Protocol for the Brain Health Support Program Study of the Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP): A Prospective 12-Month Intervention Study.

BACKGROUND/OBJECTIVES: CAN-THUMBS UP is designed as a comprehensive and innovative fully remote program to 1) develop an interactive and compelling online Brain Health Support Program intervention, with potential to positively influence dementia literacy, self-efficacy and lifestyle risk factors; 2) enroll and retain a community-dwelling Platform Trial Cohort of individuals at risk of dementia who will participate in the intervention; 3) support an open platform trial to test a variety of multidomain interventions that might further benefit individuals at risk of dementia. This manuscript presents the Brain Health Support Program Study protocol. DESIGN/SETTING: Twelve-month prospective multi-center longitudinal study to evaluate a fully remote web-based educational intervention. Participants will subsequently be part of a Platform Trial Cohort and may be eligible to participate in further dementia prevention clinical trials. PARTICIPANTS: Three hundred fifty older adults who are cognitively unimpaired or have mild cognitive impairment, with at least 1 well established dementia risk factor. INTERVENTION: Participants engage in the Brain Health Support Program intervention for 45-weeks and complete pre/post intervention measures. This intervention is designed to convey best available evidence for dementia prevention, consists of 181 chapters within 8 modules that are progressively delivered, and is available online in English and French. The program has been developed as a collaborative effort by investigators with recognized expertise in the program's content areas, along with input from older-adult citizen advisors. MEASUREMENTS: This study utilizes adapted remote assessments with accessible technologies (e.g. videoconferencing, cognitive testing via computer and mobile phone, wearable devices to track physical activity and sleep, self-administered saliva sample collection). The primary outcome is change in dementia literacy, as measured by the Alzheimer's Disease Knowledge Scale. Secondary outcomes include change in self-efficacy; engagement using the online program; user satisfaction ratings; and evaluation of usability and acceptance. Exploratory outcomes include changes in attitudes toward dementia, modifiable risk factors, performance on the Neuropsychological Test Battery, performance on self-administered online cognitive assessments, and levels of physical activity and sleep; success of the national recruitment plan; and the distribution of age adjusted polygenic hazard scores. CONCLUSIONS: This fully remote study provides an accessible approach to research with all study activities being completed in the participants' home environment. This approach may reduce barriers to participation, provide an easier and less demanding participant experience, and reach a broader geography with recruitment from all regions of Canada. CAN-THUMBS UP represents a Canadian contribution to the global World-Wide FINGERS program (alz.org/wwfingers).

Graphene oxide/waterborne polyurethane nanocoatings: effects of graphene oxide content on performance properties.

Graphene oxide (GO) is a good nanofiller candidate for waterborne coatings because of its outstanding physical and mechanical properties, good dispersibility in water, and low cost relative to graphene. Here, we report on the performance of a one-part, waterborne polyurethane (WPU) nanocoating formulated with four different GO loadings ([0.4% to 2.0%] by mass). The degree of GO dispersion/adhesion was evaluated using scanning electron microscopy, laser scanning confocal microscopy, and Raman microscopy. Nanocoating performance was evaluated using a dynamic mechanical thermal analyzer for mechanical properties, a customized coulometric permeation apparatus for oxygen barrier properties, a combustion microcalorimeter for flammability, a hot disk analyzer for thermal conductivity, thermogravimetric analysis for thermal stability, and a moisture sorption analyzer for water uptake. The results show that GO sheets were well dispersed in, and have good adhesion to, WPU. At the higher mass loadings ([1.2% or 2%] by mass), GO increased the modulus and yield strength of WPU by 300% and 200%, respectively, increased the thermal conductivity by 38%, reduced the burning heat release rate (flammability) by 43%, and reduced the oxygen permeability by up to sevenfold. The presence of GO, however, increased water vapor uptake at high humidity; the moisture content of 2% mass loading GO/WPU nanocoatings at 90% RH was almost twice that of the moisture content for unfilled WPU. Overall, with the exception of water uptake at very high humidity (> 70% RH), the observed improvements in physical and mechanical properties combined with the ease of processing suggest that GO is a viable nanofiller for WPU coatings.

[Autism spectrum disorder diagnosis in young children: a clinical-ethical study on the experiences of parents and physicians]. / Hoe ouders en hulpverleners een diagnose autismespectrumstoornis van een jong kind ervaren: een klinisch-ethische studie.

