The role of puff volume in vaping emissions, inhalation risks, and metabolic perturbations: a pilot study.

Secondhand vaping exposure is an emerging public health concern that remains understudied. In this study, saliva and exhaled emissions from ENDS users (secondhand) and non-ENDS users (baseline) were collected, firsthand emissions were generated using an automated ENDS aerosol generation system programmed to simulate puffing topography profiles collected from ENDS users. Particulate concentrations and sizes along with volatile organic compounds were characterized. We revealed puffing topography metrics as potential mediators of firsthand and secondhand particle and chemical exposures, as well as metabolic and respiratory health outcomes. Particle deposition modeling revealed that while secondhand emissions displayed smaller deposited mass, total and pulmonary particle deposition fractions were higher than firsthand deposition levels, possibly due to smaller secondhand emission particle diameters. Lastly, untargeted metabolomic profiling of salivary biomarkers of lung injury due to firsthand ENDS exposures revealed potential early indicators of respiratory distress that may also be relevant in bystanders exposed to secondhand vaping scenarios. By leveraging system toxicology, we identified 10 metabolites, including leukotriene D4, that could potentially serve as biomarkers for ENDS use, exposure estimation, and the prediction of vaping-related disease. This study highlights characterization of vaping behavior is an important exposure component in advancing our understanding of potential health effects in ENDS users and bystanders.

Composition of e-cigarette aerosols: A review and risk assessment of selected compounds.

The potential harms and benefits of e-cigarettes, or electronic nicotine delivery systems (ENDS), have received significant attention from public health and regulatory communities. Such products may provide a reduced risk means of nicotine delivery for combustible cigarette smokers while being inappropriately appealing to nicotine naive youth. Numerous authors have examined the chemical complexity of aerosols from various open- and closed-system ENDS. This body of literature is reviewed here, with the risks of ENDS aerosol exposure among users evaluated with a margin of exposure (MoE) approach for two non-carcinogens (methylglyoxal, butyraldehyde) and a cancer risk analysis for the carcinogen N-nitrosonornicotine (NNN). We identified 96 relevant papers, including 17, 13, and 5 reporting data for methylglyoxal, butyraldehyde, and NNN, respectively. Using low-end (minimum aerosol concentration, low ENDS use) and high-end (maximum aerosol concentration, high ENDS use) assumptions, estimated doses for methylglyoxal (1.78 × 10-3-135 µg/kg-bw/day) and butyraldehyde (1.9 × 10-4-66.54 µg/kg-bw/day) corresponded to MoEs of 227-17,200,000 and 271-280,000,000, respectively, using identified points of departure (PoDs). Doses of 9.90 × 10-6-1.99 × 10-4 µg/kg-bw/day NNN corresponded to 1.4-28 surplus cancers per 100,000 ENDS users, relative to a NNN-attributable surplus of 7440 per 100,000 cigarette smokers. It was concluded that methylglyoxal and butyraldehyde in ENDS aerosols, while not innocuous, did not present a significant risk of irritant effects among ENDS users. The carcinogenic risks of NNN in ENDS aerosols were reduced, but not eliminated, relative to concentrations reported in combustible cigarette smoke.

Urinary anatalline and nicotelline cut-points to distinguish between exclusive and dual use of tobacco products.

OBJECTIVE: This study measured anatalline and nicotelline, two minor tobacco alkaloids, to discriminate between exclusive smokeless tobacco (SLT) use, exclusive electronic nicotine delivery systems (ENDS) use, exclusive cigarette use, dual SLT and cigarette use, and dual ENDS and cigarette use. METHODS: N = 664 urine samples from participants in the Population Assessment of Tobacco and Health Study were analyzed for anatalline and nicotelline. Geometric means and 95% confidence intervals were calculated for biomarker levels and their ratios. Non-parametric Receiver Operating Characteristic analyses were used to determine optimal cut-points of natural log-transformed biomarker ratios for distinguishing between tobacco use groups. RESULTS: The anatalline/nicotelline ratio distinguished exclusive cigarette from exclusive SLT use (threshold = 18.1, sensitivity = 89.3%, specificity = 86.4%, AUC = 0.90), and exclusive SLT from exclusive ENDS use (threshold = 12.8, sensitivity = 96.4%, specificity = 76.3%, AUC = 0.90) very well, but had reduced sensitivity and specificity when distinguishing exclusive cigarette from exclusive ENDS or any dual use with cigarettes. CONCLUSIONS: This research fills a gap in understanding the public health consequences of SLT and ENDS use by providing objective measures that can signal use of these products alone or in combination with cigarettes.

