Patterns of Use of e-Cigarettes and Their Respiratory Effects: Protocol for an Umbrella Review.

BACKGROUND: Electronic nicotine delivery systems (ENDS)-e-cigarettes or vapes-have been shown to substantially reduce or eliminate many toxins compared with cigarette smoke, but simultaneously ENDS use also produces their own unique toxins. Yet the patterns of use among people who use ENDS are not homogeneous. Some people who use ENDS also smoke cigarettes (dual use). Other people who formerly smoked cigarettes are completely substituting ENDS (exclusive use). A small number of people who have never smoked cigarettes are using ENDS (naïve use of nicotine). Each of these patterns of use results in different exposures to toxins. Unfortunately, epidemiological studies routinely group together any ENDS use regardless of other tobacco use. OBJECTIVE: This umbrella review primarily aims to present all the evidence available on the respiratory effects of ENDS use by adults based on their pattern of use: dual use, exclusive use, and naïve use. With each of these patterns of use, are there benefits, no changes, or harmful effects on respiratory functioning? Our objective is to provide clinicians with a detailed analysis of how different patterns of ENDS use impact respiratory functioning and to point to the best sources of evidence. METHODS: This umbrella review follows the Methods for Overviews of Reviews framework and the PRIOR (Preferred Reporting Items for Overviews of Reviews) statement. Systematic reviews published since 2019 will be searched across 4 databases and 3 gray literature sources. Additional searches will include citation chasing, references lists, and referrals from respiratory specialists. The quality of included reviews will be evaluated using the AMSTAR2 (A Measurement Tool to Assess Systematic Reviews) checklist. We will document biases in 3 areas: protocol deviations, biases from the Oxford Catalogue of Bias, and internal data discrepancies. Two reviewers will independently conduct the search and quality assessments. Our analysis will focus on reviews rated as moderate or high confidence by AMSTAR2. We will use the Vote Counting Direction of Effect method to manage expected data heterogeneity, assessing whether ENDS use is beneficial or detrimental, or has no effect on respiratory functions based on the pattern of use. RESULTS: The review is expected to be completed by December 2024. The database search was concluded in April 2024, and data extraction and bias assessment were completed in June 2024. The analysis phase is planned to be completed by October 2024. CONCLUSIONS: A thorough and comprehensive assessment of the evidence will better inform the contentious debate over the respiratory effects of ENDS providing much needed clarity by linking their effects to specific usage patterns. This analysis is particularly crucial in understanding the risks associated with continued cigarette smoking. TRIAL REGISTRATION: PROSPERO CRD42024540034; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=540034. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60325.

Cigarette smoking, e-cigarette use, and sociodemographic correlates of mental health and tobacco-related disease risk in the All of Us research program.

SIGNIFICANCE: Research on the conditions under which electronic cigarette (EC) use produces a net reduction in the population harm attributable to combusted cigarette (CC) use requires the triangulation of information from cohort(s) of smokers, non-smokers, EC users, and dual-users of all varieties. MATERIALS AND METHODS: This project utilizes data from the All of Us Research Program to contrast a panel of wellness and disease-risk indicators across a range of self-reported tobacco-use profiles, including smokers, current, and former EC users. This article focuses on the tobacco use history and current tobacco use status among All of Us participants enrolled between May 2017 and February 2023 (Registered Controlled Tier Curated Data Repository [CDR] v7). RESULTS: The present analytic sample included an unweighted total of N = 412 211 individuals with information on ever-use of both CC and EC. Among them, 155 901 individuals have a history of CC use, with 65 206 identified as current smokers. EC usage is reported by 64 002 individuals, with 16 619 being current users. Model predicted analyses identified distinct patterns in CC and EC usage across demographic and socioeconomic variables, with younger ages favoring ECs. DISCUSSION: Age was observed to significantly affect EC usage, and gender differences reveal that males were significantly more likely to use CC and/or EC than females or African Americans of any gender. Higher educational achievement and income were associated with lower use of both CC and EC, while lower levels of mental health were observed to increase the likelihood of using CC and EC products. CONCLUSION: Findings suggest the potential for the All of Us Research Program for investigation of causal factors driving both behavioral use transitions and cessation outcomes.

