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1.
Mol Cell ; 83(23): 4304-4317.e8, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-37949069

ABSTRACT

RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA targets. FMRP regulates this process by sequestering YTHDF1 away from the ribosome; upon neuronal stimulation, FMRP becomes phosphorylated and releases YTHDF1 for translation upregulation. We show that a new small molecule inhibitor of YTHDF1 can reverse fragile X syndrome (FXS) developmental defects associated with FMRP deficiency in an organoid model. Our study thus reveals that FMRP and its phosphorylation are important regulators of activity-dependent translation during neuronal development and stimulation and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.


Subject(s)
Fragile X Mental Retardation Protein , Fragile X Syndrome , Humans , Phosphorylation , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Neurons/metabolism , Fragile X Syndrome/genetics , Fragile X Syndrome/metabolism , Ribosomal Proteins/metabolism , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
2.
Proc Natl Acad Sci U S A ; 119(22): e2118124119, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35617426

ABSTRACT

Fragile X­associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative disease in premutation carriers of the expanded CGG repeat in FMR1 that presents with a spectrum of neurological manifestations, such as gait ataxia, intention tremor, and parkinsonism [P. J. Hagerman, R. J. Hagerman, Ann. N. Y. Acad. Sci. 1338, 58­70 (2015); S. Jacquemont et al., JAMA 291, 460­469 (2004)]. Here, we performed whole-genome sequencing (WGS) on male premutation carriers (CGG55­200) and prioritized candidate variants to screen for candidate genetic modifiers using a Drosophila model of FXTAS. We found 18 genes that genetically modulate CGG-associated neurotoxicity in Drosophila, such as Prosbeta5 (PSMB5), pAbp (PABPC1L), e(y)1 (TAF9), and CG14231 (OSGEPL1). Among them, knockdown of Prosbeta5 (PSMB5) suppressed CGG-associated neurodegeneration in the fly as well as in N2A cells. Interestingly, an expression quantitative trait locus variant in PSMB5, PSMB5rs11543947-A, was found to be associated with decreased expression of PSMB5 and delayed onset of FXTAS in human FMR1 premutation carriers. Finally, we demonstrate evidence that PSMB5 knockdown results in suppression of CGG neurotoxicity via both the RAN translation and RNA-mediated toxicity mechanisms, thereby presenting a therapeutic strategy for FXTAS.


Subject(s)
Ataxia , Fragile X Syndrome , Proteasome Endopeptidase Complex , Tremor , Animals , Ataxia/genetics , Disease Models, Animal , Drosophila melanogaster , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , Humans , Male , Proteasome Endopeptidase Complex/genetics , Tremor/genetics
3.
Emerg Infect Dis ; 29(5): 1066-1067, 2023 05.
Article in English | MEDLINE | ID: mdl-37081604

ABSTRACT

To investigate SARS-CoV-2 transmission from humans to animals in Seoul, South Korea, we submitted samples from companion animals owned by persons with confirmed COVID-19. Real-time PCR indicated higher SARS-CoV-2 viral infection rates for dogs and cats than previously reported from the United States and Europe. Host-specific adaptations could introduce mutant SARS-CoV-2 to humans.


Subject(s)
COVID-19 , Cat Diseases , Dog Diseases , Animals , Cats , Dogs , Humans , Cat Diseases/epidemiology , COVID-19/veterinary , Dog Diseases/epidemiology , Republic of Korea/epidemiology , SARS-CoV-2/genetics , Respiratory Tract Infections
4.
BMC Pregnancy Childbirth ; 23(1): 107, 2023 Feb 11.
Article in English | MEDLINE | ID: mdl-36774497

ABSTRACT

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.


Subject(s)
Dietary Supplements , Lactation , Female , Humans , Infant , Infant, Newborn , Pregnancy , Data Collection , Prospective Studies , Retrospective Studies
5.
Matern Child Nutr ; 19(2): e13460, 2023 04.
Article in English | MEDLINE | ID: mdl-36482813

