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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/m2, whereas in regular eaters, this difference was 0.32 (95% CI 0.06,0.57) kg/m2 (pinteraction = 0.003). The effect of each MC4R rs17782313 risk allele on BMI in meal skippers (0.47 [95% CI 0.22,0.73] kg/m2) was nearly three-fold compared with regular eaters (0.18 [95% CI -0.06,0.41] kg/m2) (pinteraction = 0.016). Further, the per-allele effect of the FTO rs1421085 was 0.24 (95% CI 0.05,0.42) kg/m2 in regular eaters and 0.46 (95% CI 0.27,0.66) kg/m2 in meal skippers but the interaction between FTO genotype and meal frequencies on BMI was significant only in boys (pinteraction = 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.

Context:Maternal hypothyroidism during pregnancy is associated with adverse neuropsychological development in the offspring.

We investigate tunable hole quantum dots defined by surface gating $\mathrm{Ge}/\mathrm{Si}$ core-shell nanowire heterostructures. In single level Coulomb-blockade transport measurements at low temperatures spin doublets are found, which become sequentially filled by holes. Magnetotransport measurements allow us to extract a $g$ factor ${g}^{*}\ensuremath{\approx}2$ close to the value of a free spin-$1/2$ particle in the case of the smallest dot. In less confined quantum dots smaller $g$ factor values are observed. This indicates a lifting of the expected strong spin-orbit interaction effects in the valence band for holes confined in small enough quantum dots. By comparing the excitation spectrum with the addition spectrum we tentatively identify a hole exchange interaction strength $\ensuremath{\chi}\ensuremath{\approx}130\text{ }\text{ }\ensuremath{\mu}\mathrm{eV}$.

Background: Whether changes in consumption of sugary beverages or artificially sweetened beverages (ASBs) are associated with type 2 diabetes (T2D) risk has never been evaluated. Objective: We evaluated the association of changes in sugary beverage and ASB consumption over a 4-year period with subsequent 4-year risk of T2D among U.S. women and men. Methods: We followed-up 78,357 women in the Nurses’ Health Study (1986-2012), 82,937 women in the Nurses’ Health Study II (1991-2013) and 35,148 men in the Health Professionals Follow-up Study (1986-2012). Beverage intakes were assessed using validated food frequency questionnaires every 4 years. Cox proportional regression models were used to calculate hazard ratios (HRs) for T2D regarding 4-year changes in beverage consumption, adjusted for initial beverage intake and BMI. Results of the 3 cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. Results: During 2,849,389 person-years of follow-up, we documented 12,007 incident cases of T2D. Increasing sugary beverage intake by &amp;gt;0.5 serving/day over a 4-year period was associated with a 14% (95% CI: 7%, 21%) higher T2D risk compared with maintaining a stable consumption. Both beverages with added sugars (e.g., soft drinks) and 100% fruit juices were associated with higher T2D risk. Increasing ASB consumption by &amp;gt;0.5 serving/day was associated with a 19% (95% CI: 12%, 27%) higher T2D risk. Substituting ASB for sugary beverages was not associated with subsequent T2D risk (HR: 0.99, 95% CI: 0.96, 1.02). However, decreasing sugary beverage consumption and increasing water, coffee or tea intake by 1 serving/day was associated with a 3% to 11% lower risk of T2D. Conclusion: Increasing consumption of sugary beverages or ASBs was associated with a higher risk of T2D compared with maintaining a stable consumption of these beverages. Substituting water, coffee or tea but not ASB for sugary beverages was associated with lower T2D risk. Disclosure J. Drouin-Chartier: Other Relationship; Self; Dairy Farmers of Canada. Y. Zheng: None. Y. Li: None. V. Malik: None. A. Pan: None. J.E. Manson: None. W.C. Willett: None. F. Hu: None. Funding National Institutes of Health (UM1CA186107, UM1CA176726, UM1CA167552, DK112940, HL60712, HL118264); Canadian Institutes of Health Research (BPF-156628)

Self-assembled monolayers (SAMs), prepared by reaction of terminal n-alkynes (HC≡C(CH2)nCH3, n = 5, 7, 9, and 11) with Au(111) at 60 °C were characterized using scanning tunneling microscopy (STM), infrared reflection absorption spectroscopy (IRRAS), X-ray photoelectron spectroscopy (XPS), and contact angles of water. In contrast to previous spectroscopic studies of this type of SAMs, these combined microscopic and spectroscopic experiments confirm formation of highly ordered SAMs having packing densities and molecular chain orientations very similar to those of alkanethiolates on Au(111). Physical properties, hydrophobicity, high surface order, and packing density, also suggest that SAMs of alkynes are similar to SAMs of alkanethiols. The formation of high-quality SAMs from alkynes requires careful preparation and manipulation of reactants in an oxygen-free environment; trace quantities of O2 lead to oxidized contaminants and disordered surface films. The oxidation process occurs during formation of the SAM by oxidation of the −C≡C– group (most likely catalyzed by the gold substrate in the presence of O2).

