Spatial variations in ambient ultrafine particle concentrations and the risk of incident prostate cancer: A case-control study.

Background: Diesel exhaust contains large numbers of ultrafine particles (UFPs, <0.1µm) and is a recognized human carcinogen. However, epidemiological studies have yet to evaluate the relationship between UFPs and cancer incidence.

Monoamine oxidase B inhibitor, selegiline, reduces F-THK5351 uptake in the human brain.

Background: F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, high levels of F-THK5351 retention in brain regions thought to contain negligible concentrations of PHF raise questions about the interpretation of the positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested the effects of MAO-B inhibition on F-THK5351 brain uptake using PET and autoradiography.

Anomalous right vertebral artery arising from the arch of aorta: report of three cases.

The right vertebral artery most commonly originates as the first branch of the right subclavian artery. Although anatomical variants of the aortic arch are commonly encountered on cross-sectional imaging, certain variants of the right vertebral artery are exceedingly rare. In this report, we present 3 cases of aberrant right vertebral artery arising as the last branch of the aortic arch, a very rare variant.

Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial.

Objective: The objective of this analysis was to compare patient-reported outcomes and health-related quality of life (HRQoL) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive, well-differentiated pancreatic neuroendocrine tumors (NCT00428597).

Patients And Methods: Patients received sunitinib 37.5 mg (n = 86) or placebo (n = 85) on a continuous daily-dosing schedule until disease progression, unacceptable adverse events (AEs), or death.

Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study.

Background: In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) versus placebo (11.4 versus 5.

Insulin Signalling: The Inside Story.

Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS).

Enhanced brainstem and cortical encoding of sound during synchronized movement.

Movement to a steady beat has been widely studied as a model of alignment of motor outputs on sensory inputs. However, how the encoding of sensory inputs is shaped during synchronized movements along the sensory pathway remains unknown. To investigate this, we simultaneously recorded brainstem and cortical electro-encephalographic activity while participants listened to periodic amplitude-modulated tones.

Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study.

This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.

Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation.

Antigen presentation is essential for establishing immune tolerance and for immune responses against infectious disease and cancer. Although antigen presentation can be mediated by autophagy, here we demonstrate a pathway for mitochondrial antigen presentation (MitAP) that relies on the generation and trafficking of mitochondrial-derived vesicles (MDVs) rather than on autophagy/mitophagy. We find that PINK1 and Parkin, two mitochondrial proteins linked to Parkinson's disease (PD), actively inhibit MDV formation and MitAP.

CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis.

Mutations in the CdGAP/ARHGAP31 gene, which encodes a GTPase-activating protein for Rac1 and Cdc42, have been reported causative in the Adams-Oliver developmental syndrome often associated with vascular defects. However, despite its abundant expression in endothelial cells, CdGAP function in the vasculature remains unknown. Here, we show that vascular development is impaired in CdGAP-deficient mouse embryos at E15.

Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction.

Epidermal growth factor (EGF) and insulin receptor tyrosine kinases (RTKs) exemplify how receptor location is coupled to signal transduction. Extracellular binding of ligands to these RTKs triggers their concentration into vesicles that bud off from the cell surface to generate intracellular signaling endosomes. On the exposed cytosolic surface of these endosomes, RTK autophosphorylation selects the downstream signaling proteins and lipids to effect growth factor and polypeptide hormone action.

Multimedia information intervention and its benefits in partners of the head and neck cancer patients.

We aimed to investigate the levels of anxiety, depression, satisfaction with information provision and cancer-related knowledge in partners of head and neck cancer (HNC) patients receiving a Multimode Comprehensive Tailored Information Package (MCTIP). A non-randomised, controlled trial was conducted with partners of HNC patients recruited at two academic hospitals in Montreal. The Test participants received the MCTIP, while the Control participants received information in an ad hoc manner.

HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls.

Background: Frailty is an age-related syndrome of decreased physiological reserve and resistance to stressors, associated with increased morbidity and mortality in the general elderly population. An increased prevalence of frailty has been reported amongst HIV-infected individuals.

