Deteriorating complementary feeding practices and dietary quality in Jordan: Trends and challenges.

Quality complementary feeding (CF) of infants and young children is key to their growth and development. But in Jordan, providing appropriate CF remains a challenge. This study assesses trends in infant and young child feeding (IYCF) practices, and consumption by infants and young children aged 6-23 months of breast milk substitutes (BMSs), sugar-sweetened beverages (SSBs), and micronutrient-rich foods in Jordan from 1990 to 2017. We combined dietary data on infants and young children from six Demographic and Health Surveys (DHS) (n = 14,880 children) to compute IYCF indicators. The latter included minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable diet (MAD), as well as intake of micronutrient-rich foods and food groups, specific SSBs, and infant formula. We conducted trend analyses using logistic regression models adjusted for child's age in month, child age squared, governorates, urban/rural residence, mother's educational attainment, and household wealth quintiles. We found that the proportion of consumption of micronutrient-rich food groups declined significantly between 1990 and 2017, with fewer infants and young children consuming eggs (OR = 0.39, p ≤ 0.001, 2002 reference), meat, poultry, and fish (OR = 0.25, p ≤ 0.001, 2002 reference), dairy (OR = 0.59, p ≤ 0.001, 2002 reference) and Vitamin A-rich fruits and vegetables (OR = 0.66, p ≤ 0.001, 2002 reference). Conversely, there was increased use of BMSs and sugar-sweetened juices that paralleled a decline in the share of infants and young children meeting appropriate CF practices and consuming micronutrient-rich foods and food groups. By 2017, children aged 6-23 months were significantly less likely to meet MDD, MMF, and subsequently MAD; the odds of consuming BMSs were almost three times the reference (OR = 3.8, p ≤ 0.001, 1990 reference), as were the odds of consuming sugar sweetened juices  (OR = 3.63, p ≤ 0.001, 1990 reference). Food insecurity and undernutrition are low in Jordan; however, overweight and obesity rates are increasing concurrently as are micronutrient deficiencies. This highlights the need for policymakers to address factors at individual and household levels (behaviours and practices) as well as environmental issues (increasing access to unhealthy and ultraprocessed foods).

Relationship between Animal Sourced Food Consumption and Early Childhood Development Outcomes.

Early-childhood development (ECD) is an important determinant of a child's cognitive ability, learning, productivity, and lifetime earnings. Animal-sourced food (ASF), which is a rich source of high-quality protein and micronutrients, has been linked with ECD outcomes. This study investigates the relationship between the number, frequency, and cumulative consumption of ASF at 6, 9, 12, and 18 months of age and ECD outcomes at 24 months of age, controlling for physical growth. The study uses data collected from 701 mother−child pairs from an observational birth cohort study carried out in Banke, Nepal. ECD outcomes were assessed through a standardized ages and stages questionnaire (ASQ-3) tool. Separate multivariable ordinary least squares regression models were used to test for associations. Significant positive association was seen between total ASQ-3 score at 24 months of age and any ASF consumption at 18 months (ß = 8.98, p-value < 0.01), controlling for growth outcomes. The study findings highlight the positive contribution and the accumulating benefit of consistent ASF consumption on ECD outcomes. This study recommends support and promotion of ASF intake among young children in Nepal through policy and programming actions relevant to female education; nutrition knowledge; quality ASF production; improved market access; cold storage; and poverty reduction.

Emerging role of LETM1/GRP78 axis in lung cancer.

The selective autophagy of damaged mitochondria is called mitophagy. Mitochondrial dysfunction, mitophagy, and apoptosis have been suggested to be interrelated in various human lung carcinomas. Leucine zipper EF-hand-containing transmembrane protein-1 (LETM1) was cloned in an attempt to identify candidate genes for Wolf-Hirschhorn syndrome. LETM1 plays a role in mitochondrial morphology, ion homeostasis, and cell viability. LETM1 has also been shown to be overexpressed in different human cancer tissues, including lung cancer. In the current study, we have provided clear evidence that LETM1 acts as an anchoring protein for the mitochondria-associated ER membrane (MAM). Fragmented mitochondria have been found in lung cancer cells with LETM1 overexpression. In addition, a reduction of mitochondrial membrane potential and significant accumulation of microtubule-associated protein 1 A/1B-light chain 3 punctate, which localizes with Red-Mito, was found in LETM1-overexpressed cells, suggesting that mitophagy is upregulated in these cells. Interestingly, glucose-regulated protein 78 kDa (GRP78; an ER chaperon protein) and glucose-regulated protein 75 kDa (GRP75) were posited to interact with LETM1 in the immunoprecipitated LETM1 of H460 cells. This interaction was enhanced in cells treated with carbonyl cyanide m-chlorophenylhydrazone, a chemical mitophagy inducer. Treatment of cells with honokiol (a GRP78 inhibitor) blocked LETM1-mediated mitophagy, and CRISPR/Cas9-mediated GRP75 knockout inhibited LETM1-induced autophagy. Thus, GRP78 interacts with LETM1. Taken together, these observations support the notion that the complex formation of LETM1/GRP75/GRP78 might be an important step in MAM formation and mitophagy, thus regulating mitochondrial quality control in lung cancer.

Child stunting starts in utero: Growth trajectories and determinants in Ugandan infants.

Childhood stunting remains a public health burden worldwide. Although many studies have examined early life and in-utero risk factors; most have been observational and have used analytic techniques that make inferences limited to population means, thereby obscuring important within-group variations. This study addressed that important gap. Using data from a birth cohort of Ugandan infants (n = 4528), we applied group-based trajectory modelling to assess diverse patterns of growth among children from birth to 1-year old. A multinomial regression model was conducted to understand the relationship between risk factors and observed patterns across groups. We found that the onset of stunting occurred before birth and followed four distinct growth patterns: chronically stunted (Group 1), recovery (Group 2), borderline stunted (Group 3) and normal (Group 4). The average length-for-age z-score (LAZ) at birth was -2.6, -3.9, -0.6 and 0.5 for Groups 1-4, respectively. Although both Groups 1 and 2 were stunted at birth, stunting persisted in Group 1 while children in Group 2 recovered by the fourth month. Group 3 exhibited mild stunting while Group 4 was normal. Wasting and underweight were observed in all groups, with the highest prevalence of underweight in Group 1. Wasting gradually increased among children born already stunted (Groups 1 and 2). This showed the importance of distinguishing children by their growth patterns rather than aggregating them and only comparing population averages against global growth standards. The design of nutrition interventions should consider the differential factors and potential for growth gains relative to different risks within each group.

Dietary determinants of aflatoxin B1-lysine adduct among infants in Nepal.

BACKGROUND: Aflatoxins are mycotoxins produced by naturally occurring fungi on food, and aflatoxin B1 (AFB1) is carcinogenic, immunotoxic and hepatotoxic. This study assesses the relationship between AFB1 in Nepali infants at 12 months of age and their diet at 9 and 12 months of age. METHODS: The study used data collected from 1329 infants enrolled in the AflaCohort Study. Aflatoxin exposure was assessed at 12 months using serum AFB1-lysine pg/mg albumin biomarker measured using high performance liquid chromatography-fluorescent detection. Dietary data were collected using food frequency questionnaire. We conducted ordinary least squares and quantile regression analyses with backward elimination to assess lagged (9-month diet and 12-month AFB1) and contemporaneous (12-month diet and 12-month AFB1) associations. RESULTS: Eighty-one percent of children at 12 months had detectable levels of serum AFB1-lysine (geometric mean: 0.79 pg/mg albumin, 95% CI: 0.74-0.83). The levels ranged from 0.4 to 85 pg/mg albumin. Dietary diversity at 9 and 12 months were not associated with serum AFB1-lysine levels. Consumption of fish and groundnuts at both 9 and 12 months and infant formula and cauliflower at 9 months were associated with higher serum AFB1-lysine while consumption of bananas and mangoes at 12 months were negatively associated with serum AFB1-lysine (p < 0.05). CONCLUSIONS: High prevalence of detectable AFB1-lysine among infants, and possible links to their dietary patterns argues for more urgent research into which foods in children's diets are most contaminated, and into optimal entry points in the food chain that would allow for effective actions to minimize exposure.

