A widely distributed gene cluster compensates for uricase loss in hominids.

Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

Language acquisition in a multilingual society: English vocabulary norms and predictors in Singaporean children.

In this study, infant vocabulary development was tracked in a multilingual society (Singapore) within a socioeconomically diverse sample. The sample comprised 1316 infants from 17.4 to 27.7 months (669 females, 647 males; 88% Chinese race, 4% Malay, 4% Indian, and 0.004% mixed-race [4% declined to provide race information]). Children varied in English language exposure and socioeconomic status. Analyses focused on identifying demographic predictors of English vocabulary size in multilingually exposed infants. Adaptations of the Macarthur-Bates Communicative Development Inventory for English, Mandarin, and Malay are provided as well as English vocabulary norms that account for variation in English exposure. This manuscript reports the first set of English language norms-calibrated to English exposure-for multilingual infants in a non-Western setting.

Prevalence and associated factors of sarcopenia in community-dwelling older adults at risk of malnutrition.

BACKGROUND: There is an increasingly strong association between sarcopenia and malnutrition in research findings. We aimed to determine the prevalence and factors associated with sarcopenia in community-dwelling older adults (≥ 65 years) at risk of malnutrition based on Malnutrition Universal Screening Tool (MUST). METHODS: This was a cross-sectional study of 811 participants. Participants were recruited from the general population, community centers, senior activity centers, polyclinics, and hospital. Community-dwelling older adults at risk of malnutrition participated in the study. Participants' data and measurements were collected at the baseline visit. Data included socio-demographic information, anthropometric measurements, body composition, dietary intakes, and functional assessments. Sarcopenia was defined using the Asian Working Group for Sarcopenia 2019 consensus. RESULTS: Of the 694 participants with complete datasets, overall prevalence of sarcopenia was 76% (n = 530); 57% (n = 393) had severe sarcopenia. In the overall cohort, compared to participants without sarcopenia, those with sarcopenia were older, had lower physical activity scale for the elderly score, leg strength, handgrip endurance, mid-upper arm circumference, calf circumference, and bone mass, and had lower dietary protein intake and poorer nutritional status (all p ≤ 0.015). After adjusting for confounders, sarcopenia was significantly associated with older age, male gender, higher risk of malnutrition, lower calf circumference, and lower bone mass (all p ≤ 0.044). CONCLUSIONS: In community-dwelling older adults at risk of malnutrition, there is a high prevalence of sarcopenia and severe sarcopenia. As such, screening positive for either malnutrition risk or sarcopenia in older adults should prompt screening for the other risk factor, to allow early institution of disease modifying interventions to forestall adverse outcomes for both malnutrition and sarcopenia. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov as NCT03245047 .

Milk and Plasma Lutein and Zeaxanthin Concentrations in Chinese Breast-Feeding Mother-Infant Dyads With Healthy Maternal Fruit and Vegetable Intake.

OBJECTIVES: While others have reported that milk from coastal Chinese women contains high levels of lutein and zeaxanthin, no research has determined the corresponding infant plasma response. Whether infant plasma levels increase commensurately provides important guidance for supplementation of these increasingly intriguing carotenoids in breast-feeding mothers and formula-fed infants. METHODS: Fifty-six mother-infant pairs with a maternal diet rich in eggs, green leafy vegetables, and fruit were enrolled between 6 and 16 weeks of lactation. Milk samples and blood samples from both the mother and infant were collected at entry. Maternal 3-day dietary records and a second milk sample were collected 1 to 3 weeks later. RESULTS: Mean milk lutein concentrations in samples 1 and 2 were 6.5 and 7.7 µg/dL (range 1-22.5 µg/dL), and for zeaxanthin, 1.6 and 1.7 µg/dL (range 1-5.9 µg/dL). Lutein concentrations in infant plasma (18.2 µg/dL) were similar to those in maternal plasma (21.6 µg/dL); zeaxanthin was lower than lutein in both maternal (3.1 µg/dL) and infant (2.9 µg/dL) plasma. Infant and maternal mean plasma lutein and zeaxanthin concentrations were higher than those in both milk samples 1 and 2 (lutein, 6.9 and 8.2 µg/dL; zeaxanthin, 1.9 and 2.0 µg/dL). Infant plasma lutein and zeaxanthin concentrations positively correlated with those in milk sample 1 (lutein, r2 = 0.15, p = 0.004; zeaxanthin, r2 = 0.21, p < 0.001). CONCLUSIONS: Together, these results reveal that high milk concentrations of lutein and zeaxanthin driven by healthy maternal intakes of xanthophyll rich foods are associated with high infant plasma concentrations. These findings will be useful for determining appropriate lutein fortification strategies. Clinical Study.gov registration number: NCT01669655.

