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126-418: Whittemore Peterson Institute is a research institute and charitable foundation known for its claims that the retrovirus xenotropic murine leukemia virus–related virus (XMRV) is associated with and may cause CFS and a variety of additional diseases. A report by WPI scientists of an association between CFS and XMRV was forcibly retracted by the journal Science when the results could not be replicated, and it

252-459: A United States federal working group to determine the prevalence of XMRV in the blood supply and the suitability of different detection methods. The WPI is also collecting blood from CFS patients who received their diagnosis after a blood transfusion and are planning to conduct their own study on XMRV blood transmission. The association between XMRV and CFS reported in Science prompted Health Canada ,

378-493: A conference in 2007 and began to look for XMRV using Silverman's reagents . In late 2008, her team had two positive results out of twenty, and adjusted the experimental conditions until all twenty samples tested positive. Mikovits decided to focus all WPI resources on XMRV. She kept the project secret from Peterson and the Whittemores, fearful that skeptics would try to derail her work, but sent test samples to Bob Silverman and to

504-452: A neurodevelopmental disorder , but the autism rights movement (and some researchers) see autistic people as part of humanity's natural neurodiversity . From this point of view, autistic people may also be diagnosed with a disability of some sort, but that disability may be rooted in the systemic structures of a society rather than in the person; thus, proponents argue that autistic people should be accommodated rather than cured. On

630-440: A " kissing stem-loop ". Although virions of different retroviruses do not have the same morphology or biology, all the virion components are very similar. The main virion components are: The retroviral genome is packaged as viral particles. These viral particles are dimers of single-stranded, positive-sense, linear RNA molecules. Retroviruses (and orterviruses in general) follow a layout of 5'– gag – pro – pol – env –3' in

756-602: A "level" system, which ranks how in need of support the patient is, level 1 being the mildest and level 3 the severest, while the ICD-11 system has two axes, intellectual impairment and language impairment, as these are seen as the most crucial factors. Autism is currently defined as a highly variable neurodevelopmental disorder that is generally thought to cover a broad and deep spectrum , manifesting very differently from one person to another. Some have high support needs, may be nonspeaking , and experience developmental delays; this

882-438: A broader medical condition or syndrome , representing about 25% of ASD cases. The causes of syndromic autism are often known, and monogenic disorders account for approximately 5% of these cases. Non-syndromic autism, also known as classic or idiopathic autism, represents the majority of cases, and its cause is typically polygenic and unknown. Autism has a strong genetic basis, although the genetics of autism are complex and it

1008-453: A concern that insertional mutagenesis due to integration into the host genome might lead to cancer or leukemia. This is unlike Lentivirus , a genus of Retroviridae , which are able to integrate their RNA into the genome of non-dividing host cells. Two RNA genomes are packaged into each retrovirus particle, but, after an infection, each virus generates only one provirus . After infection, reverse transcription occurs and this process

1134-488: A letter of caution to all the blood banks. Retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm , the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backward). The new DNA

1260-648: A low demand for coordination that ameliorated many challenges associated with disruptive turns." Autistic interests, and thus conversational topics, seem to be largely driven by an intense interest in specific topics ( monotropism ). Historically, autistic children were said to be delayed in developing a theory of mind , and the empathizing–systemizing theory has argued that while autistic people have compassion ( affective empathy ) for others with similar presentation of symptoms, they have limited, though not necessarily absent, cognitive empathy . This may present as social naïvety, lower than average intuitive perception of

1386-575: A model of social patterns, and develop coping mechanisms, referred to as " masking ", which have recently been found to come with psychological costs and a higher increased risk of suicidality. ASD includes a wide variety of characteristics. Some of these include behavioral characteristics which widely range from slow development of social and learning skills to difficulties creating connections with other people. Autistic people may experience these challenges with forming connections due to anxiety or depression, which they are more likely to experience, and as

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1512-568: A more expert alternative after a different company began offering one. Lombardi argued that the test is useful and that their 36% positive test results support the science in the original paper. Mikovits has stated that XMRV has "almost certainly entered the U.S. blood supply system, but did not know whether it would be susceptible to the same heat treatments that successfully kill off the AIDS virus in blood products." The Wall Street Journal has reported that WPI and other laboratories are participating in

1638-923: A neurotypical bias in autism research, which has come to be scrutinized for "dehumanization, objectification, and stigmatization". Recent research has proposed that autistics' lack of readability and a neurotypical lack of effort to interpret atypical signals may cause a negative interaction loop, increasingly driving both groups apart into two distinct groups with different social interaction styles. Differences in verbal communication begin to be noticeable in childhood, as many autistic children develop language skills at an uneven pace. Verbal communication may be delayed or never develop ( nonverbal autism ), while reading ability may be present before school age ( hyperlexia ). Reduced joint attention seem to distinguish autistic from non-autistic infants. Infants may show delayed onset of babbling , unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with

1764-939: A newly introduced fish virus genus are retroviruses classified as complex. These viruses have genes called accessory genes, in addition to gag, pro, pol and env genes. Accessory genes are located between pol and env, downstream from the env, including the U3 region of LTR, or in the env and overlapping portions. While accessory genes have auxiliary roles, they also coordinate and regulate viral gene expression. In addition, some retroviruses may carry genes called oncogenes or onc genes from another class. Retroviruses with these genes (also called transforming viruses) are known for their ability to quickly cause tumors in animals and transform cells in culture into an oncogenic state. The polyproteins are cleaved into smaller proteins each with their own function. The nucleotides encoding them are known as subgenes . When retroviruses have integrated their own genome into

1890-563: A person can depend on context, and may vary over time. While the DSM and ICD greatly influence each other, there are also differences. For example, Rett syndrome was included in ASD in the DSM-5, but in the ICD-11 it was excluded and placed in the chapter on Developmental Anomalies. The ICD and the DSM change over time, and there has been collaborative work toward a convergence of the two since 1980 (when DSM-III

2016-505: A person's ASD diagnosis did not influence their interest level. Thus, there has been a recent shift to acknowledge that autistic people may simply respond and behave differently than people without ASD. So far, research has identified two unconventional features by which autistic people create shared understanding ( intersubjectivity ): "a generous assumption of common ground that, when understood, led to rapid rapport, and, when not understood, resulted in potentially disruptive utterances; and

