Effects of High Temperature and Heavy Precipitation on Drinking Water Quality and Child Hand Contamination Levels in Rural Kenya.

Climate change may impact human health through the influence of weather on environmental transmission of diarrhea. Previous studies have found that high temperatures and heavy precipitation are associated with increased diarrhea prevalence, but the underlying causal mechanisms have not been tested and validated. We linked measurements of Escherichia coli in source water (n = 1673), stored drinking water (n = 9692), and hand rinses from children <2 years old (n = 2634) with publicly available gridded temperature and precipitation data (at ≤0.2 degree spatial resolution and daily temporal resolution) by the GPS coordinates and date of sample collection. Measurements were collected over a 3-year period across a 2500 km2 area in rural Kenya. In drinking water sources, high 7-day temperature was associated with a 0.16 increase in log10 E. coli levels (p < 0.001, 95% CI: 0.07, 0.24), while heavy 7-day total precipitation was associated with a 0.29 increase in log10 E. coli levels (p < 0.001, 95% CI: 0.13, 0.44). In household stored drinking water, heavy 7-day precipitation was associated with a 0.079 increase in log10 E. coli levels (p = 0.042, 95% CI: 0.07, 0.24). Heavy precipitation did not increase E. coli levels among respondents who treated their water, suggesting that water treatment can mitigate effects on water quality. On child hands, high 7-day temperature was associated with a 0.39 decrease in log10 E. coli levels (p < 0.001, 95% CI: -0.52, -0.27). Our findings provide insight on how climate change could impact environmental transmission of bacterial pathogens in Kenya. We suggest water treatment is especially important after heavy precipitation (particularly when preceded by dry periods) and high temperatures.

Decisions about adopting novel COVID-19 vaccines among White adults in a rural state, USA: A qualitative study.

PURPOSE: Many people, especially in rural areas of the United States, choose not to receive novel COVID-19 vaccinations despite public health recommendations. Understanding how people describe decisions to get vaccinated or not may help to address hesitancy. METHODS: We conducted semistructured interviews with 17 rural inhabitants of Maine, a sparsely populated state in the northeastern US, about COVID-19 vaccine decisions during the early rollout (March-May 2021). We used the framework method to compare responses, including between vaccine Adopters and Non-adopters. FINDINGS: Adopters framed COVID-19 as unequivocally dangerous, if not personally, then to other people. Describing their COVID concerns, Adopters emphasized disease morbidities. By contrast, Non-adopters never mentioned morbidities, referencing instead mortality risk, which they perceived as minimal. Instead of risks associated with the disease, Non-adopters emphasized risks associated with vaccination. Uncertainty about the vaccine development process, augmented by social media, bolstered concerns about the long-term unknown risks of vaccines. Vaccine Adopters ultimately described trusting the process, while Non-adopters expressed distrust. CONCLUSION: Many respondents framed their COVID vaccination decision by comparing the risks between the disease and the vaccine. Associating morbidity risks with COVID-19 diminishes the relevance of vaccine risks, whereas focusing on low perceived mortality risks heightens their relevance. Results could inform efforts to address COVID-19 vaccine hesitancy in the rural US and elsewhere. PATIENT OR PUBLIC CONTRIBUTION: Members of Maine rural communities were involved throughout the study. Leaders of community health groups provided feedback on the study design, were actively involved in recruitment, and reviewed findings after analysis. All data produced and used in this study were co-constructed through the participation of community members with lived experience.

Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks.

BACKGROUND: Individuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. METHOD: Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells. Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. RESULTS: All lines maintained CFTR mRNA production and formation of tight junctions. CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not. Baseline expression of cytokines IL6 and CXCL8 (IL8) was not different between the lines regardless of CFTR genotype. All lines responded to TNFα and IL1ß by increasing IL6 and CXCL8 mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines. Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFα, were compared for differential expression as a function of CFTR genotype. While some genes appeared to be differentially expressed simply because of CFTR's absence, others required stimulation for differences to be apparent. CONCLUSION: Together, these data suggest cells respond to CFTR's absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation. With regards to inflammation, these data suggest a model in which CFTR's absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation.