Substantial Exposure Research Articles

Air pollutants, residential greenspace, and the risk of kidney stone disease: a large prospective cohort study from the UK Biobank.

The epidemiological evidence regarding the correlation between air pollution, residential greenspace, and the risk of kidney stone disease (KSD) is limited, with no large-scale prospective studies conducted on this relationship. We conducted a large-scale prospective study from the UK Biobank to explore the correlation between air pollution, residential greenspace, and the risk of KSD. This study included 419,835 UK Biobank participants who did not have KSD at baseline. An air pollution score was derived through the summation of concentrations for five air pollutants, including particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5), ranging from 2.5 to 10 μm (PM2.5-10), ≤10 μm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx). Various covariates were adjusted for in Cox proportional hazard regression to evaluate the risk of KSD associated with air pollution score, single air pollutant, and residential greenspace. During a follow-up period of 12.7 years, 4503 cases of KSD were diagnosed. Significant associations were found between KSD risk and air pollution score (HR: 1.08, 95% CI: 1.03-1.13), PM2.5 (1.06, 1.02-1.11), PM10 (1.04, 1.01-1.07), NO2 (1.09, 1.02-1.16), NOx (1.08, 1.02-1.11), greenspace buffered at 300 m (0.95, 0.91-0.99), and greenspace buffered at 1000 m (0.92, 0.86-0.98) increase per interquartile range (IQR). PM2.5 and NO2 reductions may be a key mechanism for the protective impact of residential greenspace on KSD (P for indirect path < 0.05). Prolonged exposure to air pollution was correlated with a higher risk of KSD, while residential greenspace exhibits an inverse association with KSD risk, partially mediated by the reduction in air pollutants concentrations. These findings emphasize the significance of mitigating air pollution and maintaining substantial greenspace exposure as preventive measures against KSD.

Measurements of dust and respirable crystalline silica during indoor demolition and renovation.

Increased focus on renovating and maintaining the existing building stock is an integral part of the circular economy, however this might pose challenges to workers health. The aim of this study was to assess the renovation workers' exposure to inhalable dust, thoracic dust, respirable dust, and respirable crystalline silica (RCS). Personal aerosol samples were collected as full shift samples from 92 workers to a total of 407 samples. Fourteen locations around Oslo, Norway was visited for multiple days with repeated measurements of the same individual. Particulate matter from 3 aerosol fractions, respirable, thoracic, and inhalable, were analyzed gravimetrically, and the respirable fraction was analyzed for RCS by NIOSH 7500 method for X-ray diffraction (XRD)with low temperature plasma ashing sample preparation. The total measured concentrations of respirable dust (n = 192) had a geometric mean (GM) of 0.88mg/m3, RCS concentrations (n = 182) had a GM of 0.040mg/m3, thoracic dust (n = 131) had GM 2.4mg/m3, and inhalable dust (n = 84) had a GM of 8.5mg/m3. The maximum measured concentrations were 29mg/m3, 3.2mg/m3, 65mg/m3, and 163mg/m3, respectively. Workdays involving tasks such as mechanical demolition and clearing out demolished materials led to the highest exposure levels of both dust and RCS. However, other workers at the renovation sites were indirectly exposed to a considerable amount of RCS. This study revealed substantial exposure to both RCS and dust during renovation, and protective measures are warranted to reduce exposure levels in the industry.

Association between the oxidative balance score and estimated glomerular filtration rate: 2007–2018 NHANES

Oxidative stress is closely associated with the estimated glomerular filtration rate (eGFR) levels. A comprehensive indicator for evaluating dietary and lifestyle exposures to oxidative stress is the Oxidative Balance Score (OBS), with higher OBS suggesting more substantial antioxidant exposures. The aim of this study is to explore the relationship between OBS and eGFR levels. A total of 20,285 subjects were selected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. One-way and multifactorial linear regression analyses were used to assess the association of OBS with eGFR. The relationship between OBS and eGFR levels was also assessed using restricted cubic splines (RCS) analysis. OBS levels were significantly and positively correlated with eGFR levels, and eGFR values were more susceptible to OBS in males than in females. Our findings suggest that higher OBS scores may be associated with higher eGFR levels, highlighting the importance of adhering to an antioxidant diet and lifestyle, which can help prevent kidney disease.

Chinese corporate biodiversity exposure

We present time series indices of corporate biodiversity risk exposure for listed Chinese companies. Utilizing recent advancements in text-as-data techniques, we analyze the annual reports of more than 4000 companies spanning a 15-year period. Our study introduces two indices: an exposure index, inspired by the work of Giglio et al., 2023, and an extensiveness index, which draws from policy uncertainty indices like Lucey et al., 2022. Our findings reveal substantial exposure to biodiversity risks among Chinese companies, notably exceeding levels observed in the USA.Corporate-level data are available as an Internet appendix to this note.

A Pooled Population Pharmacokinetic Study of Oral and Intravenous Administration of Clavulanic Acid in Neonates and Infants: Targeting Effective Beta-Lactamase Inhibition.

Data published on the oral clavulanic acid pharmacokinetics in the pediatric population is lacking. This research aimed to describe clavulanic acid disposition following oral and intravenous administration and to provide insights into clavulanic acid exposure based on threshold concentrations for (pre-)term neonates and infants. This pooled population pharmacokinetic study combined four datasets for analysis in NONMEM v7.4.3. Clavulanic acid exposure was simulated using the percentage of time above the threshold concentrations (%fT > CT). Multiple dosage regimens and amoxicillin/clavulanic acid dosage ratios were evaluated. The cohort consisted of 89 (42 oral, 47 intravenous) subjects (403 samples) with a median (range) postnatal age 54.5 days (0-365), gestational age 37.4 weeks (23.0-41.7), and current bodyweight 3.9 kg (0.6-9.0). A one-compartment model with first-order absorption best described clavulanic acid pharmacokinetics with postnatal age as a covariate on the inter-individual variability of clearance. Oral bioavailability was 24.4% in neonates up to 10 days of age. An oral dosing regimen 90 mg/kg/day amoxicillin/clavulanic acid (4:1 ratio) resulted in 40.2% of simulated patients achieving 100% fT > CT,2mg/L. An amoxicillin/clavulanic acid ratio of 4:1 is preferred for neonatal oral regimens due to the higher exposure along the entire %fT > CT range (0-100%) as ratios higher than 4:1 might result in inadequate exposure. Our results highlight substantial exposure differences (%fT > CT) when using threshold concentrations of 1 mg/L vs. 2 mg/L. This first population pharmacokinetic model for clavulanic acid in neonates may serve as a foundational step for future research, once more precise clavulanic acid targets become available.

Atypical daily visual exposure to faces in adults with autism spectrum disorder

Expert face processes are refined and tuned through a protracted development. Exposure statistics of the daily visual experience of neurotypical adults (the face diet) show substantial exposure to familiar faces. People with autism spectrum disorder (ASD) do not show the same expertise with faces as their non-autistic counterparts. This may be due to an impoverished visual experience with faces, according to experiential models of autism. Here, we present the first empirical report on the day-to-day visual experience of the faces of adults with ASD. Our results, based on over 360h of first-person perspective footage of daily exposure, show striking qualitative and quantitative differences in the ASD face diet compared with those of neurotypical observers, which is best characterized by a pattern of reduced and atypical exposure to familiar faces in ASD. Specifically, duration of exposure to familiar faces was lower in ASD, and faces were viewed from farther distances and from viewpoints that were biased toward profile pose. Our results provide strong evidence that individuals with ASD may not be getting the experience needed for the typical development of expert face processes.

Real-Time Dosimetry in Endourology: Tracking Staff Radiation Risks.

To retrospectively investigate scatter radiation (SCR) exposure among staff in the endourology operating theatre. During surgeries under fluoroscopic guidance, five professional groups (urological surgeon [US], surgical nurse [SN], assistant surgical nurse [ASN], anaesthetist [A], and anaesthesia care [AC]) wore real-time dosimeters (Philips DoseAware System) on their head and chest over lead aprons between July 2023 and February 2024. The SCR data were analysed and correlated with procedural and patient factors. In total, 249 procedures were performed, including 86 retrograde intrarenal surgeries and 10 percutaneous nephrolithotomies. Median SCR exposure was 38.81, 17.20, 7.71, 11.58, 0.63, 0.23, 0.12, and 0.15 Microsievert (µSv) for US chest (USC), US head (USH), SN chest (SNC), SN head (SNH), A chest (AC), AC chest (ACC), ASN chest (ASNC), and ASN head (ASNH), respectively. There was a significant correlation between DAP and SCR doses detected by USC, USH, SNC, SNH, AC, and ACC dosimeters (p < 0.05). The median chest-to-eye conversion factor (CECF) was 2.11 for the US and 0.71 for the SN. This study, using real-time dosimetry, is among the first to assess staff occupational SCR exposure in endourology. It highlights a substantial SCR exposure, indicating an occupational health hazard that warrants further investigation.

