Investigating the relationship between extreme weather and cryptosporidiosis and giardiasis in Colorado: A multi-decade study using distributed-lag nonlinear models.

Environmentally-mediated protozoan diseases like cryptosporidiosis and giardiasis are likely to be highly impacted by extreme weather, as climate-related conditions like temperature and precipitation have been linked to their survival, distribution, and overall transmission success. Our aim was to investigate the relationship between extreme temperature and precipitation and cryptosporidiosis and giardiasis infection using monthly weather data and case reports from Colorado counties over a twenty-one year period. Data on reportable diseases and weather among Colorado counties were collected using the Colorado Electronic Disease Reporting System (CEDRS) and the Daily Surface Weather and Climatological Summaries (Daymet) Version 3 dataset, respectively. We used a conditional Poisson distributed-lag nonlinear modeling approach to estimate the lagged association (between 0 and 12-months) between relative temperature and precipitation extremes and the risk of cryptosporidiosis and giardiasis infection in Colorado counties between 1997 and 2017, relative to the risk found at average values of temperature and precipitation for a given county and month. We found distinctly different patterns in the associations between temperature extremes and cryptosporidiosis, versus temperature extremes and giardiasis. When maximum or minimum temperatures were high (90th percentile) or very high (95th percentile), we found a significant increase in cryptosporidiosis risk, but a significant decrease in giardiasis risk, relative to risk at the county and calendar-month mean. Conversely, we found very similar relationships between precipitation extremes and both cryptosporidiosis and giardiasis, which highlighted the prominent role of long-term (>8 months) lags. Our study presents novel insights on the influence that extreme temperature and precipitation can have on parasitic disease transmission in real-world settings. Additionally, we present preliminary evidence that the standard lag periods that are typically used in epidemiological studies to assess the impacts of extreme weather on cryptosporidiosis and giardiasis may not be capturing the entire relevant period.

Improving Care for Late-Life Depression Through Partnerships With Community-Based Organizations: Results From the Care Partners Project.

OBJECTIVES: Collaborative care (CC) has demonstrated effectiveness for improving late-life depression in primary care, but clinics offering this service can find it challenging to address unmet social needs that may be contributing to their patients' depression. Clinics may benefit from better coordination and communication with community-based organizations (CBO) to strengthen depression treatment and to address unmet social needs. We evaluated the feasibility of adding a CBO to enhance standard collaborative care and the impact of such partnered care on older adults. DESIGN: Multisite, prepost evaluation. SETTING: Eight (n = 8) partnerships between primary care clinics and community-based organizations in California. PARTICIPANTS: A total of 707 depressed older adults (60 years or older) as evidenced by having a score of 10 or more on the Patient Health Questionnaire (PHQ-9) received care under the Care Partners project. INTERVENTION: A CBO partner was added to augment CC for late-life depression in primary care. MEASUREMENTS: The PHQ-9 was used to identify depressed older adults and to monitor depression symptom severity during a course of care. RESULTS: At baseline, the average PHQ-9 depression score across the partnerships was 15, indicating moderate depression severity. Participating patients saw an average 7-point reduction in their PHQ-9 score, baseline to last score assessed, with nearly half of all participants (48.4%) experiencing a 50% or greater improvement from their baseline score. CONCLUSIONS: Our findings suggest that partnering with a community-based organization is a feasible and effective way for primary care clinics to address late-life depression in their patients.

Associations between metals and metabolomic profiles related to diabetes among adults in a rural region.