Advancements in Cardiovascular Disease Research Affected by Smoking.

The harmful substances in tobacco are widely recognized to exert a significant detrimental impact on human health, constituting one of the most substantial global public health threats to date. Tobacco usage also ranks among the principal contributors to cardiovascular ailments, with tobacco being attributed to up to 30% of cardiovascular disease-related deaths in various countries. Cardiovascular disease is influenced by many kinds of pathogenic factors, among them, tobacco usage has led to an increased year by year incidence of cardiovascular disease. Exploring the influencing factors of harmful substances in tobacco and achieving early prevention are important means to reduce the incidence of cardiovascular diseases and maintain health. This article provides a comprehensive review of the effects of smoking on health and cardiovascular diseases.

Sex differences in the roles of nicotine use and puberty on youth C-reactive protein levels: Effects above and beyond adversity.

Inflammation likely mediates associations between nicotine use and negative health outcomes. Sex differences have been observed in nicotine use-inflammation links, and physiological processes during puberty might allow for these differences to arise. In this cross-sectional study of 498 youth (ages 8-13, 52% girls, 77% with history of child maltreatment (CM) investigation), sex-differentiated associations between self-reported nicotine use and high-sensitivity C-reactive protein (hs-CRP) were explored. Additionally, self-reported pubertal stage was investigated as a moderator of such nicotine use-hs-CRP links. Hierarchical generalized estimating equation models were adjusted for a wide range of adversity effects: CM investigation history derived from state records, self- and caregiver-report of traumatic life events, adversity-related demographic risk factors (i.e., identification with historically marginalized racial and ethnic groups, household income), and other characteristics that may influence the variables of interest (e.g., medication use, age, body mass index). Nicotine use had a negative main effect on hs-CRP among boys (ß = -0.50, p = 0.02), and pubertal stage did not moderate this association (ß = 0.06, p = 0.71). In contrast, pubertal stage moderated the association between nicotine use and hs-CRP among girls (ß = 0.48, p = 0.02) such that a positive association between nicotine use and hs-CRP levels was stronger at more advanced pubertal stages (ß = 0.45, SE = 0.21, 95% CI [0.03, 0.87]). Findings suggest that puberty may influence the effect of nicotine on inflammation in sex-differentiated ways and have implications for timing of prevention and treatment efforts geared toward reducing nicotine use and subsequent inflammation-related health risk among youth.

A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program.

Introduction: Patients with pulmonary nodules detected through lung cancer screening or as incidental findings are often followed in lung health and screening programs. The use of personalized pharmacotherapy for smoking cessation informed by the nicotine metabolite ratio (NMR), a measure of nicotine metabolism, has not yet been evaluated in this setting. This pilot randomized controlled trial (RCT) evaluated the feasibility of conducting a larger trial. Methods: Through a pragmatic RCT design, participants were recruited from a Mid-Atlantic lung health and screening program. Eligible participants smoked >5 cigarettes per day and completed a blood draw to determine NMR before being randomized to standard or NMR-guided care treatment arms. Standard care participants were offered nicotine replacement therapy (NRT) or varenicline and a referral to phone-based smoking cessation counseling. NMR-guided participants received standard care except they were provided a personalized medication recommendation based on their NMR. Study outcomes included measures of feasibility, medication uptake, and treatment matching (i.e., uptake of the optimal medication). Results: More than 80 % of 205 screened patients were eligible. However, only 37 (22 %) of these patients enrolled in the study, with a mean age of 65 years, 43 % female, and 25 % Black. Nearly all patients who declined cited a disinterest in smoking cessation. Participants in both treatment arms had high rates of medication uptake (68 %), with NMR-guided participants showing a trend towards greater treatment matching (55 % vs. 29 %). Conclusions: The results of this pilot study provide support for conducting a larger RCT of an NMR-guided smoking cessation intervention in a lung health and screening setting. Consideration should be given to augmenting the intervention to address barriers to study entry.

