Situational analysis of nutritional status among 1899 children presenting with cleft lip and/or palate in Indonesia

BACKGROUND: Given the increased risk of malnutrition in children with cleft lip and/or palate (CLP), determining their nutritional status is critical for preventing adverse surgical risks. However, no such disaggregated, national-level data are available in Indonesia. We aimed to determine the nutritional status of patients with clefts in Indonesia and to identify problems and solutions for malnutrition cases within the population.METHODS: In this cross-sectional study, we considered records of individuals who underwent primary surgery for CLP in Smile Train-sponsored facilities in Indonesia between 1 January 2016 and 31 December 2021 (n = 18 480). We only included children under the age of five with an evaluation date prior to admission date and excluded subjects with invalid data values. We classified their nutritional status by z-scores according to the World Health Organization Child Growth Standard (2006). Malnutrition cases cover four indicators - stunting, wasting, underweight, and overweight. We compared the prevalence for malnutrition cases in children under the age of five using national health survey data.RESULTS: We included 1899 records following data validation. The national prevalence of stunting (24.4%), wasting (12.5%), and overweight cases (12.9%) was high, while underweight cases (6.8%) were comparatively low. Statistical analyses showed significant differences in nutritional status based on length/height-for-age between girls and boys aged 0-5 months (P = 0.008) and 48-60 months (P = 0.001), and based on body mass index-for-age (P = 0.000) between girls and boys aged 0-5 months. Girls in different age groups exhibited a statistically significant difference in nutritional status based on length/height-for-age (P = 0.002) and weight-for-age (P = 0.017). Concurrent stunting and overweight were the most common forms of concurrent malnutrition (8.7%). We found a significant difference in the prevalence of underweight (P = 0.001) and overweight (P = 0.000) cases between children with CLP and those without CLP.CONCLUSIONS: Our findings highlight the importance of nutritional interventions for children with orofacial clefts in Indonesia, and the importance of age and gender in their design and implementation. Further investigation is necessary to explore the risks of overweight and concurrent malnutrition among this population.</p

Ecosystem fluxes of hydrogen: a comparison of flux-gradient methods

Our understanding of biosphere–atmosphere exchange has been considerably enhanced by eddy covariance measurements. However, there remain many trace gases, such as molecular hydrogen (H[subscript 2]), that lack suitable analytical methods to measure their fluxes by eddy covariance. In such cases, flux-gradient methods can be used to calculate ecosystem-scale fluxes from vertical concentration gradients. The budget of atmospheric H[subscript 2] is poorly constrained by the limited available observations, and thus the ability to quantify and characterize the sources and sinks of H[subscript 2] by flux-gradient methods in various ecosystems is important. We developed an approach to make nonintrusive, automated measurements of ecosystem-scale H2 fluxes both above and below the forest canopy at the Harvard Forest in Petersham, Massachusetts, for over a year. We used three flux-gradient methods to calculate the fluxes: two similarity methods that do not rely on a micrometeorological determination of the eddy diffusivity, K, based on (1) trace gases or (2) sensible heat, and one flux-gradient method that (3) parameterizes K. We quantitatively assessed the flux-gradient methods using CO[subscript 2] and H[subscript 2]O by comparison to their simultaneous independent flux measurements via eddy covariance and soil chambers. All three flux-gradient methods performed well in certain locations, seasons, and times of day, and the best methods were trace gas similarity for above the canopy and K parameterization below it. Sensible heat similarity required several independent measurements, and the results were more variable, in part because those data were only available in the winter, when heat fluxes and temperature gradients were small and difficult to measure. Biases were often observed between flux-gradient methods and the independent flux measurements, and there was at least a 26% difference in nocturnal eddy-derived net ecosystem exchange (NEE) and chamber measurements. H[subscript 2] fluxes calculated in a summer period agreed within their uncertainty and pointed to soil uptake as the main driver of H[subscript 2] exchange at Harvard Forest, with H[subscript 2] deposition velocities ranging from 0.04 to 0.10 cm s[superscript −1].National Science Foundation (U.S.) (NSF Graduate Research Fellowship)United States. National Aeronautics and Space Administration (Advanced Global Atmospheric Gases Experiment (AGAGE))Massachusetts Institute of Technology. Joint Program on the Science & Policy of Global ChangeMartin Family Society of Fellows for SustainabilityMassachusetts Institute of Technology (Ally of Nature Research Fund)Massachusetts Institute of Technology (William Otis Crosby Lectureship)Massachusetts Institute of Technology (Warren Klein Fund

Maternal underweight and obesity and risk of orofacial clefts in a large international consortium of population-based studies

Background: Evidence on association of maternal pre-pregnancy weight with risk of orofacial clefts is inconsistent

Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development