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Rationale: No previous studies examined the discriminative stimulus effects of intravenous (IV) nicotine in humans. Objectives: To evaluate a pulsed IV nicotine infusion procedure designed to mimic inhaled nicotine delivery and to identify a range of nicotine doses that may capture the threshold doses for the subjective and discriminative stimulus effects of nicotine. By determining these thresholds, we can gain valuable insights into the addictive threshold of nicotine. Methods: Eleven participants had 2 Test Sessions following overnight abstinence from smoking. Test Session 1 examined participants' ability to discriminate 0.1 mg nicotine/pulse nicotine from saline. Test Session 2 examined if participants can discriminate 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline. These nicotine doses were delivered as a cluster of 4 pulsed-nicotine infusions of 2-second duration with a 28-second interval between each pulse. Results: The lowest doses of nicotine that produced greater responses than saline for discrimination, subjective effects, and heart rate ranged from 0.05 to 0.1 mg nicotine/pulse. Conclusions: These findings support the validity of our pulsed-infusion procedure as a model for nicotine delivery by smoking and its utility in examining factors that may impact the addictive threshold of nicotine. [ABSTRACT FROM AUTHOR]

Rationale: People with tobacco addiction have deficits in cognition, in particular deficits in attention. It is not clear however, whether deficits are a cause or a consequence, or both, of chronic nicotine use. Here we set out a series of experiments in rats to address this question and, more specifically, to assess the effects of exposure to and withdrawal from chronic nicotine self-administration on attentional performance. Methods: Animals were trained in a 5-choice serial reaction time task to probe individual attentional performance and, then, were given access to a fixed versus increasing dose of intravenous nicotine for self-administration, a differential dose procedure known to induce two between-session patterns of nicotine intake: a stable versus escalation pattern. Attentional performance was measured daily before, during and also 24-h after chronic access to the differential dose procedure of nicotine self-administration. Conclusions: We found that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake. Moreover, while chronic nicotine self-administration increases attention, withdrawal from nicotine intake escalation induces attentional deficits, a withdrawal effect that is dose-dependently reversed by acute nicotine. Together, these results suggest that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake, and that part of the motivation for using nicotine during escalation might be to alleviate withdrawal-induced attentional deficits. [ABSTRACT FROM AUTHOR]

Rationale Clinical research has shown that prenatal exposure to nicotine may result in increased obesity risk later in life. Preclinical research has corroborated this finding, but few studies have investigated inhaled nicotine or the interaction with diet on obesity risk. Objective The aim of this study was to investigate the effects of prenatal nicotine exposure on both direct and indirect obesity measures, with both sex and diet as factors. Methods Pregnant rats were exposed to either vehicle or nicotine vapor (24 mg/mL or 59 mg/mL) throughout the entire gestational period. Offspring from each treatment group were given either a normal diet or a high fat diet starting at postnatal day 22. Caloric intake, body weight, spontaneous locomotion, sleep/wake activity, and voluntary exercise were measured throughout adolescence. Pregnancy weight gain and pup birthweights were collected to further measure developmental effects of prenatal nicotine exposure. Results Both maternal weight gain during pregnancy and pup weight at birth were decreased with prenatal nicotine exposure. Early adolescent males showed increased spontaneous activity in the open field following prenatal nicotine exposure compared to vehicle counterparts, particularly those given high-fat diet. Additionally, high dose nicotine prenatal treated males ran significantly less distance on the running wheel in late adolescence compared to vehicle counterparts, in the normal diet group only. Conclusion The results presented here show decreased birthweight, hyperactivity, and decreased voluntary exercise in adolescence following prenatal nicotine exposure in dose, sex, and diet dependent manners, which could lead to increased obesity risk in adulthood. [ABSTRACT FROM AUTHOR]

Electronic cigarettes (ECs) are battery-powered gadgets that heat liquid to produce an aerosol. Nicotine is a primary ingredient in some e-liquids; however, due to a lack of quality control regulations, the nicotine may become tainted, or the measured and labelled values may not correspond. To avoid such issues, it is essential to identify the components that contribute to erroneous nicotine quantification. Herein, the differences between free-base nicotine and nicotine salts are discussed, highlighting the lower volatility of nicotine salts and their longer persistence in the body. Discrepancies were noted in the concentration of nicotine salts in some e-liquid samples, with labelled and measured values of 48 and 68.8 mg/mL, respectively, in one sample, and 24 and 33.1 mg/mL, respectively, in another. Inconsistencies were also observed in e-liquids labelled as nicotine-free: one sample had a nicotine concentration of 21.80 mg/cartridge, while another had a concentration of 23.91 mg/mL. The review also covers differences in the potency, flavour, and storage of nicotine under various conditions. Additionally, the literature suggests that the components in ECs are separated into the liquid and vapour phases; thus, phase selection should be considered to ensure optimal experimental outcomes. For instance, the vapour phase comprises the greatest quantities of volatile organic compounds, even though nicotine has been detected in all phases. Finally, the role of ECs in smoking cessation is discussed. The reviewed findings underscore the need for further research on e-liquids, particularly regarding their long-term clinical effects. [ABSTRACT FROM AUTHOR]

Psychostimulants regulate behavioral responses in zebrafish via epigenetic mechanisms. We have previously shown that DNA methylation and histone deacetylase (HDAC) inhibition abolish nicotine-induced conditioned place preference (CPP) but little is known about the role of histone methylation in addictive-like behaviors. To assess the influence of histone methylation on nicotine-CPP, zebrafish were treated with a histone (H3) lysine-9 (K9) dimethyltransferase G9a/GLP inhibitor, BIX-01294 (BIX), which was administered before conditioning sessions. We observed a dual effect of the inhibitor BIX: at high doses inhibited while at low doses potentiated nicotine reward. Transcriptional expression of α6 and α7 subunits of the nicotinic acetylcholine receptor and of G9a, DNA methyl transferase-3, and HDAC-1 was upregulated in zebrafish with positive scores for nicotine-CPP. Changes in relative levels of these mRNA molecules reflected the effects of BIX on nicotine reward. BIX treatment per sé did not affect transcriptional levels of epigenetic enzymes that regulate trimethylation or demethylation of H3. BIX reduced H3K9me2 protein levels in a dose-dependent manner in key structures of the reward pathway. Thus, our findings indicated that different doses of BIX differentially affect nicotine CPP via strong or weak inhibition of G9a/GLP activity. Additionally, we found that the lysine demethylase inhibitor daminozide abolished nicotine-CPP and drug seeking. Our data demonstrate that H3 methylation catalyzed by G9a/GLP is involved in nicotine-CPP induction. Dimethylation of K9 at H3 is an important epigenetic modification that should be considered as a potential therapeutic target to treat nicotine reward and perhaps other drug addictions. [ABSTRACT FROM AUTHOR]

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The American Heart Association (AHA) recently redefined cardiovascular health (CVH) with the introduction of Life's Essential 8 (LE8), which encompasses eight areas (diet, physical activity, nicotine exposure, sleep duration body mass index, non-HDL cholesterol, blood glucose, and blood pressure). This study aimed to explore the relationships between both the aggregate and individual CVH metrics, as defined by Life's Essential 8, and cognitive function in older adults in the United States. This cross-sectional, population-based study analyzed data from the National Health and Nutrition Examination Survey conducted between 2011 and 2014, focusing on individuals aged 60 years and older. CVH was categorized as low (0–49), moderate (50–79), or high (80–100). Cognitive function was assessed through the CERAD tests, Animal Fluency test, and Digit Symbol Substitution test. Multivariable logistic models and restricted cubic spline models were employed to investigate these associations. This study included a total of 2279 older adults in the United States. Only 11% of adults achieved a high total CVH score, while 12% had a low score. After further adjustment for potential confounding factors, higher LE8 scores were significantly associated with higher scores on CERAD: delayed recall score (0.02[0.01, 0.03]; P < 0.001), CERAD: total score (3 recall trials) (0.04[0.02, 0.06]; P < 0.001), animal fluency: total score (0.09[0.05, 0.12]; P < 0.001), and digit symbol: score (0.29[0.18, 0.41]; P < 0.001), demonstrating a linear dose–response relationship. Similar patterns were also observed in the associations between health behavior and health factor scores with cognitive function tests. LE8 scores exhibited positive linear associations with cognitive function. Maintaining better levels of CVH may be associated with higher levels of cognitive function in older Americans, but further research is needed to confirm the causal and temporal relationships between LE8 and cognitive function. [ABSTRACT FROM AUTHOR]

Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression. [ABSTRACT FROM AUTHOR]

Rationale: It is unclear if e-cigarettes have reduced abuse liability relative to traditional cigarettes, especially when considering advanced devices which deliver nicotine more efficiently. Translatable and predictive animal models are needed to addresses this question. Objectives: Our goal was to explore the subjective stimulus effects of e-cigarettes by training rats to discriminate puffs of nicotine aerosol from vehicle aerosol using an aerosol delivery system designed to model e-cigarette use patterns in humans. Methods: Rats were trained to discriminate between ten, 10 s puffs of aerosol generated from 3 mg/ml nicotine e-liquid and nicotine-free e-liquid using a food-reinforced operant procedure. Following acquisition, tests were conducted to determine the specificity of the nicotine aerosol stimulus as well as the impact to the stimulus effects of nicotine resulting from the addition of menthol to e-liquid. Results: Rats learned the nicotine aerosol puff vs vehicle puff discrimination in a mean of 25 training sessions. Injected nicotine fully substituted for the stimulus effects of nicotine aerosol. The stimulus effects of nicotine aerosol were blocked by the nicotinic receptor antagonist mecamylamine. The nicotinic receptor partial agonist, varenicline as well as the stimulant d-amphetamine substituted more robustly for nicotine aerosol puffs than did the NMDA antagonist, ketamine. Menthol enhanced the stimulus effects of nicotine aerosol without altering nicotine blood plasma levels. Conclusions: Nicotine aerosol puffs can function as a training stimulus in rats. The stimulus effects were CNS-mediated and receptor specific. Menthol appears to enhance the stimulus effects of nicotine aerosol through a pharmacodynamic rather than pharmacokinetic mechanism. [ABSTRACT FROM AUTHOR]

4E approaches to affective technology tend to focus on how 'users' manage their situated affectivity, analogously to how they help themselves cognitively through epistemic actions or using artefacts and scaffolding. Here I focus on cases where the function of affective technology is to exploit or manipulate the agent engaging with it. My opening example is the cigarette, where technological refinements have harmfully transformed the affective process of consuming nicotine. I proceed to develop case studies of two very different but also harmful affective technologies. Casinos and electronic gambling machines deploy computationally intensive scaffolding to shape the onset and continuation of gambling episodes. High-heeled shoes affectively engineer wearers' relationships to their own embodied capacities and are predominantly expected to be worn by women. I conclude with a discussion of the need for study of affective technology to focus other-directed applications, some of which will serve competing or antagonistic interests. [ABSTRACT FROM AUTHOR]

U.S. Veterans and people living with HIV (PWH) experience higher rates of unhealthy alcohol and tobacco/nicotine use than non-Veterans and people without HIV (PWoH). Both groups are susceptible to adverse health outcomes associated with alcohol and tobacco/nicotine use. We explored awareness of alcohol- and tobacco/nicotine-related cancer and immune health risks among Veterans Health Administration (VA) patients with and without HIV. Among a sample of 41 (46% PWH; 73% male; 39% Black) purposively-selected VA patients receiving care 2020–2021 we conducted semi-structured interviews via telephone; interviews were recorded, transcribed and analyzed using a Rapid Assessment Process. Purposive selection was based on HIV status, alcohol and/or tobacco/nicotine use, and demographics. Among participants, 66% reported current smoking, and most screened positive for unhealthy alcohol use. Participants had high awareness of cancer and other health risks related to smoking but low awareness of synergistic risks and cancer risks associated with alcohol use despite awareness of a range of other alcohol-related risks. Awareness of alcohol and/or tobacco/nicotine's impacts on the immune system was variable. Findings did not distinctly differ between PWH and PWoH. Low awareness of alcohol-related cancer risk, risks of co-occurring use, and varying awareness of the impacts of alcohol and tobacco/nicotine on the immune system suggest a need for improved messaging regarding substance use-related cancer and immune risk. This may be especially important among PWH, for whom the prevalence and adverse effects of alcohol and tobacco use, and immune dysfunction are higher. [ABSTRACT FROM AUTHOR]

Purpose: Stressors brought on by the pandemic may have further encouraged lesbian, gay, bisexual, transgender, queer, and intersex plus (LGBTQI +) cancer survivors to smoke. The purpose of this study is to examine factors associated with smoking among LGBTQI + cancer survivors during the pandemic. Methods: We used a secondary data analysis of OUT: The National Cancer Survey. We conducted logistic regression analysis to examine the associations between psychological distress, binge drinking, and socio-demographic factors with ever use and current use of cigarettes, other tobacco, and nicotine products. Results: Of the 1629 participants in our sample, 53% used in their lifetime and 13% reported current use. Correlates of increased ever use included being of older age (AOR = 1.02; 95% CI: 1.01, 1.03) and binge drinking (AOR = 2.47; 95% CI: 1.17, 5.20) while correlates of decreased ever use were among those with a graduate or professional degree (AOR = 0.40; 95% CI: 0.23, 0.71). Correlates of increased current use included being of Latine descent (AOR = 1.89; 95% CI: 1.07, 3.36), binge drinking (AOR = 3.18; 95% CI: 1.56, 6.48), without health insurance (AOR = 2.37; 95% CI: 1.10, 5.10), and being disabled (AOR = 1.64; 95% CI: 1.19, 2.26) while correlates of decreased current use were among cisgender women (AOR = 0.30; 95% CI: 0.12, 0.77), being of younger age (AOR = 0.98; 95% CI: 0.96, 0.99), and having a graduate or professional degree (AOR = 0.33; 95% CI: 0.15, 0.70). Conclusions: Our findings demonstrate that a proportion of LGBTQI + cancer survivors continue to smoke during the pandemic despite the increased risk involved with smoking. Furthermore, individuals with intersecting marginalized identities experience additional stressors that may have been further exacerbated by the conditions of the pandemic that encourage them to smoke. Implications for Cancer Survivors: Quitting smoking after a cancer diagnosis can decrease the chances of recurrence and a new primary malignancy. In addition, practitioners and researchers should advocate towards examining and addressing systemic forms of oppression in institutions that LGBTQI + cancer survivors navigate during the pandemic. [ABSTRACT FROM AUTHOR]

The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with β-cyclodextrin (β-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-β-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-β-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development. [ABSTRACT FROM AUTHOR]

A method was developed for synthesizing previously unknown hydrazones containing two pharmacophoric fragments in their structure based on the reaction of phenyl/acylhydrazines with 1-(1-tosylpyrrolidin-2-yl)propan-2-one. Structure of the resulting hydrazones was established using 1H, 13C NMR, IR spectroscopy, and mass spectrometry (ESI-TOF) data. Based on 1D/2D correlation NMR experiments, it was found that the resulting hydrazones exist only as E-isomer. [ABSTRACT FROM AUTHOR]

