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To best prepare students for the real-world research environment, key skills, including experimental design, data analysis, communication of results, and critical thinking, should be key components of undergraduate science courses. Furthermore, the impact of the COVID-19 pandemic on in-person teaching has resulted in a need to develop courses that enable flexible learning. This paper details the laboratory component of a senior-level toxicology class that was developed to emphasize all these skills and allow for flexible learning. The aim of the laboratory class was for students to determine how curcumin protected against acetaminophen-induced hepatoxicity. To stimulate critical thinking, students were required to choose a maximum of four experiments from the six on offer. Before conducting an experiment, students stated a hypothesis and selected the appropriate treatment groups. Once an experiment was completed, students were given access to a complete dataset, on which they performed statistical analysis and drew conclusions. Students who were unable to attend the laboratory session in person were able to complete the required pre-lab work and access the dataset. Following each experiment, students could write a lab summary, and receive thorough feedback. The final assessment was a written manuscript of their findings as well as a chance to respond to reviewer comments. This teaching approach prioritized the critical thinking, analysis, and experimental design aspects of scientific research. Overall, this structure was well received by students and it could easily be adapted for use on other life science courses.

The prevalence and pervasive nature of emerging chemicals of concern have created widespread environmental injustice apprehensions in vulnerable communities. To alleviate and address these concerns, identifying, engaging, and training a diverse environmental health research workforce will be critical and necessary steps to combat and prevent the consequences of environmental injustice. While there is an obvious need to enhance diversity in environmental health research, this process is hampered by facets of systemic racism that reduce access to educational resources needed to build interest and knowledge in students and teachers. We present here a historical perspective to offer a guide for building programs and relationships with underserved schools to help overcome limiting factors that have plagued certain public school systems. With the proper training and mentorship, the untapped workforce present within these schools will be empowered to understand and address current and emerging environmental health and safety threats. Through this transformative 8-week high school research program, we will develop well-prepared, ethical researchers committed to scientific inquiry, intensive fieldwork, and collaborative problem solving to address environmental health challenges. Following the four-step risk assessment process, students, teachers, and faculty mentors will work collaboratively to identify toxicants, potential hazards and risks, and environmental disparities in urban neighborhoods, which provides the necessary training to formulate critical thinking skills for use in academic or nonacademic careers.

AIMS: The purpose of this study is to evaluate the accuracy and validity of the determination of cause of death (COD) and manner of death (MOD) at the completion of the forensic autopsy prosection. METHODS: We analysed 952 autopsy cases conducted from 2019 to 2020 and compared every patients COD, other significant contributing factors to death (OSC), and MOD after prosection to their COD, OSC and MOD after completion of the final autopsy report. RESULTS: We found that 83% of cases (790 patients) did not have an unexpected change and 17% of cases (162 patients) exhibited a true change in their final diagnosis; the relationship between age and changes in COD and MOD was significant. CONCLUSIONS: Our findings indicate that in the majority of forensic autopsy cases, medical professionals can reasonably complete death certification after the autopsy prosection. In addition to improving the accuracy of COD and MOD, advances in this field will enhance timely decedent affairs management, timely investigations of crimes and timely closure to families who have lost loved ones. We recommend implementing combined interventional education and consultation with expert pathologists, and a well-followed structured method of death classification as the best course of practice.

Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.

Background: Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990–1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. Methods: We evaluated PON1192 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1192 subgroups. Results: Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782). Conclusion: Study results suggest a complex pattern of PON1192 exposures and exposure–exposure interactions in the development of GWI.

Developmental exposures to PCBs are implicated in the etiology of neurodevelopmental disorders (NDDs). This observation is concerning given the continued presence of PCBs in the human environment and the increasing incidence of NDDs. Previous studies reported that developmental exposure to legacy commercial PCB mixtures (Aroclors) or single PCB congeners found in Aroclors caused NDD-relevant behavioral phenotypes in animal models. However, the PCB congener profile in contemporary human samples is dissimilar to that of the legacy Aroclors, raising the question of whether human-relevant PCB mixtures similarly interfere with normal brain development. To address this question, we assessed the developmental neurotoxicity of the Fox River Mixture (FRM), which was designed to mimic the congener profile identified in fish from the PCB-contaminated Fox River that constitute a primary protein source in the diet of surrounding communities. Adult female C57BL/6 J mouse dams (8-10 weeks old) were exposed to vehicle (peanut oil) or FRM at 0.1, 1.0, or 6.0 mg/kg/d in their diet throughout gestation and lactation, and neurodevelopmental outcomes were assessed in their pups. Ultrasonic vocalizations (USVs) and measures of general development were quantified at postnatal day (P) 7, while performance in the spontaneous alternation task and the 3-chambered social approach/social novelty task was assessed on P35. Triiodothyronine (T3) and thyroxine (T4) were quantified in serum collected from the dams when pups were weaned and from pups on P28 and P35. Developmental exposure to FRM did not alter pup weight or body temperature on P7, but USVs were significantly decreased in litters exposed to FRM at 0.1 or 6.0 mg/kg/d in the maternal diet. FRM also impaired male and female pups' performance in the social novelty task. Compared to sex-matched vehicles, significantly decreased social novelty was observed in male and female pups in the 0.1 and 6.0 mg/kg/d dose groups. FRM did not alter performance in the spontaneous alternation or social approach tasks. FRM increased serum T3 levels but decreased serum T4 levels in P28 male pups in the 1.0 and 6.0 mg/kg/d dose groups. In P35 female pups and dams, serum T3 levels decreased in the 6.0 mg/kg/d dose group while T4 levels were not altered. Collectively, these findings suggest that FRM interferes with the development of social communication and social novelty, but not memory, supporting the hypothesis that contemporary PCB exposures pose a risk to the developing brain. FRM had sex, age, and dose-dependent effects on serum thyroid hormone levels that overlapped but did not perfectly align with the FRM effects on behavioral outcomes. These observations suggest that changes in thyroid hormone levels are not likely the major factor underlying the behavioral deficits observed in FRM-exposed animals.

