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.

Effect of Tobacco Use on Semen in Infertile Male.

Background/Objective/Methods: Infertility is one of the major global public health issues. In a social setup like India, there is a strong emphasis on childbearing, which leads to economic and psychological stress and trauma. Various studies have shown that worldwide, there is a decline in the quality of semen. Many environmental, nutritional, and lifestyle factors are responsible for the reduced semen quality. The methods of this study are the source of data, the method of collection of data, and statistical analysis. Results: Semen analysis is an important diagnostic test in the assessment of infertility in male partners. Ninety-eight semen samples were analyzed from the patients who presented with the complaint of infertility over a period of 2 years (June 2018-May 2020). Conclusion: Based on our analysis, it can be inferred that an escalation in the intensity of tobacco consumption is directly associated with a proportional decline in sperm count and motility and a notable increase in liquefaction time.

Comparative transcriptome analysis reveals nicotine metabolism is a critical component for enhancing stress response intensity of innate immunity system in tobacco.

The pyridine alkaloid nicotine acts as one of best-studied plant resistant traits in tobacco. Previous research has shown that NtERF199 and NtERF189, acting as master regulators within the NIC1 and NIC2 locus, quantitatively contribute to nicotine accumulation levels in N. tabacum. Genome editing-created Nic1(Nterf199) and Nic2 (Nterf189) double mutant provides an ideal platform for precisely dissecting the defensive role of nicotine and the connection between the nicotine biosynthetic pathway with other putative metabolic networks. Taking this advantage, we performed a comparative transcriptomic analysis to reevaluate the potential physiological and metabolic changes in response to nicotine synthesis defect by comparing the nic1nic2 and NIC1NIC2 plants. Our findings revealed that nicotine reduction could systematically diminishes the expression intensities of genes associated with stimulus perception, signal transduction and regulation, as well as secondary metabolic flux. Consequently, this global expression reduction might compromise tobacco adaptions to environmental fitness, herbivore resistances, and plant growth and development. The up-regulation of a novel set of stress-responsive and metabolic pathway genes might signify a newly established metabolic reprogramming to tradeoff the detrimental effect of nicotine loss. These results offer additional compelling evidence regarding nicotine's critical defensive role in nature and highlights the tight link between nicotine biosynthesis and gene expression levels of quantitative resistance-related genes for better environmental adaptation.

Pharmacist-only supply of nicotine vaping products: proposing an alternative regulatory model for Australia.

Regulation of nicotine vaping products (NVPs) is an ongoing challenge across the world. Australia currently has a globally unique NVP regulatory model that requires a medical prescription to purchase and use NVPs, with further restrictions in progress in response to evidence of widespread illicit NVP sales. Against this background, we examine the new measures and consider a modification of the model to pharmacist-only supply as an option for increasing access to NVPs for smoking cessation, while retaining health practitioner oversight of supply. We describe the strengths and challenges of implementing a pharmacist-only NVP supply option in Australia. Compared with the current prescription-only model, pharmacist-only supply could increase access to a lower exposure nicotine product in a highly regulated therapeutic context while addressing youth access and purchasing for non-therapeutic use, reduce demand for illicit products for smoking cessation purposes and avoid overburdening medical services with consultations to obtain NVP prescriptions. This approach can also accommodate current government goals such as eliminating NVP advertising, youth-focused branding and supply from grocery and convenience stores.

Pharmacokinetics and pharmacodynamics of inhaled nicotine salt and free-base using an e-cigarette: A randomized crossover study.

BACKGROUND: Popular "pod-style" e-cigarettes commonly use nicotine salt-based e-liquids that cause less irritation when inhaled and can deliver higher nicotine concentrations than free-base nicotine. We aimed to investigate the pharmacokinetic and pharmacodynamic effects of different nicotine formulations (salt vs. free-base) and concentrations that might influence systemic nicotine absorption and appeal of e-cigarettes. METHODS: In this randomized, double-blind, within-subject crossover study, 20 non nicotine-naïve participants were switched among three e-liquids (free-base nicotine 20mg/mL, nicotine salt 20mg/mL, nicotine salt 40mg/mL) using a refillable pod system and a standardized vaping protocol (one puff every 30 seconds, 10 puffs total). Serum nicotine concentrations and vital signs were assessed over 180 minutes; direct effects, craving, satisfaction, withdrawal, and respiratory symptoms were measured using questionnaires. CYP2A6 genotypes and the nicotine metabolite ratio were also assessed. RESULTS: Eleven (55%) participants were male and the median age was 23.5 years (range 18-67). All three formulations differed significantly in peak serum nicotine concentration (baseline adjusted Cmax, median (range): 12.0ng/mL (1.6-27.3), 5.4ng/mL (1.9-18.7) and 3.0ng/mL (1.3-8.8) for nicotine salt 40mg/mL, nicotine salt 20mg/mL and free-base 20mg/mL, respectively). All groups reached Cmax 2.0-2.5min (median) after their last puff. Differences in subjective effects were not statistically significant. No serious adverse events were observed. CONCLUSION: Free-base 20mg/mL formulations achieved lower blood nicotine concentrations than nicotine salt 20mg/mL, while 40mg/mL nicotine salt yielded concentrations similar to cigarette smoking. The findings can inform regulatory policy regarding e-liquids and their potential use in smoking cessation. IMPLICATIONS: Nicotine salt formulations inhaled by an e-cigarette led to higher nicotine delivery compared to nicotine free-base formulations with the same nicotine concentration. These findings should be considered in future regulatory discussions. The 40mg/mL nicotine salt formulation showed similar nicotine delivery as combustible cigarettes, albeit at concentrations over the maximum limit for e-liquids allowed in the European Union. Nicotine delivery resembling combustible cigarettes might be beneficial for smokers willing to quit to adequately alleviate withdrawal symptoms. However, increased nicotine delivery can also pose a public health risk, raising concerns about abuse liability, especially among youth and non-smokers.

