Immunogenic Dendritic Cell Generation from Pluripotent Stem Cells by Ectopic Expression of Runx3.

Application of dendritic cells (DCs) to prime responses to tumor Ags provides a promising approach to immunotherapy. However, only a limited number of DCs can be manufactured from adult precursors. In contrast, pluripotent embryonic stem (ES) cells represent an inexhaustible source for DC production, although it remains a major challenge to steer directional differentiation because ES cell-derived cells are typically immature with impaired functional capacity. Consistent with this notion, we found that mouse ES cell-derived DCs (ES-DCs) represented less mature cells compared with bone marrow-derived DCs. This finding prompted us to compare the gene expression profile of the ES cell- and adult progenitor-derived, GM-CSF-instructed, nonconventional DC subsets. We quantified the mRNA level of 17 DC-specific transcription factors and observed that 3 transcriptional regulators (Irf4, Spi-B, and Runx3) showed lower expression in ES-DCs than in bone marrow-derived DCs. In light of this altered gene expression, we probed the effects of these transcription factors in developing mouse ES-DCs with an isogenic expression screen. Our analysis revealed that forced expression of Irf4 repressed ES-DC development, whereas, in contrast, Runx3 improved the ES-DC maturation capacity. Moreover, LPS-treated and Runx3-activated ES-DCs exhibited enhanced T cell activation and migratory potential. In summary, we found that ex vivo-generated ES-DCs had a compromised maturation ability and immunogenicity. However, ectopic expression of Runx3 enhances cytokine-driven ES-DC development and acts as an instructive tool for the generation of mature DCs with enhanced immunogenicity from pluripotent stem cells.

[Changing of the patient safety culture in the pilot institutes of the Hungarian accreditation program]. / A betegbiztonságot támogató szervezeti kultúra változása a hazai akkreditációs programot tesztelo intézményekben.

INTRODUCTION: The accreditation system for health care providers was developed in Hungary aiming to increase safety, efficiency, and efficacy of care and optimise its organisational operation. AIM: The aim of this study was to assess changes of organisational culture in pilot institutes of the accreditation program. METHOD: 7 volunteer pilot institutes using an internationally validated questionnaire were included. The impact study was performed in 2 rounds: the first before the introduction of the accreditation program, and the second a year later, when the standards were already known. Data were analysed using descriptive statistics and logistic regression models. RESULTS: Statistically significant (p<0.05) positive changes were detected in hospitals in three dimensions: organisational learning - continuous improvement, communication openness, teamwork within the unit while in outpatient clinics: overall perceptions of patient safety, and patient safety within the unit. CONCLUSIONS: Organisational culture in the observed institutes needs improvement, but positive changes already point to a safer care. Orv. Hetil., 2016, 157(42), 1667-1673.

Endocannabinoid Tone Regulates Human Sebocyte Biology.

We have previously shown that endocannabinoids (eCBs) (e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production in human sebaceous glands and that eCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs. We found that the major eCB synthesizing (N-acyl phosphatidylethanolamine-specific phospholipase D, and diacylglycerol lipase-α and -ß) and degrading (fatty acid amide hydrolase, monoacylglycerol lipase) enzymes are expressed in SZ95 sebocytes and also in sebaceous glands (except for diacylglycerol lipase-α, the staining of which was dubious in histological preparations). eCB uptake-inhibition with VDM11 induced a moderate increase in sebaceous lipid production and also elevated the levels of various eCBs and related acylethanolamides. Finally, we found that VDM11 was able to interfere with the proinflammatory action of the TLR4 activator lipopolysaccharide. Collectively, our data suggest that inhibition of eCB uptake exerts anti-inflammatory actions and elevates both sebaceous lipid production and eCB levels; thus, these inhibitors might be beneficial in cutaneous inflammatory conditions accompanied by dry skin.

[The objective assessment of the quality of hospital care: dream or reality?]. / A kórházi ellátás minoségének objektív megítélése: álom vagy realitás?

One of the hottest topics of the international journals is the question: what is the effect of the public indicator-based quality assessment on the quality of care and on the decision of stakeholders, and which criteria should be applied for development of public quality assessment system. According to the international literature the paper discusses 6 topics: (1) the ability of indicators to distinguish providers from the point of view of quality; (2) the appropriateness of outcome indicators to assess providers; (3) the ability of league tables to rank providers; (4) the people's behaviour during choosing providers; (5) the impact of indicator-based public report; (6) recommendations for developing quality assessment system. Based on the literature review, the ability of indicators in distinguishing providers from the point of view of quality is doubtful primarily because of risk-adjustment problems. Other reasons are: the outcomes of care do not definitely refer to the quality of care process; the rankings of providers (league tables) based on more indicators are not reliable; people take into account mainly distance and the opinions of acquaintance when they choose providers; as a result of public reports the overall quality of care is declining. The publication of the results of measurement to assess providers has to be considered as a tool. For the purpose of helping people in choosing providers, the publication of patient satisfaction survey designed according to their preferences could achieve the desired effect. The quality improvement aims are definitely helped by the direct feedback to providers about the indicator values. Furthermore, much finer picture can be made if the standardized audits of care and organisational processes are inserted into external assessment procedures.

[Development of an indicator system for evaluating the quality of health care services]. / Indikátorrendszer kialakítása az egészségügyi szolgáltatások értékelésére.

Indicator system development for evaluating the quality of health services. The National Health Insurance Fund of Hungary introduces indicators for evaluating the quality of health services. The new system starts by the end of 2003 on the Internet and it will be updated and improved on a regular base. The quality indicators provide possibility to compare the health services and follow up the changes. The Hungarian indicators came from those indicators, which are described, tested and used in the international literature and practice. The data derive from the routinely collected financial data of the National Health Insurance Fund. The conclusions drawn form the results will be arranged and interpreted according to the types of indicators. Those providers whose have out of the ordinary values should fill in a standardized questionnaire--which was developed with the representatives of the certain profession--for explaining the results and define quality improvement plan. The aim of the programme is to increase transparency of health services, to enhance quality improvement and to support the certification and accreditation programmes.