Electronic (e-) cigarette formulations containing nicotine salts from a range of organic acid conjugates and pH values have dominated the commercial market. The acids in the nicotine salt formulations may alter the redox environment in e-cigarettes, impacting free radical formation in e-cigarette aerosol. Here, the generation of aerosol mass and free radicals from a fourth-generation e-cigarette device was evaluated at 2 wt % nicotine salts (pH 7, 30:70 mixture propylene glycol to vegetable glycerin) across eight organic acids used in e-liquids: benzoic acid (BA), salicylic acid (SLA), lactic acid (LA), levulinic acid (LVA), succinic acid (SA), malic acid (MA), tartaric acid (TA), and citric acid (CA). Furthermore, 2 wt % BA nicotine salts were studied at the following nicotine to acid ratios: 1:2 (pH 4), 1:1 (pH 7), and 2:1 (pH 8), in comparison with freebase nicotine (pH 10). Radical yields were quantified by spin-trapping and electron paramagnetic resonance (EPR) spectroscopy. The EPR spectra of free radicals in the nicotine salt aerosol matched those generated from the Fenton reaction, which are primarily hydroxyl (OH) radicals and other reactive oxygen species (ROS). Although the aerosol mass formation was not significantly different for most of the tested nicotine salts and acid concentrations, notable ROS yields were observed only from BA, CA, and TA under the study conditions. The e-liquids with SLA, LA, LVA, SA, and MA produced less ROS than the 2 wt % freebase nicotine e-liquid, suggesting that organic acids may play dual roles in the production and scavenging of ROS. For BA nicotine salts, it was found that the ROS yield increased with a higher acid concentration (or a lower nicotine to acid ratio). The observation that BA nicotine salts produce the highest ROS yield in aerosol generated from a fourth-generation vape device, which increases with acid concentration, has important implications for ROS-mediated health outcomes that may be relevant to consumers, manufacturers, and regulatory agencies.

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals would benefit significantly from scalable and innovative approaches to testing using functionally comparable reproductive models such as the nematode C. elegans. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in the average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.MethodsThe present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74).ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

BackgroundA growing literature has reported associations between traffic-related air pollution and breast cancer, however there are fewer investigations into specific ambient agents and any putative risk of breast cancer development, particularly studies occurring in populations residing in higher pollution areas such as Los Angeles.ObjectivesTo estimate breast cancer risks related to ambient air toxics exposure at residential addresses.MethodsWe examined the relationships between ambient air toxics and breast cancer risk in the Multiethnic Cohort among 48,665 California female participants followed for cancer from 2003 through 2013. We obtained exposure data on chemicals acting as endocrine disruptors or mammary gland carcinogens from the National-Scale Air Toxics Assessment. Cox proportional hazards models were used to estimate breast cancer risk per one interquartile range (IQR) increase in air toxics exposure lagged by 5-years. Stratified analyses were conducted by race, ethnicity, and hormone receptor types.ResultsAmong all women, increased risks of invasive breast cancer were observed with toxicants related to industries [1,1,2,2-tetrachloroethane (hazard ratio [HR] = 4.22, 95% confidence interval [95% CI] 3.18-5.60), ethylene dichloride (HR = 2.81, 95% CI 2.20-3.59), and vinyl chloride (HR = 2.27, 95% CI 1.81, 2.85); these 3 agents were correlated (r2 = 0.45-0.77)]. Agents related to gasoline production or combustion were related to increased breast cancer risk [benzene (HR = 1.32, 95% CI 1.24, 1.41), ethylbenzene (HR = 1.20, 95% CI 1.13-1.28), toluene (HR = 1.29, 95% CI 1.20-1.38), naphthalene (HR = 1.11, 95% CI 1.02-2.22), acrolein (HR = 2.26, 95% CI 1.92, 2.65)]. Higher hazard ratios were observed in African Americans and Whites compared to other racial and ethnic groups (p-heterogeneity

BackgroundThere is a lack of research on the relationship between water fluoridation and pregnancy outcomes.ObjectivesWe assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California.MethodsWe linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7 ppm (the current level recommended by the US Department of Health and Human Services) and 0.5 ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z-scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers.ResultsFluoride levels ranged from 0 to 2.5 ppm, with a median of 0.51 ppm. There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7 ppm [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 95% CI: -10.0, -1.6). There were small negative associations with birth-weight-for-gestational-age z-scores for both hypothetical interventions (0.7 ppm: -0.004; 95% CI: -0.007, 0.000 and 0.5 ppm: -0.006; 95% CI: -0.013, 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7 ppm [risk difference (RD)=-0.001; 95% CI: -0.002, 0.000 and 0.5 ppm (-0.001; 95% CI: -0.003, 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention.ConclusionWe estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z-scores in California. https://doi.org/10.1289/EHP13732.

Academic medical institutions seek to recruit and retain a diverse workforce to foster equitable, supportive environments in which early-stage investigators, especially those who are underrepresented in medicine, can thrive. Intersectionality is a critical theoretical framework rooted in Black feminist activism and scholarship that elucidates how power and privilege are differentially structured for groups at different intersectional sociodemographic positions. As a dynamic method of analyzing multiple axes of power and inequality, intersectionality has the potential to offer a critical lens through which to view the mentor-mentee relationship. In this article, we seek to elaborate upon and extend the concept of intersectional mentoring, elucidate its essential components, and explore its application in the context of mentoring early-stage investigators in academic medicine. We propose that intersectional mentorship requires an orientation toward deep cultural humility, lifetime learning about the impact of systemic oppressions on present-day opportunities and experiences of mentees, and changing systems that perpetuate inequities by centering praxis-the application of principles of intersectionality through action to transform power dynamics in academic culture and institutions. Intersectional mentorship can help build a more equitable and representative workforce to advance intersectionally relevant and innovative approaches to achieving health equity.

