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We assessed access to vaping products and types of products used and the factors associated with vaping and smoking among young people in the state of New South Wales (NSW), Australia.A cross-sectional survey was conducted with a sample of 721 young people aged 14 to 17 years from NSW recruited through online panels. Poisson regression with robust variance was used to estimate relative risks of ever-vaping and ever-smoking.Almost one-third of the sample (32%, n=233) reported being an ever-vaper, of which more than half (54%) had never smoked prior to starting vaping. Ever-vaping was independently associated with age and being Aboriginal or Torres Strait Islander, and ever-smoking was independently associated with being male. Ever-smokers were seven times more likely to be ever-vapers than those who had never smoked, and ever-vapers were 18 times more likely to be ever-smokers than those who had never vaped. Among ever-vapers who reported which type of device they were using, 86% reported the use of disposable products. "Flavourings and taste" was rated as the most important characteristic of vapes. More than half of ever-vapers reported getting the last vape they used from their friends (55%, n=130). More than half of ever-vapers had used a vape that they knew contained nicotine (53%, n=123).Vaping was the strongest risk factor for smoking, and vice versa, suggesting there is not a straightforward, unidirectional relationship between vaping and smoking in young people. Young people appear to be readily accessing nicotine vaping products, which are often disposable and flavoured, through both social and commercial channels.Stronger enforcement of federal and state policies designed to protect young people from vaping products is urgently needed.

Tobacco smoking is reputed to be the most difficult addiction of all to give up, and nicotine has been noted as the major addictive agent in tobacco smoke. However, research shows that nicotine addiction is due to more than nicotine alone. One hypothesis is that monoamine oxidase (MAO) inhibition from non-nicotinic components in, or derived from, tobacco smoke contributes to nicotine addiction. Harman and norharman, have been recognised as major and potent MAO inhibitors in tobacco smoke, but these two inhibitors together comprise perhaps less than 10% of the total MAO A inhibitory activity in cigarette smoke suggesting other unidentified components may make significant contributions to total inhibitory activity. Therefore, we reviewed an index of the chemical components of tobacco and tobacco smoke and identified those known to be MAO inhibitors. Amongst these inhibitors, phenols and phenolic acids with MAO inhibitory activity are commonly reversible and selective MAO A inhibitors, whereas trans,trans-farnesol, 2-methyl-1,4-naphthoquinone (menadione), 1,4-naphthoquinone, scopoletin, and diosmetin with MAO inhibitory activity are reversible and selective MAO B inhibitors. The compound, 1,4-benzoquinone is an irreversible MAO A inhibitor and to the best of our knowledge, this is the first irreversible MAO A inhibitor to be reported in tobacco smoke. MAO inhibitors have been used clinically to treat depression, anxiety, and Parkinson's disease. The MAO inhibitors identified from tobacco and tobacco smoke and summarized in this review, are potential pharmacological candidates to be investigated further. This review will enhance our knowledge of the way tobacco smoke affects MAO activity in smokers and will also be important in helping to understand nicotine addiction.

Neural oscillations at specific frequency bands are associated with cognitive functions and can identify abnormalities in cortical dynamics. In this study, we analyzed EEG signals recorded from auditory and frontal cortex of awake mice across young, middle and old ages, and found multiple robust and novel age-related changes in cortical oscillations. Notably, resting, evoked, and induced gamma power diminished with age, with some changes observed even in the middle age groups. Inter-trial phase coherence of responses to time-varying stimuli is reduced in old mice. Movement-related modulation of gamma power is reduced in old mice. An acute injection of nicotine (0.5 mg/kg), but not saline, in old mice partially or fully reversed the age-related changes in EEG responses. Nicotine had no effect on auditory brainstem responses , suggesting the effects occur more centrally. The age-related changes are consistent with reduced activation of specific inhibitory interneuron subtypes. Importantly, our data suggest that the auditory circuits that generate 'young' responses to sounds are present in old mice, and can be activated by nicotine.

Electronic cigarettes (e-cigarettes) are battery-powered devices that use heat to aerosolize a liquid containing a variety of substances (usually nicotine and/or cannabinoids, flavorings, and glycerol or propylene glycol base) that is then inhaled. E-cigarettes are rapidly evolving over time, so the true health effects of e-cigarettes are difficult to study and remain largely unknown. We review the effects of e-cigarettes on nicotine addiction and on pulmonary disease including the effects of dual use and switching from combustible cigarettes to e-cigarettes. Studies show that e-cigarette use can increase the risk to nicotine dependence and combustible tobacco use. Studies show an association between e-cigarette use and pulmonary disease. Some studies suggest reduced harm from e-cigarette use compared with smoking, but this requires further study. Most adults who use e-cigarettes also smoke cigarettes; epidemiologic studies suggest that the combination of e-cigarettes and cigarettes is more harmful than using either product alone.

Negative affect was identified as an important barrier to smoking cessation. Three-part breathing exercise showed a significant effect on decreasing negative affect immediately after being practiced. Thus, this study evaluated the effect of three-part breathing exercise on smoking cessation.A 6-month cluster-randomized clinical trial was conducted. Forty-three participants recruited from 8 companies in Bangkok Metropolitan areas were randomly assigned at the cluster level into either the intervention or control groups. Control group (n = 23) received counseling for smoking cessation once a week for 12 weeks. Intervention group (n = 20) received counseling for smoking cessation plus a three-part breathing exercise program once a week for 12 weeks. The primary outcomes were 7-day point prevalence and continuous abstinence rate as validated by saliva cotinine. The secondary outcomes were cigarette cravings, nicotine withdrawal symptoms, affect and quality of life.The results revealed no significant difference in smoking abstinence rate between the three-part breathing exercise and control group. Participants demonstrated significant pre-post improvement in cigarette cravings, nicotine withdrawal symptoms, affect, and quality of life within each group.There were no statistically significant differences between the two groups. However, the improvement in abstinence rate from the three-part breathing exercise was deemed clinically relevant. Thus, it may be recommended to smokers interested in smoking cessation and more research is needed on this topic.

Tobacco-free oral nicotine products are an emerging class of noncombustible nicotine products. Oral nicotine product sales have increased since 2016, although little research has investigated consumer awareness, use, or correlates of oral nicotine product use. The purpose of this analysis was to assess the prevalence and correlates of oral nicotine product awareness and use.This paper is a cross-sectional analysis of 2,507 U.S. participants from Wave 3 (February-June 2020) of the International Tobacco Control Four Country Smoking and Vaping Survey, a population-based survey of current and former cigarette smokers and nicotine vaping product users in the U.S. Oral nicotine product awareness and use prevalence were compared with those of heated tobacco products. Analyses conducted in late 2021 assessed the correlates of oral nicotine product awareness and use such as demographic characteristics, tobacco use (cigarettes, nicotine vaping products, smokeless tobacco), and tobacco quit attempts.Almost 1 in 5 respondents claimed to have heard of oral nicotine products, 3.0% reported ever use, and 0.9% were current users, all of which were lower than for heated tobacco products. Ever use of oral nicotine products was more common among younger adults (e.g., aged 18-24 years), males, and current users of smokeless tobacco. Oral nicotine product prevalence was higher among those who reported having made attempts to stop smoking or vaping.Oral nicotine product use was low among current and former smokers and nicotine vaping product users. Oral nicotine product users were demographically similar to use among individuals who smoke/vape and also use smokeless tobacco. Future studies are needed to understand emerging oral nicotine products, particularly whether they are being used as product supplements (dual use), replacements (switching), or cessation aids (quitting).