Motivating Factors to the Success of Youth Enterprise Startups: A Study of Nepali Enterprises

Youth entrepreneurship emphasizes enterprising qualities such as initiative, innovation, creativity, and risk-taking in the work environment using appropriate knowledge and skills necessary for success in a given environment and culture. The research work is expected to provide a breakthrough in studying youth-centric entrepreneurial and new venture creation efforts as the majority of studies put youth and adult entrepreneurs with substantial experience and exposure into the same basket. The objective of this study is to assess the impact of entrepreneur’s exposure, government entrepreneurial policy and support, banking/ finance accessibility, risk propensity, and family and social support, training and education on the motivation of youth enterprise startup. The study is based on descriptive and analytical research design. Data was collected in Kathmandu Valley through structured questionnaire from 140 respondents which includes various entrepreneurs from Kathmandu Valley. The study used convenience sampling technique for the selection of sample respondents. Various statistical tests such as Karl Pearson’s correlation, and regression analysis were conducted to analyze the data with the help of statistical software SPSS. It was found that entrepreneurial exposure and training and education are the significant factors impacting the motivation of youth entrepreneurship startups. The youth startups seem particularly vulnerable to failure due to the lack of motivation and support and a conducive environment. Moreover, the skill set of conducting interaction of business ideas is an added advantage that comes as a result of entrepreneurial exposure and is key for the success of youth enterprise startups and further implied to government and managerial perspectives.

Association of pyrethroids exposure with asthma in US children and adolescents: a nationally representative cross-sectional study.

Pyrethroids (PYR) are among the most widely used insecticides in households, leading to substantial exposure. Children and adolescents, especially during growth spurts, have a reduced capacity to effectively metabolize these insecticides. The relationship between PYR exposure and asthma in these age groups remains poorly understood, highlighting the need for further research.We used data from the 2007-2014 National Health and Nutrition Examination Survey, which included 1181 children aged 6-11years and 1258 adolescents aged 12-19years. The concentration of the PYR metabolite 3-phenoxybenzoic acid (3-PBA) in urine was quantified using solid-phase extraction-high-performance liquid chromatography-heated electrospray ionization tandem mass spectrometry. Asthma was defined based on self-reported doctor diagnoses from the questionnaire. PYR exposure was measured using urine samples collected simultaneously with the questionnaire. We explored the association between PYR exposure and asthma using multiple logistic regression analyses, adjusting for potential confounders.Multiple logistic regression analyses revealed no significant association between PYR exposure and asthma in children and adolescent boys (all P > 0.05). In contrast, PYR exposure was significantly associated with asthma in adolescent girls aged 12-19years. Specifically, for "ever asthma," the odds ratios (ORs) were 2.49 (95% CI = 1.03-5.97) in the second quartile of PYR exposure and 2.48 (95% CI = 1.04-5.91) in the third quartile, each in comparison to the first quartile. For "current asthma," in comparison to the first quartile, the ORs were 3.99 (95% CI = 1.55-10.26) in the second quartile of PYR exposure, 3.39 (95% CI = 1.32-8.70) in the third quartile, and 2.93 (95% CI = 1.24-6.90) in the fourth quartile.Conclusions:Our study found a significant association between PYR exposure and asthma in adolescent girls, whereas no significant association was observed in children and adolescent boys. These findings suggest potential sex and age differences in susceptibility to PYR exposure. Further research is warranted to confirm these results and elucidate the underlying mechanisms.

