Risk-based public health impact assessment for drinking water contamination emergencies.

Chemical spills in surface waters pose a significant threat to public health and the environment. This study investigates the public health impacts associated with organic chemical spill emergencies and explores timely countermeasures deployable by drinking water facilities. Using a dynamic model of a typical multi-sourced New England drinking water treatment facility and its distribution network, this study assesses the impacts of various countermeasure deployment scenarios, including source switching, enhanced coagulation via poly­aluminum chloride (PACl), addition of powdered activated carbon (PAC), and temporary system shutdown. This study reveals that the deployment of multiple countermeasures yields the most significant reduction in total public health impacts, regardless of the demand and supply availability. With the combination PAC deployed first with other countermeasures proving to be the most effective strategies, followed by the combination of facility shutdowns. By understanding the potential public health impacts and evaluating the effectiveness of countermeasures, authorities can develop proactive plans, secure additional funding, and enhance their capacity to mitigate the consequences of such events. These insights contribute to safeguarding public health and improving the resilience of drinking water systems in the face of the ever-growing threat of chemical spills.

Non-Coding RNAs Potentially Involved in Pyrethroid Resistance of Anopheles funestus Population in Western Kenya.

Backgrounds: The resurgence of Anopheles funestus, a dominant vector of human malaria in western Kenya was partly attributed to insecticide resistance. However, evidence on the molecular basis of pyrethroid resistance in western Kenya is limited. Noncoding RNAs (ncRNAs) form a vast class of RNAs that do not code for proteins and are ubiquitous in the insect genome. Here, we demonstrated that multiple ncRNAs could play a potential role in An. funestusresistance to pyrethroid in western Kenya. Materials and Methods: Anopheles funestus mosquitoes were sampled by aspiration methods in Bungoma, Teso, Siaya, Port Victoria and Kombewa in western Kenya. The F1 progenies were exposed to deltamethrin (0.05%), permethrin (0.75%), DDT (4%) and pirimiphos-methyl (0.25%) following WHO test guidelines. A synergist assay using piperonyl butoxide (PBO) (4%) was conducted to determine cytochrome P450s' role in pyrethroid resistance. RNA-seq was conducted on a combined pool of specimens that were resistant and unexposed, and the results were compared with those of the FANG susceptible strain. This approach aimed to uncover the molecular mechanisms underlying pyrethroid resistance. Results: Pyrethroid resistance was observed in all the sites with an average mortality rate of 57.6%. Port Victoria had the highest level of resistance to permethrin (MR=53%) and deltamethrin (MR=11%) pyrethroids. Teso had the lowest level of resistance to permethrin (MR=70%) and deltamethrin (MR=87%). Resistance to DDT was observed only in Kombewa (MR=89%) and Port Victoria (MR=85%). A full susceptibility to P-methyl (0.25%) was observed in all the sites. PBO synergist assay revealed high susceptibility (>98%) to the pyrethroids in all the sites except for Port Victoria (MR=96%, n=100). Whole transcriptomic analysis showed that most of the gene families associated with pyrethroid resistance comprised non-coding RNAs (67%), followed by imipenemase (10%), cytochrome P450s (6%), cuticular proteins (5%), olfactory proteins (4%), glutathione S-transferases (3%), UDP-glycosyltransferases (2%), ATP-binding cassettes (2%) and carboxylesterases(1%). Conclusions: This study unveils the molecular basis of insecticide resistance in An. funestus in western Kenya, highlighting for the first time the potential role of non-coding RNAs in pyrethroid resistance. Targeting non-coding RNAs for intervention development could help in insecticide resistance management.

Trematode parasites as indicators of an animal component in the diet of the Water Vole Arvicola amphibius.

The intestinal trematode fauna of the Water Vole Arvicola amphibius, (previously A. terrestris), was investigated to determine whether it might provide evidence of an animal component in the diet of this aquatic herbivorous small mammal. Interrogation of the electronic Host-Parasite Database of the Natural History Museum London revealed the presence of fourteen species of intestinal trematode in water voles, infection with each of which would require the ingestion of tissue from an animal intermediate host. The results obtained using these parasite indicators provide convincing evidence of animal components in the diet of A. amphibius and support anecdotal reports of water voles feeding on animal material in the field.

