The impact of pathogen burden on leukocyte telomere length in the Multi-Ethnic Study of Atherosclerosis.

Several infections have been linked to telomere shortening and in some cases these associations have varied by sex. We assessed the association between seropositivity to four persistent pathogens (cytomegalovirus (CMV), herpes simplex virus-1, Helicobacter pylori, Chlamydia pneumoniae), and total pathogen burden on leukocyte telomere length in a diverse US sample. Data came from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study. We utilized cross-sectional survey data, and biological samples from participants tested for pathogens and telomere length (N = 163). Linear regression was used to examine the association between seropositivity for individual pathogens as well as total pathogen burden and telomere length, adjusting for various confounders. CMV seropositivity and increased total pathogen burden level were significantly associated with shorter telomere length among females (ß = -0·1204 (standard error (s.e.) 0·06), P = 0·044) and (ß = -0·1057 (s.e. = 0·05), P = 0·033), respectively. There was no statistically significant association among males. Our findings suggest that prevention or treatment of persistent pathogens, in particular CMV, may play an important role in reducing telomere shortening over the life course among women. Future research is needed to confirm these novel findings in larger longitudinal samples.

Evidence Brief--Trends and projections of obesity among Canadians.

The prevalence of obesity, defined as body mass index (BMI) of 30 kg/m2 or higher for adults and as 2 standard deviations above the World Health Organization growth standard mean for children, has increased in many parts of the world. Obese adults are at an increased risk of certain chronic conditions, including hypertension, type 2 diabetes, cardiovascular diseases and some cancers, and of premature death. Obese children have increased cardiometabolic risk, including dyslipidemia, insulin resistance and elevated blood pressure. Excess childhood body weight that continues into adulthood can affect quality of life, educational attainment and earnings over the lifecourse. The Public Health Agency of Canada has projected an annual direct health care cost (including physician, hospitalization and medication costs) of those categorized as obese in Canada in constant 2001 Canadian dollars. Calculated as $7.0 billion in 2011, this annual direct health care cost is projected to rise to $8.8 billion by 2021, based on simulated average direct health care costs, which are higher among the obese ($2,283) than the overweight ($1,726), the underweight ($1,298) and those at normal weight ($1,284). Canadian estimates from 2006 and 2008 that used different methodologies place the annual economic burden (direct and indirect costs) of obesity between $4.6 billion and $7.1 billion. The purpose of this evidence brief is to show current Canadian obesity prevalence rates and estimates for the future using objectively measured height and weight to calculate BMI. The use of objectively measured height and weight to derive BMI is strongly recommended, especially for children and adolescents, as self- or proxy-reported height and weight tend to underestimate actual weight and consequently BMI and obesity prevalence.

TITRE: Synthèse portant sur les données probantes - Tendances et projections relatives à l'obésité chez les Canadiens. INTRODUCTION: La prévalence de l'obésité ­ soit un indice de masse corporelle (IMC) supérieur ou égal à 30 kg/m2 chez les adultes ou deux écarts-types au-dessus de la médiane de la norme de croissance de l'Organisation mondiale de la santé chez les enfants ­ a augmenté dans de nombreuses régions du monde. Les adultes obèses sont plus susceptibles d'être atteints de certaines affections chroniques, notamment d'hypertension, de diabète de type 2, de cardiopathies et de certains cancers, ainsi que de mourir prématurément. Les enfants obèses présentent aussi un risque cardiométabolique accru (dyslipidémie, résistance à l'insuline et hypertension artérielle). Un excès pondéral pendant l'enfance qui se poursuit à l'âge adulte peut nuire à la qualité de vie, au rendement scolaire et au revenu tout au long de la vie. L'Agence de la santé publique du Canada a estimé les coûts annuels directs, en dollars canadiens constants de 2001, des soins de santé (coûts liés aux médecins, aux hospitalisations et aux médicaments) pour les personnes classées comme obèses au Canada. Évalués à 7,0 milliards de dollars en 2011, ils devraient atteindre 8,8 milliards de dollars d'ici 2021, d'après un calcul à partir des moyennes actuelles qui font qu'ils sont plus élevés chez les obèses (2 283 $) que chez les personnes en surpoids (1 726 $), les personnes en insuffisance pondérale (1 298 $) et les personnes de poids normal (1 284 $). Des estimations canadiennes antérieures, de 2006 et 2008 et obtenues par des méthodologies différentes, ont évalué le fardeau économique annuel (coûts directs et indirects) de l'obésité dans une fourchette allant de 4,6 à 7,1 milliards de dollars. Cette synthèse fondée sur des données probantes vise à présenter les taux de prévalence de l'obésité au Canada à la fois actuels et projetés, à partir d'un calcul de l'IMC reposant sur des mesures objectives de la taille et du poids. L'utilisation de mesures objectives de la taille et du poids pour calculer l'IMC est fortement recommandée, particulièrement chez les enfants et les adolescents, car lorsque la taille et le poids sont autodéclarés ou obtenus par procuration, le poids réel est généralement sous-estimé, ce qui fait que l'IMC et la prévalence de l'obésité le sont également.

CD8 expression up to the double-positive CD3(low/intermediate) stage of thymic differentiation is sufficient for development of peripheral functional cytotoxic T lymphocytes.

Control of CD8alpha transcription during development of alpha/beta T cell receptor (TCR) T lymphocytes is mediated by at least two distinct stage-specific cis-acting transcriptional mechanisms (i.e., enhancers). On the CD8alpha(-/-) knockout (KO) background, cis-mechanism I and cis-mechanism II together mediate appropriate stage- and sublineage-specific transgenic (Tg) CD8alpha expression and "rescue" development of peripheral CD8(+) single-positive (SP) cytotoxic T lymphocytes (CTLs). In contrast, on the wild-type (WT)/CD8(+/+) or CD8alpha(-/-)KO backgrounds, a CD8alpha Tg directed by cis-mechanism I alone is activated during the double negative [DN] to double positive [DP] transition and expressed up to the CD3(low/intermediate) DP stage but not in more mature DP or SP thymocytes or peripheral T cells. As loss of cis mechanism I activity occurs around the onset of positive selection, it is possible that events associated with TCR/major histocompatibility complex (MHC) interactions and selection are involved in initiating these changes in CD8alpha transcription. To examine this issue, phenotypic and functional studies were performed for thymocytes and T cells of CD8alpha(-/-) KO mice that expressed a CD8alpha Tg under control of cis-mechanism I only. Despite loss of CD8alpha expression at the DP CD3(low/intermediate) stage, increased populations of mature CD3(hi)CD4(-)CD8(-) thymocytes and CD3(+)CD4(-)CD8(-) peripheral T cells were detected. By several criteria, including MHC class I-restricted antigen recognition, these cells have at least partially undergone positive and negative selection. Therefore, initiation of selection and sublineage commitment are determined before loss of cis-mechanism I-mediated control of CD8alpha transcription. Further, CD8 expression beyond the CD3(low/intermediate) DP thymic stage is not essential for CTL development in vivo or function.