Urinary sodium, iodine, and volume in relation to metabolic syndrome in Mesoamerican children and their parents.

BACKGROUND AND AIMS: The roles of sodium or iodine intake on the metabolic syndrome (MetS) etiology remain controversial. We evaluated the associations of 24 h urinary sodium and iodine with MetS among Mesoamerican children and their adult parents. METHODS AND RESULTS: We conducted a cross-sectional study among 217 school-age children and 478 parents from 9 Mesoamerican cities. Exposures were high 24 h urinary sodium excretion and concentration (>2000 mg/d or mg/L, respectively) and high 24 h urinary iodine excretion and concentration (≥300 µg/d or µg/L, respectively). In children, the outcome was a standardized metabolic score from five criteria analogous to the Adult Treatment Panel (ATP) III criteria. In adults, MetS was defined according to the ATP III criteria. We estimated adjusted mean differences in the metabolic risk score and adjusted prevalence ratios of MetS between exposure categories using multivariable regression. In children, high sodium concentration was associated with a 0.10 units (43% of a SD) higher score (P = 0.001) and high iodine concentration was related to a 0.09 units (39% of a SD) higher score (P = 0.009). Unexpectedly, high 24 h urinary volume was associated with a lower metabolic score. In adults, high 24 h sodium excretion was related to hypertension and high iodine concentration was related to increased MetS prevalence. CONCLUSION: High sodium and iodine concentrations, but not 24 h iodine excretion, are significantly associated with MetS in children, whereas high 24 h urinary volume is related to a decreased metabolic score. In adults, high iodine concentration tends to be related to increased MetS prevalence, but not 24 h iodine excretion.

Seropositivity and history of hospitalisation for dengue in relation to anthropometric indices among Colombian children and adults.

The role of anthropometric status on dengue is uncertain. We investigated the relations between anthropometric characteristics (height, body mass index and waist circumference (WC)) and two dengue outcomes, seropositivity and hospitalisation, in a cross-sectional study of 2038 children (aged 2-15 years) and 408 adults (aged 18-72 years) from Bucaramanga, Colombia. Anthropometric variables were standardised by age and sex in children. Seropositivity was determined through immunoglobulin G antibodies; past hospitalisation for dengue was self-reported. We modelled the prevalence of each outcome by levels of anthropometric exposures using generalised estimating equations with restricted cubic splines. In children, dengue seropositivity was 60.8%; 9.9% of seropositive children reported prior hospitalisation for dengue. WC was positively associated with seropositivity in girls (90th vs. 10th percentile adjusted prevalence ratio (APR) = 1.19; 95% confidence interval (CI) 1.03-1.36). Among adults, dengue seropositivity was 95.1%; 8.1% of seropositive adults reported past hospitalisation. Height was inversely associated with seropositivity (APR = 0.90; 95% CI 0.83-0.99) and with hospitalisation history (APR = 0.19; 95% CI 0.04-0.79). WC was inversely associated with seropositivity (APR = 0.89; 95% CI 0.81-0.98). We conclude that anthropometry correlates with a history of dengue, but could not determine causation. Prospective studies are warranted to enhance causal inference on these questions.

Prediction of osteoporotic hip fracture in postmenopausal women through patient-specific FE analyses and machine learning.

A great challenge in osteoporosis clinical assessment is identifying patients at higher risk of hip fracture. Bone Mineral Density (BMD) measured by Dual-Energy X-Ray Absorptiometry (DXA) is the current gold-standard, but its classification accuracy is limited to 65%. DXA-based Finite Element (FE) models have been developed to predict the mechanical failure of the bone. Yet, their contribution has been modest. In this study, supervised machine learning (ML) is applied in conjunction with clinical and computationally driven mechanical attributes. Through this multi-technique approach, we aimed to obtain a predictive model that outperforms BMD and other clinical data alone, as well as to identify the best-learned ML classifier within a group of suitable algorithms. A total number of 137 postmenopausal women (81.4 ± 6.95 years) were included in the study and separated into a fracture group (n = 89) and a control group (n = 48). A semi-automatic and patient-specific DXA-based FE model was used to generate mechanical attributes, describing the geometry, the impact force, bone structure and mechanical response of the bone after a sideways-fall. After preprocessing the whole dataset, 19 attributes were selected as predictors. Support Vector Machine (SVM) with radial basis function (RBF), Logistic Regression, Shallow Neural Networks and Random Forest were tested through a comprehensive validation procedure to compare their predictive performance. Clinical attributes were used alone in another experimental setup for the sake of comparison. SVM was confirmed to generate the best-learned algorithm for both experimental setups, including 19 attributes and only clinical attributes. The first, generated the best-learned model and outperformed BMD by 14pp. The results suggests that this approach could be easily integrated for effective prediction of hip fracture without interrupting the actual clinical workflow.

Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset group B streptococcal disease: a systematic review and meta-analysis.

BACKGROUND: Early-onset group B streptococcal (EOGBS) disease (including sepsis, meningitis, and pneumonia) causes significant morbidity and mortality in newborn infants worldwide. Antibiotic prophylaxis can prevent vertical streptococcal transmission, yet no uniform criteria exist to identify eligible women for prophylaxis. Some guidelines recommend universal GBS screening to pregnant women in their third trimester (screening-based protocol), whereas others employ risk-based protocols. OBJECTIVES: To compare the effectiveness of screening-based versus risk-based protocols in preventing EOGBS disease. SEARCH STRATEGY: Key words for the database searches included GBS, Streptococcus agalactiae, pregnancy, screening, culture-based, risk-based. SELECTION CRITERIA: Studies were included if they investigated EOGBS disease incidence in newborn infants and compared screening or risk-based protocols with each other or with controls. DATA COLLECTION AND ANALYSIS: Risk ratios (RR) and 95% confidence intervals (CI) were determined using Mantel-Haenszel analyses with random effects. MAIN RESULTS: Seventeen eligible studies were included. In this meta-analysis, screening was associated with a reduced risk for EOGBS disease compared either with risk-based protocols (ten studies, RR 0.43, 95% CI 0.32-0.56) or with no policy (four studies, RR 0.31, 95% CI 0.11-0.84). Meta-analysis could not demonstrate a significant effect of risk-based protocols versus no policy (seven studies, RR 0.86, 95% CI 0.61-1.20). In studies reporting on the use of antibiotics, screening was not associated with higher antibiotic administration rates (31 versus 29%). CONCLUSIONS: Screening-based protocols were associated with lower incidences of EOGBS disease compared with risk-based protocols, while not clearly overexposing women to antibiotics. This information is of relevance for future policymaking. TWEETABLE ABSTRACT: Meta-analysis: general screening is associated with lower rates of early-onset group B strep. neonatal sepsis compared with risk-based protocols.

Vasoactivity of magnesium sulfate in chicken ductus arteriosus.

Prenatal treatment with magnesium sulfate (MgSO4) has neuroprotective effects in very preterm infants but its use has been associated with an increased rate of patent ductus arteriosus (DA). MgSO4 is a vasodilator and thus may exert a direct relaxant effect in the DA. We aimed to investigate the vasoactive effects of MgSO4 in the DA using the chicken embryo as experimental model. DA rings from 15-d (E15), 17-d (E17) and 19-d (E19) chicken embryos (total incubation: 21-d) were mounted in a wire myograph for isometric tension recordings. Exposure of DA rings to 21% O2 induced a tonic contraction which was relaxed by MgSO4 (2.4 - 7.2 mmol L-1) in a concentration-dependent manner (mean maximal relaxation E19: 51.4%, SE 6.3; EC50: 3.5 mmol L-1, SE 0.7). The relaxation evoked by MgSO4 was not significantly different between E15, E17 and E19 DA and was not affected by removal of the endothelium or by the presence of the nitric oxide synthase inhibitor L-NAME, the soluble guanylate cyclase inhibitor ODQ, or the cyclooxygenase inhibitor indomethacin. In contrast, when the DA rings were incubated in Ca2+-free solution, or in the presence of inhibitors of L-type Ca2+ channels (nifedipine), or large-conductance Ca2+-activated K+ (BKCa) channels (iberiotoxin), MgSO4-induced relaxation was impaired. Preincubation of the DA rings with MgSO4 concentrations ranging from 0 to 6.0 mmol L-1 did not significantly affect O2-induced contraction that was only impaired by a concentration of 7.2 mmol L-1. In conclusion, MgSO4 induced endothelium-independent relaxation of chicken DA and this relaxation appeared to be mediated through stimulation of BKCa channels and blockade of transmembrane flux of extracellular Ca2+. However, O2-induced DA contraction was only impaired by suprapharmacological concentrations of MgSO4 (> 6.0 mmol L-1). Therefore, our data suggest that the higher incidence of patent DA in preterm infants exposed to MgSO4 is unlikely to be due to a direct pharmacological effect of the drug on the DA.