Drug resistance and vaccine target surveillance of Plasmodium falciparum using nanopore sequencing in Ghana.

Malaria results in over 600,000 deaths annually, with the highest burden of deaths in young children living in sub-Saharan Africa. Molecular surveillance can provide important information for malaria control policies, including detection of antimalarial drug resistance. However, genome sequencing capacity in malaria-endemic countries is limited. We designed and implemented an end-to-end workflow to detect Plasmodium falciparum antimalarial resistance markers and diversity in the vaccine target circumsporozoite protein (csp) using nanopore sequencing in Ghana. We analysed 196 clinical samples and showed that our method is rapid, robust, accurate and straightforward to implement. Importantly, our method could be applied to dried blood spot samples, which are readily collected in endemic settings. We report that P. falciparum parasites in Ghana are mostly susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine resistance and no evidence of artemisinin resistance. Multiple single nucleotide polymorphisms were identified in csp, but their significance is uncertain. Our study demonstrates the feasibility of nanopore sequencing for malaria genomic surveillance in endemic countries.

The christian religious education teachers' attitudes toward the five-stage lesson plan framework in Kenya: A gender-based analysis.

New approaches have emerged in teaching Christian Religious Education (CRE). Five-stage lesson plan framework (FSLP) is one of the innovative approaches applicable in all learning areas. Even though the framework is learner-oriented, understanding teachers' attitudes towards the framework are essential. Developing a positive attitude among the stakeholders remains crucial in implementing any teaching approach. Therefore, this study assessed gender differences in the attitude toward the five-stage lesson plan framework among CRE teachers in Meru County, Kenya. A multi-stage sampling technique randomly selected 143 and 83 female and male CRE teachers. Using a semi-structured questionnaire, quantitative data were collected in a cross-sectional survey. Chi-square and t-test statistics were applied to test the statistical significance of the dummy and mean value of continuous variables using sex-disaggregated data. The study revealed that teachers' attitudes towards the FSLP framework did not significantly differ between male and female teachers. The study employed multiple linear regression modeling to assess the determinants of the attitudes towards the five-stage lesson plan framework for male, female, and pooled teachers. Similar determinants influenced teachers' attitudes towards the FSLP framework: academic qualification, teaching experience, utilization, and awareness. Researchers established that educational qualification was a negative and significant determinant of attitudes towards the FSLP framework among the participants. Teaching experience, awareness, and utilization of the FSLP framework among CRE teachers were positive and significant determinants of the attitudes towards the FSLP framework. The study findings implied development of policies inclined to the attitudes supporting the proper implementation of newly emerged teaching strategies among the stakeholders. The supplement schemes should be restructured and shaped to meet teachers' specific needs and preferences regarding the utilization of educational innovations to enable CRE teachers to select and practice the FSLP framework.

Determinants of COVID-19 Vaccine Acceptability among Healthcare Workers in Kenya-A Mixed Methods Analysis.

Healthcare workers (HCWs) were a priority group for COVID-19 vaccination. Adopting the World Health Organization's 3C and the expanded 5C vaccine hesitancy models, we assessed the factors associated with COVID-19 vaccine acceptability among HCWs in Kenya. In a mixed methods study, respondents were from eight selected counties across the country. An online survey (n = 746), key informant interviews (n = 18) and focus group discussions (n = 3) were conducted. The data were analyzed concurrently. Quantitative data showed that all the 3C antecedents were strong predictors of vaccine acceptability. The association of vaccine acceptability was strongest with convenience (aOR 20.13, 95% CI 9.01-44.96), then complacency (aOR 10.15, 95% CI 4.63-22.21) and confidence (aOR 6.37, 95% CI 2.90-14.02). Marital status was a significant independent factor associated with vaccine acceptability (aOR 2.70, 95% CI 1.20-6.08). Qualitatively, convenience presented as the no-cost availability of vaccines at the health facilities, whereas non-complacency manifested from the first-hand observed experience of COVID cases, and the need to protect oneself and family members. Confidence was mainly attributed to increased knowledge, resulting from multiple training sessions and trust in regulatory authorities. Other social factors including workplace pressure, religion and misinformation had a role in influencing HCW vaccination decisions. In the background of a pandemic, the 3C model is a strong predictor of vaccine acceptability, and making the vaccines easily available and convenient to HCWs significantly impacts their uptake.

