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TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer
Zoran Krstanoski, Nadja Kokalj-Vokač, Andreja Zagorac, Boris Pospihalj, Miha Munda, Sašo Džeroski, Rastko Golouh, 2016, izvirni znanstveni članek

Opis: Background: TMPRSS2:ERG gene aberration may be a novel marker that improves risk stratification of prostate cancer before definitive cancer therapy, but studies have been inconclusive. Methods: The study cohort consisted of 202 operable prostate cancer Slovenian patients who underwent laparoscopic radical prostatectomy. We retrospectively constructed tissue microarrays of their prostatic specimens for fluorescence in situ hybridization, with appropriate signals obtained in 148 patients for subsequent statistical analyses. Results: The following genetic aberrations were found: TMPRSS2:ERG fusion, TMPRSS2 split (a non-ERG translocation) and ERG split (an ERG translocation without involvement of TMPRSS2). TMPRSS2:ERG gene fusion happened in 63 patients (42 %), TMPRSS2 split in 12 patients and ERG split in 8 patients. Association was tested between TMPRSS2:ERG gene fusion and several clinicopathological variables, i.e., pT stage, extended lymph node dissection status, and Gleason score, correcting for multiple comparisons. Only the association with pT stage was significant at p = 0.05: Of 62 patients with pT3 stage, 34 (55 %) had TMPRSS2:ERG gene fusion. In pT3 stage patients, stronger (but not significant) association between eLND status and TMPRSS2:ERG gene fusion was detected. We detected TMPRSS2:ERG gene fusion in 64 % of the pT3 stage patients where we did not perform an extended lymph node dissection. Conclusions: Our results indicate that it is possible to predict pT3 stage at final histology from TMPRSS2:ERG gene fusion at initial core needle biopsy. FISH determination of TMPRSS2:ERG gene fusion may be particularly useful for patients scheduled to undergo a radical prostatectomy in order to improve oncological and functional results.
Ključne besede: FISH, predicting pT stage, radical prostatectomy, prostate cancer, TMPRSS2:ERG fusion
Objavljeno: 29.06.2017; Ogledov: 99; Prenosov: 1
.pdf Celotno besedilo (1,06 MB)

Typing Clostridium difficile strains based on tandem repeat sequences
N Henning Zaiß, Maja Rupnik, Ed J Kuijper, Celine Harmanus, Dolf Michielsen, Koen Janssens, Ulrich Nübel, 2009, izvirni znanstveni članek

Opis: Background: Genotyping of epidemic Clostridium difficile strains is necessary to track their emergence and spread. Portability of genotyping data is desirable to facilitate inter-laboratory comparisons and epidemiological studies. Results: This report presents results from a systematic screen for variation in repetitive DNA in the genome of C. difficile. We describe two tandem repeat loci, designated 'TR6' and 'TR10', which display extensive sequence variation that may be useful for sequence-based strain typing. Based on an investigation of 154 C. difficile isolates comprising 75 ribotypes, tandem repeat sequencing demonstrated excellent concordance with widely used PCR ribotyping and equal discriminatory power. Moreover, tandem repeat sequences enabled the reconstruction of the isolates' largely clonal population structure and evolutionary history. Conclusion: We conclude that sequence analysis of the two repetitive loci introduced here may be highly useful for routine typing of C. difficile. Tandem repeat sequence typing resolves phylogenetic diversity to a level equivalent to PCR ribotypes. DNA sequences may be stored in databases accessible over the internet, obviating the need for the exchange of reference strains.
Ključne besede: Clostridium difficile, microbiology, strain typing
Objavljeno: 29.06.2017; Ogledov: 51; Prenosov: 2
.pdf Celotno besedilo (792,24 KB)

The LexA regulated genes of the Clostridium difficile
Beata Maria Walter, Maja Rupnik, Vesna Hodnik, Gregor Anderluh, Bruno Dupuy, Nejc Paulič, Darja Žgur-Bertok, Matej Butala, 2014, izvirni znanstveni članek

