Role of thermosensitive transient receptor potential (TRP) channels in thermal preference of male and female mice.

Transient Receptor Potential (TRP) ion channels are important for sensing environmental temperature. In rodents, TRPV4 senses warmth (25-34 °C), TRPV1 senses heat (>42 °C), TRPA1 putatively senses cold (<17 °C), and TRPM8 senses cool-cold (18-26 °C). We investigated if knockout (KO) mice lacking these TRP channels exhibited changes in thermal preference. Thermal preference was tested using a dual hot-cold plate with one thermoelectric surface set at 30 °C and the adjacent surface at a temperature of 15-45 °C in 5 °C increments. Blinded observers counted the number of times mice crossed through an opening between plates and the percentage of time spent on the 30 °C plate. In a separate experiment, observers blinded as to genotype also assessed the temperature at the location on a thermal gradient (1.83 m, 4-50 °C) occupied by the mouse at 5- or 10-min intervals over 2 h. Male and female wildtype mice preferred 30 °C and significantly avoided colder (15-20 °C) and hotter (40-45 °C) temperatures. Male TRPV1KOs and TRPA1KOs, and TRPV4KOs of both sexes, were similar, while female WTs, TRPV1KOs, TRPA1KOs and TRPM8KOs did not show significant thermal preferences across the temperature range. Male and female TRPM8KOs did not significantly avoid the coldest temperatures. Male mice (except for TRPM8KOs) exhibited significantly fewer plate crossings at hot and cold temperatures and more crossings at thermoneutral temperatures, while females exhibited a similar but non-significant trend. Occupancy temperatures along the thermal gradient exhibited a broad distribution that shrank somewhat over time. Mean occupancy temperatures (recorded at 90-120 min) were significantly higher for females (30-34 °C) compared to males (26-27 °C) of all genotypes, except for TRPA1KOs which exhibited no sex difference. The results indicate (1) sex differences with females (except TRPA1KOs) preferring warmer temperatures, (2) reduced thermosensitivity in female TRPV1KOs, and (3) reduced sensitivity to cold and innocuous warmth in male and female TRPM8KOs consistent with previous studies.

Racial Disparities in Patterns and Modes of Current and Daily Marijuana Use among Adults Living with Children.

OBJECTIVE: This study sought to examine racial disparities in marijuana use among U.S. adults living with children. METHODS: Data are drawn from the 2022 Behavioral Risk Factor Surveillance System to examine the prevalence of current (past month) and frequent (≥20 days in the last 30 days) marijuana use along with the mode of marijuana use by 7 racial and ethnic groups (non-Hispanic [NH] White, NH-Black, Hispanic, NH American Indian or Alaskan Native [AI/AN], NH-Asian, NH Native Hawaiian or other Pacific Islander only [NH/PI], and other/multiple races, n=22,659). RESULTS: Compared to NH White adults with children, NH Black adults had a higher prevalence of current marijuana use (23.1% vs. 16.9%, p=0.003) and NH AI/AN adults had two times higher prevalence of frequent use (17.3% vs. 8.4%, p=0.0003). Adults living in recreational marijuana legal states (vs. no) were also more likely to report marijuana use, and there were significant age × race/ethnicity and education × race/ethnicity interactions (p<0.05) on marijuana use. Regarding the mode of use, racial minority users except Asians also reported a higher prevalence of smoking marijuana than their White counterparts. CONCLUSIONS AND RELEVANCE: Substantial racial disparities in marijuana use patterns among adults who live with children highlight a potential risk for adolescents' health. Addressing these differences is essential for promoting equitable health outcomes in diverse communities.

Pregnane X Receptor Signaling Pathway and Vitamin K: Molecular Mechanisms and Clinical Relevance in Human Health.

This review explores the likely clinical impact of Pregnane X Receptor (PXR) activation by vitamin K on human health. PXR, initially recognized as a master regulator of xenobiotic metabolism in liver, emerges as a key regulator influencing intestinal homeostasis, inflammation, oxidative stress, and autophagy. The activation of PXR by vitamin K highlights its role as a potent endogenous and local agonist with diverse clinical implications. Recent research suggests that the vitamin K-mediated activation of PXR highlights this vitamin's potential in addressing pathophysiological conditions by promoting hepatic detoxification, fortifying gut barrier integrity, and controlling pro-inflammatory and apoptotic pathways. PXR activation by vitamin K provides an intricate association with cancer cell survival, particularly in colorectal and liver cancers, to provide new insights into potential novel therapeutic strategies. Understanding the clinical implications of PXR activation by vitamin K bridges molecular mechanisms with health outcomes, further offering personalized therapeutic approaches for complex diseases.

Prevalence and Factors Associated With Vaping Cannabidiol Among US Adolescents.

Importance: e-Cigarette use and vaping marijuana (cannabis) are popular among US adolescents. Cannabidiol (CBD) is a compound found in the cannabis plant that has recently increased in use. Objectives: To examine the prevalence of and factors associated with youths vaping CBD. Design, Setting, and Participants: This cross-sectional study included a nationally representative sample of students from middle and high schools (typical age, 11-18 years) in the US from the 2022 National Youth Tobacco Survey, conducted from January to May 2022. Exposure: Demographic characteristics, harm perception of tobacco use, and vaping behaviors. Main Outcomes and Measures: The main outcomes were weighted prevalence and population estimates of ever and current (past 30-day) vaping of CBD overall and by e-cigarette use status. Multivariable logistic regression analyses were conducted to estimate the association of currently vaping CBD with demographic factors and e-cigarette and tobacco use behaviors stratified by current e-cigarette use status. Results: The study included 28 291 participants (51.1% male; mean [SD] age, 14.5 [2.0] years). Among 2448 current e-cigarette users, 21.3% (95% CI, 18.4%-24.1%) reported any past-month vaping of CBD and 6.3% (95% CI, 4.7%-7.8%) reported that they did not know whether they had vaped CBD. Hispanic e-cigarette users were more likely than their non-Hispanic White peers to report currently vaping CBD (adjusted odds ratio [AOR], 1.9; 95% CI, 1.3-2.8). Current e-cigarette users with higher frequency (≥20 days vs ≤5 days) and longer duration (2-3 years or >3 years vs <1 year) of use were more likely to report currently vaping CBD (frequency: AOR, 1.5 [95% CI, 1.1-1.9]; 2-3 years: AOR, 2.2 [95% CI, 1.2-3.9]; 3 years: AOR, 3.2 [95% CI, 1.7-6.1]). Among 25 091 noncurrent e-cigarette users, 1.2% (95% CI, 1.0%-1.5%) reported currently vaping CBD and 2.3% (95% CI, 2.1%-2.6%) reported that they did not know. High school students (vs middle school students; AOR, 4.2; 95% CI, 2.8-6.1) and gay or lesbian (AOR, 2.9; 95% CI, 1.6-5.4) or bisexual (AOR, 2.7; 95% CI, 1.8-4.0) (vs heterosexual) youths were more likely to report vaping CBD, while those who perceived tobacco as dangerous (vs not dangerous; AOR, 0.4; 95% CI, 0.3-0.6) had lower odds of reporting vaping CBD. Conclusions and Relevance: In this cross-sectional study of US middle and high school students, the prevalence of youths vaping CBD was high, particularly among e-cigarette users and Hispanic and sexual minority populations. The findings suggest that evidence-based educational campaigns, interventions, and public policy changes are needed to reduce the harmful health outcomes possible with vaping CBD among developing youths.