Coolants, organic acids, flavourings and other additives that facilitate inhalation of tobacco and nicotine products: implications for regulation.

To inform regulatory policy, this article summarises findings on inhalation facilitation from the ninth report of the WHO Study Group on Tobacco Product Regulation. Some additives counteract the harshness and bitterness of tobacco and nicotine product aerosols, making them easier to inhale. Additives that promote inhalability may perpetuate and increase the use of inhaled tobacco and nicotine products, especially by young people. Thus, as a class, additives that facilitate inhalation are an important regulatory target to prevent tobacco and nicotine product uptake. We defined inhalation facilitation as modifications to products during manufacturing that enhance the sensory experience and (potentially) behaviours associated with inhalation (eg, deeper puffs, faster inhalation, larger puff volume, shorter intervals in between puffs and use episodes). Evidence review showed that: (a) menthol and synthetic coolants decrease irritation caused by aerosol constituents by activating sensory perception receptors (eg, cooling receptors) and may promote dependence in inexperienced users; (b) acid additives and sugars, which lower the pH of aerosols and shift nicotine from free-base to protonated salt forms, reduce harshness and increase blood nicotine yield; (c) e-cigarette flavourings perceived as sweet or fruity reduce subjective bitterness, increase attractiveness and may escalate use, although their effects on perceived harshness are inconclusive; (d) sugars in tobacco impart sweet sensations, but limited industry-independent data preclude strong conclusions for sugars' roles in inhalation facilitation. Given these findings, WHO policy recommendations suggest that regulators might consider banning ingredients that facilitate inhalation in all commercial inhaled tobacco and nicotine products.

Effectiveness of mobile smoking cessation treatment with 1-week nicotine replacement therapy sampling at outdoor smoking hotspots: A cluster randomized controlled trial.

AIMS: To evaluate the effectiveness of mobile smoking cessation (SC) treatment with 1-week nicotine replacement therapy (NRT) sampling on recruitment and quitting outcomes. DESIGN: Two-arm cluster RCT (1:1 ratio), single-blinded, at 244 recruitment sessions in Hong Kong outdoor smoking hotspots from October 2018-December 2019. SETTING: Participant were recruited by ambassadors and treated at the mobile SC truck. PARTICIPANTS: 834 adult (≥18 years, male 81.3%) daily smokers, Chinese-speaking, non-NRT users in the past month, consented after nurse-led intervention in mobile SC truck were randomized to the experimental (n = 482 male 79.5%) and the control group (n = 352, male 83.8%). INTERVENTION AND COMPARATOR: The experimental group received a 1-week free NRT sample, an NRT instruction card, and mobile SC treatment including onsite nurse-led brief medication advice (about 15 minutes) and referral to SC clinics. The control group received the same mobile SC treatment. MEASUREMENTS: Primary outcome was self-reported quit attempts at 1-month follow-up. Secondary outcomes included SC service use at 1 month, and biochemically validated abstinence (exhaled carbon monoxide < 4 ppm; or saliva cotinine < 10 ng/ml) at 6-month follow-up. Additionally, a post-hoc cost analysis was conducted. FINDINGS: By intention-to-treat, the two groups showed similar prevalence of quit attempts (44·4% versus 43·5%, risk ratio (RR) = 1·04, 95% confidence interval (CI) = 0·79-1·37, P = 0·79). Compared with the control group, the experimental group showed lower SC service use at clinics (32·4% versus 44·9%, RR = 0·72, 95%CI = 0·57-0·91, P = 0·006), but no significant difference in validated abstinence (4·6% versus 2·8%, RR = 1·64, 95%CI = 0·76-3·50, P = 0·21). The experimental recruitment sessions recruited more smokers for onsite medication advice than the control session (mean 6·7 vs 5·0, adjusted incident rate ratio = 1·30, 95%CI = 1·08-1·56, P = 0·005). CONCLUSIONS: Mobile smoking cessation treatment with 1-week nicotine replacement therapy sampling did not increase quit attempts or abstinence outcomes among recruited daily smokers in Hong Kong. The intervention increased smokers' uptake of onsite medication advice but reduced subsequent smoking cessation service use at clinics.

