Endothelial cell sphingosine 1-phosphate receptor 1 restrains VE-cadherin cleavage and attenuates experimental inflammatory arthritis.

In rheumatoid arthritis, inflammatory mediators extravasate from blood into joints via gaps between endothelial cells (ECs), but the contribution of ECs is not known. Sphingosine 1-phosphate receptor 1 (S1PR1), widely expressed on ECs, maintains the vascular barrier. Here, we assessed the contribution of vascular integrity and EC S1PR1 signaling to joint damage in mice exposed to serum-induced arthritis (SIA).

Diabetes Induces Cardiac Fibroblast Activation, Promoting a Matrix-Preserving Nonmyofibroblast Phenotype, Without Stimulating Pericyte to Fibroblast Conversion.

Background Interstitial and perivascular fibrosis may contribute to diabetes-associated heart failure. Pericytes can convert to fibroblasts under conditions of stress and have been implicated in the pathogenesis of fibrotic diseases. We hypothesized that in diabetic hearts, pericytes may convert to fibroblasts, contributing to fibrosis and to the development of diastolic dysfunction.

Identification of macrophages in normal and injured mouse tissues using reporter lines and antibodies.

Reliable tools for macrophage identification in mouse tissues are critical for studies investigating inflammatory and reparative responses. Transgenic reporter mice and anti-macrophage antibodies have been used as "specific pan-macrophage" markers in many studies; however, organ-specific patterns of expression and non-specific labeling of other cell types, such as fibroblasts, may limit their usefulness. Our study provides a systematic comparison of macrophage labeling patterns in normal and injured mouse tissues, using the CX3CR1 and CSF1R macrophage reporter lines and anti-macrophage antibodies.

Validation of Specific and Reliable Genetic Tools to Identify, Label, and Target Cardiac Pericytes in Mice.

Background In the myocardium, pericytes are often confused with other interstitial cell types, such as fibroblasts. The lack of well-characterized and specific tools for identification, lineage tracing, and conditional targeting of myocardial pericytes has hampered studies on their role in heart disease. In the current study, we characterize and validate specific and reliable strategies for labeling and targeting of cardiac pericytes.

Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure.

Repair of the infarcted heart requires TGF-β/Smad3 signaling in cardiac myofibroblasts. However, TGF-β-driven myofibroblast activation needs to be tightly regulated in order to prevent excessive fibrosis and adverse remodeling that may precipitate heart failure. We hypothesized that induction of the inhibitory Smad, Smad7, may restrain infarct myofibroblast activation, and we examined the molecular mechanisms of Smad7 actions.

Collagen denaturation in the infarcted myocardium involves temporally distinct effects of MT1-MMP-dependent proteolysis and mechanical tension.

Tissue injury results in profound alterations in the collagen network, associated with unfolding of the collagen triple helix, proteolytic degradation and generation of fragments. In the infarcted myocardium, changes in the collagen network are critically involved in the pathogenesis of left ventricular rupture, adverse remodeling and chronic dysfunction. We hypothesized that myocardial infarction is associated with temporally and spatially restricted patterns of collagen denaturation that may reflect distinct molecular mechanisms of collagen unfolding.

Disciplined into good conduct: Gender constructions of users in a municipal psychiatric context in Sweden.

Aims And Objectives: To examine how gendered discursive norms and notions of masculinity and femininity were (re)produced in professional conversations about users of long-term municipality psychiatric care. Focus is on the staff's use of language in relation to gender constructions.

Background: Psychiatric care in Sweden has undergone tremendous changes in recent decades from custodian care in large hospitals to a care mainly located in a municipal context.

Subordinated masculinities: A critical inquiry into reproduction of gender norms in handovers and rounds in a forensic psychiatric care.

Aims And Objectives: To examine how gendered discursive norms and notions of masculinity are (re)produced in professional conversations about men cared for as patients in forensic psychiatric care, with a particular focus on the centrality of language and gender.

Background: During verbal handovers and ward rounds, care staff converse to share information about patients and make decisions about their mental status. Spoken language is thus a pivotal tool in verbal handovers and ward rounds, one able to reproduce discourses and gender norms.

The role of Smad2 and Smad3 in regulating homeostatic functions of fibroblasts in vitro and in adult mice.

