Reply to Commentary on "Adult Smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months After Initially Purchasing a JUUL e-Cigarette" and the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study.

BACKGROUND: This is authors' reply to the Commentary on our publication entitled "Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette." METHODS AND RESULTS: Analyses addressed questions about follow-up rates and missed responses in the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study. Results demonstrate limited potential for selection bias, as participants who missed surveys were similar to those with complete data, and re-contact of participants who missed a follow-up indicated almost half were not smoking. Imputing smoking behavior for missing data would likely introduce bias and is not appropriate. The study demonstrated that JUUL products can facilitate high rates of complete switching away from cigarettes as suggested in previous experimental and observational studies. The ADJUSST cohort, including baseline nonsmokers, demonstrates a net reduction in smoking prevalence. Moreover, population modeling considering both benefits and harms demonstrated a net population benefit. CONCLUSION: While the ADJUSST Study is not without limitations, the findings are consistent with multiple streams of real-world evidence that indicate that ENDS can facilitate switching among adults who smoke, and provide population benefits.

Switching Away From Smoking and Reduction in Cigarette Consumption among US Adult Purchasers of the JUUL System across 24 Months Including Diverse Subpopulations Disproportionately Affected by Cigarette Smoking.

OBJECTIVES: Electronic nicotine delivery systems (ENDS) can reduce tobacco-related health risks for adults who smoke cigarettes (AWS) by facilitating complete switching away from cigarettes. However, little is known about ENDS use and switching among subpopulations that have been disproportionately affected by smoking. METHODS: AWS (age≥21 years) were recruited following their first purchase of a JUUL Starter Kit in 2018. Participants self-reported switching (no past-30-day cigarette smoking) at 1-, 2-, 3-, 6-, 9-, 12-, 15-, 18-, 21-, and 24-month follow-ups. Percent switched and percent with substantial smoking reduction (≥50% decrease in cigarettes/day among those who continued smoking) were calculated. Analyses focused on racial/ethnic minorities, persons with low income and education levels, sexual minorities, and those with mental and physical health conditions. RESULTS: Overall rates of switching away from cigarettes increased across follow-ups to 51.2% (Month-12) to 58.6% (Month-24, 87% of whom used ENDS). Among those who continued to smoke at 24 months, 45.4% reduced cigarettes/day by ≥50%. Rates of switching and substantial smoking reduction were largely similar across subgroups, with some statistically significant, but small, differences in Month-24 switching rates(e.g. education, mental/physical health conditions; switch rate range: 42~57%). CONCLUSIONS: AWS demonstrated progressively increasing switching rates over two years after purchasing JUUL products. Similar trends in switching and smoking reduction were observed across populations disproportionately affected by smoking. By facilitating switching and smoking reduction, ENDS products such as JUUL may provide an opportunity to reduce smoking-related harm among some populations disproportionately affected by smoking, potentially reducing tobacco-related health disparities. IMPLICATIONS: ENDS have the potential to benefit population health if they can replace cigarettes. This benefit must extend to populations disproportionately affected by smoking. In this real-world study, 59% of JUUL purchasers reported complete switching two years later (no past-30-day smoking, with most continuing to use ENDS). Further, 45% of those who continued to smoke reduced cigarette consumption by at least half. These rates of switching and smoking reduction were largely comparable across populations disproportionately affected by smoking (defined, e.g., by ethnicity and income). ENDS can serve as an effective harm reduction strategy to complement current efforts to reduce tobacco-related disparities.

Aiouea padiformis extract exhibits anti-inflammatory effects by inhibiting the ATPase activity of NLRP3.

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.

Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.

Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette.

