Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF

There is an increase in the numbers of neural precursors in the SVZ (subventricular zone) after moderate ischaemic injuries, but the extent of stem cell expansion and the resultant cell regeneration is modest. Therefore our studies have focused on understanding the signals that regulate these processes towards achieving a more robust amplification of the stem/progenitor cell pool. The goal of the present study was to evaluate the role of the EGFR [EGF (epidermal growth factor) receptor] in the regenerative response of the neonatal SVZ to hypoxic/ischaemic injury. We show that injury recruits quiescent cells in the SVZ to proliferate, that they divide more rapidly and that there is increased EGFR expression on both putative stem cells and progenitors. With the amplification of the precursors in the SVZ after injury there is enhanced sensitivity to EGF, but not to FGF (fibroblast growth factor)-2. EGF-dependent SVZ precursor expansion, as measured using the neurosphere assay, is lost when the EGFR is pharmacologically inhibited, and forced expression of a constitutively active EGFR is sufficient to recapitulate the exaggerated proliferation of the neural stem/progenitors that is induced by hypoxic/ischaemic brain injury. Cumulatively, our results reveal that increased EGFR signalling precedes that increase in the abundance of the putative neural stem cells and our studies implicate the EGFR as a key regulator of the expansion of SVZ precursors in response to brain injury. Thus modulating EGFR signalling represents a potential target for therapies to enhance brain repair from endogenous neural precursors following hypoxic/ischaemic and other brain injuries

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

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Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study

Ronald Dahl,1 Dalal Jadayel,2 Vijay KT Alagappan,3 Hungta Chen,3 Donald Banerji31Department of Dermatology, Allergy Centre, Odense University Hospital, Odense, Denmark; 2Novartis Horsham Research Centre, Horsham, UK; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAIntroduction: The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting &beta;2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY).Methods: In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 &micro;g indacaterol/50 &micro;g glycopyrronium) or concurrent administration of indacaterol (150 &micro;g) and glycopyrronium (50 &micro;g) via the Breezhaler&reg; device (Novartis AG, Basel, Switzerland) for 4 weeks. The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment. The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0&ndash;4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.Results: Of 193 patients randomized, 187 (96.9%) completed the study. Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L &plusmn; 0.02 and 1.46 L &plusmn; 0.18, respectively. The FEV1 AUC0&ndash;4 hours at day 1 and week 4 were similar between the two treatment groups. Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period. Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity. No deaths were reported during the study or during the 30 days follow-up period.Conclusion: The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium.Keywords: COPD, LABA, LAMA, FEV1 AUC0&ndash;4 hours, rescue medicatio

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Not AvailableFishery extension personnel ought to be effective information seekers to perform their role as ‘facilitators’ for accessing farm inputs, advisory services and markets to the farming community. Study conducted among the fishery extension personnel of Department of Fisheries in Tamil Nadu and Andhra Pradesh has indicated that hardly 50% of them were information seekers and their information seeking frequency was totally insufficient (<50%). Printed publications, research wings of the Departments of Fisheries (DoF), fisheries colleges of State Agricultural Universities and Marine Products Export Development Authority were the information sources respectively for 46, 40, 36 and 30 percent of the extension personnel. Their low information seeking behaviour was manifested in their low awareness level (<50%) on the Better Management Practices advocated. It is suggested to evolve a National Fisheries Extension Mission to restructure the DoFs and to integrate fisheries research with extension functions. Alternative, cost effective and rapid communication channels also need to be explored for the mutual exchange of information among the fishery researchers, extension personnel and farming community.Not Availabl

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Not AvailablePublic-funded fisheries extension services have been blamed as poor and responsible for the slow pace of aquaculture development in India. The present investigation aimed to find concrete interventions to streamline the extension service by understanding the research-extension-farmer linkage indirectly in terms of information sources of aqua farmers and fishery extension officers and assessing the existing organizational, manpower and extension capabilities of Departments of Fisheries of sample statesNot Availabl