Patterns of flavored e-cigarette use among adult vapers in the USA: an online cross-sectional survey of 69,233 participants.

BACKGROUND: Flavored e-cigarettes remain a controversial topic with regulators planning or already implementing restrictions worldwide. In this study, we examined patterns of flavor use in e-cigarettes among a convenience sample of US adult vapers. METHODS: Participants aged ≥ 18 years who reported ever using an e-cigarette were included in the study (N = 69,233) and responded to an online questionnaire. Their smoking status was recorded as well as patterns of flavor use at e-cigarette use initiation, at the time of the survey and at the time of smoking cessation (for participants who used to smoke and were using e-cigarettes at the time of quitting). RESULTS: The most popular flavors at e-cigarette use initiation were fruit (82.8%), followed by dessert/pastry/bakery (68.6%) and candy/chocolate/sweet (52.2%). Slightly higher prevalence of using fruit and dessert/pastry/bakery flavors was observed in those who never smoked compared to those who were currently and formerly smoking. Tobacco flavors were used by 20.8% of the participants and was by far the least prevalent among participants who never smoked. Similar patterns were observed with participants' choices at the time of the survey, but tobacco flavor use was substantially reduced (7.7%). Only 2.1% reported tobacco as the single most often used flavor. The most prevalent flavor at the time of quitting smoking was again fruit (83.3%), followed by dessert/pastry/bakery (68.0%) and candy/chocolate/sweet (44.5%). These flavors were considered the most helpful for quitting smoking. Tobacco flavor use at the time of smoking cessation was reported by 15.0%, while 9.3% considered it helpful for quitting smoking. CONCLUSION: Non-tobacco flavors were popular among the US adult vapers who participated in the study, and were popular choices at the time of quitting smoking for those who formerly smoked. Tobacco flavor use prevalence was low and was further reduced over time. Regulators should consider the flavor choice of adult consumers, especially those who quit smoking, when preparing legislation on flavored e-cigarettes.

Redox Biomarkers Assessment after Oral Administration of Wine Extract and Grape Stem Extract in Rats and Mice.

Wine and by-products of the winemaking process, such as grape stems, are rich in bioactive polyphenolic compounds that might be beneficial for animal and human health. In recent years, the administration of dietary polyphenols with strong antioxidant and cytoprotective properties has constituted an emerging line of research interest toward disease prevention. However, in scientific literature, only a limited number of studies have investigated the safety and the toxicological risks of polyphenolic compounds in vivo. Based on the above, the purpose of the present study was two-fold: first, to examine the effects of oral administration of a grape stem extract, derived from the Greek red wine Mavrodaphne, on mice redox biomarkers; and second, to investigate the biological effects of oral administration of a wine extract, derived from the emblematic Greek red wine Xinomavro, on rats. Toward this purpose, body weight, growth rate, hematological, biochemical, and histopathological parameters, as well as a panel of redox biomarkers, were examined. According to our results, the administration of Mavrodaphne grape stem extract in mice induced alterations in redox homeostasis, preventing mice from the adverse effects of lipid peroxidation. Contrariwise, the administration of Xinomavro wine extract induced both beneficial and harmful outcomes on rat redox status determined by the examined tissue. Collectively, our study reports that the Mavrodaphne grape stem extract, a serious pollutant when disposed in environmental matrices, is an important source of bioactive polyphenolic compounds that could protect from oxidative damage and improve animal and human health. Finally, the Xinomavro wine extract exerts tissue-specific changes in redox balance, which are indicative of the complexity that characterizes the biological systems.

Comparative assessment of electronic nicotine delivery systems aerosol and cigarette smoke on endothelial cell migration: The Replica Project.

