Time-course of oral toxicity to contaminated groundwater in male Sprague Dawley rats.

Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study determined the time-course of toxicity (7, 14, 28, and 60 days) following ad libitum oral exposure to 0.05% v/v contaminated groundwater compared to tap water (control) in male Sprague Dawley rats (n=5 /group/time). Exposure to groundwater resulted in inflammation, indicated by a statistically significant increase in plasma lymphocyte and neutrophil counts on days 7 and 60, respectively, but a reduction in the plasma alpha 2 macroglobulin levels by day 60. Gonadotoxicity was indicated by a reduced Johnsen score (grading spermatogenesis) in all exposed groups at all time points, while seminiferous epithelial height was reduced on days 7, 14, and 28 compared to controls. Plasma testosterone was reduced in exposed groups on days 7 and 28, accompanied by elevated testicular lipid peroxidation at all time points compared to control. In contrast, lipid peroxidation in the lungs from exposed rats was elevated on days 7, 14, and 28. Plasma symmetric dimethylarginine was elevated on day 14 in the exposed group indicating renal impairment. Taken together, these results indicate that testes, kidney, immune and lung are target organs for the contaminated groundwater from this industrial site. The current study highlights the challenge in hazard assessment for complex mixtures and highlights the need for effects-directed analysis and the continued, albeit limited, use of animal models in toxicity testing.

Environmental plastics in the context of UV radiation, climate change, and the Montreal Protocol.

There are close links between solar UV radiation, climate change, and plastic pollution. UV-driven weathering is a key process leading to the degradation of plastics in the environment but also the formation of potentially harmful plastic fragments such as micro- and nanoplastic particles. Estimates of the environmental persistence of plastic pollution, and the formation of fragments, will need to take in account plastic dispersal around the globe, as well as projected UV radiation levels and climate change factors.

Opportunities and challenges for financing women's, children's and adolescents' health in the context of climate change.

Women, children and adolescents (WCA), especially in low-income and middle-income countries (LMICs), will bear the worst consequences of climate change during their lifetimes, despite contributing the least to global greenhouse gas emissions. Investing in WCA can address these inequities in climate risk, as well as generating large health, economic, social and environmental gains. However, women's, children's and adolescents' health (WCAH) is currently not mainstreamed in climate policies and financing. There is also a need to consider new and innovative financing arrangements that support WCAH alongside climate goals.We provide an overview of the threats climate change represents for WCA, including the most vulnerable communities, and where health and climate investments should focus. We draw on evidence to explore the opportunities and challenges for health financing, climate finance and co-financing schemes to enhance equity and protect WCAH while supporting climate goals.WCA face threats from the rising burden of ill-health and healthcare demand, coupled with constraints to healthcare provision, impacting access to essential WCAH services and rising out-of-pocket payments for healthcare. Climate change also impacts on the economic context and livelihoods of WCA, increasing the risk of displacement and migration. These impacts require additional resources to support WCAH service delivery, to ensure continuity of care and protect households from the costs of care and enhance resilience. We identify a range of financing solutions, including leveraging climate finance for WCAH, adaptive social protection for health and adaptations to purchasing to promote climate action and support WCAH care needs.

Climate finance opportunities for health and health systems.

Climate change poses significant risks to health and health systems, with the greatest impacts in low- and middle-income countries - which are least responsible for greenhouse gas emissions. The Conference of Parties 28 at the 2023 United Nations Climate Change Conference led to agreement on the need for holistic and equitable financing approaches to address the climate and health crisis. This paper provides an overview of existing climate finance mechanisms - that is, multilateral funds, voluntary market-based mechanisms, taxes, microlevies and adaptive social protection. We discuss these approaches' potential use to promote health, generate additional health sector resources and enhance health system sustainability and resilience, and also explore implementation challenges. We suggest that public health practitioners, policy-makers and researchers seize the opportunity to leverage climate funding for better health and sustainable, climate-resilient health systems. Emphasizing the wider benefits of investing in health for the economy can help prioritize health within climate finance initiatives. Meaningful progress will require the global community acknowledging the underlying political economy challenges that have so far limited the potential of climate finance to address health goals. To address these challenges, we need to restructure financing institutions to empower communities at the frontline of the climate and health crisis and ensure their needs are met. Efforts from global and national level stakeholders should focus on mobilizing a wide range of funding sources, prioritizing co-design and accessibility of financing arrangements. These stakeholders should also invest in rigorous monitoring and evaluation of initiatives to ensure relevant health and well-being outcomes are addressed.