INTRODUCTION: Exposure to metals is associated with increased risk of type 2 diabetes (T2D). Potential mechanisms for metals-T2D associations involve biological processes including oxidative stress and disruption of insulin-regulated glucose uptake. In this study, we assessed whether associations between metal exposure and metabolite profiles relate to biological pathways linked to T2D. MATERIALS AND METHODS: We used data from 29 adults rural Colorado residents enrolled in the San Luis Valley Diabetes Study. Urinary concentrations of arsenic, cadmium, cobalt, lead, manganese, and tungsten were measured. Metabolic effects were evaluated using untargeted metabolic profiling, which included 61,851 metabolite signals detected in serum. We evaluated cross-sectional associations between metals and metabolites present in at least 50% of samples. Primary analyses adjusted urinary heavy metal concentrations for creatinine. Metabolite outcomes associated with each metal exposure were evaluated using pathway enrichment to investigate potential mechanisms underlying the relationship between metals and T2D. RESULTS: Participants had a mean age of 58.5 years (standard deviation = 9.2), 48.3% were female, 48.3% identified as Hispanic/Latino, 13.8% were current smokers, and 65.5% had T2D. Of the detected metabolites, 455 were associated with at least one metal, including 42 associated with arsenic, 22 with cadmium, 10 with cobalt, 313 with lead, 66 with manganese, and two with tungsten. The metabolic features were linked to 24 pathways including linoleate metabolism, butanoate metabolism, and arginine and proline metabolism. Several of these pathways have been previously associated with T2D, and our results were similar when including only participants with T2D. CONCLUSIONS: Our results support the hypothesis that metals exposure may be associated with biological processes related to T2D, including amino acid, co-enzyme, and sugar and fatty acid metabolism. Insight into biological pathways could influence interventions to prevent adverse health outcomes due to metal exposure.

A method for the systematic selection of enzyme panel candidates by solving the maximum diversity problem.

Enzymes are being increasingly exploited for their potential as industrial biocatalysts. Establishing a portfolio of useful biocatalysts from large and diverse protein family is challenging and a systematic method for candidate selection promises to aid in this task. Moreover, accurate enzyme functional annotation can only be confidently guaranteed through experimental characterisation in the laboratory. The selection of catalytically diverse enzyme panels for experimental characterisation is also an important step for shedding light on the currently unannotated proteins in enzyme families. Current selection methods often lack efficiency and scalability, and are usually non-systematic. We present a novel algorithm for the automatic selection of subsets from enzyme families. A tabu search algorithm solving the maximum diversity problem for sequence identity was designed and implemented, and applied to three diverse enzyme families. We show that this approach automatically selects panels of enzymes that contain high richness and relative abundance of the known catalytic functions, and outperforms other methods such as k-medoids.

Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

HIVepsilon-seq-scalable characterization of intact persistent proviral HIV reservoirs in women.

IMPORTANCE: The lack of a reliable method to accurately detect when replication-competent HIV has been cleared is a major challenge in developing a cure. This study introduces a new approach called the HIVepsilon-seq (HIVε-seq) assay, which uses long-read sequencing technology and bioinformatics to scrutinize the HIV genome at the nucleotide level, distinguishing between defective and intact HIV. This study included 30 participants on antiretroviral therapy, including 17 women, and was able to discriminate between defective and genetically intact viruses at the single DNA strand level. The HIVε-seq assay is an improvement over previous methods, as it requires minimal sample, less specialized lab equipment, and offers a shorter turnaround time. The HIVε-seq assay offers a promising new tool for researchers to measure the intact HIV reservoir, advancing efforts towards finding a cure for this devastating disease.

Exacerbation of Renal, Cardiovascular, and Respiratory Outcomes Associated with Changes in Climate.

Exposure to environmental variables including declining air quality and increasing temperatures can exert detrimental effects on human health including acute exacerbations of chronic diseases. We aim to investigate the association between these exposures and acute health outcomes in a rural community in Colorado. Meteorological and adult emergency department visit data were retrospectively collected (2013-2017); for asthma outcomes, additional data were available (2003-2017). Daily environmental exposure data included PM10, maximum daily temperature (MDT), and mean humidity and precipitation. Total daily counts of emergency department (ED) diagnoses for myocardial infarction, congestive heart failure, urolithiasis, and exacerbation of chronic obstructive pulmonary disease (COPD) and asthma, were calculated during the study period. Time series models using generalized estimating equations were fit for each disease and included all four environmental factors. Between 2013 and 2017, asthma and COPD exacerbation accounted for 30.8% and 25.4% of all ED visits (n=5,113), respectively. We found that for every 5˚C increase in MDT, the rate of urolithiasis visits increased by 13% (95% CI: 2%, 26%) and for every 10µg/m3 increase in 3-day moving average PM10, the rate of urolithiasis visits increased by 7% (95% CI: 1%, 13%). The magnitude of association between 3-day moving average PM10 and rate of urolithiasis visits increased with increasing MDT. The rate of asthma exacerbation significantly increased as 3-day, 7-day, and 21-day moving average PM10 increased. This retrospective study on ED visits is one of the first to investigate the impact of several environmental exposures on adverse health outcomes in a rural community. Research into mitigating the negative impacts of these environmental exposures on health outcomes is needed.

