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.

Introduction Electronic nicotine delivery systems (ENDS; i.e., vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, their cardiovascular effects are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices, including a new ultrasonic vaping device, impairs endothelial function. Methods We measured arterial flow-mediated dilation (FMD) in rats (n=8/group) exposed to single session of 10 cycles of pulsatile 5s exposure over 5 minutes to aerosol from e-liquids with and without nicotine generated from a USONICIG ultrasonic vaping device, previous generation e-cigarettes, 5% nicotine JUUL pods (Virginia Tobacco, Mango, Menthol), and an IQOS heated tobacco product; with Marlboro Red cigarette smoke and clean air as controls. We evaluated nicotine absorption and serum nitric oxide levels after exposure, and effects of different nicotine acidifiers on platelet aggregation. Results Aerosol/smoke from all conditions except air significantly impaired FMD. Serum nicotine varied widely from highest in the IQOS group to lowest in USONICIG and previous generation e-cig groups. NO levels were not affected by exposure. Exposure to JUUL and similarly acidified nicotine salt e-liquids did not affect platelet aggregation rate. Despite lack of heating coil, the USONICIG under airflow conditions heated e-liquid to ~77˚C. Conclusions A wide range of ENDS, including multiple types of e-cigarettes with and without nicotine, a heated tobacco product, and an ultrasonic vaping device devoid of heating coil, all impair FMD after a single vaping session comparably to combusted cigarettes. Implications The need to understand the cardiovascular effects of various ENDS is of timely importance, as we have seen a dramatic increase in the use of these products in recent years, along with the growing assumption among its users that these devices are relatively benign. Our conclusion that a single exposure to aerosol from a wide range of ENDS impairs endothelial function comparably to cigarettes indicates that vaping can cause similar acute vascular functional impairment to smoking and is not a harmless activity.

Purpose The measurement of heart rate variability (HRV) is a non-invasive method to analyze the balance of the autonomic nervous system. The aim of this study was to compare the changes of HRV and base deficit (BD) during the treatment of trauma patients. Methods Forty-three trauma patients with a low injury severity scores (ISS < 24) and negative base excess on admission were included in this study. Based on the BD changes, patients were divided into three groups: ‘end pointed’ group ( n = 13), patients' BDs instantly cleared after primary hydration; ‘needs further resuscitation’ group ( n = 21), patients' BDs did not reach the end point and thus required further hydration or packed red blood cells transfusion; and ‘hydration minimal change’ group ( n = 9), patients' BDs lower than 2.5 mmol/L at the onset of admission and thereafter had minimal change (near normal range). The changes in HRV during fluid resuscitation were detected and compared to BD changes in their arterial blood gases. All data were analysed using the SPSS software Version 15.0. Repeated measures ANOVA was used to determine the changes in HRV, heart rate, blood pressure, and BD among groups. Results A significant reverse correlation was found between the BD ratio and the HRV ratio (r = −0.562; p = 0.01). The HRV of patients with aggravated BDs after fluid resuscitation was decreased. There was an increase in HRV at the time of BD clearance. A decrease in HRV after primary crystalloid hydration bore a significant connection with the need for an ICU ( p = 0.021) and transfusion of packed red blood cells ( p < 0.001). Conclusion Increase in HRV may be a new non-invasive index for the end point of resuscitation in trauma patients.

Objective:We conducted a triple phase project for motorcycle helmets advocacy in Darab, a city in southwest Iran. The aim of this study was to evaluate the effect of the project on decreasing the hazards of motorcycle accidents.Methods:Using a questionnaire, data for ICU admission rates, hospital costs for patients who required ICU admission, rate of helmet usage, mortality and the duration of ICU care for patients admitted to Darab hospital due to motorcycle accidents in Winter 2015 (before conducting the project) and Winter 2016 (after conducting the project) were gathered and compared. This feature was also separately done for patients younger than 17 years.Results:The rate of wearing helmets increased significantly in winter 2016 (from 3.4 % to 33%). Also ICU admission rate due to head trauma was significantly decreased after the project was done (from 14.5 % to 4%). However, hospital costs for patients required ICU admission were increased in winter 2016. This increase, though not significant, seems to be due to an increase in health service expenses in the year 2016 as compared with the year 2015. The mortality rate was not significantly changed between the two mentioned years results. For patients younger than 17 years, no ICU admissions were needed in winter 2016.Conclusion:Even a short period of intervention can have positive effects on increasing the safety of motorcycle drivers.