Increased cytotoxicity of oxidized flame soot

AbstractCombustion–generated particles released into the atmosphere undergo reactions with oxidants, which can change the particles’ physiochemical characteristics. In this work, we compare the physical and chemical properties and cellular response of particles fresh from a flame with those oxidized by ozone and nitrogen dioxide. The reaction with ozone and nitrogen dioxide does not significantly modify the physical characteristics of the particles (primary particle size, fractal dimension, and surface area). However, oxidation affects the chemical characteristics of the particles, creating more oxygen and nitrogen containing functional groups, and increases their hydrophilicity. In addition, oxidized soot generates more reactive oxygen species, as measured by the dithiothreitol (DTT) assay. Furthermore, oxidized soot is 1.5 – 2 times more toxic than soot that was not reacted with ozone, but the inflammatory response, measured by interleukin–8 (IL–8) secretion, is unchanged. These results imply that combustion–generated particles released into the atmosphere will have an increased toxicity on or after high ozone days

The Effects of Supplementing Maternal and Infant Diets with Lipid-based Nutrient Supplements on Physical Activity and Sedentary Behaviour at Preschool Age in Ghana

Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4–6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNS v. non-LNS (MMN+ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n 129) had lower VM (difference in mean −73 (95 % CI −20, −126), P = 0·007) and spent more time in SB (LNS v. non-LNS: 32·3 v. 30·5 %, P = 0·020) than the non-LNS group (n224) but did not differ in MVPA (4·4 v. 4·7 %, P = 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group

Dot1 binding induces chromatin rearrangements by histone methylation-dependent and -independent mechanisms

<p>Abstract</p> <p>Background</p> <p>Methylation of histone H3 lysine 79 (H3K79) by Dot1 is highly conserved among species and has been associated with both gene repression and activation. To eliminate indirect effects and examine the direct consequences of Dot1 binding and H3K79 methylation, we investigated the effects of targeting Dot1 to different positions in the yeast genome.</p> <p>Results</p> <p>Targeting Dot1 did not activate transcription at a euchromatic locus. However, chromatin-bound Dot1 derepressed heterochromatin-mediated gene silencing over a considerable distance. Unexpectedly, Dot1-mediated derepression was established by both a H3K79 methylation-dependent and a methylation-independent mechanism; the latter required the histone acetyltransferase Gcn5. By monitoring the localization of a fluorescently tagged telomere in living cells, we found that the targeting of Dot1, but not its methylation activity, led to the release of a telomere from the repressive environment at the nuclear periphery. This probably contributes to the activity-independent derepression effect of Dot1.</p> <p>Conclusions</p> <p>Targeting of Dot1 promoted gene expression by antagonizing gene repression through both histone methylation and chromatin relocalization. Our findings show that binding of Dot1 to chromatin can positively affect local gene expression by chromatin rearrangements over a considerable distance.</p

Prenatal and postnatal lipid-based nutrient supplementation and cognitive, social-emotional, and motor function in preschool-aged children in Ghana: a follow-up of a randomized controlled trial

Background: Adequate nutrition is necessary for brain development during pregnancy and infancy. Few randomized controlled trials of supplementation during these periods have measured later developmental outcomes. Objective: Our objective was to investigate the effects of provision of prenatal and postnatal lipid-based nutrient supplements (LNS) on child development at preschool age. Methods: We conducted a follow-up study of 966 children aged 4–6 y in 2016, born to women who participated in the International Lipid-Based Nutrient Supplements-DYAD trial conducted in Ghana in 2009–2014, representing 79% of eligible children. Women ≤20 weeks of gestation were randomized to daily LNS or multiple micronutrient (MMN) capsules during pregnancy through 6 mo postpartum or iron and folic acid (IFA) capsules during pregnancy and calcium placebo capsules during 6 mo postpartum. Children in the LNS group received LNS from 6 to 18 mo. Primary outcomes of this follow-up study were (1) a cognitive factor score based on a test battery adapted from several standard tests, 2) fine motor score (9-hole pegboard test), and (3) social-emotional difficulties (Strengths and Difficulties Questionnaire; SDQ). Eight secondary outcomes were calculated in specific domains (e.g., language, SDQ prosocial). Analysis was by a complete case intention to treat in a 2-group comparison: LNS compared with non-LNS (MMN + IFA). Results: Children in the LNS group had significantly lower social-emotional difficulties z-scores than children in the non-LNS group (adjusted for child age β = −0.12, 95% CI: −0.25, 0.02, P = 0.087; fully adjusted β = −0.16, 95% CI: −0.29, −0.03, P = 0.013). The effect of LNS on social-emotional difficulties score was larger among children living in households with lower home environment scores (P-interaction = 0.081). No other outcomes differed between the 2 intervention groups. Conclusions: Provision of LNS during the first 1000 d of development improved behavioral function, particularly for children from low nurturing and stimulation households, but did not affect cognition at preschool age in this setting. Trial Registration: clinicaltrials.gov, Identifier NCT00970866

Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso

BackgroundPrevious reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD.MethodsWe conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n&nbsp;=&nbsp;1,023), Malawi (n&nbsp;=&nbsp;675 and 1,385), and Burkina Faso (n&nbsp;=&nbsp;1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9&nbsp;months. In multiple linear regression and structural equation&nbsp;models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD.ResultsOut of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6&nbsp;months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts.ConclusionsKey elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status

Impact of a nutritional supplement during gestation and early childhood on child salivary cortisol, hair cortisol, and telomere length at 4–6 years of age: a follow-up of a randomized controlled trial