Background: Electronic nicotine delivery systems (ENDS) have the potential to benefit public health if smokers completely switch from cigarettes to ENDS. Methods: A cohort of adult smokers (age ≥ 21) who purchased a JUUL Starter Kit was followed for 12 months after the initial purchase. We defined "switching" as past-30-day abstinence from smoking (even if JUUL use had stopped), and analyzed factors associated with achievement and maintenance of self-reported repeated point-prevalence switching (RPPS) at three follow-ups, i.e., no past-30-day smoking at months 6, 9, and 12. Results: RPPS was reported by 21.6% of the 12,537 evaluable smokers. Smokers with lighter smoking history and lower cigarette dependence at baseline were more likely to report RPPS. RPPS was also associated with daily use of JUUL (Month-3: OR = 2.32, 95% CI = 2.02-2.68; Month-6: OR = 1.73, 95% CI = 1.42-2.10), and with greater subjective reinforcing effects from JUUL use (assessed by the mCEQ, Month-3: OR = 1.46, 95% CI = 1.38-1.56; Month-6: OR = 1.11; 95% CI = 1.02-1.20). Even among smokers who did not meet the criteria of RPPS (i.e., who smoked at least once), 35.5% reported past 30-day point-prevalence switching on at least one follow-up, and their cigarette consumption was substantially reduced compared to baseline. Conclusions: Approximately one-fifth of adult smokers reported 30-day point-prevalence abstinence at 6, 9, and 12 months after purchasing JUUL. Greater use of JUUL and stronger subjective reinforcing effects were associated with nonsmoking, validating the potential for ENDS to substitute for smoking, with potential for positive impacts on individual and population health.

What Substances Are Adolescents Vaping? Estimating Nicotine-Specific and Cannabis-Specific Vaping from US National Youth Surveys.

BACKGROUND: Youth use of electronic cigarettes ("e-cigarettes") is an ongoing concern. Vaping is usually assumed to be of nicotine, but survey responses may also include vaping of non-nicotine substances (particularly cannabis), which can impose different risks. The current study quantifies the proportions of nicotine-specific and cannabis-specific vaping among adolescents. METHODS: Data from the Monitoring the Future (MTF) 2021 survey were analyzed with respect to the substance vaped: nicotine, cannabis, or flavoring only. Past-30-day (P30D) nicotine-specific vaping (exclusively, or also having vaped other substances) and cannabis-specific vaping were calculated. Results were also broken down by grade level, cigarette smoking history (current, former, or never), and frequency of e-cigarette use (<20 vs. 20+ days in P30D). RESULTS: Among 4706 P30D e-cigarette users, 84.2% vaped nicotine; the remaining 15.8% reported not vaping any nicotine in P30D. Cannabis vaping was reported by 48.4% of P30D vapers. Vaping both nicotine and cannabis in P30D was more common in current and former smokers than in never-smokers, and in frequent vapers (of any substance). Conversely, never-smokers were more commonly vaping cannabis but not nicotine, compared to current and former smokers. Supplementary NYTS 2022 analyses were consistent with these findings. CONCLUSIONS: A notable proportion of self-reported P30D vapers reported not vaping nicotine; nearly half vaped cannabis. Capturing the variety of substances used in vaping devices is imperative for accurate public health surveillance of both nicotine and cannabis vaping among US adolescents, considering their different respective harms and regulatory frameworks.

US adult smokers' perceived relative risk on ENDS and its effects on their transitions between cigarettes and ENDS.

BACKGROUND: Perceived risk reduction motivates smokers to switch to electronic nicotine delivery systems (ENDS). This research examines US smokers' relative risk perceptions and their prospective association with various behavioral stages of switching to ENDS. METHODS: Data from the nationally representative, longitudinal Population Assessment of Tobacco and Health (PATH) Adult survey, Waves 1 (2014) through 5 (2019), were analyzed. We assessed the association between the perceived risk of ENDS relative to cigarettes ("less harmful" vs. "equally harmful" or "more harmful") and 1) adoption of ENDS (among never-ENDS-using smokers), 2) complete switching to ENDS (i.e., stopping smoking, among ever-ENDS-using smokers), and 3) avoiding reversion to smoking (among smokers who had switched to ENDS), at the next wave. RESULTS: The proportion of US smokers perceiving ENDS as less harmful than cigarettes continually decreased, reaching 17.4% in Wave 5 (2019). Current smokers with such belief were more likely to adopt ENDS (aOR 1.31; 95% CI 1.15-1.50) and switch completely to ENDS (aOR 2.24; 95% CI 1.89-2.65) in the subsequent wave. Among smokers who had switched within the past year, such beliefs predicted avoidance of resumption of smoking in the next wave (aOR 0.55; 95% CI 0.33-0.93). CONCLUSIONS: Smokers' beliefs about the relative risk of ENDS compared to cigarettes had a strong and consistent association with transitions between smoking and ENDS use. Addressing the growing misperception about ENDS has the potential to contribute to public health by encouraging smokers' switching to ENDS.

