Smoking Progression and Nicotine-Enhanced Reward Sensitivity Predicted by Resting-State Functional Connectivity in Salience and Executive Control Networks.

INTRODUCTION: The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC) during smoking abstinence predicts nicotine-enhanced reward sensitivity and smoking progression in young light smokers. We hypothesized that high rsFC between brain areas with high densities of nicotinic receptors (insula, anterior cingulate cortex [ACC], hippocampus, thalamus) and areas involved in reward-seeking (nucleus accumbens [NAcc], prefrontal cortex [PFC]) would predict nicotine-enhanced reward sensitivity and smoking progression. METHODS: Young light smokers (N=64, age 18-24, M = 1.89 cigarettes/day) participated in the study. These individuals smoked between 5 to 35 cigarettes per week and lifetime use never exceeded 35 cigarettes per week. Their rsFC was assessed using functional magnetic resonance imaging after 14-hour nicotine-deprivation. Subjects also completed a probabilistic reward task after smoking a placebo on one day and a regular cigarette on another day. RESULTS: The probabilistic-reward-task assessed greater nicotine-enhanced reward sensitivity was associated with greater rsFC between the right anterior PFC and right NAcc, but with reduced rsFC between the ACC and left inferior prefrontal gyrus and the insula and ACC. Decreased rsFC within the salience network (ACC and insula) predicted increased smoking progression across 18 months and greater nicotine-enhanced reward sensitivity. CONCLUSIONS: These findings provide the first evidence that differences in rsFCs in young light smokers are associated with nicotine-enhanced reward sensitivity and smoking progression. IMPLICATIONS: Weaker rsFC within the salience network predicted greater nicotine-enhanced reward sensitivity and smoking progression. These findings suggest that salience network rsFC and drug-enhanced reward sensitivity may be useful tools and potential endophenotypes for reward sensitivity and drug-dependence research.

Examining the correlates of cigarette smoking, e-cigarette use and dual use among Canadian post-secondary students.

Many Canadians use nicotine products such as cigarettes and e-cigarettes. A particular subpopulation of concern is post-secondary students given they have a higher prevalence of use. Many correlates of cigarette smoking and e-cigarette use have been identified. However, less focus has been on examining the correlates of cigarette smoking, e-cigarette use and dual use. This study explores the correlates of different nicotine modality use in post-secondary students. Using data from the Canadian Campus Wellbeing Survey (CCWS; n = 27,164), a multi-level nominal regression assessed the correlates of nicotine modality use. In comparison to individuals who were <20, individuals 20-24 (OR = .448, 95% CI .321, .625), 25-29 (OR = .140, 95% CI .093, .212), 30-34 (OR = .076, 95% CI .046, .125) and over 35 (OR = .041, 95% CI .024, .071) had lower odds of e-cigarette use compared to cigarette smoking. Identifying as a woman (OR = 1.553, 95% CI 1.202, 2.006), non-heterosexual (OR = .642, 95% CI = .485,0.851), current cannabis user (OR = 1.651, 95% CI 1.296, 2.104), and being an international student (OR = .350, 95% CI .251, .487) also impacted the odds of e-cigarette use vs only cigarette smoking. When considering dual use vs cigarette smoking, individuals aged 20-24 (OR = .491, 95% CI .337, .717), 25-29 (OR = .221, 95% CI .137, .357), 30-34 (OR = .163, 95% CI .091, .292) and over 35 (OR = .122, 95% CI .065, .230) had lower odds than individuals <20. Current cannabis use (OR = 1.680, 95% CI = 1.209, 2.138), binge drinking (OR = 1.885, 95% CI 1.384, 2.568), and international student status (OR = .689, 95% CI .476, .996) also impacted cigarette smoking vs dual-use. Overall, a minority of young adults (11.5%) at post-secondary institutions in our sample use nicotine products, and the higher prevalence of e-cigarette use warrants continued monitoring. Health promotion campaigns addressing e-cigarette use are required. Additionally, tailored intervention efforts could prioritize the treatment needs of international students studying in Canada.

Tobacco use and dependence among adults residing in an urbanized village, Delhi, India.

Introduction: Tobacco use is one of the most significant public health concerns globally as it is a risk factor for chronic illnesses. GATS-2 concluded that 28.6% of all adults currently use Tobacco in India and 17.8% in Delhi. It is important to conduct such surveys in local areas to make specific and effective action plans. Materials and Methods: Community-based cross-sectional study conducted between January 2020-June 2021 in Aliganj, an urbanized village in South Delhi. Four hundred ninety participants were enrolled using simple random sampling. The first author conducted the interview using GATS and Fagerstrom nicotine dependence test. Data was analyzed using SPSS-21. Results: Median age-35 (26.75-75.00), range-15-84 years. Of the 490 participants, 20.0% were current tobacco users (10.6% smokeless, 7.3% smoked, and 2.2% both). Among current smokers, 78.3% had low, 17.4% moderate, and 4.3% had high dependence on nicotine dependence. Among current smokeless tobacco users, 52.4% had, low, 36.5% moderate, and 11.1% had high dependence. Males had significantly higher odds [6.6 (2.9-15.1)] of tobacco use than females. Higher education [0.3 (0.2-0.8)] compared to no formal education had significantly lower odds of using tobacco. Students [0.1 (0.04-0.4)] and homemakers [0.1 (0.01-0.5)] had significantly lower odds of using tobacco as compared to those employed. Conclusions: One in every five adults is a tobacco user in Aliganj. Manufactured cigarettes, bidi, and water pipes were the most common products among smokers. Among smokeless tobacco users, the most common products were chewing tobacco gutka, and khaini. A larger proportion of smokeless tobacco users had high nicotine dependence than smoked tobacco users.

'Stopping the start': support for proposed tobacco control policies - a population-based survey in Great Britain 2021-2023.

OBJECTIVES: This study assessed public support for four proposed tobacco control policies in Great Britain: (1) Raising the sales age of tobacco by 1 year every year (Smokefree Generation); (2) Raising the sales age of tobacco from 18 years to 21 years; (3) Providing prescription e-cigarettes as smoking cessation aids to adults who smoke; (4) Restricting e-cigarette advertising to prevent youth uptake. DESIGN: Repeat cross-sectional population-based survey weighted to match the population of Great Britain. SETTING: The survey was conducted in England, Scotland and Wales in September 2021, October 2022 and October 2023. PARTICIPANTS: 6541 adults living in Great Britain. MAIN OUTCOME MEASURES: Support for each policy and year and prevalence ratios (PRs) comparing support between years and subgroups. RESULTS: The most popular policy each year was restricting e-cigarette advertising (74%/79%/85%), followed by raising the sales age to 21 years (50%/58%/64%), providing prescription e-cigarettes (45%/44%/47%) and Smokefree Generation (34%/44%/49%). The largest increases were for policies about the age of sale (Smokefree Generation: 2021/2022 PR=1.28, 95% CI 1.18 to 1.40, 2022/2023 PR=1.12, 95% CI 1.04 to 1.20; raising the age to 21 years: 2021/2022 PR=1.16, 95% CI 1.09 to 1.23, 2022/2023 PR=1.11, 95% CI 1.05 to 1.17). Only 30% opposed Smokefree Generation in 2023 down from 41% in 2021. CONCLUSIONS: Support for each policy increased each year, except for providing prescription e-cigarettes. Restricting e-cigarette advertising was the most popular policy, while support for age of sale policies, in particular for a Smokefree Generation, grew most. TRIAL REGISTRATION: The study protocol was published on the Open Science Framework (https://osf.io/46z2c/) prior to starting the analysis.

High-risk smoking in the United States: Nicotine staining predicts increased colonic adenomas and advanced adenomas on colonoscopy.

BACKGROUND: Smoking is linked with numerous adverse health effects. Nicotine staining on fingers or teeth is thought to suggest active or heavy smoking. The significance of nicotine staining within gastroenterology remains unclear. AIM: We set out to establish the predictive value of nicotine staining for adenomas and advanced adenomas. METHODS: This was a cross-section study of patients who underwent colonoscopy at the Oklahoma City Veterans Affairs Medical Center from November 2019 to November 2020. Pre-procedure patient survey ascertained current smoking status. Endoscopist performed a nicotine staining survey upon completion of the respective colonoscopy. Chart review allowed determination of patient demographics, comorbidities, and colonoscopy findings. Patients without smoking history were assigned to a control cohort. We applied one-way analysis of variance when comparing the mean of continuous variables and the Chi-square test when comparing categorical variables. Lastly, we used stepwise logistic regression to estimate adjusted odds ratio. A p-value <0.05 was considered statistically significant. RESULTS: Compared to those without smoking history or evidence of nicotine staining, patients with positive nicotine staining were older (P = 0.03), leaner (P < 0.0001), and more likely to have chronic obstructive pulmonary disease (P < 0.0001) or history of alcohol abuse (P < 0.0001). Furthermore, presence of nicotine staining independently predicted increased likelihood of multiple adenomas (OR 1.5, 95% CI [1.2-1.9]) and advanced adenomas (OR 1.6, 95% CI [1.2-2.2]). CONCLUSION: This marks the first investigation of nicotine staining within gastroenterology. We have demonstrated that the presence of nicotine staining independently predicts numerous adenomas and advanced adenomas.