Association of electronic cigarette use and suicidal behaviors: a systematic review and meta-analysis.

BACKGROUND: The proliferation of electronic cigarettes (e-cigarettes) has presented new challenges in public health, particularly among adolescents and young adults. While marketed as safer than tobacco and as cessation aids, e-cigarettes have raised concerns about their long-term health and psychosocial impacts, including potential links to increased suicidal behaviors. This study aims to evaluate the relationship between e-cigarette use and suicidal behaviors by conducting a systematic review of the current literature. METHODS: We searched PubMed, Web of Science, and EMBASE for studies up to March 10, 2024, examining the relationship between e-cigarette use and suicidal behaviors. Eligible studies included cross-sectional, longitudinal, retrospective, prospective, and case-control designs. Meta-analysis was performed to calculate pooled odds ratios (ORs). Newcastle Ottawa scale was used to assess the quality of studies. R software (V 4.3) was used to perform the meta-analysis. RESULTS: Our analysis included fourteen studies, predominantly from the US and Korea, with participants ranging from 1,151 to 255,887. The meta-analysis identified a significant association between e-cigarette use and an increased risk of suicidal ideation (OR = 1.489, 95% CI: 1.357 to 1.621), suicide attempts (OR = 2.497, 95% CI: 1.999 to 3.996), and suicidal planning (OR = 2.310, 95% CI: 1.810 to 2.810). Heterogeneity was noted among the studies. CONCLUSION: E-cigarette use is significantly associated with the risk of suicidal behaviors, particularly among adolescents. The findings underscore the necessity for caution in endorsing e-cigarettes as a safer smoking alternative and call for more extensive research to understand the underlying mechanisms. Public health strategies should be developed to address and mitigate the risks of suicidal behaviors among e-cigarette users.

The analysis of e-liquids: A study on chemical diversity and metal content using gas chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry.

This work aimed to determine the chemical composition of 22 e-liquids available on the Slovenian market. Four different gas chromatography (GC) sample introduction techniques; headspace-GC-mass spectrometry (HS-GC-MS), liquid injection-GC-MS (LI-GC-MS), HS-solid-phase microextraction-GC-MS (HS-SPME-GC-MS), and direct-immersion-SPME-GC-MS (DI-SPME-GC-MS) were employed for qualitative analysis. Various experimental parameters were assessed for each GC sample introduction technique to maximize compound identification. Despite e-liquid packaging reporting a maximum of eight compounds, GC-MS identified more compounds in most samples, especially in menthol-flavored (58 identifiable compounds by HS-SPME-GC-MS), followed by nicotine-containing and fruit-flavored samples. HS-SPME-GC-MS identified the highest number of compounds, followed by HS-GC-MS, DI-SPME-GC-MS, and LI-GC-MS. Nicotine quantification in six samples was performed by LI-GC-MS with dilution in methanol. Nicotine concentration in samples ranged from 16.5 ± 0.5 to 18.5 ± 0.4 mg/mL, which was below the declared concentration of 20 mg/mL. Additionally, quantitative analysis of metals in e-liquids was performed by inductively coupled plasma-MS after microwave-assisted wet acid digestion. Iron was the most abundant metal, with its content ranging from 0.024 to 0.354 µg/g. Barium, bismuth, copper, and tin were also determined in several e-liquids.