“I Cannot Tell Anyone:” There are Many Reasons

ABSTRACT Purpose: The purpose of this study was to investigate variables associated with difficulty disclosing past trauma. Across several prevalence studies, 26% of adults never disclosed childhood abuse until adulthood when they were asked in a research survey or interview question. In this Institutional Review Board approved study, group differences were examined (ability and inability to disclose a traumatic event) as well as predictors for difficulty disclosing past trauma. Method: A non-clinical population (N = 693) was examined to determine prevalence rates and group differences between participants unable to tell someone about a past traumatic event (10%) compared to those who could disclose past traumatic events (90%). Variables included pathological dissociative processing, internalized shame, coping strategies (task, emotion, avoidance), and cumulative trauma exposure. Logistic regression analyses were conducted to determine predicting variables for disclosure difficulties. Findings: The group that had difficulty disclosing a past traumatic event had more cumulative trauma, pathological dissociative processing, emotion-oriented coping, and shame. In the first logistic regression analyses, interpersonal traumatic events were predictors for the inability to disclose a traumatic event (classified 90% of group membership). In the second logistic regression, shame and cumulative traumatic exposure were predicting factors (classified 90% of group membership). Conclusion: Difficulty speaking about a traumatic event was associated with interpersonal adult and childhood traumatic events, more internalized shame, and cumulative trauma exposure. It is recommended that clinicians working with patients with substantial traumatic exposure address shame, pathological dissociative processing, and emotion-oriented coping strategies if they detect trauma disclosure difficulties.

Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic–pituitary–adrenal-axis dysregulation: a study protocol description

ABSTRACT Background: Trauma-focused treatments for post-traumatic stress disorder (PTSD) are effective for many patients. However, relapse may occur when acquired extinction memories fail to generalize beyond treatment contexts. A subgroup of PTSD patients – potentially with substantial exposure to early-life adversity (ELA) – show dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which results in lower cortisol levels. Glucocorticoids, including cortisol, appear to facilitate strength and generalization of emotional memories. Objective: We describe the protocol of an integrated PTSD study. We investigate (A) associations between HPA-axis dysregulation, ELA, epigenetic markers, and PTSD treatment outcome (observational study); and (B) effects of exogenous glucocorticoids on strength and generalization of extinction memories and associated neural mechanisms [pharmacological intervention study with functional magnetic resonance imaging (fMRI)]. The objective is to provide proof of concept that PTSD patients with HPA-axis dysregulation often experienced ELA and may show improved strength and generalization of extinction learning after glucocorticoid administration. Method: The observational study (n = 160 PTSD group, n = 30 control group) assesses ELA, follow-up PTSD symptoms, epigenetic markers, and HPA-axis characteristics (salivary cortisol levels during low-dose dexamethasone suppression test and socially evaluated cold-pressor test). The pharmacological intervention study (n = 80 PTSD group, with and without HPA-axis dysregulation) is a placebo-controlled fMRI study with a crossover design. To investigate strength and generalization of extinction memories, we use a differential fear acquisition, extinction, and extinction recall task with spatial contexts within a virtual environment. Prior to extinction learning, 20 mg hydrocortisone or placebo is administered. During next-day recall, strength of the extinction memory is determined by recovery of skin conductance and pupil dilation differential responding, whereas generalization is assessed by comparing responses between different spatial contexts. Conclusion: The integrated study described in the current protocol paper could inform a personalized treatment approach in which these PTSD patients may receive glucocorticoids as a treatment enhancer in trauma-focused therapies. Trial registration: The research project is registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, https://eudract.ema.europa.eu/, EudraCT number 2020-000712-30.

Exposure to Pesticides and Breast Cancer in an Agricultural Region in Brazil.

