The single-cell opioid responses in the context of HIV (SCORCH) consortium.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation.

Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system.

Habenular TCF7L2 links nicotine addiction to diabetes.

Diabetes is far more prevalent in smokers than non-smokers, but the underlying mechanisms of vulnerability are unknown. Here we show that the diabetes-associated gene Tcf7l2 is densely expressed in the medial habenula (mHb) region of the rodent brain, where it regulates the function of nicotinic acetylcholine receptors. Inhibition of TCF7L2 signalling in the mHb increases nicotine intake in mice and rats. Nicotine increases levels of blood glucose by TCF7L2-dependent stimulation of the mHb. Virus-tracing experiments identify a polysynaptic connection from the mHb to the pancreas, and wild-type rats with a history of nicotine consumption show increased circulating levels of glucagon and insulin, and diabetes-like dysregulation of blood glucose homeostasis. By contrast, mutant Tcf7l2 rats are resistant to these actions of nicotine. Our findings suggest that TCF7L2 regulates the stimulatory actions of nicotine on a habenula-pancreas axis that links the addictive properties of nicotine to its diabetes-promoting actions.

Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC. METHODS: Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets. RESULTS: We identified five CAF populations, termed CAF S1-S5. CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types. CONCLUSION: This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.

An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis: A Phase Ib/IIa Randomized Controlled Clinical Trial (DEFINE).

Rationale: High circulating galectin-3 is associated with poor outcomes in patients with coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with antiinflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis. Objectives: Primary outcomes were safety and tolerability of inhaled GB0139 as an add-on therapy for patients hospitalized with COVID-19 pneumonitis. Methods: We present the findings of two arms of a phase Ib/IIa randomized controlled platform trial in hospitalized patients with confirmed COVID-19 pneumonitis. Patients received standard of care (SoC) or SoC plus 10 mg inhaled GB0139 twice daily for 48 hours, then once daily for up to 14 days or discharge. Measurements and Main Results: Data are reported from 41 patients, 20 of which were assigned randomly to receive GB0139. Primary outcomes: the GB0139 group experienced no treatment-related serious adverse events. Incidences of adverse events were similar between treatment arms (40 with GB0139 + SoC vs. 35 with SoC). Secondary outcomes: plasma GB0139 was measurable in all patients after inhaled exposure and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc analysis of covariance [ANCOVA] over days 2-7; P = 0.0099 vs. SoC). Plasma biomarkers associated with inflammation, fibrosis, coagulopathy, and major organ function were evaluated. Conclusions: In COVID-19 pneumonitis, inhaled GB0139 was well-tolerated and achieved clinically relevant plasma concentrations with target engagement. The data support larger clinical trials to determine clinical efficacy. Clinical trial registered with ClinicalTrials.gov (NCT04473053) and EudraCT (2020-002230-32).

Antigen receptor-engineered Tregs inhibit CNS autoimmunity in cell therapy using nonredundant immune mechanisms in mice.

CD4+ FOXP3+ Tregs are currently explored to develop cell therapies against immune-mediated disorders, with an increasing focus on antigen receptor-engineered Tregs. Deciphering their mode of action is necessary to identify the strengths and limits of this approach. Here, we addressed this issue in an autoimmune disease of the CNS, EAE. Following disease induction, autoreactive Tregs upregulated LAG-3 and CTLA-4 in LNs, while IL-10 and amphiregulin (AREG) were increased in CNS Tregs. Using genetic approaches, we demonstrated that IL-10, CTLA-4, and LAG-3 were nonredundantly required for the protective function of antigen receptor-engineered Tregs against EAE in cell therapy whereas AREG was dispensable. Treg-derived IL-10 and CTLA-4 were both required to suppress acute autoreactive CD4+ T-cell activation, which correlated with disease control. These molecules also affected the accumulation in the recipients of engineered Tregs themselves, underlying complex roles for these molecules. Noteworthy, despite the persistence of the transferred Tregs and their protective effect, autoreactive T cells eventually accumulated in the spleen of treated mice. In conclusion, this study highlights the remarkable power of antigen receptor-engineered Tregs to appropriately provide multiple suppressive factors nonredundantly necessary to prevent autoimmune attacks.

