Publications

We appreciate Lucas' and Hoenselaar's comments on our metaanalysis of linoleic acid (LA) and coronary heart disease (CHD) events. 1 Lucas pointed out that evidence from epidemiological studies, including our meta-analyses, contradicts the assertion that higher consumption of omega-6 polyunsaturated fats is harmful.Despite theoretical concern about the potential proinflammatory and thrombogenic properties of omega-6 polyunsaturated fats, evidence from human studies to support a positive association between intakes of these fatty acids and biomarkers of inflammation or risk of cardiovascular disease or cancer is limited.On the contrary, epidemiological studies and randomized, clinical trials have documented beneficial effects of replacing saturated fat with omega-6 polyunsaturated fats on blood lipids and cardiovascular disease risk.We agree with Lucas that the ratio of omega-6 to omega-3 is not particularly meaningful because both types of fatty acids are essential and confer health benefits and there is little evidence that the ratio per se is related to health outcomes.Hoenselaar argued that "Effects found were largely driven by results from 2 cohorts: the Nurses' Health Study [NHS] and the Health Professional Follow-Up Study [HPFS]."To address this issue, in a sensitivity analysis, we tested the influence of an individual study on the results.With systematic removal of 1 study at a time, the summary relative risks (RRs) for CHD events for the highest versus lowest categories of LA intake did not change materially.The summary RR was 0.89 (95% confidence interval [95% CI], 0.81-0.98)after the exclusion of data from NHS and 0.85 (95% CI, 0.77-0.93)after the exclusion of data from HPFS.We found a stronger association after excluding the Malmo Diet and Cancer Cohort Study (MDC; RR=0.81; 95% CI, 0.75-0.88).Similar results were observed for LA and CHD deaths (after the exclusion of NHS: RR=0.83; 95% CI, 0.73-0.94;after the exclusion of HPFS: RR=0.80; 95% CI, 0.70-0.92;and after the exclusion of MDC: RR=0.77; 95% CI, 0.67-0.87;all data included in this meta-analysis were presented in Tables IV through IV in the online-only Data Supplement of our article).Similar results were found for an increment of 5% energy from LA and risk of either CHD events or CHD deaths after the removal of 1 study at a time.Updated dietary data during follow-up, a large number of individuals followed up for a long time, and high rates of follow-up distinguished NHS and HPFS from other cohorts. 2 Stronger associations for LA and either CHD events or CHD deaths were observed in categorical analyses (ie, highest versus lowest categories) than continuous analyses.We used the median intake of LA in each tertile or quintile to calculate the RRs for each 5% energy from LA.Because the cut points for the categories of LA differed somewhat across different studies, the estimates from the categorical analyses were more approximate, whereas the estimates from continuous analyses were more comparable across studies and hence more accurate.Via direct investigator communication, we had a unique opportunity to evaluate the association between LA intake and CHD morbidity and mortality in the largest and most complete systematic review and meta-analysis to date.Based on a funnel plot and the Begg test, no significant publication bias was noted.In addition, these robust inverse associations were not dependent on an individual study.Overall, our results are consistent with an earlier pooled analysis of the primary individual data from 11 cohort studies on LA and CHD risk 3 and a meta-analysis of randomized, clinical trials that showed a 10% lower CHD risk (RR=0.90;95% CI, 0.83-0.97)for each 5% energy increment in polyunsaturated fat intake. 4Although different dietary sources of LA might affect the relation between LA and CHD events, the cardioprotective effect of specific foods high in LA was not the subject of this meta-analysis and should be addressed in future work.

This Article describes the relationship between molecular structure, and the rectification of tunneling current, in tunneling junctions based on self-assembled monolayers (SAMs). Molecular dipoles from simple organic functional groups (amide, urea, and thiourea) were introduced into junctions with the structure AgᵀS/S(CH₂)ₙR(CH₂)ₘCH₃//Ga₂O₃/EGaIn. Here, R is an n-alkyl fragment (−CH₂−)₂ ₒᵣ ₃, an amide group (either −CONH– or −NHCO−), a urea group (−NHCONH−), or a thiourea group (−NHCSNH−). The amide, urea, or thiourea groups introduce a localized electric dipole moment into the SAM and change the polarizability of that section of the SAM, but do not produce large, electronically delocalized groups or change other aspects of the tunneling barrier. This local change in electronic properties correlates with a statistically significant, but not large, rectification of current (r⁺) at ±1.0 V (up to r⁺ ≈ 20). The results of this work demonstrate that the simplest form of rectification of current at ±1.0 V, in EGaIn junctions, is an interfacial effect, and is caused by a change in the work function of the SAM-modified silver electrode due to the proximity of the dipole associated with the amide (or related) group, and not to a change in the width or mean height of the tunneling barrier.