BACKGROUND: Many smokers report attempting to quit each year, yet most relapse, in part due to exposure to smoking-related cues. It is hypothesized that extinction of the cue-drug association could be facilitated through random nicotine delivery (RND), thus making it easier for smokers to quit. The current study aimed to evaluate the effects of RND on smoking cessation-related outcomes including cigarettes per day (CPD) and exhaled carbon monoxide (CO). METHODS: Participants were current smokers (>9 CPD) interested in quitting. Novel trans-mucosal, orally dissolving nicotine films, developed by Bionex Pharmaceuticals, were used in the study. The pharmacokinetic profile of these films was assessed in single (Experiment 1) and multiple-dose (Experiment 2) administrations prior to the smoking cessation study (Experiment 3). In Experiment 3, participants were randomized 1:1:1 to recieve 4 nicotine films per day of either: placebo delivery (0 mg), steady-state delivery (2 mg), or random nicotine delivery (RND) (0 mg or 4 mg). After two weeks, participants were advised to quit (target quit date, TQD) and were followed up 4 weeks later to collect CPD and CO and to measure dependence (Penn State Cigarette Dependence Index; PSCDI) and craving (Questionnaire of Smoking Urges; QSU-Brief). Means and frequencies were used to describe the data and repeated measures ANOVA was used to determine differences between groups. RESULTS: The pharmacokinetic studies (Experiment 1 and 2) demonstrated that the films designed for this study delivered nicotine as expected, with the 4 mg film delivering a nicotine boost of approximately 12.4 ng/mL across both the single and the multiple dose administration studies. The films reduced craving for a cigarette and were well-tolerated, overall, and caused no changes in blood pressure or heart rate. Using these films in the cessation study (Experiment 3) (n = 45), there was a significant overall reduction in cigarettes smoked per day (CPD) and in exhaled CO, with no significant differences across groups (placebo, steady-state, RND). In addition, there were no group differences in dependence or craving. Adverse events included heartburn, hiccups, nausea, and to a lesser extent, vomiting and anxiety and there were no differences across groups. CONCLUSION: Overall, this pilot study found that RND via orally dissolving films was feasible and well tolerated by participants. However, RND participants did not experience a greater reduction in self-reported CPD and exhaled CO, compared with participants in the steady-state and placebo delivery groups. Future studies to evaluate optimal RND parameters with larger sample sizes are needed to fully understand the effect of RND on smoking cessation-related outcomes.

Depression is higher among spine patients than among the general population. Some small studies, but not others, have suggested that depression may be a predictor of worse outcome after surgery.Determination whether there is an association between depression and worse response to surgery among spine patients.The national, prospective, Canadian Spine Outcome Research Network (CSORN) surgical outcome registry.All patients in the CSORN registry who received surgery for thoracic or lumbar degenerative deformity, stenosis, spondylolisthesis, disc disease, or disc herniation with a minimum of 12 months follow-up postoperation (n = 2310).Oswestry Disability Index (ODI), SF12 Physical Component Score (PCS), European Quality of Life (EuroQoL), and pain scales.Change in preoperative to 12-month postoperative ODI, and secondary measures, were compared to assess if there was an association between preoperative depression, as measured by PHQ9, and smaller response to surgery. Multivariate regression analysis was used to search for preoperative factors which might interact with PHQ9 to predict ODI outcome.Patients with PHQ95, associated with minimal to no depression, had the smallest ODI improvement (-16.8 [95%CI -18.1 to -15.3]) and patients with severe preoperative depression (PHQ9 ≥ 10) had the largest ODI improvement (-22.8 [95%CI -24.1 to -21.5]; p.00001). Similar findings were found in the EQ5D and PCS. Pain improvement was not different between depression levels. Multivariate modeling found worse baseline PHQ9 and ODI, greater age, nicotine use, more operative levels, and worse American Society of Anesthesiology score was predictive of worse ODI outcomes.Depressed patients have similar or better relative improvements in disability, quality of life, and pain, when compared to nondepressed patients, although their preoperative and postoperative levels of disability are higher. Surgeons should not be concerned that depression will reduce the patient-reported beneficial response to surgical intervention.

It has been observed that deficit and non-deficit schizophrenia (SCZ-D and SCZ-ND) might be characterized by different risk factors. Therefore, the present study aimed to assess as to whether previously reported risk factors of schizophrenia are specifically associated with SCZ-D and SCZ-ND.This study was based on a cohort of 118 stable outpatients with schizophrenia. A diagnosis of SCZ-D was established using the Schedule for the Deficit Syndrome (SDS). Risk factors were recorded using structured interview, the Operational Criteria for Psychotic Illness (OPCRIT) checklist and the Traumatic Experience Checklist (TEC). The following risk factors were explored: male sex, a history of schizophrenia in first-degree relatives, seasonality of birth, birth weight3000g, delivery by cesarean section, a history of childhood trauma (emotional abuse, emotional neglect, physical abuse and sexual abuse) as well as substance abuse (other than nicotine) and cigarette smoking at psychosis onset.Individuals with SCZ-D were more likely to be males as well as reported higher rates of birth weight3000g and any categories of childhood trauma. In turn, substance abuse (other than nicotine) at psychosis onset was significantly more frequent in patients with SCZ-ND. Binary logistic regression, controlling for multiple comparisons, revealed similar findings, except for the association with any categories of childhood trauma that appeared to be not significant.Our findings partially replicate differential patterns of risk factors for SCZ-D (male sex and birth weight3000g) and SCZ-ND (substance abuse at psychosis onset), likely attributable to the effects of timing of exposure.

Little data exists regarding the effects of vaporized nicotine on healing. Our goal was to compare vaporized nicotine, combusted nicotine and control with respect to bone healing in a rat femur fracture model.Forty-five male Sprague Dawley rats were divided into three equal cohorts. Rats were exposed to two cigarettes daily, an equivalent dose of vaporized nicotine, or control, six days a week. Exposures occurred for 4 weeks prior to iatrogenic femur fracture and intramedullary repair. Four additional weeks of exposure occurred prior to sacrifice. Radiographic, biomechanical and histologic analysis was conducted.No significant difference between the three groups was identified for total mineralized bone volume (p = 0.14), total volume of mature bone (p = 0.12) or immature bone (p = 0.15). Importantly, less total mineralized bone volume and immature bone volume was seen in the vaporized nicotine group compared to combusted tobacco, but results were not significant. Biomechanical testing revealed no significant difference in group torsional stiffness (p = 0.92) or maximum torque (p = 0.31) between the three groups. On histologic analysis, chi-square testing showed no significant difference in any category.This exploratory study compared combusted nicotine, vaporized nicotine and a control on rat femur fractures. While no statistically significant differences were identified, there were trends showing less total mineralized bone volume and immature bone volume in the vaporized nicotine group compared to the other groups. Additional study is warranted based on our findings.

