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Biomedical subjects

Matthew Lewis

Publications and source records attributed to Matthew Lewis.

11 recordsLinked to original sources

Prothrombin G20210A and Factor V Leiden Variants Are Not Associated With Thrombotic Events in Congenital Heart Disease: An Observational Trial.

BACKGROUND: Thrombotic events, including acute ischemic stroke, are more common in individuals with congenital heart disease (CHD). Whether common thrombophilia variants contribute to thrombotic risk in this population remains unclear. We evaluated whether prothrombin G20210A (F2 c.97G>A) and factor V Leiden (F5 c.1601G>A; p.Arg534Gln) are associated with thrombotic events in CHD. METHODS: Participants in the Pediatric Cardiac Genomics Consortium with exome sequencing and electronic medical record data were identified. Individuals were stratified by prothrombin G20210A and factor V Leiden genotypes, ventricular physiology, and antithrombotic therapy. The primary outcome was the presence of International Classification of Diseases (ICD) or Phecodes (phenotype codes) for thrombotic events. RESULTS: Among 4008 participants (median age, 11.4 [interquartile range, 5.1-17.9] years; 44.4% boys), thrombotic events occurred in 737 (18%), including 93 (13%) with acute ischemic stroke. Compared with the Genome Aggregation Database, the CHD cohort had a lower prevalence of heterozygous prothrombin G20210A and factor V Leiden variants. Variant prevalence did not differ between participants with and without thrombotic events. Single-ventricle CHD was associated with higher thrombosis frequency than biventricular CHD (35% versus 16%, P≤0.0001), without differences in variant prevalence. CONCLUSIONS: In this multicenter CHD cohort, prothrombin G20210A and factor V Leiden were not significantly associated with thrombotic outcomes, supporting recommendations against routine screening. Given low variant prevalence, the study was powered to exclude only large associations. Reduced variant frequency suggests survivorship bias beginning in fetal life. Larger integrated clinical-genomic studies are needed to refine thrombotic risk stratification in CHD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03347214.

Humans↗

Neurosteroids in child and adolescent psychopathology.

Neurosteroids play a significant role in neurodevelopment and are involved in a wide variety of psychopathological processes. There is accumulating evidence on their role in adult psychopathology, including Alzheimer disease, schizophrenia, mood disorder, anxiety disorders and post-traumatic stress disorder. Little is known, however, about the possible role of neurosteroids in child and adolescent psychopathology although there is increasing evidence for their critical role from the early stages of brain development until adolescence. In this review we focus on the involvement of neurosteroids in neurodevelopment and mental disorders in children and adolescents. Adequate physiological levels protect the developing neural system from insult and contribute to the regulation of brain organization and function. Neurosteroids may be involved in the pathophysiology and pharmacotherapy of a variety of disorders in children and adolescents, including schizophrenia, depression, eating disorders, aggressive behavior and attention deficit. The complex interaction between neurosteroids, neurodevelopment, life-events, genetics and mental disorders in children and adolescents merits further investigation.

Adolescent↗

Comparative genomics of emerging human ehrlichiosis agents.

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.

Animals↗

Sequence, annotation, and analysis of synteny between rice chromosome 3 and diverged grass species.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

Arabidopsis↗

The psychrophilic lifestyle as revealed by the genome sequence of Colwellia psychrerythraea 34H through genomic and proteomic analyses.

The completion of the 5,373,180-bp genome sequence of the marine psychrophilic bacterium Colwellia psychrerythraea 34H, a model for the study of life in permanently cold environments, reveals capabilities important to carbon and nutrient cycling, bioremediation, production of secondary metabolites, and cold-adapted enzymes. From a genomic perspective, cold adaptation is suggested in several broad categories involving changes to the cell membrane fluidity, uptake and synthesis of compounds conferring cryotolerance, and strategies to overcome temperature-dependent barriers to carbon uptake. Modeling of three-dimensional protein homology from bacteria representing a range of optimal growth temperatures suggests changes to proteome composition that may enhance enzyme effectiveness at low temperatures. Comparative genome analyses suggest that the psychrophilic lifestyle is most likely conferred not by a unique set of genes but by a collection of synergistic changes in overall genome content and amino acid composition.

Amino Acids↗

Football supporters' perceptions of their role in the home advantage.

Football fans' views on their role in the home advantage were obtained by placing links to an internet questionnaire on supporters' websites. Altogether, 461 fans from clubs which had been promoted, relegated or unchanged in the past season of the English football leagues rated crowd support as significantly more influential than familiarity, travel, territoriality and referee bias in contributing to the home advantage. Fans felt responsible for inspiring their team to victory, took credit for distracting opponents, and believed that they could influence officials into making decisions in their team's favour. However, they did not accept personal blame for poor results. No effects for gender, age or the team's outcome in the promotion/relegation battle emerged, though season ticket holders were more extreme in their feelings of responsibility overall. Furthermore, it was suggested that mechanisms such as the perception of being superior to rivals can encourage fans to retain their allegiance to their teams, even when outcomes are disappointing. Indeed, affiliation may become so incorporated into self-identity that supporters may not have the option of abandoning their team, but instead perceive a reciprocal relationship in which both they and the team are expected to do their best to achieve success.

Chi-Square Distribution↗

Effects of the Sagittarius dwarf tidal stream on dark matter detectors.

The Sagittarius dwarf tidal stream may be showering dark matter onto the solar neighborhood, which can change the results and interpretation of direct detection searches for weakly interacting massive particles (WIMPs). Stars in the stream may already have been detected in the solar neighborhood, and the dark matter in the stream is (0.3-25)% of the local density. Experiments should see an annually modulated steplike feature in the energy recoil spectrum that would be a smoking gun for WIMP detection. The total count rate in detectors is not a cosine curve in time and peaks at a different time of year than the standard case.

Journal Article↗

Statistical and conceptual issues in defining post-operative cognitive dysfunction.

The occurrence of post-operative cognitive dysfunction is a distressing complication following surgery. In an effort to gain a more complete understanding of patients' cognitive recovery following surgical procedures common neuropsychological assessment tools have been adopted in a repeated measures design. It is widely regarded that this represents the most comprehensive method of determining cognitive status in this population but it has resulted in a number of statistical and conceptual difficulties in attempting to infer significant change. The current paper outlines these core difficulties and provides some potential methods to overcome these.

Cognition Disorders↗

Pressure ulcer prevention and treatment: transforming research findings into consensus based clinical guidelines.

The translation of research findings into practice guidelines is an important aspect in maintaining the currency of practice and adding value to research. While there has been a large amount of published literature regarding the treatment and prevention of pressure ulcers, very few studies have attempted to provide clear clinical guidelines. The present study proposes a model to transform research into clinical guidelines whilst developing a series of guidelines that can be applied to a variety of clinical settings.

Australia↗

We're still singing.

Explore the source record for details and available documents.

England↗