Nicotine aggravates high-fat diet-induced non-alcoholic fatty liver disease in mice via inhibition of CISD3.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally. Growing data suggests that smoking plays an important role in the evolution of NAFLD. CDGSH iron sulfur domain 3 (CISD3) regulates critical biological activities. However, its role in nicotine-associated NAFLD and its underlying mechanisms have not been elucidated. Mice were given a high-fat diet for 10 weeks to induce the development of NAFLD. The results revealed that in mice with NAFLD, nicotine treatment resulted in reduced CISD3 expression, leading to mitochondrial dysfunction and impaired ß-oxidation. Notably, exacerbation of hepatic steatosis and inflammatory injury was observed. Furthermore, Cisd3-knockout exacerbated lipid accumulation, aggravating oxidative stress and apoptosis. In conclusion, these results contribute to our knowledge of the function of CISD3 in nicotine-associated NAFLD, revealing the possibility of using CISD3 as a potential molecular target for treating NAFLD.

Racial/ethnic differences in the acute effects of reduced nicotine content cigarettes among adolescents who smoke.

OBJECTIVE: Reducing the nicotine content in cigarettes decreases their addictiveness and abuse liability, including among adolescents. Whether these effects differ by race/ethnicity is unknown. This study is a secondary analysis of previously published data collected between 2014-2017. We examined racial/ethnic differences in the effects of smoking cigarettes with varying nicotine content levels on subjective effects and tobacco withdrawal among adolescents who smoke daily. METHODS: Across two counterbalanced sessions, 50 adolescents recruited from Rhode Island (ages 15-19; 30 % Underrepresented Minorities [URM], 20 % Asians and Pacific Islanders [API]; 50 % Non-Hispanic Whites) self-administered a very low nicotine content (VLNC; 0.4 mg nicotine/g of tobacco) or normal nicotine content control (NNC; 15.8 mg/g) research cigarette following overnight abstinence. Subjective effects were reported post-administration and tobacco withdrawal outcomes were calculated from pre- to post-administration scores. Multilevel linear models tested main and interactive effects between cigarette nicotine content and race/ethnicity on all study outcomes. RESULTS: Participants reported lower positive subjective effects and reductions in smoking urges after smoking a VLNC cigarette relative to smoking an NNC cigarette (ps < 0.01). A main effect of race/ethnicity emerged, such that API (vs. URM and White) adolescents reported lower positive subjective effects, greater craving reduction, and higher cigarette aversion after smoking, regardless of nicotine content (ps < 0.05). Significant interactions were found between race/ethnicity and nicotine content for cigarette aversion, such that API adolescents rated VLNC (vs. NNC) cigarettes as less aversive than White and URM adolescents did (p = 0.03). CONCLUSIONS: Findings provide evidence that VLNC cigarettes may reduce abuse liability and tobacco withdrawal symptoms for adolescents across racial/ethnic groups and particularly for API youth.

Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics.

Nicotine is widely recognized as the primary contributor to tobacco dependence. Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area (VTA) neurons, and accumulating evidence suggests that glia play prominent roles in nicotine addiction. However, VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration. Here, a male mouse model of nicotine self-administration was established and the timing of three critical phases (pre-addiction, addicting, and post-addiction phase) was characterized. Single-nucleus RNA sequencing (snRNA-seq) in the VTA at each phase was performed to comprehensively classify specific cell subtypes. Adaptive changes occurred during the addicting and post-addiction phases, with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacted the transcription in each cell subtype. Furthermore, significant transcriptional changes in energy metabolism-related genes were observed, accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration. The results provide insights into mechanisms underlying the progression of nicotine addiction, serving as important resource for identifying potential molecular targets for nicotine cessation.

Theoretically framing views of people who smoke in understanding what might work to support smoking cessation in coastal communities: adapting the TIDieR checklist to qualitative analysis for complex intervention development.

