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

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

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

Exploring Class‐II PI3K Inhibition for the treatment of Alzheimer’s Disease: Virtual Screening for PI3KC2A Inhibitors

Background: Focusing on novel AD treatments, the TREAT‐AD centers offer an array of free research tools, shared via the AD Knowledge Portal in a Target Enablement Package (TEP). This abstract showcases the research conducted by the IUSM‐Purdue TREAT‐AD Center, specifically focusing on Targeting class‐II PI3K’s as a potential breakthrough in AD therapy. Endocytosis within the brain encompasses diverse pathways for internalizing extracellular cargoes and receptors into cells. The prominent routes include clathrin‐mediated endocytosis and phagocytosis. Endocytosis plays a crucial role in processing amyloid precursor protein (APP) leading to abnormal production of Aβ peptides. Recycling endosomes are vital for delivering and eventually releasing Aβ into the brain. Recent research emphasizes the pivotal role of PI3K‐C2α, a class II PI3K member, in regulated endocytosis through its clathrin‐binding domain. Its localization spans clathrin‐coated pits, endocytic vesicles, early endosomes, and the trans‐Golgi network, generating phosphatidylinositol 3‐phosphate (PtdIns(3)P) and/or phosphatidylinositol 3,4‐bisphosphates (PtdIns(3,4)P2) in vivo. Targeting clathrin‐mediated endocytosis by inhibiting PI3K‐C2α, a key regulator in clathrin coated vesicle formation, could be a potential therapeutic strategy against Alzheimer’s disease. Method: We conducted extensive virtual screenings of vast compound libraries to determine potent small molecules inhibiting PI3K‐C2α. Employing shape‐based screening, and clustering techniques, we identified leading compounds for subsequent in vitro kinase assays. Compounds exhibiting nanomolar activity were selected for further investigation. Leveraging these findings, we conducted Structure‐Activity Relationship (SAR) studies, optimizing analogs to enhance binding affinity and cellular pharmacology. Result: We have identified novel PI3K‐C2α inhibitors and are in the initial stages of optimization. These compounds exhibit promising target engagement, pending further assessment for biochemical activity and cellular pharmacology. In silico assessments suggest their structures are ideal for CNS drug discovery plans. Conclusion: Inhibiting PI3K‐C2α stands as a promising therapeutic approach for Alzheimer’s disease. We've discovered unique molecular structures that inhibit the enzyme. Our findings suggest potential probe molecules for validating the target and developing lead compounds for clinical investigations

Interplay Between Applied Force and Radical Attack in the Mechanochemical Chain Scission of Poly(acrylic acid)

Sonication and radical attack are both known to contribute to breaking down polymers. Quantum chemical models show how the two can operate together, where radical attack is shown to reduce the effective tensile strength of the material. Using poly­(acrylic acid) (PAA) as a model, hydrogen atom abstraction in PAA was found to improve the thermodynamics and kinetics of bond scission. The force needed for bond rupture was estimated to decrease from 4.7 to 2.5 nN. This occurs because hydrogen atom abstraction drastically alters the potential energy surface of the scissile bond. Bond activation was also found to decrease the magnitude of the changes in bond scission geometries and energetics in response to the applied force. While radical abstraction is overall beneficial for mechanical bond scission, the polymer also becomes less responsive to force than the unactivated polymer. This finding places upper limits on the efficacy of the synergy between radical attack and applied force. In addition, the importance of reaction pathway optimization is also shown, where comparisons to the COGEF method show the latter to be qualitatively incapable of describing chain scission after radical activation

Interplay Between Applied Force and Radical Attack in the Mechanochemical Chain Scission of Poly(acrylic acid)

Sonication and radical attack are both known to contribute to breaking down polymers. Quantum chemical models show how the two can operate together, where radical attack is shown to reduce the effective tensile strength of the material. Using poly­(acrylic acid) (PAA) as a model, hydrogen atom abstraction in PAA was found to improve the thermodynamics and kinetics of bond scission. The force needed for bond rupture was estimated to decrease from 4.7 to 2.5 nN. This occurs because hydrogen atom abstraction drastically alters the potential energy surface of the scissile bond. Bond activation was also found to decrease the magnitude of the changes in bond scission geometries and energetics in response to the applied force. While radical abstraction is overall beneficial for mechanical bond scission, the polymer also becomes less responsive to force than the unactivated polymer. This finding places upper limits on the efficacy of the synergy between radical attack and applied force. In addition, the importance of reaction pathway optimization is also shown, where comparisons to the COGEF method show the latter to be qualitatively incapable of describing chain scission after radical activation

4,4′,4″-Trimethyl-2,2′:6′,2″-terpyridine by Oxidative Coupling of 4‑Picoline

Alkylated terpyridine ligands are an increasingly important component of catalysis and dyes but are costly because their synthesis is challenging and often low-yielding. We report an improved method for the Pd/C-catalyzed dehydrogenative coupling of 4-picoline to form the bi- and terpyridine. The addition of MnO₂ improves the yield of the reaction, making the reaction useful on a large scale (up to 200 mmol). The use of Pd­(OAc)₂ or Pd/C/pivalic acid leads to the selective formation of bipyridine

Interplay Between Applied Force and Radical Attack in the Mechanochemical Chain Scission of Poly(acrylic acid)

Sonication and radical attack are both known to contribute to breaking down polymers. Quantum chemical models show how the two can operate together, where radical attack is shown to reduce the effective tensile strength of the material. Using poly­(acrylic acid) (PAA) as a model, hydrogen atom abstraction in PAA was found to improve the thermodynamics and kinetics of bond scission. The force needed for bond rupture was estimated to decrease from 4.7 to 2.5 nN. This occurs because hydrogen atom abstraction drastically alters the potential energy surface of the scissile bond. Bond activation was also found to decrease the magnitude of the changes in bond scission geometries and energetics in response to the applied force. While radical abstraction is overall beneficial for mechanical bond scission, the polymer also becomes less responsive to force than the unactivated polymer. This finding places upper limits on the efficacy of the synergy between radical attack and applied force. In addition, the importance of reaction pathway optimization is also shown, where comparisons to the COGEF method show the latter to be qualitatively incapable of describing chain scission after radical activation

Interplay Between Applied Force and Radical Attack in the Mechanochemical Chain Scission of Poly(acrylic acid)

Sonication and radical attack are both known to contribute to breaking down polymers. Quantum chemical models show how the two can operate together, where radical attack is shown to reduce the effective tensile strength of the material. Using poly­(acrylic acid) (PAA) as a model, hydrogen atom abstraction in PAA was found to improve the thermodynamics and kinetics of bond scission. The force needed for bond rupture was estimated to decrease from 4.7 to 2.5 nN. This occurs because hydrogen atom abstraction drastically alters the potential energy surface of the scissile bond. Bond activation was also found to decrease the magnitude of the changes in bond scission geometries and energetics in response to the applied force. While radical abstraction is overall beneficial for mechanical bond scission, the polymer also becomes less responsive to force than the unactivated polymer. This finding places upper limits on the efficacy of the synergy between radical attack and applied force. In addition, the importance of reaction pathway optimization is also shown, where comparisons to the COGEF method show the latter to be qualitatively incapable of describing chain scission after radical activation