Femoral Access-Site Complications with Tenecteplase versus Alteplase before Mechanical Thrombectomy for Large-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: IV thrombolysis with alteplase before mechanical thrombectomy for emergent large-vessel-occlusion stroke is associated with access-site bleeding complications. However, the incidence of femoral access-site complications with tenecteplase before mechanical thrombectomy requires exploration. Here, femoral access-site complications with tenecteplase versus alteplase before mechanical thrombectomy for large-vessel-occlusion stroke were compared. MATERIALS AND METHODS: All patients receiving IV thrombolytics before mechanical thrombectomy for large-vessel-occlusion stroke who presented from January 2020 to August 2022 were reviewed. In May 2021, our health care system switched from alteplase to tenecteplase as the primary thrombolytic for all patients with stroke, facilitating the comparison of alteplase-versus-tenecteplase femoral access-site complication rates. Major (requiring surgery) and minor (managed conservatively) access-site complications were assessed. RESULTS: One hundred thirty-nine patients underwent transfemoral mechanical thrombectomy for large-vessel-occlusion stroke, of whom 46/139 (33.1%) received tenecteplase and 93/139 (66.9%) received alteplase. In all cases (n = 139), an 8F sheath was inserted without sonographic guidance, and vascular closure was obtained with an Angio-Seal. Baseline demographics, concomitant antithrombotic medications, and periprocedural coagulation lab findings were similar between groups. The incidence of conservatively managed groin hematomas (2.2% versus 4.3%), delayed access-site oozing requiring manual compression (6.5% versus 2.2%), and arterial occlusion requiring surgery (2.2% versus 1.1%) was similar between the tenecteplase and alteplase groups, respectively (P = not significant). No dissection, arteriovenous fistula, or retroperitoneal hematoma was observed. CONCLUSIONS: Tenecteplase compared with alteplase before mechanical thrombectomy for large-vessel-occlusion stroke is not associated with an alteration in femoral access-site complication rates.

The BR-body proteome contains a complex network of protein-protein and protein-RNA interactions.

Bacterial RNP bodies (BR-bodies) are non-membrane-bound structures that facilitate mRNA decay by concentrating mRNA substrates with RNase E and the associated RNA degradosome machinery. However, the full complement of proteins enriched in BR-bodies has not been defined. Here we define the protein components of BR-bodies through enrichment of the bodies followed by mass spectrometry-based proteomic analysis. We found 111 BR-body enriched proteins, including several RNA binding proteins, many of which are also recruited directly to in vitro reconstituted RNase E droplets, showing BR-bodies are more complex than previously assumed. While most BR-body enriched proteins that were tested cannot phase separate, we identified five that undergo RNA-dependent phase separation in vitro, showing other RNP condensates interface with BR-bodies. RNA degradosome protein clients are recruited more strongly to RNase E droplets than droplets of other RNP condensates, implying that client specificity is largely achieved through direct protein-protein interactions. We observe that some RNP condensates assemble with preferred directionally, suggesting that RNA may be trafficked through RNP condensates in an ordered manner to facilitate mRNA processing/decay, and that some BR-body associated proteins have the capacity to dissolve the condensate. Finally, we find that RNA dramatically stimulates the rate of RNase E phase separation in vitro, explaining the dissolution of BR-bodies after cellular mRNA depletion observed previously. Altogether, these results suggest that a complex network of protein-protein and protein-RNA interactions controls BR-body phase separation and RNA processing.