Catharanthine Modulates Mesolimbic Dopamine Transmission and Nicotine Psychomotor Effects via Inhibition of α6-Nicotinic Receptors and Dopamine Transporters.

Iboga alkaloids, also known as coronaridine congeners, have shown promise in the treatment of alcohol and opioid use disorders. The objective of this study was to evaluate the effects of catharanthine and 18-methoxycoronaridine (18-MC) on dopamine (DA) transmission and cholinergic interneurons in the mesolimbic DA system, nicotine-induced locomotor activity, and nicotine-taking behavior. Utilizing ex vivo fast-scan cyclic voltammetry (FSCV) in the nucleus accumbens core of male mice, we found that catharanthine or 18-MC differentially inhibited evoked DA release. Catharanthine inhibition of evoked DA release was significantly reduced by both α4 and α6 nicotinic acetylcholine receptors (nAChRs) antagonists. Additionally, catharanthine substantially increased DA release more than vehicle during high-frequency stimulation, although less potently than an α4 nAChR antagonist, which confirms previous work with nAChR antagonists. Interestingly, while catharanthine slowed DA reuptake measured via FSCV ex vivo, it also increased extracellular DA in striatal dialysate from anesthetized mice in vivo in a dose-dependent manner. Superfusion of catharanthine or 18-MC inhibited the firing rate of striatal cholinergic interneurons in a concentration dependent manner, which are known to potently modulate presynaptic DA release. Catharanthine or 18-MC suppressed acetylcholine currents in oocytes expressing recombinant rat α6/α3ß2ß3 or α6/α3ß4 nAChRs. In behavioral experiments using male Sprague-Dawley rats, systemic administration of catharanthine or 18-MC blocked nicotine enhancement of locomotor activity. Importantly, catharanthine attenuated nicotine self-administration in a dose-dependent manner while having no effect on food reinforcement. Lastly, administration of catharanthine and nicotine together greatly increased head twitch responses, indicating a potential synergistic hallucinogenic effect. These findings demonstrate that catharanthine and 18-MC have similar, but not identical effects on striatal DA dynamics, striatal cholinergic interneuron activity and nicotine psychomotor effects.

Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes.

BACKGROUND: Menthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. METHODS: 215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. RESULTS: All ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. CONCLUSIONS: Abuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.

Reinforcing and adverse observable effects of nicotine and minor tobacco alkaloids in squirrel monkeys.

The most prevalent psychoactive chemical in tobacco smoke is nicotine, which has been shown to maintain tobacco consumption as well as cause acute adverse effects at high doses, like nausea and emesis. Recent studies in laboratory animals have suggested that many non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may also contribute to tobacco's overall reinforcing and adverse effects. Here, we used intravenous (IV) self-administration (n = 3) and observation (n = 4) procedures in squirrel monkeys to, respectively, compare the reinforcing and adverse observable effects of nicotine and three prominent minor tobacco alkaloids, nornicotine, anatabine, and myosmine. In self-administration studies, male squirrel monkeys were trained to respond under a second-order fixed-interval schedule of reinforcement and dose-effects functions for nicotine and each of the minor tobacco alkaloids nornicotine, anatabine, and mysomine were determined. Observation studies were conducted in a different group of male squirrel monkeys to quantify the ability of nicotine, nornicotine, anatabine, and mysomine to produce adverse overt effects, including hypersalivation, emesis, and tremors. Results show that nicotine and to a lesser extent nornicotine were readily self-administered, whereas anatabine and myosmine were not. In observation studies, all minor tobacco alkaloids produced adverse observable effects that were either comparable or more pronounced than nicotine. Collectively, the present results showing that nicotine and the minor tobacco alkaloids nornicotine, anatabine, and myosmine produce differential reinforcing and acute adverse observable effects in monkeys provides further evidence that these constituents may differently contribute to the psychopharmacological and adverse effects of tobacco consumption.

Dopamine and Norepinephrine Tissue Levels in the Developing Limbic Brain Are Impacted by the Human CHRNA6 3'-UTR Single-Nucleotide Polymorphism (rs2304297) in Rats.

