28 research outputs found

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

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    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

    Double superior vena cavae

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    Radiology: clinical cases uncovered

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    A rationally identified panel of microRNAs targets multiple oncogenic pathways to enhance chemotherapeutic effects in glioblastoma models

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    Abstract Glioblastoma (GBM) is the most common malignant brain tumor. Available treatments have limited success because most patients develop chemoresistance. Alternative strategies are required to improve anticancer effects of current chemotherapeutics while limiting resistance. Successful targeting of microRNAs (miRNAs) as regulators of gene expression can help reprogram GBM cells to better respond to chemotherapy. We aimed to identify a panel of miRNAs that target multiple oncogenic pathways to improve GBM therapy. We first identified differentially expressed miRNAs and tested if their target genes play central roles in GBM signaling pathways by analyzing data in the Gene Expression Omnibus and The Cancer Genome Atlas databases. We then studied the effects of different combinations of these miRNAs in GBM cells by delivering synthetic miRNAs using clinically compatible PLGA-PEG nanoparticles prior to treatment with temozolomide (TMZ) or doxorubicin (DOX). The successful miRNA panel was tested in mice bearing U87-MG cells co-treated with TMZ. We identified a panel of five miRNAs (miRNA-138, miRNA-139, miRNA-218, miRNA-490, and miRNA-21) and their oncogenic targets (CDK6, ZEB1, STAT3, TGIF2, and SMAD7) that cover four different signaling pathways (cell proliferation and apoptotic signaling, invasion and metastasis, cytokine signaling, and stemness) in GBM. We observed significant in vitro and in vivo enhancement of therapeutic efficiency of TMZ and DOX in GBM models. The proposed combination therapy using rationally selected miRNAs and chemotherapeutic drugs is effective owing to the ability of this specific miRNA panel to better target multiple genes associated with the hallmarks of cancer

    Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells

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    Glioblastoma (GBM) generally exhibits high IC<sub>50</sub> values for its standard drug treatment, temozolomide (TMZ). MicroRNA-21 (miR-21) is an oncomiR overexpressed in GBM, thus controlling important aspects of glioma biology. We hypothesized that PLGA nanoparticles carrying antisense miR-21 to glioblastoma cells might beneficially knock down endogenous miR-21 prior to TMZ treatment. PLGA nanoparticles encapsulating antisense miR-21 were effective in intracellular delivery and sustained silencing (<i>p</i> < 0.01) of miR-21 function in U87 MG, LN229, and T98G cells. Prior antisense miR-21 delivery significantly reduced the number of viable cells (<i>p</i> < 0.001), and increased (1.6-fold) cell cycle arrest at G2/M phase upon TMZ treatment in U87 MG cells. There was overexpression of the miR-21 target genes <i>PTEN</i> (by 67%) and <i>caspase-3</i> (by 15%) upon cotreatment. This promising PLGA nanoparticle-based platform for antisense miR-21 delivery to GBM is an effective cotherapeutic strategy in cell culture, warranting the need for further studies prior to future clinical translation
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