Individual Exposure Research Articles

Combined effects of TiO2 nanoparticle and fipronil co-exposure on microbiota in mouse intestine

Oral exposure to nanoparticles (NPs) may affect intestinal microbiota, and this effect may be further changed by co-contaminates. In the present study, we investigated the combined effects of TiO2 NPs and fipronil (FPN) on microbiota in mouse intestines. Mice were intragastric exposed to 5.74 mg/kg TiO2 NPs, 2.5 mg/kg FPN, or both of them, once a day, for 30 days. The results showed that individual exposure to TiO2 NPs or FPN decreased body weight and induced pathological changes in intestines. The exposure was also associated with increased cleaved caspase-3 protein, oxidative stress and decreased tight junction protein expression. Furthermore, the levels of diamine oxidase (DAO), lipopolysaccharide (LPS) and inflammatory cytokines in serum were also elevated, indicating increased intestinal barrier permeability. As expected, both TiO2 NPs and FPN decreased the diversity and altered the composition of microbiota. However, the observed effects were not further enhanced after the co-exposure to TiO2 NPs and FPN, except that Romboutsia was only significantly increased after the co-exposure to TiO2 NPs + FPN. We concluded that oral exposure to TiO2 NPs and FPN showed minimal synergistic effects on microbiota in mouse intestine.

Maternal symptoms of depression and anxiety as modifiers of the relationship between prenatal phthalate exposure and infant neurodevelopment in the Atlanta African American maternal-child cohort

BackgroundPrenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study designOur analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8–14 weeks and 24–32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. ResultsHigher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: β = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, β = −0.30, 95% CI = −0.73, 0.12 for low; MEOHP: β = 0.60, 95% CI = −0.03, 1.23 for high, β = −0.12, 95% CI = −0.58, 0.33 for low; MEHHP: β = 0.54, 95% CI = −0.04, 1.11 for high, β = −0.11, 95% CI = −0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. ConclusionOur results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Exposure to fine particulate matter in the New York City subway system during home-work commute.

The New York City (NYC) subway system accommodates 5.5 million daily commuters, and the environment within the subway is known to have high concentrations of fine particulate matter (PM2.5) pollution. Naturally, subway air pollution varies among individuals according to their mobility patterns, introducing the possibility of inequality in PM2.5 exposure. This study aims to evaluate individual and community-level exposure to subway PM2.5. We simulated the intracity home-to-work trip patterns using the Longitudinal Employer-Household Dynamics (LEHD) records of 3.1 million working commuters across 34,169 census blocks in four boroughs (Manhattan, Brooklyn, Queens, and the Bronx) of NYC. We incorporated the on-platform and on-train measured PM2.5 concentration data for the entire subway system. The mean underground platform concentration in the city was 139 μg/m3 with a standard deviation of 25 μg/m3, while the on-train concentration when underground was 99 μg/m3 with a standard deviation of 21 μg/m3. Using a network model, we determined the exposure of individual commuters during their daily home-work trips. We quantified the mean per capita exposure at the census block level by considering the proportion of workers within the blocks who rely on the subway for their work commute. Results indicate statistically significant weak positive correlation between elevated subway PM2.5 exposure and economically disadvantaged and racial minority groups.

Independent and joint associations between urinary polycyclic aromatic hydrocarbon metabolites and cognitive function in older adults in the United States.

Polycyclic aromatic hydrocarbons (PAHs), as organic pollutants widely present in daily environments, have been shown by existing epidemiological studies to be significantly associated with deficits in learning and memory functions in children and adults. However, the association between exposure to PAHs and cognitive function in older adults remains unclear. Additionally, existing related studies have only assessed the association between individual PAH exposures and cognitive assessments, overlooking the risks posed by mixed exposures. This study aims to use three statistical models to investigate the individual and overall effects of mixed PAH exposures on the cognition of older adults in the United States. The study cohort was obtained from the NHANES database, which included individuals aged 60 and older from 2011 to 2014. Weighted generalized linear models (GLM), weighted quantile sum (WQS) models, and Bayesian kernel machine regression (BKMR) models were utilized to evaluate the connections between urinary PAH metabolites and the standardized Z-scores of four cognitive tests: Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Our analysis involved 899 individuals aged 60 and above. In the fully adjusted GLM, 2-hydroxynaphthalene (2-OHNa), 3-hydroxyfluorene (3-OHFlu), and 2-hydroxyfluorene (2-OHFlu) demonstrated negative associations with DSST Z-scores. In the WQS model, six urinary PAH metabolites were negatively linked to AFT Z-scores (β (95% confidence intervals [CI]): -0.120 (-0.208, -0.033), p = 0.007) and DSST Z-scores (β (95% CI): -0.182 (-0.262, -0.103), p < 0.001). In both assessments, 2-OHNa exerted the greatest influence among the urinary PAH metabolites. In the BKMR model, there was an overall negative correlation between urinary PAH metabolites and AFT and DSST Z-scores when the concentration was within the 25th to 75th percentile, where 2-OHNa dominated the main effect of the mixture. The WQS and BKMR models were adjusted for all covariates. Increased concentrations of urinary PAH metabolites are associated with cognitive decline in older adults, mainly on language ability, executive function, sustained attention, working memory, and information processing speed, with 2-OHNa playing a major effect.

Influence of gestational window on offspring vascular health in rodents with in utero exposure to electronic cigarettes.

Studies have shown cerebrovascular dysfunction in offspring with full-gestational electronic cigarette (Ecig) exposure, but little is known about how individual trimester exposure impacts offspring health. This study aimed to determine if there is a critical window during gestation that contributes to vascular and anxiety-like behavioural changes seen with full-term exposure. To test this, rats were time-mated, and the pregnant dams were randomly assigned to Ecig exposure during first trimester (gestational day, GD2-7), second trimester (GD8-14), third trimester (GD15-21) or full-term gestation (GD2-21). We also assessed the effect of maternal preconception exposure. Both male and female offspring from all maternal exposure conditions were compared to offspring from dams under ambient air (control) conditions. Ecig exposure consisted of 60-puffs/day (5days/week) using either 5 or 30watts for each respective exposure group. We found that maternal exposure to Ecig in the second and third trimesters resulted in a decrease (23-38%) in vascular reactivity of the middle cerebral artery (MCA) reactivity in 3- and 6-month-old offspring compared to Air offspring. Further, the severity of impairment was comparable to the full-term exposure (31-46%). Offspring also displayed changes in body composition, body mass, anxiety-like behaviour and locomotor activity, indicating that Ecigs influence neurodevelopment and metabolism. Maternal preconception exposure showed no impact on offspring body mass, anxiety-like behaviour, or vascular function. Thus, the critical exposure window where Ecig affects vascular development in offspring occurs during mid- to late-gestation in pregnancy, and both 5W and 30W exposure produce significant vascular dysfunction compared to Air. KEY POINTS: Exposure to electronic cigarettes (Ecigs) is known to increase risk factors for cardiovascular disease in both animals and humans. Maternal Ecig use during pregnancy in rodents is found to impair the vascular health of adolescent and adult offspring, but the critical gestation window for Ecig-induced vascular impairment is not known. This study demonstrates Ecig exposure during mid- and late-gestation (i.e. second or third trimester) results in impaired endothelial cell-mediated dilatation (i.e. middle cerebral artery reactivity) and alters anxiety-like behaviour in offspring. Maternal exposure prior to conception did not impact offspring's vascular or anxiety-like behavioural outcomes. Rodent models have been a reliable and useful predictor of inhalation-induced harm to humans. These data indicate maternal use of Ecigs during pregnancy should not be considered safe, and begin to inform clinicians and women about potential long-term harm to their offspring.

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.