Rural disparities in adolescent smoking prevalence.

INTRODUCTION: Rural residence is a well-established risk factor for risk behaviors and subsequent morbidity and mortality in the United States. Smoking is the primary cause of preventable death and is more prevalent in rural America. As chronic smoking habits typically develop during adolescence, the discrepancy in smoking rates between rural and urban youth likely contributes to a significant geographic disparity in the long-term health of adults. METHODS: Data were extracted from 12th-grader surveys of the US Monitoring the Future study from 1998 to 2018. The historic trends of smoking initiation, ever-regular and current-regular smoking rates of rural and urban adolescents were estimated with intercept-only time-varying effect models. Differences in prevalence between rural and urban youth were calculated for each smoking behavior. RESULTS: Though overall smoking prevalence continues to decline, this trend is significantly attenuated among rural adolescents compared to urban youth. The absolute difference in lifetime smoking prevalence between rural and urban youth has markedly increased from 6.9% in 1998 to 13.5% in 2018, which is among the highest in the past 20 years and is a potentially alarming upward trend. However, the absolute differences in ever-regular and current-regular smoking prevalence have shown an overall net decline, decreasing from 6.4 to 4.8%, and from 5.5 to 3.0%, respectively. CONCLUSIONS: This geographic disparity between rural and urban adolescents represents a potentially modifiable cause of increased morbidity and mortality in rural areas. Interventions and regulatory efforts should be tailored for rural adolescents to reduce the narrowing but persistent disparity in regular smoking.

Estimating causal and time-varying effects of maternal smoking on youth smoking.

INTRODUCTION: Maternal smoking is a well-known risk factor for youth smoking, yet whether this relationship is causal remains unresolved. This study utilizes propensity score methods for causal inference to robustly account for shared risk factors between maternal and offspring smoking. METHODS: An 8-year longitudinal cohort of 900 adolescents in the Chicago area were followed starting from approximately age 15.6. The effects of maternal lifetime smoking (MLS) and prenatal tobacco exposure (PTE) (among participants reporting MLS) on offspring's past 30-day smoking, daily smoking status and smoking frequency were examined using logistic regression and Poisson regression after nearest-neighbor propensity matching. Age dependency of this relationship was then examined across the age range of 15-25 using time-varying effect modeling. RESULTS: Propensity matching yielded 438 and 132 pairs for MLS and PTE study samples, respectively. MLS demonstrated significant associations with past 30-day smoking (RR 1.09; 95% CI 1.04-1.14), daily smoking (RR 1.08; 95% CI 1.05-1.12), and smoking frequency of offspring (RR 1.32; 95% CI 1.15-1.52), with stable effects across age. Among participants reporting MLS, having PTE showed significant additional effects on daily smoking (RR 1.09; 95% CI 1.02-1.17) and age-dependency that showed significance during young adulthood but not adolescence. CONCLUSION: The relationship between maternal and offspring smoking was not fully accounted for by shared risk factors, suggesting possible causation with PTE having a delayed effect across age. Targeted prevention efforts should be made on maternal smoking-exposed adolescents to mitigate their risks of developing heavy smoking habits in adulthood.

Switching away from Cigarette Smoking with JUUL: Populations of Special Interest.

Objectives: In this study, we examined complete switching away from cigarettes across various medico-socio-demographic subpopulations of adult smokers who purchased a JUUL Starter Kit (JSK) electronic nicotine delivery system. Methods: We analyzed trajectories of smoking over 12 months in 17,986 adult smokers who purchased a JSK. Populations of special interest were characterized by race/ethnicity, income, diagnoses of potentially smoking-related illness (SRI), depression, and anxiety. Results: Across all 16 subgroups examined, a consistent pattern of trends was observed where complete switching increased, and dual-use decreased over time. Non-Hispanic Asian race/ethnicity, low income, diagnoses of potential SRI, depression, and anxiety were associated with significantly lower switching rates; however, complete switching rates at month 12 were near 50% for all groups, and surpassed the dual-use rates in all subgroups except for those with potential SRI. Conclusions: Substantial rates of complete switching were consistently achieved across all medico-socio-demographic subgroups 12 months following the purchase of the JSK. The potential benefits of switching with JUUL on smokers are likely to be experienced by a wide range of adult smokers.

