Future Risk Assessment Research Articles

Impact of environmental concentrations of fipronil on DNA integrity and brain structure of Bombus atratus bumblebees

Fipronil (FP) is an insecticide used in the treatment and control of pests, but it also adversely affects bees. Currently, there is no data on the genotoxic effects of FP in the brain of bumblebees. Thus, through the comet assay and routine morphological analysis, we analyzed the morphological effects and potential genotoxicity of environmentally relevant concentrations of FP on the brain of Bombus atratus. Bumblebees were exposed at concentrations of 2.5 μg/g and 3.5 μg/g for 96 hours. After the exposure, the brains were removed for morphological and morphometric analysis, and the comet assay procedure - used to detect DNA damage in individual cells using electrophoresis. Our data showed that both concentrations (2.5 μg/g and 3.5 μg/g) caused DNA damage in brain cells. These results corroborate the morphological data. We observed signs of synapse loss in the calyx structure, intercellular spaces between compact inner and non-compact inner cells, and cell swelling. This study provides unprecedented evidence of the effects of FP on DNA and cellular structures in the brain of B. atratus and reinforces the need to elucidate its toxic effects on other species to allow future risk assessments and conservation projects.

Health-risk assessment of mercury in main market-sold foods in the Pingliang region of Gansu province, China, from 2013 to 2021

In the present study, we analyzed mercury concentrations in 742 samples across five main food categories from 2013 to 2021 using direct mercury analysis (DMA) to understand mercury pollution in major market-sold foods in the Pingliang region of Gansu Province and assess the health risks of mercury dietary exposure in adults. Health risks of adult dietary exposure were assessed through deterministic evaluation. Total mercury content ranged from non-detectable (ND) to 0.13 mg/kg, with a detection rate of 90.70% (673/742), the highest detection rates being in fresh edible mushrooms and nuts. The overall exceedance rate was 0.13% (1/742), with one sample of fresh edible mushrooms exceeding the regulatory limit for total mercury content. Additionally, we incorporated the average mercury content and consumption levels of meat and seafood from regions geographically close to Pingliang, as reported in the Fifth National Total Diet Study, to calculate the Estimated Daily Intake (EDI) by a deterministic evaluation. For adult males, the exposure was 0.120 μg/(kg BW), while for adult females, it was 0.141 μg/(kg BW). Both values are significantly lower than the provisional tolerable weekly intake (PTWI) of 4 μg/(kg BW) established by JECFA in 2010, indicating that the total mercury concentration from food intake does not pose a significant health risk to the residents of the Pingliang area. These findings offer valuable scientific data to inform food safety regulations in the region and can serve as a benchmark for future mercury pollution risk assessments in other locations.

Covenant Strictness Measures

Covenants are crucial components of loan agreements, designed to protect lenders by imposing various restrictions and obligations on borrowers. Despite extensive empirical research on covenant strictness, a universally accepted measure of covenant strictness remains elusive. Existing metrics tend to include only a limited selection of covenants from the comprehensive contract. This study utilizes loan-level credit risk data to evaluate and rank the effectiveness of several widely used covenant strictness measures. Credit risk at the loan level is assessed through two primary methods: the difference between issue ratings and issuer ratings, and the loan credit spread while controlling for fixed effects at the firm level. This approach allows for a more nuanced comparison and provides insights into which measures most accurately reflect covenant strictness and its impact on credit risk. The findings aim to contribute to a better understanding of covenant effectiveness, offering potential improvements for future loan contract structuring and risk assessment practices.

Unveiling the assessment process behind an integrated flood risk management plan

In the context of the European Floods Directive, flood risk assessment is a critical component for the definition of an integrated management plan that operates within a multidimensional landscape shaped by intricate interactions. This study explores this complex interplay using a comprehensive framework, aimed at enlightening the non-linear pathways that flood risk assessments can traverse. It adopts the Gioia Methodology within the Grounded Theory approaches, enabling a nuanced exploration of flood risk assessment dynamics. Utilizing data from an Italian case study in the Po River District, this study unveils the flood risk assessment process framework by identifying 13 first-order codes, 6 s-order themes and 3 aggregate dimensions. It introduces a qualitative self-assessment tool to facilitate integration across dimensions and enhance Directive alignment, offering valuable insights for future flood risk assessment implementations.

