Dietary energy density: a mediator of depressive symptoms and abdominal obesity or independent predictor of abdominal obesity?

BACKGROUND: In the U.S., Europe, and throughout the world, abdominal obesity prevalence is increasing. Depressive symptoms may contribute to abdominal obesity through the consumption of diets high in energy density. PURPOSE: To test dietary energy density ([DED]; kilocalories/gram of food and beverages consumed) for an independent relationship with abdominal obesity or as a mediator between depressive symptoms and abdominal obesity. METHODS: This cross-sectional study included 87 mid-life, overweight adults; 73.6% women; 50.6% African-American. Variables and measures: Beck Depression Inventory-II (BDI-II) to measure depressive symptoms; 3-day weighed food records to calculate DED; waist circumference, an indicator of abdominal obesity. Hierarchical regression tested if DED explained waist circumference variance while controlling for depressive symptoms and consumed food and beverage weight. Three approaches tested DED as a mediator. RESULTS: Nearly three-quarters of participants had abdominal obesity, and the mean waist circumference was 103.2 (SD 14.3) cm. Mean values: BDI-II was 8.67 (SD 8.34) which indicates most participants experienced minimal depressive symptoms, and 21.8% reported mild to severe depressive symptoms (BDI-II ≥ 14); DED was 0.75 (SD 0.22) kilocalories/gram. Hierarchical regression showed an independent association between DED and waist circumference with DED explaining 7.0% of variance above that accounted for by BDI-II and food and beverage weight. DED did not mediate between depressive symptoms and abdominal obesity. CONCLUSIONS: Depressive symptoms and DED were associated with elevated waist circumference, thus a comprehensive intervention aimed at improving depressive symptoms and decreasing DED to reduce waist circumference is warranted

Plasma Metabolomics in Human Pulmonary Tuberculosis Disease: A Pilot Study

We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers and may reveal pathways involved in TB disease pathogenesis and resolution

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Food group intake patterns and nutrient intake vary across low-income Hispanic and African American preschool children in Atlanta: a cross sectional study

Abstract Background The food group intake patterns of low income Hispanic and African American preschool children are not well documented. The aim of this study was to perform a food group intake analysis of low income minority preschool children and evaluate how macronutrient and micronutrient intake compares to Dietary Reference Intakes (DRI). Methods A cross sectional study design using three-day food diaries analyzed by dietary analysis software (Nutrient Database System for Research) was used. Children were recruited from well-child clinics at Children’s Healthcare of Atlanta at Hughes Spalding and North Dekalb Grady Satellite Clinic, Atlanta, GA. Low-income, African American and Hispanic preschool age children (n = 291) were enrolled. A total of 105 completed and returned the 3-day food diaries. Chi-squared tests were used to assess demographic variables. The mean percentage of intake per day of specific food groups and sub-groups were obtained (servings of given food group/total daily servings). Food intake data and proportion of children meeting DRIs for macro- and micronutrients were stratified by race/ethnicity, nutritional status, and caloric intake, and were compared using t-tests. Regression models controlling for age, BMI and sex were obtained to assess the effect of total caloric intake upon the proportional intake of each studied food group. Results The mean age of African American children was 2.24 ± 1.07 years and Hispanic children 2.84 ± 1.12 years. African Americans consumed more kcal/kg/day than Hispanics (124.7 ± 51 vs. 96.9 ± 33, p  Conclusions Food group intake patterns among low-income children differ by ethnic group. There is a need for more research to guide program design and target nutritional interventions for this population.</p

Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005–2014

Abstract Background While associated with obesity, the cause of the rapid rise in prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is highest among Hispanics, is not well understood. Animal experiments have demonstrated that arsenic exposure contributes to liver injury. Our objective was to examine the association between arsenic exposure and NAFLD in humans and to determine if race/ethnicity modifies the association. Methods Urinary inorganic arsenic concentrations among those ≥12 years in the National Health and Nutrition Examination Survey, 2005–2014 were used to assess the cross-sectional association with serum alanine aminotransferase (ALT) levels, a marker of liver dysfunction. We excluded high alcohol consumers (>4–5 drinks/day; n = 939), positive hepatitis B or C (n = 2330), those missing body mass index (n = 100) and pregnant women (n = 629) for a final sample of 8518. Arsenic was measured using liquid chromatography coupled with mass spectrometry and ALT was measured using standard methods. Sampling weights were used to obtain national estimates. Due to lack of normality, estimates were log transformed and are presented as geometric means. Logistic regression models controlling for age, sex, income, and weight category estimate adjusted odd ratios (aOR) of elevated ALT by quartile of arsenic and tested for effect modification by race/ethnicity and weight. Elevated ALT was defined as >25 IU/L and >22 IU/L for boys and girls ≤17 years, respectively and >30 IU/L and >19 IU/L for men and women, respectively. Results Among all, aOR of elevated ALT were higher among those in the highest vs. lowest arsenic quartile (referent), 1.4 (95% confidence interval [CI]: 1.1, 1.7) with a borderline significant interaction (p = 0.07) by race/ethnicity but not weight (p = 0.4). In analysis stratified by race/ethnicity, aOR of elevated ALT among those in the 4th quartile were higher among Mexican Americans, 2.0 (CI: 1.3, 3.1) and non-Hispanic whites only, aOR 1.4 (CI: 1.1, 1.8) despite the fact that obesity prevalence was highest among non-Hispanic blacks. Conclusions Our findings demonstrate a positive association between urinary arsenic exposure and risk of NAFLD among U.S. adolescents and adults that is highest among Mexican Americans and among those obese, regardless of race/ethnicity

A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children, and currently, there are no FDA-approved therapies. Plasminogen activator inhibitor-1 (PAI-1) is elevated in children with NAFLD and associated with increased disease severity. Losartan potassium (losartan) is an angiotensin II receptor blocker (ARB) that reduces PAI-1 production and improves insulin sensitivity that has been proposed as a treatment for pediatric NAFLD but has not previously been tested. Methods This was an 8-week randomized, double-blind, placebo-controlled, phase 2a, crossover study (with a 6-week washout between conditions) for safety and preliminary efficacy of losartan 50 mg a day taken orally in 12 normotensive children with biopsy proven nonalcoholic steatohepatitis (NASH). Results Twelve children enrolled in the study, and nine completed all visits. No changes in blood pressure or serious adverse events occurred during the study. Trends in improvement in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and homeostatic model assessment insulin resistance (HOMA-IR) were seen with losartan treatment compared to the placebo time-period. More participants decreased ALT on losartan as compared to placebo (89% [8 out 9] vs. 56% [5 out of 9], respectively). Conclusions This data provides preliminary evidence that losartan treatment is safe over 8 weeks in children with NAFLD and supports consideration of larger studies to test its efficacy. Trial registration URL and trial identification number: https://clinicaltrials.gov/show/NCT01913470, NCT01913470. Date registered: August 1, 2013

Alanine Aminotransferase as a Monitoring Biomarker in Children with Nonalcoholic Fatty Liver Disease: A Secondary Analysis Using TONIC Trial Data

Background: Validated noninvasive biomarkers to assess treatment response in pediatric nonalcoholic fatty liver disease (NAFLD) are lacking. We aimed to validate alanine aminotransferase (ALT), a monitoring biomarker for change in liver histology. Methods: A retrospective analysis using data from the TONIC trial. NAFLD histologic assessments were defined by: Fibrosis score, NAFLD activity score (NAS), nonalcoholic steatohepatitis (NASH), and a combination of NASH resolution and fibrosis (NASH + fibrosis). Analysis was performed using classification and regression trees (CART) as well as logistic regression. Results: Mean ALT for the child over 96 weeks and percent change of ALT from baseline to 96 weeks were significant predictors of progression of NAFLD for each histologic assessment (p &lt; 0.001 for fibrosis score, NASH, and NASH + fibrosis and p &lt; 0.05 for NAS). Mean ALT adjusted for age, sex and ethnicity was a better predictor for change in NASH (81.8 (11.0) ROC (receiver operating characteristic curve) mean (SD (Standard derivation))) and NASH + fibrosis (77.8 (11.2)), compared to change in NAS (63 (17.7)) and fibrosis (58.6 (11.1)). Conclusion: Mean ALT over 96 weeks is a reasonable proxy of histologic improvement of NASH and NASH + fibrosis. These findings support ALT as a valid monitoring biomarker of histologic change over time in children with NASH and fibrosis