Maintaining essential health services during COVID-19 in Ghana: a qualitative study.

INTRODUCTION: Evidence suggests that non-pharmaceutical interventions such as lockdown policies, restriction of movement and physical distancing to control the novel COVID-19 contributed to the decline in utilisation of essential health services. We explored healthcare providers' and policy-makers' experiences of the barriers, interventions and response actions that contributed to ensuring the continuity of essential health services during the COVID-19 pandemic in Ghana to help inform future practice and policy. METHODS: We used a qualitative study approach. Data were analysed using thematic analysis. Thirty Four participants composed of 20 healthcare providers and 14 policy-makers who worked across regions with low and high recorded COVID-19 cases in Ghana during the COVID-19 pandemic were involved in this study. RESULTS: Participants reported that essential health services including maternal, reproductive and child health services, communicable and non-communicable disease care, and elective surgeries were disrupted during the COVID-19 pandemic. Barriers to the utilisation of essential services were constructed into three subthemes: (1) fear, (2) poor quality of care at the facility and (3) financial limitation. These barriers were mitigated with population-based interventions underpinned by the socioecological model at the individual and interpersonal level (including psychosocial care for families and home visits), institutional and community levels (such as allocation of funds, training of health workers, public education, triage stations, provision of logistics, appointment scheduling, telemedicine and redeployment of health workers) and public policy level (tax relief packages, transportation arrangements and provision of incentives), which helped in maintaining essential health services during COVID-19. CONCLUSION: Disruption of essential health services during COVID-19 in Ghana instigated population-based interventions which aided in expanding the populations' continuous access to essential health services and strengthened health service delivery.

Assessing the combined effect of multiple metal exposures on pregnancy and birth outcomes: Methodological insights in systematic review research.

This systematic review focused on pregnant women and aimed to evaluate how exposure to multiple metals impacts their pregnancy and birth outcomes. Previous research has predominantly focused on the effects of individual metal exposures on adverse birth outcomes. However, it is crucial to recognize that real-world scenarios often involve simultaneous exposure to multiple pollutants. Recent studies have emphasized the significance of considering exposure to mixtures of metals to gain a more comprehensive understanding of their collective health impacts. This article outlines the essential steps taken during the systematic review process, which involved synthesizing existing evidence and evaluating the strength and consistency of the relationship between metal mixtures and pregnancy and birth outcomes.

Exposure to metal mixtures and adverse pregnancy and birth outcomes: A systematic review.

BACKGROUND: Prenatal exposure to metal mixtures is associated with adverse pregnancy and birth outcomes like low birth weight, preterm birth, and small for gestational age. However, prior studies have used individual metal analysis, lacking real-life exposure scenarios. OBJECTIVES: This systematic review aims to evaluate the strength and consistency of the association between metal mixtures and pregnancy and birth outcomes, identify research gaps, and inform future studies and policies in this area. METHODS: The review adhered to the updated Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) checklist, along with the guidelines for conducting systematic reviews and meta-analyses of observational studies of etiology (COSMOS-E). Our data collection involved searching the PubMed, MEDLINE, and SCOPUS databases. We utilized inclusion criteria to identify relevant studies. These chosen studies underwent thorough screening and data extraction procedures. Methodological quality evaluations were conducted using the NOS framework for cohort and case-control studies, and the AXIS tool for cross-sectional studies. RESULTS: The review included 34 epidemiological studies, half of which focused on birth weight, and the others investigated neonate size, preterm birth, small for gestational age, miscarriage, and placental characteristics. The findings revealed significant associations between metal mixtures (including mercury (Hg), nickel (Ni), arsenic (As), cadmium (Cd), manganese (Mn), cobalt (Co), lead (Pb), zinc (Zn), barium (Ba), cesium (Cs), copper (Cu), selenium (Se), and chromium (Cr)) and adverse pregnancy and birth outcomes, demonstrating diverse effects and potential interactions. CONCLUSION: In conclusion, this review consistently establishes connections between metal exposure during pregnancy and adverse consequences for birth weight, gestational age, and other vital birth-related metrics. This review further demonstrates the need to apply mixture methods with caution but also shows that they can be superior to traditional approaches. Further research is warranted to deeper understand the underlying mechanisms and to develop effective strategies for mitigating the potential risks associated with metal mixture exposure during pregnancy.

