Search

The immune checkpoint molecules such as PD-L1 and PD-L2 have a substantial contribution to cancer immunotherapy including breast cancer. Microarray expression profiling identified several molecular subtypes, namely luminal-type (with a good-prognosis), HER2-type (with an intermediate-prognosis), and triple-negative breast cancer (TNBC)-type (with a poor-prognosis). We found that PD-L1 and PD-L2 mRNA expressions were highly expressed in TNBC-type cell lines (HCC1937, MDA-MB-231), moderately expressed in HER2-type cell line (SK-BR-3), and poorly expressed in luminal-type cell lines (MDA-MB-361, MCF7). The PD-L1 and PD-L2 expression in SK-BR-3 cells, but not those in HCC1937 and MDA-MB-231 cells, decreased by nicotine stimulation in a dose-dependent manner. In addition, nicotine treatment decreased the phosphorylation of Akt in SK-BR-3 cells, but not in other cell lines. These results show that nicotine regulates the expression of immune checkpoint molecules, PD-L1 and PD-L2, via inhibition of Akt phosphorylation. This findings may provide the new therapeutic strategies for the treatment of breast cancer.

Background Chronic pain is a common condition which causes patients much suffering and is very costly to society. Factors known to be associated with chronic pain include female gender, acute pain, depression, and anxiety. This study investigated whether stress, sleep disturbance, and physical inactivity were risk factors for developing chronic pain among young adults, and whether there were any interactions between these. Methods This retrospective longitudinal study was based on an existing database from a cohort study on IT use and health, called Health 24 Years. A questionnaire was sent to students aged 19–24 in Sweden for five consecutive years, containing questions on pain, stress, sleep, physical activity, technology use, health, and more. In logistic regressions, stress, sleep, and physical activity at baseline were potential predictors of chronic pain one and four years later. In addition, a new variable including all possible interactions between potential predictors was created to test for effect modification between risk factors. Results At the one-year follow-up, stress, non-restorative sleep, and physical inactivity showed odds ratios of 1.6 (95% CI: 1.0–2.4), 1.5 (95% CI: 1.0–2.3), and 1.8 (95% CI: 1.1–3.0) respectively after adjusting for confounders, the reference being non-stressed, having restorative sleep and being active. At the four-year follow-up, stress showed an adjusted odds ratio of 1.9 (95% CI: 1.3–2.9), while non-restorative sleep and physical inactivity were statistically insignificant. At the one-year follow-up, the interaction between risk factors were significant. The most clear example of this effect modification was to be inactive and not have -restorative sleep, compared to individuals who were active and had restorative sleep, showing an adjusted odds ratio of 6.9 (95% CI: 2.5–19.2) for developing chronic pain one year after baseline. This in comparison of odds ratios for only inactive respectively only non-restorative sleep being 1.7 (95% CI: 0.6–5.3) respectively 1.6 (95% CI: 0.7–3.5). Conclusions Stress, non-restorative sleep, and physical inactivity were risk factors for developing chronic pain one year after baseline, and stress were also a risk factor four years after baseline. These findings suggest that non-restorative sleep and inactivity are risk factors in the short term while stress is a risk factor in both the short and the long term. In addition to the independent effects of non-restorative sleep and inactivity, their combination seems to further increase the odds of chronic pain.

Understanding implications of passive smoke exposure during pregnancy is an important public health issue under the Developmental Origins of Health and Disease paradigm. In a prospective cohort of low-risk non-smoking pregnant women (NICHD Fetal Growth Studies—Singletons, 2009–2013, N = 2055), the association between first trimester passive smoke exposure and neonatal size was assessed by race/ethnicity. Plasma biomarker concentrations (cotinine, nicotine) assessed passive smoke exposure. Neonatal anthropometric measures included weight, 8 non-skeletal, and 2 skeletal measures. Linear regression evaluated associations between continuous biomarker concentrations and neonatal anthropometric measures by race/ethnicity. Cotinine concentrations were low and the percent above limit of quantification varied by maternal race/ethnicity (10% Whites; 14% Asians; 15% Hispanics; 49% Blacks). The association between cotinine concentration and infant weight differed by race/ethnicity (Pinteraction = 0.034); compared to women of the same race/ethnicity, per 1 log-unit increase in cotinine, weight increased 48g (95%CI -44, 139) in White and 51g (95%CI -81, 183) in Hispanic women, but decreased -90g (95%CI -490, 309) in Asian and -93g (95%CI -151, -35) in Black women. Consistent racial/ethnic differences and patterns were found for associations between biomarker concentrations and multiple non-skeletal measures for White and Black women (Pinteraction

The use of e-cigarettes has been increasing in popularity among people, especially young adults. Assessing young individuals’ perceptions of e-cigarettes can help to identify factors that may influence their decision to use e-cigarettes. To examine prevalence, perceptions, and knowledge of e-cigarettes among university students in Jordan, an observational cross-sectional study using an online self-administered questionnaire was conducted among students from public and private universities between October 2020 and January 2021. A total of 1259 university students completed the questionnaire. Approximately, 11% of participants reported e-cigarettes use. Among users, 26.5% used it for the purpose of smoking cessation, while 22% of them used it out of curiosity, and 20.5% used it as they believed it is less harmful than other tobacco products. Multivariate analysis showed that conventional cigarette smokers were independently associated with a better knowledge about e-cigarettes (OR = 1.496, 95CI% = 1.018–2.197, p-value = 0.040). In addition, medical students showed a significantly better knowledge compared to non-medical students (OR = 1.710, 95CI% = 1.326–2.204, p-value =

FLT and JCP are supported by a grant from the Spanish Government (Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación; Convocatoria 2017 de Proyectos I+D de Excelencia, Spain; co-funded by the Fondo Europeo de Desarrollo Regional, FEDER, European Union), with reference number PSI2017-85488-P. AM is supported by a grant from the Spanish Government (Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación; Convocatoria 2016 de Proyectos I+D de Excelencia, Spain), with reference number PSI2016-80558-R., Co-occurrence of drug misuse with other dysregulated behaviors is common. This study was aimed at exploring the associations between the risk of presenting a clinically relevant condition involving non-substance-related addictive or dysregulated behaviors (as measured by the MultiCAGE CAD-4 screening), and cannabis abuse/dependence (CAST/SDS) scores, and the role of gender therein. Participants were recruited using stratified probabilistic sampling at the University of Granada. Mann-Whitney's U tests were used to compare male and female students in SDS and CAST scores. Associations between gender and MultiCAGE scores were estimated using the gamma ordinal correlation index, and tested with chi(2). For each MultiCAGE dimension, a Poisson-family mixed-effects model was built with either SDS or CAST as the main input variable, while controlling for nicotine and alcohol dependence, and relevant sociodemographic variables. Incidence rate ratios (IRR) were computed for SDS/CAST effects, and the significance threshold was family-wise Bonferroni-corrected. Gender differences were significant for cannabis dependence/abuse and all MultiCAGE scores for non-substance-related conditions, with males showing higher risk scores for excessive gambling, excessive internet use, excessive video gaming, and hypersexuality, and females presenting higher scores in dysregulated eating and compulsive buying. Cannabis dependence and abuse were significantly associated with a higher risk of problematic video gaming. These associations were mostly driven by males. Importantly, although risk of problematic video gaming was specifically associated with cannabis abuse/dependence, there was only a weak non-significant association between problematic video gaming and alcohol use scores. Risk of alcohol use problems, in turn, was strongly associated with all other non-substance-related problems (problematic gambling, excessive Internet use, dysregulated eating, compulsive buying, and hypersexuality). These differential associations can cast light on the etiological similarities and dissimilarities between problematic substance use and putative addictive behaviors not involving drugs., Spanish Government, Fondo Europeo de Desarrollo Regional, FEDER, European Union PSI2017-85488-P, PSI2016-80558-R

