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249 p., The main objective of the present thesis has consisted in implementing a life cycle-oriented perspective when assessing the risks associated to synthetic chemicals including biocides and engineered nanomaterials (ENMs) as examples of conventional and emerging contaminants, respectively.In the case of biocidal products, in general, once used, biocidal active substances can easily reach aquatic compartments where they are transformed in metabolites, degradation and transformation products. However, the hazard of such substances towards trophic levels representative of the freshwater compartment is less known than that of the parent compounds.For EMNs, the different processes that nanotechnology enabled products and/or applications (NEPs/NEAs) undergo throughout their life cycle need to be simulated in a controlled environment for the assessment of their potential release and associated exposure to their released forms. We have developed two nano-release assessment studies selecting (i) a NEA in solid state, generally aimed to be used at industrial scale at the indoor compartment (polypropylene based nanocomposite samplesintegrating different types of (nano)fillers) and (ii) a NEP in liquid state, aimed to be used by consumers at the indoor compartment (nano-additivated inkjet printing ink).We have demonstrated that under a holistic, life cycle-oriented perspective that includes use and end of life stages, novel risks differing from those derived from the manufacturing stage occur.Finally, we have evaluated the possibility to derive new characterization factors for human respiratory and ecotoxicity of one of the case studies for ENMs in order to account for the specific impacts of these emerging chemicals in the life cycle assessment framework according to ISO 14040.

Harmful algal blooms (HABs) are a global concern in both freshwater and coastal systems; creating dire consequences for public health, water resources, and local economies. Thus, there is a focus among scientists and environmental managers on HAB prediction, prevention, and mitigation. Current chemical mitigation methods include algicides such as copper sulphate, chlorination, and hydrogen peroxide, which can have high financial costs and secondary pollution associated with them. The use of natural allelochemicals produced by plants and bacteria has received considerable attention as an alternative to synthetic algicides, as they can have negligible toxins, be highly selective, and easily degraded in the environment. This dissertation is a coalition of research looking into new sources of plant allelochemicals and whether natural levels of allelochemicals in the water column, can impact phytoplankton communities and the presence of toxin-producing algal species. The first objective focused on the use of the waste product: brewer’s spent grain (BSG), as a new control mechanism to inhibit the growth of toxic algae. BSG extract of doses higher than 250mg/L inhibited the growth of freshwater and marine toxin-producing cyanobacteria and dinoflagellate species (Microcystis aeruginosa and Karenia brevis), while not impacting the diatom and chlorophyte tested (Scenedesmus obliquus and Prorocentrum tricornutum). This same dosage of BSG caused cyanobacteria abundance in lake water to decline by 90% within 4 days and chlorophytes to dominate the community by day 6 during a microcosm study. However, an experiment controlling bacteria levels demonstrated that the decline of K. brevis growth was likely due to the increase in abundance or presence of certain types of bacteria growing with exposure to BSG extract rather than due to chemicals released from the BSG. The second and third objectives shifted focus to the New Jersey Pinelands and whether the chemicals released into the w

Gene regulation during embryogenesis is required for executing the program fordevelopment, as well as responding to the environment in a context-specific manner. Nuclear receptors (NRs) are transcription factors that modulate gene expression, often in response to xenobiotics. However, NRs role in early development remains less understood. To address this gap, a marine model organism like the sea urchin, Strongylocentrotus purpuratus, is ideal for studying NRs during embryogenesis. This study screened 10 NRs important for cellular defense and localized mRNA through colorimetric and fluorescence whole mount in-situ hybridization at key developmental stages. With this initial screen, we found two NRs with localized expression patterns. These include: hnf1a, expressed primarily in the developing hindgut and later in larval gut and ciliary band and ppara1, which localized to the larval foregut and midgut. With hybridization chain reaction in-situ, ppara1 is confirmed to be localized in the gut along with ppargc1, a coactivator for ppara1. Coactivators are recruited after a NR is ligand bound and facilitates transactivation. NRs were further characterized with scRNA-seq data in the 72 hpf embryo and AlphaFold protein modeling to predict structure and binding. With scRNA-seq, rxr, a NR that heterodimerizes with ppara1, was found expressed in the larval gut. AlphaFold models the ligand binding domain helices and residues responsible for ligand binding and predicts Sp-PPAR:RXR heterodimer functions in binding to the pollutant tributyltin chloride. This study lays the conceptual framework for researching PPAR:RXR function to understand gene regulation by both endogenous and xenobiotic ligands.

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa2EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was >10-times more effective than CaNa2EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.

This research sought to understand health effects associated with electronic cigarettes (ECs) by: (1) analyzing EC-induced symptoms reported online and in case reports, (2) examining exposure, retention, environmental accumulation, and the relationship between symptoms and dose in JUUL Menthol users, (3) assessing the cytotoxicity of popular ECs, (4) identifying reaction products generated from aerosols of refill fluids reported to induce sickness, and (5) characterizing the toxicity of the dominant reaction product, hydroxyacetone. Using automated computer mining, self-reported symptoms and disorders were captured from a major online EC forum from 2009 to 2015. EC use was associated with respiratory, neurological, and other symptoms. Popular EC refill fluids were identified using by interviewing local store clerks. Dominant flavor chemicals (e.g., maltol, ethyl maltol) were cytotoxic to human bronchial epithelial cells (BEAS-2B) in the MTT assay. To examine the link between EC exposure and symptoms, the puffing topography, exhale, percent transfer of chemicals from pod fluid to aerosol (transfer efficiency), and commonly reported symptoms were then assessed in 11 male JUUL Menthol EC users. The dominant chemicals (nicotine, menthol, propylene glycol, and glycerol), transferred well to aerosols with high retention within participants. A dose-response was observed between the total dominant chemical mass retained and symptoms. To understand the health effects of ECs, a “sickness inducing library” (SIL) of refill fluids was purchased based on online posts linking symptoms to specific products. Reaction products were identified in aerosolized SIL fluids. Hydroxyacetone, the dominant reaction product, affected BEAS-2B cell survival, growth, metabolic activity, F-actin integrity, and oxidative stress. Air-liquid interface (ALI) exposure of 3D EpiAirway tissue to hydroxyacetone followed by proteomics analysis supported the BEAS-2B cell responses and showed effects on xeno

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 target 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.

ObjectivesWe show that participatory research approaches can be a useful tool across disciplines and data collection methods to explore the socio-exposome near one of the largest industrial harbors in Europe. We analyzed resident involvement in each project and their capacity to affect structural changes.MethodsLongitudinal participatory environmental monitoring studies on lichens, petunias, aquatic systems and groundwater were conducted under the program VOCE (Volunteers for the Citizens' Observation of the Environment), which mobilized nearly 100 volunteers to collect and report data. A community-based participatory health survey, Fos EPSEAL was also carried out during the same period. We describe citizens' involvement in each study following Davis and Ramirez-Andreotta's (2021) 'best practice' grid. We also use residents' insights to refine understanding of the socio-exposome.ResultsThe region is significantly impacted by industrial pollution and fenceline communities are disproportionately exposed. The community-based participatory health survey documented negative health outcomes among the residents, including a higher prevalence of chronic symptoms and diabetes (e.g., 11.9%) in the Fos-Berre Lagoon region than in other communities. This methodology shows the benefits of the co-production of knowledge in environmental health: not only does it enable epistemological transformations favorable to the vulnerable population, but it also triggered public action (i.e., media and public authorities' attention leading to official expertise reports, filing of collective complaints before the courts).ConclusionThis body of multiple participatory research studies over time is a useful approach to better understand the socio-exposome and health issues in an industrial zone.

We examined the associations between time perspective and mental health outcomes (N = 337; Mage = 22.74, SDage = 5.59; 76% female). Time perspective included multiple dimensions (feelings, frequency, orientation, and relation) and time periods (past, present, and future). Mental health outcomes included depressive symptoms, anxiety, and rumination. To demonstrate the reliability of the time perspective scales, test-retest analyses were completed. Multivariate analyses showed that (a) positive feelings about time were associated with lower anxiety; (b) negative feelings about time were associated with greater anxiety; and (c) more frequent thoughts about the past were associated with greater depressive symptoms and anxiety. Associations remained when controlling for anxiety and depressive symptoms, respectively. Moreover, (a) positive feelings about time were associated with lower rumination; (b) negative feelings about time were associated with greater rumination; and (c) more frequent thoughts about the past were associated with greater rumination. Time perspective scales yielded scores that were moderate to high in test-retest reliability. Findings demonstrate the value of examining separate time perspective dimensions and time periods. Results highlight the role of time perspective in mental health interventions for adults.

