Exposure Model Research Articles

Maternal exposure to nanopolystyrene induces neurotoxicity in offspring through P53-mediated ferritinophagy and ferroptosis in the rat hippocampus

There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring.Graphical

Thinking beyond the closure assumption: Designing surveys for estimating biological truth with occupancy models

Abstract Occupancy models estimate distributions of imperfectly detected species, but violations of the closure assumption can bias results. However, researchers working with mobile animals may find it impossible to eliminate such violations. Here, we tested the hypothesis that occupancy models fit to realistic sampling data can generate unbiased occupancy estimates for an itinerant Wood Thrush (Hylocichla mustelina) population. In 2013 and 2014, we tracked movements of 41 breeding Wood Thrush males. We modelled territory shift probabilities using logistic exposure models and within‐territory movements using continuous‐time stochastic process models. We then constructed an individual‐based model, simulated (1000 iterations) spatiotemporal locations for individuals and simulated sampling these populations using 162 different point count protocols with variable spatial (sampling radius and point placement method), and temporal (survey length, between‐survey intervals and number of surveys) characteristics. We compared occupancy estimates with true values of instantaneous, daily and seasonal occupancy from the simulations. We parameterized continuous time stochastic process models based on movements within 34 unique territories and estimated a daily territory shift probability of 0.0099 (95% CI: 0.0060, 0.0152). Simulated data indicated that estimates of occupancy ranged from 0.18 (0.06, 1.00) to 0.80 (0.71, 0.89) depending on protocol characteristics. Occupancy estimates increased with increasing survey radius, survey length and between‐survey interval. Protocols using shorter surveys and between‐survey intervals were good estimators for instantaneous occupancy (low bias and mean‐squared error) but poor estimators for daily and seasonal occupancy; longer surveys and intervals generated unbiased estimators of daily occupancy but underestimated seasonal occupancy. Logistic regression models that ignored imperfect detection outperformed occupancy models for estimating instantaneous occupancy but not daily or seasonal occupancy. For mobile animals, occupancy of sampling sites changes in space and time. Consequently, the spatial and temporal aspects of a sampling protocol have strong, but predictable, effects on occupancy model parameter estimates. Our results demonstrate that how these factors interact is critical for designing surveys that produce occupancy estimates representative of the biological process of interest to a researcher.

Maternal NO2 exposure and fetal growth restriction: Hypoxia transmission and lncRNAs-proinflammation-mediated abnormal hematopoiesis

Epidemiological studies show a strong correlation between air pollution and fetal growth restriction (FGR), but existing results are controversial due to inherent limitations, such as causality of specific pollutants, developmental origin, and maternal-fetal transmission. To address this controversy, we first conducted a retrospective analysis of 28,796 newborns and revealed that maternal nitrogen dioxide (NO2) exposure during the second trimester was positively associated with FGR, with an adjusted odds ratio of 1.075 (95% confidence interval: 1.020-1.133) per 10 μg/m3 NO2 increase for small for gestational age. Then, by establishing an animal model of prenatal NO2 exposure, we confirmed its adverse effects on embryonic growth and hematopoiesis in the yolk sac and fetal liver, primarily affecting the differentiation of hematopoietic stem and progenitor cells and erythroid maturation. By applying internal exposure analyses coupled with 15N isotope tracing, we found that maternal NO2 inhalation induced acquired methemoglobinemia through its byproducts and placental hypoxia in pregnant mice. Importantly, by combining transcriptional profiling, bioinformatics analysis, and RNA binding protein immunoprecipitation (RIP)/chromatin immunoprecipitation (CHIP), we clarified that placental-fetal hypoxia transmission activated hypoxia-inducible factors, disturbed hematopoiesis through the hypoxia-inducible factor 1β-long noncoding RNAs-CCAAT/enhancer binding protein alpha-proinflammatory signaling pathway, ultimately contributing to FGR progression. These findings provide insights for risk prevention and clinical intervention to promote child well-being in NO2-polluted areas.