Determinants of awareness and implementation of five-stage lesson plan framework among Christian Religious Education teachers in Meru County, Kenya.

Approaches, methods, and techniques of teaching Christian Religious Education (CRE) in Kenya have changed over time. Improved teaching strategies such as a five-stage lesson plan framework enhance students' performance. Despite the novelty of the framework, there is limited information on its spread and utilization among CRE teachers in Kenya. Therefore, this study assessed the determinants of awareness and implementation of the novel five-stage lesson plan framework in Meru County, Kenya. The study sampled 226 CRE teachers using a semi-structured questionnaire. The study employed an Ordered Probit Model to assess the determinants of the number of five-stage lesson plan stages awareness and implemented by the CRE teachers. The Ordered Probit analysis revealed that gender, academic qualification, working experience, and challenges were crucial determinants of awareness and implementation of the five-stage lesson plan framework. The findings implied that policymakers and relevant stakeholders in education should consider pre-service and in-service training, workshops, and seminars in upscaling or promoting the awareness and implementation of the five-stage lesson plan framework. Educational policies targeting improved teaching methods should enhance recognition and operation of the five-stage lesson plan framework.

Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial.

BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

Malaria artemisinin resistance: an extracellular vesicles export hypothesis.

Plasmodium falciparum causes malaria, and its resistance to artemisinin (ART) - a drug used for managing malaria - threatens to interfere with the effective control of malaria. ART resistance (ARTr) is driven by increased tolerance to oxidative stress and reduced haemoglobin trafficking to the food vacuole. We discuss how extracellular vesicles (EVs) may play a role in developing ARTr.

Detection of SARS-CoV-2 intra-host recombination during superinfection with Alpha and Epsilon variants in New York City.

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.

Genetic diversity of SARS-CoV-2 infections in Ghana from 2020-2021.

The COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, the SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 SARS-CoV-2 genomes from patient isolates (121 from arriving travellers and 1002 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineage, but the second wave was overwhelmingly driven by the Alpha variant. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta variants, which were introduced into community transmission in May 2021. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The observed rapid viral evolution demonstrates the potential for emergence of novel variants with greater mutational fitness as observed in other parts of the world.

Regulation of gene expression during ontogeny of physiological function in the brackishwater amphipod Gammarus chevreuxi.

Embryonic development is a complex process involving the co-ordinated onset and integration of multiple morphological features and physiological functions. While the molecular basis of morphological development in embryos is relatively well known for traditional model species, the molecular underpinning of the development of physiological functions is not. Here, we used global gene expression profiling to investigate the transcriptional changes associated with the development of morphological and physiological function in the amphipod crustacean Gammarus chevreuxi. We compared the transcriptomes at three timepoints during the latter half of development, characterised by different stages of the development of heart form and function: 10 days post fertilisation (dpf, Early: no heart structure visible), 15 dpf (Middle: heart present but not fully functional), and 18 dpf (Late: regular heartbeat). Gene expression profiles differed markedly between developmental stages, likely representing a change in the activity of different processes throughout the latter period of G. chevreuxi embryonic development. Differentially expressed genes belonged to one of three distinct clusters based on their expression patterns across development. One of these clusters, which included key genes relating to cardiac contractile machinery and calcium handling, displayed a pattern of sequential up-regulation throughout the developmental period studied. Further analyses of these transcripts could reveal genes that may influence the onset of a regular heartbeat. We also identified morphological and physiological processes that may occur alongside heart development, such as development of digestive caeca and the cuticle. Elucidating the mechanisms underpinning morphological and physiological development of non-model organisms will support improved understanding of conserved mechanisms, addressing the current phylogenetic gap between relatively well known model species.

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks. One-Sentence SummaryExpanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.

Adoption of climate-smart agricultural practices among smallholder farmers in Western Kenya: do socioeconomic, institutional, and biophysical factors matter?