COVID-19 outbreak control strategies and their impact on the provision of essential health services in Ghana: An exploratory-sequential study.

BACKGROUND: The COVID-19 pandemic has led to substantial interruptions in critical health services, with 90% of countries reporting interruptions in routine vaccinations, maternal health care and chronic disease management. The use of non-pharmaceutical interventions (NPIs) such as lockdowns and self-isolation had implications on the provision of essential health services (EHS). We investigated exemplary COVID-19 outbreak control strategies and explored the extent to which the adoption of these NPIs affected the provision of EHS including immunization coverage and facility-based deliveries. Finally, we document core health system strategies and practices adopted to maintain EHS during the early phase of the pandemic. METHODS: This study used an explanatory sequential study design. First, we utilized data from routine health management information systems to quantify the impact of the pandemic on the provision of EHS using interrupted time series models. Second, we explored exemplary strategies and health system initiatives that were adopted to prevent the spread of COVID-19 infections while maintaining the provision of EHS using in-depth interviews with key informants including policymakers and healthcare providers. RESULTS: The COVID-19 pandemic and the interventions that were implemented disrupted the provision of EHS. In the first month of the COVID-19 pandemic, Oral Polio and pentavalent vaccination coverage reduced by 15.2% [95% CI = -22.61, -7.87, p<0.001] and 12.4% [95% CI = 17.68, -7.13; p<0.001] respectively. The exemplary strategies adopted in maintaining the provision of EHS while also responding to the spread of infections include the development of new policy guidelines that were disseminated with modified service delivery models, new treatment and prevention guidelines, the use of telemedicine and medical drones to provide EHS and facilitate rapid testing of suspected cases. CONCLUSION: The implementation of different NPIs during the peak phase of the pandemic disrupted the provision of EHS. However, the Ministry of Health leveraged the resilient health system and deployed efficient, all-inclusive, and integrated infectious disease management and infection prevention control strategies to maintain the provision of EHS while responding to the spread of infections.

Electronic waste exposure and DNA damage: a systematic review and meta-analysis.

OBJECTIVES: Inappropriate processing and disposal of electronic waste (e-waste) expose workers and surrounding populations to hazardous chemicals, including clastogens and aneugens. Recently, considerable literature has grown around e-waste recycling, associated chemical exposures and intermediate health outcomes, including DNA damage. Micronuclei (MN) frequency has been widely used as a biomarker to investigate DNA damage in human populations exposed to genotoxic agents. We conducted a systematic review of published studies to assess DNA damage in e-waste-exposed populations and performed a meta-analysis to evaluate the association between e-waste exposure and DNA damage. METHODS: This systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement checklist. Articles published in English from January 2000 through December 2020 investigating the associations between e-waste exposure and DNA damage were retrieved from the following three major databases: MEDLINE, ProQuest, and Scopus. Studies that reported the use of MN assay as a biomarker of DNA damage were included for meta-analysis. Studies that also reported other DNA damage biomarkers such as chromosomal aberrations, comet assay biomarkers, 8-hydroxy-2'-deoxyguanosine (8-OHdG), telomere length, apoptosis rate were reported using narrative synthesis. RESULTS: A total of 20 publications were included in this review, of which seven studies were within the occupational setting, and the remaining 13 studies were ecological studies. The review found six biomarkers of DNA damage (micronuclei, comets assay parameters (tail length, % tail DNA, tail moment, and olive tail moment), 8-OHdG, telomere length, apoptosis rate and chromosomal aberrations) which were assessed using seven different biological matrices (buccal cells, blood, umbilical cord blood, placenta, urine and semen). Most studies showed elevated levels of DNA damage biomarkers among e-waste exposed populations than in control populations. The most commonly used biomarkers were micronuclei frequency (n=9) in peripheral blood lymphocytes or buccal cells and 8-OHdG (n=7) in urine. The results of the meta-analysis showed that electronic waste recycling has contributed to an increased risk of DNA damage measured using MN frequency with a pooled estimate of the standardized mean difference (SMD) of 2.30 (95% CI: 1.36, 3.24, p<0.001) based on 865 participants. CONCLUSIONS: Taken together, evidence from this systematic review with meta-analysis suggest that occupational and non-occupational exposure to e-waste processing is associated with increased risk of DNA damage measured through MN assay and other types of DNA damage biomarkers. However, more studies from other developing countries in Africa, Latin America, and South Asia are needed to confirm and increase these results' generalizability.