Introduction E-liquid flavor is typically presented by flavor category (e.g. menthol, mint, fruit, dessert). Cooling sensations produced by flavor additives such as menthol enhance appeal of e-cigarettes among youth, but not all e-liquids that produce cooling sensations are labeled as menthol. Sensory experiences produced by flavors may allow for a new way to capture e-cigarette flavor use. This study aims to examine use of flavors that produce cooling sensations among youth and its association with e-cigarette use behaviors. Methods A 2019 survey of high school students (n = 4875) examined use of e-cigarette flavors that produced cooling sensations (cooling flavors) among past 30-day e-cigarette users. E-cigarette use behaviors (flavor use, nicotine use, frequency of use) were examined between those who did and did not use cooling flavors. A binary logistic regression was used to examine associations between vaping frequency, nicotine (vs. non-nicotine) use, and vaping cooling flavors while controlling for demographics, number of flavors vaped in the past month, and vaping age of onset. Results 51.6% (n = 473/916) of the analytic sample endorsed vaping cooling flavors. There were no demographic differences by vaping cooling flavors. Vaping cooling flavors was associated with vaping more frequently (AOR:1.04,95% CI:1.03,1.05) and vaping nicotine (AOR:2.37,95% CI:1.53,3.67). Conclusion Vaping cooling flavors was associated with greater nicotine vaping and frequency of e-cigarette use. Assessing sensory experience, such as cooling, in addition to flavor category may more fully capture e-cigarette flavor use and its impacts on youth e-cigarette use behaviors.

Use of nicotine-specific monoclonal antibodies (mAbs) to sequester and reduce nicotine distribution to brain has been proposed as a therapeutic approach to treat nicotine addiction (the basis of tobacco use disorder). A series of monoclonal antibodies with high affinity for nicotine (nic•mAbs) was isolated from B-cells of vaccinated smokers. Genes encoding 32 unique nicotine binding antibodies were cloned, and the mAbs expressed and tested by surface plasmon resonance to determine their affinity for S-(–)-nicotine. The highest affinity nic•mAbs had binding affinity constants (KD) between 5 and 67 nM. The 4 highest affinity nic•mAbs were selected to undergo additional secondary screening for antigen-specificity, protein properties (including aggregation and stability), and functional in vivo studies to evaluate their capacity for reducing nicotine distribution to brain in rats. The 2 most potent nic•mAbs in single-dose nicotine pharmacokinetic experiments were further tested in a dose-response in vivo study. The most potent lead, ATI-1013, was selected as the lead candidate based on the results of these studies. Pretreatment with 40 and 80 mg/kg ATI-1013 reduced brain nicotine levels by 56 and 95%, respectively, in a repeated nicotine dosing experiment simulating very heavy smoking. Nicotine self-administration was also significantly reduced in rats treated with ATI-1013. A pilot rat 30-day repeat-dose toxicology study (4x200mg/kg ATI-1013) in the presence of nicotine indicated no drug-related safety concerns. These data provide evidence that ATI-1013 could be a potential therapy for the treatment of nicotine addiction.

As electronic cigarette (E-cig) use, also known as “vaping”, has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

Objective Pediatric providers play an important role in parental and youth smoking cessation. The goal of this study was to understand smoking cessation attitudes of parents and the behaviors, confidence and self-efficacy of pediatricians related to providing smoking cessation counseling to parents and youth. Methods A mixed methods study was conducted in a convenience sample of families (n = 1,549) and pediatric primary care clinicians (n = 95) in Connecticut using surveys and focus groups from April, 2016 to January, 2017. Results The smoking rate (cigarettes or electronic cigarettes) among all households surveyed was 21%. Interest in quitting smoking was high (71%) and did not differ based on smoking amount, duration, type of community of residence (urban, rural, etc), or race/ethnicity. For example, compared to participants who smoked for Conclusions Clinicians frequently screen parents about their smoking behaviors, but rarely provide smoking cessation counseling and express low confidence in this activity. Clinicians are more confident counseling youth than parents. Clinicians also recognize the dangers of electronic cigarettes, yet they infrequently counsel youth about these dangers.

Background Smoking prevalence in Ireland is falling in all age groups, but e-cigarette use is rising among young people. This qualitative study explores young people’s accounts of e-cigarette use in Ireland. Methods Semi-structured individual (22) and focus group (8) interviews were conducted with 62 young people aged 18–22 years, recruited from a higher-education institution and youth organisations working with early school-leavers across Dublin. All were smokers or ex-smokers; 41 had tried e-cigarettes, 11 continued as dual users. We identified themes using thematic data analysis. Results Three broad themes were identified: incentivising features, disincentivising features, and ambivalent and unsuccessful cessation, named putative smoking cessation. Incentivising features included price, pleasing taste/ flavours, and the possibility of indoor use. Disincentivising features related to adverse health effects (pain, discomfort, sore throat, coughing, headache) and unpleasant physical effects (bad taste, problems resulting from device faults). Other disincentives were over-consumption arising from inability to control intake, "greater addictiveness", product taste, and device faults. Putative cessation refers to the conflict between participants' expected use of e-cigarettes as a smoking cessation/reduction aid and their observed reality of e-cigarettes’ failure in this regard, with reported outcomes including: failure to quit or reduce; continued or resumed cigarette and/or roll-your-own smoking; dual use of e-cigarettes and other tobacco products; and inability to quit e-cigarettes. Conclusions Participants were sceptical about e-cigarettes’ "purported relative healthiness", concerned about addictiveness and potential long-term health consequences, and critically aware of advertising and industry strategies. E-cigarettes were viewed as being less denormalised, in part because they could be used in indoor spaces where smoking is banned in Ireland. Although price, taste, and perceived renormalisation were important motivators for young people's use of e-cigarettes, they wanted to quit smoking. The regulation of e-cigarettes through age restriction of access, licensing of outlets, pricing, point of sale and advertising restrictions as well as through the banning of indoor use should be considered by legislators and tobacco control policymakers.

