Search

BackgroundWe examined the association between cannabis use and cardiovascular outcomes among the general population, among never-tobacco smokers, and among younger individuals.Methods and resultsThis is a population-based, cross-sectional study of 2016 to 2020 data from the Behavioral Risk Factor Surveillance Survey from 27 American states and 2 territories. We assessed the association of cannabis use (number of days of cannabis use in the past 30 days) with self-reported cardiovascular outcomes (coronary heart disease, myocardial infarction, stroke, and a composite measure of all 3) in multivariable regression models, adjusting for tobacco use and other characteristics in adults 18 to 74 years old. We repeated this analysis among nontobacco smokers, and among men

BACKGROUND: E-cigarettes are promoted as less harmful than cigarettes. There has not been a direct comparison of health effects of e-cigarettes or dual use (concurrently using e-cigarettes and cigarettes) with those of cigarettes in the general population. METHODS: Studies in PubMed, EMBASE, Web of Science, and PsychINFO published through October 1, 2023, were pooled in a random-effects meta-analysis if five or more studies were identified with a disease outcome. We assessed risk of bias with Risk Of Bias In Non-randomized Studies of Exposure and certainty with Grading of Recommendations, Assessment, Development, and Evaluations. Outcomes with fewer studies were summarized but not pooled. RESULTS: We identified 124 odds ratios (94 cross-sectional and 30 longitudinal) from 107 studies. Pooled odds ratios for current e-cigarette versus cigarette use were not different for cardiovascular disease (odds ratio, 0.81; 95% confidence interval, 0.58 to 1.14), stroke (0.73; 0.47 to 1.13), or metabolic dysfunction (0.99; 0.91 to 1.09) but were lower for asthma (0.84; 0.74 to 0.95), chronic obstructive pulmonary disease (0.53; 0.38 to 0.74), and oral disease (0.87; 0.76 to 1.00). Pooled odds ratios for dual use versus cigarettes were increased for all outcomes (range, 1.20 to 1.41). Pooled odds ratios for e-cigarettes and dual use compared with nonuse of either product were increased (e-cigarette range, 1.24 to 1.47; dual use, 1.49 to 3.29). All included studies were assessed as having a low risk of bias. Results were generally not sensitive to study characteristics. Limited studies of other outcomes suggest that e-cigarette use is associated with additional diseases. CONCLUSIONS: There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use.

Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.

Digital contact tracing tools were developed to decrease the spread of COVID-19 by supplementing traditional manual methods. Although these tools have great potential, they were developed rather quickly resulting in tools with varying levels of success. The main issues with these tools are over privacy and who might have access to the information gathered. In general, their effectiveness varied globally, where users expressed privacy concerns associated with sharing identity, illness, and location information. This paper reviews these issues in deployments across Asia, Europe, and the United States. The goal is to begin a discussion that improves the design and development of digital technologies that not only improve the control of infectious disease spread, but also achieve an appropriate standard of privacy and security.

Impaired rennet coagulation properties in milk could lead to prolonged processing times and production losses. Heritability for milk coagulation has previously been estimated to be 0.28 to 0.45, indicating that genetic selection can be used to manipulate this trait. The CN proteins are expressed by the genes CSN1S1, CSN2, CSN1S2, and CSN3 and are located on bovine chromosome 6. To better understand the effect of genetic variation in the CN genes on milk coagulation, blood and milk samples from 30 Swedish Red Dairy Cattle (RDC) with divergent coagulation properties were investigated. DNA from the 30 cows was sequenced for the CN genes to determine the theoretical AA sequence and to look for genetic variation in the untranslated regions. The aim is to confirm the protein genetic variants previously reported, while searching for additional genetic variation in the CN genes of 30 RDC. We observed genetic variation in 116 SNPs in the known CN genes where 10% of the SNPs are exon variants and the remaining 90% are intron variants. A total of 2.5% of the SNPs are found in the 5′- or 3′-untranslated region (UTR) regions of the exons; 2% are synonymous variants and 6% are missense variants that concurred with the known protein variants for CSN1S1, CSN2, and CSN3. Furthermore, 6% of the SNPs are splice polypyrimidine tract intron variants. The 2 genetic variants in the 5′- and 3′-UTR in CSN1S1 and CSN3 are found with protein variants CSN1S1C and CSN3B. Because both UTR variants are associated with gain and loss of micro RNA and transcription factors, this could explain differences in expression of the genetic protein variants. Preliminary chi-squared analysis and comparison with previous GWAS studies showed potential connections between the identified SNPs and coagulation properties of milk. By advancing the knowledge of the connection between the DNA sequence and the functional properties of the CN proteins, we hope to learn more about the cheese coagulation properties of milk from RDC.

Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.

BackgroundExposure to tobacco or marijuana smoke, or e-cigarette aerosols, causes vascular endothelial dysfunction in humans and rats. We aimed to determine what constituent, or class of constituents, of smoke is responsible for endothelial functional impairment.MethodsWe investigated several smoke constituents that we hypothesized to mediate this effect by exposing rats and measuring arterial flow-mediated dilation (FMD) pre- and post-exposure. We measured FMD before and after inhalation of sidestream smoke from research cigarettes containing normal and reduced nicotine level with and without menthol, as well as 2 of the main aldehyde gases found in both smoke and e-cigarette aerosol (acrolein and acetaldehyde), and inert carbon nanoparticles.ResultsFMD was reduced by all 4 kinds of research cigarettes, with extent of reduction ranging from 20% to 46% depending on the cigarette type. While nicotine was not required for the impairment, higher nicotine levels in smoke were associated with a greater percent reduction of FMD (41.1±4.5% reduction versus 19.2±9.5%; P=0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% versus 40.5±4.8%; P=0.048). Inhalation of acrolein or acetaldehyde gases at smoke-relevant concentrations impaired FMD by roughly 50% (P=0.001). However, inhalation of inert carbon nanoparticles at smoke-relevant concentrations with no gas phase also impaired FMD by a comparable amount (P

Abstract In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12 years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA1c levels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37–63%)] compared to pre-T2D [36% (95% CI 31–48%), p = 0.01] and at-risk participants [34% (95% CI 27–39%), p

Abstract Digital phenotyping refers to characterizing human bio-behavior through wearables, personal devices, and digital health technologies. Digital phenotyping in populations facing a disproportionate burden of type 2 diabetes (T2D) and health disparities continues to lag compared to other populations. Here, we report our study demonstrating the application of multimodal digital phenotyping, i.e., the simultaneous use of CGM, physical activity monitors, and meal tracking in Hispanic/Latino individuals with or at risk of T2D. For 14 days, 36 Hispanic/Latino adults (28 female, 14 with non-insulin treated T2D) wore a continuous glucose monitor (CGM) and a physical activity monitor (Actigraph) while simultaneously logging meals using the MyFitnessPal app. We model meal events and daily digital biomarkers representing diet, physical activity choices, and corresponding glycemic response. We develop a digital biomarker for meal events that differentiates meal events into normal and elevated categories. We examine the contribution of daily digital biomarkers of elevated meal event count and step count on daily time-in-range 54-140 mg/dL (TIR54–140) and average glucose. After adjusting for step count, a change in elevated meal event count from zero to two decreases TIR54–140 by 4.0% (p = 0.003). An increase in 1000 steps in post-meal step count also reduces the meal event glucose response by 641 min mg/dL (p = 0.0006) and reduces the odds of an elevated meal event by 55% (p

ImportanceThe cannabis industry has sought to normalize itself and expand its markets in the 21st century. One strategy used by companies to generate positive public relations is corporate social responsibility (CSR). It is critical to understand these efforts to influence the public and politicians given the risks of increased cannabis use.ObjectivesTo analyze cannabis industry CSR behaviors, determine their characteristics, and compare their practices with those of the tobacco industry.Design, setting, and participantsThis qualitative study of CSR activities conducted between January 1, 2012, and December 31, 2021, evaluated 9 of the 10 largest publicly traded cannabis companies in the US and Canada. Data were collected from August 1 to December 31, 2021. The 10th company was excluded because it engaged in cannabis-based pharmaceutical sales but not CSR. A systematic review of corporate websites and Nexis Uni was performed, resulting in collection of 153 news articles, press releases, and Web pages. Charitable and philanthropic actions were included. Themes were identified and interpreted using modified grounded theory.Main outcomes and measuresCSR activities and spending.ResultsNine major cannabis companies in the US and Canada engaged in CSR activities that encouraged increased consumption and targeted marginalized communities. Companies claimed these activities would mitigate the harms of cannabis prohibition, promote diversity, expand access to medical cannabis, and support charitable causes. They developed educational programs, sustainability initiatives, and voluntary marketing codes and used strategies similar to those used by tobacco companies to recruit public interest organizations as allies.Conclusions and relevanceThese findings suggest that cannabis companies developed CSR strategies comparable to those used by the tobacco industry to influence regulation, suggesting that cannabis companies should be included when addressing commercial determinants of health.

