Pathways by which case managers' match support influences youth mentoring outcomes: Testing the systemic model of youth mentoring.

Keller's systemic model of youth mentoring posits there are multiple pathways through which all stakeholders in the youth mentoring process, including the program staff who support the match (or case managers), influence youth outcomes. This study examines case managers' direct and indirect contributions to match outcomes and tests how transitive interactions facilitate a theorized sequence of mentoring interactions to effect greater closeness and length, specifically in nontargeted mentoring programs. A structural equations model of case manager contributions to match outcomes was tested using data from 758 mentor-mentee matches, supported by 73 case managers across seven mentoring agencies.

Web-Based Training for School-Based Mentors of Military-Connected Youth: A Multi-Phase Development Study.

This paper describes a multi-phase effort to develop a web-based training for adults serving as mentors in school-based programs for youth with a parent in the military. In Phase 1, we conducted focus groups with military parents to: gauge their receptivity to this type of supportive intervention, identify program features that would make the option of mentoring for their children more or less appealing, and identify specific training needs for adult volunteers preparing for the role of mentor to youth in this population. In Phase 2, we used an iterative process to develop the training protocol, including cycling through multiple drafts, creating a web-based platform, reviewing and incorporating feedback from various stakeholders, and then pilot testing the training with two groups of mentor volunteers as part of a school-based mentoring program for military-connected students.

Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.

Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist).

The long noncoding RNA HOTAIR has tissue and cell type-dependent effects on HOX gene expression and phenotype of urothelial cancer cells.

Background: Urothelial carcinoma (UC) is the fifth most common cancer in the developed world. Delineation of differentiation subtypes in UC highlighted the importance of aberrant differentiation. Understanding underlying mechanisms may facilitate diagnosis and development of efficient therapy strategies.

Design and validation of a bioreactor for simulating the cardiac niche: a system incorporating cyclic stretch, electrical stimulation, and constant perfusion.

To simulate the cardiac niche, a bioreactor system was designed and constructed to incorporate cyclic stretch, rhythmic electrical stimulation, and constant perfusion. The homogeneity of surface strain distribution across the cell culture substrate was confirmed with ARAMIS deformation analysis. The proliferation marker, Ki-67, detected in human umbilical vein endothelial cells and 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay performed on human atrial fibroblasts confirmed biocompatibility of this novel device.

Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies.

Background: Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.

Methods: Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists.

Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.

Objective: To perform a 1-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci.

Methods: We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta-analysis was performed across the 7 data sets.

Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score.

Background: Prediction of susceptibility to multiple sclerosis (MS) might have important clinical applications, either as part of a diagnostic algorithm or as a means to identify high-risk individuals for prospective studies. We investigated the usefulness of an aggregate measure of risk of MS that is based on genetic susceptibility loci. We also assessed the added effect of environmental risk factors that are associated with susceptibility for MS.

Recovery of microarray-quality RNA from frozen EDTA blood samples.

Introduction: The availability of blood collection systems with RNA stabilizing additives (e.g. PAXgene) has opened the field for gene expression profiling in large multi-center clinical trials.

Biological response genes after single dose administration of interferon beta-1b to healthy male volunteers.

Treatment with interferon beta-1b (IFNB-1b) is clinically effective in multiple sclerosis patients. However, the mechanism of action is only partially understood, and validated biological response markers are lacking. We assessed IFNB-1b-induced transcriptional changes by microarray technology.

Reduction of hERG potassium currents by hyperosmolar solutions.

We investigated the effects of hyperosmolar solutions on human ether-a-go-go related gene (hERG) potassium currents in chinese hamster ovary (CHO) cells. The addition of d-mannitol to the external solution caused cell shrinkage and reduced current amplitude. The effects were at least partially reversible.

Increased expression of Wnt5a in psoriatic plaques.

Psoriasis vulgaris is characterized by hyperproliferation and incomplete terminal differentiation of epidermal keratinocytes. Despite the established role of Wnt pathways in the regulation of stem cell proliferation and differentiation, they have not yet been associated with the pathophysiology of psoriasis. Here, we took biopsies from uninvolved and from lesional skin of 20 patients with plaque-type psoriasis.

Signals from embryonic fibroblasts induce adult intestinal epithelial cells to form nestin-positive cells with proliferation and multilineage differentiation capacity in vitro.

The intestinal epithelium has one of the greatest regenerative capacities in the body; however, neither stem nor progenitor cells have been successfully cultivated from the intestine. In this study, we applied an "artificial niche" of mouse embryonic fibroblasts to derive multipotent cells from the intestinal epithelium. Cocultivation of adult mouse and human intestinal epithelium with fibroblast feeder cells led to the generation of a novel type of nestin-positive cells (intestinal epithelium-derived nestin-positive cells [INPs]).

Molecular and functional expression of voltage-operated calcium channels during osteogenic differentiation of human mesenchymal stem cells.

Unlabelled: We used the patch-clamp technique and RT-PCR to study the molecular and functional expression of VOCCs in undifferentiated hMSCs and in cells undergoing osteogenic differentiation. L-type Ca2+ channel blocker nifedipine did not influence alkaline phosphatase activity, calcium, and phosphate accumulation of hMSCs during osteogenic differentiation. This study suggests that osteogenic differentiation of hMSCs does not require L-type Ca2+ channel function.