Health Risks Associated with Informal Electronic Waste Recycling in Africa: A Systematic Review.

Informal electronic waste (e-waste) recycling in Africa has become a major public health concern. This review examined studies that report on the association between e-waste exposure and adverse human health outcomes in Africa. The review was conducted following the updated version of the Preferred Items for Systematic Review and Meta-analysis (PRISMA 2020) statement checklist. We included papers that were original peer-reviewed epidemiological studies and conference papers, written in English, and reported on e-waste exposure among human populations and any health-related outcome in the context of Africa. Our results from the evaluation of 17 studies found an association between informal e-waste recycling methods and musculoskeletal disease (MSD) symptoms and physical injuries such as back pains, lacerations, eye problems, skin burns, and noise-induced hearing loss (NIHL). In addition, the generation and release of particulate matter (PM) of various sizes, and toxic and essential metals such as cadmium (Cd), lead (Pb), zinc (Zn), etc., during the recycling process are associated with adverse systemic intermediate health outcomes including cardiopulmonary function and DNA damage. This systematic review concludes that the methods used by e-waste recyclers in Africa expose them to increased risk of adverse health outcomes. However, there is a need for more rigorous research that moves past single pollutant analysis.

Polarization-dependent wideband metamaterial absorber for ultraviolet to near-infrared spectral range applications.

The need for wideband metamaterial absorbers (WBMA) for applications other than sensing and filtering has demanded modifications to the conventional three-layer metal-insulator-metal (MIM) absorber configuration. This modification often results in complex geometries and an increased number of layers requiring complex lithographic processes for fabrication. Here, we show that a metamaterial absorber with rectangular geometry in the simple MIM configuration can provide wideband absorption covering the ultraviolet and near-infrared spectral range. Due to its asymmetric nature, the WBMA is sensitive to the polarization of the incident light and independent of the angle of incidence up to about 45° depending on the polarization of the incident light. The characteristics of the WBMA presented here may be useful for applications such as detectors for wide spectral band applications.

Humidity-Controlled Tunable Emission in a Dye-Incorporated Metal-Hydrogel-Metal Cavity.

Actively controllable photoluminescence is potent for a wide variety of applications from biosensing and imaging to optoelectronic components. Traditionally, methods to achieve active emission control are limited due to complex fabrication processes or irreversible tuning. Here, we demonstrate active emission tuning, achieved by changing the ambient humidity in a fluorescent dye-containing hydrogel integrated into a metal-insulator-metal (MIM) system. Altering the overlapping region of the MIM cavity resonance and the absorption and emission spectra of the dye used is the underlying principle to achieving tunability of the emission. We first verify this by passive tuning of cavity resonance and further experimentally demonstrate active tuning in both air and aqueous environments. The proposed approach is reversible, easy to integrate, and spectrally scalable, thus providing opportunities for developing tunable photonic devices.

Relationship between temperature and Anopheles gambiae sensu lato mosquitoes' susceptibility to pyrethroids and expression of metabolic enzymes.

BACKGROUND: Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. METHODS: Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20-25 mosquitoes from each temperature regime (25-34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, ß-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. RESULTS: Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. CONCLUSIONS: This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate.

Association between toxic and essential metals in blood and global DNA methylation among electronic waste workers in Agbogbloshie, Ghana.

