A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.

The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.

Cellular diversity through space and time: adding new dimensions to GBM therapeutic development.

The current median survival for glioblastoma (GBM) patients is only about 16 months, with many patients succumbing to the disease in just a matter of months, making it the most common and aggressive primary brain cancer in adults. This poor outcome is, in part, due to the lack of new treatment options with only one FDA-approved treatment in the last decade. Advances in sequencing techniques and transcriptomic analyses have revealed a vast degree of heterogeneity in GBM, from inter-patient diversity to intra-tumoral cellular variability. These cutting-edge approaches are providing new molecular insights highlighting a critical role for the tumor microenvironment (TME) as a driver of cellular plasticity and phenotypic heterogeneity. With this expanded molecular toolbox, the influence of TME factors, including endogenous (e.g., oxygen and nutrient availability and interactions with non-malignant cells) and iatrogenically induced (e.g., post-therapeutic intervention) stimuli, on tumor cell states can be explored to a greater depth. There exists a critical need for interrogating the temporal and spatial aspects of patient tumors at a high, cell-level resolution to identify therapeutically targetable states, interactions and mechanisms. In this review, we discuss advancements in our understanding of spatiotemporal diversity in GBM with an emphasis on the influence of hypoxia and immune cell interactions on tumor cell heterogeneity. Additionally, we describe specific high-resolution spatially resolved methodologies and their potential to expand the impact of pre-clinical GBM studies. Finally, we highlight clinical attempts at targeting hypoxia- and immune-related mechanisms of malignancy and the potential therapeutic opportunities afforded by single-cell and spatial exploration of GBM patient specimens.

CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration after radiation-induced injury.

The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivaled capacity to drive tissue repair. Yet, the nature and role of macrophages in salivary gland homeostasis and how they may contribute to tissue repair after injury are not well understood. Here, we show that at least two phenotypically and transcriptionally distinct CX3CR1+ macrophage populations are present in the adult salivary gland, which occupy anatomically distinct niches. CD11c+CD206-CD163- macrophages typically associate with gland epithelium, whereas CD11c-CD206+CD163+ macrophages associate with blood vessels and nerves. Using a suite of complementary fate mapping systems, we show that there are highly dynamic changes in the ontogeny and composition of salivary gland macrophages with age. Using an in vivo model of radiation-induced salivary gland injury combined with genetic or antibody-mediated depletion of macrophages, we demonstrate an essential role for macrophages in clearance of cells with DNA damage. Furthermore, we show that epithelial-associated macrophages are indispensable for effective tissue repair and gland function after radiation-induced injury, with their depletion resulting in reduced saliva production. Our data, therefore, provide a strong case for exploring the therapeutic potential of manipulating macrophages to promote tissue repair and thus minimize salivary gland dysfunction after radiotherapy.

Subcutaneous choriocarcinomas in captive Amargosa voles (Microtus californicus scirpensis).

Spontaneous choriocarcinomas are rare, highly vascular, malignant trophoblastic tumors that occur in humans and animals. This report describes the unusual spontaneous presentation of 4 choriocarcinomas within the subcutaneous tissues of 4, multiparous but nongravid, Amargosa voles (Microtus californicus scirpensis) from a captive breeding colony. Two subcutaneous neoplasms were composed of multifocal discohesive and infiltrative aggregates of medium to large trophoblasts and cytotrophoblasts within a fibrovascular stroma. Neoplastic cells were associated with variably sized thrombi and cavitary areas of hemorrhage and necrosis. Two subcutaneous tumors were predominantly composed of expansile, blood-filled, cystic spaces lined by neoplastic cytotrophoblasts and occasionally contained medium to large trophoblasts. Trophoblasts and cytotrophoblasts were positive for pancytokeratin and cytokeratin 8/18, negative for alpha-fetoprotein, and contained intracytoplasmic Periodic acid-Schiff (PAS)-positive glycogen in all 4 tumors. In species with hemochorial placentation, migration of trophoblasts into maternal circulation with embolization to distant nonreproductive tissues occurs and may explain the unusual subcutaneous distribution of these 4 tumors. The 2 multiloculated paucicellular tumors may represent an early stage of neoplastic transformation. To the authors' knowledge, this is the first report characterizing choriocarcinomas in extrareproductive sites in rodents.