Objective To examine the relationship between current cigarette smoking patterns and three established risk factors for suicide using nationally representative data of high school students in the United States. Methods We analyzed cross-sectional data from the national Youth Risk Behavior Surveillance Survey (YRBSS)–United States, 2017. Multivariable, logistic regressions examined the association between 3 cigarette smoking behaviors [i.e., past 30-day cigarette (n = 13,731), frequent (n = 1,093) and heavy (n = 880) smoking] and 3 risk factors for suicidal outcomes [feeling sad or hopeless, suicidal ideation, suicide plan] assessed over the previous year. Results Among high school cigarette smokers, smoking 11 or more cigarettes per day (i.e., heavy smoking) was associated with 3.43 (95% CI: 1.69, 6.94) greater odds of reporting feeling sad or hopeless, 2.97 (95% CI: 1.60, 5.51) greater odds of reporting suicidal ideations, and 2.11 (95% CI: 1.34, 3.32) greater odds of reporting having ever planned a suicide attempt, controlling for covariates. Conclusions Our study shows that it is not simply cigarette smoking, but heavy cigarette smoking that is a risk factor for suicidal outcomes among adolescents. Public health implications A comprehensive plan is needed to accommodate heavy adolescent smokers who are at increased suicidal risk.

Smoking self-efficacy, described as confidence in one’s ability to abstain from smoking in high-risk situations is a key predictor in cessation outcomes; however, there is a dearth of research on factors that influence self-efficacy surrounding smoking behavior. This study examines factors associated with baseline self-efficacy among treatment seeking participants enrolled in a pilot feasibility smoking cessation study. Participants (n = 247) were daily male smokers, residents of Doha in Qatar (18–60 years) who were enrolled in a telephone-based smoking cessation study. Baseline assessments included self-efficacy, home smoking rules, socio-demographic variables, smoking history, and psychosocial characteristics. Factors associated with self-efficacy were assessed using multiple linear regression analysis. Results showed that after controlling for relevant variables, number of cigarettes smoked (β^ = -0.22; 95% CI: -0.37, -0.06), having at least one quit attempt in the past year (β^ = 2.30; 95% CI: 0.27, 4.35), and reporting a complete home smoking ban (β^ = 3.13; 95% CI: 0.56, 5.70) were significantly associated with higher self-efficacy to quit smoking. These results provide data-driven indication of several key variables that can be targeted to increase smoking self-efficacy in this understudied population.

Prior research has suggested that a set of unique characteristics may be associated with adult cigarette smokers who are able to quit smoking using e-cigarettes (vaping). In this cross-sectional study, we aimed to identify and rank the importance of these characteristics using machine learning. During July and August 2019, an online survey was administered to a convenience sample of 889 adult smokers (age ≥ 20) in Ontario, Canada who tried vaping to quit smoking in the past 12 months. Fifty-one person-level characteristics, including a Vaping Experiences Score, were assessed in a gradient boosting machine model to classify the status of perceived success in vaping-assisted smoking cessation. This model was trained using cross-validation and tested using the receiver operating characteristic (ROC) curve. The top five most important predictors were identified using a score between 0% and 100% that represented the relative importance of each variable in model training. About 20% of participants (N = 174, 19.6%) reported success in vaping-assisted smoking cessation. The model achieved relatively high performance with an area under the ROC curve of 0.865 and classification accuracy of 0.831 (95% CI [confidence interval] 0.780 to 0.874). The top five most important predictors of perceived success in vaping-assisted smoking cessation were more positive experiences measured by the Vaping Experiences Score (100%), less previously failed quit attempts by vaping (39.0%), younger age (21.9%), having vaped 100 times (16.8%), and vaping shortly after waking up (15.8%). Our findings provide strong statistical evidence that shows better vaping experiences are associated with greater perceived success in smoking cessation by vaping. Furthermore, our study confirmed the strength of machine learning techniques in vaping-related outcomes research based on observational data.

Background We previously developed the Tobacco Craving Index (TCI) to assess craving of smokers. In the present study, we validated the relationship between the TCI grade over the 5 sessions of Japanese smoking cessation therapy (SCT) and success of quitting smoking among 889 Japanese patients. Methods The Japanese SCT consists of 5 sessions of SCT (first session and sessions 2, 4, 8 and 12 weeks later). In the TCI questionnaire, patients are asked to rate their strength of craving and frequency of craving, each on a four-point Likert scale. Patients are classified into one of four grades based on their responses (0, I, II, III, with III indicating severe craving). The TCI questionnaire was administered to each participant at each session of the SCT. This study included participants of Japanese SCT who answered the TCI at the first session of the SCT at five Japanese smoking cessation clinics. Patients who dropped out of the SCT from the second to the fifth sessions were considered to have failed smoking cessation. To elucidate how much the TCI grade predicts smoking status at the last session, we performed multivariate logistic regression analysis with adjustment for confounding factors. Results Participants who had higher TCI grade(III) in the 2nd through 5th sessions showed significantly lower probability for success of quitting smoking than those who had lower TCI grades(0 or I) (adjusted odds ratio: 2nd session: 0.30, 3rd session: 0.15, 4th session: 0.06, 5th session: 0.02). Conclusions We validated the usefulness of the TCI grade for assessing probability of quitting smoking by using a large number of smoking cessation settings.

ObjectivesThere are more than 300 million smokers in China. This study aimed to evaluate the rate of smoking cessation, smoking relapse and related factors in middle-aged and older smokers in China.MethodsWe performed a secondary analysis of data from China Health and Retirement Longitudinal Study (CHARLS) that recruited a nationally representative sample of adults aged 45 and older. Participants were 3708 smokers in 2011 who completed two waves of follow-up interviews in 2013 and 2015. Self-reported quit and relapse rates at follow-ups were estimated. Multiple logistic regressions were conducted to identify factors associated with smoking cessation and relapse.ResultsThe overall quit rate was 8.5% (95% CI 7.7% - 9.5%) at the 2-year follow-up in 2013, and 16.6% (95% CI 15.5% - 17.9%) at the 4-year follow up. Smoking cessation in 2013 was associated with not living in the northeast region (p = 0.003), fewer cigarettes smoked daily (p ConclusionThe overall quit rate was 8.5% at the 2-year follow up, and 16.6% at the 4-year follow up in the middle-aged and older smokers, but 13% of quitters returned to smoking in two years. Successful smoking cessation was associated with older age, lower nicotine dependence, and self-perceived poor health.

