Estimating the serum folate concentration that corresponds to the red blood cell folate concentration threshold associated with optimal neural tube defects prevention: A population-based biomarker survey in Southern India.

BACKGROUND: RBC folate concentrations are monitored at the population level, with a recommended threshold for optimal neural tube defect (NTD) prevention. A corresponding threshold for serum folate has not been established. OBJECTIVES: This study aimed to estimate the serum folate insufficiency threshold corresponding to the RBC folate threshold for NTD prevention and examine how this threshold is modified by vitamin B12 status. METHODS: Participants were women (15-40 y; not pregnant or lactating; n = 977) from a population-based biomarker survey in Southern India. RBC folate and serum folate were measured via microbiologic assay. RBC folate deficiency (<305 nmol/L) and insufficiency (<748 nmol/L), serum vitamin B12 deficiency (<148 pmol/L) and vitamin B12 insufficiency (<221 pmol/L), elevated plasma MMA (>0.26 µmol/L), elevated plasma homocysteine (>10.0 µmol/L), and elevated HbA1c (≥6.5%) were evaluated. Bayesian linear models were used to estimate unadjusted and adjusted thresholds. RESULTS: Compared with adequate vitamin B12 status, the estimated serum folate threshold was higher in participants with serum vitamin B12 deficiency (72.5 vs. 28.1 nmol/L) or vitamin B12 insufficiency (48.7 vs. 24.3 nmol/L) and elevated MMA (55.6 vs. 25.9 nmol/L). The threshold was lower in participants with elevated HbA1c (HbA1c ≥6.5% vs. <6.5%; 21.0 vs. 40.5 nmol/L). CONCLUSIONS: The estimated serum folate threshold for optimal NTD prevention was similar to previous reports (24.3 vs. 25.6 nmol/L) among participants with sufficient vitamin B12 status. However, this threshold was more than 2-fold higher in participants with vitamin B12 deficiency and substantially higher across all indicators of insufficient vitamin B12 status (<221 pmol/L, elevated MMA, combined B12, impaired vitamin B12 status), and lower in participants with elevated HbA1c. Findings suggest a serum folate threshold for NTD prevention may be possible in some settings; however, it may not be appropriate in populations with high prevalence of vitamin B12 insufficiency. Am J Clin Nutr 2023;xx:xx-xx. This trial was registered at https://clinicaltrials.gov as NCT04048330.

Federated Analysis in COINSTAC Reveals Functional Network Connectivity and Spectral Links to Smoking and Alcohol Consumption in Nearly 2,000 Adolescent Brains.

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Iron status and inflammation in women of reproductive age: A population-based biomarker survey and clinical study.

BACKGROUND: Women of reproductive age (WRA) are at increased risk for anemia and iron deficiency. However, there is limited population-level data in India, which could help inform evidence-based recommendations and policy. AIMS: To conduct a population-based biomarker survey of anemia, iron deficiency, and inflammation in WRA in Southern India. METHODS: Participants were WRA (15-40 y) who were not pregnant or lactating. Blood samples (n = 979) were collected and analyzed for hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and alpha-1 acid glycoprotein (AGP). Anemia and severe anemia were defined as Hb < 12.0 and < 8.0 g/dL. Serum ferritin was adjusted for inflammation using BRINDA methods. Iron deficiency was defined as SF <15.0 µg/L, iron insufficiency was defined as SF < 20.0 and < 25.0 µg/L, and iron deficiency anemia was defined as Hb < 12.0 g/dL and SF < 15.0 µg/L. Inflammation was defined as CRP > 5.0 mg/L or AGP > 1.0 g/L. Restricted cubic spline regression models were also used to determine if alternative SF thresholds should be used t to classify iron deficiency. RESULTS: A total of 41.5% of WRA had anemia, and 3.0% had severe anemia. Findings from spline analyses suggested a SF cut-off of < 15.0 µg/L, consistent with conventional cut-offs for iron deficiency. 46.3% of WRA had SF < 15.0 µg/L (BRINDA-adjusted: 61.5%), 55.0% had SF < 20.0 µg/L (72.7%), 61.8% had SF < 25.0 µg/L (81.0%), and 30.0% had IDA (34.5%). 17.3% of WRA had CRP > 5.0 mg/L and 22.2% had AGP > 1.0 g/L. The prevalence of ID (rural vs. urban: 49.1% vs. 34.9%; p = 0.0004), iron insufficiency (57.8% vs. 43.8%; p = 0.0005), and IDA (31.8% vs. 22.4%; p = 0.01) were significantly higher in rural areas, although CRP levels were lower and there were no differences in elevated CRP or AGP. CONCLUSIONS: The burden of anemia and iron deficiency in this population was substantial, and increased after adjusting for inflammation, suggesting potential to benefit from screening and interventions. REGISTRATION NUMBER: NCT04048330.

Protocol for a prospective, observational, deep phenotyping study on adipose epigenetic and lipidomic determinants of metabolic homoeostasis in South Asian Indians: the Indian Diabetes and Metabolic Health (InDiMeT) study.

INTRODUCTION: We describe the rationale and broad study design of the Indian Diabetes and Metabolic Health (InDiMeT) study, a new prospective, observational study incorporating extensive epigenetic (DNA methylation) and lipidomic signatures to examine their association with the dysregulation of adipose de novo lipogenesis (DNL) in South Asian Indians. The InDiMeT study aims to use a case-control design to identify genetic and modifiable-environmental-lifestyle associated determinants of (1) epigenomic (DNA methylome) dysregulation of adipose DNL in type 2 diabetes mellitus (T2DM) adipose tissue, (2) identify correlates of epigenomic (DNA methylome) dysregulation of adipose DNL in peripheral blood mononuclear cells (PBMCs) from T2DM subjects and (3) elucidate plasma lipidomic correlates of adipose DNL in T2DM that can be used as biomarkers of adipose tissue dysfunction. METHODS AND ANALYSIS: The InDiMeT study will involve recruitment of 176 normoglycaemic and T2DM individuals who will be undergoing laparoscopic surgery for clinical conditions. Extensive phenotyping of the subjects will be conducted and DNA methylome and lipidomic measurements will be made. The adipose DNL pathway genes are likely to be hypermethylated in patients with T2DM with corresponding reduction of gene expression. Correlates of epigenomic (DNA methylome) dysregulation of adipose DNL pathway in PBMCs and their adipose and plasma lipidomic signatures in T2DM subjects could act as early markers of development of T2DM. ETHICS AND DISSEMINATION: For the InDiMeT study, ethical approval for addressing the specific aims has been obtained from the Institutional Ethics Committee, St John's Medical College and Hospital, St John's National Academy of Health Sciences, Bangalore. Findings from this study will be disseminated through scientific publications in peer-reviewed journals, research conferences and via presentations to stakeholders, patients, clinicians, public and policymakers through appropriate channels.

Decentralized Multisite VBM Analysis During Adolescence Shows Structural Changes Linked to Age, Body Mass Index, and Smoking: a COINSTAC Analysis.

There has been an upward trend in developing frameworks that enable neuroimaging researchers to address challenging questions by leveraging data across multiple sites all over the world. One such open-source framework is the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC) that works on Windows, macOS, and Linux operating systems and leverages containerized analysis pipelines to analyze neuroimaging data stored locally across multiple physical locations without the need for pooling the data at any point during the analysis. In this paper, the COINSTAC team partnered with a data collection consortium to implement the first-ever decentralized voxelwise analysis of brain imaging data performed outside the COINSTAC development group. Decentralized voxel-based morphometry analysis of over 2000 structural magnetic resonance imaging data sets collected at 14 different sites across two cohorts and co-located in different countries was performed to study the structural changes in brain gray matter which linked to age, body mass index (BMI), and smoking. Results produced by the decentralized analysis were consistent with and extended previous findings in the literature. In particular, a widespread cortical gray matter reduction (resembling a 'default mode network' pattern) and hippocampal increase with age, bilateral increases in the hypothalamus and basal ganglia with BMI, and cingulate and thalamic decreases with smoking. This work provides a critical real-world test of the COINSTAC framework in a "Large-N" study. It showcases the potential benefits of performing multivoxel and multivariate analyses of large-scale neuroimaging data located at multiple sites.

Body composition techniques.

