Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection.

Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-α/β expression in chronic infection compared to acute infection.

Front-line emergency department nurses' and physicians' assessments of processes of elder-friendly care for quality improvement.

Introduction: Geriatric emergency department (ED) care has gained increasing importance and interest due to increasing visits in seniors.

Aim: Among ED front-line nurses and physicians, to assess and compare ratings of elder-friendly care process indicators, variability in ratings, and concurrent validity of ratings.

Methods: Four Quebec EDs' full-time registered nurses and physicians rated their geriatric care using 9 subscales.

Determinants of therapeutic lag in multiple sclerosis.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.

Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.

Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used.

Radium-223 in asymptomatic patients with castration-resistant prostate cancer and bone metastases treated in an international early access program.

Background: Radium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking.

Methods: This was a prospective, single-arm phase 3b study.

Correction to: HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis.

It has been highlighted that the original article [1] contained a typesetting mistake in the family name of Dominique Trudel.

HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis.

Background: The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined.

Methods: We evaluated the impact of HtrA1 downregulation in tumoral tissues on cancer progression and death in women with serous ovarian carcinoma. HtrA1 staining was performed on tissue microarrays (TMA) comprised of tumor samples from a cohort of 106 women who were diagnosed with primary high-grade serous ovarian carcinoma and receiving standard treatment at the Québec University Hospital between 1993 and 2006.

IκB-Kinase-epsilon (IKKε) over-expression promotes the growth of prostate cancer through the C/EBP-β dependent activation of IL-6 gene expression.

The inflammatory cytokine IL-6 has been shown to induce the nuclear translocation of androgen receptors in prostate cancer cells and to activate the androgen receptors in a ligand-independent manner, suggesting it may contribute to the development of a castrate-resistant phenotype. Elevated IL-6 serum levels have also been associated with metastasis-related morbidity in prostate cancer patients. We have previously established that over-expression of I-kappa-B-kinase-epsilon (IKKε also named IKKi or IκBKε) in hormone-sensitive prostate cancer cell lines induces IL-6 secretion.

Hemorrhagic infiltration of the aortopulmonary adventitia: A complication of acute aortic dissection.

Background: Hemorrhagic infiltration of the common aortopulmonary adventitia is an infrequent complication of acute aortic dissection, most frequently Stanford type A. The radiological interpretation of this finding may be a diagnostic challenge. The objective of this multicenter case series is to review the radiological and pathological findings of hemorrhagic infiltration of the aortopulmonary adventitia secondary to acute aortic dissection, and to describe the pathophysiology underlying this complication.

Antimicrobial susceptibility of Campylobacter jejuni and Campylobacter coli isolates obtained in Montreal, Quebec, Canada, from 2002 to 2013.

From 2002 to 2013 in Montreal, Quebec, Canada, 38 Campylobacter coli isolates were more frequently erythromycin, tetracycline, and ciprofloxacin resistant than 440 Campylobacter jejuni subsp. jejuni isolates (18.4% versus 1.

A Fano cavity test for Monte Carlo proton transport algorithms.

Purpose: In the scope of reference dosimetry of radiotherapy beams, Monte Carlo (MC) simulations are widely used to compute ionization chamber dose response accurately. Uncertainties related to the transport algorithm can be verified performing self-consistency tests, i.e.

Autologous HIV-1 clade-B Nef peptides elicit increased frequency, breadth and function of CD8+ T-cells compared to consensus peptides.

Objective: To determine the function and phenotype of CD8(+) T-cells targeting consensus and autologous sequences of entire HIV-1 Nef protein.

Methods: Multiparameter flow cytometry-based analysis was used to evaluate the responses of two treatment naïve HIV-infected individuals, during primary and the chronic phases of infection.

Results: A greater breadth and magnitude of CD8 IFN-γ responses to autologous compared to clade-B consensus peptides was observed in both subjects.

Characterization of a novel octopamine receptor expressed in the surf clam Spisula solidissima.

We have cloned and sequenced a cDNA from the surf clam (Spisula solidissima, a pelecypod mollusc) that encodes an octopamine receptor which we have named Spi-OAR. The sequence of Spi-OAR shares many similarities with two Aplysia and three Drosophila octopamine receptors belonging to a sub-group of beta-adrenergic-like octopamine receptors. Using an expression vector and transient transfections of Spi-OAR into HEK 293 cells, we observed an increase of cAMP upon addition of octopamine and, to a lesser extent, of tyramine, but not after addition of dopamine, serotonin, or histamine.

Cellular and molecular mechanisms of memory T-cell survival.

Long-term maintenance of the memory T-cell response is the hallmark of immune protection and, hence, constitutes one of the most important objectives of vaccine-development strategies. Persistent memory T cells, developed after vaccination or microbial infections, ensure the generation of an antimicrobial response upon re-exposure to the pathogen through rapid clonal proliferation and activation of effector functions. However, in the context of many pathogen infections, these memory T cells fail to persist and die.

Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination.

Epidemiological, biochemical and antimicrobial susceptibility characteristics of Streptococcus pseudoporcinus isolated in Quebec, Canada, from 1997 to 2006.

From 1997 to 2006, in the province of Quebec, Canada, 15 isolates of Streptococcus pseudoporcinus from 1 urine and 14 vaginorectal cultures were recovered from the genitourinary tract of pregnant women. All these women originated from the Caribbean or sub-Saharan Africa (P=0.00045 compared with a suitable control group).

Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells.

The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a).

Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection.

In chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)-mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery.

Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction.

The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L2, inhibits proliferation and cytokine production mediated by antibodies to CD3 (refs. 5,6,7). Blocking the PD-1-PD-L1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted CD8(+) T cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load.