VERMEER FCM: A tool integrating exposure and hazard modelling for chemicals migrating from food contact materials

A new tool, VERMEER FCM, was developed to support the risk assessment of single organic chemicals migrating from plastic food contact materials (FCM). The freely available tool is integrated into MERLIN-Expo and has been designed in line with Regulation (EU) No 10/2011 for plastic FCM. Overall, the tool consists of three modules that allow (i) to model the migration of chemicals into food, (ii) to predict toxicological endpoints relevant to risk assessment of FCM chemicals, and (iii) to automatically check whether the chemical of interest is included in Regulation (EU) No 10/2011. To apply the VERMEER FCM tool, users need to provide information regarding the chemical(s) of interest, the FCM, the food and other parameters (e.g. contact time and temperature). The three modules can be run either separately or in combination. Migration is predicted by a recently developed migration model, whereas hazard predictions for genotoxicity, subchronic toxicity, reproductive and developmental toxicity and carcinogenicity are provided by QSAR models selected from the publicly available VEGA HUB. The major novelty of the tool is that it combines information on hazard and exposure (i.e. migration) with regulatory information. Several case studies were performed to demonstrate the application of the tool.

Polymer-Interface-Tissue Model to Estimate Leachable Release from Medical Devices.

The ability to predict clinically relevant exposure to potentially hazardous compounds that can leach from polymeric components can help reduce testing needed to evaluate the biocompatibility of medical devices. In this manuscript, we compare two physics-based exposure models: 1) a simple, one-component model that assumes the only barrier to leaching is the migration of the compound through the polymer matrix and 2) a more clinically relevant, two-component model that also considers partitioning across the polymer-tissue interface and migration in the tissue away from the interface. Using data from the literature, the variation of the model parameters with key material properties were established, enabling the models to be applied to a wide range of combinations of leachable compound, polymer matrix and tissue type. Exposure predictions based on the models suggest that the models are indistinguishable over much of the range of clinically relevant scenarios. However, for systems with low partitioning and/or slow tissue diffusion, the two-component model predicted up to three orders of magnitude less mass release over the same time period. Thus, despite the added complexity, in some scenarios it can be beneficial to use the two-component model to provide more clinically relevant estimates of exposure to leachable substances from implanted devices.

Quercetin attenuates SiO2-induced ZBP-1-mediated PANoptosis in mouse neuronal cells via the ROS/TLR4/NF-κB pathway

With the increasing development of the society, silicon dioxide (SiO2) has been used in various fields, such as agriculture, food industry, etc., and its residues can pose a potential health threat to organisms. Quercetin (Que) is a potent free radical scavenger commonly found in plants. C57BL/6 mice were chosen to established a mouse model of SiO2 exposure and Que antagonism to investigate the mechanism of action of Que in rescuing the toxic damage of SiO2 on mouse cerebellum tissue. The results showed that cytoplasmic vacuolization, and inflammatory cell infiltration caused by SiO2 were alleviated by the addition of Que. and reduced oxidative stress in mouse cerebellum, alleviated the activation of TLR4 pathway induced by SiO2, and substantially reduced the occurrence of ZBP-1-mediated PANoptosis induced by SiO2 exposure in mouse cerebellum. In NS20Y cells, the oxidative stress activator (Elesclomol) and inhibitor N-acetyl cysteine (NAC), and the NF-κB activator 2 (NA2) were added. Elesclomol and NAC confirm the involvement of ROS in regulating the TLR4/NF-κB pathway, the TLR4/NF-κB pathway regulated ZBP-1-mediated PANoptosis in cerebellum and NS20Y cells induced by SiO2 exposure. In conclusion, the present experimental data suggest that Que mitigates the onset of ZBP-1-mediated PANoptosis in neuronal cells induced by SiO2 through the ROS/TLR4/NF-κB pathway. The present experimental findings help to understand the detoxification effect of Que in more tissues and provide an important reference for the rescue of organisms in long-term SiO2 environment.

Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether pre-existing chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function. Skin challenge with phenylarsine oxide (PAO), a surrogate for warfare arsenicals, led to significantly worse kidney injury, as evidenced by tubulointerstitial fibrosis, glomerulosclerosis, a persistent loss of estimated glomerular filtration rate and mortality in AA-induced CKD mice compared to mice without CKD. These PAO-challenged CKD mice exhibited enhanced production of serum/urine NGAL, and a significant rise in serum creatinine along with histological markers of kidney injury, including brush border loss, tubular atrophy, cast formation, glomerular injury, and interstitial inflammatory cell infiltration. Serum cytokines IL-4, IL-6, IFN-γ, IL-12p70, TNF-α, and IL-18 significantly elevated in CKD mice following PAO exposure when compared to animals exposed to PAO alone. Furthermore, we found increased TUNEL-positive tubular cells in the kidneys of CKD mice following PAO exposure, suggesting enhanced PAO-mediated cell death in CKD mice. Mechanistically, we determined that DNA damage-regulated p53 signaling was a major mediator of cellular responses to PAO in CKD mice. In summary, our data demonstrate that CKD significantly increased severity of AKI following exposure to arsenicals and suggest that human populations with preexisting CKD could be highly susceptible to arsenical-mediated kidney injury and associated morbidity and mortality.

Hexavalent chromium exposure induces lung injury via activation of NLRP3 and AIM2 inflammasomes in rats

Hexavalent chromium (Cr(VI)) has been identified as a Class I human carcinogen, but its carcinogenic mechanism is currently unclear. There is still a lack of understanding of its associations with early pulmonary inflammatory damages. Inflammation is an important stage before the occurrence of tumors, and under the long-term stimulation of inflammation, it can promote the development of tumors. In this study, the aim is to explore the effect of Cr(VI) exposure on pulmonary inflammation and its relationship with the mechanism of inflammation cancer transformation. We established a Cr(VI) exposure model in SD rats using tracheal instillation of potassium dichromate solution, and collected samples at the time of cessation of exposure and 14 days after cessation of exposure. Analyzing the experimental results, it was found that the lung index increased after exposure to Cr(VI), promoting the occurrence of apoptosis in lung tissue cells and exacerbating lung tissue damage. The damage situation improved after exposure termination; Inductively coupled plasma mass (ICPRQ) spectrometer detection found that the exposed group had significantly increased levels of blood chromium, blood manganese, blood copper, blood arsenic, urine chromium, urine copper, and urine lead; After two weeks of repair, blood chromium and blood manganese levels were significantly lower than those in the same dose group of the exposure group, while blood copper levels were significantly higher than those in the same dose group of the exposure group. There was no significant difference in blood arsenic levels between the exposure group and the exposure group. Urine chromium and urine lead levels were significantly lower than those in the same dose group of the exposure group, while urine copper levels only increased. At the same time, it was found that Cr(VI) exposure caused disruption of oxidative stress levels in rat lung tissues. After 14-day exposure, Cr(VI) significantly decreased and oxidative stress levels significantly decreased. Further investigation revealed that Cr(VI) induces activation of inflammasomes NLRP3, AIM2, and their signaling pathways in lung inflammatory injuries, but this condition persists even after cessation of exposure. The study suggested that in hexavalent chromium induced lung tissue injuries in rats, NLRP3 and AIM2 inflammasomes and their signaling pathways activation. Furthermore, the characteristic of sustained activation after cessation of exposure was also indicated. These results provide new ideas and references for further elucidating the mechanisms of Cr(VI), lung inflammation and inflammation cancer transformation.

Rapid onset fibrotic remodeling and ventricular dysfunction induced by phenylephrine involve targeted reprogramming of myocyte and fibroblast transcriptomes.

Catecholamine dysregulation is a common feature of multiple acute and chronic cardiac conditions, including heart failure. To investigate the role of altered α-adrenergic stimulation on cardiac function, we developed a short-term exposure model, administering phenylephrine subcutaneously to mice for one week. Compared to vehicle-injected controls, phenylephrine-treated animals exhibited increased ejection fraction, decreased chamber size, diastolic dysfunction and ventricular hypertrophy in the absence of hypertension. Remarkably, these animals developed extensive fibrotic remodeling of the tissue that plateaued at 24 hours and myocyte hypertrophy localized to regions of fibrotic deposition after 3 days of treatment. Transcriptome analyses of purified myocyte and fibroblast populations from these hearts revealed an unexpected role for myocytes in the production of extracellular matrix. Comparison with other models of cardiac stress, including pressure overload hypertrophy and cytokine activation of fibroblasts, identified stimulus-specific transcriptional circuits associated with cardiac pathology. Given the rapid, robust fibrotic response that preceded myocyte hypertrophy, intercellular communication analyses were conducted to investigate fibroblast to myocyte signaling, identifying potential crosstalk between these cells. These studies thoroughly describe and phenotypically characterize a new model of short-term catecholamine stress and provide an atlas of transcriptional remodeling in myocytes and fibroblasts.