ABSTRACT

There is growing recognition that engaging men in maternal, infant and young child nutrition (MIYCN) interventions can benefit child health and disrupt harmful gender norms. We conducted a cluster-randomized controlled trial in Tanzania, which engaged men and women in behaviour change via mobile messaging (short message service [SMS]) and traditional interpersonal communication (IPC), separately and in combination. Here, we evaluate intervention effects on individual-level men's MIYCN knowledge and discuss barriers to male engagement. Eligible clusters were dispensary catchment areas with >3000 residents. Forty clusters were stratified by population size and randomly allocated to the four study arms, with 10 clusters per arm. Data on knowledge and intervention exposure were collected from 1394 men through baseline and endline surveys (March-April 2018 and July-September 2019). A process evaluation conducted partway through the 15-18-month intervention period included focus group discussions and interviews. Data were analysed for key trends and themes using Stata and ATLAS.ti software. Male participants in the short message service + interpersonal communication (SMS + IPC) group reported higher exposure to IPC discussions than IPC-only men (43.8% and 21.9%, respectively). Knowledge scores increased significantly across all three intervention groups, with the greatest impact in the SMS + IPC group. Qualitative findings indicated that the main barriers to male participation were a lack of interest in health/nutrition and perceptions that these topics were a woman's responsibility. Other challenges included meeting logistics, prioritizing income-earning activities and insufficient efforts to engage men. The use of a combined approach fusing IPC with SMS is promising, yet countering gender norms and encouraging stronger male engagement may require additional strategies.


Subject(s)
Gender Identity , Men , Humans , Male , Female , Infant , Child , Tanzania , Qualitative Research , Focus Groups
6.
Matern Child Nutr ; 19(2): e13461, 2023 04.
Article in English | MEDLINE | ID: mdl-36468458

ABSTRACT

Given the high prevalence of child undernutrition in Bangladesh, multi-sectoral approaches involving livelihood promotion have potential to mitigate the burden of undernutrition. This study examined the impact of an economic development (ED) program providing poultry assets, gardening skills and saving training added to the Positive Deviant (PD)/Hearth program (PDH/ED), compared to PD/Hearth only (PDH). A total of 1029 children who attended PD/Hearth sessions in September-November 2018 at 6-13 months of age were enrolled in the cohort study in July-August 2019. The cohort, comprised of 532 children in the PDH/ED group and 593 children in the PDH group, was reassessed in November 2020. The program impact on child nutrition, food security, crop production, dietary quality and household income was estimated using a difference-in-differences approach accounting for the sociodemographic differences between PDH/ED and PDH groups. Compared to the PDH group, the PDH/ED group showed increases in child dietary diversity score (DDS) (+0.32), child minimum dietary diversity (13.7 percentage points [pp]), and maternal DDS (+0.28) (all p < 0.05). From 2019 to 2020, the PDH/ED households improved food security by 12.6 pp and diversified crop production (bananas (9.7 pp), papaya (11.1 pp), carrots (3.8 pp) and lemons (5.9 pp)), and increased the proportion of annual income ≥60,000 Taka by 12.4 pp and last month income ≥5000 Taka by 7.8 pp, compared to PDH group (all p < 0.05). However, there was no impact on child nutritional status, morbidity, livestock ownership and total annual/last income. Incorporating an ED program into nutrition programming could benefit food security and dietary diversity in rural Bangladesh.


Subject(s)
Nutritional Status , Child , Humans , Bangladesh/epidemiology , Child Nutritional Physiological Phenomena , Cohort Studies , Malnutrition/epidemiology , Rural Population , Food Security , Crop Production
7.
Matern Child Nutr ; 19(3): e13487, 2023 07.
Article in English | MEDLINE | ID: mdl-36924028

ABSTRACT

This study explores common factors associated with not meeting minimum dietary diversity (MDD) among 27,072 children aged 6-23 months in Eastern and Southern Africa using data from nine Demographic and Health Surveys from 2013 to 2016. MDD was defined as consumption of more than or equals to five of eight food groups including breast milk in the past 24 h. Equity gaps were calculated as the difference in MDD prevalence between the top and bottom wealth quintiles. Logistic regression was conducted to identify common factors for not meeting MDD at the household, maternal and child levels across two or more countries to inform regional policies to improve children's diets. Kenya had the highest MDD wealth equity gap (40.4 pts), and South Africa had the smallest (14.4 pts). Equity gaps for flesh foods or eggs (up to 39.8 pp) were larger than for grain or legumes (up to 20 pp). Common risk factors for not reaching MDD included younger child age (6-11 months) (n = 9 countries), no formal maternal occupation (n = 6), not receiving vitamin-A supplementation (n = 3), younger maternal age (n = 3), lower maternal education (n = 3), no media (n = 3) or newspaper (n = 3) exposure, lower household wealth quintile (n = 3), use of nonefficient cooking fuel (n = 2), longer time to get to the water source (n = 2), not listening to the radio (n = 2) and higher birth order (n = 2). Priorities for improving MDD in the region include introducing diverse foods at a young age from 6 months with early nutrition counselling, promoting higher maternal education, increasing food purchasing power and ensuring the support of younger mothers.


