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Introduction Despite policies setting a minimum legal sales age, youth continue to access electronic cigarettes (ECs). Evidence of rising youth vaping prevalence in many countries suggests existing measures have serious loopholes and raise important questions about how youth source vaping products. Aims and Methods We explored how youth source ECs using in-depth interviews with 30 adolescents aged 16–17 who vaped at least once a month and lived in Aotearoa New Zealand. Our semistructured interview guide probed participants' vaping experiences and how they developed and used social, quasi-commercial, and commercial supply routes to access ECs. We used an inductive reflexive thematic analysis approach to interpret the data. Results Nearly all participants shared ECs with peers and sharing was the sole access route for some. Many used proxies, often older relatives or people they knew socially, to purchase ECs on their behalf; however, others recruited proxies by approaching previously unknown people they identified on social media. Participants also sourced ECs via quasi-commercial networks that existed within schools and on social media, and some purchased in their own right, usually from smaller retail outlets that did not ask for ID. Conclusions Disrupting social supply will be challenging, though reducing ECs' availability, appeal, and affordability could make social supply, including sharing and proxy purchasing, more difficult. Reports that youth purchase ECs from commercial retailers known to waive age verification suggest stronger monitoring and enforcement, along with escalating retailer penalties, are required. Implications Vaping access routes sit on a continuum from informal, spontaneous sharing to carefully planned commercial purchases. While supply via friends, siblings and other social contacts is an important means of access, nicotine dependence drives some to use riskier access routes, including approaching unknown people to act as proxy purchasers. Evidence young people identify noncompliant retailers suggests policy makers should monitor and enforce existing measures more stringently and consider additional penalties for recidivist underage suppliers. A more comprehensive response that reduces the appeal, addictiveness, affordability, and availability of vaping products would address factors fostering and maintaining youth vaping. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation is designed to target accessible brain regions that underlie many psychiatric disorders. One such method, transcranial magnetic stimulation (TMS), is commonly used in patients with treatment-resistant depression (TRD). However, for non-responders, the choice of an alternative therapy is unclear and often decided empirically without detailed knowledge of precise circuit dysfunction. This is also true of invasive therapies, such as deep brain stimulation (DBS), in which responses in TRD patients are linked to circuit activity that varies in each individual. If the functional networks affected by these approaches were better understood, a theoretical basis for selection of interventions could be developed to guide psychiatric treatment pathways. The mechanistic understanding of TMS is that it promotes long-term potentiation of cortical targets, such as dorsolateral prefrontal cortex (DLPFC), which are attenuated in depression. DLPFC is highly interconnected with other networks related to mood and cognition, thus TMS likely alters activity remote from DLPFC, such as in the central executive, salience and default mode networks. When deeper structures such as subcallosal cingulate cortex (SCC) are targeted using DBS for TRD, response efficacy has depended on proximity to white matter pathways that similarly engage emotion regulation and reward. Many have begun to question whether these networks, targeted by different modalities, overlap or are, in fact, the same. A major goal of current functional and structural imaging in patients with TRD is to elucidate neuromodulatory effects on the aforementioned networks so that treatment of intractable psychiatric conditions may become more predictable and targeted using the optimal technique with fewer iterations. Here, we describe several therapeutic approaches to TRD and review clinical studies of functional imaging and tractography that identify the diverse loci of modulation. We discuss differentiating factors associated with responders and non-responders to these stimulation modalities, with a focus on mechanisms of action for non-invasive and intracranial stimulation modalities. We advance the hypothesis that non-invasive and invasive neuromodulation approaches for TRD are likely impacting shared networks and critical nodes important for alleviating symptoms associated with this disorder. We close by describing a therapeutic framework that leverages personalized connectome-guided target identification for a stepwise neuromodulation paradigm. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies report associations between use of electronic cigarettes (ECs) and cigarettes over time among young people, but do not distinguish within- from between-person effects, which complicates interpretation of findings. Further, the role of shared risk factors, such as substance use and mental health, in explaining longitudinal associations between EC and cigarette use remains unclear. This study used within- and between-person analyses to assess longitudinal associations between youths' EC and cigarette use and shared risk factors.Methods: Between 2015 and 2017, 2039 youths completed three Web-based surveys, allowing us to model EC and cigarette use from ages 16 to 20. Auto-regressive latent growth models with structured residuals (ALT-SR) examined both between-person and within-person associations between past-month frequency of EC use, cigarette use, and third variables (alcohol and marijuana use, mental health symptoms) over time.Results: Models revealed robust reciprocal associations between EC and cigarette use, such that more frequent EC use at one time predicted more frequent cigarette use at the subsequent time, and vice versa. Between-person analyses showed associations between shared risk factors and both EC and cigarette use. However, shared risk factors did not predict frequency of subsequent EC and cigarette use in within-person analyses.Conclusions: Findings add to a growing body of research suggesting that EC use among youth is prospectively associated with progression toward greater cigarette use. Shared risk factors may help explain differences in EC and cigarette use patterns between young people, but do not appear to influence longitudinal trajectories of EC and cigarette use within individuals.Implications: This study examined within- and between-person associations between e-cigarette use, cigarette use, and shared risk factors (alcohol use, marijuana use, mental health symptoms) in a longitudinal cohort of youths. Within- and between-person analyses revealed reciprocal prospective associations between e-cigarette and cigarette use, suggesting a progression toward more frequent use of both products over time. The shared risk factors examined here did not affect escalations in e-cigarette or cigarette use over time within individuals, but likely influence which youths use these products. Findings add to a growing body of evidence suggesting that e-cigarette use increases subsequent cigarette use in young people. [ABSTRACT FROM AUTHOR]

Introduction: Electronic cigarettes (ECs) seem to be a less harmful alternative for conventional cigarettes. This study aimed to assess whether the generated aerosols from ECs contain lower amount of cadmium (Cd) and lead (Pb) than cigarette smoke and to detect any changes in exposure to Cd and Pb among cigarette smokers who switched completely or partially to EC.Methods: EC aerosols and cigarette smoke were generated, and the determination of Cd and Pb in trapped samples and e-liquids was performed by the electrothermal atomic absorption spectrometry method. A cross-sectional, group-based survey was carried out using 156 volunteers classified into groups of nonsmokers, EC-only users, dual EC users-cigarette smokers, and cigarette-only smokers. Using electrothermal atomic absorption spectrometry, blood Cd and Pb levels were measured, and the results were compared by analysis of covariance.Results: Transfer of Cd and Pb to EC aerosol was found to be minimal, although the metals were present in the remaining e-liquid from tanks used for vapor generation. The geometric mean blood Cd concentration adjusted for age and sex was 0.44 (95% confidence interval = 0.37 to 0.52) µg/L in the EC-only users, which was significantly lower than those in the smokers of 1.44 (1.16 to 1.78) and dual users of 1.38 (1.11 to 1.72). The blood Pb geometric mean differed significantly only between nonsmokers of 11.9 (10.6 to 13.3) and smokers of 15.9 (13.6 to 18.6).Conclusion: The study revealed that smokers who completely switched to ECs and quit smoking conventional cigarettes may significantly reduce their exposure to Cd and probably Pb.Implications: Switching to EC use is associated with a rapid and substantial decrease in the exposure to carcinogenic Cd. Exposure to Pb is probably also decreased but may be overshadowed by other factors. The study provides empirical data based not only on the analysis of generated aerosol but also on biological indicators of recent exposure-that is, the concentrations of Cd and Pb in blood, indicating EC as a potential harm-reduction device, especially regarding Cd exposure. However, in this case, dual EC use-cigarette smoking provides doubtful benefits. [ABSTRACT FROM AUTHOR]

