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Critical and supercritical spatiotemporal calcium dynamics in beta cells
Marko Gosak, Andraž Stožer, Rene Markovič, Jurij Dolenšek, Matjaž Perc, Marjan Rupnik, Marko Marhl, 2017, original scientific article

Abstract: A coordinated functioning of beta cells within pancreatic islets is mediated by oscillatory membrane depolarization and subsequent changes in cytoplasmic calcium concentration. While gap junctions allow for intraislet information exchange, beta cells within islets form complex syncytia that are intrinsically nonlinear and highly heterogeneous. To study spatiotemporal calcium dynamics within these syncytia, we make use of computational modeling and confocal high-speed functional multicellular imaging. We show that model predictions are in good agreement with experimental data, especially if a high degree of heterogeneity in the intercellular coupling term is assumed. In particular, during the first few minutes after stimulation, the probability distribution of calcium wave sizes is characterized by a power law, thus indicating critical behavior. After this period, the dynamics changes qualitatively such that the number of global intercellular calcium events increases to the point where the behavior becomes supercritical. To better mimic normal in vivo conditions, we compare the described behavior during supraphysiological non-oscillatory stimulation with the behavior during exposure to a slightly lower and oscillatory glucose challenge. In the case of this protocol, we observe only critical behavior in both experiment and model. Our results indicate that the loss of oscillatory changes, along with the rise in plasma glucose observed in diabetes, could be associated with a switch to supercritical calcium dynamics and loss of beta cell functionality.
Keywords: beta cells, islets of Langerhans, self-organized criticality, intercellular dynamics, calcium waves, glucose oscillations, computational model, confocal calcium imaging
Published: 23.01.2018; Views: 67; Downloads: 3
.pdf Full text (3,43 MB)

Evaluating the effect of Clostridium difficile conditioned medium on fecal microbiota community structure
Sabina Horvat, Aleksander Mahnič, Martin Breskvar, Sašo Džeroski, Maja Rupnik, 2017, original scientific article

Abstract: Clostridium difficile infection (CDI) is typically associated with disturbed gut microbiota and changes related to decreased colonization resistance against C. difficile are well described. However, nothing is known about possible effects of C. difficile on gut microbiota restoration during or after CDI. In this study, we have mimicked such a situation by using C. difficile conditioned medium of six different C. difficile strains belonging to PCR ribotypes 027 and 014/020 for cultivation of fecal microbiota. A marked decrease of microbial diversity was observed in conditioned medium of both tested ribotypes. The majority of differences occurred within the phylum Firmicutes, with a general decrease of gut commensals with putative protective functions (i.e. Lactobacillus, Clostridium_XIVa) and an increase in opportunistic pathogens (i.e. Enterococcus). Bacterial populations in conditioned medium differed between the two C. difficile ribotypes, 027 and 014/020 and are likely associated with nutrient availability. Fecal microbiota cultivated in medium conditioned by E. coli, Salmonella Enteritidis or Staphylococcus epidermidis grouped together and was clearly different from microbiota cultivated in C. difficile conditioned medium suggesting that C. difficile effects are specific. Our results show that the changes observed in microbiota of CDI patients are partially directly influenced by C. difficile.
Keywords: Clostridium difficile, infection, gut microbiota
Published: 12.12.2017; Views: 46; Downloads: 3
.pdf Full text (1,82 MB)

Low overlap between carbapenem resistant Pseudomonas aeruginosa genotypes isolated from hospitalized patients and wastewater treatment plants
Andrej Golle, Sandra Janežič, Maja Rupnik, 2017, original scientific article