Dysregulation of the stress response can occur early in life and may be affected by nutrition. Our objective was to evaluate the long-term effect of nutritional supplementation during gestation and early childhood on child cortisol and buccal telomere length (a marker of cellular aging) at 4–6 years of age. We conducted a follow-up study of children born to women who participated in a nutritional supplementation trial in Ghana. In one group, a lipid-based nutrient supplement (LNS) was provided to women during gestation and the first 6 months postpartum and to their infants from age 6 to 18 months. The control groups received either iron and folic acid (IFA) during gestation or multiple micronutrients during gestation and the first 6 months postpartum, with no infant supplementation. At age 4–6 years, we measured hair cortisol, buccal telomere length, and salivary cortisol before and after a stressor. Salivary cortisol was available for 364 children across all three trial arms and hair cortisol and telomere length were available for a subset of children (n = 275 and 278, respectively) from the LNS and IFA groups. Telomere length, salivary cortisol, and hair cortisol did not differ by supplementation group. Overall, these findings suggest that nutritional supplementation given during gestation and early childhood does not have an effect on child stress response or chronic stress in children at 4–6 years

Maternal and Infant Lipid-Based Nutritional Supplementation Increases Height of Ghanaian Children at 4–6 Years Only if the Mother Was Not Overweight Before Conception

Background Few studies have evaluated the long-term effects of nutritional supplementation during the first 1000 d of life. We previously reported that maternal and child lipid-based nutrient supplements (LNS) increased child length by 18 mo. Objective The aim of this study was to examine the effects of LNS on later growth and body composition at 4–6 y of age. Design This was a follow-up of children in the International Lipid-based Nutrient Supplements (iLiNS)-DYAD trial in Ghana. Women (n = 1320) at ≤20 weeks of gestation were randomly assigned to: 1) iron and folic acid during pregnancy and 200 mg calcium/d for 6 mo postpartum, 2) multiple micronutrients (1–2 RDA of 18 vitamins and minerals) during both periods, or 3) maternal LNS during both periods plus child LNS from 6 to 18 mo. At 4–6 y, we compared height, height-for-age z score (HAZ), and % body fat (deuterium dilution method) between the LNS group and the 2 non-LNS groups combined. Results Data were available for 961 children (76.5% of live births). There were no significant differences between LNS compared with non-LNS groups in height [106.7 compared with 106.3 cm (mean difference, MD, 0.36; P = 0.226)], HAZ [−0.49 compared with −0.57 (MD = 0.08; P = 0.226)], stunting (\u3c -2 SD) [6.5 compared with 6.3% (OR = 1.00; P = 0.993)], or % body fat [15.5 compared with 15.3% (MD = 0.16; P = 0.630)]. However, there was an interaction with maternal prepregnancy BMI (kg/m2) (P-interaction = 0.046 before correction for multiple testing): among children of women with BMI \u3c 25 , LNS children were taller than non-LNS children (+1.1 cm, P = 0.017), whereas there was no difference among children of women with BMI ≥ 25 (+0.1 cm; P = 0.874). Conclusions There was no overall effect of LNS on height at 4–6 y in this cohort, which had a low stunting rate, but height was greater in the LNS group among children of nonoverweight/obese women. There was no adverse impact of LNS on body composition. This trial was registered at clinicaltrials.gov as NCT00970866

The Association of Early Linear Growth and Haemoglobin Concentration with Later Cognitive, Motor, and Social–Emotional Development at Preschool Age in Ghana

It is important to identify the periods during childhood when exposure to environmental risk factors results in long‐term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4–6 years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow‐up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4–6 years, cognitive, motor, and social–emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length‐for‐age z‐score (LAZ) at birth and postnatal linear growth (n = 710) and Hb (n = 617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4–6 years was significantly associated with LAZ at birth (β = 0.12, 95% CI = 0.05, 0.19), ΔLAZ from 6 to 18 months (β = 0.16, 95% CI = 0.04, 0.28), and Hb at 18 months (β = 0.13, 95% CI = 0.06, 0.20), but not with ΔLAZ during 0–6 months, ΔLAZ from 18 months to 4–6 years, Hb at 6 months, or Hb at 4–6 years. No evidence of associations with motor or social–emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18 months are more sensitive to risk factors for long‐term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development

The impact of maternal supplementation during pregnancy and the first 6 months postpartum on the growth status of the next child born after the intervention period: Follow‐up results from Bangladesh and Ghana

Pregnancy and breastfeeding make demands on maternal nutrient stores. The extent of depletion and the degree to which nutrient stores are replenished between pregnancies has implications for a mother\u27s nutritional status at conception of the subsequent child and therefore that child\u27s birth outcomes and growth. Using follow‐up data collected several years after a randomized effectiveness trial conducted in rural Bangladesh and a randomized efficacy trial conducted in semiurban Ghana, we evaluated the impact of maternal supplementation with small‐quantity lipid‐based nutrient supplements (LNS) or multiple micronutrients (MMN) through pregnancy (the index pregnancy) and 6 months postpartum on the growth status of the next living younger sibling conceived and born after the index pregnancy. In both Bangladesh (n = 472 younger siblings) and Ghana (n = 327 younger siblings), there were no overall differences in the growth status or the prevalence of undernutrition among younger siblings whose mothers had received LNS (or MMN, Ghana only) during and after the index pregnancy compared with the younger siblings of mothers who had received iron plus folic acid (IFA) during the index pregnancy (Ghana) or during and for 3 months after the index pregnancy (Bangladesh). These findings do not indicate that preconception nutrition interventions do not improve child growth. Rather, they suggest that any benefits of maternal LNS or MMN supplementation during one pregnancy and for 6 months postpartum are unlikely to extend to the growth of her next child beyond any effects due to IFA alone