Acute analgesic effect of nicotine vaping using three experimental pain induction tasks: a randomized, placebo-controlled laboratory study.

RATIONALE: Pain and nicotine use are co-occurring conditions with a significant impact on health. Experimental evidence supports an acute analgesic effect of nicotine which may reinforce nicotine use among those with chronic pain. Evidence for nicotine analgesia have primarily been gathered in combustible cigarette users and have not been extended to electronic nicotine delivery systems (ENDS or vaping). Furthermore, the mechanisms of nicotine analgesia in humans are not well understood. OBJECTIVES: Assess the effect of acute vaped nicotine on subjective and behavioral indices of pain sensitivity using three tasks designed to probe distinct mechanisms of analgesia. METHODS: This study recruited ENDS users (N = 86) to undergo a paced vaping protocol followed by pain tasks in counterbalanced order. Across four sessions, participants vaped e-liquid containing nicotine or placebo, and flavor or no-flavor in a 2 × 2 within-subject design. Assessments included cold pressor, submaximal effort tourniquet to induce ischemic pain, and temporal summation of heat pain, an index of central sensitization. RESULTS: Compared to placebo, nicotine increased cold pressor pain tolerance (ηp2 = 0.031), ischemic pain threshold (ηp2 = 0.073) and tolerance (ηp2 = 0.056) but had no effect on temporal summation of pain. Flavor did not affect pain sensitivity. Females reported greater ischemic pain sensitivity (ηp2 = 0.027) and greater reductions in craving (ηp2 = 0.086). CONCLUSIONS: Consistent with research from tobacco smoking, analgesia may be reinforcing and contribute to nicotine dependence among ENDS users. More research on sex differences is warranted.

The Public Health Impact of a Ban on Flavored Cigars: A Decision-Theoretic Policy Framework.

INTRODUCTION: Half of adult cigar users report flavored cigars as their usual brand. The FDA proposed prohibiting "all characterizing flavors in cigars" and "menthol… in cigarettes." We provide evidence on cigar and cigarette transitions and a framework to assess the impact of a U.S. flavored cigar ban. METHODS: Using PATH Waves 1-4, we estimated use patterns and annual transitions among flavored cigars, non-flavored cigars, cigarettes, and among adults aged 18-34 and aged 35+. We also consider ENDS-related transitions. We developed a decision-theoretic framework for examining the impact of a flavored cigar ban alone, and the impact of a flavored cigar with a menthol cigarette ban with and without a non-tobacco flavored ENDS ban. RESULTS: Cigar users exhibited less stable use than cigarette users, with a large portion of cigar users switching to cigarette use each year. Past studies provide limited information on transitions between cigar and ENDS use. Our policy framework suggests that imposing a flavored cigar ban alone may be partially undermined by the substitution of menthol cigarettes for flavored cigars. While adding a menthol cigarette to a flavored cigar ban is expected to improve public health, a simultaneously implemented ENDS may offset some of the gains. DISCUSSION: Our analysis suggests the information necessary to gauge the public health impact of a cigar flavor ban alone and with flavor bans on cigarettes and ENDS. Further research is needed on ENDS vis-a'-vis cigar use, and the impact of enforcement and non-flavor-related policies on flavor ban effectiveness. IMPLICATIONS: Unlike menthol cigarette use and menthol bans, flavored cigar use and flavored cigar bans have received minimal attention. Transitions from cigars, especially dual and flavored use, are generally common compared to cigarettes. Our policy framework suggests important public health impacts. A flavored cigar ban absent a menthol cigarette ban may be partially undermined by the substitution of menthol cigarettes for flavored cigars. Adding a menthol cigarette ban is expected to offset such substitution and improve public health. However, simultaneously adding an ENDS with a flavored cigar and menthol cigarette ban may reduce the public health impact of a menthol cigarette and cigar flavor ban since flavored cigar users would be less able to substitute a lower-risk alternative.