Menthol upregulates nicotinic acetylcholine receptors and is associated with tobacco dependence. The effects of menthol when smoking cigarettes with varying low nicotine content up to 98 % (e.g., non-addicting) less than commercial cigarettes is not well understood. The U.S. Food and Drug Administration is considering two tobacco product standards in cigarettes including banning menthol and reducing nicotine content. These new standards have the potential to significantly reduce smoking initiation and maintenance by limiting the mechanistic effects of nicotine and menthol on the brain.We conducted two parallel randomized clinical trials of gradually reduced nicotine in cigarettes from 11.6 mg down to 0.2 mg nicotine/cigarette (very low nicotine content; VLNC) vs. usual nicotine content (11.6 mg; UNC) over an 18-week period in people who smoke cigarettes with low socioeconomic status (SES) and mental health conditions.Compared to UNC, VLNC was associated with significant reductions in cotinine, cigarettes per day, expired carbon monoxide levels, nicotine dependence and symptomology. These associations did not differ between menthol and non-menthol cigarettes, except people who smoke menthol cigarettes had less of a cotinine reduction in the SES trial. The pooled odds ratio of being adherent with using only VLNC study cigarettes in the gradual nicotine reduction arm for people who smoke non-menthol vs. menthol cigarettes was 2.6 (95 % CI:1.0, 6.4; p-value: 0.04).When nicotine is lowered to non-addicting levels, the results indicate an independent effect of menthol on the need to sustain nicotine intake in addicted people who smoke cigarettes.

Nicotine use continues to be a major public health concern, with an alarming recent rise in electronic cigarette consumption. Heritability estimates of nicotine use and abuse range from 40% to 80%, providing strong evidence that genetic factors impact nicotine addiction-relevant phenotypes. Although nicotine use during adolescence is a key factor in the development of addiction, it remains unclear how genetic factors impact adolescent nicotine use and abuse. This review will discuss studies investigating genetic factors impacting nicotine use during adolescence. Evidence from both rodent and human studies will be summarized and integrated when possible. Human adolescent studies have largely included candidate gene studies for genes identified in adult populations, such as genes involved in nicotine metabolism, nicotinic acetylcholine receptor signaling, dopaminergic signaling, and other neurotransmitter signaling systems. Alternatively, rodent studies have largely taken a discovery-based approach identifying strain differences in adolescent nicotine addiction-relevant behaviors. Here, we aim to answer the following three questions by integrating human and rodent findings: (1) Are there genetic variants that uniquely impact nicotine use during adolescence? (2) Are there genetic variants that impact both adolescent and adult nicotine use? and (3) Do genetic factors in adolescence significantly impact long-term consequences of adolescent nicotine use? Determining answers for these three questions will be critical for the development of preventative measures and treatments for adolescent nicotine use and addiction.

Nicotine has both rewarding and aversive effects. In this issue of Neuron, Liu et al. show that nicotine aversion depends on both desensitization of high-affinity nicotinic acetylcholine receptors (nAChRs) that activate midbrain dopamine neurons and activation of low-affinity nAChRs that inhibit dopamine neurons via the laterodorsal tegmental nucleus (LDT).

Smoking is a risk factor for post-operative complications following breast reconstruction. Abruptly refraining from all nicotine products may be difficult for patients with a new cancer diagnosis. The goal of this study is to assess complications following a distinct approach to tissue expander reconstruction in nicotine users.Patients who underwent tissue expander reconstruction after mastectomy were retrospectively reviewed. The approach to optimize outcomes in smokers was to delay reconstruction at least 7 days after the mastectomy and place the expander submuscularly (Group I). The other patients underwent standard immediate reconstruction on the day of mastectomy and were divided into Group II (active smokers) and Group III (non-smokers). Group III was considered the control group.There was a total of 195 patients (323 breast reconstructions): Group I (10 patients, 19 expanders); Group II (11 patients, 19 expanders) and Group III (174 patients, 285 expanders). In Group I, n = 1/19 breasts had wound dehiscence requiring surgical management, compared to n = 18/285 in Group III (p = 1.0). Group II exhibited more wound dehiscence (n = 6/19) compared to Group III (p = 0.002). There was no significant difference when comparing wound dehiscence in prepectoral expander placement (7.0%) versus submuscular placement (4.8%) in Group III (p = 0.60).Nicotine users who are offered tissue expander breast reconstruction 1) at least 7 days after the mastectomy (to allow for vascular delay and demarcation) and 2) in the submuscular plane can normalize their risk of skin necrosis to that of non-smokers who have standard (prepectoral or submuscular) reconstruction on the day of mastectomy.

Systemic nicotine administration regulates neuronal activities in mouse auditory cortex. How nicotine regulates the spread of the activities across auditory cortical areas is not well known. We investigate this using flavoprotein fluorescence imaging. 20 kHz amplitude-modulated (AM) tones increased the peak intensity of flavoprotein fluorescence in presumptive primary auditory cortex (A1). 5 kHz AM tones activated at least three cortical areas, which are presumably A1, anterior auditory field, and secondary auditory cortex. Nicotine enlarged tone-activated cortical areas and enhanced both 20 kHz and 5 kHz tone-evoked fluorescence intensities at their respective, optimal frequency peak sites and at non-optimal frequency peak sites in A1. The extent of this enhancement was greater at non-optimal frequency sites than at optimal frequency sites. A cortical injection of dihydro-β-erythroidine, an inhibitor of nicotinic acetylcholine receptors composed of α4 and β2-subunits (α4β2*-nAChRs), blocked the enhancement of fluorescence intensity at the peak sites but did not appear to block the enlargement of activated areas. These results suggest that nicotine exposure activates cortical α4β2*-nAChRs to enhance tone-evoked local neuronal activities at an optimal frequency site. The nicotine-induced enlargement of a tone-activated area may depend on the nicotinic enhancement of cortical inputs or other activities.

To determine the geographical location and characteristics of on-demand delivery services operating in New Zealand.We systematically searched the web and application (app) stores for on-demand services offering rapid delivery of food, alcohol, cigarettes or vaping products in New Zealand and mapped their geographic location as of May 2021. Using desktop review, data on service characteristics were collected and stratified including: types of commodities available, promotion strategies, and the legal aspects of access to age-restricted items.On-demand services for food, alcohol and nicotine products operate across urban and rural New Zealand. All services offered personal memberships and 97% used promotions. All services offering restricted items had an age verification process, however, only 87% had birth date entry and 73% had an 18+ message pop-up on website entry. Only 60% of services appeared to have number limits on restricted items.Much of New Zealand is serviced by on-demand delivery services.The trend towards on-demand delivery services may increase unhealthy food, alcohol and nicotine-related harms and it undermines current government actions, e.g. the Smokefree 2025 goal. This research informs policy to reduce the future health burden.

PurposeEvaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 pandemic using data from a prospective nationwide cohort: the Adolescent Brain Cognitive Development Study.MethodsIn 2018-2019, 9,270 youth aged 11.5-13.0 completed a prepandemic assessment of past-month alcohol and drug use, then up to seven during-pandemic assessments between May 2020 and May 2021. We compared the prevalence of substance use among same-age youth across these eight timepoints.ResultsPandemic-related decreases in the past-month prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% prepandemic, p

It is known that cigarette smoke compromises the immune system and increases the risk of vaccine-preventable diseases. We reported that nicotine, the immunosuppressive component of cigarette smoke, disrupts the functional properties of DC and DC crosstalk with NK cells, which is pivotal in the initiation of immune responses to vaccines. We also showed that select TLR agonists could reduce the degrading effects of nicotine on DC-NK mediated immune responses in vitro. In this study, we further investigated the magnitude and mechanism of immune responses to a protein antigen formulated with alum or TLR agonists using WT, NK-depleted, and IFN-γ deficient mice exposed to nicotine. We found that R848 followed by Poly(I:C) acted as the most effective adjuvants to increase the percentage and number of IFN-γ-producing effector NK cells in the lymph nodes of immunized mice. In addition, we observed that the protein antigen formulated with Poly(I:C) or R848 improved the antigen-specific immune response in nicotine-exposed mice through NK-independent and -dependent mechanisms, respectively. These findings extend our understanding of the hyporesponsiveness of smokers to vaccines and provides the means to increase the efficacy of vaccines in this large population.

