...without a strategic transition plan in place, communities that used to benefit from lymphatic filariasis control activities run the risk of undermining the gains already made for soil-transmitted ...helminthiasis control once GPELF is discontinued. ...the Committee welcomes the recent approval of a new, rapidly disintegrating chewable formulation of mebendazole. ...as for other chronic infections (e.g., tuberculosis, human immune deficiency virus HIV, and malaria), combination therapy against soil-transmitted helminthiasis might decrease this risk and could enhance efficacy 25. ...the need for combination therapy is further supported by coendemicity of multiple helminth infections. ...there is a need to develop a new survey design that (1) is sufficiently powered to assess if the prevalence of moderate- or heavy-intensity infections falls below 1% and (2) is feasible and affordable, considering the limited resources and capacity of national soil-transmitted helminthiasis control programs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many water, sanitation, and hygiene (WASH) interventions target improvements in personal hygiene behaviors. Yet measuring personal hygiene behaviors is a challenge due to a lack of reliable, valid, ...objective, and simple-to-use approaches. The purpose of this study was to examine differences between two types of hygiene outcome measures and their ability to detect relationships between WASH-related behavioral factors and behaviors. We compared hygiene outcomes generated by the Quantitative Personal Hygiene Assessment Tool (qPHAT), which yields objective measures of cleanliness on an 11-point scale, and those generated by conventional, dichotomous indicators of cleanliness. We used cross-sectional data on hygiene outcomes related to facial and hand cleanliness collected during the Andilaye Trial, an impact evaluation of a community-based WASH intervention implemented in Amhara, Ethiopia. We fit multivariable models to examine associations between measures of children's facial and hand cleanliness, via both qPHAT and dichotomous indicators, and 1) household WASH conditions, 2) psychosocial factors, and 3) reported personal hygiene practices. The qPHAT-generated outcomes were able to detect relationships between intermediate behavioral factors and hygiene outcomes that dichotomous indicators were not, including associations with water insecurity and various psychosocial factors. qPHAT-generated outcomes were negatively associated with reported face washing practices, suggesting a bias in reported behaviors. Our study highlights the limitations of reported practices and dichotomous hygiene indicators and indicates that using more quantitative hygiene outcome measures, such as those generated by qPHAT, may reveal important intermediate factors that influence hygiene behavior and support improved monitoring and evaluation of interventions.
Ion channel function is fundamental to the existence of life. In metazoans, the coordinate activities of voltage-gated Na(+) channels underlie cellular excitability and control neuronal ...communication, cardiac excitation-contraction coupling, and skeletal muscle function. However, despite decades of research and linkage of Na(+) channel dysfunction with arrhythmia, epilepsy, and myotonia, little progress has been made toward understanding the fundamental processes that regulate this family of proteins. Here, we have identified β(IV)-spectrin as a multifunctional regulatory platform for Na(+) channels in mice. We found that β(IV)-spectrin targeted critical structural and regulatory proteins to excitable membranes in the heart and brain. Animal models harboring mutant β(IV)-spectrin alleles displayed aberrant cellular excitability and whole animal physiology. Moreover, we identified a regulatory mechanism for Na(+) channels, via direct phosphorylation by β(IV)-spectrin-targeted calcium/calmodulin-dependent kinase II (CaMKII). Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain.
Human gene variants affecting ion channel biophysical activity and/or membrane localization are linked to potentially fatal cardiac arrhythmias. However, the mechanism for many human arrhythmia ...variants remains undefined despite more than a decade of investigation. Posttranslational modulation of membrane proteins is essential for normal cardiac function. Importantly, aberrant myocyte signaling has been linked to defects in cardiac ion channel posttranslational modifications and disease. We recently identified a novel pathway for posttranslational regulation of the primary cardiac voltage-gated Na(+) channel (Na(v)1.5) by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). However, a role for this pathway in cardiac disease has not been evaluated.
We evaluated the role of CaMKII-dependent phosphorylation in human genetic and acquired disease. We report an unexpected link between a short motif in the Na(v)1.5 DI-DII loop, recently shown to be critical for CaMKII-dependent phosphorylation, and Na(v)1.5 function in monogenic arrhythmia and common heart disease. Experiments in heterologous cells and primary ventricular cardiomyocytes demonstrate that the human arrhythmia susceptibility variants (A572D and Q573E) alter CaMKII-dependent regulation of Na(v)1.5, resulting in abnormal channel activity and cell excitability. In silico analysis reveals that these variants functionally mimic the phosphorylated channel, resulting in increased susceptibility to arrhythmia-triggering afterdepolarizations. Finally, we report that this same motif is aberrantly regulated in a large-animal model of acquired heart disease and in failing human myocardium.