Abstract Markers of biological ageing have potential utility in primary care and public health. We developed an elastic net regression model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum (almost 100,000 features assayed), within a large sample (N=2,239) from the UK occupational Airwave cohort. We investigated the determinants of accelerated ageing, including genetic, lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (r=0.85 in independent test set). Increased metabolomic age acceleration (mAA) was associated (p<0.0025) with overweight/obesity and depression and nominally associated (p<0.05) with high alcohol use and low income. DNA methylation age acceleration (N=1,102) was nominally associated (p<0.05) with high alcohol use, anxiety and post-traumatic stress disorder, but not correlated with mAA. Biological age acceleration may present an important mechanism linking psycho-social stress to age-related disease.

Additional file 8: Table S6A-C. Associations between DNA methylation and BMI in children, excluding studies with > 30% overweight or obesity. Results for CpGs with p-values < 1x10-4 are shown.

Composite stamps composed of two layersa stiff layer supported by a flexible layerextend the capabilities of soft lithography to the generation of 50−100-nm features. The preparation of these stamps was adapted from a procedure originally developed by Schmid et al. (Macromolecules 2000, 33, 3042) for microcontact printing. This paper demonstrates how pattern transfer using other soft lithographic techniquesmicromolding in capillaries, microtransfer molding, and phase-shifting lithographycan be improved using two-layer stamps relative to stamps made of Sylgard 184 poly(dimethylsiloxane).

Avoiding adult weight gain itself may confer protection against certain types of cancers, particularly among HRT nonusers.

Background: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for cardiovascular disease (CVD). Whether healthy lifestyle practices can mitigate this risk is unclear. Aims: To prospectively assess associations of healthy lifestyle factors with CVD risk in women with a history of GDM. Methods: We included 4,372 women from the Nurses’ Health Study II with a prior clinician diagnosis of GDM who were free of cancer or CVD at the time of the index pregnancy. Healthy lifestyle factors, which were updated every 2-4 years, included non-current smoking, body mass index<25 kg/m 2 , regular physical activity (>500 MET-min/week), high-quality diet (above median on the Alternative Healthy Eating Index), and moderate alcohol consumption (>0-15 g/day). A composite outcome of CVD was defined as the combination of nonfatal/fatal myocardial infarction (MI), stroke, angiographically confirmed angina, and coronary artery bypass surgery or angioplasty/stenting. Multivariate-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: During a median 28 years of follow-up, 179 incident CVD events were ascertained. Compared to women with 0 or 1 healthy lifestyle factor, HR (95% CI) for risk of CVD among those who had 2, 3, and ≥4 factors were 1.02 (0.68, 1.53), 0.45 (0.28, 0.74), and 0.32 (0.18, 0.60), respectively ( P trend < 0.001) ( Table 1 ). Similar results were observed for clinical CVD events (nonfatal/fatal MI or stroke) and total MI. When modeled continuously, each additional healthy lifestyle factor was associated with a lower risk of the composite outcome, HR (95% CI): 0.67 (0.57, 0.80); clinical CVD, HR (95% CI): 0.74 (0.58, 0.94); and MI, HR (95% CI): 0.61 (0.43, 0.86). We estimated that 62.5% (95% CI: 34.9%, 79.0%) of the CVD risk in this population was potentially avoidable with adherence to ≥4 healthy lifestyle factors. Conclusion: Greater adherence to healthy lifestyle factors was associated with a significant reduction in CVD risk in women with a history of GDM.