Cigarette smoking is associated with impairment of repair mechanisms necessary for vascular endothelium homeostasis. Reducing the exposure to smoke toxicants may result in the mitigation of the harmful effect on the endothelium and cardiovascular disease development. Previous investigations evaluated in vitro the effect of electronic cigarette (EC) compared with cigarette smoke demonstrating a significant reduction in human umbilical vein endothelial cells (HUVECs) migration inhibition following EC aerosol exposure. In the present study, we replicated one of these studies, evaluating the effects of cigarette smoke on endothelial cell migration compared with aerosol from EC and heated tobacco products (HTPs). We performed an in vitro scratch wound assay on endothelial cells with a multi-center approach (ring-study) to verify the robustness and reliability of the results obtained in the replicated study, also testing the effect of aerosol from two HTPs on endothelial cells. Consistently with the original study, we observed a substantial reduction of the effects of aerosol from EC and HTPs on endothelial cell migration compared with cigarette smoke. While cigarette smoke reduced endothelial wound healing ability already at low concentrations (12.5%) and in a concentration-dependent manner, EC and HTPs aerosol showed no effect on endothelial cells until 80%-100% concentrations. In conclusion, our study further confirms the importance of EC and tobacco heated products as a possible harm reduction strategy for cardiovascular diseases development in smokers.

Myasthenia gravis genome-wide association study implicates AGRN as a risk locus.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Here, we investigate the genetic architecture of MG via a genome-wide association study (GWAS) of the largest MG data set analysed to date. METHODS: We performed GWAS meta-analysis integrating three different data sets (total of 1401 cases and 3508 controls). We carried out human leucocyte antigen (HLA) fine-mapping, gene-based and tissue enrichment analyses and investigated genetic correlation with 13 other autoimmune disorders as well as pleiotropy across MG and correlated disorders. RESULTS: We confirmed the previously reported MG association with TNFRSF11A (rs4369774; p=1.09×10-13, OR=1.4). Furthermore, gene-based analysis revealed AGRN as a novel MG susceptibility gene. HLA fine-mapping pointed to two independent MG loci: HLA-DRB1 and HLA-B. MG onset-specific analysis reveals differences in the genetic architecture of early-onset MG (EOMG) versus late-onset MG (LOMG). Furthermore, we find MG to be genetically correlated with type 1 diabetes (T1D), rheumatoid arthritis (RA), late-onset vitiligo and autoimmune thyroid disease (ATD). Cross-disorder meta-analysis reveals multiple risk loci that appear pleiotropic across MG and correlated disorders. DISCUSSION: Our gene-based analysis identifies AGRN as a novel MG susceptibility gene, implicating for the first time a locus encoding a protein (agrin) that is directly relevant to NMJ activation. Mutations in AGRN have been found to underlie congenital myasthenic syndrome. Our results are also consistent with previous studies highlighting the role of HLA and TNFRSF11A in MG aetiology and the different risk genes in EOMG versus LOMG. Finally, we uncover the genetic correlation of MG with T1D, RA, ATD and late-onset vitiligo, pointing to shared underlying genetic mechanisms.

Electronic nicotine delivery systems exhibit reduced bronchial epithelial cells toxicity compared to cigarette: the Replica Project.

Electronic nicotine delivery systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. We aimed to replicate three published studies on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multi-center ring study. We aimed to establish the reliability of results and the robustness of conclusions by replicating the authors' experimental protocols and further validating them with different techniques. Human bronchial epithelial cells (NCI-H292) were exposed to cigarette whole smoke and vapor phase and to aerosol from ENDS. We also assessed the inflammatory cytokines interleukin-6 and interleukin-8 and the remodeling mediator matrix metalloproteinase-1. We replicated cell viability results and confirmed that almost 80% of cytotoxic effects are due to volatile compounds in the vapor phase of smoke. Our findings substantiated the reduced cytotoxic effects of ENDS aerosol. However, our data on inflammatory and remodeling activity triggered by smoke differed significantly from those in the original reports. Taken together, independent data from multiple laboratories clearly demonstrated the reduced toxicity of ENDS products compared to cigarettes.

Is SARS-CoV-2 Spike glycoprotein impairing macrophage function via α7-nicotinic acetylcholine receptors?

The innate immune cells play an important role in handling early infections, and can eliminate them completely up to a certain threshold. Beyond that threshold they take up their role in "The Resolution of Inflammation". The recognition of the SARS-CoV-2 antigen triggers an eicosanoid storm and initiates a robust inflammatory response. This establishes a positive feedback loop which develops into a sustained cytokine storm which interferes with the activation of adaptive immune cells. The mechanism of this interaction, and hence the pathogenesis of the virus with the immune system, is yet to be determined. In silico studies predict a direct SARS-CoV-2 spike glycoprotein interaction with nicotinic acetylcholine receptors, which could impair macrophage function and initiate the cascade of events in severe infections. We here, add to the hypothesis that immune dysregulation can be caused by the interaction of the SARS-CoV-2 spike glycoprotein via a cryptic epitope with the α7-nAChR in Type-1 macrophages, discuss its implications for the treatment of COVID-19 patients, and present better prospects for the design and dissemination of more effective vaccines and their importance.