Development and application of an evidence-based directed acyclic graph to evaluate the associations between metal mixtures and cardiometabolic outcomes.

Objectives: Specifying causal models to assess relationships among metal mixtures and cardiometabolic outcomes requires evidence-based models of the causal structures; however, such models have not been previously published. The objective of this study was to develop and evaluate a directed acyclic graph (DAG) diagraming metal mixture exposure and cardiometabolic outcomes. Methods: We conducted a literature search to develop the DAG of metal mixtures and cardiometabolic outcomes. To evaluate consistency of the DAG, we tested the suggested conditional independence statements using linear and logistic regression analyses with data from the San Luis Valley Diabetes Study (SLVDS; n=1795). We calculated the proportion of statements supported by the data and compared this to the proportion of conditional independence statements supported by 1,000 DAGs with the same structure but randomly permuted nodes. Next, we used our DAG to identify minimally sufficient adjustment sets needed to estimate the association between metal mixtures and cardiometabolic outcomes (i.e., cardiovascular disease, fasting glucose, and systolic blood pressure). We applied them to the SLVDS using Bayesian kernel machine regression, linear mixed effects, and Cox proportional hazards models. Results: From the 42 articles included in the review, we developed an evidence-based DAG with 74 testable conditional independence statements (43 % supported by SLVDS data). We observed evidence for an association between As and Mn and fasting glucose. Conclusions: We developed, tested, and applied an evidence-based approach to analyze associations between metal mixtures and cardiometabolic health.

Open-source environmental data as an alternative to snail surveys to assess schistosomiasis risk in areas approaching elimination.

BACKGROUND: Although the presence of intermediate snails is a necessary condition for local schistosomiasis transmission to occur, using them as surveillance targets in areas approaching elimination is challenging because the patchy and dynamic quality of snail host habitats makes collecting and testing snails labor-intensive. Meanwhile, geospatial analyses that rely on remotely sensed data are becoming popular tools for identifying environmental conditions that contribute to pathogen emergence and persistence. METHODS: In this study, we assessed whether open-source environmental data can be used to predict the presence of human Schistosoma japonicum infections among households with a similar or improved degree of accuracy compared to prediction models developed using data from comprehensive snail surveys. To do this, we used infection data collected from rural communities in Southwestern China in 2016 to develop and compare the predictive performance of two Random Forest machine learning models: one built using snail survey data, and one using open-source environmental data. RESULTS: The environmental data models outperformed the snail data models in predicting household S. japonicum infection with an estimated accuracy and Cohen's kappa value of 0.89 and 0.49, respectively, in the environmental model, compared to an accuracy and kappa of 0.86 and 0.37 for the snail model. The Normalized Difference in Water Index (an indicator of surface water presence) within half to one kilometer of the home and the distance from the home to the nearest road were among the top performing predictors in our final model. Homes were more likely to have infected residents if they were further from roads, or nearer to waterways. CONCLUSION: Our results suggest that in low-transmission environments, leveraging open-source environmental data can yield more accurate identification of pockets of human infection than using snail surveys. Furthermore, the variable importance measures from our models point to aspects of the local environment that may indicate increased risk of schistosomiasis. For example, households were more likely to have infected residents if they were further from roads or were surrounded by more surface water, highlighting areas to target in future surveillance and control efforts.

Perioperative risk assessment.