Le changement climatique fait peser des risques considérables sur la santé et les systèmes de santé, affectant principalement les pays à revenu faible et intermédiaire ­ alors qu'ils contribuent le moins aux émissions de gaz à effet de serre. Lors de la Conférence des Nations Unies sur le changement climatique de 2023, la 28e Conférence des Parties a abouti à un accord sur la nécessité d'adopter des approches de financement équitables et holistiques pour résoudre la crise climatique et sanitaire. Le présent document offre un aperçu des dispositifs de financement climatique existants ­ à savoir des fonds multilatéraux, des mécanismes de marché volontaires, des micro-taxes et une protection sociale adaptative. Nous évoquons la possibilité de recourir à ces approches en vue de promouvoir la santé, de générer des ressources supplémentaires pour le secteur de la santé et de renforcer la viabilité et la résilience des systèmes de santé; nous nous intéressons également aux défis que représente leur mise en œuvre. Nous suggérons que les professionnels de la santé publique, les responsables politiques et les chercheurs profitent de cette occasion pour obtenir des fonds climatiques afin d'améliorer la santé et de développer des systèmes de santé durables et adaptés au changement climatique. Souligner tout l'intérêt, pour l'économie, d'investir dans la santé peut aider à inscrire la santé en priorité dans les initiatives de financement climatique. Réaliser des progrès significatifs implique que la communauté internationale prenne conscience des enjeux sous-jacents en matière d'économie politique, enjeux qui ont jusqu'à présent limité le potentiel du financement climatique dans l'atteinte des objectifs de santé. Pour y remédier, nous devons restructurer les institutions financières afin d'accroître l'autonomie des communautés en première ligne face à la crise climatique et sanitaire, et de faire en sorte que leurs besoins soient satisfaits. Les efforts des parties prenantes à l'échelle nationale et mondiale doivent porter sur la mobilisation d'un large éventail de sources de financement, en mettant l'accent sur la conception conjointe et l'accessibilité des modalités financières. Ces parties prenantes doivent en outre investir dans un suivi étroit et une évaluation rigoureuse des initiatives pour veiller à obtenir des résultats pertinents en termes de santé et de bien-être.

El cambio climático plantea riesgos importantes para la salud y los sistemas sanitarios, con mayores impactos en los países de ingresos bajos y medios, que son los menos responsables de las emisiones de gases de efecto invernadero. La 28.ª Conferencia de las Partes en la Conferencia de las Naciones Unidas sobre el Cambio Climático de 2023 condujo a un acuerdo sobre la necesidad de enfoques de financiación holísticos y equitativos para abordar la crisis climática y sanitaria. Este documento ofrece una visión general de los mecanismos de financiación climática existentes, es decir, los fondos multilaterales, los mecanismos voluntarios basados en el mercado, los impuestos, los microimpuestos y la protección social adaptable. Analizamos el uso potencial de estos enfoques para promover la salud, generar recursos adicionales para el sector sanitario y mejorar la sostenibilidad y la resiliencia de los sistemas sanitarios. Sugerimos que los profesionales de la salud pública, los responsables de formular las políticas y los investigadores aprovechen la oportunidad de utilizar la financiación climática para mejorar la salud y los sistemas sanitarios sostenibles y resilientes al cambio climático. Destacar los beneficios más amplios de invertir en salud para la economía puede ayudar a priorizar la salud dentro de las iniciativas de financiación climática. Para lograr avances significativos será necesario que la comunidad mundial reconozca los problemas de economía política subyacentes que hasta ahora han limitado el potencial de la financiación para abordar los objetivos de salud. Para superar estos desafíos, necesitamos reestructurar las instituciones financieras para empoderar a las comunidades que se encuentran en primera línea de la crisis climática y sanitaria y asegurar que se satisfacen sus necesidades. Los esfuerzos de las partes interesadas a nivel mundial y nacional deben centrarse en movilizar una gran variedad de fuentes de financiación y priorizar el diseño conjunto y la accesibilidad de los acuerdos de financiación. Estas partes interesadas también deben invertir en la supervisión y evaluación rigurosas de las iniciativas para garantizar que se abordan los resultados pertinentes en materia de salud y bienestar.

