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Epidemiology (Cambridge, Mass.) Jul 2024Cannabis exposures reported to the California Poison Control System increased following the initiation of recreational cannabis sales on 1 January 2018 (i.e.,...
BACKGROUND
Cannabis exposures reported to the California Poison Control System increased following the initiation of recreational cannabis sales on 1 January 2018 (i.e., "commercialization"). We evaluated whether local cannabis control policies adopted by 2021 were associated with shifts in harmful cannabis exposures.
METHODS
Using cannabis control policies collected for all 539 California cities and counties in 2020-2021, we applied a differences-in-differences design with negative binomial regression to test the association of policies with harmful cannabis exposures reported to California Poison Control System (2011-2020), before and after commercialization. We considered three policy categories: bans on storefront recreational retail cannabis businesses, overall restrictiveness, and specific recommended provisions (restricting product types or potency, packaging and labeling restrictions, and server training requirements).
RESULTS
Localities that ultimately banned storefront recreational retail cannabis businesses had fewer harmful cannabis exposures for children aged <13 years (rate ratio = 0.82; 95% confidence interval = 0.65, 1.02), but not for people aged >13 years (rate ratio = 0.97; 95% confidence interval = 0.85, 1.11). Of 167 localities ultimately permitting recreational cannabis sales, overall restrictiveness was not associated with harmful cannabis exposures among children aged <13 years, but for people aged >13 years, a 1-standard deviation increase in ultimate restrictiveness was associated with fewer harmful cannabis exposures (rate ratio = 0.93; 95% confidence interval = 0.86, 1.01). For recommended provisions, estimates were generally too imprecise to detect associations with harmful cannabis exposures.
CONCLUSION
Bans on storefront retail and other restrictive approaches to regulating recreational cannabis may be associated with fewer harmful cannabis exposures for some age groups following statewide commercialization.
Topics: Humans; California; Poison Control Centers; Cannabis; Child; Adolescent; Commerce; Adult
PubMed: 38912711
DOI: 10.1097/EDE.0000000000001737 -
Frontiers in Nutrition 2024Vitamin D plays a major role in the musculoskeletal and immune system. Understanding the comprehensive mechanism of vitamin D receptors and the enzyme of vitamin D...
INTRODUCTION
Vitamin D plays a major role in the musculoskeletal and immune system. Understanding the comprehensive mechanism of vitamin D receptors and the enzyme of vitamin D induction (CYP2R1) and inhibition (CYP24A1) in its metabolism is interesting. This study aims to understand vitamin D metabolism in Indonesian pediatrics, specifically in Jakarta, which has abundant sun exposure.
METHODOLOGY
A cross-sectional study with comparative, correlative, and multivariate analysis on vitamin D, vitamin D receptor, CYP2R1, and CYP24A1 levels was conducted on 46 children with no known morbidity.
RESULT
Subjects were mostly male (52.2%), age group of 2-6 years (34.8%), and had sufficient vitamin D status (43.5%, median 27.55 ng/mL). Age was found to have a negative correlation with vitamin D levels ( < 0.001; = -0.625) and CYP2R1 ( = 0.035; = -0.311). Significant positive associations were found between CYP24A1 and CYP2R1 ( = 0.046; = 0.296). Participants aged 0-2 are more likely to have a higher level of vitamin D status compared to those aged >2 years (OR 42.092, 95% CI [4.532-390.914], = 0.001). VDR levels were significantly lower in insufficient vitamin D levels than in the sufficient group ( = 0.018). VDR and vitamin D status had a positive relation (OR 7.023, 95% CI [1.864-26.453], = 0.004).
CONCLUSION
Vitamin D levels decrease with the increase in age. Vitamin D receptor level has an inline-level progression with vitamin D level. CYP2R1 and CYP24A1 suggest a directly proportional relationship. Vitamin D screening and supplementation in children older than 2 years old are suggested.
PubMed: 38912300
DOI: 10.3389/fnut.2024.1394367 -
Blood Science (Baltimore, Md.) Jul 2024Ivosidenib, an isocitrate dehydrogenase 1 () inhibitor, has demonstrated clinical benefits in a pivotal study (AG120-C-001) in patients with -mutated (m) acute myeloid...