Perioperative risk assessment refers to estimating a patient's risk of adverse outcomes in the perioperative period.

Open-source environmental data as an alternative to snail surveys to assess schistosomiasis risk in areas approaching elimination.

Background: Although the presence of intermediate snails is a necessary condition for local schistosomiasis transmission to occur, using them as surveillance targets in areas approaching elimination is challenging because the patchy and dynamic quality of snail host habitats makes collecting and testing snails labor-intensive. Meanwhile, geospatial analyses that rely on remotely sensed data are becoming popular tools for identifying environmental conditions that contribute to pathogen emergence and persistence. Methods: In this study, we assessed whether open-source environmental data can be used to predict the presence of human Schistosoma japonicum infections among households with a similar or improved degree of accuracy compared to prediction models developed using data from comprehensive snail surveys. To do this, we used infection data collected from rural communities in Southwestern China in 2016 to develop and compare the predictive performance of two Random Forest machine learning models: one built using snail survey data, and one using open-source environmental data. Results: The environmental data models outperformed the snail data models in predicting household S. japonicum infection with an estimated accuracy and Cohen’s kappa value of 0.89 and 0.49, respectively, in the environmental model, compared to an accuracy and kappa of 0.86 and 0.37 for the snail model. The Normalized Difference in Water Index (NDWI) within half to one kilometer of the home and the distance from the home to the nearest road were among the top performing predictors in our final model. Homes were more likely to have infected residents if they were further from roads, or nearer to waterways. Conclusion: Our results suggest that in low-transmission environments, investing in training geographic information systems professionals to leverage open-source environmental data could yield more accurate identification of pockets of human infection than using snail surveys. Furthermore, the variable importance measures from our models point to aspects of the local environment that may indicate increased risk of schistosomiasis. For example, households were more likely to have infected residents if they were further from roads or were surrounded by more surface water, highlighting areas to target in future surveillance and control efforts.

"We are the sun for our community:" Partnering with community health workers/promotores to adapt, deliver and evaluate a home-based collaborative care model to improve equity in access to quality depression care for older U.S. Latino adults who are underserved.

Background: While depression is a leading cause of poor health, less than half of older adults receive adequate care. Inequities in both access and outcomes are even more pronounced for socially disadvantaged older adults. The collaborative care model (CCM) has potential to reduce this burden through community-based organizations (CBOs) who serve these populations. However, CCM has been understudied in diverse cultural and resource-constrained contexts. We evaluated the implementation and effectiveness of PEARLS, a home-based CCM adapted with and for community health workers/promotores (CHWs/Ps). Methods: We used an instrumental case study design. Our case definition is a community-academic partnership to build CHW/P capacity for evidence-based depression care for older U.S. Latino adults in the Inland Empire region of California (2017-2020). We aimed to understand adaptations to fit local context; acceptability, feasibility, and fidelity; clinical effectiveness; and contextual determinants of implementation success or failure. Data sources included quantitative and qualitative administrative and evaluation data from participants and providers. We used descriptive statistics and paired t-tests to characterize care delivery and evaluate effectiveness post-intervention, and deductive thematic analysis to answer other aims. Findings: This case study included 152 PEARLS participants and nine data sources (N = 67 documents). The CBO including their CHWs/Ps partnered with the external implementation team made adaptations to PEARLS content, context, and implementation strategies to support CHWs/Ps and older adults. PEARLS was acceptable, feasible and delivered with fidelity. Participants showed significant reductions in depression severity at 5 months (98% clinical response rate [mean (SD), 13.7 (3.9) drop in pre/post PHQ-9; p < 0.001] and received support for 2.6 social needs on average. PEARLS delivery was facilitated by its relative advantage, adaptability, and trialability; the team's collective efficacy, buy-in, alignment with organization mission, and ongoing reflection and evaluation during implementation. Delivery was challenged by weak partnerships with clinics for participant referral, engagement, reimbursement, and sustainability post-grant funding. Discussion: This case study used existing data to learn how home-based CCM was adapted by and for CHWs/Ps to reduce health inequities in late-life depression and depression care among older Latino immigrants. The CBOs and CHWs/Ps strong trust and rapport, addressing social and health needs alongside depression care, and regular internal and external coaching and consultation, appeared to drive successful implementation and effectiveness.

