Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.

Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART). This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men

Magnetopause Reconnection as Influenced by the Dipole Tilt Under Southward IMF Conditions: Hybrid Simulation and MMS Observation

Using a three‐dimensional (3‐D) global‐scale hybrid code, the Magnetospheric Multiscale (MMS) reconnection event around 02:13 UT on 18 November 2015, highlighted in the Geospace Environment Modeling (GEM) Dayside Kinetic Challenge, is simulated, in which the interplanetary magnetic field (IMF) points southward and the geomagnetic field has a −27° dipole tilt angle. Strong southward plasma jets are found near the magnetopause as a result of the dayside reconnection. Our results indicate that the subsolar magnetopause reconnection X line shifts from the subsolar point toward the Northern Hemisphere due to the effect of the tilted geomagnetic dipole angle, consistent with the MMS observation. Subsequently, the reconnection X lines or sites and reconnection flux ropes above the equator propagate northward along the magnetopause. The formation and global distribution of the X lines and the structure of the magnetopause reconnection are investigated in detail with the simulation. Mirror mode waves are also found in the middle of the magnetosheath downstream of the quasi‐perpendicular shock where the plasma properties are consistent with the mirror instability condition. As a special outcome of the GEM challenge event, the spatial and temporal variations in reconnection, the electromagnetic power spectra, and the associated D‐shaped ion velocity distributions in the simulated reconnection event are compared with the MMS observation.Key PointsSubsolar magnetopause X lines shift toward the Northern Hemisphere due to the effect of the negative tilted geomagnetic dipole angleThe hybrid simulation magnetic fields and plasma date match MMS3 observations well during the magnetopause crossingMirror mode waves appear in the middle of the magnetosheath downstream of the quasi‐perpendicular shockPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162687/2/jgra55909_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162687/1/jgra55909.pd

The effects of acute experimental hip muscle pain on dynamic single-limb balance performance in healthy middle-aged adults

Middle-aged adults with painful hip conditions show balance impairments that are consistent with an increased risk of falls. Pathological changes at the hip, accompanied by pain, may accelerate pre-existing age-related balance deficits present in midlife. To consider the influence of pain alone, we investigated the effects of acute experimental hip muscle pain on dynamic single-limb balance in middle-aged adults. Thirty-four healthy adults aged 40–60 years formed two groups (Group-1: n\ua0=\ua016; Group-2: n\ua0=\ua018). Participants performed four tasks: Reactive Sideways Stepping (ReactSide); Star Excursion Balance Test (SEBT); Step Test; Single-Limb Squat; before and after an injection of hypertonic saline into the right gluteus medius muscle (Group-1) or ∼5\ua0min rest (Group-2). Balance measures included the range and standard deviation of centre of pressure (CoP) movement in mediolateral and anterior-posterior directions, and CoP total path velocity (ReactSide, Squat); reach distance (SEBT); and number of completed steps (Step Test). Data were assessed using three-way analysis of variance. Motor outcomes were altered during the second repetition of tasks irrespective of exposure to experimental hip muscle pain or rest, with reduced SEBT anterior reach (−1.2\ua0±\ua04.1\ua0cm, P\ua0=\ua00.027); greater step number during Step Test (1.5\ua0±\ua01.7 steps, P\ua

Health Literacy, Medication Adherence, and Patient Satisfaction in Community Pharmacy

Background: Health literacy is defined as the ability to read, understand, and act on health information; almost half of adults have inadequate health literacy. Since inadequate health literacy is often followed by many negative outcomes, such as poor medication adherence, it is important to address health literacy, in order to rectify the low levels and improve outcomes. Patients see pharmacists regularly, and therefore, the pharmacist is crucial In improving medication adherence. If health literacy is a barrier to medication adherence, the community pharmacist should be able to provide health literacy-appropriate counseling to improve medication adherence. Objectives: To determine if pharmacists\u27 perception of patient health literacy and actual patient health literacy align, to assess the relationship between health literacy and medication adherence In patients who visit independent community pharmacies, to evaluate patients\u27 satisfaction with their pharmacists\u27 patient counseling, and to determine the pharmacists\u27 willingness to improve their communication technique with their patients according to their health literacy. Methods: Independent pharmacies were selected from the Cedarvlle network. Patients will complete Instruments to assess health literacy (Newest Vital Signs®), medication adherence (8-item Morisky Medication Adherence Scale©), and patient satisfaction with counseling (Likert-type questions derived from the literature). The patient satisfaction items will be peer-reviewed before finalizing the version given to the patients. Patients will consist of those at least 18 years of age, who speak English, and are obtaining a refill for a chronic condition. Results In Progress: Thus far, the selection process of pharmacies is being conducted, as well as securing the health literacy test, the medication adherence test, and formulating questions for patient satisfaction. Completion is anticipated by the end of spring 2014