Aim: Much research has been conducted on the acute effects of nicotine on human cognitive performance, demonstrating both enhancing and impairing cognitive effects. With the relatively recent introduction of electronic cigarettes ('e-cigarettes') as a smoking cessation device, little is known about the cognitive effects of e-cigarettes specifically, either as a nicotine replacement device or in the absence of nicotine. The purpose of this review was to present an overview of evidence from empirical studies on the effect of e-cigarettes on cognitive function. Approach: Guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines (PRISMA-ScR), SCOPUS, PubMed, and EBSCOhost were searched from 2006, the year e-cigarettes were introduced, to June 2023 for relevant papers, along with reference lists checked for additional papers. Key findings: Seven experimental and four cross-sectional survey studies were identified and included. The majority of the studies only include regular and current cigarette smokers and primarily assessed the acute cognitive effect of e-cigarettes relative to nicotine. While the findings primarily suggest either no or positive effect of e-cigarettes on cognition in cigarette smokers, associations between e-cigarettes and cognitive impairments in memory, concentration and decision making were reported in both cigarette smokers and never-smokers. Implications and conclusions: The acute cognitive effect of e-cigarettes on regular cigarette smokers appears minimal. However, long-term cognitive effect and their effects on never-smokers are unclear. Given that the increased numbers of e-cigarette users are non-smokers and/or adolescents, research with those naïve to nicotine and a developmentally vulnerable adolescent population on its long-term effect is needed. [ABSTRACT FROM AUTHOR]

Rationale: The 5-choice serial reaction time task (5-CSRTT) is commonly used to assess attention in rodents. Manipulation of this task by decreasing the light stimulus duration is often used to probe attentional capacity and causes a decrease in accuracy and an increase in omissions. However, although a decrease in response accuracy is commonly interpreted as a decrease in attention, it is more difficult to interpret an increase in omissions in terms of attentional performance. Methods: Here we present a series of experiments in rats that seeks to investigate the origins of these key behavioral measures of attention in the 5-CSRTT. After an initial training in the 5-CSRTT, rats were tested in a variable stimulus duration procedure to increase task difficulty and probe visual attentional capacity under several specific controlled conditions. Conclusions: We found that response accuracy reflects visuospatial sustained attentional processing, as commonly interpreted, while response omission reflects rats' ignorance about the stimulus location, presumably due to failure to pay attention to the curved wall during its presentation. Moreover, when rats lack of relevant information, they choose not to respond instead of responding randomly. Finally, pretreatment with nicotine selectively decreased response omissions, without affecting response accuracy, particularly when the attentional demand was high. Overall, our results indicate that response accuracy and response omission thus correspond to two distinct attentional states. [ABSTRACT FROM AUTHOR]

Nicotine (3-(1-methyl-2-pyrrolidinyl)pyridine) is one of the most common addictive substances, causing the trace detection of nicotine to be very necessary. Herein, we designed and prepared a functionalized nanocomposite CS-PAA (NaYF4:19.5%Yb,0.5%Tm@NaYF4-PAA) using a simple method. The nicotine concentration was quantitatively detected through the inhibition of choline oxidase activity by nicotine and the luminescence intensity of CS-PAA being quenched by Fe3+. The mechanism of Fe3+ quenching CS-PAA emission was inferred by luminescence lifetime and UV–vis absorption spectra characterization. During the nicotine detection, both excitation (980 nm) and emission (802 nm) wavelengths of CS-PAA enable the avoidance of the interference of background fluorescence in complicated food objects, thus providing high selectivity and sensitivity with a linear range of 5–750 ng/mL and a limit of detection of 9.3 nM. The method exhibits an excellent recovery and relative standard deviation, indicating high accuracy and repeatability of the detection of nicotine. [ABSTRACT FROM AUTHOR]

Nicotine is one of the main pollutants in cigarette smoke that trapped in the filter. Nicotine leakage from cigarette butts is one of the concerns associated with this hazardous waste. In this study, the concentration of nicotine leaked from cigarette butts into the urban environment was investigated under the influence of three parameters including rainfall, density, and the durability of the littered cigarette butt. The leakage of nicotine into the environment was estimated in six scenarios based on the difference in the durability of cigarette butts in the urban environment and the humidity ratio. The results showed that the density of littered cigarette butts was 0.0019–0.294 number/m2. The density of littered cigarette butts in residential land-use was 52.38% lower than commercial land-use. Nicotine leakage from cigarette butts in commercial, residential, and recreational land-uses was 1.1, 0.484, and.0065 mg/m2, respectively. In the studied scenarios, in the best and worst case, 335,070 and 481,950 gr/year of nicotine will leak from the cigarette butt into the water resources. Considering that cigarette butts are a serious source of toxins including nicotine to the environment, control measures are necessary to reduce its density in the urban environment. [ABSTRACT FROM AUTHOR]

Hispanic/Latinx (hereafter Latinx) persons are an established tobacco disparities population in the United States (US). Past work has suggested that individual differences in anxiety sensitivity, or the fear of arousal-based sensations, is one important cognitive construct for smoking maintenance and relapse among Latinx persons who smoke. However, previous research has not examined if anxiety sensitivity is associated with motivational facets of smoking dependence among this tobacco disparities population. In the current study, anxiety sensitivity was explored in terms of smoking motives for primary, secondary, and overall cigarette dependence. Participants included 336 English-speaking Latinx adults in the US who smoked cigarettes daily (Mage = 35.53, SD = 8.65, 37.3% Female). Results indicated that anxiety sensitivity was statistically significantly and positively related to higher primary and secondary dependence motives and marginally statistically significant to cigarette dependence; findings were evident after adjusting for numerous theoretically relevant variables (e.g., depression). Overall, the current study is the first to document linkages between anxiety sensitivity and numerous motivational bases of tobacco dependence among Latinx persons who smoke from the US. [ABSTRACT FROM AUTHOR]

Lifestyles maybe associated with the immune and inflammatory state of human body. We aimed to comprehensively explore the relationship between lifestyles and circulating immune-inflammatory markers in the general population. Data from NHANES 1999–2014 was used. Lifestyle factors included leisure-time physical activity (LTPA), diet quality (Healthy Eating Index-2015, HEI-2015), alcohol consumption, cigarettes smoking, sleep hour and sedentary time. Immune makers included C-reactive protein (CRP), neutrophil–lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet–lymphocyte ratio (PLR) and monocyte–lymphocyte ratio (MLR). Generalized linear regression models were used to adjust confounders. Regressions of restricted cubic splines were utilized to evaluate the potentially non-linear relationships between exposures and outcomes. As results, HEI was negatively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P < 0.001). Cigarettes per day was positively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P = 0.008). Alcohol consumption was negatively associated with CRP (P < 0.001), but positively associated with PLR (P = 0.012) and MLR (P < 0.001). Physical activity was negatively associated with CRP (P < 0.001), SII (P = 0.005), and NLR (P = 0.002), but positively associated with PLR (P = 0.010). Participants with higher healthy lifestyle score had significantly lower CRP, SII and NLR (all P values < 0.05). Most of the sensitivity analyses found similar results. In conclusion, we found significant associations between lifestyles and immune markers in the general population, which may reflect a systemic inflammatory response to unhealthy lifestyles. [ABSTRACT FROM AUTHOR]

Rationale: Nicotine is a principal psychoactive agent in tobacco, contributing to tobacco's addictive potential. Preclinical studies on the effects of voluntary nicotine intake typically use self-administration procedures that provide continuous nicotine access during each self-administration session. However, many smokers consume cigarettes intermittently rather than continuously throughout each day. For drugs including cocaine and opioids, research in laboratory rats shows that intermittent intake can be more effective than continuous intake in producing patterns of drug use relevant to addiction. Objective: We determined how intermittent versus continuous nicotine self-administration influences nicotine seeking and taking behaviours. Methods: Female and male rats had continuous (i.e., Long Access; LgA, 6 h/day) or intermittent (IntA; 12 min ON, 60 min OFF, for 6 h/day) access to intravenous nicotine (15 µg/kg/infusion), for 12 daily sessions. We then assessed intake, responding for nicotine under a progressive ratio schedule of drug reinforcement and cue- and nicotine-induced reinstatement of drug seeking. We also estimated nicotine pharmacokinetic parameters during LgA and IntA self-administration. Results: Overall, LgA rats took twice more nicotine than did IntA rats, yielding more sustained increases in estimated brain concentrations of the drug. However, the two groups showed similar motivation to seek and take nicotine, as measured using reinstatement and progressive ratio procedures, respectively. Conclusions: Intermittent nicotine use is just as effective as continuous use in producing addiction-relevant behaviours, despite significantly less nicotine exposure. This has implications for modeling nicotine self-administration patterns in human smokers and resulting effects on brain and behaviour. [ABSTRACT FROM AUTHOR]