Abstract: The variability of carbapenem-resistant Pseudomonas aeruginosa strains (CRPA) isolated from urine and respiratory samples in a large microbiological laboratory, serving several health care settings, and from effluents of two wastewater treatment plants (WWTP) from the same region was assessed by PFGE typing and by resistance to 10 antibiotics. During the 12-month period altogether 213 carbapenem-resistant P. aeruginosa isolates were cultured and distributed into 65 pulsotypes and ten resistance profiles. For representatives of all 65 pulsotypes 49 different MLSTs were determined. Variability of clinical and environmental strains was comparable, 130 carbapenem-resistant P. aeruginosa obtained from 109 patients were distributed into 38 pulsotypes, while 83 isolates from WWTPs were classified into 31 pulsotypes. Only 9 pulsotypes were shared between two or more settings (hospital or WWTP). Ten MLST were determined for those prevalent pulsotypes, two of them (ST111 and ST235) are among most successful CRPA types worldwide. Clinical and environmental carbapenem-resistant P. aeruginosa strains differed in antibiotic resistance. The highest proportion of clinical isolates was resistant to piperacillin/tazobactam (52.3%) and ceftazidime (42.3%). The highest proportion of environmental isolates was resistant to ceftazidime (37.1%) and ciprofloxacin (35.5%). The majority of isolates was resistant only to imipenem and/or meropenem. Strains with additional resistances were distributed into nine different patterns. All of them included clinically relevant strains, while environmental strains showed only four additional different patterns.
Keywords: carpabenem resistance, antibiotic resistance, Pseudomonas aeruginosa, isolates
Published: 12.12.2017; Views: 53; Downloads: 7
.pdf Full text (2,44 MB)

Variations in patient safety climate and perceived quality of collaboration between professions in out-of-hours care
Zalika Klemenc-Ketiš, Ellen Tveter Deilkås, Dag Hofoss, Gunnar Tschudi Bondevik, 2017, original scientific article

Abstract: Purpose: To get an overview of health care workers perceptions of patient safety climates and the quality of collaboration in Slovenian out-of-hours health care (OOHC) between professional groups. Materials and methods: This was a cross-sectional study carried out in all (60) Slovenian OOHC clinics; 37 (61.7%) agreed to participate with 438 employees. The questionnaire consisted of the Slovenian version of the Safety Attitudes Questionnaire - Ambulatory Version (SAQ-AV). Results: The study sample consisted of 175 (70.0%) physicians, nurse practitioners, and practice nurses. Practice nurses reported the highest patient safety climate scores in all dimensions. Total mean (standard deviation) SAQ-AV score was 60.9+-15.2. Scores for quality of collaboration between different professional groups were high. The highest mean scores were reported by nurse practitioners on collaboration with practice nurses (4.4+-0.6). The lowest mean scores were reported by practice nurses on collaboration with nurse practitioners (3.8+-0.9). Conclusion: Due to large variations in Slovenian OOHC clinics with regard to how health care workers from different professional backgrounds perceive safety culture, more attention should be devoted to improving the team collaboration in OOHC. A clearer description of professional team roles should be provided.
Keywords: primary health care, out-of-hours medical care, patient care management
Published: 27.11.2017; Views: 85; Downloads: 2
.pdf Full text (169,11 KB)

Efficacy of a bundle approach in preventing the incidence of ventilator associated pneumonia (VAP)
Sandra Burja, Tina Belec, Nika Bizjak, Jernej Mori, Andrej Markota, Andreja Sinkovič, 2017, original scientific article

Abstract: Ventilator-associated pneumonia (VAP) is a potentially preventable iatrogenic illness that may develop following mechanical ventilation. A bundle for the prevention of VAP consists of different measures which may vary between institutions, and may include: elevation of the head of the bed, oral care with chlorhexidine, subglottic suctioning, daily assessment for extubation and the need for proton-pump inhibitors, use of closed suction systems, and maintaining endotracheal cuff pressure at 25 cmH2O. Our aim was to determine the efficacy of a VAP prevention bundle, consisting of the above-mentioned measures, by evaluating the incidence of VAP before (no-VAP-B group) and after (VAP-B group) the introduction of the bundle. We retrospectively evaluated the data for patients who were mechanically ventilated with an endotracheal tube, in the period between 1 September and 31 December 2014 (no-VAP-B group, n = 55, 54.5% males, mean age 67.8 ± 14.5 years) and between 1 January to 30 April 2015 (VAP-B group, n = 74, 62.1% males, mean age 64.8 ± 13.7 years). There were no statistically significant differences between no-VAP-B and VAP-B groups in demographic data, intensive care unit (ICU) mortality, hospital mortality, duration of ICU treatment, and duration of mechanical ventilation. No significant differences in the rates of VAP and early VAP (onset ≤7 days after intubation) were found between no-VAP-B and VAP-B groups (41.8% versus 25.7%, p = 0.06 and 10.9% versus 12.2%, p > 0.99, respectively). However, a significant decrease in the late VAP (onset >8 days after intubation) was found in VAP-B group compared to no-VAP-B group (13.5% versus 30.9%, p = 0.027). Overall, our results support the use of VAP prevention bundle in clinical practice.
Keywords: ventilator-associated pneumonia, VAP, primary prevention, epidemiology, medical devices, intratracheal intubation, bundle
Published: 13.11.2017; Views: 44; Downloads: 8
.pdf Full text (96,15 KB)