Effects of Iron and Vitamin A Levels on Pregnant Women and Birth Outcomes: Complex Relationships Untangled Using a Birth Cohort Study in Uganda.

INTRODUCTION: Women and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants' growth. METHODS: We determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers (ferritin, soluble transferrin receptor [sTFR], body iron stores [BIS], hemoglobin and retinol binding protein [RBP]) and birth outcomes (body weight, Z-scores, head circumference, small-for-gestational-age and preterm birth) in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes. RESULTS: After adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births (AOR: 0.67; 95% CI 0.48-0.94). For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (ß = 0.12, p < 0.030). DISCUSSION: These findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes. CLINICALTRIALS: gov as NCT04233944.

Exposure to multiple mycotoxins, environmental enteric dysfunction and child growth: Results from the AflaCohort Study in Banke, Nepal.

Evidence of the impact of exposure to multiple mycotoxins and environment enteric dysfunction (EED) on child growth is limited. Using data from a birth cohort study, the objectives of this study were to (a) quantify exposure to multiple mycotoxins (serum aflatoxin [AFB1 ] and ochratoxin A [OTA], urinary fumonisin [UFB1 ] and deoxynivalenol [DON]), as well EED (lactulose:mannitol [L:M] ratio); (b) examine the potential combined effects of multiple mycotoxin exposure and EED on growth. Multivariate regressions were used to identify associations between growth measurements (length, weight, anthropometric z-scores, stunting and underweight) at 24-26 months of age and exposure to mycotoxins and EED at 18-22 months (n = 699). Prevalence of AFB1 , DON, OTA and UFB1 exposure ranged from 85% to 100%; average L:M ratio was 0.29 ± 0.53. In individual mycotoxin models, AFB1 exposure was negatively associated with weight, WAZ, increased odds of stunting (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.08, 1.52; p = 0.004) and underweight (OR: 1.18, 95% CI: 1.00, 1.38; p = 0.046). Irrespective of other mycotoxin exposure and presence of EED, AFB1 was negatively associated with length, weight, head circumference, LAZ and WAZ, and with increased odds of stunting and underweight, UFB1 was associated with increased odds of underweight, and DON was negatively associated with head circumference. EED was associated with the impaired length and weight. These findings suggest that certain mycotoxins and EED may have independent impacts on different facets of growth and that aflatoxin dominates such impacts. Thus, programs reducing exposure to mycotoxin and EED through multi-sectoral nutrition-sensitive interventions have the potential to improve child growth.

Measuring Governance: Developing a Novel Metric for Assessing Whether Policy Environments are Conducive for the Development and Implementation of Nutrition Interventions in Nepal.

BACKGROUND: The Nutrition Governance Index (NGI) defines a first standardized approach to quantifying the 'quality of governance' in relation to national plans of action to accelerate improvements in nutrition. It was created in response to growing demand for evidence-based measures that reveal opportunities and challenges as nutrition-related policies on paper are translated into outcomes on the ground. Numerous past efforts to measure 'governance,' most notably World Health Organization's (WHO's) NGI and the separate Hunger and Nutrition Commitment Index (HANCI), both of which lack granularity below the national level and each of which fails to capture pinch points related to necessary cross-sectoral actions. This paper addresses such caveats by introducing an innovative metric to assess self-reported practices of, and perceptions held by, administration officials tasked with implementing government policy at the sub-national level. The paper discusses the development of this metric, its methodology, and explores its application in the context of Nepal. METHODS: Conducted as part of a nationally representative longitudinal survey across 21 of Nepal's 75 districts, the substudy??? on which this paper is based used data from 520 government and non-government officials at different geographic and administrative tiers of authority. Using robust statistical techniques, structured questionnaire data were condensed into a score using a scale from 0 to 100. RESULTS: Six domains were identified through the analysis: Understanding Nutrition and related responsibilities; Collaboration; Financial Resources; Nutrition Leadership, Capacity, and Support. About half of all health sector representatives achieved a high score (>3 on 5-point scale) compared to representatives in other sectors of government activity (such as agriculture or education) (χ2=12.99, P<.003). The health sector also showed the most improvement in mean NGI score over a two-year follow-up period. CONCLUSION: This paper shows that self-reported perceptions and behaviors of those responsible for policy implementation can be usefully quantified. The NGI can be used to assess countries' readiness for the application of nutrition policies.

