Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration. ObjectiveTo determine whether pharmaceutical glucocorticoids induce senescence in tenocytes.MethodsFeatures of senescence (β-galactosidase activity at pH 6 (SA-β-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes. Evidence of senescence-inducing pathway induction in vivo was obtained using immunohistochemistry on tendon biopsy specimens taken before and 7 weeks after subacromial Depo-Medrone injection.ResultsDexamethasone treatment of tenocytes resulted in an increased percentage of SA-βgal-positive cells. Levels of phosphorylated p70S6K did not decrease with glucocorticoid treatment indicating mTOR remained active. Increased levels of acetylated p53 as well as increased RNA levels of its pro-senescence effector p21 were evident in dexamethasone-treated tenocytes. Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls. Knockdown of p53 or inhibition of p53 activity prevented dexamethasone-induced senescence. Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence. Immunohistochemical analysis of tendon biopsies taken before and after glucocorticoid injection revealed a significant increase in the percentage of p53-positive cells (p=0.03). The percentage of p21-positive cells also tended to be higher post-injection (p=0.06) suggesting glucocorticoids activate the p53/p21 senescence-inducing pathway in vivo as well as in vitro.ConclusionAs cell senescence is irreversible in vivo, glucocorticoid-induced senescence may result in long-term degenerative changes in tendon tissue.

YouTube contains a large volume of medical educational material. This study assessed the quality of respiratory auscultation videos contained in YouTube. Videos were searched for using the terms 'breath sounds', 'respiratory sounds', 'respiratory auscultation' and/or 'lung sounds'. In total, 6,022 videos were located, 36 of which were considered suitable for scoring for video accuracy, comprehensiveness and quality. The average score was 3.32/6 (55.3%±1.30). Video score correlated with time-adjusted YouTube metadata: hits per day (0.496, p=0.002) and likes per day (0.534, p=0.001). Video score also correlated with the fi rst search page on which the video was located in the 'breath sounds' and 'lung sounds' searches (-0.571, p=0.001; -0.445, p=0.014, respectively). The quality of videos was variable. Correlation between video score and some metadata values suggests that there is value for their use in judging video quality. However, the large number of videos found and inability to fi lter these results quickly makes locating educational content diffi cult.

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