Spatial distribution of old neighborhoods based on heat-related health risks assessment: A case study of Changsha City, China

Assessing the heat-related health risks is crucial for promoting the sustainable development of cities, particularly in the face of extreme climates and urban human settlement governance. Heat health risk assessment serves as a foundational element within the risk governance framework, serving to mitigate heat-related morbidity and mortality rates. The revitalization of old neighborhoods, especially those situated in city centers with deficient facilities, emerges as a critical imperative within this context. This study chose Changsha, a city in Central China that is severely affected by high temperatures and has numerous old neighborhoods, as a case study. We developed a heat risk framework that incorporates city level risk, exposure, vulnerability, and the adaptation of old neighborhoods. Validated through data accessed from medical facilities visit, the framework effectively reflects the distribution of heat risks. By combining qualitative and quantitative methods, we investigated the correlation between heat health risk levels and the behaviors of residents in old neighborhoods. The results indicate that urban planners should prioritize comprehensive renovations in medium-risk neighborhoods, resident behavior management in low-risk neighborhoods, and the indoor thermal environment in high-risk neighborhoods. This framework plays an important role in the assessment of future spatial risk for old neighborhoods renewal.

Variability in Constituents of E-Cigarette Products Containing Nicotine Analogues

This study characterizes and quantifies constituents in 2 e-cigarette products to assess product consistency and inform future risk assessments.

When less is more: The association between the expression of polymorphic CYPs and AFB1-induced HCC.

An individual's genetic fingerprint is emerging as a pivotal predictor of numerous disease- and treatment-related factors. Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes play key roles in an individual's exposure to a malignancy-associated risk, such as Aflatoxin B1 (AFB1)-induced hepatocellular carcinoma (HCC). This study aimed at reviewing literature on the polymorphisms that exist in CYP enzymes and their possible link with susceptibility to AFB1-induced HCC. A set of keywords associated with the study subject of interest was used to search the Google Scholar and the PubMed database. The last ten years' worth of research projects were included in the results filter. The research involved HCC patients and any connection between polymorphic forms of CYP enzymes and their susceptibility to AFB1-induced HCC, including older but significant data. Variations in CYP1A2 and CYP3A4 were reported to impact the rate and magnitude of AFB1 bio-activation, thus influencing an individual's vulnerability to develop HCC. In HCC patients, the activity of CYP isoforms varies, where increased activity has been reported with CYP2C9, CYP2D6, and CYP2E1, while CYP1A2, CYP2C8, and CYP2C19 exhibit decreased activity. CYP2D6*10 frequency has been discovered to differ considerably in HCC patients. Rs2740574 (an upstream polymorphism in CYP3A4 as detected in CYP3A4*1B) and rs776746 (which affects CYP3A5 RNA splicing), both of which influence CYP3A expression, thus impacting the variability of AFB1-epoxide adducts in HCC patients. CYP1A2 is the primary enzyme accountable for the formation of harmful AFBO globally. CYP3A4, CYP3A5, CYP3A7, CYP2B7, and CYP3A3 are also implicated in the bio-activation of AFB1 to mutagenic metabolites. It is thought that CYP3A4 is the protein that interacts with AFB1 metabolism the most. Polymorphic variants of CYP enzymes have a functional impact on the susceptibility to AFB1-induced HCC. Outlining such variation and their implications may provide deeper insights into approaching HCC in a more personalized manner for guiding future risk-assessment, diagnosis, and treatment.

