Multi-day Exposure Research Articles

UV-C Light Intervention as a Barrier against Airborne Transmission of SARS-CoV-2.

SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode of transmission. In addition to tools like vaccination and testing, countermeasures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model. Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to untreated air. Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from the experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a multi-day exposure period during peak viral shedding by hamsters. These findings demonstrate the efficacy of the UV-C light to mitigate against airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool for reducing infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

Does a single ethanol exposure prior to burn injury in mice worsen pulmonary inflammation as much as episodic multi-day exposure of ethanol?

Does a single ethanol exposure prior to burn injury in mice worsen pulmonary inflammation as much as episodic multi-day exposure of ethanol?

Direct ingestion, trophic transfer, and physiological effects of microplastics in the early life stages of Centropristis striata, a commercially and recreationally valuable fishery species

Microplastics are ubiquitous in marine and estuarine ecosystems, and thus there is increasing concern regarding exposure and potential effects in commercial species. To address this knowledge gap, we investigated the effects of microplastics on larval and early juvenile life stages of the Black Sea Bass (Centropristis striata), a North American fishery. Larvae (13–14 days post hatch, dph) were exposed to 1.0 × 104, 1.0 × 105, and 1.0 × 106 particles L−1 of low-density polyethylene (LDPE) microspheres (10–20 μm) directly in seawater and via trophic transfer from microzooplankton prey (tintinnid ciliates, Favella spp.). We also compared the ingestion of virgin and chemically-treated microspheres incubated with either phenanthrene, a polycyclic aromatic hydrocarbon, or 2,4-di-tert-butylphenol (2,4-DTBP), a plastic additive. Larval fish did not discriminate between virgin or chemically-treated microspheres. However, larvae did ingest higher numbers of microspheres through ingestion of microzooplankton prey than directly from the seawater. Early juveniles (50–60 dph) were directly exposed to the virgin and chemically-treated LDPE microspheres, as well as virgin LDPE microfibers for 96 h to determine physiological effects (i.e., oxygen consumption and immune response). There was a significant positive relationship between oxygen consumption and increasing microfiber concentration, as well as a significant negative relationship between immune response and increasing virgin microsphere concentration. This first assessment of microplastic pollution effects in the early life stages of a commercial finfish species demonstrates that trophic transfer from microzooplankton can be a significant route of microplastic exposure to larval stages of C. striata, and that multi-day exposure to some microplastics in early juveniles can result in physiological stress.

Resting-state posterior alpha power changes with prolonged exposure in a natural environment

Exposure to environments that contain natural features can benefit mood, cognition, and physiological responses. Previous research proposed exposure to nature restores voluntary attention – attention that is directed towards a task through top down control. Voluntary attention is limited in capacity and depletes with use. Nature provides unique stimuli that do not require voluntary attention; therefore, the neural resources needed for attention to operate efficiently are theorized to restore when spending time in nature. Electroencephalography reflects changes in attention through fluctuations in power within specific frequencies. The current study (N = 29) measured changes in averaged resting state posterior alpha power before, during, and after a multiday nature exposure. Linear mixed-effects models revealed posterior alpha power was significantly lower during the nature exposure compared to pre-trip and post-trip testing, suggesting posterior alpha power may be a potential biomarker for differences related to exposure to natural and urban environments.

Durational effect of particulate matter air pollution wave on hospital admissions for schizophrenia

BackgroundShort-term exposure to high level of ambient particulate matters (PM) concentrations has been linked with increased hospital admissions (HA) for schizophrenia. However, evidence is inconclusive about the added effect of multi-day exposure to high-level PM concentration on schizophrenia. This study aims to evaluate the durational effect of PM air pollution wave on schizophrenia. MethodData on daily HA for schizophrenia, PM (PM2.5 and PM10) and meteorological variables over the period of 2014–2017 was collected in Jining, Shandong, China. Air pollution wave of PM was defined as ≥2 or ≥3 or ≥4 consecutive days with PM concentration ≥90th or ≥92.5th or ≥95th or ≥97.5th percentiles, respectively. A time-series Poisson regression model with duration as the variable of interest was used to evaluate the associations of PM air pollution wave with HA for schizophrenia. ResultsA total of 14650 hospital admissions for schizophrenia were identified. Under various air pollution wave definitions, both PM2.5 and PM10 had significant adverse effects on schizophrenia HA. PM2.5 wave defined as ≥2 consecutive days with concentration ≥90th, ≥92.5th, ≥95th and ≥97.5th percentile was associated with 4.8% (2.0%–7.6%), 4.9% (1.9%–7.9%), 5.5% (2.0%–9.2%), and 7.6% (2.9%–12.6%) increase of HA for schizophrenia at lag 6. PM2.5 waves defined as ≥3 consecutive days with concentration ≥90th, ≥92.5th, ≥95th and ≥97.5th percentile respectively corresponded to 5.0% (2.3%–7.8%), 5.1% (1.9%–8.4%), 6.9% (3.0%–10.8%) and 12.0% (5.3%–19.1%) increases in HA for schizophrenia at lag 6. The most significant associations were observed on the sixth day in different lag models. ConclusionsPM air pollution wave was associated with increased risk of hospital admissions for schizophrenia, with stronger associations among married and female patients.

Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers

The objective of this study was to evaluate the association between carbon nanotube and nanofiber (CNT/F) exposure and ex vivo responses of whole blood challenged with secondary stimulants, adjusting for potential confounders, in a cross-sectional study of 102 workers. Multi-day exposure was measured by CNT/F structure count (SC) and elemental carbon (EC) air concentrations. Demographic, lifestyle and other occupational covariate data were obtained via questionnaire. Whole blood collected from each participant was incubated for 18 hours with and without two microbial stimulants (lipopolysaccharide/LPS and staphylococcal enterotoxin type B/SEB) using TruCulture technology to evaluate immune cell activity. Following incubation, supernatants were preserved and analyzed for protein concentrations. The stimulant:null response ratio for each individual protein was analyzed using multiple linear regression, followed by principal component (PC) analysis to determine whether patterns of protein response were related to CNT/F exposure. Adjusting for confounders, CNT/F metrics (most strongly, the SC-based) were significantly (p < 0.05) inversely associated with stimulant:null ratios of several individual biomarkers: GM-CSF, IFN-γ, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-17, and IL-23. CNT/F metrics were significantly inversely associated with PC1 (a weighted mean of most biomarkers, explaining 25% of the variance in the protein ratios) and PC2 (a biomarker contrast, explaining 14%). Among other occupational exposures, only solvent exposure was significant (inversely related to PC2). CNT/F exposure metrics were uniquely related to stimulant responses in challenged whole blood, illustrating reduced responsiveness to a secondary stimulus. This approach, if replicated in other exposed populations, may present a relatively sensitive method to evaluate human response to CNT/F or other occupational exposures.

Systemic availability of lipophilic organic UV filters through dermal sunscreen exposure

BackgroundChemical UV filters are common components in sunscreens and cosmetic products and used to protect the skin against harmful effects of sunlight like sunburn. However, the effectiveness of sunscreens in the prevention of skin cancer is in some parts still controversial. Meanwhile, questions about negative effects of the chemical UV filters on human health arise and request an effective risk assessment. Real-life exposure data in humans after application of these products are still rare. Thus, we explored whether and to what extent UV filters are absorbed through the skin into the human body. Material and methodsPlasma and urine samples from 20 healthy volunteers were collected before, during and after a real-life exposure scenario (1st application: 2 mg/cm2; 2nd and 3rd (after 2 and 4 h): 1 mg/cm2 each) using a commercial sunscreen formulation for one day. These samples were analyzed for their content of the currently prominent UV filters octocrylene and avobenzone as well as 2-cyano-3,3-diphenylacrylic acid (CDAA) as the main octocrylene metabolite by using different liquid chromatography electrospray-ionization tandem mass spectrometric procedures. ResultsFollowing dermal sunscreen exposure, avobenzone, octocrylene and CDAA reached concentrations up to 11 μg/L, 25 μg/L and 1352 μg/L in plasma. In urine detection rates of avobenzone and octocrylene were low while CDAA showed a high detection rate and reached up to 5207 μg/g creatinine. Kinetic models could be fitted for octocrylene and CDAA in plasma and CDAA in urine. Concentration peaks were reached between 10 and 16 h after first application and half-life periods were in the range of 1.5 to 2 days. The lipophilic UV filter octocrylene and its metabolite CDAA showed a much slower elimination than other more hydrophilic UV filters. Concordantly, the metabolite CDAA in particular showed a markedly increased renal excretion over the whole sampling period and indicated high internal exposure to OC. DiscussionReal-life sunscreen usage leads to considerable bioavailability of organic UV filters and their metabolites which is rarely seen for other environmental exposures. A combined monitoring of the parent compound and its metabolites is important to fully address internal exposure to the UV filter in humans. Considering the kinetic profiles a prolonged systemic release due to depot formation in skin and a potential accumulation through multi-day exposure is presumed. High in-vivo loads call for a critical toxicological assessment of the UV filters and their metabolites.

Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure.

Chemical UV filters are common components in sunscreens and cosmetic products. The question of adverse health risks is not completely resolved, partly owing to lacking human data from dermal exposure, which are essential for sound risk assessment. Therefore, we investigated the urinary toxicokinetics of 2-ethylhexyl salicylate (EHS) after a 1-day dermal real-life sunscreen application scenario. Twenty human volunteers were dermally exposed to a commercial sunscreen for 9h under real-life conditions (2mg/cm2 body surface area; double re-application; corresponding to 3.8g EHS). Urine samples were analyzed for EHS and one of its specific metabolites 2-ethyl-5-hydroxyhexyl salicylate (5OH-EHS) using a two-dimensional liquid chromatographic electrospray-ionization tandem mass spectrometric procedure. EHS and 5OH-EHS were excreted after sunscreen application and reached up to 525µg/g and 213µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8h after first application. First-phase terminal half-lives were 8-9h. For 5OH-EHS, a second-phase terminal half-life could be determined (87h). EHS and 5OH-EHS showed a faster elimination with 70-80% of the overall excretion occurring within 24h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24h reached up to 334µg EHS and 124µg of 5OH-EHS. Simulated real-life sunscreen use for 1day leads to the bioavailability of the UV filter EHS in humans. The kinetic profiles with a prolonged systemic availability indicate a skin depot and make accumulation during consecutive multi-day exposure likely.

Association between air pollution and cardiovascular mortality in Hefei, China: A time-series analysis

In recent years, air pollution has become an alarming problem in China. However, evidence on the effects of air pollution on cardiovascular mortality is still not conclusive to date. This research aimed to assess the short-term effects of air pollution on cardiovascular morbidity in Hefei, China. Data of air pollution, cardiovascular mortality, and meteorological characteristics in Hefei between 2010 and 2015 were collected. Time-series analysis in generalized additive model was applied to evaluate the association between air pollution and daily cardiovascular mortality. During the study period, the annual average concentration of PM10, SO2, and NO2 was 105.91, 20.58, and 30.93 μg/m3, respectively. 21,816 people (including 11,876 man, and 14,494 people over 75 years of age) died of cardiovascular diseases. In single pollutant model, the effects of multi-day exposure were greater than single-day exposure of the air pollution. For every increase of 10 μg/m3 in SO2, NO2, and PM10 levels, CVD mortality increased by 5.26% (95%CI: 3.31%–7.23%), 2.71% (95%CI: 1.23%–4.22%), and 0.68% (95%CI: 0.33%–1.04%) at a lag03, respectively. The multi-pollutant models showed that PM10 and SO2 remained associated with CVD mortality, although the effect estimates attenuated. However, the effect of NO2 on CVD mortality decreased to statistically insignificant. Subgroup analyses further showed that women were more vulnerable than man upon air pollution exposure. These findings showed that air pollution could significantly increase the CVD mortality.

Abstract 288: Use of hiPSC-Derived Cardiomyocytes to Explore Functional Cardiotoxicities of Direct Acting Antiviral Nucleoside Based Structures

Nucleoside-derived structures constitute important Direct-Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment. BMS-986094 (BMS-094: a 2’-C-modified guanosine (G) derivative prodrug) was discontinued in phase II due to heart/kidney failure and cardiomyopathy, whereas sofosbuvir (a 2’-C-modified uridine prodrug) is an effective HCV DAA. Given the importance of purine nucleosides in cardiac signaling, we investigated BMS-094 in the human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) model (iCells, CDI Fujifilm). Beating myocyte monolayer impedance signals were monituored for up to 7 days in the RTCA Cardio platform (ACEA-Biosystems). BMS-094 was acutely myotoxic at high concentrations (≥ 17 μM), as evidenced by cessation of myocyte beating and loss of baseline impedance or ‘Cell Index’ (C.I.), a measure of cell adherence, within hours. On prolonged exposure to BMS-094 at concentrations not associated with loss of C.I. (&lt; 1 μM), we observed progressive, dose-dependent decreases in impedance amplitude (myocyte contractility) which were accompanied by increases in the spontaneous myocyte beating rate. The same beating phenotype could be elicited over a multi-day exposure duration by extracellular application of the BMS-094 core nucleoside (2’-C-methyl-guanosine) alone, but not by unmodified G. Loss of contractility with the G derivatives was accompanied by a decrease of the Ca 2+ transient amplitude in a Ca 2+ influx fluorescence assay (FDSS μCell, Hamamatsu). We investigated the impact of purine or pyrimidine base substitutions in the 2’-CMe-modified nucleoside: 2’-CMe-adenosine, -cytidine, -G, and -uridine. The uridine analog had the most limited effects on hiPSC-CMs beating parameters. The effect of 2’-CMe-cytidine on beating rate and impedance amplitude was similar to that of the G derivative, including a progressive multi-day onset. In contrast, 2’-CMe-adenosine slowed beating acutely, and led to loss of C.I. at higher concentrations. These results demonstrate the varied effects on CM function of base substitutions in antiviral nucleoside chemistry and support the utility of hiPSC-CMs as a model for screening in-vitro the potential cardiotoxicities of nucleoside derivative drugs.