Evaluation of genome skimming to detect and characterise human and livestock helminths.

The identification of gastrointestinal helminth infections of humans and livestock almost exclusively relies on the detection of eggs or larvae in faeces, followed by manual counting and morphological characterisation to differentiate species using microscopy-based techniques. However, molecular approaches based on the detection and quantification of parasite DNA are becoming more prevalent, increasing the sensitivity, specificity and throughput of diagnostic assays. High-throughput sequencing, from single PCR targets through to the analysis of whole genomes, offers significant promise towards providing information-rich data that may add value beyond traditional and conventional molecular approaches; however, thus far, its utility has not been fully explored to detect helminths in faecal samples. In this study, low-depth whole genome sequencing, i.e. genome skimming, has been applied to detect and characterise helminth diversity in a set of helminth-infected human and livestock faecal material. The strengths and limitations of this approach are evaluated using three methods to characterise and differentiate metagenomic sequencing data based on (i) mapping to whole mitochondrial genomes, (ii) whole genome assemblies, and (iii) a comprehensive internal transcribed spacer 2 (ITS2) database, together with validation using quantitative PCR (qPCR). Our analyses suggest that genome skimming can successfully identify most single and multi-species infections reported by qPCR and can provide sufficient coverage within some samples to resolve consensus mitochondrial genomes, thus facilitating phylogenetic analyses of selected genera, e.g. Ascaris spp. Key to this approach is both the availability and integrity of helminth reference genomes, some of which are currently contaminated with bacterial and host sequences. The success of genome skimming of faecal DNA is dependent on the availability of vouchered sequences of helminths spanning both taxonomic and geographic diversity, together with methods to detect or amplify minute quantities of parasite nucleic acids in mixed samples.

Depletion of HIV reservoir by activation of ISR signaling in resting CD4+T cells.

HIV reservoirs are extremely stable and pose a tremendous challenge to clear HIV infection. Here, we demonstrate that activation of ISR/ATF4 signaling reverses HIV latency, which also selectively eliminates HIV+ cells in primary CD4+T cell model of latency without effect on HIV-negative CD4+T cells. The reduction of HIV+ cells is associated with apoptosis enhancement, but surprisingly is largely seen in HIV-infected cells in which gag-pol RNA transcripts are detected in HIV RNA-induced ATF4/IFIT signaling. In resting CD4+ (rCD4+) T cells isolated from people living with HIV on antiretroviral therapy, induction of ISR/ATF4 signaling reduced HIV reservoirs by depletion of replication-competent HIV without global reduction in the rCD4+ T cell population. These findings suggest that compromised ISR/ATF4 signaling maintains stable and quiescent HIV reservoirs whereas activation of ISR/ATF4 signaling results in the disruption of latent HIV and clearance of persistently infected CD4+T cells.

Occurrence of Occupational Injuries and Within Day Changes in Wet Bulb Temperature Among Sugarcane Harvesters.