Maternal nutritional adequacy and gestational weight gain and their associations with birth outcomes among Vietnamese women.

BACKGROUND: During pregnancy, a mother's nutritional needs increase to meet the added nutrient demands for fetal growth and development. An enhanced understanding of adequate nutrition and sufficient weight gain during pregnancy can guide development of policies and strategies for maternal nutrition care, actions that will ultimately promote better pregnancy outcomes. In a sample of pregnant women in Vietnam, this study characterized maternal nutrition status and gestational weight gain at a mid-pregnancy baseline, then examined the association of these variables with specific birth outcomes. METHODS: The study used baseline data from a randomized, controlled trial that compared pregnant Vietnamese women who received a nutritional intervention group with those who received only standard dietary counseling (control group). At baseline (26-29 weeks gestation), mothers' dietary reports were collected, and intake of 10 macro- and micronutrients was estimated; data for baseline gestational weight gain was collected for all pregnant women enrolled into the study (n = 228). This analysis also used weights, lengths, and head circumferences at birth for infants of mothers in the control group. RESULTS: At baseline, 95% of the pregnant women had concurrent inadequacies for more than five nutrients, and nearly half had concurrent inadequacies for more than ten nutrients. Almost two-thirds of the pregnant women did not meet recommendations for gestational weight gain. We found a significant, inverse association between the number of nutrient inadequacies and gestational weight gain (overall p ≤ 0.045). After adjusting for potential confounders, gestational weight gain was positively associated with birth weight, length at birth, birth weight-for-age z-score and length-for-age z-score (all p ≤ 0.006). CONCLUSIONS: Our findings raise concern over the high proportion of pregnant women in Vietnam who have multiple concurrent nutrient inadequacies and who fall short of meeting recommended gestational weight gain standards. To ensure better birth outcomes in this population, policies and strategies to improve the status of maternal nutrition are greatly needed. TRIAL REGISTRATION: The trial was retrospectively registered at clinicaltrials.gov on December 20, 2013, registration identifier: NCT02016586.

Chemistry-Wide Association Studies (CWAS): A Novel Framework for Identifying and Interpreting Structure-Activity Relationships.

Quantitative structure-activity relationships (QSAR) models are often seen as a "black box" because they are considered difficult to interpret. Meanwhile, qualitative approaches, e.g., structural alerts (SA) or read-across, provide mechanistic insight, which is preferred for regulatory purposes, but predictive accuracy of such approaches is often low. Herein, we introduce the chemistry-wide association study (CWAS) approach, a novel framework that both addresses such deficiencies and combines advantages of statistical QSAR and alert-based approaches. The CWAS framework consists of the following steps: (i) QSAR model building for an end point of interest, (ii) identification of key chemical features, (iii) determination of communities of such features disproportionately co-occurring more frequently in the active than in the inactive class, and (iv) assembling these communities to form larger (and not necessarily chemically connected) novel structural alerts with high specificity. As a proof-of-concept, we have applied CWAS to model Ames mutagenicity and Stevens-Johnson Syndrome (SJS). For the well-studied Ames mutagenicity data set, we identified 76 important individual fragments and assembled co-occurring fragments into SA both replicative of known as well as representing novel mutagenicity alerts. For the SJS data set, we identified 29 important fragments and assembled co-occurring communities into SA including both known and novel alerts. In summary, we demonstrate that CWAS provides a new framework to interpret predictive QSAR models and derive refined structural alerts for more effective design and safety assessment of drugs and drug candidates.