2142-547: A pervasive feature of the individual's functioning observable in all settings, although they may vary according to social, educational, or other context. Individuals along the spectrum exhibit a full range of intellectual functioning and language abilities. ICD-11 was produced by professionals from 55 countries out of the 90 involved and is the most widely used reference worldwide. The American Psychiatric Association 's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision ( DSM-5-TR ), released in 2022,

2268-628: A result isolate themselves. Other behavioral characteristics include abnormal responses to sensations (such as sights, sounds, touch, taste and smell) and problems keeping a consistent speech rhythm. The latter problem influences social skills, leading to potential problems in understanding for interlocutors. Autistic people's behavioral characteristics typically influence development, language, and social competence. Their behavioral characteristics can be observed as perceptual disturbances, disturbances of development rate, relating, speech and language, and motility. The second core symptom of autism spectrum

2394-423: A set of closely related and overlapping diagnoses such as Asperger syndrome and the syndrome formerly known as Kanner syndrome . This created unclear boundaries between the terms, so for the DSM-5 and ICD-11, a spectrum approach was taken. The new system is also more restrictive, meaning fewer people qualify for diagnosis. The DSM-5 and ICD-11 use different categorization tools to define this spectrum. DSM-5 uses

2520-491: A small effect, and some of which are rare and have a large effect. The most common gene disrupted with large effect rare variants appeared to be CHD8 , but less than 0.5% of autistic people have such a mutation. The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8, which is a chromatin regulator enzyme that is essential during fetal development. CHD8 is an adenosine triphosphate (ATP)–dependent enzyme. The protein contains an Snf2 helicase domain that

2646-399: A steady course without remission (different developmental timelines are described in more detail below). Autistic people may be severely impaired in some respects but average, or even superior, in others. Clinicians consider assessment for ASD when a patient shows: These features are typically assessed with the following, when appropriate: There are many signs associated with autism;

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2772-448: A substantial fraction of autism cases may be traceable to genetic causes that are highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome. As of 2018 , understanding of genetic risk factors had shifted from a focus on a few alleles to an understanding that genetic involvement in ASD is probably diffuse, depending on a large number of variants, some of which are common and have

2898-468: A tendency to be associated with sedation and weight gain . Melatonin supplementation has been shown to improve insomnia related to autism. Stimulant therapy may improve mental processing speed when there is comorbid ADHD. Before the DSM-5 (2013) and ICD-11 (2022) diagnostic manuals were adopted, ASD was found under the diagnostic category pervasive developmental disorder . The previous system relied on

3024-493: A trend of increasing prevalence over time. This increasing prevalence has reinforced the myth perpetuated by anti-vaccine activists that autism is caused by vaccines . Boys are also significantly far more frequently diagnosed than girls. There is no known cure for autism, and some advocates dispute the need to find one. Early intervention services based on applied behavior analysis (ABA) aim to teach children self-care, social and communicative skills. Guidelines from

3150-681: Is "not like taking an aspirin". There is currently no consensus that XMRV is capable of infecting humans, much less causing disease; the rush to prescribe antiretrovirals has been described as premature and based on "an unproven hypothesis". Another criticism is that even if XMRV did cause CFS and antiviral medications were effective against the virus, rigorous trials would be needed to establish safety, efficacy, and optimal dosing. Anecdotal treatments, they say, are unhelpful and possibly harmful to "the million or more individuals experiencing these serious conditions". The editors at Science in May 2011 requested that

3276-402: Is a neurodevelopmental disorder characterized by repetitive, restricted, and inflexible patterns of behavior, interests, and activities, as well as deficits in social interaction and social communication. Autism generally affects a person's ability to understand and connect with others, as well as their adaptability to everyday situations, with its severity and support needs varying widely across

3402-708: Is a pattern of restricted and repetitive behaviors, activities, and interests. In order to be diagnosed with ASD under the DSM-5-TR, a person must have at least two of the following behaviors: Autistic people can display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R) categorizes as follows. Self-injurious behaviors are relatively common in autistic people, and can include head-banging, self-cutting, self-biting, and hair-pulling. Some of these can result in serious injury or death. Following are theories about

3528-427: Is a retrovirus. This virus passes to newborn mice through mammary milk. When they are 6 months old, the mice carrying the virus get mammary cancer because of the retrovirus. In addition, leukemia virus I (HTLV-1), found in human T cell, has been found in humans for many years. It is estimated that this retrovirus causes leukemia in the ages of 40 and 50. It has a replicable structure that can induce cancer. In addition to

3654-450: Is accompanied by recombination . Recombination involves template strand switching between the two genome copies (copy choice recombination) during reverse transcription. From 5 to 14 recombination events per genome occur at each replication cycle. Genetic recombination appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes. The DNA formed after reverse transcription (the provirus)

3780-734: Is acquired during childhood. Autistic people display atypical nonverbal behaviors or show differences in nonverbal communication . They may make infrequent eye contact , even when called by name, or avoid it altogether. This may be due to the high amount of sensory input received when making eye contact. Autistic people often recognize fewer emotions and their meaning from others' facial expressions, and may not respond with facial expressions expected by their non-autistic peers. Temple Grandin , an autistic woman involved in autism activism, described her inability to understand neurotypicals ' social communication as leaving her feeling "like an anthropologist on Mars". Autistic people struggle to understand

3906-661: Is bidirectional, research on communication difficulties has since also begun to study non-autistic behavior, with researcher Catherine Crompton writing in 2020 that non-autistic people "struggle to identify autistic mental states, identify autistic facial expressions, overestimate autistic egocentricity, and are less willing to socially interact with autistic people. Thus, although non-autistic people are generally characterised as socially skilled, these skills may not be functional, or effectively applied, when interacting with autistic people." Any previously observed communication deficits of autistic people may thus have been constructed through

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4032-519: Is currently no expert consensus on the etiology of these diseases and conditions. Initial funding for the institute was provided by the Whittemores, who in 2004 committed $ 5   million, successfully lobbied the Nevada legislature for support and arranged an affiliation with their alma mater , the University of Nevada, Reno . The Nevada legislature agreed to provide $ 3   million, and additional funding