We previously demonstrated that a genetic single-nucleotide polymorphism (SNP, rs2304297) in the 3' untranslated region (UTR) of the human CHRNA6 gene has sex- and genotype-dependent effects on nicotine-induced locomotion, anxiety, and nicotine + cue-induced reinstatement in adolescent rats. This study aims to investigate how the CHRNA6 3'-UTR SNP influences dopaminergic and noradrenergic tissue levels in brain reward regions during baseline and after the reinstatement of drug-seeking behavior. Naïve adolescent and adult rats, along with those undergoing nicotine + cue reinstatement and carrying the CHRNA6 3'-UTR SNP, were assessed for dopamine (DA), norepinephrine (NE), and metabolites in reward pathway regions. The results reveal age-, sex-, and genotype-dependent baseline DA, NE, and DA turnover levels. Post-reinstatement, male α6GG rats show suppressed DA levels in the Nucleus Accumbens (NAc) Shell compared to the baseline, while nicotine+ cue-induced reinstatement behavior correlates with neurotransmitter levels in specific brain regions. This study emphasizes the role of CHRNA6 3'-UTR SNP in the developmental maturation of the dopaminergic and noradrenergic system in the adolescent rat brain, with tissue levels acting as predictors of nicotine + cue-induced reinstatement.

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Socioecological factors associated with multiple nicotine product use among U.S. youth: Findings from the population assessment of tobacco and health (PATH) study 2013-2018.

OBJECTIVE: This study utilized a socioecological approach to prospectively identify intrapersonal, familial, and environmental factors associated with single nicotine product use (NPU) and multiple NPU among U.S. youth. METHODS: Participants were 10,029 youths (ages 12-17 years) who had completed the Population Assessment of Tobacco Health study's Wave 1 (2013-2014) and Wave 4 (2016-2018) assessments and data on past 30-day nicotine product use. Multinomial logistic regression was fit for the 3-level outcome (no use, single NPU, multiple NPU) to estimate adjusted associations between the predictors and the outcome. RESULTS: The current study found that intrapersonal (sex, age, race/ethnicity, internalizing symptoms, sensation seeking, harm perceptions, lifetime history of using two or more tobacco products), familial (parental discussion about not using tobacco and living with someone who uses tobacco products) and environmental factors (exposure to tobacco advertising) commonly associated with tobacco use differentiated between individuals who later reported past 30-day NPU (either multiple or single NPU) from those who did not report past 30-day NPU. One familial factor only differentiated between lifetime users who were single NPUs from those who reported no NPU: non-combustible tobacco product use allowed anywhere in the home. Intrapersonal factors differentiated multiple NPU from single NPU: older age, being male, lifetime history of using nicotine product and less harm perceptions. CONCLUSIONS: This study identified factors that may be studied to prevent any NPU, along with factors that may be studied to promote harm reduction by preventing escalation of single NPU to problematic patterns of multiple NPU.

Do traumatic events and substance use co-occur during adolescence? Testing three causal etiologic hypotheses.

BACKGROUND: Why do potentially traumatic events (PTEs) and substance use (SU) so commonly co-occur during adolescence? Causal hypotheses developed from the study of posttraumatic stress disorder (PTSD) and substance use disorder (SUD) among adults have not yet been subject to rigorous theoretical analysis or empirical tests among adolescents with the precursors to these disorders: PTEs and SU. Establishing causality demands accounting for various factors (e.g. genetics, parent education, race/ethnicity) that distinguish youth endorsing PTEs and SU from those who do not, a step often overlooked in previous research. METHODS: We leveraged nationwide data from a sociodemographically diverse sample of youth (N = 11,468) in the Adolescent Brain and Cognitive Development Study. PTEs and substance use prevalence were assessed annually. To account for the many pre-existing differences between youth with and without PTE/SU (i.e. confounding bias) and provide rigorous tests of causal hypotheses, we linked within-person changes in PTEs and SU (alcohol, cannabis, nicotine) across repeated measurements and adjusted for time-varying factors (e.g. age, internalizing symptoms, externalizing symptoms, and friends' use of substances). RESULTS: Before adjusting for confounding using within-person modeling, PTEs and SU exhibited significant concurrent associations (ßs = .46-1.26, ps < .05) and PTEs prospectively predicted greater SU (ßs = .55-1.43, ps < .05) but not vice versa. After adjustment for confounding, the PTEs exhibited significant concurrent associations for alcohol (ßs = .14-.23, ps < .05) and nicotine (ßs = .16, ps < .05) but not cannabis (ßs = -.01, ps > .05) and PTEs prospectively predicted greater SU (ßs = .28-.55, ps > .05) but not vice versa. CONCLUSIONS: When tested rigorously in a nationwide sample of adolescents, we find support for a model in which PTEs are followed by SU but not for a model in which SU is followed by PTEs. Explanations for why PTSD and SUD co-occur in adults may need further theoretical analysis and adaptation before extension to adolescents.

