WaSH CQI: Applying continuous quality improvement methods to water service delivery in four districts of rural northern Ghana

Continuous, safely managed water is critical to health and development, but rural service delivery faces complex challenges in low- and middle-income countries (LMICs). We report the first application of continuous quality improvement (CQI) methods to improve the microbial quality of household water for consumption (HWC) and the functionality of water sources in four rural districts of northern Ghana. We further report on the impacts of interventions developed through these methods. A local CQI team was formed and trained in CQI methods. Baseline data were collected and analyzed to identify determinants of service delivery problems and microbial safety. The CQI team randomized communities, developed an improvement package, iteratively piloted it in intervention communities, and used uptake survey data to refine the package. The final improvement package comprised safe water storage containers, refresher training for community WaSH committees and replacement of missing maintenance tools. This package significantly reduced contamination of HWC (p<0.01), and significant reduction in contamination persisted two years after implementation. Repair times in both intervention and control arms decreased relative to baseline (p<0.05), but differences between intervention and control arms were not significant at endline. Further work is needed to build on the gains in household water quality observed in this work, sustain and scale these improvements, and explore applications of CQI to other aspects of water supply and sanitation

The N-Terminal Region of the PA Subunit of the RNA Polymerase of Influenza A/HongKong/156/97 (H5N1) Influences Promoter Binding

BACKGROUND: The RNA polymerase of influenza virus is a heterotrimeric complex of PB1, PB2 and PA subunits which cooperate in the transcription and replication of the viral genome. Previous research has shown that the N-terminal region of the PA subunit of influenza A/WSN/33 (H1N1) virus is involved in promoter binding. METHODOLOGY/PRINCIPAL FINDINGS: Here we extend our studies of the influenza RNA polymerase to that of influenza strains A/HongKong/156/97 (H5N1) and A/Vietnam/1194/04 (H5N1). Both H5N1 strains, originally isolated from patients in 1997 and 2004, showed significantly higher polymerase activity compared with two classical human strains, A/WSN/33 (H1N1) and A/NT/60/68 (H3N2) in vitro. This increased polymerase activity correlated with enhanced promoter binding. The N-terminal region of the PA subunit was the major determinant of this enhanced promoter activity. CONCLUSIONS/SIGNIFICANCE: Overall we suggest that the N-terminal region of the PA subunit of two recent H5N1 strains can influence promoter binding and we speculate this may be a factor in their virulence

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Urinary heavy metals, phthalates, perchlorate, nitrate, thiocyanate, hydrocarbons, and polyfluorinated compounds are associated with adult hearing disturbance: USA NHANES, 2011–2012

Background Links between environmental chemicals and human health have emerged, but the effects on hearing were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and the hearing conditions in a national and population-based setting. Methods Data was retrieved from the US National Health and Nutrition Examination Surveys, 2011–2012 including demographics, serum measurements, lifestyle factors, self-reported hearing conditions, and urinary environmental chemical concentrations. Chi-square test, t test, and survey-weighted logistic regression models were performed. Results Among the American adults aged 20–69 (n=5560), 462 (8.3 %) people reported their hearing condition as moderate trouble to deaf. They had higher levels of urinary hydrocarbons and polyfluorinated compounds but not heavy metals, phthalates, arsenic, pesticides, phenols, parabens, perchlorate, nitrate, and thiocyanate concentrations. Also, 466 (10.0 %) people had hearing difficulties during conversation. They had higher levels of urinary cobalt (odds ratio (OR) 1.27, 95 % confidence interval (95%CI) 1.00–1.63), molybdenum (OR 1.45, 95%CI 1.04–2.02), strontium (OR 1.56, 95%CI 1.10–2.21), phthalates, perchlorate (OR 1.27, 95%CI 1.05– 1.54), nitrate (OR 1.60, 1.03–2.49) and thiocyanate (OR 1.22, 95%CI 1.01–1.48) concentrations but not arsenic, pesticides, phenols, parabens, hydrocarbons, and polyfluorinated compounds. Moreover, people who reported difficulties in following conversation with background noise had higher levels of urinary tin concentrations (OR 1.17, 1.00–1.36). Conclusions Urinary heavy metals, phthalates, perchlorate, nitrate, thiocyanate, hydrocarbons, and polyfluorinated compounds were associated with the adult hearing disturbance, although the causality cannot be established. Elimination of these environmental chemicals might need to be considered in future environmental health policy and health intervention programs

Misfolded human tRNA isodecoder binds and neutralizes a 3′ UTR-embedded Alu element

Several classes of small noncoding RNAs are key players in cellular metabolism including mRNA decoding, RNA processing, and mRNA stability. Here we show that a tRNAAsp isodecoder, corresponding to a human tRNA-derived sequence, binds to an embedded Alu RNA element contained in the 3′ UTR of the human aspartyl-tRNA synthetase mRNA. This interaction between two well-known classes of RNA molecules, tRNA and Alu RNA, is driven by an unexpected structural motif and induces a global rearrangement of the 3′ UTR. Besides, this 3′ UTR contains two functional polyadenylation signals. We propose a model where the tRNA/Alu interaction would modulate the accessibility of the two alternative polyadenylation sites and regulate the stability of the mRNA. This unique regulation mechanism would link gene expression to RNA polymerase III transcription and may have implications in a primate-specific signal pathway

Quantifying Preferences and Responsiveness of Marine Zooplankton to Changing Environmental Conditions using Microfluidics

<div><p>Global environmental change significantly affects marine species composition. However, analyzing the impact of these changes on marine zooplankton communities was so far mostly limited to assessing lethal doses through mortality assays and hence did not allow a direct assessment of the preferred conditions, or preferendum. Here, we use a microfluidic device to characterize individual behavior of actively swimming zooplankton, and to quantitatively determine their ecological preferendum. For the annelid zooplankton model <i>Platynereis dumerilii</i> we observe a broader pH preferendum than for the copepod <i>Euterpina acutifrons</i>, and reveal previously unrecognized sub-populations with different pH preferenda. For <i>Platynereis</i>, the minimum concentration difference required to elicit a response (responsiveness) is ~1 μM for H⁺ and ~13.7 mM for NaCl. Furthermore, using laser ablations we show that olfactomedin-expressing sensory cells mediate chemical responsiveness in the <i>Platynereis</i> foregut. Taken together, our microfluidic approach allows precise assessment and functional understanding of environmental perception on planktonic behaviour.</p></div