Epigenetic regulation of H3K27me3 in laying hens with fatty liver hemorrhagic syndrome induced by high-energy and low-protein diets.

BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.

Creating culturally-informed protocols for a stunting intervention using a situated values-based approach (WeValue InSitu): a double case study in Indonesia and Senegal.

International development work involves external partners bringing expertise, resources, and management for local interventions in LMICs, but there is often a gap in understandings of relevant local shared values. There is a widespread need to better design interventions which accommodate relevant elements of local culture, as emphasised by recent discussions in global health research regarding neo-colonialism. One recent innovation is the concept of producing 'cultural protocols' to precede and guide community engagement or intervention design, but without suggestions for generating them. This study explores and demonstrates the potential of an approach taken from another field, named WeValue InSitu, to generate local culturally-informed protocols. WeValue InSitu engages stakeholder groups in meaning-making processes which 'crystallize' their envelope of local shared values, making them communicable to outsiders.Our research context is understanding and reducing child stunting, including developing interventions, carried out at the Senegal and Indonesia sites of the UKRI GCRF Action Against Stunting Hub. Each national research team involves eight health disciplines from micro-nutrition to epigenetics, and extensive collection of samples and questionnaires. Local culturally-informed protocols would be generally valuable to pre-inform engagement and intervention designs. Here we explore generating them by immediately following the group WeValue InSitu crystallization process with specialised focus group discussions exploring: what local life practices potentially have significant influence on the environments affecting child stunting, and which cultural elements do they highlight as relevant. The discussions will be framed by the shared values, and reveal linkages to them. In this study, stakeholder groups like fathers, mothers, teachers, market traders, administrators, farmers and health workers were recruited, totalling 83 participants across 20 groups. Themes found relevant for a culturally-informed protocol for locally-acceptable food interventions included: specific gender roles; social hierarchies; health service access challenges; traditional beliefs around malnutrition; and attitudes to accepting outside help. The concept of a grounded culturally-informed protocol, and the use of WeValue InSitu to generate it, has thus been demonstrated here. Future work to scope out the advantages and limitations compared to deductive culture studies, and to using other formative research methods would now be useful.

Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition.

BACKGROUND: Childhood undernutrition is a major global health challenge with devastating lifelong consequences. Linear growth stunting due to undernutrition has been linked to poor health outcomes, and mothers who experience growth stunting in childhood are more likely to give birth to stunted children later in life. Based on these findings, we hypothesized that intergenerational colonization of mice with microbiota from human donors with undernutrition may recapitulate certain immune and growth changes observed in this disorder. RESULTS: To test this hypothesis, we developed a gnotobiotic murine model of undernutrition using microbiota from human infants with healthy or stunted growth trajectories. Intergenerational colonization with microbiota derived from children with growth stunting lead to less linear growth and the development of immune features of undernutrition and enteropathy, including intestinal villus blunting, lower liver IGF-1 and accumulation of intraepithelial lymphocytes and plasma cells in the small intestine. In contrast, colonization after weaning lead to fewer host phenotypic changes between these distinct microbial communities. CONCLUSIONS: These results are broadly consistent with previous findings demonstrating that exposure of the immune system to microbial products during the weaning phase is a critical determinant of later life immune function. Overall, our results suggest intergenerational colonization with human microbiota samples is a useful approach with which to investigate microbiota-dependent changes in growth and immunity in early life. Murine models that capture the intergenerational and multifactorial nature of undernutrition are critical to understanding the underlying biology of this disorder. Video Abstract.

Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments.

BACKGROUND: Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. METHODS: Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. RESULTS: Reduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3ß, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females. CONCLUSIONS: Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Understanding the physiological role of pregnancy-associated plasma protein-A2 (PAPP-A2), a proteinase involved in the insulin-like growth factor-1 (IGF1) availability to regulate growth, could provide insight into new treatments for patients with short stature and skeletal abnormalities. Although progressive postnatal growth retardation in patients with PAPP-A2 mutations can differ between males and females, we do not know the underlying differences in IGF1 system and signaling, and their response to treatment that contribute to growth improvement. The present study examines whether Pappa2 deficiency and pharmacological administration of rhGH, rhIGF1 and rhPAPP-A2 are associated with sex-specific differences in IGF1 ternary complexes and IGF1 signaling pathways. Reduced body and femur length of Pappa2-deficient mice was associated with sex- and tissue-specific alteration of IGF ternary/binary complexes and IGF1 signaling pathways. rhPAPP-A2 treatment induced female-specific increase in body and femur length and reduction in IGF ternary/binary complexes through STAT5-AKT-ERK2-AMPK signaling pathways in liver. The involvement of PAPP-A2 in sex-based growth physiology supports the use of promising drugs to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Burden of undernutrition among under-five Bengali children and its determinants: Findings from Demographic and Health Surveys of Bangladesh and India.