The Tara Microplastics mission was conducted for 7 months to investigate plastic pollution along nine major rivers in Europe—Thames, Elbe, Rhine, Seine, Loire, Garonne, Ebro, Rhone, and Tiber. An extensive suite of sampling protocols was applied at four to five sites on each river along a salinity gradient from the sea and the outer estuary to downstream and upstream of the first heavily populated city. Biophysicochemical parameters including salinity, temperature, irradiance, particulate matter, large and small microplastics (MPs) concentration and composition, prokaryote and microeukaryote richness, and diversity on MPs and in the surrounding waters were routinely measured onboard the French research vessel Tara or from a semi-rigid boat in shallow waters. In addition, macroplastic and microplastic concentrations and composition were determined on river banks and beaches. Finally, cages containing either pristine pieces of plastics in the form of films or granules, and others containing mussels were immersed at each sampling site, 1 month prior to sampling in order to study the metabolic activity of the plastisphere by meta-OMICS and to run toxicity tests and pollutants analyses. Here, we fully described the holistic set of protocols designed for the Mission Tara Microplastics and promoted standard procedures to achieve its ambitious goals: (1) compare traits of plastic pollution among European rivers, (2) provide a baseline of the state of plastic pollution in the Anthropocene, (3) predict their evolution in the frame of the current European initiatives, (4) shed light on the toxicological effects of plastic on aquatic life, (5) model the transport of microplastics from land towards the sea, and (6) investigate the potential impact of pathogen or invasive species rafting on drifting plastics from the land to the sea through riverine systems.

Particle matter (PM) is a complex mixture of particles suspended in the air, mainly caused by fuel combustion from vehicles and industry, and has been related to pulmonary and cardiovascular diseases. The Metropolitan Area of Aburrá Valley in Colombia is the second most populous urban agglomeration in the country and the third densest in the world, composed of ten municipalities. Examining the physicochemical properties of PM is crucial in comprehending its composition and its effects on human health, as it varies based on the socioeconomic dynamics specific to each city. This study characterized the PM collected from the north, south, and central zones to evaluate its chemical composition and morphology. Different elements such as silicon, carbon, aluminum, potassium, calcium, sodium, iron, magnesium, and copper and the presence of unburned fuel, motor oil, and silicon fibers were identified. In vitro and in silico studies were conducted to evaluate the toxicity of the PM, and it was found that the PM collected from the central zone had the greatest impact on cell viability and caused DNA damage. The in silico study demonstrated that PM has concentration-dependent proarrhythmic effects, reflected in an action potential duration shortening and an increased number of reentries, which may contribute to the development of cardiac arrhythmias. Overall, the results suggest that the size and chemical composition of ambient PM can induce toxicity and play an important role in the generation of arrhythmias, This work was supported by the Ministerio de Ciencia Tecnología e Innovación (MINCIENCIAS) from Colombia, through grant No. 120677757994 and by the Dirección General de Política Científica de la Generalitat Valenciana PROMETEO/2020/043. The work of Palacio was supported by the “Programa de excelencia doctoral del Bicentenario 2019” of MINCIENCIAS. The work of Durango-Giraldo and Zapata-Hernandez was supported by the “Convocatoria para el fortalecimiento de proyectos en ejecución de CTeI en ciencias de la salud con talento joven e impacto regional” of MINCIENCIAS, Postprint (published version)

Wildfire smoke is a global issue affecting nearly all humans on the surface of this Earth. Smoke dispersion from wildfires can span continents and cross oceans with amazing ease. Furthermore, total acres of land burned per year in the United States has roughly doubled since 1980, meaning this issue will persist for an indeterminate amount of time. Exposure to wildfire smoke is hazardous and promotes aging-associated events in the cardiopulmonary systems. Yet long- and short-term effects on the brain remain relatively unknown. From these, it is critically important to understand the neurological impacts from wildfire smoke exposure; to compare these effects to a more replicable woodsmoke exposure systems in a lab setting; and to endeavor mitigation strategies. In our first study, we serendipitously exposed mice to wildfire smoke at a distance >1,000 km from the fire source (California, 2020). The exposure quantification revealed an ebb and flow of PM2.5 (particulate matter 2.5 µM diameter)concentration intensities, and variations in the levoglucosan abundance (measure of woodsmoke content). Upon sacrifice, we found markers of blood brain barrier (BBB) permeability, neuronal damage, inflammation, peripheral immune infiltration, and markers that indicated an acceleration of brain aging. Initial follow-up studies utilized an in-lab woodchip smoldering exposure system to determine the neuroinflammatory temporal dynamics and metabolomic effects of inhaled wildfire smoke. We attempted to model our exposure paradigm based on a lower concentration than millions of Americans receive during yearly wildfires. Our results revealed that vascular inflammation resolved before our experimental cutoff timepoint of 28 days. However, peripheral immune infiltration increased 14 days post exposure, and inflammation persisted in the brain until our final timepoint of 28 days. Slightly more alarming, markers of brain aging and damage were observed at the 28-day

Introduction: E-cigarettes are advertised as safer alternative to tradicional cigarettes. However, they contain chemicals that can exhibit toxic effects on the organism. Notably, effects of e-cigarettes on in utero development are not well studied. We wanted to compare potential toxic effects of e-cigarette liquid and vapor condensate on development of zebrafish embryos. Methods: Six hour old zebrafish embryos were exposed to different concentrations of e-cigarette liquid or vapour condensate – 0.1% and 1%. Untreated embryos were used as control. Each treatment and control were set up in triplicate, with at least 20 embryos per treatment. The effects on survival, hatching and developmental malformations were monitored using light microscopy, at 3 timepoints - 24, 48 and 72 hours post fertilization (hpf). Results: No noticeable differences between control and treated groups were observed 24 hpf. Hatched larvae (35%) treated with 0.1% condensate had scoliosis and malformations- yolk sac and pericardial edema at 48 hpf. In groups treated with 1% of condensate or liquid, hatching was delayed and did not start 48 hpf. At 72 hpf timepoint, in wells with 1% condensate, less than 30% of larvae hatched in total, which was comparable to wells with e-cigarette liquid (25%). Malformations that were observed in all treatements are hemagglutionation, pericardial or yolk sac edema, and scoliosis. In groups with 0.1% condensate these maformations were observed in lower number of embryos, but the percentage of hatched larvae was higher (approximately 80%) at 72 hpf. Conclusions: Chronic exposure to e-cigarette vapor condensate and liquid leads to severe disorders of zebrafish embryonic development.

The work presented here is an innovative teaching experience in the Toxicology module of the Pharmacy Laboratory course taught both in the Degree in Pharmacy and in the Double Degree in Pharmacy and Optics and Optometry. To this end, the usual way of teaching the theoretical part of the laboratory practices, which was carried out through lectures, has been changed to a teaching methodology in which both students and teachers develop the theoretical part of the practices in a pleasant and joint way through the elaboration of a content map that allows establishing connections between the different theoretical concepts. In this way, the students will obtain the necessary knowledge to be able to carry out the practices in such a way that they are able to think critically. The aim is to show the students the benefit and significance of the knowledge they will acquire, not only in order to be able to pass the subject exam, but also so that it will be useful in their working life. Based on the results obtained by the students in the initial and final questionnaires, it has been possible to verify the usefulness of the content maps when teaching classes. Therefore, and as a conclusion, I will continue to introduce new teaching methodologies that will be useful to students in my future teaching., El trabajo que se presenta se trata de una experiencia de innovación docente en el módulo de Toxicología de la asignatura de Laboratorio de Farmacia que se imparte tanto en el Grado en Farmacia como en el Doble Grado en Farmacia y Óptica y Optometría. Para ello, se ha modificado el modo de impartición habitual de la parte teórica de las prácticas, la cual se realizaba mediante clases magistrales, por una metodología docente en la que tanto alumnos como profesor van desarrollando de modo ameno y conjunto la parte teórica de las prácticas mediante la elaboración de un mapa de contenidos que permite establecer conexiones entre los diferentes conceptos teóricos. De este modo los alumnos obtendrán los conocimientos necesarios para poder llevar a cabo la realización de las prácticas de modo que sean capaces de pensar de modo crítico. Con ello se pretende, mostrarles a los alumnos el beneficio y significación de los conocimientos que van a adquirir no solo con el objetivo de poder aprobar el examen de la asignatura, sino también con el fin de que les sea útil en su vida laboral. En base a los resultados obtenidos por los alumnos en los cuestionarios iniciales y finales, se ha podido comprobar la utilidad de los mapas de contenidos a la hora de impartir las clases. Por ello y como conclusión, seguiré introduciendo nuevas metodologías de enseñanza que les sean útiles a los alumnos en mi futura docencia.

