Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P = 1.9×10−32) and in the IL1 gene family region of chromosome 2 for IL-1ra (rs6743376, P = 2.3×10−26). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P = 2.7×10−19). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4.

Objective: This paper describes the development and ef®cacy of a diet quality index (DQI) for China. Design: The Dietary Guidelines for Chinese Residents motivated the selection of 10 DQI components. These components were weighted and assigned cut-offs and point schemes based on the Chinese Food Guide Pagoda, Chinese andaor international dietary reference values. The ef®cacy of resulting DQI scores was assessed relative to a priori expectations. Subjects: The Chinese DQI was evaluated using cross-sectional 3 day diet record and anthropometric data on 7450 adults from the 1991 China Health and Nutrition Survey. Methods: For each individual, a DQI total score was calculated as the sum of components, and DQI pattern scores calculated to re¯ect the underlying composition of diet quality problems. The DQI scores were compared with component scores, food and nutrient intake, weight status and sociodemographic variables. Results: The total DQI score simultaneously represented all component aspects of diet quality as well as micronutrients not explicitly built into the index. The total DQI score was signi®cantly correlated with food and nutrient intakes, BMI, urban residence and income. The DQI pattern scores correlated with DQI components and weight status as expected. Conclusions: The China DQI captures variation along several components of diet quality, appears sensitive to under-and overnutrition, as well as sociodemographic variables. The China DQI may prove useful for monitoring the nutrition transition and epidemiologic trends in China. Sponsorship: National Institutes of Health (HD 38700 and R01-HD30880) and the Chinese Academy of Preventive Medicine. Descriptors: China; dietary intake; diet quality

OBJECTIVE:To investigate the effect of adjusting for differences in timing of maturation when assessing overweight prevalence among adolescents in different populations by using an international reference recommended by the WHO. DESIGN: Cross-sectional, comparative study in three large samples from China, Russia and the United States. SUBJECTS: A total of 2014 American, 1316 Chinese and 744 Russian non-pregnant adolescent girls aged 10 ± 18 y. MEASUREMENTS: Data on body weight, height, menarcheal status and age at menarche (AAM) were collected. Overweight was de®ned as age-sex-speci®c body mass index (BMI) greater than the 85th percentiles from the US NHANES I data (collected in 1971 ± 1974), which is recommended by the WHO for international use. Maturity adjustments were made using population differences in median age at menarche (MAM), calculated using the status quo method. MAM was 12.8 in the WHO reference population, 13.7 in China, 13.2 in Russia, and 12.6 in the US (NHANES III data). Maturation age-matched BMI cut-offs were used to compute the adjusted prevalence. We also compared population-adjusted results with individually adjusted results in post-menarcheal American girls (based on each girl's AAM) and in pre-menarcheal girls (based on breast stage). RESULTS: Maturity adjustment increased the estimated prevalence of overweight in China and Russia where girls mature later than the reference population, and decreased it in the NHANES III sample. The unadjusted and adjusted prevalence was 3.5 vs 4.9% in the China sample, 8.3 vs 9.7% in Russia, and 29.2 vs 28.0% in the US. The adjustment had a greater effect in younger adolescent girls (10 ± 13 y) than in older girls (14 ± 18 y). In general, we found a good agreement between the population and individual adjustments. Viewing the individual adjustment as a`gold standard', the population method has a high sensitivity and speci®city. CONCLUSION: This is the ®rst study to assess WHO recommendations for maturation adjustment when estimating overweight prevalence in different countries. While the overall effects of adjustment are small, maturation status should be considered, particularly when assessing young adolescents, and populations with markedly different timing of maturation relative to the international reference. Population-based adjustment is useful and practical in situations where individual maturity data are not available.

In recent years, there has been a dramatic increase in the use of poly(dimethylsiloxane) (PDMS) devices for cell-based studies. Commonly, the negative tone photoresist, SU8, is used to pattern features onto silicon wafers to create masters (SU8-Si) for PDMS replica molding. However, the complexity in the fabrication process, low feature reproducibility (master-to-master variability), silane toxicity, and short life span of these masters have been deterrents for using SU8-Si masters for the production of cell culture based PDMS microfluidic devices. While other techniques have demonstrated the ability to generate multiple devices from a single master, they often do not match the high feature resolution ($0.1 lm) and low surface roughness that soft lithography masters offer. In this work, we developed a method to fabricate epoxy-based masters that allows for the replication of features with high fidelity directly from SU8-Si masters via their PDMS replicas. By this method, we show that we could obtain many epoxy based masters with equivalent features to a single SU8-Si master with a low feature variance of 1.54%. Favorable feature transfer resolutions were also obtained by using an appropriate Tg epoxy based system to ensure minimal shrinkage of features ranging in size from $100 lm to <10 lm in height. We further show that surface coating epoxy masters with Cr/Au lead to effective demolding and yield PDMS chambers that are suitable for long-term culturing of sensitive primary hippocampal neurons. Finally, we incorporated pillars within the Au-epoxy masters to eliminate the process of punching media reservoirs and thereby reducing substantial artefacts and wastage. V C 2015 AIP Publishing LLC. [http://dx

Summary Background While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z‐score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence. Objectives We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS). Methods We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS). Results We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni‐corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%). Conclusion Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.