Genetic Risk for Obesity Predicts Nucleus Accumbens Size and Responsivity to Real-World Food Cues

Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life

FTO genotype and weight status among preadolescents: Assessing the mediating effects of obesogenic appetitive traits

Polymorphisms in the Fat Mass and Obesity Associated (FTO) gene are robustly associated with overweight and obesity among children, although the underlying mechanisms are poorly understood. We tested if appetitive traits partially mediated the association between FTO genotype and increased BMI among a sample of US preadolescents. Data were from 178 unrelated 9–10 year olds who participated in an experimental study between 2013 and 2015. Children\u27s DNA was isolated from buccal swabs, and the rs9939609 SNP in the FTO gene was genotyped. Children\u27s age- and sex-adjusted BMI z-scores were computed using height and weight measured at the laboratory. Parents completed the Child Eating Behavior Questionnaire that includes three validated scales of habitual appetitive traits related to drive and regulation: satiety responsiveness, enjoyment of food and food responsiveness. Structural equation modeling was used to assess if those traits mediated the relationship between FTO and BMI z-score. The sample of children was 48.9% male and 91.0% non-Hispanic white. FTO distribution was in Hardy Weinberg equilibrium, and 16.3% of participants were homozygous for the high-risk allele. Mean BMI z-score was greatest among those with the high-risk genotype (ANOVA P \u3c 0.01). In separate structural equation models adjusted for the child\u27s sex and maternal education, decreased satiety responsiveness and increased food responsiveness each partially mediated the positive association between the high-risk genotype and increased BMI z-score (P-value for each indirect effect \u3c0.05). Continued research is needed to better understand how other known genetic obesity risk factors may impact appetitive traits among children

Rice Consumption and Urinary Arsenic Concentrations in U.S. Children

Background: In adult populations, emerging evidence indicates that humans are exposed to arsenic by ingestion of contaminated foods such as rice, grains, and juice; yet little is known about arsenic exposure among children. Objectives: Our goal was to determine whether rice consumption contributes to arsenic exposure in U.S. children. Methods: We used data from the nationally representative National Health and Nutrition Examination Survey (NHANES) to examine the relationship between rice consumption (measured in 0.25 cups of cooked rice per day) over a 24-hr period and subsequent urinary arsenic concentration among the 2,323 children (6–17 years of age) who participated in NHANES from 2003 to 2008. We examined total urinary arsenic (excluding arsenobetaine and arsenocholine) and dimethylarsinic acid (DMA) concentrations overall and by age group: 6–11 years and 12–17 years. Results: The median [interquartile range (IQR)] total urinary arsenic concentration among children who reported consuming rice was 8.9 μg/L (IQR: 5.3–15.6) compared with 5.5 μg/L (IQR: 3.1–8.4) among those who did not consume rice. After adjusting for potentially confounding factors, and restricting the study to participants who did not consume seafood in the preceding 24 hr, total urinary arsenic concentration increased 14.2% (95% confidence interval: 11.3, 17.1%) with each 0.25 cup increase in cooked rice consumption. Conclusions: Our study suggests that rice consumption is a potential source of arsenic exposure in U.S. children

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

A Dietary-Wide Association Study (DWAS) of Environmental Metal Exposure in US Children and Adults

Background: A growing body of evidence suggests that exposure to toxic metals occurs through diet but few studies have comprehensively examined dietary sources of exposure in US populations. Purpose: Our goal was to perform a novel dietary-wide association study (DWAS) to identify specific dietary sources of lead, cadmium, mercury, and arsenic exposure in US children and adults. Methods: We combined data from the National Health and Nutrition Examination Survey with data from the US Department of Agriculture’s Food Intakes Converted to Retail Commodities Database to examine associations between 49 different foods and environmental metal exposure. Using blood and urinary biomarkers for lead, cadmium, mercury, and arsenic, we compared sources of dietary exposure among children to that of adults. Results: Diet accounted for more of the variation in mercury and arsenic than lead and cadmium. For instance we estimate 4.5% of the variation of mercury among children and 10.5% among adults is explained by diet. We identified a previously unrecognized association between rice consumption and mercury in a US study population – adjusted for other dietary sources such as seafood, an increase of 10 g/day of rice consumption was associated with a 4.8% (95% CI: 3.6, 5.2) increase in blood mercury concentration. Associations between diet and metal exposure were similar among children and adults, and we recapitulated other known dietary sources of exposure. Conclusion: Utilizing this combination of data sources, this approach has the potential to identify and monitor dietary sources of metal exposure in the US population

