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.The overall goal of the research plan is to determine the factors that contribute to or are protective against vascular cognitive impairment and dementia (VCIND). The study will take a candidate gene approach using a large, well characterized sample of cognitively intact and impaired older men and women. It is expected that the data produced by this study will lead to a better understanding of which individuals are most susceptible and will provide further support for the rationale that vascular disease is an important, common risk factor for cognitive impairment and dementia. A number of strategies will be employed to identify the genetic factors associated with cognitive impairment and dementia. Initial screening of candidate genes will be performed using both a candidate gene approach and a genome scan. Candidate genes identified through initial screening will be typed in a second, selected sample of cognitively impaired and cognitively intact subjects in order to determine if there is an association between the individual candidate gene and cognitive impairment and dementia. Single nucleotide polymorphisms (SNPs) will be identified from genomic DNA and screened for association with cognitive impairment and dementia. The association of the SNPs in cognitively impaired and cognitively intact subjects will be examined to determine the extent to which these SNPs contribute to the dementia phenotype. The final aim of this proposal will be to screen for copy number variation within the candidate genes. Copy number variants (CNVs) will be screened in the second sample of subjects using either polymerase chain reaction (PCR) based methods or next generation sequencing. The presence of CNVs will be evaluated in the first sample of cognitively normal and cognitively impaired subjects in order to determine their contribution to the cognitive impairment phenotype. These data will shed further light on the role of CNVs in the etiology of cognitive impairment and dementia. [unreadable] [unreadable] [unreadable]Prednisone Improves the Efficacy of the Early Treatment of Sepsis in Patients Without Shock.
Prednisone has been shown to reduce systemic inflammatory response syndrome and to reduce mortality in patients with severe sepsis and septic shock. However, the impact of prednisone in a setting of early treatment remains unclear. We sought to assess the effect of 1 g prednisone on the early treatment of sepsis in patients without shock. Randomized, open-label, multicenter, controlled study. Twenty-four intensive care units (15 medical, 9 surgical) in France and South
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