Opis: Background: The SOS response including two main proteins LexA and RecA, maintains the integrity of bacterial genomes after DNA damage due to metabolic or environmental assaults. Additionally, derepression of LexA-regulated genes can result in mutations, genetic exchange and expression of virulence factors. Here we describe the first comprehensive description of the in silico LexA regulon in Clostridium difficile, an important human pathogen. Results: We grouped thirty C. difficile strains from different ribotypes and toxinotypes into three clusters according to lexA gene/protein variability. We applied in silico analysis coupled to surface plasmon resonance spectroscopy (SPR) and determined 16 LexA binding sites in C. difficile. Our data indicate that strains within the cluster, as defined by LexA variability, harbour several specific LexA regulon genes. In addition to core SOS genes: lexA, recA, ruvCA and uvrBA, we identified a LexA binding site on the pathogenicity locus (PaLoc) and in the putative promoter region of several genes involved in housekeeping, sporulation and antibiotic resistance. Conclusions: Results presented here suggest that in C. difficile LexA is not merely a regulator of the DNA damage response genes but also controls the expression of dozen genes involved in various other biological functions. Our in vitro results indicate that in C. difficile inactivation of LexA repressor depends on repressor`s dissociation from the operators. We report that the repressor`s dissociation rates from operators differentiate, thus the determined LexA-DNA dissociation constants imply on the timing of SOS gene expression in C. difficile.
Ključne besede: Clostridium difficile, antibiotic resistance, toxin regulation, SOS system, surface plasmon resonance, SPR, LexA repressor
Objavljeno: 29.06.2017; Ogledov: 55; Prenosov: 2
.pdf Celotno besedilo (1,16 MB)

International Clostridium difficile animal strain collection and large diversity of animal associated strains
Sandra Janežič, Valerija Tkalec, Bart Pardon, Alexander Indra, Branko Kokotovic, Jose Luis Blanco, Christian Seyboldt, Rodriguez Diaz, Ian Poxton, Vincent Perreten, Ilenia Drigo, Alena Jiraskova, Matjaž Ocepek, Scott Weese, Glenn Songer, Mark Wilcox, Maja Rupnik, 2014, izvirni znanstveni članek

Opis: Background: Clostridium difficile is an important cause of intestinal infections in some animal species and animals might be a reservoir for community associated human infections. Here we describe a collection of animal associated C. difficile strains from 12 countries based on inclusion criteria of one strain (PCR ribotype) per animal species per laboratory. Results: Altogether 112 isolates were collected and distributed into 38 PCR ribotypes with agarose based approach and 50 PCR ribotypes with sequencer based approach. Four PCR ribotypes were most prevalent in terms of number of isolates as well as in terms of number of different host species: 078 (14.3% of isolates; 4 hosts), 014/020 (11.6%; 8 hosts); 002 (5.4%; 4 hosts) and 012 (5.4%; 5 hosts). Two animal hosts were best represented; cattle with 31 isolates (20 PCR ribotypes; 7 countries) and pigs with 31 isolates (16 PCR ribotypes; 10 countries). Conclusions: This results show that although PCR ribotype 078 is often reported as the major animal C. difficile type, especially in pigs, the variability of strains in pigs and other animal hosts is substantial. Most common human PCR ribotypes (014/020 and 002) are also among most prevalent animal associated C. difficile strains worldwide. The widespread dissemination of toxigenic C. difficile and the considerable overlap in strain distribution between species furthers concerns about interspecies, including zoonotic, transmission of this critically important pathogen.
Ključne besede: Clostridium difficile, animals, ribotyping, geographic distribution, strain collection
Objavljeno: 29.06.2017; Ogledov: 46; Prenosov: 2
.pdf Celotno besedilo (985,16 KB)

Clostridium difficile genotypes other than ribotype 078 that are prevalent among human, animals and environmental isolates
Sandra Janežič, Matjaž Ocepek, Valerija Tkalec, Maja Rupnik, 2012, izvirni znanstveni članek

Opis: Background: Characterising the overlap of C. difficile genotypes in different reservoirs can improve our understanding of possible transmission routes of this pathogen. Most of the studies have focused on a comparison of the PCR ribotype 078 isolated from humans and animals. Here we describe for the first time a comparison of C. difficile genotypes isolated during longer time intervals from different sources including humans, animals and the non-hospital environment. Results: Altogether 786 isolates from time interval 2008-2010 were grouped into 90 PCR ribotypes and eleven of them were shared among all host types and the environment. Ribotypes that were most common in humans were also present in water and different animals (014/020, 002, 029). Interestingly, non-toxigenic isolates were very common in the environment (30.8%) in comparison to humans (6.5%) and animals (7.7%). A high degree of similarity was observed for human and animal isolates with PFGE. In human isolates resistance to erithromycin, clindamycin and moxifloxacin was detected, while all animal isolates were susceptible to all antibiotics tested. Conclusion: Our results show that many other types in addition to PCR Ribotype 078 are shared between humans and animals and that the most prevalent genotypes in humans have the ability to survive also in the environment and several animal hosts. The genetic relatedness observed with PFGE suggests that transmission of given genotype from one reservoir to the other is likely to occur.
Ključne besede: Clostridium difficile, genotypes, PCR ribotype 078, isolates
Objavljeno: 29.06.2017; Ogledov: 44; Prenosov: 1
.pdf Celotno besedilo (2,29 MB)

A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5
Danijela Krgović, Ana Blatnik, Ante Burmas, Andreja Zagorac, Nadja Kokalj-Vokač, 2014, izvirni znanstveni članek

