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Baccarelli A.,Landmark Center | Baccarelli A.,Harvard University | Ghosh S.,Harvard University
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2012

Purpose of review: Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD). Recent findings: An era of cataloging epigenetic marks of the various diseased states has recently commenced, including those within the genes responsible for atherosclerosis, ischemia, hypertension and heart failure. From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD. Signatures of epigenetic dysregulation can be detected in peripheral blood samples, even within a few hours of environmental exposure. However, the field now faces the demand for thorough, systematic, rationalized approaches to establish the relation of exposure-driven epigenetic changes to clinical outcomes, by using sophisticated and reliable research designs and tools. Summary: An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Grandjean P.,University of Southern Denmark | Grandjean P.,Harvard University | Grandjean P.,Landmark Center | Henriksen J.E.,University of Southern Denmark | And 5 more authors.
Epidemiology | Year: 2011

Background: Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after the age of 70. This concern was examined in a cross-sectional study of elderly subjects from a fishing population with elevated contaminant exposures from seafood species high in the food chain. Methods: Clinical examinations of 713 Faroese residents aged 70-74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results: Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In nondiabetic subjects, the fasting insulin concentration decreased by 7% (95% CI = -12% to -2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (-1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions: Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants. Copyright © 2011 by Lippincott Williams & Wilkins. Source

Sequist T.D.,Brigham and Womens Hospital | Fitzmaurice G.M.,Brigham and Womens Hospital | Marshall R.,Harvard University | Shaykevich S.,Brigham and Womens Hospital | And 3 more authors.
Annals of Internal Medicine | Year: 2010

Background: Increasing clinician awareness of racial disparities and improving communication may enhance diabetes care among black patients. Objective: To evaluate the effect of cultural competency training and performance feedback for primary care clinicians on diabetes care for black patients. Design: Cluster randomized, controlled trial conducted between June 2007 and May 2008. (ClinicalTrials.gov registration number: NCT00436176) Setting: 8 ambulatory health centers in eastern Massachusetts. Participants: 124 primary care clinicians caring for 2699 (36%) black and 4858 (64%) white diabetic patients. Intervention: Intervention clinicians received cultural competency training and monthly race-stratified performance reports that highlighted racial differences in control of hemoglobin A1c (HbA 1c) and low-density lipoprotein (LDL) cholesterol levels and blood pressure. Measurements: Clinician awareness of racial differences in diabetes care and rates of achieving clinical control targets among black patients at 12 months. Results: White and black patients differed significantly in baseline rates of achieving an HbA1c level less than 7% (46% vs. 40%), an LDL cholesterol level less than 2.59 mmol/L (<100 mg/dL) (55% vs. 43%), and blood pressure less than 130/80 mm Hg (32% vs. 24%) (all P < 0.050). At study completion, intervention clinicians were significantly more likely than control clinicians to acknowledge the presence of racial disparities in the 8 health centers as a whole (82% vs. 59%; P = 0.003), within their local health center (70% vs. 51%; P = 0.020), and among their own patients (63% vs. 43%; P = 0.037). Black patients of clinicians in the intervention and control groups did not differ at 12 months in rates of controlling HbA1c level (48% vs. 45%; P = 0.24), LDL cholesterol level (48% vs. 49%; P = 0.40), or blood pressure (23% vs. 25%; P = 0.47). Limitation: 11% of primary care teams did not attend cultural competency training sessions. Conclusion: The combination of cultural competency training and race-stratified performance reports increased clinician awareness of racial disparities in diabetes care but did not improve clinical outcomes among black patients. © 2010 American College of Physicians. Source

Herrick R.F.,Landmark Center
New solutions : a journal of environmental and occupational health policy : NS | Year: 2010

The issue of polychlorinated biphenyls (PCB) exposures resulting from occupancy of PCB-contaminated buildings is not new, but the contribution of building materials to that contamination is largely unrecognized. A rapidly emerging base of evidence shows that PCBs can be widely found in caulking and paint in masonry buildings constructed or renovated from about 1950 to the late 1970s. These materials can cause extensive PCB contamination of the building interiors and surrounding soil, and people who teach, live, or attend school in these buildings can have elevated serum PCB levels. The potential risk associated with this source of PCB exposure is not known; however, it is worth noting that the specific PCB congeners found at high levels in the building environments, and in biological samples from the occupants, include some that are suspected of being potent neurotoxins. The U. S. Environmental Protection Agency (EPA) is moving to address this issue in schools; however, the costs of remediating contaminated buildings will pose a formidable obstacle to most school districts. Source

Fuller C.H.,Landmark Center | Fuller C.H.,Georgia State University | Brugge D.,Tufts University | Williams P.L.,Harvard University | And 4 more authors.
Atmospheric Environment | Year: 2012

Ultrafine particles (UFP; aerodynamic diameter < 0.1 μm) are a ubiquitous exposure in the urban environment and are elevated near highways. Most epidemiological studies of UFP health effects use central site monitoring data, which may misclassify exposure. Our aims were to: (1) examine the relationship between distant and proximate monitoring sites and their ability to predict hourly UFP concentration measured at residences in an urban community with a major interstate highway and; (2) determine if meteorology and proximity to traffic improve explanatory power. Short-term (1-3 weeks) residential monitoring of UFP concentration was conducted at 18 homes. Long-term monitoring was conducted at two near-highway monitoring sites and a central site. We created models of outdoor residential UFP concentration based on concentrations at the near-highway site, at the central site, at both sites together and without fixed sites. UFP concentration at residential sites was more highly correlated with those at a near-highway site than a central site. In regression models of each site alone, a 10% increase in UFP concentration at a near-highway site was associated with a 6% (95% CI: 6%, 7%) increase at residences while a 10% increase in UFP concentration at the central site was associated with a 3% (95% CI: 2%, 3%) increase at residences. A model including both sites showed minimal change in the magnitude of the association between the near-highway site and the residences, but the estimated association with UFP concentration at the central site was substantially attenuated. These associations remained after adjustment for other significant predictors of residential UFP concentration, including distance from highway, wind speed, wind direction, highway traffic volume and precipitation. The use of a central site as an estimate of personal exposure for populations near local emissions of traffic-related air pollutants may result in exposure misclassification. © 2012 Elsevier Ltd. Source

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