Nicotine replacement therapy for vaping cessation among mono and dual users: A mixed methods preliminary study.

Many adults express interest in e-cigarette cessation; however, there are few empirically tested interventions for quitting vaping. This study seeks to (1) evaluate reasons for quitting e-cigarettes in treatment-seeking adults, and (2) assess the feasibility and acceptability of nicotine replacement therapy (NRT) for e-cigarette cessation. Adult daily e-cigarette users completed qualitative interviews about quitting e-cigarettes, then were randomized to either 28-day supply of combination NRT (21 mg patches, 4 mg lozenges) + supportive booklet or Quitline referral. Primary aims were feasibility (number who enrolled) and acceptability (NRT use, adverse side effects). Exploratory aims evaluated abstinence (7-day point-prevalence) at end of treatment. Of the 30 participants who were enrolled, 50 % (n = 15) were dual users, and 50 % (n = 15) were mono-vapers, 26.6 % (n = 8) of whom were former smokers. Participants reported seeking treatment due to health concerns, dependence, stigma, and cost. Anticipated challenges of quitting vaping were withdrawal, negative mood, sensorimotor habits, and convenience. Most completed the end of treatment survey (n = 24; 80 %). Participants who received NRT reported using the patch M = 10.89 days and lozenges M = 6.39 days, with few days of adverse effects (M = 2.67). At end of treatment, 6/18 (33.3 %; 6 mono and 0 dual users) in the intervention group reported abstinence from vaping, compared to 0 in the control group (Fisher = 5.00, p =.057). In conclusion, adults are interested in quitting e-cigarettes due to negative consequences of use and are willing to use pharmacotherapy. Future research should confirm these results in a larger trial, address cigarette smoking in dual users, and aim to disseminate treatments.

Proteasome inhibition suppress microgravity elevated RANK signaling during osteoclast differentiation.

Microgravity (µXg) induces bone loss in astronauts during space missions. Therefore, it is necessary to delineate the underlying mechanisms which leads to bone loss for developing countermeasures. Osteoclasts (OCLs) are multinucleated cells, which resorb bone. Previously, we have demonstrated that simulated µXg enhances OCL formation. However, control of osteoclast bone resorption activity under µXg remains unclear. The OCL formation has been shown to be regulated by ubiquitin-proteasome pathway. Hence, we hypothesized that proteasome inhibition could regulate osteoclast differentiation under µXg. In this study, we identified that RAW264.7 preosteoclast cells treated with proteasome inhibitor (MG-132) suppress RANK receptor expression essential for OCL differentiation, but no effect on TRAF-6. We identified that MG-132 treatment abolished K48-linked poly-ubiquitination under µXg. Immunostaining confirms inhibition of protein ubiquitination and RANK expression in preosteoclast cells. Furthermore, proteasome inhibition suppresses the expression of SQSTM1/p62 under both the ground based Xg and µXg conditions. Also, confocal microscopy using Lyso-Tracker demonstrated that proteasomal inhibition suppress the co-localization of p62 and lysosomes. MG-132 inhibited RANKL induced proteasome activity. RAW264.7 cells treated with the proteasome inhibitor showed an increased level of p-c-Jun activity in control cultures, however decreased under µXg. In contrast, c-Fos and NFATc1 expression was decreased. In-addition, mouse bone marrow cultures treated with MG-132 suppress OCL formation and bone resorption activity. Thus, our findings suggest that proteasome inhibition represents a novel therapeutic approach for bone loss under µXg in space environment.