Analysis of a National Institutes of Health (NIH) trial shows that cigarette smoking protected tissue plasminogen activator (tPA)-treated patients from hemorrhage transformation (HT); however, the underlying mechanism is not clear. Damage to the integrity of the blood-brain barrier (BBB) is the pathological basis of HT. Here, we investigated the molecular events of BBB damage after acute ischemic stroke (AIS) using in vitro oxygen-glucose deprivation (OGD) and in vivo mice middle cerebral artery occlusion (MCAO) models. Our results showed that the permeability of bEND.3 monolayer endothelial cells was significantly increased after being exposed to OGD for 2 h. Mice were subjected to 90-min ischemia with 45-min reperfusion, and BBB integrity was significantly damaged, accompanied by tight junction protein occludin degradation, downregulation of microRNA-21 (miR-21), transforming growth factor-β (TGF-β), phosphorylated Smad (p-Smad), plasminogen activator inhibitor-1 (PAI-1), and the upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that has been shown to regulate TGF-β-Smad3 pathway. In addition, pretreatment with two-week nicotine significantly reduced AIS-induced BBB damage and its associated protein dysregulation via downregulating Pdlim5. Notably, AIS did not significantly induce BBB damage in Pdlim5 deficit mice, but overexpression of Pdlim5 in the striatum with adeno-associated virus produced BBB damage and associated protein dysregulation which could be ameliorated by two-week nicotine pretreatment. More important, AIS induced a significant miR-21 decrease, and miR-21 mimics treatment decreased AIS-induced BBB damage by decreasing Pdlim5. Together, these results demonstrate that nicotine treatment alleviates the AIS-compromised integrity of BBB by regulating Pdlim5. [ABSTRACT FROM AUTHOR]

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects. [ABSTRACT FROM AUTHOR]

While smoking is widely acknowledged as a risk factor for rheumatoid arthritis (RA), the connection between secondhand smoke (SHS) exposure and RA in never-smoking adults remains limited and inconsistent. This study aims to explore and quantify this association using serum cotinine levels. We conducted a cross-sectional study with 14,940 adults who self-report as never smokers, using National Health and Nutrition Examination Survey data from 1999 to 2018. Based on previous literature, SHS exposure was categorized into four groups according to serum cotinine levels. Compared to individuals in the unexposed group (serum cotinine < 0.05 ng/mL), the adjusted odds ratio (OR) for RA was 1.37 (95% CI 1.14–1.64, p = 0.001) in the low exposure group (serum cotinine at 0.05 to 0.99 ng/mL) after adjusting for covariates. However, no significant association was found in the moderate exposure group (serum cotinine at 1 to 10 ng/mL) or the heavy exposure group (serum cotinine ≥ 10 ng/mL). Furthermore, we detected a non-linear, positively saturated correlation between the cotinine levels after log2 transformation and RA, with a turning point at approximately − 2.756 ng/mL (OR = 1.163, 95% CI 1.073–1.261, p = 0.0002). The stability of the results was confirmed by subgroup analysis. [ABSTRACT FROM AUTHOR]

Addiction is a leading cause of disease burden worldwide and remains a challenge in current neuroscience research. Drug-induced lasting changes in gene expression are mediated by transcriptional and epigenetic regulation in the brain and are thought to underlie behavioral adaptations. Emerging evidence implicates astrocytes in regulating drug-seeking behaviors and demonstrates robust transcriptional response to several substances of abuse. This review focuses on the astrocytic transcriptional and epigenetic mechanisms of drug action. [ABSTRACT FROM AUTHOR]

Clinical and preclinical studies have identified immunosuppressive effects of nicotine, with potential implications for treating nicotine addiction. Here we review how nicotine can regulate microglia, the resident macrophages in the brain, and corresponding effects of nicotine on neuroimmune signaling. There is significant evidence that activation of α7 nicotinic acetylcholine receptors (nAChRs) on microglia can trigger an anti-inflammatory cascade that alters microglial polarization and activity, cytokine release, and intracellular calcium concentrations, leading to neuroprotection. These anti-inflammatory effects of nicotine-dependent α7 nAChR signaling are lost during withdrawal, suggesting that neuroimmune signaling is potentiated during abstinence, and thus, heightened microglial activity may drive circuit disruption that contributes to withdrawal symptoms and hyperkatifeia. In sum, the clinical literature has highlighted immunomodulatory effects of nicotine and the potential for anti-inflammatory compounds to treat addiction. The preclinical literature investigating the underlying mechanisms points to a role of microglial engagement in the circuit dysregulation and behavioral changes that occur during nicotine addiction and withdrawal, driven, at least in part, by activation of α7 nAChRs on microglia. Specifically targeting microglial signaling may help alleviate withdrawal symptoms in people with nicotine dependence and help to promote abstinence. [ABSTRACT FROM AUTHOR]

Cigarette smoking is positively and robustly associated with cardiovascular disease (CVD), including hypertension, atherosclerosis, cardiac arrhythmias, stroke, thromboembolism, myocardial infarctions, and heart failure. However, after more than a decade of ENDS presence in the U.S. marketplace, uncertainty persists regarding the long-term health consequences of ENDS use for CVD. New approach methods (NAMs) in the field of toxicology are being developed to enhance rapid prediction of human health hazards. Recent technical advances can now consider impact of biological factors such as sex and race/ethnicity, permitting application of NAMs findings to health equity and environmental justice issues. This has been the case for hazard assessments of drugs and environmental chemicals in areas such as cardiovascular, respiratory, and developmental toxicity. Despite these advances, a shortage of widely accepted methodologies to predict the impact of ENDS use on human health slows the application of regulatory oversight and the protection of public health. Minimizing the time between the emergence of risk (e.g., ENDS use) and the administration of well-founded regulatory policy requires thoughtful consideration of the currently available sources of data, their applicability to the prediction of health outcomes, and whether these available data streams are enough to support an actionable decision. This challenge forms the basis of this white paper on how best to reveal potential toxicities of ENDS use in the human cardiovascular system—a primary target of conventional tobacco smoking. We identify current approaches used to evaluate the impacts of tobacco on cardiovascular health, in particular emerging techniques that replace, reduce, and refine slower and more costly animal models with NAMs platforms that can be applied to tobacco regulatory science. The limitations of these emerging platforms are addressed, and systems biology approaches to close the knowledge gap between traditional models and NAMs are proposed. It is hoped that these suggestions and their adoption within the greater scientific community will result in fresh data streams that will support and enhance the scientific evaluation and subsequent decision-making of tobacco regulatory agencies worldwide. Models for Cardiovascular Toxicity Testing E-cigarettes and nicotine delivery systems can be examined using multiple model systems. In silico models might predict adverse cardiovascular effects that can be screened for using 2-D and 3-D models using induced pluripotent stem cell (iPSC) derived cardiac tissue and "omics" profiling such as single-cell RNA sequencing (scRNA-seq) or high-throughput functional analysis with a multiple electrode array (MEA). Biologic plausibility of detected effects can be corroborated using ex vivo or in vivo models, which may also lead to the discovery of new biomarkers or treatments for CVD. [ABSTRACT FROM AUTHOR]

