Orthostatic Blood Pressure and Arterial Stiffness in Persons with Spinal Cord Injury: The Effect of the Renin Angiotensin Aldosterone System

With advances in acute medical care, longevity has increased in persons with SCI; however, morbidity due to cardiovascular disease (CVD) occurs at an earlier age compared to the general population. Arterial stiffness (AS) is recognized as an independent risk factor for CVD and, specifically, pulse wave velocity (PWV) has been proven to be a valid tool to predict and track structural arterial changes that reflect arteriosclerosis. Evidence has shown that persons with SCI have increased AS compared to uninjured able-bodied controls; however, possible contributors to this increase are not yet fully understood. After a SCI, sympathetic control in the regions below the lesion level are severely disrupted; however, parasympathetic function is preserved. Due to the dissociation between the two systems, those with lesions above T6 experience low resting blood pressure (BP) and further decreases in BP when changing postures (orthostatic hypotension (OH)). As a consequence, individuals with high-level injuries have a heightened reliance on the renin-angiotensin-aldosterone system (RAAS) to maintain and stabilize BP. A mechanism for increased AS in the uninjured population is over activation of the RAAS. In this study, individuals with high-level SCI (injured above T1) and low-level SCI (injured between T6-T12) had increased AS compared to age-matched controls. The change in renin from supine rest to 60-degree head-up tilt (HUT) was a significant predictor to the change in systolic BP; however, the group predictor was not significant. Additionally, group and change in renin were significant predictors to AS. The data indicate that individuals with high-level injuries rely heavily on RAAS to maintain and normalize BP during OH, which is correlated to increased AS. A better way to treat asymptomatic OH in the SCI population is needed to decrease CVD

Orthostatic Blood Pressure and Arterial Stiffness in Persons with Spinal Cord Injury: The Effect of the Renin Angiotensin Aldosterone System

With advances in acute medical care, longevity has increased in persons with SCI; however, morbidity due to cardiovascular disease (CVD) occurs at an earlier age compared to the general population. Arterial stiffness (AS) is recognized as an independent risk factor for CVD and, specifically, pulse wave velocity (PWV) has been proven to be a valid tool to predict and track structural arterial changes that reflect arteriosclerosis. Evidence has shown that persons with SCI have increased AS compared to uninjured able-bodied controls; however, possible contributors to this increase are not yet fully understood. After a SCI, sympathetic control in the regions below the lesion level are severely disrupted; however, parasympathetic function is preserved. Due to the dissociation between the two systems, those with lesions above T6 experience low resting blood pressure (BP) and further decreases in BP when changing postures (orthostatic hypotension (OH)). As a consequence, individuals with high-level injuries have a heightened reliance on the renin-angiotensin-aldosterone system (RAAS) to maintain and stabilize BP. A mechanism for increased AS in the uninjured population is over activation of the RAAS. In this study, individuals with high-level SCI (injured above T1) and low-level SCI (injured between T6-T12) had increased AS compared to age-matched controls. The change in renin from supine rest to 60-degree head-up tilt (HUT) was a significant predictor to the change in systolic BP; however, the group predictor was not significant. Additionally, group and change in renin were significant predictors to AS. The data indicate that individuals with high-level injuries rely heavily on RAAS to maintain and normalize BP during OH, which is correlated to increased AS. A better way to treat asymptomatic OH in the SCI population is needed to decrease CVD

An Improved Approximation Algorithm for the Max-3-Section Problem

We consider the Max--Section problem, where we are given an undirected graph G=(V,E)equipped with non-negative edge weights w: E ? R_+ and the goal is to find a partition of V into three equisized parts while maximizing the total weight of edges crossing between different parts. Max-3-Section is closely related to other well-studied graph partitioning problems, e.g., Max-Cut, Max-3-Cut, and Max-Bisection. We present a polynomial time algorithm achieving an approximation of 0.795, that improves upon the previous best known approximation of 0.673. The requirement of multiple parts that have equal sizes renders Max-3-Section much harder to cope with compared to, e.g., Max-Bisection. We show a new algorithm that combines the existing approach of Lassere hierarchy along with a random cut strategy that suffices to give our result

Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort.

This is the author accepted manuscript. The final version is available from National Academy of Sciences via http://dx.doi.org/10.1073/pnas.1522136113The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses that infect ∼ 390 million people annually; up to 100 million infections are symptomatic, and 500,000 cases progress to severe disease. Exposure to a heterologous DENV serotype, the specific infecting DENV strains, and the interval of time between infections, as well as age, ethnicity, genetic polymorphisms, and comorbidities of the host, are all risk factors for severe dengue. In contrast, neutralizing antibodies (NAbs) are thought to provide long-lived protection against symptomatic infection and severe dengue. The objective of dengue vaccines is to provide balanced protection against all DENV serotypes simultaneously. However, the association between homotypic and heterotypic NAb titers and protection against symptomatic infection remains poorly understood. Here, we demonstrate that the titer of preinfection cross-reactive NAbs correlates with reduced likelihood of symptomatic secondary infection in a longitudinal pediatric dengue cohort in Nicaragua. The protective effect of NAb titers on infection outcome remained significant when controlled for age, number of years between infections, and epidemic force, as well as with relaxed or more stringent criteria for defining inapparent DENV infections. Further, individuals with higher NAb titers immediately after primary infection had delayed symptomatic infections compared with those with lower titers. However, overall NAb titers increased modestly in magnitude and remained serotype cross-reactive in the years between infections, possibly due to reexposure. These findings establish that anti-DENV NAb titers correlate with reduced probability of symptomatic DENV infection and provide insights into longitudinal characteristics of antibody-mediated immunity to DENV in an endemic setting.This work was supported by the FIRST (Fighting Infections through Research, Science, and Technology) grant from the Bill and Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (to E.H.) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) Grants R01 AI099631 (to A.B.) and P01 AI106695 (to E.H.). The Nicaraguan Pediatric Dengue Cohort Study was also supported by Pediatric Dengue Vaccine Initiative Grant VE-1 (to E.H.). L.C.K. was supported by the Gates Cambridge Scholarship Programme and the NIH Oxford-Cambridge Scholars Program