Birth Outcomes Associated With E-Cigarette and Non-E-Cigarette Tobacco Product Use During Pregnancy: An Examination of PATH Data Waves 1-5.

OBJECTIVES: To examine associations of prenatal e-cigarette use to pregnancy and birth outcomes. METHODS: Currently pregnant women (n = 1 037) from Waves 1 through 4 of the Population Assessment of Tobacco and Health Study who had pregnancy or live birth outcome data in a subsequent wave (Waves 2-5; 2013 to 2019). Weighted bivariate and multivariable models\ examined associations between past 30-day tobacco use assessed during pregnancy (any past 30-day e-cigarette use, any past 30-day non-e-cigarette tobacco use, or no past 30-day tobacco use) with adverse pregnancy (miscarriage, abortion, ectopic or tubal pregnancy, stillbirth) and birth outcomes (preterm birth, low birth weight, birth defect, placenta previa, placental abruption, pre-eclampsia) reported in the subsequent wave. RESULTS: Approximately 1% of pregnant women reported past 30-day exclusive e-cigarette use and 3.2% used e-cigarettes and one other tobacco product. Compared to no tobacco use, past 30-day e-cigarette use (exclusive or use with another tobacco product) during pregnancy was not associated with increased odds of an adverse pregnancy or birth outcome in bivariate or multivariable models. Past 30-day non-e-cigarette tobacco use was associated with increased odds of an adverse pregnancy outcome in multivariable models, but not an adverse live birth outcome. Compared to past 30-day cigarette use, past 30-day e-cigarette use during pregnancy was not associated with lowered odds of a birth or pregnancy outcome. CONCLUSIONS: E-cigarette use during pregnancy is rare. Understanding the positive and negative impacts of pre-natal e-cigarette use on women's health may guide public health messaging campaigns. IMPLICATIONS: Results showed that past 30-day e-cigarette use during pregnancy was low, with cigarette smoking remaining the most prevalent form of tobacco use during pregnancy. Current e-cigarette use during pregnancy used either exclusively or with another tobacco product, was not associated with increased risk of an adverse pregnancy, or birth outcome. A small sample size of e-cigarette users and limited information on quantity and frequency of e-cigarette use before and during pregnancy may limit conclusions. Healthcare providers may use this information when discussing the harms and consequences associated with e-cigarette and tobacco use during pregnancy.

Exploring glioblastoma stem cell heterogeneity: Immune microenvironment modulation and therapeutic opportunities.

Despite its growing use in cancer treatment, immunotherapy has been virtually ineffective in clinical trials for gliomas. The inherently cold tumor immune microenvironment (TIME) in gliomas, characterized by a high ratio of pro-tumor to anti-tumor immune cell infiltrates, acts as a seemingly insurmountable barrier to immunotherapy. Glioma stem cells (GSCs) within these tumors are key contributors to this cold TIME, often functioning indirectly through activation and recruitment of pro-tumor immune cell types. Furthermore, drivers of GSC plasticity and heterogeneity (e.g., reprogramming transcription factors, epigenetic modifications) are associated with induction of immunosuppressive cell states. Recent studies have identified GSC-intrinsic mechanisms, including functional mimicry of immune suppressive cell types, as key determinants of anti-tumor immune escape. In this review, we cover recent advancements in our understanding of GSC-intrinsic mechanisms that modulate GSC-TIME interactions and discuss cutting-edge techniques and bioinformatics platforms available to study immune modulation at high cellular resolution with exploration of both malignant (i.e., GSC) and non-malignant (i.e., immune) cell fractions. Finally, we provide insight into the therapeutic opportunities for targeting immunomodulatory GSC-intrinsic mechanisms to potentiate immunotherapy response in gliomas.