Decision times in orthographic processing: a cross-linguistic study.

Reading comparisons across transparent and opaque orthographies indicate critical differences that may reveal the mechanisms involved in orthographic decoding across orthographies. Here, we address the role of criterion and speed of processing in accounting for performance differences across languages. We used binary tasks involving orthographic (words-pseudowords), and non-orthographic materials (female-male faces), and analyzed results based on Ratcliff's Diffusion model. In the first study, 29 English and 28 Italian university students were given a lexical decision test. English observers made more errors than Italian observers while showing generally similar reaction times. In terms of the diffusion model, the two groups differed in the decision criterion: English observers used a lower criterion. There was no overall cross-linguistic difference in processing speed, but English observers showed lower values for words (and a smaller lexicality effect) than Italians. In the second study, participants were given a face gender judgment test. Female faces were identified slower than the male ones with no language group differences. In terms of the diffusion model, there was no difference between groups in drift rate and boundary separation. Overall, the new main finding concerns a difference in decision criterion limited to the orthographic task: English individuals showed a more lenient criterion in judging the lexicality of the items, a tendency that may explain why, despite lower accuracy, they were not slower. It is concluded that binary tasks (and the Diffusion model) can reveal cross-linguistic differences in orthographic processing which would otherwise be difficult to detect in standard single-word reading tasks.

Comparing POD and MOD ENDS Users' Product Characteristics, Use Behaviors, and Nicotine Exposure.

INTRODUCTION: POD electronic nicotine delivery systems (ENDS), often containing high concentrations of nicotine salts, have replaced MODs (ie, open/modifiable devices) as the most popular devices. The purpose of this study was to compare device/liquid characteristics, use behavior, and nicotine exposure between POD and MOD users. METHODS: Data from the initial visit of a prospective observational study of exclusive ENDS users compared MOD (n = 48) and POD (n = 37) users. Participants completed questionnaires on demographic characteristics, patterns of ENDS use, and ENDS features. A urine sample was collected to test for cotinine and an ENDS liquid sample was collected to test for nicotine and salts. Puff topography was captured during an ad libitum bout at the end of the session. RESULTS: MOD and POD users did not differ on demographic characteristics. MOD users reported purchasing more liquid in the past month than POD users (180.4 ±â€…28.0 vs. 50.9 ±â€…9.0 ml, p < .001). Differences in characteristics of devices used by MOD and POD users included flavor type (p = .029), nicotine concentration (liquids used by MOD users contained less nicotine than those used by POD users: 8.9 ±â€…2.0 vs. 41.6 ±â€…3.2 mg/ml, p < .001), and presence of the nicotine salt (fewer MOD liquids had salts present than POD liquids: 11.9% vs. 77.4%, p < .001). User groups did not differ on urinary cotinine levels or puff topography (ps > .05). CONCLUSIONS: Despite different characteristics of MOD and POD ENDS, users of those products are exposed to similar amounts of nicotine, likely due to using more liquid among MOD users. IMPLICATIONS: This study directly compares ENDS product characteristics, user behavior, and nicotine exposure between MOD and POD ENDS users. Although POD products contained higher nicotine concentrations compared to MOD products, users of PODs reported consuming less liquid than MOD users. Ultimately, MOD and POD users were exposed to similar levels of nicotine, suggesting users behaviorally compensate for differences in product characteristics.

Chemicals in cigarette flavor capsules from Guatemala and Mexico.