The US Food and Drug Administration (FDA) issued orders in July 2020 authorising Philip Morris Products S.A. to market its heated tobacco product (HTP) IQOS inside the USA with claims that it reduces exposure to some dangerous substances. FDA's 'reduced-exposure' orders explicitly prohibit the marketing of IQOS with claims that IQOS will reduce harm or the risk of tobacco-related diseases. Under US law, FDA's IQOS orders are problematic because FDA disregarded valid scientific evidence that IQOS increases exposure to other dangerous toxins and that Philip Morris Products S.A. failed to demonstrate that consumers understand the difference between reduced-exposure and reduced-harm claims. Unfortunately, both 'reduced-exposure' and 'reduced-harm' are classified as 'modified risk tobacco products' under US law. Exploiting this confusion, Philip Morris International used the FDA decision as the basis for marketing and public relations campaigns outside the USA to press governments to reverse policies that ban or regulate the sales and marketing of HTPs, including IQOS. Parties to the WHO Framework Convention on Tobacco Control should reject tobacco companies' unsubstantiated explicit or implied claims of reduced harm associated with HTPs and resist Philip Morris International's and other companies' calls to relax HTP regulations based on the FDA's actions. Instead, parties should adopt policies aligned with the Framework Convention on Tobacco Control when dealing with HTPs and other novel tobacco products.

Two-year colleges provide the opportunity for students of all ages to try new subjects, change careers, upskill, or begin exploring higher education, at affordable rates. Many might begin their exploration by taking a course at a local two-year college. Currently, not many of these institutions in the U.S. offer data science courses. This article introduces the perspective lens of students who have gone through the Montgomery College Data Science Certificate Program. We found that, contrary to many other educational fields at the College, data science students tend to come from diverse backgrounds and career paths. A common theme emerged that all students learned valuable skills and applications such as coding in various programming languages and approaches to machine learning. Other meaningful themes included an appreciation of course accessibility, especially catered toward busy professionals who might only be able to take evening courses. Students appreciated learning that data science and ethics are intertwined. Finally, it was evident that going through the data science program positively impacted the lives and careers of these students. The implications of the themes of these student experiences are discussed as they relate to data science education. Supplementary materials for this article are available online.

Although current stem cell therapies exhibit promising potential, the extended process of employing autologous cells and the necessity for donor–host matching to avert the rejection of transplanted cells significantly limit the widespread applicability of these treatments. It would be highly advantageous to generate a pluripotent universal donor stem cell line that is immune-evasive and, therefore, not restricted by the individual’s immune system, enabling unlimited application within cell replacement therapies. Before such immune-evasive stem cells can be moved forward to clinical trials, in vivo testing via transplantation experiments in immune-competent animals would be a favorable approach preceding preclinical testing. By using human stem cells in immune competent animals, results will be more translatable to a clinical setting, as no parts of the immune system have been altered, although in a xenogeneic setting. In this way, immune evasiveness, cell survival, and unwanted proliferative effects can be assessed before clinical trials in humans. The current study presents the generation and characterization of three human embryonic stem cell lines (hESCs) for xenogeneic transplantation in immune-competent mice. The major histocompatibility complexes I- and II-encoding genes, B2M and CIITA, have been deleted from the hESCs using CRISPR-Cas9-targeted gene replacement strategies and knockout. B2M was knocked out by the insertion of murine CD47. Human-secreted embryonic alkaline phosphatase (hSEAP) was inserted in a safe harbor site to track cells in vivo. The edited hESCs maintained their pluripotency, karyotypic normality, and stable expression of murine CD47 and hSEAP in vitro. In vivo transplantation of hESCs into immune-competent BALB/c mice was successfully monitored by measuring hSEAP in blood samples. Nevertheless, transplantation of immune-evasive hESCs resulted in complete rejection within 11 days, with clear immune infiltration of T-cells on day 8. Our results reveal that knockout of B2M and CIITA together with species-specific expression of CD47 are insufficient to prevent rejection in an immune-competent and xenogeneic context.