Synthesis and Evaluation of Functionalized Aryl and Biaryl Isothiocyanates against Human MCF-7 Cells.

Organic isothiocyanates (ITCs) are a class of anticancer agents which naturally result from the enzymatic degradation of glucosinolates produced by Brassica vegetables. Previous studies have demonstrated that the structure of an ITC impacts its potency and mode(s) of anticancer properties, opening the way to preparation and evaluation of synthetic, non-natural ITC analogues. This study describes the preparation of a library of 79 non-natural ITC analogues intended to probe further structure-activity relationships for aryl ITCs and second-generation, functionalized biaryl ITC variants. ITC candidates were subjected to bifurcated evaluation of antiproliferative and antioxidant response element (ARE)-induction capacity against human MCF-7 cells. The results of this study led to the identification of (1) several key structure-activity relationships and (2) lead ITCs demonstrating potent antiproliferative properties.

Differences in reasons for little cigar/cigarillo use across white and black/African American young adult users.

INTRODUCTION: The prevalence of little cigar and cigarillo (LCC) use among young adults is high. Research shows there are racial/ethnic differences in this prevalence, with Black/African American users more likely to report current LCC use. Given these discrepancies in LCC use, the present study aimed to assess potential differences in reasons for LCC use between White and Black/African American young adult ever and past 30-day users. METHODS: Participants were White (n = 2150), and Black/African American (n = 308) young adults (aged 18 to 24) recruited from Amazon Mechanical Turk who completed an online survey of tobacco use (December 2018-January 2019). LCC users were asked eight reasons for using LCCs. RESULTS: Flavoring was cited as the most popular reason for LCC use among White ever users while affordability was the most popular among Black/African American ever users. Adjusted logistic regressions among ever users revealed that Black/African American respondents (vs White) were more likely to use LCCs because of their affordability, the perception that LCCs are less harmful than cigarettes, and because of LCC advertising appeal. Among past 30-day users, adjusted logistic regression models showed that Black/African American respondents (vs White) were more likely to use LCCs because of their affordability. CONCLUSIONS: Findings align with previous studies showing that LLCs are more heavily marketed in predominantly Black/African American communities. Prevention efforts should account for racial differences in reasons for use in message development.

Urothelial carcinoma in the urinary bladder of a Japanese macaque (Macaca fuscata).

Tumors of urinary origin are infrequently reported in non-human primates. Urothelial carcinoma involving the urinary bladder was diagnosed in an adult female Japanese macaque that extended transmurally to the uterus and cervix. To our knowledge, this is the first report of a primary cystic urothelial carcinoma in a Japanese macaque.

Adolescent Susceptibility to E-Cigarettes: An Update From the 2018 National Youth Tobacco Survey.

PURPOSE: Examine correlates of e-cigarette susceptibility among adolescents. DESIGN: Secondary data analyses using the 2018 National Youth Tobacco Survey, excluding participants under 12 and over 17. SETTING: United States middle and high schools. SUBJECTS: Never e-cigarette users (n = 12,439) ages 12-17. MEASURES: Relationships between e-cigarette susceptibility and age, sex, race/ethnicity, ever tobacco use, perceived ease of purchasing tobacco products, perceived harm, relative addictiveness, household use of e-cigarettes/tobacco were examined. ANALYSIS: Odds of susceptibility were modeled with weighted multivariable logistic regressions. RESULTS: Thirty-five percent (unweighted n = 4,436) of adolescents were susceptible to e-cigarettes. Adolescents who were female (aOR = 1.2), Hispanic (aOR = 1.3), perceived e-cigarettes as anything less than "a lot of harm" (aOR = 2.2-4.9) and "easy" to purchase (aOR = 1.4), had ever used combustible tobacco (aOR = 2.9), or reported household use of e-cigarettes (aOR = 1.5) were susceptible. Non-Hispanic black respondents (vs. non-Hispanic white; aOR = 0.72) had significantly lower odds of susceptibility to e-cigarettes. CONCLUSION: In the 2018 NYTS adolescent sample, perceptions of harm and ease of tobacco product purchase appear to be significantly related to higher odds of e-cigarette susceptibility, in addition to other demographic factors. Longitudinal data, particularly cohort data following adolescents from susceptible to actual or no use, are needed to assess predictors of e-cigarette use initiation.