Abstract Tu149: FDA-Approved Antidepressant Trazodone Potentially Increases the Risk of Dyslipidemia

Cardiovascular disease is the leading cause of death. Many cardiovascular health problems, such as atherosclerosis, are caused by dyslipidemia. One xenobiotic nuclear receptor, Pregnane X Receptor (PXR), plays a significant role in atherosclerosis and dyslipidemia, and is activated by various environmental chemicals, including endocrine-disrupting chemicals (EDCs). EDCs are found in common household items such as plastics, medications, and food. Trazodone is a clinically used medication to treat depression by aiding in restoring the balance of serotonin in the brain. But it is unclear if Trazodone has possible impacts on cardiovascular risk factors such as dyslipidemia. Our preliminary data suggested that Trazodone activated human PXR in both intestinal (LS180) and hepatic (HepG2) cells. We hypothesize that Trazodone could regulate the cholesterol uptake mediated by PXR signaling. In this study we use cell-based transfection assay to evaluate the underlying mechanisms by which Trazodone activates PXR. We found that Trazodone was a more potent agonist of human PXR than mouse PXR. Trazodone could activate PXR more intensely in human liver cells compared with human intestinal cells. Our data suggested that Trazodone was a selective PXR agonist and promoted the dissociation between PXR and its nuclear corepressors. Next, we are to identify the key amino acid residues within PXR ligand binding pocket that interact with Trazodone by using computational docking study along with site-mutagenesis assay. Furthermore, we plan to estimate if Trazodone altered cholesterol uptake by human intestinal cells using fluorescence-labeled cholesterol. In conclusion, we explore the potential molecular mechanisms of how FDA-approved antidepressant Trazodone activates human PXR and increases the possible risk of dyslipidemia, which provides potential evidence on future cardiovascular disease risk assessment for Trazodone as well as other antidepressant drugs.

Predictors of Mortality Following Mitral Valve Replacement: A SystematicReview

Introduction: Valvular heart diseases are some of the most common causes of cardiovascular morbidity and mortality worldwide. The mitral valve is estimated to be the cause of 15% of deaths in heart valve disease. Mitral valve dysfunction can be treated with a variety of operative options, one of whichis mitral valve replacement. Although it is less desirable than repair, in some situations, it is the only viable option. Thus, we conducted this systematic review to help guide future risk assessment for mitral valve replacement patients and help in the construction of pre-operative risk assessment tools. Methods: This is a systematic review of original articles discussing the topic of predictors of mortality for patients undergoing mitral valve replacement surgery. A systematic search was conducted via independent researchers across a number of databases, starting with PubMed databases utilizing its MeSH database, followed by a complementary search through Google Scholar. Results: In total, 27 original articles were included in a collective cohort of 145005 patients. Older age was the most commonly cited variable as a mortality predictor, followed by decreased left ventricular ejection fraction. EuroSCORE is a well-known scoring system that predicts in-hospital mortality following major cardiac surgeries. It was found that it overestimated mortality greatly, while another study found that the revised EuroSCORE II system was a better predictor of mortality. Overall, we note that both versions usually overestimate mortality. Conclusion: There seems to be an overall agreement over several factors, including older age, decreased ejection fraction, and the expertise of the surgeon and the institution on being clear predictors of postoperative mortality. There is also an obvious need for new tools to better predict mortality rates preoperatively, as the currently used scores often result in greatly inaccurate predictions

In vitro tungsten bioaccessibility in Chinese residential soils: Implications for human health risk assessments and soil screening level derivation