An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence.

BACKGROUND: As well as being associated with serious negative health outcomes, smoking has been reported to have an array of physiological and psychological effects, including effects on mood and cognitive function. Post-cessation, loss of such effects (including temporary deficits in cognitive function) have been cited as reasons for resumption of smoking. The effects of e-cigarettes and nicotine delivered by e-cigarettes on these functions have not been widely researched but may play a role in the effectiveness of e-cigarettes as a satisfactory alternative to combustible cigarettes for people who smoke, and in encouraging individuals who would otherwise continue to smoke, to transition to e-cigarettes. METHODS: The study was an exploratory, randomised, partially-blinded, single-centre, five-arm crossover trial that recruited 40 healthy male and female people who smoke. At 5 study sessions, following a 12-h period of nicotine abstinence, participants were randomly assigned to use either a combustible cigarette, an e-cigarette of three varying nicotine strengths (18 mg/mL, 12 mg/mL or 0 mg/mL respectively) or observe a no product usage session. Participants completed pre- and post-product usage assessments to examine the product usage effect on cognitive performance (using the Cambridge Neuropsychological Test Automated Battery (CANTAB)), subjective mood and smoking urges. RESULTS: A significant improvement in sustained attention task performance was observed following use of both the nicotine containing e-cigarettes and combustible cigarette compared to no product use. Additionally, there were no significant differences between the nicotine containing products, indicating that nicotine use enhanced sustained attention regardless of delivery format. Nicotine containing e-cigarette and combustible cigarette use also significantly improved overall mood of participants compared to no product use, with no significant differences observed between the nicotine containing products. Nicotine containing e-cigarette and combustible cigarette use significantly reduced smoking urges compared to no product use, though combustible cigarette use elicited the greatest reduction in smoking urges. CONCLUSIONS: Overall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke. Trial registration ISRCTN (identifier: ISRCTN35376793).

Protective effect of Enicostemma axillare - Swertiamarin on oxidative stress against nicotine-induced liver damage in SD rats.

OBJECTIVE: The current investigation was aimed to determine the hepatoprotective benefits of Swertiamarin (ST) administration against nicotine-induced hepatotoxicity in SD rats. MATERIAL AND METHODS: A total of 48 adult male SD rats were allocated into six groups using a fully randomised approach. As a control, group I was given oral (PO) normal saline. For 65 days, the animals in groups II, III, IV, V and VI received 2.5mg/kg/day of nicotine intraperitoneally (IP), 100mg/kg/day of ST orally (PO), 200mg/kg/day of ST orally (PO), 2.5mg/kg/day of nicotine (IP)+100mg/kg/day of ST (PO), and 2.5mg/kg/day of nicotine (IP)+200mg/kg/day of ST (PO), respectively. Animals were killed on 66thday, liver tissue was removed and used for histopathological analysis as well as biochemical testing (oxidative stress parameters and liver function enzymes). RESULTS: When compared to control animals, the animals in group II showed a substantial rise in their aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels (P˂0.001). Furthermore, compared to control animals, these animals displayed enhanced hepatic oxidative stress as indicated by significantly higher Malondialdehyde (MDA) levels (P˂0.001) and lower levels of Catalase (CAT), Glutathione (GSH), Glutathione peroxidase (GSH-Px) and Superoxide dismutase (SOD) (P˂0.001). Further, more histological anomalies were seen in the liver of nicotine-treated rats compared to control rats, including significant vacuolization, poor tissue architecture, the growth of pycnotic nuclei, and dilated sinusoids. Contrary to nicotine-treated rats, the co-administration of ST and nicotine was observed to prevent the abnormalities caused by nicotine (groups V and VI). CONCLUSION: The results of the current study show that nicotine can seriously harm liver tissue and that swertiamarin can prevent the harmful effects of nicotine on rat liver. Future research is necessary to delve deeply into the mechanisms behind swertiamarin protective impact against nicotine-induced hepatotoxicity.

