A Method for Estimating Caribou Consumption by Northern Canadians

Caribou is an important source of protein in the diet of northern Canadians. It is also an important pathway for airborne environmental contaminants that concentrate in the lichen - caribou - human food chain. We present a method for estimating caribou consumption that is independent of questionnaires and dietary surveys. The method is based on direct, whole-body measurements of fallout radiocesium in northern caribou consumers and on measurements of the concentrations of radiocesium in the meat. From the 1989-90 surveys of five Arctic communities, we obtained the following mean (90th percentile) intakes of caribou meat in grams per day: Baker Lake - males 65 (141), females 41 (88); Rae-Edzo - males 42 (103), females 31 (80); Old Crow - males 41 (108), females 23 (59); Fort McPherson - males 41 (77), females 32 (68); Aklavik - males 20 (47), females 15 (37). Compared with surveys carried out in the late 1960s, these values indicate a twofold to fourfold decrease in caribou consumption over a period of 20 years. A dietary survey questionnaire administered during the 1989-90 survey provided useful information on the consumption of various caribou organs, methods of meat preparation, and consumption of other traditional foods.Le caribou constitue une importante source de protéines dans le régime alimentaire des Canadiens. Il représente également une voie d'entrée majeure pour les contaminants environnementaux en suspension dans l'air, qui se concentrent dans la chaîne alimentaire lichen - caribou - être humain. Nous présentons une méthode d'évaluation de la consommation de caribou qui n'est pas fondée sur des questionnaires et sondages alimentaires. La méthode s'appuie sur des mesures directes du césium radioactif provenant de retombées, mesures effectuées sur le corps entier de consommateurs nordiques de caribou, ainsi que sur des mesures de la concentration de césium radioactif dans la viande. À partir des enquêtes menées en 1989 et 1990 dans cinq communautés de l'Arctique, nous avons obtenu les apports moyens suivants (90e percentile) de viande de caribou en grammes par jour: Baker Lake - hommes 65 (141), femmes 41 (88); Rae-Edzo - hommes 42 (103), femmes 31 (80); Old Crow - hommes 41 (108), femmes 23 (59); Fort McPherson - hommes 41 (77), femmes 32 (68); Aklavik - hommes 20 (47), femmes 15 (37). Quand on les compare aux sondages menés à la fin des années 1960, ces valeurs révèlent une baisse de 50 à 75 p. cent dans la consommation de caribou sur une période de 20 ans. Une enquête alimentaire réalisée de 1989 à 1990 à l'aide d'un questionnaire a fourni des renseignements utiles sur la consommation de divers abats, les méthodes d'apprêt de la viande ainsi que la consommation d'autres aliments traditionnels

Time perception and its neuropsychological correlates in patients with schizophrenia and in healthy volunteers

Disordered time perception has been reported in schizophrenia. We investigated time perception dysfunction and its neuropsychological correlates in patients with schizophrenia. Participants comprised 38 patients and 38 age- and sex-matched healthy volunteers who were compared in an auditory temporal bisection paradigm using two interval ranges (a 400/800 ins condition and a 1000/2000 ms condition). In the temporal bisection, subjects were required to categorise a probe duration as short or long, based upon the similarity with two reference durations. All subjects also completed a battery of neuropsychological tests measuring sustained attention, short- and long-term memory and executive function. In the 400/800 ins condition, patients judged durations significantly shorter than did control subjects. Patients also exhibited decreased temporal sensitivity in both conditions. We found in both groups a negative association between temporal sensitivity and sustained attention for the 400/800 ms condition, and between temporal sensitivity and long-term memory for the 1000/200 ms condition. In patients, short-term memory performance was negatively associated with duration judgement in both conditions, while executive dysfunction was correlated to a general performance deficit in the 400/800 ms condition. These findings suggest the possibility that time perception abnormalities in schizophrenia are part of neuropsychological dysfunction and are likely to adversely impact upon activity of daily living. (c) 2008 Elsevier Ireland Ltd. All rights reserved

Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials

Clonal Hematopoiesis Is Associated with Higher Risk of Stroke

Background and Purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke. Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke. Results: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke. Conclusions: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed

Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease