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Which positive factors determine the GP satisfaction in clinical practice?
Bernard Le Floch, Hilde Bastiaens, Jean-Yves Le Reste, H. Lingner, Robert Hoffman, Sĺawomir Czachowski, Radost Spiridonova Assenova, Tuomas Koskela, Zalika Klemenc-Ketiš, P. Nabbe, A. Sowinska, T. Montier, Lieve Peremans, 2016, pregledni znanstveni članek

Opis: Background: Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Methods: Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. Results: The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. Conclusions: A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.
Ključne besede: family medicine, primary health care, career
Objavljeno: 28.06.2017; Ogledov: 35; Prenosov: 0
.pdf Polno besedilo (429,53 KB)

Process quality indicators in family medicine
Danica Rotar-Pavlič, Maja Sever, Zalika Klemenc-Ketiš, Igor Švab, 2015, izvirni znanstveni članek

Opis: Background: The aim of our study was to describe variability in process quality in family medicine among 31 European countries plus Australia, New Zealand, and Canada. The quality of family medicine was measured in terms of continuity, coordination, community orientation, and comprehensiveness of care. Methods: The QUALICOPC study (Quality and Costs of Primary Care in Europe) was carried out among family physicians in 31 European countries (the EU 27 except for France, plus Macedonia, Iceland, Norway, Switzerland, and Turkey) and three non-European countries (Australia, Canada, and New Zealand). We used random sampling when national registers of practitioners were available. Regional registers or lists of facilities were used for some countries. A standardized questionnaire was distributed to the physicians, resulting in a sample of 6734 participants. Data collection took place between October 2011 and December 2013. Based on completed questionnaires, a three-dimensional framework was established to measure continuity, coordination, community orientation, and comprehensiveness of care. Multilevel linear regression analysis was performed to evaluate the variation of quality attributable to the family physician level and the country level. Results: None of the 34 countries in this study consistently scored the best or worst in all categories. Continuity of care was perceived by family physicians as the most important dimension of quality. Some components of comprehensiveness of care, including medical technical procedures, preventive care and health care promotion, varied substantially between countries. Coordination of care was identified as the weakest part of quality. We found that physician-level characteristics contributed to the majority of variation. Conclusions: A comparison of process quality indicators in family medicine revealed similarities and differences within and between countries. The researchers found that the major proportion of variation can be explained by physicians' characteristics.
Ključne besede: family physician, process quality, comparison
Objavljeno: 28.06.2017; Ogledov: 30; Prenosov: 0
.pdf Polno besedilo (697,85 KB)

Biomedical question answering using semantic relations
Dimitar Hristovski, Dejan Dinevski, Andrej Kastrin, Thomas Rindflesch, 2015, izvirni znanstveni članek

Opis: Background: The proliferation of the scientific literature in the field of biomedicine makes it difficult to keep abreast of current knowledge, even for domain experts. While general Web search engines and specialized information retrieval (IR) systems have made important strides in recent decades, the problem of accurate knowledge extraction from the biomedical literature is far from solved. Classical IR systems usually return a list of documents that have to be read by the user to extract relevant information. This tedious and time-consuming work can be lessened with automatic Question Answering (QA) systems, which aim to provide users with direct and precise answers to their questions. In this work we propose a novel methodology for QA based on semantic relations extracted from the biomedical literature. Results: We extracted semantic relations with the SemRep natural language processing system from 122,421,765 sentences, which came from 21,014,382 MEDLINE citations (i.e., the complete MEDLINE distribution up to the end of 2012). A total of 58,879,300 semantic relation instances were extracted and organized in a relational database. The QA process is implemented as a search in this database, which is accessed through a Web-based application, called SemBT (available at We conducted an extensive evaluation of the proposed methodology in order to estimate the accuracy of extracting a particular semantic relation from a particular sentence. Evaluation was performed by 80 domain experts. In total 7,510 semantic relation instances belonging to 2,675 distinct relations were evaluated 12,083 times. The instances were evaluated as correct 8,228 times (68%). Conclusions: In this work we propose an innovative methodology for biomedical QA. The system is implemented as a Web-based application that is able to provide precise answers to a wide range of questions. A typical question is answered within a few seconds. The tool has some extensions that make it especially useful for interpretation of DNA microarray results.
Ključne besede: semantic relations, biomedical question
Objavljeno: 28.06.2017; Ogledov: 45; Prenosov: 1
.pdf Polno besedilo (2,76 MB)

Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor in the period 2000-2009
Nina Fokter Dovnik, Darja Arko, Nina Čas-Sikošek, Iztok Takač, 2017, izvirni znanstveni članek

Opis: Introduction: Breast cancer is increasingly diagnosed in the early stages without regional nodal involvement. The aim of the present study was to determine the 5-year overall (OS) and breast cancer specific survival (BCSS) for patients with node-negative breast cancer treated at the University Medical Centre Maribor, and compare it with survival at the national level. Methods: Medical records were searched for information on patients with lymph node-negative invasive breast cancer who received primary treatment at the University Medical Centre Maribor in the period 2000–2009. Information on all Slovenian node-negative breast cancer patients diagnosed in the same period was obtained from the Cancer Registry of Republic of Slovenia. Time trends in survival were assessed by comparing the periods 2000–2004 and 2005–2009. Results: The 5-year OS and BCSS of patients treated in Maribor in the period 2000–2009 were 92.3% (95% CI, 90.5%– 94.1%) and 96.4% (95% CI, 95.2%–97.6%), respectively, and did not differ from the corresponding OS and BCSS for Slovenian patients. Although the improvement in OS for patients from Maribor diagnosed in the period 2005–2009 compared to 2000–2004 did not reach statistical significance (HR 0.73; 95% CI, 0.51–1.05; p=0.086), BCSS significantly improved over the same time periods (HR 0.53; 95% CI, 0.30–0.94; p=0.028). Conclusions: Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor is comparable to survival of corresponding patients at the national level. The rising number of long-term breast cancer survivors places additional importance on survivorship care.
Ključne besede: breast cancer, survival, time trends, regional differences, Slovenia
Objavljeno: 26.06.2017; Ogledov: 44; Prenosov: 1
.pdf Polno besedilo (854,97 KB)

Single-cell analysis reveals IGF-1 potentiation of inhibition of the TGF-ß/Smad pathway of fibrosis in human keratocytes in vitro
Tomislav Šarenac, Martin Trapečar, Lidija Gradišnik, Marjan Rupnik, Dušica Pahor, 2016, izvirni znanstveni članek

Opis: Corneal wound healing is often affected by TGF-β–mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1. Extracellular matrix proteoglycans keratocan and biglycan were quantified using ELISAs. On the TGF-β2 background, the keratocytes were treated with IGF-1, and suberoylanilidehydroxamic acid (SAHA) or halofuginone ± IGF-1. IGF-1 alone decreased Smad3 nuclearization and increased aldehyde dehydrogenase 3A1 expression, with favorable extracellular matrix proteoglycan composition. SAHA induced higher Smad7 levels and inhibited translocation of Smad3 to the nucleus, also when combined with IGF-1. Immunofluorescence showed that myofibroblast transdifferentiation is attenuated and appearance of fibroblasts is favored by IGF-1 alone and in combination with the antifibrotic substances. The TGF-β/Smad pathway of fibrosis and opacity was inhibited by IGF-1, and further with SAHA in particular, and with halofuginone. IGF-1 is thus a valid aid to antifibrotic treatment, with potential for effective and transparent corneal wound healing.
Ključne besede: cornea, wounds, treatment, antifibrotic treatment, keratocytes
Objavljeno: 23.06.2017; Ogledov: 115; Prenosov: 0
.pdf Polno besedilo (1,89 MB)

Membrane potential and calcium dynamics in beta cells from mouse pancreas tissue slices
Marjan Rupnik, Andraž Stožer, Jurij Dolenšek, Borut Žalik, Maša Skelin, Marko Gosak, Denis Špelič, 2015, pregledni znanstveni članek

