Ending the reign of short-acting β2-agonists in Australia?

Acknowledgements We would like to acknowledge and thank Steph James, Kiran Dhillon, Sophie Jones, Rob Campbell, Ying Liu, Marion Magee, Ondrej Rejda, Lisa Sugg, and Nicole O'Sullivan for their valuable contributions.Peer reviewe

The association between short-acting β2-agonist over-prescription, and patient-reported acquisition and use on asthma control and exacerbations : data from Australia

Acknowledgements Author Contribution The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas. The first draft of the manuscript was written by Dr. Rebecca Vella and all authors took part in drafting, revising or critically reviewing the article. All authors gave final approval of the version to be published. All authors have agreed on the journal to which the article has been submitted and agree to be accountable for all aspects of the work. All authors have given approval for the submission of this article. The authors received no direct compensation related to the development of the manuscript. Funding This study was conducted by Optimum Patient Care Australia (OPCA) and was partially funded by AstraZeneca and Optimum Patient Care Australia (OPCA). The cost of the Open Access Fees were provided by AstraZeneca. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.Peer reviewedPostprin

Endoplasmic reticulum stress-mediated induction of sestrin 2 potentiates cell survival

Upregulation of SESTRIN 2 (SESN2) has been reported in response to diverse cellular stresses. In this study we demonstrate SESTRIN 2 induction following endoplasmic reticulum (ER) stress. ER stress-induced increases in SESTRIN 2 expression were dependent on both PERK and IRE1/XBP1 arms of the unfolded protein response (UPR). SESTRIN 2 induction, post ER stress, was responsible for mTORC1 inactivation and contributed to autophagy induction. Conversely, knockdown of SESTRIN 2 prolonged mTORC1 signaling, repressed autophagy and increased ER stress-induced cell death. Unexpectedly, the increase in ER stress-induced cell death was not linked to autophagy inhibition. Analysis of UPR pathways identified prolonged eIF2 alpha, ATF4 and CHOP signaling in SESTRIN 2 knockdown cells following ER stress. SESTRIN 2 regulation enables UPR derived signals to indirectly control mTORC1 activity shutting down protein translation thus preventing further exacerbation of ER stress