We identify the mechanism for 2 human arrhythmia variants that affect Na(v)1.5 channel activity through direct effects on channel posttranslational modification. We propose that the CaMKII phosphorylation motif in the Na(v)1.5 DI-DII cytoplasmic loop is a critical nodal point for proarrhythmic changes to Na(v)1.5 in congenital and acquired cardiac disease.
IntroductionDespite evidence for the efficacy and effectiveness of hand hygiene in reducing the transmission of infectious diseases, there are gaps in global normative guidance around hand hygiene in ...community settings. The goal of this review is to systematically retrieve and synthesise available evidence on hand hygiene in community settings across four areas: (1) effective hand hygiene; (2) minimum requirements; (3) behaviour change and (4) government measures.Methods and analysisThis protocol entails a two-phased approach to identify relevant studies for multiple related systematic reviews. Phase 1 involves a broad search to capture all studies on hand hygiene in community settings. Databases, trial registries, expert consultations and hand searches of reference lists will be used to ensure an exhaustive search. A comprehensive, electronic search strategy will be used to identify studies indexed in PubMed, Web of Science, EMBASE, CINAHL, Global Health, Cochrane Library, Global Index Medicus, Scopus, PAIS Index, WHO IRIS, UN Digital Library and World Bank eLibrary published in English from January 1980 to March 2023. The outcome of phase 1 will be a reduced sample of studies from which further screening, specific to research questions across the four key areas can be performed. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Quantitative and qualitative data will be extracted following best practices. We will assess all studies using the Mixed Method Appraisal Tool. All effect measures pertaining to review outcomes will be reported and a narrative synthesis of all studies will be presented including ‘data-driven’ descriptive themes and ‘theory-driven’ analytical themes as applicable.Ethics and disseminationThis systematic review is exempt from ethics approval because the work is carried out on published documents. The findings of the reviews will be disseminated in related peer-reviewed journals.PROSPERO registration numberCRD42023429145.
Personal hygiene practices, including facewashing and handwashing, reduce transmission of pathogens, but are difficult to measure. Using color theory principles, we developed and tested a novel ...metric that generates quantitative measures of facial and hand cleanliness, proxy indicators of personal hygiene practices. In this cross-sectional study, conventional qualitative cleanliness metrics (e.g., presence or absence of nasal and ocular discharge, dirt under nails or on finger pads and palms) were also recorded. We generated Gwet's agreement coefficients to determine the inter-rater reliability of novel and conventional metrics between various rating groups, where appropriate, including two non-blinded raters, non-blinded vs. blinded raters, three blinded raters, and blinded vs. computer raters. Inter-rater reliability of the novel metric was high across all rating groups, ranging from 0.98 (95% CI: 0.97, 0.99) to 0.90 (95% CI: 0.90, 0.91) for facial cleanliness, and 0.97 (95% CI: 0.96, 0.98) to 0.92 (95% CI: 0.91, 0.93) for hand cleanliness. Our novel metric generates more nuanced data than conventional qualitative metrics, and allows for quantifiable assessments of facial and hand cleanliness.
Unimproved water, sanitation, and hygiene (WASH) behaviors are key drivers of infectious disease transmission and influencers of mental well-being. While WASH is seen as a critical enabler of health, ...important knowledge gaps related to the content and delivery of effective, holistic WASH programming exist. Corresponding impacts of WASH on mental well-being are also underexplored. There is a need for more robust implementation research that yields information regarding whether and how community-based, demand-side interventions facilitate progressive and sustained adoption of improved sanitation and hygiene behaviors and downstream health impacts. The purpose of this protocol is to detail the rationale and design of a cluster-randomized trial evaluating the impact of a demand-side sanitation and hygiene intervention on sustained behavior change and mental well-being in rural and peri-urban Amhara, Ethiopia.
Together with partners, we developed a theoretically-informed, evidence-based behavioral intervention called Andilaye. We randomly selected and assigned 50 sub-districts (kebeles) from three purposively selected districts (woredas); half to receive the Andilaye intervention, and half the standard of care sanitation and hygiene programming (i.e., community-led total sanitation and hygiene CLTSH). During baseline, midline, and endline, we will collect data on an array of behavioral factors, potential moderators (e.g., water and sanitation insecurity, collective efficacy), and our primary study outcomes: sanitation and hygiene behaviors and mental well-being. We will perform a process evaluation to assess intervention fidelity and related attributes.
