51. Chemokines during anaphylaxis : the importance of CCL2 and CCL2-dependent chemotactic activity for basophilsRomana Vantur, Maruša Rihar, Ana Koren, Matija Rijavec, Peter Kopač, Urška Bidovec, Renato Eržen, Peter Korošec, 2020, izvirni znanstveni članek Povzetek: Background: The role of chemokines in anaphylaxis is unclear. Methods: We prospectively recruited 49 patients presenting to the emergency department with an acute episode of anaphylaxis and 28 healthy subjects. We measured serum levels of the chemokines CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL21, CCL22, CCL24, and CCL26, tryptase, the absolute number of circulating basophils, monocytes, lymphocytes, and PMNs, and whole blood FCER1A, CPA3 and HDC gene expression at two time points: during the anaphylactic episode and in convalescent samples collected approximately 3 months later. We then investigated the in vitro chemotactic activity of chemokines induced during anaphylaxis for the in vitro migration of the corresponding cells. Results: Only CCL2 chemokine levels were signifcantly increased in anaphylaxis samples (median 514 pg/ml) compared to convalescent samples (284 pg/ml, P<0.0001) and healthy subjects (279 pg/ml, P<0.0001); there was no signifcant diference in any of the other chemokines. There was a signifcant positive correlation between the rates of increase of serum CCL2 (median [range]: 106.0% [-44.7% to 557.4%]) and tryptase (133.8% [-6.6% to 893.4%]; r=0.68, P<0.0001) and between the acute concentration of serum CCL2 and the acute concentration of serum tryptase (r=0.77, P<0.0001). The number of circulating basophils, but not other blood cells, signifcantly decreased during anaphylaxis (median 5.0 vs. 19.1 cells/[micro]l in convalescent samples; P<0.0001); a decrease in whole-blood gene expression of basophil markers (P=0.0018) confirmed these changes. Anaphylactic serum enhances the in vitro migration of basophils via CCL2-dependent chemotactic activity; in contrast, no CCL2-dependent chemotactic activity was observed for convalescent samples. Conclusions: Our findings imply an important and specifc role for CCL2-mediated chemotactic activity in the pathophysiology of human anaphylaxis. Ključne besede: anaphylaxis, chemokines, tryptases, basophils, chemotaxis, CCL2, cell migration Objavljeno v DiRROS: 18.01.2021; Ogledov: 1396; Prenosov: 638 Celotno besedilo (2,04 MB) |
52. GLCCI1 polymorphism rs37973 and asthma treatment response to inhaled corticosteroidsMatija Rijavec, Mateja Žavbi, Anton Lopert, Matjaž Fležar, Peter Korošec, 2018, izvirni znanstveni članek Povzetek: 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. Ključne besede: asthma -- diagnosis -- therapy, pharmacogenetics, genetic polymorphism, smoking, inhaled corticosteroids, atopy, GLCCI1, FEV1, rs37973 Objavljeno v DiRROS: 16.12.2020; Ogledov: 1474; Prenosov: 398 Povezava na datoteko |
53. 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, pregledni znanstveni članek Povzetek: 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. Ključne besede: hereditary angioedemas -- genetics -- Croatia, inborn genetic diseases -- Croatia, pediatrics -- Croatia, C1 inhibitor, SERPING1 gene, children Objavljeno v DiRROS: 16.12.2020; Ogledov: 1279; Prenosov: 986 Celotno besedilo (477,81 KB) Gradivo ima več datotek! Več... |
54. Important and specific role for basophils in acute allergic reactionsPeter Korošec, Bernhard F. Gibbs, Matija Rijavec, Adnan Custovic, Paul J. Turner, 2018, pregledni znanstveni članek Povzetek: 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. Ključne besede: allergy and immunology, basophils, anaphylaxis Objavljeno v DiRROS: 14.12.2020; Ogledov: 1287; Prenosov: 834 Celotno besedilo (511,01 KB) Gradivo ima več datotek! Več... |
55. 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, izvirni znanstveni članek Povzetek: 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. Ključne besede: hereditary angioedemas -- genetics -- Macedonia, C1 inhibitor, SERPING1 gene, C1 inhibitor, SERPING1 gene Objavljeno v DiRROS: 30.11.2020; Ogledov: 1313; Prenosov: 286 Povezava na datoteko |
56. 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, izvirni znanstveni članek Ključne besede: electrocatalysis, dealloying, fuel cells, identical location TEM, kinetic Monte Carlo Objavljeno v DiRROS: 23.11.2020; Ogledov: 1472; Prenosov: 1051 Celotno besedilo (14,10 MB) Gradivo ima več datotek! Več... |
57. 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, izvirni znanstveni članek Ključne besede: oxygen reduction reaction, proton exchange membrane fuel cell, platinum alloy, metal dissolution, electrochemical flow cell coupled to inductively coupled plasma mass spectrometer Objavljeno v DiRROS: 23.11.2020; Ogledov: 1515; Prenosov: 1101 Celotno besedilo (4,12 MB) Gradivo ima več datotek! Več... |
58. 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, izvirni znanstveni članek Povzetek: 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. Ključne besede: epidemiology, rheumatology, tuberculosis Objavljeno v DiRROS: 12.11.2020; Ogledov: 1211; Prenosov: 575 Celotno besedilo (445,46 KB) |
59. 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, drugi znanstveni članki Povzetek: 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. Ključne besede: chronic rhinosinusitis, CD3+ T-cells, CD4- T-cells, CD8- T-cells Objavljeno v DiRROS: 22.10.2020; Ogledov: 1619; Prenosov: 529 Povezava na datoteko |
60. 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, izvirni znanstveni članek Ključne besede: carbon, forest reference levels, forest management, harvesting scenarios, yield curves, UNFCCC, prirastne krivulje, UNFCCC Objavljeno v DiRROS: 19.10.2020; Ogledov: 1304; Prenosov: 915 Celotno besedilo (3,39 MB) Gradivo ima več datotek! Več... |