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.

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.

Multifaceted Applications of Luminescent Metalloporphyrin Derivatives: Fluorescence Turn-On Sensing of Nicotine and Antimicrobial Activity.

In this study, we designed and synthesized metalloporphyrin derivatives (with Ni and Zn) specifically intended for the fluorescence detection of nicotine in aqueous solutions. Our results showcased a notable selectivity for nicotine over other naturally occurring food toxins, exhibiting an exceptional sensitivity with a limit of detection as low as 7.2 nM. Through mechanistic investigations (1H NMR, FT-IR, etc.), we elucidated the binding mechanism, revealing the specific interaction between the pyridine ring of nicotine and the metal center, while the N atom pyrrolidine unit engaged in the hydrogen bonding with the side chain of the porphyrin ring. Notably, we observed that the nature of the metal center dictated the extent of interaction with nicotine; particularly, Zn-porphyrin demonstrated a superior response compared to Ni-porphyrin. Furthermore, we performed the quantitative estimation of nicotine in commercially available tobacco products. Additionally, we conducted the antibacterial (Staphylococcus aureus and Escherichia coli) and antifungal (Candida albicans) activities of the porphyrin derivatives.

Breaking the habit: isolating nicotine-degrading bacteria in undergraduate microbiology teaching labs.

Nicotine is a major alkaloid in tobacco plants and an addictive component of tobacco products. Some bacteria grow on tobacco plants and have evolved the ability to metabolize nicotine. As part of our microbiology teaching lab, we used minimal media with nicotine as the sole carbon source to isolate nicotine-degrading bacteria from tobacco leaves and commercial tobacco products. Students then identified these bacteria using 16S rRNA sequencing and biochemical assays and assessed their ability to catabolize nicotine using UV spectroscopy. Students were able to isolate and identify 14 distinct genera that can metabolize nicotine. This modification of the commonly used unknown project gave students firsthand experience using selective media, and students got the opportunity to work with largely uncharacterized microbes with a real-world connection to public health, which increased student engagement. Students had the opportunity to think critically about why nicotine-degrading microorganisms associate with tobacco plants, why there are different bacteria that use the same specialized metabolism, and how these organisms are isolated from other bacteria using selective media.

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.

Neurocircuitry underlying the actions of glucagon-like peptide 1 and peptide YY3-36 in the suppression of food, drug-seeking, and anxiogenesis.

Obesity is a critical health condition worldwide that increases the risks of comorbid chronic diseases, but it can be managed with weight loss. However, conventional interventions relying on diet and exercise are inadequate for achieving and maintaining weight loss, thus there is significant market interest for pharmaceutical anti-obesity agents. For decades, receptor agonists for the gut peptide glucagon-like peptide 1 (GLP-1) featured prominently in anti-obesity medications by suppressing appetite and food reward to elicit rapid weight loss. As the neurocircuitry underlying food motivation overlaps with that for drugs of abuse, GLP-1 receptor agonism has also been shown to decrease substance use and relapse, thus its therapeutic potential may extend beyond weight management to treat addictions. However, as prolonged use of anti-obesity drugs may increase the risk of mood-related disorders like anxiety and depression, and individuals taking GLP-1-based medication commonly report feeling demotivated, the long-term safety of such drugs is an ongoing concern. Interestingly, current research now focuses on dual agonist approaches that include GLP-1 receptor agonism to enable synergistic effects on weight loss or associated functions. GLP-1 is secreted from the same intestinal cells as the anorectic gut peptide, Peptide YY3-36 (PYY3-36), thus this review assessed the therapeutic potential and underlying neural circuits targeted by PYY3-36 when administered independently or in combination with GLP-1 to curb the appetite for food or drugs of abuse like opiates, alcohol, and nicotine. Additionally, we also reviewed animal and human studies to assess the impact, if any, for GLP-1 and/or PYY3-36 on mood-related behaviors in relation to anxiety and depression. As dual agonists targeting GLP-1 and PYY3-36 may produce synergistic effects, they can be effective at lower doses and offer an alternative approach for therapeutic benefits while mitigating undesirable side effects.

Nicotine exposure from packaged cigarettes in tobacco retail settings.