Additional file 10: Table S8. Look-up of the CpGs associated with BMI in previously reported candidate gene studies and smaller EWAS (N

Recent studies suggest that meal frequencies influence the risk of obesity in children and adolescents. It has also been shown that multiple genetic loci predispose to obesity already in youth. However, it is unknown whether meal frequencies could modulate the association between single nucleotide polymorphisms (SNPs) and the risk of obesity. We examined the effect of two meal patterns on weekdays -5 meals including breakfast (regular) and ≤ 4 meals with or without breakfast (meal skipping) - on the genetic susceptibility to increased body mass index (BMI) in Finnish adolescents. Eight variants representing 8 early-life obesity-susceptibility loci, including FTO and MC4R, were genotyped in 2215 boys and 2449 girls aged 16 years from the population-based Northern Finland Birth Cohort 1986. A genetic risk score (GRS) was calculated for each individual by summing the number of BMI-increasing alleles across the 8 loci. Weight and height were measured and dietary data were collected using self-administered questionnaires. Among meal skippers, the difference in BMI between high-GRS and low-GRS (<8 and ≥ 8 BMI-increasing alleles) groups was 0.90 (95% CI 0.63,1.17) kg/m(2), whereas in regular eaters, this difference was 0.32 (95% CI 0.06,0.57) kg/m(2) (p interaction = 0.003). The effect of each MC4R rs17782313 risk allele on BMI in meal skippers (0.47 [95% CI 0.22,0.73] kg/m(2)) was nearly three-fold compared with regular eaters (0.18 [95% CI -0.06,0.41] kg/m(2)) (p interaction = 0.016). Further, the per-allele effect of the FTO rs1421085 was 0.24 (95% CI 0.05,0.42) kg/m(2) in regular eaters and 0.46 (95% CI 0.27,0.66) kg/m(2) in meal skippers but the interaction between FTO genotype and meal frequencies on BMI was significant only in boys (p interaction = 0.015). In summary, the regular five-meal pattern attenuated the increasing effect of common SNPs on BMI in adolescents. Considering the epidemic of obesity in youth, the promotion of regular eating may have substantial public health implications.

BACKGROUND: Emerging evidence has implicated gut microbiota in type 2 diabetes (T2D); and recent studies have associated gut microbiota metabolites including choline, betaine and trimethylamine‐N‐oxide (TMAO), with cardiovascular disease, obesity, and other diabetes risk factors. Little is known about the association between the major diet sources of these metabolites and T2D. OBJECTIVE: The objective was to evaluate the associations of diet sources of gut microbial metabolites, including phosphatidylcholine, other choline‐containing components, and betaine with incident T2D METHODS: We followed 69, 993 women from the Nurses' Health Study (NHS 1980‐2008), 89, 337 women from NHS II (1991‐2009) and 37,481 men from the Health Professionals Follow‐up Study (1986‐2008) who were free of diabetes, cardiovascular disease and cancer at baseline. RESULTS: We documented in total 14, 370 incident cases of T2D during 18‐28 years of follow‐up in the three cohorts. Comparing to individuals in the lowest quintile of dietary phosphatidylcholine intakes, the multivariate adjusted relative risk (RR; 95% confident interval (CI)) of T2D associated with the highest quintile of intake was 1.33 (1.20‐1.47) in NHS, 1.34 (1.17‐1.53) in NHS II and 1.18 (1.02‐1.37) in HPFS, resulted in a pooled RR of 1.30 (1.21‐1.39%). Dietary free choline, choline from glycerophocholine, and betaine were all consistently associated with reduced risk of T2D, while choline from sphingomyelin associated with increased risk of T2D, with RRs (95% CI) of 0.84 (0.77‐0.91), 0.88 (0.82‐0.94), 0.88 (0.83‐0.94) and 1.11 (1.00‐1.22), respectively, in the pooled analysis of the three cohorts, comparing the highest to the lowest quintiles of intakes. CONCLUSION: our data provide consistent evidence from the three separate cohorts that diet major sources of gut microbiota metabolites are related to risk of T2D. Grant Funding Source : CA87969, CA176726, and CA167552 from NIH

Single-source molecular precursors were used to synthesize II-VI compound semiconductor nanowires for the first time. Cadmium sulfide and zinc sulfide nanowires were prepared using cadmium diethyldithiocarbamate, Cd(S2CNEt2)2, and zinc diethyldithiocarbamate, Zn(S2CNEt2)2, respectively, as precursors in a gold nanocluster-catalyzed vapor-liquid-solid growth process. High-resolution transmission electron microscopy studies show that the CdS and ZnS nanowires are single-crystal wurtzite structures with stoichiometric compositions. In addition, photoluminescence measurements demonstrate that these nanowires exhibit high-quality optical properties. The applicability of our approach to the synthesis of other compound and alloy semiconductors nanowires as well as nanowire heterostructures of these materials is discussed.