Strategies for controlling axial shoulder rotation change shoulder muscle activity during external rotation exercises.

BACKGROUND: The infraspinatus muscle has a crucial role in shoulder stability. Although axial shoulder rotation is useful for selective activation of the infraspinatus, no study has examined the influence of exercise position on axial shoulder rotation during shoulder external rotation (ER) exercises. Thus, this study investigated the muscle activity in the infraspinatus, posterior deltoid, and middle trapezius during shoulder ER exercises performed with and without controlled axial shoulder rotation in 2 different positions. METHODS: Twenty healthy subjects performed prone external rotation (PER) exercises with and without pressure biofeedback and seated external rotation (SITER) exercises with and without posterior humeral head gliding. Muscle activity during each ER exercise was measured using surface electromyography. RESULTS: Exercise strategy (P < .001) and position (P < .001) had a significant main effect on muscle activity in the infraspinatus and posterior deltoid. However, no significant interaction between strategy and position was observed. For muscle activity in the middle trapezius, strategy and position had a significant interaction effect (P = .014). Muscle activity in the infraspinatus increased significantly with the use of strategies to control axial shoulder rotation, whereas muscle activity in the posterior deltoid and middle trapezius decreased significantly. For all 3 muscles, greater activity was observed in the prone position than the seated position. CONCLUSION: We suggest that PER with pressure biofeedback can be useful to improve selective activation of the infraspinatus muscle while further eliciting infraspinatus muscle activity.

The Anti-Inflammatory Effect of Trichilia martiana C. DC. in the Lipopolysaccharide-Stimulated Inflammatory Response in Macrophages and Airway Epithelial Cells and in LPS-Challenged Mice.

A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1ß, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

Electronic cigarettes may not be a "safer alternative" of conventional cigarettes during pregnancy: evidence from the nationally representative PRAMS data.

BACKGROUND: Conventional cigarette (CC) smoking is one of the most preventable causes of adverse birth outcomes. Although electronic cigarettes (ECs) are considered to be safer than CCs during pregnancy, the evidence is yet to be presented. This study examines the effects of prenatal EC use on neonatal birth outcomes compared to those of CC smokers and complete tobacco abstainers. METHODS: Data was extracted from 55,251 pregnant women who participated in the Phase 8 survey of the Pregnancy Risk Assessment Monitoring System between 2016 and 2018. Participants were classified into three groups based on their smoking behaviors in the third trimester: complete tobacco abstinence, exclusive CC smoking, or exclusive EC use. Adverse outcomes included infants being small-for-gestational-age (SGA), having low birthweight (LBW), and being born at preterm. EC users were matched to complete abstainers and CC smokers who share the same baseline characteristics in race/ethnicity, age, educational attainment, income, prenatal care adequacy, and first- and second-trimester CC smoking statuses. The association between EC use and adverse birth outcomes were examined by survey-weighted logistic regression analyses in the matched population. RESULTS: Among participants, 1.0% of women reported having used ECs during the third trimester, 60% of which reported using ECs exclusively. Neonates of EC users were significantly more likely to be SGA (OR 1.76; 95% CI 1.04, 2.96), have LBW (OR 1.53; 95% CI 1.06, 2.22), or be born preterm (OR 1.86; 95% CI 1.11, 3.12) compared to tobacco abstainers. However, odds of EC users' pregnancies resulting in SGA (OR 0.67; 95% CI 0.30, 1.47), LBW (OR 0.71; 95% CI 0.37, 1.37), or preterm birth (OR 1.06; 95% CI 0.46, 2.48) were not significantly lower than those of CC smokers. CONCLUSIONS: Even after accounting for shared risk factors between prenatal tobacco use and adverse birth outcomes, EC use remains an independent risk factor for neonatal complications and is not a safer alternative to CC smoking during pregnancy. Until further research is completed, all pregnant women are encouraged to abstain from all tobacco products including ECs.

Changes in Multiple and Different Tobacco Product Use Behaviors in Women Before and During Pregnancy: An Analysis of Longitudinal Population Assessment of Tobacco and Health Data.