IntroductionElectronic cigarette use (vaping) has become popular in recent years. The number of Americans with a variety of cognitive deficits has been increasing dramatically. This study aimed to examine the potential association of vaping with subjective cognitive complaints in US adults.MethodsA combined 2016 and 2017 Behavioral Risk Factor Surveillance System (BRFSS) national survey dataset yielded 886,603 adults who indicated their smoking and vaping status, as well as whether they had subjective cognitive complaints. With this dataset, the cross-sectional association of electronic cigarette use with subjective cognitive complaints was examined using multivariable weighted logistic regression models.ResultsBoth dual users (adjusted Odds Ratio [aOR] = 2.07; 95% Confidence Interval [CI] = 1.66 to 2.60) and current vapers who were either ex-smokers (aOR = 1.94; 95% CI = 1.40 to 2.71) or never smoked (aOR = 1.96; 95% CI = 1.16 to 3.30) showed a significantly higher association with subjective cognitive complaints than never users. Current smokers (aOR = 1.49; 95% CI = 1.32 to 1.69) and ex-smokers (aOR = 1.25; 95% CI = 1.11 to 1.41) had a significantly higher association with subjective cognitive complaints compared to never users. Compared to current smokers, the ex-smokers showed a lower association with subjective cognitive complaints (aOR = 0.84; 95% CI = 0.73 to 0.96). Finally, the association of vaping with subjective cognitive complaints was not statistically significant in individual age group.ConclusionSimilar to smoking, vaping is associated with subjective cognitive complaints in US adults. These results provide preliminary evidence for a cross-sectional association of vaping with potential cognitive health effects in adults.

PurposeThis study investigated nicotine dependence as an independent risk factor for upper aerodigestive tract (UADT) cancers, including lung and head and neck cancers (HNC). The study aimed to isolate the direct effect of nicotine dependence, independent of tobacco smoking.MethodsA case-control study with a total of 4957 participants was conducted in Ontario, Canada, of which 2964 categorized as either current or former smokers were used in the analysis. Nicotine dependence of ever-smokers (2360 UADT cases and 604 controls) was measured using the Fagerström Test for Nicotine Dependence. Using mediation analyses and adjusted logistic regression models, we decomposed the direct effect of nicotine dependence and the mediated effect of smoking duration to quantify the risks of lung and HNC. The role of human papillomavirus (HPV) and cancer subtypes were assessed.ResultsMost individual nicotine dependence behaviours showed positive associations with lung cancer with approximately 1.8 to 3.5-fold risk increase, and to lesser extent with 1.4 to 2.3-fold risk for HNC. Nicotine dependence is partially accountable for increased risks of lung cancer (OR = 1.20, 95%CI = 1.13-1.28) and HNC (1.12, 95%CI = 1.04-1.19). Nicotine dependence had a greater effect on the risk of HPV-negative oropharyngeal cancer (OR = 3.06, 95%CI = 1.65-5.66) in comparison to HPV-positive oropharyngeal cancer (OR = 1.05, 95%CI = 0.67-1.65). The direct effects of nicotine dependence remained significant after accounting for cumulative tobacco exposures.ConclusionNicotine dependence increases the risks of lung and HNC cancers after accounting for tobacco smoking, suggesting potential toxic effects of nicotine. These results are informative for the safety consideration of nicotine exposures.

Background E-cigarette (EC) use is increasing worldwide. Understanding the practices and perceptions of e-cigarette users and profiling the symptoms they experience is essential for regulating the use of such products. This study aims to investigate the practices and perceptions of e-cigarette users in Jordan and examine the symptoms (e.g. respiratory) they associate with e-cigarette use. Methods A cross-sectional online survey was conducted to assess EC use and tobacco smoking behaviors and the corresponding health symptoms among EC users in Jordan. EC use expectancies were also assessed using the Short Form Vaping Consequences Questionnaire, which was first translated into Arabic and tested for validity and reliability. Results Out of the 400 EC users surveyed, 95.5% were male, 76.2% used nicotine-containing juice, and 56.8% were concurrent tobacco smokers. Further, the participants had a mean age of 28.9 years (±10.2). Among dual EC/cigarette users, 88.6% reported that they tried to quit cigarette smoking, with e-cigarette use being the most commonly tried method of smoking cessation. The smoking-related symptoms reported by regular cigarette smokers mainly included sputum production (77.5%). The participants reported that using e-cigarettes instead of tobacco cigarettes had led to improvements in their sputum production (60.8%), breathing (59%), and general wellbeing (52%). Pleasant taste, enjoyable taste sensation, and flavor were significantly stronger (P-value < 0.05) among e-cigarette users compared to dual users. Dual EC/cigarette users reported stronger perceptions in the negative consequences scale, particularly with regards to the hazardous effects of smoking on health (P-value < 0.05). Conclusion Dual daily use of e-cigarettes and regular cigarettes is a common practice among EC users. We recommend that further research is conducted on dual EC/cigarette use and the potential health risks this may have (e.g. higher nicotine intake as compared to the single use of either products).

Neonicotinoids, a class of insecticides structurally similar to nicotine that target biting and sucking insects, are the most widely used insecticides today, in part due to their supposed low toxicity in other organisms. However, a growing body of research has found that even low doses of neonicotinoids can induce unexpected negative effects on the physiology and survival of a wide range of non-target organisms. Importantly, no work has been done on the commercial formulations of pesticides that include imidacloprid as the active ingredient, but that also contain many other components. The present study examines the sublethal effects of "Tree and Shrub"™ ("T+S"), a commercial insecticide containing the neonicotinoid imidacloprid as its active ingredient, on Caenorhabditis elegans. We discovered that "T+S" significantly stunted the overall growth in wildtype nematodes, an effect that was exacerbated by concurrent exposure to heat stress. "T+S" also negatively impacted fecundity as measured by increased germline apoptosis, a decrease in egg-laying, and fewer viable offspring. Lastly, exposure to "T+S" resulted in degenerative changes in nicotinic cholinergic neurons in wildtype nematodes. As a whole, these findings demonstrate widespread toxic effects of neonicotinoids to critical functions in nematodes.

BackgroundIdentifying the functional materials inside vaping devices can help inform efforts to understand risk. While nicotine E-cigarette components and metals have been characterized in several previous studies, the internal component compositions of tetrahydrocannabinol (THC) cartridge designs are not as well known. The 2019-20 e-cigarette or vaping product use associated lung injury (EVALI) outbreak has been associated with THC devices containing vitamin E acetate (VEA), possibly mediated by chemical reactions with internal cartridge components and high filament temperatures.MethodsWe investigate the composition and internal components of 2019 EVALI patient-associated THC vaping devices compared to other THC and nicotine devices from 2016-19, specifically the metal, ceramic, and polymer components likely to be exposed to heat. To do this, we have disassembled forty-eight components from eight used and unused vaping devices under a microscope and analyzed them using X-ray fluorescence, scanning electron microscopy, and Fourier-transform infrared micro-spectroscopy.ConclusionsThe two THC cartridges used by EVALI patients exhibited evidence of localized high temperatures, including charring of the ceramic heating elements and damaged wire surfaces. The newer THC cartridges possessed more ceramic and polymer insulation than older THC or nicotine devices. The combination of ceramics, metals, and high temperatures in newer THC cartridges is consistent with conditions hypothesized to produce VEA reactions during vaping. Nickel and chromium components were detected in all devices, and others contained copper, lead, tin, gold, silicon-rich rubbers, or fluorinated microplastics. These components have the potential to thermally degrade and volatilize if heated sufficiently. These findings do not imply that harmful exposures would occur under all usage conditions, and are most relevant to harm reduction efforts based on avoiding higher internal temperatures. This study was limited to a small sample of cartridges obtained from investigations. Future work should test more device types and internal temperatures under controlled usage conditions.