Introduction: The aerosol composition of electronic cigarettes (ECs) suggests that exposure to toxicants during use is greatly reduced compared to exposure from combustible cigarettes (CCs).Methods: This randomized, parallel-group, clinical study enrolled smokers to switch to Vuse Solo (VS) Digital Vapor Cigarettes (Original or Menthol) or Nicorette 4 mg nicotine gum (NG) in a controlled setting. Subjects who smoked CCs ad libitum for 2 days during a baseline period were then randomized to ad libitum use of either VS or NG for 5 days. Biomarkers of 23 toxicants were measured in 24-hour urine samples and blood collected at baseline and following product switch.Results: A total of 153 subjects completed the study. Total nicotine equivalents decreased in all groups, but higher levels were observed in the VS groups compared to the NG groups, with decreases of 38% and 60%-67%, respectively. All other biomarkers were significantly decreased in subjects switched to VS, and the magnitude of biomarker decreases was similar to subjects switched to NG. Decreases ranged from 30% to greater than 85% for constituents such as benzene and acrylonitrile.Conclusions: These results indicate that exposure to toxicants when using VS is significantly reduced compared to CC smoking, and these reductions are similar to those observed with use of NG. Although statistically significantly decreased, nicotine exposure is maintained closer to CC smoking with VS use compared to NG use. This research suggests that use of VS exposes consumers to fewer and lower levels of smoke toxicants than CCs while still providing nicotine to the consumer.Implications: This is the first study to report changes in nicotine delivery and biomarkers of tobacco exposure following a short-term product switch from CCs to either an EC or NG in a controlled environment. The study shows that nicotine exposure decreased in both groups but was maintained closer to CC smoking with the EC groups. Biomarkers of tobacco combustion decreased to similar levels in both EC and gum groups. [ABSTRACT FROM AUTHOR]

Introduction: The demand for alternative nicotine/tobacco products is not well established. This paper uses a behavioral economic approach to test whether smokers have differential demand for conventional factory-made, electronic, and very low nicotine content cigarettes (FMCs/ECs/VLNCs) and uses the prospective cohort design to test the predictive validity of demand indices on subsequent use of commercially available FMCs and ECs.Methods: Daily smokers (≥16 years) from the Netherlands completed an online survey in April 2014 (N = 1215). Purchase tasks were completed for FMCs, ECs, and VLNCs. Participants indicated the number of cigarettes they would consume in 24 h, across a range of prices (0-30 euro). The relationship between consumption and price was quantified into four indices of demand (intensity, Pmax, breakpoint, and essential value). A follow-up survey in July 2015 measured FMC and EC use.Results: At baseline, greater demand was observed for FMCs relative to ECs and VLNCs across all demand indices, with no difference between ECs and VLNCs. At follow-up, greater baseline FMC demand (intensity, essential value) was associated with lower quit rates and higher relapse. EC demand (Pmax, breakpoint, essential value) was positively associated with any EC use between survey waves, past 30 day EC use, and EC purchase between waves.Conclusions: Smokers valued FMCs more than ECs or VLNCs, and FMCs were less sensitive to price increases. Demand indices predicted use of commercially available products over a 15 month period. To serve as viable substitutes for FMCs, ECs and VLNCs will need to be priced lower than FMCs.Implications: Purchase tasks can be adapted for novel nicotine/tobacco products as a means to efficiently quantify demand and predict use. Among current daily smokers, the demand for ECs and VLNCs is lower than FMCs. [ABSTRACT FROM AUTHOR]

Given the increasing popularity of electronic cigarettes (ECs) and a lack of regulation of EC advertising, this study aimed to analyse online videos promoting ECs to assess the main marketing messages that could influence consumers' perceptions of associated risks and benefits. A web search of EC advertising videos was performed on YouTube by using keywords related to EC promotion. An evaluation grid was used to analyse promotional messages contained in each video. The most frequent promotional messages were related to health benefits (67.7%) and to the possibility of quitting smoking (57.4%). Messages that could also be appealing to adolescents and young adults, such as those promoting the multiple flavors available and the technological improvement of ECs, were present in 41.2% and 42.7% of the videos respectively. ECs similar to traditional cigarettes in appearance were included in 52.9% of the videos. EC promotional videos address messages not only to smokers who want to quit or decrease tobacco consumption but also to nonsmokers, especially young people. The use of ECs similar to traditional cigarettes may be a gateway to tobacco cigarette use. Since EC use may represent an important public health concern, regulatory policies on EC advertising should be established. [ABSTRACT FROM AUTHOR]

