Classification of patterns of tobacco and cannabis co-use based on temporal proximity: A qualitative study among young adults.

PURPOSE: Co-use of tobacco and cannabis is a common and complex behavior. The lack of harmonized measures of co-use yields confusion and inconsistencies in synthesizing evidence about the health effects of co-use. We aimed to classify co-use patterns based on temporal proximity and describe preferred products and motives for each pattern in order to improve co-use surveillance. METHODS: We conducted semi-structured interviews in a sample of 34 young adults (Mage = 22.8 years, 32.4 % female) during 2017-2019 in California, USA. We employed a qualitative thematic analysis to identify timing, reasons, and contexts for tobacco and cannabis co-use and classify co-use patterns. RESULTS: Four emergent patterns of co-use with increasing temporal proximity between tobacco use and cannabis use were: Same-month different-day co-use (Pattern 1); Same-day different-occasion co-use (Pattern 2); Same-occasion sequential co-use (Pattern 3); and Same-occasion simultaneous co-use (Pattern 4). Participants used various product combinations within each pattern. Similar motives for all patterns were socialization, product availability, and coping with stress/anxiety. Unique motive for temporally distant patterns (Patterns 1 and 2) was seeking substance-specific effects (e.g., stimulant effect from nicotine, relaxation effects from cannabis), while unique motives for temporally close patterns (Patterns 3 and 4) were seeking combined effects from both substances (e.g., more intense psychoactive effects, mitigating cannabis adverse effects) and behavioral trigger (e.g., cannabis use triggers tobacco use). CONCLUSIONS: Our classification of co-use patterns can facilitate consistency for measuring co-use and assessing its health impacts. Future research should also measure product types and motives for different patterns to inform intervention efforts.

Determination of psilocybin and psilocin content in multiple Psilocybe cubensis mushroom strains using liquid chromatography - tandem mass spectrometry.

A method for clinical potency determination of psilocybin and psilocin in hallucinogenic mushroom species Psilocybe cubensis was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Five strains of dried, intact mushrooms were obtained and analyzed: Blue Meanie, Creeper, B-Plus, Texas Yellow, and Thai Cubensis. An extraction protocol was developed; this included an evaluation of sample milling technique, extraction solvents, and recovery/stability. Reversed phase chromatography on fused-core particle phases was developed for the determination of the two analytes using internal standard calibration with deuterated isotopologues of each analyte. The separation takes less than 5 min. Matrix effects were investigated by comparing signal response of calibration samples in neat solution and several mushroom matrices; no significant matrix effects were observed. The limit of detection for psilocybin was 1.5 ng/mL (1.5 pg on-column; 300 ng/g mushroom) and for psilocin was 0.15 ng/mL (0.15 pg on-column; 30 ng/g mushroom) using a Shimadzu LCMS-8050 triple quadrupole mass spectrometer. Assessment of the accuracy and precision of the method indicated percent error and RSD were <6 % at all concentration levels. Three whole, intact mushrooms from each strain were analyzed individually to obtain average content differences both between strains and between mushrooms of the same strain. From most to least potent, the study found that the average total psilocybin and psilocin concentrations for the Creeper, Blue Meanie, B+, Texas Yellow, and Thai Cubensis strains were 1.36, 1.221, 1.134, 1.103, and 0.879 % (w/w), respectively. A subset of these mushrooms was also tested in a separate non-affiliated laboratory, and the results were comparable between the two laboratories. Results from the secondary laboratory showed improved precision when multiple mushrooms were homogenized together, prior to extraction.

Computational screening of natural MtbDXR inhibitors for novel anti-tuberculosis compound discovery.