Menthol and Mint Cigarettes and Cigars: Initiation and Progression in Youth, Young Adults and Adults in Waves 1-4 of the PATH Study, 2013-2017.

INTRODUCTION: This study examined in youth (12-17 years), young adults (18-24 years), and adults (25+ years): (1) the prevalence of the first menthol cigarette and menthol/mint cigar use among new tobacco users; (2) association between the first menthol/mint use, subsequent tobacco use, and nicotine dependence ~1 year later compared with the first non-menthol/mint use. AIMS AND METHODS: Longitudinal analysis of data from Waves 1 to 4 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2017; 10 086 youth and 21 281 adults). Main outcome measures were past 12-month and past 30-day cigarette and cigar use, and nicotine dependence. RESULTS: Youth and young adult new cigarette users are more likely to smoke a menthol cigarette or indicate that they do not know the flavor compared with adults aged 25+. A greater proportion of adults aged 25+ first used menthol/mint-flavored cigars (13.4%) compared with youth (8.5%) and young adults (7.4%). Among young adults, first use of a menthol cigarette is associated with past 12-month use of cigarettes at the subsequent wave and first use of any menthol/mint-flavored cigars is associated with past 30-day use of these products at the subsequent wave in both youth and young adults. In youth and adults, there were no significant relationships between first use of a menthol/mint cigarette or cigar and nicotine dependence scores at a subsequent wave in multivariable analyses. CONCLUSIONS: The first use of menthol/mint cigarettes and cigars is associated with subsequent cigarette and cigar use in young people aged 12-24. IMPLICATIONS: This study examined the relationship between initiation with menthol cigarettes and menthol/mint cigars, subsequent tobacco use, and nicotine dependence in US youth, young adults, and adults who participated in Waves 1-4 of the Population Assessment of Tobacco and Health study. New use of menthol cigarettes was associated with greater past 12-month cigarette use in young adults and new use of menthol/mint-flavored cigars was associated with greater past 30-day cigar use in youth and young adults compared with non-menthol use. Initiation with menthol/mint cigarette and cigar products may lead to subsequent use of those products.

Youth Vaping and Tobacco Use in Context in the United States: Results From the 2018 National Youth Tobacco Survey.

INTRODUCTION: According to the National Youth Tobacco Survey (NYTS), youth e-cigarette use (vaping) rose between 2017 and 2018. Frequency of vaping and concurrent past 30-day (p30d) use of e-cigarettes and tobacco products have not been reported. METHODS: We analyzed the 2018 NYTS (N = 20 189) for vaping among all students (middle and high school; 6-12th grades; 9-19 years old) by frequency of vaping, exclusive vaping, p30d poly-product use (vaping and use of one or more tobacco product), and any past tobacco product use. RESULTS: In 2018, 81.4% of students had not used any tobacco or vapor product in the p30d, and 86.2% had not vaped in the p30d. Among all students, of the 13.8% vaped in the p30d, just over half vaped on ≤5 days (7.0%), and roughly a quarter each vaped on 6-19 days (3.2%) and on 20+ days (3.6%). Almost three quarters of p30d vapers (9.9%) reported past or concurrent tobacco use and the remainder (3.9%) were tobacco naïve. 2.8% of students were tobacco naïve and vaped on ≤5 days; 0.7% were tobacco-naïve and vaped on 6-19 days, and 0.4% were tobacco-naïve and vaped on 20+ days. CONCLUSIONS: Vaping increased among US youth in 2018 over 2017. The increases are characterized by patterns of low p30d vaping frequency and high poly-product use, and a low prevalence of vaping among more frequent but tobacco naïve vapers. IMPLICATIONS: Results underscore the importance of including the full context of use patterns. The majority of vapers (60.0%-88.9% by use frequency) were concurrent p30d or ever tobacco users. About 4% of students were tobacco naïve and vaped in the p30d, but few (0.4%) vaped regularly on 20 or more days. Reporting youth vaping data with frequency and tobacco product co-use will give public health decision-makers the best possible information to protect public health.

