51. GLCCI1 polymorphism rs37973 and asthma treatment response to inhaled corticosteroidsMatija Rijavec, Mateja Žavbi, Anton Lopert, Matjaž Fležar, Peter Korošec, 2018, original scientific article Abstract: Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS). Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year. Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response. Conclusions. Rs37973 was associated with short- and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS. Keywords: asthma -- diagnosis -- therapy, pharmacogenetics, genetic polymorphism, smoking, inhaled corticosteroids, atopy, GLCCI1, FEV1, rs37973 Published in DiRROS: 16.12.2020; Views: 1431; Downloads: 393 Link to file |
52. Hereditary angioedema due to C1-inhibitor deficiency in pediatric patients in Croatia : first national study, diagnostic and prophylactic challengesLjerka Karadža-Lapić, Marko Barešić, Renata Vrsalović, Irena Ivković-Jureković, Saša Sršen, Ingrid Prkačin, Matija Rijavec, Draško Cikojević, 2019, review article Abstract: Hereditary angioedema (HAE) is a rare autosomal dominant disease with deficiency (type I) or dysfunction (type II) of C1 inhibitor, caused by mutations in the C1-INH gene, characterized by recurrent submucosal or subcutaneous edemas including skin swelling, abdominal pain and life-threatening episodes of upper airway obstruction. The aim of this study was to investigate healthcare experiences in children with HAE due to C1 inhibitor deficiency (C1-INH-HAE) in Croatia in order to estimate the number of affected children and to recommend management protocols for diagnosis, short-term prophylaxis and acute treatment. Patients were recruited during a 4-year period at five hospitals in Croatia. Complement testing was performed in patients with a positive family history. This pilot study revealed nine pediatric patients positive for C1-INH- HAE type I, aged 1-16 years, four of them asymptomatic. Before the age of one year, C1-INH levels may be lower than in adults; it is advisable to confirm C1-INH-HAE after the age of one year. Plasma-derived C1- INH is recommended as acute and short-term prophylactic treatment. Recombinant C1-INH and icatibant are licensed for the acute treatment of pediatric patients. In Croatia, HAE is still underdiagnosed in pediatric population. Keywords: hereditary angioedemas -- genetics -- Croatia, inborn genetic diseases -- Croatia, pediatrics -- Croatia, C1 inhibitor, SERPING1 gene, children Published in DiRROS: 16.12.2020; Views: 1268; Downloads: 981 Full text (477,81 KB) This document has many files! More... |
53. Important and specific role for basophils in acute allergic reactionsPeter Korošec, Bernhard F. Gibbs, Matija Rijavec, Adnan Custovic, Paul J. Turner, 2018, review article Abstract: IgE-mediated allergic reactions involve the activation of effector cells, predominantly through the high-affinity IgE receptor (FceRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis, and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma. Keywords: allergy and immunology, basophils, anaphylaxis Published in DiRROS: 14.12.2020; Views: 1267; Downloads: 821 Full text (511,01 KB) This document has many files! More... |
54. Hereditary angioedema due to C1-inhibitor deficiency in Macedonia : clinical characteristics, novel SERPING1 mutations, and genetic factors modifying the clinical phenotypeVesna Grivčeva-Panovska, Mitja Košnik, Peter Korošec, Slađana Andrejević, Ljerka Karadža-Lapić, Matija Rijavec, 2018, original scientific article Abstract: Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease, characterized by swellings. We aimed to characterize on a clinical and molecular basis C1-INH-HAE patients in the Republic of Macedonia. Results: All 15 patients from six unrelated families were diagnosed with C1-INHHAE type I, with a mean age of symptom onset of 11 years and an average delay of diagnosis of 7 years. Patients reported on average 31 angioedema attacks/year, with a median