Virginia Commonwealth University

About: Virginia Commonwealth University is a education organization based out in Richmond, Virginia, United States. It is known for research contribution in the topics: Population & Health care. The organization has 23822 authors who have published 49587 publications receiving 1787046 citations. The organization is also known as: VCU.

“Inside-Out” Signaling of Sphingosine-1-Phosphate: Therapeutic Targets

Abstract: Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes including proliferation, survival, and migration, as well as angiogenesis and allergic responses. S1P levels inside cells are tightly regulated by the balance between its synthesis by sphingosine kinases and degradation. S1P is interconvertible with ceramide, which is a critical mediator of apoptosis. It has been postulated that the ratio between S1P and ceramide determines cell fate. Activation of sphingosine kinase by a variety of agonists increases intracellular S1P, which in turn can function intracellularly as a second messenger or be secreted out of the cell and act extracellularly by binding to and signaling through S1P receptors in autocrine and/or paracrine manners. Recent studies suggest that this “inside-out” signaling by S1P may play a role in many human diseases, including cancer, atherosclerosis, inflammation, and autoimmune disorders such as multiple sclerosis. In this review we summarize metabolism of S1P, mechanisms of sphingosine kinase activation, and S1P receptors and their downstream signaling pathways and examine relationships to multiple disease processes. In particular, we describe recent preclinical and clinical trials of therapies targeting S1P signaling, including 2-amino-2-propane-1,3-diol hydrochloride (FTY720, fingolimod), S1P receptor agonists, sphingosine kinase inhibitors, and anti-S1P monoclonal antibody.

A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease.

Abstract: Aims The role of aspirin in patients with coronary artery disease (CAD) is well established, yet patients happen to discontinue aspirin according to physician’s advice or unsupervised. We thus undertook a systematic review to appraise the hazards inherent to aspirin withdrawal or non-compliance in subjects at risk for or with CAD. Methods and results Electronic databases were systematically searched (updated January 2006). Study designs, patient characteristics, and outcomes were abstracted. Pooled estimates for odds ratios (OR) were computed according to random-effect methods. From the 612 screened studies, six were selected (50 279 patients). One study (31 750 patients) focused on adherence to aspirin therapy in the secondary prevention of CAD, two studies (2594) on aspirin discontinuation in acute CAD, two studies (13 706) on adherence to aspirin therapy before or shortly after coronary artery bypass grafting, and another (2229) on aspirin discontinuation among patients undergoing drug-eluting stenting. Overall, aspirin non-adherence/withdrawal was associated with three-fold higher risk of major adverse cardiac events (OR ¼ 3.14 [1.75–5.61], P ¼ 0.0001). This risk was magnified in patients with intracoronary stents, as discontinuation of antiplatelet treatment was associated with an even higher risk of adverse events (OR ¼ 89.78 [29.90–269.60]). Conclusion Non-compliance or withdrawal of aspirin treatment has ominous prognostic implication in subjects with or at moderate-to-high risk for CAD. Aspirin discontinuation in such patients should be advocated only when bleeding risk clearly overwhelms that of atherothrombotic events.

12 Structural Equation Modeling in Management Research: A Guide for Improved Analysis

Abstract: A large segment of management research in recent years has used structural equation modeling (SEM) as an analytical approach that simultaneously combines factor analysis and linear regression models for theory testing. With this approach, latent variables (factors) represent the concepts of a theory, and data from measures (indicators) are used as input for statistical analyses that provide evidence about the relationships among latent variables. This chapter first provides a brief introduction to SEM and its concepts and terminology. We then discuss four issues related to the measurement component of such models, including how indicators are developed, types of relationships between indicators and latent variables, approaches for multidimensional constructs, and analyses needed when data from multiple time points or multiple groups are examined. In our second major section, we focus on six issues related to the structural component of structural equation models, including how to examine mediatio...

Forgiveness is an emotion-focused coping strategy that can reduce health risks and promote health resilience: theory, review, and hypotheses

Abstract: Experimental evidence suggests that when people are transgressed against interpersonally, they often react by experiencing unforgiveness. Unforgiveness is conceptualized as a stress reaction. Forgiveness is one (of many) ways people reduce unforgiveness. Forgiveness is conceptualized as an emotional juxtaposition of positive emotions (i.e., empathy, sympathy, compassion, or love) against the negative emotions of unforgiveness. Forgiveness can thus be used as an emotion-focused coping strategy to reduce a stressful reaction to a transgression. Direct empirical research suggests that forgiveness is related to health outcomes and to mediating physiological processes in such a way as to support the conceptualization that forgiveness is an emotion-focused coping strategy. Indirect mechanisms might also affect the forgiveness-health relationship. Namely, forgiveness might affect health by working through social support, relationship quality, and religion.

Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection

Abstract: methods We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks’ gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously). results In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, i ∞ to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects. conclusions Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.