Opis: Beta cells in the pancreatic islets of Langerhans are precise biological sensors for glucose and play a central role in balancing the organism between catabolic and anabolic needs. A hallmark of the beta cell response to glucose are oscillatory changes of membrane potential that are tightly coupled with oscillatory changes in intracellular calcium concentration which, in turn, elicit oscillations of insulin secretion. Both membrane potential and calcium changes spread from one beta cell to the other in a wave-like manner. In order to assess the properties of the abovementioned responses to physiological and pathological stimuli, the main challenge remains how to effectively measure membrane potential and calcium changes at the same time with high spatial and temporal resolution, and also in as many cells as possible. To date, the most wide-spread approach has employed the electrophysiological patch-clamp method to monitor membrane potential changes. Inherently, this technique has many advantages, such as a direct contact with the cell and a high temporal resolution. However, it allows one to assess information from a single cell only. In some instances, this technique has been used in conjunction with CCD camera-based imaging, offering the opportunity to simultaneously monitor membrane potential and calcium changes, but not in the same cells and not with a reliable cellular or subcellular spatial resolution. Recently, a novel family of highly-sensitive membrane potential reporter dyes in combination with high temporal and spatial confocal calcium imaging allows for simultaneously detecting membrane potential and calcium changes in many cells at a time. Since the signals yielded from both types of reporter dyes are inherently noisy, we have developed complex methods of data denoising that permit for visualization and pixel-wise analysis of signals. Combining the experimental approach of high-resolution imaging with the advanced analysis of noisy data enables novel physiological insights and reassessment of current concepts in unprecedented detail.
Ključne besede: calcium sensors, membrane potential sensors, calcium imaging, membrane potential imaging, beta cell, pancreas, denoising, patch-clamp
Objavljeno: 22.06.2017; Ogledov: 80; Prenosov: 3
.pdf Polno besedilo (4,17 MB)

Adapted user-centered design
Emilija Stojmenova, Bojan Imperl, Tomaž Žohar, Dejan Dinevski, 2012, izvirni znanstveni članek

Opis: Being familiar with all the benefits of e-Health and the strategic plan for the Slovenian health sectors informatization, Telekom Slovenia and the Faculty of Medicine from the University of Maribor, along with other partners, have initiated an e-Health project. The project group is developing various e-Health services that are based on modern ICT (information and communications technology) solutions and will be available on several screens. In order to meet the users needs and expectations and, consequently, achieve the high acceptance of e-Health services, the user-centered design (UCD) approach was employed in the e-Health project. However, during the research it was found that conventional UCD methods are not completely appropriate for older adults: the target population of the e-Health services. That is why the selected UCD methods were modified and adapted for older adults. The modified UCD methods used in the research study are presented in this paper. Using the results of the adapted UCD methods, a prototype for a service named MedReminder was developed. The prototype was evaluated by a group of 12 study participants. The study participants evaluated the MedReminder service as acceptable with a good potential for a high adoption rate among its target population, i.e., older adults.
Ključne besede: ICT, e-Health, MedReminder, user-centered design, modification, adaptation, older adults
Objavljeno: 21.06.2017; Ogledov: 44; Prenosov: 0
.pdf Polno besedilo (1,04 MB)

The SOS response master regulator LexA is associated with sporulation, motility and biofilm formation in Clostridium difficile
Beata Maria Walter, Stephen Cartman, Nigel Peter Minton, Matej Butala, Maja Rupnik, 2015, izvirni znanstveni članek

Opis: The LexA regulated SOS network is a bacterial response to DNA damage of metabolic or environmental origin. In Clostridium difficile, a nosocomial pathogen causing a range of intestinal diseases, the in-silico deduced LexA network included the core SOS genes involved in the DNA repair and genes involved in various other biological functions that vary among different ribotypes. Here we describe the construction and characterization of a lexA ClosTron mutant in C. difficile R20291 strain. The mutation of lexA caused inhibition of cell division resulting in a filamentous phenotype. The lexA mutant also showed decreased sporulation, a reduction in swimming motility, greater sensitivity to metronidazole, and increased biofilm formation. Changes in the regulation of toxin A, but not toxin B, were observed in the lexA mutant in the presence of sub-inhibitory concentrations of levofloxacin. C. difficile LexA is, therefore, not only a regulator of DNA damage but also controls many biological functions associated with virulence.
Ključne besede: toxins, bacterial sporulation, DNA damage, antibiotics
Objavljeno: 19.06.2017; Ogledov: 84; Prenosov: 0
.pdf Polno besedilo (6,06 MB)

