Personal exposure of dairy workers to dust, endotoxin, muramic acid, ergosterol, and ammonia on large-scale dairies in the high plains Western United States.

Dairy workers experience a high degree of bioaerosol exposure, composed of an array of biological and chemical constituents, which have been tied to adverse health effects. A better understanding of the variation in the magnitude and composition of exposures by task is needed to inform worker protection strategies. To characterize the levels and types of exposures, 115 dairy workers grouped into three task categories on nine farms in the high plains Western United States underwent personal monitoring for inhalable dust, endotoxin, 3-hydroxy fatty acids (3-OHFA), muramic acid, ergosterol, and ammonia through one work shift. Eighty-nine percent of dairy workers were exposed to endotoxin at concentrations exceeding the recommended exposure guidelines (adjusted for a long work shift). The proportion of workers with exposures exceeding recommended guidelines was lower for inhalable dust (12%), and ammonia (1%). Ergosterol exposures were only measurable on 28% of samples, primarily among medical workers and feed handlers. Milking parlor workers were exposed to significantly higher inhalable dust, endotoxin, 3-OHFA, ammonia, and muramic acid concentrations compared to workers performing other tasks. Development of large modern dairies has successfully made progress in reducing worker exposures and lung disease prevalence. However, exposure to endotoxin, dust, and ammonia continues to present a significant risk to worker health on North American dairies, especially for workers in milking parlors. This study was among the first to concurrently evaluate occupational exposure to assayable endotoxin (lipid A), 3-hydroxy fatty acids or 3-OHFA (a chemical measure of cell bound and noncell-bound endotoxins), muramic acid, ergosterol, and ammonia among workers on Western U.S. dairies. There remains a need for cost-effective, culturally acceptable intervention strategies integrated in OHS Risk Management and production systems to further optimize worker health and farm productivity.

Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells.

Exposure to the agricultural work environment is a risk factor for the development of respiratory symptoms and chronic lung diseases. Inflammation is an important contributor to the pathogenesis of tissue injury and disease. Cellular and molecular mechanisms mediating lung inflammatory responses to agricultural dust are not yet fully understood. We studied the effects of poultry dust extract on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter activity was due to enhanced binding of activator protein 1 and NF-κB. IL-8 induction was associated with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8 increase was not inhibited by polymyxin B or l-nitroarginine methyl ester, indicating lack of involvement of lipopolysaccharide and nitric oxide in the induction. Lung epithelial and THP-1 cells share common mechanisms for induction of IL-8 levels. Our findings identify key roles for transcriptional mechanisms and protein kinase signaling pathways for IL-8 induction and provide insights into the mechanisms regulating lung inflammatory responses to organic dust exposure.

Differential response of human nasal and bronchial epithelial cells upon exposure to size-fractionated dairy dust.

Exposure to organic dusts is associated with increased respiratory morbidity and mortality in agricultural workers. Organic dusts in dairy farm environments are complex, polydisperse mixtures of toxic and immunogenic compounds. Previous toxicological studies focused primarily on exposures to the respirable size fraction; however, organic dusts in dairy farm environments are known to contain larger particles. Given the size distribution of dusts from dairy farm environments, the nasal and bronchial epithelia represent targets of agricultural dust exposures. In this study, well-differentiated normal human bronchial epithelial cells and human nasal epithelial cells were exposed to two different size fractions (PM10 and PM>10) of dairy parlor dust using a novel aerosol-to-cell exposure system. Levels of proinflammatory transcripts (interleukin [IL]-8, IL-6, and tumor necrosis factor [TNF]-α) were measured 2 h after exposure. Lactate dehydrogenase (LDH) release was also measured as an indicator of cytotoxicity. Cell exposure to dust was measured in each size fraction as a function of mass, endotoxin, and muramic acid levels. To our knowledge, this is the first study to evaluate the effects of distinct size fractions of agricultural dust on human airway epithelial cells. Our results suggest that both PM10 and PM>10 size fractions elicit a proinflammatory response in airway epithelial cells and that the entire inhalable size fraction needs to be considered when assessing potential risks from exposure to agricultural dusts. Further, data suggest that human bronchial cells respond differently to these dusts than human nasal cells, and therefore that the two cell types need to be considered separately in airway cell models of agricultural dust toxicity.

Multiresidue analysis of pesticides in urine of healthy adult companion dogs.

The objective of this study was to determine the background exposures to pesticides as detected in urine from 21 healthy companion dogs in Northern Colorado. A panel of 301 pesticides was used to screen urine samples collected from dogs using an established ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) platform. Canine food intakes were controlled for one month on diets that were also screened for pesticide contents. Fifteen distinct pesticides were detected in urine. The most frequently detected compounds in canine urine samples collected over a 1 month period were atrazine, fuberidazole, imidacloprid, terbumeton, and clopyralid. Fuberidazole was the only pesticide detected in both the diets and urine. Companion dogs develop many similar chronic diseases as humans and represent a relevant model for biomonitoring combinations of environmental pesticide exposures, as well as for evaluating the potential relationships between environmental exposures and disease risk.

Effects of acute cannabis inhalation on reaction time, decision-making, and memory using a tablet-based application.

BACKGROUND: Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, these effects have not been widely investigated among individuals with a pattern of daily use, who may have acquired tolerance. The purpose of this study was to examine the impact of tolerance to cannabis on the acute effects as measured by reaction time, decision-making (gap acceptance), and short-term memory. METHODS: Participants (ages 25-45) completed a tablet-based (iPad) test battery before and approximately 60 min after smoking cannabis flower. The change in performance from before to after cannabis use was compared across three groups of cannabis users: (1) occasional use (n = 23); (2) daily use (n = 31); or (3) no current use (n = 32). Participants in the occasional and daily use group self-administered ad libitum, by smoking or vaping, self-supplied cannabis flower with a high concentration of total THC (15-30%). RESULTS: The occasional use group exhibited decrements in reaction time (slowed) and short-term memory (replicated fewer shapes) from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change. CONCLUSIONS: The findings are consistent with acquired tolerance to certain acute psychomotor effects with daily cannabis use. The finding from the gap acceptance task which showed a decline in speed but not accuracy may indicate a prioritization of accuracy over response time. Cognitive and psychomotor assessments may have utility for identifying impairment associated with recent cannabis use.

Consuming oral cannabidiol prior to a standard alcohol dose has minimal effect on breath alcohol level and subjective effects of alcohol.

RATIONALE: Cannabidiol (CBD) is found in the cannabis plant and has garnered attention as a potential treatment for alcohol use disorder (AUD). CBD reduces alcohol consumption and other markers of alcohol dependence in rodents, but human research on CBD and alcohol is limited. It is unknown whether CBD reduces drinking in humans, and mechanisms through which CBD could impact behavioral AUD phenotypes are unknown. OBJECTIVES: This study explores effects of oral CBD on breath alcohol level (BrAC), and subjective effects of alcohol in human participants who report heavy drinking. METHODS: In this placebo-controlled, crossover study, participants consumed 30 mg CBD, 200 mg CBD, or placebo CBD before receiving a standardized alcohol dose. Participants were blind to which CBD dose they received at each session and completed sessions in random order. Thirty-six individuals completed at least one session and were included in analyses. RESULTS: Differences in outcomes across the three conditions and by sex were explored using multilevel structural equation models. BrAC fell fastest in the placebo condition, followed by 30 mg and 200 mg CBD. Stimulation decreased more slowly in the 200 mg CBD condition than in placebo (b = - 2.38, BCI [- 4.46, - .03]). Sedation decreased more slowly in the 30 mg CBD condition than in placebo (b = - 2.41, BCI [- 4.61, - .09]). However, the magnitude of condition differences in BrAC and subjective effects was trivial. CONCLUSIONS: CBD has minimal influence on BrAC and subjective effects of alcohol. Further research is needed to test whether CBD impacts alcohol consumption in humans, and if so, what mechanism(s) may explain this effect.

The minor cannabinoid cannabigerol (CBG) is a highly specific blood biomarker of recent cannabis smoking.

INTRODUCTION: The determination of recent cannabis use is of forensic interest in the investigation of automotive crashes, workplace incidents and other mishaps. Because Δ9-tetrahydrocannabinol may persist in blood after psychoactive effects of intoxication resolve, particularly in regular users, short-lived minor cannabinoids such as cannabigerol have merited examination as adjunct indicators of recent cannabis inhalation. METHODS: As part of an observational cohort study, whole blood cannabinoids including cannabigerol were measured in whole blood by liquid chromatography with tandem mass spectrometry at baseline, and 30 minutes after initiation of a 15-minute supervised interval of ad libitum cannabis smoking in occasional (1-2 days/week over the past 30 days) (n = 24) and daily cannabis smokers (n = 32). Per protocol, subjects self-reported abstention from inhaling cannabis (>8 h) or ingesting cannabis (>12 h) prior to baseline measurement. RESULTS: At baseline, none of the occasional users had detectable cannabigerol (limit of detection = 0.2 µg/L), whereas cannabigerol was detectable post-smoking in 7 of 24 (29%). Among daily cannabis users, 2 of 32 (6%) had detectable cannabigerol at baseline, increasing to 21 of 32 (66%) post-smoking. The odds ratio for recent cannabis smoking associated with a detectable cannabigerol was 27 (95% confidence interval: 6.6, 110.3). In this mixed cohort of occasional and daily cannabis users, receiver operator characteristic curve analysis indicated that whole blood cannabigerol concentration of ≥ 0.2 µg/L had 96% specificity, 50% sensitivity, and 73% accuracy for identifying a 15-minute interval of ad libitum cannabis smoking initiated 30 minutes earlier. Post smoking blood Δ9-tetrahydrocannabinol (median = 5.6 µg/L in occasional users, 21.3 µg/L in daily users) was significantly correlated with post-smoking cannabigerol (P < 0.0001). CONCLUSION: Whole blood cannabigerol may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking.

Factors affecting urinary organophosphate pesticide metabolite levels among Californian agricultural community members.

Organophosphate (OP) pesticides are widely used in California for agricultural pest and weed control despite their well-documented adverse health effects among infants, children, and adults. We sought to identify factors affecting urinary OP metabolites among families living in high-exposure communities. Our study included 80 children and adults who lived within 61 m (200 ft) of agricultural fields in the Central Valley of California in January and June 2019, which are pesticide non-spraying and spraying seasons, respectively. We collected one urine sample per participant during each visit to measure dialkyl phosphate (DAP) metabolites; these were coupled with in-person surveys to identify health, household, sociodemographic, pesticide exposure, and occupational risk factors. We used a data-driven, best subsets regression approach to identify key factors that influenced urinary DAPs. Participants were mostly Hispanic/Latino(a) (97.5 %), over half were female (57.5 %), and most households reported having a member who worked in agriculture (70.6 %). Among the 149 urine samples suitable for analysis, DAP metabolites were detected in 48.0 % and 40.5 % of samples during January and June, respectively. Total diethyl alkylphosphates (EDE) were only detected in 4.7 % (n = 7) of samples, but total dimethyl alkylphosphates (EDM) were detected in 41.6 % (n = 62) of samples. No differences were observed in urinary DAP levels by visit month or by occupational exposure to pesticides. Best subsets regression identified several individual- and household-level variables that influenced both urinary EDM and total DAPs: the number of years spent living at the current address, household use of chemical products to control mice/rodents, and seasonal employment status. Among adults only, we identified educational attainment (for total DAPs) and age category (for EDM) as significant factors. Our study found consistent urinary DAP metabolites among participants, regardless of spraying season, and identified potential mitigating factors that members of vulnerable populations can implement to protect their health against OP exposure.

Blood cannabinoid molar metabolite ratios are superior to blood THC as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis use is a growing concern in transportation and workplace incidents. Because Δ9-tetrahydrocannabinol is detectable after acute psychoactive effects have resolved, it has limitations as an indicator of recent usage or potential impairment. METHODS: In an observational study of driving and psychomotor performance, we measured whole blood Δ9-tetrahydrocannabinol plus its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol by liquid chromatography with tandem mass spectrometry at baseline and 30 min after starting a 15-minute interval of smoking cannabis in 24 occasional and 32 daily cannabis smokers. We calculated two blood cannabinoid molar metabolite ratios: 1) [Δ9-tetrahydrocannabinol] to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol] and 2) ([Δ9-tetrahydrocannabinol] + [11-hydroxy-Δ9-tetrahydrocannabinol]) to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol]. We compared these to blood [Δ9-tetrahydrocannabinol] alone as indicators of recent cannabis smoking. RESULTS: Median Δ9-tetrahydrocannabinol concentrations increased from 0 ( 0.38). By comparison, a cut-point for Δ9-tetrahydrocannabinol of 5.3 µg/L yielded 88% specificity, 73% sensitivity, and 80% accuracy. CONCLUSIONS: In occasional and daily users, the blood cannabinoid molar metabolite ratios were superior to whole blood Δ9-tetrahydrocannabinol as indicators of recent cannabis smoking. We recommend measurement and reporting of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, and their molar metabolite ratios in forensic and safety investigations.

Characterization of endotoxin collected on California dairies using personal and area-based sampling methods.

Endotoxin, found in the cell wall of gram negative bacteria, is an important contributor to the biological activity of agriculture particulate matter (PM). We analyzed endotoxin in PM collected on 13 California dairies and from the breathing zone of 226 workers during the summer months of 2008. Two particle size fractions were measured: PM(2.5) and inhalable PM. Recombinant factor C assays were used to analyze biologically active endotoxin, while gas chromatography coupled with mass spectrometry in tandem was used to quantify total lipopolysaccharide. Biologically active endotoxin concentrations in the inhalable PM size fraction from area-based samples ranged from 11-2095 EU/m(3) and from 45-2061 EU/m(3) for personal samples. Total endotoxin in the inhalable PM size fraction ranged from 75-10,166 pmol/m(3) for area-based samples and 34-11,689 pmol/m(3) for personal samples. Area-based geometric mean concentrations for biologically active endotoxin and total endotoxin in PM(2.5) and inhalable PM size fractions were 3 EU/m(3), 149 EU/m(3), 60 pmol/m(3), and 515 pmol/m(3), respectively. Personal geometric mean concentrations in the inhalable PM size fraction were 334 EU/m(3), and 1178 pmol/m(3). Biologically active and total endotoxin concentration variation was best explained by meteorological data, wind speed, relative humidity, and dairy waste management practices. Differences in endotoxin concentration and composition were found across locations on the dairy.

Morphine Accumulates in the Retina Following Chronic Systemic Administration.

Opioid transport into the central nervous system is crucial for the analgesic efficacy of opioid drugs. Thus, the pharmacokinetics of opioid analgesics such as morphine have been extensively studied in systemic circulation and the brain. While opioid metabolites are routinely detected in the vitreous fluid of the eye during postmortem toxicological analyses, the pharmacokinetics of morphine within the retina of the eye remains largely unexplored. In this study, we measured morphine in mouse retina following systemic exposure. We showed that morphine deposits and persists in the retina long after levels have dropped in the serum. Moreover, we found that morphine concentrations (ng/mg tissue) in the retina exceeded brain morphine concentrations at all time points tested. Perhaps most intriguingly, these data indicate that following chronic systemic exposure, morphine accumulates in the retina, but not in the brain or serum. These results suggest that morphine can accumulate in the retina following chronic use, which could contribute to the deleterious effects of chronic opioid use on both image-forming and non-image-forming visual functions.

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function.

Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m2) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.

Edible marijuana and cycle ergometer exercise.

Purpose: There is extensive public and scientific interest in the influence of cannabis and the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC), on exercise performance. Unfortunately, recent, up-to-date studies are lacking. The aim of the current study was to address the hypothesis that ingestion of edible marijuana, prior to exercise, would have unfavorable effects on the physiological response to exercise and on exercise performance. Methods: 17 Healthy adult male and female habitual exercisers, who were regular users of cannabis products, were screened for study participation. 10 were enrolled, and data from 9 [8 males, 1 female, aged 25±3 years, with peak oxygen uptake of 56.5±11.7 ml/kg/min (mean ± SD)] were retained. Participation included two exercise sessions, each preceded by self-administration and ingestion of either edible marijuana (containing 10 mg THC) or placebo. Cardio-respiratory responses (via indirect calorimetry) to stationary cycle ergometer exercise (8 min at 50, 100 and 150 W) were recorded before completion of a 20-min Functional Threshold Power test (FTP20) and a sprint test involving maximal effort until volitional fatigue. Results: Edible marijuana increased the concentration of circulating THC and THC metabolites, and evoked sensations of intoxication and altered psychoactive state. Cardio-respiratory responses to staged cycle ergometer exercise were normal and were unaffected by edible marijuana. Compared with placebo, edible marijuana did not influence FTP20 (Placebo 253±75 vs THC: 251±72 W (mean±SD); p > 0.45) or peak power output during the sprint test (Placebo: 710±201 vs. THC: 732±136 W; p = 0.864). Conclusion: 10 mg of THC, when ingested prior to exercise by regular exercisers and habitual users of cannabis, had little effect on the physiological response to standardized cycle ergometer exercise, and was neither ergogenic nor ergolytic.