Patient safety culture in Slovenian out-of-hours primary care clinics
Zalika Klemenc-Ketiš, Ellen Tveter Deilkås, Dag Hofoss, Gunnar Tschudi Bondevik, 2017, original scientific article

Abstract: Introduction: Patient safety culture is a concept which describes how leader and staff interaction, attitudes, routines and practices protect patients from adverse events in healthcare. We aimed to investigate patient safety culture in Slovenian out-of-hours health care (OOHC) clinics, and determine the possible factors that might be associated with it. Methods: This was a cross-sectional study, which took place in Slovenian OOHC, as part of the international study entitled Patient Safety Culture in European Out-of-Hours Services (SAFE-EUR-OOH). All the OOHC clinics in Slovenia (N=60) were invited to participate, and 37 agreed to do so; 438 employees from these clinics were invited to participate. We used the Slovenian version of the Safety Attitudes Questionnaire % an ambulatory version (SAQAV) to measure the climate of safety. Results: Out of 438 invited participants, 250 answered the questionnaire (57.1% response rate). The mean overall score % standard deviation of the SAQ was 56.6%16.0 points, of Perceptions of Management 53.6%19.6 points, of Job Satisfaction 48.5%18.3 points, of Safety Climate 59.1%22.1 points, of Teamwork Climate 72.7%16.6, and of Communication 51.5%23.4 points. Employees working in the Ravne na Koroškem region, employees with variable work shifts, and those with full-time jobs scored significantly higher on the SAQ-A V. Conclusion: The safety culture in Slovenian OOHC clinics needs improvement. The variations in the safety culture factor scores in Slovenian OOHC clinics point to the need to eliminate variations and improve working conditions in Slovenian OOHC clinics.
Keywords: safety culture, out-of-hours medical care, primary health care, Slovenia
Published: 03.11.2017; Views: 55; Downloads: 5
.pdf Full text (397,20 KB)

Implementing quality indicators for diabetes and hypertension in family medicine in Slovenia
Zalika Klemenc-Ketiš, Igor Švab, Tonka Poplas-Susič, 2017, original scientific article

Abstract: Introduction: A new form of family practices was introduced in 2011 through a pilot project introducing nurse practitioners as members of team and determining a set of quality indicators. The aim of this article was to assess the quality of diabetes and hypertension management. Methods: We included all family medicine practices that were participating in the project in December 2015 (N=584). The following data were extracted from automatic electronic reports on quality indicators: gender and specialisation of the family physician, status (public servant/self-contracted), duration of participation in the project, region of Slovenia, the number of inhabitants covered by a family medicine practice, the name of IT provider, and levels of selected quality indicators. Results: Out of 584 family medicine practices that were included in this project at the end of 2015, 568 (97.3%) had complete data and could be included in this analysis. The highest values were observed for structure quality indicator (list of diabetics) and the lowest for process and outcome quality indicators. The values of the selected quality indicators were independently associated with the duration of participation in the project, some regions of Slovenia where practices were located, and some IT providers of the practices. Conclusion: First, the analysis of data on quality indicators for diabetes and hypertension in this primary care project pointed out the problems which are currently preventing higher quality of chronic patient management at the primary health care level.
Keywords: family practices, healthcare quality indicator, diabetes mellitus, hypertension, Slovenia
Published: 03.11.2017; Views: 52; Downloads: 4
.pdf Full text (424,82 KB)

Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors
Matjaž Zwitter, Antonio Rossi, Massimo Di Maio, Maja Pohar Perme, Gilberto Lopes, 2017, original scientific article

Abstract: Background: When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment. Methods: Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson's correlation coefficient and the coefficient of determination, separately for first-line and second-line setting. Results: The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with nonsquamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months. Conclusions: Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.
Keywords: lung cancer, NSCLC, intercalated treatment, EGFR, tyrosine -kinase inhibitors
Published: 30.10.2017; Views: 50; Downloads: 2
.pdf Full text (622,21 KB)

A novel mutation in the FOXC2 gene
Tanja Planinšek Ručigaj, Matija Rijavec, Jovan Miljković, Julij Gyula Šelb, Peter Korošec, 2017, original scientific article

Abstract: Background: Primary lymphoedema is a rare genetic disorder characterized by swelling of different parts of the body and highly heterogenic clinical presentation. Mutations in several causative genes characterize specific forms of the disease. FOXC2 mutations are associated with lymphoedema of lower extremities, usually distichiasis and late onset. Patients and methods: Subjects from three generations of a family with lymphoedema of lower limbs without distichiasis were searched for mutations in the FOXC2 gene. Results: All affected family members with lymphoedema of lower limbs without distichiasis, and still asymptomatic six years old girl from the same family, carried the same previously unreported insertion of adenosine (c.867insA) in FOXC2. Conclusions: Identification of a novel mutation in the FOXC2 gene in affected family members of three generations with lymphoedema of lower limbs without distichiasis, highlights the high phenotypic variability caused by FOXC2 mutations.
Keywords: primary lymphedema, FOXC2 mutation, distichiasis, lower limbs lymphedema
Published: 30.10.2017; Views: 57; Downloads: 2
.pdf Full text (538,46 KB)

Vaskularni kognitivni upad in vaskularna demenca
Klavdija Ovčar Štante, Jure Potočnik, Martin Rakuša, 2017, professional article

Abstract: V razvitem svetu ima 5–10 % prebivalstva nad 65 let demenco, katere pojavnost še vedno narašča. Demence zaradi možganskih žilnih bolezni – vaskularna demenca (VaD) predstavljajo dobro petino vseh vzrokov za demenco. Milejša oblika je vaskularni kognitivni upad (VaKU). Za postavitev diagnoze VaD je pomembno, da sta upad spoznavnih sposobnosti in možgansko-žilna bolezen jasno časovno povezana ter ni popravljivih vzrokov za kognitivni upad. Pri postavitvi diagnoze uporabimo nevropsihološko testiranje in slikovne preiskave. Glavni dejavniki tveganja za VaKU in VaD so starost, ateroskleroza, sladkorna bolezen in arterijska hipertenzija, ki sprožijo kaskado dogodkov v patogenezi kognitivne okvare. Ta je zelo raznolika in poteka z ali brez pridruženih nevroloških simptomov. Klinična slika je odvisna od področja in velikosti možganske spremembe. Pri zdravljenju VaKU in VaD je najbolj pomembna primarna preventiva. Za zdravljenje simptomov VaKU in VaD se uporabljajo enaka zdravila kot za zdravljenje simptomov Alzheimerjeve bolezni. Pomembni sta še rehabilitacija in sekundarna preventiva ponovne možganske kapi. Glavni dejavniki tveganja za VaD so starost, ateroskleroza, sladkorna bolezen in arterijska hipertenzija, ki sprožijo kaskado dogodkov v patogenezi kognitivne okvare. Ta je zelo raznolika in poteka z ali brez pridruženih nevroloških simptomov. Klinična slika je odvisna od področja in velikosti možganske lezije. Pri zdravljenju VaKU in VaD je najbolj pomembna primarna preventiva. Za zdravljenje simptomov VaKU in VaD se uporabljajo enaka zdravila kot za zdravljenje simptomov Alzheimerjeve bolezni. Pomembni sta še rehabilitacija in sekundarna preventiva ponovne možganske kapi.
Keywords: vaskularna demenca, vaskularni kognitivni upad, možganske žilne bolezni, spoznavne sposobnosti
Published: 09.10.2017; Views: 97; Downloads: 12
.pdf Full text (137,66 KB)

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