Influence of maternal and neonatal continuum of care on the risk of intergenerational cycle of stunting: a cross-sectional study.

OBJECTIVES: This study aimed to analyse the influence of the continuum of care during pregnancy and neonatal periods on the risk of intergenerational cycle of stunting. DESIGN: This study was a cross-sectional study, with data analysed from the 2018 Basic Health Research in Indonesia. SETTINGS: Basic Health Research 2018 was conducted throughout 513 cities/regencies in 34 provinces in Indonesia. The households were selected through two-stage sampling methods. First, census blocks (CB) were selected using probability proportional to size methods in each urban/rural stratum from each city/regency. Ten households were then selected from each CB using systematic sampling methods. All family members of the selected households were measured and interviewed. PARTICIPANTS: This study analyses 31 603 children aged 0-24 months. OUTCOMES MEASURES: The dependent variable was the risk of the intergenerational cycle of stunting. Mothers who had a height less than 150.1 cm (short stature mothers) and had children (≤ 24 months of age) with length-for-age Z-score less than -2 Standard Deviation (SD) of the WHO Child Growth Standard (stunted children) were defined as at risk of the intergenerational cycle of stunting. RESULTS: Mothers with incomplete maternal and neonatal care visits were 30% more likely to be at risk on the intergenerational cycle of stunting (OR (95% CI): 1.3 (1.00 to 1.63)) after adjusting for economic status. CONCLUSION: The continuum of maternal and neonatal healthcare visits could potentially break the intergenerational cycle of stunting, especially in populations where stunted mothers are prevalent.

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.

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.

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.

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.

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.

[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.

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.

Prevalence of childhood stunting and determinants in low and lower-middle income African countries: Evidence from standard demographic and health survey.

INTRODUCTION: Undernutrition poses a significant global public health challenge, adversely affecting childhood cognitive and physical development while increasing the risk of disease and mortality. Stunting, characterized by impaired growth and development in children due to insufficient psychological stimulation, frequent infections, and inadequate nutrition, remains a critical issue. Although economic growth alone cannot fully address the prevalence of stunting, there exists a robust correlation between a country's income level and childhood stunting rates. Countries with higher incomes tend to have lower rates of childhood stunting. Notably, while childhood stunting is declining worldwide, it remains persistent in Africa. Consequently, this study aims to assess the prevalence of childhood stunting and its determinants in low- and lower-middle-income African countries. METHOD: This study conducted a secondary analysis of standard demographic and health surveys in low- and lower-middle-income African countries spanning the period from 2010 to 2022. The analysis included a total sample of 204,214 weighted children under the age of five years. To identify the determinants of stunting, we employed a multilevel mixed-effect model, considering the three levels of variables. The measures of association (fixed effect) were determined using the adjusted odds ratio at a 95% confidence interval. Significance was declared when the association between the outcome variable and the explanatory variable had a p-value less than 0.05. RESULT: In low and lower-middle-income African countries, 31.28% of children under five years old experience stunting, with a 95% confidence interval ranging from 31.08% to 31.48%. The results from a multilevel mixed-effect analysis revealed that 24 months or more of age of child, male gender, low and high birth weight, low and high maternal BMI, no and low maternal education, low household wealth index, multiple (twin or triplet) births, rural residence, and low income of countries were significantly associated with childhood stunting. CONCLUSION: Stunting among children under five years of age in low- and lower-middle-income African countries was relatively high. Individual, community, and country-level factors were statistically associated with childhood stunting. Equally importantly, with child, maternal, and community factors of stunting, the income of countries needs to be considered in providing nutritional interventions to mitigate childhood stunting in Africa.

ANTXR1 deficiency promotes fibroblast senescence: implications for GAPO syndrome as a progeroid disorder.

ANTXR1 is one of two cell surface receptors mediating the uptake of the anthrax toxin into cells. Despite substantial research on its role in anthrax poisoning and a proposed function as a collagen receptor, ANTXR1's physiological functions remain largely undefined. Pathogenic variants in ANTXR1 lead to the rare GAPO syndrome, named for its four primary features: Growth retardation, Alopecia, Pseudoanodontia, and Optic atrophy. The disease is also associated with a complex range of other phenotypes impacting the cardiovascular, skeletal, pulmonary and nervous systems. Aberrant accumulation of extracellular matrix components and fibrosis are considered to be crucial components in the pathogenesis of GAPO syndrome, contributing to the shortened life expectancy of affected individuals. Nonetheless, the specific mechanisms connecting ANTXR1 deficiency to the clinical manifestations of GAPO syndrome are largely unexplored. In this study, we present evidence that ANTXR1 deficiency initiates a senescent phenotype in human fibroblasts, correlating with defects in nuclear architecture and actin dynamics. We provide novel insights into ANTXR1's physiological functions and propose GAPO syndrome to be reconsidered as a progeroid disorder highlighting an unexpected role for an integrin-like extracellular matrix receptor in human aging.

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.

Continuum of care for maternal and child health and child undernutrition in Angola.