DXR (1-deoxy-d-xylulose-5-phosphate reductoisomerase) is an essential enzyme in the Methylerythritol 4-phosphate (MEP) pathway, which is used by M. tuberculosis and a few other pathogens. This essential enzyme in the isoprenoid synthesis pathway has been previously reported as an important target for antibiotic drug design. However, till now, there is no record of any drug-like safe molecule to inhibit MtbDXR. Numerous plant species have been traditionally used for tuberculosis therapies. In this study, we selected six plant species with anti-tubercular properties. The chemoinformatic screening was performed on 352 phytochemicals from those plants against the MtbDXR protein. After molecular docking analysis, we filtered the top five compounds, CID: 5280443 (Apigenin), CID: 3220 (Emodin), CID: 5280863 (Kaempferol), CID: 5280445 (Luteolin), and CID: 6101979 (beta-Hydroxychalcone), based on binding affinity. Molecular dynamics simulations disclosed the stability of the compounds at the active site of the proteins. Finally, in silico ADME and toxicity evaluations confirmed the compounds to be effective and safe for oral administration. Thus, our findings identified three drug-like safe molecules- Apigenin, Kaempferol, and beta-Hydroxychalcone, that showed good stability in the protein's active site. The results of this computational approach may act as an initial instruction for future in vitro and in vivo testing to identify natural drug-like compounds to treat tuberculosis.Communicated by Ramaswamy H. Sarma.

The effect of tread patterns on slip resistance of footwear outsoles based on composite materials in icy conditions.

INTRODUCTION: Falls on icy surfaces are the leading cause of injuries for outdoor workers. Footwear outsole material and geometrical design parameters are the most significant factors affecting slips-and-falls. Recently, composite materials have been incorporated into outsoles to improve traction, yet the best design parameters are not fully understood. METHOD: In this effort, based on Taguchi orthogonal array design, 27 outsole prototypes were fabricated with different tread pattern features using our patented composites and tested in a simulated winter condition. RESULTS: An analysis of variance (ANOVA) showed that surface area (p = 0.041, Contribution = 15.63%) was the only factor significantly affecting the slip-resistance of our prototypes. The best performance was observed for the maximized surface area covered by our composite material with circular and half circular plugs laid obliquely, mostly in the forefoot area. PRACTICAL APPLICATIONS: These findings suggest that some tread design features of composite-based footwear have a great role in affecting slip-resistance properties of composite-based footwear.

Lp(a) and risk of cardiovascular disease - A review of existing evidence and emerging concepts.

Cardiovascular disease (CVD) remains the leading cause of death among adults in the United States. There has been significant advancement in the diagnosis and treatment of atherosclerotic cardiovascular disease (ASCVD) and its underlying risk factors. In certain populations, there remains a significant residual risk despite adequate lowering of low-density lipoprotein cholesterol (LDL-C) and control of traditional risk factors. This has led to an interest in research to identify additional risk factors that contribute to atherosclerotic cardiovascular disease. Elevated lipoprotein (a) [Lp(a)] has been identified as an independent risk factor contributing to an increased risk for CVD. There are also ethnic and racial disparities in Lp(a) inheritance that need to be understood. This paper reviews the current literature on lipoprotein a, proposed mechanisms of actions for cardiovascular disease, recommendations for testing, and the current and emerging therapies for lowering Lp(a).

Biomechanical effects of different loads and constraints on finite element modeling of the humerus.

Currently, there is no established finite element (FE) method to apply physiologically realistic loads and constraints to the humerus. This FE study showed that 2 'simple' methods involving direct head loads, no head constraints, and rigid elbow or mid-length constraints created excessive stresses and bending. However, 2 'intermediate' methods involving direct head loads, but flexible head and elbow constraints, produced lower stresses and bending. Also, 2 'complex' methods involving muscles to generate head loads, plus flexible head and elbow constraints, generated the lowest stresses and moderate bending. This has implications for FE modeling research on intact and implanted humeri.

Lesbian, Gay, Bisexual, Queer, Questioning and Transgender, Nonbinary, Genderqueer, and Gender Questioning Adult Alcohol Use Outcomes Associated with State Alcohol-Related Laws During the Coronavirus Pandemic in the United States.