INTRODUCTION: People living in coastal communities have some of the worst health outcomes in the UK, driven in part by high smoking rates. Deprived coastal communities include socially disadvantaged groups that struggle to access traditional stop smoking services. The study aimed to seek the views of people who smoke living in coastal communities, to assess the optimal smoking cessation intervention for this population. In addition, the Template for Intervention Description Replication (TIDieR) checklist was adapted as an analytical framework for qualitative data to inform intervention design. METHODS: Current or recent ex-smokers (n = 25) were recruited to participate in qualitative interviews from a range of community locations in a deprived English seaside town. A thematic analysis of the interview data was undertaken adapting the TIDieR framework. This analysis was triangulated with relevant literature and notes from stakeholder meetings and observations to map onto the TIDieR checklist to describe the optimal intervention. RESULTS: Barriers to quitting smoking in the target population included low motivation to quit, high anxiety/boredom, normalisation of smoking and widespread illicit tobacco use. There was broad support for combining behavioural support, e-cigarettes and financial incentives, with a strong preference for the intervention to be delivered opportunistically and locally within (non-healthcare) community settings, in a non-pressurising manner, ideally by a community worker specially trained to give stop smoking support. CONCLUSIONS: An intensive community-based smoking cessation intervention was acceptable to the target population. Adapting the TIDieR checklist as a deductive qualitative analytical framework offered a systematic approach to intervention development. Combined with other intervention development activities, this ensured that the intervention design process was transparent and the proposed intervention was well defined. It is recommended that prior to intervention development researchers speak to members of the target population who may give valuable insight into the optimal intervention.

Awareness and use of nicotine pouches in a nationwide sample of adults in Poland.

INTRODUCTION: Nicotine pouches are a new type of nicotine-containing product that have been marketed in many countries worldwide, generating growing acceptance among consumers. The aim of this study was to assess factors associated with public awareness and use of nicotine pouches among adults in Poland. METHODS: A cross-sectional survey was conducted with a nationally representative sample of 1080 adults in Poland (February 2024). Awareness of nicotine pouches, history of use, current (past 30-day) use of nicotine pouches, as well as perception of harm was assessed using a purpose-designed questionnaire. RESULTS: Awareness of nicotine pouches was reported by 24% of the sample, while 9.2% reported ever having used a nicotine pouch product, and 4.3% using a nicotine pouch in the past 30 days. Among all respondents, 60.7% perceived nicotine pouches as harmful as combustible cigarettes, 28.2% perceived nicotine pouches as less harmful, and 11% as more harmful than combustible cigarettes. In multivariable logistic regression model, women (adjusted odds ratio, AOR=1.40; 95% CI: 1.03-1.91; p<0.05), individuals aged <60 years (p<0.05), current tobacco smokers (AOR=2.59; 95% CI: 1.75-3.82; p<0.001), former tobacco smokers (AOR=1.53; 95% CI: 1.01-2.32; p<0.05) and ever users of e-cigarette or heated tobacco (AOR=2.90; 95% CI: 2.07-4.05; p<0.001) were more likely to declare that had ever heard of nicotine pouches. Moreover, individuals aged <60 years (p<0.05), occupationally active individuals (AOR=1.82; 95% CI: 1.01-3.31; p<0.05), current tobacco smokers (AOR=2.71; 95% CI: 1.48-4.97; p<0.01), and ever users of e-cigarette or heated tobacco (AOR=5.29; 95% CI: 2.96-9.44; p<0.001) were more likely to declare ever use of nicotine pouches. CONCLUSIONS: This study provides the first national data on public awareness and use (ever and current) of nicotine pouches in Poland. Young adults, current smokers, and ever e-cigarette and heated tobacco users are at higher risk of ever use of nicotine pouches, so policy interventions are needed to protect young people from nicotine pouch marketing and nicotine initiation.

Correcting misperceptions about very low nicotine cigarettes for cigarette-only smokers, dual/poly smokers, other tobacco users, and non-tobacco users.