Background Migrant populations usually report higher smoking rates. Among those migrant populations, Turkish- and Kurdish-speaking migrants are often overrepresented. Providing equal access to health services is one of the major challenges of our time. The need for adapted smoking-cessation treatments for Turkish-speaking populations to achieve equity in health led, in 2006, to the development and implementation of the Tiryaki-Kukla smoking-cessation program. The aims of the current study were to evaluate one-year quit rates for smoking-cessation courses held from 2006–2018 and investigate whether certain characteristics predict long-term smoking cessation or reduction. Methods Program evaluation included a pre/post questionnaire (session 1/ 3 months after the quit day) and a follow-up telephone call twelve months after the quit day. To elucidate factors associated with long-term smoking cessation and reduction, Cox regression analysis and Weighted Generalized Equation Models were used. Results Of the 478 who participated in smoking-cessation courses, 45.4% declared themselves non-smokers at one-year follow-up. This quit rate is higher than that achieved during the preliminary evaluation of the program involving 61 participants (37.7%). Predictors of long-term smoking cessation were course length (eight vs. six sessions) (95% CI = 1.04–1.36, p = .01), adherence to the course (95% CI = 0.98–0.99, pp = .02), and time passed in the morning until the first cigarette is smoked (95% CI5min = 1.17–1.77, p30min = 1.09–1.65, pp < .001; 30min p < .001; 60min p < .01)-, gender (p < .001), and level of motivation to quit at baseline (p = .04). Conclusions Our findings are consistent with existing evidence supporting adapted smoking cessation interventions to reduce health inequity in migrant populations. However, achieving harm reduction in smokers with higher dependence scores remains challenging.

Background The popularity of electronic cigarettes (E-cigarettes) has risen considerably. Several studies have suggested that nicotine may affect insulin resistance, however, the impact of E-cigarette exposure on insulin resistance, an early measure of cardiometabolic risk, is not known. Methods and results Using experimental animals and human data obtained from 3,989 participants of the United States National Health and Nutrition Examination Survey (NHANES), respectively, we assessed the association between E-cigarette and conventional cigarette exposures and insulin resistance, as modelled using the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose tolerance tests (GTT). C57BL6/J mice (on standard chow diet) exposed to E-cigarette aerosol or mainstream cigarette smoke (MCS) for 12 weeks showed HOMA-IR and GTT levels comparable with filtered air-exposed controls. In the NHANES cohort, there was no significant association between defined tobacco product use categories (non-users; sole E-cigarette users; cigarette smokers and dual users) and insulin resistance. Compared with non-users of e-cigarettes/conventional cigarettes, sole E-cigarette users showed no significant difference in HOMA-IR or GTT levels following adjustment for age, sex, race, physical activity, alcohol use and BMI. Conclusion E-cigarettes do not appear to be linked with insulin resistance. Our findings may inform future studies assessing potential cardiometabolic harms associated with E-cigarette use.

Background Limited information exist on tobacco and e-cigarette use patterns in cancer survivors. The purpose of this study is to report on use patterns in cancer survivors compared with non-cancer participants from the Population Assessment of Tobacco and Health (PATH) Study. Methods Sociodemographic data and tobacco product use were analyzed for 32,244 adult participants from the PATH Study in 2013–2014 by cancer status and age. Logistic regression examined the patterns of and factors associated with tobacco use by cancer status. Results Overall, cancer survivors represented 7.1% (n = 1,527) of participants, were older, and had a higher proportion of females and non-Hispanic whites than non-cancer participants. In cancer survivors, current and former cigarette smoking was reported in 12.7% and 32.9% respectively, compared with 18.5% and 19.0% in non-cancer adults. Current e-cigarette use was reported by 3.8% of survivors compared with 5.7% of non-cancer participants. Dual tobacco use was reported by 25.0% and poly use by 6.9% of cancer survivors who currently smoked. All other forms of current tobacco use were individually reported by

The first symptoms of schizophrenia (SCHZ) are usually observed during adolescence, a developmental period during which first exposure to psychoactive drugs also occurs. These epidemiological findings point to adolescence as critical for nicotine addiction and SCHZ comorbidity, however it is not clear whether exposure to nicotine during this period has a detrimental impact on the development of SCHZ symptoms since there is a lack of studies that investigate the interactions between these conditions during this period of development. To elucidate the impact of a short course of nicotine exposure across the spectrum of SCHZ-like symptoms, we used a phencyclidine-induced adolescent mice model of SCHZ (2.5mg/Kg, s.c., daily, postnatal day (PN) 38-PN52; 10mg/Kg on PN53), combined with an established model of nicotine minipump infusions (24mg/Kg/day, PN37-44). Behavioral assessment began 4 days after the end of nicotine exposure (PN48) using the following tests: open field to assess the hyperlocomotion phenotype; novel object recognition, a declarative memory task; three-chamber sociability, to verify social interaction and prepulse inhibition, a measure of sensorimotor gating. Phencyclidine exposure evoked deficits in all analyzed behaviors. Nicotine history reduced the magnitude of phencyclidine-evoked hyperlocomotion and impeded the development of locomotor sensitization. It also mitigated the deficient sociability elicited by phencyclidine. In contrast, memory and sensorimotor gating deficits evoked by phencyclidine were neither improved nor worsened by nicotine history. In conclusion, our results show for the first time that nicotine history, restricted to a short period during adolescence, does not worsen SCHZ-like symptoms evoked by a phencyclidine-induced mice model.

Introduction Recently, electric cigarettes with liquid (e-liquid) were introduced as an alternative to tobacco smoking. They were promoted as possible cessation aids and were considered to be potentially less harmful than traditional tobacco-based cigarettes. However, there is little information on the toxicants present in e-liquids and their possible carcinogenic effects. Methods Western blot analysis was performed to identify the protein levels of cancer progression related signal transducers. Patient-derived brain tumor cells (CSC2) were injected into mouse brains and tumor growth was then observed by performing magnetic resonance imaging (MRI) and hematoxylin and eosin (H&E) staining of the whole brain. Immunohistochemistry (IHC) staining and Immunofluorescence staining were performed to study the expression of pEGFR and pERK. Results Western blotting revealed that e-liquids increased pEGFR and pERK expression in a dose dependent manner. Animal experiments revealed that the e-liquid treated group had accelerated tumor growth and poor prognosis compared to the vehicle group. Histological staining showed activation of pEGFR and pERK in the e-liquid treated group. Conclusion Our study revealed that e-liquid activates pEGFR and pERK, leading to accelerated brain tumor growth and poor prognosis.