Opis: Background: Rearrangements involving chromosome 5p often result in two syndromes, Cri-du-chat (CdC) and Trisomy 5p, caused by a deletion and duplication, respectively. The 5p15.2 has been defined as a critical region for CdC syndrome; however, genotype-phenotype studies allowed isolation of particular characteristics such as speech delay, cat-like cry and mental retardation, caused by distinct deletions of 5p. A varied clinical outcome was also observed in patients with Trisomy 5p. Duplications of 5p10-5p13.1 manifest themselves in a more severe phenotype, while trisomy of regions distal to 5p13 mainly causes mild and indistinct features. Combinations of a terminal deletion and inverted duplication of 5p are infrequent in literature. Consequences of these chromosomal rearrangements differ, depending on size of deletion and duplication in particular cases, although authors mainly describe the deletion as the cause of the observed clinical picture. Case presentation: Here we present a 5-month-old Slovenian girl, with de novo terminal deletion and inverted duplication of chromosome 5p. Our patient presents features of both CdC and Trisomy 5. The most prominent features observed in our patient are a cat-like cry and severe malformations of the right ear. Conclusion: The cat-like cry, characteristic of CdC syndrome, is noted in our patient despite the fact that the deletion is not fully consistent with previously defined cat-like cry critical region in this syndrome. Features like dolichocephaly, macrocephaly and ear malformations, associated with duplication of the critical region of Trisomy 5p, are also present, although this region has not been rearranged in our case. Therefore, the true meaning of the described chromosomal rearrangements is discussed.
Ključne besede: deletion with inverted duplication of 5p, trisomy 5, cri-du-chat syndrome, cat-like cry, ear agenesis
Objavljeno: 28.06.2017; Ogledov: 76; Prenosov: 1
.pdf Celotno besedilo (1,07 MB)

Using movies to teach professionalism to medical students
Zalika Klemenc-Ketiš, Janko Kersnik, 2011, izvirni znanstveni članek

Opis: Background: Professionalism topics are usually not covered as a separate lesson within formal curriculum, but in subtler and less officially recognizededucational activities, which makes them difficult to teach and assess. Interactive methods (e.g. movies) could be efficient teaching methods but are rarely studied. The aims of this study were: 1) to test the relevance and usefulness of movies in teaching professionalism to fourth year medical students and, 2) to assess the impact of this teaching method on students' attitudes towards some professionalism topics. Method: This was an education study with qualitative data analysis in a group of eleven fourth year medical students from the Medical School of University Maribor who attended an elective four month course on professionalism. There were 8 (66.7%) female students in the group. The mean age of the students was 21.9 +/- 0.9 years. The authors used students' written reports and oral presentations as the basisfor qualitative analysis using thematic codes. Results: Students recognised the following dimensions in the movie: communication, empathy, doctors' personal interests and palliative care. It also made them think abouttheir attitudes towards their own life, death and dying. Conclusion: The controlled environment of movies successfully enables students to explore their values, beliefs, and attitudes towards features of professionalism without feeling that their personal integrity had been threatened. Interactiveteaching methods could become an indispensible aid in teaching professionalism to new generations.
Ključne besede: teaching methods, movies, medical students
Objavljeno: 28.06.2017; Ogledov: 99; Prenosov: 1
.pdf Celotno besedilo (246,35 KB)

Regional coordinators
Davorina Petek, Polona Vidič Hudobivnik, Viktorija Jančar, Bojana Petek, Zalika Klemenc-Ketiš, 2016, izvirni znanstveni članek

Opis: Background: A new project on education in family medicine training was implemented last year in Slovenia by establishing regional coordinators in the specialist training programme. They are responsible for conducting regular small-group meetings with family medicine trainees. This study wanted to explore the attitudes and opinions of regional coordinators and family medicine trainees concerning this new method. Methods: This was a qualitative study based on focus groups. The participants were regional coordinators and family medicine specialist trainees. The data were analysed based on the principles of thematic content analysis with inductive technique. Results: The study revealed five themes which were the same for the analysis of transcripts of both regional coordinators and family medicine trainees: 1) Meetings with trainees; 2) Coordination; 3) Characteristics of regional coordinators; 4) Position of regional coordinators, and 5) Evaluation of regional coordinators. Conclusion: Participants of the study have many expectations for this new programme. They expect progress in trainees' clinical knowledge through experience-based group learning and with the help of the tutorship role of regional coordinators. The role of regional coordinators represents a new possibility for solving problems in the training programme in their coordinating role. In future, they have the potential to develop into an expert body that supervises the quality of training. A close follow-up is necessary to see if the position of regional coordinators is adequate and if they meet the expectations of the trainees as well as their own goals. Administrative and financial support for the programme is necessary. The project is important also in enabling the adaptation of the training programme's needs and the regional characteristics of medical care.
Ključne besede: family practice, education, mentors
Objavljeno: 28.06.2017; Ogledov: 53; Prenosov: 2
.pdf Celotno besedilo (467,20 KB)