Associations between ENDS and cigarette use, and compromised immunity in US adults: Findings from the 2021-2022 NHIS.

BACKGROUND: Tobacco use presents increased risks for individuals with weakened immune systems (WIS). We investigated the association between cigarette and electronic nicotine delivery systems (ENDS or e-cigarettes) use and WIS in US adults using data from the 2021-2022 National Health Interview Survey. METHODS: Data from 57,133 adults were analyzed, focusing on WIS prevalence due to health conditions, prescriptions, or both. Cigarette and ENDS use were categorized as never, former, or current. Weighted multivariable regression models adjusted for demographics and other health conditions to assess associations between tobacco use and WIS. RESULTS: Among US adults, 4.3% had prescription-related WIS, 4.6% had health condition-related WIS, and 7% had WIS due to either reason. Adjusted results from multivariable regression models indicated that adults with WIS due to health conditions were more likely to be current (AOR = 1.21, 95%CI: 1.05-1.40) and former (AOR = 1.25, 95%CI: 1.11-1.39) cigarette smokers compared to counterparts without WIS. Adults with WIS due to prescriptions were more likely to be former cigarette smokers (AOR = 1.19, 95%CI: 1.06-1.34). Those with WIS for any reason were more likely to be current (AOR = 1.19, 95%CI: 1.05-1.35) and former (AOR = 1.24, 95%CI: 1.13-1.36) cigarette smokers. Adults with WIS due to health conditions (AOR = 1.23, 95%CI: 1.06-1.41) or any reasons (AOR = 1.19, 95%CI:1.05-1.34) were more likely to be former ENDS users compared to those without WIS. CONCLUSIONS: In this nationally representative study, we found a notable link between cigarette and ENDS use with WIS, particularly among those with health condition-related or prescription-related WIS, underscoring the importance of addressing tobacco use in this vulnerable population.

Formaldehyde and the Transient Receptor Potential Ankyrin-1 Contribute to Electronic Cigarette Aerosol-induced Endothelial Dysfunction in Mice.

Electronic Nicotine Delivery Systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and 'respiratory braking' - biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or formaldehyde (FA, 5 ppm). Short-term exposures to PG: VG and FA induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N  -1,3-thiazolidine-4-carboxylic acid, TCA; N  -1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h).13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0-3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS.

Inhalation of nicotine-containing electronic cigarette vapor exacerbates the features of COPD by inducing ferroptosis in ßENaC-overexpressing mice.

Introduction: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood. Methods: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics. Results: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells. Discussion: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.

Trends in vaping and smoking following the rise of disposable e-cigarettes: a repeat cross-sectional study in England between 2016 and 2023.

Background: There has been a rapid rise in disposable (single-use) e-cigarette vaping among young adults in England since June 2021 (leading to a planned ban on these products). We examined how this has affected population trends in current (i) vaping, (ii) tobacco smoking, and (iii) inhaled nicotine use. Methods: We used data from a nationally-representative monthly repeat cross-sectional survey of adults (≥18) in England (n = 132,252; July-2016-May-2023). Using interrupted time-series analyses (segmented logistic regression), we estimated yearly trends in current tobacco smoking, vaping, and inhaled nicotine use (smoking and/or vaping) before ('pre-disposables') and after June-2021 ('post-disposables'), stratified by age group (18 to 24, 25 to 44, 45 and over). We also examined trends in daily use and in vaping among never-smokers. Findings: Pre-disposables, vaping and smoking prevalence had been stable or declining across all age groups. However, post-disposables, the odds of current vaping increased by 99% per year among 18 to 24-year-olds (odds ratio [OR] = 1.99; 95% confidence interval [CI] = 1.71 to 2.31), compared with 39% (OR = 1.39; 95% CI = 1.26 to 1.52) in 25 to 44-year-olds and 23% (OR = 1.23; 95% CI = 1.12 to 1.35) in those aged 45 or older. Smoking rates continued to decline - albeit modestly - in 18 to 24-year-olds (OR = 0.88, 95% CI = 0.77 to 1.00) and 25 to 44-year-olds (OR = 0.93, 95% CI = 0.86 to 1.00), but increased among those aged 45 or older (OR = 1.12, 95% CI = 1.05 to 1.20). As a result, post-disposables, the overall prevalence of inhaled nicotine use increased across all age groups. Trends were similar for daily use, but post-disposables increases in vaping were greatest among people who had never regularly smoked (e.g., 18 to 24-year-olds: OR = 2.50, 95% CI = 1.82 to 3.43). Interpretation: Since disposable vapes started becoming popular in England, historic declines in nicotine use have reversed. Now, nicotine use appears to be rising, driven primarily by sharp increases in vaping among young people. Smoking declines have been most pronounced in age groups with the largest increases in vaping. Funding: Cancer Research UK.

