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11.
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of $Ca^{2+}$ oscillations in $\beta$ cell networks
Teresa Daraio, Lidija Križančić Bombek, Marko Gosak, Ismael Valladolid-Acebes, Maša Skelin, Essam Refai, Per-Olof Berggren, Kerstin Brismar, Marjan Rupnik, Christina Bark, 2017, izvirni znanstveni članek

Opis: SNAP-25 is a protein of the core SNARE complex mediating stimulus-dependent release of insulin from pancreatic $\beta$ cells. The protein exists as two alternatively spliced isoforms, SNAP-25a and SNAP-25b, differing in 9 out of 206 amino acids, yet their specific roles in pancreatic $\beta$ cells remain unclear. We explored the effect of SNAP-25b-deficiency on glucose-stimulated insulin release in islets and found increased secretion both in vivo and in vitro. However, slow photo-release of caged $Ca^{2+}$ in $\beta$ cells within pancreatic slices showed no significant differences in $Ca^{2+}$-sensitivity, amplitude or rate of exocytosis between SNAP-25b-deficient and wild-type littermates. Therefore, we next investigated if $Ca^{2+}$ handling was affected in glucose-stimulated [beta] cells using intracellular $Ca^{2+}$-imaging and found premature activation and delayed termination of [$Ca^{2+}$] i elevations. These findings were accompanied by less synchronized $Ca^{2+}$-oscillations and hence more segregated functional $\beta$ cell networks in SNAP-25b-deficient mice. Islet gross morphology and architecture were maintained in mutant mice, although sex specific compensatory changes were observed. Thus, our study proposes that SNAP-25b in pancreatic [beta] cells, except for participating in the core SNARE complex, is necessary for accurate regulation of $Ca^{2+}$-dynamics.
Ključne besede: insulin secretion, pre-diabetes
Objavljeno: 23.08.2017; Ogledov: 54; Prenosov: 4
.pdf Polno besedilo (3,80 MB)

12.
Klinična uporabnost biokemijskih označevalcev in testa agregacije trombocitov pri ishemični možganski kapi
Marija Menih, 2017, doktorsko delo/naloga

Opis: Visoki nivoji VWF so bili napovedniki tako teže možganske kapi kot tudi slabega kliničnega izhoda, ne pa podvrste IMK. VWF bi lahko služil kot prognostični napovednik kliničnega izhoda pri IMK. Nivoji DD, FG in HC niso bili povezani s podvrsto IMK, ne s težo možganske kapi in ne s kliničnim izhodom, zato DD, FG in HC nimajo pomembne diagnostične vrednosti za določeno vrsto IMK ali prognostične vrednosti za klinični izhod po IMK. Visoki nivoji NT-proBNP so bili povezani s kardioembolično IMK ter s težo možganske kapi, ne pa tudi s slabim kliničnim izhodom, zato bi lahko NT-proBNP služil kot diagnostični napovednik za kardioembolično IMK. Merjenje AT je koreliralo z jemanjem aspirina, kar pa ni imelo kliničnega pomena; kljub nizki AT so bolniki utrpeli IMK. Nivoji AT niso bili napovedniki podvrste IMK, teže kapi ali slabega kliničnega izhoda. Z multivariatno regresijsko analizo s posplošenim linearnim modelom smo ugotovili, da so med BKO in AT edini pomembni napovedniki: 1. kardioembolične IMK: NT-proBNP; 2. za težo kapi, ocenjeno z NIHSS: NT-proBNP in VWF:Ag; 3. za klinični izhod, ocenjen z MRL: VWF:Ag.
Ključne besede: akutna ishemična možganska kap, TOAST klasifikacija, biokemijski označevalci, agregacija trombocitov, NIHSS, MRL
Objavljeno: 21.08.2017; Ogledov: 87; Prenosov: 18
.pdf Polno besedilo (4,39 MB)

13.
High resolution melting curve analysis for high-throughput SNP genotyping in IL23R gene and association of IL23R with Slovenian inflammatory bowel diseases patients
Mitja Mitrovič, Uroš Potočnik, 2010, izvirni znanstveni članek