Nicotine ingested from smoking exerts neuroprotection and developmental neurotoxicity in central nervous system. It can produce several changes of cognitive behaviors through regulating the release of different neurotransmitters in the brain. However, the effects of nicotine exposure or withdrawal on neurotransmitter metabolism of hippocampus are still unclear. In this study, we real-time evaluated the dynamic alterations in neurotransmitter metabolism of hippocampal neuronal (HT22) cells induced by nicotine exposure and withdrawal at relevant exposure levels of smoking and secondhand smoke by using a microfluidic chip-coupled with liquid chromatography-mass spectrometry (MC-LC-MS) system. We found HT22 cells mainly released related neurotransmitters of tryptophan and choline metabolism, both nicotine exposure and withdraw altered its neurotransmitters and their metabolites release. Exposure to nicotine mainly altered the secretion of serotonin, kynurenic acid, choline and acetylcholine of HT22 cells to improve hippocampal dependent cognition, and the change are closely related to the dose and duration of exposure. Moreover, the altered metabolites could rapidly recover after nicotine withdrawal, but picolinic acid was elevated. MC-LC-MS system used in present study showed a greater advantage to detect unstable metabolites than conventional method by using in vitro model, and the results of dynamic alterations of neurotransmitter metabolism induced by nicotine might provide a potential targets for drug development of neuroprotection or cognitive improvement.

OBJECTIVE To describe the placental characteristics and neonatal outcomes of Central Australian Aboriginal women based on maternal self-report of tobacco use. METHODS Placental and neonatal variables were collected from a prospective maternal cohort of 19 smokeless tobacco chewers, 23 smokers and 31 no-tobacco users. RESULTS Chewers had the lowest placental weight (460 g) while the no-tobacco group had the heaviest placental weight (565 g). Chewers and the no-tobacco group had placental areas of similar size (285 cm2 and 288 cm2 , respectively) while the placentas of smokers were at least 13 cm2 smaller (272 cm2 ). There were two stillbirths in the study and more than one-third (36%) of neonates (newborns) were admitted to the Special Care Nursery, with the chewers' neonates having a higher admission rate compared with smokers' neonates (44% vs. 23%). The cohort mean birthweight (3348 g) was not significantly different between the groups. When stratified for elevated maternal glucose, the chewers' neonates had the lowest mean birthweight (2906 g) compared to the neonates of the no-tobacco group (3242 g) and smokers (3398 g). CONCLUSIONS This research is the first to demonstrate that the maternal use of Australian Nicotiana spp. (pituri) as smokeless tobacco may negatively impact placental and neonatal outcomes. Implications for public health: Maternal smokeless tobacco use is a potential source of placental and foetal nicotine exposure. Maternal antenatal screening should be expanded to capture a broader range of tobacco and nicotine products, and appropriate cessation support is required.

Consumer demands and innovation have led to an increasingly diverse range of nicotine delivery systems, driven by a desire to reduce risk associated with traditional combustible cigarettes. This speed of change provides a mandate for rapid new product assessment. We have used the validated technology ToxTracker®, to assess biomarkers of DNA damage, protein misfolding, oxidative and cellular stress, across the categories of cigarette (1R6F), tobacco heating product (THP 1.4) and electronic cigarette (ePen 3). In addition, we compared the commonly used test matrices for tobacco and nicotine products; whole aerosol aqueous extracts (AqE) and gas vapour phase (GVP), determining their suitability across the product categories. We demonstrated a significant reduction in oxidative stress and cytotoxicity for THP 1.4 over cigarette, further reduced for ePen 3, when assessed by both dilution and nicotine dosimetry. We also identified that while the extraction matrices AqE and GVP from combustible products were equivalent in the induced responses, this was not true of the other category examples, moreover THP 1.4 GVP demonstrates a50 % reduction in both toxicity and cytotoxicity endpoints over AqE. This indicates that unlike cigarette, the active components or toxicants for THP and electronic cigarette are associated with the aerosol fraction of these categories.

Chronic pain frequently develops after limb injuries, and its pathogenesis is poorly understood. We explored the hypothesis that the autonomic nervous system regulates adaptive immune system activation and nociceptive sensitization in a mouse model of chronic post-traumatic pain with features of complex regional pain syndrome (CRPS). In studies sympathetic signaling was reduced using 6- hydroxydopamine (6-OHDA) or lofexidine, while parasympathetic signaling was augmented by nicotine administration. Hindpaw allodynia, unweighting, skin temperature, and edema were measured at 3 and 7 weeks after fracture. Hypertrophy of regional lymph nodes and IgM deposition in the skin of injured limbs were followed as indices of adaptive immune system activation. Passive transfer of serum from fracture mice to recipient B cell deficient (muMT) mice was used to assess the formation of pain-related autoantibodies. We observed that 6-OHDA or lofexidine reduced fracture-induced hindpaw nociceptive sensitization and unweighting. Nicotine had similar effects. These treatments also prevented IgM deposition, hypertrophy of popliteal lymph nodes, and the development of pronociceptive serum transfer effects. We conclude that inhibiting sympathetic or augmenting parasympathetic signaling inhibits pro-nociceptive immunological changes accompanying limb fracture. These translational results support the use of similar approaches in trials potentially alleviating persistent post-traumatic pain and, possibly, CRPS. Perspective: Selective treatments aimed at autonomic nervous system modulation reduce fracture-related nociceptive and functional sequelae. The same treatment strategies limit pain-supporting immune system activation and the production of pro-nociceptive antibodies. Thus, the therapeutic regulation of autonomic activity after limb injury may reduce the incidence of chronic pain.

INTRODUCTION: Nicotine and marijuana vaping among U.S. adolescents are public health priorities. Research has assessed demographic and risk factors related to vaping, but there is a dearth of research on protective factors for vaping. Based on the healthy youth development perspective, the developmental assets framework is used to assess cumulative protective factors and vaping in a national sample of adolescents. METHODS: Data came from the nationally representative Monitoring the Future study, consisting of 12th graders (n=6,982) from the 48 contiguous U.S. states (2017–2019). Past 30–day nicotine and marijuana vaping and developmental assets (low, medium, or high) were examined. Covariates included demographics and other substance use. Weighted descriptive statistics, logistic regression, post-estimation analyses, and multiple imputation were used. RESULTS: Students with higher assets were less likely to vape nicotine and marijuana, even after adjusting for covariates. The odds of nicotine vaping were lower for students with medium assets (AOR=0.65, 95% CI=0.54, 0.78) and high assets (AOR=0.22, 95% CI=0.16, 0.29) compared with students with low assets. Similarly, the odds of marijuana vaping were lower for youth with medium assets (AOR=0.54, 95% CI=0.42, 0.69) and high assets (AOR=0.09, 95% CI=0.05, 0.18) compared with low assets. Social competence and positive peer norms were strongly protective against both forms of vaping. CONCLUSIONS: The healthy youth development perspective applies to the critical issues of nicotine and marijuana vaping among adolescents. Promoting cumulative assets may help prevent vaping among U.S. adolescents, and increasing the specific assets of social competence and positive peer norms could be particularly fruitful.