clinical severity score (CSS) of 7. We identified three known mutations, and two mutations (c.813_818delCAACAA and c.1488T>G) were reported for the first time. To address the genotype-phenotype association, a pooled analysis including 78 C1-INH-HAE south-eastern European patients was performed, with additional analysis of F12-46C/T and KLKB1- 428G/A polymorphisms. We demonstrated that patients with nonsense and frameshift mutations, large deletions/insertions, splicing defects, and mutations at Arg444 exhibited an increased CSS compared with missense mutations, excluding mutations at Arg444. In addition, the CC F12-46C/T polymorphism was suggestive of earlier disease onset. Discussion: Genetic analysis helped identify the molecular basis of C1-INH-HAE given that causative mutations in SERPING1 were detected in all patients, including an infant before the appearance of clinical symptoms. We identified two novel mutations and further corroborated the genotype-phenotype relationship, wherein mutations with a clear effect on C1-INH function predispose patients to a more severe disease phenotype and CC F12-46C/T predisposes patients to earlier disease onset. Keywords: hereditary angioedemas -- genetics -- Macedonia, C1 inhibitor, SERPING1 gene, C1 inhibitor, SERPING1 gene Published in DiRROS: 30.11.2020; Views: 1294; Downloads: 284 Link to file |
55. Atomically resolved anisotropic electrochemical shaping of nano-electrocatalystFrancisco Ruiz-Zepeda, Matija Gatalo, Andraž Pavlišič, Goran Dražić, Primož Jovanovič, Marjan Bele, Miran Gaberšček, Nejc Hodnik, 2019, original scientific article Keywords: electrocatalysis, dealloying, fuel cells, identical location TEM, kinetic Monte Carlo Published in DiRROS: 23.11.2020; Views: 1457; Downloads: 1042 Full text (14,10 MB) This document has many files! More... |
56. Comparison of Pt-Cu/C with benchmark Pt-Co/C : metal dissolution and their surface interactionsMatija Gatalo, Primož Jovanovič, Urša Petek, Martin Šala, Vid Simon Šelih, Francisco Ruiz-Zepeda, Marjan Bele, Nejc Hodnik, Miran Gaberšček, 2019, original scientific article Keywords: oxygen reduction reaction, proton exchange membrane fuel cell, platinum alloy, metal dissolution, electrochemical flow cell coupled to inductively coupled plasma mass spectrometer Published in DiRROS: 23.11.2020; Views: 1492; Downloads: 1095 Full text (4,12 MB) This document has many files! More... |
57. Tuberculosis among patients treated with TNF inhibitors for rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis in slovenia : a cohort studyŽiga Rotar, Petra Svetina, Matija Tomšič, Alojzija Hočevar, Sonja Praprotnik, 2020, original scientific article Abstract: Objectives: This study aimed to assess the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with any of the commercially available tumour necrosis factor inhibitors (TNFis) in Slovenia. Design: This is a cohort, registry (biorx.si) cross-linked with the Slovenian National TB Registry. Setting: National, involving all Slovenian rheumatology centres (six secondary and two secondary/tertiary). Participants: 2429 patients with RA, AS or PsA exposed to at least one TNFi participated in the study. Primary and secondary outcome measures: The primary outcome measures were age-adjusted and sex-adjusted TB incidence rates (IRs) and the standardised incidence ratios (SIRs) compared with the general population exploring different TNFi exposure windows. The secondary outcome measures were a detailed characterisation of the national latent tuberculosis infection (LTBI) screening and TB chemoprophylaxis protocol implementation. Results: Among the 2429 patients exposed to at least one TNFi for a total of 10 445 (49% RA, 33% AS and 18% PsA) person-years (PY), 99% completed LTBI screening and 6% required TB chemoprophylaxis. Six RA (three adalimumab, three certolizumab), two PsA (two golimumab) and zero AS patients developed TB. Five out of eight had miliary TB, three out of eight had pulmonary