Opis: Single nucleotide polymorphism (SNP) analysis is important tool in the studies of genetic factors associated with complex diseases and with genetically influenced response to drug therapy (pharmacogenetics). Recently, a new generation of generic dsDNA binding dyes (LCGreen$^{TM}$) contributed to the development of fast and low-cost method for SNP detection and/or genotyping based on high resolution melting (HRM) analysis. The aim of our study was to develop HRM assay for IL23R gene (rs7517847) and to perform association study in Slovenian inflammatory bowel diseases (IBD) patients. We genotyped 345 Slovenian healthy controls and 295 IBD patients including 159 with Crohn's disease (CD) and 136 with ulcerative colitis (UC) for rs7517847 polymorphism in IL23R gene using standard RFLP and optimized HRM methods. In this study, we showed, that HRM is a simple, fast and reliable method for genotyping of clinical samples where homozygotes (GG and TT) were determined by Tm calling method and difference between homozygotes and heterozygotes was determined by different melting curve shape using gene scanning method. With combination of results from Tm calling and gene scanning methods, we achieved 98,6% concordance between PCR-RFLP and PCRHRM results, based on the analysis of 640 samples. We found statistically significant association of IL23R polymorphism with Slovenian Crohn's disease patients when comparing genotype and allele frequencies between CD patients and controls. Allele frequency of minor allele G was 0,46 in controls and was reduced to 0,33 in CD patients (p < 0,001, OR = 0,588). The frequency of T/T genotype carriers was higher in CD patients (50,3%) than in controls (26,7%, p = 0,002, OR = 2,558). We found weak association between IL23R polymorphism and Slovenian UC patients. Carriers of T/T genotype have higher risk for UC (p = 0,035, OR = 1,599). These results suggest IL23R plays important role in CD and UC development in Slovenian patients.
Ključne besede: SNP genotyping, high resolution melting, DNA dyes, inflammatory bowel diseases, LC Green Plus
Objavljeno: 18.08.2017; Ogledov: 119; Prenosov: 0
.pdf Polno besedilo (232,19 KB)

14.
Rentgenska ocena arterijskih kacifikacij pri bolnikih, zdravljenih s kronično hemodializo
Silva Breznik, 2017, doktorsko delo/naloga

Opis: Uvod Žilne kalcifikacije so pri bolnikih s kronično ledvično boleznijo (KLB) eden najpomembnejših dejavnikov tveganja za povečano srčno-žilno umrljivost in obolevnost. Predstavljajo odziv na motnjo metabolizma serumskega kalcija in fosfata. Celoten sklop motenj zajema uveljavljena kratica KLB - MKB (kronična ledvična bolezen – mineralna in kostna bolezen), ki kot posledica motnje metabolizma mineralov in kosti vodi v kostno diferenciacijo gladkomišičnih celic ter nastanek žilnih kalcifikacij v tuniki mediji (srednji mišični plasti arterij). Prisotnost žilnih kalcifikacij lahko ugotavljamo z različnimi metodami. Bolniki in metode V raziskavo smo vključili 102 bolnika, zdravljena s kronično hemodializo, od teh je bilo 60 (58,8 %) moških, srednja starost bolnikov je bila 61,8 let (razpon 24-85 let). Povprečen čas hemodializnega zdravljenja je bil 52,3 meseca (razpon 1-208 mesecev). Ocena razsežnosti koronarnih kalcifikacij s pomočjo Agatstonove skale (CACS) je bila opravljena pri 28 bolnikih. Pri 102 bolnikih so bili opravljeni lateralni radiogram trebušne aorte za oceno kalcifikacij trebušne aorte (AACS), radiogram medenice in dlani za oceno kalcifikacij medeničnih arterij (SVCS medenica) in arterij rok (SVCS dlan) ter ultrazvok karotidnih arterij za oceno debeline intime-medije (IMT). Pri 93 bolnikih smo izmerili hitrost karotidno-femoralnega oziroma aortnega pulznega vala (PWV) ter pri 88 bolnikih gleženjski indeks (ABI). Določili smo tudi serumsko vrednost fibroblastnega rastnega faktorja-23 (FGF-23). Rezultati Ugotovili smo visoko prevalenco kalcifikacij. Koronarne kalcifikacije (CACS) smo našli pri 92 % (26 od 28) bolnikov. Z radiografsko oceno smo našli kalcifikacije pri 91,2 % bolnikov, od tega na lateralnem radiogramu pri 82,4 % (84 od 102), pri 76,5 % bolnikov na radiogramu medenice ter pri 55,9 % bolnikov na radiogramu rok. Zlati standard CACS je bil v pozitivni korelaciji z AACS (p<0,000, rho=0,665), SVCS medenice (p<0,000,rho=0,654), SVCS roke (p<0,007, rho=0,497) in s PWV (p<0,002, rho=0,594). Ugotovili smo tudi statistično značilno korelacijo med AACS in PWV (p<0,000, rho=0,442), SVCS medenice in PWV (p<0,000, rho=0,466) ter SVCS roke in PWV (p<0,000, rho=0,427). IMT je bila v pozitivni korelaciji z AACS (p<0,000, rho=0,590), s SVCS medenice (p<0,000, rho=0,401), s SVCS roke (p<0,005, rho=0,279) ter tudi s PWV (p<0,000, rho=0,533). Ugotovili smo negativno korelacijo med ABI in z AACS (p<0,002, rho=-0,321), s SVCS medenice (p<0,025, rho=-0,240), s SVCS roke (p<0,012, rho=-0,267) ter s PWV (p<0,006, rho=-0,300). FGF-23 ni bil statistično pomembno povezan z nobenim od preiskovanih parametrov kalcifikacij. Zaključek Naši rezultati so pokazali zelo dobro povezavo med enostavnimi metodami ugotavljanja srčno-žilnih kalcifikacij ter bolj kompleksnimi metodami, kot je CACS. Tako lahko zlati standard CACS nadomestimo s cenejšimi in enostavnejšimi metodami z manj rentgenskega sevanja kot sta AACS in SVCS. PWV, ABI in IMT so se pokazali kot prav tako dobri primerljivi označevalci ocene kalcifikacij v primerjavi s klasičnimi rentgenskimi metodami. FGF-23 ni bil povezan z drugimi preiskovanimi parametri.
Ključne besede: debelina intime medije, fibroblastni rastni faktor, gleženjski indeks, hitrost aortnega pulznega vala, kronična ledvična bolezen, kalcifikacije koronarnih arterij, lateralni radiogram, rentgenska ocena žilnih kalcifikacij
Objavljeno: 17.08.2017; Ogledov: 101; Prenosov: 10
.pdf Polno besedilo (1014,28 KB)

