Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis.

DNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here, we report that testis-specific disruption of RAD1 in mice resulted in impaired DSB repair, germ cell depletion, and infertility. Unlike Hus1 or Rad9a disruption, Rad1 loss in meiocytes also caused severe defects in homolog synapsis, impaired phosphorylation of ATR targets such as H2AX, CHK1, and HORMAD2, and compromised meiotic sex chromosome inactivation. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion.

Occurrence of Lead and Other Toxic Metals Derived from Drinking-Water Systems in Three West African Countries.

BACKGROUND: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs). However, few robust studies report on TM contamination in low- and middle-income countries (LMICs). OBJECTIVES: We characterized the occurrence and investigated sources of TM contamination in 261 rural water systems in three West African LMICs to inform prevention and management. METHODS: Water samples were collected from 261 community water systems (handpumps and public taps) across rural Ghana, Mali, and Niger. Scrapings were collected from accessible components of a subset of these systems using a drill with acid-washed diamond-tipped bits. Samples were analyzed by inductively coupled plasma (ICP) mass spectrometry or ICP optical emission spectroscopy. RESULTS: Of the TMs studied, lead most frequently occurred at levels of concern in sampled water system components and water samples. Lead mass fractions exceeded International Plumbing Code (IPC) recommended limits (0.25% wt/wt) for components in 82% (107/130) of systems tested; brass components proved most problematic, with 72% (26/36) exceeding IPC limits. Presence of a brass component in a water system increased expected lead concentrations in drinking-water samples by 3.8 times. Overall, lead exceeded World Health Organization (WHO) guideline values in 9% (24/261) of drinking-water samples across countries; these results are broadly comparable to results observed in many HICs. Results did not vary significantly by geography or system type. DISCUSSION: Ensuring use of lead-free (<0.25%) components in new water systems and progressively remediating existing systems could reduce drinking-water lead exposures and improve health outcomes for millions. However, reflexive decommissioning of existing systems may deprive users of sufficient water for health or drive them to riskier sources. Because supply chains for many water system components are global, TM monitoring, prevention, and management may be warranted in other LMICs beyond the study area as well. https://doi.org/10.1289/EHP7804.

How we assess water safety: A critical review of sanitary inspection and water quality analysis.

Sanitary inspection is used in low-, medium- and high-income settings to assess the risk of microbial contamination at water sources. However, the relationship between sanitary inspection and water quality is not well understood. We conducted a critical literature review and synthesized the findings of 25 studies comparing the results of sanitary inspection and microbial water quality analysis. Most studies used sub-standard sanitary inspection and water quality analysis methods, and applied simplistic comparisons that do not characterize the complexity of the relationship. Sanitary risk score was used to represent sanitary inspection results in 21 (84%) studies; of which 12 (57%) found a significant association between score and microbial water quality and nine (43%) did not. Participatory sanitary inspection (12%) and reporting results back to communities (24%) were uncommon. Most studies relied on laboratory-based water quality analysis as an independently sufficient measure of safety, but reported inadequate quality control (52%) and/or sub-standard sample processing methods (66%). We found that sanitary inspections could contribute to improving water safety through four mechanisms: guiding remedial action at individual water sources, allowing operators and external support programs to prioritize repairs, identifying programmatic issues, and contributing to research. The purpose of the sanitary inspection should be considered when planning sanitary inspection execution, data analysis, and reporting to ensure appropriate methods are employed and results are fit for purpose. Further exploration should recognize that sanitary risk factors represent sources of contamination, pathways for contaminants to enter water supplies, and breakdowns in barriers to contamination. These different sanitary risk factor types have different and inter-dependent effects on water quality.

Availability of Hospital Resources and Specialty Services for Stroke Care in North Carolina.

OBJECTIVES: Effective regionalization of acute stroke care requires assessment and coordination of limited hospital resources. We described the availability of stroke-specific hospital resources (neurology specialty physicians and neuro-intensive care unit [neuro-ICU] bed capacity) for North Carolina overall and by region and population density. We also assessed daily trends in hospital bed availability. METHODS: This statewide descriptive study was conducted with data from the State Medical Asset Resource Tracking Tool (SMARTT), a Web-based system used by North Carolina to track available medical resources within the state. The SMARTT system was queried for stroke-specific physician and bed resources at each North Carolina hospital during a 1-year period (June 2015-May 2016), including daily availability of neuro-ICU beds. We compared hospital resources by geographic region and population density (metropolitan, urban, and rural). RESULTS: Data from 108 acute care hospitals located in 75 of 100 counties in North Carolina were included in the analysis. Fifty-seven percent of hospitals had no neurology specialty physicians. Western and eastern North Carolina had the lowest prevalence of these physicians. Most hospitals (88%) had general ICUs, whereas only 17 hospitals (16%) had neuro-ICUs. Neuro-ICUs were concentrated in metropolitan areas and in central North Carolina. On average, there were 276 general ICU and 27 neuro-ICU beds available statewide each day. Daily neuro-ICU bed availability was lowest in eastern and southeastern regions and during the week compared with weekends. CONCLUSIONS: In North Carolina, stroke-specific hospital subspecialists and resources are not distributed evenly across the state. Daily bed availability, particularly in neuro-ICUs, is lacking in rural areas and noncentral regions and appears to decrease on weekdays. Regionalization of stroke care needs to consider the geographic distribution and daily variability of hospital resources.

External support programs to improve rural drinking water service sustainability: A systematic review.

Achieving sufficient, safe, continuously-available drinking water services in rural areas is a challenge, in high- and especially low-and middle-income countries. External support programs (ESPs) - which may include administrative, financial, and technical assistance - have been hypothesized to contribute to sustainable rural water services. While there are many descriptions of ESPs, a standard terminology and typology of ESP activities does not exist and the effect of ESP activities on system sustainability remains inadequately characterized. We conducted a systematic review of ESPs for rural drinking water systems to identify ESP terminology and describe ESP activities. Findings from 218 publications from low-, middle-, and high-income countries were analyzed. ESP terms were used inconsistently between regions and income classifications. There were few studies describing ESP activities related to mechanized piped water systems. Few studies quantitatively assess the effect of ESPs. Those that did found positive associations with functionality, household satisfaction, household participation, and financial stability. This review is the first comprehensive evaluation of the ESP literature and we derive a definition of external support programs and typology of ESP activities from the descriptions of ESPs. A common understanding of ESPs facilitates discussion and knowledge transfer between stakeholders. Consistent terminology creates a foundation for adapting ESPs to water services in community institutions and for mechanized piped water systems.

A Systematic Review and Meta-Analysis of Fecal Contamination and Inadequate Treatment of Packaged Water.

BACKGROUND: Packaged water products provide an increasingly important source of water for consumption. However, recent studies raise concerns over their safety. OBJECTIVES: To assess the microbial safety of packaged water, examine differences between regions, country incomes, packaged water types, and compare packaged water with other water sources. METHODS: We performed a systematic review and meta-analysis. Articles published in English, French, Portuguese, Spanish and Turkish, with no date restrictions were identified from online databases and two previous reviews. Studies published before April 2014 that assessed packaged water for the presence of Escherichia coli, thermotolerant or total coliforms were included provided they tested at least ten samples or brands. RESULTS: A total of 170 studies were included in the review. The majority of studies did not detect fecal indicator bacteria in packaged water (78/141). Compared to packaged water from upper-middle and high-income countries, packaged water from low and lower-middle-income countries was 4.6 (95% CI: 2.6-8.1) and 13.6 (95% CI: 6.9-26.7) times more likely to contain fecal indicator bacteria and total coliforms, respectively. Compared to all other packaged water types, water from small bottles was less likely to be contaminated with fecal indicator bacteria (OR = 0.32, 95%CI: 0.17-0.58) and total coliforms (OR = 0.10, 95%CI: 0.05, 0.22). Packaged water was less likely to contain fecal indicator bacteria (OR = 0.35, 95%CI: 0.20, 0.62) compared to other water sources used for consumption. CONCLUSIONS: Policymakers and regulators should recognize the potential benefits of packaged water in providing safer water for consumption at and away from home, especially for those who are otherwise unlikely to gain access to a reliable, safe water supply in the near future. To improve the quality of packaged water products they should be integrated into regulatory and monitoring frameworks.