Association of Electronic Nicotine Delivery System Use With Cigarette Smoking Progression or Reduction Among Young Adults.

Importance: The prevalence of electronic nicotine delivery systems (ENDS) use, including e-cigarettes, among US young adults (YAs) has raised questions about how these products may affect future tobacco and nicotine use among YAs. Given this prevalence and that young adulthood is a critical period for the establishment of tobacco and nicotine use, it is important to consider the association between ENDS use and cigarette smoking specifically in this age group. Objective: To examine whether ENDS use frequency or intensity is associated with changes in cigarette smoking among US YA ever smokers during 1 year. Design, Setting, and Participants: This cohort study used 3 waves of data (2013-2014, 2014-2015, and 2015-2016) from the Population Assessment of Tobacco and Health (PATH) Study, an ongoing longitudinal cohort study of adults and youth. Unweighted 1:6 propensity score matching was used to match participants on wave 1 risk factors for ENDS use at wave 2. The changes in smoking between wave 2 and wave 3 were assessed using the matched sample. In total, 1096 ENDS-naive, ever cigarette-smoking YAs (18-24 years of age) at wave 1 who participated in wave 2 and wave 3 and who had complete data in the PATH Study were included in the analyses, which were conducted from August 2018 to October 2019. Exposures: Never ENDS use (n = 987), any previous 30-day ENDS use (n = 109), 1 to 5 days of ENDS use in the previous 30 days (n = 75), and 6 or more days ENDS use in the previous 30 days at wave 2 (n = 34). Main Outcomes and Measures: The analytic sample was selected using multiple variables based on peer-reviewed literature supporting associations with ENDS use. The main outcomes-changes in cigarette smoking behavior between wave 2 and wave 3-were defined using 2 measures: (1) change in smoking frequency, defined as the number of smoking days in the previous 30 days at wave 3 vs wave 2, and (2) change in smoking intensity, defined as the number smoking days in the previous 30 days multiplied by the mean number of cigarettes consumed on smoking days at wave 3 vs wave 2. Results: The present cohort analyses included 1096 YA ever smokers who were ENDS naive at wave 1. The majority of the sample were women (609 [55.6%]) and White individuals (698 [63.7%]), and the mean (SD) age was 21.4 (1.9) years. In wave 1, 161 YAs (14.7%) were daily smokers in the previous 30 days. After propensity score matching, no statistically significant associations were observed between any definition of wave 2 ENDS use and changes in either the frequency or intensity of smoking at wave 3. Conclusions and Relevance: In this cohort study of US YA ever smokers, ENDS use was not associated with either decreased or increased cigarette smoking during a 1-year period. However, it is possible that the rapidly evolving marketplace of vaping products may lead to different trajectories of YA cigarette and ENDS use in the future.

Impact of flavors and humectants on waterpipe tobacco smoking topography, subjective effects, toxicant exposure and intentions for continued use.