BACKGROUND: Although many studies on exposure to environmental tobacco smoke from passive smoking have been conducted, most of such studies have only focused on the chemicals produced by active combustion. The current study examined the extent to which uncombusted and packaged cigarettes in cigarette racks at retail stores diffuse airborne nicotine. METHODS: Airborne nicotine samples were collected for 15 days on passive monitors mounted near the indoor cigarette racks (Point 1) and farthest point from the cigarette racks (Point 2) in tobacco retailer stores (N=95) in South Korea (5 months, data collection from January to May in 2022. RESULTS: The average airborne nicotine level was 0.0908 ug/m3 at Point 1 and 0.0345 ug/m3 at Point 2. We found a positive correlation (r=0.647, p <0.001) in nicotine concentration between the two measurement points. The interior size of the target stores was positively correlated (r=0.334, p <0.001) with the within-store difference in nicotine concentration between the two measurement points. The airborne nicotine concentration at Point 1 was statistically significantly higher than at Point 2 (z=-2.326, p=0.020, effect size: 0.2215), especially at larger stores. CONCLUSIONS: Our findings indicate that packaged, unopened, and uncombusted cigarettes in cigarette racks at tobacco retailers emits airborne nicotine, which is a previously unrecognized source of nicotine exposure. This result has implications for policy considerations, such as the potential installation of ventilation systems on cigarette racks or the exploration of alternative packaging methods.

Multi-endpoint in vitro toxicological assessment of snus and tobacco-free nicotine pouch extracts.

'Modern' oral tobacco-free nicotine pouches (NPs) are a nicotine containing product similar in appearance and concept to Swedish snus. A three-step approach was taken to analyse the biological effects of NPs and snus extracts in vitro. ToxTracker was used to screen for biomarkers for oxidative stress, cell stress, protein damage and DNA damage. Cytotoxicity, mutagenicity, and genotoxicity were assessed in the following respective assays: Neutral Red Uptake (NRU), Ames and Mouse Lymphoma Assay (MLA). Targeted analysis of phosphorylation signalling and inflammatory markers under non-toxic conditions was used to investigate any potential signalling pathways or inflammatory response. A reference snus (CRP1.1) and four NPs with various flavours and nicotine strengths were assessed. Test article extracts was generated by incubating one pouch in 20 mL of media (specific to each assay) with the inclusion of the pouch material. NP extracts did not induce any cytotoxicity or mutagenic response, genotoxic response was minimal and limited signalling or inflammatory markers were induced. In contrast, CRP1.1 induced a positive response in four toxicological endpoints in the absence of S9: Srxn1 (oxidative stress), Btg2 (cell stress), Ddit3 (protein damage) and Rtkn (DNA damage), and three endpoints in presence of S9: Srxn1, Ddit3 and Rtkn. CRP1.1 was genotoxic when assessed in MLA and activated signalling pathways involved in proliferation and cellular stress and specifically induced phosphorylation of c-JUN, CREB1, p53, p38 MAPK and to a lesser extent AKT1S1, GSK3α/ß, ERK1/2 and RSK1 in a dose-dependent manner. CRP 1.1 extracts resulted in the release of several inflammatory mediators including cytokines IL-1α, IL5, IL6, IL8, IL-1RA, MIF and TNF-ß, receptor IL-2RA, and growth factors FGF-basic, VEGF and M-CSF. In conclusion these assays contribute to the weight of evidence assessment of the potential comparative health risks of NPs and snus.

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.

Self-assembled core-shell nanoparticles with embedded internal standards for SERS quantitative detection and identification of nicotine released from snus products.

Surface enhanced Raman spectroscopy (SERS) is a unique analytical technique with excellent performance in terms of sensitivity, non-destructive detection and resolution. However, due to the randomness and poor repeatability of hot spot distribution, SERS quantitative analysis is still challenging. Meanwhile, snus is a type of tobacco product that can release nicotine and other components in the mouth without burning, and the rapid detection technique based on SERS can reliably evaluate the amount of nicotine released from snus, which is of great significance for understanding its characteristics and regulating its components. Herein, the strategy was proposed to solve the feasibility of SERS quantitative detection based on self-assembled core-shell nanoparticles with embedded internal standards (EIS) due to EIS signal can effectively correct SERS signal fluctuations caused by different aggregation states and measurement conditions, thus allowing reliable quantitative SERS analysis of targets with different surface affinity. By means of process control, after the Au nanoparticles (Au NPs) were modified with 4-Mercaptobenzonitrile (4-MBN) as internal standard molecules, Ag shell with a certain thickness was grown on the surface of the AuNP@4-MBN, and then the Au@4-MBN@Ag NPs were used to regulate and control the assembly of liquid-liquid interface. The high-density nano-arrays assembled at the liquid-liquid interface ensure high reproducibility as SERS substrates, and which could be used for SERS detection of nicotine released from snus products. In addition, time-mapping research shows that this method can also be used to dynamically monitor the release of nicotine. Moreover, such destruction-free evaluation of the release of nicotine from snus products opens up new perspectives for further research about the impact of nicotinoids-related health programs.