Methodological approaches for developing and reporting living evidence synthesis: a study protocol.

Background: Living evidence (LE) refers to the methodological processes that permit new research findings to be continually incorporated into evidence synthesis. This approach is of great value in the resolution of relevant and rapidly changing clinical questions. To date, the methods to carry out this type of synthesis are not completely defined, and great variability is observed in the approaches used by different groups of authors. Objective: To identify, evaluate and summarise the current methods used for living evidence synthesis Methods: We will conduct a methodological study based on a systematic literature search to identify any type of evidence synthesis such as systematic reviews, network metanalyses and overviews that used "living evidence synthesis" as part of their methods. The search will be conducted in Medline (via PubMed) and Epistemonikos databases. Additionally, we will search websites of the organisations publishing any living evidence synthesis retrieved in the two databases, in order to identify unpublished subsequent reports. Two reviewers will independently assess each article against the selection criteria, extract data on methods and procedures, and assess the methodological quality of each publication. Data will be analysed descriptively.

Generation and characterization of human insulin-releasing cell lines.

BACKGROUND: The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. RESULTS: We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. CONCLUSION: We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction.