Benchmark dose modeling for epidemiological dose-response assessment using prospective cohort studies.

Benchmark dose (BMD) methodology has been employed as a default dose-response modeling approach to determine the toxicity value of chemicals to support regulatory chemical risk assessment. Especially, a relatively standardized BMD analysis framework has been established for modeling toxicological data regarding the formats of input data, dose-response models, definitions of benchmark response, and model uncertainty consideration. However, the BMD approach has not been well developed for epidemiological data mainly because of the diverse designs of epidemiological studies and various formats of data reported in the literature. Although most of the epidemiological BMD analyses were developed to solve a particular question, the methods proposed in two recent studies are able to handle cohort and case-control studies using summary data with consideration of adjustments for confounders. Therefore, the purpose of the present study is to investigate and compare the "effective count"-based BMD modeling approach and adjusted relative risk (RR)-based BMD analysis approach to identify an appropriate BMD modeling framework that can be generalized for analyzing published data of prospective cohort studies for BMD analysis. The two methods were applied to the same set of studies that investigated the association between bladder and lung cancer and inorganic arsenic exposure for BMD estimation. The results suggest that estimated BMDs and BMDLs are relatively consistent; however, with the consideration of established common practice in BMD analysis, modeling adjusted RR values as continuous data for BMD estimation is a more generalizable approach harmonized with the BMD approach using toxicological data.

Phenotype, genotype, and management of congenital fibrosis of extraocular muscles type 1 in 16 Chinese families.

PURPOSE: Congenital fibrosis of extraocular muscles type 1 (CFEOM1), a classical subtype of CFEOM, is characterized by restrictive ophthalmoplegia and ptosis. It is mainly caused by aberrant neural innervation of the extraocular muscles. This study aimed to investigate the genetic characteristics and clinical manifestations of CFEOM1 in Chinese families. METHODS: The clinical data, including ocular examinations, magnetic resonance imaging (MRI), and surgical procedures of affected individuals from 16 Chinese CFEOM1 families, were collected. The genomic DNA of 16 probands and their family members were sequenced for causative KIF21A gene mutations. Linkage analysis using microsatellite markers across KIF21A was also conducted. RESULTS: Affected individuals were presented with bilateral non-progressive ptosis, restricted horizontal eye movement, fixed infraduction of both eyes, compensatory chin-up head position, and neuromuscular abnormalities. Three heterozygous KIF21A mutations, c.2860C > T (p.R954W) (in eight families), c.2861G > T (p.R954L) (in two families), and c.2861G > A (p.R954Q) (in two families) were identified, which implied that hotspot mutations were common in Chinese CFEOM1 families. Germline Mosaicism was likely to be the cause of affected individuals with asymptomatic parents without KIF21A mutations presented in the eight families. Two affected individuals underwent modified levator muscle complex suspension surgery and achieved a good result without any complications. CONCLUSION: Instead of evaluating the whole CFEOM1 gene variant, hotspot mutations could be given priority for screening. The occurrence of germline mosaicism has to be taken into account in genetic counseling. Patients with CFEOM1 who have ptosis may benefit from an innovative surgical procedure called modified levator muscle complex suspension.

Efficacy and safety of a specific commercial high-protein meal-replacement product line in weight management: meta-analysis of randomized controlled trials.

BACKGROUND: Protein is suggested to be the nutrient providing the most satiety and is frequently used in meal-replacement products to achieve weight loss. Commercial products such as Herbalife high-protein (HP) products have been studied in various clinical trials, but controversy remains regarding their efficacy and safety. METHODS: We searched the PubMed, Center for Clinical and Translational Research (CCTR), and Google Scholar databases for randomized controlled trials of Herbalife HP products used as meal replacement (MR) published through July 2019 in peer-reviewed journals. We reviewed changes in efficacy and safety-related outcomes in treatment and control groups, and we estimated the pooled standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) with a DerSimonian and Laird random-effects method. RESULTS: By pooling data from nine identified studies (934 participants: 463 in treatment groups and 471 in control groups), we found that participants who consumed HP products experienced significantly larger decreases in body weight (SMD = -0.24; 95% CI: -0.37 to -0.10), body mass index (SMD = -0.31; 95% CI: -0.50 to -0.11), and fat mass (SMD = -0.37; 95% CI: -0.65 to -0.09) than did individuals consuming control diets. Concerning safety outcomes, the participants in the treatment group had a significantly larger decrease in aspartate aminotransferase (SMD = -0.23; 95% CI: -0.42 to -0.03). There were no significant between-group differences in alanine aminotransferase or creatinine. However, blood urea nitrogen levels increased in both groups, with a significantly larger increase in the treatment group (SMD = 0.53; 95% CI: 0.15 to 0.92). CONCLUSIONS: Herbalife HP MR products appear effective and do not evidence significant risk in reducing body weight.