Accumulating evidence suggests that the detrimental effect of nicotine and tobacco smoke on the central nervous system (CNS) is caused by the neurotoxic role of nicotine on blood-brain barrier (BBB) permeability, nicotinic acetylcholine receptor expression, and the dopaminergic system. The ultimate consequence of these nicotine associated neurotoxicities can lead to cerebrovascular dysfunction, altered behavioral outcomes (hyperactivity and cognitive dysfunction) as well as future drug abuse and addiction. The severity of these detrimental effects can be associated with several biological determinants. Sex and age are two important biological determinants which can affect the pharmacokinetics and pharmacodynamics of several systemically available substances, including nicotine. With regard to sex, the availability of gonadal hormone is impacted by the pregnancy status and menstrual cycle resulting in altered metabolism rate of nicotine. Additionally, the observed lower smoking cessation rate in females compared to males is a consequence of differential effects of sex on pharmacokinetics and pharmacodynamics of nicotine. Similarly, age-dependent alterations in the pharmacokinetics and pharmacodynamics of nicotine have also been observed. One such example is related to severe vulnerability of adolescence towards addiction and long-term behavioral changes which may continue through adulthood. Considering the possible neurotoxic effects of nicotine on the central nervous system and the deterministic role of sex as well as age on these neurotoxic effects of smoking, it has become important to consider sex and age to study nicotine induced neurotoxicity and development of treatment strategies for combating possible harmful effects of nicotine. In the future, understanding the role of sex and age on the neurotoxic actions of nicotine can facilitate the individualization and optimization of treatment(s) to mitigate nicotine induced neurotoxicity as well as smoking cessation therapy. Unfortunately, however, no such comprehensive study is available which has considered both the sex- and age-dependent neurotoxicity of nicotine, as of today. Hence, the overreaching goal of this review article is to analyze and summarize the impact of sex and age on pharmacokinetics and pharmacodynamics of nicotine and possible neurotoxic consequences associated with nicotine in order to emphasize the importance of including these biological factors for such studies.

Introduction With concerns about tobacco use being a risk factor for severe disease from COVID-19, understanding nicotine- and tobacco-use patterns is important for preventive efforts. This study aims to understand changes in combustible cigarette and E-cigarette use among U.S. adults. Methods In August 2020, a cross-sectional survey of a nationally representative sample of adults aged ≥18 years in the National Opinion Research Center's AmeriSpeak Panel who reported past 6–month use of combustible cigarettes or E-cigarettes was conducted. Multivariable logistic regression assessed the factors associated with increased product use and quit attempts since hearing about COVID-19. Results A total of 1,024 past 6–month cigarette smokers/E-cigarette users were surveyed. Among cigarette smokers, 45% reported no change in cigarette smoking, and 33% reported increased cigarette smoking since hearing about COVID-19. Higher stress was associated with increased cigarette smoking. Among E-cigarette users, 41% reported no change in E-cigarette use, and 23% reported increasing E-cigarette use. A total of 26% of cigarette smokers and 41% of E-cigarette users tried to quit because of COVID-19. Higher perceived risk of COVID-19 was associated with attempts to quit combustible cigarettes (AOR=2.37, 95% CI=1.59, 3.55) and E-cigarettes (AOR=3.14, 95% CI=1.73, 5.70). Conclusions Cigarette and E-cigarette use patterns varied in response to the COVID-19 pandemic. Most cigarette smokers and E-cigarette users perceived product use as increasing COVID-19‒related health risks, and this was associated with attempts to quit. Some cigarette smokers, especially those reporting higher stress, increased product use. Proactive provision of cessation support to smokers and E-cigarette users may help mitigate the stress-related increases in product use during the COVID-19 pandemic.

Summary Introduction We report a case of intoxication following the application of the plant Nicotiana Glauca.L for the traditional treatment of skin burns. Observation It is about a 5 years old girl, without remarkable medical history, who was the victim of a 3rd degree skin burn. The family applied the ground leaves of the plant Nicotiana Glauca.L. on all the skin lesions. After half an hour, the little girl presented vomiting and dizziness. The symptoms developed into hypotonia with consciousness disorders, which motivated the family to consult the emergency room. On admission, clinical examination found a dehydrated patient, unconscious, a pupil in mydriasis. After resuscitation measures, the patient was recovered. A biological check-up showed signs of rhabdomyolysis and multi-visceral damage. Toxicological research revealed the presence of anabasin and nicotine by gas and liquid chromatography coupled with mass spectrometry in the patient's urine. Botanical identification also determined the species of the plant. Despite resuscitation measures and symptomatic treatment, the evolution was unfortunately marked by death. Conclusion Intoxication by Nicotiana Glauca.L. is rarely described in literature. The clinical picture is characterized by a nicotinic syndrome. The evolution can be fatal.

Nicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. Estradiol modulates expression of nicotinic acetylcholine receptors in rats, and plays critical roles in neurodevelopmental processes, including sexual differentiation of the brain. Here, we examined the effects of developmental nicotine exposure on the sexual differentiation of the preoptic area (POA), a brain region that normally displays robust structural sexual dimorphisms and controls adult mating behavior in rodents. Using a rat model of gestational exposure, developing pups were exposed to nicotine (2 mg/kg/day) via maternal osmotic minipump (subcutaneously, sc) throughout the critical window for brain sexual differentiation. At postnatal day (PND) 4, a subset of offspring was analyzed for epigenetic effects in the POA. At PND40, all offspring were gonadectomized, implanted with a testosterone-releasing capsule (sc), and assessed for male sexual behavior at PND60. Following sexual behavior assessment, the area of the sexually dimorphic nucleus of the POA (SDN-POA) was measured using immunofluorescent staining techniques. In adults, normal sex differences in male sexual behavior and in the SDN-POA area were eliminated in nicotine-treated animals. Using novel analytical approaches to evaluate overall masculinization of the adult POA, we identified significant masculinization of the nicotine-treated female POA. In neonates (PND4), nicotine exposure induced trending alterations in methylation-dependent masculinizing gene expression and DNA methylation levels at sexually-dimorphic differentially methylated regions, suggesting that developmental nicotine exposure is capable of triggering masculinization of the rat POA via epigenetic mechanisms.

Introduction Nationally, mental illness prevalence is comparable among Native Americans and Whites experiencing alcohol and nicotine use disorders. However, authors are concerned that mental illness in Native Americans with substance use disorders may be disparately underdiagnosed in medical settings. For 3 states with large Native American populations, this study compares the prevalence of mental illness diagnoses among Native Americans and Whites hospitalized with alcohol/nicotine use disorders. Methods In 2021, hospital discharge data were used to compare non-Hispanic Native Americans with non-Hispanic Whites in Arizona and New Mexico (2016-2018) and (regardless of Hispanic ethnicity) Native Americans with Whites in Oklahoma (2016-2017). Differences in any mental illness, mood, and anxiety diagnoses were assessed using multilevel regressions (adjusted for demographics, payor, comorbidities, facility). Adjusted predicted probabilities were constructed. Results Among alcohol-related discharges, probabilities of non-Hispanic Native Americans and non-Hispanic Whites receiving any mental illness diagnoses in Arizona were 18.0% (95% CI=16.1, 19.9) and 36.8% (95% CI=34.1, 39.5), respectively; in New Mexico, they were 24.5% (95% CI=20.7, 28.3) and 43.4% (95% CI=38.7, 48.1). Oklahoma's probabilities for Native Americans and Whites were 30.7% (95% CI=27.4, 34.0) and 36.8% (95% CI=33.5, 40.2), respectively. Among nicotine-related discharges, any mental illness diagnosis probabilities for non-Hispanic Native Americans and non-Hispanic Whites in Arizona were 21.2% (95% CI=18.9, 23.5) and 33.1% (95% CI=30.3, 35.9), respectively; in New Mexico, they were 25.9% (95% CI=22.7, 29.1) and 37.4% (95% CI=33.8, 40.9). Oklahoma's probabilities for Native Americans and Whites were 27.3% (95% CI=25.1, 29.6) and 30.2% (95% CI=28.0, 32.4), respectively. Mood and anxiety diagnoses were also significantly lower for non-Hispanic Native Americans in Arizona/New Mexico and Native Americans in Oklahoma. Conclusions Findings suggest disparate underdiagnosis of mental illness among Native Americans hospitalized with alcohol/nicotine use disorders in the examined states.