Metabolic signatures of population exposure to metal mixtures: A metabolome-wide association study

Numerous studies have explored the health impacts of individual metal exposures, yet the effects of metal mixtures on human endogenous metabolism remain largely unexplored. We aimed to assess the serum metabolic signatures of people exposed to metal mixtures. Serum and urine samples were collected from 186 workers at a steel factory in Anhui, China, in September 2019. Inductively coupled plasma mass spectrometry was used to analyze the concentrations of 23 metal elements. The serum metabolome was determined by liquid chromatography-mass spectrometry (LC-MS). A metabolome-wide association study (MWAS) was performed across the metal exposures and metabolism using quantile g-computation modeling. Pathway enrichment analysis was performed using MetaboAnalyst. We identified 226 metabolites associated with metal mixtures, primarily involving lipid metabolism (glycerophospholipids, sphingolipids), amino acid metabolism (arginine and proline, alanine, aspartate and glutamate metabolism) and caffeine metabolic pathways. Exposure to metal mixtures is mainly associated with alterations in lipid metabolism and amino acid metabolism, particularly in the glycerophospholipid and arginine and proline metabolism pathways.

Thermal performance of native and invasive crab species: investigating the invasion potential of Hemigrapsus takanoi in southern European Carcinus maenas’ habitats

Invasive species’ plasticity and latitudinal spread have become an increasing matter of concern in rapidly changing climate. The brush-clawed shore crab (Hemigrapsus takanoi), native along northwestern Pacific shores, has established dense populations in northern European coasts. Detrimental effects in natura have been reported, such as displacement of native species and competition for shelter, rasing concerns regarding shellfish early life stages and food webs-posing a threat to wild stocks’ recruitment and aquaculture. The species has not yet been observed in southern European countries (e.g., Portugal), where niche habitats such as harbours, mudflats, and lagoons reach higher temperatures than the invaded northern range. The aims of this study were to determine H. takanoi potential to acclimate to a southern thermal range, assess thermal performance, and identify potential competitive advantages over the native shore crab Carcinus maenas. This was accomplished through individual exposure to one of three treatments, resembling a southern European thermal range (17 °C, 21 °C, or 25 °C), for 30 days. H. takanoi thrived in temperatures as high as 25 °C, a realistic thermal scenario in Óbidos Lagoon (the biggest Portuguese lagoon)—while the native shore crab C. maenas underperformed at that treatment, showing lower survival, growth, and feed intake than H. takanoi. These results suggest that H. takanoi may be able to colonise southern and warmer European locations and have higher plasticity than the native species already inhabiting areas close to its upper thermal limits. Under global warming scenarios, inferences of further latitudinal spread and increased invaded range may also be taken to the invaded northern European habitats.

Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study.

Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure. Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7 days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60 mg·h/L. Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non-Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7 days was above 60 mg·h/L in 29 out of 77 (37.7%) patients. This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment.

ELEKTROFIZJOLOGICZNE POMIARY UPOŚLEDZENIA SŁUCHU U NARAŻONYCH NA HAŁAS ŻOŁNIERZY ZE SŁUCHEM W NORMIE

IntroductionSome electrophysiological changes can occur in the auditory system in response to noise exposure with or without any permanent auditory threshold shift. The purpose of this study was to identify and measure cochlear function after noise exposure in individuals with normal hearing according to standard audiometric thresholds.Material and methodsPure tone audiometry (PTA) over the standard 0.250–8 kHz range and at 12 kHz, as well as distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing, were performed on 42 soldiers who had participated in combat. A control group of 40 participants underwent the same tests.ResultsIn the noise-exposed group, significantly poorer PTA thresholds were recorded at 12 kHz. DPOAE levels were significantly low only at 4 kHz. On ABR testing, both wave I and wave V demonstrated a significant decrease in amplitude and a significant increase in latency for the noise-exposed group.ConclusionsOur findings reveal that high levels of noise can not only damage outer hair cells but also cause changes at the level of the synapses (synaptopathy) which are not evident using standard PTA tests. However, electrophysiological methods can detect some changes in cochlear function.

On the informative value of community-based indoor radon values in relation to lung cancer.