Body fatness across the adult life course and ovarian cancer risk.

Excess body fatness in late adulthood has been observed to increase ovarian cancer risk, but the association is relatively weak. Body fatness can change over time, and timing may differently influence risk. We used a life course epidemiology approach to identify whether the relation between body fatness and ovarian cancer risk is best described by a critical period, accumulation or sensitive period hypothesis. In a population-based case-control study of ovarian cancer in Montreal, Canada (2011-16), data on body mass index (BMI) at each decade starting at age 20 was available. Among 363 cases and 707 controls aged ≥ 50 years, we used a Bayesian relevant life course exposure model to estimate the relative importance of BMI for three pre-specified periods across the adult life course, i.e., early childbearing years, late childbearing years, and peri/postmenopause, on ovarian cancer risk. The accumulation hypothesis best described BMI in relation to ovarian cancer overall, with an odds ratio (OR) for the lifetime effect of BMI (per 5kg/m2 increase) of 1.10 (95% credible interval [CrI]: 0.90-1.35). For invasive ovarian cancer, the OR (95% CrI) for the lifetime effect was 1.16 (0.92-1.48), with BMI during early childbearing years showing the highest relative importance, suggesting this may be a sensitive period. For borderline cancer, the lifetime effect OR was not strongly supportive of an association (OR: 0.90, 95% CrI: 0.53-1.32). The results suggest that a sensitive period of early childbearing years is a candidate hypothesis for further investigation.

CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID.

Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.

Modeling of Biologically Effective Daily Radiant Exposures over Europe from Space Using SEVIRI Measurements and MERRA-2 Reanalysis

Ultraviolet solar radiation at the Earth’s surface significantly impacts both human health and ecosystems. A biologically effective daily radiant exposure (BEDRE) model is proposed for various biological processes with an analytical formula for its action spectrum. The following processes are considered: erythema formation, previtamin D3 synthesis, psoriasis clearance, and inactivation of SARS-CoV-2 virions. The BEDRE model is constructed by multiplying the synthetic BEDRE value under cloudless conditions by a cloud modification factor (CMF) parameterizing the attenuation of radiation via clouds. The CMF is an empirical function of the solar zenith angle (SZA) at midday and the daily clearness index from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) measurements on board the second-generation Meteosat satellites. Total column ozone, from MERRA-2 reanalysis, is used in calculations of clear-sky BEDRE values. The proposed model was trained and validated using data from several European ground-based spectrophotometers and biometers for the periods 2014–2023 and 2004–2013, respectively. The model provides reliable estimates of BEDRE for all biological processes considered. Under snow-free conditions and SZA < 45° at midday, bias and standard deviation of observation-model differences are approximately ±5% and 15%, respectively. The BEDRE model can be used as an initial validation tool for ground-based UV data.

Involvement of autophagy and gut dysbiosis in ambient particulate matter-induced colonic inflammation

Ambient fine particulate matter (PM2.5), a vital environmental toxicant, not only adversely affects the cardiovascular and respiratory systems but also potentially exhibits an association with intestinal inflammation and colorectal cancer (CRC). The underlying molecular mechanisms of PM2.5 impacts on CRC are still unclear. In this study, we utilized collected ambient PM2.5 and standard reference material SRM2786 to investigate the toxic effects on the colon through in vivo chronic exposure mouse and in vitro cell culture models. We employed a chronic mouse exposure model to clarify the colonic injury and gut microbiome biomarkers. Prolonged exposure to PM2.5 via oropharyngeal aspiration led to a significant rise in colonic epithelial proliferation and reduced colon length in mice. It triggered characteristics indicative of gut microbiota dysbiosis linked to inflammatory bowel disease. The gut microbiome alternations may serve as a biomarker indicating the colonic health impacts of PM2.5 exposure. PM2.5 and SRM2786-induced cytotoxicity manifested as autophagy dysregulation-mediated abnormal proliferation, IL-8 production, p62/SQSTM1 accumulation, and lysosomal membrane damage in human colon cells WiDr and Caco-2. Both PM2.5 and SRM2786 exposures led to the accumulation of p62/SQSTM1 and compromised lysosomal membrane integrity, showing impaired autophagic flux in WiDr and Caco-2 cells. Finally, we examined the correlations between atmospheric PM2.5 data and biomarkers of colonic inflammation in human population. The serum level of IL-8 was significantly correlated with regional anthropogenic pollutants. In conclusion, our findings elucidate that ambient PM2.5 exhibits adverse effects on colon health manifested as inflammation, aberrant proliferation, and gut dysbiosis, potentially mediated through autophagy dysregulation, thereby highlighting the importance of further research on the impact of environmental pollutants on gastrointestinal health.