OBJECTIVE: Climate change has implications for human health worldwide, with workers in outdoor occupations in low- to middle-income countries shouldering the burden of increasing average temperatures and more frequent extreme heat days. An overlooked aspect of the human health impact is the relationship between heat exposure and increased risk of occupational injury. In this study, we examined the association between occupational injury occurrence and changes in outdoor temperatures through the workday among a cohort of Guatemalan sugarcane harvesters. METHODS: Occupational injuries recorded for the 2014/2015 to 2017/2018 harvest seasons were collected from a large agribusiness employing male sugarcane harvesters in Southwest Guatemala. Wet Bulb Globe Temperature (WBGT) for the same period was collected from the El Balsamo weather station. We used a logistic mixed effects model to examine the association between injury occurrence and (1) the average WBGT during the hour injury was recorded, (2) the average WBGT during the hour prior to the injury being recorded, and (3) the change in the hourly average WBGT prior to the injury being recorded. RESULTS: There were 155 injuries recorded during the study period. Injuries were recorded most often between 14:00 and 16:00 (n = 62, 40%) followed by 8:00 and 10:00 (n = 56, 36%). There were significant differences in the average hourly WBGT and the hour in which injuries were recorded (p-value <.001). There were no observable associations between average hourly WBGT (OR: 1.00, 95%CI: 0.94, 1.05; p-value: 0.87), lagged average hourly WBGT (OR: 1.01, 95%CI: 0.97, 1.05; p-value: 0.71), or change in average hourly WBGT (OR: 0.96, 95%CI: 0.89, 1.04; p-value: 0.35) and recorded occupational injury. CONCLUSIONS: This is the first study that has examined how changes in WBGT throughout the day are related to occupational injury among agricultural workers. Although this study did not demonstrate an association, there is a need for future research to examine how various measurements of WBGT exposure are related to occupational injury in agricultural worker populations.

Urinary concentrations of metals before and after volcanic eruption: a natural experiment surrounding the eruption of Volcán de Fuego, 2018.

Volcanic eruptions increase environmental heavy metal concentrations, yet little research has been performed on their extrapulmonary human health effects. We fortuitously collected biological samples in a cohort of Guatemalan sugarcane cutters in the area surrounding Volcán de Fuego before and after the June 2018 eruption. We sought to determine whether stratovolcanic activity was associated with changes in urinary concentrations of heavy metals in a cohort of sugarcane workers. In this exploratory analysis, we found significant increases in urinary arsenic, (ß = 1.46, P < 0.0001), cadmium (ß = 1.03, P < 0.0001), and lead (ß = 0.87, P = 0.003) in participants with residential proximity to Volcán de Fuego as compared to participants farther away, suggesting that volcanic activity could be associated with acute heavy metal exposures. This natural experiment is, to our knowledge, the first of its kind and suggests a need for more research into heavy metal exposure-related health impacts of volcanic eruptions.

The S.I.T.E. Framework: A Novel Approach for Sustainably Integrating Trauma-Informed Approaches in Schools.

Students who present as dysregulated due to the impacts of trauma and toxic stress can challenge educators and find themselves improperly or insufficiently supported, punitively consequenced and unable to equitably access education. Trauma-informed approaches based on an understanding of brain development and function have been put forth as best practice for supporting students with trauma histories. The novel Sustainably Integrated Trauma-Informed Education Framework (S.I.T.E. Framework) facilitates systemic integration of trauma-informed approaches across a school and was developed through a community-informed process to address implementation challenges traditionally linked to trauma-informed initiatives. The S.I.T.E Framework promotes the science-based content of the Neurosequential Model in Education (NME) and was piloted during the 2017-18 school year at a metropolitan elementary school in Colorado. Mixed analytic methods identified four components, 1) establish and facilitate school-based Core Team, 2) deliver school-wide professional development training, 3) provide on-site staff support and consultation and 4) conduct a comprehensive evaluation as critical to the successful implementation of the framework. Pilot testing of the S.I.T.E. Framework's innovative, multicomponent structure illustrates the potential for sustainable, whole-school integration of brain-based, trauma-informed approaches that are supportive of both educators and students regardless of their trauma history.

A Longitudinal Study of Exposure to Manganese and Incidence of Metabolic Syndrome.

The association between manganese (Mn) and metabolic syndrome (MetS) is unclear, and no prior study has studied this association longitudinally. The aim of this study was to assess longitudinal associations of Mn exposure with MetS and metabolic outcomes. We used data from the San Luis Valley Diabetes Study (SLVDS), a prospective cohort from rural Colorado with data collected from 1984−1998 (n = 1478). Urinary Mn was measured at baseline (range = 0.20−42.5 µg/L). We assessed the shape of the cross-sectional association between Mn and MetS accounting for effect modification by other metals at baseline using Bayesian kernel machine regression. We assessed longitudinal associations between baseline quartiles of Mn and incident MetS using Fine and Gray competing risks regression models (competing risk = mortality) and between quartiles of Mn and metabolic outcomes using linear mixed effects models. We did not observe evidence that quartiles of Mn were associated with incident MetS (p-value for trend = 0.52). Quartiles of Mn were significantly associated with lower fasting glucose (p-value for trend < 0.01). Lead was found to be a possible effect modifier of the association between Mn and incident MetS. Mn was associated with lower fasting glucose in this rural population. Our results support a possible beneficial effect of Mn on diabetic markers.