Subject(s)
Diet , Feeding Behavior , Female , Child , Infant , Humans , Child, Preschool , Socioeconomic Factors , Vegetables , Milk, Human , Africa, Southern
8.
Matern Child Nutr ; 18(3): e13340, 2022 07.
Article in English | MEDLINE | ID: mdl-35313062

ABSTRACT

The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6-month follow-up visit. Height and weight were measured at baseline and a 6-month follow-up. Baseline minimum dietary diversity (MDD) for children 6-23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A-rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6-23 months of age. Linear growth faltering was defined as a significant decline (p < 0.05) in length-for-age Z-scores (LAZ) between baseline and follow-up. Regression models were performed. The study was conducted in rural eastern Democratic Republic of the Congo (DRC). MDD was positively associated with change in LAZ (coefficient: 0.87 [95% confidence interval [CI]: 0.33, 1.40]), and a reduced odds of stunting (LAZ < -2) (odds ratio: 0.21 [95% CI: 0.07, 0.61]). MDD was also associated with a significantly higher combined EASQ-Z-scores (coefficient: 0.34 [95% CI: 0.003, 0.68], higher communication EASQ-Z-scores [0.50 {95% CI: 0.14, 0.85}], and higher personal social EASQ-Z-scores [0.46 {95% CI: 0.11, 0.82}]). This study provides further evidence demonstrating the need for interventions to improve dietary diversity among young children.


Subject(s)
Child Development , Diet , Child , Child, Preschool , Democratic Republic of the Congo/epidemiology , Female , Growth Disorders/epidemiology , Humans , Infant , Prospective Studies , Vegetables
9.
Public Health Nutr ; 24(9): 2640-2649, 2021 06.
Article in English | MEDLINE | ID: mdl-32933590

ABSTRACT

OBJECTIVE: To explore the influence of obstetrical care factors on dietary diversity and individual food group consumption in Indonesia. DESIGN: Cross-sectional study to assess the association between pregnancy care factors and dietary diversity score, minimum dietary diversity (MDD) and consumption of seven food groups. SETTING: Data from the Indonesia Demographic and Health Survey 2017. PARTICIPANTS: A total of 5113 children aged 6-23 months. RESULTS: Dietary diversity score was significantly higher for children whose mothers received four or more prenatal care visits, were delivered at a health facility, had a professionally trained delivery assistant and were delivered by C-section. Children born at a health facility and delivered by a health professional had higher odds of meeting MDD (adjusted OR (AOR) 1·45, 95 % CI 1·18, 1·79 and OR 2·10, 95 % CI 1·54, 2·87, respectively). Four or more antenatal visits, delivering at a health facility and having a professional delivery attendant were associated with higher odds of consumption of lentils (AOR 1·66, 95 % CI 1·23, 2·25, AOR 1·30, 95 % CI 1·02, 1·65 and AOR 1·79, 95 % CI 1·19, 2·69). Four or more antenatal visits, delivering at a health facility and having a professional delivery attendant had higher odds of consumption of other fruits and vegetables (AOR 1·70, 95 % CI 1·23, 2·35, OR 1·23, 95 % CI 1·03, 1·61 and OR 1·90, 95 % CI 1·29, 2·79). CONCLUSIONS: Efforts focusing on providing nutritional education during antenatal care and delivery should be encouraged, especially for mothers seeking care outside of a health facility.


Subject(s)
Diet , Prenatal Care , Child , Cross-Sectional Studies , Demography , Female , Humans , Indonesia , Pregnancy
10.
Public Health Nutr ; 24(16): 5514-5523, 2021 11.
Article in English | MEDLINE | ID: mdl-34348815