Dietary changes during pregnancy and the postpartum period in Singaporean Chinese, Malay and Indian women: the GUSTO birth cohort study.

OBJECTIVE: To examine changes in food consumption during pregnancy and the postpartum period in women of major Asian ethnic groups. DESIGN: Using interviewer-administered questionnaires, we assessed changes in food consumption during pregnancy (26-28 weeks' gestation) and the postpartum period (3 weeks after delivery) as compared with the usual pre-pregnancy diet. SETTING: Singapore. SUBJECTS: Pregnant women (n 1027) of Chinese, Malay and Indian ethnicity (mean age 30·4 (SD 5·2) years) who participated in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. RESULTS: During pregnancy, participants tended to increase their consumption of milk, fruit and vegetables and decrease their consumption of tea, coffee, soft drinks and seafood (all P < 0·001). Most participants reported adherence to traditional restrictions ('confinement') during the early postpartum period (Chinese: 94·8 %, Malay: 91·6 %, Indian: 79·6 %). During the postpartum period, participants tended to increase their consumption of fish and milk-based drinks and decrease their consumption of noodles, seafood, and chocolates and sweets (all P < 0·001). Ethnic differences in food consumption were pronounced during the postpartum period. For example, most Chinese participants (87·2 %) increased their ginger consumption during the postpartum period as compared with smaller percentages of Malays (31·8 %) and Indians (40·8 %; P for ethnic difference <0·001). Similar ethnic differences were observed for cooking wine/alcohol, herbs and spices, and herbal tea consumption. CONCLUSIONS: Marked changes in food consumption that reflect both modern dietary recommendations and the persistence of traditional beliefs were observed in Singaporean women during pregnancy and the postpartum period. Traditional beliefs should be considered in interventions to improve dietary intakes during these periods.

Effects of Oral Nutritional Supplement with ß-Hydroxy-ß-methylbutyrate (HMB) on Biochemical and Hematological Indices in Community-Dwelling Older Adults at Risk of Malnutrition: Findings from the SHIELD Study.

Malnutrition may result in abnormal biochemical and hematological indices. This planned prespecified analysis investigated the effects of a specialized oral nutritional supplement (ONS) on biochemical and hematological indices in community-dwelling older adults at risk of malnutrition. In the Strengthening Health in ELDerly through nutrition (SHIELD) study, 811 older adults aged 65 years and above took part in this randomized, double-blind, placebo-controlled, multi-center study. Participants were randomly allocated to either a complete and balanced specialized ONS (each serving provides 262 kcal, 10.5 g protein, 7.75 µg vitamin D3, and 0.74 g calcium ß-hydroxy-ß-methylbutyrate) and dietary counselling (intervention group) or a placebo and dietary counselling (placebo group). Both groups consumed study products twice a day for 180 days. Data were collected at baseline, day 90, and day 180. Blood analysis results at follow-up visits were analyzed using repeated measures analysis of covariance with adjustments for confounders. Overall, when compared with the placebo group, the intervention group showed significantly greater urea (6.0 mmol/L vs. 5.4 mmol/L, p < 0.001), urea to creatinine ratio (4.39 vs. 4.26, p < 0.001), prealbumin (24.9 mg/dL vs. 24.0 mg/dL, p < 0.001), vitamin B12 (480.0 pmol/L vs. 420.1 pmol/L, p < 0.001), and globulin levels (26.8 g/L vs. 26.5 g/L, p = 0.032). The intervention group also had a significantly higher absolute reticulocyte count (62.0 × 103/µL vs. 58.2 × 103/µL, overall p < 0.001) and mean platelet volume (10.0 fL vs. 9.9 fL, overall p = 0.003). Furthermore, significant improvements were seen in total protein at day 90 (71.7 g/L vs. 71.1 g/L, p = 0.017) and in absolute monocyte count at day 90 (0.50 × 103/µL vs. 0.47 × 103/µL, p = 0.009) in the intervention group. In conclusion, daily consumption of a specialized ONS for six months led to significant improvements in biochemical and hematological indices in community-dwelling older adults at risk of malnutrition.