Ivosidenib, an isocitrate dehydrogenase 1 () inhibitor, has demonstrated clinical benefits in a pivotal study (AG120-C-001) in patients with -mutated (m) acute myeloid leukemia (AML). A registry study (CS3010-101: NCT04176393) was conducted to assess the pharmacokinetic (PK) characteristics, safety, and efficacy of ivosidenib in Chinese patients with relapsed or refractory (R/R) m AML. Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression. Ten subjects underwent intensive PK/progressive disease (PD) assessments. All subjects had the clinical response assessed at screening, every 28 days through month 12, and then every 56 days. Between November 12, 2019, and April 2, 2021, 30 patients were enrolled; 26 (86.7%) had de novo AML and 18 (60.0%) were transfusion-dependent at baseline. Following single and repeated doses of ivosidenib, median time to maximum plasma concentration ( ) was 4.0 and 2.0 hours, respectively. The inter-individual variability of pharmacokinetic exposure was moderate to high (coefficient of variation [CV], 25%-53%). No obvious accumulation was observed after repeated doses at cycle 2 day 1. Regarding the clinical response, the CR + CRh rate was 36.7% (95% confidence interval [CI]: 19.9%-56.1%), the median duration of CR + CRh was 19.7 months (95% CI: 2.9 months-not reached [NR]), and median duration of response (DoR) was 14.3 months (95% CI: 6.4 months-NR). Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months, as compared with primary data cutoff, and the data from Chinese R/R m AML patients were also consistent with results from pivotal study.
PubMed: 38911469
DOI: 10.1097/BS9.0000000000000196 -
Environment International Jun 2024There has been an increased concern on indoor air quality (IAQ) in residences since the majority of individuals' time is mainly spent indoors. We inspected and measured...
There has been an increased concern on indoor air quality (IAQ) in residences since the majority of individuals' time is mainly spent indoors. We inspected and measured indoor environmental parameters in 399 homes in northeast China in order to study IAQ. We systematically measured multilevel environmental parameters (physical, chemical, and biological) in children's bedrooms during all seasons. The results indicated that the median values for indoor temperature, relative humidity, total volatile organic compounds (TVOC), and formaldehyde concentrations throughout the year were within the Chinese national standards. However, the median carbon dioxide concentrations exceeded 1000 ppm during spring, autumn, and winter. In the same seasons, the air change rate (ACR) was below the minimum required level of 0.5 h. Di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) were predominantly detected in settled dust, displaying median concentrations of 126.9, 41.5, and 16.3 μg/g, respectively. Notably, phthalate concentrations were significantly higher in urban houses as compared to rural houses. Furthermore, median concentrations of Dermatophagoides farinae (Der f) and endotoxin were 689.4 ng/g and 3689.1 EU/g, respectively, trending higher in winter than summer. There was a negative correlation between ACR and chemical pollutants (TVOC, formaldehyde, and DiBP). In conclusion, northeast Chinese homes had poor indoor air quality with ubiquitous exposure to modern chemical compounds and insufficient ventilation.
PubMed: 38908271
DOI: 10.1016/j.envint.2024.108825 -
Food Chemistry Jun 2024Shark meat consumption may pose a significant risk to human health as high levels of toxic pollutants bioaccumulate in muscular tissue. Commercial harvest of...
Shark meat consumption may pose a significant risk to human health as high levels of toxic pollutants bioaccumulate in muscular tissue. Commercial harvest of Carcharhinus brachyurus meat in South Africa is estimated at 100-300 filleted tons per annum. Muscle tissue samples from 41 sharks were collected from the southern and eastern coastlines of South Africa in 2022 and analysed for 10 trace elements and 8 polychlorinated biphenyl congeners. All trace elements were found to be lower than the regulatory maximum limits for human consumption in most samples irrespective of shark length, sex, and sampling region. However, the estimated daily intake for Mercury and Arsenic exceeded the oral reference dose set by international agencies. The meat from this shark may be consumed due to its low toxic potential for human health, however long-term exposure to C. brachyurus meat should be avoided as it could pose detrimental health risks to consumers.