Vaping Behaviors and Criminal Activity among a Nationally Representative Sample of U.S. Adults.

Background: Prior research has discovered an association between vaping activities and increased delinquent behaviors. However, this relationship has been exclusively studied among adolescents and has not been examined among an adult sample. Methods: The current study uses a nationally representative sample of approximately 45,000 adults from the 2021 National Survey on Drug Use and Health. Logistic regression and negative binomial regression are employed to assess the association between three types of vaping (marijuana, nicotine, flavor) and five crime measures (arrest, sold drugs, stole >$50, attack, crime index), net of covariates. A vaping index is also examined to determine whether the number of substances vaped is related to criminal outcomes. Results: Results indicate that past year and past month marijuana and nicotine vaping are associated with higher odds of almost all crime measures, but flavor vaping was not significantly associated with the crime outcomes. Additionally, the vaping index suggests that the number of substances vaped is associated with the likelihood of engaging in certain crimes. Conclusions: The findings of the current study indicate the need for more awareness of the negative social consequences associated with vaping, particularly marijuana vaping. Additionally, the crime patterns among adults in this study are different from previous studies using adolescent samples. Specifically, flavor vaping is not associated with criminal behavior among the adult only sample. Thus, vaping studies that use adolescent samples may not generalize to adults.

Attitudes of people diagnosed with cancer and cancer care providers towards use of nicotine vaping products in high-income countries: a scoping review.

PURPOSE: To investigate the attitudes, beliefs and perceptions of people diagnosed with cancer and health practitioners on use of nicotine vaping products. METHODS: Scopus and OVID Medline were searched for papers published between 2013 and 2023. Two authors independently selected the studies and extracted data, with conflicts resolved through discussion. Nine studies were selected for further synthesis. Reporting follows the PRISMA Scoping Reviews checklist. RESULTS: E-cigarettes were commonly perceived as less harmful compared to conventional cigarettes and less detrimental to cancer treatment effectiveness among people with a current or previous cancer diagnosis. This population also cited smoking cessation, smoking in non-smoking areas and less risky alternative as the most common reasons for e-cigarette use. Nevertheless, low levels of clinician support on the effectiveness of e-cigarettes as a smoking cessation tool/alternative were identified. CONCLUSION: Findings show differences in beliefs and attitudes of e-cigarettes between clinicians and people diagnosed with cancer. Additional research into the health impacts of e-cigarettes in people with a current or previous cancer diagnosis will allow for greater congruence between patients and clinicians and assist providers in recommending effective tools for smoking cessation within this population. IMPLICATIONS FOR CANCER SURVIVORS: This study provides an overview of the attitudes, beliefs and perceptions of e-cigarette use among people with a current or previous diagnosis of cancer and health practitioners. Given the increased prevalence of e-cigarette use within this population, these findings highlight a greater need for dialogue between patients and clinicians regarding the safety and efficacy of these devices.

Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

BACKGROUND: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. METHODS: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R-) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. RESULTS: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R- HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. CONCLUSIONS: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Unfolding Protein-Based Hapten Coupling via Thiol-Maleimide Click Chemistry: Enhanced Immunogenicity in Anti-Nicotine Vaccines Based on a Novel Conjugation Method and MPL/QS-21 Adjuvants.

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

Integrated use of biofeedback and neurofeedback techniques in treating pathological conditions and improving performance: a narrative review.