Group Antenatal Care in Ghana: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: While group antenatal care (ANC) has been delivered and studied in high-income countries for over a decade, it has only recently been introduced as an alternative to individual care in sub-Saharan Africa. Although the experimental design of the studies from high-resource countries have been scientifically rigorous, findings cannot be generalized to low-resource countries with low literacy rates and high rates of maternal and newborn morbidity and mortality. The Group Antenatal Care Delivery Project (GRAND) is a collaboration between the University of Michigan in the United States and the Dodowa Health Research Centre in Ghana. GRAND is a 5-year, cluster randomized controlled trial (RCT). Our intervention-group ANC-consists of grouping women by similar gestational ages of pregnancy into small groups at the first ANC visit. They then meet with the same group and the same midwife at the recommended intervals for care. OBJECTIVE: This study aims to improve health literacy, increase birth preparedness and complication readiness, and optimize maternal and newborn outcomes among women attending ANC at seven rural health facilities in the Eastern Region of Ghana. METHODS: Quantitative data will be collected at four time points using a secure web application for data collection and a database management tool. Data will be analyzed on an intention-to-treat basis to test the differences between the two arms: women randomized to group-based ANC and women randomized to routine individual ANC. We will conduct a process evaluation concurrently to identify and document patient, provider, and system barriers and facilitators to program implementation. RESULTS: The study was funded in September 2018. Recruitment and enrollment of participants and data collection started in July 2019. In November 2021, we completed participant enrollment in the study (n=1761), and we completed data collection at the third trimester in May 2022 (n=1284). Data collection at the additional three time points is ongoing: 6 weeks postpartum, 6 months postpartum, and 1 year postpartum. CONCLUSIONS: This study is significant and timely because it is among the first RCTs to be conducted to examine the effects of group ANC among low-literacy and nonliterate participants. Our findings have the potential to impact how clinical care is delivered to low-literacy populations, both globally and domestically, to improve maternal and newborn outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033003; https://clinicaltrials.gov/ct2/show/NCT04033003. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40828.

Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights.

Environmental causes of cardiovascular diseases (CVDs) are global health issues. In particular, an association between metal exposure and CVDs has become evident but causal evidence still lacks. Therefore, this symposium at the Society of Toxicology 2022 annual meeting addressed epidemiological, clinical, pre-clinical animal model-derived and mechanism-based evidence by five presentations: 1) An epidemiologic study on potential CVD risks of individuals exposed occupationally and environmentally to heavy metals; 2) Both presentations of the second and third were clinical studies focusing on the potential link between heavy metals and pulmonary arterial hypertension (PAH), by presenting altered blood metal concentrations of both non-essential and essential metals in the patients with PAH and potential therapeutic approaches; 3) Arsenic-induced atherosclerosis via inflammatory cells in mouse model; 4) Pathogenic effects on the heart by adult chronic exposure to very low-dose cadmium via epigenetic mechanisms and whole life exposure to low dose cadmium via exacerbating high-fat-diet-lipotoxicity. This symposium has brought epidemiologists, therapeutic industry, physicians, and translational scientists together to discuss the health risks of occupational and environmental exposure to heavy metals through direct cardiotoxicity and indirect disruption of homeostatic mechanisms regulating essential metals, as well as lipid levels. The data summarized by the presenters infers a potential causal link between multiple metals and CVDs and defines differences and commonalities. Therefore, summary of these presentations may accelerate the development of efficient preventive and therapeutic strategies by facilitating collaborations among multidisciplinary investigators.