ABSTRACT

OBJECTIVE: To examine the difference in the rehabilitation rate from underweight by child age at enrolment in the Positive Deviance (PD)/Hearth programme. DESIGN: This secondary data analysis used programme monitoring records of underweight children aged 6-60 months attending a 2-week PD/Hearth session and followed up for 6 months from September 2018 to March 2019. Data were analysed using multilevel mixed-effect regression and Poisson regression with robust variance. SETTING: Rajshahi Division, Bangladesh. PARTICIPANTS: A total of 5227 underweight (weight-for-age Z-score (WAZ) <-2) children attended the PD/Hearth sessions. RESULTS: From enrolment to 6 months follow-up, the mean WAZ improved from -2·80 to -2·09, and the percentage of underweight children decreased to 54·5 %. Compared to the enrolment age of 6-11 months, the estimated monthly change in WAZ at 6 months of follow-up were 0·05 lower for 12-23 months, 0·06 lower for 24-35 months, and 0·09 lower for 36-60 months of the enrolment age (all P < 0·001). The probability of rehabilitation at 6 months of follow-up were lower by 16·7 % for 12-23 months (RR = 0·83; 95 % CI 0·77, 0·91), 15·5 % for 24-35 months (RR = 0·84; 95 % CI 0·78, 0·92), and 34·9 % for 36-60 months of the enrolment age (RR = 0·65; 95 % CI 0·59, 0·72), compared to the enrolment age of 6-11 months. CONCLUSIONS: Enrolment in the PD/Hearth programme at a younger age had the advantage of greater rehabilitation from underweight than older age. Our findings provide a better understanding of the successes and failures of the PD/Hearth programme to achieve more sustainable and cost-effective impacts.


Subject(s)
Nutritional Status , Rural Population , Aged , Bangladesh/epidemiology , Child , Humans , Infant , Infant, Newborn , Thinness/epidemiology
11.
BMC Public Health ; 21(1): 2009, 2021 11 04.
Article in English | MEDLINE | ID: mdl-34736426

ABSTRACT

BACKGROUND: School closures and family economic instability caused by the COVID-19 lockdown measures have threatened the mental health and academic progress of adolescents. Through secondary data analysis of World Vision Asia Pacific Region's COVID-19 response-assessments in May-June 2020, this study examined whether adolescents' study, physical, and leisure activities, psychosocial status, and sources of COVID-19 information differed by gender. METHODS: The assessments used cross-sectional surveys of adolescents in poor communities served by World Vision (n = 5552 males and n = 6680 females) aged 10-18 years old in six countries. The study households of adolescents were selected either by random sampling or non-probability convenience sampling and assessed using telephone or in-person interviews. Multivariate logistic regression analyses examined the relationship between gender and psychosocial status; daily activities (e.g., play, study); and sources of information about COVID-19. RESULTS: Participation in remote education was low (range: 0.5-20.7% across countries), with gender difference found only in Vietnam. Compared to males, female adolescents were less likely to play physically with a range of AOR: 0.36-0.55 (n = 5 countries) or play video games with a range of AOR: 0.55-0.72 (n = 2 countries). Female adolescents were more likely to feel isolated or stressed (India, AOR = 1.13, 95%CI:1.00, 1.26); feel unsafe (the Philippines, AOR = 2.22, 95%CI:1.14, 4.33; Vietnam, AOR = 1.31, 95%CI:1.03, 1.47); be concerned about education (India, AOR = 1.24, 95%CI:1.09, 1.41; Myanmar, AOR = 1.59, 95%CI:1.05, 2.40); or be concerned about household income (India, AOR = 1.13, 95%CI:1.00, 1.28; Vietnam, AOR = 1.31, 95%CI:1.09, 1.58). Female adolescents were also less likely to obtain COVID-19 related information through internet/social media (Bangladesh, AOR = 0.51, 95%CI:0.41, 0.64; India, AOR = 0.84, 95%CI:0.73, 0.96; and Myanmar, AOR = 0.65, 95%CI:0.43, 0.97) and mobile call or short message (India, AOR = 0.88, 95%CI:0.80, 0.98) but more likely to get the information from friends (Vietnam, AOR = 1.18, 95%CI:1.02, 1.36) and family (Bangladesh, AOR = 1.44, 95% CI:1.21, 1.70; India, AOR = 1.29, 95% CI:1.15, 1.45). CONCLUSIONS: An understanding of gender differences in the impacts of COVID-19 on adolescents' schooling, physical, and mental health can inform adolescent protection interventions. Psychosocial support during response and recovery phases needs to pay special attention to gender differences, since female adolescents' psychosocial status is at higher risk when facing the challenges of this pandemic.