Associations of dietary PUFA with dyslipidaemia among the US adults: the findings from National Health and Nutrition Examination Survey (NHANES) 2009-2016.

Dyslipidaemia, a significant risk factor of CVD, is threatening human health worldwide. PUFA are crucial long-chain fatty acids for TAG synthesis and removal, potentially decreasing dyslipidaemia risk. We examined dyslipidaemia prevalence among 15 244 adults aged ≥ 20 years from National Health and Nutrition Examination Survey 2009-2016. Dyslipidaemia was defined as total cholesterol ≥ 240 mg/dl, or HDL-cholesterol < 40 mg/dl/50 mg/dl for males/females, respectively, or LDL-cholesterol ≥ 160 mg/dl, or TAG ≥ 200 mg/dl, or taking lipid-modifying medications. We measured the daily PUFA intake using a 24-h dietary recall. Demographics, social economics, and lifestyle factors were collected using questionnaires/interviews. Additionally, we measured Se and Hg levels in the whole blood. Logistic regression models were used to examine the association between PUFA and dyslipidaemia. The unweighted and weighted dyslipidaemia prevalences were 72·4% and 71·0 %, respectively. When grouped into tertiles, PUFA intake above 19·524 g/d was associated with an independent 19 % decrease in dyslipidaemia risk (OR = 0·81 (95 % CI 0·71, 0·94)) compared with the lowest tertile (PUFA intake ≤ 12·349 g/d). A threshold inverse association was further determined by the restricted cubic spline analysis. When PUFA intake was increased to its turning point, that is, 19 g/d, the lower nadir risk for dyslipidaemia was obtained (OR = 0·72 (95 % CI 0·56, 0·89)). When the exposure was the sum of α-linolenic acid and octadecatetraenoic acid, the inverse linear association remained. Dietary PUFA intake is a beneficial factor for dyslipidaemia among American adults, independent of many potential confounders, including Hg and Se.

Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study.

PURPOSE: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. METHODS: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. CONCLUSIONS: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.

Association of Self-Paced Physical and Cognitive Activities Across the First Week Postconcussion With Symptom Resolution in Youth.

OBJECTIVE: To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth. SETTING: Emergency department or concussion clinics. PARTICIPANTS: Youth aged 11 to 17 years with physician-confirmed concussion. DESIGN: Prospective cohort with repeated measures. MAIN MEASURES: Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively. RESULTS: A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27). CONCLUSION: Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.

Physical activity and risk of bladder cancer among postmenopausal women.

Physical activity is associated with decreased risk for many cancers. Studies on the association between physical activity and risk of bladder cancer are limited, and findings are inconsistent. Postmenopausal women (mean age = 63.3) were recruited into the Women's Health Initiative from 1993 to 1998. Self-reported baseline information on physical activity and other covariates were available in 141 288 participants. Incident bladder cancer cases were collected through 2018 and centrally adjudicated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazard regression models. Effect modification due to smoking was assessed. During an average of 18.5 years of follow-up, 817 bladder cancer cases were identified. Compared to physically inactive women, those who engaged in ≥15 MET-hours/week of total physical activity, ≥8.75 MET-hours/week of walking or ≥11.25 MET-hours/week of moderate to vigorous physical activity had lower risk of bladder cancer (HR = 0.74, 95% CI: 0.59-0.94, P for linear trend = .02; HR = 0.79, 95% CI: 0.63-0.98, P for linear trend = .03; and HR = 0.76, 95% CI: 0.61-0.94, P for linear trend = .02, respectively). No effect modification was found by smoking status (P for interaction = .06, 0.91 and 0.27, respectively). We found that total physical activity, walking and moderate to vigorous physical activity were inversely associated with bladder cancer incidence among postmenopausal women in a dose-response manner. Physical activity may play a potential role in the primary prevention of bladder cancer. Further studies with objective measurements of physical activity are needed to confirm these findings.

