Publications

Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate gene for coronary heart disease (CHD) because of its impact on eNOS activity. We systematically examined the associations of eight variants of the eNOS gene (two potentially functional variants [−786T>C and Glu298Asp] and six tagging single nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients. Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up Study, 220 developed CHD, and 641 men without cardiovascular disease were used as control subjects. Genotype distributions of −786T>C and Glu298Asp polymorphisms were not significantly different between case and control subjects. CHD risk was significantly higher among men with the variant allele at the rs1541861 locus (intron 8 A/C) than men without it (adjusted odds ratio 1.5 [95% confidence interval 1.1–2.1]). Moreover, among control subjects, plasma soluble vascular cell adhesion molecule concentrations were significantly higher among carriers of this allele (P 0.019) and carriers of the variant allele of the −786T>C (P 0.010), or the Glu298Asp polymorphism (P 0.002), compared with noncarriers. In conclusion, our data suggested that −786T>C, Glu298Asp, and an intron 8 polymorphism of the eNOS gene are potentially involved in the atherogenic pathway among U.S. diabetic men.

Abstract Background People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for prevention of T2D in South Asians, that are cost-effective, generalisable and scalable across settings. Hypothesis Compared to usual care, risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12 month lifestyle modification programme delivered by community health workers. Design Cluster randomised clinical trial (1:1 allocation to Intervention or Usual care), carried out in India, Pakistan, Sri Lanka, and UK, with 30 sites per country (120 sites total). Target recruitment 3,600 (30 participants per site) with annual follow-up for three years. Entry criteria South Asian, men or women, age 40-70 years with i. Central obesity (waist circumference ≥100cm in India and Pakistan; ≥90cm in Sri Lanka) and / or ii. Prediabetes (HbA1c 6.0-6.4% inclusive). Exclusion criteria: known type 1 or 2 diabetes, normal or underweight (body mass index<22kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; serious illness. Endpoints The primary end point is new onset T2D at 3 years, defined as: i. HbA1c≥6.5% or ii. Physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are: i. Physical measures: waist circumference, weight and blood pressure; ii. Lifestyle measures: smoking status, alcohol intake, physical activity, dietary intake; iii. Biochemical measures: Fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and iv. Treatment compliance. Intervention Lifestyle intervention (60 sites) or Usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one session, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving e a 7% reduction in body mass index and a 10 cm reduction in waist circumference through i. improved diet and ii. increased physical activity. Usual care comprised a single 30 minute session of lifestyle modification advice from the community health worker. Results We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom, 3,682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between Intervention and Usual care sites. More than 90% of follow-up visits are scheduled to be complete December 2020. Based on follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). Conclusion The iHealth-T2D study will advance understanding of strategies for prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB approval 16/WM/0171 Trial registration EudraCT 2016-001350-18. Registered 14 April 2016 https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/ihealth-t2d/ ; ClinicalTrials.gov NCT02949739 . Registered 31 October 2016, https://clinicaltrials.gov/ct2/show/NCT02949739 , First posted 31/10/2016. Funder European Commission (award 643774) and National Institute for Health Research (award 16/136/68)

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

Several non-photolithographic methods for growing patterned films of parylene-based polymers prepared by chemical vapor deposition are presented. These patterns were generated using transition metals and metal salts known to inhibit polymer deposition, in combination with alkanethiols deposited by microcontact printing. By patterning the alkanethiols on gold or silver surfaces, well-defined selectively grown structures of vapor-deposited parylene-N and parylene-C were realized, with lateral dimensions ranging from 1.5 to 35 μm. Using carboxylic acid-terminated alkanethiols deposited by microcontact printing to define regions of iron salt exposure on the surface, selectively grown films of poly(p-phenylene vinylene) were generated, with features having lateral dimensions of 12.5 μm separated by 2.5 μm, and thicknesses of 750 Å. The structures fabricated with this approach have dimensions relevant to applications in microelectromechanical systems and polymer-based displays.

No abstract is provided for this article.

<h3>Background and aims</h3> Severely preterm birth is associated with low physical activity and cardiorespiratory fitness. We studied the association of gestational age across its full range with physical activity (self-reported) and cardiorespiratory fitness in adolescence. <h3>Methods</h3> Of the 16-year-old members of the population-based Northern Finland Birth Cohort 1986, 6675 singletons with no major physical disability reported the amount of light, brisk and commuting physical activity outside school hours and 4706 completed a submaximal cycle ergometer test for the assessment of cardiorespiratory fitness. Physical activity was summarised as metabolic equivalent hours (METhours) per week and peak oxygen uptake relative to body weight (ml/kg/min) calculated by heart rate responses. To assess the effect of gestational age on the outcomes, the adequate data were analysed by multiple linear regression. <h3>Results</h3> There was an inverse U-shaped association between gestational age and physical activity such that adolescents born at both ends of the full range of gestational age undertook less physical activity than others (Figure). These adolescents also seemed to have low cardiorespiratory fitness; however only the linear inverse trend was statistically significant (Figure), suggesting low fitness in those born later gestational ages. <h3>Conclusion</h3> Our results are consistent with previous findings of low levels of physical activity in adolescents born severely preterm. We found no evidence of low physical activity and fitness among adolescents born less preterm. Our results also suggest lower physical activity and fitness among adolescents born at later gestational ages; this was post hoc and requires replication.