60 research outputs found

    Barn med låtsaskompisar - självbild och ensamhet i åldrarna 8, 9 och 10 år

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    Undersökningens syfte var att studera ensamhet och självbild hos barn med och utan låtsaskompis. Undersökningen genomfördes med frågeformulär till föräldrar och barn samt självskattningsformulär till barnen i åldrarna 8 till 10 år (n=77 varav 46 flickor och 31 pojkar). Resultatet visade att de med låtsaskompis hade något lägre total självbild och signifikant lägre självbild på delskalan ”relationer till andra”. För övrigt upplevde sig de med låtsaskompis sig själva som något mer ensamma och de var något oftare ensambarn än de som inte hade låtsaskompis men resultaten var inte signifikanta. Detta diskuteras i förhållande till tidigare forskning

    An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

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    Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    On the role of HMGB1 and resistin in severe sepsis and septic shock

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    Severe sepsis and septic shock are serious manifestations of infectious diseases. Mortality ranges from over 30 % in severe sepsis up to 60% in septic shock. Early antibiotic treatment and intensive care are mainstays of therapy, but outside of this, new treatments have only marginally improved survival. The innate immune response is a powerful part of vertebrate defence against infections. It is likely that an over-reactive innate response, rather than infections themselves, causes much of the mortality in severe infections. Subduing that immune response could improve survival. The most important signalling proteins in innate immunity are cytokines. Clinical trials aimed at reducing proinflammatory cytokines in sepsis have been disappointing, probably because the brief, powerful cytokine burst has often passed by the time patients are admitted for treatment. The hunt has therefore been on for pro-inflammatory proteins which are still elevated, and thus susceptible to therapy, when patients are admitted to hospital. This thesis focuses on two proinflammatory proteins with cytokine-like properties, High Mobility Group Box 1 protein (HMGB1) and resistin. Both exert a wide array of inflammatory effects, and HMGB1 reducing therapy in animal sepsis models considerably reduces mortality. We performed two prospective studies, with a total of 109 patients with severe sepsis or septic shock, primarily treated in the intensive care unit. We showed that both proteins had sustained secretion profiles, and remained elevated up to one week, long after other studied cytokines had returned to low values. For resistin, but not for HMGB1, we could also show significant correlations to disease severity as measured by SOFA and APACHE II scores, and also to other laboratory markers of sepsis. We studied putative sources of both proteins and could show that HMGB1 was secreted from endothelial cells and that resistin, previously believed to be secreted only from monocytes or adipocytes, was secreted from neutrophils, systemically and in biopsies from soft tissue infections. This is very interesting since both endothelial cells and neutrophils play critical roles in innate immunity. We found that resistin was secreted at higher concentrations in gram-positive infections compared to gram-negative, in vitro as well as in patients. In pathophysiological studies, we showed that HMGB1 induces resistin release from monocytes which might explain their similar secretion profiles. Resistin in itself induces the upregulation of the cell adhesion protein ICAM-1 on monocytes. Furthermore, we could show that the proinflammatory effects of HMGB1 on monocytes and endothelial cells were dose-dependently inhibited by Dexamethasone, a glucocorticoid, and that CNI-1493, an experimental pharmacological agent, and A-box of HMGB1, inhibited HMGB1 effects on monocytes, but not on endothelium. In summary, HMGB1 and resistin have pro-inflammatory properties, are secreted by important cells of the innate immune system and have persisting secretion profiles in severe sepsis and septic shock. Some further research is required, but both proteins are interesting potential targets in severe infections. Successful reduction could tame hyperinflammation and improve survival in these life-threatening syndromes
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