Effects of Prosthetic Mismatch and Subscapularis Tear on Glenohumeral Contact Patterns in Total Shoulder Arthroplasty: A Numerical Musculoskeletal Analysis.

Prosthetic components' mismatch and subscapularis (SC) tear are determining factors for glenoid failure complication in nonconforming total shoulder arthroplasty (NC-TSA). Risk factors are linked to glenoid prosthetic loading. However, the mechanisms underlying the clinical observations remain unclear.

Proinflammatory isoforms of IL-32 as novel and robust biomarkers for control failure in HIV-infected slow progressors.

HIV-infected slow progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Under conditions that remain poorly understood, a subgroup of these subjects experience failure of spontaneous immunological and virological control. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV(+) Slow Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure.

Identification of novel HIV-1 dependency factors in primary CCR4(+)CCR6(+)Th17 cells via a genome-wide transcriptional approach.

Background: The HIV-1 infection is characterized by profound CD4(+) T cell destruction and a marked Th17 dysfunction at the mucosal level. Viral suppressive antiretroviral therapy restores Th1 but not Th17 cells. Although several key HIV dependency factors (HDF) were identified in the past years via genome-wide siRNA screens in cell lines, molecular determinants of HIV permissiveness in primary Th17 cells remain to be elucidated.

Running for your life: A review of physical activity and cardiovascular disease risk reduction in individuals with schizophrenia.

Individuals with schizophrenia have a greater risk for cardiometabolic risk factors (e.g. central obesity, insulin resistance, hypertension and dyslipidaemia), cardiovascular diseases and mortality.

Immigrants' outcome after a first-episode psychosis.

Aim: Immigration is a risk factor for psychosis emergence, and previous studies show that immigrants are less likely to engage in treatment for psychosis. However, the literature on outcome is scant and heterogeneous. This study was designed to compare first-generation (FGI) and second-generation immigrants (SGI) to non-immigrants' symptomatic and functional outcomes 2 years after a first-episode psychosis (FEP).

Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts.

Background: CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non-AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time.

Methods: Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated.

The longitudinal effects of neighbourhood social and material deprivation change on psychological distress in urban, community-dwelling Canadian adults.

Objective: The purpose of this study was to assess how longitudinal changes in neighbourhood material and social deprivation affect distress outcomes in adult Canadians.

Study Design: This study used a prospective cohort approach.

Methods: We paired data from 2745 urban participants of Canada's National Population Health Survey-who completed the Kessler 6-Item psychological distress screening tool at baseline and follow-up-with neighbourhood social and material deprivation data from the census-based Pampalon Deprivation Index.

Achieving patient engagement in multiple sclerosis: A perspective from the multiple sclerosis in the 21st Century Steering Group.

While advances in medicine, technology and healthcare services offer promises of longevity and improved quality of life (QoL), there is also increasing reliance on a patient׳s skills and motivation to optimize all the benefits available. Patient engagement in their own healthcare has been described as the 'blockbuster drug of the century'. In multiple sclerosis (MS), patient engagement is vital if outcomes for the patient, society and healthcare systems are to be optimized.

Impaired Th17 polarization of phenotypically naive CD4(+) T-cells during chronic HIV-1 infection and potential restoration with early ART.

Background: Depletion of mucosal Th17 cells during HIV/SIV infections is a major cause for microbial translocation, chronic immune activation, and disease progression. Mechanisms contributing to Th17 deficit are not fully elucidated. Here we investigated alterations in the Th17 polarization potential of naive-like CD4(+) T-cells, depletion of Th17-commited subsets during HIV pathogenesis, and Th17 restoration in response to antiretroviral therapy (ART).

The influence of comorbid chronic physical conditions on depression recognition in primary care: a systematic review.

Objective: People with depression often suffer from comorbid chronic physical conditions and such conditions are widely believed to interfere with primary care providers' ability to recognize their depression. We aimed to examine the evidence related to the influence of chronic physical comorbidity burden on depression recognition in routine, community-based primary care settings.

Methods: We conducted a systematic review of the literature on depression recognition in primary care that featured comparisons between patient groups with higher and lower burdens of chronic physical comorbidity.

Chronic physical comorbidity burden and the quality of depression treatment in primary care: a systematic review.

Objective: We examined whether the treatment and follow-up care for depression in routine primary care differs between adults with higher chronic physical comorbidity burden compared to adults with lower chronic physical comorbidity burden and explored factors leading to divergent results across studies.

Methods: We conducted a systematic review of English and French articles using Medline, Embase, PsycINFO, CINAHL and Cochrane Controlled Trials Register from inception to July 2013. Reference list and reverse citation searches were also conducted.

Immunosuppressive Tryptophan Catabolism and Gut Mucosal Dysfunction Following Early HIV Infection.

Background: Tryptophan (Trp) catabolism into kynurenine (Kyn) contributes to immune dysfunction in chronic human immunodeficiency virus (HIV) infection. To better define the relationship between Trp catabolism, inflammation, gut mucosal dysfunction, and the role of early antiretroviral therapy (ART), we prospectively assessed patients early after they acquired HIV.

Methods: Forty patients in the early phase of infection were longitudinally followed for 12 months after receiving a diagnosis of HIV infection; 24 were untreated, and 16 were receiving ART.