The use of electronic cigarettes (ECs) has been on the rise with increased number of battery explosions causing burns. This study is a retrospective review of patients who presented with burns caused by EC explosions.Here, we present a case series of eight patients sustaining burns from EC explosions, within a year, to elucidate the pattern of such burns and to provide a treatment guideline.All of them were males. Five patients had partial-thickness burns and three had full-thickness burns. TBSA ranged from 4 to 16% (burns to lower extremity [n = 7], hand [n =3], scrotum/penis [n =2], chest [n = 1]). None had inhalation injuries. Two patients (29%) required skin grafting. EC explosion is predominantly attributed to its lithium-ion battery. Several types of injuries can occur, including chemical and thermal burns, inhalation injuries, metal poisoning, etc. There are currently no specific guidelines on the management of burns due to lithium-ion battery exposure. Herein, we recommend the following: Initial assessment of injuries should accompany the Advanced Trauma Life Support guidelines; serum levels of lithium, cobalt, and manganese should be checked and elevated levels should be monitored; patients should be monitored for signs of metal toxicity; wound should be extensively debrided and irrigated to remove any residual materials; and litmus test should be performed to check for alkali pH prior to irrigation with water or other aqueous solutions. [ABSTRACT FROM AUTHOR]

Introduction: The purpose was to measure nicotine levels to the tobacco and levels emitted to the aerosol of a heat-not-burn product (HnB, IQOS) compared to e-cigarettes (ECs) and a tobacco cigarette.Methods: The HnB device and regular and menthol sticks were purchased from Italy. Three types of ECs (ciga-like, eGo-style, and variable wattage) and a commercially-available tobacco cigarette were also tested. A custom-made liquid containing 2% nicotine was used with ECs. Products were tested using Health Canada Intense puffing regime while HnB and ECs were additionally tested using a 4-second puff duration regime while maintaining the same puff volume.Results: Nicotine content in HnB regular and menthol tobacco sticks was 15.2 ± 1.1 mg/g and 15.6 ± 1.7 mg/g tobacco respectively. The levels of nicotine to the aerosol were similar for regular and menthol HnB products (1.40 ± 0.16 and 1.38 ± 0.11 mg/12 puffs respectively) and did not change significantly with prolonged puff duration. The tobacco cigarette delivered the highest level of nicotine (1.99 ± 0.20 mg/cigarette), with levels being higher than HnB and ECs under Health Canada Intense regime but similar to eGo-style and variable wattage ECs at prolonged puff duration regime.Conclusions: The HnB product delivers nicotine to the aerosol at levels higher than ECs but lower than a tobacco cigarette when tested using Health Canada Intense puffing regime. No change in HnB nicotine delivery was observed at prolonged puff duration with the same puff volume, unlike ECs which deliver more nicotine with longer puff duration.Implications: Nicotine delivery to the smoker is expected to play an important role in the ability of any harm-reduction product to successfully substitute smoking. This study evaluated the content and nicotine delivery to the aerosol of a heat-not-burn tobacco product (IQOS) in comparison with e-cigarettes and a tobacco cigarette. The main findings were that the heat-not-burn tobacco sticks contained similar nicotine concentration to tobacco cigarettes, and that the levels of nicotine delivered to the aerosol of the heat-not-burn products were lower than tobacco cigarette, higher than e-cigarettes at low puff duration but lower than high-power e-cigarettes at longer puff duration. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (ECs) can influence nicotine addiction by delivering aerosolized nicotine. We investigated if nicotine from ECs is delivered to the brain β2*-nicotinic acetylcholine receptors (β2*-nAChR) and how this relates to the behavioral effects and nicotine delivery from cigarettes.Methods: Seven nicotine users participated in positron emission tomography (PET) studies with (-)-[18F]Flubatine before and after nicotine challenge with 0, 8, and 36 mg/ml nicotine in a 3.3 Volt, 1.5 Ohm EC or a standard tobacco cigarette. Craving was evaluated before and after product use.Results: Average β2*-nAChR occupancy was higher after 36 mg/ml EC challenge compared to 8 mg/ml EC at trend level. Average β2*-nAChR occupancy after tobacco cigarette smoking was 68 ± 18% and was not different compared with 8 mg/ml (64 ± 17%,) or 36 mg/ml (84 ± 3%) nicotine