Leveraging a substantial biorepository that interlinks biological samples and electronic medical records, the effects of B vitamins and homocysteine on a wide array of health outcomes will be studied.
In the UK Biobank, a PheWAS study evaluated the connections between genetically predicted circulating concentrations of folate, vitamin B6, vitamin B12, and their metabolite homocysteine and a comprehensive range of health outcomes, encompassing both existing and new disease events, utilizing 385,917 participants. Using a 2-sample Mendelian randomization (MR) approach, the observed associations were replicated and a causal inference was sought. Statistical significance for replication was set at MR P less than 0.05. Third, investigations using dose-response, mediation, and bioinformatics analyses were undertaken to ascertain any non-linear patterns and to discern the underlying mediating biological mechanisms for the identified correlations.
1117 phenotypes, in total, were scrutinized in each PheWAS analysis. After undergoing multiple rounds of correction, a catalogue of 32 phenotypic correlations emerged, specifically relating B vitamins and homocysteine. A two-sample Mendelian randomization analysis indicated three potential causal relationships: higher plasma vitamin B6 levels were associated with a lower likelihood of kidney stones (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.42, 0.97; p = 0.0033), elevated homocysteine levels with a heightened risk of hypercholesterolemia (OR 1.28; 95% CI 1.04, 1.56; p = 0.0018), and chronic kidney disease (OR 1.32; 95% CI 1.06, 1.63; p = 0.0012). The observed connections between folate and anemia, vitamin B12 and vitamin B-complex deficiencies, anemia and cholelithiasis, and homocysteine and cerebrovascular disease were characterized by non-linear dose-response relationships.
This investigation reveals conclusive evidence regarding the associations of B vitamins and homocysteine with conditions affecting both endocrine/metabolic and genitourinary health.
This study provides compelling evidence that B vitamins and homocysteine are associated with endocrine/metabolic and genitourinary disorders.
Elevated levels of branched-chain amino acids (BCAAs) are significantly associated with diabetes, but the influence of diabetes on the levels of BCAAs, branched-chain ketoacids (BCKAs), and the comprehensive metabolic state following a meal is still poorly understood.
A multiracial cohort, diabetic and non-diabetic, was evaluated for quantitative BCAA and BCKA levels after a mixed meal tolerance test (MMTT). Further, the kinetics of related metabolites and their potential associations with mortality were investigated specifically in self-identified African Americans.
Using an MMTT, we collected data from 11 participants without obesity or diabetes and 13 individuals with diabetes treated only with metformin. BCKAs, BCAAs, and 194 other metabolites were quantified at each of eight time points over five hours. Genetic-algorithm (GA) Mixed models, with adjustment for baseline and repeated measures, were used to compare the metabolite differences between groups across each time point. Subsequently, utilizing data from the Jackson Heart Study (JHS), we analyzed the association of top metabolites with different kinetic patterns to all-cause mortality, involving 2441 participants.
Baseline-adjusted BCAA levels remained constant across all time points between groups. Conversely, adjusted BCKA kinetics varied significantly by group, particularly for -ketoisocaproate (P = 0.0022) and -ketoisovalerate (P = 0.0021), displaying the greatest disparity 120 minutes post-MMTT. A significant difference in kinetic patterns for 20 additional metabolites was observed between groups over time, and mortality in the JHS cohort was significantly linked to 9 of these, including several acylcarnitines, regardless of diabetes status. Individuals categorized into the highest quartile of the composite metabolite risk score presented a considerably greater mortality rate (hazard ratio 1.57, 95% confidence interval 1.20-2.05, p = 0.000094) than those in the lowest quartile.
Following the MMTT, diabetic subjects displayed sustained elevation of BCKA levels, suggesting that the breakdown of BCKA might be a pivotal dysregulated process in how BCAAs and diabetes interact. In self-identified African Americans, metabolites displaying distinct kinetics after MMTT could be indicators of dysmetabolism and an increased risk of death.
Elevated BCKA levels after MMTT in diabetic participants suggest dysregulation of BCKA catabolism as a possible pivotal factor within the complex interaction of BCAA metabolism and diabetes. Mortality rates might be increased in self-identified African Americans, potentially linked to dysmetabolism evidenced by differing metabolite kinetics subsequent to an MMTT.
The investigation of gut microbiota-derived metabolites, encompassing phenylacetyl glutamine (PAGln), indoxyl sulfate (IS), lithocholic acid (LCA), deoxycholic acid (DCA), trimethylamine (TMA), trimethylamine N-oxide (TMAO), and its precursor trimethyllysine (TML), as predictors of outcomes in patients with ST-segment elevation myocardial infarction (STEMI) is demonstrably restricted.