BACKGROUND: The global market share for cigarettes with flavor capsules has grown exponentially over the last decade, particularly in Latin America. When smoking, consumers crush a liquid capsule in the filter that flavors the smoke. Little is known about the chemical constituents of the liquids in capsules or their potential health risks. METHODS: Based on consumer data and availability in Mexico and Guatemala, 31 flavor capsule brands were purchased (19 and 12, respectively) in 2020. Since some cigarettes included multiple capsules in a stick (up to 2) or pack (up to 4), the final analytic sample included 50 capsules. We conducted qualitative and quantitative analysis using gas chromatography with mass spectrometry (GC-MS, Agilent Technologies, Inc.). RESULTS: The qualitative analysis detected 296 compounds (range=9 to 67 per capsule), and all capsules contained menthol. Among the compounds detected in more than half the sample were limonene, menthone, benzaldehyde, eucalyptol and triacetin. Traces of nicotine were found in 22% of the capsules. In the quantitative analysis, menthol concentrations were 33 times greater than the next most common compound (limonene). Benzyl alcohol and vanillin were also found in high concentrations. Comparing same brand varieties across countries showed substantial variability in the concentration of menthol and other compounds. CONCLUSION: Menthol is an omnipresent constituent in capsule cigarettes, perhaps because of its anesthetizing and reinforcing addictive properties. Other compounds found are toxic, potentially carcinogenic, and may enhance addictiveness. Variance in the presence and concentrations of such compounds highlights the importance of product standards to regulate capsule content. IMPLICATIONS: This study evaluated the chemical content of capsule cigarettes from two Latin American countries that have two of the highest market shares for capsule cigarettes worldwide. Compared to other studies, our assessment included brand varieties from two countries to compare the differences in chemical content by country. Our results yield that menthol is found in all capsules, and that other chemicals found may prolong nicotine exposure and therefore reinforce the addictive properties of cigarettes.

Patterns of Premium and Nonpremium Cigar Use in the United States: Findings from Wave 6 (2021) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: Understanding the characteristics of premium cigar use patterns is essential for minimizing public health harms. Typically, premium cigars are handmade, larger, more expensive, and without the characterizing flavors that are present in other cigar types: Nonpremium traditional cigars, cigarillos, and filtered cigars. AIMS AND METHODS: Self-reported brand and price data were used from Wave 6 of the Population Assessment of Tobacco and Health (PATH) Study to define and estimate premium versus nonpremium cigar use among U.S. adults, as well as to explore cigar smoking patterns, purchasing behavior, and reasons for use by cigar type. RESULTS: In 2021, 0.9% (95% CI = 0.7-1.0) of adults were premium cigar users, compared to 0.4% of nonpremium traditional cigar users (95% CI = 0.3-0.5), 1.1% of cigarillo users (95% CI = 1.0-1.2), and 0.6% filtered cigar users (95% CI = 0.5-0.7). Premium cigar users were overwhelmingly male (97.7%), and 35.8% were aged ≥55 years. The average premium cigar price/stick was $8.67, $5.50-7.00 more than other cigar types. Compared to other cigar types, significantly fewer premium cigar users had a regular brand with a flavor other than tobacco (~15% vs. 38%-53%). Though flavors remained the top reason for premium cigar use, they were less likely to endorse flavors as a reason for use than other cigar users (~40% vs. 68-74%). Premium cigar users had a lower prevalence (aRR: 0.37, 95% CI = 0.25-0.55) of dual use of cigars and cigarettes. CONCLUSIONS: Although <1% of U.S. adults use premium cigars, their use and purchasing characteristics continue to differ from other cigar types, highlighting the importance of capturing data specific to premium cigar use. IMPLICATIONS: This manuscript extends previous research from the National Academies of Science, Engineering, and Medicine report, "Premium cigars: Patterns of use, marketing, and health effects" by utilizing the most recent PATH Study data (Wave 6) to examine patterns of cigar use, including purchasing behavior and reasons for use, by cigar type (eg, premium traditional cigars, nonpremium traditional cigars, cigarillos, and filtered cigars). The findings support continued research on patterns of premium cigar use, which differ from use patterns of other cigar types.

Trends in e-cigarette brands, devices and the nicotine profile of products used by youth in England, Canada and the USA: 2017-2019.