Consumption of animal source foods, especially fish, is associated with better nutritional status among women of reproductive age in rural Bangladesh.

In rural Bangladesh, intake of nutrient-rich foods, such as animal source foods (ASFs), is generally suboptimal. Diets low in nutrients and lacking in diversity put women of reproductive age (WRA) at risk of malnutrition as well as adverse birth outcomes. The objective of this study was to assess the relationship between maternal dietary diversity, consumption of specific food groups and markers of nutritional status, including underweight [body mass index (BMI) < 18.5 kg/m2 ], overweight (BMI ≥ 23 kg/m2 ) and anaemia (haemoglobin < 120 g/dl) among WRA in Bangladesh. This analysis used data from the third round of a longitudinal observational study, collected from February through May of 2017. Dietary data were collected with a questionnaire, and Women's Dietary Diversity Score (WDDS) was calculated. Associations between WDDS, food group consumption and markers of nutritional status were assessed with separate adjusted logistic regression models. Among WRA, the prevalence of underweight, overweight and anaemia was 13.38%, 40.94% and 39.99%, respectively. Women who consumed dark green leafy vegetables (DGLV) or eggs were less likely to be anaemic or underweight, respectively, and women who consumed ASFs, particularly fish, were less likely to be underweight compared with women who did not consume these foods. WDDS did not show any consistent relationship with WRA outcomes. Interventions that focus on promoting optimal nutritional status among WRA in Bangladesh should emphasise increasing consumption of specific nutrient-rich foods, including ASFs, DGLV and eggs, rather than solely focusing on improving diet diversity in general.

Effective nutrition governance is correlated with better nutrition outcomes in Nepal.

BACKGROUND: The public health burden of undernutrition remains heavy and widespread, especially in low-income countries like Nepal. While predictors of undernutrition are well documented, few studies have examined the effects of political will and quality of policy or program implementation on child growth. METHODS: Data were collected from two nationwide studies in Nepal to determine the relationship between a metric of nutrition 'governance' (the Nutrition Governance Index), derived from interviews with 520 government and non-government officials responsible for policy implementation and anthropometry measured for 6815 children in 5556 households. We employed Generalized Estimating Equation (GEE) and multilevel regression models. RESULTS: A higher NGI (more effective nutrition governance) is positively associated with height-for-age as well as weight-for-height in children over 2 years of age compared to younger children (HAZ; ß = 0.02, p < 0.004, WHZ; ß = 0.01, p < 0.37). Results from the hierarchical model show that a one-point increase in the NGI is significantly associated with a 12% increase in HAZ and a 4% increase in WHZ in older children (> 24 months old). Mothers' education, child's age, BMI and no fever in the past 30 days were also protective of stunting and wasting. Seven percent and 17% of the overall variance in HAZ and WHZ, respectively, are accounted for by variations across the 21 district locations in which sampled households were located. Mean HAZ differs considerably across districts (intercept = 0.116, p < 0.001). CONCLUSIONS: These results highlight the importance of effective management of policy-based programming and resource use to bring about nutrition gains on the ground. The NGI explained a non-negligible amount of variation in HAZ and WHZ, which underscores the fundamental role that good governance plays in promoting child nutrition and growth, and the value of seeking to measure it to assist governments in moving policies from paper to practice.

Aflatoxin exposure and child nutrition: measuring anthropometric and long-bone growth over time in Nepal.