Enhanced removal of per- and polyfluoroalkyl substances in complex matrices by polyDADMAC-coated regenerable granular activated carbon.

Granular activated carbon (GAC) has been used to remove per- and polyfluoroalkyl substances (PFASs) from industrial or AFFF-impacted waters, but its effectiveness can be low because adsorption of short-chained PFASs is ineffective and its sites are exhausted rapidly by co-contaminants. To increase adsorption of anionic PFASs on GAC by electrostatic attractions, we modified GAC's surface with the cationic polymer poly diallyldimethylammonium chloride (polyDADMAC) and tested its capacity in complex water matrices containing dissolved salts and humic acid. Amending with concentrations of polyDADMAC as low as 0.00025% enhanced GAC's adsorption capacity for PFASs, even in the presence of competing ions. This suggests that electrostatic interactions with polyDADMAC's quaternary ammonium functional groups helped bind organic and inorganic ions as well as the headgroup of short-chain PFASs, allowing more overall PFAS removal by GAC. Evaluating the effect of polymer dose is important because excessive addition can block pores and reduce overall PFAS removal rather than increase it. To decrease the waste associated with this adsorption strategy by making the adsorbent viable for more than one saturation cycle, a regeneration method is proposed which uses low-power ultrasound to enhance the desorption of PFASs from the polyDADMAC-GAC with minimum disruption to the adsorbent's structure. Re-modification with the polymer after sonication resulted in a negligible decrease in the sorbent's capacity over four saturation rounds. These results support consideration of polyDADMAC-modified GAC as an effective regenerable adsorbent for ex-situ concentration step of both short and long-chain PFASs from real waters with high concentrations of competing ions and low PFAS loads.

Relationships between plasma fatty acids in adults with mild, moderate, or severe COVID-19 and the development of post-acute sequelae.

Background: SARS-CoV-2 has infected millions across the globe. Many individuals are left with persistent symptoms, termed post-acute sequelae of COVID-19 (PASC), for months after infection. Hyperinflammation in the acute and convalescent stages has emerged as a risk factor for poor disease outcomes, and this may be exacerbated by dietary inadequacies. Specifically, fatty acids are powerful inflammatory mediators and may have a significant role in COVID-19 disease modulation. Objective: The major objective of this project was to pilot an investigation of plasma fatty acid (PFA) levels in adults with COVID-19 and to evaluate associations with disease severity and PASC. Methods and procedures: Plasma from adults with (N = 41) and without (N = 9) COVID-19 was analyzed by gas chromatography-mass spectrometry (GC-MS) to assess differences between the concentrations of 18 PFA during acute infection (≤14 days post-PCR + diagnosis) in adults with varying disease severity. Participants were grouped based on mild, moderate, and severe disease, alongside the presence of PASC, a condition identified in patients who were followed beyond acute-stage infection (N = 23). Results: Significant differences in PFA profiles were observed between individuals who experienced moderate or severe disease compared to those with mild infection or no history of infection. Palmitic acid, a saturated fat, was elevated in adults with severe disease (p = 0.04), while behenic (p = 0.03) and lignoceric acid (p = 0.009) were lower in adults with moderate disease. Lower levels of the unsaturated fatty acids, γ-linolenic acid (GLA) (p = 0.03), linoleic (p = 0.03), and eicosapentaenoic acid (EPA) (p = 0.007), were observed in adults with moderate disease. Oleic acid distinguished adults with moderate disease from severe disease (p = 0.04), and this difference was independent of BMI. Early recovery-stage depletion of GLA (p = 0.02) and EPA (p = 0.0003) was associated with the development of PASC. Conclusion: Pilot findings from this study support the significance of PFA profile alterations during COVID-19 infection and are molecular targets for follow-up attention in larger cohorts. Fatty acids are practical, affordable nutritional targets and may be beneficial for modifying the course of disease after a COVID-19 diagnosis. Moreover, these findings can be particularly important for overweight and obese adults with altered PFA profiles and at higher risk for PASC. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04603677].