Exposure Assessment of Pesticides in Surface Waters of Ontario, Canada Reveals Low Probability of Exceeding Acute Regulatory Thresholds.

The objectives of this study were to: (1) characterize the exposure of aquatic ecosystems in Southern Ontario, Canada to pesticides between 2002 and 2016 by constructing environmental exposure distributions (EEDs), including censored data; and (2) predict the probability of exceeding acute regulatory guidelines. Surface water samples were collected over a 15-year period by Environment and Climate Change Canada. The dataset contained 167 compounds, sampled across 114 sites, with a total of 2,213 samples. There were 67,920 total observations of which 55,058 were non-detects (81%), and 12,862 detects (19%). The most commonly detected compound was atrazine, with a maximum concentration of 18,600 ngL- 1 and ~ 4% chance of exceeding an acute guideline (1,000 ngL- 1) in rivers and streams. Using Southern Ontario as a case study, this study provides insight into the risk that pesticides pose to aquatic ecosystems and the utility of EEDs that include censored data for the purpose of risk assessment.

Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023.

This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment.

When the microbiome shapes the host: immune evolution implications for infectious disease.

The microbiome includes both 'mutualist' and 'pathogen' microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests hosts can selectively activate innate immunity upon pathogenic infection, but not mutualist colonization. Another idea posits that hosts can selectively attack pathogens, but not mutualists. Here I review evolutionary principles of microbe recognition and immune activation, and reflect on newly observed immune effector-microbe specificity perhaps supporting the latter idea. Recent work in Drosophila has found a surprising importance for single antimicrobial peptides in combatting specific ecologically relevant microbes. The developing picture suggests these effectors have evolved for this purpose. Other defence responses like reactive oxygen species bursts can also be uniquely effective against specific microbes. Signals in other model systems including nematodes, Hydra, oysters, and mammals, suggest that effector-microbe specificity may be a fundamental principle of host-pathogen interactions. I propose this effector-microbe specificity stems from weaknesses of the microbes themselves: if microbes have intrinsic weaknesses, hosts can evolve effectors that exploit those weaknesses. I define this host-microbe relationship as 'the Achilles principle of immune evolution'. Incorporating this view helps interpret why some host-microbe interactions develop in a coevolutionary framework (e.g. Red Queen dynamics), or as a one-sided evolutionary response. This clarification should be valuable to better understand the principles behind host susceptibilities to infectious diseases. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

FIGO Preconception Checklist: Preconception care for mother and baby.

The preconception period is a unique and opportunistic time in a woman's life when she is motivated to adopt healthy behaviors that will benefit her and her child, making this time period a critical "window of opportunity" to improve short- and long-term health. Improving preconception health can ultimately improve both fetal and maternal outcomes. Promoting health before conception has several beneficial effects, including an increase in seeking antenatal care and a reduction in neonatal mortality. Preconception health is a broad concept that encompasses the management of chronic diseases, including optimal nutrition, adequate consumption of folic acid, control of body weight, adoption of healthy lifestyles, and receipt of appropriate vaccinations. Use of the FIGO Preconception Checklist, which includes the key elements of optimal preconception care, will empower women and their healthcare providers to better prepare women and their families for pregnancy.

Disparities in Access to Diagnostic Evaluation for Alzheimer's Disease in Individuals Dually Eligible for Medicare and Medicaid: A Modeling Study.

Background: Individuals dually eligible for Medicare and Medicaid (duals) may face greater obstacles to access to disease-modifying Alzheimer's treatments in spite of their higher disease burden, because of clinicians' reluctance to accept Medicaid and the so-called "lesser of" policy, under which Medicaid may pay providers lower rates. Objective: To project differential wait times for duals compared to Medicare-only beneficiaries by state. Methods: We used State Medicaid payment policy and Medicare enrollment data and a Markov model to predict differential wait times for duals and non-duals from 2023 to 2050. We estimated available diagnostic appointments by state for both groups based on reluctance of clinicians to accept Medicaid and the "lesser of" policy for each year. Results: We estimate overall average wait times of almost two years (22.9 months) but almost three times as long for duals (59.8 months) than non-duals (20.7 months) because of higher disease burden. The effects of Medicaid payment policy would increase average wait times for duals to 89 months with 20 states having wait times of 99 months or more, which would effectively deprive duals of access. Conclusions: The added average wait times in many states would effectively deprive duals from access to treatment and translate into avoidable disease progression and mortality. Policy interventions to reduce financial and nonfinancial obstacles are dearly needed to avoid deepening disparities. Examples are coverage arrangements that integrate Medicare and Medicaid coverage, covering the co-payment for physician services in full, and stricter network adequacy requirements for Medicaid Managed Care plans.

