65 research outputs found

    The impact of blood glucose on community-acquired pneumonia:a retrospective cohort study

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    Hyperglycaemia is common in patients with community-acquired pneumonia (CAP) and is a predictor of severe outcomes. Data are scarce regarding whether this association is affected by diabetes mellitus (DM) and also regarding its importance for severe outcomes in hospital. We determined the impact of blood glucose on severe outcomes of CAP in hospital. We studied 1318 adult CAP patients hospitalised at three Danish hospitals. The association between blood glucose and DM status and severe clinical outcome (admission to an intensive care unit (ICU) and/or in-hospital mortality) was assessed by logistic regression. Models were adjusted for CURB-65 score and comorbidities. 12% of patients had DM. In patients without DM an increase in admission blood glucose was associated with risk for ICU admittance (OR 1.25, 95% CI 1.13–1.39), but not significantly associated with in-hospital mortality (OR 1.10, 95% CI 0.99–1.23). In patients with DM an increase in admission blood glucose was not associated with ICU admittance (OR 1.05, 95% CI 1.00–1.12) or in-hospital mortality (OR 1.05, 95% CI 0.99–1.12). An increase in admission blood glucose (only in patients without DM) was associated with a higher risk for ICU admittance and a trend towards higher in-hospital mortality. DM was not associated with a more severe outcome of CAP

    Microbial biopesticides for integrated crop management : an assessment of environmental and regulatory sustainability

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    Herbivorous insects and mites, plant diseases and weeds are major impediments to the production of food crops and are increasingly difficult to control with conventional chemicals. This paper focuses on microbial control agents with an emphasis on augmentation. There are marked differences in the availability of products in different countries which can be explained in terms of differences in their regulatory systems. Regulatory failure arises from the application of an inappropriate synthetic pesticides model. An understanding of regulatory innovation is necessary to overcome these problems. Two attempts at remedying regulatory failure in the UK and the Netherlands are assessed. Scientific advances can feed directly into the regulatory process and foster regulatory innovation

    Target-dependence of sensory neurons: An ultrastructural comparison of axotomised dorsal root ganglion neurons with allowed or denied reinnervation of peripheral targets

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    Evidence is emerging for a role of rough endoplasmic reticulum (RER) in the form of stress granules, the unfolded protein response and protein bodies in the response of neurons to injury and in neurodegenerative diseases. Here, we have studied the role of the peripheral target in regulating the RER and polyribosomes of Nissl bodies in axotomised adult cat dorsal root ganglion (DRG) neurons where axonal regeneration and peripheral target reinnervation was either allowed or denied. Retrograde labelling with horseradish peroxidise was used as an independent marker to enable selection of only those DRG neuronal cell bodies with axons in the injured intercostal nerves. Indications of polyribosomal dispersal were seen by 6 h following axotomy, and by 24 h the normal orderly arrangement of lamellae of RER in Nissl bodies had become disorganised. These ultrastructural changes preceded light microscopical chromatolysis by 1–3 d. The retrograde response was maximal 8–32 d after axotomy. Clusters of debris-laden satellite cells/macrophages were present at this time but no ultrastructural evidence of neuronal apoptosis or necrosis was seen and there were no differences in the initial retrograde response according to the type of injury. By 64 d following axotomy with reinnervation, approximately half the labelled DRG neurons showed restoration of the orderly arrangement of RER and polyribosomes in their Nissl bodies. This was not seen after axotomy with reinnervation denied. We propose that the target-dependent changes in Nissl body ultrastructure described here are part of a continuum that can modify neuronal protein synthesis directed towards growth, maintenance or death of the neuron. This represents a possible structural basis for mediating the varied effects of neurotrophic interactions.I. P. Johnson and T. A. Sear

    Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

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    The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments

    Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

    Get PDF
    The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments

    Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study

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    Background The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D. Methods Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts. Results We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling. Conclusions Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.Peer reviewe
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