Tobacco smoking is a prevalent and detrimental habit practiced worldwide, increasing the risk of various diseases, including chronic obstructive pulmonary disease (COPD), cardiovascular disease, liver disease, and cancer. Although previous research has explored the detrimental health effects of tobacco smoking, recent studies suggest that gut microbiota dysbiosis may play a critical role in these outcomes. Numerous tobacco smoke components, such as nicotine, are found in the gastrointestinal tract and interact with gut microbiota, leading to lasting impacts on host health and diseases. This review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and functionality. We also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host health. Furthermore, this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers. [ABSTRACT FROM AUTHOR]

The gradual nature of age-related neurodegeneration causes Parkinson's disease (PD) and impairs movement, memory, intellectual ability, and social interaction. One of the most prevalent neurodegenerative conditions affecting the central nervous system (CNS) among the elderly is PD. PD affects both motor and cognitive functions. Degeneration of dopaminergic (DA) neurons and buildup of the protein α-synuclein (α-Syn) in the substantia nigra pars compacta (SNpc) are two major causes of this disorder. Both UPS and ALS systems serve to eliminate α-Syn. Autophagy and UPS deficits, shortened life duration, and lipofuscin buildup accelerate PD. This sickness has no cure. Innovative therapies are halting PD progression. Bioactive phytochemicals may provide older individuals with a natural substitute to help delay the onset of neurodegenerative illnesses. This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction. At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS. We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Not all pregnant individuals want to become parents and "parenting intention" can also vary within individuals during different pregnancies. Nevertheless, the potential impact of parenting intention on health-related behavior during pregnancy has been heavily underexplored. In this study, we employed a within-person between pregnancy design to estimate the effect of parenting-specific influences on smoking, separate from pregnancy-specific and individual-level influences. We quantified within-mother differences in smoking during pregnancies of infants they reared (n = 84) versus pregnancies of infants they placed for adoption at birth (n = 65) using multivariate mixed-effects Poisson regression models. Mean cigarettes/day declined as the pregnancy progressed regardless of whether infants were reared or placed. However, participants smoked fewer cigarettes/day during reared pregnancies. Relative to "adopted" pregnancies, smoking during "reared" pregnancies was lower by 24%, 41%, and 54% in first (95% CI 0.64–0.90; p = 0.001), second (95% CI 0.48–0.72; p < 0.001), and third trimesters (95% CI 0.36–0.59; p < 0.001), respectively, independent of between-pregnancy differences in maternal age, fetal sex, parity, and pregnancy complications. Female sex and nulliparity were protective. Parenting intention was associated with a protective effect on pregnancy smoking independent of pregnancy-specific influences and individual characteristics. Failure to consider the impact of parenting intention on health-related behavior during pregnancy could perpetuate an unrealistic expectation to "do what's best for the baby" and stigmatize women with unintended or unwanted pregnancies. [ABSTRACT FROM AUTHOR]

Previous reviews of smoking prevalence among individuals with primary psychosis have largely been internationally focused, with little attention given to within- and among subgroup comparisons of U.S. individuals with such disorders. Nationally, smoking prevalence has been decreasing among the general population. We aimed to review national and divisional samples to determine if this downward trend is being reflected among individuals with primary psychotic disorders, if geographical differences exist, and which demographic characteristics are associated with reported rates. We conducted a systematic search of the PubMed, PsycINFO, and Cochrane databases using a floor of 2010. Studies found during a review of references, and studies previously known to the authors but not found during the initial search, were also reviewed. We found 7 papers which reported the prevalence of smoking among individuals with psychotic disorders, and 2 papers which reported the prevalence of general tobacco and/or vaped nicotine use in this population. One eligible paper was excluded due to the same authors publishing more recent data of the same sample. In all, 1 national and 7 divisional samples were included for analysis. Individuals with psychotic disorders still smoke at rates far higher than the general population. We did not find strong support for a downward trend in smoking in this population but did find support for geographical heterogeneity. Smoking interventions must be tested and implemented nationwide. [ABSTRACT FROM AUTHOR]

Several countries have exempted synthetic nicotine from existing regulatory frameworks, resulting in the widespread substitution of synthetic nicotine (SN) in almost all e-cigarette products available. However, it remains uncertain whether the purported synthetic nicotine is indeed genuine SN. There is a need to develop biological indicators and an analytical method that more clearly distinguishes between the two sources. Impurities in neat tobacco-derived nicotine (TDN) were characterized and identified through non-targeted and targeted analysis. Gas chromatography-tandem mass spectrometry (GC–MS/MS) conditions were optimized for detecting biological indicators in e-cigarette products. Nine tobacco-related alkaloids were identified and selected as biological indicators for TDN. A liquid–liquid extraction and GC–MS/MS quantitative method were developed to detect nine biological indicators in e-cigarette products with the limit of quantification ranging from 0.2 to 4.2 µg L−1 using 0.5 mL of e-liquid. This method was applied to 50 e-cigarette brands purchased in the Korean market. The developed method was able to easily and accurately identify the origin of nicotine even using a small amount of e-liquid sample. It is expected that effective e-cigarette regulation will be possible if the nicotine biological indicator and high-sensitivity analysis method developed in this study are used. [ABSTRACT FROM AUTHOR]

The gender role influences vulnerability to mental illness. Substance use, even critical in scale, is perceived as masculine, just like hard (over-)work, while not seeking help. With the ongoing separation between gender and sex, masculine norms become more relevant also to females' mental health. The male depression concept highlights the role of male symptoms in affective disorders. However, the empirical evidence is still limited. Here, we use the denomination 'masculine depression' to open the category for female patients and tested substance use patterns, health services' utilization, and working hours as predictors in a case–control study of 163 depressed in-patients (44% women; masculine vs. non-masculine depression according to a median split of the Male Depression Rating Scale-22) and 176 controls (51% women). We assessed higher depression severity in patients with masculine (vs. non-masculine) depression. Masculine depression (vs. non-masculine depression and vs. no depression) was predicted by more frequent and critical use of alcohol (including binge drinking), tobacco, and illicit drugs, and by longer working times. Moreover, fewer health services contacts due to mental complaints during the previous year were associated with masculine (vs. non-masculine) depression. Alarmingly, even critical substance misuse was not significantly associated with more frequent health services contacts; however, the higher the depression severity, the more contacts the patients reported. Here, we provide evidence that patients with masculine depression are highly burdened and undertreated, which applies equally to female and male patients. This study identified promising targets to establish specialized care offers. [ABSTRACT FROM AUTHOR]

Rationale: Use of electronic drug delivery systems (EDDS, "e-cigarettes") to ingest nicotine and Δ9-tetrahydrocannabinol (THC) has surged in adolescents in the USA; five times as many high-school seniors vape nicotine daily using tobacco. At the same time, 19.5% of seniors use cannabis at least monthly, with 12% using EDDS to deliver it. Objectives: This study was conducted to examine the impact of repeated adolescent vapor inhalation of nicotine and THC in rats. Methods: Female Sprague–Dawley rats were exposed to 30-min sessions of vapor inhalation, twice daily, from post-natal day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle, nicotine (60 mg/mL in the PG), THC (100 mg/mL in the PG), or the combination of nicotine (60 mg/mL) and THC (100 mg/mL). Rats were assessed on wheel activity, heroin anti-nociception and nicotine and heroin vapor volitional exposure during adulthood. Results: Nicotine-exposed rats exhibited few differences as adults, but were less sensitive to anti-nociceptive effects of heroin (1 mg/kg, s.c.). THC- and THC + nicotine–exposed rats were less spontaneously active, and obtained fewer nicotine vapor deliveries as adults. In contrast, THC-exposed rats obtained volitional heroin vapor at rates indistinguishable from the non-THC-exposed groups. Repeated THC exposure also caused tolerance to temperature-disrupting effects of THC (5 mg/kg, i.p.). Conclusions: These studies further confirm that the effects of repeated vapor exposure to THC in adolescence last into early to middle adulthood, including decreased volitional consumption of nicotine. Effects of repeated nicotine in adolescence were comparatively minor. [ABSTRACT FROM AUTHOR]