4158-590: Is heritable. After an older child is diagnosed with ASD, 7% to 20% of subsequent children are likely to be as well. If parents have one autistic child, they have a 2% to 8% chance of having a second child who is autistic. If the autistic child is an identical twin, the other will be affected 36% to 95% of the time. A fraternal twin is affected up to 31% of the time. The large number of autistic people with unaffected family members may result from spontaneous structural variation , such as deletions , duplications or inversions in genetic material during meiosis . Hence,

4284-698: Is intended to settle the XMRV-CFS question conclusively. Samples from 150 CFS patients and 150 healthy but comparable donors are to be tested at WPI, the NIH , and the CDC . In the preliminary phase of this project, published in Science in January 2011, four patients initially tested positive at WPI and the CDC, but no XMRV was detected at NCI and no patient was positive after repeated testing. Some researchers were concerned about contamination from

4410-500: Is longer than the RNA genome because each of the terminals have the U3 - R - U5 sequences called long terminal repeat (LTR). Thus, 5' terminal has the extra U3 sequence, while the other terminal has the U5 sequence. LTRs are able to send signals for vital tasks to be carried out such as initiation of RNA production or management of the rate of transcription. This way, LTRs can control replication, hence,

4536-420: Is lowered activity in the fusiform face area of the brain, which is associated with impaired perception of people versus objects. It has been proposed to classify autism using genetics as well as behavior. Autism spectrum disorder (ASD) can be classified into two categories: "syndromic autism" and "non-syndromic autism". Syndromic autism refers to cases where ASD is one of the characteristics associated with

4662-522: Is more likely with other co-existing diagnoses. Others have relatively low support needs; they may have more typical speech-language and intellectual skills but atypical social/conversation skills, narrowly focused interests , and wordy, pedantic communication. They may still require significant support in some areas of their lives. The spectrum model should not be understood as a continuum running from mild to severe, but instead means that autism can present very differently in each person. How it presents in

4788-597: Is no consensus that XMRV is a human pathogen or even associated with any disease, Mikovits has stated her opinion that the virus "undoubtedly causes some of the symptoms that are associated with" CFS. Elsewhere, however, she notes that causation has not been proven. According to Mikovits, XMRV "is clearly circulating through the population as is our fear and your fear" and has entered the US blood supply. She has also associated XMRV not only with CFS, but also with autism , Alzheimer's disease , multiple sclerosis , and other diseases. There

4914-430: Is no evidence that XMRV is associated with these diseases: all studies that have looked for a connection have produced negative results. Virologist Vincent Racaniello has accused Mikovits of "inciting fear". In response to the contradictory British results, Mikovits stated that scientists had doctored their studies to reach a predetermined conclusion as part of an insurance company conspiracy. Annette Whittemore expressed

5040-509: Is now commonly used to describe a cancer-causing virus. This family now includes the following genera: Note that according to ICTV 2017, genus Spumavirus has been divided into five genera, and its former type species Simian foamy virus is now upgraded to genus Simiispumavirus with not less than 14 species, including new type species Eastern chimpanzee simian foamy virus . Both families in Group VII have DNA genomes contained within

5166-711: Is possible to identify general factors, but much more difficult to pinpoint specific ones. Given the current state of knowledge, prediction can only be of a global nature and so requires the use of general markers. Research into causes has been hampered by the inability to identify biologically meaningful subgroups within the autistic population and by the traditional boundaries between the disciplines of psychiatry , psychology , neurology and pediatrics . Newer technologies such as fMRI and diffusion tensor imaging can help identify biologically relevant phenotypes (observable traits) that can be viewed on brain scans , to help further neurogenetic studies of autism; one example

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5292-422: Is responsible for the hydrolysis of ATP to adenosine diphosphate (ADP). CHD8 encodes a DNA helicase that functions as a repressor of transcription, remodeling chromatin structure by altering the position of nucleosomes. CHD8 negatively regulates Wnt signaling . Wnt signaling is important in the vertebrate early development and morphogenesis. It is believed that CHD8 also recruits the linker histone H1 and causes

5418-664: Is the current version of the DSM. It is the predominant mental health diagnostic system used in the United States and Canada, and is often used in Anglophone countries. Its fifth edition, DSM-5 , released in May 2013, was the first to define ASD as a single diagnosis, which is still the case in the DSM-5-TR. ASD encompasses previous diagnoses, including the four traditional diagnoses of autism— classic autism , Asperger syndrome , childhood disintegrative disorder , and pervasive developmental disorder not otherwise specified (PDD-NOS)—and

5544-875: Is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus . The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds. Retroviruses have many subfamilies in three basic groups. The specialized DNA-infiltration enzymes in retroviruses make them valuable research tools in molecular biology, and they have been used successfully in gene delivery systems. Evidence from endogenous retroviruses (inherited provirus DNA in animal genomes) suggests that retroviruses have been infecting vertebrates for at least 450 million years. Virions , viruses in

5670-537: Is translated into molecules of the capsid protein, and for the pol gene; it is translated into molecules of reverse transcriptase. Retroviruses need a lot more of the Gag proteins than the Pol proteins and have developed advanced systems to synthesize the required amount of each. As an example, after Gag synthesis nearly 95 percent of the ribosomes terminate translation, while other ribosomes continue translation to synthesize Gag–Pol. In

5796-399: Is unclear whether ASD is explained more by rare mutations with major effects, or by rare multi-gene interactions of common genetic variants. Complexity arises due to interactions among multiple genes, the environment, and epigenetic factors which do not change DNA sequencing but are heritable and influence gene expression . Many genes have been associated with autism through sequencing

5922-507: The Baltimore classification system, which groups viruses together based on their manner of messenger RNA synthesis, they are classified into two groups: Group VI: single-stranded RNA viruses with a DNA intermediate in their life cycle, and Group VII: double-stranded DNA viruses with an RNA intermediate in their life cycle. All members of Group VI use virally encoded reverse transcriptase , an RNA-dependent DNA polymerase, to produce DNA from