AbstractThe distribution of personality disorders (PDs) was explored in hospital-treated subjects and in a population subsample. This study forms a part of the Northern Finland 1966 Birth Cohort study. Hospital case records of psychiatric treatment periods of all cohort members (n=11 017) were reviewed and re-checked against DSM-III-R criteria. A subsample of the cohort members living in Oulu (n=1609) were invited to a two-stage psychiatric field survey with Structured Clinical Interview for DSM-III-R (SCID) as a diagnostic method. The most common PDs in hospital-treated sample were cluster B PDs (erratic). In the population subsample, cluster C PDs (anxious) formed the majority.Cohort studyEpidemiologyPersonality disordersSCID

Aims Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase (LPL) and represent emerging drug targets to lower circulating triglycerides and reduce cardiovascular risk. To investigate the molecular effects of genetic mimicry of ANGPTL3 and ANGPTL4 inhibition and compare them to the effects of genetic mimicry of LPL enhancement. Methods and results Associations of genetic variants in ANGPTL3 (rs11207977-T), ANGPTL4 (rs116843064-A), and LPL (rs115849089-A) with an extensive serum lipid and metabolite profile (208 measures) were characterized in six cohorts of up to 61 240 participants. Genetic associations with anthropometric measures, glucose-insulin metabolism, blood pressure, markers of kidney function, and cardiometabolic endpoints via genome-wide summary data were also explored. ANGPTL4 rs116843064-A and LPL rs115849089-A displayed a strikingly similar pattern of associations across the lipoprotein and lipid measures. However, the corresponding associations with ANGPTL3 rs11207977-T differed, including those for low-density lipoprotein and high-density lipoprotein particle concentrations and compositions. All three genotypes associated with lower concentrations of an inflammatory biomarker glycoprotein acetyls and genetic mimicry of ANGPTL3 inhibition and LPL enhancement were also associated with lower C-reactive protein. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower waist-to-hip ratio, improved insulin-glucose metabolism, and lower risk of coronary heart disease and type 2 diabetes, whilst genetic mimicry of ANGPTL3 was associated with improved kidney function. Conclusions Genetic mimicry of ANGPTL4 inhibition and LPL enhancement have very similar systemic metabolic effects, whereas genetic mimicry of ANGPTL3 inhibition showed differing metabolic effects, suggesting potential involvement of pathways independent of LPL. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower risk of coronary heart disease and type 2 diabetes. These findings reinforce evidence that enhancing LPL activity (either directly or via upstream effects) through pharmacological approaches is likely to yield benefits to human health.

Abstract Background Lipids are proposed to be important in developing adaptive immunity and allergy. However, studies to date reported inconsistent findings. Objective To examine newborn lipidome (a comprehensive profiling of circulating lipid metabolites) on child's risk of developing food allergy (FA). The maternal‐cord joint effects of lipid metabolites on FA development were also investigated. Methods This study included 647 mother‐child pairs from the Boston Birth Cohort and analyzed 202 lipid metabolites in cord plasma profiled by liquid chromatography tandem mass spectrometry. FA was defined based on standard clinical criteria. Logistic regression was applied to examine the relationships between individual metabolites and risk of FA. Results Of the 647 children, 61 developed FA. Cord triacylglycerols of long carbon chains and multiple double bonds were significantly associated with decreased risk of FA. These associations were comparable across strata of pertinent maternal and child covariates, and were independent of maternal triacylglycerols when assessed simultaneously. Besides, cord and maternal triacylglycerols had an additive effect in association with risk of FA: Children having high (≥Median) C56:8 triacylglycerol levels in both cord and maternal plasma were at the lowest risk of developing FA (OR = 0.24, 95% CI = 0.10–0.56, p = .001), compared to those having low levels in both cord and maternal plasma. Conclusion This is the first birth cohort study to link altered cord plasma lipidome with future risk of development FA during childhood. It calls for further investigation on triacylglycerols of long carbon chains and multiple double bonds as potential novel predictive biomarkers and therapeutic targets for FA.