Tissue distribution of a human Ca v 1.2 alpha1 subunit splice variant with a 75 bp insertion.

Mesenchymal stem cells from human bone marrow (MSC) express mRNA encoding the L-type Ca2+ channel Ca v 1.2 alpha1 subunit (alpha(1)1.2).

Beta adrenergic receptor-mediated atrial specific up-regulation of RGS5.

Previous investigations had suggested that signaling from the overexpressed beta(2) adrenergic in the heart of transgenic TG4 mice was dampened in the atria. Using an RT-PCR based strategy, we have identified Regulator of G-protein Signaling 5 (RGS5) as being up-regulated in the atria of TG4 mice. Northern blot analysis demonstrated that RGS5 levels were 3 fold higher in the atria of TG4 mice.

Role of IKur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation.

Background: The ultrarapid outward current I(Kur) is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of I(Kur) by low concentrations of 4-aminopyridine or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials (APs) in trabeculae from patients in sinus rhythm (SR) or chronic atrial fibrillation (AF).

Methods And Results: AP duration at 90% repolarization (APD90) was shorter in AF than in SR (300+/-16 ms, n=6, versus 414+/-10 ms, n=15), whereas APD20 was longer (35+/-9 ms in AF versus 5+/-2 ms in SR, P<0.

Epinephrine activates both Gs and Gi pathways, but norepinephrine activates only the Gs pathway through human beta2-adrenoceptors overexpressed in mouse heart.

Isoproterenol increases and decreases contractile force at low and high concentrations, respectively, through beta(2)-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both G(s) and G(i) proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, but norepinephrine does not. Epinephrine both increased (-log EC(50)M = 9.

Electrophysiological properties of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSC) have gained considerable interest due to their potential use for cell replacement therapy and tissue engineering. One strategy is to differentiate these bone marrow stem cells in vitro into cardiomyocytes prior to implantation. In this context ion channels can be important functional markers of cardiac differentiation.

Cardiostimulant and cardiodepressant effects through overexpressed human beta2-adrenoceptors in murine heart: regional differences and functional role of beta1-adrenoceptors.

(-)-Isoprenaline enhances cardiac contractility through beta-adrenoceptors. However, in cardiac tissue from transgenic mice with a 200-400-fold cardiac overexpression of the human beta(2)-adrenoceptor (TG4) we observed a pronounced cardiodepression at high (-)-isoprenaline concentrations. Here, we investigated the functional role of the coexisting beta(1)-, beta(2)-, and beta(3)-adrenoceptor subtypes in several regions of the TG4 heart, and in particular their contribution to the negative inotropic effect.

Cardiac tissue engineering.

Recent progress in implantations of differentiated cardiac and non-cardiac cells as well as adult stem cells into the heart suggests that the irreversible loss of viable cardiac myocytes that occurs during myocardial infarction can be at least partly substituted. We evaluated an alternative approach by reconstituting cardiac tissue grafts in vitro and implanting them as spontaneously and coherently contracting tissues. For this purpose we have optimized a method to generate ring-shaped three-dimensional engineered heart tissue (EHT) in vitro from neonatal rat cardiac myocytes.

Specific beta(2)AR blocker ICI 118,551 actively decreases contraction through a G(i)-coupled form of the beta(2)AR in myocytes from failing human heart.

Background: We have observed direct (noncatecholamine-blocking) negative inotropic effects of the selective beta(2)-adrenoceptor (AR) antagonist ICI 118,551 in myocytes from failing human ventricle. In this study we characterize the effect in parallel in human myocytes and in myocytes from animal models where beta(2)ARs or G(i) proteins are overexpressed.

Methods And Results: Enzymatically isolated, superfused ventricular myocytes were exposed to betaAR agonists and antagonists/inverse agonists, and contraction amplitude was measured.

Physiological antagonism between ventricular beta 1-adrenoceptors and alpha 1-adrenoceptors but no evidence for beta 2- and beta 3-adrenoceptor function in murine heart.

1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice.

Tissue engineering of a differentiated cardiac muscle construct.

Cardiac tissue engineering is an emerging field. The suitability of engineered heart tissue (EHT) for both in vitro and in vivo applications will depend on the degree of syncytoid tissue formation and cardiac myocyte differentiation in vitro, contractile function, and electrophysiological properties. Here, we demonstrate that cardiac myocytes from neonatal rats, when mixed with collagen I and matrix factors, cast in circular molds, and subjected to phasic mechanical stretch, reconstitute ring-shaped EHTs that display important hallmarks of differentiated myocardium.

The hyperpolarization-activated current If in ventricular myocytes of non-transgenic and beta2-adrenoceptor overexpressing mice.

In transgenic mice (TG4) overexpressing the human beta2-adrenoceptor (beta2-AR), unoccupied receptors are supposed to activate spontaneously the signalling cascade, leading to enhanced levels of cAMP. This second messenger shifts activation curves of the hyperpolarization-activated current If towards less negative potentials. Here, we characterize If of ventricular myocytes from non-transgenic littermate (LM) and TG4 mice and investigate whether If is modulated by spontaneous beta2-AR signalling.