BACKGROUND: Continuum of care (CoC) for maternal and child health provides opportunities for mothers and children to improve their nutritional status, but many children remain undernourished in Angola. This study aimed to assess the achievement level of CoC and examine the association between the CoC achievement level and child nutritional status. METHODS: We used nationally representative data from the Angola 2015-2016 Multiple Indicator and Health Survey. Completion of CoC was defined as achieving at least four antenatal care visits (4 + ANC), delivery with a skilled birth attendant (SBA), child vaccination at birth, child postnatal check within 2 months (PNC), and a series of child vaccinations at 2, 4, 6, 9 and 15 months of child age. We included under 5 years old children who were eligible for child vaccination questionnaires and their mothers. The difference in CoC achievement level among different nutritional status were presented using the Kaplan-Meier method and examined using the Log-Lank test. Additionally, the multivariable logistic regression analysis examined the associations between child nutritional status and CoC achievement levels. RESULTS: The prevalence of child stunting, underweight and wasting was 48.3%, 23.2% and 5.9% respectively. The overall CoC completion level was 1.2%. The level of achieving CoC of mother-child pairs was 62.8% for 4 + ANC, 42.2% for SBA, 23.0% for child vaccination at birth, and 6.7% for PNC, and it continued to decline over 15 months. The Log-Lank test showed that there were significant differences in the CoC achievement level between children with no stunting and those with stunting (p < 0.001), those with no underweight and those with underweight (p < 0.001), those with no wasting and those with wasting (p = 0.003), and those with malnutrition and those with a normal nutritional status (p < 0.001). Achieving 4 + ANC (CoC1), 4 + ANC and SBA (CoC 2), and 4 + ANC, SBA, and child vaccination at birth (CoC 3) were associated with reduction in child stunting and underweight. CONCLUSIONS: The completion of CoC is low in Angola and many children miss their opportunity of nutritional intervention. According to our result, improving care utilization and its continuity could improve child nutritional status.

[Growth hormone - 30 years of clinical practice: past, present, future].

The recombinant technologies era, which began in the second half of the XX century, made it possible to produce recombinant growth hormone (rGH) necessary for the treatment of stunting of various genesis. The time of practically unlimited possibilities of rGH production has come, which served as a stimulus for studying the efficacy and safety of rGH application, searching for optimal ways of its use and dosing regimes. Many years of experience in the use of somatropin in clinical practice allowed us to obtain data on its effectiveness primarily in somatotropic insufficiency in children, to study its effect on the functional state of various organs and systems, and to expand the indications for the use of RGR.

Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study.

Objectives: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings. Methods: This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation. Results: Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection. Discussion: Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS.

PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS.

The plant homeodomain zinc-finger protein, PHF6, is a transcriptional regulator, and PHF6 germline mutations cause the X-linked intellectual disability (XLID) Börjeson-Forssman-Lehmann syndrome (BFLS). The mechanisms by which PHF6 regulates transcription and how its mutations cause BFLS remain poorly characterized. Here, we show genome-wide binding of PHF6 in the developing cortex in the vicinity of genes involved in central nervous system development and neurogenesis. Characterization of BFLS mice harbouring PHF6 patient mutations reveals an increase in embryonic neural stem cell (eNSC) self-renewal and a reduction of neural progenitors. We identify a panel of Ephrin receptors (EphRs) as direct transcriptional targets of PHF6. Mechanistically, we show that PHF6 regulation of EphR is impaired in BFLS mice and in conditional Phf6 knock-out mice. Knockdown of EphR-A phenocopies the PHF6 loss-of-function defects in altering eNSCs, and its forced expression rescues defects of BFLS mice-derived eNSCs. Our data indicate that PHF6 directly promotes Ephrin receptor expression to control eNSC behaviour in the developing brain, and that this pathway is impaired in BFLS.

Association between Child Nutritional Anthropometric Indices and Iron Deficiencies among Children Aged 6-59 Months in Nepal.

Developmental impairment remains an important public health problem among children in many developing countries, including Nepal. Iron deficiency in children may affect development and lead to anaemia. This study on 1702 children aged 6-59 months aimed to assess the association between nutritional anthropometric indices and iron deficiencies. Data for this study were extracted from the 2016 Nepal National Micronutrient Status Survey. Three nutritional anthropometric indices (stunting, wasting and underweight) and their association with anaemia and iron deficiencies (ferritin and sTfR biomarkers) were assessed by conducting multivariate statistical analyses. The prevalence of stunting, wasting and underweight among children aged 6-59 months was 35.6%, 11.7% and 29.0%, respectively. Most of the children were not stunted (64.4%), not wasted (71.0%) and not underweight (88.3%). Belonging to castes other than the Janajati, Dalit and Brahmin castes increased the odds of anaemia and iron deficiency (ferritin biomarker). Children in the age group 6-23 months were significantly at higher odds of having anaemia and iron deficiency (ferritin and sTfR biomarkers). Stunting significantly increased the odds of anaemia [adjusted odds ratio (OR): 1.55; 95% confidence interval (CI): (1.11, 2.17)], iron deficiency (ferritin biomarker [OR: 1.56; 95% CI: (1.16, 2.08)] and sTfR biomarker [OR: 1.60; 95% CI: (1.18, 2.15)]). Further, underweight significantly increased the odds of anaemia [OR: 1.69; 95% CI: (1.12, 2.54)] and iron deficiency (sTfR biomarker [OR: 1.48; 95% CI: (1.14, 1.93)]). Interventions to minimise the occurrence of anaemia and iron deficiencies among children in Nepal should focus on providing appropriate healthcare services that would reduce the burden of stunting and underweight.