BACKGROUND: Naturally occurring aflatoxins may contribute to poor growth and nutritional statuses in children. OBJECTIVES: We analyzed the relationship between contemporary and lagged aflatoxin exposure and 1) length-for-age z-score (LAZ); and 2) length, knee-heel length, stunting, weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ). METHODS: We conducted a longitudinal birth cohort study involving 1675 mother-infant dyads in rural Nepal. Participants were repeatedly visited from pregnancy to 2 years of age (2015-2019). One blood sample was collected during pregnancy and 4 samples were collected from the children at 3, 6, 12, and 18-22 months of age to measure concentrations of aflatoxin B1 (AFB1)-lysine adduct. Multivariate linear fixed-effects and logistic models with generalized estimating equations were used to identify associations between child growth and aflatoxin exposure. RESULTS: AFB1-lysine adducts were detected in the majority of children (at 3 months, 80.5%; at 6 months, 75.3%; at 12 months, 81.1%; and at 18-22 months, 85.1%) and in 94.3% of pregnant women. Changes in contemporary ln child AFB1-lysine adduct concentrations were significantly associated with changes in LAZ (ß, -0.05; 95% CI, -0.09 to -0.02; P = 0.003), length (ß, -0.19; 95% CI, -0.29 to -0.10; P < 0.001), knee-heel length (ß, -0.09; 95% CI, -0.13 to -0.05; P < 0.001), and WAZ (ß, -0.04; 95% CI, -0.07 to -0.005; P = 0.022). Serum aflatoxin concentrations were associated with stunting (OR, 1.18; 95% CI, 1.05-1.32; P = 0.005). Similar results were found in the models using changes in contemporary ln AFB1 adjusted for changes in child weight, with significant associations with changes in WLZ (ß, -0.07; 95% CI, -0.10 to -0.03; P < 0.001). Changes in time-lagged ln AFB1 (unadjusted and adjusted for changes in child weight) were associated with changes in length and knee-heel length. CONCLUSIONS: Our results add to the growing body of evidence confirming chronic aflatoxin exposure and suggest that exposure is significantly correlated with various negative growth outcomes, which may vary by child weight status. This trial was registered at clinicaltrials.gov as NCT03312049.

Sustained intake of animal-sourced foods is associated with less stunting in young children.

The value of animal-sourced foods (ASFs) in providing key nutrients, particularly for child growth and where diets are of low quality, is understood mainly from cross-sectional assessment of current consumption. Longitudinal panel data from Nepal, Bangladesh and Uganda were used here to assess associations among previous (lagged) and contemporaneous ASF intake with linear growth of children aged 6-24 months. Lagged ASF consumption was significantly correlated with a 10% decline in stunting in Nepali children who consumed any ASF in the previous year, while current intake was associated with a 9% decline in stunting in Uganda. Previous consumption of two or more ASFs showed a stronger association, ranging from a 10% decline in stunting in Bangladesh to a 16% decline in Nepal. This novel lagged analysis emphasizes the need for regular and appropriate levels of ASF intake by young children to support healthy growth in resource-constrained settings.

Using mobile phone data helps estimate community-level food insecurity: Findings from a multi-year panel study in Nepal.

Household food insecurity remains a major policy challenge in low-income countries. Identifying accurate measures that are relatively easy to collect has long been an important priority for governments seeking to better understand and fund solutions for communities in remote settings. Conventional approaches based on surveys can be time-consuming and costly, while data derived from satellite imagery represent proxies focused on biological processes (such as rainfall and crop growth) lack granularity in terms of human behaviors. As a result, there has recently been interest in tapping into the large digital footprint offered by mobile phone usage. This paper explores empirical relationships between data relating to mobile phones (ownership and spending on service use), and food insecurity in rural Nepal. The work explores models for estimating community-level food insecurity through aggregated mobile phone variables in a proof-of-concept approach. In addition, sensitivity analyses were performed by considering the performance of the models under different settings. The results suggest that mobile phone variables on ownership and expenditure can be used to estimate food insecurity with reasonable accuracy. This suggests that such an approach can be used in and beyond Nepal as an option for collecting timely food insecurity information, either alone or in combination with conventional approaches.

Household Engagement in Both Aquaculture and Horticulture Is Associated with Higher Diet Quality than Either Alone.

