Control of the Intracellular Redox State by Glucose Participates in the Insulin Secretion Mechanism

Background: Production of reactive oxygen species (ROS) due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS). In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out. Methodology/Principal Findings: Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP). Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. Conclusions: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)(CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazi

Promoting independence, health and well-being for older people: : a feasibility study of computer-aided health and social risk appraisal system in primary care

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Walters et al, BMC Family Practice (2017), 18:47, DOI: 10.1186/s12875-017-0620-6Abstract Background: With population ageing, research is needed into new low-cost, scalable methods of effective promotion of health and wellbeing for older people. We aimed to assess feasibility, reach and costs of implementing a new tailored computer-aided health and social risk appraisal system in primary care. Methods: Design: Feasibility study. Setting: Five General Practices in London (Ealing) and Hertfordshire, United Kingdom (UK) Participants: Random sample of patients aged 65+years. Intervention: The Multi-dimensional Risk Appraisal for Older people (MRA-O) system includes: 1) Postal questionnaire including health, lifestyle, social and environmental domains; 2) Software system generating a personalised feedback report with advice on health and wellbeing; 3) Follow-up of people with new concerning or complex needs by GPs or practice nurses. Evaluation: Feasibility of implementation; participant wellbeing, functional ability and quality of life; social needs, health risks, potential lifestyle changes; and costs of implementation. Results: Response rates to initial postal invitations were low (526/1550, 34%). Of these, 454/526 (86%) completed MRA-O assessments. Compared to local UK Census data on older people, participants were younger, more were owner-occupiers and fewer were from ethnic minority groups than expected. A range of problems was identified by participants, including pain in last week (269/438, 61.4%), low physical activity (173/453, 38.2%), sedentary lifestyle (174/447, 38.3%), falls (117/439, 26.7%), incontinence (111/441 25.2%), impaired vision 116/451 (25.7%), impaired hearing (145/431, 33.6%), depressed mood (71/451, 15.7%), impaired memory (44/444 9.9%), social isolation (46/449, 10.2%) and loneliness (31/442, 7.0%). Self-rated health was good/excellent in 312/437 (71.4%), and quality of life and well-being were slightly above age-specific population norms. Implementation costs were low. Practices reviewed medical records of 143/454 (31.5%) of participants as a consequence of their responses, and actively followed up 110/454 (24.2%) of their patients. Conclusions: A computer-aided risk appraisal system was feasible for General Practices to implement, yields useful information about health and social problems, and identifies individual needs. Participation rates were however low, particularly for the oldest old, the poorest, and ethnic minority groups, and this type of intervention may increase inequalities in access. Widespread implementation of this approach would require work to address potential inequalities.Peer reviewedFinal Published versio

High performing hospitals: a qualitative systematic review of associated factors and practical strategies for improvement.

BACKGROUND: High performing hospitals attain excellence across multiple measures of performance and multiple departments. Studying high performing hospitals can be valuable if factors associated with high performance can be identified and applied. Factors leading to high performance are complex and an exclusive quantitative approach may fail to identify richly descriptive or relevant contextual factors. The objective of this study was to undertake a systematic review of qualitative literature to identify methods used to identify high performing hospitals, the factors associated with high performers, and practical strategies for improvement. METHODS: Methods used to collect and summarise the evidence contributing to this review followed the 'enhancing transparency in reporting the synthesis of qualitative research' protocol. Peer reviewed studies were identified through Medline, Embase and Cinahl (Jan 2000-Feb 2014) using specified key words, subject terms, and medical subject headings. Eligible studies required the use of a quantitative method to identify high performing hospitals, and qualitative methods or tools to identify factors associated with high performing hospitals or hospital departments. Title, abstract, and full text screening was undertaken by four reviewers, and inter-rater reliability statistics were calculated for each review phase. Risk of bias was assessed. Following data extraction, thematic syntheses identified contextual factors important for explaining success. Practical strategies for achieving high performance were then mapped against the identified themes. RESULTS: A total of 19 studies from a possible 11,428 were included in the review. A range of process, output, outcome and other indicators were used to identify high performing hospitals. Seven themes representing factors associated with high performance (and 25 sub-themes) emerged from the thematic syntheses: positive organisational culture, senior management support, effective performance monitoring, building and maintaining a proficient workforce, effective leaders across the organisation, expertise-driven practice, and interdisciplinary teamwork. Fifty six practical strategies for achieving high performance were catalogued. CONCLUSIONS: This review provides insights into methods used to identify high performing hospitals, and yields ideas about the factors important for success. It highlights the need to advance approaches for understanding what constitutes high performance and how to harness factors associated with high performance