Tungsten (W) contamination presents emerging environmental challenges, necessitating the need to establish soil screening levels (SSLs), especially for residential soils. This study assessed the health exposure risk and derived national and regional residential SSLs for W in Chinese residential soils, incorporating machine-learning prediction of in-vitro soil W bioaccessibility. We analyzed 204 residential soil samples collected across 24 provinces, recording a wide range of W concentrations (0.01–3063.2 mg/kg). Synchrotron-based X-ray fluorescence spectroscopy, chemical extractions, and random forest modeling indicated that the key determinants of soil W bioaccessibility were soil pH, cation exchange capacity, organic matter, and clay contents. Monte Carlo simulations demonstrated that soil W contamination predominantly results in noncarcinogenic health risks to residents via oral exposure, especially in mining-affected regions. A national residential SSL (NRSSL) of 35.5 mg/kg and regional residential SSLs (RRSSLs) of 34.5–49.2 mg/kg were established. Incorporating predicted bioaccessibility increased the NRSSL to 73.8 mg/kg and the RRSSLs to 69.8–112.5 mg/kg. Southern China, which is rich in W ore, exhibited lower RRSSLs, underscoring a need for enhanced safety management. Our framework and findings provide a robust scientific foundation for future soil contamination risk assessment studies, and we present customized SSLs that can guide targeted W risk control strategies.

Regional Assessment of Groundwater Contamination Risk from Crude Oil Spillages in the Niger Delta: A Novel Application of the Source-Pathway-Receptor Model

AbstractOnshore oil spills are known for their disastrous environmental impacts and potential to cause lasting damage to underlying groundwater. The Niger Delta is particularly vulnerable to widespread spillages linked to extensive oil exploration, transportation, and theft-related incidents. This research employed a geospatial approach in formulating risk equations, based on the source-pathway-receptor (S-P-R) model using multiple openly available data sets, to assess groundwater contamination risk in the Niger Delta Region (NDR), Nigeria. To develop the overall risk equation, the study combined fourteen thematic data layers including the volume of oil spilled, type of spill, slope, elevation, proximity to spill site, pipeline, oil wells and streams, drainage density, mean annual precipitation and population density. These layers were integrated into source potency, pathway transmissivity, and receptor susceptibility. The NDR was systematically categorized into low, moderate, and high groundwater risk zones. The delineation revealed that high-risk zones predominantly span the central areas, extending from southeast to northwest, effectively encircled by regions of low to medium risk located in both the northern and southern extents of the delta. The efficacy of the risk model was corroborated by existing knowledge. Moderate to high-risk zones were found to be in about 16% of the NDR, revealing previously unknown areas of risk. This spatial configuration underscores a significant gradient in contamination risk across the NDR, with the central corridor emerging as a critical focus for groundwater protection and remediation efforts. In line with UN Sustainable Development Goal (SDG) #6, this study recommends targeted strategies to ensure clean water provision in these identified high-risk areas. By leveraging the S-P-R model within this complex and sensitive ecological area, this research both advances environmental risk assessment and sets a precedent for future large-scale environmental risk assessments utilizing open-source data.

Balancing water conservation and health: do water-saving showerheads impact the microbes we breathe in during showering?

Low-flow showerheads offer consumers economic and water-saving benefits, yet their use may inadvertently affect the microbial content of produced water and water-associated aerosols. This study aimed to compare the abundance and microbial composition of bacteria in shower water and associated respirable aerosols produced by various low flow rate (1, 1.5, and 1.8 gpm) showerheads. Our findings indicate that the lowest-flow showerhead produces water with lower total microbial and opportunistic bacterial pathogen densities compared to higher low flow rate counterparts. However, microbiome analysis revealed that 1.8 gpm flow rate showerheads exhibit reduced abundance of Gram-negative organisms and common biofilm-forming organisms, suggesting potentially lower pathogenicity compared to 1 and 1.5 gpm low-flow showerheads. Additionally, the number of respirable aerosols produced by showerheads as well as the partitioning of certain microorganisms from the water to aerosol phases was negatively correlated with flow rate, suggesting that there may be increasing exposure potential to pathogenic bioaerosols when using a 1gpm showerhead compared to a 1.8 gpm showerhead. However, the 1.5 gpm showerhead seemed to balance microbial partitioning, aerosol generation, and water conservation. Moreover, the microbial composition of aerosols produced from shower water was more influenced by the age of the showerhead than the flow rate, highlighting the significance of biofilm formation on the microbial community. Overall, our findings underscore the importance of evaluating the microbial risk associated with low-flow showerheads using multiple metrics in both water and aerosols, and dynamically assessing this over time, to ensure accurate future risk assessment.

