The importance of maternal dietary choline for fetal neural development and later cognitive function has been well-documented in experimental studies. Although choline is an essential dietary ...nutrient for humans, evidence that low maternal choline in pregnancy impacts neurodevelopment in human infants is lacking. We determined potential associations between maternal plasma free choline and its metabolites betaine and dimethylglycine in pregnancy and infant neurodevelopment at 18 months of age.
This was a prospective study of healthy pregnant women and their full-term, single birth infants. Maternal blood was collected at 16 and 36 weeks of gestation and infant neurodevelopment was assessed at 18 months of age for 154 mother-infant pairs. Maternal plasma choline, betaine, dimethylglycine, methionine, homocysteine, cysteine, total B12, holotranscobalamin and folate were quantified. Infant neurodevelopment was evaluated using the Bayley Scales of Infant Development-III. Multivariate regression, adjusting for covariates that impact development, was used to determine the associations between maternal plasma choline, betaine and dimethylglycine and infant neurodevelopment.
The maternal plasma free choline at 16 and 36 weeks gestation was median (interquartile range) 6.70 (5.78-8.03) and 9.40 (8.10-11.3) µmol/L, respectively. Estimated choline intakes were (mean ± SD) 383 ± 98.6 mg/day, and lower than the recommended 450 mg/day. Betaine intakes were 142 ± 70.2 mg/day. Significant positive associations were found between infant cognitive test scores and maternal plasma free choline (B=6.054, SE=2.283, p=0.009) and betaine (B=7.350, SE=1.933, p=0.0002) at 16 weeks of gestation. Maternal folate, total B12, or holotranscobalamin were not related to infant development.
We show that choline status in the first half of pregnancy is associated with cognitive development among healthy term gestation infants. More work is needed on the potential limitation of choline or betaine in the diets of pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In metabolomic analysis of human milk amines, we found a previously unidentified compound. This was tentatively identified as hypaphorine, an indole alkaloid composed of tryptophan and three methyls, ...and with neurological and glucose-lowering effects in rodents. Hypaphorine identity was confirmed by hypaphorine synthesis, and then a fluorometric method was developed to quantify hypaphorine in milk and foods. Using dietary records, we identified peanut products as probable sources of hypaphorine. Milk from 24 lactating women showed widely varying hypaphorine, with a mean ± SD 0.34 ± 0.33 μM, and the highest concentration of 1.24 μM. Peanuts showed high hypaphorine of 70 μg/g compared to 60 and 100 μg/g in dried chickpeas and lentils. Dietary challenge in lactating women with hypaphorine-rich foods demonstrated transfer of hypaphorine into milk with hypaphorine appearance peaking 5–18 h after consumption and prolonged disappearance indicative of slow excretion or metabolism. The potential functional roles of hypaphorine in human nutrition remain to be addressed.
To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers.
This was a prospective, two-arm, unblinded, ...parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up.
Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (
= 135) or the control group (
= 135). The SH+ group had significantly lower stress at the 3-month follow-up (
= -1.23, 95% CI = -2.36, -0.10,
= 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (
= -0.89, 95% CI = -1.50, -0.27,
= 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness.
This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.
Background: Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. ...Vitamin B-12 deficiency increases choline use for homocysteine methylation.Objectives: We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants.Design: Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference.Results: The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148–220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient.Conclusion: This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.
Aims/hypothesis
The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers.
...Methods
From a prospective cohort of individuals with type 2 diabetes, baseline sera (
N
=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m
2
) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts.
Results
At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762,
p
=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797,
p
=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts.
Conclusions/interpretation
Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.
Graphical Abstract
Cyanobacteria from a diversity of marine and freshwater habitats are known to produce neurotoxic secondary metabolites. Herein, we describe the complete stereostructure, synthesis, and biological ...properties of kalkitoxin (1), a novel neurotoxic lipopeptide from a Caribbean collection of Lyngbya majuscula. The organic extract of this L. majuscula exhibited potent brine shrimp and fish toxicity. Using these assays, the toxic metabolite kalkitoxin (1), was isolated by sequential silica gel VLC, CC, and normal-phase HPLC (12.8 mg, 0.3% of extract). Subsequently, bioassay-guided fractionation using a primary cell culture of rat neurons in a microphysiometer or inhibition of IL-1 beta stimulation of sPLA sub(2) in hepatocarcinoma cells led to re-isolation of 1 in small yield from various Caribbean collections of L. majuscula.
We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.
In a phase 3, double-blind, placebo-controlled trial, we ...randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants.
No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo.
Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo.
NCT00818662.
This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.
A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)–cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6–18 months old; 226 children (59%) were seronegative for PIV3. ...Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature ⩾38°C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a ⩾4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1:25 in the vaccine group and <1:4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial
Summary
Background Japanese encephalitis is a major cause of death and disability throughout Asia, including the Indian subcontinent. Although an effective vaccine for Japanese encephalitis is ...available, hundreds of millions of susceptible individuals remain unimmunised because of the vaccine's cost. In 1988, an inexpensive live-attenuated vaccine (SA14-14-2) was licensed in China. We have measured the effectiveness of this vaccine.
Methods In a case-control study in rural Sichuan Province, China, the 56 cases consisted of children admitted to hospital with acute Japanese encephalitis, and were confirmed serologically. 1299 village-matched and age-matched controls were identified, and vaccination histories obtained from pre-existing written records.
Findings The effectiveness of one dose was 80% (95% Cl 44 to 93%); that of two doses was 97·5% (86 to 99·6%). Controlling for multiple potential confounders did not alter these results.
Interpretation We conclude that a regimen of two doses of live-attenuated Japanese encephalitis vaccine, administered 1 year apart, is effective in the prevention of clinically important disease. Subsequent study is needed to assure the safety of this vaccine.
Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 ...deficiency increases choline use for homocysteine methylation.
We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants.
Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference.
The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148–220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient.
This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.
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