Background We examined the association between cannabis use and cardiovascular outcomes among the general population, among never‐tobacco smokers, and among younger individuals. Methods and Results This is a population‐based, cross‐sectional study of 2016 to 2020 data from the Behavioral Risk Factor Surveillance Survey from 27 American states and 2 territories. We assessed the association of cannabis use (number of days of cannabis use in the past 30 days) with self‐reported cardiovascular outcomes (coronary heart disease, myocardial infarction, stroke, and a composite measure of all 3) in multivariable regression models, adjusting for tobacco use and other characteristics in adults 18 to 74 years old. We repeated this analysis among nontobacco smokers, and among men

In this paper, we examine efforts by health organizations seeking comprehensive smokefree ordinances over Louisiana casinos and bars between 2010 and 2020 to determine best practices for increasing coverage. Bars and casinos remain less protected from secondhand smoke compared to other workplaces in the United States. Casino behavior is compared to the Policy Dystopia Model (PDM), a tobacco industry strategy framework. We performed a historical case study using snowball searches for news on the Access World News Database and the internet. We performed web searches using the names of key actors, organizations, and locations and interviewed nine participants. Starting in 2010, the Louisiana Campaign for Tobacco-Free Living ran ordinance campaigns supplemented by an ongoing statewide smokefree media initiative. Utilizing consistent strategies, including promoting performers as cultural emblems deserving protection, health organizations coalesced in New Orleans during 2014 and Baton Rouge in 2016 and 2017 to pursue ordinances. The coalitions secured ordinances in Louisiana's population and tourism centers despite business resistance. Organizations obtained 30 smokefree laws across Louisiana by 2021. Casinos used PDM strategies to resist ordinances, indicating the framework may predict strategies by non-tobacco entities resisting tobacco control. Louisiana shows that ongoing local campaigns, social justice themes and cultural messaging with coalitions in cities can secure smokefree laws covering casinos and bars and that local ordinance campaigns are a viable method for advancing smokefree protections over those venues in states where the state legislatures are resistant to action.

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.

BackgroundClonal immunoglobulin and T-cell receptor rearrangements serve as tumor-specific markers that have become mainstays of the diagnosis and monitoring of lymphoid malignancy. Next-generation sequencing (NGS) techniques targeting these loci have been successfully applied to lymphoblastic leukemia and multiple myeloma for minimal residual disease detection. However, adoption of NGS for primary diagnosis remains limited.MethodsWe addressed the bioinformatics challenges associated with immune cell sequencing and clone detection by designing a novel web tool, CloneRetriever (CR), which uses machine-learning principles to generate clone classification schemes that are customizable, and can be applied to large datasets. CR has 2 applications-a "validation" mode to derive a clonality classifier, and a "live" mode to screen for clones by applying a validated and/or customized classifier. In this study, CR-generated multiple classifiers using 2 datasets comprising 106 annotated patient samples. A custom classifier was then applied to 36 unannotated samples.ResultsThe optimal classifier for clonality required clonal dominance ≥4.5× above background, read representation ≥8% of all reads, and technical replicate agreement. Depending on the dataset and analysis step, the optimal algorithm yielded sensitivities of 81%-90%, specificities of 97%-100%, areas under the curve of 91%-94%, positive predictive values of 92-100%, and negative predictive values of 88%-98%. Customization of the algorithms yielded 95%-100% concordance with gold-standard clonality determination, including rescue of indeterminate samples. Application to a set of unknowns showed concordance rates of 83%-96%.ConclusionsCR is an out-of-the-box ready and user-friendly software designed to identify clonal rearrangements in large NGS datasets for the diagnosis of lymphoid malignancies.

BackgroundThe Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12.MethodsThis study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD).Primary resultsAt baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine,

Little is known about the extent of variation and activity of naturally occurring milk glycosidases and their potential to degrade milk glycans. A multi-omics approach was used to investigate the relationship between glycosidases and important bioactive compounds such as free oligosaccharides and O-linked glycans in bovine milk. Using 4-methylumbelliferone (4-MU) assays activities of eight indigenous glycosidases were determined, and by mass spectrometry and 1H NMR spectroscopy various substrates and metabolite products were quantified in a subset of milk samples from eight native North European cattle breeds. The results showed a clear variation in glycosidase activities among the native breeds. Interestingly, negative correlations between some glycosidases including β-galactosidase, N-acetyl-β-d-glucosaminidase, certain oligosaccharide isomers as well as O-linked glycans of κ-casein were revealed. Further, a positive correlation was found for free fucose content and α-fucosidase activity (r = 0.37, p-value < 0.001) indicating cleavage of fucosylated glycans in milk at room temperature. The results obtained suggest that milk glycosidases might partially degrade valuable glycans, which would result in lower recovery of glycans and thus represent a loss for the dairy ingredients industry if these activities are pronounced.