Cyclic nucleotide-dependent relaxation in human umbilical vessels.

Umbilical vessels have a low sensitivity to dilate, and this property is speculated to have physiological implications. We aimed to investigate the different relaxing responses of human umbilical arteries (HUAs) and veins (HUVs) to agonists acting through the cAMP and cGMP pathways. Vascular rings were suspended in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U44069, concentration-response curves to the nitric oxide (NO) donor sodium nitroprusside (SNP), the soluble guanylate cyclase (sGC) stimulator BAY 41-2272, the adenylate cyclase (AC) activator forskolin, the ß-adrenergic receptor agonists isoproterenol (ADRB1), salmeterol (ADRB2), and BRL37344 (ADRB3), and the phosphodiesterase (PDE) inhibitors milrinone (PDE3), rolipram (PDE4), and sildenafil (PDE5) were performed. None of the tested drugs induced a relaxation higher than 30% of the U44069-induced tone. Rings from HUAs and HUVs showed a similar relaxation to forskolin, SNP, PDE inhibitors, and ADRB agonists. BAY 41-2272 was significantly more efficient in relaxing veins than arteries. ADRB agonists evoked weak relaxations (< 20%), which were impaired in endothelium-removed vessels or in the presence of the NO synthase inhibitor L-NAME, sGC inhibitor ODQ. PKA and PKG inhibitors impaired ADBR1-mediated relaxation but did not affect ADRB2-mediated relaxation. ADRB3-mediated relaxation was impaired by PKG inhibition in HUAs and by PKA inhibition in HUVs. Although HUA and HUV rings were relaxed by BRL37344, immunohistochemistry and RT-qPCR analysis showed that, compared to ADRB1 and ADRB2, ADRB3 receptors are weakly or not expressed in umbilical vessels. In conclusion, our study confirmed the low relaxing capacity of HUAs and HUVs from term infants. ADRB-induced relaxation is partially mediated by endothelium-derived NO pathway in human umbilical vessels.

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children.

BACKGROUND AND AIMS: Polyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica. METHOD AND RESULTS: We conducted a cross-sectional study among 468 parents and 201 children aged 7-12 y from the capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, and Tuxtla Gutiérrez in Mexico. We measured PUFA biomarkers in gluteal adipose tissue by gas chromatography. In adults, MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III definition. In children, we created an age- and sex-standardized metabolic risk score using abdominal circumference, the homeostasis model of insulin resistance, blood pressure, serum HDL cholesterol, and triglycerides. We estimated prevalence ratios of MetS and mean differences in metabolic score across quartiles of PUFA using multivariable-adjusted Poisson and linear regression models, respectively. Among adults, MetS was associated with low alpha-linolenic acid (ALA), high eicosapentaenoic acid (EPA), and low gamma-linolenic acid (GLA). It was linearly, positively associated with dihomo-gamma-linolenic acid (DGLA) and estimated Δ6-desaturase (D6D) activity. Among children, the metabolic score was positively associated with docosapentaenoic acid (DPA), DGLA, and D6D activity. CONCLUSIONS: Among Mesoamerican adults, MetS prevalence is inversely associated with adipose tissue ALA and GLA, and positively associated with EPA, DGLA, and the D6D index. Among children, metabolic risk score is positively associated with DPA, DGLA, and the D6D index.

Vitamin D-binding protein is inversely associated with the incidence of gastrointestinal and ear infections in school-age children.