BACKGROUND: The e-cigarette market has rapidly evolved, with a shift towards higher nicotine concentration and salt-based products, such as JUUL; however, the implications for youth vaping remain unclear. METHODS: Repeat cross-sectional online surveys were conducted in 2017, 2018 and 2019, with national samples of youth aged 16-19 years recruited from commercial panels in Canada (n=12 018), England (n=11 362) and the USA (n=12 110). Regression models examined differences between countries and over time in the types of e-cigarette products used (design and nicotine content), reasons for using brands and differences in patterns of use, sociodemographics and dependence symptoms by brand/nicotine content. RESULTS: In 2019, the use of pod- or cartridge-style e-cigarettes was greater in Canada and the USA than England, with Smok and JUUL the leading brands in all countries. In 2019, youth vapers in England were less likely to report using e-cigarettes with ≥2% nicotine (12.8%) compared with Canada (40.5%; adjusted OR (AOR)=4.96; 95% CI 3.51 to 7.01) and the USA (37.0%; AOR=3.99, 95% CI 2.79 to 5.71) and less likely to report using nicotine salt-based products (12.3%) compared with Canada (27.1%; AOR=2.77, 95% CI 1.93 to 3.99) and the USA (21.9%; AOR=2.00, 95% CI 1.36 to 2.95). In 2019, self-reported use of products with higher nicotine concentration was associated with significantly greater frequency of vaping, urges to vape and perceived vaping addiction (p<0.05 for all). CONCLUSIONS: The use of high-nicotine salt-based products is associated with greater symptoms of dependence, including JUUL and other higher-nicotine brands. Greater use of high-nicotine salt-based products may account for recent increases in the frequency of vaping among youth in Canada and the USA.

Over 1 year later: smokers' EVALI awareness, knowledge and perceived impact on e-cigarette interest.

OBJECTIVES: The e-cigarette or vaping product use-associated lung injury (EVALI) outbreak caused serious lung injuries in over 2800 people in the USA in 2019. By February 2020, most cases were determined as linked with vaping tetrahydrocannabinol (THC), including black market products using vitamin E acetate. This study examined smokers' EVALI awareness, knowledge and perceived impact on their e-cigarette interest approximately 16 months after its peak. DESIGN: Between January and February 2021, we surveyed 1018 adult current smokers from a nationally representative US research panel. Participants were asked if they had heard about EVALI prior to COVID-19, knew its main cause, and if EVALI had impacted their interest in future e-cigarette use. RESULTS: Approximately 54% of smokers had heard of EVALI. Among those who had heard of EVALI (n=542), 37.3% believed its main cause was e-cigarettes used to vape nicotine, like JUUL. Fewer (16.6%) thought the main cause was products for vaping marijuana/THC, and 20.2% did not know. About 29% had heard vitamin E acetate was associated with EVALI, and 50.9% indicated EVALI made them less interested in using e-cigarettes in the future. EVALI awareness was significantly associated with e-cigarette risk perceptions (ie, that e-cigarettes are as harmful as smoking). CONCLUSIONS: Despite the passage of time, considerable lack of knowledge and misperceptions about EVALI remain among those who smoke. Our findings suggest the need for continued efforts to promote better understanding of EVALI and appropriate behavioural and policy responses.

Heavy metals in ENDS: a comparison of open versus closed systems purchased from the USA, England, Canada and Australia.