Subject(s)
COVID-19 , Adolescent , Child , Communicable Disease Control , Cross-Sectional Studies , Female , Humans , Male , SARS-CoV-2 , Sex Factors
12.
Hum Mol Genet ; 27(22): 3936-3950, 2018 11 15.
Article in English | MEDLINE | ID: mdl-30107516

ABSTRACT

N6-methyladenosine (m6A) is the most prevalent internal modification of mammalian messenger RNAs (mRNAs) and long non-coding RNAs. The biological functions of this reversible RNA modification can be interpreted by cytoplasmic and nuclear 'm6A reader' proteins to fine-tune gene expression, such as mRNA degradation and translation initiation. Here we profiled transcriptome-wide m6A sites in adult mouse cerebral cortex, underscoring that m6A is a widespread epitranscriptomic modification in brain. Interestingly, the mRNA targets of fragile X mental retardation protein (FMRP), a selective RNA-binding protein, are enriched for m6A marks. Loss of functional FMRP leads to Fragile X syndrome (FXS), the most common inherited form of intellectual disability. Transcriptome-wide gene expression profiling identified 2035 genes differentially expressed in the absence of FMRP in cortex, and 92.5% of 174 downregulated FMRP targets are marked by m6A. Biochemical analyses indicate that FMRP binds to the m6A sites of its mRNA targets and interacts with m6A reader YTHDF2 in an RNA-independent manner. FMRP maintains the stability of its mRNA targets while YTHDF2 promotes the degradation of these mRNAs. These data together suggest that FMRP regulates the stability of its m6A-marked mRNA targets through YTHDF2, which could potentially contribute to the molecular pathogenesis of FXS.


Subject(s)
Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , RNA-Binding Proteins/genetics , Adenosine/analogs & derivatives , Adenosine/genetics , Animals , Cerebral Cortex/metabolism , Cerebral Cortex/physiopathology , Disease Models, Animal , Epigenomics/methods , Fragile X Syndrome/physiopathology , Gene Expression Regulation/genetics , Genome/genetics , Humans , Mice , Proteolysis , RNA, Messenger/genetics , Transcriptome/genetics
13.
J Nutr ; 150(1): 118-127, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31504681

ABSTRACT

BACKGROUND: Evidence on the prospective association between grain consumption and metabolic syndrome (MetS) is lacking. OBJECTIVE: This study explored the association between grain intake by subtype or various combinations of grain intake and the risk of developing MetS in South Korean adults using data from a community-based prospective cohort study. METHODS: A total of 5717 participants (2984 men and 2733 women) aged 40-69 y without MetS were followed up for 10 y (2001-2012). Grain consumption was assessed using a semiquantitative FFQ at baseline (2001-2002) and a follow-up examination (2005-2006). A multivariate Cox proportional hazards model was used to examine the risk of incident MetS and its components according to grain consumption (<1, 1 to <3, or ≥3 servings/d) by sex. RESULTS: In total, 2218 participants (38.8%) developed MetS. Frequent consumers of whole grains (≥3 servings/d) had a lower risk of incident MetS (men-HR: 0.51; 95% CI: 0.41, 0.63; P  = 0.0001; women-HR: 0.73; 95% CI: 0.60, 0.90; P = 0.0029), whereas frequent consumers of refined grains had a higher risk of incident MetS (men-HR: 1.63; 95% CI: 1.31, 2.03; P < 0.0001; women-HR: 2.25; 95% CI: 1.82, 2.78; P < 0.0001) compared with rare consumers (<1 serving/d). The combination of low whole grains (<2 servings/d) and high refined grains (≥2 servings/d) was associated with a higher risk of MetS than the combination of high whole grains and low refined grains (men-HR: 1.21; 95% CI: 1.04, 1.41; P = 0.012; women-HR: 1.43; 95% CI: 1.23, 1.66; P < 0.0001). CONCLUSIONS: Higher consumption of whole grains was associated with lower risk of incident MetS, whereas higher refined-grain consumption was associated with a higher risk in a middle-aged and older Korean population.


Subject(s)
Dietary Carbohydrates , Edible Grain , Food Preferences , Metabolic Syndrome/etiology , Adult , Aged , Cohort Studies , Diet , Female , Humans , Male , Middle Aged , Risk Factors
14.
J Nutr ; 150(11): 3024-3032, 2020 11 19.
Article in English | MEDLINE | ID: mdl-32840613