Methods: Fried frailty phenotype was systematically assessed in predominantly virologically suppressed HIV type 1 (HIV-1)-infected and otherwise comparable HIV-uninfected participants aged at least 45 at enrollment into the AGEhIV Cohort Study.

Potential sites of CFTR activation by tyrosine kinases.

The CFTR chloride channel is tightly regulated by phosphorylation at multiple serine residues. Recently it has been proposed that its activity is also regulated by tyrosine kinases, however the tyrosine phosphorylation sites remain to be identified. In this study we examined 2 candidate tyrosine residues near the boundary between the first nucleotide binding domain and the R domain, a region which is important for channel function but devoid of PKA consensus sequences.

A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity.

Objectives: Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity.

Design And Methods: This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004-2014.

PCSK9 deficiency unmasks a sex- and tissue-specific subcellular distribution of the LDL and VLDL receptors in mice.

Proprotein convertase subtilisin kexin type 9 (PCSK9), the last member of the family of Proprotein Convertases related to Subtilisin and Kexin, regulates LDL-cholesterol by promoting the endosomal/lysosomal degradation of the LDL receptor (LDLR). Herein, we show that the LDLR cell surface levels dramatically increase in the liver and pancreatic islets of PCSK9 KO male but not female mice. In contrast, in KO female mice, the LDLR is more abundant at the cell surface enterocytes, as is the VLDL receptor (VLDLR) at the cell surface of adipocytes.

Microcirculatory response during on-pump versus off-pump coronary artery bypass graft surgery.

Objectives: The use of cardiopulmonary bypass (CPB) during coronary artery bypass graft surgery (CABG) is associated with a systemic inflammatory response, resulting in altered microcirculation. The aim of this study was to evaluate whether beating heart surgery can preserve the microcirculation.

Methods: Sublingual microcirculation was characterized by a Sidestream Darkfield Imaging Microscope during off-pump (OPCABG) and on-pump (ONCABG) surgery.

Regulation of the cystic fibrosis transmembrane conductance regulator anion channel by tyrosine phosphorylation.

The cystic fibrosis transmembrane conductance regulator (CFTR) channel is activated by PKA phosphorylation of a regulatory domain that interacts dynamically with multiple CFTR domains and with other proteins. The large number of consensus sequences for phosphorylation by PKA has naturally focused most attention on regulation by this kinase. We report here that human CFTR is also phosphorylated by the tyrosine kinases p60c-Src (proto-oncogene tyrosine-protein kinase) and the proline-rich tyrosine kinase 2 (Pyk2), and they can also cause robust activation of quiescent CFTR channels.

Cinacalcet Treatment in an Adolescent With Concurrent 22q11.2 Deletion Syndrome and Familial Hypocalciuric Hypercalcemia Type 3 Caused by AP2S1 Mutation.

Context: The 22q11.2 deletion syndrome (DS) is a common multiple anomaly syndrome in which typical features include congenital heart defects, facial dysmorphism, and palatal anomalies. Hypocalcemia due to hypoparathyroidism is a common endocrine manifestation resulting from variable parathyroid hypoplasia, but hypercalcemia has not previously been reported in 22q11.

Expectant parents' understanding of the implications and management of fever in the neonate.

Objective: We estimated the extent to which Canadian expectant parents would seek medical care in a febrile neonate (age 30 days or less). We also evaluated expectant parents' knowledge of signs and symptoms of fever in a neonate, and explored the actions Canadian expectant parents would take to optimize the health of their child.

Methods: We conducted a cross-sectional survey of a sample of expectant parents from a large urban center in Canada.

Weight gain after orthotopic liver transplantation: is nonalcoholic fatty liver disease cirrhosis a risk factor for greater weight gain?

Posttransplant weight gain is common after orthotopic liver transplantation. We sought to determine the extent of weight gain at 5 years after transplantation in patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis versus patients with other types of cirrhosis (non-NAFLD). We studied 126 liver transplants performed between 2005 and 2007 at Saint Luc Hospital, University of Montreal.