Recent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by acute organophosphate (OP) intoxication. However, there are concerns that combined midazolam and allopregnanolone increases risk of adverse cardiovascular events. To address this, we used telemetry devices to record cardiovascular responses in adult male Sprague-Dawley rats acutely intoxicated with diisopropylfluorophosphate (DFP). Animals were administered DFP (4 mg/kg, sc), followed immediately by atropine (2 mg/kg, i.m.) and 2-PAM (25 mg/kg, i.m.). At 40 min post-exposure, a subset of animals received midazolam (0.65 mg/kg, im); at 50 min, these rats received a second dose of midazolam or allopregnanolone (12 mg/kg, im). DFP significantly increased blood pressure by ~ 80 mmHg and pulse pressure by ~ 34 mmHg that peaked within 12 min. DFP also increased core temperature by ~ 3.5 °C and heart rate by ~ 250 bpm that peaked at ~ 2 h. Heart rate variability (HRV), an index of autonomic function, was reduced by ~ 80%. All acute (within 15 min of exposure) and two-thirds of delayed (hours after exposure) mortalities were associated with non-ventricular cardiac events within 10 min of cardiovascular collapse, suggesting that non-ventricular events should be closely monitored in OP-poisoned patients. Compared to rats that survived DFP intoxication without treatment, midazolam significantly improved recovery of cardiovascular parameters and HRV, an effect enhanced by allopregnanolone. These data demonstrate that midazolam improved recovery of cardiovascular and autonomic function and that the combination of midazolam and allopregnanolone may be a better therapeutic strategy than midazolam alone.

BackgroundPrEP, a biomedical HIV prevention option, continues to be underutilized among transgender women who could benefit from sustained use, especially women of color and those who identify as Latina and/or reside in the southeastern US.ObjectiveWe explored the barriers and facilitators experienced by transgender women who live in Florida regarding accessing, using, and/or staying on PrEP.MethodsIn-depth interviews and focus groups were conducted in either Spanish or English with adult transgender women living in Florida (N = 22). The interviews were audio-recorded, transcribed, and coded in ATLAS.ti using thematic analyses.ResultsThe mean age of the participants was 42.2 years. Among the participants, 73% were Hispanic/Latina, 59% were foreign-born, and approximately one-third were living with HIV (but had past experience with PrEP). Transgender women cited the following barriers to accessing or considering PrEP: (1) costs and benefits of PrEP use; (2) under-representation in clinical trials resulting in unknown or misinformation regarding PrEP side effects; (3) chronic poverty; and (4) trauma and discrimination. Other stressors, such as behavioral healthcare needs, were identified.ConclusionsOur analysis revealed interlocking systems of oppression like transphobia, discrimination, and misgendering, which were common barriers experienced by our participants. These synergistically epidemic (i.e., syndemic) barriers contributed to their feelings of being systematically excluded in social spaces, research, public health planning and policies, laws, and social programs related to PrEP. These structural barriers are impediments to HIV preventive care but also act as a source of stress that contributes to mental health problems, financial vulnerability, substance abuse, and other deleterious health outcomes.

BackgroundHydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration.MethodsA total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally (n = 15), (ii) slow drip saline intratracheally (n = 15), (iii) fast drip saline intratracheally (n = 15), and (iv) slow drip cobinamide intratracheally (n = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy.ResultsThe mean (± standard deviation) weight for all animals (n = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups (P

(1) Background: American Indians are disproportionately affected by air pollution, an important risk factor for dementia. However, few studies have investigated the effects of air pollution on the risk of dementia among American Indians. (2) Methods: This retrospective cohort study included a total of 26,871 American Indians who were 55+ years old in 2007, with an average follow-up of 3.67 years. County-level average air pollution data were downloaded from land-use regression models. All-cause dementia was identified using ICD-9 diagnostic codes from the Indian Health Service’s (IHS) National Data Warehouse and related administrative databases. Cox models were employed to examine the association of air pollution with dementia incidence, adjusting for co-exposures and potential confounders. (3) Results: The average PM2.5 levels in the IHS counties were lower than those in all US counties, while the mean O3 levels in the IHS counties were higher than the US counties. Multivariable Cox regressions revealed a positive association between dementia and county-level O3 with a hazard ratio of 1.24 (95% CI: 1.02–1.50) per 1 ppb standardized O3. PM2.5 and NO2 were not associated with dementia risk after adjusting for all covariates. (4) Conclusions: O3 is associated with a higher risk of dementia among American Indians.

Introduction: Mushroom toxicity is an important etiology of acute liver injury in a patient with gastrointestinal symptoms.Case Report: We present the case of a male patient presenting to the emergency department (ED) with gastrointestinal distress who was placed under ED observation for elevated liver function tests. During his hospital course, it was revealed he had consumed wild mushrooms believed to be Amanita phalloides.Conclusion: While mushroom ingestion and subsequent toxicity are rare, a high index of suspicion in foraging hobbyists is essential to arriving at the correct diagnosis and directing the patient to the appropriate management.

BackgroundFluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA.ObjectiveTo identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.MethodsThe proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes.ResultsPathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation.ConclusionMaternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

BackgroundPrior studies suggested that air pollution exposure may increase the risk of Parkinson's Disease (PD). We investigated the long-term impacts of traffic-related and multiple sources of particulate air pollution on PD in central California.MethodsOur case-control analysis included 761 PD patients and 910 population controls. We assessed exposure at residential and occupational locations from 1981 to 2016, estimating annual average carbon monoxide (CO) concentrations - a traffic pollution marker - based on the California Line Source Dispersion Model, version 4. Additionally, particulate matter (PM2.5) concentrations were based on a nationwide geospatial chemical transport model. Exposures were assessed as 10-year averages with a 5-year lag time prior to a PD diagnosis for cases and an interview date for controls, subsequently categorized into tertiles. Logistic regression models were used, adjusting for various factors.ResultsTraffic-related CO was associated with an increased odds ratio for PD at residences (OR for T3 vs. T1: 1.58; 95% CI: 1.20, 2.10; p-trend = 0.02) and workplaces (OR for T3 vs. T1: 1.91; 95% CI: 1.22, 3.00; p-trend

BackgroundAutism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.MethodsIn Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (

The Delta Smelt is a largely zooplank­tivorous, endangered fish endemic to the San Francisco Estuary (the estuary). High flows increase the availability of fresh and brackish water habitat for Delta Smelt, but also may mobilize contaminants, potentially increasing toxicological stress. Here, we examine the association between contaminants and Delta Smelt health across contrasting water year types and flow-related management actions. Our study spanned the fall season of three years: 1 dry year (2018) bracketed by 2 wet years (2017 and 2019) and coincided with several management actions meant to benefit Delta Smelt. We collected field water from six sites in the estuary that encompass the freshwater and low-salinity habitat of Delta Smelt and analyzed the water for contaminant concentrations. After a 96-hour exposure to the field water, we assessed cultured Delta Smelt survival and the histopathological condition of the gill and liver. Insecticides, particularly fipronil metabolites, were the most prevalent contaminants detected in 2017 and 2018, and a variety of contaminants associated with the rice harvest were detected in 2019. No acute toxicity was observed during any exposure, but we observed negative effects in the livers of Delta Smelt exposed to agricultural water from the Toe Drain and Cache Slough during a 2019 pulse flow action, which coincided with elevated detections and concentrations of organic pesticides. Other noteworthy sub-lethal effects, likely occurring in response to contaminant mixtures, included severe gill lesions in Delta Smelt exposed to Decker Island water in 2019. In the drier year of 2018, lesions were generally mild or absent. Thus, the trade-offs between increased habitat availability and contaminant loading may provide one explanation for why Delta Smelt abundance does not consistently respond positively to outflow.

BackgroundOrganophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans.MethodsWe recruited 190 participants from a community-based epidemiologic study of Parkinson's disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson's disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray-Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders.ResultsOP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6.ConclusionIn support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.

INTRODUCTION: While known animal exposures to human drugs of abuse (DA) were previously considered relatively uncommon in veterinary medicine, the trends are changing. Marijuana and amphetamines are among the 20 toxicants most frequently consulted about with the Pet Poison Helpline. When such exposures occur, they are typically considered emergencies. METHODS: This retrospective study describes confirmed cases of DA exposure in pets from the California Animal Health and Food Safety Laboratory System (CAHFS), 2013-2023. RESULTS: Fifty-seven samples tested positive for DA through liquid chromatography with tandem mass spectrometry analysis (qualitative method). In 75% (43/57) of the DA screen tests, the detected drugs included amphetamine-type stimulants and metabolites (methamphetamine, amphetamine, or both). In 47% (27/57) of cases, a combination of more than one drug group was found. Most cases were diagnosed from a urine specimen. In at least 32% (18/57) of cases, the samples were submitted due to suspicions of animal cruelty, and at least 41% (23/57) of the patients were deceased when the samples were submitted. DISCUSSION: More studies on the prevalence of illicit drugs in small animals, using confirmatory testing, are warranted to fully understand the significance of this emerging toxicological hazard in veterinary medicine.

BackgroundA growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD).MethodsA total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group.ResultsA phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium.ConclusionsEarly childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in "non-survival sex work" had little difficulty staying on PrEP, while those engaged in "survival sex work" struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in "survival sex work" experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

BackgroundWidespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results.ObjectivesWe conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.MethodsWe included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex.ResultsThree OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (β for detect vs. nondetect=0.04-0.07); other chemicals showed null associations.DiscussionIn the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

BackgroundNeonatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk.Materials and methodsThis study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether an interquartile range (IQR) increase of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We assessed children of US-born and Mexico-born mothers, separately.Results and discussionAmong all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each IQR increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.06; 95% CI: 0.98, 1.16 per IQR increase). PFNA was not associated with retinoblastoma risk.ConclusionsOur results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California.

Cornified envelopes (CEs) of human epidermis ordinarily consist of transglutaminase-mediated cross-linked proteins and are essential for skin barrier function. However, in addition to enzyme-mediated isopeptide bonding, protein cross-linking could also arise from oxidative damage. Our group recently demonstrated abnormal incorporation of cellular proteins into CEs by pro-oxidants in woodsmoke. In this study, we focused on 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), mesquite liquid smoke (MLS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to further understand the mechanisms through which environmental pro-oxidants induce CE formation and alter the CE proteome. CEs induced by the ionophore X537A were used for comparison. Similar to X537A, DMNQ- and MLS-induced CE formation was associated with membrane permeabilization. However, since DMNQ is non-adduct forming, its CEs were similar in protein profile to those from X537A. By contrast, MLS, rich in reactive carbonyls that can form protein adducts, caused a dramatic change in the CE proteome. TCDD-CEs were found to contain many CE precursors, such as small proline-rich proteins and late cornified envelope proteins, encoded by the epidermal differentiation complex. Since expression of these proteins is mediated by the aryl hydrocarbon receptor (AhR), and its well-known downstream protein, CYP1A1, was exclusively present in the TCDD group, we suggest that TCDD alters the CE proteome through persistent AhR activation. This study demonstrates the potential of environmental pro-oxidants to alter the epidermal CE proteome and indicates that the cellular redox state has an important role in CE formation.