ABSTRACT

BACKGROUND: The prevalence of stunting in central rural Malawi is ∼50%, which prompted a multipronged nutrition program in 1 district from 2014 to 2016. The program distributed a daily, fortified, small-quantity lipid-based nutritional supplement, providing 110 kcal and 2.6 g of protein to children aged 6-23 mo, and behavior change messages around optimal infant and young child feeding (IYCF) and water, sanitation, and hygiene. OBJECTIVES: Our objective was to perform an impact evaluation of the program using a neighboring district as comparison. METHODS: Using a quasi-experimental study design, with cross-sectional baseline (January-March, 2014; n = 2404) and endline (January-March, 2017; n = 2453) surveys, we evaluated the program's impact using a neighboring district as comparison. Impact on stunting was estimated using propensity score weighted difference-in-differences regression analyses to account for baseline differences between districts. RESULTS: No differences in mean length-for-age z-score or prevalence of stunting were found at endline. However, mean weight, weight-for-length z-score, and mid-upper arm circumference were higher at endline by 150 g, 0.22, and 0.19 cm, respectively, in the program compared with the comparison district (all P < 0.05). Weekly reports of high fever and malaria were also lower by 6.4 and 4.7 percentage points, respectively, in the program compared with the comparison district (both P < 0.05). There was no impact on anemia. Children's dietary diversity score improved by 0.17, and caregivers' infant and young child feeding and hand-washing practices improved by 8-11% in the program compared with the comparison district (all P < 0.05). CONCLUSIONS: An impact evaluation of a comprehensive nutrition program in rural Malawi demonstrated benefit for child ponderal growth and health, improved maternal IYCF and hand-washing practices, but a reduction in stunting prevalence was not observed.


Subject(s)
Food Assistance , Government Programs , Growth Disorders/prevention & control , Infant Nutrition Disorders/prevention & control , Rural Population , Child Development , Cross-Sectional Studies , Female , Humans , Infant , Infant Nutritional Physiological Phenomena , Malawi , Male , Nutritional Status
15.
Hum Mol Genet ; 26(13): 2398-2411, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28398475

ABSTRACT

Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- and oxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity and intellectual disability. The role of FTO in neurodevelopment and neurogenesis, however, remains largely unknown. Here we show that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to decreased brain size and body weight. We find that FTO deficiency could reduce the proliferation and neuronal differentiation of adult neural stem cells in vivo, which leads to impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we went on to perform genome-wide m6A profiling and observed dynamic m6A modification during postnatal neurodevelopment. The loss of FTO led to the altered expression of several key components of the brain derived neurotrophic factor pathway that were marked by m6A. These results together suggest FTO plays important roles in neurogenesis, as well as in learning and memory.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Neurogenesis/genetics , Animals , Body Weight/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cell Differentiation/genetics , Gene Expression Regulation , Memory , Mice , Mice, Knockout , Neurons/metabolism , Obesity/genetics
16.
Public Health Nutr ; 22(4): 697-705, 2019 03.
Article in English | MEDLINE | ID: mdl-30378520

ABSTRACT

OBJECTIVE: To examine the association between household food insecurity and dietary diversity in the past 24h (dietary diversity score (DDS, range: 0-9); minimum dietary diversity (MDD, consumption of three or more food groups); consumption of nine separate food groups) among pregnant and lactating women in rural Malawi. DESIGN: Cross-sectional study. SETTING: Two rural districts in Central Malawi. SUBJECTS: Pregnant (n 589) and lactating (n 641) women. RESULTS: Of surveyed pregnant and lactating women, 66·7 and 68·6 %, respectively, experienced moderate or severe food insecurity and only 32·4 and 28·1 %, respectively, met MDD. Compared with food-secure pregnant women, those who reported severe food insecurity had a 0·36 lower DDS (P<0·05) and more than threefold higher risk (OR; 95 % CI) of not consuming meat/fish (3·19; CI 1·68, 6·03). The risk of not consuming eggs (3·77; 1·04, 13·7) was higher among moderately food-insecure pregnant women. Compared with food-secure lactating women, those who reported mild, moderate and severe food insecurity showed a 0·36, 0·44 and 0·62 lower DDS, respectively (all P<0·05). The risk of not achieving MDD was higher among moderately (1·95; 1·06, 3·59) and severely (2·82; 1·53, 5·22) food-insecure lactating women. The risk of not consuming meat/fish and eggs increased in a dose-response manner among lactating women experiencing mild (1·75; 1·01, 3·03 and 2·81; 1·09, 7·25), moderate (2·66; 1·47, 4·82 and 3·75; 1·40, 10·0) and severe (5·33; 2·63, 10·8 and 3·47; 1·19, 10·1) food insecurity. CONCLUSIONS: Addressing food insecurity during and after pregnancy needs to be considered when designing nutrition programmes aiming to increase dietary diversity in rural Malawi.