Radon is a radioactive gas and a major risk factor for lung cancer (LC). We investigated the dose-response relationship between radon and LC risk in the International Lung Cancer Consortium with 8927 cases and 5562 controls from Europe, North America, and Israel, conducted between 1992 and 2016. Spatial indoor radon exposure in the residential area (sIR) obtained from national surveys was linked to the participants' residential geolocation. Parametric linear and spline functions were fitted within a logistic regression framework. We observed a non-linear spatial-dose response relationship for sIR < 200 Bq/m3. The lowest risk was observed for areas of mean exposure of 58 Bq/m3 (95% CI: 56.1-59.2 Bq/m3). The relative risk of lung cancer increased to the same degree in areas averaging 25 Bq/m3 (OR = 1.31, 95% CI: 1.01-1.59) as in areas with a mean of 100 Bq/m3 (OR = 1.34, 95% CI: 1.20-1.45). The strongest association was observed for small cell lung cancer and the weakest for squamous cell carcinoma. A stronger association was also observed in men, but only at higher exposure levels. The non-linear association is primarily observed among the younger population (age < 69 years), but not in the older population, which can potentially represent different biological radiation responses. The sIR is useful as proxy of individual radon exposure in epidemiological studies on lung cancer. The usual assumption of a linear, no-threshold dose-response relationship, as can be made for individual radon exposures, may not be optimal for sIR values of less than 200 Bq/m3.

NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review.

Fluoride is a common exposure in our environment that comes from a variety of sources and is widely promoted for its dental and overall oral health benefits. Contributions to an individual's total exposure come primarily from fluoride in drinking water, food, beverages and dental products. A 2006 evaluation by the National Research Council (NRC) found support for an association between consumption of high levels of naturally occurring fluoride in drinking water and adverse neurological effects in humans and recommended further investigation. The evidence reviewed at that time was from dental and skeletal fluorosis-endemic regions of China. Since the NRC evaluation, the number and location of studies examining cognitive and neurobehavioral effects of fluoride in humans have grown considerably, including several recent North American prospective cohort studies evaluating prenatal fluoride exposure. In 2016, the National Toxicology Program (NTP) published a systematic review of the evidence from experimental animal studies on the effects of fluoride on learning and memory. That systematic review found a low-to-moderate level of evidence that deficits in learning and memory occur in non-human mammals exposed to fluoride. To conduct a systematic review of the human, experimental animal, and mechanistic literature to evaluate the extent and quality of the evidence linking fluoride exposure to neurodevelopmental and cognitive effects in humans. A systematic review protocol was developed and utilized following the standardized OHAT systematic review approach for conducting literature-based health assessments. This monograph presents the current state of evidence associating fluoride exposure with cognitive or neurodevelopmental health effects and incorporated predefined assessments of study quality and confidence levels. Benefits of fluoride with respect to oral health are not addressed in this monograph. The bodies of experimental animal studies and human mechanistic evidence do not provide clarity on the association between fluoride exposure and cognitive or neurodevelopmental human health effects. Human mechanistic studies were too heterogenous and limited in number to make any determination on biological plausibility. This systematic review identified studies that assessed the association between estimated fluoride exposure and cognitive or neurodevelopmental effects in both adults and children, which were evaluated separately. The most common exposure assessment measures were drinking water concentrations and estimates of total fluoride exposure, as reflected in biomarkers such as urinary fluoride. In adults, only two high-quality cross-sectional studies examining cognitive effects were available. The literature in children was more extensive and was separated into studies assessing intelligence quotient (IQ) and studies assessing other cognitive or neurodevelopmental outcomes. Eight of nine high-quality studies examining other cognitive or neurodevelopmental outcomes reported associations with estimated fluoride exposure. Seventy-two studies assessed the association between fluoride exposure and IQ in children. Nineteen of those studies were considered to be high quality; of these, 18 reported an inverse association between estimated fluoride exposure and IQ in children. The 18 studies, which include 3 prospective cohort studies and 15 cross-sectional studies, were conducted in 5 different countries. Forty-six of the 53 low-quality studies in children also found evidence of an inverse association between estimated fluoride exposure and IQ in children. Existing animal studies provide little insight into the question of whether fluoride exposure affects IQ. In addition, studies that evaluated fluoride exposure and mechanistic data in humans were too heterogenous and limited in number to make any determination on biological plausibility. The body of evidence from studies in adults is also limited and provides low confidence that fluoride exposure is associated with adverse effects on adult cognition. There is, however, a large body of evidence on associations between fluoride exposure and IQ in children. There is also some evidence that fluoride exposure is associated with other neurodevelopmental and cognitive effects in children; although, because of the heterogeneity of the outcomes, there is low confidence in the literature for these other effects. This review finds, with moderate confidence, that higher estimated fluoride exposures (e.g., as in approximations of exposure such as drinking water fluoride concentrations that exceed the World Health Organization Guidelines for Drinking-water Quality of 1.5 mg/L of fluoride) are consistently associated with lower IQ in children. More studies are needed to fully understand the potential for lower fluoride exposure to affect children's IQ.