The " Scientific dissemination conference: Contributions of Toxicology in substance safety research and for society" were held on May 19th, 2023 at the Faculty of Pharmacy of the University of Seville, thanks to a financial support received by the VII Plan Propio of the University of Seville (VII PPIT-US) for scientific dissemination activities. The objective was to disseminate scientific knowledge among our students by highly qualified teaching and scientific personnel, and also to inform society in general of the high-level scientific research work that is being carried out in the University of Seville. The activity was aimed at students of the subjects of "Toxicology", "Chemoinformatics, Research and History of Pharmacy", " Laboratory of Pharmacy" (of the Degree in Pharmacy, Degree in Optics and Optometry, and Double Degree in Pharmacy and Optics and Optometry), and the subjects of "Toxicology of the Drugs of Abuse" or "Introduction to Forensic Sciences" (Degree in Criminology). During the Conference, which lasted 5.5 hours, 6 oral communications were given on graphene, cyanotoxins, alliaceous additives in human and animal feed, stilbenes in wines, or biopesticides. All of them were synthesized in informative triptychs distributed among the attendees for their dissemination in their social environment. Likewise, 2 invited presentations were given by experts in Forensic and Environmental Toxicology, respectively. The activity had 75 attendees and the results of the surveys generally showed a high degree of satisfaction with them, showing the Conference as an enriching outreach activity, due to the variety of topics covered, the new knowledge acquired and the approach to research and interest aroused among attendees., Las “Jornadas de divulgación científica: Aportaciones de la Toxicología en la investigación de la seguridad de las sustancias y para la sociedad” se celebraron el 19 de mayo de 2023 en la Facultad de Farmacia de la Universidad de Sevilla, gracias a una Ayuda recibida por el VII Plan Propio de la Universidad de Sevilla (VII PPIT-US) para actividades de divulgación científica. El objetivo fue divulgar entre nuestros alumnos los conocimientos científicos por parte de personal docente e investigador altamente cualificado, y también dar a conocer a la sociedad en general el trabajo de investigación científica de alto nivel que se está realizando en la US. La actividad iba dirigida a los alumnos de las asignaturas de “Toxicología”, “Quimioinformática, Investigación e Historia de la Farmacia”, “Laboratorio de Farmacia” (del Grado en Farmacia, Grado en Óptica y Optometría, y Doble Grado en Farmacia y Óptica y Optometría), y las asignaturas de “Toxicología de las Drogas de Abuso” o “Introducción a las Ciencias Forenses” (Grado en Criminología). Durante las Jornadas, que duraron 5,5 horas, se impartieron un total de 6 comunicaciones orales con diferente temática: el grafeno, las cianotoxinas, los aditivos aliáceos en alimentación humana y animal, los estilbenos en los vinos, o los bioplaguicidas; todas ellas sintetizadas en unos trípticos divulgativos repartidos entre los asistentes para su divulgación en su entorno social. Asimismo, se realizaron 2 ponencias invitadas por parte de expertos en Toxicología Forense y Ambiental, respectivamente. La actividad contó con casi un total de 75 asistentes y los resultados de las encuestas mostraron en general un alto grado de satisfacción con las mismas, mostrando las Jornadas como una enriquecedora actividad de divulgación científica, por la variedad de temas tratados, los nuevos conocimientos adquiridos y el acercamiento a la investigación e interés suscitado entre los asistentes.

Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country-specific environmental risks could drive regulatory actions towards eco-friendlier drug utilization and disposal practices. By starting from a list of 25 environmentally hazardous pharmaceuticals developed by Region Stockholm, we integrated eco-toxicological and 2019-2021 Italian drug utilization data to estimate the environmental impact of pharmaceuticals in Italy. We calculated the risk as the ratio between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC). We found a high risk for levonorgestrel, ciprofloxacin, amoxicillin, azithromycin, venlafaxine, sertraline and diclofenac and a moderate risk for ethinyloestradiol, oestradiol and clarithromycin. This analysis can be periodically performed to identify the pharmaceuticals with the highest risk for the environment and ascertain if containment measures should be implemented.

Producción Científica, After more than 50 years of research, studies on the structure and biological activities of ribosome-inactivating proteins (RIPs) continue to provide a field of great interest within the scientific community, both for the health risks they pose and their applications in medicine and biotechnology. This Special Issue of Toxins offers a sample of the main research topics when studying these proteins. RIPs are ribosomal RNA N-glycosylases (EC 3.2.2.22), mainly isolated from plants, some bacteria, and fungi, that specifically catalyze the hydrolysis of the second N-glycosidic bond of the GAGA tetraloop located in the sarcin-ricin loop (SRL) of the major ribosomal RNA. Because SRL is crucial for anchoring elongation factors in the ribosome, the removal of adenine causes the irreversible inactivation of ribosomes, leading to cell death. In addition, RIPs usually demonstrate other enzymatic activities, including,most relevantly, their adenine polynucleotide glycosylase (APG) activity on all nucleic acid types; that is, some RIPs can remove adenines from both ribosomal and non-ribosomal RNA and DNA [1]. [Texto extraído del artículo de Lucía Citores González].

In drug-facilitated sexual assault (DFSA), the victim is unable to provide consent or resists sexual activity due to substance intoxication by voluntary or covert consumption. Obtaining forensic evidence of the assault is challenged by rapid drug metabolism and late sample collection. The objective of this study was to present toxicological findings and associated demographics from police reported sexual assault cases in Eastern Denmark from 2015 to 2022. A total of 369 sexual assault cases were submitted for analysis and a subgroup of 268 cases were categorized as suspected DFSA cases. The majority of the total sexual assault victims were women at the age 15–25 and the perpetrators were often unknown or an acquaintance. Time from assault to sample collection was slightly longer for suspected DFSA cases (12–24 h) compared to non-DFSA (<12 h). Positive toxicology was observed in 86 % of cases and the most common drug groups included alcohol (45 %), drugs of abuse (38 %), antidepressants (14 %), antihistamines (12 %), and benzodiazepines (11 %). Hypnotics were detected to a smaller extent (7 %). A total of 77 drugs were detected and the most commonly observed were cocaine, tetrahydrocannabinol (THC), cetirizine, amphetamine, diazepam and sertraline. The high level of observed alcohol and drugs of abuse indicated that most DFSA cases in Eastern Denmark were of an opportunistic approach rather than proactive.

Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country-specific environmental risks could drive regulatory actions towards eco-friendlier drug utilization and disposal practices. By starting from a list of 25 environmentally hazardous pharmaceuticals developed by Region Stockholm, we integrated eco-toxicological and 2019-2021 Italian drug utilization data to estimate the environmental impact of pharmaceuticals in Italy. We calculated the risk as the ratio between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC). We found a high risk for levonorgestrel, ciprofloxacin, amoxicillin, azithromycin, venlafaxine, sertraline and diclofenac and a moderate risk for ethinyloestradiol, oestradiol and clarithromycin. This analysis can be periodically performed to identify the pharmaceuticals with the highest risk for the environment and ascertain if containment measures should be implemented.

