Comparison of Systematic Ticagrelor-Based Dual Antiplatelet Therapy to Selective Triple Antithrombotic Therapy for Left Ventricle Dysfunction Following Anterior STEMI.

Antithrombotic management of STEMI patients with apical dysfunction, but without demonstrable thrombus, is controversial. Triple antithrombotic therapy (TATT, defined as the addition of oral anticoagulation to dual antiplatelet therapy, or DAPT) may be associated with increased bleeding, while DAPT alone may not adequately protect against cardio-embolic events. We undertook a dual-center study of anterior STEMI patients treated with primary PCI (pPCI) from 2013 to 2015 and presenting presumed new apical dysfunction.

Viruses Seen by Our Cells: The Role of Viral RNA Sensors.

The role of the innate immune response in detecting RNA viruses is crucial for the establishment of proper inflammatory and antiviral responses. Different receptors, known as pattern recognition receptors (PRRs), are present in the cytoplasm, endosomes, and on the cellular surface. These receptors have the capacity to sense the presence of viral nucleic acids as pathogen-associated molecular patterns (PAMPs).

Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis.

Background: The success of clinical trials of selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates B cells are important contributors to peripheral immune responses involved in the development of new relapses. Such B cell contribution to peripheral inflammation likely involves antibody-independent mechanisms. Of growing interest is the potential that B cells, within the MS central nervous system (CNS), may also contribute to the propagation of CNS-compartmentalized inflammation in progressive (non-relapsing) disease.

Effects of SYN1 mutation on cortical gray matter microstructure.

A new Q555X mutation on the SYN1 gene was recently found in several members of a family segregating dyslexia, epilepsy, and autism spectrum disorder. To describe the effects of this mutation on cortical gray matter microstructure, we performed a surface-based group study using novel diffusion and quantitative multiparametric imaging on 13 SYN1 mutation carriers and 13 age- and sex-matched controls. Specifically, diffusion kurtosis imaging (DKI) and neurite orientation and dispersion and density imaging (NODDI) were used to analyze multi-shell diffusion data and obtain parametric maps sensitive to tissue structure, while quantitative metrics sensitive to tissue composition (T1, T2* and relative proton density [PD]) were obtained from a multi-echo variable flip angle FLASH acquisition.

Interleukin (IL)-6 Inhibits IL-27- and IL-30-Mediated Inflammatory Responses in Human Monocytes.

Interleukin (IL)-30, the IL-27p28 subunit of the heterodimeric cytokine IL-27, acts as an antagonist of IL-27 and IL-6 signaling in murine cells via glycoprotein 130 (gp130) receptor and additional binding partners. Thus far, functions of IL-30 have not been fully elucidated in human cells. We demonstrate that like IL-27, IL-30 upregulated TLR4 expression to enhance lipopolysaccharide-induced TNF-α production in human monocytes; however, these IL-30-mediated activities did not reach the same levels of cytokine induction compared to IL-27.

An injectable chitosan/chondroitin sulfate hydrogel with tunable mechanical properties for cell therapy/tissue engineering.

Chitosan (CH) hydrogels with remarkable mechanical properties and rapid gelation rate were recently synthesized by combining sodium hydrogen carbonate (SHC) with another weak base, such as beta-glycerophosphate (BGP). To improve their biological responses, in the present study, chondroitin sulfate (CS) was added to these CH hydrogels. Hydrogel characteristics in terms of pH and osmolarity, as well as rheological, mechanical, morphological and swelling properties, were studied in the absence and presence of CS.

Occupational exposures to leaded and unleaded gasoline engine emissions and lung cancer risk.

Objectives: To determine whether occupational exposure to gasoline engine emissions (GEE) increased the risk of lung cancer and more specifically whether leaded or unleaded GEE increased the risk.

Methods: Two population-based case-control studies were conducted in Montreal, Canada. The first was conducted in the early 1980s and included many types of cancer including lung cancer.

Imaging viscosity of intragranular mucin matrix in cystic fibrosis cells.

Abnormalities of mucus viscosity play a critical role in the pathogenesis of several respiratory diseases, including cystic fibrosis. Currently, there are no approaches to assess the rheological properties of mucin granule matrices in live cells. This is the first example of the use of a molecular rotor, a BODIPY dye, to quantitatively visualize the viscosity of intragranular mucin matrices in a large population of individual granules in differentiated primary bronchial epithelial cells using fluorescence lifetime imaging microscopy.

Unlocking HIV-1 Env: implications for antibody attack.

Collective evidence supporting a role of Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) in controlling HIV-1 transmission and disease progression emerged in the last few years. Non-neutralizing antibodies (nnAbs) recognizing conserved CD4-induced epitopes on Env and able to mediate potent ADCC against HIV-1-infected cells exposing Env in its CD4-bound conformation have been shown to be present in some RV144 vaccinees and most HIV-1-infected individuals. HIV-1 evolved sophisticated strategies to decrease exposure of this Env conformation by downregulating CD4 and by limiting the overall amount of cell-surface Env.

1st Workshop of the Canadian Society for Virology.

The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine.

Importin β1 targeting by hepatitis C virus NS3/4A protein restricts IRF3 and NF-κB signaling of IFNB1 antiviral response.

In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating the innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection.

The Comparative Reliability and Feasibility of the Past-Year Canadian Diet History Questionnaire II: Comparison of the Paper and Web Versions.

Advances in technology-enabled dietary assessment include the advent of web-based food frequency questionnaires, which may reduce costs and researcher burden but may introduce new challenges related to internet connectivity and computer literacy. The purpose of this study was to evaluate the intra- and inter-version reliability, feasibility and acceptability of the paper and web Canadian Diet History Questionnaire II (CDHQ-II) in a sub-sample of 648 adults (aged 39-81 years) recruited from Alberta's Tomorrow Project. Participants were randomly assigned to one of two groups: (1) paper, web, paper; or (2) web, paper, web over a six-week period.