Background: The U.S. Food and Drug Administration authorized the sale and marketing of two very low nicotine cigarettes (VLNC) as modified risk tobacco products. The misperception that VLNC are healthier than regular cigarettes is common. This study explores effective message strategies to inform the public about health risks associated with VLNC use, encourage cigarette smokers to try VLNC, and prevent other tobacco users and non-users from product initiation. Methods: Following the Reasoned Action approach, a VLNC educational message was developed based on the salient beliefs associated with behavioral intention. The message was tested in an online survey conducted in 2018, where 410 participants were randomly assigned to one of the two message conditions (no-message, VLNC message). Message effects were assessed across four tobacco-use groups (non-tobacco users, cigarette-only smokers, cigarette dual/poly smokers, other tobacco users). Results: Compared to the no-message control, the VLNC message condition showed lower nicotine risk perception for all participants, lower misbelief in VLNC safety for non-users and cigarette-only smokers, higher belief in VLNC carcinogenicity for other tobacco users, stronger belief in second-hand smoke harm for cigarette dual/poly smokers and other tobacco users, and higher VLNC intention for cigarette-only smokers. Conclusions: Different messages are needed for different types of tobacco users. Both cigarette smokers and other tobacco users could benefit from messages that acknowledge the non-addictiveness but emphasize the health risks of VLNC. Regulators could consider making physical harm statements a requirement for VLNC packaging and marketing. New strategies need to be explored to inform cigarette dual/poly smokers.

Adverse Cardiovascular Effects of Nicotine Delivered by Chronic Electronic Cigarettes or Standard Cigarettes Captured by Cardiovascular Intrinsic Frequencies.

BACKGROUND: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system. METHODS AND RESULTS: One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine-rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle-arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine. CONCLUSIONS: Our IF results suggest that nicotine-containing electronic cigarettes adversely affect vascular function and left ventricle-arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.

The Fat Body-Specific GST Gene SlGSTe11 Enhances the Tolerance of Spodoptera litura to Cyantraniliprole and Nicotine.

Spodoptera litura is a significant agricultural pest, and its glutathione S-transferase (GST) plays a crucial role in insecticide resistance. This study aimed to investigate the relationship between the SlGSTe11 gene of S. litura and resistance to cyantraniliprole and nicotine. Transcriptome analysis revealed that SlGSTe11 is highly expressed mainly in fat bodies, with a significant increase in SlGSTe11 gene expression under induction by cyantraniliprole and nicotine. The ectopic expression of the SlGSTe11 gene in transgenic fruit flies resulted in a 5.22-fold increase in the tolerance to cyantraniliprole. Moreover, compared to the UAS-SlGSTe11 line, the Act5C-UAS>SlGSTe11 line laid more eggs and had a lower mortality after nicotine exposure. RNAi-mediated inhibition of SlGSTe11 gene expression led to a significant increase in the mortality of S. litura under cyantraniliprole exposure. In vitro metabolism experiments demonstrated that the recombinant SlGSTe11 protein efficiently metabolizes cyantraniliprole. Molecular docking results indicated that SlGSTe11 has a strong affinity for both cyantraniliprole and nicotine. These findings suggest that SlGSTe11 is involved in the development of resistance to cyantraniliprole and nicotine in S. litura.

The Impact of Potent Addictive Substances on Angiogenic Behavior: A Comprehensive Review.

Angiogenesis, the formation of new vasculature from preexisting vasculature, is involved in the development of several diseases as well as various physiological processes. Strict cooperation of proangiogenic and antiangiogenic factors mediates the control of angiogenesis. The fundamental steps in angiogenesis include endothelial cell proliferation, migration, and invasion. Addictive substances, which are considered therapeutic candidates in research and medicine, are classified as natural substances, such as nicotine, or synthetic substances, such as synthetic cannabinoids. Addictive substances have been shown to either enhance or suppress angiogenesis. This review article provides an overview of recent studies concerning the effects of several addictive substances on the process of angiogenesis. Google Scholar and PubMed were used to collect the scientific literature used in this review. The addictive substances addressed in this review are nicotine, opioids such as morphine and heroin, alcohol, cocaine, methamphetamine, and cannabinoids. An accurate assessment of the influence of these substances on the angiogenic process may help to construct a potentially effective therapeutic protocol to control and treat several angiogenesis-related diseases.