Safety of COVID-19 vaccines administered in the EU: Should we be concerned?

The COVID-19 pandemic has had an unprecedented and devastating impact on public health, society and economics around the world. As a result, the development of vaccines to protect individuals from symptomatic COVID-19 infections has represented the only feasible health tool to combat the spread of the disease. However, at the same time the development and regulatory assessment of different vaccines has challenged pharmaceutical industries and regulatory agencies as this process has occurred in the shorter time ever though. So far, two mRNA and two adenovirus-vectored vaccines have received a conditional marketing authorisation in the EU and other countries. This review summarized and discusses the assessment reports of the European Medicine Agency (EMA) concerning the safety of the 3 vaccines currently used in the EU (Pfizer, Moderna and Astra-Zeneca). A particular focus has been paid to safety information from pre-clinical (animal) and clinical (phase 3 trials) studies. Overall, the most frequent adverse effects reported after the administration of these vaccines consisted of local reactions at the injection site (sore arm and erythema) followed by non-specific systemic effects (myalgia, chills, fatigue, headache, and fever), which occurred soon after vaccination and resolved shortly. Rare cases of vaccine-induced immune thrombotic thrombocytopenia have been reported for Vaxzevria. Data on long-term studies, interaction with other vaccines, use in pregnancy/breast-feeding, use in immunocompromised subjects, and in subjects with comorbidities, autoimmune or inflammatory disorders are still missing for these vaccines. Therefore, careful follow-up and surveillance studies for continued vaccine safety monitoring will be needed to ascertain the potential risks of such adverse events or diseases. In conclusion, the benefits and risks of current COVID-19 vaccines must be weighed against the real possibility of contract the disease and develop complications and long-term sequels; all this on the basis of the available scientific evidence and in the absence of unmotivated biases.

Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins.

SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. Studies have shown that smokers are less likely to be diagnosed with or be hospitalized for COVID-19 but, once hospitalized, have higher odds for an adverse outcome. We have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a "toxin-like" epitope on the Spike glycoprotein, with homology to a sequence of a snake venom toxin. This epitope coincides with the well-described cryptic epitope for the human anti-SARS-CoV antibody CR3022. In this study, we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike glycoproteins, at their open or closed conformations, with the model of the human α7 nAChR. We found that all studied protein complexes' interface involves a large part of the "toxin-like" sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human α7 nAChR. Our findings provide further support to the hypothesis about the protective role of nicotine and other cholinergic agonists. The potential therapeutic role of CR3022 and other similar monoclonal antibodies with increased affinity for SARS-CoV-2 Spike glycoprotein against the clinical effects originating from the dysregulated cholinergic pathway should be further explored.

Nicotinic cholinergic system and COVID-19: In silico evaluation of nicotinic acetylcholine receptor agonists as potential therapeutic interventions.

SARS-CoV-2 infection was announced as a pandemic in March 2020. Since then, several scientists have focused on the low prevalence of smokers among hospitalized COVID-19 patients. These findings led to our hypothesis that the Nicotinic Cholinergic System (NCS) plays a crucial role in the manifestation of COVID-19 and its severe symptoms. Molecular modeling revealed that the SARS-CoV-2 Spike glycoprotein might bind to nicotinic acetylcholine receptors (nAChRs) through a cryptic epitope homologous to snake toxins, substrates well documented and known for their affinity to the nAChRs. This binding model could provide logical explanations for the acute inflammatory disorder in patients with COVID-19, which may be linked to severe dysregulation of NCS. In this study, we present a series of complexes with cholinergic agonists that can potentially prevent SARS-CoV-2 Spike glycoprotein from binding to nAChRs, avoiding dysregulation of the NCS and moderating the symptoms and clinical manifestations of COVID-19. If our hypothesis is verified by in vitro and in vivo studies, repurposing agents currently approved for smoking cessation and neurological conditions could provide the scientific community with a therapeutic option in severe COVID-19.

Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication.

BACKGROUND: There is a lot of debate about the effects of smoking on COVID-19. A recent fixed-effects meta-analysis found smoking to be associated with disease severity among hospitalized patients, but other studies report an unusually low prevalence of smoking among hospitalized patients. The purpose of this study was to expand the analysis by calculating the prevalence odds ratio (POR) of smoking among hospitalized COVID-19 patients, while the association between smoking and disease severity and mortality was examined by random-effects meta-analyses considering the highly heterogeneous study populations. METHODS: The same studies as examined in the previous meta-analysis were analyzed (N = 22, 20 studies from China and 2 from USA). The POR relative to the expected smoking prevalence was calculated using gender and age-adjusted population smoking rates. Random-effects meta-analyses were used for all other associations. RESULTS: A total of 7162 patients were included, with 482 being smokers. The POR was 0.24 (95%CI 0.19-0.30). Unlike the original study, the association between smoking and disease severity was not statistically significant using random-effects meta-analysis (OR 1.40, 95%CI 0.98-1.98). In agreement with the original study, no statistically significant association was found between smoking and mortality (OR 1.86, 95%CI 0.88-3.94). CONCLUSION: An unusually low prevalence of smoking, approximately 1/4th the expected prevalence, was observed among hospitalized COVID-19 patients. Any association between smoking and COVID-19 severity cannot be generalized but should refer to the seemingly low proportion of smokers who develop severe COVID-19 that requires hospitalization. Smokers should be advised to quit due to long-term health risks, but pharmaceutical nicotine or other nicotinic cholinergic agonists should be explored as potential therapeutic options, based on a recently presented hypothesis.

Larvicidal Action of Cannabidiol Oil and Neem Oil against Three Stored Product Insect Pests: Effect on Survival Time and in Progeny.

SStored product pests can be detrimental to agricultural produce. As much as chemical pesticides are effective control agents, they involve several environmental and health risks. Within the framework of studies on alternative pest management methods, interest has focused on a plethora of plants whose extracts have demonstrated promising action as insecticides. Azadirachta indica and the derived neem oil have been extensively tested against many harmful insect species. In contrast, Cannabis sativa L. and its main compound, CBD, a highly concentrated cannabinoid, have not been investigated much. The present study examined the potential insecticidal activity of CBD and neem oils against 4th instar larvae of Tribolium confusum, Oryzaephilus surinamensis and Plodia interpunctella on wheat, rice and corn seeds. Treatment efficacy was expressed in terms of larval mortality. Mortality was observed in relation to dosage, time exposure intervals and product types. The results showed clear pesticidal activity for both oils, which at high doses induced significant mortality. The treatments produced significantly fewer offspring in the insect species tested than the control. The efficacy of treatment in progeny suppression was, as expected, dose dependent.

The flavoring and not the nicotine content is a decisive factor for the effects of refill liquids of electronic cigarette on the redox status of endothelial cells.

Electronic cigarettes are constantly gaining ground as they are considered less harmful than conventional cigarettes, and there is also the perception that they may serve as a potential smoking cessation tool. Although the acute effects of electronic cigarette use have been extensively studied, the long-term potential adverse effects on human health remain largely unknown. It has been well-established that oxidative stress is involved in the development of various pathological conditions. So far, most studies on e-cigarettes concern the effects on the respiratory system while fewer have focused on the vascular system. In the present study, we attempted to reveal the effects of electronic cigarette refill liquids on the redox state of human endothelial cells (EA.hy926 cell line). For this purpose, the cytotoxic effect of three e-liquids with different flavors (tobacco, vanilla, apple/mint) and nicotine concentrations (0, 6, 12, 18 mg/ml) were initially examined for their impact on cell viability of EA.hy926 cells. Then, five redox biomarkers [reduced form of glutathione (GSH), reactive oxygen species (ROS), total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyls (CARBS)] were measured. The results showed a disturbance in the redox balance in favor of free radicals in tobacco flavored e-liquids while vanilla flavored e-liquids exhibited a more complex profile depending on the nicotine content. The most interesting finding of the present study concerns the apple/mint flavored e-liquids that seemed to activate the cellular antioxidant defense and, thus, to protect the cells from the adverse effects of free radicals. Conclusively, it appears that the flavorings and not the nicotine content play a key role in the oxidative stress-induced toxicity of the e-liquids.