INTRODUCTION: Changes in tobacco use behaviors among women with respect to pregnancy are expected to be significant and dynamic, with a strong desire for smoking cessation, diversification of tobacco products, and perceived relative safety on noncigarette tobacco products. This study aims to illustrate how multiple and different tobacco use behaviors change before and during pregnancy. METHODS: Data were extracted from 864 pregnant, nationally representative U.S. women, who were prospectively followed with the Population Assessment of Tobacco and Health study between 2013 and 2017. Smoking statuses were defined on the basis of the number and type of 7 different tobacco products under current use. Differences in maternal characteristics were investigated in relation to tobacco cessation statuses during pregnancy. Weighted percentages and 95% CIs were calculated. RESULTS: Only 50.4% of prepregnancy tobacco users achieved complete abstinence with varying rates of cessation, depending on the number and type of products used prepregnancy. The lowest cessation rates were observed among prepregnancy poly-tobacco users (23.3%) and conventional cigarette smokers (45.5%). During pregnancy, 11.3% and 2.8% of women reported smoking cigarettes and e-cigarettes, respectively. Persistent tobacco users during pregnancy were more likely to be white, be older, and have nonprivate or no medical insurance (all p<0.05). CONCLUSIONS: This study demonstrates a widespread prenatal tobacco use and low rates of complete cessation in major subgroups of tobacco users. Current findings on the concurrent use of multiple products and noncigarette tobacco products highlight the urgent need for further research and comprehensive public health intervention for smoking cessation during pregnancy.

Scapula muscle exercises using the Neurac technique for a patient after radical dissection surgery: a case report.

Background: After radical neck dissection, spinal accessory nerve damage can result in scapular muscle weakness, which causes shoulder pain, dysfunction, and a limited range of motion (ROM); scapular muscle strengthening exercises are used to reduce these symptoms. This report focuses on the importance of trapezius and serratus anterior strength exercises to reduce symptoms after radical neck dissection. Case Description: The patient was a 30-year-old female who had received radical neck dissection 3 years previously. She complained of shoulder pain, dysfunction, and limited ROM during shoulder elevation. Outcome: She was successfully treated by increasing trapezius and serratus anterior strength and improving pain, function, and range of motion by applying the Neurac technique for 12 weeks. Further controlled studies are required to identify the generalizability of these findings.

The Relationship Between Electronic Cigarette Use and Conventional Cigarette Smoking Is Largely Attributable to Shared Risk Factors.

INTRODUCTION: The growing popularity of electronic cigarettes (e-cigarettes) among youth raises concerns about possible causal effects on conventional cigarette smoking. However, past research remains inconclusive due to heavy confounding between cigarette and e-cigarette use. This study uses propensity score methods to robustly adjust for shared risk in estimating the relationship between e-cigarette use and conventional smoking. METHODS: Cross-sectional data from 8th and 10th graders were drawn from the 2015-2016 waves of Monitoring the Future (n = 12 421). The effects of (1) lifetime and (2) current e-cigarette use on (A) lifetime and (B) current conventional cigarette smoking were examined using logistic regression analyses with inverse propensity weighting based on 14 associated risk factors. RESULTS: After accounting for the propensity for using e-cigarettes based on 14 risk factors, both lifetime and current e-cigarette use significantly increased the risk of ever smoking a conventional cigarette (OR = 2.49, 95% CI = 1.77 to 3.51; OR = 2.32, 95% CI = 1.66 to 3.25, respectively). However, lifetime (OR = 2.17, 95% CI = 0.62 to 7.63) and current e-cigarette use (OR = 0.95, 95% CI = 0.55 to 1.63) did not significantly increase the risk of current conventional cigarette smoking. CONCLUSIONS: E-cigarette use does not appear to be associated with current, continued smoking. Instead, the apparent relationship between e-cigarette use and current conventional smoking is fully explained by shared risk factors, thus failing to support claims that e-cigarettes have a causal effect on concurrent conventional smoking among youth. E-cigarette use has a remaining association with lifetime cigarette smoking after propensity score adjustment; however, future research is needed to determine whether this is a causal relationship or merely reflects unmeasured confounding. IMPLICATIONS: This study examines the relationship between e-cigarette use and conventional smoking using inverse propensity score weighting, an innovative statistical method that produces less-biased results in the presence of heavy confounding. Our findings show that the apparent relationship between e-cigarette use and current cigarette smoking is entirely attributable to shared risk factors for tobacco use. However, e-cigarette use is associated with lifetime cigarette smoking, though further research is needed to determine whether this is a causal relationship or merely reflects unaccounted-for confounding. Propensity score weighting produced significantly weaker effect estimations compared to conventional regression control.