PubMed: 38908246
DOI: 10.1016/j.foodchem.2024.140081 -
Ecotoxicology and Environmental Safety Jun 2024The objectives of this study were to measure the mediation effect of plasma proteins and to clarify their mediating role in the relationship between stroke risk and...
The objectives of this study were to measure the mediation effect of plasma proteins and to clarify their mediating role in the relationship between stroke risk and particulate matter 2.5 (PM) exposure. The possible mediating role of plasma proteins on the causative link between PM exposure and stroke incidence were examined using a two-step Mendelian randomization (MR) approach based on two-sample Mendelian randomization (TSMR). The findings revealed a significant positive causal relationship between PM exposure and stroke, with an inverse variance weighted odds ratio of 1.219 (95 % CI: 1.002 - 1.482, P < 0.05). Additionally, a positive causal association was identified between PM exposure and several plasma proteins, including FAM134B, SAP, ITGB7, Elafin, and DCLK3. Among these, FAM134B, ITGB7, Elafin, and DCLK3 also demonstrated a positive causal association with stroke, whereas only SAP was found to be negatively causally associated with stroke. Remarkably, four plasma proteins, namely DCLK3, FAM134B, Elafin, and ITGB7, were identified as mediators, accounting for substantial proportions (14.5 %, 13.6 %, 11.1 %, and 9.9 %) of the causal association between PM and stroke. These results remained robust across various sensitivity analyses. Consequently, the study highlights the significant and independent impact of PM on stroke risk and identifies specific plasma proteins as potential targets for preventive interventions against PM-induced stroke.
PubMed: 38908058
DOI: 10.1016/j.ecoenv.2024.116624 -
Ecotoxicology and Environmental Safety Jun 2024Exposure to carbon disulfide (CS) is a recognized risk factor in the pathogenesis of Parkinson's disease, yet the underlying mechanisms of deleterious effects on...
Exposure to carbon disulfide (CS) is a recognized risk factor in the pathogenesis of Parkinson's disease, yet the underlying mechanisms of deleterious effects on mitochondrial integrity have remained elusive. Here, through establishing CS exposure models in rat and SH-SY5Y cells, we demonstrated that highly expressed α-synuclein (α-Syn) is transferred to mitochondria via membrane proteins such as Tom20 and leads to mitochondrial dysfunction and mitochondrial oxidative stress, which ultimately causes neuronal injury. We first found significant mitochondrial damage and oxidative stress in CS-exposed rat midbrain and SH-SY5Y cells and showed that mitochondrial oxidative stress was the main factor of mitochondrial damage by Mitoquinone intervention. Further experiments revealed that CS exposure led to the accumulation of α-Syn in mitochondria and that α-Syn co-immunoprecipitated with mitochondrial membrane proteins. Finally, the use of an α-Syn inhibitor (ELN484228) and small interfering RNA (siRNA) effectively mitigated the accumulation of α-Syn in neurons, as well as the inhibition of mitochondrial membrane potential, caused by CS exposure. In conclusion, our study identifies the translocation of α-Syn to mitochondria and the impairment of mitochondrial function, which has important implications for the broader understanding and treatment of neurodegenerative diseases associated with environmental toxins.
PubMed: 38908057
DOI: 10.1016/j.ecoenv.2024.116613 -
NanoImpact Jun 2024Micro- and nanoplastics have emerged as critical pollutants in various ecosystems, posing potential environmental and human health risks. Washing of polyester textiles...
