Hyper-Activation of pp60(Src) Limits Nitric Oxide Signaling by Increasing Asymmetric Dimethylarginine Levels During Acute Lung Injury

The molecular mechanisms by which the endothelial barrier becomes compromised during lipopolysaccharide (LPS) mediated acute lung injury (ALI) are still unresolved. We have previously reported that the disruption of the endothelial barrier is due, at least in part, to the uncoupling of endothelial nitric oxide synthase (eNOS) and increased peroxynitrite-mediated nitration of RhoA. The purpose of this study was to elucidate the molecular mechanisms by which LPS induces eNOS uncoupling during ALI. Exposure of pulmonary endothelial cells (PAEC) to LPS increased pp60Src activity and this correlated with an increase in nitric oxide (NO) production, but also an increase in NOS derived superoxide, peroxynitrite formation and 3-nitrotyrosine (3-NT) levels. These effects could be simulated by the over-expression of a constitutively active pp60Src (Y527FSrc) mutant and attenuated by over-expression of dominant negative pp60Src mutant or reducing pp60Src expression. LPS induces both RhoA nitration and endothelial barrier disruption and these events were attenuated when pp60Src expression was reduced. Endothelial NOS uncoupling correlated with an increase in the levels of asymmetric dimethylarginine (ADMA) in both LPS exposed and Y527FSrc over-expressing PAEC. The effects in PAEC were also recapitulated when we transiently over-expressed Y527FSrc in the mouse lung. Finally, we found that the pp60Src-mediated decrease in DDAH activity was mediated by the phosphorylation of DDAH II at Y207 and that a Y207F mutant DDAH II was resistant to pp60Src-mediated inhibition. We conclude that pp60Src can directly inhibit DDAH II and this is involved in the increased ADMA levels that enhance eNOS uncoupling during the development of ALI

Report of the Task Force on Enhancing technology use in agriculture insurance

Pradhan Mantri Fasal Bima Yojana (PMFBY) is a flagship scheme of the Government of India to provide insurance coverage and financial support to farmers in the event of failure of any of the notified crops, unsown area and damage to harvest produce as a result of natural calamities, pests and diseases to stabilise the income of farmers, and to encourage them to adopt modern agricultural practices. The scheme is a considerable improvement over all previous insurance schemes in India and is heavily subsidised by the state and central governments. The scheme aims to cover 50 percent of the farming households within next 3 years. During its implementation in the last one season, several challenges relating to enrolment, yield estimation, loss assessment, and claim settlement were reported by farmers, insurance companies as well as the state governments. It was also noted that several technological opportunities existed for possibly leveraging support to the Indian crop insurance program for enhanced efficiency and effectiveness. NITI Aayog of the Government of India, therefore, constituted a Task Force to deliberate on this subject and identify such potential opportunities. This report summarises the recommendations of the Task Force. The Task Force constituted to address the issue of technology support to crop insurance comprised the following 5 sub-groups: (1) Remote Sensing & Drones; (2) Decision Support Systems, Crop Modelling & Integrated Approaches; (3) IT/ICT in Insurance; (4) Crop Cutting Experiments (CCEs); and (5) Technologies for Livestock and Aquaculture Insurance. Each sub-group had several discussions with experts in the respective areas, and submitted draft reports. More than 100 experts related to professional research agencies, insurance industry, banks, and the government contributed to these discussions. Technological options available in the country and abroad were considered by all groups. The Task Force together with the sub-groups then deliberated on key issues and formulated its recommendations as presented in this report. During the discussions it was realised that there were many administrative and institutional issues that needed to be addressed in PMFBY. However, the focus of the Task Force was on its main mandate, technology use in crop insurance. We hope these recommendations would help the Indian crop insurance sector take full advantage of the technological options suggested so as to increase its efficacy and effectiveness leading to reduced agrarian distress in the country

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

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

Extraperitoneal Pelvic laparoscopic disconnection of accessory urethra from normal urethra in a case of urethral duplication

We report an extraperitoneal pelvic laparoscopic approach to disconnect accessory urethra from normal urethra in complete urethral duplication. First stage consisted of chordee correction, partial excision of the accessory urethra and glansplasty. In the second stage the remaining accessory urethra was disconnected from the normal urethra through a pre-peritoneal minimal access approach to the retropubic space. The remaining distal mucosa was ablated using monopolar cautery

Use of pre and intra-operative bronchoscopy in management of bronchial injury following blunt chest trauma

Blunt chest trauma resulting in right bronchial tear in an 8-year-old girl is reported. Use of bronchoscopy in the management of such an injury is highlighted