In patients with ST-elevation myocardial infarction (STEMI), an analysis of plasma metabolite levels' relationship to major adverse cardiovascular events (MACEs), encompassing nonfatal myocardial infarction, nonfatal stroke, all-cause mortality, and heart failure, is undertaken.
A cohort of 1004 patients experiencing ST-elevation myocardial infarction (STEMI) and undergoing percutaneous coronary intervention (PCI) was recruited. By utilizing targeted liquid chromatography/mass spectrometry, plasma levels of these metabolites were assessed. The impact of metabolite levels on MACEs was investigated through the lens of Cox regression and quantile g-computation.
A median follow-up of 360 days revealed that 102 patients had experienced major adverse cardiac events (MACEs). Traditional risk factors notwithstanding, elevated plasma concentrations of PAGln (hazard ratio [HR] 317 [95% CI 205, 489]), IS (267 [168, 424]), DCA (236 [140, 400]), TML (266 [177,399]), and TMAO (261 [170, 400]) were each strongly correlated with MACEs, as demonstrated by statistically significant p-values (P < 0.0001 for all). The joint impact of all these metabolites, as determined by quantile g-computation, was 186 (95% CI 146-227). PAGln, IS, and TML were the primary drivers of the mixture's positive effect, proportionally. Plasma PAGln and TML, coupled with coronary angiography scores, specifically including the Synergy between PCI with Taxus and cardiac surgery (SYNTAX) score (AUC 0.792 vs. 0.673), the Gensini score (0.794 vs. 0.647), and the Balloon pump-assisted Coronary Intervention Study (BCIS-1) jeopardy score (0.774 vs. 0.573), demonstrated an improved capacity to predict major adverse cardiac events (MACEs).
Elevated plasma levels of PAGln, IS, DCA, TML, and TMAO are independently associated with major adverse cardiovascular events (MACEs) in STEMI patients, implying these metabolites could serve as valuable prognostic markers.
Major adverse cardiovascular events (MACEs) are independently associated with elevated plasma levels of PAGln, IS, DCA, TML, and TMAO in patients with ST-elevation myocardial infarction (STEMI), suggesting these metabolites as potentially useful prognostic indicators.
Text messages present a potentially useful avenue for breastfeeding promotion, yet their efficacy remains under-investigated in many published studies.
To research the effect of mobile phone text messaging on the long-term persistence of breastfeeding practices.
In Yangon's Central Women's Hospital, a 2-arm, parallel, individually randomized controlled trial was performed on a cohort of 353 pregnant participants. trait-mediated effects Text messages on breastfeeding promotion were sent to the intervention group (179 participants), in contrast to the control group (174 participants) who received communications concerning other maternal and child health issues. The primary outcome of interest was the rate of exclusive breastfeeding in the first one to six months following delivery. Other breastfeeding indicators, breastfeeding self-efficacy, and child morbidity served as secondary outcome measures. The intention-to-treat approach guided the analysis of outcome data using generalized estimation equation Poisson regression models. Estimated risk ratios (RRs) and 95% confidence intervals (CIs) were calculated, while controlling for within-person correlation and time. Interactions between treatment group and time were also investigated.
A substantial difference in exclusive breastfeeding rates was observed between the intervention and control groups, notably higher in the intervention group for the combined six follow-up visits (RR 148; 95% CI 135-163; P < 0.0001), and at each subsequent monthly follow-up. The intervention group showed a significantly higher rate of exclusive breastfeeding at six months of age (434%) than the control group (153%), presenting a relative risk of 274 (95% confidence interval: 179 to 419), and exhibiting statistically highly significant findings (P < 0.0001). The intervention, at six months, demonstrably enhanced current breastfeeding (RR 117; 95% CI 107-126; p < 0.0001), resulting in a decrease in bottle feeding (RR 0.30; 95% CI 0.17-0.54; p < 0.0001). TAK-652 Each follow-up revealed a higher rate of exclusive breastfeeding in the intervention group compared to the control group, a statistically significant pattern (P for interaction < 0.0001) mirrored in current breastfeeding rates. The intervention led to a higher average score for breastfeeding self-efficacy (adjusted mean difference of 40; 95% confidence interval 136 to 664; P = 0.0030). The intervention effectively decreased the likelihood of diarrhea by 55% over the subsequent six months of observation (Relative Risk = 0.45; 95% Confidence Interval = 0.24 to 0.82; P < 0.0009).
Text messages, directed specifically at pregnant women and mothers in urban areas, delivered via mobile phones, markedly improve breastfeeding practices and lower infant morbidity within the first six months of life.
Trial ACTRN12615000063516, managed by the Australian New Zealand Clinical Trials Registry, is available for review at this site: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367704.