Release of soil colloids during flow interruption increases the pore-water PFAS concentration in saturated soil.

Groundwater flow through aquifer soils or packed bed systems can fluctuate for various reasons, which could affect the concentration of natural colloids and per- and polyfluoroalkyl substances (PFAS) in the pore water. In such cases, PFAS concentration could either decrease due to matrix diffusion of PFAS or increase by the detachment of colloids carrying PFAS. Yet, the effect of flow fluctuation on PFAS transport or release in porous media has not been examined. To examine the relative importance of either process, we interrupted the flow during an injection of groundwater spiked with perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA), and bromide as conservative tracer through clay-rich soil, so that diffusive transport would be prominent during flow interruption. After flow interruption, the PFAS concentration did not decrease indicating an insignificant contribution of matrix diffusion. The concentration increased, potentially due to enhanced release of colloid-associated PFAS. Analysis of samples before and after flow interruption by particle size analysis and SEM confirmed an increase in soil colloid concentration after the flow interruption. XRD analysis of soil and the colloids proved that PFAS were associated with specific sites of the colloids. Due to a higher affinity of PFOA to soil colloids, the total PFOA concentration in the effluent samples increased more than PFBA after the flow interruption process. The results indicate that colloids may have a disproportionally higher role in the transport of PFAS in conditions that release colloids from porous media. Thus, fluctuations in groundwater flow can increase this colloid facilitated mobility of PFAS.

Pharmacokinetic Investigation of Commercially Available Edible Marijuana Products in Humans: Potential Influence of Body Composition and Influence on Glucose Control.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10 mg of delta-9-tetrahydrocannabinol (THC). Thirty minutes following marijuana ingestion, participants imbibed a 75 g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 min; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-30 min were detected (p = 0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; p > 0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow recreational marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability.

Data supporting the physiological effects of cannabidiol (CBD) ingestion in humans are conflicting. Differences between CBD preparations and bioavailability may contribute to these discrepancies. Further, an influence of body composition on CBD bioavailability is feasible, but currently undocumented. The aims of this study were to: (1) compare the pharmacokinetics of five oral CBD preparations over 4 h; (2) examine the relationship between body composition and CBD pharmacokinetics; and, (3) explore the influence of CBD on heart rate variability. In total, five preparations of CBD, standardized to 30 mg, were orally administered to 15 healthy men and women (21-62 years) in a randomized, crossover design. Prior to and 60 min following CBD ingestion, heart rate variability was determined. Body composition was assessed using dual energy X-ray absorptiometry. Peak circulating CBD concentration, time to peak concentration, and area under the curve was superior in a preparation comprising 5% CBD concentration liquid. Fat free mass was a significant predictor (R 2 = 0.365, p = 0.017) of time to peak concentration for this preparation. Several heart rate variability parameters, including peak frequency of the high frequency band, were favorably, but modestly modified following CBD ingestion. These data confirm an influence of CBD preparation and body composition on CBD bioavailability, and suggest that acute CBD ingestion may have a modest influence on autonomic regulation of heart rate.

Simulated driving performance among daily and occasional cannabis users.