6048-772: The Centres for Disease Control (CDC), NICE, and European Society for Child & Adolescent Psychiatry endorse the use of ABA as it reduces symptoms that impair daily functioning and quality of life, although NICE acknowledges that ABA does not meet the highest level of evidence quality. Additionally, some in the autism rights movement oppose its application due to a perception that it emphasises normalisation. Speech and occupational therapy , as well as augmentative and alternative modes of communication , are effective adjunctive therapies . At present, no medication has been shown to reduce ASD's "core symptoms". Some atypical antipsychotics can alleviate comorbid irritability, though with

6174-558: The PLoS ONE study team biased their study so as to not find the virus in its samples, and that Mikovits "suspected insurance companies in the United Kingdom are behind attempts to sully the findings of the Reno study". A steady stream of consistently negative results followed the PLoS ONE report. One study, later retracted, found no XMRV but did report evidence of murine retroviral sequences in

6300-486: The Review Journal of Autism and Developmental Disorders published a systematic review of 21 studies investigating associations between ASD, problematic internet use, and gaming disorder where the majority of the studies found positive associations between the disorders. Exactly what causes autism remains unknown. It was long mostly presumed that there is a common cause at the genetic, cognitive, and neural levels for

6426-427: The germ line , their genome is passed on to a following generation. These endogenous retroviruses (ERVs), contrasted with exogenous ones, now make up 5–8% of the human genome. Most insertions have no known function and are often referred to as " junk DNA ". However, many endogenous retroviruses play important roles in host biology, such as control of gene transcription, cell fusion during placental development in

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6552-879: The underlying spectrum . For example, some are nonverbal , while others have proficient spoken language. A formal diagnosis of ASD according to either the DSM-5 or the ICD-11 criteria requires not merely the presence of ASD symptoms, but symptoms that cause significant impairment in multiple domains of functioning, in addition to being atypical or excessive for the individual's age and sociocultural context. Common signs of ASD include difficulty with social interaction and verbal and nonverbal communication , along with perseverative interests , stereotypic body movements , rigid routines, and hyper- or hypo-reactivity to sensory input . The World Health Organization (WHO), UK National Institute for Health and Care Excellence (NICE), and American Psychological Association classify autism as

6678-473: The 18th Conference on Retroviruses and Opportunistic Infections (CROI). At CROI, WPI representatives were absent, and a large amount of negative data was presented. Two groups showed evidence that XMRV is a recombinant of two mouse retroviruses, which infected a prostate cancer cell line during passage through nude mice. Virologist John Coffin, who had previously expressed optimism about the initial WPI data, declared, "It's all contamination." Robert Silverman, who

6804-566: The 2009 paper. The first follow-up study was published in PLoS ONE in 2010; it was conducted in the UK and found no evidence of XMRV in CFS patients. The publication sparked what The Economist dubbed a transatlantic "fight". Supporters of the two teams traded accusations of conflicts of interest, technical sloppiness, and failure to care about patients. The Reno Gazette-Journal reported that Mikovits stated

6930-452: The DSM-5, the DSM separated social deficits and communication deficits into two domains. Further, the DSM-5 changed to an onset age in the early developmental period, with a note that symptoms may manifest later when social demands exceed capabilities, rather than the previous, more restricted three years of age. These changes remain in the DSM-5-TR. For many autistic people, characteristics first appear during infancy or childhood and follow

7056-505: The HIV life cycle . Combination of several (typically three or four) antiretroviral drugs is known as highly active antiretroviral therapy (HAART). Feline leukemia virus and Feline immunodeficiency virus infections are treated with biologics , including the only immunomodulator currently licensed for sale in the United States, Lymphocyte T-Cell Immune Modulator (LTCI). Autism Autism , or autism spectrum disorder ( ASD ),

7182-706: The National Institute of Aging, the La Jolla Institute for Allergy and Immunology, and Kings College, UK. The WPI's stated mission is to "bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by acquired dysregulation of both the immune system and the nervous system, often resulting in life long disease and disability." The Institute considers such diseases as CFS , fibromyalgia , atypical multiple sclerosis and autism to be "Neuro Immune Diseases" with an underlying infectious or environmental exposure etiology. However, there

7308-690: The New Zealand Blood Service, and The Australian Red Cross Blood Service to restrict individuals with CFS from donating blood in 2010. In June 2010, the American Association of Blood Banks recommended actively discouraging persons diagnosed with CFS from donating blood or blood components. Similar action was taken in Norway in December 2010, when the Norwegian health agency Helsedirektoratet issued

7434-482: The RNA genome. gag and pol encode polyproteins, each managing the capsid and replication. The pol region encodes enzymes necessary for viral replication, such as reverse transcriptase, protease and integrase. Depending on the virus, the genes may overlap or fuse into larger polyprotein chains. Some viruses contain additional genes. The lentivirus genus, the spumavirus genus, the HTLV / bovine leukemia virus (BLV) genus, and

7560-679: The RNA to DNA transcription processes used by retroviruses may have first caused DNA to be used as genetic material. In this model, the RNA world hypothesis , cellular organisms adopted the more chemically stable DNA when retroviruses evolved to create DNA from the RNA templates. An estimate of the date of evolution of the foamy-like endogenous retroviruses placed the time of the most recent common ancestor at > 450  million years ago . Gammaretroviral and lentiviral vectors for gene therapy have been developed that mediate stable genetic modification of treated cells by chromosomal integration of

7686-584: The University of Nevada, Reno campus under the direction of Judy Mikovits. WPI registered as a 501(c)(3) public charity in 2006. The Institute opened a new facility in August 2010 in the University of Nevada's Center for Molecular Medicine. Daniel Peterson left the Whittemore Peterson Institute in 2010 because of concerns about the "singular pursuit of XMRV" that was conducted without his input. His name

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7812-625: The Whittemore family, with all net proceeds donated to the WPI. In September 2009, WPI announced that Mikovits and collaborator Jonathan Kerr of St. George’s College in London received a $ 1.6   million, five-year grant from the National Institute of Allergy and Infectious Diseases for their proposal to develop new "strategies to decipher the pathophysiology of chronic fatigue syndrome ". Judy Mikovits

7938-406: The authors of the 2009 Lombardi et al. study retract the article due to many independent studies that did not find an association of XMRV with CFS, and studies that have presented data showing contaminated laboratory reagents may have led to false positive results. Science reported that Mikovits declined the request on behalf of the original authors, labeled the request "premature", and asserted that

