Understanding the Perspectives of Women Who Use Intravenous Drugs and are Experiencing Homelessness in an Urban Centre in Canada: An Analysis of Ethnographic Data.

Injection drug use has long been a topic of investigation, whether through a health or criminal justice lens. Whilst these bodies of literature offer important perspectives, missing from the extant literature is evidence, particularly involving women who use drugs, and more specifically evidence about the health beliefs of these women. To address this knowledge gap, we undertook an ethnographic study of homeless women in downtown Ottawa who inject drugs.

The Process of Injection Drug Use Among Homeless Women in Ottawa, Canada: A Qualitative Study.

Background: The literature on women who use injection drugs (WUIDs) is antiquated and diluted by data from men. Due to the higher rates of morbidity and mortality among WUID, we undertook a qualitative study to better understand their drug use practices.

Methods: We adopted a Deleuze-Guattarian lens and engaged in semi-structured interviews with 35 women in Ottawa, Canada.

The Experience of Violence Against Women Who Use Injection Drugs: An Exploratory Qualitative Study.

Background: While literature exists about persons who use injection drugs, few studies explore the experience of women who use these substances. Furthermore, even less research specifically focuses on the lives and experiences of homeless women who use injection drugs. What literature does exist, moreover, is often dated and primarily addresses concerns about infectious disease transmission among these women; and some highlight that these women have lives fraught with violence.

Chemogenomic Profiling of Antileishmanial Efficacy and Resistance in the Related Kinetoplastid Parasite Trypanosoma brucei.

The arsenal of drugs used to treat leishmaniasis, caused by spp., is limited and beset by toxicity and emergent resistance. Furthermore, our understanding of drug mode of action and potential routes to resistance is limited.

Consideration of sexually transmitted infections in the differential diagnosis: Case studies.

Background And Purpose: The rates of many sexually transmitted infections (STIs) have increased in recent years. Many health care professionals miss these potential diagnoses in clinical practice.

Methods: Two case studies are presented, one an adult female with dysuria; the other an adult male with a rash.

Characterization of CD28 T cells in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Previous reports have shown that increased T-cell numbers and CD28 phenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Flow cytometric analysis of explanted lung cellular suspensions showed a significant increase in CD8 CD28 T cells in IPF relative to normal lung explants.

Modeling and measuring extracellular matrix alterations in fibrosis: challenges and perspectives for antifibrotic drug discovery.

An imbalance of extracellular matrix (ECM) deposition and turnover is a hallmark of fibrotic pathologies as opposed to normal repair response to injury across several organs. Antifibrotic approaches to date have targeted multiple mechanisms and pathways involved in inflammation, angiogenesis, injury, wound repair, ECM biosynthesis, assembly, crosslinking and degradation. Many of these approaches have been unsuccessful which may in part be due to suboptimal models and the lack of validated functional ECM end points relevant to fibrosis.

Clinical ethics issues in HIV care in Canada: an institutional ethnographic study.

Background: This is a study involving three HIV clinics in the Canadian provinces of Newfoundland and Labrador, and Manitoba. We sought to identify ethical issues involving health care providers and clinic clients in these settings, and to gain an understanding of how different ethical issues are managed by these groups.

Methods: We used an institutional ethnographic method to investigate ethical issues in HIV clinics.

The ethical case for providing cost-free access to lifesaving HIV medications in Canada: Implications of a qualitative study.

Antiretroviral therapy for HIV can be expensive if paid for out of pocket. In Canada, there are a variety of federal, provincial, and private prescription drug plans that lower the cost of these lifesaving medications for people living with HIV, and in some cases, these plans result in cost-free access. However, many people living with HIV must contend with high deductibles for their antiretroviral therapies, and many experience difficulty managing the administrative requirements of their drug plans.

Combined inhibition of tumor necrosis factor α and interleukin-17 as a therapeutic opportunity in rheumatoid arthritis: development and characterization of a novel bispecific antibody.

Objective: Rheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin-6 (IL-6), produce clinically meaningful responses in only about half of the treated patients.

HIV status and sexual behaviour among gay men in Ottawa: considerations for public health.

Objectives: HIV prevention efforts, particularly among men who have sex with men (MSM), have not achieved maximum effectiveness. A survey of MSM in Ottawa, Canada was completed to ascertain whether there were differences in how the perceived HIV status of participants and their partners influenced sexual practices.

Methods: Self-directed surveys were administered to a convenience sample of 721 MSM in Ottawa, Canada from November 2011 through May 2012.

Overviewing a Nurse-Led, Community-Based HIV PEP Program: Applying the Extant Literature in Frontline Practice.

This clinical concept paper overviews a program to facilitate access to postexposure prophylaxis (PEP) for gay, bisexual, and other men who have sex with men. The project, which was a collaborative initiative involving the local School of Nursing, public health unit, AIDS service organization, hospital-based HIV clinic, and an outpatient pharmacy, was implemented to circumvent common barriers to care identified in the literature. In this project, persons who present to one of the two participating clinics after having come, or likely having come, into contact with HIV within the previous 72 hr, are offered rapid HIV testing, also known as point-of-care (POC) testing, to rule out existing HIV infection, and provided with a follow-up appointment booked at the HIV clinic.

Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of high unmet medical need. Although bromodomain (Brd) and extra terminal domain isoforms have recently been implicated in mediating inflammatory and oncologic indications, their roles in lung fibrosis have not been comprehensively assessed. We investigated the role of Brd on the profibrotic responses of lung fibroblasts (LFs) in patients with rapidly progressing IPF and a mouse bleomycin model of lung fibrosis.

Development of a pharmacodynamic assay based on PLCγ2 phosphorylation for quantifying spleen tyrosine kinase (SYK)-Bruton's tyrosine kinase (BTK) signaling.

Spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK) are key mediators in coupling cell surface receptors, such as the B-cell receptor (BCR), to downstream signaling events affecting diverse biological functions. There is therefore tremendous interest in the development of pharmacological inhibitors targeting the SYK-BTK axis for the treatment of inflammatory disorders and hematological malignancies. A good pharmacodynamic (PD) assay, ideally a blood-based assay that measures proximal events, is warranted for evaluation of such inhibitors.

Natural regulatory T cells are resistant to calcium release-activated calcium (CRAC/ORAI) channel inhibition.

Organ transplant patients are often treated with immunosuppressants, such as the calcineurin phosphatase inhibitor, cyclosporin A, to block T cell-mediated graft rejection. The calcium release-activated calcium (CRAC/ORAI) channels, which act upstream of calcineurin, are essential for calcium entry and CD4(+) T-cell activation. Although cyclosporine A has also been shown to inhibit FoxP3(+) Tregs both in vitro and in vivo, the role of ORAI channel inhibition in natural Tregs (nTregs) or inducible Tregs (iTregs) has not been investigated.

Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients.

BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin-induced pulmonary fibrosis.

Epigenetic alterations, such as histone acetylation, regulate the signaling outcomes and phenotypic responses of fibroblasts after growth factor stimulation. The bromodomain and extra-terminal domain-containing proteins (Brd) bind to acetylated histone residues, resulting in recruitment of components of the transcriptional machinery and subsequent gene transcription. Given the central importance of fibroblasts in tissue fibrosis, this study sought to determine the role of Brd proteins in human lung fibroblasts (LFs) after growth factor stimulation and in the murine bleomycin model of lung fibrosis.

Comparing the differential effects of LPA on the barrier function of human pulmonary endothelial cells.

Lysophosphatidic acid (LPA) is a class of bioactive lyso-phospholipid that mediates most of its biological effects through a family of G protein-coupled receptors of which six have been identified. The role of the LPA pathway in driving chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) has gained considerable academic and industry attention. Modulation of the pulmonary artery endothelial barrier function by the LPA1 receptor has been shown to drive pulmonary fibrosis in murine models of disease.

Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling.

Signaling via the methylation of lysine residues in proteins has been linked to diverse biological and disease processes, yet the catalytic activity and substrate specificity of many human protein lysine methyltransferases (PKMTs) are unknown. We screened over 40 candidate PKMTs and identified SETD6 as a methyltransferase that monomethylated chromatin-associated transcription factor NF-κB subunit RelA at Lys310 (RelAK310me1). SETD6-mediated methylation rendered RelA inert and attenuated RelA-driven transcriptional programs, including inflammatory responses in primary immune cells.

Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a mouse model of ischaemic retinopathy.

Background: Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models.

Methodology/principal Findings: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml).

A model to identify novel targets involved in oxidative stress-induced apoptosis in human lung epithelial cells by RNA interference.

Chronic obstructive pulmonary disease (COPD) is an increasing health problem primarily associated with cigarette smoking, and one of the leading causes of morbidity and mortality worldwide. Despite recent advances in understanding the pathogenesis of the disease, overall patient outcome remains poor with limited therapeutic intervention. Chronic inflammation, an imbalance between proteolytic and anti-proteolytic activities (leading to lung parenchyma destruction) and excessive oxidative stress contribute to COPD pathophysiology.

Relating chemical and biological diversity space: a tunable system for efficient gene transfection.

Polyethyleneimine (PEI), a well-established nonviral transfection reagent, was combinatorially modified with varying proportions of methyl, benzyl, and n-dodecyl groups to create a library of 435 derivatized polymers. Screening of this library for transfection, DNA binding, and toxicity allows systematic correlation of the biological properties of our polymers to their derivatizations. Combinations of derivatizations bring about a 100-fold variation in transfection efficiency between library members.

Dual relationships between clinical psychologists and their clients: a survey of UK clinical psychologists' attitudes.

Objectives: To collect information from a large number and broad range of UK clinical psychologists in order to examine the relationships between their attitudes towards dual relationships and various other characteristics, for comparison with the results of previous studies (mainly in the USA).

Design: The study was an anonymous postal survey.

Method: Questionnaires were sent out by the British Psychological Society Direct Mail Service to 1,000 randomly selected full members of the Division of Clinical Psychology (total membership 3,330).