The human health effects of unconventional oil and gas (UOG) chemical exposures: a scoping review of the toxicological literature.

Many chemicals associated with unconventional oil and natural gas (UOG) are known toxicants, leading to health concerns about the effects of UOG. Our objective was to conduct a scoping review of the toxicological literature to assess the effects of UOG chemical exposures in models relevant to human health. We searched databases for primary research studies published in English or French between January 2000 and June 2023 on UOG-related toxicology studies. Two reviewers independently screened abstracts and full texts to determine inclusion. Seventeen studies met our study inclusion criteria. Nine studies used solely invitro models, while six conducted their investigation solely in animal models. Two studies incorporated both types of models. Most studies used real water samples impacted by UOG or lab-made mixtures of UOG chemicals to expose their models. Most invitro models used human cells in monocultures, while all animal studies were conducted in rodents. All studies detected significant deleterious effects associated with exposure to UOG chemicals or samples, including endocrine disruption, carcinogenicity, behavioral changes and metabolic alterations. Given the plausibility of causal relationships between UOG chemicals and adverse health outcomes highlighted in this review, future risk assessment studies should focus on measuring exposure to UOG chemicals in human populations.

Baseline study of biomarkers of exposure to metal and polycyclic aromatic hydrocarbon in wild Mugil cephalus from the coastal waters of Fiji

The indirect exposure and effects of marine pollutants such as metals and polycyclic aromatic hydrocarbons, present significant health concerns for human coastal communities that rely on fish consumption as a regular nutritional source. This study verified Mugil cephalus (“mullet”) as an adequate sentinel species for biomonitoring environmental health and conducting risk assessments using biomarkers in Fiji. A non-parametric Kruskall Wallis Test was employed at a 5 % significant difference level to test sample group differences. Sampling was performed over five months in two Fijian study areas, i.e., Laucala Bay and the Ba River Delta by local fishers based on Fiji’s wet season (Nov-Mar). The K factor and hepatosomatic index (HSI) were relatively lower in mullet from Laucala Bay compared to the Ba River Delta, with HSI having a significant difference (χ2= 3.64, d.f. = 1, p-value = 0.057). No significant differences were observed for metals (Pb and Cr) at an instrumental limit of detection of 0.05 mg kg−1, but an important finding was that the levels of Cr in edible tissues of mullet from both study sites exceeded the permissible limits for human consumption set by the World Health Organisation (0.05–0.15 mg kg−1) by approximately 2-fold in Laucala Bay and 3-fold in Ba River Delta. The levels of Hg and Cd in the two sample groups were determined to be below the instrumental limit of detection of 0.1 mg kg−1. Total biliary polycyclic aromatic hydrocarbons (PAHs) were significantly higher in mullet from the Ba River Delta (χ2 = 21.14, d.f. = 1, p-value < 0.001), particularly for phenanthrene (χ2 = 24.678, d.f. = 1, p-value < 0.001). No statistical variations were observed in phase I biotransformation (ethoxyresorufin O-deethylase); however, phase II biotransformation activity (glutathione S-transferase) was found to be significantly higher in mullet from the Ba River Delta compared to Laucala Ba (χ2 = 35.85, d.f. = 1, p-value < 0.001). Similarly, no remarkable variations were observed in glutathione peroxidase activity, but glutathione reductase activity was significantly higher in mullet (χ2 = 5.05, d.f. = 1, p-value = 0.025) from Laucala Bay compared to Ba River Delta. Considering biological damages from oxidative stress, levels of lipid peroxidation were significantly higher (χ2= 4.10, d.f. = 1, p-value = 0.043) in mullet from Ba River Delta, including higher occurrences of micronuclei (χ2= 12.66, d.f. = 1, p-value = <0.001) and other abnormal erythrocyte nuclei (χ2= 26.67, d.f. = 2, p-value < 0.001), suggesting genotoxic damage. These findings 1) support the use of mullet as a suitable reference species for future ecotoxicology studies in Fiji, 2) are essential to take informed health and safety considerations regarding mullet consumption, 3) provide a baseline to compare future monitoring results and, 4) underscore the importance of incorporating biomonitoring practices in future environmental risk assessments.

