Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects Prevention Study.

Conotruncal heart defects (CTDs) are heart malformations that affect the cardiac outflow tract and typically cause significant morbidity and mortality. Evidence from epidemiological studies suggests that maternal folate intake is associated with a reduced risk of heart defects, including CTD. However, it is unclear if folate-related gene variants and maternal folate intake have an interactive effect on the risk of CTDs. In this study, we performed targeted sequencing of folate-related genes on DNA from 436 case families with CTDs who are enrolled in the National Birth Defects Prevention Study and then tested for common and rare variants associated with CTD. We identified risk alleles in maternal MTHFS (ORmeta = 1.34; 95% CI 1.07 to 1.67), maternal NOS2 (ORmeta = 1.34; 95% CI 1.05 to 1.72), fetal MTHFS (ORmeta = 1.35; 95% CI 1.09 to 1.66), and fetal TCN2 (ORmeta = 1.38; 95% CI 1.12 to 1.70) that are associated with an increased risk of CTD among cases without folic acid supplementation. We detected putative de novo mutations in genes from the folate, homocysteine, and transsulfuration pathways and identified a significant association between rare variants in MGST1 and CTD risk. Results suggest that periconceptional folic acid supplementation is associated with decreased risk of CTD among individuals with susceptible genotypes.

Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans.

Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin "mining" conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit time, and changed expression of genes that regulate circadian rhythm in the liver and colon. In human studies, dose-dependent, orange-fiber-specific fecal accumulation of N-methylserotonin positively correlated with levels of microbiome genes encoding enzymes that digest pectic glycans. Identifying this type of microbial mining activity has potential therapeutic implications.

A Microbiota-Directed Food Intervention for Undernourished Children.

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota. METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples. RESULTS: A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment. CONCLUSIONS: These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).

Mindfulness Meditation Targets Transdiagnostic Symptoms Implicated in Stress-Related Disorders: Understanding Relationships between Changes in Mindfulness, Sleep Quality, and Physical Symptoms.

Mindfulness-Based Stress Reduction (MBSR) is an 8-week meditation program known to improve anxiety, depression, and psychological well-being. Other health-related effects, such as sleep quality, are less well established, as are the psychological processes associated with therapeutic change. This prospective, observational study (n = 213) aimed to determine whether perseverative cognition, indicated by rumination and intrusive thoughts, and emotion regulation, measured by avoidance, thought suppression, emotion suppression, and cognitive reappraisal, partly accounted for the hypothesized relationship between changes in mindfulness and two health-related outcomes: sleep quality and stress-related physical symptoms. As expected, increased mindfulness following the MBSR program was directly correlated with decreased sleep disturbance (r = -0.21, p = 0.004) and decreased stress-related physical symptoms (r = -0.38, p < 0.001). Partial correlations revealed that pre-post changes in rumination, unwanted intrusive thoughts, thought suppression, experiential avoidance, emotion suppression, and cognitive reappraisal each uniquely accounted for up to 32% of the correlation between the change in mindfulness and change in sleep disturbance and up to 30% of the correlation between the change in mindfulness and change in stress-related physical symptoms. Results suggest that the stress-reducing effects of MBSR are due, in part, to improvements in perseverative cognition and emotion regulation, two "transdiagnostic" mental processes that cut across stress-related disorders.

Phenolic profile and antioxidant activity of extracts prepared from fermented heat-stabilized defatted rice bran.

Heat-stabilized, defatted rice bran (HDRB) serves as a potential source of phenolic compounds which have numerous purported health benefits. An estimated 70% of phenolics present in rice bran are esterified to the arabinoxylan residues of the cell walls. Release of such compounds could provide a value-added application for HDRB. The objective of this study was to extract and quantify phenolics from HDRB using fermentation technology. Out of 8 organisms selected for rice bran fermentation, Bacillus subtilis subspecies subtilis had the maximum phenolic release of 26.8 mg ferulic acid equivalents (FAE) per gram HDRB. Response surface methodology was used to further optimize the release of rice bran phenolics. An optimum of 28.6 mg FAE/g rice bran was predicted at 168 h, 0.01% inoculation level, and 100 mg HDRB/mL. Fermentation of HDRB for 96 h with B. subtilis subspecies subtilis resulted in a significant increase in phenolic yield, phenolic concentration, and radical scavenging capacity. Fermented rice bran had 4.86 mg gentistic acid, 1.38 mg caffeic acid, 6.03 mg syringic acid, 19.02 mg (-)-epicatechin, 4.08 mg p-courmaric acid, 4.64 mg ferulic acid, 10.04 mg sinapic acid, and 17.59 mg benzoic acid per 100 g fermented extract compared to 0.65 mg p-courmaric acid and 0.36 mg ferulic acid per 100 g nonfermented extract. The high phenolic content and antioxidant activity of fermented HDRB extract indicates that rice bran fermentation under optimized condition is a potential means of meeting the demand for an effective and affordable antioxidant.