Effects of Multiday Exposure to Ozone on Airway Inflammation as Determined Using Sputum Induction

Single short-term exposures to ozone are known to cause acute changes in pulmonary function and neutrophilic airway inflammation. The respiratory health effects of repeated exposures are not as well studied. Pulmonary function decrements are known to attenuate, but it is less clear how injury and inflammation are affected. Using sputum induction (SI) to sample respiratory tract lining fluid after single- and multiday exposures, we designed a study to test the hypothesis that neutrophils would increase after multiday exposure compared with single-day exposure. In a randomized, crossover design, 15 normal healthy subjects were exposed to O3 (0.2 ppm) under two conditions: for 4 hr for 1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing was performed immediately before and after each 4-hr exposure. The SI was performed 18 hr after the end of the 1D and 4D conditions. The symptom and pulmonary function data followed a pattern seen in other multiday O3 exposure studies, with the greatest changes occurring on the second day. In contrast to previous studies using bronchoalveolar lavage, however, there was a significant increase in the percentage of neutrophils and a significant decrease in the percentage of macrophages after the 4D condition compared with the 1D condition. Given that SI likely samples proximal airways better than distal lung, these results add to the body of evidence that differential airway compartmental responses to O3 occur in humans and other species.

Impaired accumulation of granulocytes in the lung during ozone adaptation

Respiratory alterations induced by an acute exposure to ozone (O 3) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung neutrophilia. As maintenance of neutrophilia at the site of inflammation is due to cytokine-mediated delayed neutrophil apoptosis, which is associated with reduced levels of Bax, a proapoptotic protein, we sought to determine whether defects in these mechanisms could account for O 3 adaptation. Lung granulocytes obtained at different time points from calves exposed to 0.75 ppm O 3 for 12 h/d for 7 consecutive days neither showed enhancement of survival nor Bax deficiency, when compared to blood granulocytes. To further investigate the effects of an exogenous oxidative stress on neutrophil survival, human granulocytes were treated with hydrogen peroxide alone, or in combination with granulocyte/macrophage colony-stimulating factor, an antiapoptotic cytokine. Both treatments led to rapid apoptosis associated with downregulation of Bcl-x L and Bcl-2, two antiapoptotic proteins. This study shows that O 3 adaptation is associated with a failure in the mechanisms leading to accumulation of neutrophils at the site of inflammation, and suggests that this defect is due to direct proapoptotic effects of exogenous oxidative stress on granulocytes.

Opposing effects of anesthetics on pressure tolerance and compression rate effect.

Inert gas narcotics increase intrinsic pressure tolerance (1,000Pc) in CD-1 mice but interfere with development of the protective responses raising seizure thresholds during slower compression (e.g., 60Pc). This secondary narcotic effect can block up to 40% of the total attainable increase in Pc. The narcosis susceptible moiety of this compression rate effect develops early, whereas a narcosis resistant remnant accounts for increase in Pc occurring after 90 min of compression or pressure exposure. Pressure conditioning by multiday pressure exposure entails increases in both 60Pc and 1,000Pc and in virtual annullment of the compression rate effect. The effect can be completely blocked by narcotic gases in the conditioning atmosphere. In addition to blocking part of the compression rate effect the presence of narcotic gases under these conditions can reverse the effects of previously established pressure conditioning. 60Pc regresses much more slowly under these conditions than 1,000Pc. Either reversal rate is much more rapid in air at 1 ATA than at 80 ATA under 0.9 atm N2O. The implications of these data are discussed with regard to evaluation of the hypothesis of antagonism between inert gas narcotics and high pressures and to elaboration of the monoamine hypothesis to account for the modification of the compression rate effect by narcotic gases.