Impact of contaminated household environment on stunting in children aged 12-59 months in Burkina Faso.

Background: Stunting affects 165 million children worldwide, with repercussions on their survival and development. A contaminated environment is likely to contribute to stunting: frequent faecal-oral transmission possibly causes environmental enteropathy, a chronic inflammatory disorder that may contribute to faltering growth in children. This study's objective was to assess the effect of contaminated environment on stunting in Burkina Faso, where stunting prevalence is persistently high.

Validation and application of a nondestructive and contactless method for rheological evaluation of biomaterials.

Hydrogels are extensively used for tissue engineering, cell therapy or controlled release of bioactive factors. Nondestructive techniques that can follow their viscoelastic properties during polymerization, remodeling, and degradation are needed, since these properties are determinant for their in vivo efficiency. In this work, we proposed the viscoelastic testing of bilayered materials (VeTBiM) as a new method for nondestructive and contact-less mechanical characterization of soft materials.

Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response.

Spliceosomal SNRNP200 is a Ski2-like RNA helicase that is associated with retinitis pigmentosa 33 (RP33). Here we found that SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its amino-terminal Sec63 domain (Sec63-1) to bind RNA and to interact with TBK1. We show that SNRNP200 relocalizes into TBK1-containing cytoplasmic structures upon infection, in contrast to the RP33-associated S1087L mutant, which is also unable to rescue antiviral response of SNRNP200 knockdown cells.

Cytokine-Defined B Cell Responses as Therapeutic Targets in Multiple Sclerosis.

Important antibody-independent pathogenic roles of B cells are emerging in autoimmune diseases, including multiple sclerosis (MS). The contrasting results of different treatments targeting B cells in patients (in spite of predictions of therapeutic benefits from animal models) call for a better understanding of the multiple roles that distinct human B cell responses likely play in MS. In recent years, both murine and human B cells have been identified with distinct functional properties related to their expression of particular cytokines.

Value of mechanical dyssynchrony as assessed by radionuclide ventriculography to predict the cardiac resynchronization therapy response.

Aims: To assess the value of mechanical dyssynchrony measured by equilibrium radionuclide angiography (ERNA) in predicting long-term outcome in cardiac resynchronization therapy (CRT) patients.

Methods And Results: We reviewed 146 ERNA studies performed in heart failure patients between 2001 and 2011 at our institution. Long-term follow-up focused on death from any cause or heart transplantation.

Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.

B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls.

Role of HIV-1 Envelope Glycoproteins Conformation and Accessory Proteins on ADCC Responses.

The role of antibody Fc-mediated effector functions in controlling or preventing infections by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) viruses has been recently highlighted in multiple studies. One of those effector functions, antibody-dependent cellular cytotoxicity (ADCC) was suggested as correlating with decreased HIV-1 acquisition risk in the recent Thai RV144 vaccine trial. RV144-elicited antibodies with potent ADCC activity were recently found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction.

Early life adversity and C-reactive protein in diverse populations of older adults: a cross-sectional analysis from the International Mobility in Aging Study (IMIAS).

Background: Recent studies suggest potential associations between childhood adversity and chronic inflammation at older ages. Our aim is to compare associations between childhood health, social and economic adversity and high sensitivity C-reactive protein (hsCRP) in populations of older adults living in different countries.

Methods: We used the 2012 baseline data (n = 1340) from the International Mobility in Aging Study (IMIAS) of community-dwelling people aged 65-74 years in Natal (Brazil), Manizales (Colombia) and Canada (Kingston, Ontario; Saint-Hyacinthe, Quebec).

A morphometric 3D model of coronary artery bypass graft dysfunction with multidetector computed tomography.

Objective: The objective was to assess, with computed tomography (CT) angiography, quantitative morphological parameters of a composite coronary artery bypass grafting (CABG) strategy and to correlate these with graft dysfunction.

Findings: Forty patients [median postoperative time, 32 (14-51) months] underwent CT angiography. Graft patency was assessed, and specific quantitative morphological parameters of the graft were collected.

Adrenal Vein Sampling in Primary Aldosteronism: Sensitivity and Specificity of Basal Adrenal Vein to Peripheral Vein Cortisol and Aldosterone Ratios to Confirm Catheterization of the Adrenal Vein.

Purpose: To assess the sensitivity and specificity for ratios of adrenal vein cortisol level (Ca) to peripheral vein cortisol level (Cp), adrenal vein aldosterone level (Aa) to peripheral vein aldosterone level (Ap), and combined cortisol and aldosterone levels ("combined ratio") for the detection of successful adrenal vein catheterization ("selectivity") in adrenal vein sampling (AVS) without adrenocorticotropic hormone (ACTH) injection at different cutoff values.

Materials And Methods: This retrospective study was approved by the institutional review board, and informed consent was waived. AVS was performed in 160 consecutive patients (49 women and 111 men; mean age, 53.

Multiple aberrant hormone receptors in Cushing's syndrome.

The mechanisms regulating cortisol production when ACTH of pituitary origin is suppressed in primary adrenal causes of Cushing's syndrome (CS) include diverse genetic and molecular mechanisms. These can lead either to constitutive activation of the cAMP system and steroidogenesis or to its regulation exerted by the aberrant adrenal expression of several hormone receptors, particularly G-protein coupled hormone receptors (GPCR) and their ligands. Screening for aberrant expression of GPCR in bilateral macronodular adrenal hyperplasia (BMAH) and unilateral adrenal tumors of patients with overt or subclinical CS demonstrates the frequent co-expression of several receptors.