Starch phosphorylation-A needle in a haystack.

Phosphoesterification is the only naturally occurring covalent starch modification identified to date, and it has a major impact on overall starch metabolism. The incorporation of phosphate groups mediated by dikinases [α-glucan, water dikinase (GWD), EC 2.7.9.4; phosphoglucan, water dikinase (PWD), EC 2.7.9.5] massively alters the starch granule properties; however, previous studies did not determine whether the starch-related dikinases bind the phosphate to the glucosyl units within the amylopectin molecules in a specific pattern or randomly. In order to answer this challenging question, a number of approaches were initially pursued until a protocol could be established that enabled a massive step forward in the in vitro analysis of phosphorylated glucan chains obtained from starch. For this purpose, phosphorylation by GWD was investigated, including the final state of phosphorylation i.e., the state of substrate saturation when GWD lacks further free hydroxyl groups at OH-C6 for the catalysis of monophosphate esters. Since the separated phosphorylated glucan chains were required for the analysis, isoamylase digestion was performed to cleave the α-1,6-glycosidic bonds and to allow for the removal of the huge number of existing neutral chains by means of anion exchange chromatography. Via Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) MS and MALDI-MS/MS, the phosphorylated α-glucan chains were analysed, and the position of the phosphate group within the chain in relation to the reducing end was determined. Here, we demonstrate a protocol that enables the analysis of phosphorylated oligosaccharides, even in small quantities.

The "Gateway" hypothesis: evaluation of evidence and alternative explanations.

BACKGROUND: Electronic nicotine delivery systems (ENDS) offer a substantial harm reduction opportunity for adults who smoke and are unlikely to quit. However, a major concern about ENDS is their use by non-smoking youth, and particularly whether ENDS are acting as a "gateway" that leads youth to later start smoking cigarettes. However, evidence for the gateway hypothesis can be interpreted in alternative ways, e.g. that youth who have certain characteristics were already predisposed to use both ENDS and cigarettes ("common liability" explanation). AIMS: This commentary provides an evaluation of the gateway hypothesis that is accessible by a lay audience. This paper first reviews and evaluates the evidence interpreted as supporting the gateway hypothesis. Important alternative explanations (i.e., common liability) are discussed, as are different types of evidence (i.e., population-level trends) that can help differentiate between these competing explanations. OVERVIEW: Evidence for the gateway hypothesis is based on the finding that youth who use ENDS are more likely to also smoke cigarettes. However, this evidence suffers from an important flaw: these studies fail to fully account for some youths' pre-existing tendency to use products containing nicotine, and inappropriately interpret the results as ENDS use causing some youth to smoke. Common liability studies suggest that ENDS use does not, in and of itself, directly cause youth to later smoke cigarettes, beyond their pre-existing tendency to use products containing nicotine. Population-level trends show that youth cigarette smoking declined faster after ENDS use became common, which contradicts the central prediction of the gateway hypothesis (i.e. that youth smoking would be more common following ENDS uptake, than otherwise be expected). CONCLUSION: Evidence offered in support of the gateway hypothesis does not establish that ENDS use causes youth to also smoke cigarettes. Instead, this evidence is better interpreted as resulting from a common liability to use both ENDS and cigarettes. Population-level trends are inconsistent with the gateway hypothesis, and instead are consistent with (but do not prove) ENDS displacing cigarettes. Policies based on misinterpreting a causal gateway effect may be ineffective at best, and risk the negative unintended consequence of increased cigarette smoking.