Human health and environmental risk assessment of metals in community gardens of Winnipeg, Manitoba, Canada.

Fresh produce is an important component of maintaining cognitive and physical health, particularly for children. A mechanism to increase access to fresh produce is the construction of community gardens in urban centres. While reducing barriers to nutritious food, the soil of the community garden can contain contaminants (e.g. metals) depending on the location and how the garden was constructed. This study quantified, for the first time, seven metals (As, Cd, Cr, Cu, Pb, Mn, and Ni) in soil from 83 community gardens across the City of Winnipeg in Manitoba, Canada. Concentrations of metals in soil were used to create distributions for environmental exposure and estimated daily intake, which were then used to determine exceedances of soil quality guidelines and acceptable daily intakes, respectively. Raised garden beds and gardens further from roads had typically lower concentrations of metals in surface gardens and those nearer to roads. While some concentrations of metals exceeded CCME guidelines levels for the protection of environmental health, the vast majority represent a low risk. For human health, only As posed a quantifiable risk of exceeding the USEPA acceptable daily intake via the consumption of produce from gardens, though this was < 1.2% for the whole population and < 10.2% for children aged 1 to 2 years. Overall, this study is the first to show that the concentration of the metals in soil from gardens typically poses a low risk to environmental and human health. We recommend the use of raised gardens to further mitigate risk.

Focused UTUC pathways with a risk-stratified approach to diagnostic ureteroscopy: is it the need of the hour? A retrospective cohort analysis.

INTRODUCTION: Upper urinary tract urothelial cancer is a rare, aggressive variant of urinary tract cancer. There is often delay to diagnosis and management for this entity in view of diagnostic and staging challenges needing additional investigations and risk stratifications for improved outcomes. In this article, we share our experience in developing a dedicated diagnostic and treatment pathway for UTUC and assess its impact on time lines to radical nephroureterectomy (RNU). We also evaluate the impact of diagnostic ureteroscopy (DUR) on UTUC care pathways timelines. MATERIALS AND METHODS: A prospective database was maintained for all patients who underwent a RNU from January 2015 to August 2022 in a high-volume single tertiary care centre in the UK. In 2019, a Focused UTUC pathway (FUP) was implemented at the centre to streamline diagnostic and RNU pathways. A retrospective analysis of the database was conducted to compare time lines and diagnostic trends between the pre-FUP and FUP cohorts. Primary outcome measures were time to RNU from MDT. Secondary outcome measures were: impact of DUR on time to RNU from MDT and negative UTUC rates between DUR and non-DUR cohorts. Differences in continuous variables across categories were assessed using the independent sample t test. Categorical variables between cohorts were analysed using the chi-square (χ2). Statistical significance in this study was set as p < 0.05. RESULTS: A total of 500 patients with complete data were included in the analysis. The pre-FUP and FUP cohorts consisted of 313 patients and 187 patients, respectively. The overall cohort had a mean age (SD) of 70 years (9.3). 66% of the overall cohort were males. The median time to RNU from MDT in the FUP was significantly lower compared to the pre-FUP cohort; 62 days (IQR 59) vs. 48 days (IQR 41.5), p < 0.0001. The median time to RNU from MDT in patients who underwent a diagnostic URS in the FUP cohort was significantly lower compared to the pre-FUP cohort; 78.5 days (IQR 54.8) vs. 68 days (IQR 48), p-NS. The non-UTUC rates in the DUR and non-DUR cohorts were 6/248 (2.4%) and 14/251 (5.6%), respectively (NS). CONCLUSION: In this series, we illustrate the effectiveness of integrating a multidisciplinary approach with specialised personnel, ring-fenced clinics, efficient diagnostic assessment and optimised theatre capacity. By adopting a risk-stratified approach to diagnostic ureteroscopy, we have achieved a significant reduction in time to RNU.

Projected health and economic effects of the increase in childhood obesity during the COVID-19 pandemic in England: The potential cost of inaction.