Subject(s)
Diet/statistics & numerical data , Family Characteristics , Food Supply/statistics & numerical data , Lactation , Rural Population/statistics & numerical data , Adult , Cross-Sectional Studies , Feeding Behavior , Female , Humans , Malawi/epidemiology , Nutrition Surveys , Pregnancy , Prenatal Nutritional Physiological Phenomena , Socioeconomic Factors , Young Adult
17.
Matern Child Nutr ; 15(4): e12821, 2019 10.
Article in English | MEDLINE | ID: mdl-30919554

ABSTRACT

The prevalence of childhood stunting in Myanmar is one of the highest among the countries of Southeast Asia. Cross-sectional data from the Myanmar Demographic Health Survey 2015-2016 were used to examine risk factors for stunting, wasting, and underweight among children aged 0-59 months. The prevalence of stunting, wasting, and underweight was 29.0%, 7.3%, and 19.2%, respectively. Accounting for sampling design and weights, multivariable logistic regression was conducted with 35 household, maternal, and child characteristics. Current pregnancy and maternal height <145 cm, home delivery, child's small birth size recalled by mother, and older age (ref: 0-5 months) predicted both stunting and underweight. Larger than average birth size was protective for all stunting, wasting, and underweight. Maternal body mass index <18.5 kg m-2 was a common risk factor for wasting and underweight. Lower wealth quintiles, maternal engagement in nonagricultural occupation, and male child predicted stunting only. Younger child age and not receiving vitamin A supplementation in the previous 6 months were risk factors for wasting only. Regional variation was also seen, with a higher odds of stunting in the West-South Region, North-East States, and West States, compared with the Central Regions. In Myanmar, socio-economic and demographic factors, poor maternal nutritional status, and living in certain geographical locations are affecting children's undernutrition. It is recommended that interventions for growth faltering focus on the first 1,000 days of life; optimum maternal nutrition be ensured during and before pregnancy and at adolescence; societal support be provided for mothers in poverty or engaged in nonagriculture; and region-specific undernutrition pathways be understood.


Subject(s)
Child Nutrition Disorders/epidemiology , Growth Disorders/epidemiology , Malnutrition/epidemiology , Wasting Syndrome/epidemiology , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Myanmar/epidemiology , Prevalence , Risk Factors , Thinness/epidemiology
18.
Matern Child Nutr ; 15(4): e12870, 2019 10.
Article in English | MEDLINE | ID: mdl-31278831

ABSTRACT

Anaemia is prevalent among preschool-aged children in Myanmar, but few epidemiological studies of anaemia at the national level were reported. Using data from the Myanmar Demographic and Health Survey 2015-2016, we examined risk factors for anaemia at household, maternal, and individual levels for children aged 6-23 months (n = 1,133) and 24-59 months (n = 2,393) separately. Survey design and sampling weights were adjusted for in multivariate regression analyses. The prevalence of anaemia was 77.2% in children aged 6-23 months and 50.8% in those aged 24-59 months. Living in geographic zones other than the hilly zone was associated with a higher odds of anaemia in both age groups (OR = 1.86-2.51 [95% lower limit > 1.0]). Maternal anaemia predicted child anaemia in a dose-response manner in both groups (6-23 months of age, OR = 2.01, 95% CI [1.38, 2.92; mild] and OR = 2.41, 95% CI [1.12, 5.19; moderate]; and 24-59 months of age, OR = 1.42, 95% CI [1.12, 1.81; mild] and OR = 2.92, 95% CI [1.91,4.46; moderate]). A maternal age of 14-24 years (ref: 25-34 years, OR = 1.67, 95% CI [1.06, 2.64]) and maternal tolerant attitude to domestic violence (OR = 1.61, 95% CI [1.13, 2.31]) predicted anaemia in children aged 6-23 months only. Younger child age (OR = 0.97, 95% CI [0.96, 0.98]), stunting (OR = 1.35, 95% CI [1.08, 1.69]) and using unimproved drinking water sources (OR = 1.38, 95% CI [1.10, 1.75]) were associated with anaemia in children aged 24-59 months. Consideration of age-specific risks factors for child anaemia will help in planning anaemia control programmes in Myanmar.