Sensitivity of Mouse Lung Nuclear Receptors to Electronic Cigarette Aerosols and Influence of Sex Differences: A Pilot Study.

The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT2 profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.

Investigative analysis of blood-brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models.

INTRODUCTION: Seizures are known potential side effects of nicotine toxicity and have been reported in electronic nicotine delivery systems (ENDS, e-cigarettes) users, with the majority involving youth or young adults. AREAS COVERED: Using chemoinformatic computational models, chemicals (including flavors) documented to be present in ENDS were compared to known neuroactive compounds to predict the blood-brain barrier (BBB) penetration potential, central nervous system (CNS) activity, and their structural similarities. The literature search used PubMed/Google Scholar, through September 2023, to identify individual chemicals in ENDS and neuroactive compounds.The results show that ENDS chemicals in this study contain >60% structural similarity to neuroactive compounds based on chemical fingerprint similarity analyses. The majority of ENDS chemicals we studied were predicted to cross the BBB, with approximately 60% confidence, and were also predicted to have CNS activity; those not predicted to passively diffuse through the BBB may be actively transported through the BBB to elicit CNS impacts, although it is currently unknown. EXPERT OPINION: In lieu of in vitro and in vivo testing, this study screens ENDS chemicals for potential CNS activity and predicts BBB penetration potential using computer-based models, allowing for prioritization for further study and potential early identification of CNS toxicity.

A systematic review of the modelling and economic evaluation studies assessing regulatory options for e-cigarette use.

BACKGROUND: Governments around the world are considering regulating access to nicotine e-cigarettes to prevent uptake among youth however people that smoke tobacco may use them to assist with smoking cessation. The health and cost implications of regulating e-cigarette use among populations are unknown but have been explored in modelling studies. We reviewed health economic evaluation and simulation modelling studies that assessed long-term consequences and interpret their potential usefulness for decision-makers. METHODS: A systematic review with a narrative synthesis was undertaken. Six databases were searched for modelling studies evaluating population-level e-cigarette control policies or interventions restricting e-cigarette use versus more liberalized use. Studies were required to report the outcomes of life years, quality-adjusted life years (QALYs) and/or healthcare costs. The quality of the studies was assessed using two quality assessment tools. RESULTS: In total, 15 studies were included with nine for the United States and one each for the United Kingdom, Italy, Australia, Singapore, Canada, and New Zealand. Three studies included cost-utility analyses. Most studies involved health state transition (or Markov) closed cohort models. Many studies had limitations with their model structures, data input quality and transparency, and insufficient analyses handling model uncertainty. Findings were mixed with 11 studies concluding that policies permitting e-cigarette use lead to net benefits and 4 studies concluding net losses in life-years or QALYs and/or healthcare costs.Five studies had industry conflicts of interest. CONCLUSIONS: While authors did conclude net benefit than net harm in more of the studies so far conducted, the significant limitations that we identified with many of the studies in this review, make it uncertain whether or not countries can expect net population harms or benefits of restrictive versus unrestrictive e-cigarette policies. The generalizability of the findings is limited for decision-makers. In light of the deep uncertainty around the health and economic outcomes of e-cigarettes, simulation modelling methods and uncertainty analyses should be strengthened.

Effect of cellulose reducing ends and primary hydroxyl groups modifications on cellulose-cellulase interactions and cellulose hydrolysis.