Integrative chemical-biological read-across approach for chemical hazard classification.

Traditional read-across approaches typically rely on the chemical similarity principle to predict chemical toxicity; however, the accuracy of such predictions is often inadequate due to the underlying complex mechanisms of toxicity. Here, we report on the development of a hazard classification and visualization method that draws upon both chemical structural similarity and comparisons of biological responses to chemicals measured in multiple short-term assays ("biological" similarity). The Chemical-Biological Read-Across (CBRA) approach infers each compound's toxicity from both chemical and biological analogues whose similarities are determined by the Tanimoto coefficient. Classification accuracy of CBRA was compared to that of classical RA and other methods using chemical descriptors alone or in combination with biological data. Different types of adverse effects (hepatotoxicity, hepatocarcinogenicity, mutagenicity, and acute lethality) were classified using several biological data types (gene expression profiling and cytotoxicity screening). CBRA-based hazard classification exhibited consistently high external classification accuracy and applicability to diverse chemicals. Transparency of the CBRA approach is aided by the use of radial plots that show the relative contribution of analogous chemical and biological neighbors. Identification of both chemical and biological features that give rise to the high accuracy of CBRA-based toxicity prediction facilitates mechanistic interpretation of the models.

Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility.

Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML)-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (p(global) = 0.034) and endometrial (p(global) = 0.052) cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (p(global) = 0.008) and endometrial cancer (p(global) = 0.014). The sub-pathway association was validated in the Finnish sample of breast cancer (p(global) = 0.015). Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (p(global) = 0.0003). Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite genetic determinants related to the androgen-estrogen conversion are important for the induction of two hormone-associated cancers, particularly for the hormone-driven breast tumour subtypes.

Association of ESR1 gene tagging SNPs with breast cancer risk.

We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.

Predicting drug-induced hepatotoxicity using QSAR and toxicogenomics approaches.

Quantitative structure-activity relationship (QSAR) modeling and toxicogenomics are typically used independently as predictive tools in toxicology. In this study, we evaluated the power of several statistical models for predicting drug hepatotoxicity in rats using different descriptors of drug molecules, namely, their chemical descriptors and toxicogenomics profiles. The records were taken from the Toxicogenomics Project rat liver microarray database containing information on 127 drugs ( http://toxico.nibio.go.jp/datalist.html ). The model end point was hepatotoxicity in the rat following 28 days of continuous exposure, established by liver histopathology and serum chemistry. First, we developed multiple conventional QSAR classification models using a comprehensive set of chemical descriptors and several classification methods (k nearest neighbor, support vector machines, random forests, and distance weighted discrimination). With chemical descriptors alone, external predictivity (correct classification rate, CCR) from 5-fold external cross-validation was 61%. Next, the same classification methods were employed to build models using only toxicogenomics data (24 h after a single exposure) treated as biological descriptors. The optimized models used only 85 selected toxicogenomics descriptors and had CCR as high as 76%. Finally, hybrid models combining both chemical descriptors and transcripts were developed; their CCRs were between 68 and 77%. Although the accuracy of hybrid models did not exceed that of the models based on toxicogenomics data alone, the use of both chemical and biological descriptors enriched the interpretation of the models. In addition to finding 85 transcripts that were predictive and highly relevant to the mechanisms of drug-induced liver injury, chemical structural alerts for hepatotoxicity were identified. These results suggest that concurrent exploration of the chemical features and acute treatment-induced changes in transcript levels will both enrich the mechanistic understanding of subchronic liver injury and afford models capable of accurate prediction of hepatotoxicity from chemical structure and short-term assay results.

Prevalence of low muscle mass and associated factors in community-dwelling older adults in Singapore.