AbstractThe plant species C. sativum L. is a staple in cuisine and holds significant ethnopharmacological value. Its essential oil (EO) is of particular interest, yet its toxicity profile remains a subject of inquiry. This study aimed to elucidate the chemical constituents of C. sativum L. EO and evaluate its toxicity through various parameters, including cytotoxicity assays on HaCaT keratinocytes, in vivo toxicity tests on Galleria mellonella larvae, in vivo genotoxicity assessments on mice and cytotoxicity assays on human erythrocytes. Notably, major constituents such as 2-decen-1-ol, dec-(2E)-enal, and 1,6-octadien-3-ol were found to remain predominant. The IC50 value for the essential oil on the keratinocyte cell line was determined to be 60.13 ± 2.02 µg/mL. However, in vivo toxicity tests with G. mellonella larvae demonstrated safety at doses below 4.5 g/kg. Additionally, genotoxicity assessment revealed that a single dose of 20 mg/mL (5 mg/kg) did not induce a significant increase in micronuclei formation. EO concentrations above 250 µg/mL led to significant changes in human erythrocytes cell viability (p < 0.0001), resulting in over 60% hemolysis. These findings collectively suggest that the essential oil of C. sativum L. exhibits a suitable toxicity profile for conducting preclinical studies in vertebrate animal models. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionsChlorine and chloramine gas inhalation can occur when household cleaners are mixed. The increased emphasis on disinfecting practices during the COVID-19 pandemic may have contributed to an increase in chlorine and chloramine gas exposures in the United States, which has not been studied.In a retrospective review, reported data on chlorine and chloramine gas exposures in the National Poison Data System were collected from January 1, 2015, to December 31, 2022. Data included demographics and exposure details, including location, dose, formulation, co-exposures, treatments, and outcomes. Demographic analyses and descriptive statistics were conducted.During the study period, 85,104 total exposures to chlorine and chloramine gas were reported, consisting of 79,281 isolated exposures and 5,823 co-exposures. Total exposures increased by 61% from 8,385 in 2015 to 13,503 in 2022, with the largest increase of 38.3% occurring from 2019 to 2020. Total exposures remained increased through 2022 with no return to pre-pandemic levels. Most exposures occurred in “own residence” (n = 72,213, 84.9%), with a larger proportion of exposures occurring at home peri-pandemic versus pre-pandemic (88.4% versus 81.7%). One percent (n = 1,030) of exposures were admitted to a non-critical care unit, 0.73% (n = 619) were admitted to a critical care unit, and 0.03% (n = 26) resulted in death.The onset of the COVID-19 pandemic and increased emphasis on cleaning practices were likely contributing factors to the marked increase in exposures in 2020, which persisted through 2022. Cleaning practices that developed during the beginning of the pandemic likely persisted despite returning to more normal daily routines, which may explain the ongoing increase in reported exposures. Most reported exposures were unintentional, mild in symptomatology, and required the use of non-invasive therapies, if any.Future efforts should focus on public education on the safe use of cleaning products to prevent exposure to toxic chlorine and chloramine gases. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions In recent years gamma hydroxybutyrate (GHB) use appears to have increased. This study aimed to determine: (i) population rates of GHB‐related death in Australia, 2001–2021; and (ii) whether there have been changes in the characteristics of GHB‐related death in Australia over the period 2001–2023.Retrospective study of all Australian cases in which GHB was a mechanism contributory to death retrieved from the National Coronial Information System (n = 217). Joinpoint regression models were used to analyse trends in overall rates.Death rates were stable between 2001 and 2015 (‘stable period’) (annual percent change [APC] = 3.7) but showed marked acceleration between 2016 and 2021 (‘accelerated period’) (APC = 44.4). Circumstances of death were: unintentional toxicity (81.6%), intentional toxicity (5.1%), self‐harm (6.0%), traumatic injury (7.4%). Compared to the stable period, later cases were slightly older (34.2 vs. 30.7 years, p < 0.05), less likely to be employed (odds ratio [OR] 0.4), but more likely to have substance use problems (OR 3.9), a history of injecting drug use (OR 3.5), mental health problems (OR 3.6), and to have present in their blood at toxicological screening opioids (OR 3.2) and hypnosedatives (OR 3.7). The median blood GHB concentration was 170 mg/L, (range 0–3210), which did not change significantly. There were no differences in major organ pathology, but the proportion with aspiration pneumonia declined (OR 0.4).GHB‐related death rates increased from 2016, accompanied by changes in case characteristics. In recent years GHB use appears to have extended to a population more likely to have substance use problems and use other respiratory depressants. [ABSTRACT FROM AUTHOR]

Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma in situ. Cancer is the second-leading cause of mortality worldwide, and a more than 61% increase is expected by 2040. A detailed exploration of cancer progression pathways, including the NF-κβ signaling pathway, Wnt-B catenin signaling pathway, JAκ-STAT pathway, TNF-α-mediated pathway, MAPκ/mTOR pathway, and apoptotic and angiogenic pathways and effector molecules involved in cancer development, has been discussed in the manuscript. Critical evaluation of these effector molecules through molecular approaches using phytomolecules can intersect cancer formation and its metastasis. Manipulation of effector molecules liκe NF-κβ, SOCS, β-catenin, BAX, BAκ, VEGF, STAT, Bcl2, p53, caspases, and CDκs has played an important role in inhibiting tumor growth and its spread. Plant-derived secondarymetabolites obtained fromnatural sources have been extensively studied for their cancer-preventing potential in the last few decades. Eugenol, anethole, capsaicin, sanguinarine, EGCG, 6-gingerol, and resveratrol are some examples of such interesting lead molecules and are mentioned in the manuscript. This worκ is an attempt to put forward a comprehensive approach to understanding cancer progression pathways and their management using effector herbal molecules. The role of different plant metabolites and their chronic toxicity profiling in modulating cancer development pathways has also been highlighted. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsDiscussionConclusionCo-use of stimulants and opioids is often deliberate. However, the possibility remains that some people are unintentionally consuming fentanyl. To advance understanding of overdose risk, we examined the rate of concordance between self-reported fentanyl use and corresponding urine toxicology screen results.Between August 2022–August 2023, 411 participants (adults who reported any non-medical drug use in the past three months) in Nevada and New Mexico completed a cross-sectional survey, of whom 64% (n = 270; the analytical sample) also completed a urine toxicology screen, which detects fentanyl use in the past three days. Positive predictive value, negative predictive value, sensitivity, and specificity were calculated using self-reported past three-day fentanyl use (yes/no) and urine toxicology screen results for the presence of fentanyl (positive/negative).Of the 270 participants who provided a urine sample, 268 are included in the descriptive statistics (two with inconclusive urine toxicology screen results were excluded). Of the 268 participants, 146 (54.5%) had a fentanyl-positive urine toxicology screen result, 122 (45.5%) had a fentanyl-negative urine toxicology screen result, 137 (51.1%) reported past three-day fentanyl use, and 130 (48.5%) reported no past three-day fentanyl use. Only 6.9% of those with a fentanyl-positive urine toxicology screen did not report recent fentanyl use. The sensitivity of self-reported fentanyl use was 93%, specificity was 97%, positive predictive value was 97%, and negative predictive value was 92%.The rate of unanticipated exposure to fentanyl (that is, positive urine screen and negative self-report) in this sample was low, at 6.9%. This runs counter to the national narrative that there is widespread unknown contamination of fentanyl in the drug supply.Future research is needed to further explore how people who use multiple substances interpret their overdose risk and what harm reduction methods they employ. [ABSTRACT FROM AUTHOR]

Background: Metabolomics is the study of metabolites in cells, tissues, live organisms, and biological fluids to elucidate their composition and possible roles. Metabolomics and its biomarkers have emerged as a powerful tool for evaluating the efficacy of probiotics in various pathological conditions, including toxicological settings. This review explores the use of metabolomics-based markers to assess the safety and efficacy of probiotics in toxicological settings. Result: This review aims to determine biomarkers for measuring the effectiveness of probiotic therapies in toxicological contexts based on exposure, effects, susceptibility, prognostic, and therapeutic biomarkers. In this study, 1979 articles were systematically searched in PubMed (PM), Scopus (Sc), Google Scholar (GS), and Web of Science (WOS) between the years 2013 and 2023 inclusive using keywords, inclusion, and exclusion criteria. The result showed that 1439 human samples were used from 2013 to 2023 publications with the UK having the highest number of publications, data, and sample types in 2023. Again, the result showed most of the publications are on susceptibility-based biomarkers. Conclusion: Metabolomics-based biomarkers may provide insight into metabolism-related alterations related to probiotic therapies while clarifying their biological mechanisms, especially in toxicology enabling specific probiotic therapy. [ABSTRACT FROM AUTHOR]

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The present study explores the synthesis and bio-safety evaluation of gadolinium-doped carbon quantum dots (GCQDs) as a potential dual-contrast agent for diagnostic imaging. GCQDs exhibit both fluorescent and magnetic properties, making them suitable for UV–Vis and magnetic resonance imaging (MRI). The synthesis of GCQDs was achieved via hydrothermal treatment, incorporating gadolinium into the carbon quantum dot matrix. The magnetic properties of GCQDs were analyzed, showing significantly enhanced values compared to gadobutrol, a common MRI contrast agent. However, synthesis constraints limit the gadolinium content achievable in nanodots. To assess the safety of GCQDs, their effects on the embryonic development of zebrafish (Danio rerio) were examined. Various concentrations of GCQDs were tested, observing mortality rates, hatchability, malformations, heartbeats, spontaneous movement, and GCQDs uptake. Dialysis studies indicated that gadolinium ions are incorporated into the internal structure of the carbon nanodots. Zebrafish toxicity tests revealed that while survival rates were comparable to control groups, hatchability decreased significantly with higher gadolinium concentrations in GCQDs. Fluorescence microscopy showed no statistical differences in the fluorescence intensity between groups. These findings suggest that GCQDs could serve as an effective dual-contrast agent, combining the optical imaging capabilities of CQDs with the enhanced MRI contrast provided by gadolinium. This study underscores the need for further research on the synthesis methods and biological interactions of GCQDs to ensure their safety and efficacy in medical applications. [ABSTRACT FROM AUTHOR]

Background and aims: Lysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD‐ and psilocybin‐related death in Australia, 2000–23; and (2) determine the toxicological profile and major autopsy findings of these cases. Methods: This was a retrospective exploratory study of all cases of LSD‐ and psilocybin‐related death in Australia, 2000–23, retrieved from the National Coronial Information System. Results: A total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16–53] (LSD) and 26 years (IQR = 18.5, range = 20–58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD 36.4%, psilocybin 40.0%). There were 12 cases of self‐harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD 18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD 27.3%, psilocybin 20.0%). Median blood concentrations were LSD 0.8 μg/l (IQR = 1.7, range = 0.1–3), psilocin 20 μg/l (IQR = 53.5, range = 6–83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre‐existing organ pathology was uncommon. Conclusions: Lysergic acid diethylamide (LSD)‐ and psilocybin‐related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self‐harm. Cases of acute toxic reactions that were attributed solely to LSD were rare. [ABSTRACT FROM AUTHOR]