OBJECTIVE: Daily cannabis users develop tolerance to some drug effects, but the extent to which this diminishes driving impairment is uncertain. This study compared the impact of acute cannabis use on driving performance in occasional and daily cannabis users using a driving simulator. METHODS: We used a within-subjects design to observe driving performance in adults age 25 to 45 years with different cannabis use histories. Eighty-five participants (43 males, 42 females) were included in the final analysis: 24 occasional users (1 to 2 times per week), 31 daily users and 30 non-users. A car-based driving simulator (MiniSim™, National Advanced Driving Simulator) was used to obtain two measures of driving performance, standard deviation of lateral placement (SDLP) and speed relative to posted speed limit, in simulated urban driving scenarios at baseline and 30 min after a 15 min ad libitum cannabis smoking period. Participants smoked self-supplied cannabis flower product (15% to 30% tetrahydrocannabinol (THC). Blood samples were collected before and after smoking (30 min after the start of smoking). Non-users performed the same driving scenarios before and after an equivalent rest interval. Changes in driving performance were analyzed by repeated measures general linear models. RESULTS: Mean whole blood THC cannabinoids concentrations post smoking were use THC = 6.4 ± 5.6 ng/ml, THC-COOH = 10.9 ± 8.79 ng/mL for occasional users and THC = 36.4 ± 37.4 ng/mL, THC-COOH = 98.1 ± 90.6 ng/mL for daily users. On a scale of 0 to 100, the mean post-use score of subjective high was similar in occasional users and daily users (52.4 and 47.2, respectively). In covariate-adjusted analysis, occasional users had a significant increase in SDLP in the straight road segment from pre to post compared to non-users; non-users decreased by a mean of 1.1 cm (25.5 cm to 24.4 cm) while occasional users increased by a mean of 1.9 cm (21.7 cm to 23.6 cm; p = 0.02). Daily users also increased adjusted SDLP in straight road segments from baseline to post-use (23.2 cm to 25.0 cm), but the change relative to non-users was not statistically significant (p = 0.08). The standardized mean difference in unadjusted SDLP from baseline to post-use in the straight road segments comparing occasional users to non-users was 0.64 (95% CI 0.09 - 1.19), a statistically significant moderate increase. When occasional users were contrasted with daily users, the baseline to post changes in SDLP were not statistically significant. Daily users exhibited a mean decrease in baseline to post-use adjusted speed in straight road segments of 1.16 mph; a significant change compared to slight speed increases in the non-users and occasional users (p = 0.02 and p = 0.01, respectively). CONCLUSION: We observed a decrement in driving performance assessed by SDLP after acute cannabis smoking that was statistically significant only in the occasional users in comparison to the nonusers. Direct contrasts between the occasional users and daily users in SDLP were not statistically significant. Daily users drove slower after cannabis use as compared to the occasional use group and non-users. The study results do not conclusively establish that occasional users exhibit more driving impairment than daily users when both smoke cannabis ad libitum.

Muramic acid, endotoxin, 3-hydroxy fatty acids, and ergosterol content explain monocyte and epithelial cell inflammatory responses to agricultural dusts.

In agricultural and other environments, inhalation of airborne microorganisms is linked to respiratory disease development. Bacterial endotoxins, peptidoglycans, and fungi are potential causative agents, but relative microbial characterization and inflammatory comparisons amongst agricultural dusts are not well described. The aim of this study was to determine the distribution of microbial endotoxin, 3-hydroxy fatty acids (3-OHFA), muramic acid, and ergosterol and evaluate inflammatory responses in human monocytes and bronchial epithelial cells with various dust samples. Settled surface dust was obtained from five environments: swine facility, dairy barn, grain elevator, domestic home (no pets), and domestic home with dog. Endotoxin concentration was determined by recombinant factor C (rFC). 3-OHFA, muramic acid, and ergosterol were measured using gas chromatography-mass spectrometry. Dust-induced inflammatory cytokine secretion in human monocytes and bronchial epithelial cells was evaluated. Endotoxin-independent dust-induced inflammatory responses were evaluated. Endotoxin and 3-OHFA levels were highest in agricultural dusts. Muramic acid, endotoxin, 3-OHFA, and ergosterol were detected in dusts samples. Muramic acid was highest in animal farming dusts. Ergosterol was most significant in grain elevator dust. Agricultural dusts induced monocyte tumor necrosis factor (TNF) alpha, interleukin (IL)-6, IL-8, and epithelial cell IL-6 and IL-8 secretion. Monocyte and epithelial IL-6 and IL-8 secretion was not dependent on endotoxin. House dust(s) induced monocyte TNFalpha, IL-6, and IL-8 secretion. Swine facility dust generally produced elevated responses compared to other dusts. Agricultural dusts are complex with significant microbial component contribution. Large animal farming dust(s)-induced inflammation is not entirely dependent on endotoxin. Addition of muramic acid to endotoxin in large animal farming environment monitoring is warranted.