The role of oxytocin in cardiovascular regulation.

Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart.

Graft durability and fatigue after in situ fenestration of endovascular stent grafts using radiofrequency puncture and balloon dilatation.

Objectives: In situ fenestration of endovascular stent grafts is a technique that is becoming more common, as it has the advantages of decreased cost, increased availability, and more anatomic configuration than other methods of branch revascularization. However, a significant concern is the short- and long-term durability of the stent graft fabric during and after fenestration.

Methods: This study utilizes the textiles analysis techniques of macro- and microscopic imaging, tear strength testing, burst strength testing, and accelerated cyclic fatigue testing on the fabrics of the Cook Zenith, Medtronic Talent, and Medtronic Endurant stent grafts (three polyester grafts), as well as two different expanded polytetrafluoroethylene (ePTFE) membranes.

Restless legs syndrome-associated MEIS1 risk variant influences iron homeostasis.

Restless legs syndrome (RLS) is a frequent sleep disorder that is linked to disturbed iron homeostasis. Genetic studies identified MEIS1 as an RLS-predisposing gene, where the RLS risk haplotype is associated with decreased MEIS1 mRNA and protein expression. We show here that RNA interference treatment of the MEIS1 worm orthologue increases ferritin expression in Caenorhabditis elegans and that the RLS-associated haplotype leads to increased expression of ferritin and DMT1 in RLS brain tissues.

Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors.

Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly.

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy.

Mutations in FUS cause FALS and SALS in French and French Canadian populations.

Background: The identification of mutations in the TARDBP and more recently the identification of mutations in the FUS gene as the cause of amyotrophic lateral sclerosis (ALS) is providing the field with new insight about the mechanisms involved in this severe neurodegenerative disease.

Methods: To extend these recent genetic reports, we screened the entire gene in a cohort of 200 patients with ALS. An additional 285 patients with sporadic ALS were screened for variants in exon 15 for which mutations were previously reported.

Effect of hemodialysis, coronary artery disease and diabetes on cardiac troponin T: a prospective survey over one year.

Background: Limited data is available about the effects of hemodialysis sessions, coronary artery disease (CAD), and diabetes on serum cardiac troponin T (cTnT) levels in patients with end-stage renal disease (ESRD).

Objectives: To test whether hemodialysis could be associated with an increase in cTnT concentration. To evaluate if coronary artery disease (CAD) or diabetes are associated with higher cTnT levels in ESRD.

The oral anti-diabetic agent, gliclazide, inhibits oxidized LDL-mediated LOX-1 expression, metalloproteinase-9 secretion and apoptosis in human aortic endothelial cells.

The mechanisms linking diabetes to plaque rupture and thrombotic occlusion remain largely speculative, yet matrix metalloproteinases (MMP) and endothelial apoptosis may represent central elements. Binding of oxidized low-density lipoprotein (oxLDL) to endothelial lectin-like oxidized LDL receptor-1 (LOX-1) induces oxidative stress, MMP expression and apoptosis. In the present study, we examined the effect of gliclazide, a second generation sulfonylurea with antioxidant properties, on LOX-1 expression and LOX-1-mediated MMP-9 expression and apoptosis in oxLDL-treated human aortic endothelial cells (HAECs).

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a relevant target for diabetic vasculopathy?

Mechanisms through which major risk factors accelerate diabetic angiopathy include low density lipoprotein (LDL) oxidation and advanced glycation end products (AGEs) formation. Lectin-like oxidized LDL receptor (LOX-1) is a newly identified vascular receptor for oxidized LDL (oxLDL) and AGEs. LOX-1 is up-regulated in vascular endothelium of diabetic animals and thus may be relevant to the development and progression of human diabetic vasculopathy.

Novel de novo SHANK3 mutation in autistic patients.

A number of studies have confirmed that genetic factors play an important role in autism spectrum disorder (ASD). More recently de novo mutations in the SHANK3 gene, a synaptic scaffolding protein, have been associated with the ASD phenotype. As part of our gene discovery strategy, we sequenced the SHANK3 gene in a cohort of 427 ASD subjects and 190 controls.

HMSN/ACC truncation mutations disrupt brain-type creatine kinase-dependant activation of K+/Cl- co-transporter 3.

The potassium-chloride co-transporter 3 (KCC3) is mutated in hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC); however, the molecular mechanisms of HMSN/ACC pathogenesis and the exact role of KCC3 in the development of the nervous system remain poorly understood. The functional regulation of this transporter by protein partners is also largely unknown. Using a yeast two-hybrid approach, we discovered that the C-terminal domain (CTD) of KCC3, which is lost in most HMSN/ACC-causing mutations, directly interacts with brain-specific creatine kinase (CK-B), an ATP-generating enzyme that is also a partner of KCC2.

Diabetic vasculopathy and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).

Type 2 diabetes is associated with an increased incidence of coronary heart disease and cardiovascular complications. One crucial step in the initiation and progression of atherosclerosis is the unregulated uptake of oxidized low-density lipoprotein (oxLDL) by vascular wall components through scavenger receptors. Identification of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as the major receptor for oxLDL in endothelial cells has provided a new clue to the mechanisms involved in oxLDL accumulation in the vessel wall.