INTRODUCTION: The present study examined how the lack of characterising flavours and low levels of humectants may affect users' waterpipe tobacco (WT) smoking topography, subjective effects, toxicant exposure and intentions for continued use. METHODS: 89 WT smokers completed four ad libitum smoking sessions (characterising flavor/high humectant (+F+H); characterising flavor/low humectant (+F-H); no characterising flavor/high humectant (-F+H); no characterising flavor/low humectant (-F-H)) in a randomised cross-over design. WT was commercially available; same brand but nicotine levels were not held constant. A subsample (n=50) completed a standardised, 10-puff session preceding ad libitum smoking. Participants completed questionnaires, exhaled carbon monoxide (eCO) testing and provided blood samples for plasma nicotine. Smoking topography was measured throughout the session. Post hoc analyses showed that -F+H and -F-H did not differ significantly in humectant levels. Therefore, these groups were collapsed in analyses (-F-H). RESULTS: WT smokers reported significantly greater satisfaction, liking, enjoyment and greater intentions for continued use when smoking +F+H compared with other WT products, with -F-H receiving the lowest ratings. Significant differences in topography were observed during standardised and ad libitum sessions, with the -F-H preparation leading to greater total inhaled volume and eCO boost, but lower nicotine boost compared with +F+H (all p<0.05). DISCUSSION: The findings demonstrate the importance of flavours and humectants on improving WT smoking experience and increasing the likelihood that users will want to initiate and continue smoking. Moreover, it demonstrates that flavours and humectants influence smoking behaviour and toxicant exposure in some unexpected ways that are important for regulatory efforts.

Challenges Associated With Cervical Cancer Screening and Management in Obese Women: A Provider Perspective.

OBJECTIVES: Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women. MATERIALS AND METHODS: We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy. RESULTS: Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training. CONCLUSIONS: Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.

Young Adult Tobacco and E-cigarette Use Transitions: Examining Stability Using Multistate Modeling.

INTRODUCTION: The objective of this study was to describe tobacco and nicotine product use state transition probabilities among youth and young adults over time. METHODS: A national sample of young adult tobacco product users and nonusers between the ages of 18 and 34 years at baseline was surveyed at 6-month intervals for 3 years. Use and nonuse states were defined as mutually exclusive categories based on self-reported, past 30-day use of the various products. Never use, noncurrent use, and current use of combustible, noncombustible tobacco, and electronic cigarette (e-cigarette) products was assessed at each interval. A multistate model was fit to estimate transition probabilities between states and length of stay within each state. RESULTS: After 6 months, same-state transition probabilities were high for all use states (0.76-0.96), except for dual product use (0.48). After 3 years, transition probabilities were smaller and tended to converge toward combustible product use for baseline e-cigarette (0.42), combustible (0.51), and dual product users (0.52). Age was inversely associated with transition risk from never or noncurrent use to use of combustible or e-cigarette products. CONCLUSIONS: Never and noncurrent users, followed by combustible product users, were most likely to remain in those states throughout the 3-year observation interval. Users of any tobacco or e-cigarette product at baseline were most likely to transition to combustible product use or noncurrent use by the final follow-up. IMPLICATIONS: This study describes the probability of transitioning between various states of tobacco product use, including never and no current use, over a span of 3 years in a sample of young adults. This type of longitudinal description, which includes all tobacco product use states, is lacking in most studies that tend to focus on one or only a few products. The results suggest that it is important to assess outcomes over a sufficiently long period to capture true variability in patterns of product use.

Flavour types used by youth and adult tobacco users in wave 2 of the Population Assessment of Tobacco and Health (PATH) Study 2014-2015.