BACKGROUND After decades of research and clinical experience, autism spectrum disorder (ASD) turns out to be heterogeneous in every sense, including phenotype and etiology. How is this heterogeneous view translated in information that is useful and significant to parents and clinicians?
AIM: To formulate recommendations with regard to clinical ASD care in young children.
METHOD: We conducted in-depth interviews on how parents (11 mothers and 6 fathers of 11 children) and physicians (n = 16) view and experience a young child's ASD diagnosis. The interviews were analysed in Nvivo 11 according to the guidelines of interpretative phenomenological analysis.
RESULTS: The interviewed parents and physicians addressed psycho-relational implications of an ASD diagnosis as much as treatment-oriented implications. Twelve months after their child got an ASD diagnosis, some disappointment regarding these implications led parents to a pragmatic understanding of an ASD diagnosis.
CONCLUSION: Our results may be useful to both clinicians and policy makers with regard to clinical ASD care in young children. An ASD diagnosis in itself may be of limited help to parents and clinicians but can be of use if it is embedded in a request-oriented diagnostic process guided by a communication model of shared decision making and aimed at elaborating a treatment-oriented profile of the child.

Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change (P < 0.001), and baseline glucose levels explained 10% of variation (P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 (P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

Oxylipin profiling in endothelial cells in vitro - Effects of DHA and hydrocortisone upon an inflammatory challenge.

Omega-3 poly-unsaturated fatty acids have been shown to have beneficial effects on several inflammatory-driven endpoints such as cardiovascular diseases. The anti-inflammatory effects of docosahexaenoic acid (DHA) are largely mediated through various oxylipins. Yet, mechanistic insights are limited. Here, we measured 53 oxylipins using LC-MS/MS in an in vitro model of endothelial cell inflammation, and compared the changes induced by DHA to hydrocortisone, a well-established anti-inflammatory drug. DHA modified several oxylipins derived from different precursors such as DHA, AA, LA and EPA. In response to a TNFα and IL-1-ß challenge, DHA clearly reduced many COX-derived pro-inflammatory oxylipins, yet to a minor extent when compared to hydrocortisone. DHA also upregulated metabolites from the CYP and LOX pathways as opposed to hydrocortisone. Thus, DHA reduced pro-inflammation and enhanced pro-resolution, while hydrocortisone blunted both the pro- and anti-inflammatory pathways. Our results may fuel further research on the mitigation of corticosteroids adverse side-effects.

White Matter Lesion Penumbra Shows Abnormalities on Structural and Physiologic MRIs in the Coronary Artery Risk Development in Young Adults Cohort.

BACKGROUND AND PURPOSE: White matter lesions are 1 age-related manifestation of cerebrovascular disease, but subthreshold abnormalities have been identified in nonlesional WM. We hypothesized that structural and physiologic MR imaging findings of early cerebrovascular disease can be measured in middle-aged subjects in tissue adjacent to WM lesions, termed "penumbra." MATERIALS AND METHODS: WM lesions were defined using automated segmentation in 463 subjects, 43-56 years of age, from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal observational cohort study. We described 0- to 2-mm and 2- to 4-mm-thick spatially defined penumbral WM tissue ROIs as rings surrounding WM lesions. The remaining WM was defined as distant normal-appearing WM. Mean signal intensities were measured for FLAIR, T1-, and T2-weighted images, and from fractional anisotropy, mean diffusivity, CBF, and vascular reactivity maps. Group comparisons were made using Kruskal-Wallis and pair-wise t tests. RESULTS: Lesion volumes averaged 0.738 ± 0.842 cm3 (range, 0.005-7.27 cm3). Mean signal intensity for FLAIR, T2, and mean diffusivity was increased, while T1, fractional anisotropy, and CBF were decreased in white matter lesions versus distant normal-appearing WM, with penumbral tissues showing graded intermediate values (corrected P < .001 for all group/parameter comparisons). Vascular reactivity was significantly elevated in white matter lesions and penumbral tissue compared with distant normal-appearing white matter (corrected P ≤ .001). CONCLUSIONS: Even in relatively healthy 43- to 56-year-old subjects with small white matter lesion burden, structural and functional MR imaging in penumbral tissue reveals significant signal abnormalities versus white matter lesions and other normal WM. Findings suggest that the onset of WM injury starts by middle age and involves substantially more tissue than evident from focal white matter lesions visualized on structural imaging.

Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique.

PURPOSE: To compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI). METHODS: Between 2011 and 2016 women ≥60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 × 23.3 Gy) or photon EB-APBI (10 × 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year. RESULTS: HRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS). CONCLUSIONS: EB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels.

Incidence and risk factors for healthcare utilisation among patients discharged on outpatient parenteral antimicrobial therapy.

Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case-control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09-0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05-2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23-17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.

Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients.

BACKGROUND AND PURPOSE: We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients. MATERIALS AND METHODS: Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0-10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires. RESULTS: In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00). CONCLUSION: Acute toxicity after IORT and EB-APBI treatment is acceptable.

Association of plasma phospholipid polyunsaturated and trans fatty acids with body mass index: results from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND/OBJECTIVE: Previous research has focused on associations between dietary fat and body mass index (BMI), but the contributions of different types of fat to BMI remain unclear. The purpose of this study is to estimate whether plasma phospholipid omega-3 (n-3), omega-6 (n-6) or trans fatty acids are associated with BMI at baseline and with subsequent BMI changes over time; and whether total phospholipid n-6 or trans fatty acids modify any association between phospholipid n-3 and BMI. METHODS: Cross-sectional and longitudinal linear mixed models include 6243 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Participants were 45-84 years old, had no history of cardiovascular disease at baseline (2000-2002) and were followed for up to 10 years. Plasma phospholipid fatty acids were measured using fasting plasma samples at baseline. Fully adjusted models include demographics, health behaviors and other fatty acids (n-3, n-6 and trans) as appropriate. RESULTS: In fully adjusted models, phospholipid n-3 fatty acid levels were inversely associated with baseline BMI (Ptrend <0.001). Baseline BMI was 1.14 (95% confidence interval (CI): 0.71, 1.57) kg m-2 lower among participants with total n-3 values in the highest vs the lowest quartiles, but was not associated with changes in BMI. Total phospholipid n-6 was positively associated with baseline BMI in partially adjusted but not fully adjusted models. No overall association was observed between fatty acid levels and changes in BMI. No clear association was observed between trans fatty acids and baseline BMI or BMI change. No effect modification in the association between phospholipid n-3 and baseline BMI or BMI change was observed by either phospholipid n-6 or trans fatty acids. CONCLUSIONS: Phospholipid total and specific n-3 fatty acid levels were inversely associated with BMI at baseline, whereas associations tended to be positive for total n-6 fatty acids. Significant associations between fatty acid levels and BMI changes were not observed.

Preferential binding effects on protein structure and dynamics revealed by coarse-grained Monte Carlo simulation.

The effect of preferential binding of solute molecules within an aqueous solution on the structure and dynamics of the histone H3.1 protein is examined by a coarse-grained Monte Carlo simulation. The knowledge-based residue-residue and hydropathy-index-based residue-solvent interactions are used as input to analyze a number of local and global physical quantities as a function of the residue-solvent interaction strength (f). Results from simulations that treat the aqueous solution as a homogeneous effective solvent medium are compared to when positional fluctuations of the solute molecules are explicitly considered. While the radius of gyration (Rg) of the protein exhibits a non-monotonic dependence on solvent interaction over a wide range of f within an effective medium, an abrupt collapse in Rg occurs in a narrow range of f when solute molecules rapidly bind to a preferential set of sites on the protein. The structure factor S(q) of the protein with wave vector (q) becomes oscillatory in the collapsed state, which reflects segmental correlations caused by spatial fluctuations in solute-protein binding. Spatial fluctuations in solute binding also modify the effective dimension (D) of the protein in fibrous (D ∼ 1.3), random-coil (D ∼ 1.75), and globular (D ∼ 3) conformational ensembles as the interaction strength increases, which differ from an effective medium with respect to the magnitude of D and the length scale.

Persistent organic pollutants in adipose tissue should be considered in obesity research.