Body composition is known to be associated with several diseases, such as cardiovascular disease, diabetes, cancers, osteoporosis and osteoarthritis. Body composition measurements are useful in assessing the effectiveness of nutritional interventions and monitoring the changes associated with growth and disease conditions. Changes in body composition occur when there is a mismatch between nutrient intake and requirement. Altered body composition is observed in conditions such as wasting and stunting when the nutritional intake may be inadequate. Overnutrition on the other hand leads to obesity. Many techniques are available for body composition assessment, which range from simple indirect measures to more sophisticated direct volumetric measurements. Some of the methods that are used today include anthropometry, tracer dilution, densitometry, dual-energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance analysis. The methods vary in their precision and accuracy. Imaging techniques such as nuclear magnetic resonance imaging and computed tomography have become powerful tools due to their ability of visualizing and quantifying tissues, organs, or constituents such as muscle and adipose tissue. However, these methods are still considered to be research tools due to their cost and complexity of use. This review was aimed to describe the commonly used methods for body composition analysis and provide a brief introduction on the latest techniques available.

Relationship between lifestyle behaviors and obesity in children ages 9-11: Results from a 12-country study.

OBJECTIVE: The aim was to assess associations between lifestyle behaviors and obesity in a multinational study of children from 12 countries representing a wide range of human development. METHODS: The sample included 6,025 children 9-11 years of age. Behavioral risk factors included nocturnal sleep duration, moderate to vigorous physical activity (MVPA), television viewing (TV time), and healthy and unhealthy diet pattern scores. Multilevel analyses were used to obtain odds ratios for obesity expressed per standard deviation of each behavioral risk factor. RESULTS: The odds ratios (95% confidence intervals) for obesity from multilevel, multivariable models were 0.79 (0.71-0.90) for nocturnal sleep duration, 0.52 (0.45-0.60) for MVPA, 1.15 (1.05-1.27) for TV time, 1.08 (0.96-1.20) for healthy diet score, and 0.93 (0.83-1.04) for unhealthy diet score in boys and 0.71 (0.63-0.80) for nocturnal sleep duration, 0.43 (0.35-0.53) for MVPA, 1.07 (0.96-1.19) for TV time, 1.05 (0.93-1.19) for healthy diet score, and 0.96 (0.82-1.11) for unhealthy diet score in girls. CONCLUSIONS: Behavioral risk factors are important correlates of obesity in children, particularly low MVPA, short sleep duration, and high TV viewing.

A model for presenting accelerometer paradata in large studies: ISCOLE.

BACKGROUND: We present a model for reporting accelerometer paradata (process-related data produced from survey administration) collected in the International Study of Childhood Obesity Lifestyle and the Environment (ISCOLE), a multi-national investigation of >7000 children (averaging 10.5 years of age) sampled from 12 different developed and developing countries and five continents. METHODS: ISCOLE employed a 24-hr waist worn 7-day protocol using the ActiGraph GT3X+. Checklists, flow charts, and systematic data queries documented accelerometer paradata from enrollment to data collection and treatment. Paradata included counts of consented and eligible participants, accelerometers distributed for initial and additional monitoring (site specific decisions in the face of initial monitoring failure), inadequate data (e.g., lost/malfunction, insufficient wear time), and averages for waking wear time, valid days of data, participants with valid data (≥4 valid days of data, including 1 weekend day), and minutes with implausibly high values (≥20,000 activity counts/min). RESULTS: Of 7806 consented participants, 7372 were deemed eligible to participate, 7314 accelerometers were distributed for initial monitoring and another 106 for additional monitoring. 414 accelerometer data files were inadequate (primarily due to insufficient wear time). Only 29 accelerometers were lost during the implementation of ISCOLE worldwide. The final locked data file consisted of 6553 participant files (90.0% relative to number of participants who completed monitoring) with valid waking wear time, averaging 6.5 valid days and 888.4 minutes/day (14.8 hours). We documented 4762 minutes with implausibly high activity count values from 695 unique participants (9.4% of eligible participants and <0.01% of all minutes). CONCLUSIONS: Detailed accelerometer paradata is useful for standardizing communication, facilitating study management, improving the representative qualities of surveys, tracking study endpoint attainment, comparing studies, and ultimately anticipating and controlling costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01722500.

Improving wear time compliance with a 24-hour waist-worn accelerometer protocol in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE).