INTRODUCTION: Electronic nicotine delivery systems (ENDS) are known to contain heavy metals such as lead (Pb), nickel (Ni) and chromium (Cr). The presence of heavy metals in ENDS may be due to contamination of e-liquids or leaching from elements of the ENDS device. This study investigates differences in ENDS metal concentrations between product type, year of purchase, country of purchase and e-liquid flavour. METHODS: Various open-system (refill e-liquids; n=116) and closed-system (prefilled with e-liquid; n=120) products were purchased in 2017 and 2018 from the USA, England, Canada and Australia. Electrothermal atomic absorption spectroscopy was used to analyse each product for Pb, Ni and Cr. Multiple linear regression and Kruskal-Wallis non-parametric statistical tests were conducted using GraphPad. RESULTS: Linear regression showed system type, year of purchase (not supported by Kruskal-Wallis), country of purchase and flavour type each had significant impacts on heavy metal concentrations. Open-system e-liquid samples showed no quantifiable levels of heavy metals. Closed-system samples contained concerningly high concentrations of Pb, Ni and Cr. Closed-system samples from the USA commonly displayed higher average heavy metal concentrations than those from England. Some fruit and mint-flavoured closed-system products showed higher heavy metal concentrations than tobacco-flavoured products. CONCLUSION: The presence of heavy metals only in closed-system products suggests that metals may be leaching from ENDS device parts. Highly variable heavy metal concentrations between ENDS products demonstrate that various product characteristics may affect the degree of leaching and that there is a need for further regulation of these products.

Risk perceptions and continued smoking as a function of cigarette filter ventilation level among US youth and young adults who smoke.

BACKGROUND: While evidence demonstrates that the industry's marketing of cigarettes with higher filter ventilation (FV) misleads adults about their health risks, there is no research on the relationships between FV, risk perceptions and smoking trajectories among youth (ages 12-17) and young adults (ages 18-24). METHODS: Data on FV levels of major US cigarette brands/sub-brands were merged with the Population Assessment of Tobacco and Health Study to examine whether FV level in cigarettes used by wave 1 youth/young adults (n=1970) predicted continued smoking at waves 2-4, and whether those relationships were mediated by perceived risk of their cigarette brand. FV was modelled based on tertiles (0.2%-11.8%, low; 11.9%-23.2%, moderate; 23.3%-61.1%, high) to predict daily smoking, past 30-day smoking and change in number of days smoking at successive waves. RESULTS: The odds of perceiving one's brand as less harmful than other cigarette brands was 2.21 times higher in the high versus low FV group (p=0.0146). Relationships between FV and smoking outcomes at successive waves were non-significant (all p>0.05). CONCLUSION: Youth and young adults who use higher FV cigarettes perceived their brand as less harmful compared with other brands. However, level of FV was not associated with continued smoking.

Switching to cigarette brand variants with different filter ventilation levels: a descriptive analysis.

BACKGROUND: Regulation of filter ventilation (FV) has been proposed to reduce misperceptions that ventilation reduces the health risks of smoking. We describe smoking behaviour and exposure after switching to a cigarette brand variant (CBV) with a different FV level. METHODS: Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health Study was merged with FV levels of participants' CBV and restricted to adults with a usual CBV, smoked daily and included in wave 4 (2016-2017; n=371). Generalised estimation equations method modelled changes in FV and cigarettes per day (CPD), quit interest, total nicotine equivalents (TNE) and total NNAL (biomarker of a tobacco-specific carcinogen). FV change was defined as a change in CBV resulting in a ≥20% increase or decrease in FV. Secondary analyses used FV change based on an increase from <5% to >10% or a decrease from >10% to <5%. RESULTS: A non-significant pattern indicating an increase of 0.97 and 0.49 CPD was observed among those who switched to a CBV and increased FV by ≥20% and from <5% to >10%, respectively. A non-significant pattern indicating a decrease of 1.31 and 1.97 CPD was observed among those who decreased FV by ≥20% and from >10% to <5%, respectively. Changes in quit interest and biomarkers were also non-significant with one exception: greater reduction in TNE among those who decreased from >10% to <5% FV versus no change (-8.51 vs -0.25 nmol/mg creatinine; p=0.0447). CONCLUSIONS: Switching to CBV with lower FV does not appear to increase exposure and may even reduce exposure for some. Additional investigations are recommended to confirm these descriptive findings.

Still 'Cool': tobacco industry responds to state-wide menthol ban with synthetic coolants.