Circulating 25-hydroxy vitamin D (25(OH)D) is related to decreased rates of gastrointestinal and ear infections in school-age children. Vitamin D-binding protein (DBP) transports 25(OH)D and exerts immunological functions; however, it is unknown whether DBP is associated with infectious morbidity in children. We quantified plasma DBP concentrations in 540 school-age children at the time of recruitment into a cohort study in Bogotá, Colombia and obtained daily information on infectious morbidity symptoms and doctor visits during the school year. We compared the incidence rates of gastrointestinal and respiratory symptoms across quartiles of DBP concentration by estimating adjusted incidence rate ratios (IRRs) with 95% confidence interval (CI). We also estimated the per cent of the associations between DBP and morbidity that were mediated through 25(OH)D using a counterfactual frame. Mean ± s.d. DBP concentration was 2650 ± 1145 nmol/l. DBP was inversely associated with the rates of diarrhoea with vomiting (IRR for quartiles 2-4 vs. 1 = 0.48; 95% CI 0.25-0.92; P = 0.03) and earache/ear discharge with fever (IRR for quartiles 2-4 vs. 1 = 0.29; 95% CI 0.12-0.71; P = 0.006). The DBP-morbidity associations were not mediated through 25(OH)D. We conclude that plasma DBP predicts lower incidence of gastrointestinal and ear infections in school-age children independent of 25(OH)D.

The highs and lows of programmed cardiovascular disease by developmental hypoxia: studies in the chicken embryo.

It is now established that adverse conditions during pregnancy can trigger a fetal origin of cardiovascular dysfunction and/or increase the risk of heart disease in later life. Suboptimal environmental conditions during early life that may promote the development of cardiovascular dysfunction in the offspring include alterations in fetal oxygenation and nutrition as well as fetal exposure to stress hormones, such as glucocorticoids. There has been growing interest in identifying the partial contributions of each of these stressors to programming of cardiovascular dysfunction. However, in humans and in many animal models this is difficult, as the challenges cannot be disentangled. By using the chicken embryo as an animal model, science has been able to circumvent a number of problems. In contrast to mammals, in the chicken embryo the effects on the developing cardiovascular system of changes in oxygenation, nutrition or stress hormones can be isolated and determined directly, independent of changes in the maternal or placental physiology. In this review, we summarise studies that have exploited the chicken embryo model to determine the effects on prenatal growth, cardiovascular development and pituitary-adrenal function of isolated chronic developmental hypoxia.

Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome.

Vitamin D could modulate pathways leading to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We examined the associations of serum total 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) concentrations in patients with uncomplicated dengue fever (DF) with risk of progression to DHF/DSS. In a case-control study nested in a cohort of DF patients who were followed during the acute episode in Bucaramanga, Colombia, we compared 25(OH)D and VDBP at onset of fever between 110 cases who progressed to DHF/DSS and 235 DF controls who did not progress. 25(OH)D concentrations were also compared between the acute sample and a sample collected >1 year post-convalescence in a subgroup. Compared with 25(OH)D ⩾75 nmol/l, adjusted odds ratios (95% CI) for progression were 0·44 (0·22-0·88) and 0·13 (0·02-1·05) for 50 to 75 nmol/l (vitamin D insufficiency) and <50 nmol/l (vitamin D deficiency), respectively (P, trend = 0·003). Mean 25(OH)D concentrations were much lower post-convalescence compared with the acute episode, regardless of case status. Compared with controls, mean VDBP was non-significantly lower in cases. We conclude that low serum 25(OH)D concentrations in DF patients predict decreased odds of progression to DHF/DSS.

Age at menarche in relation to prenatal rainy season exposure and altitude of residence: results from a nationally representative survey in a tropical country.

Intrauterine exposure to the rainy season in the tropics may be accompanied by high rates of infection and nutritional deficiencies. It is unknown whether this exposure is related to the extrauterine timing of development. Our aim was to evaluate the relations of prenatal exposure to the rainy season and altitude of residence with age at menarche. The study included 15,370 girls 10 to <18 years old who participated in Colombia's 2010 National Nutrition Survey. Primary exposures included the number of days exposed to the rainy season during the 40 weeks preceding birth, and altitude of residence at the time of the survey. We estimated median menarcheal ages and hazard ratios with 95% confidence interval (CI) according to exposure categories using Kaplan-Meier cumulative probabilities and Cox proportional hazards models, respectively. All tests incorporated the complex survey design. Girls in the highest quintile of gestation days exposed to the rainy season had an earlier age at menarche compared with those in the lowest (adjusted hazard ratios (HR)=1.08; 95% CI 1.00-1.18, P-trend=0.03). Girls living at altitudes ⩾2000 m had a later age at menarche compared with those living <1000 m (adjusted HR=0.88; 95% CI 0.82-0.94, P-trend <0.001). The inverse association between gestation days during the rainy season and menarche was most apparent among girls living at altitudes ⩾2000 m (P, interaction=0.04). Gestation days exposed to the rainy season and altitude of residence were associated with the timing of sexual maturation among Colombian girls independent of socioeconomic status and ethnicity.

Vasomotor effects of hydrogen sulfide in human umbilical vessels.

Hydrogen sulfide (H2S) has recently emerged as a biologically active gas with multiple effects on the cardiovascular system. We aimed to investigate the vasomotor actions of sodium sulfide (Na2S), which forms H2S and HS- in solution, in human umbilical artery (HUA) and vein (HUV) rings. In addition, we examined by immunocytochemistry the expression and localization of cystathionine ß-synthase (CBS), cystathionine lyase (CSE), and 3-mercaptopyruvate sulphurtransferase (MPST), the enzymes responsible for endogenous H2S production. Human umbilical vessels were compared with chicken embryo umbilical vessels. HUA and HUV expressed a robust signal for CSE, CBS, and 3-MPST in both endothelial and smooth muscle cells. However, HUA rings did not respond to Na2S (10-6M-10-3M) either at resting tone or during contraction evoked by serotonin or KCl. Similarly, the extraembryonic part of chicken allantoic artery did not respond to Na2S. In contrast, Na2S induced a concentration-dependent contraction in HUV rings under resting tone and a concentration-dependent relaxation when the H2UV rings were contracted with serotonin (42 ± 5% relaxation) or KCl (12 ± 5% relaxation). Na2S-induced contraction of HUV was impaired following removal of extracellular Ca2+, endothelial denudation, NO synthase inhibition (L-NAME), or soluble guanylate cyclase (sGC) inhibition (ODQ). Na2S-induced relaxation of HUV was impaired by the KATP channel inhibitor glibenclamide. In conclusion, H2S does not have vasomotor effects on HUA but induced contraction (mediated through inactivation of the NO/sGC axis) and relaxation (mediated through KATP channels) in HUV. Our data suggest a role for H2S in the venous side of human umbilical circulation.

Embedded purification for electron beam induced Pt deposition using MeCpPtMe3.

Two different room-temperature processes for the electron beam induced deposition of high purity platinum (Pt), using the standard MeCpPtMe3 precursor and oxygen for purification, have been investigated. The first process is a sequential method, which uses two independent gas injector systems (GIS) in order to perform a standard Pt deposition, followed by an e-beam post-irradiation under oxygen flux. The second process is a parallel, single-step process that includes a simultaneous flow of both precursor and oxygen, using an add-on device that can be mounted on the standard GIS needle. Both processes are effective in producing high purity Pt depositions close to 100 at%. The first method requires a high current and irradiation dose in the clean-up phase, and provides Pt structures with small voids, a maximum thickness of around 100 nm and resistivity of 88 ± 10 µΩ cm. The second method requires a high oxygen/precursor flux ratio and produces void-free structures with resistivity of 60 ± 5 µΩ cm, only six times the bulk value for Pt. The second method is easier to use and produces a void-free deposition of high purity Pt.

Alpha-linolenic acid (ALA) is inversely related to development of adiposity in school-age children.

BACKGROUND/OBJECTIVES: Studies in adults indicate that dietary polyunsaturated fatty acid (PUFA) composition may play a role in development of adiposity. Because adipocyte quantity is established between late childhood and early adolescence, understanding the impact of PUFAs on weight gain during the school-age years is crucial to developing effective interventions. SUBJECTS/METHODS: We quantified N-3 and N-6 PUFAs in serum samples of 668 Colombian schoolchildren aged 5-12 years at the time of recruitment into a cohort study, using gas-liquid chromatography. Serum concentrations of N-3 (alpha-linolenic acid (ALA), eicosapentaenoic acid, docosahexaenoic acid) and N-6 PUFAs (linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, arachidonic acid) were determined as percentage total fatty acids. Children's anthropometry was measured annually for a median of 30 months. We used mixed-effects models with restricted cubic splines to construct population body mass index-for-age z-score (BAZ) growth curves for age- and sex-specific quartiles of each PUFA. RESULTS: N-3 ALA was inversely related to BAZ gain after adjustment for sex, baseline age and weight status, as well as household socioeconomic level. Estimated BAZ change between 6 and 14 years among children in the highest quartile of ALA compared with those in the lowest quartile was 0.45 (95% confidence interval: 0.07, 0.83) lower (P-trend=0.006). CONCLUSIONS: N-3 ALA may be protective against weight gain in school-age children. Whether improvement in PUFA status reduces adiposity in pediatric populations deserves evaluation in randomized trials.

