body to the stresses of physical conditioning and aerobic exercise. People diagnosed with athletes heart commonly display three signs that would usually indicate a heart condition when seen in a regular person: bradycardia, cardiomegaly, and cardiac hypertrophy. Bradycardia is a slower than normal heartbeat, at around 40–60 beats per minute. Cardiomegaly is the state of an enlarged heart, and cardiac hypertrophy the thickening of the muscular wall of the heart, specifically the left ventricle, which pumps oxygenated blood to the aorta. Especially during an intensive workout, more blood and oxygen are required to the peripheral tissues of the arms and legs in highly trained athletes bodies. A larger heart results in higher cardiac output, which also allows it to beat more slowly, as more blood is pumped out with each beat.Another sign of athletes heart syndrome is an S3 gallop, which can be heard through a stethoscope. This sound can be heard as the diastolic pressure of the irregularly shaped heart creates a disordered blood flow. However, if an S4 gallop is heard, the patient should be given immediate attention. An S4 gallop is a stronger and louder sound created by the heart, if diseased in any way, and is typically a sign of a serious medical condition.

Cause
Athletes heart is a result of dynamic physical activity, such as aerobic training more than 5 hours a week rather than static training such as weightlifting. During intensive prolonged endurance or strength training, the body signals the heart to pump more blood through the body to counteract the oxygen deficit building in the skeletal muscles. Enlargement of the heart is a natural physical adaptation of the body to deal with the high pressures and large amounts of blood that can affect the heart during these periods of time. Over time, the body will increase both the chamber size of the left ventricle, and the muscle mass and wall thickness of the heart.Cardiac output, the amount of blood that leaves the heart in a given time period (i.e. liters per minute), is proportional to both the chamber sizes of the heart and the rate at which the heart beats. With a larger left ventricle, the heart rate can decrease and still maintain a level of cardiac output necessary for the body. Therefore, athletes with AHS commonly have lower resting heart rates than nonathletes.The heart becomes enlarged, or hypertrophic, due to intense cardiovascular workouts, creating an increase in stroke volume, an enlarged left ventricle (and right ventricle), and a decrease in resting heart rate along with irregular rhythms. The wall of the left ventricle increases in size by about 15–20% of its normal capacity. No decrease of the diastolic function of the left ventricle occurs. The athlete may also experience an irregular heartbeat and a resting pulse rate between 40 and 60 beats per minute (bradycardia).The level of physical activity in a person determines what physiological changes the heart makes. The two types of exercise are static (strength-training) and dynamic (endurance-training). Static exercise consists of weight lifting and is mostly anaerobic, meaning the body does not rely on oxygen for performance. It also moderately increases heart rate and stroke volume (oxygen debt). Dynamic exercises include running, swimming, skiing, rowing, and cycling, which rely on oxygen from the body. This type of exercise also increases both heart rate and stroke volume of the heart. Both static and dynamic exercises involve the thickening of the left ventricular wall due to increased cardiac output, which leads to physiologic hypertrophy of the heart. Once athletes stop training, the heart returns to its normal size.

Diagnosis
Athletes heart is usually an incidental finding during a routine screening or during tests for other medical issues. An enlarged heart can be seen at echocardiography or sometimes on a chest X-ray. Similarities at presentation between athletes heart and clinically relevant cardiac problems may prompt electrocardiography (ECG) and exercise cardiac stress tests. The ECG can detect sinus bradycardia, a resting heart rate of fewer than 60 beats per minute. This is often accompanied by sinus arrhythmia. The pulse of a person with athletes heart can sometimes be irregular while at rest, but usually returns to normal after exercise begins.Regarding differential diagnosis, left ventricular hypertrophy is usually indistinguishable from athletes heart and at ECG, but can usually be discounted in the young and fit.It is important to distinguish between athletes heart and hypertrophic cardiomyopathy (HCM), a serious cardiovascular disease characterised by thickening of the hearts walls, which produces a similar ECG pattern at rest. This genetic disorder is found in one of 500 Americans and is a leading cause of sudden cardiac death in young athletes (although only about 8% of all cases of sudden death are actually exercise-related). The following table shows some key distinguishing characteristics of the two conditions.Athletes heart should not be confused with bradycardia that occurs secondary to Relative energy deficiency in sport or Anorexia nervosa, which involve slowing of metabolic rate and sometimes shrinkage of the heart muscle and reduced heart volume.
The medical history of the patient (endurance sports) and physical examination (bradycardia, and maybe a third or fourth heart sound), can give important hints.

