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Aims Design, setting, participants Measurements Findings Conclusions To measure nicotine delivery, vaping topography and subjective effects of current generations of disposable, cartridge‐based and other types of electronic cigarettes (e‐cigarettes) among young adults.Observational, human laboratory assessment of e‐cigarette use in Columbus, Ohio, USA (July 2020 to June 2021). Participants (n = 96, 60.4% female, age mean = 21.7 [standard deviation = 1.7] years, 82.4% white race) were identified via their participation in a cohort study or other convenience sampling and were 18 to 25 years old, vaped ≥4 days/week for ≥4 weeks and used other tobacco products for ≤5 days of past 30 days. Participants completed a pre‐vaping questionnaire, vaped their usual brand of e‐cigarette ad libitum for 30 min and completed a post‐vaping questionnaire.Outcome variables included pre‐ and post‐vaping measures of plasma nicotine (t = 0 and t = 30, respectively) and craving and withdrawal symptoms, as well as vaping topography (e.g. flow rate and inter‐puff interval), pre‐vaping expectancies and post‐vaping product appeal. Variables used to characterize the sample included demographics, e‐cigarette and other tobacco use history, e‐cigarette dependence and e‐cigarette device characteristics (e.g. device type, flavor and nicotine form).Participants reported moderate nicotine dependence on average via the E‐Cigarette Dependence Scale (mean = 6.9 [standard deviation = 4.0]). Following 30 min of ad libitum vaping, participants achieved substantial plasma nicotine boost (mean = 18.8 [standard deviation = 14.5] ng/mL), corresponding with statistically significant decreases in withdrawal symptoms measured via the Minnesota Nicotine Withdrawal Scale (pre‐vaping mean = 9.0 [standard deviation = 5.1], post‐vaping mean = 4.3 [standard deviation = 3.9]; P‐value <0.0001). Pre‐vaping, participants reported moderate vaping expectancies (e.g. mean = 2.5 [standard deviation = 1.0] on a scale from 0 to 4 for smell and taste expectancies); post‐vaping, participants reported high satisfaction (mean = 4.6 [standard deviation = 1.2] on a scale from 1 to 7) and moderate reward (mean = 2.9 [standard deviation = 1.2]) and respiratory sensations (mean = 3.7 [standard deviation = 1.6]). Nearly half of participants (47.9%) used disposable e‐cigarettes, and most used a mint/menthol or fruit flavored (99.0%) and nicotine salt (98.9%) e‐liquid.Among young adults in the United States, the latest generations of e‐cigarettes appear to deliver large quantities of nicotine (similar to cigarettes) and significantly relieve withdrawal symptoms, and they are appealing. [ABSTRACT FROM AUTHOR]

Microbial secondary metabolites have emerged as alternative novel drugs for the treatment of human cancers. Violacein, a purple pigment produced by Chromobacterium violaceum, was investigated in the present study for its anti-tumor properties in tumor cell lines. Clinically applicable concentrations of violacein were demonstrated to inhibit the proliferative capacity of tumor cell lines according to a crystal violet proliferation assay. The underlying mechanism was the promotion of apoptotic cell death, as indicated by poly(ADP ribose) polymerase cleavage and p44/42 mitogen-activated protein kinase signaling determined by western blot analysis. Collectively, this provided mechanistic evidence that violacein elicits extracellular-signal regulated kinase-induced apoptosis via the intrinsic pathway. The anti-malignant properties of violacein in the present study were further demonstrated by its inhibitory effects on brain tumor cell migration, specifically glioblastomas, one of the most invasive and therapeutically resistant neoplasms in the clinic. Additionally, solid tumors examined in the present study displayed differential cellular responses and sensitivities to violacein as observed by morphologically induced cellular changes that contributed to its anti-migratory properties. In conclusion, violacein is a novel natural product with the potential to kill several types of human tumor cell lines, as well as prevent disease recurrence by antagonizing cellular processes that contribute to metastatic invasion. [ABSTRACT FROM AUTHOR]