Prenatal exposure to hyperoxia modifies the thromboxane prostanoid receptor-mediated response to H2O2 in the ductus arteriosus of the chicken embryo.

O2 tension plays a critical role in the control of prenatal patency and postnatal closure of the ductus arteriosus (DA). We hypothesized that exposure of chicken embryos to hyperoxia alters the morphology and function of DA. Hyperoxia was induced by incubating fertilized eggs at 60% O2 from day 15 to 19 of the 21-d incubation period. DA reactivity (assessed by wire myography), morphometry and mRNA expression of antioxidant enzymes were studied on day 19. Hyperoxic incubation neither affected embryonic growth nor induced signs of DA constriction or changed the mRNA expression of superoxide dismutase and catalase. The contractions induced by O2 (21%), KCl, 4-aminopyridine, phenylephrine, and endothelin-1 and the relaxations induced by acetylcholine (ACh), sodium nitroprusside, isoproterenol, and hydroxyfasudil were similar in DA from embryos incubated under normoxic or hyperoxic conditions. In contrast, hyperoxic incubation impaired the thromboxane prostanoid (TP) receptor-mediated contractions evoked by U46619, 15-E2t-Isoprostane and high concentrations (≥3 µM) of ACh. Exogenous hydrogen peroxide (H2O2) evoked endothelium-dependent contraction in the normoxic DA and endothelium-dependent relaxation in the hyperoxic group. The presence of the TP receptor antagonist SQ 29548 unmasked a relaxant response to H2O2 in the normoxic DA and the cyclooxygenase (COX) inhibitor indomethacin blocked H2O2-induced contraction (in the normoxic group) and relaxation (in the hyperoxic group). Altogether our functional data suggest that, in the chicken DA, exogenous H2O2 induces the release of endothelium-derived COX metabolite(s) with contractile and relaxant properties. Under normal conditions H2O2-induced contraction prevails and relaxation is unmasked after pharmacological or functional (i.e.hyperoxia) TP receptor impairment.

Dietary intake, plasma homocysteine, and repetitive element DNA methylation in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: DNA methylation of repetitive elements may explain the relations between dietary intake, hyperhomocysteinemia, and cardiovascular disease risk. We investigated associations of methyl micronutrient intake and plasma total homocysteine with LINE-1 and Alu methylation in a cross-sectional study of 987 adults aged 45-84 y who participated in the Multi-Ethnic Study of Atherosclerosis (MESA) Stress Study. METHODS AND RESULTS: DNA methylation was estimated using pyrosequencing technology. A 120-item food frequency questionnaire was used to ascertain daily intake of folate, vitamin B12, vitamin B6, zinc, and methionine. Plasma total homocysteine was quantified using a fluorescence polarization immunoassay. Associations of micronutrient intake and homocysteine with LINE-1 and Alu methylation were examined using linear regression. Adjusted differences in %5-methylated cytosines (%5 mC) were examined by categories of predictors using multivariable linear regression models. Intake of methyl-donor micronutrients was not associated with DNA methylation. After adjustment for covariates, each 3 µmol/L increment of homocysteine corresponded with 0.06 (-0.01, 0.13) %5 mC higher LINE-1 methylation. Additionally, BMI was positively associated with LINE-1 methylation (P trend = 0.03). Participants with BMI ≥ 40 kg/m² had 0.35 (0.03, 0.67) %5 mC higher LINE-1 than those with normal BMI. We also observed a 0.10 (0.02, 0.19) %5 mC difference in Alu methylation per 10 cm of height. These associations did not differ by sex. CONCLUSION: Dietary intake of methyl-donor micronutrients was not associated with measures of DNA methylation in our sample. However, higher BMI was related to higher LINE-1 methylation, and height was positively associated with Alu methylation.