In recent years, the scientific community has begun tо explore the efficacy оf an integrated neurofeedback + biofeedback approach іn various conditions, both pathological and non-pathological. Although several studies have contributed valuable insights into its potential benefits, this review aims tо further investigate its effectiveness by synthesizing current findings and identifying areas for future research. Our goal іs tо provide a comprehensive overview that may highlight gaps іn the existing literature and propose directions for subsequent studies. The search for articles was conducted on the digital databases PubMed, Scopus, and Web of Science. Studies to have used the integrated neurofeedback + biofeedback approach published between 2014 and 2023 and reviews to have analyzed the efficacy of neurofeedback and biofeedback, separately, related to the same time interval and topics were selected. The search identified five studies compatible with the objectives of the review, related to several conditions: nicotine addiction, sports performance, Autism Spectrum Disorder (ASD), and Attention Deficit Hyperactivity Disorder (ADHD). The integrated neurofeedback + biofeedback approach has been shown to be effective in improving several aspects of these conditions, such as a reduction in the presence of psychiatric symptoms, anxiety, depression, and withdrawal symptoms and an increase in self-esteem in smokers; improvements in communication, imitation, social/cognitive awareness, and social behavior in ASD subjects; improvements in attention, alertness, and reaction time in sports champions; and improvements in attention and inhibitory control in ADHD subjects. Further research, characterized by greater methodological rigor, is therefore needed to determine the effectiveness of this method and the superiority, if any, of this type of training over the single administration of either. This review іs intended tо serve as a catalyst for future research, signaling promising directions for the advancement оf biofeedback and neurofeedback methodologies.

Former smoking, but not active smoking, is associated with delirium in postoperative ICU patients: a matched case-control study.

Objective: To examine the relationship between current and former smoking and the occurrence of delirium in surgical Intensive Care Unit (ICU) patients. Methods: We conducted a single center, case-control study involving 244 delirious and 251 non-delirious patients that were admitted to our ICU between 2018 and 2022. Using propensity score analysis, we obtained 115 pairs of delirious and non-delirious patients matched for age and Simplified Acute Physiology Score II (SAPS II). Both groups of patients were further stratified into non-smokers, active smokers and former smokers, and logistic regression was performed to further investigate potential confounders. Results: Our study revealed a significant association between former smoking and the incidence of delirium in ICU patients, both in unmatched (adjusted odds ratio (OR): 1.82, 95% confidence interval (CI): 1.17-2.83) and matched cohorts (OR: 3.0, CI: 1.53-5.89). Active smoking did not demonstrate a significant difference in delirium incidence compared to non-smokers (unmatched OR = 0.98, CI: 0.62-1.53, matched OR = 1.05, CI: 0.55-2.0). Logistic regression analysis of the matched group confirmed former smoking as an independent risk factor for delirium, irrespective of other variables like surgical history (p = 0.010). Notably, also respiratory and vascular surgeries were associated with increased odds of delirium (respiratory: OR: 4.13, CI: 1.73-9.83; vascular: OR: 2.18, CI: 1.03-4.59). Medication analysis showed that while Ketamine and Midazolam usage did not significantly correlate with delirium, Morphine use was linked to a decreased likelihood (OR: 0.27, 95% CI: 0.13-0.55). Discussion: Nicotine's complex neuropharmacological impact on the brain is still not fully understood, especially its short-term and long-term implications for critically ill patients. Although our retrospective study cannot establish causality, our findings suggest that smoking may induce structural changes in the brain, potentially heightening the risk of postoperative delirium. Intriguingly, this effect seems to be obscured in active smokers, potentially due to the recognized neuroprotective properties of nicotine. Our results motivate future prospective studies, the results of which hold the potential to substantially impact risk assessment procedures for surgeries.

Vaping: Public Health, Social Media, and Toxicity.

This viewpoint aims to provide a comprehensive understanding of vaping from various perspectives that contribute to the invention, development, spread, and consequences of e-cigarette products and vaping. Our analysis showed that the specific characteristics of e-cigarette products as well as marketing strategies, especially social media marketing, fostered the spread of vaping and the subsequent effects on human health and toxicity. We analyzed the components of e-cigarette devices and e-liquids, including the latest variants whose impacts were often overlooked. The different forms of nicotine, including salts and freebase nicotine, tobacco-derived nicotine, tobacco-free nicotine, and cooling agents (WS3 and WS23), have brought more choices for vapers along with more ways for e-cigarette manufacturers to advertise false understandings and present a greater threat to vapers' health. Our work emphasized the products of brands that have gained significant influence recently, which are contributing to severe public health issues. On the other hand, we also discussed in detail the toxicity of e-liquid components and proposed a toxicity mechanism. We also noticed that nicotine and other chemicals in e-liquids promote each other's negative effects through the oxidative stress and inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, a mechanism leading to pulmonary symptoms and addiction. The impact of government regulations on the products themselves, including flavor bans or regulations, has been limited. Therefore, we proposed further interventions or harm reduction strategies from a public health perspective.