BACKGROUND: Most youth and young adult (YA) tobacco users use flavoured products; however, little is known about specific flavours used. METHODS: We report flavour types among US tobacco users from the Population Assessment of Tobacco and Health Study, wave 2, 2014-2015. At wave 2, we examined (1) flavour use and type at past 30-day use; (2) new flavoured tobacco product use and type; (3) product-specific flavour patterns across youth (ages 12-17) (n=920), YA (18-24) (n=3726) and adult (25+) (n=10 346) past 30-day and new tobacco users and (4) concordance between self-coded and expert-coded brand flavour type among all adults (18+). RESULTS: Prevalence of flavoured tobacco product use was highest among youth, followed by YA and adult 25+ any tobacco users. Within each age group, flavoured use was greatest among hookah, e-cigarette and snus users. Overall, menthol/mint, fruit and candy/sweet were the most prevalent flavour types at first and past 30-day use across age groups. For past 30-day use, all flavour types except menthol/mint exhibited an inverse age gradient, with more prevalent use among youth and YAs, followed by adults 25+. Prevalence of menthol/mint use was high (over 50% youth, YAs; 76% adults 25+) and exhibited a positive age gradient overall, though the reverse for cigarettes. Brand-categorised and self-reported flavour use measures among adults 18+ were moderately to substantially concordant across most products. CONCLUSIONS: Common flavours like menthol/mint, fruit and candy/sweet enhance appeal to young tobacco users. Information on flavour types used by product and age can inform tobacco flavour regulations to addess flavour appeal especially among youth.

People in E-Cigarette Ads Attract More Attention: An Eye-Tracking Study.

OBJECTIVES: Minimally regulated electronic cigarettes (e-cigarette) advertising may be one potential factor driving the increasing prevalence of young adult e-cigarette use. Using eye-tracking, the current study examined which e-cigarette advertising features were the most appealing to young adults as a first step to examine how e-cigarette advertising may be regulated. METHODS: Using a within-subjects design, 30 young adults (M age = 20.0 years) viewed e-cigarette ads in a laboratory. Ad features or areas of interest (AOIs) included: 1) brand logo, 2) product descriptor, and 3) people. During ad viewing, eye-tracking measured participants' dwell time and time to first fixation for each AOI as well as each ad brand. Harm perceptions pre- and post-viewing were measured. RESULTS: Participants spent the longest dwell time on people (M = 2701 ms), then product descriptors (M = 924 ms), then brand logos (M = 672 ms; ps < .001). They also fixated fastest on AOIs in that order. Participant sex significantly impacted dwell time of ad brand, and harm perceptions decreased after viewing the ads (ps < .05). CONCLUSIONS: This study provides initial evidence about which e-cigarette ad features may appeal most to young adults and may be useful when designing evidence-based policy.

Tobacco use and the interplay of internalizing, externalizing and substance use problems: A latent class analysis of data from the Population Assessment of Tobacco and Health Study.

BACKGROUND: Cigarette smoking is disproportionately high among adults with two or more psychiatric disorders (psychiatric comorbidities), yet research on non-cigarette tobacco use among this population is scant. Additionally, most studies on tobacco use this among this population rely on psychiatric diagnoses rather than individual symptoms, potentially excluding individuals with symptom-specific issues that increase their risk for tobacco use but do not meet the criteria for diagnosis. The objectives of this study were to identify unique classes of individuals based on symptoms of psychiatric disorders and to assess differences in demographic characteristics and tobacco use behaviors between classes. METHODS: This study used data from Wave 2 of the Population Assessment of Tobacco and Health Study adult dataset. Latent class analysis was used to classify individuals based on internalizing, externalizing and substance use problems. Bivariate and multivariable models examined the association between latent class membership and current use of cigarettes, cigar products, electronic nicotine delivery systems, pipe, hookah and smokeless tobacco products. Poly tobacco use was also examined. RESULTS: Three latent classes were identified. The "normative" class reported low prevalence of all symptoms, the "severe internalizing and non-violent externalizing" class reported severe internalizing problems and non-violent externalizing problems and the "severe" class reported high prevalence of all symptoms. Tobacco use was highest for the "severe" class and lowest for the "normative" class across products. CONCLUSIONS: Individuals in the "severe" class may be at elevated risk of tobacco-related morbidity and mortality and would likely benefit from targeted tobacco control interventions.

Association of Flavored Tobacco Use With Tobacco Initiation and Subsequent Use Among US Youth and Adults, 2013-2015.