Although low doses of persistent organic pollutants (POPs), strong lipophilic chemicals with long half-lives, have been linked to various endocrine, immune, nervous and reproductive system diseases, few obesity studies have considered adipose tissue as an important POPs exposure source. Because the toxicodynamics of POPs relate directly to the dynamics of adiposity, POPs might explain puzzling findings in obesity research. In two people exposed to the same amounts of environmental POPs, the one having more adipose tissue may be advantaged because POPs storage in adipose tissue can reduce burden on other critical organs. Therefore, adipose tissue can play a protective role against the POPs effects. However, two situations increase the POPs release from adipose tissue into the circulation, thereby increasing the risk that they will reach critical organs: (i) weight loss and (ii) insulin resistance. In contrast, weight gain reduces this possibility. Therefore, avoiding harmful health effects of POPs may mostly contradict conventional judgments about obesity and weight change. These contradictory situations can explain the obesity paradox, the adverse effects of intensive intentional weight loss and the protective effects of obesity against dementia. Future studies should consider that adipose tissue is widely contaminated with POPs in modern society.

Ventilation, indoor air quality, and health in homes undergoing weatherization.

Ventilation standards, health, and indoor air quality have not been adequately examined for residential weatherization. This randomized trial showed how ASHRAE 62-1989 (n=39 houses) and ASHRAE 62.2-2010 (n=42 houses) influenced ventilation rates, moisture balance, indoor air quality, and self-reported physical and mental health outcomes. Average total airflow was nearly twice as high for ASHRAE 62.2-2010 (79 vs. 39 cfm). Volatile organic compounds, formaldehyde and carbon dioxide were all significantly reduced for the newer standard and first-floor radon was marginally lower, but for the older standard, only formaldehyde significantly decreased. Humidity in the ASHRAE 62.2-2010 group was only about half that of the ASHRAE 62-1989 group using the moisture balance metric. Radon was higher in the basement but lower on the first floor for ASHRAE 62.2-2010. Children in each group had fewer headaches, eczema, and skin allergies after weatherization and adults had improvements in psychological distress. Indoor air quality and health improve when weatherization is accompanied by an ASHRAE residential ventilation standard, and the 2010 ASHRAE standard has greater improvements in certain outcomes compared to the 1989 standard. Weatherization, home repair, and energy conservation projects should use the newer ASHRAE standard to improve indoor air quality and health.

Post-surgical mediastinitis due to carbapenem-resistant Enterobacteriaceae: Clinical, epidemiological and survival characteristics.

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), including polymyxin-resistant (PR-CRE) strains, are being increasingly reported. However, there is a lack of clinical data for several life-threatening infections. Here we describe a cohort of patients with post-surgical mediastinitis due to CRE, including PR-CRE. This study was a retrospective cohort design at a single cardiology centre. Patients with mediastinitis due to CRE were identified and were investigated for clinically relevant variables. Infecting isolates were studied using molecular techniques. Patients infected with polymyxin-susceptible CRE (PS-CRE) strains were compared with those infected with PR-CRE strains. In total, 33 patients with CRE mediastinitis were studied, including 15 patients (45%) with PR-CRE. The majority (61%) were previously colonised. All infecting isolates carried blaKPC genes. Baseline characteristics of patients with PR-CRE mediastinitis were comparable with those with PS-CRE mediastinitis. Of the patients studied, 70% received at least one agent considered active in vitro and most patients received at least three concomitant antibiotics. Carbapenem plus polymyxin B was the most common antibiotic combination (73%). Over 90% of patients underwent surgical debridement. Overall, in-hospital mortality was 33% and tended to be higher in patients infected with PR-CRE (17% vs. 53%; P=0.06). In conclusion, mediastinitis due to CRE, including PR-CRE, can become a significant challenge in centres with CRE and a high cardiac surgery volume. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE.

A systematic review of commercial weight loss programmes' effect on glycemic outcomes among overweight and obese adults with and without type 2 diabetes mellitus.

OBJECTIVE: We examined the glycemic benefits of commercial weight loss programmes as compared with control/education or counselling among overweight and obese adults with and without type 2 diabetes mellitus (T2DM). METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and references cited by individual programmes. We included randomized controlled trials of ≥12 weeks duration. Two reviewers extracted information on study design, population characteristics, interventions, and mean changes in haemoglobin A1c and glucose. RESULTS: We included 18 randomized controlled trials. Few trials occurred among individuals with T2DM. In this population, Jenny Craig reduced A1c at least 0.4% more than counselling at 12 months, Nutrisystem significantly reduced A1c 0.3% more than counselling at 6 months, and OPTIFAST reduced A1c 0.3% more than counselling at 6 months. Among individuals without T2DM, few studies evaluated glycemic outcomes, and when reported, most did not show substantial reductions. DISCUSSION: Few trials have examined whether commercial weight loss programmes result in glycemic benefits for their participants, particularly among overweight and obese individuals without T2DM. Jenny Craig, Nutrisystem and OPTIFAST show promising glycemic lowering benefits for patients with T2DM, although additional studies are needed to confirm these conclusions. © 2016 World Obesity.

Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study.

Depression may be accompanied by increased oxidative stress and decreased circulating anti-oxidants. This study examines the association between depressive symptoms, F2-isoprostanes and carotenoids in a US community sample. The study includes 3009 participants (mean age 40.3, 54.2% female) from CARDIA (Coronary Artery Risk Development in Young Adults). Cross-sectional analyses were performed on data from the year 15 examination (2000-2001) including subjects whose depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and had measurements of plasma F2-isoprostanes (gas chromatography/mass spectrometry) or serum carotenoids (high-performance liquid chromatography). Carotenoids zeaxanthin/lutein, ß-cryptoxanthin, lycopene, α-carotene, ß-carotene were standardized and summed. Longitudinal analyses were conducted using the data from other examinations at 5-year intervals. Cross-lagged analyses investigated whether CES-D predicted F2-isoprostanes or carotenoids at the following exam, and vice versa. Regression analyses were controlled for sociodemographics, health and lifestyle factors. F2-isoprostanes were higher in subjects with depressive symptoms (CES-D ⩾ 16) after adjustment for sociodemographics (55.7 vs 52.0 pg ml(-1); Cohen's d = 0.14, P < 0.001). There was no difference in F2-isoprostanes after further adjustment for health and lifestyle factors. Carotenoids were lower in those with CES-D scores ⩾ 16, even after adjustment for health and lifestyle factors (standardized sum 238.7 vs 244.0, Cohen's d = -0.16, P < 0.001). Longitudinal analyses confirmed that depression predicts subsequent F2-isoprostane and carotenoid levels. Neither F2-isoprostanes nor carotenoids predicted subsequent depression. In conclusion, depressive symptoms were cross-sectionally and longitudinally associated with increased F2-isoprostanes and decreased carotenoids. The association with F2-isoprostanes can largely be explained by lifestyle factors, but lower carotenoids were independently associated with depressive symptoms.

Higher pericardial adiposity is associated with prevalent diabetes: The Coronary Artery Risk Development in Young Adults study.

BACKGROUND AND AIMS: Pericardial adipose tissue (PAT) is located on both sides of the pericardium. We tested whether PAT was associated with prevalent diabetes at the year 25 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS AND RESULTS: The CARDIA Year 25 exam (2010-2011) included complete data for all covariates on 3107 participants. Prevalent diabetes (n = 436) was defined as high fasting (≥126 mg/dl) or 2-h postload glucose (≥200 mg/dl) or HbA1c (≥6.5%) or use of diabetes medications. Volume of PAT was measured from computed tomographic scans. Logistic regression was performed to examine the relationship between quartiles of PAT and diabetes. In regression models adjusted for field center, sex, race, age, systolic blood pressure, total cholesterol, log triglycerides, and treatment with blood pressure and cholesterol lowering medication, PAT volume in the 4th quartile was significantly associated with diabetes status after adjustment for BMI (OR 2.57, 95% CI 1.66, 3.98) or visceral adipose tissue (OR 2.08, 95% CI 1.32, 3.29). PAT volume in the 2nd and 3rd quartiles was not significantly associated with diabetes status relative to the first quartile. CONCLUSIONS: Metabolically active pericardial adipose tissue is associated with prevalent diabetes only at higher volumes independent of overall obesity.

Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat.

BACKGROUND: To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). SUBJECTS AND METHODS: Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. RESULTS: A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (P<1.0 × 10(-6)) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; P=1.10 × 10(-7)), an association that was replicated (P=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; P=2.42 × 10(-7)). Our sex-specific analyses identified one genome-wide significant (P<5.0 × 10(-8)) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 10(-8) to 1.13 × 10(-8)). The THNSL2 gene previously associated with VAT in women was also replicated (P=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. CONCLUSIONS: Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women.