Veterinary anesthesia: an opportunity to reduce the environmental footprint of clinical care.

Volatile anesthetic agents are potent greenhouse gases with warming potential hundreds to thousands of times greater than CO2. As health systems, both human and veterinary, seek to reduce their environmental impacts, responsible anesthetic stewardship is a topic of great interest. Through an online survey, we explored the levels of awareness, beliefs, interest, needs, and current actions of veterinary anesthesia professionals around the climate impacts of anesthetic care. We found that even within a respondent group with specialized training and experience, there were significant knowledge gaps about anesthesia's environmental impacts. We also found there is much interest in learning more about climate-friendly anesthesia and broader sustainability initiatives for the veterinary profession. Fortunately, there already exist many ways for the profession to reduce our environmental impact while still providing excellent patient care. In this article, we explore 5 broad categories of action: (1) reducing the overall quantity of anesthetic agent used; (2) choosing lower-impact anesthetics; (3) considering the fate of the anesthetic end product; (4) expanding learning through formal education, experience, and research; and (5) reaching beyond anesthesia to implement a range of sustainability initiatives at veterinary workplaces. Together, we have an opportunity to create a healthier future for our world, our patients, and each other.

Sensitivity of osteosarcoma cell lines to autophagy inhibition as determined by pharmacologic and genetic manipulation.

Pharmacologic inhibition of autophagy can be achieved using lysosomotropic agents such as hydroxychloroquine (HCQ) that interfere with fusion of the autophagosome to the lysosome thus preventing completion of the recycling process. The goal of the present study is to determine the sensitivity of eight canine (cOSA) and four human (hOSA) osteosarcoma tumour cell lines to antiproliferative and cytotoxic effects of lysosomal autophagy inhibitors, and to compare these results to the autophagy-dependence measured using a CRISPR/Cas9 live-cell imaging assay in OSA and other tumour cell lines. Antiproliferative and cytotoxic response to HCQ and Lys05 was determined using live cell imaging and YOYO-1 staining. CRISPR/Cas9 live cell imaging screen was done using species specific guide RNA's and transfection of reagents into cells. Response to autophagy core genes was compared to response to an essential (PCNA) and non-essential (FOXO3A) gene. cOSA and hOSA cell lines showed similar antiproliferative and cytotoxic responses to HCQ and Lys05 with median lethal dose (Dm ) values ranging from 4.6-15.8 µM and 2.1-5.1 µM for measures of anti-proliferative response, respectively. A relationship was observed between antiproliferative responses to HCQ and Lys05 and VPS34 CRISPR score with Dm values correlating with VPS34 response (r = 0.968 and 0.887) in a species independent manner. The results show that a subset of cOSA and hOSA cell lines are autophagy-dependent and sensitive to HCQ at pharmacologically-relevant exposures.