Purpose: We assessed how COVID-19-related alcohol sales policies influenced alcohol use behaviors during the pandemic for U.S. adults of diverse sexual (lesbian, gay, bisexual, queer, questioning [LGBQ]) and gender identities (transgender, nonbinary, genderqueer, and gender questioning [T/NB/GQ]). Methods: Time-specific, state-level, restaurant, bar, and off-premise alcohol policy data were collected from the National Institute on Alcohol Abuse and Alcoholism-sponsored Alcohol Policy Information System and merged with the 2020 Behavioral Risk Factor Surveillance System survey data. Treatments included bar, restaurant, and delivery alcohol sales policies. Outcomes included past 30-day drinking frequency, quantity, and heavy episodic drinking (HED). We fitted negative binomial regression models for all outcomes, clustered standard errors by state and used sample weights. We also controlled for seasonality, state Alcohol Policy Scale scores, pre-/postpandemic time period, and included demographic control variables in our cross-sectional analyses. Results: The sample included 10,505 adults identifying as LGBQ and 809 as T/NB/GQ from 32 states. Restaurant and bar closures were associated with less alcohol use for LGBQ respondents. Outdoor-only policies at bars were also associated with significantly less quantity of use and HED for T/NB/GQ adults in the sample. Off-premise home delivery was associated with greater quantity of use for LGBQ respondents and less frequency for T/NB/GQ respondents. Conclusion: The COVID-19-related alcohol sales policy changes offer an opportunity to better understand alcohol policy and availability's influence on drinking behaviors among sexual and gender-diverse populations in the United States.

Assessing and Addressing Social Determinants of Cardiovascular Health: JACC State-of-the-Art Review.

Social determinants of health (SDOH) are the social conditions in which people are born, live, and work. SDOH offers a more inclusive view of how environment, geographic location, neighborhoods, access to health care, nutrition, socioeconomics, and so on are critical in cardiovascular morbidity and mortality. SDOH will continue to increase in relevance and integration of patient management, thus, applying the information herein to clinical and health systems will become increasingly commonplace. This state-of-the-art review covers the 5 domains of SDOH, including economic stability, education, health care access and quality, social and community context, and neighborhood and built environment. Recognizing and addressing SDOH is an important step toward achieving equity in cardiovascular care. We discuss each SDOH within the context of cardiovascular disease, how they can be assessed by clinicians and within health care systems, and key strategies for clinicians and health care systems to address these SDOH. Summaries of these tools and key strategies are provided.

COVID-19 Restrictions and Adolescent Cigarette and E-cigarette Use in California.

INTRODUCTION: Shelter-in-place orders altered facilitators and barriers to tobacco use (e.g., outlet closures, restricted social gatherings). This study examined whether the duration of time in shelter in place and compliance with different shelter-in-place orders influenced adolescent cigarette and E-cigarette use and how the use may differ by demographic characteristics. METHODS: Shelter-in-place policy data obtained from government websites were merged with cross-sectional 2020 survey data on adolescents in California. Treatment variables included the proportion of time in shelter in place and self-reported compliance with shelter-in-place orders (for essential businesses and retail spaces and social and outdoor contexts). Multilevel logit models for dichotomous past 6-month cigarette and E-cigarette use and multilevel negative binomial regression models for past 6-month frequency of use were used. Moderation analyses were conducted on demographic measures. The sample included 1,196 adolescents (mean age=15.8 years, age range=13-19 years, 49.2% female, 50.0% White). Analyses were conducted in 2022. RESULTS: No associations were found between the proportion of time in shelter in place and outcomes. Shelter-in-place compliance with essential business and retail space orders was associated with lower odds of using cigarettes and E-cigarettes in the past 6 months. Compliance with social and outdoor context-related orders were associated with lower odds of using E-cigarettes and fewer days using cigarettes and E-cigarettes. Being aged ≥18 years moderated the associations between essential business/retail space and social/outdoor context-related shelter-in-place compliance orders and past 6-month frequency of cigarette smoking. CONCLUSIONS: Findings support tailored interventions for less compliant and older adolescents for future pandemic mitigation measures.

"I don't know whose mouth has been on this": youth nicotine and cannabis vaping practices in the context of the COVID-19 pandemic.

Early COVID-19 safety protocols urged physical and social distancing, resulting in minimal contact with others. As social contexts are central to vaping among youth, we used semi-structured interviews to describe how youth who vape are making sense of their use practices and adaptations. The qualitative analyses revealed changes in vaping frequency and access, social isolation shaping substance- and product-specific use, and motivations and outcomes of dual use of nicotine and cannabis which were closely linked to the pandemic. The findings indicate variation of youth vaping experiences within the early stages of the pandemic that should be attended to in future studies.