Barriers and facilitators in implementing a pilot, pragmatic, telemedicine-delivered healthy lifestyle program for obesity management in a rural, academic obesity clinic

Few evidence-based strategies are specifically tailored for disparity populations such as rural adults. Two-way video-conferencing using telemedicine can potentially surmount geographic barriers that impede participation in high-intensity treatment programs offering frequent visits to clinic facilities. We aimed to understand barriers and facilitators of implementing a telemedicine-delivered tertiary-care, rural academic weight-loss program for the management of obesity

Feasibility and acceptability of a rural, pragmatic, telemedicine‐ delivered healthy lifestyle programme

Background: The public health crisis of obesity leads to increasing morbidity that are even more profound in certain populations such as rural adults. Live, two‐way video‐conferencing is a modality that can potentially surmount geographic barriers and staffing shortages. Methods: Patients from the Dartmouth‐Hitchcock Weight and Wellness Center were recruited into a pragmatic, single‐arm, nonrandomized study of a remotely delivered 16‐week evidence‐based healthy lifestyle programme. Patients were provided hardware and appropriate software allowing for remote participation in all sessions, outside of the clinic setting. Our primary outcomes were feasibility and acceptability of the telemedicine intervention, as well as potential effectiveness on anthropometric and functional measures. Results: Of 62 participants approached, we enrolled 37, of which 27 completed at least 75% of the 16‐week programme sessions (27% attrition). Mean age was 46.9 ± 11.6 years (88.9% female), with a mean body mass index of 41.3 ± 7.1 kg/m2 and mean waist circumference of 120.7 ± 16.8 cm. Mean patient participant satisfaction regarding the telemedicine approach was favourable (4.48 ± 0.58 on 1‐5 Likert scale—low to high) and 67.6/75 on standardized questionnaire. Mean weight loss at 16 weeks was 2.22 ± 3.18 kg representing a 2.1% change (P \u3c .001), with a loss in waist circumference of 3.4% (P = .001). Fat mass and visceral fat were significantly lower at 16 weeks (2.9% and 12.5%; both P \u3c .05), with marginal improvement in appendicular skeletal muscle mass (1.7%). In the 30‐second sit‐to‐stand test, a mean improvement of 2.46 stands (P = .005) was observed. Conclusion: A telemedicine‐delivered, intensive weight loss intervention is feasible, acceptable, and potentially effective in rural adults seeking weight loss

A Population-Based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association

Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort.

INTRODUCTION: Accumulating evidence indicates that arsenic (As), a potent environmental toxicant, may increase cardiovascular disease risk and adversely affect endothelial function at high levels of exposure. Pregnancy is a vulnerable time for both mother and child; however, studies examining the association between prenatal As exposure and plasma biomarkers of inflammation and endothelial function in mothers and newborns are lacking. METHODS: We examined maternal urinary As levels at gestational weeks 24-28 and levels of inflammatory biomarkers in plasma from 563 pregnant women and 500 infants' cord blood. We assessed a multiplexed panel of circulating inflammatory and endothelial function markers, including tumor necrosis factor alpha (TNFα), monocyte chemoattractant protein 1 (MCP1), intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1). RESULTS: Compared with the bottom tertile, the highest tertile of maternal urinary As during pregnancy was associated with a 145.2ng/ml (95% CI 4.1, 286.3; p=0.04) increase in cord blood ICAM1 and 557.3ng/ml (95% CI -56.4, 1171.1; p=0.09) increase in cord blood VCAM1. Among mothers, the highest tertile of maternal urinary As during pregnancy was related to a 141.8ng/ml (95% CI 26.1, 257.5; p=0.02) increase maternal plasma VCAM1 levels. Urinary As was unrelated to MCP1 or TNFα in maternal plasma and cord blood. In structural equation models, the association between maternal urinary As and infant VCAM was mediated by maternal levels of VCAM (βmediation: 0.024, 95% CI: 0.002, 0.050). CONCLUSION: Our observations indicate that As exposure during pregnancy may affect markers of vascular health and endothelial function in both pregnant women and children, and suggest further investigation of the potential impacts on cardiovascular health in these susceptible populations