Importance: Flavors in tobacco products may appeal to young and inexperienced users. Objective: To examine among youth (aged 12-17 years), young adults (aged 18-24 years), and adults (aged ≥25 years) the prevalence of first use of flavored tobacco products among new tobacco users and the association between first flavored use of a given tobacco product and tobacco use 1 year later, including progression of tobacco use. Design, Setting, and Participants: This cohort study represents a longitudinal analysis of data from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative study with data collected in 2013 to 2014 (wave 1) and 2014 to 2015 (wave 2). Participants were noninstitutionalized individuals, including 11 996 youth and 26 447 adults, in selected households who participated in both waves of the PATH Study. Data analysis was conducted from July 2016 to June 2019. Main Outcomes and Measures: Prevalence of tobacco product use at wave 2. Results: The mean (SE) age of the participants was 14.5 (0.0) years for youth, 21.1 (0.0) years for young adults, and 50.3 (0.0) for adults. Most youth (71.9%; 95% CI, 69.7%-74.0%) and young adults (57.6%; 95% CI, 54.9%-60.3%) who were new users of tobacco products over the 10- to 13-month follow-up period used flavored products. First use of a menthol or mint or other flavored cigarette documented at wave 1 was positively associated with past 12-month and past 30-day cigarette use in all age groups at wave 2 compared with first use of a nonflavored cigarette (youth, flavored cigarette, past 12-month use adjusted prevalence ratio [aPR], 1.14 [95% CI, 1.05-1.25] and past 30-day use aPR, 1.15 [95% CI, 1.00-1.31]; youth, menthol or mint cigarette, past 12-month use aPR, 1.18 [95% CI, 1.08-1.29] and past 30-day use aPR, 1.19 [95% CI, 1.04-1.37]; young adult, flavored cigarette, past 12-month use aPR, 1.09 [95% CI, 1.04-1.15] and past 30-day use aPR, 1.13 [95% CI, 1.06-1.21]; young adult menthol or mint cigarette, past 12-month use aPR, 1.10 [95% CI, 1.05-1.16] and past 30-day use aPR, 1.15 [95% CI, 1.07-1.23]; adult flavored cigarette, past 12-month use aPR, 1.10 [95% CI, 1.05-1.15] and past 30-day use aPR, 1.09 [95% CI, 1.04-1.14]; adult menthol or mint cigarette, past 12-month use aPR, 1.13 [95% CI, 1.08-1.18] and past 30-day use aPR, 1.12 [95% CI, 1.07-1.17]). Among young adults, first use of flavored e-cigarettes (aPR, 2.05; 95% CI, 1.61-2.61), any cigars (aPR, 1.60; 95% CI, 1.26-2.02), cigarillos (aPR, 1.49; 95% CI, 1.08-2.05), filtered cigars (aPR, 3.69; 95% CI, 2.08-6.57), hookah (aPR, 1.91; 95% CI, 1.23-2.98), and any smokeless tobacco (aPR, 1.54; 95% CI, 1.08-2.20) was prospectively associated with current regular use of those products at wave 2 compared with first nonflavored use. Among adults aged 25 years and older, first use of flavored e-cigarettes (aPR, 1.60; 95% CI, 1.41-1.82), any cigars (aPR, 1.56; 95% CI, 1.29-1.87), cigarillos (aPR, 1.29; 95% CI, 1.01-1.64), filtered cigars (aPR, 1.79; 95% CI, 1.25-2.54), hookah (aPR, 5.66; 95% CI, 2.04-15.71), and any smokeless tobacco (aPR, 1.55; 95% CI, 1.32-1.82) was prospectively associated with current regular use of those products at wave 2 compared with first nonflavored use. Conclusions and Relevance: In this longitudinal cohort study, flavors in tobacco products were associated with youth and young adult tobacco experimentation. First use of a flavored tobacco product may place youth, young adults, and adults at risk of subsequent tobacco use.