BACKGROUND: Globally, undernutrition is the leading cause of mortality among under-five children. Bangladesh and India were in the top ten countries in the world for under-five mortality. The aim of the study was to investigate the nutritional status of Bengali under-five children. METHODS: Data on 25938 under-five children were retrieved from the Bangladesh Demographic and Health Survey 2017-18 (BDHS) and the National Family Health Survey of India 2015-16 (NFHS-4). Stunting, wasting, underweight and thinness were considered to understand the nutritional status of under-five children. Binary logistic regression was used to identify associated factors of undernutrition among children. RESULTS: Over one-quarter of Bengali under-five children were found to be suffering from the problem of stunting (31.9%) and underweight (28.1%), while other nutritional indicators raised serious concern and revealed inter-country disparities. In the cases of wasting, underweight and thinness, the mean z-scores and frequency differences between Bangladesh and India were significant. The nutritional status of Bengali under-five children appeared to have improved in Bangladesh compared to India. Child undernutrition had significant relations with maternal undernutrition in both countries. Girls in Bangladesh had slightly better nutritional status than boys. In Bangladesh, lack of formal education among mothers was a leading cause of child undernutrition. Stunting and underweight coexist with low household wealth index in both counties. CONCLUSIONS: The research revealed that various factors were associated with child undernutrition in Bengalis. It has been proposed that programmes promoting maternal education and nutrition, along with household wealth index be prioritised. The study recommends that the Governments of Bangladesh and India should increase the budget for health of children so as to reach the sustainable development goals.

Long-acting growth hormone in the treatment of growth hormone deficiency in children: a systematic literature review and network meta-analysis.

The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.

Determinants of coexistence of undernutrition and anemia among under-five children in Rwanda; evidence from 2019/20 demographic health survey: Application of bivariate binary logistic regression model.

BACKGROUND: Undernutrition and anemia are significant public health issues among under-5 children, with potential long-term consequences for growth, development, and overall health. Thus, this study aims to conduct a bivariate binary logistic regression model by accounting for the possible dependency of childhood undernutrition and anemia. METHODS: The data came from the DHS program's measurement. A total of 3,206 under-five children were involved in this study. A single composite index measure was calculated for stunting, wasting, and underweight using principal component analysis. A bivariate binary logistic regression model is used to assess the association between undernutrition and anemia given the effect of other predictors. RESULTS: Among 3,206 under-five children considered in this study, 1482 (46.2%) and 658 (20.5%) children were agonized by anemia and undernutrition, respectively. In bivariate binary logistic regression model; Urban children [AOR = 0.751, 96% CI: 0.573-0.984; AOR = 0.663, 95% CI: 0.456-0.995] and anemic mothers [AOR = 1.160, 95% CI: 1.104-1.218; AOR = 1.663, 95% CI: 1.242-2.225] were significantly associated with both childhood anemia and undernutrition, respectively. Improved water sources [AOR = 0.681, 95% CI: 0.446-0.996], average-sized children [AOR = 0.567, 95% CI: 0.462-0.696], and diarrhea [AOR = 1.134, 95% CI: 1.120-2.792] were significantly associated with childhood anemia. Large-sized children [AOR = 0.882, 95% CI: 0.791-0.853] and those with fever [AOR = 1.152, 95% CI: 1.312-2.981] were significantly associated with under-five children's undernutrition. CONCLUSION: The prevalence of both undernutrition and anemia among under-five-year-old children was high in Rwanda. The following determinants are statistically associated with both childhood undernutrition and anemia: place of residence; source of drinking water; maternal anemia; being a twin; birth size of children; diarrhea; fever; and child age. Anemia and nutritional deficiencies must be treated concurrently under one program, with evidence-based policies aimed at vulnerable populations.

Clinical and nutritional correlates of bacterial diarrhoea aetiology in young children: a secondary cross-sectional analysis of the ABCD trial.