INTRODUCTION: In December 2022, California (CA) enforced a voter-approved regulation restricting the retail sale of flavoured tobacco products, including menthol cigarettes. Shortly after, new products emerged on the market containing similar blue and green package colours yet with 'non-menthol' descriptors. Using chemical analyses, we measured the content of menthol and 15 other cooling chemicals in Californian cigarettes with 'non-menthol' descriptors and compared concentrations to similar 'menthol'-labelled counterparts available in New York State (NY). METHODS: A convenience sample of 10 brands and types of cigarettes in CA were purchased based on package colours suggesting a cooling effect and/or 'non-menthol' descriptors. The exact brand and type of cigarettes (with menthol descriptors) were purchased in NY. Cigarettes from CA were compared with equivalent cigarettes from NY on package design and colours, cigarette physical characteristics and the presence of cooling additives. RESULTS: Menthol was not detected in any CA cigarette, except for Maverick-green box type, while its presence was confirmed in most NY counterpart products. A synthetic cooling chemical WS-3 was not detected in any NY cigarettes but was detected in four CA brands and types with implied cooling effect, ranging from 1.24±0.04 to 1.97±0.05 mg/cigarette. CONCLUSION: While manufacturers have removed menthol descriptors from CA packaging and the menthol ingredient from cigarettes, synthetic cooling chemicals detected in several CA brands suggest that cooling sensory effects may still be sustained. Policymakers must consider both the chemical ingredients themselves and sensory effects in future regulatory approaches.

Impact of Canada's menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre-post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA.

INTRODUCTION: Between 2015 and 2018, Canada banned menthol cigarettes. This study pooled data from two pre-post cohort studies (the Ontario Menthol Ban Study, and the International Tobacco Control Policy Evaluation (ITC) Canada Survey, conducted in seven provinces) to derive more precise estimates of the impact of Canada's menthol ban on quitting and to apply these estimates to project the impact of a menthol ban in the USA. METHODS: Weighted multivariable logistic analyses compared post-ban quit success of menthol smokers with non-menthol smokers (for daily smokers and for all (daily + non-daily) smokers), controlling for sex, age, ethnicity, education, baseline smoking status, baseline cigarettes per day and study regions. Projections to the USA were created by multiplying the effect size of the Canadian menthol ban on quitting (percentage of increased quitting among menthol smokers) by the number of menthol smokers overall and among African Americans, from the 2019 National Survey on Drug Use and Health. RESULTS: After the menthol cigarette ban, menthol smokers were more likely than non-menthol smokers to have quit smoking among daily smokers (difference=8.0%; 95% CI: 2.4% to 13.7%,p=0.005) and all (daily+non-daily) smokers (difference=7.3%; 95% CI: 2.1% to 12.5%,p=0.006). The projected number of smokers who would quit after a US menthol ban would be 789 724 daily smokers (including 199 732 African Americans) and 1 337 988 daily+non-daily smokers (including 381 272 African Americans). CONCLUSIONS: This pooled analysis of Canada's menthol cigarette ban provides the foundation for estimating the impact of menthol bans in the USA and other countries. Projections suggest that a US menthol cigarette ban would have a substantial impact on increasing quitting.

The effect of survival processing on memory for pictures depends on how memory is tested.

ABSTRACTTwo experiments investigated the effects of survival processing on memory for pictures of objects. In experiment 1, participants were presented with 32 pictures of common objects and rated them for their relevance to a survival scenario, a moving home scenario, or for pleasantness. In a surprise recall test, participants in the survival condition recalled more of the verbal labels of the objects than participants in the moving and pleasantness conditions. In experiment 2, participants rated 64 pictures of objects in survival, moving home, or pleasantness conditions. Memory for visual detail was assessed using a forced-choice recognition test in which participants had to decide which of two highly similar pictures was the one they rated at study. In contrast to the results of experiment 1, correct recognition scores were highest in the pleasantness condition and lowest in the survival condition. This pattern suggests that survival processing enhances memory for objects but not for precise visual detail. The findings are consistent with the view that rating objects for their survival value directs attention to the potential uses of the objects. They also emphasise the importance of the match between encoding and retrieval processes in the survival processing paradigm.