Landscape analysis of environmental data sources for linkage with SEER cancer patients database.

One of the challenges associated with understanding environmental impacts on cancer risk and outcomes is estimating potential exposures of individuals diagnosed with cancer to adverse environmental conditions over the life course. Historically, this has been partly due to the lack of reliable measures of cancer patients' potential environmental exposures before a cancer diagnosis. The emerging sources of cancer-related spatiotemporal environmental data and residential history information, coupled with novel technologies for data extraction and linkage, present an opportunity to integrate these data into the existing cancer surveillance data infrastructure, thereby facilitating more comprehensive assessment of cancer risk and outcomes. In this paper, we performed a landscape analysis of the available environmental data sources that could be linked to historical residential address information of cancer patients' records collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The objective is to enable researchers to use these data to assess potential exposures at the time of cancer initiation through the time of diagnosis and even after diagnosis. The paper addresses the challenges associated with data collection and completeness at various spatial and temporal scales, as well as opportunities and directions for future research.

Degradation of Three Herbicides and Effect on Bacterial Communities under Combined Pollution.

Pesticide residues in soil, especially multiple herbicide residues, cause a series of adverse effects on soil properties and microorganisms. In this work, the degradation of three herbicides and the effect on bacterial communities under combined pollution was investigated. The experimental results showed that the half-lives of acetochlor and prometryn significantly altered under combined exposure (5.02-11.17 d) as compared with those of individual exposure (4.70-6.87 d) in soil, suggesting that there was an antagonistic effect between the degradation of acetochlor and prometryn in soil. No remarkable variation in the degradation rate of atrazine with half-lives of 6.21-6.85 d was observed in different treatments, indicating that the degradation of atrazine was stable. 16S rRNA high-throughput sequencing results showed that the antagonistic effect of acetochlor and prometryn on the degradation rate under combined pollution was related to variation of the Sphingomonas and Nocardioide. Furthermore, the potential metabolic pathways of the three herbicides in soil were proposed and a new metabolite of acetochlor was preliminarily identified. The results of this work provide a guideline for the risk evaluation of combined pollution of the three herbicides with respect to their ecological effects in soil.

Rapid kilonova evolution: Recombination and reverberation effects

Kilonovae (KNe) are one of the fastest types of optical transients known, cooling rapidly in the first few days following their neutron-star merger origin. We show here that KN spectral features go through rapid recombination transitions, with features due to elements in the new ionisation state emerging quickly. Due to time-delay effects of the rapidly expanding KN, a ‘wave’ of these new features passing though the ejecta should be a detectable phenomenon. In particular, isolated line features will emerge as blueshifted absorption features first, gradually evolving into P Cygni features and then pure emission features. In this analysis, we present the evolution of individual exposures of the KN AT2017gfo observed with VLT/X-shooter, which together comprise X-shooter’s first epoch spectrum (1.43 days post-merger). The spectra of these ‘sub-epochs’ show a significant evolution across the roughly one hour of observations, including a decrease in the blackbody temperature and photospheric velocity. The early cooling is even more rapid than that inferred from later photospheric epochs and suggests that a fixed power-law relation between the temperature and time does not describe the data. The cooling constrains the recombination wave, where a Sr II interpretation of the AT2017gfo ∼1 μm feature predicts both a specific timing for the feature emergence and its early spectral shape, including the very weak emission component observed at about 1.43 days. This empirically indicates a strong correspondence between the radiation temperature of the blackbody and the ejecta’s electron temperature. Furthermore, this reverberation analysis suggests that temporal modelling is important for interpreting individual spectra and that higher-cadence spectral series, especially when concentrated at specific times, can provide strong constraints on KN line identifications and the ejecta physics. Given the use of such short-timescale information, we lay out improved observing strategies for future KN monitoring.

Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study.

The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM). This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results. A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found. Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.