Rigorous efforts should be channeled to the current low adoption of climate-smart agricultural practices (CSAPs) in sub-Saharan African countries to improve food production. What determines the adoption level and intensity of CSAPs among smallholder farmers in Kenya? While considering their joint adoption, smallholder farmers' CSAPs adoption determinants were assessed based on a sample size of 300 smallholder farmers in Western Kenya. The CSAPs considered were animal manure, soil water conservation, agroforestry, crop diversification, and crop-livestock integration. A multivariate and ordered probit models were used to assess the determinants of joint adoption of CSAPs in Western Kenya. Both complements and substitutes between CSAPs were established. The multivariate probit analysis revealed that household head's gender, education, age, family size, contact with extension agents, access to weather information, arable land, livestock owned, perceived climate change, infertile soil, and persistent soil erosion influenced CSAPs adoption. The ordered probit model revealed that gender, arable land, livestock owned, soil fertility, and constant soil erosion were crucial determinants of CSAPs adoption. The findings implied that policymakers and relevant stakeholders should consider farmer, institutional, and biophysical factors in upscaling or promoting the adoption of CSAPs.

Capturing intrahost recombination of SARS-CoV-2 during superinfection with Alpha and Epsilon variants in New York City

Recombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, recombination can only be detected when two genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was simultaneously infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts revealed that Alpha variant alleles comprised between 70-80% of the genomes, whereas the Epsilon variant alleles comprised between 20-30% of the sample. Further investigation revealed the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.

Pilot Study on Music in the Waiting Room of Outpatient Pain Clinics.

BACKGROUND: This study explores live and recorded music listening in the outpatient pain clinic. There is evidence demonstrating the effectiveness of live and recorded music in a hospital setting but a comparison study of this kind has yet to be conducted. METHODS: A multimethod survey study design was used. A questionnaire utilizing rating scales was self-administered across two outpatient pain clinic waiting rooms. Patients were included through convenience sampling. In one clinic, a playlist of recorded music curated by two of the authors was provided. In the second clinic, a music therapy student played live music using guitar, flute, and voice. The questionnaire gathered data on music's impact on pain and emotional states, as well as attitudes toward music in the waiting room. Quantitative data was analyzed using descriptive statistics and qualitative data, gathered in the questionnaires open ended question, was analyzed using thematic analysis. RESULTS: The questionnaire was completed by 200 adult patients. Patients reported lowered levels of anxiety, stress, and pain in both clinics, as well as a shorter waiting time and more caring experience. Patients in the live music clinic reported that music lowered levels of stress, nervousness, agitation, and pain more than in the recorded music clinic. CONCLUSIONS: Participants in this study identified that music is a useful tool in the pain clinic waiting room. This study contributes to evidence that music should be considered as a complimentary treatment for people living with pain and in the wider hospital setting. Additional research is warranted with a control group, pre- and posttesting, and studies of music in hospitals in a range of cultural contexts.

Differentiation of self: A scoping review of Bowen Family Systems Theory's core construct.

Bowen Family Systems Theory's central construct, differentiation of self (DoS), is one of the most recognized constructs to systemic researchers and psychology professionals. The present study reviewed the available evidence on DoS from the inception of the construct until July 31, 2020. A scoping review was conducted and a total of 295 primary studies were eligible for inclusion. Literature was categorized according to the hypotheses postulated by Bowen regarding: the associations between DoS and psychological and health outcomes and how DoS stability and similarity in partner levels operate within family systems. Descriptive data regarding studies on the measurement of DoS and in the area of psychotherapy were also compiled. Results revealed that there is ample support for DoS as a predictor of psychological health and marital quality, and that there are positive associations between DoS and better physical health and intergenerational relationships. Results of this review show that there continue to be underexplored hypotheses and a paucity of longitudinal or causal research designs to test the stability of DoS, the intergenerational transmission of DoS, and the efficacy of clinical interventions in modifying DoS to promote optimal well-being. Recommendations and next steps for researchers and practitioners are outlined.

Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function.

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.