The Protective Effect of the Supplementation with an Extract from Aronia melanocarpa L. Berries against Cadmium-Induced Changes of Chosen Biomarkers of Neurotoxicity in the Brain-A Study in a Rat Model of Current Lifetime Human Exposure to This Toxic Heavy Metal.

Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3-24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy.

Evaluation of TRPM2 Channel-Mediated Autophagic Signaling Pathway in Hippocampus and Cortex Tissues of Rat Offspring Following Prenatal Exposure to Elevated Alcohol Levels.

Fetal alcohol syndrome (FAS) can occur because of high amount of alcohol intake during pregnancy and is characterized by both physical and neurological problems. Children diagnosed with FAS have difficulties in learning, memory, and coordination. Hippocampus has a major role in memory and learning. We aimed to determine whether alcohol exposure during pregnancy had any effect on offspring by evaluating learning ability as well as oxidative stress and autophagy in the hippocampus and cortex tissues of litters. Attention was also paid to sex differences. To do so, TRPM2, Beclin1, p62, LC3B, IBA1, parvalbumin, GAD65, and mGluR5 expression levels were evaluated by immunohistochemistry. Lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels, as well as total oxidant (TOS) and total antioxidant (TAS) status were determined by ELISA. Learning experiments were evaluated by the Morris water maze (MWM) test. Our findings demonstrated that IBA1, LC3B, GAD65, and mGluR5 expression levels were higher in female rats of the chronic alcohol exposure (CAE) model. Our IHC results revealed that TRPM2 expression levels were significantly increased in both males and females in the CAE group. Likewise, TAS was lower, and TOS was higher in CAE animals. Moreover, MWM outcomes supported a learning deficiency in CAE litters compared to controls and indicated that female offspring outperformed males in learning experiments. Therefore, our results revealed the detrimental effects of alcohol exposure during pregnancy on autophagy signaling in the hippocampus and cortex tissue of litters, which could affect the learning ability of animals.

Impact of elevated fine particulate matter (PM2.5) during landscape fire events on cardiorespiratory hospital admissions in Perth, Western Australia

BackgroundAustralia has experienced extreme fire weather in recent years. Information on the impact of fine particulate matter (PM2.5) from landscape fires (LFs) on cardiorespiratory hospital admissions is limited.MethodsWe conducted a...

The High Estradiol Environment after IVF Causes the Increased Risk of Glucose Metabolic Dysfunction in Offspring.

Assisted reproductive technology (ART) is associated with increased metabolic risks in offspring. The effect of high maternal estradiol (E2) levels during early pregnancy on the glucose metabolism of offspring remains unclear. To evaluate glucose metabolism in in vitro fertilization (IVF)-conceived children and assess whether high E2 exposure during early pregnancy is associated with metabolic alterations. This retrospective analysis included 500 singletons aged 3-10 years born after fresh embryo transfer (ET) (n=200), frozen ET (n=100), and natural conception (NC) (n=200) from a university hospital. Children underwent anthropometric measurements and examinations for fasting glucose, insulin, and lipid levels. A mouse model of high E2 exposure during early pregnancy was established to study glucose and insulin tolerance, and insulin secretion. Compared with NC, children born after fresh ET showed higher fasting glucose/insulin levels, increased insulin resistance, and higher incidence of impaired fasting glucose, which might be associated with a higher maternal E2 levels. Frozen ET showed intermediate results. In mice, offspring exposed to high E2 levels during gestation exhibited impaired glucose/insulin tolerance and defects in insulin secretion. High maternal E2 levels in early pregnancy are associated with altered glucose metabolism and increased metabolic risks in IVF-conceived children. Further studies are needed to elucidate the underlying mechanisms.