Combined Toxicity of Cannabidiol Oil with Three Bio-Pesticides against Adults of Sitophilus Zeamais, Rhyzopertha Dominica, Prostephanus Truncatus and Trogoderma Granarium.

The present study investigates the interaction between cannabidiol (CBD) oil and three biopesticides: Azatin and two baculovirus formulations (Madex and Helicovex), both separately and in combination, in order to investigate their interaction against adults of four major coleopteran stored-product pests: Sitophilus zeamais (Coleoptera: Curculionidae), Rhyzopertha dominica (Coleoptera: Bostrichidae), Prostephanus truncatus (Coleoptera: Bostrichidae) and Trogoderma granarium (Coleoptera: Dermestidae). CBD, which has been understudied for its insecticidal properties, was applied at three different doses (500, 1500 and 3000 ppm). The biopesticides were administered at 1500 ppm. Interactions in the combined treatments were mathematically estimated as not synergistic and mostly competitive except for the combined treatments of CBD (1500 and 3000 ppm) with Azatin (1500 ppm) which were marked by an additive interaction. In its individual application, CBD oil generated the highest insect mortality while its effect was clearly dose-dependent. The findings reveal a promising effect of CBD oil against these coleopterans which had not been previously tested together.

Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications.

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors. Based on the clinical observation of low prevalence of smoking among hospitalized COVID-19 patients, we examined and identified a "toxin-like" amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375-390), which is homologous to a sequence of the Neurotoxin homolog NL1, one of the many snake venom toxins that are known to interact with nicotinic acetylcholine receptors (nAChRs). We present the 3D structural location of this "toxin-like" sequence on the Spike Glycoprotein and the superposition of the modelled structure of the Neurotoxin homolog NL1 and the SARS-CoV-2 Spike Glycoprotein. We also performed computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 Spike Glycoprotein and the extracellular domain of the nAChR α9 subunit. We identified a main interaction between the aa 381-386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189-192 of the extracellular domain of the nAChR α9 subunit, a region which forms the core of the "toxin-binding site" of the nAChRs. The mode of interaction is very similar to the interaction between the α9 nAChR and α-bungarotoxin. A similar interaction was observed between the pentameric α7 AChR chimera and SARS-CoV-2 Spike Glycoprotein. The findings raise the possibility that SARS-CoV-2 may interact with nAChRs, supporting the hypothesis of dysregulation of the nicotinic cholinergic system being implicated in the pathophysiology of COVID-19. Nicotine and other nicotinic cholinergic agonists may protect nAChRs and thus have therapeutic value in COVID-19 patients.

Imiquimod - A toll like receptor 7 agonist - Is an ideal option for management of COVID 19.

According to numerous recent publications, the COVID-19 patients have lymphopenia, higher infection-related biomarkers and several elevated inflammatory cytokines (i.e. tumor necrosis factor (TNF)-α, interleukin IL-2R and IL-6). The total number of B cells, T cells and NK cells are significantly decreased. RNA viruses, SARS-CoV-2 included, hit the innate immune system in order to cause infection, through TLRs 3, 7 and 8. Imiquimod is an immune-stimulator that activates TLR 7 and can be used to enhance the innate and adaptive immunity. Preclinical and clinical trials are proposed.

Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. METHODS: A systematic review of the literature (PubMed) identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted and gender and age-adjusted, population-based expected prevalence by calculating prevalence odds ratio (POR). The association between current, compared with non-current and former, smoking and adverse outcome was examined. A secondary analysis was performed by including 12 pre-publications (30 studies in total). All analyses were performed using random-effects meta-analysis. RESULTS: Among 6515 patients, the pooled prevalence of current smoking was 6.8% [95% confidence interval (CI): 4.8-9.1%]. The gender-adjusted POR was 0.20 (95% CI: 0.16-0.25, p < 0.001), and the gender and age-adjusted POR was 0.24 (95% CI: 0.19-0.30, p < 0.001). Current smokers were more likely to have an adverse outcome compared with non-current smokers [odds ratio (OR): 1.53, 95%CI: 1.06-2.20, p = 0.022] but less likely compared with former smokers (OR: 0.42, 95% CI: 0.27-0.74, p = 0.003). When pre-publications were added (n = 10,631), the gender-adjusted POR was 0.27 (95% CI: 0.19-0.38, p < 0.001) and the gender and age-adjusted POR was 0.34 (95% CI: 0.24-0.48, p < 0.001). CONCLUSION: This meta-analysis of retrospective observational case series found an unexpectedly low prevalence of current smoking among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for an adverse outcome. Smoking cannot be considered a protective measure for COVID-19. However, the hypothesis that nicotine may have a protective effect in COVID-19 that is partially masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored in laboratory studies and clinical trials using pharmaceutical nicotine products.

Grape Stem Extracts From Three Native Greek Vine Varieties Exhibit Strong Antioxidant and Antimutagenic Properties.

BACKGROUND/AIM: The winemaking procedure results in the generation of stems, a by-product that is harmful to the environment. Concomitantly, stems are rich in polyphenols and, hence, they are putatively beneficial for human health. MATERIALS AND METHODS: In this study, the grape stem extracts derived from three native Greek vine varieties, namely Mavrodaphne, Muscat and Rhoditis were examined for their chemical composition and antioxidant and antimutagenic properties using a battery of in vitro biomarkers. RESULTS: All extracts are rich in polyphenols. Moreover, they exhibit potent antioxidant and antimutagenic properties with the extract of Mavrodaphne being the strongest in reducing the DPPH• and O2 -• radicals and the Fe3+ and in protecting plasmid DNA from peroxyl radical-induced oxidative modification. CONCLUSION: Therefore, although they are serious pollutants, grape stems contain phytochemicals with important biological properties and can be used as (ingredients of) bio-functional foods to improve certain aspects of human health.

In vivo quantification and pharmacokinetic studies of cotinine in mice after smoke exposure by LC-MS/MS.

A sensitive analytical method was developed and validated for the quantification of cotinine in mouse plasma after exposure to smoke of 0.5, 1.0, and 1.5 commercially available cigarettes, using liquid chromatography tandem mass spectrometry. The method was validated over a linear concentration range of 0.075-20.0 ng/mL with the R2 value being higher than 0.99. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. The lower limit of quantification (LLOQ) for cotinine was 0.075 ng/mL with sufficient specificity, accuracy, and precision. Following exposure to 0.5, 1.0, and 1.5 cigarette smoke, it was observed that the AUC and the Cmax increased linearly as the doses increased. The pharmacokinetics of cotinine was found linear for the range of 0.5-1.5 commercial cigarette smoke. The quantification of the concentration of cotinine in mouse plasma after smoke exposure will facilitate future behavioral and toxicological experiments in animals and may prove useful in predicting cotinine levels in humans during smoking.

Electronic Nicotine Delivery Systems (ENDS) and Their Relevance in Oral Health.

The number and popularity of electronic nicotine delivery systems (ENDS) and especially e-cigarettes (e-cigs) have been increasing in the last decade. Although ENDS owe their popularity to excluding the harmful chemicals that are present in tobacco smoke, there is a debate whether they are safe, regulated, and as harmless as they are assumed to be and have potential unknown long-term effects. Involvement of cigarette smoking to the progression of periodontal diseases, other adverse oral health outcomes, and its detrimental effects to oral health are well-described. ENDS producer companies claim that these products can improve oral health by providing alternatives to smoking. However, the effect of e-cigs on oral health is not fully understood and is still debated among many scientists and clinicians. The number of studies addressing the potential toxic effect of ENDS or e-cig aerosol on oral cells is limited along with the clinical studies which are still preliminary, and their sample size is limited. The long-term effects of inhaled aerosols and the potential synergistic effect of the e-cigs components are not known. It is essential and of utmost importance to determine whether exposure to ENDS aerosol contributes to the progression of periodontal diseases and how it affects periodontal ligament and gingival cells which are believed to be its first targets. This review briefly summarizes the available evidence about the effects of e-cigs on periodontal health including several pathophysiological events, such as oxidative stress, DNA damage, inflammation, cellular senescence, dysregulated repair, and periodontal diseases.