Disentangling the physical, social, and situational contexts of young adolescents' initiation to alcohol use and intoxication: A mixed methods study.

BACKGROUND: The onset of alcohol use during adolescence is associated with concurrent and subsequent related problems. Research on drinking contexts that underly these key first-time experiences and how they differ by initiation type is needed. The current study examined the physical, social, and situational characteristics of three types of initiation: first drink, first heavy episodic drinking (HED), and first intoxication and considered variations between early and later initiating adolescents. METHODS: A mixed-methods approach was used to survey and interview adolescents who reported lifetime drinking. Survey responses from 471 participants were analyzed using multilevel multinomial and logistic regressions accounting for nesting of drinking events (i.e., type of initiation) within respondents. A subsample of 50 participants recruited at baseline took part in-depth interviews that were thematically coded. RESULTS: After controlling for demographics, initiation of HED and intoxication, compared to initiation of a whole drink, were more likely to occur when more close friends are present and when those close friends are also drinking. The likelihood of early initiation of a whole drink and intoxication was also positively associated with being in an outdoor setting. Narratives identified distinct and shared patterns of context characteristics across the types of alcohol initiation. CONCLUSION: The quantitative and qualitative findings revealed several parallels as well as aspects that differ, enriching our understanding of early drinking contexts. Results highlight the importance of considering contextual characteristics by initiation type for prevention efforts.

Adolescent alcohol initiation: Context of close friendships and the role of trust.

PURPOSE: Adolescent initiation of drinking and intoxication is associated with concurrent and later problems among adolescents. This study explores the mechanisms by which the context of close friendships is important to adolescents' decisions to initiate drinking and heavy alcohol use. METHODS: In-depth face-to-face qualitative interviews were conducted online with 50 adolescents (12-16 years) who reported lifetime drinking. These semi-structured interviews allowed adolescents to describe their first experiences with drinking, reflecting on their social and environmental contexts, decision-making process, and expectations. We conducted a thematic analysis of the narratives, which revealed the nuances of social relationships and trusting peers and their impacts on alcohol use initiation patterns. RESULTS: In contrast to common perceptions of peer pressure, youth described decision-making about alcohol that was influenced by feelings of safety and security produced by close relationships. Specifically, social relationships, especially the presence of close friends, influenced decisions to initiate alcohol use. CONCLUSION: Results of this study suggest that close peer relationships enhanced feelings of safety even while engaging in risky behaviors. These results suggest the importance of understanding the complex relationships between social contexts, close friendships, and perceived trust and can inform future research and interventions on alcohol prevention or delayed initiation among adolescents.

Associations of California's Tobacco 21 Minimum Sales Age Law with Tobacco Use Among Sexual Minority Adolescents: A Trends Analysis.

INTRODUCTION: In 2016, California enacted a law (T21) prohibiting tobacco product sales to individuals under 21 years of age. Given tobacco use disparities among sexual minority (SM) youth, this study investigated whether California's T21 law was differentially associated with changes in tobacco use for SM and non-SM adolescents. AIMS AND METHODS: Secondary analyses of California Healthy Kids Survey data from 2013-2014 to 2018-2019 for 7th, 9th, and 11th graders (N = 2 229 401). RESULTS: Multilevel mixed-effects logistic regression analyses showed that SM students were more likely than non-SM students to report past-30-day and lifetime cigarette (odds ratio (OR) = 2.47; OR = 2.37), e-cigarette (OR = 1.21; OR = 1.10), smokeless tobacco use (OR = 1.95; OR = 1.56), and use of any tobacco product (OR = 1.94; OR = 1.61). Among SM youth, T21 was associated with significant reductions in lifetime e-cigarette use (OR = 0.66), and lifetime use of any tobacco products (OR = 0.75). These decreases generally were greater than or equivalent to those observed for non-SM youth. For 30-day e-cigarette and any tobacco use, SM youth showed no significant increases, whereas non-SM youth showed significant increases (OR = 1.06; OR = 1.11) following T21. T21 was associated with smaller increases in lifetime cigarette use (OR = 1.34), and larger increases for past-30-day and lifetime smokeless tobacco use (OR = 1.34; OR = 1.28) among SM students, to those observed for non-SM students. CONCLUSIONS: California's T21 policy may help reduce tobacco use disparities among SM students who are more at risk for tobacco use than their non-SM peers. IMPLICATIONS: Research on associations of T21 laws with tobacco use among sexual minority (SM) adolescents is lacking. The potential for unintended consequences of T21 for these adolescents raises concerns about increased health disparities. Importantly, our study generally found California's T21 was associated with reductions in tobacco use among SM students that were equivalent to or greater than those for non-SM students. Future research should investigate whether T21 laws and similar policies have differential effects for other marginalized groups and, if so, identify mechanisms that can be targeted in prevention efforts.