Anti-inflammatory effects of ethanol extract from the leaves and shoots of Cedrela odorata L. in cytokine-stimulated keratinocytes.

Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.

Peroxisome-targeted Supramolecular Nanoprobes Assembled with Pyrene-labelled Peptide Amphiphiles.

Despite the versatile metabolic functions of peroxisomes such as lipid synthesis and fatty acid oxidation and their relevance to genetically inherited diseases, namely, peroxisome biogenesis disorders and peroxisomal enzyme deficiency, there is not much research on peroxisome-targeting therapeutics. Herein we present supramolecular nanostructured probes based on the self-assembly of peptide amphiphiles (PAs) having peroxisome-targeting ability in mammalian cells. The PA was designed to include the peroxisome-targeting tripeptide (SKL) and a fluorescent dye (pyrene). It was revealed that the presence of the SKL-appended carboxyl terminal group of PA, the extent of α-helical nature of the peptide block, and the fibrillar morphology of nano-assemblies affected the targeting efficiency of PA supramolecular nanoprobe. The simple modification of PAs by the peroxisome-targeting strength prediction showed an enhanced peroxisome specificity, as expected. This work provides important insights into designing subcellular organelle-targeting nanoparticles for next-generation nanomedicines.

Tussilago farfara L. augments TRAIL-induced apoptosis through MKK7/JNK activation by inhibition of MKK7­TIPRL in human hepatocellular carcinoma cells.

Induction of apoptosis through activation of the TRAIL pathway is considered to be a promising anticancer strategy due to its ability to selectively induce apoptosis in cancer cells. However, the ability of cancer cells to acquire TRAIL resistance has limited the clinical translation of this approach. We previously reported that the TOR signaling pathway regulator-like (TIPRL) protein contributes to the resistance to TRAIL-induced apoptosis by inhibiting the MKK7-c-Jun N-terminal kinase (JNK) pathway via MKK7­TIPRL interaction. In the present study, we identified Tussilago farfara L. (TF) as a novel TRAIL sensitizer among 500 natural products using an ELISA system that specifically detects the MKK7-TIPRL interaction, and we validated candidates by GST-pull down assay. Co-treatment of Huh7 cells with TF and TRAIL induced apoptosis via inhibition of the MKK7-TIPRL interaction and an increase in MKK7/JNK phosphorylation. This is the first report to describe TF as a novel TRAIL sensitizer, unveiling a potentially novel therapeutic strategy in cancer therapy.

Purification and characterization of antioxidant peptide from hoki (Johnius belengerii) frame protein by gastrointestinal digestion.

To extract antioxidant peptide from hoki frame protein hydrolysate (APHPH), we employed six proteases (pepsin, trypsin, papain, alpha-chymotrypsin, Alcalase and Neutrase) for enzymatic hydrolysis, and the antioxidant activities of their hydrolysates were investigated using both lipid peroxidation inhibition assay and free radical scavenging assay by electron spin resonance spin-trapping technique. Among hydrolysates, peptic hydrolysate, having the highest antioxidant activity, further separated into four groups using ultrafiltration membranes and purified consecutive chromatographic methods. Finally, the purified peptide had a molecular mass of 1801 Da, and amino acid sequence was identified as Glu-Ser-Thr-Val-Pro-Glu-Arg-Thr-His-Pro-Ala-Cys-Pro-Asp-Phe-Asn. APHPH inhibited lipid peroxidation higher than that of alpha-tocopherol as positive control and efficiently quenched different sources of free radical: 1,1-diphenyl-2-pycryl-hydrazyl (IC(50)=41.37 microM), hydroxyl (IC(50)=17.77 microM), peroxyl (IC(50)=18.99 microM) and superoxide radicals (IC(50)=172.10 microM). Furthermore, APHPH decreased t-butylhydroperoxide-induced cytotoxicity on human embryonic lung fibroblasts and efficiently protected free-radical-induced DNA damage.