BACKGROUND: The prevalence of overweight and obesity in young children rose sharply during the COVID-19 pandemic. Here we estimate the potential future health and economic effects of these trends in England. METHODS: Using publicly available annual Body Mass Index (BMI) data from 2006-2022, we calculated the increase in overweight/obesity prevalence (BMI ≥85th reference percentile) during the COVID-19 pandemic among children aged 4-5 and 10-11, and variation by deprivation and ethnicity. We projected the impact of child BMI trends on adult health measures to estimate added lifelong medical and social costs. RESULTS: During 2020-2021 there were steep increases in overweight and obesity prevalence in children. By 2022, overweight and obesity prevalence in children aged 4-5 returned to expected levels based on pre-pandemic trends. However, overweight and obesity prevalence in children aged 10-11 persisted and was 4 percentage points (p<0.001) higher than expected, representing almost 56,000 additional children. The increase was twice as high in the most compared with the least deprived areas. The additional lifelong healthcare cost in this cohort will amount to £800 million with a cost to society of £8.7 billion. We did not find an increase in maternal obesity associated with the COVID-19 pandemic, however, prevalence grew faster in the post pandemic period. DISCUSSION: The return of overweight and obesity prevalence to pre-pandemic trends in children aged 4-5 provides a clear policy target for effective intervention to tackle this growing and serious population health concern.

Patient Engagement in Medical Trainee Selection: A Scoping Review.

PURPOSE: The stakes of medical trainee selection are high, making it ironic and somewhat paradoxical that patients and the public often get little say in selection practices. The authors sought to undertake a knowledge synthesis to uncover what is known about patient engagement across the medical trainee selection continuum. METHOD: The authors conducted a scoping review aimed at exploring the current state of practice and research on patient engagement in medical trainee selection in 2017-2021. MeSH headings and keywords were used to capture patient, community, and standardized patient engagement in selection processes across multiple health professions. The authors employed broad inclusion criteria and iteratively refined the corpus, ultimately, limiting study selection to those reporting engagement of actual patients in selection within medicine, but maintaining a broad focus on any patient contributions across the entire selection continuum. The Cambridge Framework was adapted and used to organize the included studies. RESULTS: In total, 2,858 abstracts were reviewed, and ultimately, 28 papers were included in the final corpus. The included studies were global but nascent. Most of the literature on this topic appears in the form of individual projects advocating for patient engagement in selection rather than cohesive programs with empirical exploration of patient engagement in selection. Job analysis methodology was particularly prominent for incorporating the patient voice into identifying competencies of relevance to selection. Direct patient engagement in early selection activities allowed the patient voice to assist candidates in determining their fit for medicine. CONCLUSIONS: Patient engagement has not been made a specific focus of study in its own right, leading the authors to encourage researchers to turn their lens more directly on patient engagement to explore how it complements the professional voice in medical trainee selection.

Expected wait times for access to a disease-modifying Alzheimer's treatment in England: A modelling study.

OBJECTIVES: We previously analysed the preparedness to deliver a disease-modifying Alzheimer's treatment in the United Kingdom and predicted substantial wait times. This study updates the prediction for the National Health Service (NHS) in England, using an improved model and newer data. METHODS: We reviewed published data on capacity for diagnosis of cognitive impairment combined with expert input and constructed a model for wait times to access from 2023 to 2043. The model tracks patients from initial evaluation in primary care, cognitive testing by a dementia specialist, confirmatory biomarker testing with positron emission tomography (PET) scans or examination of cerebrospinal fluid and infusion delivery. Capacity for specialist visits and PET scans are assumed to be capacity constrained, and cerebrospinal fluid testing and infusion delivery to be scalable. RESULTS: Capacity constraints were projected to result in substantial wait times: patients referred to specialists based on a brief cognitive test, which is the current standard of care, would expect an overall initial wait times of 56 months in 2023, increasing to 129 months in 2029 and then falling slowly to around 100 months. Use of a blood test for the confirmation of Alzheimer's pathology as an additional triage step, would reduce wait times to around 17 to 25 months. DISCUSSION: The NHS England lacks capacity to provide timely access to a disease-modifying treatment, which is estimated to result in significant wait times and potentially avoidable disease progression. Better diagnostic tools at initial evaluation may reduce delays.