Cellulose reducing ends are believed to play a vital role in the cellulose recalcitrance to enzymatic conversion. However, their role in insoluble cellulose accessibility and hydrolysis is not clear. Thus, in this study, reducing ends of insoluble cellulose derived from various sources were modified by applying reducing and/or oxidizing agents. The effects of cellulose reducing ends modification on cellulose reducing ends, cellulose structure, and cellulose accessibility to cellulase were evaluated along with the impact on cellulose hydrolysis with complete as well purified cellulase components. Sodium borohydride (NaBH4) reduction and sodium chlorite-acetic acid (SC/AA) oxidation were able to modify more than 90% and 60% of the reducing ends, respectively, while the bicinchoninic acid (BCA) reagent applied for various cycles oxidized cellulose reducing ends to various extents. X-ray diffractograms of the treated solids showed that these treatments did not change the cellulose crystalline structure and the change in crystallinity index was insignificant. Surprisingly, it was found that the cellulose reducing ends modification, either through selective NaBH4 reduction or BCA oxidation, had a negligible impact on cellulose accessibility as well on cellulose hydrolysis rates or final conversions with complete cellulase at loadings as low as 0.5 mg protein/g cellulose. In fact, in contrast to what is traditionally believed, modifications of cellulose reducing ends by these two methods had no apparent impact on cellulose conversion with purified cellulase components and their synergy. However, SC/AA oxidation resulted in significant drop in cellulose conversion (10%-50%) with complete as well purified cellulase components. Nonetheless, further research revealed that the cause for drop in cellulose conversion for the SC/AA oxidation case was due to primary hydroxyl groups (PHGs) oxidation and not the oxidation of reducing ends. Furthermore, it was found that the PHGs modification affects cellulose accessibility and slows the cellulase uptake as well resulting in significant drop in cellulose conversions.

Leads with the Cut Proximal Ends Migrated into the Heart and Vasculature: A Rare Phenomenon among 3847 Lead Extraction Procedures.

Background: The study aimed to describe the phenomenon of leads migrated (MPLE) into the cardiovascular system (CVS). Methods: Retrospective analysis of 3847 transvenous lead extractions (TLE). Results: Over a 17-year period, 72 (1.87%) MPLEs (median dwell time 137.5 months) were extracted, which included mainly ventricular leads (56.94%). Overall, 68.06% of MPLEs had their cut proximal ends in the venous system. Most of them were pacing (95.83%) and passive fixation (98.61%) leads. Independent risk factors for MPLE included abandoned leads (OR = 8.473; p < 0.001) and leads located on both sides of the chest (2.981; p = 0.045). The higher NYHA class lowered the probability of MPLE (OR = 0.380; p < 0.001). Procedure complexity was higher in the MPLE group (procedure duration, unexpected procedure difficulties, use of additional (advanced) tools and alternative venous approach). There were no more major complications in the MPLE group, but the rate of procedural success was lower due to more frequent retention of non-removable lead fragments. Extraction of MPLEs did not influence long-term survival. Conclusions: 1. Extraction of leads with MPLE is rare among other TLE procedures (1.9%), 2. risk factors include abandoned leads and presence of leads on both sides of the chest but a higher NYHA class lowers the probability of MPLE, 3. complexity of MPLE extraction is higher regarding procedure duration, unexpected procedure difficulties, use of advanced tools and techniques but rates of major complications are comparable, and 4. extraction of MPLEs did not influence long-term survival.

The impact of chronic electronic cigarette use on endothelial dysfunction measured by flow-mediated vasodilation: A systematic review and meta-analysis.

INTRODUCTION: Despite electronic cigarettes (e-cigarettes) being marketed as a safer alternative to combustible cigarettes, the effects of chronic e-cigarette use on vascular health remain uncertain. Our meta-analysis aimed to assess the health implications of chronic exclusive e-cigarette use on endothelial dysfunction, as measured by flow-mediated vasodilation (FMD). METHODS: PubMed, Embase and Scopus were searched for studies from 1 January 2004 to 31 March 2024. Four cross-sectional studies (n=769) were pooled using a random-effects model. The mean differences (MD) of FMD were reported by comparing exclusive e-cigarette use versus non-use; exclusive e-cigarette use versus combustible cigarette use; and combustible cigarette use versus non-use. RESULTS: A non-significant reduction in FMD in exclusive e-cigarette use compared to non-use was reported (MD of FMD: -1.47%; 95% CI: -3.96 - 1.02; I2= 84%). Similar MD of FMD in exclusive e-cigarette use and exclusive combustible cigarette use (vs non-use) suggested that both of these products might have comparable adverse influences on endothelial health. CONCLUSIONS: The limited availability of studies assessing the chronic impact of e-cigarette use restricted our ability to provide definitive findings. We emphasize the importance of additional research that explores the long-term impact of e-cigarette use on endothelial dysfunction, and identify key areas and give suggestions for further study.