8064-489: The blood of some CFS patients. Mikovits and Ruscetti attributed the failure to replicate their results to the use of different PCR reactions and to the examination of patients who did not satisfy the same CFS diagnostic criteria. A study using the original reaction conditions did not detect XMRV in UK patients who "not only had CFS, but had considerable disability". WPI has been included in a multi-center trial, led by Ian Lipkin , that

8190-516: The caregiver. In the second and third years, autistic children may have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Autistic children are less likely to make requests or share experiences and more likely to simply repeat others' words ( echolalia ). The CDC estimated in 2015 that around 40% of autistic children do not speak at all. Autistic adults' verbal communication skills largely depend on when and how well speech

8316-417: The cause of self-injurious behavior in children with developmental delay, including autistic children: The suicide rate for verbal autistics is nine times that of the general population. Studies have supported the common belief that autistic people become exhausted or burnt out in some situations. Autistic people may have symptoms that do not contribute to the official diagnosis, but that can affect

8442-461: The contrary, other scientists argue that ASD impairs functioning in many ways that are inherent to the disorder itself and unrelated to society. The neurodiversity perspective has led to significant controversy among those who are autistic and advocates, practitioners, and charities. The precise causes of autism are unknown in most individual cases. Research shows that the disorder is highly heritable and polygenic, and neurobiological risks from

8568-399: The course of the germination of an embryo , and resistance to exogenous retroviral infection. Endogenous retroviruses have also received special attention in the research of immunology -related pathologies, such as autoimmune diseases like multiple sclerosis , although endogenous retroviruses have not yet been proven to play any causal role in this class of disease. While transcription

8694-513: The current disorder-focused spectrum model deconstruct autism into at least two separate phenomena: (1) a non-pathological spectrum of behavioral traits in the population, and (2) the neuropathological burden of rare genetic mutations and environmental risk factors potentially leading to neurodevelopmental and psychological disorders, (3) governed by an individual's cognitive ability to compensate. The World Health Organization 's International Classification of Diseases (11th revision), ICD-11 ,

8820-400: The development of the autism spectrum, but it cannot be guaranteed that they are determinants for the development. ASD may be under-diagnosed in women and girls due to an assumption that it is primarily a male condition, but genetic phenomena such as imprinting and X linkage have the ability to raise the frequency and severity of conditions in males, and theories have been put forward for

8946-409: The disruption of cellular proto-oncogenes. Rous sarcoma virus contains the src gene that triggers tumor formation. Later it was found that a similar gene in cells is involved in cell signaling, which was most likely excised with the proviral DNA. Nontransforming viruses can randomly insert their DNA into proto-oncogenes, disrupting the expression of proteins that regulate the cell cycle. The promoter of

9072-419: The entire progress of the viral cycle. Although located in the nucleus, the non-integrated retroviral cDNA is a very weak substrate for transcription. For this reason, an integrated provirus is a necessary for permanent and an effective expression of retroviral genes. This DNA can be incorporated into host genome as a provirus that can be passed on to progeny cells. The retrovirus DNA is inserted at random into

9198-449: The environment are also relevant. Autism frequently co-occurs with attention deficit hyperactivity disorder (ADHD), epilepsy and intellectual disability , and research indicates that autistic people have significantly higher rates of LGBTQ+ identities and feelings than the general population. Disagreements persist about what should be included as part of the diagnosis, whether there are meaningful subtypes or stages of autism, and

9324-471: The established knowledge on this topic. However, although later research disproved some of the claims made about retroviruses, there are several controversial figures who continue to make claims which overall are considered to not have any valid basis or consensus in support of these claims. Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV . Different classes of antiretroviral drugs act on different stages of

9450-682: The exposure starts at a younger age. In April 2021, Research in Autism Spectrum Disorders published a systematic review of 12 studies of video game addiction in ASD subjects that found that children, adolescents, and adults with ASD are at greater risk of video game addiction than those without ASD, and that the data from the studies suggested that internal and external factors (sex, attention and oppositional behavior problems, social aspects, access and time spent playing video games, parental rules, and game genre) were significant predictors of video game addiction in ASD subjects. In March 2022,

9576-404: The fact that the gene sequences that code for the protease and the reverse transcriptase quickly mutate. These changes in bases cause specific codons and sites with the enzymes to change and thereby avoid drug targeting by losing the sites that the drug actually targets. Because reverse transcription lacks the usual proofreading of DNA replication, a retrovirus mutates very often. This enables

9702-446: The first reports of XMRV-disease associations, and these concerns spread as study after study failed to replicate WPI's results. In December 2010, four independent articles published in the journal Retrovirology presented evidence that reported XMRV detection could be explained by contamination of laboratory reagents, tissue samples and blood. Samples that were positive for XMRV were also positive for mouse DNA contaminants. Furthermore,

9828-435: The form of independent particles of retroviruses, consist of enveloped particles about 100  nm in diameter. The outer lipid envelope consists of glycoprotein. The virions also contain two identical single-stranded RNA molecules 7–10 kilobases in length. The two molecules are present as a dimer, formed by base pairing between complementary sequences. Interaction sites between the two RNA molecules have been identified as

9954-412: The generation and insertion of new copies of retrotransposons into the host genome. These inserts are transcribed by enzymes of the host into new RNA molecules that enter the cytosol. Next, some of these RNA molecules are translated into viral proteins. The proteins encoded by the gag and pol genes are translated from genome-length mRNAs into Gag and Gag–Pol polyproteins. In example, for the gag gene; it

10080-562: The genomes of affected people and their parents. But most of the mutations that increase autism risk have not been identified. Typically, autism cannot be traced to a Mendelian (single-gene) mutation or to a single chromosome abnormality , and none of the genetic syndromes associated with ASD have been shown to selectively cause ASD. Numerous genes have been found, with only small effects attributable to any particular gene. Most loci individually explain less than 1% of cases of autism. As of 2018 , it appeared that between 74% and 93% of ASD risk