Comparing Brane Inflation to WMAP

We compare the simplest realistic brane inflationary model to recent cosmological data, including WMAP 3-year cosmic microwave background (CMB) results, Sloan Digital Sky Survey luminous red galaxies (SDSS LRG) power spectrum data and Supernovae Legacy Survey (SNLS) Type 1a supernovae distance measures. Here, the inflaton is simply the position of a $D3$-brane which is moving towards a $\bar{D}3$-brane sitting at the bottom of a throat (a warped, deformed conifold) in the flux compactified bulk in Type IIB string theory. The analysis includes both the usual slow-roll scenario and the Dirac-Born-Infeld scenario of slow but relativistic rolling. Requiring that the throat is inside the bulk greatly restricts the allowed parameter space. We discuss possible scenarios in which large tensor mode and/or non-Gaussianity may emerge. Here, the properties of a large tensor mode deviate from that in the usual slow-roll scenario, providing a possible stringy signature. Overall, within the brane inflationary scenario, the cosmological data is providing information about the properties of the compactification of the extra dimensions.Comment: 45 pages 11 figure

Cosmology of the Tachyon in Brane Inflation

In certain implementations of the brane inflationary paradigm, the exit from inflation occurs when the branes annihilate through tachyon condensation. We investigate various cosmological effects produced by this tachyonic era. We find that only a very small region of the parameter space (corresponding to slow-roll with tiny inflaton mass) allows for the tachyon to contribute some e-folds to inflation. In addition, non-adiabatic density perturbations are generated at the end of inflation. When the brane is moving relativistically this contribution can be of the same order as fluctuations produced 55 e-folds before the end of inflation. The additional contribution is very nearly scale-invariant and enhances the tensor/scalar ratio. Additional non-gaussianities will also be generated, sharpening current constraints on DBI-type models which already predict a significantly non-gaussian signal.Comment: 30 pages, 2 figures; v3, minor revision, JCAP versio

Intergenomic and epistatic interactions control free radical mediated pancreatic β-cell damage.

Alloxan (AL)-generated Reactive Oxygen Species (ROS) selectively destroy insulin-producing pancreatic β-cells. A previous genome-wide scan (GWS) using a cohort of 296 F2 hybrids between NOD (AL-sensitive) and ALR (AL-resistant) mice identified linkages contributing to β-cell susceptibility or resistance to AL-induced diabetes on Chromosomes (Chr) 2, 3, 8, and a single nucleotide polymorphism i

Exome-Wide Association Study of Endometrial Cancer in a Multiethnic Population

Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome- wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC

The Effects of Caffeic Acid Phenethyl Ester (Cape) on Oxidative Stress and Hypoxia

Oxidative stress has been implicated in pathogenesis of hypoxia and ischemia/reperfusion (I/R) injury. In previous studies, we have shown that the antioxidant CAPE exerted cardioprotection in an isolated rat heart I (30 min)/R (60 min) injury model. In this study, we further evaluated the effects of CAPE on oxidative stress and hypoxia-induced cell damage. We evaluated the inhibition of absorbance in the phorbol 12-myristate 13-acetate (30 nM) induced superoxide production spectrophotometrically in isolated rat neutrophils via reduction of exogenous cytochrome C. We found that CAPE (0.5 µM- 40 µM; n=4-13) reduced phorbol 12-myristate 13-acetate induced neutrophil superoxide release dose-dependently from 29±3% to 95±2%. In a rat hind limb I (30 min)/R (60 min) model, blood hydrogen peroxide levels serves as an indicator of blood oxidative stress and was measured in real-time via a hydrogen peroxide microsensor (100 μm) inserted into both femoral veins (one served as sham, the other as I/R). We found that in the control group, I/R significantly increased blood hydrogen peroxide levels to 2.1±0.8 μM relative to the sham limb at 60 minutes reperfusion when saline was given at the beginning of reperfusion (n=5). By contrast, CAPE when given at reperfusion (40 µM, n=5) significantly reduced blood hydrogen peroxide levels from 30 min reperfusion and throughout the rest of experiment (p This study was supported by Division of Research and Department of Bio-Medical Sciences at Philadelphia College of Osteopathic Medicine