Aberrant global DNA methylation status is a known biomarker for increased disease risk, especially cancer. There is little published data on the association between toxic and essential metal mixtures and global DNA methylation in electronic waste (e-waste) workers. We aimed to establish the association between toxic and essential metals in blood and the effect of their interactions on global DNA methylation among e-waste recyclers and a reference group in Ghana. We used ICP-MS to measure the level of five metals (Se, Zn, Mn, Cd, and Pb) in the blood of 100 e-waste workers and 51 controls. We quantified blood DNA methylation levels of LINE-1 as an indicator of global DNA methylation. Cd, Mn, and Se levels were significantly higher in the reference group than in e-waste workers. Only Pb was significantly higher in the e-waste workers compared to the controls. Our linear regression analysis results showed a significant inverse association between Zn and LINE-1 DNA methylation (ßZn = - 0.912; 95% CI, - 1.512, - 0.306; p = 0.003) which corresponds to a 0.009 decrease in %LINE-1 methylation (95% CI, - 0.015, - 0.003; p = 0.003) for a 1% increase in Zn concentration. Potential interactions between Cd and Zn on global DNA methylation were observed. In summary, co-exposure to toxic and essential metals is associated with global (LINE-1) DNA methylation.

Effects of Elevated Temperatures on the Growth and Development of Adult Anopheles gambiae (s.l.) (Diptera: Culicidae) Mosquitoes.

Higher temperatures expected in a future warmer climate could adversely affect the growth and development of mosquitoes. This study investigated the effects of elevated temperatures on longevity, gonotrophic cycle length, biting rate, fecundity, and body size of Anopheles gambiae (s.l.) (Diptera: Culicidae) mosquitoes. Anopheles gambiae (s.l.) eggs obtained from laboratory established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40°C), and 80 ± 10% RH. All adults were allowed to feed on a 10% sugar solution soaked in cotton wool; however, some mosquitoes were provided blood meal using guinea pig. Longevity was estimated for both blood-fed and non-blood-fed mosquitoes and analyzed using the Kaplan-Meier survival analysis. One-way ANOVA was used to test the effect of temperature on gonotrophic cycle length, biting rate, and fecundity. Adult measurement data were log-transformed and analyzed using ordinary least square regression with robust standard errors. Increasing temperature significantly decreased the longevity of both blood-fed (Log-rank test; X2(4) = 904.15, P < 0.001) and non-blood-fed (Log-rank test; X2(4) = 1163.60, P < 0.001) mosquitoes. In addition, the fecundity of mosquitoes decreased significantly (ANOVA; F(2,57) = 3.46, P = 0.038) with an increase in temperature. Body size (ß = 0.14, 95% CI, 0.16, 0.12, P < 0.001) and proboscis length (ß = 0.13, 95% CI, 0.17, 0.09, P < 0.001) significantly decreased with increasing temperature from 25 to 34°C. Increased temperatures expected in a future warmer climate could cause some unexpected effects on mosquitoes by directly influencing population dynamics and malaria transmission.

Mechanism of emitters coupled with a polymer-based hyperbolic metamaterial.

We study a polymer-based hyperbolic metamaterial (HMM) structure composed of three Au-polymer bilayers with a hyperbolic dispersion relation. Using an effective refractive index retrieval algorithm, we obtain the effective permittivity of the experimentally fabricated polymer-based structure. In particular, the unique polymer-based HMM shows the existence of high-k modes that propagate in the metal-dielectric multilayered structure due to the excitation of bulk plasmon-polaritonic modes. Moreover, we compare the experimental luminescence and fluorescence lifetime results of the multilayered Au and a dye-doped polymer (PMMA) to investigate the dynamics of three different emitters, each incorporated within the unique polymer-based HMM structure. With emitters closer to the epsilon-near-zero region of the HMM, we observed a relatively high shortening of the average lifetime as compared to other emitters either close or far from the epsilon-near-zero region. This served as evidence of coupling between the emitters and the HMM as well as confirmed the increase in the non-radiative recombination rate of the different emitters. We also show that the metallic losses of a passive polymer-based HMM can be greatly compensated by a gain material with an emission wavelength close to the epsilon-near-zero region of the HMM. These results demonstrate the unique potential of an active polymer-based hyperbolic metamaterial in loss compensation, quantum applications, and sub-wavelength imaging techniques.