Insect herbivores and plants together are a crucial component of terrestrial macro-biodiversity. Within the realm of plant-insect interactions, phytophagy by insects triggered an “arms-race” dynamic resulting in escalatory adaptation and counter-adaptation over time. This coevolution led to complex phenomena such as sequestration of plant toxins by specialized insects, with the main aim to deter predators. Although sequestration is an extensively reported phenomenon, many physiological aspects and underlying mechanisms remain largely unexplored. Milkweed bugs (Heteroptera: Lygaeinae) constitute a versatile model ideally suited for studying both areas due to their particular evolutionary history. They are primarily associated with plant species in the Apocynaceae which commonly produce cardenolides, but remarkably some milkweed bug species secondarily evolved novel associations with phylogenetically disparate plant families supplying new sources of chemically related or unrelated toxins. Using as model milkweed bugs the cardenolide specialist Oncopeltus fasciatus and Spilostethus saxatilis, a species that shifted to sequestration of the chemically unrelated colchicoids, the present thesis first aimed to develop a new artificial diet that allowed the incorporation of the desired types and amounts of toxins without impairing insect performance. Taking a simplified approach, an artificial diet presented in a pill form and made of 100% organic sunflower meal was established. Despite the fact that the new diet has remarkable energy and nutrient differences with sunflower seeds (the laboratory diet), no differences in terms of insect performance were found between the two diets in O. fasciatus and S. saxatilis. Moreover, the new diet presented an acceptable concentration accuracy and shelf-life for short-term toxin feeding assays. Once established, the new diet was used to investigate the effects of cardenolides and colchicoids on several life-history traits of S. saxatili, Herbivore Insekten und Pflanzen stellen gemeinsam eine entscheidende Komponente der terrestrischen Makrobiodiversität dar. Innerhalb der Pflanzen-Insekten-Interaktionen verursacht insbesondere die Phytophagie bei Insekten eine „arms-race“ Dynamik, die im Laufe der Zeit zu einer Eskalierung der Anpassungs- und Gegenanpassungsstrategien führte. Diese Koevolution führt zu komplexen Phänomenen wie der Sequestrierung von Pflanzentoxinen durch spezialisierte Insekten, deren Hauptziel die Abschreckung von Räubern ist. Obwohl Sequestrierung ein gut dokumentiertes Phänomen ist, sind viele physiologische Aspekte und die zugrunde liegenden Mechanismen weitgehend unerforscht. Ritterwanzen (Heteroptera: Lygaeinae) stellen ein vielseitiges Modellsystem dar, das sich aufgrund der besonderen evolutionären Geschichte ideal für die Untersuchung beider Bereiche eignet. Ritterwanzen sind in erster Linie mit Pflanzenarten der Familie Apocynaceae (Hundsgiftgewächse) assoziiert, die häufig Cardenolide produzieren. Dennoch haben einige Ritterwanzen bemerkenswerterweise sekundär neue Assoziationen mit phylogenetisch unverwandten Pflanzenfamilien entwickelt, die neue Quellen für mit Cardenoliden chemisch-verwandte oder nicht-verwandte Toxine darstellen. Unter Verwendung des Cardenolid-Spezialisten Oncopeltus fasciatus, und Spilostethus saxatilis, einer Art, die zur Sequestrierung der chemisch nicht-verwandten Colchicoide übergegangen ist, als Modelle, zielte die vorliegende Dissertation zunächst darauf ab, eine neue künstliche Diät zu entwickeln, die die Darreichung der gewünschten Klassen von Toxinen in definierter Menge ermöglicht, ohne die Fitness der Wanzen per se zu beeinträchtigen. Unter Verwendung eines einfachen Ansatzes wurde eine künstliche Diät in Tablettenform aus 100% Sonnenblumenmehl entwickelt. Trotz der Tatsache, dass diese neue Diät bemerkenswerte Energie- und Nährstoffunterschiede zu Sonnenblumenkernen (der üblichen Aufzuchtdiät) aufweist, wurden zwischen den beiden Diäten

During pregnancy, maternal, placental, and fetal metabolism are highly coordinated to support healthy fetal development, including brain development. Prenatal environmental factors such as endocrine-disrupting chemicals or maternal nutritional status have been linked to increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD). Maternal, placental, and fetal metabolomics is a valuable tool for understanding both physiological and disrupted metabolism. Further, a growing body of evidence suggests that prenatal metabolic disruption may provide insight into mechanisms underlying ASD risk. The purpose of this dissertation is to characterize the relationships between maternal, placental, and fetal metabolism; maternal prenatal exposures to endocrine-disrupting chemicals known as phthalates and prenatal vitamin supplements (PNV); and neurodevelopmental outcomes in a prospective birth cohort recruited from families with risk of ASD recurrence. In Chapter 2, investigation of the correlations between the maternal serum, placental, and fetal umbilical cord serum metabolomes revealed that placental and fetal metabolism were highly correlated with each other and with non-typically developing (Non-TD) outcomes. Across all three tissues, 3-hydroxybutyrate was identified as an important metabolite associated with Non-TD risk. In Chapter 3, the relationships between prenatal phthalate exposure, maternal and placental metabolism, and neurodevelopmental outcomes were evaluated. Phthalate exposure was associated with changes in the placental metabolome, including lipid-related metabolites, but these changes were not associated with neurodevelopmental outcomes. In Chapters 4 and 5, the relationships between PNV use in the first month of pregnancy, neurodevelopmental outcomes, and placental and fetal metabolism, respectively, were investigated. PNV use in the first month of pregnancy was associated with placental and fetal amino acid and energy metabolism

Mercury (Hg) is a highly toxic global environmental pollutant because of its ability to bioaccumulate in living organisms and persist in the environment. Hg has been historically mined because of its unique properties and ability to form a gold amalgam. Although direct Hg mining is not as prevalent today, legacy mine waste still remains in many of the historic mining areas and continues to be a source of contamination to the local environment. Mine waste emits gaseous Hg and, with subsequent deposition, contaminates the local environment. However, this atmospheric contamination pathway remains largely understudied in historic mine sites. Thus, this study aims to determine the atmospheric Hg impact on the local environment in the New Almaden Mining District (NAMD), using lichens as a bioindicator. To accomplish this, we first concluded some properties of using lichens as a bioindicator. Then, we determined the Hg emission sources and their spatial distribution. Furthermore, we gained insight into the overall biogeochemical cycling of Hg in NAMD and how lichens may contribute to the contamination through their litterfall. Our data suggest that atmospheric Hg significantly contributes to the contamination of the local environment and reservoirs in NAMD.

The etiology of neurodevelopmental disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), are complex as it is known that both genetic and environmental factors influence the development of attentional dysfunction. One known environmental risk factor for developing attention deficits is having elevated exposure to the toxicant manganese (Mn) during childhood and adolescence, however, the underlying mechanisms that may contribute to the risk of attention deficits remain unresolved. In Chapter 1 of my dissertation I present a review of the current understanding of cellular Mn regulation in mammalian systems, the importance of studying early life development as a period of vulnerability to environmental insults, potential epigenetic and neuroinflammatory mechanisms for how developmental Mn exposure may cause attention deficits, and finally how our developmental Mn exposure rodent model may be used to investigate ADHD etiology to inform therapeutic interventions for treating attention disorders. In my Chapter 2, I propose a novel mechanism of our hypofunctioning catecholaminergic system and associated attention deficit Mn neurotoxicity phenotype, involving lasting epigenomic and gene transcriptomic dysregulation of mTOR and Wnt signaling. Lastly, my Chapter 3 addresses how chronic administration of a low dose of methylphenidate that is associated with ameliorating developmental Mn-induced attentional function in a rat model alters gene expression pathways related to epigenetic regulation, inflammation, cell development (Wnt and mTOR), and hypofunctioning catecholaminergic systems in the prefrontal cortex. The following findings may aid future studies to target therapeutic interventions for children at risk of elevated Mn exposure.