Electronic cigarettes (ECs) have gained popularity among the general public. ECs have varying nicotine levels from one e-liquid to another. Thus, a standardised method for analysing the nicotine content in e-liquids is needed. Here, a method was developed for quantitative analysis using high-performance liquid chromatography (HPLC) with mechanical agitation (MA). The same elution conditions were applied without mechanical agitation (WMA) to investigate the effect of processing on nicotine separation efficiency. The proposed method resulted in increased linearity in a concentration range of 25–500 ppm. This method also resulted in an increase in the correlation coefficient from 0.2415 to 0.9991, with a limit of detection (LOD) and limit of quantification (LOQ) of 0.09 ppm and 0.29 ppm, respectively, making it more applicable to a wide range of e-liquids in domestic and foreign markets. The analysis of seven e-liquids with concentrations of 0–50 mg/mL revealed that 67% of the samples had a lower nicotine content than that stated on the label. The opposite was true for 33% of samples. No sample matched the nicotine content stated on the label. A sample that was claimed to contain 3 mg/mL actually contained 17 mg/mL. Moreover, a sample labelled as nicotine-free contained 7 mg/mL of nicotine. Another sample was claimed to contain 50 mg/mL, but the measured value was 24 mg/mL. This value exceeds the Saudi Food and Drug Administration (SFDA) standard, which specifies that e-liquids should not contain more than 20 mg/mL of nicotine. [ABSTRACT FROM AUTHOR]

Addictive behaviors are characterized by information processing biases, including substance-related interpretation biases. In the field of cigarette smoking, such biases have not been investigated yet. The present study thus adopted an open-ended scenario approach to measure smoking-related interpretation biases. Individuals who smoke, those who ceased smoking, and those without a smoking history (total sample N = 177) were instructed to generate spontaneous continuations for ambiguous, open-ended scenarios that described either a smoking-related or neutral context. Overall, people who smoke generated more smoking-related continuations in response to smoking-relevant situations than non-smoking individuals or people who had stopped smoking, providing evidence for a smoking-related interpretation bias. When differentiating for situation type within smoking-relevant scenarios, smoking individuals produced more smoking-related continuations for positive/social and habit/addictive situations compared to negative/affective ones. Additionally, the tendency to interpret habit/addictive situations in a smoking-related manner was positively associated with cigarette consumption and levels of nicotine dependence. Exploratory analyses indicated that other substance-related continuations were correlated with their respective behavioral counterparts (e.g., the level of self-reported alcohol or caffeine consumption). The present study is the first to demonstrate smoking-related interpretation biases in relation to current cigarette smoking. Future studies should investigate the causal role of such biases in the initiation and/or maintainance of nicotine addiction and the merit of Interpretation-Bias-Modification training to support smoking cessation. [ABSTRACT FROM AUTHOR]

Smoking is a major environmental factor causing nearly a third of cancer-related deaths. Nicotine accounts for 95% of tobacco's alkaloid content and 1.5% of the commercial cigarette products weight. With most cigarettes containing 1.2–2.9 mg of nicotine, heavy smokers can absorb 20–40 mg/day, resulting in plasma concentrations of 23–35 ng/ml. Nicotine exert potential oncogenic effects primarily through nicotinic acetylcholine receptors, without involving signal pathways or other receptors. Recent reviews have recognized the relationship between nicotine and a certain type of tumor. However, there is no systematic overview on the signal pathways related to nicotine via receptors or non-receptors in a variety of tumors. This review discusses emerging evidence of the relationship between cancer progression and nicotine. The list of cancers reportedly connected to nicotine is expanding and presently contains lung carcinoma, as well as cervical, colon, gastric, pancreatic, breast, liver, bladder, head and neck cancers including nasopharynx, tongue and oral cavity. There is growing evidence through the use of animal xenograft models and cell culture systems, that (1) nicotine's carcinogenic role stems from multiple signaling mechanisms, primarily involving both non-receptor-mediated actions and receptor-mediated effects, including nicotinic acetylcholine receptors, β-adrenergic receptors and epidermal growth factor receptors, as well as transforming growth factor β receptors; (2) nicotine could induce chromosomal abnormalities, DNA damage, and micronuclei formation; (3) nicotine also can enhance oxidative stress, leading to tumor initiation or progression due to excessive production of reactive oxygen species. Based on these findings, nicotine seems to be a potent oncogenic agent in modulating tumor cell proliferation, invasion and migration by various signaling pathways associated with chemical carcinogenicity. [ABSTRACT FROM AUTHOR]

Background: Co-use of cannabis is increasing in nicotine users and presents additional challenges in addressing nicotine dependence. This study examined the links between regular co-use of cannabis and nicotine with biobehavioral and affective changes in response to stress during nicotine withdrawal and ad libitum use. Methods: Participants (N = 79) who regularly used nicotine-only, cannabis-only, both substances, or neither substance were invited to attend two laboratory stress assessment sessions. For nicotine users, one session occurred during ad libitum nicotine use and one occurred after abstinence from nicotine. During the stress sessions, participants provided saliva samples for cortisol assay and completed measures of subjective states. Cardiovascular measures were collected during resting baseline, exposure to acute stressors, and a recovery rest period. Results: Nicotine-only users had higher average cortisol levels in the second lab session (nicotine withdrawal) relative to the first lab session (ad libitum nicotine use). Compared to nicotine non-users, nicotine users reported less positive affect and exhibited attenuated cortisol and systolic blood pressure (BP) stress responses. Cannabis users exhibited exaggerated diastolic BP responses to stress compared to cannabis non-users, and co-users of nicotine and cannabis had higher levels of cannabis craving than cannabis-only users (p <.01). Conclusions: This study partially replicated earlier findings on the effects of chronic nicotine use and provided novel results regarding the influence of cannabis co-use on physiological and affective responses to stress in nicotine users during nicotine withdrawal. [ABSTRACT FROM AUTHOR]

Nicotine and tobacco product (NTP) use remains prevalent in adolescence/young adulthood. The effects of NTPs on markers of brain health during this vulnerable neurodevelopmental period remain largely unknown. This report investigates associations between NTP use and gray matter cerebral blood flow (CBF) in adolescents/young adults. Adolescent/young adult (16–22 years-old) nicotine users (NTP; N = 99; 40 women) and non-users (non-NTP; N = 95; 56 women) underwent neuroimaging sessions including anatomical and optimized pseudo-continuous arterial spin labeling scans. Groups were compared on whole-brain gray matter CBF estimates and their relation to age and sex at birth. Follow-up analyses assessed correlations between identified CBF clusters and NTP recency and dependence measures. Controlling for age and sex, the NTP vs. non-NTP contrast revealed a single cluster that survived thresholding which included portions of bilateral precuneus (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥7 contiguous voxels). An interaction between NTP group contrast and age was observed in two clusters including regions of the left posterior cingulate (PCC)/lingual gyrus and right anterior cingulate cortex (ACC): non-NTP exhibited positive correlations between CBF and age in these clusters, whereas NTP exhibited negative correlations between CBF and age. Lower CBF from these three clusters correlated with urine cotinine (rs=-0.21 – − 0.16; ps < 0.04) and nicotine dependence severity (rs=-0.16 – − 0.13; ps < 0.07). This is the first investigation of gray matter CBF in adolescent/young adult users of NTPs. The results are consistent with literature on adults showing age- and nicotine-related declines in CBF and identify the precuneus/PCC and ACC as potential key regions subserving the development of nicotine dependence. [ABSTRACT FROM AUTHOR]