Effects of elevated temperatures on the development of immature stages of Anopheles gambiae (s.l.) mosquitoes.

OBJECTIVE: This study investigated the effects of temperature on the development of the immature stages of Anopheles gambiae (s.l.) mosquitoes. METHODS: Mosquito eggs were obtained from laboratory established colonies and reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38 and 40°C), and 80 ± 10% relative humidity. Larvae were checked daily for development to the next stage and for mortality. Pupation success, number of adults produced and sex ratio of the newly emerged adults were recorded. Larval survival was monitored every 24 h, and data were analysed using Kaplan-Meier survival analysis. Analysis of variance was used where data followed normal distribution, and a Kruskal-Wallis test where data were not normally distributed. Larval and pupal measurements were log-transformed and analysed using ordinary least square regression with robust standard errors. RESULTS: Increasing the temperature from 25 to 36°C decreased the development time by 10.57 days. Larval survival (X2 (6) = 5353.12, p < 0.001) and the number of adults produced (X2 (5) = 28.16, p < 0.001) decreased with increasing temperature. Increasing temperatures also resulted in significantly smaller larvae and pupae (p < 0.001). At higher temperatures, disproportionately more male than female mosquitoes were produced. CONCLUSIONS: Increased temperature affected different developmental stages in the life cycle of An. gambiae (s.l.) mosquitoes, from larval to adult emergence. This study contributes to the knowledge on the relationship between temperature and Anopheles mosquitoes and provides useful information for modelling vector population dynamics in the light of climate change.

Association between global DNA methylation (LINE-1) and occupational particulate matter exposure among informal electronic-waste recyclers in Ghana.

This study examined the associations between PM (2.5 and 10) and global DNA methylation among 100 e-waste workers and 51 non-e-waste workers serving as controls. Long interspersed nucleotide repetitive elements-1 (LINE-1) was measured by pyrosequencing. Personal PM2.5 and PM10 were measured over a 4-hour work-shift using real-time particulate monitors incorporated into a backpack . Linear regression models were used to assess the association between PM and LINE-1 DNA methylation. The concentrations of PM2.5 and PM10 were significantly higher among the e-waste workers than the controls (77.32 vs 34.88, p < 0.001 and 210.21 vs 121.92, p < 0.001, respectively). PM2.5 exposure was associated with increased LINE-1 CpG2 DNA methylation (ß = 0.003; 95% CI; 0.001, 0.006; p = 0.022) but not with the average of all 4 CpG sites of LINE-1. In summary, high levels of PM2.5 exposure was associated with increased levels of global DNA methylation in a site-specific manner.

Humidity- and Temperature-Tunable Metal-Hydrogel-Metal Reflective Filters.

A tunable reflectance filter based on a metal-hydrogel-metal structure responsive to humidity and temperature is reported. The filter employs a poly(N-isopropylacrylamide)-acrylamidobenzophenone (PNIPAm-BP) hydrogel as an insulator layer in the metal-insulator-metal (MIM) assembly. The optical resonance of the structure is tunable by water immersion across the visible and near-infrared range. Swelling/deswelling and the volume phase transition of the hydrogel allow continuous reversible humidity- and/or temperature-induced tuning of the optical resonance. This work paves the way toward low-cost large-area fabrication of actively tunable reversible photonic devices.

Wavefront Control with Nanohole Array-Based Out-of-Plane Metasurfaces.

Planar metasurfaces provide exceptional wavefront manipulation at the subwavelength scale by controlling the phase of the light. Here, we introduce an out-of-plane nanohole-based metasurface design with the implementation of a unique self-rolling technique. The photoresist-based technique enables the fabrication of the metasurface formed by nanohole arrays on gold (Au) and silicon dioxide (SiO2) rolled-up microtubes. The curved nature of the tube allows the fabrication of an out-of-plane metasurface that can effectively control the wavefront compared to the common planar counterparts. This effect is verified by the spectral measurements of the fabricated samples. In addition, we analytically calculated the dispersion relation to identify the resonance wavelength of the structure and numerically calculate the phase of the transmitted light through the holes with different sizes. Our work forms the basis for the unique platform to introduce a new feature to the metasurfaces, which may find many applications from stacked metasurface layers to optical trapping particles inside the tube.