E-cigarette dependence and cooling flavor use are linked among youth.

BACKGROUND: E-cigarette flavors that produce cooling sensations may reduce nicotine harshness and enhance appeal among youth. While previous research has shown that use of cooling flavors is associated with more frequent vaping among youth, it is unknown whether the same holds true for e-cigarette dependence. This study examines the relationship between cooling flavor use and e-cigarette dependence among youth accounting for vaping frequency. METHODS: In Fall 2022, a survey was conducted among Connecticut high school students to assess past-month nicotine e-cigarette use, ever use of cooling flavors, cooling flavor types (e.g., fruit-cooling), and e-cigarette dependence. Analyses were restricted to those with past-month nicotine and nicotine-free e-cigarette use and complete data (n=204). Multivariable linear regressions were run to examine the association between cooling flavor use and e-cigarette dependence, adjusting for demographics, e-cigarette use characteristics, and other tobacco product use. RESULTS: 78.4% of the sample used cooling e-cigarette flavors, with 55.0% using mint-cooling flavors and 52.5% using fruit-cooling flavors. Regression results observed that cooling flavor use was associated with higher e-cigarette dependence (ꞵ=1.53, SE=0.63, p=0.017), with those who used cooling flavors having higher e-cigarette dependence than those who did not (M=5.78 [SD=5.33] vs. 2.84 [3.19]). CONCLUSIONS: Our results suggest that cooling flavor use is significantly associated with e-cigarette dependence among youth. While regulations often target menthol flavor, tobacco control agencies should consider restricting any flavor that can produce cooling sensations, even if they are not traditional menthol products, as cooling flavors is associated with youth e-cigarette dependence.

Electronic nicotine delivery systems (ENDS): Frequency of use and smoking-cessation efforts among U.S. women of reproductive age.

OBJECTIVE: Reducing harm from combustible cigarette use among women of reproductive age (WRA) is critical given their potential vulnerability to multigenerational adverse impacts of cigarette smoking. Although electronic nicotine delivery systems (ENDS) are not approved smoking cessation aids in the US, many WRA who smoke report using ENDS to help quit smoking. Associations between ENDS use patterns and smoking-cessation efforts among US WRA remain unclear. METHODS: Using the Population Assessment of Tobacco and Health (PATH) Study, we examined whether baseline (Wave 3 or 4) ENDS use frequency predicted (a) making a cigarette quit attempt (QA) and (b) successful quitting by follow-up (Wave 4 or 5, respectively) among WRA (N = 2834; 72.1% non-Hispanic White). RESULTS: Daily ENDS use predicted greater adjusted odds of making a QA than non-daily (AOR = 1.63, 95% CI = 1.03, 2.59) and no ENDS use (AOR = 1.97, 95% CI = 1.23, 3.14), and greater odds of successful smoking cessation than non-daily use (AOR = 2.37, 95% CI = 1.31, 4.26). Daily ENDS use did not significantly improve odds of successful smoking cessation compared to no ENDS use (AOR = 1.62, 95% CI = 0.97, 2.69). Non-daily ENDS use did not significantly improve odds of making a QA (AOR = 1.21, 95% CI = 0.94, 1.56) and hindered successful smoking cessation compared to no ENDS use (AOR = 0.68, 95% CI = 0.48, 0.98). CONCLUSIONS: These findings suggest that benefits of ENDS for smoking cessation in WRA may be greatest among those who use ENDS daily. WRA who choose to use ENDS to help quit would be well-informed by evidence that non-daily ENDS use may impede smoking cessation.