10206-496: The host genome. Because of this, it can be inserted into oncogenes . In this way some retroviruses can convert normal cells into cancer cells. Some provirus remains latent in the cell for a long period of time before it is activated by the change in cell environment. Studies of retroviruses led to the first demonstrated synthesis of DNA from RNA templates, a fundamental mode for transferring genetic material that occurs in both eukaryotes and prokaryotes . It has been speculated that

10332-413: The idea", and decided that, "if there was a place of our own where we could find the answers, we could do it more quickly." Her husband Harvey said that his wife also wanted to recognize Peterson for his history of treating the illness since 1984. The Whittemores and Peterson established the Whittemore Peterson Institute in 2005. Research began in 2006 with the opening of a small laboratory and an office on

10458-515: The illness. Peterson left WPI in 2010 due to concerns related to the XMRV research. The institute is affiliated with the University of Nevada, Reno . Judy Mikovits joined as research director in 2006, but was terminated by WPI in October 2011 for not turning her work over to another scientist while also coming under investigation for alleged manipulation of data in her publications related to XMRV. WPI moved to

10584-410: The individual's age and sociocultural context. The onset of the disorder occurs during the developmental period, typically in early childhood, but symptoms may not become fully manifest until later, when social demands exceed limited capacities. Deficits are sufficiently severe to cause impairment in personal, family, social, educational, occupational or other important areas of functioning and are usually

10710-430: The initial virion RNA genome. This DNA is often integrated into the host genome, as in the case of retroviruses and pseudoviruses , where it is replicated and transcribed by the host. Group VI includes: The family Retroviridae was previously divided into three subfamilies ( Oncovirinae , Lentivirinae , and Spumavirinae ), but are now divided into two: Orthoretrovirinae and Spumaretrovirinae . The term oncovirus

10836-815: The interpersonal relationship difficulties between autistic people and their non-autistic counterparts and how to solve them through teaching neurotypical social skills, but newer research has also evaluated what autistic people want from friendships, such as a sense of belonging and good mental health. Children with ASD are more frequently involved in bullying situations than their non-autistic peers, and predominantly experience bullying as victims rather than perpetrators or victim-perpetrators, especially after controlling for comorbid psychopathology. Prioritizing dependability and intimacy in friendships during adolescence, coupled with lowered friendship quantity and quality, often lead to increased loneliness in autistic people. As they progress through life, autistic people observe and form

10962-513: The invading virus particles. The DNA genome is transcribed into both mRNA, for use as a transcript in protein synthesis, and pre-genomic RNA, for use as the template during genome replication. Virally encoded reverse transcriptase uses the pre-genomic RNA as a template for the creation of genomic DNA. Group VII includes: The latter family is closely related to the newly proposed whilst families Belpaoviridae , Metaviridae , Pseudoviridae , Retroviridae , and Caulimoviridae constitute

11088-479: The journal Nature praised Mikovits's defense of her work, but also asked her and her critics to keep an open mind and to be motivated by patients without allowing their scientific programme to be influenced by patients' beliefs. WPI has also generated criticism for statements defending the use of antiretroviral medications as a treatment for CFS. For some individuals, these medications can have substantial side effects. Jay Levy states that taking anti-HIV medications

11214-532: The lab of her mentor at NCI, Frank Ruscetti. Mikovits submitted the first version of the Science paper in May 2009. In 2009, Lombardi et al. reported in the journal Science that they had detected XMRV DNA in 68 of 101 (67%) CFS patients, versus 8 of 218 (3.7%) healthy control subjects. Co-authors included Mikovits, her former mentor Ruscetti at the NCI , and Bob Silverman of the Cleveland Clinic . The WPI study

11340-492: The long history of proposed retrovirus-disease connections that were later debunked. John Coffin and Jonathan Stoye in a Science commentary accompanying the WPI publication were cautiously optimistic. In September 2011, the original authors published a "Partial Retraction" of their 2009 findings, in which they acknowledged that "some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA." In December 2011, Science retracted

11466-425: The need for more research before drawing conclusions. In the scientific community, initial reactions were mixed. Immediately after the Science paper publication, Patrick Moore and Masahiro Shuda wrote a highly critical F1000 dissent pointing out basic errors in the paper's methods, results and conclusions, "...this manuscript has flaws that leave the reader unsure of knowing precisely what was measured". Others noted

11592-459: The newly constructed Center for Molecular Medicine in August 2010. Annette Whittemore, co-founder and president of the institute, stated that the inspiration for the institute came from her daughter, Andrea Whittemore-Goad, who was diagnosed with chronic fatigue syndrome (CFS) at the age of twelve. Whittemore stated that numerous doctors were unable to help her daughter, and that the first major improvement came ten years after her diagnosis when she

11718-440: The opinion that the response to her organization's claims was political, while the director of clinical services, Deckoff-Jones, characterized the negative research findings as a "cover-up and baseless attacks against Dr. Mikovits". Mikovits stated that those who reported negative findings did not "believe" in chronic fatigue syndrome and sought to discredit the disorder itself. Critics disputed these charges. A March 2011 editorial in

11844-424: The order Ortervirales . Endogenous retroviruses are not formally included in this classification system, and are broadly classified into three classes, on the basis of relatedness to exogenous genera: Retroviruses have been the focus of several recent claims and assertions which have been largely discredited by the science community. An initial study in 2009 seemed to make new findings which might change some of

11970-413: The original study results were accurate. The editor-in-chief of the journal Science subsequently published an expression of concern, "Because the validity of the study by Lombardi et al. is now seriously in question". In December 2011, Science retracted the 2009 paper. WPI was criticized for offering non-FDA-approved XMRV testing through its subsidiary, Viral Immune Pathology Diagnostics (VIP Dx), which

12096-443: The other hand, genes controlling expression of glial and immune cells in the brain, e.g. astrocytes and microglia , respectively, are over-expressed, which correlates with increased number of glial and immune cells found in postmortem ASD brains. Some genes under investigation in ASD pathophysiology are those that affect the mTOR signaling pathway, which supports cell growth and survival. All these genetic variants contribute to

12222-572: The person or the family. In September 2018, the Review Journal of Autism and Developmental Disorders published a systematic review of 47 studies published from 2005 to 2016 that concluded that associations between autism spectrum disorder (ASD) and screen time was inconclusive. In May 2019, the Journal of Developmental and Behavioral Pediatrics published a systematic review of 16 studies that found that children and adolescents with ASD are exposed to more screen time than typically developing peers and that