The consumption of high-quality diverse diets is crucial for optimal growth, health, and wellbeing. OBJECTIVE: This study assessed the diet quality of households by their type of engagement in homestead aquaculture and/or horticulture. Socio-demographic determinants of diet quality were also studied. METHOD: Diet quality was assessed using a nutrient adequacy ratio (NAR), based on the preceding 7 days' dietary recall at the household level. Adult male equivalent units (AMEs) were used for age- and sex-specific intra-household distribution of household intakes. Mean adequacy ratios (MAR) were computed as an overall measure of diet quality, using NAR. RESULTS: Better diet quality (mean ± SD) was associated with households engaged in both homestead aquaculture and horticulture (0.43 ± 0.23; p < 0.001) compared to only one type of agriculture (0.38 ± 0.20) or none (0.36 ± 0.20). Tukey's post-hoc test confirmed significant differences in diet quality between both and either engagement (0.05 ± 0.01, p < 0.001), both and no engagement (0.07 ± 0.01, p < 0.001), and either and no engagement households (0.02 ± 0.01, p < 0.001). Beyond farm production of nutrient-rich foods, generalized estimating equations showed that diet quality was influenced by the higher educational level and occupation of adult household members, higher daily per capita food expenditure, sex, family size and region. CONCLUSIONS: Projects that promote and support household engagement in both homestead aquaculture and horticulture have the potential to improve the diet quality of households.

Predictors of low birth weight and preterm birth in rural Uganda: Findings from a birth cohort study.

BACKGROUND: Approximately 20.5 million infants were born weighing <2500 g (defined as low birthweight or LBW) in 2015, primarily in low- and middle-income countries (LMICs). Infants born LBW, including those born preterm (<37 weeks gestation), are at increased risk for numerous consequences, including neonatal mortality and morbidity as well as suboptimal health and nutritional status later in life. The objective of this study was to identify predictors of LBW and preterm birth among infants in rural Uganda. METHODS: Data were derived from a prospective birth cohort study conducted from 2014-2016 in 12 districts across northern and southwestern Uganda. Birth weights were measured in triplicate to the nearest 0.1 kg by trained enumerators within 72 hours of delivery. Gestational age was calculated from the first day of last menstrual period (LMP). Associations between household, maternal, and infant characteristics and birth outcomes (LBW and preterm birth) were assessed using bivariate and multivariable logistic regression with stepwise, backward selection analyses. RESULTS: Among infants in the study, 4.3% were born LBW (143/3,337), and 19.4% were born preterm (744/3,841). In multivariable analysis, mothers who were taller (>150 cm) (adjusted Odds Ratio (aOR) = 0.42 (95% CI = 0.24, 0.72)), multigravida (aOR = 0.62 (95% CI = 0.39, 0.97)), or with adequate birth spacing (>24 months) (aOR = 0.60 (95% CI = 0.39, 0.92)) had lower odds of delivering a LBW infant Mothers with severe household food insecurity (aOR = 1.84 (95% CI = 1.22, 2.79)) or who tested positive for malaria during pregnancy (aOR = 2.06 (95% CI = 1.10, 3.85)) had higher odds of delivering a LBW infant. In addition, in multivariable analysis, mothers who resided in the Southwest (aOR = 0.64 (95% CI = 0.54, 0.76)), were ≥20 years old (aOR = 0.76 (95% CI = 0.61, 0.94)), with adequate birth spacing (aOR = 0.76 (95% CI = 0.63, 0.93)), or attended ≥4 antenatal care (ANC) visits (aOR = 0.56 (95% CI = 0.47, 0.67)) had lower odds of delivering a preterm infant; mothers who were neither married nor cohabitating (aOR = 1.42 (95% CI = 1.00, 2.00)) or delivered at home (aOR = 1.25 (95% CI = 1.04, 1.51)) had higher odds. CONCLUSIONS: In rural Uganda, severe household food insecurity, adolescent pregnancy, inadequate birth spacing, malaria infection, suboptimal ANC attendance, and home delivery represent modifiable risk factors associated with higher rates of LBW and/or preterm birth. Future studies on interventions to address these risk factors may be warranted.

Dietary determinants of aflatoxin B1-lysine adduct in pregnant women consuming a rice-dominated diet in Nepal.