The advancement of medical toxicology knowledge has traditionally relied on case reports and case series because of the ethical challenges involved in studying poisoned patients. The growing availability of several large databases and registries now allows researchers to describe and analyze patterns in poisoned patients who share a particular exposure, outcome, or condition. A large database or registry can be useful in generating hypotheses, supporting extramural funding applications, and planning more rigorous studies. Knowing how to access and interpret data in registries such as NPDS, NHAMCS, and HCUP is essential for all stakeholders engaged in medical toxicology research. This review describes the strengths and limitations of different toxicology-relevant registries and databases and how to leverage these powerful tools to advance the science in the field of medical toxicology. [ABSTRACT FROM AUTHOR]

The Toxicology Investigators Consortium (ToxIC) was launched as a prospective multi-center registry of cases who receive medical toxicology consultations. Now, with over 100,000 cases, the Core Registry continues to address many medical toxicology research questions and has served as the foundation for multiple sub-registries, including the North American Snakebite Registry and the Medications for Opioid Use Disorder sub-registry. ToxIC also has evolved a portfolio of non-registry-based projects utilizing medical toxicology physician site principal investigators who enroll patients through emergency departments, irrespective of whether they received a medical toxicology consultation. These studies include the FDA-ACMT COVID-19 ToxIC Pharmacovigilance Project, which identifies adverse drug reactions related to the treatment of COVID-19, the Fentalog Study a toxico-surveillance study of suspected opioid overdose cases, the Drug Overdose Toxico-Surveillance Reporting Program which enrolls either suspected stimulant or opioid overdose cases, and the just being launched Real-World Examination of Naloxone for Drug Overdose Reversal project. Given ToxIC's experience in multi-center studies and its well-developed infrastructure, it is well-positioned to provide a nimble response on the part of the medical toxicology community to addressing evolving toxicological threats, drug and chemical toxicosurveillance, and other important medical toxicology priorities. [ABSTRACT FROM AUTHOR]

Given environmental persistence, potential for bioaccumulation, and toxicity of Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the scientific community has increasingly focused on researching their toxicology and degradation methods. This paper presents a survey of recent research advances in the toxicological effects and degradation methods of PFOA and PFOS. Their adverse effects on the liver, nervous system, male reproductive system, genetics, and development are detailed. Additionally, the degradation techniques of PFOA and PFOS, including photochemical, photocatalytic, and electrochemical methods, are analyzed and compared, highlighted the potential of these technologies for environmental remediation. The biotransformation pathways and mechanisms of PFOA and PFOS involving microorganisms, plants, and enzymes are also presented. As the primary green degradation pathway for PFOA and PFOS, Biodegradation uses specific microorganisms, plants or enzymes to remove PFOA and PFOS from the environment through redox reactions, enzyme catalysis and other pathways. Currently, there has been a paucity of research conducted on the biodegradation of PFOA and PFOS. However, this degradation technology is promising owing to its specificity, cost-effectiveness, and ease of implementation. Furthermore, novel materials/methods for PFOA and PFOS degradation are presented in this paper. These novel materials/methods effectively improve the degradation efficiency of PFOA and PFOS and provide new ideas and tools for the degradation of PFOA and PFOS. This information can assist researchers in identifying flaws and gaps in the field, which can facilitate the formulation of innovative research ideas. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd‐exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd‐exposed rats had increased liver cholesterol levels, insulin receptor beta (IRβ) and peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats. [ABSTRACT FROM AUTHOR]

Background/ Objectives: Rosacea is a common chronic inflammatory skin disorder. Endocrinedisrupting chemicals (EDC) are toxic substances, that may gain entry through the skin and subsequently interfere with hormonal and immune functions. Bisphenol A (BPA) and pentachlorophenol sodium (PCS) are two of these EDCs, incriminated in the pathogenesis of certain inflammatory skin disorders. We aimed to test the hypothesis that exposure to BPA and PCS might be involved in the pathogenesis of rosacea. Methods: This prospective cross-sectional study involved 34 patients with rosacea (18F/16 M; mean age 48.5 ± 11 years) and 34 age and sex-matched healthy controls (20 F/14 M; mean age 48.2 ± 10.2 years). Main anthropometric measures, fasting plasma glucose (FPG), insulin, HOMA-IR, lipids, C-reactive protein (CRP), BPA, and PCS levels were quantified and recorded. Results: Serum CRP (9.6 ± 3.4 vs. 3.7 ± 1.6 mg/L, respectively, p0.05 for all). Serum BPA levels were 55.8 ± 14.4 and 51.9 ± 19.2 ng/mL, and PCS levels were 63.3 ± 45.9 ng/mL and 68.6 ± 40.8 ng/mL for patients and healthy controls, respectively. There was no significant difference in BPA and PCS levels between the two groups (p > 0.05 for both). No significant association was found among HOMAIR, CRP, BPA, and PCS levels (p > 0.05 for all). Conclusions: Although the present study fails to provide presumptive evidence for the role of BPA and PCS in rosacea, the question as to other EDCs might be involved in its etiopathogenesis remains. This hypothesis requires confirmation in large-scale future prospective trials. [ABSTRACT FROM AUTHOR]

Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects. [ABSTRACT FROM AUTHOR]

Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network‐based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network‐based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data‐driven approaches for the hazard assessment of nanomaterials and other advanced materials. [ABSTRACT FROM AUTHOR]