TB and two patients died. The age-standardised and sex-standardised TB IR (95% CI) per 100 000 PYs/SIRs (95% CI) compared with the general Slovenian population for the current TNFi exposure were 52 (0 to 110)/6.7 (0.6 to 80), 47 (0 to 110)/6.1 (0.3 to 105), 45 (0 to 109)/5.8 (0.3 to 112) overall, in RA and PsA, respectively. Conclusions: The TB IR in the Slovenian patients with RA, AS and PsA treated with TNFi was comparable with TB IRs in TB non-endemic countries with less than a tenth of the patients requiring TB chemoprophylaxis. Keywords: epidemiology, rheumatology, tuberculosis Published in DiRROS: 12.11.2020; Views: 1202; Downloads: 573 Full text (445,46 KB) |
58. CD3+CD4-CD8- mucosal T cells are associated with uncontrolled chronic rhinosinusitis with nasal polypsTanja Soklič, Mira Šilar, Matija Rijavec, Ana Koren, Izidor Kern, Irena Hočevar-Boltežar, Peter Korošec, 2019, other scientific articles Abstract: Increased mucosal double-negative (DN) CD3+CD4-CD8- T cells were found for the first time in CRS and were much more abundant in uncontrolled CRSwNP than in well-controlled CRSwNP. Keywords: chronic rhinosinusitis, CD3+ T-cells, CD4- T-cells, CD8- T-cells Published in DiRROS: 22.10.2020; Views: 1597; Downloads: 517 Link to file |
59. The effect of harvesting on national forest carbon sinks up to 2050 simulated by the CBM-CFS3 model : a case study from SloveniaJernej Jevšenak, Matija Klopčič, Boštjan Mali, 2020, original scientific article Keywords: carbon, forest reference levels, forest management, harvesting scenarios, yield curves, UNFCCC, prirastne krivulje, UNFCCC Published in DiRROS: 19.10.2020; Views: 1283; Downloads: 901 Full text (3,39 MB) This document has many files! More... |
60. Transcription factors gene expression in chronic rhinosinusitis with and without nasal polypsTanja Soklič, Matija Rijavec, Mira Šilar, Ana Koren, Izidor Kern, Irena Hočevar-Boltežar, Peter Korošec, 2019, original scientific article Abstract: Background. Chronic rhinosinusitis (CRS) current therapeutic approaches still fail in some patients with severe persistent symptoms and recurrences after surgery. We aimed to evaluate the master transcription factors gene expression levels of T cell subtypes in chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) that could represent new, up-stream targets for topical DNAzyme treatment. Patients and methods. Twenty-two newly diagnosed CRS patients (14 CRSwNP and 8 CRSsNP) were prospectively biopsied and examined histopathologically. Gene expression levels of T-box transcription factor (T-bet, TBX21), GATA binding protein 3 (GATA3), Retinoic acid-related orphan receptor C (RORC) and Forkhead box P3 (FOXP3) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Results. Eosinophilic CRSwNP was characterized by higher level of GATA3 gene expression compared to noneosinophilic CRSwNP, whereas there was no difference in T-bet, RORC and FOXP3 between eosinophilic and noneosinophilic CRSwNP. In CRSsNP, we found simultaneous upregulation of T-bet, GATA3 and RORC gene expression levels in comparison to CRSwNP; meanwhile, there was no difference in FOXP3 gene expression between CRSwNP and CRSsNP. Conclusions. In eosinophilic CRSwNP, we confirmed the type 2 inflammation by elevated GATA3 gene expression level. In CRSsNP, we unexpectedly found simultaneous upregulation of T-bet and GATA3 that is currently unexplained; however, it might originate from activated CD8+ cells, abundant in nasal mucosa of CRSsNP patients. The elevated RORC in CRSsNP could be part of homeostatic nasal immune response that might be better preserved in CRSsNP patients compared to CRSwNP patients. Further data on transcription factors expression rates in CRS phenotypes are needed. Keywords: sinusitis, nasal polyps, Th1 cells, Th2 cells, Th17 cells, transcription factors, chronic rhinosinusitis Published in DiRROS: 09.10.2020; Views: 1522; Downloads: 830 Full text (698,54 KB) This document has many files! More... |