Viral respiratory infections in a nursing home
Tina Uršič, Nina Gorišek Miksić, Lara Lusa, Franc Strle, Miroslav Petrovec, 2016, izvirni znanstveni članek

Opis: Background: The knowledge on viral respiratory infections in nursing home (NH) residents and their caregivers is limited. The purpose of the present study was to assess and compare the incidence of acute respiratory infections (ARI) in nursing home (NH) residents and staff, to identify viruses involved in ARI and to correlate viral etiology with clinical manifestations of ARI. Methods: The prospective surveillance study was accomplished in a medium-sized NH in Slovenia (central Europe). Ninety NH residents and 42 NH staff were included. Nasopharyngeal swabs were collected from all participants at enrollment (December 5th, 2011) and at the end of the study (May 31st, 2012), and from each participant that developed ARI within this timeframe. Molecular detection of 15 respiratory viruses in nasopharyngeal swab samples was performed. Results: The weekly incidence rate of ARI in NH residents and NH staff correlated; however, it was higher in staff members than in residents (5.9 versus 3.8/1,000 person-days, P=0.03), and was 2.5 (95 % CI: 1.36-4.72) times greater in residents without dementia than in residents with dementia. Staff members typically presented with upper respiratory tract involvement, whereas in residents lower respiratory tract infections predominated. Respiratory viruses were detected in 55/100 ARI episodes. In residents, influenza A virus, respiratory syncytial virus, and human metapneumovirus were detected most commonly, whereas in NH staff rhinovirus and influenza A virus prevailed. 38/100 ARI episodes (30/56 in residents, 8/44 in staff) belonged to one of three outbreaks (caused by human metapneumovirus, influenza A virus and respiratory syncytial virus, respectively). NH residents had higher chances for virus positivity within outbreak than HN staff (OR=7.4, 95 % CI: 1.73-31.48, P<0.01). Conclusions: ARI are common among NH residents and staff, and viruses were detected in a majority of the episodes of ARI. Many ARI episodes among NH residents were outbreak cases and could be considered preventable. Trial registration The study was registered on the 1th of December 2011 at ClinicalTrials (NCT01486160).
Ključne besede: respiratory infections, nursing home, residents nursing home
Objavljeno: 28.06.2017; Ogledov: 54; Prenosov: 2
.pdf Celotno besedilo (688,60 KB)

The safety attitudes questionnaire - ambulatory version
Zalika Klemenc-Ketiš, Matjaž Maletič, Vesna Stropnik, Ellen Tveter Deilkås, Dag Hofoss, Gunnar Tschudi Bondevik, 2017, izvirni znanstveni članek

Opis: Background: Several tools have been developed to measure safety attitudes of health care providers, out of which the Safety Attitudes Questionnaire (SAQ) is regarded as one of the most appropriate ones. In 2007, it was adapted to outpatient (primary health care) settings and in 2014 it was tested in out-of-hours health care settings in Norway. The purpose of this study was to translate the English version of the SAQ-Ambulatory Version (SAQ-AV) to Slovenian language; to test its reliability; and to explore its factor structure. Methods: This was a cross-sectional study that took place in Slovenian out-of-hours primary care clinics in March- May 2015 as a part of an international study entitled Patient Safety Culture in European Out-of-hours services. The questionnaire consisted of the Slovenian version of the SAQ-AV. The link to the questionnaire was emailed to health care workers in the out-of-hours clinics. A total of 438 participants were invited. We performed exploratory factor analysis. Results: Out of 438 invited participants, 250 answered the questionnaire (response rate 57.1%). Exploratory factor analysis put forward five factors: 1) Perceptions of management, 2) Job satisfaction, 3) Safety climate, 4) Teamwork climate, and 5) Communication. Cronbach's alpha of the whole SAQ-AV was 0.922. Cronbach's alpha of the five factors ranged from 0.587 to 0.791. Mean total score of the SAQ-AV was 56.6 +- 16.0 points. The factor with the highest average score was Teamwork climate and the factor with the lowest average was Job satisfaction. Conclusions: Based on the results in our study, we cannot state that the SAQ-AV is a reliable tool for measuring safety culture in the Slovenian out-of-hours care setting. Our study also showed that there might be other safety culture factors in out-of-hours care not recognised before. We therefore recommend larger studies aiming to identify an alternative factor structure.
Ključne besede: patient safety, quality assurance, health care
Objavljeno: 28.06.2017; Ogledov: 91; Prenosov: 8
.pdf Celotno besedilo (515,91 KB)

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