Acceptability measures of water, sanitation and hygiene interventions in low- and middle-income countries, a systematic review

BACKGROUND: Inadequate access to water, sanitation, and hygiene (WASH) is an environmental risk factor for poor health outcomes globally, particularly for children in low- and middle-income countries (LMIC). Despite technological advancements, many interventions aimed at improving WASH access return less than optimal results on long term impact, efficacy and sustainability. Research focus in the 'WASH sector' has recently expanded from investigating 'which interventions work' to 'how they are best implemented'. The 'acceptability' of an intervention is a key component of implementation that can influence initial uptake and sustained use. Acceptability assessments are increasingly common for health interventions in clinical settings. A broad scale assessment of how acceptability has been measured in the WASH sector, however, has not yet been conducted. METHODS/PRINCIPAL FINDINGS: We conducted a systematic literature review of intervention studies published between 1990 and 2021 that evaluated the acceptability of WASH interventions in LMIC settings. Using an implementation science approach, focused outcomes included how acceptability was measured and defined, and the timing of acceptability assessment. We conducted quality assessment for all included studies using the Cochrane Risk of Bias tool for randomised studies, and the Newcastle-Ottawa Scale for non-randomised studies. Of the 1238 records; 36 studies were included for the analysis, 22 of which were non-randomized interventions and 16 randomized or cluster-randomized trials. We found that among the 36 studies, four explicitly defined their acceptability measure, and six used a behavioural framework to inform their acceptability study design. There were few acceptability evaluations in schools and healthcare facilities. While all studies reported measuring WASH acceptability, the measures were often not comparable or described. CONCLUSIONS: As focus in WASH research shifts towards implementation, a consistent approach to including, defining, and measuring acceptability is needed

Microarray evidence for off target effects in tick RNA interference experiments, and the lack of strong correlation between DSRNA and antibody phenotypes in tick In vitro treatments for vaccine candidate screening

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The double burden of malnutrition and dietary patterns in rural Central Java, Indonesia

Background: Indonesia is undergoing a nutrition transition (NT) comprised of rising rates of over- weight/obesity and consumption of high fat food/snacks but is still struck by undernutrition, causing a double burden of malnutrition. Little research pertains to the double burden of malnutrition and its associations with diet in rural Indonesia using primary village level data. Methods: We conducted a 24-hour food recall and food frequency questionnaire and assessed anthropo- metric status of rural villagers from four villages in Central Java, Indonesia. Exploratory principal compo- nent analysis was used to identify dietary patterns and multi-level modeling was performed to identify variables associated with dietary pattern indicative of the NT. Findings: 1,521 participants were included in analysis. Double burden of malnutrition was prevalent whereby 32.3% of children were stunted, 68.8% of women 35-49 years-old were overweight, and 39% of homes were classified as double burden. The NT was evident in a dietary pattern associated with soft drink, snacks, and animal products. There was small but significant correlation between undernutri- tion and stunting status among children (r = −0.139, p < 0.01). The NT was associated with young age (B = 1.696, 95% CI = 1.508-1.885) but not with overweight (B = −0.099, 95% CI = −0.184-−0.013). Interpretation: Our findings suggest that whilst the typical pattern of the double burden of malnutrition (stunted child/overweight adult) exists in rural Central Java, dietary patterns indicative of the NT are predominant among children, not adults. Overweight among adults may not be necessarily due to a diet indicative of the NT, and nutrition interventions in rural Central Java should focus on educating parents of young children about the health-risks of a diet associated with a NT. Funding: Funding was obtained from the UBS-Optimus Foundation and the National Health and Medical Research Council

Association of soybean-based food with the prevalence of anemia among reproductive aged men and women in rural Central Java, Indonesia