Rural workers are disproportionally exposed to pesticides and might be at an increased risk of developing chronic diseases. Here, we investigated the impact of pesticide exposure on breast cancer (BC) risk and disease profile in rural female workers. This is a case-control study that prospectively included 758 individuals. The study was conducted in the Southwest region of Paraná state in Brazil, a region characterized by family-based agriculture and intensive use of pesticides. We found that this region has a 41% higher BC diagnosis rate and 14% higher BC mortality rate than the mean rates in Brazil, as well as a pesticide trade volume about 6 times higher than the national average. We showed substantial exposure in this population and found that even women who did not work in the fields but performed equipment decontamination and clothes washing of male partners who worked in the fields had urine samples positive for glyphosate, atrazine, and/or 2,4-D. The crude association showed a significantly higher risk of BC among women exposed to pesticides (OR: 1.58, 95% CI 1.18-2.13). Adjusted analyses showed a lower and nonstatistically significant association (OR: 1.30, 95% CI 41 0.87-1.95). Stratification on disease profile showed a significantly higher risk of lymph node metastasis (adjusted OR: 2.19, 95% CI 1.31-3.72) in women exposed to pesticides. Our findings suggest that female populations exposed to pesticides are at a higher risk of developing BC with a more aggressive profile and draw attention to the need to monitor rural populations potentially exposed to pesticides in the field or at home.

Point-of-use chlorine residuals and disinfection byproduct occurrences in rural households served by public water utilities in Appalachian Virginia

ABSTRACT We characterized concentrations of trihalomethanes (THMs), a measure of disinfection byproducts (DBPs), in tap water samples collected from households with utility-supplied water in two rural counties in Appalachian Virginia, and assessed associations with pH, free chlorine, and metal ions which can impact THM formation. Free chlorine concentrations in all samples (n = 27 homes) complied with EPA drinking water guidelines, though 7% (n = 2) of first draw samples and 11% (n = 3) of 5-min flushed-tap water samples exceeded the US Safe Drinking Water Act (SDWA) maximum contaminant level (MCL) for THM (80 ppb). Regression analyses showed that free chlorine and pH were positively associated with the formation of THM levels above SDWA MCLs (OR = 1.04, p = 0.97 and OR = 1.74, p = 0.79, respectively), while temperature was negatively associated (OR = 0.78, p = 0.38). Of the eight utilities serving study households, samples from water served by three different utilities exceeded the EPA MCL for THM. Overall, these findings do not indicate substantial exposures to DBPs for rural households with utility-supplied water in this region of southwest Virginia. However, given the observed variability in THM concentrations between and across utilities, and established adverse health impacts associated with chronic and acute DBP exposure, more research on DBPs in rural Central Appalachia is warranted.

Skin pharmacokinetics of miltefosine in the treatment of post-kala-azar dermal leishmaniasis in South Asia.

Post-kala-azar dermal leishmaniasis (PKDL) arises as a dermal complication following a visceral leishmaniasis (VL) infection. Current treatment options for PKDL are unsatisfactory, and there is a knowledge gap regarding the distribution of antileishmanial compounds within human skin. The present study investigated the skin distribution of miltefosine in PKDL patients, with the aim to improve the understanding of the pharmacokinetics at the skin target site in PKDL. Fifty-two PKDL patients underwent treatment with liposomal amphotericin B (20 mg/kg) plus miltefosine (allometric dosing) for 21 days. Plasma concentrations of miltefosine were measured on study days 8, 15, 22 and 30, while a punch skin biopsy was taken on day 22. A physiologically based pharmacokinetic (PBPK) model was developed to evaluate the distribution of miltefosine into the skin. Following the allometric weight-based dosing regimen, median miltefosine concentrations on day 22 were 43.73 µg/g (IQR: 21.94-60.65 µg/g) in skin and 33.29 µg/mL (IQR: 25.9-42.58 µg/mL) in plasma. The median individual concentration ratio of skin to plasma was 1.19 (IQR: 0.79-1.9). In 87% (45/52) of patients, skin exposure was above the suggested EC90 PK target of 10.6 mg/L associated with in vitro susceptibility. Simulations indicated that the residence time of miltefosine in the skin would be more than 2-fold longer than in plasma, estimated by a mean residence time of 604 versus 266 hours, respectively. This study provides the first accurate measurements of miltefosine penetration into the skin, demonstrating substantial exposure and prolonged retention of miltefosine within the skin. These findings support the use of miltefosine in cutaneous manifestations of leishmaniasis. In combination with parasitological and clinical data, these results are critical for the future optimization of combination therapies with miltefosine in the treatment of PKDL.

In-depth exploration of the radiation exposure to staff performing endoscopic retrograde cholangiopancreatography procedures (ERCP) through RANDO phantom and TLDs.