Micronutrient supplementation and T cell-mediated immune responses in patients with tuberculosis in Tanzania.

Limited studies exist regarding whether incorporating micronutrient supplements during tuberculosis (TB) treatment may improve cell-mediated immune response. We examined the effect of micronutrient supplementation on lymphocyte proliferation response to mycobacteria or T-cell mitogens in a randomized trial conducted on 423 patients with pulmonary TB. Eligible participants were randomly assigned to receive a daily dose of micronutrients (vitamins A, B-complex, C, E, and selenium) or placebo at the time of initiation of TB treatment. We found no overall effect of micronutrient supplements on lymphocyte proliferative responses to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV-positive TB patients. Of HIV-negative TB patients, the micronutrient group tended to show higher proliferative responses to concanavalin A than the placebo group, although the clinical relevance of this finding is not readily notable. The role of nutritional intervention in this vulnerable population remains an important area of future research.

Iron status and linear growth: a prospective study in school-age children.

BACKGROUND: Studies regarding the role of iron on linear growth have yielded heterogeneous results. Some trials indicate that iron supplementation of iron-replete infants leads to slower-length gain. However, little is known of the relation between iron status and linear growth in school-age children. METHODS: We quantified plasma ferritin, mean corpuscular volume (MCV), and hemoglobin in 2714 children aged 5-12 years at recruitment into a cohort study. Height was measured periodically for a median of 30 months. Height-for-age Z-scores (HAZ) were calculated using the World Health Organization growth reference. Mixed effects models with restricted cubic splines were used to construct population HAZ-for-age growth curves for sex- and age-specific quartiles of each iron status indicator. RESULTS: Ferritin and MCV were each inversely related to attained HAZ among boys after the adjustment for baseline age, baseline body mass index-for-age Z-score and socioeconomic status. There was a decreasing monotonic relation between quartiles of ferritin and estimated change in HAZ from ages 6 to 14 years (P trend=0.001); boys in the 4th quartile experienced a HAZ change that was 0.46 Z lower than that of boys in the 1st quartile (P=0.0006). Similarly, we observed smaller HAZ change among boys in the highest quartile of MCV in comparison with those in the 1st quartile (P trend=0.001). Hemoglobin was not related to linear growth in boys. None of the iron-status indicators were associated with linear growth in girls. CONCLUSIONS: Higher iron status, as indicated by ferritin and MCV, is related to slower linear growth in iron-replete school-age boys.

High birth weight and obesity--a vicious circle across generations.

OBJECTIVES: Rates of high birth weight infants, overweight and obese children and adults are increasing. The associations between birth weight and adult weight may have consequences for the obesity epidemic across generations. We examined the association between mothers' birth weight for gestational age and adult body mass index (BMI) and these factors' joint effect on risk of having a large-for-gestational-age (LGA) offspring (>+2 s.d. above the mean). DESIGN: A cohort of 162 676 mothers and their first-born offspring with birth information recorded on mothers and offspring in the nation-wide Swedish Medical Birth Register 1973-2006. RESULTS: Compared with mothers with appropriate birth weight for gestational age (AGA; -1 to +1 s.d.), mothers born LGA had increased risks of overweight (BMI 25.0-29.9; odds ratio (OR), 1.50; 95% CI 1.39-1.61), obesity class I (BMI 30.0-34.9; OR 1.77; 95% CI 1.59-1.98), obesity class II (BMI 35.0-39.9; OR 2.77; 95% CI 2.37-3.24) and obesity class III (BMI ≥40.0; OR 2.04; 95% CI 1.49-2.80). In each stratum of mother's birth weight for gestational age, risk of having an LGA offspring increased with mother's BMI. The risk of an LGA offspring was highest among women with a high (≥30) BMI who also had a high birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI (≤24.9). However, the strongest increase in risk by BMI was seen among mothers born SGA: the OR of having an LGA offspring was 13 times as high among SGA mothers with BMI ≥35.0 compared with the OR among SGA mothers with normal BMI (ORs=4.61 and 0.35, respectively). CONCLUSIONS: Prenatal conditions are important for the obesity epidemic. Prevention of LGA births may contribute to curtail the intergenerational vicious cycle of obesity.