While CLTSH has fostered sanitation and hygiene improvements in Ethiopia, evidence of behavioral slippage, or regression to unimproved practices in communities previously declared open defecation free exists. Other limitations of CLTSH, such as its focus on disgust, poor triggering, and over-saturation of Health Extension Workers have been documented. We employed rigorous formative research and practically applied social and behavioral theory to develop Andilaye, a scalable intervention designed to address these issues and complement existing service delivery within Ethiopia's Health Extension Program. Evidence from this trial may help address knowledge gaps related to scalable alternatives to CLTSH and inform sanitation and hygiene programming and policy in Ethiopia and beyond.
This trial was registered with clinicaltrials.gov ( NCT03075436 ) on March 9, 2017.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and ...generalizability. However, programmatic deworming continues throughout low and middle-income countries.
We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1-4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005-2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI -1.9, -0.5%; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI -2.1, -0.2%; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI -2.8, -0.7%; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings.
Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are considerable challenges to achieving the Sustainable Development Goals’ target of universal access to basic sanitation in schools. Schools require safe, clean, and sex-segregated facilities ...for a large number of students. Robust and affordable solutions are needed to address the economic, spatial, social, institutional, and political factors which contribute to poor sanitary conditions in informal settlements. In 2015, we undertook a randomized controlled trial to assess the feasibility of private sector sanitation delivery (PSSD) in 20 primary schools, in informal settlements of Nairobi, Kenya. Our preliminary evaluation after one year of service delivery suggested that PSSD of urine-diverting dry latrines with routine waste collection and maintenance provided a feasible, lower-cost alternative to the government standard delivery (GSD) of cistern-flush toilets or ventilated improved pit latrines. We conducted a mixed-methods follow-up study to assess sanitation delivery over 3–4 years and investigate prevailing drivers and barriers that may influence the scalability of PSSD. The conditions of newly constructed and rehabilitated GSD facilities diminished quickly, reverting to the conditions of existing facilities, indicating lower sustainability compared to sanitation delivered from the private sector. Barriers in financial aspects related to the ongoing implementation of PSSD emerged, particularly among public schools, and few were able to pay for continued service. Our study demonstrates that the engagement of the private sector may lead to improvements in affordable, safely managed sanitation for schools and their students. Yet, to reach a sustained scale, additional guidance is needed on how to develop these partnerships, streamline procurement and contracting processes, and incorporate appropriate financing mechanisms.
Recent studies suggest that proarrhythmic effects of cardiac glycosides (CGs) on cardiomyocyte Ca(2+) handling involve generation of reactive oxygen species (ROS). However, the specific pathway(s) of ...ROS production and the subsequent downstream molecular events that mediate CG-dependent arrhythmogenesis remain to be defined.
We examined the effects of digitoxin (DGT) on Ca(2+) handling and ROS production in cardiomyocytes using a combination of pharmacological approaches and genetic mouse models. Myocytes isolated from mice deficient in NADPH oxidase type 2 (NOX2KO) and mice transgenically overexpressing mitochondrial superoxide dismutase displayed markedly increased tolerance to the proarrhythmic action of DGT as manifested by the inhibition of DGT-dependent ROS and spontaneous Ca(2+) waves (SCW). Additionally, DGT-induced mitochondrial membrane potential depolarization was abolished in NOX2KO cells. DGT-dependent ROS was suppressed by the inhibition of PI3K, PKC, and the mitochondrial KATP channel, suggesting roles for these proteins, respectively, in activation of NOX2 and in mitochondrial ROS generation. Western blot analysis revealed increased levels of oxidized CaMKII in WT but not in NOX2KO hearts treated with DGT. The DGT-induced increase in SCW frequency was abolished in myocytes isolated from mice in which the Ser 2814 CaMKII phosphorylation site on RyR2 is constitutively inactivated.
These results suggest that the arrhythmogenic adverse effects of CGs on Ca(2+) handling involve PI3K- and PKC-mediated stimulation of NOX2 and subsequent NOX2-dependent ROS release from the mitochondria; mitochondria-derived ROS then activate CaMKII with consequent phosphorylation of RyR2 at Ser 2814.
PDF
