Lkb1 Deficiency Alters Goblet and Paneth Cell Differentiation in the Small Intestine

The Lkb1 tumour suppressor is a multitasking kinase participating in a range of physiological processes. We have determined the impact of Lkb1 deficiency on intestinal homeostasis, particularly focussing on secretory cell differentiation and development since we observe strong expression of Lkb1 in normal small intestine Paneth and goblet cells. We crossed mice bearing an Lkb1 allele flanked with LoxP sites with those carrying a Cyp1a1-specific inducible Cre recombinase. Lkb1 was efficiently deleted from the epithelial cells of the mouse intestine after intraperitoneal injection of the inducing agent β-naphthoflavone. Bi-allelic loss of Lkb1 led to the perturbed development of Paneth and goblet cell lineages. These changes were characterised by the lack of Delta ligand expression in Lkb1-deficient secretory cells and a significant increase in the levels of the downstream Notch signalling effector Hes5 but not Hes1. Our data show that Lkb1 is required for the normal differentiation of secretory cell lineages within the intestine, and that Lkb1 deficiency modulates Notch signalling modulation in post-mitotic cells

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

Tris(8-hydroxyquinolinato)gallium(III)-loaded copolymer micelles as cytotoxic nanoconstructs for cosolvent-free organometallic drug delivery

Therapeutically useful concentrations of the water-insoluble organometallic drug, tris(8-hydroxyquinolinato)gallium(III), are delivered to haematological cell lines without the need for toxic cosolvents. Delivery is by sequestration into aqueous micelles of a poly(ethylene glycol)/poly(propylene glycol)/poly(ethylene glycol) triblock copolymer using a facile method based on emulsion-mediated evaporation. The drug-loaded micelles function as a cell cycle inhibitor and cause cell death by a dose-dependent increase in apoptosis

Spray retention on whole plants: modelling, simulations and experiments

Retention of sprays on plants is a critical component influencing the effectiveness of agrichemical applications. Previous simulations of spray retention by plants gave poor agreement for hard-to-wet species when compared with actual measured retention. A new model is developed here that accounts for: species wettability, impaction angle, droplet bounce, partial retention on shatter, a variable time to shatter, and the number of daughter droplets produced. The aim of this study was to compare predictions from the new model with data obtained by spraying five mixtures via five nozzles onto easy-to-wet cotton (Gossypium hirsutum L.), and hard-to-wet wheat (Triticum aestivum L.) and fat hen (Chenopodium album L.). The new model correctly predicts retention to be highest on cotton and lowest on wheat. The trend in both measured data and the model predictions is for retention to decrease with increasing droplet size, on all three plant species. Formulation is correctly predicted to have little influence on retention by easy-to-wet cotton plants and to enhance retention by the harder-to-wet wheat and fat hen plants. The parameters that describe partial retention on shatter and variable time to shatter have a substantial influence on retention, as they affect primary or secondary droplet capture. A better understanding of the kinetic energy effects and the interactions between the formulation and the leaf surface are needed to refine their input values