Adverse childhood experiences (ACEs) are common and increase the risk of poor health outcomes. Resilience may offer protection against the impacts of ACEs. This study examined the association between maternal ACEs and mental/behavioral health outcomes during pregnancy overall and by resilience. The sample comprised pregnant patients in two pilot studies screened for eight ACEs and resilience during standard prenatal care in Kaiser Permanente Northern California from 1 March 2016 to 30 July 2016 (Study 1, medical centers A, B) and from 1 April 2018 to 31 March 2019 (Study 2, medical centers A, C). Early pregnancy outcomes included anxiety and depressive disorders, depression symptoms, intimate partner violence (IPV), and substance use. Multivariable logistic regression was used in this cross-sectional study to examine associations between maternal ACEs (0, 1-2, ≥3) and mental/behavioral health outcomes overall and among those with low and high resilience. Patients (n = 1084) averaged 30.8 years (SD 5.1); 41.7% were non-Hispanic White; 41.7% experienced ≥1 ACE, and 40.3% had low resilience. Patients with 1-2 ACEs or ≥3 ACEs (versus 0 ACEs) had higher odds of anxiety and depressive disorders, depressive symptoms, IPV, and any prenatal substance use (OR 1.44-4.40, p < 0.05). Each individual ACE was associated with ≥2 mental/behavioral health outcomes. In stratified analyses, having ≥1 ACE (vs. 0) was associated with a greater number of mental/behavioral health outcomes among patients with low versus high resilience. ACEs were associated with prenatal mental/behavioral health conditions, particularly in the context of low resilience, highlighting the importance of trauma-informed prenatal care and the need to study resilience-building interventions during pregnancy.

Directed evolution has been used to produce enzymes with many unique properties. The technique of directed evolution comprises two essential steps: mutagenesis of the gene encoding the enzyme to produce a library of variants, and selection of a particular variant based on its desirable catalytic properties. In this course we will examine what kinds of enzymes are worth evolving and the strategies used for library generation and enzyme selection. We will focus on those enzymes that are used in the synthesis of drugs and in biotechnological applications. This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. These seminars are tailored for students with an interest in using primary research literature to discuss and learn about current biological research in a highly interactive setting. Many instructors of the Advanced Undergraduate Seminars are postdoctoral scientists with a strong interest in teaching.

Since the 1980s, college students in the U.S. have self-reported a decline in their physical and emotional health. With these conditions compounded by the COVID-19 pandemic and its physical distancing restrictions, higher education institutions have an increased responsibility to establish strategic interventions and health-promoting programs for their students. Research collaborations between public health professionals and environmental designers have highlighted the benefits of environmental factors, such as wildlife, street trees, and public parks, on mental health. This pilot project aims to build upon the transdisciplinary dialogue between ecology, design, and public health by examining the social benefits of grazing lawnscape management, which is the practice of using herbivorous livestock to manage turfgrass areas. Through the design of an accessible central campus grazing space for a flock of 25 sheep and use of online questionnaires, a smartphone-based single-item survey, and open-ended feedback given via social media, the UC Davis Sheepmower Project addresses three primary questions: (1) Are there differences in self-reported stress levels and well-being between people who did not watch grazing sheep (no sheepmower group) compared with those who did watch grazing sheep (sheepmower group)? (2) Does holding sheep grazing events create opportunities for education about well-being and engagement with the campus community? (3) Can this type of urban grazing installation ultimately contribute to the overall identity of a college campus? Web-based questionnaire results indicate there is no significant difference in self-reported stress levels between the two groups; however, the moment-in-time smartphone-based single item question suggests that the presence of sheep provides temporary, noticeable relief and enhanced mood for those who observe the animals. Reflections posted on social media suggested that participants found the sheep grazing events fostered feeli

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson's disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity.Objectives: We used an ex vivo system to evaluate the effect of in vivo inhalation exposure to FP and UFP on motor activity and dopaminergic transmission.Materials and Methods: Male adult Wistar rats were exposed to FP, UFP, or filtered air for 8 weeks (subchronic exposure; 5 h/day, 5 days/week) in a particle concentrator. Motor activity was evaluated using the open-field test. Uptake and release of [3H]-dopamine were assessed in striatal synaptosomes, and dopamine D2 receptor (D2R) affinity for dopamine was evaluated by the displacement of [3H]-spiperone binding to striatal membranes.Results: Exposure to FP or UFP significantly reduced spontaneous motor activity (ambulatory distance: FP -25%, UFP -32%; ambulatory time: FP -24%, UFP -22%; ambulatory episodes: FP -22%, UFP -30%), decreased [3H]-dopamine uptake (FP -18%, UFP -24%), and increased, although not significantly, [3H]-dopamine release (113.3 ± 16.3 and 138.6 ± 17.3%). Neither FP nor UFP exposure affected D2R density or affinity for dopamine.Conclusions: These results indicate that exposure to ambient particulate matter reduces locomotion in rats, which could be related to altered striatal dopaminergic transmission: UFP was more potent than FP. Our results contribute to the evidence linking environmental factors to changes in brain function that could turn into neurological and psychiatric disorders.HIGHLIGHTSYoung adult rats were exposed to fine (FP) or ultrafine (UFP) particles for 40 days.Exposure to FP or UFP reduced motor activity.Exposure to FP or UFP reduced dopamine uptake by striatal synaptosomes.Neither D2R density or aff

Atopic dermatitis (AD) has increased in prevalence to become the most common inflammatory skin condition globally, and geographic variation and migration studies suggest an important role for environmental triggers. Air pollution, especially due to industrialization and wildfires, may contribute to the development and exacerbation of AD. We provide a comprehensive, multidisciplinary review of existing molecular and epidemiologic studies on the associations of air pollutants and AD symptoms, prevalence, incidence, severity, and clinic visits. Cell and animal studies demonstrated that air pollutants contribute to AD symptoms and disease by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, initiating a proinflammatory response, and disrupting the skin barrier function. Epidemiologic studies overall report that air pollution is associated with AD among both children and adults, though the results are not consistent among cross-sectional studies. Studies on healthcare use for AD found positive correlations between medical visits for AD and air pollutants. As the air quality worsens in many areas globally, it is important to recognize how this can increase the risk for AD, to be aware of the increased demand for AD-related medical care, and to understand how to counsel patients regarding their skin health. Further research is needed to develop treatments that prevent or mitigate air pollution-related AD symptoms.

IntroductionIn March 2016, the Centers for Disease Control and Prevention released the Guideline for Prescribing Opioids for Chronic Pain, intended for primary care clinicians. One recommendation advised against concurrent prescription of opioids and benzodiazepines. Although existing research suggests a reduction in co-prescribing of these drug classes by clinicians after guideline release, there are limited data assessing its possible effect on patient medical outcomes, such as overdoses.MethodsThis retrospective observational study analyzed opioid and benzodiazepine exposures, alone or in combination, reported to the California Poison Control System from January 2012 to June 2021. Interrupted time series analyses identified the difference in monthly call volume between pre- and post-guideline release. For exposures resulting in serious medical outcomes, additional analyses assessed trends and identified associated variables.ResultsThere was no significant change in concomitant opioid and benzodiazepine exposures reported to California Poison Control System between pre- and post-guideline release. Compared to pre-guideline release, exposures to a single opioid or to a single benzodiazepine significantly decreased by 1.07 (95% CI: -1.62, -0.51) and 1.82 (95% CI: -2.33, -1.31) calls per month, respectively, after the guideline release. For exposure calls associated with serious medical outcomes, there was a significant increase of 0.11 (95% CI: 0.04, 0.18) and 0.2 (95% CI: 0.05, 0.34) calls per month for concomitant opioid and benzodiazepine and single opioid exposures, respectively, following guideline release.DiscussionThe guideline release appeared to have a variable association with exposures to single opioid, single benzodiazepines, and concomitant opioid and benzodiazepine cases reported to California Poison Control System. Although exposures to opioids or benzodiazepines alone significantly decreased after guideline release, there was no significant change in

BackgroundThe molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.ObjectivesTo assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.MethodsOur study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis.ResultsWe found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionOur results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warra

Cyanide-a fast-acting poison-is easy to obtain given its widespread use in manufacturing industries. It is a high-threat chemical agent that poses a risk of occupational exposure in addition to being a terrorist agent. FDA-approved cyanide antidotes must be given intravenously, which is not practical in a mass casualty setting due to the time and skill required to obtain intravenous access. Glyoxylate is an endogenous metabolite that binds cyanide and reverses cyanide-induced redox imbalances independent of chelation. Efficacy and biochemical mechanistic studies in an FDA-approved preclinical animal model have not been reported. Therefore, in a swine model of cyanide poisoning, we evaluated the efficacy of intramuscular glyoxylate on clinical, metabolic, and biochemical endpoints. Animals were instrumented for continuous hemodynamic monitoring and infused with potassium cyanide. Following cyanide-induced apnea, saline control or glyoxylate was administered intramuscularly. Throughout the study, serial blood samples were collected for pharmacokinetic, metabolite, and biochemical studies, in addition, vital signs, hemodynamic parameters, and laboratory values were measured. Survival in glyoxylate-treated animals was 83% compared with 12% in saline-treated control animals (p < .01). Glyoxylate treatment improved physiological parameters including pulse oximetry, arterial oxygenation, respiration, and pH. In addition, levels of citric acid cycle metabolites returned to baseline levels by the end of the study. Moreover, glyoxylate exerted distinct effects on redox balance as compared with a cyanide-chelating countermeasure. In our preclinical swine model of lethal cyanide poisoning, intramuscular administration of the endogenous metabolite glyoxylate improved survival and clinical outcomes, and ameliorated the biochemical effects of cyanide.

