20 research outputs found

    The Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery

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    ACKNOWLEDGEMENTS Review and editing: S.R. Brown, Professor of Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. Email [email protected]. Patient summary: R.G. Arnott, Retired Professor, Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK. Email [email protected]. Delphi review: C.P. Macklin. BMedSci BM BS FRCS DM, Consultant Colorectal Surgeon, Mid Yorkshire Hospitals, UK. Email [email protected] reviewedPublisher PD

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

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    Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

    A Putative Gene Cluster for Aminoarabinose Biosynthesis Is Essential for Burkholderia cenocepacia Viability

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    Using a conditional mutagenesis strategy we demonstrate here that a gene cluster encoding putative aminoarabinose (Ara4N) biosynthesis enzymes is essential for the viability of Burkholderia cenocepacia. Loss of viability is associated with dramatic changes in bacterial cell morphology and ultrastructure, increased permeability to propidium iodide, and sensitivity to sodium dodecyl sulfate, suggesting a general cell envelope defect caused by the lack of Ara4N

    STING-mediated intestinal barrier dysfunction contributes to lethal sepsisResearch in context

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    Background: Gut integrity is compromised in abdominal sepsis with increased cellular apoptosis and altered barrier permeability. Intestinal epithelial cells (IEC) form a physiochemical barrier that separates the intestinal lumen from the host's internal milieu and is strongly involved in the mucosal inflammatory response and immune response. Recent research indicates the involvement of the stimulator of interferons genes (STING) pathway in uncontrolled inflammation and gut mucosal immune response. Methods: We investigated the role of STING signaling in sepsis and intestinal barrier function using intestinal biopsies from human patients with abdominal sepsis and with an established model of abdominal sepsis in mice. Findings: In human abdominal sepsis, STING expression was elevated in peripheral blood mononuclear cells and intestinal biopsies compared with healthy controls, and the degree of STING expression in the human intestinal lamina propria correlated with the intestinal inflammation in septic patients. Moreover, elevated STING expression was associated with high levels of serum intestinal fatty acid binding protein that served as a marker of enterocyte damage. In mice, the intestinal STING signaling pathway was markedly activated following the induction of sepsis induced by cecal ligation perforation (CLP). STING knockout mice showed an alleviated inflammatory response, attenuated gut permeability, and decreased bacterial translocation. Whereas mice treated with a STING agonist (DMXAA) following CLP developed greater intestinal apoptosis and a more severe systemic inflammatory response. We demonstrated that mitochondrial DNA (mtDNA) was released during sepsis, inducing the intestinal inflammatory response through activating the STING pathway. We finally investigated DNase I administration at 5 hours post CLP surgery, showing that it reduced systemic mtDNA and inflammatory cytokines levels, organ damage, and bacterial translocation, suggesting that inhibition of mtDNA-STING signaling pathway protects against CLP-induced intestinal barrier dysfunction. Interpretation: Our results indicate that the STING signaling pathway can contribute to lethal sepsis by promoting IEC apoptosis and through disrupting the intestinal barrier. Our findings suggest that regulation of the mtDNA-STING pathway may be a promising therapeutic strategy to promote mucosal healing and protect the intestinal barrier in septic patients. Fund: National Natural Science Foundation of China. Keywords: STING, Sepsis, IEC apoptosis, Intestinal inflammatio

    The Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery.

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    AIM: There is a requirement for an expansive and up to date review of the management of emergency colorectal conditions seen in adults. The primary objective is to provide detailed evidence-based guidelines for the target audience of general and colorectal surgeons who are responsible for an adult population and who practise in Great Britain and Ireland. METHODS: Surgeons who are elected members of the Association of Coloproctology of Great Britain and Ireland Emergency Surgery Subcommittee were invited to contribute various sections to the guidelines. They were directed to produce a pathology-based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. Each author was asked to provide a set of recommendations which were evidence-based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after two votes were included in the guidelines. RESULTS: All aspects of care (excluding abdominal trauma) for emergency colorectal conditions have been included along with 122 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence-based summary of the current surgical knowledge in the management of emergency colorectal conditions and should serve as practical text for clinicians managing colorectal conditions in the emergency setting.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Accepted version (12 month embargo
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