Objective We assessed the prevalence of, and factors associated with, heated tobacco product (HTP) use and analysed the association between HTP use and quitting combustible cigarettes (CCs) in Korean adults. Methods We conducted an online survey with 7,000 adults (males, 2,300; females, 4,700; ages 20–69) out of 70,000 age-, sex- and provincial-distribution-matched individuals based on 2018 national population statistics. Females were oversampled because the prevalence of tobacco product use is very low among women in Korea. Chi-square tests were used for bivariate analyses, and odds ratios were assessed after adjusting for sociodemographic variables. Results The prevalence of current CC, electronic cigarette (EC), and HTP use was 24.8% (males, 40.4%; females, 9.3%), 6.8% (males, 10.1%; females, 3.4%), and 10.2% (males, 16.2%; females, 4.3%), respectively. Among the 574 current HTP users, 77 (13.4%) were HTP-only users and >80% were either dual users of HTP and CC/EC, or triple users of HTP, EC, and CC. Among the current CC users, the odds of having attempted to quit CCs in the past year were greater among EC-only users (aOR 2.92; 95% CI 1.81–4.69) and dual users of HTPs and ECs (aOR 8.42; 95% CI 4.85–14.62) than among non-HTP and non-EC users. Among 2,121 ever CC smokers, the likelihood of being a former CC smoker was 0.19 (95% CI 0.15–0.24) for HTP users, 0.29 (95% CI 0.20–0.42) for EC users, and 0.03 (95% CI 0.01–0.06) for users of both HTPs and ECs compared with non-HTP and non-EC users. Conclusion EC-only use and dual use of HTPs and ECs were associated with increased attempts to quit CCs; however, HTP and EC use was associated with lower odds of CC smoking abstinence.

Introduction Exposure to media content can shape public opinions about tobacco. In early September 2019, the outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI) became headline news in the United States. Methods In August and September 2019, we conducted two cross-sectional online surveys with current and former smokers assessing attitudes and beliefs about e-cigarettes. Study one (n = 865) was collected before the EVALI outbreak was widely covered and study two (n = 344) was collected after the outbreak had become nation-wide news. We examined differences in perceptions and beliefs between time points. Results E-cigarette harm perceptions increased between study one (mean = 2.67) and study two (mean = 2.90, p < .05). Ever-users of e-cigarettes largely account for this change. Endorsement of the belief that e-cigarettes were risky and more likely to cause lung damage compared to cigarettes increased between studies (p < .05). Seventy eight percent of participants at study two were aware of the vaping illness story. Being aware of the story was associated with more endorsement of the belief that e-cigarettes were risky to use, but not that using e-cigarettes would make the participant more likely to get damaged lungs. Discussion When the stories about the health and safety of tobacco products dominate the public information environment, it presents an opportunity to change beliefs that are frequently targeted by paid health campaigns. Changes in participant’s perceptions of e-cigarettes were associated with coverage of this large news story, underscoring the importance of working to ensure that coverage is a scientifically accurate as possible.

Paraquat (PQ), one of the most widely used herbicides worldwide, causes severe toxic effects in humans and animals. 1-methylhydantoin (MH) is an active ingredient of Ranae Oviductus, which has broad pharmacological activities, e.g., eliminating reactive oxygen species and inhibiting inflammation. This study investigated the effects of MH on lung injury induced by PQ. A PQ poisoning model was established by intragastric infusion of PQ (25 mg/kg), and the control group was simultaneously gavaged with the same dose of saline. The MH group was intraperitoneally injected with 100 mg/kg once per day after intragastric infusion of PQ (25 mg/kg) for five consecutive days. All animals were sacrificed on the sixth day, and the lung tissues were dissected for metabolomics analysis. The lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, TNF-α and malondialdehyde (MDA) content were determined according to the instructions of the detection kit. Compared with that in the control group, the content of LDH, TNF-α and MDA in the lung tissue of the PQ group was significantly higher, and the activity of SOD in the lung tissue was significantly lower (all p 0.05). There were significant differences in MDA and TNF-α content between the PQ group and MH group (all p

Cigarette smoking and tuberculosis are a significant cause of death worldwide. Several epidemiological studies have demonstrated cigarette smoking is a risk factor for tuberculosis. Electronic cigarettes have recently appeared as a healthier alternative to conventional smoking, although their impact in tuberculosis is not well understood. The aim of this study was to explore the effect of electronic cigarettes in phagocytosis of Mycobacterium tuberculosis and cytokines production. In vitro infection was carried out by exposing THP-1 macrophages to four electronic vapor extracts and the intracellular burden of M. tuberculosis was determined. The percentage of infection was evaluated by confocal microscopy and the cytokine production by Luminex. A reduction of intracellular M. tuberculosis burden in THP- 1 macrophages was found after its exposure to electronic vapor extract; the same trend was observed by confocal microscopy when Mycobacterium bovis BCG-GFP strain was used. Electronic cigarettes stimulate a pro-inflammatory cytokine response. We conclude that electronic cigarettes impair the phagocytic function and the cytokine response to M. tuberculosis.

Introduction Patients with advanced non-small cell lung cancer (NSCLC) are most of the time treated with a first-line cytotoxic chemotherapy. Tobacco use is responsible for 90% of lung cancer. The aim of this study was to evaluate the impact of smoking continuation during first-line chemotherapy on tumor response in advanced-stage NSCLC. Materials and methods All patients with an advanced-stage NSCLC (IIIb or IV), treated with first-line platinum-based chemotherapy in our Department between June 2013 and July 2017 were included. Smoking status was assessed at inclusion by self-report, then at the tumor assessment consultation after 2 months of treatment, by both self-report and plasmatic cotinine measurement. Chemotherapy response, progression-free survival (PFS), overall survival (OS) and stage 3-4 toxicity were registered. Results Ninety-seven patients were included: 8 (8%) declared to be non-smokers, 56 (58%) current smokers and 33 (34%) former smokers at diagnosis. At the first tumor evaluation, 24 (25%) self-reported as active smokers and 73 (75%) as non-smokers; overall response rate (ORR) was respectively 38% and 48% (p = 0.373). Fifty-four patients had a plasmatic cotinine evaluation at the first tumor evaluation. Seventeen patients (32%) had a positive cotinine rate (median 108ng/mL, IQR 31-236). Six patients (35%) had positive cotinine rate whereas declaring to be non-smokers at the first tumor evaluation. ORR was 18% in case of positive cotinine rate, and 57% when negative (p = 0.007). Regardless of the method for smoking status evaluation, PFS, OS and grade 3-4 toxicities were similar between smoker and non-smoker patients at the first tumor evaluation. Conclusion Smoking continuation during platinum-based chemotherapy, reflected by positive plasma cotinine rate, was associated with a poor ORR.