The association between type 2 diabetes mellitus and bladder cancer risk among postmenopausal women.

INTRODUCTION: Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent. METHODS: A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk. RESULTS: During a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes. CONCLUSION: Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.

Intakes of long-chain omega-3 polyunsaturated fatty acids and non-fried fish in relation to incidence of chronic kidney disease in young adults: a 25-year follow-up.

PURPOSE: The prevalence of chronic kidney disease (CKD) is increasing rapidly in many countries and has become a major public health concern. Although intakes of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) and its food source-fish-may have renal protective effects, little is known about the longitudinal association between these dietary factors and CKD incidence. METHODS: A total of 4133 healthy individuals of black and white race aged 18-30 at baseline (1985-1986) from the Coronary Artery Risk Development in Young Adults study were enrolled and followed up over 25 years. LCω3PUFA and fish intake were assessed by an interview-based dietary history questionnaire at baseline, year 7 (1992-1993) and 20 (2005-2006). RESULTS: Four hundred and eighty-nine incident cases of CKD were identified. After adjustment for potential confounders, LCω3PUFA intake was inversely associated with CKD incidence [HR = 0.73 (95% CI 0.60-0.89), P = 0.002, with one standard division (0.19 g/day) increment in LCω3PUFA]. This inverse association was persisted among females [0.64 (95% CI 0.48, 0.84; P = 0.002], but not males (Pinteraction = 0.070). A marginal significant inverse association was also found between non-fried fish consumption and CKD incidence (HR = 0.86, 95% CI 0.73, 1.01; P = 0.073). CONCLUSIONS: Dietary LCω3PUFA intake was inversely associated with incidence of CKD among American young adults over 25 years of follow-up. The suggestive evidence of the inverse association between non-fried fish consumption with CKD incidence needs further confirmation.

Magnesium intake is inversely associated with risk of obesity in a 30-year prospective follow-up study among American young adults.

PURPOSE: Although laboratory studies suggest a potential role of magnesium (Mg) in weight regulation, human studies relating Mg intake to body weight are limited. This study sought to prospectively examine the association between Mg intake and incidence of obesity and related anthropometric and biochemical indicators. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study recruited 5115 American young adults, aged 18-30 years, at baseline in 1985-6, and re-examined them in eight follow-ups. Incident obesity was defined as body mass index (BMI) ≥ 30 kg/m2. Dietary Mg intake was collected using the CARDIA Diet History at baseline and exam years 7 and 20. RESULTS: During the 30-year follow-up, 1675 incident cases of obesity were identified. After adjustment for potential confounders, Mg intake was inversely associated with incidence of obesity. The multivariable-adjusted hazard ratios (95% confidence interval) from quintile 1 (Q1) (lowest intake group) to quintile 5 (Q5) (highest intake group) were 1 (referent), 0.86 (0.74, 1.00), 0.83 (0.71, 0.97), 0.55 (0.46, 0.66), and 0.49 (0.40, 0.60); P for trend < 0.01. Consistently, Mg intake was inversely associated with the levels of BMI, triceps skinfold, suprailiac skinfold, subscapular skinfold, fasting insulin, and C-reactive protein. The observed associations were not materially modified by age, sex, race, or BMI at baseline. In addition, the intakes of foods rich in Mg, including whole grains, nuts and seeds, legumes, and dark-green vegetables, were associated with lower incidence of obesity. CONCLUSIONS: This longitudinal study suggests that Mg intake is inversely associated with incidence of obesity.

Intake of Vegetables and Fruits Through Young Adulthood Is Associated with Better Cognitive Function in Midlife in the US General Population.