Digital, Background Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. Methods We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. Findings In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65–2·12) than in MICs (1·41, 1·34–1·49) and LICs (1·35, 1·25–1·46; interaction p, Funding Full funding sources are listed at the end of the paper (see Acknowledgments)., Ciencias Médicas y de la Salud

Nicotine is one of the most abused substances worldwide. Just as in adolescence and adulthood, tobacco use is also problematic in the elderly. Older people are more vulnerable to smoking consequences because of the additive effects of smoke. Cardiovascular diseases are the most common health problems associated with smoking; however, other systems are also affected, including the respiratory, nervous, integumentary, and many other systems. Smoking cessation is a difficult task especially in the elderly; therefore, physicians should encourage older patients to quit with every patient-physician encounter by offering counseling and replacement therapy.

Purpose The landscape of youth tobacco product use has changed dramatically in recent years; however, little is known about current youth cessation behaviors. This study aims to assess prevalence and correlates of quit intentions and past-year quit attempts among U.S. middle and high school students who report current use of any tobacco product, cigarettes, and e-cigarettes. Methods Data came from the 2020 National Youth Tobacco Survey, a nationally representative cross-sectional school-based survey of students in grades 6–12. Weighed prevalence estimates of quit intentions and past-year quit attempts among users of any tobacco product, cigarettes, and e-cigarettes are presented. Multivariable-adjusted logistic regression with predictive marginals was used to assess sociodemographic correlates of quit intentions and quit attempts for each tobacco product user group. Results Quit intentions were reported by 62.5% of current users of any tobacco product, 68.1% of cigarette smokers, and 63.9% of e-cigarette users. Similarly, past-year quit attempts were reported by 65.4% of current users of any tobacco product, 65.8% of cigarettes smokers, and 67.4% for e-cigarette users. Harm perceptions toward tobacco, nicotine dependency, and the use of ≥2 tobacco products were significantly correlated with quit intentions, quit attempts, or both among different tobacco product user groups. Conclusions Most students who use tobacco products want to quit and have attempted to do so. Development of youth-focused cessation interventions, particularly those addressing the most commonly used products, could potentially accelerate progress in a comprehensive approach to youth tobacco prevention and control.

Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8-12 % of children and4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl cyclase-c KO mice, and latrophilin-3 KO mice and rats. Environmental factors thought to contribute to ADHD include ethanol, nicotine, PCBs, lead (Pb), ionizing irradiation, 6-hydroxydopamine, neonatal hypoxia, some pesticides, and organic pollutants. Model validation criteria are outlined, and current genetic models evaluated against these criteria. Future research should explore induced multiple gene KOs given that ADHD is polygenic and epigenetic contributions. Furthermore, genetic models should be combined with environmental agents to test for interactions.

We have reported that nicotine has a neurotrophic action on peripheral adrenergic nerves in vivo, which is mediated by α7 nicotinic acetylcholine receptors (nAChRs). To clarify the possible mechanisms, the present study further investigated the effect of nicotine on neurite outgrowth in tyrosine hydroxylase (TH)-positive superior cervical ganglia (SCG) cells isolated from neonatal rats in vitro. Nicotine at low concentrations (0.01–0.3 mM) increased the number of neurite outgrowths in TH-immunopositive SCG cells, while high concentrations of nicotine (1–10 mM) gradually reduced it, and only 10 mM nicotine was markedly inhibited compared to the control. A 100 μM of nicotine-induced increase in neurite numbers depended on the exposure time and was inhibited by treatment with the nAChR antagonist hexamethonium (Hex) and α7 nAChR antagonist α-bungarotoxin (α-Bgtx). The nicotine (10 mM)-induced a significant decrease in neurite outgrowth in SCG, which was perfectly canceled by Hex to the control level but not by α-Bgtx. These results suggest that nicotine has a regulatory neurotrophic action mediated by both α7 nAChR and other subtypes in TH-positive SCG cells of rats.

Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately after nicotine cessation and was significantly higher than that of mice continued on nicotine. Mice switched to vehicle consumed more food than nicotine-continued mice during the first week of cessation, while oxygen consumption was comparable. Elevated expression of orexigenic agouti-related peptide was observed in the hypothalamic appetite center. Pair-feeding experiment revealed that the accelerated weight gain after nicotine withdrawal is explained by enhanced energy intake. As a showcase of an efficacy of pharmacologic intervention, exendin-4 was administered and showed a potent suppression of energy intake and weight gain in mice withdrawn from nicotine. Our current model provides a unique platform for the investigation of the changes of energy regulation after smoking cessation.

Detecting substance use as a predictor of bipolar disorder (BD) is important for clinicians to perform accurate and early diagnosis, as well as better manage the treatment of individuals with BD. The aim of this systematic review was to describe whether substance use is a predictor of BD. A literature search was conducted using the following databases: PubMed, PsycINFO, and Embase. All eligible studies published up to February 9, 2021 were included. This systematic review included 22 studies. We found that 66.7% of the studies assessing overall substance use found that overall substance use was a risk factor for BD. Regarding the specific substances assessed, cannabis use was described as a risk factor for BD in 55.6% of the studies, nonmedical use of prescription medications was a risk factor for BD in 50% of the studies, nicotine was found as a risk factor for BD in 50% of the studies, and alcohol use was described as a risk factor for BD in 42.9% of the studies assessing it. Only one study assessed whether cocaine use was a risk factor for BD and found a significant association. Interestingly, some studies suggested that the greater frequency of cannabis use was associated with greater risk to develop BD or hypomanic/manic symptoms. In conclusion, there is evidence supporting that substance use is a risk factor for BD. Importantly, when assessing the risk factors for BD related to psychoactive substance use, special attention should be given for the frequency of cannabis use.

The association between alcohol and liver disease, including alcoholic hepatitis, cirrhosis, acute-on-chronic liver failure, and hepatocellular carcinoma, has been well described, but the same cannot be said for the association between smoking, water pipe or tobacco chewing. A review of cumulative evidence suggests that smoking is independently a risk factor for liver fibrosis and contributes to carcinogenesis in HCC. Smoking-related fibrosis has been reported in patients with nonalcoholic fatty liver disease, primary biliary cholangitis, alcoholic liver disease and chronic viral hepatitis. Heavy smoking leads to systemic inflammation, oxidative stress, insulin resistance, and results in tissue hypoxia, as well as free radical damage. Other than damaging the liver, patients also suffer from the systemic effects of the 4000 chemicals associated with tobacco, which include nitrosamines, aromatic hydrocarbons, nicotine, nornicotine, and other alkaloids. These include respiratory ailments, cancer of the lungs, oral cavity, esophagus, pancreas and colon, atherosclerotic vascular disease, and stroke.