Youth tobacco and cannabis use and co-use: Associations with daily exposure to tobacco marketing within activity spaces and by travel patterns.

BACKGROUND: We investigated youth daily activity spaces, travel patterns, exposure to tobacco retail marketing, and tobacco and cannabis use and co-use. METHODS: Data included 1,060 daily assessments from 100 participants (16-20 years old) in 8 California cities. Using GPS-enabled smartphones with a survey application, youth completed brief daily surveys, and location coordinates were obtained at one-minute intervals. Tobacco outlets in study cities were visited by observers to record outlet GPS point locations and data concerning tobacco marketing. Tobacco outlet addresses and GPS location coordinates were geocoded. Activity spaces were constructed by joining sequential location points. Measures included the number of outlets with outdoor tobacco marketing within 50 m of activity space polylines and the amount of time participants were within 50 m of these outlets each day. Participants also reported tobacco and cannabis use and whether they saw tobacco ads by their neighborhood, school, workplace, and anywhere else each day. Additionally each day they reported how much time they traveled by different modes of transportation, with parents/guardians, and with friends. RESULTS: In mixed effects multinomial regression models, perceived exposure to tobacco marketing was associated with co-use of tobacco and cannabis on a given day (RRR = 1.66, p < 0.05). Although perceived exposure to tobacco marketing was not associated with tobacco use only, moderation analysis indicated that the likelihood of tobacco use was greater among youth who walked/biked/skated more (RRR = 5.22, p < 0.05). CONCLUSION: Perceived exposure to tobacco marketing contributes to youth tobacco and cannabis use or co-use, especially for those who travel by walking/biking/skating.

Mycobacterium avium Subsp. hominissuis Interactions with Macrophage Killing Mechanisms.

Non-tuberculosis mycobacteria (NTM) are ubiquitously found throughout the environment. NTM can cause respiratory infections in individuals with underlying lung conditions when inhaled, or systemic infections when ingested by patients with impaired immune systems. Current therapies can be ineffective at treating NTM respiratory infections, even after a long course or with multidrug treatment regimens. NTM, such as Mycobacterium avium subspecies hominissuis (M. avium), is an opportunistic pathogen that shares environments with ubiquitous free-living amoeba and other environmental hosts, possibly their evolutionary hosts. It is highly likely that interactions between M. avium and free-living amoeba have provided selective pressure on the bacteria to acquire survival mechanisms, which are also used against predation by macrophages. In macrophages, M. avium resides inside phagosomes and has been shown to exit it to infect other cells. M. avium's adaptation to the hostile intra-phagosomal environment is due to many virulence mechanisms. M. avium is able to switch the phenotype of the macrophage to be anti-inflammatory (M2). Here, we have focused on and discussed the bacterial defense mechanisms associated with the intra-phagosome phase of infection. M. avium possesses a plethora of antioxidant enzymes, including the superoxide dismutases, catalase and alkyl hydroperoxide reductase. When these defenses fail or are overtaken by robust oxidative burst, many other enzymes exist to repair damage incurred on M. avium proteins, including thioredoxin/thioredoxin reductase. Finally, M. avium has several oxidant sensors that induce transcription of antioxidant enzymes, oxidation repair enzymes and biofilm- promoting genes. These expressions induce physiological changes that allow M. avium to survive in the face of leukocyte-generated oxidative stress. We will discuss the strategies used by M. avium to infect human macrophages that evolved during its evolution from free-living amoeba. The more insight we gain about M. avium's mode of pathogenicity, the more targets we can have to direct new anti-virulence therapies toward.

