Effect of gonococcal lipooligosaccharide variation on human monocytic cytokine profile

BACKGROUND: Neisseria gonorrhoeae is an obligate human pathogen that causes significant worldwide morbidity. N. gonorrhoeae expresses lipooligosaccharide (LOS), a phase variable molecule that plays an important role during pathogenesis of the organism. Alteration in the structure of gonococcal LOS correlates with altered disease presentation. In addition, LOS sialylation occurs readily in vivo, though the role of this sialylation during disease is unknown. RESULTS: Challenge of human monocytes with purified LOS preparations isolated from strains expressing distinct structurally defined LOSs resulted in identical production of the proinflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-12 (IL-12). Similar results were seen when monocytes were challenged with either live or gentamicin-killed whole cell gonococcal variants expressing these LOS structures, although greater cytokine production was observed in comparison with challenge by purified LOS. Challenge of a human primary monocyte model with distinct LOS variants resulted in similar production of TNFα, IL-12, interleukin-10 (IL-10), and interleukin-8 (IL-8). A cytokine array was employed to allow measurement of a broad range of cytokines in samples challenge with gonococcal LOS variants as well as variants expressing sialylated LOS. Challenge of primary monocytes with sialylated gonococci was shown to elicit the production of more MCP-2 (monocyte chemoattractant protein-2) in comparison with challenge by unsialylated gonococci. CONCLUSION: We demonstrated that while alterations in the carbohydrate moiety of LOS do not impact the production of most cytokines by human monocytes, whole-cell bacterial challenge is more stimulatory than challenge with purified LOS, implying that other gonococcal cell surface antigens are important for the elicitation of cytokines. Challenge with gonococci expressing sialylated LOS resulted in elicitation of more of the chemokine MCP-2 from challenged cells in comparison with gonococci expressing unsialylated LOS. As MCP-2 is an important chemoattractant, this indicates that in vivo sialylation may play an important role during the pathogenesis of N. gonorrhoeae

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