ECG – typical findings in resting position are, for example, sinus bradycardia, atrioventricular block (primary and secondary) and incomplete (IRBBB) or complete right bundle branch block (RBBB) – all those findings normalize during exercise.
Echocardiography – differentiation between physiological and pathological increases of the hearts size is possible, especially by estimating the mass of the wall (not over 130 g/m2) and its end diastolic diameter (not much less 60 mm) of the left ventricle.
X-ray examination of the chest may show increased heart size (mimicking other possible causes of enlargement).
Cardiac MRI - In athletes heart, there is balanced atrioventricular remodeling, reduced thickening of the heart after detraining, no late gadolinium enhancement, low to normal T1 signal, and normal extracellular volume.

Screening related conditions
Because several well-known and high-profile cases of athletes experiencing sudden unexpected death due to cardiac arrest, such as Reggie White and Marc-Vivien Foé, a growing movement is making an effort to have both professional and school-based athletes screened for cardiac and other related conditions, usually through a careful medical and health history, a good family history, a comprehensive physical examination including auscultation of heart and lung sounds and recording of vital signs such as heart rate and blood pressure, and increasingly, for better efforts at detection, such as an electrocardiogram.An electrocardiogram (ECG) is a relatively straightforward procedure to administer and interpret, compared to more invasive or sophisticated tests; it can reveal or hint at many circulatory disorders and arrhythmias. Part of the cost of an ECG may be covered by some insurance companies, though routine use of ECGs or other similar procedures such as echocardiography (ECHO) are still not considered routine in these contexts. Widespread routine ECGs for all potential athletes during initial screening and then during the yearly physical assessment could well be too expensive to implement on a wide scale, especially in the face of the potentially very large demand. In some places, a shortage of funds, portable ECG machines, or qualified personnel to administer and interpret them (medical technicians, paramedics, nurses trained in cardiac monitoring, advanced practice nurses or nurse practitioners, physician assistants, and physicians in internal or family medicine or in some area of cardiopulmonary medicine) exist.If sudden cardiac death occurs, it is usually because of pathological hypertrophic enlargement of the heart that went undetected or was incorrectly attributed to the benign "athletic" cases. Among the many alternative causes are episodes of isolated arrhythmias which degenerated into lethal VF and asystole, and various unnoticed, possibly asymptomatic cardiac congenital defects of the vessels, chambers, or valves of the heart. Other causes include carditis, endocarditis, myocarditis, and pericarditis whose symptoms were slight or ignored, or were asymptomatic.The normal treatments for episodes due to the pathological look-alikes are the same mainstays for any other episode of cardiac arrest: cardiopulmonary resuscitation, defibrillation to restore normal sinus rhythm, and if initial defibrillation fails, administration of intravenous epinephrine or amiodarone. The goal is avoidance of infarction, heart failure, and/or lethal arrhythmias (ventricular tachycardia, ventricular fibrillation, asystole, or pulseless electrical activity), so ultimately to restore normal sinus rhythm.

Management
Athletes heart is not dangerous for athletes (though if a nonathlete has symptoms of bradycardia, cardiomegaly, and cardiac hypertrophy, another illness may be present). Athletes heart is not the cause of sudden cardiac death during or shortly after a workout, which mainly occurs due to hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy (ARVC), two genetic disorders. Although a link between intensive exercise and exercise-induced arythmogenic right ventricular cardiomyopathy exists.No treatment is required for people with athletic heart syndrome; it does not pose any physical threats to the athlete, and despite some theoretical concerns that the ventricular remodeling might conceivably predispose for serious arrhythmias, no evidence has been found of any increased risk of long-term events. Athletes should see a physician and receive a clearance to be sure their symptoms are due to athletes heart and not another heart disease, such as cardiomyopathy. If the athlete is uncomfortable with having athletes heart or if a differential diagnosis is difficult, deconditioning from exercise for a period of three months allows the heart to return to its regular size </s>