The population is rapidly aging worldwide, and there is an age-related decline in muscle mass. Therefore, it is important to examine the prevalence and associated factors of low appendicular skeletal muscle mass index (ASMI) in older adults. The objectives of this cross-sectional study were (i) to determine the prevalence of low ASMI (ASM/height2) and (ii) to identify factors associated with low ASMI. This study included 1211 community-dwelling adults aged ≥ 65 years. Low ASMI was defined as < 7.0 kg/m2 in males and < 5.7 kg/m2 in females (bioelectrical impedance analysis). Gender-specific cut-off values of calf circumference for low ASMI were determined. The prevalence of low ASMI in the overall cohort was 59.9%, i.e., 57.0% among males and 61.8% among females, with no significant difference between genders (P = 0.1068). The prevalence of low ASMI was 81.3% in individuals at risk of malnutrition compared to 20.6% in their counterparts with normal nutritional status (P < 0.0001). Participants with low ASMI were older, had lower physical activity scores, and greater likelihood of hospitalization in prior 6 months compared with normal ASMI (all P < 0.0001). Low ASMI was associated with risk of malnutrition (odds ratio: 3.58 for medium risk, odds ratio: 12.50 for high risk), older age, smoking, drinking, smaller calf circumference, and lower bone mass (all P ≤ 0.0328). Cut-off values of calf circumference for low ASMI for males was 33.4 cm and for females was 32.2 cm. In conclusion, we found that low ASMI was highly prevalent among community-dwelling older adults at risk of malnutrition. Other significant factors associated with low ASMI were age, smoking, drinking, calf circumference, and bone mass. Screening community-dwelling older adults for risk of malnutrition can prevent or delay onset of low ASMI.

Effect of Oral Nutritional Supplementation on Growth in Children with Undernutrition: A Systematic Review and Meta-Analysis.

Oral nutritional supplements (ONS) are used to promote catch-up growth in children with undernutrition. We conducted a systematic review and meta-analysis to summarize the evidence of ONS intervention effects on growth for 9-month- to 12-year-old children who were undernourished or at nutritional risk. Eleven randomized controlled trials met the inclusion criteria; trials compared changes in anthropometric measures in children using ONS or ONS + DC (dietary counselling) to measures for those following usual diet or placebo or DC alone. The RCTs included 2287 children without chronic diseases (mean age 5.87 years [SD, 1.35]; 56% boys). At follow-up time points up to 6 months, results showed that children in the ONS intervention group had greater gains in weight (0.423 kg, [95% confidence interval 0.234, 0.613], p < 0.001) and height (0.417 cm [0.059, 0.776], p = 0.022) versus control; greater gains in weight (0.089 kg [0.049, 0.130], p < 0.001) were evident as early as 7-10 days. Longitudinal analyses with repeated measures at 30, 60, and 90 days showed greater gains in weight parameters from 30 days onwards (p < 0.001), a trend towards greater height gains at 90 days (p = 0.056), and significantly greater gains in height-for-age percentiles and Z-scores at 30 and 90 days, respectively (p < 0.05). Similar results were found in subgroup analyses of studies comparing ONS + DC to DC alone. For children with undernutrition, particularly those who were mildly and moderately undernourished, usage of ONS in a nutritional intervention resulted in significantly better growth outcomes when compared to control treatments (usual diet, placebo or DC alone).

Impact of specialized oral nutritional supplement on clinical, nutritional, and functional outcomes: A randomized, placebo-controlled trial in community-dwelling older adults at risk of malnutrition.