BACKGROUND: Vegetables and fruits (VF) may differentially affect cognitive functions, presumably due to their various nutrient contents, but evidence from epidemiologic studies is limited. OBJECTIVES: The aim of this study was to examine the long-term association between VF intakes, including VF subgroups, in young adulthood and cognitive function in midlife. METHODS: A biracial cohort of 3231 men and women aged 18-30 y at baseline in 1985-1986 were followed up for 25 y in the Coronary Artery Risk Development in Young Adults Study. Diet was measured at baseline, and in examination years 7 and 20. Cognitive function was assessed at examination year 25 through the use of 3 tests: the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST), and the Stroop test. The mean differences (MDs) with 95% CIs in cognitive scores across intake categories were estimated through the use of the multivariable-adjusted general linear regression model. RESULTS: Excluding potatoes, intake of whole vegetables was significantly associated with a better cognitive performance after adjustment for potential confounders in all 3 cognitive tests (quintile 5 compared with quintile 1-RAVLT, MD: 0.33; 95% CI: 0.01, 0.64; P-trend = 0.08; DSST, MD: 2.84; 95% CI: 0.93, 4.75; P-trend < 0.01; Stroop test, MD: -2.87; 95% CI: -4.24, -1.50; P-trend < 0.01]. Similarly, intake of fruits, except fruit juices, was significantly related to a better cognitive performance (quintile 5 compared with quintile 1-DSST, MD: 2.41; 95% CI: 0.70, 4.12; P-trend = 0.03). CONCLUSIONS: This study supports the long-term benefits of VF consumption on cognitive performance, except those VF with relatively low fiber content such as potatoes and fruit juices, among the middle-aged US general population.

Low to moderate toenail arsenic levels in young adulthood and incidence of diabetes later in life: findings from the CARDIA Trace Element study.

Some studies suggest a positive association between arsenic exposure and risk of diabetes. However, the findings are inconsistent and inconclusive, particularly at a low to moderate arsenic exposure level, and longitudinal data are lacking. We examined toenail arsenic at low to moderate level in young adulthood in relation to incidence of diabetes later in life. This study included 4102 black and white participants aged 20-32 at baseline (1987-88) who completed up to 7 follow-up exams through 2015-16. Toenail arsenic was measured by collision-cell inductively-coupled-plasma mass-spectrometry. Incident diabetes was defined as fasting glucose ≥ 126 mg/dL, non-fasting glucose ≥ 200 mg/dL, 2-h postchallenge glucose ≥ 200 mg/dL, hemoglobin A1c ≥ 6.5%, or use of glucose-lowering medications. Cox proportional hazards model and generalized estimating equations (GEEs) were used to determine the associations of quintiles of toenail arsenic with incident diabetes and other metabolic parameters. The median (inter-quartile range) toenail arsenic level was 0.097 (0.065-0.150) ppm in this study. During the follow-up period, 599 incident cases of diabetes were identified. After adjustment for potential confounders, the hazards ratio (95% confidence interval) was 0.96 (0.73, 1.27) (P for linear trend= 0.85) comparing the highest to the lowest quintile of toenail arsenic levels. No significant association was observed between toenail arsenic and levels of fasting glucose, insulin, homeostatic model assessment of insulin resistance, homeostatic model assessment of beta cell function, or C-reactive protein. The null associations persisted across subgroups of age, sex, race, and body mass index. Findings from this longitudinal study do not support the hypothesis that low to moderate toenail arsenic levels in young adulthood is associated with diabetes risk later in life.

The association between parental weight status and risk of hypertension in children aged 6 to 12 years.

BACKGROUND AND OBJECTIVES: Parents may play important roles in the regulation of children's weight status and consequently the development of childhood hypertension. Thus, this study aimed to examine parental weight status, as a marker of parents' diet and lifestyle, in relation to risk of hypertension in their children. METHODS AND STUDY DESIGN: A total of 1,949 children aged 6 to 12 years (1,012 girls, 52%) and their parents were included. Information on demographics, anthropometrics, lifestyle, diet, and medical history were obtained from the participants and their parents through self-administered questionnaires. Childhood hypertension and elevated blood pressure were defined as SBP and/or DBP ≥95th and ≥90th age- and gender-specific percentile, respectively. Parental overweight was defined as BMI ≥24.0 kg/m2. RESULTS: The prevalence of childhood hypertension was 8.4%, with no significant gender difference (p=0.36). Parents' weight status, especially maternal, was associated with childhood hypertension. After adjustment for potential confounders, children with two parents being overweight were two times more likely to have hypertension as compared with children who had both parents being of normal weight [multivariable-adjusted odds ratio=2.09; 95% confidence interval: (1.26, 3.46)]. After further adjustment for children's body mass index, the observed association was substantially attenuated and became statistically non-significant. CONCLUSIONS: Findings from this study suggest that parental weight status is associated with the prevalence of hypertension in children presumably through influencing children's weight. Further studies are needed to establish causal inference. This study highlights the importance of parental lifestyle in children's health.

Obesity perception survey among youth in Turkey: instrument development and test-retest reliability

Background/aim: We aimed to develop an instrument that can assess the perceptions and opinions of young people regarding the causes and consequences of obesity and the role of individuals, families, communities, and government in addressing obesity. Materials and methods: A 36-question (101-item) survey was developed by adopting, translating, and revising multiple-choice or Likert-scale questions from existing surveys to assure construct cross-cultural validity. A two-factor mixed-effects model estimated the intraclass correlation coefficient (ICC) to measure the test-retest reliability of questions administered 2 weeks apart to a convenient sample of Istanbul high school and university students, aged 15­25 years (n = 122). Results: The meanICC for university and high school was 0.70 and 0.63, respectively. University students were more consistent in relating the problem to society and public policy preferences. High school students were more consistent in relating the problem and solution to themselves and their immediate environments. Using a 0.5 cutoff for the ICC's lower 95% confidence limit, followed by reevaluation of the question flow, a 19-question (36-item) survey was retained for adolescents and a 26-question (52-item) survey for young adults. Conclusion: While the survey items have moderate to excellent reliability for high school and university students, it can be administered longitudinally to suggest changes to policies and interventions, and after cross-cultural validation, it can be utilized to compare obesity perceptions across different populations.

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. METHODS: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. RESULTS: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. CONCLUSIONS: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

In utero exposure to 25-hydroxyvitamin D and risk of childhood asthma, wheeze, and respiratory tract infections: A meta-analysis of birth cohort studies.

BACKGROUND: Studies of the associations between in utero 25-hydroxyvitamin D (25[OH]D) exposure and risk of childhood asthma, wheeze, and respiratory tract infections are inconsistent and inconclusive. OBJECTIVES: We sought to assess associations between 25(OH)D levels in cord blood or maternal venous blood and risk of offspring's asthma, wheeze, and respiratory tract infections. METHODS: Data were derived from PubMed, Embase, Google Scholar, references from relevant articles, and de novo results from published studies until December 2015. A random-effects meta-analysis was conducted among 16 birth cohort studies. RESULTS: Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratios were 0.84 (95% CI, 0.70-1.01; P = .064) for asthma, 0.77 (95% CI, 0.58-1.03; P = .083) for wheeze, and 0.85 (95% CI, 0.66-1.09; P = .187) for respiratory tract infections. The observed inverse association for wheeze was more pronounced and became statistically significant in the studies that measured 25(OH)D levels in cord blood (0.43; 95% CI, 0.29-0.62; P < .001). CONCLUSIONS: Accumulated evidence generated from this meta-analysis suggests that increased in utero exposure to 25(OH)D is inversely associated with the risk of asthma and wheeze during childhood. These findings are in keeping with the results of 2 recently published randomized clinical trials of vitamin D supplementation during pregnancy.

Genome-wide association study of selenium concentrations.

Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis of toenail Se concentrations, which reflect a longer duration of exposure than blood Se concentrations, including 4162 European descendants from four US cohorts. Toenail Se was measured using neutron activation analysis. We identified a GW-significant locus at 5q14 (P < 1 × 10(-16)), the same locus identified in the published GWAS of blood Se based on independent cohorts. The lead single-nucleotide polymorphism (SNP) explained ∼1% of the variance in toenail Se concentrations. Using GW-summary statistics from both toenail and blood Se, we observed statistical evidence of polygenic overlap (P < 0.001) and meta-analysis of results from studies of either trait (n = 9639) yielded a second GW-significant locus at 21q22.3, harboring CBS (P < 4 × 10(-8)). Proteins encoded by genes at 5q14 and 21q22.3 function in homocysteine (Hcy) metabolism, and index SNPs for each have previously been associated with betaine and Hcy levels in GWAS. Our findings show evidence of a genetic link between Se and Hcy pathways, both involved in cardiometabolic disease.