BackgroundPrevious literature has shown the relationship between emotional intelligence (EI) and smoking. However, the mechanisms underlying the role of EI in smoking behaviour are still unclear. The aim of the present study was to analyse how EI abilities protect against relapse in a 12-month smoking cessation program.MethodsOne hundred and seventy-three volunteer smokers were enrolled in a well-established smoking cessation program, accompanied by a 12-month follow-up, through the Spanish Association Against Cancer. Moderation and moderated mediation analyses were conducted to explore the influence of EI abilities on the effect of stress reactivity and nicotine dependence on the likelihood of relapse.ResultsEmotional repair ability moderated the effect of stress reactivity on relapse. Higher levels of stress reactivity were associated with a higher likelihood of relapse, but only in those individuals with lower emotional repair abilities. In addition, the moderated mediation analyses revealed that emotional clarity and emotional repair abilities moderated the indirect effect of nicotine dependence on smoking relapse through its influence on stress reactivity.ConclusionsEmotional management is a central concept in explaining smoking behaviour. Our findings suggest that the inclusion of EI training could be particularly useful for improving current smoking cessation programs. A good ability to manage emotions allows smokers to effectively apply psychological coping strategies to deal with stressful situations, thus protecting against relapse.

Despite the increased risks of cancers and cardiovascular related diseases, tobacco smoking continues to be prevalent in the population due largely in part to the addictive nature of nicotine. Nicotine vaccines are an attractive alternative to the current smoking cessation options but have yet to be successful enough in clinical trials to reach the market due to a lack of neutralizing antibodies and inconsistent results. Using AFPL1 derived from the Cuban meningococcal vaccine as an adjuvant, we have previously published promising results with an intranasally administered nicotine vaccine. In order to examine the immunogenicity and safety of this vaccine in mice we set up a pilot trial administering the vaccine either intranasally, intramuscularly or utilizing both routes simultaneously and evaluated immune responses and clinical symptoms throughout the duration of the vaccination protocol and post-mortem. These data further demonstrate the ability of the AFPL1 nicotine conjugate vaccine to be a safe and potential candidate for clinical use.

Childhood adversity is a potent risk factor for mental health conditions via disruptions to stress response systems. Dysregulations in oxidative stress systems have been associated with both childhood adversity and several psychological disorders (e.g., major depressive disorder) in adult populations. However, few studies have examined associations between childhood adversity, oxidative stress, and mental health in pediatric populations. Childhood adversity (Adverse Childhood Events [ACE]), oxidative stress [F2t-isoprostanes (IsoPs)], and mental health pathology were assessed in 50 adolescent females recruited primarily through the Department of Youth Services. Standard ordinary least squares regression models were run co-varying for age, race/ethnicity, adolescent nicotine use, study condition, and parent history of ACEs. Adolescents who reported experiencing four or more ACEs had significantly elevated IsoP levels. Further, internalizing symptom scores across diagnoses were significantly associated with elevated IsoPs, whereas no externalizing symptoms scores, except Attention Deficit Hyperactivity Disorder, were related to altered oxidative stress. Results indicate that IsoPs may be a global marker of childhood adversity and mental health symptomatology, particularly within internalizing symptom domains. A limitation is that body mass index was not collected for this sample. Future studies are needed to replicate and extend these findings in larger, more diverse samples.

To comprehensively characterize the metabolic roles of crustacean hyperglycemic hormone (CHH), metabolites in two CHH target tissues of the crayfish Procambarus clarkii, whose levels were significantly different between CHH knockdown and control (saline-treated) animals, were analyzed using bioinformatics tools provided by an on-line analysis suite (MetaboAnalyst). Analysis with Metabolic Pathway Analysis (MetPA) indicated that in the muscle Glyoxylate and dicarboxylate metabolism, Nicotinate and nicotinamide metabolism, Alanine, aspartate and glutamate metabolism, Pyruvate metabolism, and Nitrogen metabolism were significantly affected by silencing of CHH gene expression at 24 hours post injection (hpi), while only Nicotinate and nicotinamide metabolism remained significantly affected at 48 hpi. In the hepatopancreas, silencing of CHH gene expression significantly impacted, at 24 hpi, Pyruvate metabolism and Glycolysis or gluconeogenesis, and at 48 hpi, Glycine, serine and threonine metabolism. Moreover, analysis using Metabolite Set Enrichment Analysis (MSEA) showed that many metabolite sets were significantly affected in the muscle at 24hpi, including Ammonia recycling, Nicotinate and nicotinamide metabolism, Pyruvate metabolism, Purine metabolism, Warburg effect, Citric acid cycle, and metabolism of several amino acids, and at 48 hpi only Nicotinate and nicotinamide metabolism, Glycine and serine metabolism, and Ammonia recycling remained significantly affected. In the hepatopancreas, MSEA analysis showed that Fatty acid biosynthesis was significantly impacted at 24 hpi. Finally, in the muscle, levels of several amino acids decreased significantly, while those of 5 other amino acids or related compounds significantly increased in response to CHH gene silencing. Levels of metabolites related to nucleotide metabolism significantly decreased across the board at both time points. In the hepatopancreas, the effects were comparatively minor with only levels of thymine and urea being significantly decreased at 24 hpi. The combined results showed that the metabolic effects of silencing CHH gene expression were far more diverse than suggested by previous studies that emphasized on carbohydrate and energy metabolism. Based on the results, metabolic roles of CHH on the muscle and hepatopancreas are suggested: CHH promotes carbohydrate utilization in the hepatopancreas via stimulating glycolysis and lipolysis, while its stimulatory effect on nicotinate and nicotinamide metabolism plays a central role in coordinating metabolic activity in the muscle with diverse and wide-ranging consequences, including enhancing the fluxes of glycolysis, TCA cycle, and pentose phosphate pathway, leading to increased ATP supply and elevated protein and nucleic acid turnovers.

BackgroundRecent studies reported that transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) reduced craving and cigarette smoking. We aimed to evaluate whether 3 sessions of tDCS over the DLPFC modulate cigarette smoking which is a critical factor in tobacco smokers.MethodsIn a double-blinded, sham-controlled, parallel experimental study, 22 participants who wished to quit smoking received tDCS with the cathodal over the right DLPFC and anodal over the left DLPFC based on the 10-20 EEG international system (F4, F3) at an intensity of 1.5 mA for 20 minutes during three consecutive days. For sham stimulation, the electrodes placement was the same as for the active stimulation.ResultsFor the short time interval (8 days after the end of the tDCS regimen), the number of smoked cigarettes was reduced similarly in the active and sham groups (p < 0.001). Also, at the long time-interval (4 months after the end of the tDCS regimen) as compared to pre-tDCS, there was no significant difference in the number of smoked cigarettes in the active (p = 0.806) or the sham (p = 0.573) groups. Overall, there were no statistically significant differences between the active and sham tDCS groups on cigarette smoking.ConclusionThese findings suggested that 3 sessions of tDCS over the right and left DLPFC may reduce number of smoked cigarettes for short-time period but might not be significantly more effective than sham to decrease cigarette smoking.