BACKGROUND & AIMS: The world's over-65 population is expanding rapidly, and the risk of malnutrition is prevalent in this population. Meeting nutritional needs is a recognized strategy to reduce and address multiple debilitating adverse health outcomes associated with malnutrition. The objective of this randomized, controlled trial was to determine the effects of oral nutritional supplement (ONS) containing beta-hydroxy-beta-methylbutyrate (HMB), along with dietary counseling, on health outcomes in community-dwelling older adults at risk of malnutrition. METHODS: Strengthening Health In ELDerly through nutrition (SHIELD) studied adults aged ≥ 65 years in Singapore who were recruited between August 2017 and March 2019. Participants were community ambulant and classified as medium or high risk for malnutrition using Malnutrition Universal Screening Tool (MUST). Participants (n = 811) were randomly assigned to one of two study treatments for 180 days: (i) two servings/day of ONS containing HMB with dietary counseling (n = 405) or (ii) two servings/day of placebo supplement with dietary counseling (n = 406). The primary composite outcome was 'survival without hospital (re)admission and with at least 5% weight gain to day 180'. Dietary intakes, nutritional and functional outcomes were measured at baseline, 30, 90, and 180 days. RESULTS: A higher proportion in intervention group met the 180-day primary composite outcome compared to placebo (33.4% vs. 8.7%, P < 0.001), largely driven by body weight component (36.2% vs. 9.4%, P < 0.001). Survival and hospital (re)admission rate were not significantly different between the groups. Weight, BMI, and mid upper arm circumference were significantly greater in the intervention group compared to placebo during the study (all P < 0.001), and at days 30, 90, and 180 (all P < 0.05). The odds of having better nutritional status during the study were also significantly higher in the intervention group compared to placebo, as measured using MUST risk (OR = 2.68, P < 0.001) and vitamin D status (OR = 4.23, P < 0.001). Intervention group had significantly higher energy, protein, fat, and carbohydrate intakes than the placebo group (all P ≤ 0.017). Leg strength at day 90 was significantly greater for the intervention group than for the placebo group (LSM ± SE: 12.85 ± 0.22 vs. 12.17 ± 0.22; P = 0.030). Handgrip strength for females was significantly higher at day 180 for the intervention group compared to placebo (LSM ± SE: 14.18 ± 0.17 vs. 13.70 ± 0.17; P = 0.048). Within the low appendicular skeletal muscle mass index (ASMI) subgroup, the intervention group had significantly greater calf circumference at days 90 and 180 compared to placebo (both P ≤ 0.0289). CONCLUSIONS: For community-dwelling older adults at risk of malnutrition, daily consumption of specialized ONS containing HMB and vitamin D for six months, along with dietary counseling, significantly improved nutritional and functional outcomes compared to placebo supplement with dietary counseling. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.govNCT03245047.

Dietary factors, myopia, and axial dimensions in children.

PURPOSE: To evaluate the possible associations between dietary factors and myopia. DESIGN: Cross-sectional study. PARTICIPANTS: Eight hundred fifty-one Chinese schoolchildren from the Singapore Cohort Study of Risk Factors for Myopia. METHODS: Diet was assessed using a semiquantitative food-frequency questionnaire. Spherical equivalent (SE) refraction was assessed with an autorefractometer, and axial length (AL) by contact ultrasound A-scan biometry. MAIN OUTCOME MEASURES: Myopia was defined as SE< or =-0.5 diopters (D). Spherical equivalent and AL were analyzed by quartile groups. RESULTS: The mean age (+/-standard deviation) was 12.81+/-0.83 years, approximately half were male (422 children [49.6%]), and 653 (73.8%) children had myopia. In multivariate models, AL was longest in the highest quartile group of total cholesterol intake compared with the lowest (adjusted mean [95% confidence interval], 24.66 [24.62-24.71] mm vs. 24.32 [24.27-24.36] mm; P = 0.026, for trend) and was longest in the highest quartile group of saturated fat intake compared with the lowest (24.65 [24.60-24.70] vs. 24.36 [24.32-24.41] mm; P = 0.039, for trend). None of the nutrients was associated with SE or a diagnosis of myopia. CONCLUSIONS: Higher saturated fat and cholesterol intake are associated with longer AL in otherwise healthy Singapore Chinese schoolchildren.

Nutritional Biomarkers and Associated Factors in Community-Dwelling Older Adults: Findings from the SHIELD Study.

Aging is associated with intrinsic and extrinsic changes which affect the nutrient intake and nutritional status of an older individual. Suboptimal nutritional status is linked with adverse health outcomes. There are limited data in this area for community-dwelling older adults who are not at risk of malnutrition. The objective of this study was to describe the nutritional biomarkers in 400 community-dwelling older adults (aged ≥65 years) with normal nutritional status (Malnutrition Universal Screening Test score of 0) in Singapore and to identify factors associated with these biomarkers. The majority of the participants had normal levels of pre-albumin, albumin, total protein, creatinine, zinc, corrected calcium, vitamin B12, ferritin and hemoglobin. Females had significantly higher levels of corrected calcium and vitamin B12 than males, whereas males had significantly higher levels of pre-albumin, albumin, creatinine, serum ferritin, 25-hydroxyvitamin D (25(OH)D) and hemoglobin than females. About half of the participants (52%) had low level of 25(OH)D (<30 µg/L) and 10% had low zinc level (<724 µg/L). Among those with low level of 25(OH)D, 74% had 25(OH)D insufficiency (20-<30 µg/L) and 26% had 25(OH)D deficiency (<20 µg/L). Younger age, female gender, non-Chinese ethnicity and no intake of vitamin D supplement were associated with lower serum 25(OH)D level, whereas higher body mass index (BMI) was associated with low zinc level. These findings highlight the problem of hidden nutritional insufficiencies can be missed in seemingly normal nourished community-dwelling older adults.