12348-537: The plasma membrane after further glycosylation. It is important to note that a retrovirus must "bring" its own reverse transcriptase in its capsid , otherwise it is unable to utilize the enzymes of the infected cell to carry out the task, due to the unusual nature of producing DNA from RNA. Industrial drugs that are designed as protease and reverse-transcriptase inhibitors are made such that they target specific sites and sequences within their respective enzymes. However these drugs can quickly become ineffective due to

12474-438: The presence of other disorders or factors that likely contribute to the symptoms, other neurodevelopmental or mental disorders, intellectual disability, or language impairment). The symptom domains are (a) social communication and (b) restricted, repetitive behaviors, and there is the option of specifying a separate severity—the negative effect of the symptoms on the person—for each domain, rather than just overall severity. Before

12600-1396: The presentation varies widely: The broader autism phenotype describes people who may not have ASD but do have autistic traits , such as abnormalities in eye contact and stimming . According to the medical model, autistic people experience social communications impairments . Until 2013, deficits in social function and communication were considered two separate symptom domains. The current social communication domain criteria for autism diagnosis require people to have deficits across three social skills: social-emotional reciprocity, nonverbal communication, and developing and sustaining relationships. A deficit-based view predicts that autistic–autistic interaction would be less effective than autistic–non-autistic interactions or even non-functional. But recent research has found that autistic–autistic interactions are as effective in information transfer as interactions between non-autistics are, and that communication breaks down only between autistics and non-autistics. Also contrary to social cognitive deficit interpretations, recent (2019) research recorded similar social cognitive performances in autistic and non-autistic adults, with both of them rating autistic individuals less favorably than non-autistic individuals; however, autistic individuals showed more interest in engaging with autistic people than non-autistic people did, and learning of

12726-437: The provirus DNA can also cause over expression of regulatory genes. Retroviruses can cause diseases such as cancer and immunodeficiency. If viral DNA is integrated into host chromosomes, it can lead to permanent infections. It is therefore important to discover the body's response to retroviruses. Exogenous retroviruses are especially associated with pathogenic diseases. For example, mice have mouse mammary tumor virus (MMTV), which

12852-419: The range of diagnoses that included the word "autism". Rather than distinguishing among these diagnoses, the DSM-5 and DSM-5-TR adopt a dimensional approach with one diagnostic category for disorders that fall under the autism spectrum umbrella. Within that category, the DSM-5 and the DSM include a framework that differentiates each person by dimensions of symptom severity, as well as by associated features (i.e.,

12978-917: The regulation of long non-coding RNAs (lncRNAs), and the regulation of X chromosome inactivation (XCI) initiation, via regulation of Xist long non-coding RNA, the master regulator of XCI, though competitive binding to Xist regulatory regions. Some ASD is associated with clearly genetic conditions, like fragile X syndrome , but only around 2% of autistic people have fragile X. Hypotheses from evolutionary psychiatry suggest that these genes persist because they are linked to human inventiveness, intelligence or systemising. Current research suggests that genes that increase susceptibility to ASD are ones that control protein synthesis in neuronal cells in response to cell needs, activity and adhesion of neuronal cells, synapse formation and remodeling, and excitatory to inhibitory neurotransmitter balance. Therefore, although up to 1,000 different genes are thought to increase

13104-772: The repression of β-catenin and p53 target genes. The importance of CHD8 can be observed in studies where CHD8-knockout mice died after 5.5 embryonic days because of widespread p53-induced apoptosis. Some studies have determined the role of CHD8 in autism spectrum disorder (ASD). CHD8 expression significantly increases during human mid-fetal development. The chromatin remodeling activity and its interaction with transcriptional regulators have shown to play an important role in ASD aetiology . The developing mammalian brain has conserved CHD8 target regions that are associated with ASD risk genes. The knockdown of CHD8 in human neural stem cells results in dysregulation of ASD risk genes that are targeted by CHD8. Recently CHD8 has been associated with

13230-448: The risk of ASD, all of them eventually affect normal neural development and connectivity between different functional areas of the brain in a similar manner that is characteristic of an ASD brain. Some of these genes are known to modulate production of the GABA neurotransmitter, the nervous system's main inhibitory neurotransmitter. These GABA-related genes are under-expressed in an ASD brain. On

13356-479: The rough endoplasmic reticulum glycosylation begins and the env gene is translated from spliced mRNAs in the rough endoplasmic reticulum, into molecules of the envelope protein. When the envelope protein molecules are carried to the Golgi complex, they are divided into surface glycoprotein and transmembrane glycoprotein by a host protease. These two glycoprotein products stay in close affiliation, and they are transported to

13482-409: The significance of autism-associated traits in the wider population. The combination of broader criteria, increased awareness, and the potential increase of actual prevalence, has led to considerably increased estimates of autism prevalence since the 1990s. The WHO estimates about 1 in 100 children had autism between 2012 and 2021, as that was the average estimate in studies during that period, with

13608-546: The social and non-social components of ASD's symptoms, described as a triad in the classic autism criteria. But it is increasingly suspected that autism is instead a complex disorder whose core aspects have distinct causes that often cooccur. It is unlikely that ASD has a single cause; many risk factors identified in the research literature may contribute to ASD. These include genetics, prenatal and perinatal factors (meaning factors during pregnancy or very early infancy), neuroanatomical abnormalities, and environmental factors. It

13734-523: The social context and subtext of neurotypical conversational or printed situations, and form different conclusions about the content. Autistic people may not control the volume of their voice in different social settings. At least half of autistic children have atypical prosody . What may look like self-involvement or indifference to non-autistic people stems from autistic differences in recognizing how other people have their own personalities, perspectives, and interests. Most published research focuses on

13860-461: The striking identity of XMRV genomic sequences and their similarity to xenotropic MLVs in several human cell lines suggested that XMRV is not a transmissible human pathogen. The British Medical Journal responded with an article entitled, "Chronic fatigue syndrome is not caused by XMRV virus, study shows". A fifth study supporting the contamination hypothesis was published in February, 2011, just ahead of

