Indiana University

About: Indiana University is a education organization based out in Bloomington, Indiana, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 64480 authors who have published 150058 publications receiving 6392902 citations. The organization is also known as: Indiana University system & indiana.edu.

Elevated Circulating Free Fatty Acid Levels Impair Endothelium-Dependent Vasodilation

Abstract: We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low- or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans. After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/-95 to 1,303+/-188 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by approximately 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA). In contrast, similar FFA elevation did not change leg blood flow responses to sodium nitroprusside. During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA). Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 228+/-61 micromol, and prevented the impairment of Mch-induced vasodilation seen with SRIF alone. In conclusion, (a) elevated circulating FFA levels cause endothelial dysfunction, and (b) impaired endothelial function in insulin-resistant humans may be secondary to the elevated FFA concentrations observed in these patients.

Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions

Abstract: Background The highly pathogenic H5N1 avian influenza virus, which is now widespread in Southeast Asia and which diffused recently in some areas of the Balkans region and Western Europe, has raised a public alert toward the potential occurrence of a new severe influenza pandemic. Here we study the worldwide spread of a pandemic and its possible containment at a global level taking into account all available information on air travel. Methods and Findings We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We investigated the effect of the use of AV drugs in the event that therapeutic protocols can be carried out with maximal coverage for the populations in all countries. In view of the wide diversity of AV stockpiles in different regions of the world, we also studied scenarios in which only a limited number of countries are prepared (i.e., have considerable AV supplies). In particular, we compared different plans in which, on the one hand, only prepared and wealthy countries benefit from large AV resources, with, on the other hand, cooperative containment scenarios in which countries with large AV stockpiles make a small portion of their supplies available worldwide. Conclusions We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%–50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use.

Detection of Huntington’s disease decades before diagnosis: The Predict HD study

Abstract: Objective: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington’s disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis. Methods: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor. Results: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies. Conclusions: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.