Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy.

The medical treatment of chronic heart failure has undergone a dramatic transition in the past decade. Short-term approaches for altering hemodynamics have given way to long-term, reparative strategies, including beta-adrenergic receptor (betaAR) blockade. This was once viewed as counterintuitive, because acute administration causes myocardial depression. Cardiac myocytes from failing hearts show changes in betaAR signaling and excitation-contraction coupling that can impair cardiac contractility, but the role of these abnormalities in the progression of heart failure is controversial. We therefore tested the impact of different manipulations that increase contractility on the progression of cardiac dysfunction in a mouse model of hypertrophic cardiomyopathy. High-level overexpression of the beta(2)AR caused rapidly progressive cardiac failure in this model. In contrast, phospholamban ablation prevented systolic dysfunction and exercise intolerance, but not hypertrophy, in hypertrophic cardiomyopathy mice. Cardiac expression of a peptide inhibitor of the betaAR kinase 1 not only prevented systolic dysfunction and exercise intolerance but also decreased cardiac remodeling and hypertrophic gene expression. These three manipulations of cardiac contractility had distinct effects on disease progression, suggesting that selective modulation of particular aspects of betaAR signaling or excitation-contraction coupling can provide therapeutic benefit.

Differential predictability of four dimensions of affect intensity.

Individual differences in affect intensity are typically assessed with the Affect Intensity Measure (AIM). Previous factor analyses suggest that the AIM is comprised of four weakly correlated factors: Positive Affectivity, Negative Reactivity, Negative Intensity and Positive Intensity or Serenity. However, little data exist to show whether its four factors relate to other measures differently enough to preclude use of the total scale score. The present study replicated the four-factor solution and found that subscales derived from the four factors correlated differently with criterion variables that assess personality domains, affective dispositions, and cognitive patterns that are associated with emotional reactions. The results show that use of the total AIM score can obscure relationships between specific features of affect intensity and other variables and suggest that researchers should examine the individual AIM subscales.

CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network Formation of Blood-Derived Endothelial Outgrowth Cells.

Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) represent promising cell sources for angiogenic therapies. There are, however, conflicting reports regarding the ability of MSCs to support network formation of endothelial cells. The goal of this study was to assess the ability of human bone marrow-derived MSCs to support network formation of endothelial outgrowth cells (EOCs) derived from umbilical cord blood EPCs. We hypothesized that upon in vitro coculture, MSCs and EOCs promote a microenvironment conducive for EOC network formation without the addition of angiogenic growth supplements. EOC networks formed by coculture with MSCs underwent regression and cell loss by day 10 with a near 4-fold and 2-fold reduction in branch points and mean segment length, respectively, in comparison with networks formed by coculture vascular smooth muscle cell (SMC) cocultures. EOC network regression in MSC cocultures was not caused by lack of vascular endothelial growth factor (VEGF)-A or changes in TGF-β1 or Ang-2 supernatant concentrations in comparison with SMC cocultures. Removal of CD45+ cells from MSCs improved EOC network formation through a 2-fold increase in total segment length and number of branch points in comparison to unsorted MSCs by day 6. These improvements, however, were not sustained by day 10. CD45 expression in MSC cocultures correlated with EOC network regression with a 5-fold increase between day 6 and day 10 of culture. The addition of supplemental growth factors VEGF, fibroblastic growth factor-2, EGF, hydrocortisone, insulin growth factor-1, ascorbic acid, and heparin to MSC cocultures promoted stable EOC network formation over 2 weeks in vitro, without affecting CD45 expression, as evidenced by a lack of significant differences in total segment length (p=0.96). These findings demonstrate the ability of MSCs to support EOC network formation correlates with removal of CD45+ cells and improves upon the addition of soluble growth factors.

Dust in the wind: How climate variables and volcanic dust affect rates of tooth wear in Central American howling monkeys.

OBJECTIVES: Two factors have been considered important contributors to tooth wear: dietary abrasives in plant foods themselves and mineral particles adhering to ingested food. Each factor limits the functional life of teeth. Cross-population studies of wear rates in a single species living in different habitats may point to the relative contributions of each factor. MATERIALS AND METHODS: We examine macroscopic dental wear in populations of Alouatta palliata (Gray, 1849) from Costa Rica (115 specimens), Panama (19), and Nicaragua (56). The sites differ in mean annual precipitation, with the Panamanian sites receiving more than twice the precipitation of those in Costa Rica or Nicaragua (∼3,500 mm vs. ∼1,500 mm). Additionally, many of the Nicaraguan specimens were collected downwind of active plinian volcanoes. Molar wear is expressed as the ratio of exposed dentin area to tooth area; premolar wear was scored using a ranking system. RESULTS: Despite substantial variation in environmental variables and the added presence of ash in some environments, molar wear rates do not differ significantly among the populations. Premolar wear, however, is greater in individuals collected downwind from active volcanoes compared with those living in environments that did not experience ash-fall. DISCUSSION: Volcanic ash seems to be an important contributor to anterior tooth wear but less so in molar wear. That wear is not found uniformly across the tooth row may be related to malformation in the premolars due to fluorosis. A surge of fluoride accompanying the volcanic ash may differentially affect the premolars as the molars fully mineralize early in the life of Alouatta.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide.

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

How did varying levels of intensity of the 2005 Pakistan earthquake differentially affect women’s fertility decisions and children’s health outcomes?

This paper uses a difference in difference model to investigate the impact of a large scale and high mortality 2005 earthquake in Pakistan on women’s fertility decisions and children’s health outcomes. Using a nationally representative, cross sectional DHS data from 2006 and geographical data from USGS, this paper investigates how variation in earthquake intensity levels can differentially impact total fertility for women and the likelihood of children suffering from diseases such as diarrhea, Acute Respiratory Infections (ARI) and fever. The post-earthquake results demonstrate a statistically significant increase in total fertility for areas closer to the epicenter of the earthquake, within a 100km radius of the rupture surface and at higher altitudes. Similarly, for children who were in-utero at the time of the earthquake, the probability of having early symptoms of ARI or fever was much smaller in lower earthquake intensity zones compared to the highest intensity zone.

How does family drug treatment court participation affect child welfare outcomes?

© 2014 Elsevier Ltd.Parental substance use is a risk factor for child maltreatment. Family drug treatment courts (FDTCs) have emerged in the United States as a policy option to treat the underlying condition and promote family preservation. This study examines the effectiveness of FDTCs in North Carolina on child welfare outcomes. Data come from North Carolina records from child protection services, court system, and birth records. Three types of parental participation in a FDTC are considered: referral, enrolling, and completing an FDTC. The sample includes 566 children who were placed into foster care and whose parents participated in a FDTC program. Findings indicate that children of parents who were referred but did not enroll or who enrolled but did not complete had longer stays in foster care than children of completers. Reunification rates for children of completers were also higher. Outcomes for children in the referred and enrolled groups did not differ in the multivariate analyses. While effective substance use treatment services for parents may help preserve families, future research should examine factors for improving participation and completion rates as well as factors involved in scaling programs so that more families are served.