Chemotherapy and radiotherapy resistance are major obstacles in the long-term efficacy of head and neck squamous cell carcinoma (HNSCC) treatment. Secondhand smoke (SHS) exposure is common and has been proposed as an independent predictor of HNSCC recurrence and disease-free survival. However, the underlying mechanisms responsible for these negative patient outcomes are unknown. To assess the effects of SHS exposure on cisplatin efficacy in cancer cells, three distinct HNSCC cell lines were exposed to sidestream (SS) smoke, the main component of SHS, at concentrations mimicking the nicotine level seen in passive smokers' saliva and treated with cisplatin (0.01–100 µM) for 48 h. Compared to cisplatin treatment alone, cancer cells exposed to both cisplatin and SS smoke extract showed significantly lower cisplatin-induced cell death and higher cell viability, IC50, and indefinite survival capacity. However, SS smoke extract exposure alone did not change cancer cell viability, cell death, or cell proliferation compared to unexposed control cancer cells. Mechanistically, exposure to SS smoke extract significantly reduced the expression of cisplatin influx transporter CTR1, and increased the expression of multidrug-resistant proteins ABCG2 and ATP7A. Our study is the first to document that exposure to SHS can increase cisplatin resistance by altering the expression of several proteins involved in multidrug resistance, thus increasing the cells' capability to evade cisplatin-induced cell death. These findings emphasize the urgent need for clinicians to consider the potential role of SHS on treatment outcomes and to advise cancer patients and caregivers on the potential benefits of avoiding SHS exposure. [ABSTRACT FROM AUTHOR]

Objectives: E-cigarettes pose significant risks to youth, but smokers may benefit from switching to e-cigarettes by reducing their exposure to toxicants, which creates a challenge for the Food and Drug Administration (FDA) in regulating e-cigarettes to protect population health. This study aims to develop e-liquid product standards for nicotine form and concentration that reduce the appeal of e-cigarettes to young people while keeping e-cigarettes available as a safer alternative for smokers. Design and participants: A single-visit, double-blinded, randomized crossover design will be used to examine the effects of e-liquids with varying fractions of free-base nicotine (5%, 25%, 45%, 65%, 85%) among a sample of 66 young adult EC users and 66 older adult smokers, across ecologically valid total nicotine concentrations (20 mg or 50 mg/mL). Interventions and outcomes: A 2-puff session will be conducted to test each of the 10 e-liquids in randomly assigned sequences, followed by a 10-minute washout period and participant ratings on appeal and sensory attributes such as throat hit and harshness, as well as behavioral intentions for continued use. Generalized linear mixed models will be used to determine a free-base nicotine level that has limited or no appeal to young adult e-cigarette users while remaining acceptable to smokers. Conclusions: This study will provide the FDA with scientific evidence regarding the effect of product standards that mandate a minimum threshold for the fraction of free-base nicotine. Trial registration: The study is registered on clinicaltrials.gov under the identifier NCT05864586. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMP-2 and -9) play an important role in the tumor metastasis through cleavage of proinflammatory cytokines. Violacein a small molecule produced by Chromobacterium violaceum and has been implicated with anti-cancer effects. In this study we investigated the molecular basis of violacein mediated downregulation of CXCL12/CXCR4, chemokine–receptor ligand interaction. Zymography analysis demonstrated that violacein significantly inhibited the cytokine (TNFα and TGFβ) mediated MMP-2 activation in MCF-7 breast cancer cell line. MMP-2 plays a critical role in the secretion of inflammatory chemokine, CXCL12, involved in cell migration and cancer metastasis. ELISA analysis demonstrated that violacein inhibited the secretion of CXCL12 from the activated MCF-7 cells. Further, we show that MMP-2/-9 act synergistically at two distinct steps towards the membrane expression of the tumor metastasis chemokine receptor, CXCR4. Violacein efficiently downregulated the CXCR4 membrane expression through MMP-9 inhibition. Taken together, these studies demonstrate a unique anti-tumor mechanism of action of violacein through reduction of CXCL12/CXCR4 interaction. These studies could offer a novel venue for violacein in cancer therapy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In 2004, the Philippine Guidelines on Periodic Health Examination (PHEX): Effective Screening for Diseases among Apparently Healthy Filipinos was published with recommendations for screening for vision impairment. Since that time, the Philippine education system has shifted to the K to 12 curriculum, and with full implementation of Republic Act 10157 (Kindergarten Education Act), Filipino children entered school earlier at age 5 years. This made the previous recommendations unenforceable in this new age group. NEW RECOMMENDATIONS: The 2014 revised recommendations were: (1) Vision screening for amblyopia and strabismus is recommended for all children at least once using an age-appropriate chart (Level 2); and (2) Screening infants at 6 months of age for ocular problems, and at age 2 to 3 years, at 5 years, and every 1 to 2 years thereafter for visual acuity and ocular alignment may be done (Level 4). COMMENT: The Philippine Eye Research Institute (PERI) incorporated the LEA Symbols in its vision screening kit, as the LEA Symbols was not only an age-appropriate chart but also had the added features of equal blurring of the optotypes precluding guesswork, and fulfilled the criteria set by international bodies. Included in this kit was a LEA symbol and number chart, right occluder glasses, left occluder glasses, and a 10-foot string to measure distance consistently. The vision screening kit has been pilot tested in several public schools and have gained the reputation for ease of use, reliability, and reproducibility CONCLUSION: The younger age of Filipino children at school entry, pegged at 5 years of age or more, meant that the initial recommendations for students age 7 years were no longer enforceable. The LEA symbols chart, now endorsed internationally as an effective preschool vision test, offered the advantages of being validated and having undergone repeated calibration; lacking in cultural bias as symbols were easy to recognize across cultures; and having the actual screening process akin to a "play" situation. Currently, the LEA symbols chart form part of the PERI Vision Screening kit and is available locally through the PERI. [ABSTRACT FROM AUTHOR]