Micro- and nanoplastics have emerged as critical pollutants in various ecosystems, posing potential environmental and human health risks. Washing of polyester textiles has been identified as one of the sources of nanoplastics. However, other stages of the textile life cycle may also release nanoparticles. This study aimed to examine nanoparticle release during UV degradation of polyester textiles under controlled and real-world conditions. Fleece polyester textiles were weathered under simulated sunlight for up to two months, either in air or submerged in water. We conducted bi-weekly SEM image analyses and quantified released nanoparticles using nanoparticle tracking analysis (NTA). At week 0, the fiber surface appeared smooth after prewashing. In the air group, nanoparticles appeared on the fiber surface after UV-exposure. In the group of textiles submerged in water, the surfaces developed more pits over time. The cumulative nanoparticle emission from the weathered textiles ranged from 1.4 × 10 to 4.0 × 10 particles per gram of fabric in the air group and from 1.6 × 10 to 4.4 × 10 particles per gram of fabric in the water group over two months. The predominant particle size fell into the 100 to 200 nm range. The estimated mass of the released nanoparticles was 0.06-0.26 g per gram of fabric, which is lower than the amount released during the washing of new textiles. Additionally, Scanning Transmission X-ray Microscopy (STXM) images indicated that the weathered nanoparticles underwent oxidation. Overall, the research offers valuable insights into nanoparticle formation and release from polyester textiles during UV degradation.
PubMed: 38906250
DOI: 10.1016/j.impact.2024.100520 -
European Journal of Pharmaceutical... Jun 2024Tacrolimus (FK506) is a cornerstone of GVHD-prophylaxis treatment in paediatrics undergoing haematopoietic stem cell transplantation (HSCT). However, due to concerns...
Tacrolimus (FK506) is a cornerstone of GVHD-prophylaxis treatment in paediatrics undergoing haematopoietic stem cell transplantation (HSCT). However, due to concerns about highly inter/intra-individual variability, precision dosing of FK506 is crucial. Cytochrome P450(CYP) 3A4 and 3A5 are considered important sources of FK506 pharmacokinetic variability. Nevertheless, the impact of age-related maturation in hepatic and intestinal CYP3A4/3A5 enzymes remains unknown in paediatric HSCT patients. Physiologically-based pharmacokinetic (PBPK) models were developed and verified in adult volunteers and adult HSCT patients using GastroPlus (version 9.0), and then extrapolated to paediatric HSCT patients, taking into account the maturation of CYP3A4 and CYP3A5. Default CYP3A4 and CYP3A5 ontogeny profiles were updated based on the latest reports. The paediatric PBPK model was evaluated with independent data collected from Sun Yat-sen Memorial Hospital (86 paediatric HSCT patients, 1 to 16 -year-old). Simulations were performed to evaluate a reported FK506 dosing regimen in infants and children with different CYP3A5 genotypes. Extensive PBPK model validation indicated good predictability, with the predicted/observed (P/O) ratios within the range of 0.80-fold to 1.25-fold. Blood tacrolimus concentration-time curves were comparable between the real and virtual patients. Simulations showed that the higher levels of tacrolimus in 9-month-old to 3-year-old infants were mainly attributed to the CYP3A4/3A5 ontogeny profiles, which resulted in lower clearance and higher exposure relative to dose. The oral dosage of 0.1 mg/kg/day (q12 h) is considered appropriate for paediatric HSCT patients 9 months to 15 years of age with CYP3A5 *1/*1 genotypes. Lower doses were required for paediatric HSCT patients with CYP3A5 *1/*3 (0.08 mg/kg/day, q12h) or CYP3A5 *3/*3 genotypes (0.07 mg/kg/day, q12h), and analyses demonstrated 12.5%-20% decreases in ≤3-year-old patients. The study highlights the feasibility of PBPK modelling to explore age-related enzyme maturation in infants and children(≤3-year-old) undergoing HSCT and emphasizes the need to include hepatic and gut CYP3A4/3A5 maturation parameters.
PubMed: 38906231
DOI: 10.1016/j.ejps.2024.106839 -
Ecotoxicology and Environmental Safety Jun 2024Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human...
BACKGROUND
Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation.
OBJECTIVES
To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers.
METHODS
Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LAN < 5 lx, 10 LAN ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis.
RESULTS
At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LAN ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators.
CONCLUSION
Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.
PubMed: 38905938
DOI: 10.1016/j.ecoenv.2024.116590