BACKGROUND: We compared 24-hour waist-worn accelerometer wear time characteristics of 9-11 year old children in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) to similarly aged U.S. children providing waking-hours waist-worn accelerometer data in the 2003-2006 National Health and Nutrition Examination Survey (NHANES). METHODS: Valid cases were defined as having ≥4 days with ≥10 hours of waking wear time in a 24-hour period, including one weekend day. Previously published algorithms for extracting total sleep episode time from 24-hour accelerometer data and for identifying wear time (in both the 24-hour and waking-hours protocols) were applied. The number of valid days obtained and a ratio (percent) of valid cases to the number of participants originally wearing an accelerometer were computed for both ISCOLE and NHANES. Given the two surveys' discrepant sampling designs, wear time (minutes/day, hours/day) from U.S. ISCOLE was compared to NHANES using a meta-analytic approach. Wear time for the 11 additional countries participating in ISCOLE were graphically compared with NHANES. RESULTS: 491 U.S. ISCOLE children (9.92±0.03 years of age [M±SE]) and 586 NHANES children (10.43 ± 0.04 years of age) were deemed valid cases. The ratio of valid cases to the number of participants originally wearing an accelerometer was 76.7% in U.S. ISCOLE and 62.6% in NHANES. Wear time averaged 1357.0 ± 4.2 minutes per 24-hour day in ISCOLE. Waking wear time was 884.4 ± 2.2 minutes/day for U.S. ISCOLE children and 822.6 ± 4.3 minutes/day in NHANES children (difference = 61.8 minutes/day, p < 0.001). Wear time characteristics were consistently higher in all ISCOLE study sites compared to the NHANES protocol. CONCLUSIONS: A 24-hour waist-worn accelerometry protocol implemented in U.S. children produced 22.6 out of 24 hours of possible wear time, and 61.8 more minutes/day of waking wear time than a similarly implemented and processed waking wear time waist-worn accelerometry protocol. Consistent results were obtained internationally. The 24-hour protocol may produce an important increase in wear time compliance that also provides an opportunity to study the total sleep episode time separate and distinct from physical activity and sedentary time detected during waking-hours. TRIAL REGISTRATION: ClinicalTrials.gov NCT01722500 .

Innovations in nutrition education and global health: the Bangalore Boston nutrition collaborative.

BACKGROUND: India has a wide range of nutrition and health problems which require professionals with appropriate skills, knowledge and trans-disciplinary collaborative abilities to influence policy making at the national and global level. METHODS: The Bangalore Boston Nutrition Collaborative (BBNC) was established as collaboration between St. John's Research Institute (SJRI), Harvard School of Public Health and Tufts University, with a focus on nutrition research and training. The goals of the BBNC were to conduct an interdisciplinary course, develop web-based courses and identify promising Indian students and junior faculty for graduate training in Boston. RESULTS: From 2010, an annual two-week short course in nutrition research methods was conducted on the SJRI campus taught by international faculty from Indian and US universities. More than 100 students applied yearly for approximately 30 positions. The course had didactic lectures in the morning and practical hands-on sessions in the afternoon. Student rating of the course was excellent and consistent across the years. The ratings on the design and conduct of the course significantly improved (p <0.001) from 2010 to 2012. Through open-ended questions, students reported the main strengths of the course to be the excellent faculty and practical "hands-on" sessions. A web based learning system TYRO, was developed, which can be used for distance learning. Four faculty members/graduate students from SJRI have visited Boston for collaborative research efforts. CONCLUSION: The BBNC has become a well-established capacity building and research training program for young professionals in nutrition and global health. Efforts are ongoing to secure long term funding to sustain and expand this collaboration to deliver high quality nutrition and global health education enabled by information and communication technologies.

Potential factors related to waist circumference in urban South Indian children.

OBJECTIVES: To identify important factors (linked to lifestyle, eating and sedentary behaviors) relating to waist circumference among urban South Indian children aged 3 to 16 years. DESIGN: Cross sectional. SETTING: Urban schools of Bangalore, from August 2008 to January 2010. PARTICIPANTS: 8444 children; 4707 children aged 3-10 years and 3737 children aged 10-16 years. METHODS: Data were collected on the frequency of consumption of certain foods, physical activity patterns, sedentary habits at home, sleep duration and behaviors such as habits of snacking, skipping breakfast, eating in front of television and frequency of eating out. Simple linear regression analysis of waist circumference on various food items, physical activity, behavior and parental BMI were performed. A path model was developed to identify potential causal pathways to increase in waist circumference. RESULTS: Increased consumption of bakery items, non vegetarian foods, increased television viewing, decreased sleep duration, eating while watching television, snacking between meals, family meals, skipping breakfast (in older children), and parental BMI were found to be related to waist circumference. Older children possibly under-reported their intake of unhealthy foods, but not behaviors. CONCLUSIONS: This study identified potential behaviors related to waist circumference in urban school children in India. Longitudinal studies with better measures of morbidity and adiposity are warranted in order to derive casual relationships between various determinants and waist circumference.