OBJECTIVE: The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD). DESIGN: A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114). PATIENTS: Children with MSD (defined as >3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample. STUDY PERIOD: June 2017-July 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Likely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology. RESULTS: A total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools. CONCLUSION: The presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics.

Shorter telomere length increases the risk of lymphocyte immunodeficiency: A Mendelian randomization study.

BACKGROUND: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear. METHODS: The two-sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome-Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results. RESULTS: The IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014-1.472, p = .035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281-1.935, p < .001). Analysis of B cell subsets revealed that shorter TL may be associated with a higher percentage of Naive-mature B cells, and a lower percentage of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings. CONCLUSION: In summary, our findings suggest that shorter TL may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. The relevant mechanisms and potential therapeutic avenues still need further investigation.

[Clinical study on growth impairment induced by oral glucocorticoids based on FGF23/Klotho homeostasis observations]. / 基于FGF23/Klothoç¨³æ€è§‚å¯Ÿå£æœç³–çš®è´¨æ¿€ç´ è‡´ç”Ÿé•¿éšœç¢çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To observe the correlation between growth impairment induced by long-term oral glucocorticoids (GC) therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome (PNS). METHODS: A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022. After monitoring qualitative and quantitative urine protein levels upon admission, the children with proteinuria relapse were treated with GC (GC group; n=29), while those without relapse did not receive GC treatment (non-GC group; n=27). In addition, 29 healthy children aged 3 to prepuberty were selected as the control group. Height, bone age, growth rate, and the FGF23/Klotho ratio were compared among the groups. The correlations of the FGF23/Klotho ratio with height, bone age, and growth rate were analyzed. RESULTS: The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy (P<0.05), and the height and bone age growth rates within 6 months were lower than those in the non-GC group (P<0.05). Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS (r=-0.356 and -0.436, respectively; P<0.05). CONCLUSIONS: The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.

Growth hormone resistance induced by amino acid deprivation in fao cells is independent of FGF21.

Adequate dietary intake of amino acids is imperative for normal animal growth. Our previous work using rat hepatocarcinoma Fao cells demonstrated that growth hormone (GH) resistance, coupled with a concurrent reduction in insulin-like growth factor 1 (Igf1) mRNA levels, may underlie the growth retardation associated with a low-protein diet (LPD). In this study, we investigated whether FGF21 contributes to liver GH resistance in Fao rat hepatoma cells under amino acid deprivation conditions. Mice subjected to an LPD exhibited growth retardation, compromised GH signaling in the liver, and decreased blood IGF-1 levels compared with those on a control diet. To assess the potential involvement of fibroblast growth factor (FGF) 21, produced in response to amino acid deficiency, in the development of GH resistance, we examined GH signaling and Igf1 mRNA levels in Fao cells cultured in amino acid-deprived medium. Despite the inhibition of Fgf21 expression by the integrated stress response inhibitor, an inhibitor of the eukaryotic initiation factor 2-activating transcription factor 4 pathway, GH resistance persisted in response to amino acid deprivation. Additionally, the introduction of FGF21 into the control medium did not impair either GH signaling or GH-induced Igf1 transcription. These data suggest that, in Fao cells, amino acid deprivation induces GH resistance independently of FGF21 activity. By shedding light on the mechanisms behind growth retardation-associated GH resistance linked to amino acid deficiencies, our findings provide valuable insights for clinicians in formulating effective treatment strategies for individuals facing these challenges.

Global relevance of MGRS growth standards: the case of India.

The most common measures of childhood undernutrition are based on anthropometric measures such as height-for-age (stunting/chronic undernutrition) and weight-for-height (wasting/acute undernutrition). It is well recognised that the determinants of undernutrition are multiple, including food intake, dietary diversity, health, sanitation and women's status. Currently, most countries across the world including India use the globally accepted WHO-Multicentre Growth Reference Study (MGRS) growth standards (2006) for the purposes of measurement as well as for evaluating progress on these metrics. However, there is some discussion on the universal relevance of these standards, and in the Indian context, whether these standards overestimate the prevalence of stunting, considering differences in genetic potential for growth. This is especially relevant in the context of increasing burden of obesity and non-communicable diseases in India. Based on a detailed review of literature, policy documents and expert inputs, this review paper discusses the relevance of the WHO growth standards for height/stunting, in the context of India. Issues discussed related to the MGRS methodology include pooling of data and intersite and intrasite variability, opting for standards as opposed to references, and external validity. Other issues related to plasticity of stunting and the influence of maternal heights are also discussed, in the context of analysing the appropriateness of using universal growth standards. Based on the review, it is recommended that the current standards may continue to be used until a newer global standard is established through a similar study.