Dexpanthenol (DEX), a subtype of vitamin B5, plays an important role in anabolic reactions, cellular energy and regeneration in the body. Nicotine has been shown to induce kidney damage through the mechanisms of oxidative stress and apoptosis. The purpose of this study was to investigate the potential protective effects of DEX against nicotine-induced kidney damage through modulation of the AKT/Nrf2/HO-1 signaling pathway. Male rats were intraperitoneally administered with 0.5 mg/kg/day nicotine and/or 500 mg/kg/day DEX for 8 weeks. Following administration, renal function tests were conducted on serum samples, and histopathological examinations and analysis of oxidative stress markers and antioxidant enzymes were performed on tissue samples. Protein levels of Akt, Nrf-2, HO-1, Bcl-xL, and Caspase-9 were also evaluated. Nicotine administration resulted in decreased protein levels of p-Akt, Nrf-2, HO-1, and Bcl-xL and increased Caspase-9 protein levels. In addition, nicotine administration caused an increase in MDA, TOS, and OSI levels and a decrease in GSH, GSH-Px, GST, CAT, SOD, and TAS levels. Additionally, BUN and Creatinine levels increased after nicotine administration. DEX administration positively regulated these parameters and brought them closer to control levels. Nicotine-induced kidney injury caused apoptosis and oxidative stress through Caspase-9 activation. DEX effectively prevented nicotine-induced kidney damage by increasing intracellular antioxidant levels and regulating apoptosis through Bcl-xL activation. These findings suggest that DEX has potential as a protective agent against nicotine-induced kidney damage. [ABSTRACT FROM AUTHOR]

Vascular calcification (VC) is a major risk factor for cardiovascular events. A mutual interplay between inflammation, oxidative stress, apoptosis, and autophagy is implicated in its development. Herein, we aimed to evaluate the potential protective effects of canagliflozin in a vitamin D3 plus nicotine (VDN) model of VC, and to explore potential mechanisms. VC was induced by VDN in adult male Wistar rats on day one. Then, rats were randomly assigned into three groups to receive canagliflozin (10 mg or 20 mg/kg/day) or its vehicle for 4 weeks. Age-matched normal rats served as a control group. After euthanization, aorta and kidneys were harvested for biochemical and histopathological evaluation of calcification. Aortic markers of oxidative stress, alkaline phosphatase (ALP) activity, runt-related transcription factor (Runx2) and bone morphogenic protein-2 (BMP-2) levels were determined. Additionally, the protein expression of autophagic markers, LC3 and p62, and adenosine monophosphate activated protein kinase (AMPK) were also assessed in aortic homogenates. Canagliflozin dose-dependently improved renal function, enhanced the antioxidant capacity of aortic tissues and reduced calcium deposition in rat aortas and kidneys. Both doses of canagliflozin attenuated ALP and osteogenic markers while augmented the expression of autophagic markers and AMPK. Histopathological examination of aortas and kidneys by H&E and Von Kossa stain further support the beneficial effect of canagliflozin. Canagliflozin could alleviate VDN-induced vascular calcification, in a dose dependent manner, via its antioxidant effect and modulation of autophagy. Further studies are needed to verify whether this effect is a member or a class effect. [ABSTRACT FROM AUTHOR]

Aim: Although people with mental illness show a greater severity of nicotine dependence and have a significantly reduced life expectancy because of it, psychiatric staff rarely offer their patients smoking cessation support and are reluctant to encourage patients to quit. In order to improve smoking cessation treatment for psychiatric patients, such staff resistance must be better understood. Subjects and methods: A total of 448 members of staff in eight psychiatric units in Berlin were surveyed in relation to their attitudes towards smoking cessation. Results: Although most participants recognize the importance of smoking cessation in psychiatric patients, they state that they do not adhere to international guidelines which recommend regularly asking patients about their smoking habits and offering cessation support. Staff have little knowledge about how to facilitate smoking cessation treatment and about the influences of smoking on the metabolism of drugs. They also harbor misconceptions about how smoking affects their patients' mental well-being. Many express concern that a quit attempt might thwart psychiatric treatment and lead to aggressive behavior—assumptions unsupported by scientific evidence. The overwhelming majority does not believe it to be realistic that patients can manage to give up smoking during treatment. Conclusions: Staff training should be directed to heighten awareness of the international guidelines and treatment options for smoking cessation and impart knowledge on how smoking impacts both the physical and mental health of psychiatric patients. [ABSTRACT FROM AUTHOR]

Background: Smoking is a major preventable risk factor for cardiovascular morbidity and mortality. Tobacco smoking induces atherosclerosis, ischemic heart diseases, and arrhythmias. The impact of electronic cigarettes on cardiovascular health is still controversial. This study aimed to evaluate the electrocardiographic parameters in chronic electronic cigarette users compared to chronic conventional cigarette smokers and a non-smoker control group of matched age and gender. Results: The study involved 105 volunteers with no history of chronic or cardiovascular diseases or cardioactive drug use. Participants were assigned into three study groups, chronic e-cigarette users, conventional cigarette smokers, and non-smokers, each consisting of 35 participants. Demographic data, smoking history, vital signs, and 12-lead electrocardiogram (ECG) were evaluated. Demographic data were insignificantly different among all study groups. The mean heart rate was significantly higher in chronic electronic cigarette users and conventional cigarette smokers compared to non-smokers (p < 0.001).QRS complex duration was significantly shorter in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). Prolonged QT and QTc intervals duration were recorded in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). All the ventricular repolarization indices (T wave—peak to T-end (Tpe) interval, TPe/QT ratio, and TPe/QTc ratio were significantly prolonged in chronic e-cigarette users, and conventional smokers compared to non-smokers (p < 0.001). Mean systolic, diastolic blood pressure, P wave amplitude and duration, and PR interval were insignificantly different between all groups (P > 0.05). Conclusions: Chronic e-cigarette use is associated with higher heart rates, shorter QRS complex, prolonged QT, QTc duration, and prolonged ventricular repolarization indices compared to non-smokers of matched age and gender. Conclusively, e-cigarette use is associated with negative cardiovascular effects like conventional cigarette smoking. [ABSTRACT FROM AUTHOR]

Nicotine-loaded polyvinyl alcohol (PVA) nanofibers were successfully produced by the electrospinning technique. Nicotine-loaded PVA solutions of varying concentrations were prepared, and their chemical composition, conductivity, and viscosity were determined using attenuated total reflectance-Fourier transform infrared spectroscopy and a rheometer. The formulations were spun at flow rates of 0.4 mL/h with a fixed voltage of 11 kV. A scanning electron microscope was then used to characterize the morphology and diameters of electrospun mats. Differential scanning calorimetry and thermogravimetric analysis were used to investigate the thermal properties and structural changes during the oxidative stabilization process. From the result, conductivity and viscosity decreased with decreasing nicotine concentrations, resulting in smooth and nonbeaded nanofibers. In contrast, as the nicotine solution concentration increases, beaded nanofibers with smaller diameter fibers are produced, resulting in a smaller average fiber diameter. The average fiber diameter of different nicotine concentrations at 0%, 0.5%, 1.0%, 1.5%, and 2.0% solution were found to be 348.05 ± 71.42 nm, 439.73 ± 48.16 nm, 415.36 ± 41.41 nm, 348.07 ± 71.42 nm, and 317.42 ± 42.45 nm respectively. The release test exhibits Higuchi's release kinetics with about 95% nicotine released over 6 h at a monophasic flux of 0.152 mg/cm2/h1/2. This study indicates that nicotine-loaded nanofibers are a potential candidate as a transdermal patch for smoking cessation. [ABSTRACT FROM AUTHOR]