Silicon nanowires (NWs) could enable low-cost and efficient photovoltaics, though their performance has been limited by nonideal electrical characteristics and an inability to tune absorption properties. We overcome these limitations through controlled synthesis of a series of polymorphic core/multishell NWs with highly crystalline, hexagonally-faceted shells, and well-defined coaxial ( p / n ) and p / intrinsic / n ( p / i / n ) diode junctions. Designed 200–300 nm diameter p / i / n NW diodes exhibit ultralow leakage currents of approximately 1 fA, and open-circuit voltages and fill-factors up to 0.5 V and 73%, respectively, under one-sun illumination. Single-NW wavelength-dependent photocurrent measurements reveal size-tunable optical resonances, external quantum efficiencies greater than unity, and current densities double those for silicon films of comparable thickness. In addition, finite-difference-time-domain simulations for the measured NW structures agree quantitatively with the photocurrent measurements, and demonstrate that the optical resonances are due to Fabry-Perot and whispering-gallery cavity modes supported in the high-quality faceted nanostructures. Synthetically optimized NW devices achieve current densities of 17 mA/cm 2 and power-conversion efficiencies of 6%. Horizontal integration of multiple NWs demonstrates linear scaling of the absolute photocurrent with number of NWs, as well as retention of the high open-circuit voltages and short-circuit current densities measured for single NW devices. Notably, assembly of 2 NW elements into vertical stacks yields short-circuit current densities of 25 mA/cm 2 with a backside reflector, and simulations further show that such stacking represents an attractive approach for further enhancing performance with projected efficiencies of &gt; 15% for 1.2 μm thick 5 NW stacks.

Background The 2010 Dietary Guidelines for Americans recommend breakfast for children but found insufficient evidence to make recommendations for adult eating habits (the timing and frequency of meals, snacks, and caloric beverages). Objective To conduct the first long‐term prospective study of eating habits and risk of incident coronary heart disease (CHD) in women. Methods Eating habits including breakfast eating and eating frequency were assessed in 2002 in 56,593 women from the Nurses' Health Study who were free of cardiovascular disease and cancer. During 8 years of follow‐up, 770 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for CHD, adjusted for demographics, diet, lifestyle, and other CHD risk factors. Results Among women less than 60 years old, those who skipped breakfast regularly had a higher risk of CHD (RR=3.82, 95% CI:1.07‐13.67) as compared to women who ate breakfast at least 5 times/week. However, this association was not present among women 60 years or over (RR=0.98, 95% CI:0.74‐1.30) (p, interaction = 0.05). No associations were observed between eating frequency (times/day) and risk of CHD. Conclusion Eating breakfast was associated with a lower CHD risk in women under 60 years of age, but not in older women. Support NIH Grants CA176726, HL034594

Objective Women with a history of gestational diabetes mellitus (GDM) have an exceptionally high risk for type 2 diabetes (T2D). Yet, little is known about genetic determinants for T2D in this population. We examined the association of a genetic risk score (GRS) with risk of T2D in two independent populations of women with a history of GDM and how this association might be modified by non-genetic determinants for T2D. Research design and methods This cohort study included 2434 white women with a history of GDM from the Nurses’ Health Study II (NHSII, n=1884) and the Danish National Birth Cohort (DNBC, n=550). A GRS for T2D was calculated using 59 candidate single nucleotide polymorphisms for T2D identified from genome-wide association studies in European populations. An alternate healthy eating index (AHEI) score was derived to reflect dietary quality after the pregnancy affected by GDM. Results Women on average were followed for 21 years in NHSII and 13 years in DNBC, during which 446 (23.7%) and 155 (28.2%) developed T2D, respectively. The GRS was generally positively associated with T2D risk in both cohorts. In the pooled analysis, the relative risks (RRs) for increasing quartiles of GRS were 1.00, 0.97, 1.25 and 1.19 (p trend=0.02). In both cohorts, the association appeared to be stronger among women with poorer (AHEI &lt;median) than better dietary quality (AHEI ≥median), although the interaction was not significant. For example, in NHSII, the RRs across increasing quartiles of GRS were 1.00, 0.99, 1.51 and 1.29 (p trend=0.06) among women with poorer dietary quality and 1.00, 0.83, 0.81 and 0.94 (p trend=0.79) among women with better dietary quality (p interaction=0.11). Conclusions Among white women with a history of GDM, higher GRS for T2D was associated with an increased risk of T2D.