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males.

PURPOSE: Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function. METHODS: Participants (n = 29) received an oral dose of 10,000 IU day(-1) vitamin D3 (VITD) or a visually identical placebo (PLB) for 3 months. Serum 25[OH]D and intact parathyroid hormone (iPTH) were measured at baseline and at week 4, 8 and 12. Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12. RESULTS: Baseline mean total serum 25[OH]D was 40 ± 17 and 41 ± 20 nmol L(-1) for PLB and VITD, respectively. VITD showed a significant improvement in total 25[OH]D at week 4 (150 ± 31 nmol L(-1)) that remained elevated throughout the trial (P < 0.005). Contrastingly, PLB showed a significant decrease in 25[OH]D at week 12 (25 ± 15 nmol L(-1)) compared with baseline. Despite marked increases in total serum 25[OH]D in VITD and a decrease in PLB, there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group (P > 0.05). CONCLUSIONS: Elevating total serum 25[OH]D to concentrations > 120 nmol L(-1) has no effect on skeletal muscle function. We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency (<12.5 nmol L(-1)).

Changes in spirituality partly explain health-related quality of life outcomes after Mindfulness-Based Stress Reduction.

Mindfulness-Based Stress Reduction is a secular behavioral medicine program that has roots in meditative spiritual practices. Thus, spirituality may partly explain Mindfulness-Based Stress Reduction outcomes. Participants (N = 279; M (SD) age = 45(12); 75% women) completed an online survey before and after an 8-week Mindfulness-Based Stress Reduction program. Structural equation modeling was used to test the hypothesis that, following Mindfulness-Based Stress Reduction, the relationship between enhanced mindfulness and improved health-related quality of life is mediated by increased daily spiritual experiences. Changes in both spirituality and mindfulness were significantly related to improvement in mental health. Although the initial mediation hypothesis was not supported, an alternate model suggested that enhanced mindfulness partly mediated the association between increased daily spiritual experiences and improved mental health-related quality of life (indirect effect: ß = 0.07, P = 0.017). Effects on physical health-related quality of life were not significant. Findings suggest a novel mechanism by which increased daily spiritual experiences following Mindfulness-Based Stress Reduction may partially explain improved mental health as a function of greater mindfulness.

Modifiable disease risk, readiness to change, and psychosocial functioning improve with integrative medicine immersion model.

BACKGROUND: Stroke, diabetes, and coronary heart disease (CHD) remain leading causes of death in the United States and are largely attributable to lifestyle behaviors. Integrative medicine can provide a supportive partnership that focuses on improving health by identifying and implementing lifestyle changes based upon personal values and goals. OBJECTIVE: This prospective observational study was designed to assess the effectiveness of an integrative medicine intervention on modifiable disease risk, patient activation, and psychosocial risk factors for stroke, diabetes, and CHD. DESIGN: Sixty-three adults participated in a 3-day comprehensive, multimodal health immersion program at Duke Integrative Medicine, Duke University Medical Center, Durham, North Carolina. Participants received follow-up education, physician support, and telephonic health coaching between the immersion program and the endpoint 7 to 9 months later. PRIMARY OUTCOME MEASURES: Psychosocial functioning, readiness to change health behaviors, and risk of developing diabetes, stroke, and CHD were assessed at baseline and endpoint. RESULTS: Although cardiac risk remained unchanged (P = .19) during the study period, risk of diabetes (P = .02) and stroke (P < .01) decreased significantly. Perceived stress remained unchanged, but improvements were seen in mood (P < .05) and relationship satisfaction (P < .004). Patients became more activated towards self-management of health (P <.001), endorsed greater readiness to change health behaviors (P <.01), and reported increased aerobic exercise (P <.001) and stretching (P = .006) following the intervention. CONCLUSION: An integrative health model can help patients become more engaged in self-management of health and support them in making and maintaining healthy lifestyle changes. These findings provide support for use of an integrative health model in adult disease risk reduction.