Tobacco cigarette(TC) smoking has never been lower in the US, but EC vaping has reached epidemic proportions amongst our youth. Endothelial dysfunction, as measured by flow mediated vasodilation(FMD) is a predictor of future atherosclerosis and adverse cardiovascular events, and is impaired in TC smokers, but whether FMD is also reduced in EC vapers is uncertain. The aim of this study in otherwise healthy young people was to compare the effects of acute and chronic TC smoking and EC vaping on FMD. FMD was compared in 47 non-smokers(NS), 49 chronic EC-vapers and 40 chronic TC-smokers at baseline, and then after EC-vapers(n=31) and non-smokers(n= 47) acutely used an EC-with-nicotine(ECN), EC-without-nicotine(EC0), and nicotine inhaler(NI) at ~4week intervals, and after TC-smokers(n=33) acutely smoked a TC, compared to sham-control. Baseline FMD was not different among the groups (NS:7.7±4.5%∆ vs EC:6.6±3.6%∆ vs TC:7.9±3.7%∆, p=0.35), even when compared by group and sex. Acute TC smoking vs control impaired FMD(FMD pre/post smoking: -2.52±0.92%∆ vs 0.65±0.93%∆, p=0.02). Although the increase in plasma nicotine was similar, acute EC vaping did not impair FMD. In otherwise healthy young people who regularly smoke TCs or ECs, impaired FMD was not present. However, FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose"(estimated plasma nicotine) of an EC, consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment. Although it is reassuring that acute EC-vaping did not acutely impair FMD, it would be dangerous and premature to conclude that ECs do not lead to atherosclerosis.

Abnormal ventricular repolarization, as indicated by prolonged Tpeak-end (Tp-e), is associated with increased sudden death risk. Baseline ECG indexes of repolarization, Tp-e, Tp-e/QT, and Tp-e/QTc, were not different among tobacco cigarette (TC) smokers, electronic cigarette (EC) users, and nonsmokers at baseline, but when TC smokers smoked one TC, all parameters were prolonged. Using an electronic cigarette with nicotine, but not without nicotine, increased the Tp-e/QT. Smoking induces changes in ECG indexes of ventricular repolarization associated with increased sudden death risk.

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is a causative gene for three different clinical forms of incurable retinal degeneration. However, the completely unknown function of limits our understanding of the pathogenicity of mutations. Here, we performed a comprehensive phenotypic characterization of a KO mouse line, generated using CRISPR/Cas9 technology. Both KO male and female mice exhibited progressive and simultaneous degeneration of rod and cone photoreceptors but no non-ocular phenotypes. The major ultrastructural feature of KO photoreceptors was massive disorganization of the outer segment (OS) membrane discs starting from the onset of disc morphogenesis during development. At the molecular level, the amounts of multiple OS-specific membrane proteins, including proteins involved in membrane disc organization, were reduced, although these proteins were targeted normally to the OS. Considering the distribution of C8ORF37 throughout the photoreceptor cell body, the normal structure of the KO photoreceptor connecting cilium, and the absence of defects in other ciliary organs of the KO mice, our findings do not support the previous notion that C8ORF37 was a ciliary protein. Because C8ORF37 is absent in the photoreceptor OS, C8ORF37 may participate in the secretory pathway of OS membrane proteins in the photoreceptor cell body and thus maintain the homeostasis of these proteins. This study established a valid animal model for future therapeutic studies of-associated retinal degeneration. This study also shed new light on the role of C8ORF37 in photoreceptors and on the pathogenic mechanism underlying retinal degeneration caused by mutations. Inherited retinal degeneration is a group of incurable conditions with poorly understood underlying molecular mechanisms. We investigated , a causative gene for three retinal degenerative conditions: retinitis pigmentosa, cone-rod dystrophy, and Bardet-Biedl syndrome. encodes a protein with no known functional domains and thus its biological function is unpredictable. We knocked out the ortholog in mice, which resulted in a retinal phenotype similar to that observed in patients. We further demonstrated that C8ORF37 is required for photoreceptor outer segment disc formation and alignment, a process that is critical for photoreceptor function and survival. This study advances our understanding of the pathogenesis of retinal degeneration and establishes a valuable mouse model for future therapeutic development.