Tobacco smoking is the leading preventable cause of cancer. Moreover, continued smoking during cancer therapy reduces overall survival. Aware of the negative consequences of tobacco smoking and the challenges of smoking cessation, cancer patients are inquiring whether they should switch to electronic cigarettes (e-cigarettes). To obtain evidence-based data to inform this decision, we examined the effects of e-cigarette aerosol exposure on cisplatin resistance in head and neck cancer cells. Our results show that cancer cells exposed to e-cigarette aerosol extracts and treated with cisplatin have a significant decrease in cell death, increase in viability, and increase in clonogenic survival when compared to non-exposed cells. Moreover, exposure to e-cigarette aerosol extracts increased the concentration of cisplatin needed to induce a 50% reduction in cell growth (IC50) in a nicotine-independent manner. Tobacco smoke extracts induced similar increases in cisplatin resistance. Changes in the expression of drug influx and efflux transporters, rather than activation of cell growth-promoting pathways or DNA damage repair, contribute to e-cigarette induced cisplatin resistance. These results suggest that like combustible tobacco, e-cigarette use might increase chemotherapy resistance, and emphasize the urgent need for rigorous evaluation of e-cigarettes health effects to ensure evidence-based public health policies. [ABSTRACT FROM AUTHOR]

Objectives: American Indian/Alaska Native (AI/AN) adults use smokeless tobacco products (eg, chewing and dip tobacco) more often than other racial/ethnic groups do. Although US adults increasingly use potentially reduced exposure tobacco products (PREPs), such as electronic cigarettes and snus, no studies have examined the use of PREPs among AI/AN smokeless tobacco users. We examined associations between current PREPs use and smokeless tobacco–related measures, including cessation attempts and cotinine levels, in a sample of American Indian adults who currently use smokeless tobacco. Methods: We collected survey and tobacco biomarker data from 299 adult American Indian smokeless tobacco users at Cherokee Nation health care facilities and events in 2016 and 2017. We used multivariable analyses to determine associations between current PREPs use and smokeless tobacco–related characteristics. Results: Current PREPs users were younger, less likely to be married or living with a partner, less likely to report a chronic medical condition, and more likely to report other tobacco use than PREPs nonusers. Among participants with annual household incomes ≤$30 000, current PREPs users were less likely than PREPs nonusers to report a definite desire to quit smokeless tobacco (P =.02). PREPs use was not associated with planning to quit smokeless tobacco, past 12-month smokeless tobacco quit attempts, amount of smokeless tobacco used per week, cotinine levels, or scores on the Fagerström Test for Nicotine Dependence–Smokeless Tobacco. Conclusions: Our study suggests that American Indian smokeless tobacco users may not be using PREPs as a smokeless tobacco cessation aid. Future studies should take this finding into consideration when evaluating the role of PREPs use in smokeless tobacco cessation and in total tobacco cessation in this population. [ABSTRACT FROM AUTHOR]