Factors associated with muscle mass in community-dwelling older people in Singapore: Findings from the SHIELD study.

OBJECTIVES: Aging is associated with low muscle mass and has been linked to adverse health outcomes. The objectives of this cross-sectional study were: (1) to describe anthropometry, body composition, appendicular skeletal muscle mass index (ASMI; appendicular skeletal muscle mass/height2), and prevalence of low ASMI in older people with normal nutritional status (Malnutrition Universal Screening Tool score = 0); (2) to determine factors associated with ASMI, and odds ratios of having low ASMI. METHODS: SHIELD is a study of community-dwelling older people aged 65 years and above in Singapore. ASMI was determined using bioelectrical impedance analysis and low ASMI was defined as <7.0 kg/m2 for males and <5.7 kg/m2 for females (Asian Working Group for Sarcopenia, 2014). RESULTS: A total of 400 older people (183 males and 217 females) took part in this study. The overall prevalence of low ASMI was 20.6% (15.5% in males and 24.9% in females). Females had significantly lower ASMI than males (P < 0.0001), age was inversely associated with ASMI (P = 0.0024) while BMI and calf circumference were positively associated with ASMI (both P < 0.0001) in the total cohort. In addition, ASMI was positively associated with bone mass in both genders (both P < 0.0001). After adjusting for covariates, the odds ratios of having low ASMI with every 1 year and 10 years increase in age were 1.13 (95% CI: 1.06, 1.20) and 3.36 (95% CI: 1.82, 6.21) respectively. CONCLUSIONS: The high prevalence of low ASMI in community-dwelling older people with normal nutritional status highlights the need for early screening. There was a strong inverse association between age and ASMI while BMI, calf circumference and bone mass were positively associated with ASMI. These findings will give further weight to the importance and development of public health strategies in maintaining and improving muscle health in this population group.

ESR1 and EGF genetic variation in relation to breast cancer risk and survival.

INTRODUCTION: Oestrogen exposure is a central factor in the development of breast cancer. Oestrogen receptor alpha (ESR1) is the main mediator of oestrogen effect in breast epithelia and has also been shown to be activated by epidermal growth factor (EGF). We sought to determine if common genetic variation in the ESR1 and EGF genes affects breast cancer risk, tumour characteristics or breast cancer survival. METHODS: We genotyped 157 single nucleotide polymorphisms (SNPs) in ESR1 and 54 SNPs in EGF in 92 Swedish controls and selected haplotype tagging SNPs (tagSNPs) that could predict both single SNP and haplotype variation in the genes with an R2 of at least 0.8. The tagSNPs were genotyped in 1,590 breast cancer cases and 1,518 controls, and their association with breast cancer risk, tumour characteristics and survival were assessed using unconditional logistic regression models, Cox proportional hazard models and haplotype analysis. RESULTS: The single tagSNP analysis did not reveal association evidence for breast cancer risk, tumour characteristics, or survival. A multi-locus analysis of five adjacent tagSNPs suggested a region in ESR1 (between rs3003925 and rs2144025) for association with breast cancer risk (p = 0.001), but the result did not withstand adjustment for multiple comparisons (p = 0.086). A similar region was also implicated by haplotype analyses, but its significance needs to be verified by follow-up analysis. CONCLUSION: Our results do not support a strong association between common variants in the ESR1 and EGF genes and breast cancer risk, tumour characteristics or survival.