Assessment of physical activity using accelerometry, an activity diary, the heart rate method and the Indian migration study questionnaire in south Indian adults.

OBJECTIVE: To validate questionnaire-based physical activity level (PAL) against accelerometry and a 24 h physical activity diary (24 h AD) as reference methods (Protocol 2), after validating these reference methods against the heart rate-oxygen consumption (HRVO2) method (Protocol 1). DESIGN: Cross-sectional study. SETTING: Two villages in Andhra Pradesh state and Bangalore city, South India. SUBJECTS: Ninety-four participants (fifty males, forty-four females) for Protocol 2; thirteen males for Protocol 1. RESULTS: In Protocol 2, mean PAL derived from the questionnaire (1.72 (sd 0.20)) was comparable to that from the 24 h AD (1.78 (sd 0.20)) but significantly higher than the mean PAL derived from accelerometry (1.36 (sd 0.20); P < 0.001). Mean bias of PAL from the questionnaire was larger against the accelerometer (0.36) than against the 24 h AD (-0.06), but with large limits of agreement against both. Correlations of PAL from the questionnaire with that of the accelerometer (r = 0.28; P = 0.01) and the 24 h AD (r = 0.30; P = 0.006) were modest. In Protocol 1, mean PAL from the 24 h AD (1.65 (sd 0.18)) was comparable, while that from the accelerometer (1.51 (sd 0.23)) was significantly lower (P < 0.001), than mean PAL obtained from the HRVO2 method (1.69 (sd 0.21)). CONCLUSIONS: The questionnaire showed acceptable validity with the reference methods in a group with a wide range of physical activity levels. The accelerometer underestimated PAL in comparison with the HRVO2 method.

Physical activity ratio of selected activities in Indian male and female subjects and its relationship with body mass index.

The physical activity level of an individual can be determined by assigning physical activity ratios (PAR) to different activities. The PAR is the ratio of the energy expended in a particular activity and the BMR, and is thought to be independent of body weight. PAR values of selected activities in Indian male and female subjects were measured and their association with BMI was assessed. The BMR and energy cost of selected activities were measured in thirty male and thirty female subjects in the age group of 20-40 years, who were categorised into different groups of BMI. The PAR values of the underweight male subjects were significantly lower than the overweight subjects for activities such as walking at 3.2 and 4.8 km/h and walking at 3.2 km/h with a 5 kg load. In the female subjects, the underweight subjects had significantly lower PAR values for floor swabbing, and walking at 3.2 and 4.8 km/h when compared with overweight females. The mean data of the male and female subjects of the present study were slightly but significantly different to the previously reported FAO, WHO and United Nations University values and other compilations. The BMI was significantly correlated with the PAR value of the studied activities. In India, where a large proportion of the population have BMI below 18.5 and above 25 kg/m2, considerations of the influence of body weight and BMI on PAR become important in accurately determining total energy expenditure.

Use of rice bran oil in patients with hyperlipidaemia.

BACKGROUND: The quantity and type of dietary fat is known to affect plasma lipid concentration and hence the choice of cooking oil is important to lower the risk of coronary heart disease. Rice bran oil, which was not popular worldwide, is slowly being recognized as a 'healthy' oil in India. We assessed if rice bran oil had hypolipidaemic effects in subjects with elevated lipid levels. METHODS: The study had a cross-over design with subjects (n = 14) randomly assigned to consume either rice bran oil or refined sunflower oil in their homes, for a period of 3 months (period 1). After a washout period of 3 weeks, they were crossed over to the other oil (period 2). The serum lipid values were estimated at the beginning, on day 45 and day 90 of each phase. Additional parameters assessed included anthropometry, dietary and physical activity patterns. RESULTS: The use of rice bran oil significantly reduced plasma total cholesterol and triglyceride levels compared with sunflower oil. The reduction in plasma LDL-cholesterol with rice bran oil was just short of statistical significance (p = 0.06). HDL-cholesterol levels were unchanged. CONCLUSION: The use of rice bran oil as the main cooking oil significantly reduced serum cholesterol and triglyceride levels. The use of rice bran oil together with dietary and lifestyle modifications may have implications for reducing the risk of cardiovascular disease.