Subject(s)
Anemia, Iron-Deficiency/epidemiology , Adolescent , Adult , Age Factors , Child, Preschool , Female , Health Surveys , Humans , Infant , Male , Malnutrition/epidemiology , Mothers/statistics & numerical data , Myanmar/epidemiology , Risk Factors , Young Adult
19.
Matern Child Nutr ; 14(1)2018 01.
Article in English | MEDLINE | ID: mdl-28714283

ABSTRACT

Few studies have explored the potential of social capital in improving child nutritional status; however, most components of pathways between social capital and nutritional status have remained unexplained. Complementary feeding practice is a strong mediator of child nutritional status. This study examined the association between complementary feeding practice and maternal social capital in rural Ethiopia, using cross-sectional data of infant aged 6-12 months and their mother pairs (n = 870). The Short Social Capital Assessment Tool was used to assess maternal structural (i.e., community group membership, having emotional/economic support from individuals, and citizenship activities) and cognitive social capital (i.e., trust, social harmony, and sense of belonging) in the past 12 months. Infant's dietary diversity score (DDS, range: 0-7), minimum dietary diversity (MDD), and minimum meal frequency (MMF) were assessed using a 24-hr dietary recall. Multivariable ordinal/binary logistic regression analyses were conducted. Having support from two or more individuals was associated with higher DDS (OR = 1.84) and meeting a minimum level of dietary diversity (MDD: OR = 5.20) but not with MMF, compared to those having no support. Having two or more group memberships was associated with higher DDS (OR = 2.2) but not with MDD or MMF, compared to those without group membership. Citizenship activities showed mixed associations with MMF and no association with DDS or MDD. Cognitive social capital showed no association with DDS or MDD and lower odds of meeting MMF (OR = 0.56). These mixed results call for further studies to examine other potential pathways (e.g., hygiene and caring behaviours) in which social capital could improve child nutritional status.


Subject(s)
Diet, Healthy , Feeding Methods , Infant Nutritional Physiological Phenomena , Models, Psychological , Mothers , Rural Health , Social Capital , Child Development , Cross-Sectional Studies , Diet, Healthy/ethnology , Diet, Healthy/psychology , Ethiopia , Feeding Methods/adverse effects , Feeding Methods/psychology , Female , Follow-Up Studies , Humans , Infant , Infant Nutritional Physiological Phenomena/ethnology , Male , Mothers/psychology , Nutrition Surveys , Nutritional Status/ethnology , Parenting/ethnology , Parenting/psychology , Patient Compliance/ethnology , Patient Compliance/psychology , Power, Psychological , Rural Health/ethnology
20.
Matern Child Nutr ; 14 Suppl 4: e12684, 2018 11.
Article in English | MEDLINE | ID: mdl-30499257

ABSTRACT

Stunting (length-for-age z score < -2) before 2 years of age has shown associations with poor child developmental indicators, but information at the population level is scarce in South Asia, the region with the highest burden of stunting. We examined associations between z scores (i.e., height for age [HAZ], weight for age [WAZ], and weight for height [WHZ]) and undernutrition (i.e., stunting [HAZ < -2], wasting [WHZ < -2], and underweight [WAZ < -2]) with learning/cognition and social-emotional development among children 36-59 months of age. Data from Multiple Indicator Cluster Surveys in Bangladesh (n = 8,659), Bhutan (n = 2,038), Nepal (n = 2,253), and Pakistan (Punjab n = 11,369 and Sindh n = 6,718) were used. Children were considered developmentally "on-track" in learning/cognition or social-emotional domains if they met specific early child development criteria. Meta-analysis was conducted to examine regional associations, adjusting for socio-economic status, early childhood education, and quality of care. In a pooled sample, on-track learning/cognition development was positively associated with HAZ (OR = 1.17, 95% CI [1.07, 1.27]) and WAZ (OR = 1.18, 95% CI [1.07, 1.31]) and negatively associated with stunting (OR = 0.72, 95% CI [0.60, 0.86]) and underweight (OR = 0.75, 95% CI [0.66, 0.86]) but not associated with WHZ or wasting. On-track development of social-emotional domain was not associated with any z scores or undernutrition indicators. Across several countries of South Asia, stunted children were less likely to be developmentally "on track" for learning/cognition. It is likely that interventions that prevent stunting may benefit child development, leading to significant individual and societal gains given the large burden of child stunting in regions like South Asia.


Subject(s)
Child Development/physiology , Growth Disorders/epidemiology , Asia, Western/epidemiology , Body Weight/physiology , Cross-Sectional Studies , Female , Health Surveys , Humans , Infant , Male , Nutritional Status
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