Relationships Between Social Host Policies, Youth Drinking Contexts, and Age.

OBJECTIVE: We examined associations of city-level policies and enforcement operations (i.e., social host laws and party patrol operations) with youth drinking, heavy drinking, and drinking-related problems in private and public drinking contexts. We also examined whether these associations were modified by age. METHOD: We surveyed 580 youth (ages 16-20 years; 53% male) living in 24 midsized California cities. We used mixed-effects negative binomial and logistic regression to calculate the frequency of youth drinking and heavy drinking and odds of drinking-related problems in each context (own home, friend's home, restaurant, bar, music venue, and outdoors). RESULTS: There were positive associations between more comprehensive city-level social host policies and frequency of youth drinking and heavy drinking at music venues, and youth heavy drinking and drinking-related problems at restaurants. Younger youth who lived in cities with more comprehensive social host laws drank heavily less frequently in their own home than younger youth living in cities with less comprehensive social host laws. Youth ages 17 or under who lived in cities with more party patrol enforcement had higher odds of problems related to drinking outdoors in the past 12 months than those in cities with fewer party patrol operations. CONCLUSIONS: City-level alcohol policies and enforcement targeting underage drinking may have differential effects depending on youth drinking contexts and age. Comprehensive social host policies, which aim to decrease drinking in private contexts, may displace or increase youth drinking in other contexts, such as restaurants and music venues. Comprehensive social host policies and party patrol operations may be more influential for younger youth drinking in their own home or outdoors.

Aortic Mural Thrombus and Acute Coronary Syndrome in a Patient With Cannabinoid Hyperemesis Syndrome.

A 36-year-old woman with cannabinoid hyperemesis syndrome presented with chest pain and was found to have single-vessel coronary artery disease and an aortic mural thrombus. This case describes unique management with coronary artery bypass and surgical thrombectomy because of the patient's inability to tolerate uninterrupted antiplatelet therapy given her cannabinoid hyperemesis syndrome. (Level of Difficulty: Intermediate.).

Malignancy-Related Pulmonary Hypertension Presenting as a Pulmonary Veno-Occlusive-Like Syndrome: A Single-Center Case Series.

Tumoral obstruction is a small, but broadly defined, category of pulmonary hypertension that encompasses microvascular tumor emboli, tumor thrombotic microangiopathy, and macrovascular tumor obstruction within the pulmonary circulation. We present 4 patients with solid tumors, severe pre-capillary pulmonary hypertension, right ventricular failure, and pulmonary veno-occlusive-like disease. (Level of Difficulty: Advanced.).

Perceptions of Psychological Intimate Partner Violence: The Influence of Sexual Minority Stigma and Childhood Exposure to Domestic Violence among Bisexual and Lesbian Women.

Sexual minority women (SMW; bisexual, lesbian) experience psychological intimate partner violence (IPV) disproportionately more than physical forms and have higher lifetime victimization rates than heterosexual women. This study presents an examination of perceptions of psychological IPV, sexual minority stigma, and childhood exposure to domestic violence among a sample of 183 SMW residing within the U.S. With an emphasis on group differences between bisexual and lesbian women, findings indicate that bisexual women evaluated vignettes depicting psychological IPV occurring among women in same-gender relationships with more negative sentiment than lesbian women. Significant associations between enacted and internalized forms of stigma and perceptions of psychological IPV also varied among bisexual and lesbian women. No significant relationships were found between perceived stigma and perceptions of IPV in either group. Furthermore, no moderation effects were detected for childhood exposure to domestic violence or sexual orientation in the relationship between sexual minority stigma and perceptions of IPV. Implications and suggestions are discussed with particular attention to the heterogeneity of experiences among SMW as a necessary area of further study.