The Exxon Valdez oil spill occurred March 24, 1989, when herring were preparing to spawn in Prince William Sound. The herring population experienced an unanticipated, abrupt decline three years later, due–in part–to a mortality from infectious and parasitic diseases. Linking the oil spill to subsequent population collapse remains controversial. A major insight from years of studying the spill is that embryonic herring are profoundly sensitive to crude oil; exposure to vanishingly low levels of oil over a brief time early in a herring’s life-cycle can have long-lasting health effects, and oil exposure can disturb immune function. Could crude oil exposure during early life have compromised their immune system development, thereby increasing the risk of major disease outbreak in later life? To address this question, over the past few years we have sought to simulate the events surrounding the 1993 herring collapse using 1) experimental exposures to environmentally relevant levels of Alaska north slope crude oil, 2) fish from the Prince William Sound population and others, and 3) exposing fish in the laboratory to the same pathogens that caused the disease outbreak. To facilitate our investigation into the molecular effects of oil exposure on a non-traditional model organism, we sequenced and annotated a reference transcriptome for the Pacific herring, and conducted extensive research into a cost-effective, high-throughput RNA-sequencing library construction method for our samples. To that end we compared the effectiveness of two methods for generating sequencing libraries for gene expression analysis: 3'-end sequencing and whole transcript sequencing. We found similar levels of precision and power for detecting differentially expressed genes with both methods, but whole transcript sequencing performed better in non-traditional model species. Next, embryonic herring sourced from Prince William Sound, AK were exposed to a range of crude oil and transcriptomically

Hexafluoropropylene oxide-dimer acid (HFPO-DA) is one of the emerging replacements for the "forever" carcinogenic and toxic long-chain PFAS. HFPO-DA is a polymerization aid used for manufacturing fluoropolymers, whose global distribution and undetermined toxic properties are a concern regarding human and ecological health. To assess embryotoxic potential, zebrafish embryos were exposed to HFPO-DA at concentrations of 0.5-20,000 mg/L at 24-, 48-, and 72-h post-fertilization (hpf). Heart rate increased significantly in embryos exposed to 2 mg/L and 10 mg/L HFPO-DA across all time points. Spinal deformities and edema phenotypes were evident among embryos exposed to 1000-16,000 mg/L HFPO-DA at 72 hpf. A median lethal concentration (LC50) was derived as 7651 mg/L at 72 hpf. Shallow RNA sequencing analysis of 9465 transcripts identified 38 consistently differentially expressed genes at 0.5 mg/L, 1 mg/L, 2 mg/L, and 10 mg/L HFPO-DA exposures. Notably, seven downregulated genes were associated with visual response, and seven upregulated genes were expressed in or regulated the cardiovascular system. This study identifies biological targets and molecular pathways affected during animal development by an emerging, potentially problematic, and ubiquitous industrial chemical.

BackgroundChronic pain and somatosensory impairment are common following a stroke. It is possible that an interaction exists between pain and somatosensory impairment and that a change in one may influence the other. We therefore investigated the presence of chronic pain and self-reported altered somatosensory ability in individuals with stroke, aiming to determine if chronic pain is more common in stroke survivors with somatosensory impairment than in those without.MethodsStroke survivors were invited to complete an online survey that included demographics, details of the stroke, presence of chronic pain, and any perceived changes in body sensations post-stroke.ResultsSurvivors of stroke (n = 489) completed the survey with 308 indicating that they experienced chronic pain and 368 reporting perceived changes in somatosensory function. Individuals with strokes who reported altered somatosensory ability were more likely to experience chronic pain than those who did not (OR = 1.697; 95% CI 1.585, 2.446). Further, this difference was observed for all categories of sensory function that were surveyed (detection of light touch, body position, discrimination of surfaces and temperature, and haptic object recognition).ConclusionsThe results point to a new characteristic of chronic pain in strokes, regardless of nature or region of the pain experienced, and raises the potential of somatosensory impairment being a rehabilitation target to improve pain-related outcomes for stroke survivors.

Major wildfires and their smoke pose a threat to public health and are becoming more frequent in the United States, particularly in California and other populated, fire-prone states. Therefore, it is crucial to understand how California residents view wildfires and engage in risk-reducing behaviors during wildfire events. Currently, there is a knowledge gap concerning this area of inquiry. We disseminated a 40-question cross-sectional survey to explore wildfire perception and knowledge along with related risk-reducing measures and policies among 807 adult residents in the fire-prone region of Orange County, California. Results demonstrated that nearly all (>95%) participants had (or knew someone who had) previously experienced a wildfire. Female gender, knowing a wildfire victim and reporting to have a general interest/passion for environmental issues were the three factors most strongly associated with (1) wildfires (and smoke) being reported as a threat, (2) participants' willingness to evacuate if threatened by a nearby wildfire, and (3) participants' willingness to support a wildfire-related tax increase (p < 0.05). The majority (57.4%) of participants agreed that the occurrence of wildfires is influenced by climate change, with the most commonly reported risk-reducing actions (by 44% of participants) being informational actions (e.g., tracking the news) rather than self-motivated physical safety actions (e.g., using an air purifier) (29%). The results of this study can help to inform decision- and policy-making regarding future wildfire events as well as allow more targeted and effective public health messaging and intervention measures, in turn helping to reduce the risk associated with future wildfire/smoke episodes.

BackgroundUnderstanding, characterizing, and quantifying human exposures to environmental chemicals is critical to protect public health. Exposure assessments are key to determining risks to the general population and for specific subpopulations given that exposures differ between groups. Exposure data are also important for understanding where interventions, including public policies, should be targeted and the extent to which interventions have been successful. In this review, we aim to show how inadequacies in exposure assessments conducted by polluting industries or regulatory agencies have led to downplaying or disregarding exposure concerns raised by communities; that underestimates of exposure can lead regulatory agencies to conclude that unacceptable risks are, instead, acceptable, allowing pollutants to go unregulated; and that researchers, risk assessors, and policy makers need to better understand the issues that have affected exposure assessments and how appropriate use of exposure data can contribute to health-protective decisions.MethodsWe describe current approaches used by regulatory agencies to estimate human exposures to environmental chemicals, including approaches to address limitations in exposure data. We then illustrate how some exposure assessments have been used to reach flawed conclusions about environmental chemicals and make recommendations for improvements.ResultsExposure data are important for communities, public health advocates, scientists, policy makers, and other groups to understand the extent of environmental exposures in diverse populations. We identify four areas where exposure assessments need to be improved due to systemic sources of error or uncertainty in exposure assessments and illustrate these areas with examples. These include: (1) an inability of regulatory agencies to keep pace with the increasing number of chemicals registered for use or assess their exposures, as well as complications added by use of 'confidential bu

Despite previous studies indicating the thermal stability of vitamin E acetate (VEA) at low temperatures, VEA has been shown to readily decompose into various degradation products such as alkenes, long-chain alcohols, and carbonyls such as duroquinone (DQ) at vaping temperatures of <200 °C. While most models simulate the thermal decomposition of e-liquids under pyrolysis conditions, numerous factors, including vaping behavior, device construction, and the surrounding environment, may impact the thermal degradation process. In this study, we investigated the role of the presence of molecular oxygen (O2) and transition metals in promoting thermal oxidation of e-liquids, resulting in greater degradation than predicted by pure pyrolysis. Thermal degradation of VEA was performed in inert (N2) and oxidizing atmospheres (clean air) in the absence and presence of Ni-Cr and Cu-Ni alloy nanopowders, metals commonly found in the heating coil and body of e-cigarettes. VEA degradation was analyzed using thermogravimetric analysis (TGA) and gas chromatography/mass spectrometry (GC/MS). While the presence of O2 was found to significantly enhance the degradation of VEA at both high (356 °C) and low (176 °C) temperatures, the addition of Cu-Ni to oxidizing atmospheres was found to greatly enhance VEA degradation, resulting in the formation of numerous degradation products previously identified in VEA vaping emissions. O2 and Cu-Ni nanopowder together were also found to significantly increase the production of OH radicals, which has implications for e-liquid degradation pathways as well as the potential risk of oxidative damage to biological systems in real-world vaping scenarios. Ultimately, the results presented in this study highlight the importance of oxidation pathways in VEA thermal degradation and may aid in the prediction of thermal degradation products from e-liquids.

Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this "bright line" approach assumes that there is minimal risk below the RfD/RfC with some undefined level of increased risk at exposures above the RfD/RfC and has limited utility for decision-making. Rather than this dichotomous approach, non-cancer risk assessment can benefit from incorporating probabilistic methods to estimate the amount of risk across a wide range of exposures and define a risk-specific dose. We identify and review existing approaches for conducting probabilistic non-cancer risk assessments. Using perchloroethylene (PCE), a priority chemical for the U.S. Environmental Protection Agency under the Toxic Substances Control Act, we calculate risk-specific doses for the effects on cognitive deficits using probabilistic risk assessment approaches. Our probabilistic risk assessment shows that chronic exposure to 0.004 ppm PCE is associated with approximately 1-in-1,000 risk for a 5% reduced performance on the Wechsler Memory Scale Visual Reproduction subtest with 95% confidence. This exposure level associated with a 1-in-1000 risk for non-cancer neurocognitive deficits is lower than the current RfC for PCE of 0.0059 ppm, which is based on standard point of departure and uncertainty factor approaches for the same neurotoxic effects in occupationally exposed adults. We found that the population-level risk of cognitive deficit (indicating central nervous system dysfunction) is estimated to be greater than the cancer risk level of 1-in-100,000 at a similar chronic exposure level. The extension of toxicological endpoints to more clinically relevant endpoints, along with consideration of magnitude and severity of effect, will help in the selection of acceptable risk targets for non-cancer effects. We find that probabilistic

Because COVID-19 is a respiratory and cardiovascular disease, understanding behaviors that impact cardiopulmonary health, such as tobacco use, is particularly important. While early studies suggested no change in prevalence of tobacco use as COVID-19 emerged, pandemic fatigue, shifting levels of COVID-19 transmission, and vaccine availability have all changed since the start of the pandemic. The current study examined whether time, COVID-19 surges, and/or vaccination status were associated with likelihood of daily and non-daily tobacco use over the first 24 months of the pandemic. Data were obtained from electronic health records of healthcare visits (n = 314,787) to four Southern California VA healthcare systems. Multinomial logistic regression analyses indicated that the likelihood of reporting both daily and non-daily tobacco use (versus non-use) increased over time. Daily and non-daily tobacco use were less common at visits that occurred during COVID-19 surges, as well as among veterans vaccinated against COVID-19. Our findings provide new insight into changes of tobacco use patterns and correlates across the first two years of this pandemic, and understanding these associations may facilitate understanding of health-related behaviors and inform clinical treatment of tobacco use disorder during the COVID-19 pandemic.

BackgroundHazard identification, risk assessment, regulatory, and policy activity are usually conducted on a chemical-by-chemical basis. Grouping chemicals into categories or classes is an underutilized approach that could make risk assessment and management of chemicals more efficient for regulators.Objective and methodsWhile there are some available methods and regulatory frameworks that include the grouping of chemicals (e.g.,same molecular mechanism or similar chemical structure) there has not been a comprehensive evaluation of these different approaches nor a recommended course of action to better consider chemical classes in decision-making. This manuscript: 1) reviews current national and international approaches to grouping; 2) describes how groups could be defined based on the decision context (e.g., hazard/risk assessment, restrictions, prioritization, product development) and scientific considerations (e.g., intrinsic physical-chemical properties); 3) discusses advantages of developing a decision tree approach for grouping; 4) uses ortho-phthalates as a case study to identify and organize frameworks that could be used across agencies; and 5) discusses opportunities to advance the class concept within various regulatory decision-making scenarios.ResultsStructural similarity was the most common grouping approach for risk assessment among regulatory agencies (national and state level) and non-regulatory organizations, albeit with some variations in its definition. Toxicity to the same target organ or to the same biological function was also used in a few cases. The phthalates case study showed that a decision tree approach for grouping should include questions about uses regulated by other agencies to encourage more efficient, coherent, and protective chemical risk management.Discussion and conclusionOur evaluation of how classes of chemicals are defined and used identified commonalities and differences based on regulatory frameworks, risk assessments, and b

BackgroundThe financial hardships and social isolation experienced during the COVID-19 pandemic have been found to adversely affect children's developmental outcomes. While many studies thus far have focused on school-aged children and the pandemic-related impacts on their academic skills and behavior problems, relatively less is known about pandemic hardships and associations with children's development during their early years. Using a racially and economically diverse sample, we examined whether hardships experienced during the pandemic were associated with children's development with a particular focus on communication and socioemotional development.MethodsParticipants from eight cohorts of the Environmental influences on Child Health Outcomes program provided data on pandemic-related financial and social hardships as well as child developmental outcomes. Financial hardship was defined as at least one parent experiencing job loss or change, and social hardship was defined as families' quarantining from household members or extended family and friends. The development of children under 4 was assessed longitudinally, before and during the pandemic (N = 684), using the Ages and Stages Questionnaire (ASQ). The Generalized Estimating Equations, which accounted for within-child correlation, were used for analysis.ResultsFamilies from minority backgrounds and low socioeconomic status disproportionately experienced pandemic-related hardships. Male children had higher odds of experiencing negative changes in communication and personal social skills from pre- to during-pandemic visits (ORs ranged between 2.24 and 3.03 in analysis with binary ASQ outcomes and ranged from -0.34-0.36 in analyses with ASQ z-scores, ps = 0.000). Pandemic-related hardships in the social and financial areas did not explain within-individual changes in children's developmental outcomes.ConclusionNegative developmental changes from pre- to during-pandemic were found in boys, yet we did not find an

The SARS-CoV-2 pandemic has had a deleterious impact on human health since its beginning in 2019. The purpose of this study was to examine the psychosocial impact of the COVID-19 pandemic in the Philippines and determine if there were differential impacts on women compared to men. A web-based survey was conducted in the Luzon Islands of the Philippines, during the pandemic quarantine. A total of 1879 participants completed online surveys between 28 March-12 April 2020. A bivariate analysis of both men and women for each psychological measure (stress, anxiety, depression, and impact of COVID-19) was conducted. Multivariable logistic regression models were built for each measure, dichotomized as high or low, separately for men and women. Younger age (p < 0.001), being married (p < 0.001), and being a parent (p < 0.004) were associated with women's poor mental health. Marriage and large household size are protective factors for men (p < 0.002 and p < 0.0012, respectively), but marriage may be a risk factor for women (p < 0.001). Overall, women were disproportionately negatively impacted by the pandemic compared to men.

Available research suggests that patients with diabetes do not regularly receive preconception counseling, but information on patients' experiences of counseling is scant. We conducted a qualitative study involving semi-structured interviews with 22 patients between October 2020 and February 2021. Pregnant patients with preexisting diabetes were recruited from a specialty diabetes and pregnancy clinic at a large academic medical center in Northern California. Interviews were transcribed, coded, and analyzed using an inductive and deductive content analysis approach. A total of 27% reported they did not have any pregnancy-related discussions with a health care provider before pregnancy. Of those that did, many sought out counseling; this was often connected to how "planned" the pregnancy was. Few participants, nearly all with type 1 diabetes, reported having a formal preconception care visit. Participants described receiving information mostly about the risks associated with diabetes and pregnancy. While participants who sought out counseling generally reported their providers were supportive of their desire for pregnancy, there were a few exceptions, notably all among patients with type 2 diabetes. The varied experiences of participants indicate gaps in the delivery of pre-pregnancy counseling to patients with diabetes and suggest counseling may vary based on diabetes type. There are opportunities to improve the patient-centeredness of counseling.