This study provides a comprehensive evaluation of the occupational radiation exposure faced by healthcare professionals during Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures. Utilizing an anthropomorphic RANDO phantom equipped with Thermoluminescent Dosimeters (TLDs), we replicated ERCP scenarios to measure radiation doses received by medical staff. The study meticulously assessed radiation exposure in various corresponding body regions typically occupied by medical staff during ERCP, with a focus on eyes, thyroid, hands, and reproductive corresponding organ regions. The findings revealed significant variations in radiation doses across different body parts, highlighting areas of higher exposure and underscoring the need for improved protective measures and procedural adjustments. The effective radiation doses were calculated using standard protocols, considering the varying levels of protection offered by lead aprons and thyroid shields. The results demonstrate the substantial radiation exposure experienced by healthcare staff, particularly in regions not adequately shielded. This study emphasizes the necessity for enhanced radiation safety protocols in clinical settings, advocating for advanced protective equipment, training in radiation safety, and the exploration of alternative imaging modalities. The findings have crucial implications for both patient and staff safety, ensuring the continued efficacy and safety of ERCP and similar interventional procedures. This research contributes significantly to the field of occupational health and safety in interventional radiology, providing vital data for the development of safer medical practices.

Cross-shift changes in pulmonary function and occupational exposure to particulate matter among e-waste workers in Ghana.

Little is known on the association between cross-shift changes in pulmonary function and personal inhalation exposure to particulate matter (PM) among informal electronic-waste (e-waste) recovery workers who have substantial occupational exposure to airborne pollutants from burning e-waste. Using a cross-shift design, pre- and post-shift pulmonary function assessments and accompanying personal inhalation exposure to PM (sizes <1, <2.5 μm, and the coarse fraction, 2.5-10 μm in aerodynamic diameter) were measured among e-waste workers (n = 142) at the Agbogbloshie e-waste site and a comparison population (n = 65) in Accra, Ghana during 2017 and 2018. Linear mixed models estimated associations between percent changes in pulmonary function and personal PM. Declines in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) per hour were not significantly associated with increases in PM (all sizes) among either study population, despite breathing zone concentrations of PM (all sizes) that exceeded health-based guidelines in both populations. E-waste workers who worked "yesterday" did, however, have larger cross-shift declines in FVC [-2.4% (95%CI: -4.04%, -0.81%)] in comparison to those who did not work "yesterday," suggesting a possible role of cumulative exposure. Overall, short-term respiratory-related health effects related to PM exposure among e-waste workers were not seen in this sample. Selection bias due to the "healthy worker" effect, short shift duration, and inability to capture a true "pre-shift" pulmonary function test among workers who live at the worksite may explain results and suggest the need to adapt cross-shift studies for informal settings.

Investigating the discriminatory potential of urinary DNA adductomics in smokeless tobacco-treated rats and head-neck cancer patients

The genotoxicity of smokeless tobacco (ST) remains an essential public health issue. We conducted a comprehensive study of rats exposed to ST and head and neck cancer patients to elucidate the DNA adduct profiles. ST exposure assessment used alkaloids and tobacco-specific nitrosamines in rat urine. High ST doses led to significantly elevated nicotine, cotinine, N-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) levels, indicating substantial exposure. DNA adductomics identified 17 significant DNA adducts using a neutral loss scan in liquid chromatography-mass spectrometry in rat urine samples upon ST exposure, highlighting the intricate landscape of DNA modifications associated with ST using univariate and multivariate statistical analyses. LC-ESI-QTOF-MS/MS analysis and accurate mass measurements of DNA adducts unveiled specific adducts upregulated in response to ST exposure, particularly those associated with methylation and NNK release. Intriguing correlations emerged between DNA adducts and alkaloids-TSNA in ST-exposed rat urine. Nicotine correlated positively with N2-paraldol-dG and O2/O4-[4-(3-Pyridyl)-4-oxobut-1-yl] thymidine in high-dose rats. NNK correlated with 6O-methylgaunine, while NNN correlated with 6-hydroxy-1-N2-propanodeoxyguanosine and 7-methylguanine. With this aim, we also applied analysis to human samples, where we observed specific DNA adducts for ST users, controls, and subjects with HNC. Two-way ANOVA showed that ST users and cancer patients had higher DNA adduct levels in human urine, which aids cancer risk assessment, early detection, and environmental exposure evaluation. This comprehensive study explores DNA adducts caused by ST exposure across rats and head and neck cancer patients, illuminating genotoxic mechanisms and health risks and providing valuable insights for future preventive and therapeutic strategies.