A Systematic Review of the Effects of Temperature on Anopheles Mosquito Development and Survival: Implications for Malaria Control in a Future Warmer Climate.

The rearing temperature of the immature stages can have a significant impact on the life-history traits and the ability of adult mosquitoes to transmit diseases. This review assessed published evidence of the effects of temperature on the immature stages, life-history traits, insecticide susceptibility, and expression of enzymes in the adult Anopheles mosquito. Original articles published through 31 March 2021 were systematically retrieved from Scopus, Google Scholar, Science Direct, PubMed, ProQuest, and Web of Science databases. After applying eligibility criteria, 29 studies were included. The review revealed that immature stages of An. arabiensis were more tolerant (in terms of survival) to a higher temperature than An. funestus and An. quadriannulatus. Higher temperatures resulted in smaller larval sizes and decreased hatching and pupation time. The development rate and survival of An. stephensi was significantly reduced at a higher temperature than a lower temperature. Increasing temperatures decreased the longevity, body size, length of the gonotrophic cycle, and fecundity of Anopheles mosquitoes. Higher rearing temperatures increased pyrethroid resistance in adults of the An. arabiensis SENN DDT strain, and increased pyrethroid tolerance in the An. arabiensis SENN strain. Increasing temperature also significantly increased Nitric Oxide Synthase (NOS) expression and decreased insecticide toxicity. Both extreme low and high temperatures affect Anopheles mosquito development and survival. Climate change could have diverse effects on Anopheles mosquitoes. The sensitivities of Anopeheles mosquitoes to temperature differ from species to species, even among the same complex. Notwithstanding, there seem to be limited studies on the effects of temperature on adult life-history traits of Anopheles mosquitoes, and more studies are needed to clarify this relationship.

Global DNA (LINE-1) methylation is associated with lead exposure and certain job tasks performed by electronic waste workers.

OBJECTIVE: This study assessed the associations between blood and urine levels of toxic metals; cadmium (Cd) and lead (Pb), and methylation levels of the LINE-1 gene among e-waste and control populations in Ghana. METHODS: The study enrolled 100 male e-waste workers and 51 all-male non-e-waste workers or controls. The concentrations of Cd and Pb were measured in blood and urine using inductively coupled plasma mass spectrometry, while LINE1 methylation levels were assessed by pyrosequencing of bisulfite-converted DNA extracted from whole blood. Single and multiple metals linear regression models were used to determine the associations between metals and LINE1 DNA methylation. RESULTS: Blood lead (BPb) and urine lead (UPb) showed higher median concentrations among the e-waste workers than the controls (76.82 µg/L vs 40.25 µg/L, p ≤ 0.001; and 6.89 µg/L vs 3.43 µg/L, p ≤ 0.001, respectively), whereas blood cadmium (BCd) concentration was lower in the e-waste workers compared to the controls (0.59 µg/L vs 0.81 µg/L, respectively, p = 0.003). There was no significant difference in LINE1 methylation between the e-waste and controls (85.16 ± 1.32% vs 85.17 ± 1.11%, p = 0.950). In our single metal linear regression models, BPb was significantly inversely associated with LINE1 methylation in the control group (ßBPb = - 0.027, 95% CI - 0.045, - 0.010, p = 0.003). In addition, a weak association between BPb and LINE1 was observed in the multiple metals analysis in the e-waste worker group (ßBPb = - 0.005, 95% CI - 0.011, 0.000, p = 0.058). CONCLUSION: Continuous Pb exposure may interfere with LINE1 methylation, leading to epigenetic alterations, thus serving as an early epigenetic marker for future adverse health outcomes.

Pharmacoinformatics-based identification of potential bioactive compounds against Ebola virus protein VP24.