Aberrant splicing caused by a novel KMT2A variant in Wiedemann-Steiner syndrome.

INTRODUCTION: Wiedemann-Steiner syndrome (WSS) is a rare autosomal-dominant disorder caused by KMT2A variants. The aim of this study was to characterize a novel KMT2A variant in a child with WSS and demonstrate integrated diagnostic approaches. METHODS: A 3-year-old female with developmental delay, distinctive facial features, and anal fistula underwent whole exome sequencing (WES). RNA analysis was performed to assess splicing effects caused by a novel variant. RESULTS: WES identified novel heterozygous KMT2A c.5664+6T>C variant initially classified as a variant of uncertain significance. RNA analysis provided evidence of aberrant splicing (exon 20 skipping), allowing reclassification to likely pathogenic. The patient exhibited typical WSS features along with a potential novel finding of anal fistula. CONCLUSION: This report describes a novel non-canonical splice site variant in KMT2A associated with WSS. RNA analysis was critical for variant reclassification. Detailed phenotypic evaluation revealed common and expanded WSS manifestations. This case highlights the importance of combining clinical assessment, DNA testing, and RNA functional assays for the diagnosis of rare genetic disorders.

Care groups in an integrated nutrition education intervention improved infant growth among South Sudanese refugees in Uganda's West Nile post-emergency settlements: A cluster randomized trial.

OBJECTIVE: This study examined the effects of a peer-led integrated nutrition education intervention with maternal social support using Care Groups on infant growth among South Sudanese refugees in Uganda. METHODS: A community-based cluster-randomized trial (RCT) was conducted among 390 pregnant women (third trimester). Two intervention study arms were Mothers-only(n = 131) and Parents-combined (n = 142) with a Control (n = 117). WHO infant growth standards defined length-for-age z-scores (LAZ) for stunting, weight-for-age z-scores (WAZ) for underweight and weight-for-length z-scores (WLZ) for wasting. The Medical Outcomes Study (MOS) social support index was a proxy measure for social support. A split-plot ANOVA tested the interaction effects of social support, intervention, and time on infant growth after adjusting for covariates. Further, pairwise comparisons explained mean differences in infant growth among the study arms. RESULTS: The mean infant birth weight was 3.1 ± 0.5 kg. Over the study period, infant stunting was most prevalent in the Control (≥ 14%) compared to Mothers-only (< 9.5%) and Parents-combined (< 7.4%) arms. There were significant interaction effects of the Care Group intervention and social support by time on infant mean LAZ (F (6, 560) = 28.91, p < 0.001), WAZ (F (5.8, 539.4) = 12.70, p = < 0.001) and WLZ (F (5.3, 492.5) = 3.38, p = 0.004). Simple main effects by the end of the study showed that the intervention improved infant mean LAZ (Mothers-only vs. Control (mean difference, MD) = 2.05, p < 0.001; Parents-combined vs. Control, MD = 2.00, p < 0.001) and WAZ (Mothers-only vs. Control, MD = 1.27, p < 0.001; Parents-combined vs. Control, MD = 1.28, p < 0.001). CONCLUSION: Maternal social support with an integrated nutrition education intervention significantly improved infant stunting and underweight. Nutrition-sensitive approaches focused on reducing child undernutrition among post-emergency refugees may benefit from using Care Groups in programs. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05584969.

Factors related to stunting in children under 2 years old in the Papua, Indonesia: Does the type of residence matter?

OBJECTIVES: To analyze factors related to stunting in Papua region. METHODS: Secondary data from the 2021 Indonesian National Nutrition Status Survey were used in this study. Samples of 2,937 Papuan children under the age of two were gathered for the study. This study analyzed independent variables (type of residence, mother's age, marriage, mother's education, employment, wealth, child's age, gender, and early breastfeeding initiation (EBFI) with stunting. The relationship was analyzed using logistic regression tests. RESULTS: Stunting is more common among children in Papua's rural areas than in urban (AOR 1.168, 95% CI, 1.128-1.209). Stunting is more common in children who mother do not work than in mothers who do (AOR 1.174, 95% CI, 1.142- 1.207). Stunting is more common in children aged 12-23 months compared to children <12 months (AOR 3.381, 95% CI, 3.291-3.474). Compared to girls, boys are more likely to become stunted (AOR 1.348, 95% CI, 1,314-1,383). Children under the age of two who do not experience EBFI are at higher risk than those who have (AOR 1.078, 95% CI, 1.050-1.106). CONCLUSION: There are eight variables associated with stunting, namely residence, age of mother, mother's education, mother's occupation, economic status, child's age, gender, and EBFI. Prioritization of stunting interventions in Papua should be targeted at mothers who living in rural, having low education, and not doing early breastfeeding initiation.