The relationship between membrane potential and calcium dynamics in glucose-stimulated beta cell syncytium in acute mouse pancreas tissue slices
Jurij Dolenšek, Andraž Stožer, Maša Skelin, Evan Miller, Marjan Rupnik, 2013, izvirni znanstveni članek

Opis: Oscillatory electrical activity is regarded as a hallmark of the pancreatic beta cell glucose-dependent excitability pattern. Electrophysiologically recorded membrane potential oscillations in beta cells are associated with in-phase oscillatory cytosolic calcium activity ([Ca2+]i) measured with fluorescent probes. Recent high spatial and temporal resolution confocal imaging revealed that glucose stimulation of beta cells in intact islets within acute tissue slices produces a [Ca2+]i change with initial transient phase followed by a plateau phase with highly synchronized [Ca2+]i oscillations. Here, we aimed to correlate the plateau [Ca2+]i oscillations with the oscillations of membrane potential using patch-clamp and for the first time high resolution voltage-sensitive dye based confocal imaging. Our results demonstrated that the glucose-evoked membrane potential oscillations spread over the islet in a wave-like manner, their durations and wave velocities being comparable to the ones for [Ca2+]i oscillations and waves. High temporal resolution simultaneous records of membrane potential and [Ca2+]i confirmed tight but nevertheless limited coupling of the two processes, with membrane depolarization preceding the [Ca2+]i increase. The potassium channel blocker tetraethylammonium increased the velocity at which oscillations advanced over the islet by several-fold while, at the same time, emphasized differences in kinetics of the membrane potential and the [Ca2+]i. The combination of both imaging techniques provides a powerful tool that will help us attain deeper knowledge of the beta cell network.
Ključne besede: glucose, pancreas, mice
Objavljeno: 19.06.2017; Ogledov: 98; Prenosov: 0
.pdf Polno besedilo (2,57 MB)

The analysis of intracellular and intercellular calcium signaling in human anterior lens capsule epithelial cells with regard to different types and stages of the cataract
Marko Gosak, Rene Markovič, Aleš Fajmut, Marko Marhl, Marko Hawlina, Sofija Andjelić, 2015, izvirni znanstveni članek

Opis: In this work we investigated how modifications of the Ca2+ homeostasis in anterior lens epithelial cells (LECs) are associated with different types of cataract (cortical or nuclear) and how the progression of the cataract (mild or moderate) affects the Ca2+ signaling. We systematically analyzed different aspects of intra- and inter-cellular Ca2+ signaling in the human LECs, which are attached to surgically isolated lens capsule (LC), obtained during cataract surgery. We monitored the temporal and spatial changes in intracellular Ca2+ concentration after stimulation with acetylcholine by means of Fura-2 fluorescence captured with an inverted microscope. In our analysis we compared the features of Ca2+ signals in individual cells, synchronized activations, spatio-temporal grouping and the nature of intercellular communication between LECs. The latter was assessed by using the methodologies of the complex network theory. Our results point out that at the level of individual cells there are no significant differences when comparing the features of the signals with regard either to the type or the stage of the cataract. On the other hand, noticeable differences are observed at the multicellular level, despite inter-capsule variability. LCs associated with more developed cataracts were found to exhibit a slower collective response to stimulation, a less pronounced spatio-temporal clustering of LECs with similar signaling characteristics. The reconstructed intercellular networks were found to be sparser and more segregated than in LCs associated with mild cataracts. Moreover, we show that spontaneously active LECs often operate in localized groups with quite well aligned Ca2+ activity. The presence of spontaneous activity was also found to affect the stimulated Ca2+ responses of individual cells. Our findings indicate that the cataract progression entails the impairment of intercellular signaling thereby suggesting the functional importance of altered Ca2+ signaling of LECs in cataractogenesis.
Ključne besede: intracellular calcium signaling, anterior lens, epithelial cells, cataract
Objavljeno: 19.06.2017; Ogledov: 99; Prenosov: 0
.pdf Polno besedilo (1,45 MB)

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