Preventing opioid misuse and opioid use disorder is critical among at-risk adolescents and young adults (AYAs). An Emergency Department (ED) visit provides an opportunity for delivering interventions during a rapidly changing opioid landscape. This paper describes pilot data and the protocol for a 2 × 2 factorial randomized controlled trial testing efficacy of early interventions to reduce escalation of opioid (prescription or illicit) misuse among at-risk AYAs. Interventions are delivered using technology by health coaches. AYAs ages 16-30 in the ED screening positive for prescription opioid use (+ ≥ 1 risk factor) or opioid misuse will be stratified by risk severity, sex, and age group. Participants will be randomly assigned to a condition at intake, either a live video health coach-delivered single session or a control condition of an enhanced usual care (EUC) community resource brochure. They are also randomly assigned to one of two post-intake conditions: health coach-delivered portal-like messaging via web portal over 30 days or EUC delivered at 30 days post-intake. Thus, the trial has four groups: health coach-delivered session+portal, health coach-delivered session+EUC, EUC + portal, and EUC + EUC. Outcomes will be measured at 3-, 6-, and 12-months. The primary outcome is opioid misuse based on a modified Alcohol Smoking and Substance Involvement Screening Test. Secondary outcomes include other opioid outcomes (e.g., days of opioid misuse, overdose risk behaviors), other substance misuse and consequences, and impaired driving. This study is innovative by testing the efficacy of feasible and scalable technology-enabled interventions to reduce and prevent opioid misuse and opioid use disorder. Trial Registration:ClinicalTrials.gov University of Michigan HUM00177625 NCT Registration: NCT04550715.

In the present study, digestion pattern of purified bovine κ-casein (κ-CN) variants A, B, E as well as desialylated variant B, using INFOGEST 2.0 in vitro gastrointestinal digestion were investigated using peptidomics. Peptide profiles of the digests were identified and quantified using ion abundancies by liquid chromatography electrospray quadropole time of flight mass spectrometry (LC-ESI/Q-TOF MS/MS). Results showed that the κ-CN variants A and E had comparable digestion patterns at most digestion time points. In the in vitro gastric and in the initial intestinal phases fewer peptides and with lower total abundances were identified for variant B compared to variants A and E, indicating a slower digestion rate for κ-CN B. By desialylation, the digestion rate of desialylated variant B in both gastric and initial intestinal phases increased compared to the natural sialylated counterpart. Bioinformatics search revealed nine potential bioactive peptides released from all three variants A, B and E by the in vitro intestinal digestion, with four additional potential bioactive peptides being released after desialylation of κ-CN B.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Milk oligosaccharides are of high interest due to their bioactive properties. This study is the first to characterise milk oligosaccharides from native North European cattle breeds, as represented by 80 milk samples collected from eight native breeds originated from Norway (Norwegian Doela cattle and Norwegian Telemark cattle), Sweden (Swedish Mountain cattle), Denmark (Danish Red anno 1970), Iceland (Icelandic cattle), Lithuania (native Lithuanian Black and White) and Finland (Western Finncattle and Eastern Finncattle). Using high-performance liquid-chromatography chip/quadrupole time-of-flight mass-spectrometry, 18 unique monosaccharide compositions and a multitude of isomers were identified. No N-glycolylneuraminic acid was identified among these breeds. Western Finncattle milk was most abundant in neutral, acidic and fucosylated oligosaccharides. Further, Eastern Finncattle milk was significantly higher in acidic oligosaccharides and Icelandic cattle milk significantly higher in fucosylated oligosaccharides, compared to the mean. This study highlights specific native breeds of particular interest for future exploitation of milk oligosaccharides and breeding strategies.

BackgroundIn June 2018, San Francisco voters upheld the first comprehensive prohibition on sales of flavoured tobacco products (all products including menthol, everywhere in the city with no exceptions).MethodsThis paper used data collected by the San Francisco Department of Public Health as part of its implementation and enforcement of San Francisco's city-wide ban on the sale of flavoured tobacco products. Every licensed tobacco retailer was visited and inspected. The San Francisco Department of Public Health and volunteers conducted an educational campaign from September 2018 to December 2018, including emailing all licensed tobacco retailers about the law, mailing a fact sheet poster, conducting four listening sessions and visiting permitted tobacco retailers to educate them about the law and solicit questions.ResultsCompliance inspections started in December 2018, which found that compliance was 17%. Compliance increased in January 2019 and averaged 80% between January 2019 and December 2019. After the phase-in period, all retailers were visited as part of routine inspections. This effort resulted in 80% compliance.ConclusionIncluding retailer education prior to enforcement can result in compliance with a comprehensive ban on the sale of menthol and other flavoured tobacco products.

