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

One-Compound-Multi-Targets at Amyloid β Cascade Offered By Bis(7)-Cognitin, a Novel Anti-Alzheimer’s Dimer

Alzheimer's disease (AD) is a progressive, degenerative disorder of the brain and the most common form of dementia among the elderly. The neuropathological hallmarks of AD are senile plaques, which are extracellular deposits predominantly composed of fibrillar amyloid β peptide (Aβ), and intracellular neurofibrillary tangles composed of filamentous aggregates called paired helical filaments of hyperphosphorylated tau protein. Aβ is proposed to play a key role in the pathogenesis of AD. Therefore, treatments targeting the biosynthesis, oligomerization/aggregation, and toxicity of Aβ are likely to be the promising disease-modifying therapeutics. Bis(7)-Cognitin, one of our promising anti-Alzheimer's dimers, has previously been shown to possess potent acetylcholinesterase (AChE) inhibition, memory-enhancement, and neuroprotection against several stimuli that go beyond the inhibition of AChE. Our recent studies have further demonstrated that bis(7)-Cognitin exerts profound neuroprotective effects by targeting the multiple stages of the Aβ pathological cascade of AD, i.e. the biosynthesis, oligomerization/aggregation and toxicity of Aβ. These findings may offer not only a new and clinically significant modality as to how the agent exerts neuroprotective effects, but also a novel direction to rationally develop one-compound-multi-targets drugs for the prevention and treatment of AD, even of other neurodegenerative diseases.Department of Applied Biology and Chemical Technolog

The Inhalation Anesthetic Desflurane Induces Caspase Activation and Increases Amyloid β-Protein Levels under Hypoxic Conditions*

Perioperative factors including hypoxia, hypocapnia, and certain anesthetics have been suggested to contribute to Alzheimer disease (AD) neuropathogenesis. Desflurane is one of the most commonly used inhalation anesthetics. However, the effects of desflurane on AD neuropathogenesis have not been previously determined. Here, we set out to assess the effects of desflurane and hypoxia on caspase activation, amyloid precursor protein (APP) processing, and amyloid β-protein (Aβ) generation in H4 human neuroglioma cells (H4 naïve cells) as well as those overexpressing APP (H4-APP cells). Neither 12% desflurane nor hypoxia (18% O2) alone affected caspase-3 activation, APP processing, and Aβ generation. However, treatment with a combination of 12% desflurane and hypoxia (18% O2) (desflurane/hypoxia) for 6 h induced caspase-3 activation, altered APP processing, and increased Aβ generation in H4-APP cells. Desflurane/hypoxia also increased levels of β-site APP-cleaving enzyme in H4-APP cells. In addition, desflurane/hypoxia-induced Aβ generation could be reduced by the broad caspase inhibitor benzyloxycarbonyl-VAD. Finally, the Aβ aggregation inhibitor clioquinol and γ-secretase inhibitor L-685,458 attenuated caspase-3 activation induced by desflurane/hypoxia. In summary, desflurane can induce Aβ production and caspase activation, but only in the presence of hypoxia. Pending in vivo confirmation, these data may have profound implications for anesthesia care in elderly patients, and especially those with AD