Modeling the growth behavior of Salmonella spp. in grated carrots inoculated with different inoculum levels stored at various temperatures

AbstractThe consumption of fresh and fresh‐cut fruits and vegetables, such as carrots, has increased for the last decades for a healthy life and an adequate diet, but concerns regarding the microbial safety of them have been raised. The present study was conducted to develop predictive models for Salmonella spp. in grated carrots. The results showed that Salmonella spp. did not display growth at 5°C, but it grew in grated carrots at other temperatures (10, 15, 20, 25, and 37°C) for both inoculum levels. Also, the inoculum levels affected the growth of this pathogen in grated carrots when the storage temperatures ranged from 15 to 25°C. The theoretical minimum temperatures calculated using the Huang model were 3.48 and 5.79°C for inoculum levels of 101 and 102 CFU/g, respectively. The primary and secondary models performed well in terms of agreement between experimental and estimated values. Furthermore, compared to the Ratkowsky model, the theoretical minimum temperature was given a more reasonable value using the Huang model. The models developed in the present study will be a useful input for future quantitative microbial risk assessment to appraise the proliferation of Salmonella spp. in grated carrots throughout the production process, storage, and distribution.

Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

Microplastics and Anthropogenic Particles in Recreationally Caught Freshwater Fish from an Urbanized Region of the North American Great Lakes.

Microplastics are a pervasive contaminant cycling through food webs-leading to concerns regarding exposure and risk to humans. We aimed to quantify and characterize anthropogenic particle contamination (including microplastics) in fish caught for human consumption from the Humber Bay region of Lake Ontario. We related quantities of anthropogenic particles to other factors (e.g., fish size) that may help in understanding accumulation of microplastics in fish. A total of 45 samples of six fish species collected from Humber Bay in Lake Ontario near Toronto, Ontario, Canada, were examined for anthropogenic particles in their gastrointestinal (GI) tracts and fillets. Using microscopy and spectroscopy, suspected anthropogenic particles were identified and characterized. We observed anthropogenic particles in the GI tracts and fillets of all species. Individual fish had a of anthropogenic particles, with a single fish containing up to 1,508 particles. GI tracts had particles/fish ( particles/gram), and fillets had particles/fish ( particles/gram). Based on a consumption rate of 2 servings/week, the average yearly human exposure through the consumption of these fish fillets would be particles. Our findings suggest that consumption of recreationally caught freshwater fish can be a pathway for human exposure to microplastics. The elevated number of particles observed in fish from Humber Bay highlights the need for large-scale geographic monitoring, especially near sources of microplastics. Currently, it is unclear what the effects of ingesting microplastics are for humans, but given that recreationally caught freshwater fish are one pathway for human exposure, these data can be incorporated into future human health risk assessment frameworks for microplastics. https://doi.org/10.1289/EHP13540.

Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid of cannabis, is therapeutically used as an analgesic, anti-convulsant, anti-inflammatory, and anti-psychotic drug. There is a growing concern about the adverse side effects posed by CBD usage. Pregnane X receptor (PXR) is a nuclear receptor activated by a variety of dietary steroids, pharmaceutical agents, and environmental chemicals. In addition to the role in xenobiotic metabolism, the atherogenic and dyslipidemic effects of PXR have been revealed in animal models. CBD has a low affinity for cannabinoid receptors, thus it is important to elucidate the molecular mechanisms by which CBD activates cellular signaling and to assess the possible adverse impacts of CBD on pro-atherosclerotic events in cardiovascular system, such as dyslipidemia. Our study aims to explore the cellular and molecular mechanisms by which exposure to CBD activates human PXR and increases the risk of dyslipidemia. Both human hepatic and intestinal cells were used to test if CBD was a PXR agonist via cell-based transfection assay. The key residues within PXR's ligand-binding pocket that CBD interacted with were investigated using computational docking study together with site-directed mutagenesis assay. The C57BL/6 wildtype mice were orally fed CBD in the presence of PXR antagonist resveratrol (RES) to determine how CBD exposure could change the plasma lipid profiles in a PXR-dependent manner. Human intestinal cells were treated with CBD and/or RES to estimate the functions of CBD in cholesterol uptake. CBD was a selective agonist of PXR with higher activities on human PXR than rodents PXRs and promoted the dissociation of human PXR from nuclear co-repressors. The key amino acid residues Met246, Ser247, Phe251, Phe288, Trp299, and Tyr306 within PXR's ligand binding pocket were identified to be necessary for the agonistic effects of CBD. Exposure to CBD increased the circulating total cholesterol levels in mice which was partially caused by the induced expression levels of the key intestinal PXR-regulated lipogenic genes. Mechanistically, CBD induced the gene expression of key intestinal cholesterol transporters, which led to the increased cholesterol uptake by intestinal cells. CBD was identified as a selective PXR agonist. Exposure to CBD activated PXR signaling and increased the atherogenic cholesterol levels in plasma, which partially resulted from the ascended cholesterol uptake by intestinal cells. Our study provides potential evidence for the future risk assessment of CBD on cardiovascular disease, such as dyslipidemia.

Dietary exposure from food colours by Brazilian adolescents using the ERICA 2013–2014 food consumption database

Colouring food additives are added for the purpose of restoring, intensifying or imparting colour. Although food colours exposure estimates are available in Brazil, no comprehensive assessments were found covering all food colours allowed in the country and no study considered consumption data from ERICA (Study of Cardiovascular Risks in Adolescents), which covers data from more than 70,000 Brazilian students from 12 to 17 years old. This study estimated dietary exposure to 33 food colours authorized in Brazil and for which numerical safety values have been established, followed by risk characterization. Consumption data were obtained from two days dietary recalls applied to students in public and private schools from Brazilian cities with more than 100,000 residents. Exposure estimates were performed in two scenarios: mean and high exposures levels, undertaking conservative assumptions. Estimates were compared with the Acceptable Daily Intake (ADI) values established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Prioritization for future risk assessment was made based on ADI exceedance, with 14 colours as a low priority, 10 as a medium and 9 as a high priority. For high priority food colours, refined estimates are encouraged to evaluate more precisely real exposures and the need of implementation of management actions to reduce exposure.

Changes in the severity of compound hot-dry-windy events over global land areas

Hot-dry-windy events (HDWEs), characterized by concurrent high temperature, low humidity, and strong wind speeds, are associated with reduced crop yields, accelerated spread of wildfire, increased human health risks, and dust storms across various regions. A comprehensive understanding of global HDWE severity is crucial for mitigating these detrimental consequences. However, current assessments of HDWE show notable regional constraints due to the lack of a universal definition for its severity. In this study, we introduce a standardized hot-dry-windy index (SHDWI) using multi-source datasets to assess spatial and temporal changes in the severity of HDWEs across the globe. Influenced by significantly rising temperatures, intensified wind speeds, and declining humidity, a notable decreasing trend (-0.09/decade, p < 0.01) in SHDWI indicates a rise in warm-season HDWE severity on average across the global land areas, particularly in South America, North Africa, western Europe, and southeastern Asia. Geospatially, Europe, Africa, South America, and Asia have experienced substantial increases in HDWE severity and expanded areas affected by strong HDWEs between 1980–1998 and 1999–2017. Notably, HDWE severity is predominated by temperature in the south of 30°N but by humidity in the north of 30°N. The standardized index proposed in this study would be beneficial for a worldwide assessment of future HDWE risks under climate change.