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Patel S.R.,Harvard University | Patel S.R.,Beth Israel Deaconess Medical Center | Rueschman M.,Harvard University | Bhatt D.L.,Harvard University | And 8 more authors.
Journal of Sleep Research | Year: 2013

The objective of this study is to examine whether increasing obstructive sleep apnea (OSA) severity is associated with worsening endothelial function. The design is a cross-sectional examination of the baseline assessment of a multi-centre randomized controlled clinical trial examining the effects of oxygen, continuous positive airway pressure (CPAP) therapy or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an apnea-hypopnea index (AHI) of 15-50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices [oxygen desaturation index (ODI), AHI and percentage of sleep time below 90% oxygen saturation (total sleep time <90)] and a measure of endothelium-mediated vasodilatation [Framingham reactive hyperaemia index (F-RHI) derived from peripheral arterial tonometry (PAT)] were assessed. The sample included 267 individuals with a mean AHI of 25.0 ± 8.5 SD and mean F-RHI 0.44 ± 0.38. In adjusted models, the slope of the relationship between ODI and F-RHI differed above and below an ODI of 24.6 (P = 0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% [95% confidence interval (CI): 0%, 5%; P = 0.05], while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: 0%, 27%; P = 0.05) per 5-unit increase in ODI. A similar pattern was observed between AHI and F-RHI. No relation was noted with total sleep time <90 and F-RHI. There was evidence of a graded decline in endothelial function in association with higher levels of intermittent hypoxaemia. © 2013 European Sleep Research Society. Source


Thompson C.L.,Case Western Reserve University | Thompson C.L.,Case Center for Transdisciplinary Research on Energetics and Cancer | Plummer S.J.,University of Southern California | Tucker T.C.,University of Kentucky | And 4 more authors.
Cancer Causes and Control | Year: 2010

Interleukin-22 (IL-22) is a member of the IL-10 family of anti-inflammatory cytokines that mediates epithelial immunity. IL-22 expression is enhanced in inflamed colon mucosa in individuals with inflammatory bowel disease. We carried out an association study to examine the hypothesis that common variation in the IL-22 gene is associated with risk of colon cancer. Seven tagging SNPs were genotyped in 561 colon cancer cases and 722 population controls. Information on lifestyle risk factors was collected via a self-administered questionnaire. The rs1179251 SNP conferred an estimated odds ratio (OR) of 1.46 (95% CI = 1.04-2.05) and 2.10 (95% CI = 0.66-6.66), respectively, for those heterozygous and homozygous for the G variant (p additive = 0.013) after adjustment for age, gender, and race; the OR assuming a dominant model was 1.50 (95% CI = 1.05-2.08, p dominant = 0.016). No other SNP was statistically significantly associated with colon cancer risk. Haplotype analysis found that one haplotype containing the rs1179251 G allele gave an estimated 52% increase in risk of colon cancer for individuals with at least one copy (OR = 1.52, 95% CI = 1.12-2.06, p = 0.0073). Our findings suggest that the rs1179251 SNP in IL-22 is associated with risk of colon cancer. © 2010 Springer Science+Business Media B.V. Source


Ortiz A.P.,University of Puerto Rico at San Juan | Thompson C.L.,Case Western Reserve University | Chak A.,Case Center for Transdisciplinary Research on Energetics and Cancer | Chak A.,University Hospitals Case Medical Center | And 2 more authors.
Cancer | Year: 2012

BACKGROUND: Increasing evidence supports insulin resistance (IR) as the underpinning of the obesity-colorectal neoplasia link. The homeostasis model assessment-IR (HOMA-IR) is a widely accepted index of evolving hyperinsulinemia and early IR. Studies of the relation between HOMA-IR and colorectal adenomas are limited. Therefore, the authors sought to determine the associations of HOMA-IR and central obesity (waist to hip ratio [WHR]) with risk of colorectal adenomas in a screening colonoscopy-based study. METHODS: The authors collected lifestyle information and fasting blood samples from 1222 participants (320 incident adenoma cases and 902 without adenomas) before their screening colonoscopies. Unconditional logistic regression models were used to assess risk associations. RESULTS: In multivariate analysis of participants (n = 1093) reporting no antidiabetic medication use, those in the top quartile of WHR were twice as likely (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.33-3.57; P-trend =.003) and those in the top quartile of HOMA-IR were 63% more likely (OR, 1.63; 95% CI, 1.09-2.44; P-trend = .01) to have adenomas compared with those in the bottom quartiles. Stratified analysis revealed a statistically significant interaction between HOMA-IR and sex (P-interaction = .04), with the association largely limited to men; compared with those in the bottom tertile, men in the top tertile of HOMA-IR were twice more likely to have adenomas (OR, 2.11; 95% CI, 1.18-3.78; P-trend = .01). CONCLUSIONS: The results support central obesity and insulin resistance, particularly in men, as important risk factors for the development of early colorectal neoplasia. © 2011 American Cancer Society. Source