Abstract Objective Despite the frequent comorbidity of substance use disorders (SUDs) and psychiatric disorders, it remains unclear if screening for substance use in behavioral health clinics is a common practice. The aim of this review is to examine what is known about systematic screening for substance use in outpatient behavioral health clinics. Methods We conducted a PRISMA-based systematic literature search assessing substance use screening in outpatient adult and pediatric behavioral health settings in PubMed, Embase, and PsycINFO. Quantitative studies published in English before May 22, 2020 that reported the percentage of patients who completed screening were included. Results Only eight articles met our inclusion and exclusion criteria. Reported prevalence of screening ranged from 48 to 100%, with half of the studies successfully screening more than 75% of their patient population. There were limited data on patient demographics for individuals who were and were not screened (e.g., gender, race) and screening practices (e.g., electronic versus paper/pencil administration). Conclusions The results of this systematic review suggest that successful screening for substance use in behavioral health settings is possible, yet it remains unclear how frequently screening occurs. Given the high rates of comorbid SUD and psychopathology, future research is necessary regarding patient and clinic-level variables that may impact the successful implementation of substance use screening. Trial registry A methodological protocol was registered with the PROSPERO systematic review protocol registry (ID: CRD42020188645).

ObjectiveTo determine if the declining trend in U.S. youth cigarette smoking changed after e-cigarettes were introduced, and if youth e-cigarette users would have been likely to smoke cigarettes based on psychosocial and demographic predictors of smoking.MethodsAn interrupted time series analysis was used for cross-sectional data from the 2004 to 2018 National Youth Tobacco Surveys (NYTS) to assess changes in cigarette and e-cigarette use over time. A multivariable logistic regression model used 2004-2009 NYTS data on psychosocial risk factors to predict individual-level cigarette smoking risk from 2011 to 2018. Model-predicted and actual cigarette smoking behavior were compared.ResultsThe decline in current cigarette smoking slowed in 2014 (-0.75 [95% CI: -0.81, -0.68] to -0.26 [95% CI: -0.40, -0.12] percentage points per year). The decline in ever cigarette smoking accelerated after 2012 (-1.45 [95% CI: -1.59, -1.31] to -1.71 [95% CI: -1.75, -1.66]). Ever and current combined cigarette and/or e-cigarette use declined during 2011-2013 and increased during 2013-2014 with no significant change during 2014-2018 for either variable. The psychosocial model estimated that 69.0% of current cigarette smokers and 9.3% of current e-cigarette users (who did not smoke cigarettes) would smoke cigarettes in 2018.ConclusionsThe introduction of e-cigarettes was followed by a slowing decline in current cigarette smoking, a stall in combined cigarette and e-cigarette use, and an accelerated decline in ever cigarette smoking. Traditional psychosocial risk factors for cigarette smoking suggest that e-cigarette users do not fit the traditional risk profile of cigarette smokers.

Cigarette smoking patterns vary within the population, with some individuals remaining never smokers, some remaining occasional users, and others progressing to daily use or quitting. There is little research on how population-level tobacco control policy interventions affect individuals within different smoking trajectories. We identified associations between tobacco control policy interventions and changes across different smoking trajectories among adolescents and young adults. Using 15 annual waves of data drawn from the National Longitudinal Survey of Youth 1997 (NLSY97), we applied a group-based trajectory model to identify associations between days smoked per month, comprehensive smoke-free laws, cigarette tax rates, and known socio-demographic risk factors for membership in different smoking trajectories. Comprehensive smoke-free laws were associated with reduced risk of initiation and reductions in days smoked per month for all trajectories other than occasional users. Higher tax rates were associated with reduced risk of initiation and days smoked for all trajectories other than established users. Overall, population-based tobacco control policies, particularly comprehensive smoke-free laws, were associated with reduced smoking. Tobacco taxes primarily reduced risk of initiation and use among never smokers, experimenters, and quitters, consistent with previous research suggesting that tobacco manufacturers lower prices after tax increases to reduce the cost of continued smoking for established users. These results provide support for expanding smoke-free laws and establishing a minimum tobacco floor price, which could improve public health by reducing the risk of initiation as well as use among occasional and established smokers.

