Background: Electronic cigarettes (e-cigarettes) have experienced a tremendous increase in use. Unlike cigarette smoking, the effects of e-cigarettes and their constituents on mediating vascular health remain understudied. However, given their increasing popularity, it is imperative to evaluate the health risks of e-cigarettes, including the effects of their ingredients, especially nicotine and flavorings. Objectives: To investigate the effects of flavored e-cigarette liquids (e-liquids) and serum isolated from e-cigarette users on endothelial health and endothelial cell dependent macrophage activation. Methods: We used human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and a high-throughput screening approach to assess endothelial integrity following exposure to 6 different e-liquids with varying nicotine concentrations and to serum from e-cigarette users. Results: The cytotoxicity of the e-liquids varied considerably, with the cinnamon-flavored product being most potent and leading to significantly decreased cell viability, increased reactive oxygen species (ROS) levels, caspase 3/7 activity, and low-density lipoprotein uptake, activation of oxidative stress-related pathway, and impaired tube formation and migration, confirming endothelial dysfunction. Upon exposure of ECs to e-liquid, conditioned media induced macrophage polarization into a pro-inflammatory state, eliciting the production of interleukin-1β (IL-1β) and IL-6, leading to increased ROS. After exposure of iPSC-ECs to serum of e-cigarette users, we observed increased ROS linked to endothelial dysfunction, as indicated by impaired pro-angiogenic properties. We also noted an increase in inflammatory cytokine expression in serum of e-cigarette users. Conclusions: Acute exposure to flavored e-liquids or e-cigarette use exacerbates endothelial dysfunction, which often precedes cardiovascular diseases.Abbreviations CRP = c-reactive protein CVD = cardiovascular disease E-cigarette = electronic cigarette E-liquids = electronic cigarette liquids iPSC-ECs = induced pluripotent stem cell-derived endothelial cells PG = propylene glycol PLT = platelet ROS = reactive oxygen species VG = vegetable glycerin Condensed Abstract E-cigarettes have seen a rapid increase in use although their effects on vascular health remain understudied. Here, we investigated the effects of flavored e-cigarette liquids (e-liquids) on endothelial health by exposing human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to different e-liquids with varying nicotine concentrations. While cytotoxicity varied among the tested flavors, the cinnamon-flavored product was most potent leading to decreased cell viability, increased oxidative stress and caspase activity, and impaired tube formation confirming endothelial dysfunction; results which were further corroborated using e-cigarette

Background: The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function. Methods: Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants’ sera, or e-cigarette aerosol condensate, on NO and H 2 O 2 release and cell permeability in cultured endothelial cells (ECs). Results: E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H 2 O 2 , and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production. Conclusions: Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

This unpublished, original research from Philip Morris Inc. demonstrates that majority of the nicotine and tobacco-specific nitrosamines in the secondhand smoke from each cigarette smoked indoors remains on indoor surfaces for months after the cigarette is extinguished. It also demonstrates that elevated concentrations of nicotine, ammonia, formaldehyde and the gas-phase nitrosamine, N-nitrosopyrrolidine, can be found in the air for over 12 hours after smoking, that surface chemistry affects nitrosamine formation and persistence and that the amount of the carcinogenic nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) that persists months after smoking ends can exceed the amount that actually came out of the cigarettes.

Emerging adulthood is a time of identity exploration during which youth actively engage with beliefs and values that shape their political orientation. In this study, we examine the processes and consequences of young adults' exploration of their Jewish identity as it is embedded in the Birthright trip (a free 10-day trip to Israel that is offered to Jewish American emerging adults). In a pretrip/posttrip survey, we found significant increases in Birthright participants' endorsement of the Jewish root narrative on the Israeli-Palestinian conflict (Jewish people want to live in peace but must defend themselves), disavowal of the Palestinian narrative and understanding of the conflict, sense of collective victimhood, and understanding of the conflict as a zero-sum game. In a separate interview study, participants' narratives of the trip suggested that identification with the Israeli soldiers as being "just like us" as well as border-making between safe (Jewish) and unsafe (Arab) spaces, led to an understanding of the conflict that was based on the Jewish root narrative. Our findings highlight some less examined consequences of identity exploration among emerging adults who are members of groups enmeshed in violent conflict.