in EC users. Area under the curve (AUC) of blood nicotine level was higher in the cigarette smoking group compared with the 8mg/ml group (p = 0.03), but similar compared with the 36 mg/ml EC (p = 0.29). Drug craving was reduced after use of the tobacco cigarette, 8 mg/ml EC, and 36 mg/ml EC.Conclusions: In this novel investigation of EC effects at β2*-nAChRs, we show that average β2*-nAChR occupancy was higher after 36 mg/ml EC challenge compared with 8 mg/ml EC. Receptor occupancy and arterial blood nicotine levels after cigarette smoking were similar to 36 mg/ml EC use under controlled conditions. These findings suggest that the ECs studied here have abuse liability and may provide an adequate alternative nicotine delivery system for cigarette smokers.Implications: This is the first study to directly determine the neurologic effects of electronic cigarettes on human brain beta-2 nicotinic acetylcholine receptors using PET neuroimaging with (-)-[18F]Flubatine, a novel radiotracer. Our findings suggest that the e-cigarettes studied here have abuse liability and may provide an adequate alternative nicotine delivery system for cigarette smokers. [ABSTRACT FROM AUTHOR]

Background: There is considerable debate about the benefits and risks of electronic cigarettes (ECs). To better understand the risk-benefit ratio of ECs, more information is needed about net nicotine consumption and toxicant exposure of cigarette smokers switching to ECs.Methods: Forty cigarette smokers (≥1 year of smoking) interested in switching to ECs but not necessarily quitting smoking were enrolled in a 4-week observational study and provided an e-Go C non-variable battery and refillable atomizers and choice of eight flavors in 12 or 24 mg nicotine dosage. Measurement of urinary cotinine (metabolite of nicotine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a pulmonary carcinogen), and eight volatile organic compounds (VOCs) that are toxic tobacco smoke constituents was conducted at baseline and week 4.Results: All participants with follow-up data (92.5%) reported using the study EC. Of the 40 smokers, 16 reported no cigarettes at week 2 (40%) and six continued to report no cigarettes at week 4 (15%). Change in nicotine intake over the 4 weeks was non-significant (p = .90). Carbon monoxide (p < .001), NNAL (p < .01) and metabolites of benzene (p < .01) and acrylonitrile (p = .001) were significantly decreased in the study sample. Smokers switching exclusively to ECs for at least half of the study period demonstrated significant reductions in metabolites of ethylene oxide (p = .03) and acrylamide (p < .01).Conclusion: Smokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.Implications: This study extends current literature by measuring change in smoking dependence and disease-associated biomarkers, NNAL and a panel of eight common VOCs that are toxic tobacco smoke constituents in smokers who switch to ECs. The findings support the idea of harm reduction, however some levels of toxicant exposure are still of clinical concern, particularly for dual users. Extrapolation of these results must be careful to separate the different toxic exposure results for exclusive switchers versus dual cigarette + EC users, and not to equate harm reduction with the idea that using ECs is harmless. [ABSTRACT FROM AUTHOR]

Intratumoral heterogeneity greatly hinders efficiency of target therapy in glioblastoma (GBM). To decipher the underlying mechanisms of heterogeneity, patient-derived adult GBM cells were separately isolated from margins of T1 gadolinium enhancing tumor lesions (PNCs) and T1 gadolinium enhancing core lesions (ECs). Single clone culture was conducted in ECs and U87MG cell line to screen clones with distinct biological phenotypes. Single cell clones with diverse phenotypes were simultaneously separated from ECs and U87 cell line. PNCs, GCs(H) and U87(H) exhibited longer cellular protrusion than ECs, GCs(L) and U87(L), respectively. Cell strains with longer protrusion exhibited higher invasive ability and lower sensitivity to temozolomide (TMZ) and radiation. Subsequently, TPD52L2 was verified as the functional protein to regulate the cellular heterogeneity by the proteomics analysis. Downregulation of TPD52L2 enhanced cell invasion whereas inhibited cell proliferation rate and sensitivity to chemotherapy in vivo and in vitro, this condition was reversed when TPD52L2 was overexpressed. The invasiveness was facilitated by up-regulating CTNNB1/β-catenin and SNAI1/Snail mediated EMT process. In addition, the clinical data of 88 GBM cases in our neurosurgery center was analyzed to reveal the influence of TPD52L2 in the prognosis of GBM. Low expression of TPD52L2 exacerbated prognosis of GBM patients received standard radiotherapy plus concomitant and adjuvant TMZ (Stupp strategy). Taken together, TPD52L2 is an important biomarker influencing GBM prognosis. [ABSTRACT FROM AUTHOR]