60 research outputs found
Barn med låtsaskompisar - självbild och ensamhet i åldrarna 8, 9 och 10 år
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
Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1
Variants with markedly different expression of virulence factors can arise in invasive infection in humans
Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor
High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins
An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data
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
[This corrects the article DOI: 10.1186/s13054-016-1208-6.]
Sepsis induced changes of adipokines and cytokines - septic patients compared to morbidly obese patients
On the role of HMGB1 and resistin in severe sepsis and septic shock
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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