BACKGROUND: The impact of Ebola virus disease (EVD) is devastating with concomitant high fatalities. Currently, various drugs and vaccines are at different stages of development, corroborating the need to identify new therapeutic molecules. The VP24 protein of the Ebola virus (EBOV) plays a key role in the pathology and replication of the EVD. The VP24 protein interferes with the host immune response to viral infections and promotes nucleocapsid formation, thus making it a viable drug target. This study sought to identify putative lead compounds from the African flora with potential to inhibit the activity of the EBOV VP24 protein using pharmacoinformatics and molecular docking. METHODS: An integrated library of 7675 natural products originating from Africa obtained from the AfroDB and NANPDB databases, as well as known inhibitors were screened against VP24 (PDB ID: 4M0Q) utilising AutoDock Vina after energy minimization using GROMACS. The top 19 compounds were physicochemically and pharmacologically profiled using ADMET Predictor™, SwissADME and DataWarrior. The mechanisms of binding between the molecules and EBOV VP24 were characterised using LigPlot+. The performance of the molecular docking was evaluated by generating a receiver operating characteristic (ROC) by screening known inhibitors and decoys against EBOV VP24. The prediction of activity spectra for substances (PASS) and machine learning-based Open Bayesian models were used to predict the anti-viral and anti-Ebola activity of the molecules, respectively. RESULTS: Four natural products, namely, ZINC000095486070, ZINC000003594643, ZINC000095486008 and sarcophine were found to be potential EBOV VP24-inhibitiory molecules. The molecular docking results showed that ZINC000095486070 had high binding affinity of -9.7 kcal/mol with EBOV VP24, which was greater than those of the known VP24-inhibitors used as standards in the study including Ouabain, Nilotinib, Clomiphene, Torimefene, Miglustat and BCX4430. The area under the curve of the generated ROC for evaluating the performance of the molecular docking was 0.77, which was considered acceptable. The predicted promising molecules were also validated using induced-fit docking with the receptor using Schrödinger and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations. The molecules had better binding mechanisms and were pharmacologically profiled to have plausible efficacies, negligible toxicity as well as suitable for designing anti-Ebola scaffolds. ZINC000095486008 and sarcophine (NANPDB135) were predicted to possess anti-viral activity, while ZINC000095486070 and ZINC000003594643 to be anti-Ebola compounds. CONCLUSION: The identified compounds are potential inhibitors worthy of further development as EBOV biotherapeutic agents. The scaffolds of the compounds could also serve as building blocks for designing novel Ebola inhibitors.

Electrochemical Response of Saccharomyces cerevisiae Corresponds to Cell Viability upon Exposure to Dioclea reflexa Seed Extracts and Antifungal Drugs.

Dioclea reflexa bioactive compounds have been shown to contain antioxidant properties. The extracts from the same plant are used in traditional medical practices to treat various diseases with impressive outcomes. In this study, ionic mobility in Saccharomyces cerevisiae cells in the presence of D. reflexa seed extracts was monitored using electrochemical detection methods to link cell death to ionic imbalance. Cells treated with ethanol, methanol, and water extracts were studied using cyclic voltammetry and cell counting to correlate electrochemical behavior and cell viability, respectively. The results were compared with cells treated with pore-forming Amphotericin b (Amp b), as well as Fluconazole (Flu) and the antimicrobial drug Rifampicin (Rif). The D. reflexa seed water extract (SWE) revealed higher anodic peak current with 58% cell death. Seed methanol extract (SME) and seed ethanol extract (SEE) recorded 31% and 22% cell death, respectively. Among the three control drugs, Flu revealed the highest cell death of about 64%, whereas Amp b and Rif exhibited cell deaths of 35% and 16%, respectively, after 8 h of cell growth. It was observed that similar to SWE, there was an increase in the anodic peak current in the presence of different concentrations of Amp b, which also correlated with enhanced cell death. It was concluded from this observation that Amp b and SWE might follow similar mechanisms to inhibit cell growth. Thus, the individual bioactive compounds from the water extracts of D. reflexa seeds could further be purified and tested to validate their potential therapeutic application. The strategy to link electrochemical behavior to biochemical responses could be a simple, fast, and robust screening technique for new drug targets and to understand the mechanism of action of such drugs against disease models.