Javaheri S.,Harvard University | Storfer-Isser A.,Case Western Reserve University | Storfer-Isser A.,Case Center for Transdisciplinary Research on Energetics and Cancer | Rosen C.L.,Case Western Reserve University | And 3 more authors.
Journal of Pediatrics | Year: 2011

Objective: To characterize the relationship between insulin sensitivity, assessed with the homeostasis model of insulin (HOMA), and objective measurements of sleep duration in adolescents. Study design: We conducted a cross-sectional analysis from two examinations conducted in the Cleveland Children's Sleep and Health Cohort (n = 387; 43% minorities). Biochemical and anthropometry measurements were made in a clinical research unit. Sleep duration was measured with actigraphy. Results: Decreased sleep duration was associated with increased adiposity and minority race. Sleep duration had a quadratic "u-shape" association with HOMA. When adjusted for age, sex, race, preterm status, and activity, adolescents who slept 7.75 hours had the lowest predicted HOMA (1.96, 95% confidence interval [CI], 1.82-2.10), and adolescents who slept 5.0 hours or 10.5 hours had HOMA indices that were approximately 20% higher (2.36; 95% CI, 1.94-2.86; and 2.41; 95% CI, 1.93-3.01, respectively). After adjusting for adiposity, the association between shorter sleep and HOMA was appreciably attenuated, but the association with longer sleep persisted. Conclusions: Shorter and longer sleep durations are associated with decreased insulin sensitivity in adolescents. Although the association between shorter sleep duration with insulin sensitivity likely is explained by the association between short sleep duration and obesity, the association between longer sleep and insulin sensitivity is independent of obesity. Copyright © 2011 Mosby Inc. All rights reserved. Source


Weiss A.R.,Case Western Reserve University | Weiss A.R.,Case Center for Transdisciplinary Research on Energetics and Cancer | Johnson N.L.,Case Western Reserve University | Berger N.A.,Case Western Reserve University | And 3 more authors.
Journal of Clinical Sleep Medicine | Year: 2010

Study Objectives: The aim of this study was to examine the feasibility of sleep estimation using a device designed and marketed to measure core physical activity. Methods: Thirty adolescent participants in an epidemiological research study wore 3 actigraphy devices on the wrist over a single night concurrent with polysomnography (PSG). Devices used include Actical actigraph, designed and marketed for placement around the trunk to measure physical activity, in addition to 2 standard actigraphy devices used to assess sleep-wake states: Sleepwatch actigraph and Actiwatch actigraph. Sleepwake behaviors, including total sleep time (TST) and sleep efficiency (SE), were estimated from each wrist-device and PSG. Agreements between each device were calculated using Pearson product movement correlation and Bland-Altman plots. Results: Statistical analyses of TST revealed strong correlations between each wrist device and PSG (r = 0.822, 0.836, and 0.722 for Sleepwatch, Actiwatch, and Actical, respectively). TST measured using the Actical correlated strongly with Sleepwatch (r = 0.796), and even stronger still with Actiwatch (r = 0.955). In analyses of SE, Actical correlated strongly with Actiwatch (r = 0.820; p < 0.0001), but not with Sleepwatch (0.405; p = 0.0266). SE determined by PSG correlated somewhat strongly with SE estimated from the Sleepwatch and Actiwatch (r = 0.619 and 0.651, respectively), but only weakly with SE estimated from the Actical (r = 0.348; p = 0.0598). Conclusions: The results from this study suggest that a device designed for assessment of physical activity and truncal placement can be used to measure sleep duration as reliably as devices designed for wrist use and sleep wake inference. Source

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