15.
Domestic violence and abuse in intimate relationship from public health perspective
Zlatka Rakovec-Felser, 2014, pregledni znanstveni članek

Opis: In this article we pay attention to the violence which, due to the fear of social stigma, could be hidden from the public eye for a long time but could have serious health consequences for the individual, family, and society-physical and psychological forms of domestic violence and abuse in male-female intimate relationship. Besides its nature and extent data in general population, we review also the surveys data about its theoretical basis, its risk factors and possible effects on mental and physical health, not only on in conflicts involved partners, but also on family as a whole, and especially on the children that growing up in such a problematic domestic circumstances.
Ključne besede: domestic violence, perpetrator, victim, gender differences
Objavljeno: 08.08.2017; Ogledov: 69; Prenosov: 0
.pdf Polno besedilo (674,83 KB)

16.
Clostridium difficile ribotypes in humans and animals in Brazil
Rodrigo Otávio Silveira Silva, Maja Rupnik, Amanda Nádia Diniz, Eduardo Garcia Vilela, Francisco Carlos Faria Lobato, 2015, izvirni znanstveni članek

Opis: Clostridium difficile is an emerging enteropathogen responsible for pseudomembranous colitis in humans and diarrhoea in several domestic and wild animal species. Despite its known importance, there are few studies aboutC. difficile polymerase chain reaction (PCR) ribotypes in Brazil and the actual knowledge is restricted to studies on human isolates. The aim of the study was therefore to compare C. difficileribotypes isolated from humans and animals in Brazil. Seventy-six C. difficile strains isolated from humans (n = 25), dogs (n = 23), piglets (n = 12), foals (n = 7), calves (n = 7), one cat, and one manned wolf were distributed into 24 different PCR ribotypes. Among toxigenic strains, PCR ribotypes 014/020 and 106 were the most common, accounting for 14 (18.4%) and eight (10.5%) samples, respectively. Fourteen different PCR ribotypes were detected among human isolates, nine of them have also been identified in at least one animal species. PCR ribotype 027 was not detected, whereas 078 were found only in foals. This data suggests a high diversity of PCR ribotypes in humans and animals in Brazil and support the discussion of C. difficile as a zoonotic pathogen.
Ključne besede: Clostridium difficile, pseudomembranous colitis, zoonosis
Objavljeno: 07.08.2017; Ogledov: 74; Prenosov: 2
.pdf Polno besedilo (185,91 KB)