Smoking is the main modifiable risk factor for stroke and myocardial infarction, particularly in women; its prevalence in France is evolving, and new patterns of nicotine consumption have emerged.To present contemporary data on smoking prevalence and the use of electronic cigarettes, and to describe current knowledge of the cardiovascular risk specificities and the effectiveness of withdrawal methods in women.We identified studies by searching the MEDLINE bibliographic database between 1995 and 2020, and the Weekly Epidemiological Bulletin (Bulletin Épidémiologique Hebdomadaire) published by the French health authorities.In recent years, smoking prevalence among French women has decreased overall, except in the oldest age group (aged55 years). At the same time, the incidence of hospitalization for cardiovascular events has increased worryingly among women smokers aged65 years. Active smoking in women is associated with an increased risk of premature myocardial infarction, and a risk of stroke that increases with the number of cigarettes consumed per day; it is also responsible for increased cardiovascular events in women taking oestrogen-progestin contraception. Quitting smoking reverses these effects in the long term, and women are just as likely to quit smoking as men.Stopping smoking must be a priority objective for women smokers, for primary and secondary prevention, and they should systematically be offered a validated method of cessation or even electronic cigarettes.

Cytochrome P450 1A1 (CYP1A1) is a member of a subfamily of enzymes involved in the metabolism of both endogenous and exogenous substrates and the chemical activation of xenobiotics to carcinogenic derivatives. Here, the effects of nicotine, a major psychoactive compound present in cigarette smoke, on CYP1A1 expression and human hepatocellular carcinoma (HepG2) cell proliferation were investigated. Nicotine stimulated CYP1A1 expression via the transcription factors, activator protein 1, nuclear factor-kappa B, and the aryl hydrocarbon receptor (AhR) signaling pathway. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen-activated protein kinase, as well as RelA (or p65), mediated the upregulation of CYP1A1 of nicotine in HepG2 cells. The antioxidant compound, N-acetyl-cysteine, abrogated nicotine-activated production of reactive oxygen species and inhibited CYP1A1 expression by nicotine. Furthermore, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was inhibited by diphenyleneiodonium (an NADPH oxidase inhibitor). Thus, these results demonstrated that AhR played an important role in nicotine-induced CYP1A1 expression. Additionally, liver hepatocellular carcinoma HepG2 cells treated with nicotine exhibited markedly enhanced proliferation via CYP1A1 expression and Akt activation.

Introduction The contribution of neuroinflammation in cognitive impairment is increasingly recognized. Non-steroidal anti-inflammatory drugs had been proven that it could improve cognitive impairment in large dose but with more side effect, which limited the application. The main objective of this study was to investigate whether the combined use of nicotine and celecoxib could obtain synergistic neuroprotective effect in ischemic rats. Methods Twenty adult Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four groups with different interventions: nicotine (1.5 mg/kg/d), celecoxib (15 mg/kg/d), nicotine (1.5 mg/kg/d) +celecoxib (15 mg/kg/d), or saline after surgery. The other five SD rats also underwent same surgery by injecting saline instead of endothelin-1, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. Micro PET/CT with 2-[18F]-A-85380 were performed for α4β2-nAChRs detection in vivo. Western blot, real-time PCR and immunohistochemical staining were adopted to detect the expression of α4β2-nAChRs and inflammatory factors which included TNF-α, IL-1β, IL-6 in brain tissue. Microglial activation in the brain was monitored by immunofluorescence with IBA1 staining. Results The MWM test showed rats given with nicotine or celecoxib alone showed much better memory than rats with saline, no difference was observed between nicotine and celecoxib. The rat memory was recovered most significant when the nicotine and celecoxib were combined (p Conclusions The study revealed the combined use of nicotine and celecoxib may improve the cognitive function in ischemic rats, with a better effect than either alone. Both nicotine and celecoxib can inhibit inflammation, but through different mechanisms: nicotine can activate α4β2-nAChRs while celecoxib is cyclooxygenase-2 inhibitor. Our findings suggest the combined application of two drugs with different anti-inflammation mechanism could attenuate cognitive impairment more effectively in ischemic rats, which may hold therapeutic potential in the clinical practice.

Purpose To evaluate the biomechanical and histologic effects on Achilles tendon repair of inhaled combusted tobacco versus nicotine exposure via electronic cigarette versus a control group in a small-animal model (Sprague-Dawley rat). Methods Fifty-four Sprague-Dawley rats were randomized into 3 groups: combusted tobacco, e-cigarettes, or control. Experimental rats were exposed to research cigarettes or e-cigarette vapor in a smoking chamber for 4 weeks. Surgical transection and repair of the Achilles tendon were then completed, followed by 2 additional weeks of exposure. Achilles tendons were harvested, and biomechanical tensile testing was performed. Histologic evaluation was completed, including hematoxylin-eosin staining, trichrome staining, and immunohistochemistry analysis for type I and type III collagen. Results The control group showed the highest mean tensile load to failure, at 41.0 ± 10.4 N (range, 18.3-55.1 N); the cigarette cohort had the second highest mean, at 37.3 ± 11.1 N (range, 14.0-54.7 N); and finally, the vaping group had the lowest mean, at 32.3 ± 8.4 N (range, 17.8-45.1 N). One-way analysis of variance showed a significant difference in load to failure when comparing the control group with the e-cigarette group (P = .026). No statistical difference was detected between the control group and cigarette group (P = .35) or between the e-cigarette group and cigarette group (P = .23). Stiffness and qualitative histologic analysis showed no difference among groups. Conclusions This investigation shows that in a rat model, nicotine exposure via e-cigarette significantly impedes the biomechanical healing properties of Achilles tendon surgical repair. Clinical Relevance The results indicate that although e-cigarettes are often used as a perceived “safer” alternative to smoking, their use may have a detrimental effect on tendon load to failure.

We report comparative results, over three months, of the impact of SARS-CoV2 in our patients injected with botulinum toxin for functional purposes, compared to the general population. Botulinum neurotoxin type A (BoNT/A) is known to block acetylcholine (ACh) as well as many other neuroreceptors and neuromodulators. The recent mention of a potential protective effect of nicotine in COVID 19, by blocking ACh, attracted our attention and guided the present study. Our results show a significant difference between the number of infected individuals in the general population and the number of patients injected with BoNT/A who showed signs of COVID 19.

Purpose The tobacco and nicotine market is diversifying. Implications for public health will depend on trends in use, including overall use, and who is using these products. This study examined differences over time (2017–2019), across countries (Canada, England, the United States (US)), and by smoking and vaping, in use of other tobacco/nicotine products and overall use. Methods The study includes online repeat cross-sectional surveys of youth aged 16–19 years in Canada (N = 11,714), England (N = 11,170), US (N = 11,838) in 2017, 2018, and 2019. Past 30-day use of tobacco/nicotine products (any, cigarette, e-cigarette, other combusted [cigars/cigarillos/waterpipe], other non-combusted [smokeless tobacco/nicotine replacement therapies) were examined by country, year, and, for other combusted and non-combusted products, past 30-day cigarette smoking and vaping. Use of emerging products (IQOS, nicotine pouches) was explored in 2018–2019. Results From 2017 to 2019, use of any product increased in Canada (17.1%–23.2%, AOR = 1.07 [95% CI = 1.04–1.09]) and the US (18.0%–24.0%, AOR = 1.06 [1.04–1.09]) but not England (20.8%–21.7%, AOR = 1.01 [.99–1.03]). Use of other combusted products (cigars/cigarillos/waterpipe) showed little change (Canada: 8.1%–7.8%; England: 6.3%–7.3%; US: 8.6%–8.5%; p ≥ .151). Use of other non-combusted products (smokeless/nicotine replacement therapies) increased in all countries (Canada: 1.5%–3.2%, AOR = 1.02 [1.01–1.02]; England: 1.4%–2.6%, AOR = 1.02 [1.01–1.03]; US: 3.3%–4.9%, AOR = 1.02 [1.01–1.02]). Vaping increased in all countries (Canada: 8.4%–17.8%; England: 8.7%–12.6%; United States: 11.1%–18.5%; all p Conclusions Youth past 30-day tobacco and nicotine product use increased from 2017 to 2019 in Canada and the United States, largely due to increases in vaping and other non-combusted products. “Other” tobacco/nicotine products were used predominantly by youth who smoked cigarettes and/or vaped.