Strategies for Using Quaternary Ammonium Salts as Alternative Reagents in Alkylations.

Alkylation reactions are pivotal in organic chemistry, with wide-ranging utilization across various fields of applied synthetic chemistry. However, conventional reagents employed in alkylations often pose substantial health and exposure risks. Quaternary ammonium salts (QAS) present a promising alternative for these transformations offering significantly reduced hazards as they are non-cancerogenic, non-mutagenic, non-flammable, and non-corrosive. Despite their potential, their use in direct organic transformations remains relatively unexplored. This review outlines strategies for utilizing QAS as alternative reagents in alkylation reactions, providing researchers with safer approaches to chemical synthesis.

Comparative Pharmacokinetic Assessment of Innovative Sublingual, Rectal and Vaporizer Cannabis Products Versus Approved Cannabis Products in Healthy Volunteers.

Background: Over the last years, there is a dramatic increase in the use of medical cannabis products for an expanding range of clinical indications. The type of the drug product and its administration route affect substantially the rate and the extent of absorption of cannabinoids and the effects induced by them in the patients. The current challenge for the cannabis pharmaceutical industry is to develop formulations that allow predictable and stable absorption of cannabinoids. This article reports the results of the clinical trial that investigated the pharmacokinetics (PKs) of innovative cannabis products in healthy volunteers. Materials and Methods: This was a single-center study with a single-dose, randomized, crossover, partially blinded controlled design. Each of the 12 healthy volunteers received 8 different products, of the 10 products that were assessed in this trial: novel sublingual (SL) tablet, vaporizer, and rectal products, comparator products (Sativex® and oil-based oromucosal products), and placebo products. Serial blood samples were collected, plasma concentrations of the THC, 11-OH-THC, and CBD were quantified and subjected to noncompartmental PK analysis. Results: Novel medical cannabis products that were investigated in the study induced substantial exposure of the volunteers to the active ingredients, had more rapid absorption, and in some cases also less variable absorption of THC and CBD, in comparison with the approved comparison products. The bioavailability of the novel SL tablet-based and suppositories products was somewhat lower than that of the oromucosal products. The vaporizer provided immediate systemic absorption with highest maximal concentration. The safety profile of the novel cannabis products, namely vaporizer, SL tablets, and suppositories, was not inferior to the Sativex and oil-based oromucosal formulations. Conclusions: The novel cannabis products that were assessed in this study have PK properties that may be advantageous for management of specific medical conditions or in specific subgroups of patients that are prescribed medical cannabis.

Aflatoxin M1 Exposure and Health Risk Assessment in Children and Adults due to Pasteurized Milk Consumption in Addis Ababa, Ethiopia

Milk and dairy products stand as essential sources of nutrition across all age groups. However, the presence of Aflatoxin M1, particularly common and risky for young children, necessitates careful assessment of milk. This study, conducted in Addis Ababa, Ethiopia, aimed to evaluate the prevalence of Aflatoxin M1 using High-Performance Liquid Chromatography in pasteurized milk and assess associated health risks using deterministic techniques. The prevalence of Aflatoxin M1 in pasteurized milk was 56.6%, with Aflatoxin M1 levels ranging from 0 to 6.27 μg/L and a mean value of 1.237 μg/L. The risk assessment revealed substantial Aflatoxin M1 exposure risk from pasteurized milk consumption, as reflected by margin of exposure values &lt;10,000, specifically 25.9, 109.6, and 380 for children aged 2–5, 6–9, and adults, respectively. The hazard index values for pasteurized milk consumers were 110, 26, and 7.5 for children aged 2–5, 6–9, and adults, respectively. Furthermore, cancer risk calculations yielded values of 0.18, 0.04, and 0.01 per 100,000 population for children aged 2–5, 6–9, and adults, respectively, with an average potency of 0.007978 cases per 100,000/yr ng Aflatoxin M1/kg bw/day. Notably, children aged 2–5 and 6–7 face elevated risks, whereas adults face relatively lower risks.