Reliability of toxicokinetic modelling for PFAS exposure assessment in contaminated water in northern Italy

IntroductionLong-term contamination of tap water and groundwater by perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been documented in the Veneto region of northern Italy. This study aimed to assess the exposure of individuals residing in the contaminated area and to test several toxicokinetic (TK) models of varying complexities to identify an efficient method for predicting perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in human serum using observed data.The ultimate goal is to provide public health officials with guidance on selecting the appropriate TK model for specific contexts, a reliable and rapid tool to support human bio-monitoring (HBM) studies. MethodsTwo simpler empirical TK models and a more complex multi-compartment physiologically based toxicokinetic (PBTK) model were compared with individual and aggregate data from an HBM study. In addition, the PBPK model was modified by adjusting input parameters and introducing new terms into the equations within the original model code. These modifications aimed to optimize the results compared to the original model, with some versions incorporating adjustments to account for the influence of menstruation in women. All models were evaluated to understand their strengths and weaknesses, providing guidance on the appropriate model to use according to specific scenarios. ResultsThe results obtained from the tested models were quite similar, with significant improvements observed only in the modified models. Simpler models also provided satisfactory results in scenarios involving low PFOS serum concentrations and recent exposure cessation. In many cases, predictions demonstrated high accuracy, particularly at the aggregate level and for women. ConclusionsThese findings suggest that environmental protection agencies and health authorities may benefit from employing the tested models at the aggregate level as an initial step in HBM studies, rather than conducting more invasive and expensive screening campaigns.

White and wholewheat bread consumption and the risk of exposure to acrylamide and 5-hydroxymethylfurfural

This study used a green validated method to evaluate the risk of exposure of individuals of different ages to acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) by consuming white and wholewheat bread. Recoveries of AA and 5-HMF were 100.7% and 100.1%, respectively, while uncertainty was 2.3% and 6.2%. Levels of AA ranged from 617.22 to 3151.8 μg/kg while levels of 5-HMF ranged from 180.5 to 648.2 μg/kg. Female adolescents were almost 2-fold exposed to AA when they consumed 100% wholewheat bread (2.93 μg/kg bw/day) by comparison with white bread (1.72 μg/kg bw/day). Estimated daily exposure to AA was 1.5-fold higher than international recommendations. These findings raise concern for health risks associated with exposure to processing contaminant as the result of bread consumption, especially made from whole grains. Since development of those compounds is inevitable during breadmaking, it is crucial to standardize processing conditions and recipes to mitigate it.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease

BackgroundRadiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic.MethodsIntraventricular radioimmunotherapy (RIT) with 925–1850 MBq (25–50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 min, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3–10 y/o, 10–18 y/o, and 18+.ResultsPost-administration exposure rates for patients ranged from 0.16 to 0.46 µSv/hr/MBq at 0.3 m and 0.03–0.08 µSv/hr/MBq at 1 m. Radiation exposure precautions ranged from 1 to 10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring.Conclusion131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine’s ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402.

Long-Term Survival after Coronary Artery Surgical Revascularization-Does Ambient Temperature Matter?

Background and Objectives: The progression of global warming results in an increased exposure to extreme heat, leading to exaggeration of preexisting diseases and premature deaths. The aim of the study was to present possible risk factors for all-cause long-term mortality in patients who underwent surgical revascularization, including an assessment of the influence of ambient temperature exposure. Materials and Methods: Retrospective analysis included 153 (123 (80%) males and 30 (20%) females) patients who underwent off-pump revascularization and were followed for a median time of 2533 (1035-3250) days. The demographical, clinical data and ambient temperature exposure were taken into analysis for prediction of all-cause mortality. Individual exposure was calculated based on the place of habitation. Results: In the multivariate logistic regression model with backward stepwise elimination method, risk factors such as dyslipidaemia (p = 0.001), kidney disease (p = 0.005), age (p = 0.006), and body mass index (p = 0.007) were found to be significant for late mortality prediction. In addition to traditional factors, environmental characteristics, including tropical nights (p = 0.043), were revealed to be significant. Conclusions: High night-time ambient temperatures known as tropical nights may be regarded as additional long-term mortality risk factor after surgical revascularization.