The aim of this review is to highlight our knowledge of the various drugs of abuse that can prove potential teratogens affecting the brain and cognitive development in an individual exposed to maternal consumption of such agents. Among several drugs of abuse in women, we specifically highlighted the commonly used alcohol, nicotine, opioids, cannabis, cocaine and marijuana. These drugs can affect the fetal development and slow the cognitive maturation apart from physical disabilities. However, no known therapy exists to counter the toxic potential of these drugs. Several researchers used animal models of drug abuse to understand the underlying mechanisms affecting brain development and the relevant neurotransmitter system. Identifying such targets can potentially help in drug discovery research. We reported in depth analysis of such mechanisms and discussed the potential targets for drug development research.

Here we examined the effect of nicotine on angiogenesis in the brain after intracerebral hemorrhage (ICH), as angiogenesis is considered to provide beneficial effects on brain tissues during recovery from injury after stroke. Nicotine was administered to C57BL/6 mice suffering from collagenase-induced ICH in the striatum, either by inclusion in drinking water or by daily intraperitoneal injection. Nicotine administration by both routes enhanced angiogenesis within the hematoma-affected regions, as revealed by increased CD31-immunopositive area at 7 and 14 d after ICH. Double immunofluorescence histochemistry against CD31 and proliferating cell nuclear antigen revealed that nicotine increased the number of newly generated vascular endothelial cells within the hematoma. In spite of enhanced angiogenesis, nicotine did not worsen vascular permeability after ICH, as assessed by Evans Blue extravasation. These effects of nicotine were accompanied by an increased number of surviving neurons in the hematoma at 7 d after ICH. Unexpectedly, nicotine did not increase expression of vascular endothelial growth factor mRNA in the brain and did not enhance recruitment of endothelial progenitor cells from the bone marrow. These results suggest that nicotine enhances angiogenesis in the brain after ICH, via mechanisms distinct from those involved in its action on angiogenesis in peripheral tissues.

Objective To assess prevalence of suicidal ideation and suicide attempt among South Brazilian tobacco growers and to analyze the associated factors related to the suicidal ideation. Methods A cross-sectional study was conducted in 2011 with a random sample of 2469 tobacco growers in Sao Lourenco do Sul/RS. Suicidal ideation was characterized by the question “Has the thought of ending your life been on your mind?”. Suicide attempt was assessed by the question “Have you ever tried to kill yourself?”. Investigation of factors associated with suicidal ideation was done by means of Poisson regression. Results Prevalence of suicidal ideation and suicide attempt was 2.5 % and 1.2 % respectively. In the adjusted analysis, suicidal ideation was associated with being female, older age, moderate participation in religious activities and difficulty in paying debts. Those who worked in activities that required inadequate postures (hunched over or other forced positions), as well as farmers who performed 6–9 pesticide-related tasks demonstrated greater risk of suicidal ideation. Regarding health conditions, medical diagnosis of asthma, chronic low back pain, number of lifetime green tobacco sickness episodes and lifetime pesticide poisoning were positively associated with suicidal ideation. Conclusion Suicidal thoughts and attempts are relevant mental health problems among tobacco growers. Reducing pesticide use, as well as exposure to nicotine and improving socio-economic conditions, can reduce suicidal ideation and improve the mental health of exposed workers.

Nicotine exerts its reinforcing actions by activating nicotinic acetylcholine receptors (nAChRs), but the detailed mechanisms remain unclear. Nicotine releases 3, 4-dihydroxyphenylalanine (DOPA), a neurotransmitter candidate in the central nervous system. Here, we investigated the distribution of GPR143, a receptor of DOPA, and nAChR subunits in the nigrostriatal and mesolimbic regions. We found GPR143 mRNA-positive cells in the striatum and nucleus accumbens. Some of them were surrounded by tyrosine hydroxylase (TH)-immunoreactive fibers. There were some GPR143 mRNA-positive cells coexpressing TH, and nAChR subunit α4 or α7 in the substantia nigra and ventral tegmental area. These findings suggest that DOPA-GPR143 signaling may be involved in the nicotine action in the nigrostriatal and mesolimbic dopaminergic systems.

Cigarette smoking has detrimental effects on rheumatoid arthritis (RA), characterized by muscle wasting. Linalyl acetate (LA), the main component of Lavandula angustifolia Mill (lavender) oil, has anti-inflammatory properties. We investigated the detrimental effects of chronic nicotine exposure in rats with RA, as well as the abilities of lavender oil and LA to prevent muscle wasting. Rats with RA induced by type II collagen were exposed to nicotine for 22 days from day 1. Lavender oil or LA was administered twice a week during the experiment. Compared with control, collagen-induced arthritis (CIA) and chronic nicotine exposure plus CIA (NicoCIA) showed increases in hind paw thickness and serum interleukin (IL)-6 and decreases in body weight and serum insulin-like growth factor (IGF)-1 levels. Moreover, weight and fiber cross-sectional area of the gastrocnemius muscle were much lower, and mitochondrial membrane potential of the gastrocnemius muscle was higher, in the NicoCIA than in the CIA. These alterations in the NicoCIA were prevented by lavender oil and LA. Importantly, LA showed greater activity than lavender oil in preventing IGF-1 reduction in the NicoCIA. These findings suggest that lavender oil and LA may have preventive benefit in RA by counteracting muscle wasting associated with chronic nicotine exposure.

Nicotine administration enhances object recognition memory. However, target brain regions and cellular mechanisms underlying the nicotine effects remain unclear. In mice, the novel object recognition test revealed that systemic nicotine administration before training enhanced object recognition memory. Moreover, this effect was inhibited by infusion of retigabine, a selective voltage-dependent potassium 7 (Kv7) channel opener, into the medial prefrontal cortex (mPFC) before nicotine administration. Additionally, infusion of XE-991, a selective Kv7 channel blocker, into the mPFC before training enhanced object recognition memory. Therefore, Kv7 channels in the mPFC may be at least partly involved in nicotine-induced enhancement of object recognition memory.

Purpose The purpose of this study was to evaluate the sensitivity of a tobacco use screening question, modified to include the word “e-cigarette,” in detecting past 12-month nicotine vaping and past 12-month tobacco product use inclusive of nicotine vaping, among adolescent primary care patients. Methods We conducted secondary analysis of data from a pilot trial of adolescent substance use screening and brief intervention in pediatric primary care. Participants were patients aged 12–18 years (N = 278) presenting for annual well-visits at five practices in Massachusetts in 2015–2017. Study measures consisted of a clinical brief screener item and tobacco/electronic cigarette items on a confidential, self-administered research questionnaire (criterion measure). Results The clinical brief screener item identified 24 of 30 adolescents with past 12-month tobacco use (sensitivity 80%); 15 of 30 with past 12-month electronic cigarette use (sensitivity 50.0%), and 25 of 42 with tobacco and/or electronic cigarette use (sensitivity 59.5%). Conclusions These findings support the need to develop and test a screening measure that is sensitive for capturing electronic cigarette use.