BackgroundThe tobacco industry works to block, delay, and weaken national tobacco control legislation to implement the WHO Framework Convention on Tobacco Control (FCTC). This article reviews how Nepal overcame industry opposition and to a comprehensive tobacco control law implementing the FCTC.MethodsWe triangulated newspaper articles and policy documents with key informant interviews.ResultsWith the support of international health groups, local tobacco control advocates worked with policymakers in Nepal to pass a comprehensive tobacco control law that exceeded FCTC obligations. The tobacco industry exploited a time of political transition to block consideration by Parliament, arranged and sponsored foreign tours for legislators, made death threats to tobacco control advocates and their families, and argued for the economic importance of tobacco farms. Despite strong interference from Health, and Law and Justice ministers, a 2009 Supreme Court ruling helped tobacco control advocates secure a comprehensive tobacco control law in 2011 that included rotating pictorial health warning labels covering 75% of both sides of cigarette packages, 100% smoke free public places and workplaces, private homes and vehicles, and a tobacco advertising, promotion, and sponsorship ban.ConclusionsAdvocates in developing countries should utilize Nepal's experience to reject tobacco industry offers of compromise and continue educating politicians and legislators to generate political support to pass a comprehensive tobacco control law. Technical and financial support from international agencies, and effective collaboration and coordination of civil societies, and utilization of domestic litigation are helpful in LMICs where governance is weak (the abstract in Nepali is available as a Supplementary Material).ImplicationsThe tobacco industry exploited a time of political transition in Nepal in its effort to block comprehensive tobacco control policy in Parliament by sponsoring foreign tours of legislatures, making death threats to tobacco control advocates and their families, and arguing for the economic importance of tobacco farms. Tobacco control advocates used litigation to raise awareness and educate legislators and promote strong legislation with the involvement of international health groups. Technical and financial support from international agencies, and effective collaboration and coordination of civil societies, and utilization of domestic litigation are helpful in LMICs where governance is weak.

IntroductionNepal passed a comprehensive tobacco control law in 2011. Tobacco control advocates successfully countered tobacco industry (TI) interference to force implementation of law.Aims and methodsPolicy documents, news stories, and key informant interviews were triangulated and interpreted using the Policy Dystopia Model (PDM).ResultsThe TI tried to block and weaken the law after Parliament passed it. Tobacco control advocates used litigation to force implementation of the law while the TI used litigation in an effort to block implementation. The TI argued that tobacco was socially and economically important, and used front groups to weaken the law. Tobacco control advocates mobilized the media, launched public awareness campaigns, educated the legislature, utilized lawsuits, and monitored TI activities to successfully counter TI opposition.ConclusionsBoth tobacco control advocates and the industry used the discursive and instrumental strategies described in the PDM. The model was helpful for understanding TI activities in Nepal and could be applied to other low- and middle-income countries. Civil society, with the help of international health groups, should continue to track TI interference and learn the lessons from other countries to proactively to counter it.ImplicationsThe PDM provides an effective framework to understand battles over implementation of a strong tobacco control law in Nepal, a low- and middle-income country. The TI applied discursive and instrumental strategies in Nepal in its efforts to weaken and delay the implementation of the law at every stage of implementation. It is important to continuously monitor TI activities and learn lessons from other countries, as the industry often employ the same strategies globally. Tobacco control advocates utilized domestic litigation, media advocacy, and engaged with legislators, politicians, and other stakeholders to implement a strong tobacco control law. Other low- and middle-income countries can adapt these lessons from Nepal to achieve effective implementation of their laws.

BackgroundIncreasing the price of tobacco products has the potential to reduce tobacco consumption. As other forms of promotion have been increasingly restricted over time, tobacco manufacturers have relied more on trade discounts. Minimum price laws that prevented the use of manufacturer promotions were once common; however in most US jurisdictions these discounts are now legally protected.MethodsWe collected tobacco industry documents, state legislation and court cases between 1987 and 2016 to review tobacco manufacturer strategies to change minimum price laws in the USA.ResultsBeginning in 2000, tobacco manufacturers lobbied to amend minimum price legislation after state regulators indicated that manufacturer promotions were illegal under existing laws. Companies viewed changing these laws as critical to maintaining tobacco sales, and after the initiation of an industry lobbying campaign, at least 20 states changed the way they calculated tobacco prices.ConclusionsModifying existing minimum price laws so that manufacturer discounts are no longer protected, and implementing new minimum price policies with comparable scope, would likely increase prices and reduce tobacco use.