13986-783: The transferred vector genomes. This technology is of use, not only for research purposes, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells. Retroviral vector particles with tropism for various target cells have been designed. Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases. Retroviral mutations can be developed to make transgenic mouse models to study various cancers and their metastatic models . Retroviruses that cause tumor growth include Rous sarcoma virus and mouse mammary tumor virus . Cancer can be triggered by proto-oncogenes that were mistakenly incorporated into proviral DNA or by

14112-405: The usual gene sequence of retroviruses, HTLV-1 contains a fourth region, PX. This region encodes Tax, Rex, p12, p13 and p30 regulatory proteins. The Tax protein initiates the leukemic process and organizes the transcription of all viral genes in the integrated HTLV proviral DNA. Exogenous retroviruses are infectious RNA- or DNA-containing viruses that are transmitted from one organism to another. In

14238-482: The utility or meaning of body language , social reciprocity, or social expectations, including the habitus , social cues , and some aspects of sarcasm, which to some degree may also be due to comorbid alexithymia . But recent research has increasingly questioned these findings, as the " double empathy problem " theory (2012) argues that there is a lack of mutual understanding and empathy between both non-autistic persons and autistic individuals. As communication

14364-481: The virus to grow resistant to antiviral pharmaceuticals quickly, and impedes the development of effective vaccines and inhibitors for the retrovirus. One difficulty faced with some retroviruses, such as the Moloney retrovirus, involves the requirement for cells to be actively dividing for transduction. As a result, cells such as neurons are very resistant to infection and transduction by retroviruses. This gives rise to

14490-512: Was a co-author of the original XMRV-CFS article but is no longer collaborating with Mikovits, told the Chicago Tribune that he was "concerned about lab contamination, despite our best efforts to avoid it". The Whittemore Peterson Institute and its employees have issued statements that have generated additional controversy. Some of these statements have been made to the press, while others are made in presentations to patient groups. Although there

14616-406: Was added to the Science paper only after a reviewer's comment. Peterson was reported to be working with Jay Levy , one of the original discoverers of HIV , to try to determine whether XMRV was truly present in the same patients examined in the Science study. Annette Whittemore serves as president and Institute Administrator of the WPI. Vincent Lombardi, first author of the 2009 Science paper,

14742-518: Was appointed as Research Director in March 2011. Lombardi, a biochemist, along with Harvey Whittemore, co-founded RedLabs USA, Inc., now Viral Immune Pathology Diagnostics (VIP Dx). Virologist Judy Mikovits was the previous research director. Her employment was terminated in October 2011. The Institute has stated that their research unit is composed of scientists from the National Cancer Institute,

14868-549: Was classically thought to occur only from DNA to RNA, reverse transcriptase transcribes RNA into DNA. The term "retro" in retrovirus refers to this reversal (making DNA from RNA) of the usual direction of transcription. It still obeys the central dogma of molecular biology , which states that information can be transferred from nucleic acid to nucleic acid but cannot be transferred back from protein to either protein or nucleic acid. Reverse transcriptase activity outside of retroviruses has been found in almost all eukaryotes , enabling

14994-445: Was discovered that XMRV was a laboratory-created recombinant of two mouse viruses. Amid allegations of sloppiness and scientific misconduct, WPI personnel criticised the methods and motives of other scientists, implying that the negative results were part of a "cover-up" or a "bias against this disease (CFS)". WPI was created by the parents of a CFS patient, Annette and Harvey Whittemore , and by Daniel Peterson , an early researcher of

15120-552: Was followed by worldwide media coverage, including reports by the BBC , National Public Radio , The New York Times and The Wall Street Journal . Discover Magazine listed it as one of the top 100 stories of 2009. Many CFS patients greeted the report enthusiastically, feeling that XMRV granted legitimacy to their condition and hoping that XMRV would be established as a treatable cause of CFS; some, assuming causation, even "hurry(ied) to doctors for tests and antiretroviral drugs". Others urged

15246-435: Was founded by WPI's Vincent Lombardi and was headed by Harvey Whittemore. The tests, which over 1,000 patients purchased, cost $ 249 to $ 450. Virologist John Coffin observed that the original paper established the virus neither as a cause of CFS nor as a viable marker; in a Science news article, Sam Kean notes that the utility of the test for a patient or a physician is unclear. VIP Dx asserted that it introduced its XMRV test as

15372-527: Was from private donations. $ 10   million was secured from the governor and legislature by the University of Nevada School of Medicine and the WPI for the Center for Molecular Medicine, where WPI would share space. Nevada senators John Ensign and Harry Reid separately introduced legislation requesting federal funding for the institute. Supplemental funding for WPI came from the sale of XMRV diagnostic tests by Viral Immune Pathology Diagnostics (VIP Dx), owned by

15498-475: Was introduced to Annette Whittemore at an HHV-6 Foundation conference in the spring of 2006, and soon after was hired as the research director of WPI. Mikovits had left the National Cancer Institute (NCI) and moved to California to get married in 2001. As WPI research director, Mikovits attempted to find a connection between CFS and infections . She met Bob Silverman, the co-discoverer of XMRV, at

15624-574: Was published and ICD-9 was current), including more rigorous biological assessment—in place of historical experience—and a simplification of the classification system. As of 2023, empirical and theoretical research is leading to a growing consensus among researchers that the established ASD criteria are ineffective descriptors of autism as a whole, and that alternative research approaches must be encouraged, such as going back to autism prototypes, exploring new causal models of autism, or developing transdiagnostic endophenotypes . Proposed alternatives to

15750-462: Was released in June 2018 and came into full effect as of January 2022. It describes ASD as follows: Autism spectrum disorder is characterised by persistent deficits in the ability to initiate and to sustain reciprocal social interaction and social communication, and by a range of restricted, repetitive, and inflexible patterns of behaviour, interests or activities that are clearly atypical or excessive for

15876-455: Was treated by Peterson with the experimental antiviral drug Ampligen . Hemispherx 's new drug application for Ampligen, which permits sale and marketing, was rejected by the FDA in December 2009 and the agency asked for another clinical study. Interviewed by The New York Times , Whittemore said that "she had long believed that the syndrome was an infectious disease, but that scientists had rejected

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