Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Clathrin-mediated endocytosis of gold nanoparticles in vitro

10.1002/ar.23051Anatomical Record2982418-42

TOXIN TO LEAD: AN INHIBITOR OF FACTOR XIA ENGINEERED FROM BANDED KRAIT VENOM TOXIN FASXIATOR SHOWED SUPERIOR IN VIVO EFFICACY-SAFETY PROFILE COMPARED TO HEPARIN

10.1016/j.toxicon.2019.12.022TOXICON177S27-S2

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis

Activated factor XI (FXIa) is an important antithrombotic drug target. Clinical and pre-clinical data have demonstrated that its inhibition attenuates thrombosis with minimal risk of excessive bleeding. We isolated Fasxiator from the venom of banded krait Bungarus fasciatus and subsequently engineered FasxiatorN17R,L19E, with improved affinity (Ki = 0.9 nM) and selectivity towards FXIa. Here, we assess the in vivo efficacy and bleeding risk of rFasxiatorN17R, L19E in pre-clinical animal models. Rats injected intravenously (i.v.) with bolus rFasxiatorN17R, L19E showed the specific in vivo attenuation of the intrinsic coagulation pathway, lasting for at least 60 min. We performed the in vivo dose-ranging experiments for rFasxiatorN17R, L19E as follows: FeCl3-induced carotid artery occlusion in rats (arterial thrombosis); inferior vena cava ligation in mice (venous thrombosis); tail bleeding time in both rats and mice (bleeding risk). Head-to-head comparisons were made using therapeutic dosages of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) for arterial and venous thrombosis, respectively. In the arterial thrombosis model, 2 mg/kg i.v. rFasxiatorN17R,L19E achieved a similar antithrombotic efficacy to that of UFH, with >3-fold lower bleeding time. In the venous thrombosis model, the 10 mg/kg subcutaneous (s.c.) injection of rFasxiatorN17R,L19E achieved similar efficacy and bleeding levels to those of LMWH enoxaparin. Overall, rFasxiatorN17R,L19E represents a promising molecule for the development of FXIa-targeting anticoagulants

Antimicrobial potential of Chlorella sorokiniana on MRSA – An in vitro study and an in silico analysis on ClpP protease

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) strains are a leading cause of communicable disease in community and nosocomial settings. They are responsible for high morbidity and mortality. Researchers currently pursue novel antimicrobials from natural sources against non-traditional drug targets of staphylococci to ensure a pipeline of potent drugs, in the face of rising drug resistance. The focus of this study was to screen compounds from a freshwater isolate of Chlorella sorokiniana for anti-staphylococcal activity, using traditional microbiology, phytochemical analysis and bioinformatics approaches. Methods: Chlorella sorokiniana methanol extract was investigated for its antimicrobial potential on Staphylococcus aureus strains (ATCC and MRSA isolates) by Kirby Bauer disc diffusion, broth microdilution, cell cytotoxicity and thin layer chromatography-bioautography (TLC-BA). Two antimicrobial TLC-BA antimicrobial fractions (A and B) were subject to gas chromatography mass spectrometry (GCMS). The structures of 9 compounds representing GCMS peaks were tested in silico, for their pharmacokinetic properties and binding energy efficiency with the target, using Molinspiration tool and Autodock 4.2. Results: Mean zone diameter of inhibition of growth by CSME (20 mg) was 21 mm, MIC/MBC was 0.31/2.5 mg/L. GCMS analysis of TLC fraction-A revealed 31 phytochemicals, of which 2-pentanone,4-hydroxy-4-methyl- had the highest area % (65.61) and TLC fraction-B revealed 4 peaks of which pentadecanoic acid and 1-(+)-ascorbic acid 2,6-dihexadecanoate had the highest area % (45.57, 48.09).In silico analysis of 9 peak compounds on the target of interest showed that compound 2: 2-pentanone,4-hydroxy-4-methyl- and compound 7: 1,2 – benzene dicarboxylic acid, mono (2- ethylhexyl) ester, satisfied Lipinski’s rule of 5, and displayed the least binding energies −6.93 and −5.74 with ClpP protease, thus holding pharmaceutical potential, and supporting further investment into in vitro and in vivo studies. Conclusions: C. sorokiniana, a less studied microalga thus offers a promising natural resource for anti-MRSA phytochemicals, capable of targeting ClpP1 protease.(290 words

Gold nanoparticles in cancer therapy

10.1038/aps.2011.82Acta Pharmacologica Sinica328983-990CYLP