AbstractThis article aims to provide a comprehensive critical, yet readable, review of general interest to the chemistry community on molecular similarity as applied to chemical informatics and predictive modeling with a special focus on read-across (RA) and read-across structure–activity relationships (RASAR). Molecular similarity-based computational tools, such as quantitative structure–activity relationships (QSARs) and RA, are routinely used to fill the data gaps for a wide range of properties including toxicity endpoints for regulatory purposes. This review will explore the background of RA starting from how structural information has been used through to how other similarity contexts such as physicochemical, absorption, distribution, metabolism, and elimination (ADME) properties, and biological aspects are being characterized. More recent developments of RA’s integration with QSAR have resulted in the emergence of novel models such as ToxRead, generalized read-across (GenRA), and quantitative RASAR (q-RASAR). Conventional QSAR techniques have been excluded from this review except where necessary for context. [ABSTRACT FROM AUTHOR]

Bioherbicides are expected to be a supplement to integrated pest management, assisting in the control of problematic weed species. For instance, bioherbicides (Phoma and BioPhoma) were recently registered in Canada and the USA for the control of some perennial dicotyledonous weeds in lawns. These products are based on strains of the fungus Didymella macrostoma (syn. Phoma macrostoma) that causes white tip disease (WTD) in Canada thistle (Cirsium arvense). In this study, WTD was reported for the first time in the Russian Federation. Analysis of the internal transcribed spacer (ITS) region of nuc rDNA and secondary metabolite profiling confirmed the identity of Russian WTD isolates to Canadian biocontrol strains identified as D. macrostoma. Multilocus phylogenetic analysis based on sequencing of the ITS region, partial large subunit nuc rDNA region (28S), RNA polymerase II second largest subunit gene (rpb2), and partial β-tubulin gene (tub2) has differentiated the WTD isolates from C. arvense and D. macrostoma isolates from other plant hosts. Based on phylogenetic, morphological, and chemotaxonomic features, these WTD isolates were described as a new species named Didymella baileyae, sp. nov. This study also demonstrated the low pathogenicity of the ex-type D. baileyae isolate VIZR 1.53 to C. arvense seedlings and its asymptomatic development in the leaves of aboveground shoots. The organic extracts from mycelium and culture filtrate of D. baileyae, as well as macrocidin A and macrocidin Z, displayed phytotoxicity both to C. arvense leaves and seedlings. Macrocidin A was only detected in the naturally infected leaf tissues of C. arvense showing WTD symptoms. Macrocidins A and Z demonstrated low antimicrobial and cytotoxic activities, exhibiting no entomotoxic properties. The data obtained within this study on the pathogenicity and metabolites of D. baileyae may be important for the rational evaluation of its prospects as a biocontrol agent. [ABSTRACT FROM AUTHOR]

This study focuses on developing machine learning models to detect subtle alterations in hepatocyte chromatin organization due to Iron (II, III) oxide nanoparticle exposure, hypothesizing that exposure will significantly alter chromatin texture. A total of 2000 hepatocyte nuclear regions of interest (ROIs) from mouse liver tissue were analyzed, and for each ROI, 5 different parameters were calculated: Long Run Emphasis, Short Run Emphasis, Run Length Nonuniformity, and 2 wavelet coefficient energies obtained after the discrete wavelet transform. These parameters served as input for supervised machine learning models, specifically random forest and gradient boosting classifiers. The models demonstrated relatively robust performance in distinguishing hepatocyte chromatin structures belonging to the group exposed to IONPs from the controls. The study's findings suggest that iron oxide nanoparticles induce substantial changes in hepatocyte chromatin distribution and underscore the potential of AI techniques in advancing hepatocyte evaluation in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionsTricyclic antidepressants often cause drug-induced QRS complex prolongation in overdose but are now less commonly prescribed. We sought to determine, among a contemporary cohort of patients, the pharmaceuticals independently associated with QRS complex prolongation in acute overdose.We performed secondary analysis of data from the Toxicology Investigators Consortium (ToxIC) Core Registry. We included adult patients presenting from January 2016 through March 2023 with acute or acute-on-chronic pharmaceutical exposures. The primary outcome was QRS complex prolongation >0.12 s. Secondary outcomes included cardiac arrest, death, ventricular dysrhythmia, intensive care unit admission, initiation of vasopressors, and treatment with sodium bicarbonate. We used a multivariable logistic regression model with QRS complex prolongation as the outcome and individual pharmaceuticals of interest as independent variables. We assessed yearly trends of the contribution of relevant pharmaceuticals to QRS complex prolongation since 2016.Of 11,945 patients in the total cohort (median age 37 years, 6,652 [55.7%] female), 366 (3.1%) developed QRS complex prolongation. Of 9,417 patients included in the model, 290 (3.1%) developed QRS complex prolongation. Amitriptyline, nortriptyline, doxepin, imipramine, noxiptiline, bupropion, flecainide, carvedilol, propranolol, diphenhydramine, and lamotrigine poisonings were independent predictors of QRS complex prolongation. Flecainide poisoning conferred the greatest odds of QRS complex prolongation (OR 574.1; 95% CI: 88.3–12,747). The contribution of tricyclic antidepressants to QRS complex prolongation decreased from 38.8% to 17.6% of all patients with QRS complex prolongation from 2016 to 2022. In 2022, the proportion of QRS complex prolongation from diphenhydramine (20.6%) surpassed that of tricyclic antidepressants.This study provides insights into contemporary pharmaceutical poisoning associated with QRS complex prolongation. Tricyclic antidepressants remain clinically relevant exposures but are no longer the most common cause of drug-induced QRS complex prolongation.Bupropion, diphenhydramine, and antidysrhythmics are increasingly common causes of QRS complex prolongation, each associated with numerous severe outcomes in poisoning. Greater safety measures to protect patients from cardiovascular toxicity from these pharmaceuticals are warranted. [ABSTRACT FROM AUTHOR]