We investigated the content of liberal and conservative news media Facebook posts on race and ethnic health disparities. A total of 3,327,360 liberal and conservative news Facebook posts from the United States (US) from January 2015 to May 2022 were collected from the Crowd Tangle platform and filtered for race and health-related keywords. Qualitative content analysis was conducted on a random sample of 1750 liberal and 1750 conservative posts. Posts were analyzed for a continuum of hate speech using a newly developed method combining faceted Rasch item response theory with deep learning. Across posts referencing Asian, Black, Latinx, Middle Eastern, and immigrants/refugees, liberal news posts had lower hate scores compared to conservative posts. Liberal news posts were more likely to acknowledge and detail the existence of racial/ethnic health disparities, while conservative news posts were more likely to highlight the negative consequences of protests, immigration, and the disenfranchisement of Whites. Facebook posts from liberal and conservative news focus on different themes with fewer discussions of racial inequities in conservative news. Investigating the discourse on race and health in social media news posts may inform our understanding of the public's exposure to and knowledge of racial health disparities, and policy-level support for ameliorating these disparities.

Acute exposure to high concentrations of hydrogen sulfide (H2S) leads to sudden death and, if survived, lingering neurological disorders. Clinical signs include seizures, loss of consciousness, and dyspnea. The proximate mechanisms underlying H2S-induced acute toxicity and death have not been clearly elucidated. We investigated electrocerebral, cardiac and respiratory activity during H2S exposure using electroencephalogram (EEG), electrocardiogram (EKG) and plethysmography. H2S suppressed electrocerebral activity and disrupted breathing. Cardiac activity was comparatively less affected. To test whether Ca2+ dysregulation contributes to H2S-induced EEG suppression, we developed an in vitro real-time rapid throughput assay measuring patterns of spontaneous synchronized Ca2+ oscillations in cultured primary cortical neuronal networks loaded with the indicator Fluo-4 using the fluorescent imaging plate reader (FLIPR-Tetra®). Sulfide >5 ppm dysregulated synchronous calcium oscillation (SCO) patterns in a dose-dependent manner. Inhibitors of NMDA and AMPA receptors magnified H2S-induced SCO suppression. Inhibitors of L-type voltage gated Ca2+ channels and transient receptor potential channels prevented H2S-induced SCO suppression. Inhibitors of T-type voltage gated Ca2+ channels, ryanodine receptors, and sodium channels had no measurable influence on H2S-induced SCO suppression. Exposures to > 5 ppm sulfide also suppressed neuronal electrical activity in primary cortical neurons measured by multi-electrode array (MEA), an effect alleviated by pretreatment with the nonselective transient receptor potential channel inhibitor, 2-APB. 2-APB also reduced primary cortical neuronal cell death from sulfide exposure. These results improve our understanding of the role of different Ca2+ channels in acute H2S-induced neurotoxicity and identify transient receptor potential channel modulators as novel structures with potential therapeutic benefits.

The novel coronavirus disease 2019 (COVID-19) pandemic abruptly disrupted the daily lives and health of college students across the United States. This study investigated several stressors (e.g., financial strain/uncertainty), psychological distress, and dietary behaviors among college students attending a large state university during the pandemic. A cross-sectional online survey was administered to students from the California State University, Los Angeles between April and May 2021 (final analytic sample n = 736). Differences in gender and race/ethnicity were examined using chi-square, t-test, and one-way ANOVA tests. Paired t-tests were performed to compare variables before and during the pandemic. Negative binomial regression models examined the associations between various stressors, psychological distress, and three key dietary outcomes. Descriptive results showed that the consumption of fruits and vegetables, fast food, and sugary beverages, along with psychological distress, all increased during the pandemic. Significant differences in fruit and vegetable and fast food consumption by gender and race/ethnicity were also observed. In the regression models, several stressors, including financial strain and psychological distress, were associated with unfavorable food and beverage consumption, thereby suggesting that college students may need more support in mitigating these stressors so they do not manifest as poor dietary behaviors. Poor diet quality is associated with poor physical health outcomes such as premature development of type 2 diabetes or hypertension.

Previous research suggests that affectionate touch such as hugs might downregulate stress systems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks in generalizability beyond the laboratory setting and outside the context of romantic relationships. The cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily fluctuations in stress and social information. However, associations between affectionate touch and the CAR have never been assessed. This study used ecological momentary assessment (EMA) to measure daily hugging behaviors in 104 first-year college students and salivary cortisol to assess the CAR. Participants who reported more daily hugs in their social interactions had significantly smaller CARs the next morning compared to days they reported fewer hugs. This study contributes to the literature on social interactions and stress responsive systems and emphasizes the importance of assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of romantic relationships.

US schools have fast-food restaurants nearby, encouraging student patronage, unhealthy consumption, and weight gain. Geographers have developed an activity space framework which suggests this nearby location effect will be moderated by whether people perceive the location as their activity space. Therefore, we study whether students perceive a fast-food restaurant near school as their activity space, and whether social marketing messages can change that perception. We conducted six studies: a secondary data analysis with 5986 students, a field experiment with 188 students, and four lab experiments with 188, 251, 178, and 379 students. We find that students who strongly identify with their student community patronize a fast-food restaurant near school (vs. farther away) because they view it as their activity space, while students who weakly identify do not. For example, in our field experiment, 44% vs. 7% of students who strongly identified with the student community patronized the near versus farther restaurant, while only 28% versus 19% of students who weakly identified patronized the near and farther restaurants comparably. We also find that to deter the strong identifiers, messages should convey that patronage is a social liability, e.g., portray student activism against fast food. We show that standard health messages do not change perceptions of restaurants as social activity spaces. Thus, to combat the problem of fast-food restaurants near schools causing unhealthy consumption, policy and educational interventions should focus on students who strongly identify with their student community and find ways to weaken their perceptions that fast-food restaurants near schools are their activity spaces.

Low back pain and depression have been globally recognized as key public health problems and they are considered co-morbid conditions. This study explores both cross-sectional and longitudinal comorbid associations between back pain and major depression in the adult population in the United States. We used data from the Midlife in the United States survey (MIDUS), linking MIDUS II and III with a sample size of 2358. Logistic regression and Poisson regression models were used. The cross-sectional analysis showed significant associations between back pain and major depression. The longitudinal analysis indicated that back pain at baseline was prospectively associated with major depression at follow-up (PR 1.96, CI: 1.41, 2.74), controlling for health behavioral and demographic variables. Major depression at baseline was also prospectively associated with back pain at follow-up (PR 1.48, CI: 1.04, 2.13), controlling for a set of related confounders. These findings of a bidirectional comorbid association fill a gap in the current understanding of these comorbid conditions and could have clinical implications for the management and prevention of both depression and low back pain.

Public trust in medical institutions is essential for ensuring compliance with medical directives. However, the politicization of public health issues and the polarized nature of major news outlets suggest that partisanship and news consumption habits can influence medical trust. This study employed a survey with 858 participants and used regression analysis to assesses how news consumption habits and information assessment traits (IATs) influence trust in medical scientists. IATs included were conscientiousness, openness, need for cognitive closure (NFCC), and cognitive reflective thinking (CRT). News sources were classified on the basis of factuality and political bias. Initially, readership of liberally biased news was positively associated with medical trust (p < 0.05). However, this association disappeared when controlling for the news source's factuality (p = 0.28), while CRT (p < 0.05) was positively associated with medical trust. When controlling for conservatively biased news sources, factuality of the news source (p < 0.05) and NFCC (p < 0.05) were positively associated with medical trust. While partisan media bias may influence medical trust, these results suggest that those who have higher abilities to assess information and who prefer more credible news sources have a greater trust in medical scientists.