Epidemiological studies and clinical observations suggest that nicotine, a major contributor of the global burden of disease, acts in a partially sex specific manner. Still, preclinical research has primarily been conducted in males. More research is thus required to define the effects displayed by nicotine on the female brain. To this end, female rats received 15 injections of either nicotine (0.36mg/kg) or saline, over a 3-week period and were then followed for up to 3 months. Behavioral effects of nicotine were assessed using locomotor activity measurements and elevated plus maze, while neurophysiological changes were monitored using ex vivo electrophysiological field potential recordings conducted in subregions of the dorsal and ventral striatum. Behavioral assessments demonstrated a robust sensitization to the locomotor stimulatory properties of nicotine, but monitored behaviors on the elevated plus maze were not affected during acute (24 h) or protracted (3 months) withdrawal. Electrophysiological recordings revealed a selective increase in excitatory neurotransmission in the nucleus accumbens shell and dorsomedial striatum during acute withdrawal. Importantly, accumbal neuroadaptations in nicotine-treated rats correlated with locomotor behavior, supporting a role for the nucleus accumbens in behavioral sensitization. While no sustained neuroadaptations were observed following 3 months withdrawal, there was an overall trend towards reduced inhibitory tone. Together, these findings suggest that nicotine produces selective transformations of striatal brain circuits that may drive specific behaviors associated with nicotine exposure. Furthermore, our observations suggest that sex-specificity should be considered when evaluating long-term effects by nicotine on the brain. [ABSTRACT FROM AUTHOR]

Ethylene oxide (EtO) is a widely used industrial chemical with recognized health risks. While its carcinogenic properties have been extensively studied, emerging evidence suggests potential associations with cardiovascular diseases. Using the recently introduced Life's Essential 8 (LE8) score as a comprehensive cardiovascular health (CVH) measure, this study aimed to elucidate the relationship between EtO exposure and CVH. Data from the National Health and Nutrition Examination Survey (NHANES) encompassing 3748 adults was analyzed. CVH was assessed using the LE8 score, which incorporates diet, physical activity, tobacco/nicotine exposure, sleep duration, BMI, non-HDL cholesterol, blood glucose, and blood pressure. The association between EtO exposure, gauged by Hemoglobin adduct (HbEtO) levels, and CVH was examined using linear regression and Cox regression models. An inverse relationship between EtO exposure and the overall CVH score was identified. Specifically, for every 1-unit increase in ln-transformed HbEtO, a 3.69-point decrease in the total CVH score was observed. An inverted J-shaped association between ln-transformed HbEtO and CVH score emerged, with an inflection point at 3.15 pmol/g Hb. Elevated EtO exposure was not significantly linked to all-cause mortality but was robustly associated with increased cardiovascular mortality. Elevated EtO exposure is negatively associated with CVH, as outlined by the LE8 metrics. Beyond a certain threshold, this association underscores the cardiovascular risks of EtO exposure and highlights the importance of further research to determine underlying mechanisms and recommend preventive strategies. [ABSTRACT FROM AUTHOR]

This study sought to understand reactions to very low nicotine (VLN) cigarette advertising compared with conventional cigarette advertising with consideration of warning labels and social media context. The online experimental study recruited young adult cigarette smokers and nonsmokers (N = 1,608). Participants completed a discrete choice task with a 2 × 2 × 3 mixed design: brand, (VLN, Marlboro), context (Ad only, Ad on social media), and warning (Text-only, Well-known risk pictorial, or Lesser-known risk pictorial). Participants made choices about attention, appeal, harm, buying, and quitting intentions. Social media context increased attention and appeal. A well-known risk pictorial warning outperformed a text-only warning. Smokers had increased odds of quit intentions for VLN ads, yet nonsmokers had increased intentions to buy cigarettes on social media with a text-only warning. Results indicate differences in how young adults react to cigarette ads on social media, especially with the warnings they portray. [ABSTRACT FROM AUTHOR]

Objective: Smoking cessation for individuals with Chronic Obstructive Pulmonary Disease (COPD) is medically critical, but smoking for coping motives is a common barrier. Method: In this evaluation of three treatment components (Mindfulness, Practice Quitting, and Countering Emotional Behaviors), we conducted two studies guided by the ORBIT model. Study 1 was a single-case design experiment (N = 18); Study 2 was a pilot feasibility study (N = 30). In both studies, participants were randomized to receive one of the three treatment modules. Study 1 examined implementation targets, changes in smoking for coping motives, and changes in smoking rate. Study 2 examined overall feasibility and participant-rated acceptability, and changes in smoking rate. Results: Study 1: Treatment implementation targets were met by 3/5 Mindfulness participants, 2/4 Practice Quitting participants, and 0/6 Countering Emotional Behaviors participants. The Practice Quitting condition led to 100% of participants meeting the clinically significant threshold in smoking for coping motives. Incidence of quit attempts ranged from 0–50%, and smoking rate was reduced by 50% overall. Study 2: Recruitment and retention met feasibility targets, with 97% of participants completing all four treatment sessions. Participants reported high treatment satisfaction by qualitative responses and rating scales (M = 4.8/ 5.0). Incidence of quit attempts ranged from 25–58%, and smoking rate was reduced by 56% overall. Conclusions: These two small-N studies provide complementary findings on internal validity and implementation of the novel intervention. While Study 1 provided initial support for plausibility of clinically significant change, Study 2 provided data on key feasibility parameters. Implications: Smoking cessation for individuals with COPD is medically critical. We conducted an early-phase evaluation of a novel behavioral treatment focused on reducing smoking for coping motives. Results provided initial support for plausibility of clinically significant change and feasibility of the intervention. [ABSTRACT FROM AUTHOR]

Background: Tramadol is one of the most commonly abused substances in the Middle East. Furthermore, smoking is extremely common among the population. Methods: An experimental study was performed on Sprague–Dawley rats to explore the effects of both nicotine and tramadol on the liver and testes. The tramadol was administered at 10 and 20 mg/kg, respectively, while the nicotine was administered at 125 mg/kg. Histological examination and androgen receptor ELISA assay showed mild effects on the liver and proofed safety on the testis. Western blot analysis of BIP (immunoglobulin heavy-chain binding protein) and CHOP (CCAAT-enhancer-binding protein homologous protein) revealed that fewer problems were induced by adding nicotine to tramadol. Autophagy marker LCIII and apoptosis marker caspase-8 showed similar effects to CHOP and BIP on liver samples. The real-time PCR of BIP expression showed similar but not identical results. Conclusions: The results showed mild endoplasmic reticulum stress, autophagy, and apoptosis in the liver samples. Histological examination revealed stable spermatogenesis with average androgen receptor blood levels in the different groups. [ABSTRACT FROM AUTHOR]

Objective: The present study aims to find occupational health hazards during agricultural operations performed by tobacco farmworkers and their relationship with different personal and occupational parameters. Methods: A study was carried out among 120 tobacco farmworkers in Andhra Pradesh, India. Two soil regions (Northern light and Southern light soils) were selected based on the Tobacco Board of India (2019–20) to collect data through personal interviews with the help of a developed survey proforma. Gender-stratified and odds ratio (OR) analyses were used to examine variables associated with occupational health problems. Results: Tobacco farm workers frequently experienced symptoms of Green Tobacco Sickness (GTS), namely headache (14.2%), nausea (11.7%), dizziness and increased sweating (9.2%), weakness (7.5%), exposed running eyes (2.5%), and breathing difficulty (1.7%). They also occasionally had skin diseases, with the highest percentage of allergy (4.2), itching (3.33), rashes (2.5), and 1.0 % for superficial wounds, contact dermatitis, and traumatic skin lesions. The odds ratio (OR > 1) exposure was associated with higher odds of outcome; the values for the female gender, age (20–40 years), working months (1 to 4) per year, protective clothes, without protective gloves, headcovers, and footwear were 2.22, 1.80, 1.28, 5.39, 4.15, 3.39, and 5.78, respectively, showing higher odds of GTS. Conclusions: GTS symptoms are a common illness that causes discomfort and loss of productivity. In tobacco cultivation, few operations involve working with bare hands, making the workers vulnerable to nicotine absorption and skin diseases. Few injuries were observed associated with the loading and unloading of tobacco leaves during curing in the barns. To prevent occupational health hazards, development of appropriate, cost-effective interventions suitable for farmworkers is needed, along with creating awareness of the potential hazards among them. [ABSTRACT FROM AUTHOR]