Ontology of active and passive environmental exposure

Exposure is a central concept of the health and behavioural sciences needed to study the influence of the environment on the health and behaviour of people within a spatial context. While an increasing number of studies measure different forms of exposure, including the influence of air quality, noise, and crime, the influence of land cover on physical activity, or of the urban environment on food intake, we lack a common conceptual model of environmental exposure that captures its main structure across all this variety. Against the background of such a model, it becomes possible not only to systematically compare different methodological approaches but also to better link and align the content of the vast amount of scientific publications on this topic in a systematic way. For example, an important methodical distinction is between studies that model exposure as an exclusive outcome of some activity versus ones where the environment acts as a direct independent cause (active vs. passive exposure). Here, we propose an information ontology design pattern that can be used to define exposure and to model its variants. It is built around causal relations between concepts including persons, activities, concentrations, exposures, environments and health risks. We formally define environmental stressors and variants of exposure using Description Logic (DL), which allows automatic inference from the RDF-encoded content of a paper. Furthermore, concepts can be linked with data models and modelling methods used in a study. To test the pattern, we translated competency questions into SPARQL queries and ran them over RDF-encoded content. Results show how study characteristics can be classified and summarized in a manner that reflects important methodical differences.

A multi-pathogen behavioral exposure model for young children playing in public spaces in developing communities.

Diarrheal disease is the second leading cause of death among children under five in developing communities, despite active interventions to improve access to water, sanitation, and hygiene resources. Even interventions with high fidelity and compliance saw minimal improvements in health outcomes, necessitating a need for looking beyond traditionally targeted exposure pathways. This study focuses on the pathogen exposure a young child may receive while playing in the public spaces of informal settlements, where animal feces, human feces, and garbage are frequently observed. The study utilized 79 soil samples previously collected across ten cluster sites in Corail, Haiti and processed using DelAgua cultural assays and quantitative Polymerase Chain Reaction methods. Molecular assays screened for Aeromonas, Vibrio cholera, and several pathogenic Escherichia coli species. Behavioral observations of young children (<5 years old) were also conducted in overlapping areas with the environmental sampling to quantify frequency of risky and mitigating behaviors. Environmental and behavioral data were combined to obtain the posterior distribution of children's pathogen exposure from playing in a public space for one hour. The model estimated that children have a likelihood of approximately 70% of being exposed to a pathogen during one hour of play and a greater than 30% chance of being exposed to multiple pathogens in the same period. While children and toddlers practice fewer risky behaviors compared to infants, they were shown to have higher likelihood of exposure and slightly higher pathogen dose per exposure. As anticipated, a high correlation between genes from the same E. coli species was observed in the model output. These findings demonstrate the need to consider public spaces as an important exposure pathway for young children for both future research and interventions.

Model of occupational exposure of workers performing inspection of welded joints

A model of occupational exposure to gamma flaw detector operators working with portable flaw detectors in the field has been developed. The initial data for the development and verification of the model were the results of measurements of the characteristics of the gamma radiation field at the workplaces of flaw detectors and data from individual dosimetric monitoring. The relationships between the measured (H*(10), Hp(10)) and protection (effective dose) quantities (conversion coefficients) were determined using calculations and phantom experiments simulating three main operations of the full production cycle: transportation of the flaw detector to the place of X-raying of the product, installation of a flaw detector to perform x-raying and X-raying of the product. As a result of the study, it was found that more than 90% of the dose contribution to the readings of an individual dosimeter is due to the installation of the flaw detector in the working position and X-raying of the product. The values of the conversion coefficients for these operations in the form of the ratio of the effective dose values and the readings of dosimeters (Hp(10)) located on the worker's body at chest level (standard place) and abdominal level differ little for both positions of individual dosimeters. The use of maximum conversion coefficient value of 0.8 Sv/Sv corresponding to the operation of X-raying of the product will ensure conservatism in the assessment of the effective dose for the entire production cycle by no more than 15% and 25% for dosimeters located at the chest level and abdominal level, respectively.