BackgroundNepal was a monarchy, then a dictatorship, then a democracy. This paper reviews how tobacco control progressed in Nepal in the context of these changes in government from 1950 through 2006.MethodsWe triangulated tobacco industry documents, newspaper articles and key informant interviews.ResultsUntil 1983, the tobacco industry was mostly state owned. Transnational tobacco companies entered the Nepalese market through ventures with Surya Tobacco Company Private Limited (with Imperial Tobacco Company and British American Tobacco) in 1983 and Seti Cigarette Factory Limited (with Philip Morris International [PMI]) in 1985. Seminars and conferences on tobacco, celebrations of World No Tobacco Day (WNTD) and efforts by WHO helped promote tobacco control in Nepal beginning in the 1970s. Tobacco advocates in Nepal pushed the government to issue executive orders banning smoking in public places in 1992 and tobacco advertising in electronic media in 1998, and to introduce a tobacco health tax in 1993. The tobacco industry lobbied against these measures and succeeded in keeping the tobacco tax low by challenging it in court. Tobacco advocates sued the government in 2003 and 2005, resulting in a June 2006 Supreme Court decision upholding the smoking and advertising bans and requiring the government to enact a comprehensive tobacco control law.ConclusionsPolitical instability, conflict, weak governance and the dictatorship significantly affect tobacco control activities in low-income and middle-income countries. Nepal shows that tobacco control advocates can take advantage of global events, such as WNTD, and use domestic litigation to maintain support from civil societies and to advocate for stronger tobacco control policies.

BackgroundIncreasing tobacco taxes, and through them, prices, is an effective public health strategy to decrease tobacco use. The tobacco industry has developed multiple promotional strategies to undercut these effects; this study assessed promotions directed to wholesalers and retailers and manufacturer price changes that blunt the effects of tax and price increases.MethodsWe reviewed tobacco industry documents and contemporaneous research literature dated 1987 to 2016 to identify the nature, extent, and effectiveness of tobacco industry promotions and price changes used after state-level tobacco tax increases.ResultsTobacco companies have created promotions to reduce the effectiveness of tobacco tax increases by encouraging established users to purchase tobacco in lower-tax jurisdictions and sometimes lowering manufacturer pricing to "undershift" smaller tax increases, so that tobacco prices increased by less than the amount of the tax.ConclusionsPolicymakers should address industry efforts to undercut an effective public health intervention through regulating minimum prices, limiting tobacco industry promotions, and by enacting tax increases that are large, immediate, and result in price increases.ImplicationsTobacco companies view excise tax increases on tobacco products as a critical business threat. To keep users from quitting or reducing tobacco use in response to tax increases, they have shifted manufacturer pricing and developed specific promotions that encourage customers to shop for lower-taxed products. Health authorities should address tobacco industry efforts to undercut the effects of taxes by regulating prices and promotions and passing large and immediate tax increases.

Objectives. To investigate the transfer of marketing knowledge and infrastructure for targeting racial/ethnic minorities from the tobacco to the food and beverage industry in the United States.Methods. We analyzed internal industry documents between April 2018 and April 2019 from the University of California San Francisco Truth Tobacco Industry Documents Library, triangulated with other sources.Results. In the 1980s, Philip Morris Companies purchased General Foods and Kraft Foods and created Kraft General Foods. Through centralized marketing initiatives, Philip Morris Companies directly transferred expertise, personnel, and resources from its tobacco to its food subsidiaries, creating a racial/ethnic minority-targeted food and beverage marketing program modeled on its successful cigarette program. When Philip Morris Companies sold Kraft General Foods in 2007, Kraft General Foods had a fully integrated minority marketing program that combined target marketing with racial/ethnic events promotion, racial/ethnic media outreach, and corporate donations to racial/ethnic leadership groups, making it a food industry leader.Conclusions. The tobacco industry directly transferred racial/ethnic minority marketing knowledge and infrastructure to food and beverage companies. Given the substantial growth of food and beverage corporations, their targeting of vulnerable populations, and obesity-related disparities, public policy and community action is needed to address corporate target marketing.

Forthcoming in the Marquette Law Review