17.
Hypodontia prevalence and pattern in women with epithelial ovarian cancer
Anita Fekonja, Andrej Čretnik, Iztok Takač, 2014, izvirni znanstveni članek

Opis: Objective: To analyze the possible association between hypodontia and epithelial ovarian cancer (EOC), with the special interest in hypodontia pattern. Materials and Methods: One hundred twenty women with EOC treated at the Department of Gynecologic and Breast Oncology at the University Clinical Centre and 120 gynecologically healthy women of the same average age were reviewed for the presence and pattern of hypodontia. Collected data were analyzed for frequency, tooth type, location per jaw and side, number of missing teeth per person, and family history of hypodontia. Results: The results of the study showed prevalence of hypodontia in 19.2% of women with EOC and in 6.7% of women in the control group (P = .004). The most frequently missing teeth for women with EOC and women in the control group were maxillary second premolars and maxillary lateral incisors, respectively. Unilateral occurrence of hypodontia was more common than bilateral occurrence in women with EOC (P = .034). Of women with EOC and hypodontia, 21.7% reported a positive family history of hypodontia compared with no report in the control group of women with hypodontia (P = .150). Conclusions: The results statistically support possible association between EOC and hypodontia. Because hypdontia can be recognized early in life, this finding could possibly help in earlier detection of EOC, resulting in better prognosis and treatment in earlier stages of the disease. Earlier EOC diagnosis and treatment could save many lives.
Ključne besede: hypodontia, tooth agenesis, ovarian cancer, neoplasms
Objavljeno: 07.08.2017; Ogledov: 57; Prenosov: 1
.pdf Polno besedilo (64,81 KB)

18.
Defining rural, remote and isolated practices
Rok Petrovčič, 2016, pregledni znanstveni članek

Opis: There is no single definition of rural practice available. Definitions vary from one country to another, as countries differ in geography and have different health care systems with varying organizational specificities, even within the same country. In spite of increased urbanization and the specific health-related problems it brings with it, a large proportion of the world population still dwells in rural, remote, and isolated areas. In fact, there are many countries in the world with extensive rural areas. Rural areas are unique in organization, demographics, and infrastructure, and so are the specific health-related problems of people living in them. Healthcare in such areas is generally provided by general practitioners or by physicians specialized in family medicine. One of the basic challenges in rural health is defining which areas are rural and finding the characteristics that define “rural”. There are several criteria and combinations of criteria that can be used to define rural areas. Their use mostly depends on the purpose for which the definition is used, and can thus vary from application to application. This paper addresses issues in rural family practice and criteria that may be used to define such practices. It also presents the use of criteria for defining rural practices in a small European country, on the example of Slovenia.
Ključne besede: Slovenia, rural health, rural population, family practice
Objavljeno: 07.08.2017; Ogledov: 43; Prenosov: 2
.pdf Polno besedilo (174,94 KB)

19.
Low-dose gemcitabine in long infusion
Matjaž Zwitter, 2012, kratki znanstveni prispevek

Ključne besede: lung cancer, gemcitabine
Objavljeno: 04.08.2017; Ogledov: 105; Prenosov: 3
.pdf Polno besedilo (293,79 KB)

20.
Independent clinical research may alleviate disparities in cancer treatment
Matjaž Zwitter, 2016, izvirni znanstveni članek

Opis: Disparities in cancer care are a reality of the modern world. Unfortunately, current clinical research is in the hands of for-profit pharmaceutical companies and of researchers from the developed world. Problems specific to cancer care in developing countries and among deprivileged populations are ignored. Independent clinical research can offer new valuable knowledge and identify affordable and cost-effective treatments. As such, research not depending on commercial sponsors should become one of the important avenues to alleviate the problem of cancer disparities.
Ključne besede: clinical research, disparities in cancer care, cost-effective treatment
Objavljeno: 04.08.2017; Ogledov: 95; Prenosov: 0
.pdf Polno besedilo (472,46 KB)

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