Antioxidant Supplementation Is Not Associated with Long-term Quality of Life in Stage-II Colorectal Cancer Survivors: A Follow-up of the Study of Colorectal Cancer Survivors Cohort.

Cancer survivors are motivated to change lifestyle following diagnosis, but studies investigating the outcomes are scarce. The purpose of this study was to examine the associations between antioxidant supplementation and quality of life (QoL) in stage-II colorectal cancer survivors. Four-hundred-fifty-three survivors were enrolled from the North Carolina Cancer Registry from 2009 to 2011. Interview data on demography, treatment, health behaviors, and QoL were collected at diagnosis, and at 12 and 24 mo post-diagnosis. Antioxidant supplementation was self-reported as use of selenium, zinc, beta-carotene, vitamin A, vitamin E, or vitamin C at baseline. Two-hundred-sixty-one subjects completed the 24-mo interview. After adjusting for multiple confounders, there was no association between antioxidant use and the Functional Assessment of Cancer Treatment-Colorectal [ß = 1.41; 95% confidence interval (CI): -2.48, 5.30] or the medical outcomes 12-item short form (physical composite score: ß = 0.84; 95% CI: -1.39, 3.07; mental composite score: ß = -0.61; 95% CI: -2.65, 1.43). This study revealed no benefit of antioxidant use among survivors, possibly explained by a limited sample size of antioxidant users. More prospective studies are necessary to assess the benefits of antioxidants.

New and Recurrent Concussions in High-School Athletes Before and After Traumatic Brain Injury Laws, 2005-2016.

OBJECTIVES: To examine the trends of new and recurrent sports-related concussions in high-school athletes before and after youth sports traumatic brain injury laws. METHODS: We used an interrupted time-series design and analyzed the concussion data (2005-2016) from High School Reporting Injury Online. We examined the trends of new or recurrent concussion rates among US representative high-school athletes participating in 9 sports across prelaw, immediate-postlaw, and postlaw periods by using general linear models. We defined 1 athlete exposure as attending 1 competition or practice. RESULTS: We included a total of 8043 reported concussions (88.7% new, 11.3% recurrent). The average annual concussion rate was 39.8 per 100 000 athlete exposures. We observed significantly increased trends of reported new and recurrent concussions from the prelaw, through immediate-postlaw, into the postlaw period. However, the recurrent concussion rate showed a significant decline 2.6 years after the laws went into effect. Football exhibited different trends compared with other boys' sports and girls' sports. CONCLUSIONS: Observed trends of increased concussion rates are likely attributable to increased identification and reporting. Additional research is needed to evaluate intended long-term impact of traumatic brain injury laws.

Accumulated evidence on Helicobacter pylori infection and the risk of asthma: A meta-analysis.

BACKGROUND: Helicobacter pylori (H pylori) infection has been suggested to be related to a decreased risk of asthma, but findings in the literature are inconsistent. OBJECTIVE: To quantitatively summarize the existing evidence on the association between H pylori infection and asthma risk. METHODS: The PubMed database was searched for observational studies of H pylori infection in relation to the risk of asthma published in English through May 2017. Measurements of association were pooled using a meta-analytic approach and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Twenty-four studies were identified in this meta-analysis, including 8 case-control studies composed of 1,247 cases and 2,410 controls, and 16 cross-sectional studies composed of 50,290 participants (4,185 cases and 46,105 noncases). The average H pylori infection rates were 40.01% and 48.74% in case-control and cross-sectional studies, respectively. Five studies subcategorized H pylori infection according to CagA status, in which 59.37% of H pylori-infected participants were identified as having CagA positivity. Helicobacter pylori infection was significantly inversely associated with the risk of asthma in case-control studies (OR 0.83, 95% CI 0.71-0.98) but was borderline significant in cross-sectional studies (OR 0.88, 95% CI 0.76-1.02). The observed inverse association persisted for CagA-positive H pylori infection (OR 0.77, 95% CI 0.63-0.93, P for interaction = .03) but not for CagA-negative strains (OR 1.08, 95% CI 0.66-1.78). No significant difference was observed across age or region subgroups. CONCLUSION: The accumulated evidence supports that H pylori infection, especially CagA-positive H pylori infection, is inversely associated with the risk of asthma.