BACKGROUND: Aflatoxins are found in diverse foods widely consumed worldwide. This study investigated the association between aflatoxin exposure and (a) consumption of specific foods, (b) dietary diversity (DD), and (c) seasonality. METHODS: Women enrolled in the AflaCohort Study in Banke, Nepal (n = 1648) were asked how often they ate certain food items in the past 7 days and 24 h. Serum aflatoxin B1-lysine (AFB1-lys) adduct levels, measured during pregnancy, were determined using high-performance liquid chromatography. Multivariable ordinary least squares and quantile regression models were used to examine incremental increases in AFB1-lys adduct levels per frequency of food consumption and the relationship between DD, seasonality, and increases in AFB1-lys adduct. RESULTS: Roughly 94% of women were exposed to aflatoxin (geometric mean 1.37 pg/mg). Women in the 30th, 50th, and 70th quantiles of aflatoxin exposure who reported one more occasion of maize consumption in the past week showed increases in AFB1-lys adduct levels: 0.094, 0.112, and 0.109 pg/mg (p < 0.05, all). Women in the 30th, 50th, 70th, and 90th quantiles of exposure who reported one more occasion of groundnut consumption in the past week also showed increases in AFB1-lys adduct levels: 0.058 (p < 0.001), 0.085 (p < 0.01), 0.133 (p < 0.001), and 0.133 (p < 0.001) pg/mg. Winter month recruitment was positively associated with AFB1-lys adduct levels at all quantiles of aflatoxin exposure (range: 0.313-1.101 pg/mg, p < 0.001). DD was not predictive of aflatoxin exposure. CONCLUSIONS: Our findings justify integrated approaches to aflatoxin reduction, including regulatory, agricultural, and food safety interventions across the value chain and at the household level.

Relatively Low Maternal Aflatoxin Exposure Is Associated with Small-for-Gestational-Age but Not with Other Birth Outcomes in a Prospective Birth Cohort Study of Nepalese Infants.

BACKGROUND: Exposure to aflatoxin has garnered increased attention as a possible contributor to adverse birth outcomes. OBJECTIVE: The objective of this study was to investigate the relation of maternal aflatoxin exposure with adverse birth outcomes such as birth weight, birth length, anthropometric z scores, low birth weight (LBW), small-for-gestational-age (SGA), stunting, and preterm birth (PTB). METHODS: This study used maternal and newborn data from the AflaCohort Study, an ongoing birth cohort study in Banke, Nepal (n = 1621). Data on aflatoxin B1 (AFB1)-lysine adducts in maternal serum were collected once during pregnancy (at mean ± SD: 136 ± 43 d of gestation). Maternal serum AFB1-lysine adduct concentration was measured via HPLC. Linear and logistic regression analyses were used to determine if maternal aflatoxin exposure was associated with 1) birth weight and length (primary outcomes) and 2) anthropometric z scores, LBW (weight <2.5 kg), SGA (weight <10th percentile for gestational age and sex), stunting at birth (length-for-age z score less than -2), or PTB (born <37 weeks of gestation) (secondary outcomes). RESULTS: The geometric mean of maternal serum AFB1-lysine adduct concentration was 1.37 pg/mg albumin (95% CI: 1.30, 1.44 pg/mg albumin). Twenty percent of infants were of LBW and 32% were SGA. Sixteen percent of infants were stunted at birth. In addition, 13% of infants were born preterm. In logistic multivariate regression models, mean maternal serum AFB1-lysine adduct concentrations were significantly associated with SGA (OR: 1.13; 95% CI: 1.00, 1.27; P < 0.05). CONCLUSIONS: Findings from this study suggest a small but significant association between serum AFB1-lysine adduct concentrations in pregnant women and SGA. Maternal aflatoxin exposure was not associated with other birth outcomes. These results highlight the need for future research on a threshold level of aflatoxin exposure needed to produce detectable adverse birth outcomes. This trial was registered at clinicaltrials.gov as NCT03312049.

LETM1 is required for mitochondrial homeostasis and cellular viability (Review).