The prevalence of electronic cigarette (e-cigarette) use has rapidly increased among young people, while conventional cigarette use has decreased in this age group. However, some evidence suggests that e-cigarette use is likely to induce conventional cigarette smoking. The present study explored the social influence of the prevalence of e-cigarette use in the peer network and in the general population as a potential mechanism by which e-cigarette use affects adolescents' overall smoking behaviours. For this purpose, we developed an agent-based model in which young agents repeatedly choose to smoke conventional cigarettes and/or e-cigarettes, or to remain non-smokers. The choice is based on the agent's evaluation of the utility derived from smoking and attitude towards smoking ('openness'), which is influenced by smoking prevalence in the agent's peer network and in the broader society. We also assumed a 'crossover' effect between the different types of smoking. The model was calibrated with United States National Youth Tobacco Survey data to reflect real-world numbers. We further simulated the prevalence of different types of smoking under counterfactual scenarios with different levels of openness and crossover effects. The models developed successfully reproduced actual prevalence trends in different types of smoking from 2011 to 2014. Openness to smoking is associated with a dramatic increase in e-cigarette smoking and especially in dual smoking, which cancels out the decline in sole conventional smoking. Larger crossover effects are associated with a higher prevalence of conventional smoking. The simulation results indicate that the social influence of the prevalence of e-cigarette use may influence young people to initiate or continue conventional cigarette smoking. Assessing the impact of e-cigarettes in the general population as a 'healthier' alternative to conventional smoking may require carefully monitoring trends in young people's smoking behaviours.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

The use of emerging tobacco products, such as waterpipe or hookah and electronic cigarettes (e-cigs), has gained significant popularity and are promoted as safer alternatives to conventional cigarettes. Circadian systems are internal biological oscillations that are considered important regulators of immune functions in mammals. Tobacco induced inflammatory lung diseases frequently exhibit time-of-day/night variation in lung function and symptom severity. We investigated the impact of inhaled e-cig vapor and waterpipe smoke (WPS) on pulmonary circadian molecular clock disruption by determining the changes in expression levels and abundance of core clock component genes (BMAL1, CLOCK) and clock-controlled output genes (Rev-erbα, Per2, Rev-erbβ, Cry2, Rorα) in mouse lungs. We showed that the expression levels of these pulmonary core clock genes and clock-controlled output genes were altered significantly following exposure to WPS (Bmal1, Clock, and Rev-erbα). We further showed a significant yet differential effect on expression levels of core clock and clock-controlled genes (Bmal1, Per2) in the lungs of mice exposed to e-cig vapor containing nicotine. Thus, acute exposure to WPS and e-cig vapor containing nicotine contributes to altered expression of circadian molecular clock genes in mouse lungs, which may have repercussions on lung cellular and biological functions.

The pathway from the medial habenular nucleus to the interpeduncular nucleus, in which nicotinic acetylcholine receptor (nAChR) including the α3 and α5 subunits (α3 * and α5 * nAChRs) are expressed, is implicated in nicotine dependence. We investigated whether α3 * and α5 * nAChRs are regulated by cAMP using SH-SY5Y cells to clarify the significance of these receptors in nicotine dependence. We analyzed the nicotine-induced elevation of intracellular Ca2+ ([Ca2+]i). Nicotine induces a concentration-dependent increase in [Ca2+]i. The elimination of Ca2+ from extracellular fluid or intracellular stores demonstrated that the nicotine-induced [Ca2+]i elevation was due to extracellular influx and intracellular mobilization. The effects of tubocurarine on nicotine-induced [Ca2+]i elevation and current suggest that intracellular mobilization is caused by plasma membrane-permeating nicotine. The inhibition of α3 *, α5 *, α7 nAChR and voltage-gated Ca2+ channels by using siRNAs and selective antagonists revealed the involvement of these nAChR subunits and channels in nicotine-induced [Ca2+]i elevation. To distinguish and characterize the α3 * and α5 * nAChR-mediated Ca2+ influx, we measured the [Ca2+]i elevation induced by nonmembrane-permeating acetylcholine when muscarinic receptors, α7nAChR and Ca2+ channels were blocked. Under this condition, the [Ca2+]i elevation was significantly inhibited with a 48-h treatment of dibutyryl cAMP, which was accompanied by the downregulation of α3 and β4 mRNA. These findings suggest that α3 * and α5 * nAChR-mediated Ca2+ influx is possibly regulated by cAMP at the transcriptional level.

Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. Nevertheless, very little is known about the effect of prolonged cigarette smoke exposure on inflammatory modulators in the gut. We examined the effect of cigarette smoke on cytokine profiles in the healthy and inflamed gut of human subjects and in the trinitrobenzene sulphonic acid mouse model, which mimics distal Crohn-like colitis. In addition, the effect of cigarette smoke on epithelial expression of transient receptor potential channels and their concurrent increase with cigarette smoke-augmented cytokine production was investigated. Active smoking was associated with increased IL-8 transcription in ileum of controls (p < 0,001; n = 18-20/ group). In the ileum, TRPV1 mRNA levels were decreased in never smoking Crohn's disease patients compared to healthy subjects (p

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse.

Introduction Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous “pouches.” Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. Methods Moisture, pH, nicotine, and tobacco-specific N’-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. Results Among all product types, moisture (27.4%–59.5%), pH (pH 5.87–9.10), total nicotine (6.81–20.6 mg/g, wet), unprotonated nicotine (0.083–15.7 mg/g), and total TSNAs (390–4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. Conclusion Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered “equivalent”. Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.

Previous pre-clinical studies demonstrated a promising role of alpha-type peroxisome proliferator-activated receptors (PPARα) agonists in decreasing nicotine self-administration and nicotine-seeking behavior in animals. Our goal was to investigate the potential of gemfibrozil, a PPARα agonist, on reducing tobacco smoking in humans. Methods This was a double-blind, placebo-controlled, crossover study evaluating the effects of gemfibrozil (1200 mg/day) on smoking in 27 treatment-seeking smokers. The study had two 2-week phases separated by a washout period of at least 1 week. In each phase and after 1 week on medication, participants underwent a lab session where cue reactivity and forced choice paradigms were conducted. Physiological responses and self-reported craving were monitored during the presentation of smoking and neutral cues. In addition, two types of cigarettes were used in the forced choice paradigms: the Nicotinized cigarettes (Nic) and the Denicotinized cigarettes (Denic). The goal of the forced choice was to calculate the percentage of choice of Nic cigarettes while taking gemfibrozil or placebo. The number of quit days was calculated during the two quit attempts weeks (one while taking gemfibrozil and one while taking placebo) of the study. Results There were no significant differences between gemfibrozil and placebo groups in the percentage of choice of Nic cigarettes, the cue-reactivity (both physiological and subjective measures), or in the number of days of abstinence. Conclusions Although preclinical studies with PPAR α agonists showed promising results, this preliminary study did not demonstrate positive effect of gemfibrozil on tobacco use and cessation indices.