OBJECTIVE: To assess the association between soybean consumption and anemic status in Central Java, Indonesia. DESIGN: As part of an overarching sanitation improvement intervention in Central Java, Indonesia, we conducted a cross-sectional study in four rural villages. The study consisted of a 24-hour food recall, anthropometric measurements, blood hemoglobin measurement and stool sampling to test for soil-transmitted helminth (STH) infection status. A binary logistic regression model was fitted to test the association between soybean consumption and anemic status after adjusting for socio-demographic factors, STH infection, dietary diversity and anthropometric status. SETTING: This study took place in four rural villages of Wonosobo regency, Central Java, Indonesia. PARTICIPANTS: Participants were rural villagers aged between 15 and 49 years. RESULTS: A total sample size of 763 was attained, of which 231 were anemic. The prevalence of anemia was 30.2% among men and women of reproductive age, and highest among young males. Consumption of soybean was high (79.8%). After adjusting for covariates, the protective association between soybean consumption and anemia was statistically significant (AOR = 0.53, 95% CI = 0.30-0.95, p<0.05). There was a positive association with anemia among underweight (AOR = 2.75, 95% CI = 1.13-6.69, p<0.05) and those with high diet diversity (AOR = 1.40, 95% CI = 1.00-1.97, p<0.05). CONCLUSIONS: Our results were consistent with studies from other countries finding a protective association between soybean consumption and anemia. This association appeared stronger for tofu than for tempeh. The prevalence of anemia in rural Central Java is relatively consistent with nationwide statistics indicating that interventions targeting anemia are still largely required

Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison.

Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). Objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples, i.e. 65 glioblastoma and 5 non-tumoral tissues. As MethylCap-seq coverages were limited, we focused on the inherent capacity of the methodology to detect methylated loci rather than a quantitative analysis. MethylCap-seq and HM450 data were dichotomized and performances were compared using a gold standard free Bayesian modelling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. In addition, genome-wide characteristics were compared, revealing that HM450 probes identified substantially fewer regions compared to MethylCap-seq. Although results indicated that the latter method can detect more potentially relevant DNA-methylation, this did not translate into the discovery of more differentially methylated loci between tumours and controls compared to HM450. Our results therefore indicate that both methodologies are complementary, with a higher sensitivity for HM450 and a far larger genome-wide coverage for MethylCap-seq, but also that a more comprehensive character does not automatically imply more significant results in biomarker studies

Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma.

BACKGROUND: HOX genes are a family of developmental genes that are expressed neither in the developing forebrain nor in the normal brain. Aberrant expression of a HOX-gene dominated stem-cell signature in glioblastoma has been linked with increased resistance to chemo-radiotherapy and sustained proliferation of glioma initiating cells. Here we describe the epigenetic and genetic alterations and their interactions associated with the expression of this signature in glioblastoma. RESULTS: We observe prominent hypermethylation of the HOXA locus 7p15.2 in glioblastoma in contrast to non-tumoral brain. Hypermethylation is associated with a gain of chromosome 7, a hallmark of glioblastoma, and may compensate for tumor-driven enhanced gene dosage as a rescue mechanism by preventing undue gene expression. We identify the CpG island of the HOXA10 alternative promoter that appears to escape hypermethylation in the HOX-high glioblastoma. An additive effect of gene copy gain at 7p15.2 and DNA methylation at key regulatory CpGs in HOXA10 is significantly associated with HOX-signature expression. Additionally, we show concordance between methylation status and presence of active or inactive chromatin marks in glioblastoma-derived spheres that are HOX-high or HOX-low, respectively. CONCLUSIONS: Based on these findings, we propose co-evolution and interaction between gene copy gain, associated with a gain of chromosome 7, and additional epigenetic alterations as key mechanisms triggering a coordinated, but inappropriate, HOX transcriptional program in glioblastoma

Gene silencing in tick cell lines using small interfering or long double-stranded RNA

Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

Spatial analysis of schistosomiasis in Hunan and Jiangxi provinces in the People's Republic of China

Understanding the spatial distribution of schistosome infection is critical for tailoring preventive measures to control and eliminate schistosomiasis. This study used spatial analysis to determine risk factors that may impact Schistosoma japonicum infection and predict risk in Hunan and Jiangxi Provinces in the People's Republic of China. The study employed survey data collected in Hunan and Jiangxi in 2016. Independent variable data were obtained from publicly available sources. Bayesian-based geostatistics was used to build models with covariate fixed effects and spatial random effects to identify factors associated with the spatial distribution of infection. Prevalence of schistosomiasis was higher in Hunan (12.8%) than Jiangxi (2.6%). Spatial distribution of schistosomiasis varied at pixel level (0.1 x 0.1 km), and was significantly associated with distance to nearest waterbody (km, beta = -1.158; 95% credible interval [CrI]: -2.104, -0.116) in Hunan and temperature ( degrees C, beta = -4.359; 95% CrI: -9.641, -0.055) in Jiangxi. The spatial distribution of schistosomiasis in Hunan and Jiangxi varied substantially and was significantly associated with distance to nearest waterbody. Prevalence of schistosomiasis decreased with increasing distance to nearest waterbody in Hunan, indicating that schistosomiasis control should target individuals in close proximity to open water sources as they are at highest risk of infection

Correlation of immune phenotype with IDH mutation in diffuse glioma.

Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database. TIL and PD-L1 expression were observed in approximately half of WHO grade II/III gliomas. IDH-wt status was associated with significantly higher TIL infiltration and PD-L1 expression among all (grades II-IV) cases (n = 174, P &lt; 0.001) and within the cohort of glioblastomas (n = 131, P &lt; 0.001). In low-grade glioma (LGG) and glioblastoma cohorts of TCGA, significantly higher PD-L1 gene expression levels were evident in IDH-wt compared with IDH-mut samples (LGG: N = 516; P = 1.933e-11, GBM: N = 161; P &lt; 0.009). Lower PD-L1 gene expression was associated with increased promoter methylation (Spearman correlation coefficient -0.36; P &lt; 0.01) in the LGG cohort of TCGA. IDH-mut gliomas had higher PD-L1 gene promoter methylation levels than IDH-wt gliomas (P &lt; 0.01). The immunological tumor microenvironment of diffuse gliomas differs in association with IDH mutation status. IDH-wt gliomas display a more prominent TIL infiltration and higher PD-L1 expression than IDH-mut cases. Mechanistically this may be at least in part due to differential PD-L1 gene promoter methylation levels. Our findings may be relevant for immune modulatory treatment strategies in glioma patients

The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033.

The optimal treatment for patients with low-grade glioma (LGG) WHO grade II remains controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk-adjusted treatments are required for optimizing outcome and quality of life. We aim at identifying mechanisms and associated molecular markers predictive for benefit from radiotherapy (RT) or temozolomide (TMZ) in LGG patients treated in the randomized phase III trial EORTC 22033. As candidate biomarkers for these genotoxic treatments, we considered the DNA methylome of 410 DNA damage response (DDR) genes. We first identified 62 functionally relevant CpG sites located in the promoters of 24 DDR genes, using the LGG data from The Cancer Genome Atlas. Then we tested their association with outcome [progression-free survival (PFS)] depending on treatment in 120 LGG patients of EORTC 22033, whose tumors were mutant for isocitrate dehydrogenase 1 or 2 (IDHmt), the molecular hallmark of LGG. The results suggested that seven CpGs of four DDR genes may be predictive for longer PFS in one of the treatment arms that comprised MGMT, MLH3, RAD21, and SMC4. Most interestingly, the two CpGs identified for MGMT are the same, previously selected for the MGMT-STP27 score that is used to determine the methylation status of the MGMT gene. This score was higher in the LGG with 1p/19q codeletion, in this and other independent LGG datasets. It was predictive for PFS in the TMZ, but not in the RT arm of EORTC 22033. The results support the hypothesis that a high score predicts benefit from TMZ treatment for patients with IDHmt LGG, regardless of the 1p/19q status. This MGMT methylation score may identify patients who benefit from first-line treatment with TMZ, to defer RT for long-term preservation of cognitive function and quality of life