Leucine zipper/EF­hand­containing transmembrane protein 1 (LETM1) has been identified as the gene responsible for Wolf­Hirschhorn syndrome (WHS), which is characterized by intellectual disability, epilepsy, growth delay and craniofacial dysgenesis. LETM1 is a mitochondrial inner membrane protein that encodes a homolog of the yeast protein Mdm38, which is involved in mitochondrial morphology. In the present review, the importance of LETM1 in WHS and its role within the mitochondrion was explored. LETM1 governs the mitochondrion ion channel and is involved in mitochondrial respiration. Recent studies have reported that LETM1 acts as a mitochondrial Ca2+/H+ antiporter. LETM1 has also been identified as a K+/H+ exchanger, and serves a role in Mg2+ homeostasis. The function of LETM1 in mitochondria regulation is regulated by its binding partners, carboxyl­terminal modulator protein and mitochondrial ribosomal protein L36. Therefore, we describe the remarkable role of LETM1 in mitochondrial network physiology and its function in mitochondrion­mediated cell death. In the context of these findings, we suggest that the participation of LETM1 in tumorigenesis through the alteration of cancer metabolism should be investigated. This review provides a comprehensive description of LETM1 function, which is required for mitochondrial homeostasis and cellular viability.

Measuring Nutrition Governance: An Analysis of Commitment, Capability, and Collaboration in Nepal.

BACKGROUND: Global commitments to nutrition have supported calls for better evidence to support effective investments at national level. However, too little attention has so far been paid to the role of governance in achieving impacts. OBJECTIVE: This article explores the ways by which the commitment and capabilities of policy implementers affect collaborative efforts for achieving nutrition goals. METHODS: Over 1370 structured interviews were held with government and nongovernment officials over 3 years in 21 districts. Coded responses supported quantitative analysis of stakeholders' knowledge, attitudes, and practices regarding policy implementation. RESULTS: Stakeholder commitment was already high in 2013 when a new national policy was adopted, but capabilities were weak. Only one-third of interviewed respondents had any nutrition training. Rollout of training focusing on districts targeted for early implementation of multisector programming. This raised levels of nutrition training among interviewed respondents to 57% in 2015, which raised demand for technical information to support actions. Better understanding of the complexity of cross-sector work led to calls for higher budgets and more effective cross-sectoral collaboration. CONCLUSION: Nepal offers an example of effective efforts to improve nutrition governance across sectors at all levels of administration. The promotion of awareness, capacity, and new ways of working shows promise. Trainings, information sharing, and management support led to growing willingness among civil servants to engage across sectors. Structured surveys offer a viable way to track change across institutions and sectors.

SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells.

Antipsychotic drugs are regularly used for the treatment of many types of psychiatric disorders. The administration of second-generation antipsychotics is often associated with weight gain and the development of diabetes mellitus; however, the molecular mechanisms underlying the effects of these drugs remain poorly understood. Leptin and insulin play key roles in the regulation of energy balance and glucose homeostasis, and resistance to the actions of these hormones can occur with obesity and inflammation, resulting in the pathogenesis of obesity and type 2 diabetes. In this study, the effects of risperidone on the insulin-induced protein kinase B (PKB) phosphorylation and leptin-stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation were investigated in the human SH-SY5Y neuroblastoma cell line. The treatment of these cells with risperidone induced the activation of extracellular signal-related kinase (ERK) by cellular cyclic adenosine 3-monophosphate (cAMP)-dependent protein kinase (also known as protein kinase A; PKA) and the mechanisms involved include the induction of suppressor of cytokine signaling 3 (SOCS3) and suppressor of cytokine signaling 6 (SOCS6) expression. The risperidone-induced ERK activation induced an upregulation of SOCS3 and SOCS6 mRNA expression levels. Taken together, these results suggest that risperidone modulates SOCS3 and SOCS6 expression through adenylate cyclase-mediated ERK activation, which, in turn, leads to an inhibition of insulin-induced PKB phosphorylation and leptin-stimulated STAT3 phosphorylation. Eventually, these effects result in excessive body weight gain due to the inhibition of both the leptin and insulin signaling pathways.