The heart contains an abundant fibroblast population that may play a role in homeostasis, by maintaining the extracellular matrix (ECM) network, by regulating electrical impulse conduction, and by supporting survival and function of cardiomyocytes and vascular cells. Despite an explosion in our understanding of the role of fibroblasts in cardiac injury, the homeostatic functions of resident fibroblasts in adult hearts remain understudied. TGF-β-mediated signaling through the receptor-activated Smads, Smad2 and Smad3 critically regulates fibroblast function.

Diffusion and spillover effects of an evidence-based mental health intervention among peers and caregivers of high risk youth in Sierra Leone: study protocol.

Background: Evidence-based mental health interventions have helped address health services gaps, but their reach and societal benefit can be limited in low resource settings. The current study extends an ongoing scale-up study of a cognitive behavioral therapy (CBT)-based intervention, the Youth Readiness Intervention (YRI), among high risk youth in post-conflict Sierra Leone to investigate mechanisms of diffusion and spillover effects of the YRI among peers and caregivers of youth who receive the intervention.

Methods: We will recruit and enroll YRI index participants and control index participants (ages 18-30).

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF.

Distinct roles of myofibroblast-specific Smad2 and Smad3 signaling in repair and remodeling of the infarcted heart.

TGF-βs regulate fibroblast responses, by activating Smad2 or Smad3 signaling, or via Smad-independent pathways. We have previously demonstrated that myofibroblast-specific Smad3 is critically implicated in repair of the infarcted heart. However, the role of fibroblast Smad2 in myocardial infarction remains unknown.

Pericytes in the infarcted heart.

The adult mammalian heart lacks regenerative capacity and heals through activation of an inflammatory cascade that leads to the formation of a collagen-based scar. Although scar formation is important to preserve the structural integrity of the ventricle, unrestrained inflammation and excessive fibrosis have been implicated in the pathogenesis of adverse post-infarction remodeling and heart failure. Interstitial cells play a crucial role in the regulation of cardiac repair.

The Importance of Being Acceptable - Psychiatric Staffs' Talk about Women Patients in Forensic Care.

Currently, women comprise about ten percent of those sentenced to psychiatric forensic clinics in Sweden. Those who are sentenced to forensic care because of offending and violent behaviour have already taken a step away from the usually expected female behaviour. On the other hand, there are many women in forensic care who have not committed crimes, but who instead self-harm.

Characterization of a mouse model of obesity-related fibrotic cardiomyopathy that recapitulates features of human heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is caused, or exacerbated by, a wide range of extracardiac conditions. Diabetes, obesity, and metabolic dysfunction are associated with a unique HFpEF phenotype, characterized by inflammation, cardiac fibrosis, and microvascular dysfunction. Development of new therapies for HFpEF is hampered by the absence of reliable animal models.

Left atrial remodeling, hypertrophy, and fibrosis in mouse models of heart failure.

Left ventricular dysfunction increases left atrial pressures and causes atrial remodeling. In human subjects, increased left atrial size is a powerful predictor of mortality and adverse events in a broad range of cardiac pathologic conditions. Moreover, structural remodeling of the atrium plays an important role in the pathogenesis of atrial tachyarrhythmias.

"I have surly passed a limit, it is simply too much": women's and men's experiences of stress and wellbeing when living within a process of housework resignation.

Background: Gender inequality within paid and unpaid work exposes women and men to different environments and responsibilities. These gender patterns shape living conditions for women and men, either negatively or positively, by affecting the prospect of good health. Most public health studies of gender and housework are quantitative, and knowledge about the relationship between housework experiences and health for women and men is limited.

Recipient Criteria Predictive of Graft Failure in Kidney Transplantation.

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.

Genetic polymorphisms associated with breast cancer in malaysian cohort.

Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia.

Gendered discourses of youth sexualities--an exploration of PubMed articles on prevention of sexually transmissible infections.

Objective: To explore how gender is addressed in medical articles on the prevention of sexually transmissible infections (STI) among adolescents.

Methods: Sixtyone articles were retrieved from a PubMed search and scrutinized by qualitative content analysis.

Results: Most articles were affiliated with North American research institutions, but there were also reports from Europe, Africa, South America, and Asia.

Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia.

Background & Objectives: Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs.

Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men.

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity.