Effectiveness of a home-environmental intervention package and an early child development intervention on child health and development in high-altitude rural communities in the Peruvian Andes: a cluster-randomised controlled trial

Unsafe drinking water, poor sanitation and hygiene, exposure to household air pollution and low cognitive and socio-emotional stimulation are risk factors affecting children in low- and middle-income countries. We implemented an integrated home-environmental intervention package (IHIP), comprising a kitchen sink, hygiene education and a certified improved biomass cookstove, and an early child development (ECD) programme to improve children´s health and developmental outcomes in the rural high-altitude Andes of Peru

Improving household air, drinking water and hygiene in rural Peru : a community-randomized-controlled trial of an integrated environmental home-based intervention package to improve child health

Diarrhoea and acute lower respiratory infections are leading causes of childhood morbidity and mortality, which can be prevented by simple low-cost interventions. Integrated strategies can provide additional benefits by addressing multiple health burdens simultaneously.; We conducted a community-randomized-controlled trial in 51 rural communities in Peru to evaluate whether an environmental home-based intervention package, consisting of improved solid-fuel stoves, kitchen sinks, solar disinfection of drinking water and hygiene promotion, reduces lower respiratory infections, diarrhoeal disease and improves growth in children younger than 36 months. The attention control group received an early child stimulation programme.; We recorded 24 647 child-days of observation from 250 households in the intervention and 253 in the attention control group during 12-month follow-up. Mean diarrhoea incidence was 2.8 episodes per child-year in the intervention compared with 3.1 episodes in the control arm. This corresponds to a relative rate of 0.78 [95% confidence interval (CI): 0.58-1.05] for diarrhoea incidence and an odds ratio of 0.71 (95% CI: 0.47-1.06) for diarrhoea prevalence. No effects on acute lower respiratory infections or children's growth rates were observed.; Combined home-based environmental interventions slightly reduced childhood diarrhoea, but the confidence interval included unity. Effects on growth and respiratory outcomes were not observed, despite high user compliance of the interventions. The absent effect on respiratory health might be due to insufficient household air quality improvements of the improved stoves and additional time needed to achieve attitudinal and behaviour change when providing composite interventions

Household-level risk factors for water contamination and antimicrobial resistance in drinking water among households with children under 5 in rural San Marcos, Cajamarca, Peru

Household water contamination at point of use depends on human, animal and environmental factors embodying all aspects of a One Health approach. This study investigated the association between household factors, the presence of thermotolerant coliform, and the presence of antibiotic resistant bacteria in drinking water among 314 households with children under 5 in Cajamarca, Peru. This study analysed data from a baseline sampling of a randomized controlled trial, including household surveys covering household water management and factors such as household animals, as well as microbiological data from samples collected from drinking water. Data were analysed using generalized linear models. Drinking water samples collected from narrow-mouthed containers were less likely to be contaminated than samples collected from the faucet (OR = 0.55, p = 0.030) or wide mouthed containers. The presence of thermotolerant coliform was associated with owning farm birds, which increased the proportion of contamination from 42.2% to 59.1% (OR = 1.98, p = 0.017) and with animal waste observed in the kitchen area, which increased the prevalence of contamination from 51.4% to 65.6% (OR = 1.80, p = 0.024). Resistance to any antibiotic was higher among pig owners at 60%, relative to non-pig owners at 36.4% (OR = 1.97, p = 0.012) as well as households with free-roaming animals in the kitchen area at 59.6% compared to households without free-roaming animals at 39.7% (OR = 2.24, p = 0.035). Recent child antibiotic use increased the prevalence of trimethoprim-sulfamethoxazole resistance among E. coli isolates to 22.3% relative to 16.7% (OR = 3.00, p = 0.037). Overall, these findings suggest that water storage in a secure container to protect from in-home contamination is likely to be important in providing safe drinking water at point of use. In addition, transmission of thermotolerant coliform and AMR between domestic animals and human drinking water supplies is likely. Further research should explore transmission pathways and methods to support safe drinking water access in multi-species households

Function of SSA Subfamily of Hsp70 Within and Across Species Varies Widely in Complementing Saccharomyces cerevisiae Cell Growth and Prion Propagation

BACKGROUND:The cytosol of most eukaryotic cells contains multiple highly conserved Hsp70 orthologs that differ mainly by their spatio-temporal expression patterns. Hsp70s play essential roles in protein folding, transport or degradation, and are major players of cellular quality control processes. However, while several reports suggest that specialized functions of Hsp70 orthologs were selected through evolution, few studies addressed systematically this issue. METHODOLOGY/PRINCIPAL FINDINGS:We compared the ability of Ssa1p-Ssa4p from Saccharomyces cerevisiae and Ssa5p-Ssa8p from the evolutionary distant yeast Yarrowia lipolytica to perform Hsp70-dependent tasks when expressed as the sole Hsp70 for S. cerevisiae in vivo. We show that Hsp70 isoforms (i) supported yeast viability yet with markedly different growth rates, (ii) influenced the propagation and stability of the [PSI(+)] and [URE3] prions, but iii) did not significantly affect the proteasomal degradation rate of CFTR. Additionally, we show that individual Hsp70 orthologs did not induce the formation of different prion strains, but rather influenced the aggregation properties of Sup35 in vivo. Finally, we show that [URE3] curing by the overexpression of Ydj1p is Hsp70-isoform dependent. CONCLUSION/SIGNIFICANCE:Despite very high homology and overlapping functions, the different Hsp70 orthologs have evolved to possess distinct activities that are required to cope with different types of substrates or stress situations. Yeast prions provide a very sensitive model to uncover this functional specialization and to explore the intricate network of chaperone/co-chaperone/substrates interactions

Factors associated with compliance among users of solar water disinfection in rural Bolivia

ABSTRACT: BACKGROUND: Diarrhoea is the second leading cause of childhood mortality, with an estimated 1.3 million deaths per year. Promotion of Solar Water Disinfection (SODIS) has been suggested as a strategy for reducing the global burden of diarrhoea by improving the microbiological quality of drinking water. Despite increasing support for the large-scale dissemination of SODIS, there are few reports describing the effectiveness of its implementation. It is, therefore, important to identify and understand the mechanisms that lead to adoption and regular use of SODIS. METHODS: We investigated the behaviours associated with SODIS adoption among households assigned to receive SODIS promotion during a cluster-randomized trial in rural Bolivia. Distinct groups of SODIS-users were identified on the basis of six compliance indicators using principal components and cluster analysis. The probability of adopting SODIS as a function of campaign exposure and household characteristics was evaluated using ordinal logistic regression models. RESULTS: Standardised, community-level SODIS-implementation in a rural Bolivian setting was associated with a median SODIS use of 32% (IQR: 17-50). Households that were more likely to use SODIS were those that participated more frequently in SODIS promotional events (OR = 1.07, 95%CI: 1.01-1.13), included women (OR = 1.18, 95%CI: 1.07-1.30), owned latrines (OR = 3.38, 95%CI: 1.07-10.70), and had severely wasted children living in the home (OR = 2.17, 95%CI: 1.34-3.49). CONCLUSIONS: Most of the observed household characteristics showed limited potential to predict compliance with a comprehensive, year-long SODIS-promotion campaign; this finding reflects the complexity of behaviour change in the context of household water treatment. However, our findings also suggest that the motivation to adopt new water treatment habits and to acquire new knowledge about drinking water treatment is associated with prior engagements in sanitary hygien and with the experience of contemporary family health concerns.Household-level factors like the ownership of a latrine, a large proportion of females and the presence of a malnourished child living in a home are easily assessable indicators that SODIS-programme managers could use to identify early adopters in SODIS promotion campaigns. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073149

The Schizosaccharomyces pombe Hsp104 Disaggregase Is Unable to Propagate the [PSI+] Prion

The molecular chaperone Hsp104 is a crucial factor in the acquisition of thermotolerance in yeast. Under stress conditions, the disaggregase activity of Hsp104 facilitates the reactivation of misfolded proteins. Hsp104 is also involved in the propagation of fungal prions. For instance, the well-characterized [PSI+] prion of Saccharomyces cerevisiae does not propagate in Δhsp104 cells or in cells overexpressing Hsp104. In this study, we characterized the functional homolog of Hsp104 from Schizosaccharomyces pombe (Sp_Hsp104). As its S. cerevisiae counterpart, Sp_hsp104+ is heat-inducible and required for thermotolerance in S. pombe. Sp_Hsp104 displays low disaggregase activity and cannot propagate the [PSI+] prion in S. cerevisiae. When overexpressed in S. cerevisiae, Sp_Hsp104 confers thermotolerance to Δhsp104 cells and reactivates heat-aggregated proteins. However, overexpression of Sp_Hsp104 does not propagate nor eliminate [PSI+]. Strikingly, [PSI+] was cured by overexpression of a chimeric chaperone bearing the C-terminal domain (CTD) of the S. cerevisiae Hsp104 protein. Our study demonstrates that the ability to untangle aggregated proteins is conserved between the S. pombe and S. cerevisiae Hsp104 homologs, and points to a role of the CTD in the propagation of the S. cerevisiae [PSI+] prion

The effects of Δ9-tetrahydrocannabinol on the dopamine system

Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, is a pressing concern to global mental health. Patterns of use are changing drastically due to legalisation, availability of synthetic analogues (‘spice’), cannavaping and aggrandizements in the purported therapeutic effects of cannabis. Many of THC’s reinforcing effects are mediated by the dopamine system. Due to complex cannabinoid-dopamine interactions there is conflicting evidence from human and animal research fields. Acute THC causes increased dopamine release and neuron activity, whilst long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of the drug