Does acute malnutrition in young children increase the risk of treatment failure following artemisinin-based combination therapy? A WWARN individual patient data meta-analysis.

BACKGROUND: The geographical, demographic, and socioeconomic distributions of malaria and malnutrition largely overlap. It remains unknown whether malnutrition affects the efficacy of WHO-recommended artemisinin-based combination therapies (ACTs). A previous systematic review was inconclusive as data were sparse and heterogeneous, indicating that other methodological approaches, such as individual patient data meta-analysis, should be considered. The objective of this study was to conduct such a meta-analysis to assess the effect of malnutrition (wasting and stunting) on treatment outcomes in children younger than 5 years treated with an ACT for uncomplicated falciparum malaria. METHODS: We conducted a meta-analysis of individual patient data from studies identified through a systematic review of literature published between 1980 and 2018 in PubMed, Global Health, and Cochrane Libraries (PROSPERO CRD42017056934) and inspection of the WorldWide Antimalarial Resistance Network (WWARN) repository for ACT efficacy studies, including children younger than 5 years with uncomplicated falciparum malaria. The association of either acute (wasting) or chronic (stunting) malnutrition with day 42 PCR-adjusted risk of recrudescence (ie, return of the same infection) or reinfection after therapy was investigated using Cox regression, and with day 2 parasite positivity using logistic regression. FINDINGS: Data were included from all 36 studies targeted, 31 from Africa. Of 11 301 eligible children in 75 study sites, 11·5% were wasted (weight-for-height Z score [WHZ] <-2), and 31·8% were stunted (height-for-age Z score [HAZ] <-2). Decrease in WHZ was associated with increased risk of day 2 positivity (adjusted odds ratio 1·12, 95% CI 1·05-1·18 per unit; p=0·0002), treatment failure (adjusted hazard ratio [AHR] 1·14, 95% CI 1·02-1·26, p=0·016), and reinfection after therapy (AHR 1·09, 1·04-1·13, p=0·0003). Children with milder wasting (WHZ -2 to -1) also had a higher risk of recrudescence (AHR 1·85, 1·29-2·65, p=0·0008 vs WHZ ≥0). Stunting was not associated with reduced ACT efficacy. INTERPRETATION: Children younger than 5 years with acute malnutrition and presenting with uncomplicated falciparum malaria were at higher risk of delayed parasite clearance, ACT treatment failure, and reinfections. Stunting was more prevalent, but not associated with changes in ACT efficacy. Acute malnutrition is known to impact medicine absorption and metabolism. Further study to inform dose optimisation of ACTs in wasted children is urgently needed. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Functional difficulty among young children in Bangladesh: An analysis of nationally representative data.

Functional difficulty in children is a crucial public health problem still undervalued in developing countries. This study explored the socio-demographic factors and anthropometry associated with children's functional difficulty in Bangladesh. Data for 2-4-year-old children, obtained from Multiple Indicator Cluster Survey 2019, were used in this study. The mixed-effects logistic regression model was used to analyse the data. Children whose mothers had functional difficulty were found to be 2.75 times more likely to have functional difficulty than children whose mothers had no functional difficulty (95% CI 1.63-4.63). Male children were more likely to experience functional difficulty than female children (OR = 1.48). Furthermore, stunting was found to be significantly associated with functional difficulty (OR = 1.50). The study also revealed that division and mother's education, specifically, children with mothers having higher secondary + education, had significant association with the outcome variable. The findings provided a vital overview of child disability in a developing country.

Determinants of concurrent wasting and stunting among children 6 to 23 mo in Indonesia.

OBJECTIVES: Concurrent wasting and stunting (WaSt) in a child is a health problem that leads to detrimental effects. However, to our knowledge, there is limited research regarding the prevalence and determinants of WaSt, including in Indonesia. The aim of this study was to analyze the prevalence and determinants of WaSt in children 6 to 23 mo of age. METHODS: This cross-sectional study was conducted with data sets from the Indonesia Nutritional Status Survey (INSS). Data was collected between January and December 2021. About 15 641 children, ages 23 mo, were included. A χ2 analysis examined the association between the dependent and independent variables. A multivariate test analyzed the risk for the independent variable to the dependent, seen through the adjusted odds ratio (aOR). RESULTS: The prevalence of WaSt was 2.4%. Higher odds for WaSt were seen in the following: • Boys: 2.15 times (95% confidence interval [CI], 1.72-2.68); • Children ages 12 to 23 mo 3.15 times (95% CI, 2.33-4.25); • Those with low birth weight 3.11 times (95% CI, 2.33-4.15) • Those with small birth size: 2 times (95% CI, 1.59-2.54) • Babies born from mothers >35 y of age: 1.5 times (95% CI, 1.19-1.89); • Children who experienced infection: 1.43 times (95% CI, 1.16-1.76); • Children not using the Integrated Health and Nutrition Services (Posyandu): 1.17 times (95% CI; 1.29-2.27); • Children from middle- income families:2.54 times higher odds (95% CI, 1.75-3.7); and • Children from rural areas: 1.37 times (95% CI, 1.1-1.71). CONCLUSION: WaSt is associated with multiple factors in Indonesia. Hence, policymakers need to address this problem comprehensively.

Stunting and food insecurity among children from low socioeconomic family during COVID-19 pandemic in urban area in Selangor.

INTRODUCTION: Food insecurity is often link with nutritional status. An increased rate of food insecurity can have a severe impact on children's growth. During the COVID-19 outbreak, little is known regarding its effect on food security and nutritional status, especially concerning vulnerable groups such as children. The purpose of this study was to assess household food security status, children's nutritional status along with their association, and the determinants of food insecurity during the COVID-19 pandemic. MATERIALS AND METHODS: This cross-sectional study was conducted from May to July 2022 in urban areas in Selangor among children aged less than two years old from B40 households using purposive sampling through both online surveys and face-to-face interviews. There were 112 children aged < 2 years old from B40 households participating in this study. The data obtained on maternal sociodemographic, Household Food Insecurity Scale (HFIAS), and children's anthropometric measurements were analysed by using the WHO Anthro Survey, descriptive analysis, Person's Chisquare test and Fischer's exact test. RESULTS: The prevalence of food insecurity was more significant than the prevalence of food secured, at 55.4% and 44.6% respectively. The stunting among the children rated at 34.8%, followed by 7.2% of the sample found underweight, 7.8% (BAZ) and 16.1% (BAZ) of them were wasted, and overweight & obese, proportionately. This study discovered that household size was the sole determinant of household food security status. This finding suggested that size of a household influenced the odds of a household being food insecure. CONCLUSION: The findings of this study provide insights into how the COVID-19 pandemic have an impact on children's nutritional status especially those from low-income and bigger size households. Therefore, more thorough and effective interventions should be designed particularly targeting this urban poor community to enhance their nutritional status and health.

Characterization of HMGA2 variants expands the spectrum of Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation. HMGA2 variants are a rare cause of SRS and its functional role in human linear growth is unclear. Patients with suspected SRS negative for 11p15LOM/mUPD7 underwent whole-exome and/or targeted-genome sequencing. Mutant HMGA2 protein expression and nuclear localization were assessed. Two Hmga2-knockin mouse models were generated. Five clinical SRS patients harbored HMGA2 variants with differing functional impacts: 2 stop-gain nonsense variants (c.49G>T, c.52C>T), c.166A>G missense variant, and 2 frameshift variants (c.144delC, c.145delA) leading to an identical, extended-length protein. Phenotypic features were highly variable. Nuclear localization was reduced/absent for all variants except c.166A>G. Homozygous knockin mice recapitulating the c.166A>G variant (Hmga2K56E) exhibited a growth-restricted phenotype. An Hmga2Ter76-knockin mouse model lacked detectable full-length Hmga2 protein, similarly to patient 3 and 5 variants. These mice were infertile, with a pygmy phenotype. We report a heterogeneous group of individuals with SRS harboring variants in HMGA2 and describe the first Hmga2 missense knockin mouse model (Hmga2K56E) to our knowledge causing a growth-restricted phenotype. In patients with clinical features of SRS but negative genetic screening, HMGA2 should be included in next-generation sequencing testing approaches.