A study of recurrence, complication and survival rates in patients with early stage vulval cancer undergoing sentinel lymph node sampling: a single-centre experience.

PURPOSE: Groin sentinel lymph node (SLN) identification and removal has become a standard of care for women with clinical early stage vulval cancer. There is evidence to support safe detection of the SLN with minimal morbidity. The purpose of this study is to report our experience of managing patients focusing on patient selection, adverse events, quality assurance of the procedure and any benefits and/or disadvantages to patients. METHODS: This was a retrospective study of patients with clinical early stage vulval cancer in a cancer centre over 5 years. Notes and hospital data were reviewed including admissions to emergency departments. Statistical software was used for the statistical analysis and the Kaplan Meier survival curve was generated to present survival rates. RESULTS: 61 cases were analysed. A total of 156 nodes have been removed and positive nodes were identified in 14 cases. In total, 9 women (14.75%) had disease recurrence within 5 years from primary surgery. Overall, 4 patients (6.5%) developed groin recurrence. In 3 of these patients there was isolated groin recurrence (4.9%). The median length of admission was 3 days and 6 cases were managed as day cases. CONCLUSIONS: Since the closure of the GROINNS-2 trial we have continued the procedure of SLN identification for women with clinical early stage vulval cancer. We have shown high level of adherence to our protocol and survival and complication rates comparable to other studies on the same field. There were a few patients managed as day-case which was of benefit to the patients.

Characterizing Heated Tobacco Product Use Among Adult Cigarette Smokers and Nicotine Vaping Product Users in the 2018 ITC Four Country Smoking & Vaping Survey.

INTRODUCTION: Heated tobacco products (HTP) have diversified global tobacco markets, and user characteristics remain understudied. This study evaluated sociodemographic characteristics, nicotine-related perceptions, and behaviors of current HTP users within a sample of adult (18+ years) nicotine users across four countries. AIMS AND METHODS: Data were from current smokers or nicotine vaping product (NVP; known as "e-cigarettes") users from Canada, England, the United States, and Australia (n = 11 421) who participated in the 2018 ITC Four Country Smoking and Vaping Survey. Current (at-least-monthly) HTP users were characterized (n = 441), and weighted multivariable logistic regressions examined correlates of HTP use. RESULTS: Compared to nonusers, current HTP users were younger (mean age: 44.4 vs 31.0 years; p < .001) and had higher socioeconomic status (p < .001). A majority of current HTP users used HTPs nondaily (daily: 40.3% vs nondaily: 59.7%). Most HTP users concurrently used both cigarettes and NVPs (90.5%). Among concurrent cigarette-HTP-NVP users, 36.2% used all three products daily. Use of other combusted tobacco products (cigars, cigarillos, pipe, waterpipe/hookah), cannabis, and binge drinking were each associated with current HTP use. HTP use was more common among smokers intending to quit within 6 months or reporting a quit attempt in the past 18 months, and vapers who had experienced negative side effects. CONCLUSION: HTP users in this sample tended to be younger and more affluent. Most reported concurrent use of multiple nicotine products and other substances. Those cigarette smokers who used HTPs appeared more interested in smoking cessation, while some characteristics of concurrent HTP-NVP users were suggestive of dissatisfaction with NVPs. IMPLICATIONS: Few studies have scrutinized characteristics of HTP early adopters in emerging markets. Our results indicate that in 2018, characteristics of established nicotine users who adopted HTP use in four high-income Western countries mirror those of HTP users in East Asian markets (South Korea and Japan) where HTPs are popular. HTP users reported high levels of concurrent use of noncigarette-combusted tobacco products (e.g., cigars, pipe tobacco). These findings point to the need for future longitudinal studies of HTP use given the implications of those use patterns on the harm reduction potential of HTPs. HTP user characteristics may yield important information to consider in regulation of these products.