Nicotine interacts with DNA lesions induced by alpha radiation which may contribute to erroneous repair in human lung epithelial cells.

PURPOSE: Epidemiological studies show that radon and cigarette smoke interact in inducing lung cancer, but the contribution of nicotine in response to alpha radiation emitted by radon is not well understood. MATERIALS AND METHODS: Bronchial epithelial BEAS-2B cells were either pre-treated with 2 µM nicotine during 16 h, exposed to radiation, or the combination. DNA damage, cellular and chromosomal alterations, oxidative stress as well as inflammatory responses were assessed to investigate the role of nicotine in modulating responses. RESULTS: Less γH2AX foci were detected at 1 h after alpha radiation exposure (1-2 Gy) in the combination group versus alpha radiation alone, whereas nicotine alone had no effect. Comet assay showed less DNA breaks already just after combined exposure, supported by reduced p-ATM, p-DNA-PK, p-p53 and RAD51 at 1 h, compared to alpha radiation alone. Yet the frequency of translocations was higher in the combination group at 27 h after irradiation. Although nicotine did not alter G2 arrest at 24 h, it assisted in cell cycle progression at 48 h post radiation. A slightly faster recovery was indicated in the combination group based on cell viability kinetics and viable cell counts, and significantly using colony formation assay. Pan-histone acetyl transferase inhibition using PU139 blocked the reduction in p-p53 and γH2AX activation, suggesting a role for nicotine-induced histone acetylation in enabling rapid DNA repair. Nicotine had a modest effect on reactive oxygen species induction, but tended to increase alpha particle-induced pro-inflammatory IL-6 and IL-1ß (4 Gy). Interestingly, nicotine did not alter gamma radiation-induced γH2AX foci. CONCLUSIONS: This study provides evidence that nicotine modulates alpha-radiation response by causing a faster but more error-prone repair, as well as rapid recovery, which may allow expansion of cells with genomic instabilities. These results hold implications for estimating radiation risk among nicotine users.

Electronic cigarettes: "wolves in sheep's clothing".

OBJECTIVE: To provide cutting-edge information on the impact and risks of using Electronic Nicotine Delivery Systems (ENDS) by children and adolescents, based on the latest evidence published in the literature. DATA SOURCE: A comprehensive search was carried out on PubMed, using the expressions ''electronic cigarettes'' OR ''electronic nicotine delivery systems" OR "vaping" AND ''adolescent'' AND "risks" AND ''acute lung injury'. All retrieved articles had their titles and abstracts read to identify and fully read the papers reporting the most recent evidence on each subject. SUMMARY OF FINDINGS: The use of ENDS has alarmingly increased in Brazil and around the world. The possibility of customizing use, the choice of flavors and nicotine content, and the general notion that these devices are harmless when compared to conventional cigarettes are some of the factors responsible for this increase. Numerous scientific studies have proven that electronic cigarettes have serious consequences for the respiratory system, such as EVALI (E-cigarette or Vaping-Associated Lung Injury) and difficult-to-control asthma, as well as harmful effects on the neurological, cardiovascular, gastrointestinal, and immunological systems. High concentrations of nicotine make many young people addicted to this substance. In Brazil, commercialization, import, and advertising are prohibited. The viable interventions to address the use of these devices in children and adolescents are prevention and behavioral counseling. CONCLUSION: There is clear scientific evidence that these devices pose a risk to the physical and mental health of children and adolescents.