Mario Poljak

University of Ljubljana, Lubliano, Ljubljana, Slovenia

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Publications (243)584.85 Total impact

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    ABSTRACT: An increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) was observed in several population-based registries and has been attributed to human papillomavirus (HPV) infection. In the present study, we aimed to assess the contribution of HPV infection to the burden of mucosal head and neck squamous cell carcinoma (HNSCC) in Slovenia. For this purpose, data from the nationwide Cancer Registry of Slovenia for cases diagnosed between 1983 and 2009 were analyzed to determine time trends of age-adjusted incidence rates and survival in terms of annual percentage change (APC) for HNSCC in potentially HPV-related and HPV-unrelated sites. In addition, determination of p16 protein, HPV DNA and E6/E7 mRNA was performed in a cohort of OPSCC patients identified from the prospective database for the years 2007-2008. In total, 2,862 cases of HNSCC in potentially HPV-related sites and 7,006 cases in potentially HPV-unrelated sites were identified with decreased incidence observed over the time period in both groups (-0.58; 95 % CI -1.28 to -0.13 and -0.90; 95 % CI -1.23 to -0.57). Regardless of the group, incidence trends for both genders showed a significant decrease in men and increase in women. In a cohort of 99 OPSCC patients diagnosed between 2007 and 2008, 20 (20.2 %) patients had HPV positive tumors and exhibited a superior outcome compared to HPV-negative patients. In conclusion, results of the epidemiologic and histopathologic study confirmed that HPV infection had no major impact on the incidence trends in the Slovenian patients with HNSCC and, specifically, OPSCC during the studied period.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 12/2014; · 1.61 Impact Factor
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    ABSTRACT: To determine the prevalence of a broad spectrum of human papillomavirus (HPV) types in conjunctival papillomas and a possible difference in clinical and histopathological presentation of HPV-positive and HPV-negative papillomas. Formalin-fixed, paraffin-embedded papilloma tissue specimens obtained from 25 patients were analysed using six different PCR-based methods targeting 87 HPV types from four different papillomavirus (PV) genera: α-PV, β-PV, γ-PV and µ-PV, and in situ hybridisation for HPV-6/HPV-11. Slides were reviewed for pedunculated or sessile growth, the presence of goblet cells, keratinising or non-keratinising epithelium, elastosis, atypia and koilocytes. α-PV types HPV-6 and HPV-11 were detected in 19/25 (76%) conjunctival papilloma tissue specimens, 9 (47%) of which were also HPV-6/HPV-11 positive with in situ hybridisation. Six different β-PV types-HPV-9, HPV-12, HPV-20, HPV-21, HPV-22, HPV-24-were additionally detected in four cases, all of which were also HPV-6/HPV-11 positive. No γ-PVs or µ-PVs were found in any of the tested tissues samples. Extralimbal location (p=0.021), presence of goblet cells (p=0.005), non-keratinising squamous epithelium (p=0.005), and absence of elastosis (p=0.005) were associated with the presence of HPV-6/HPV-11. We demonstrated that certain clinical and histological features are more frequently associated with HPV infection and that HPV genera other than α-PV are most probably not significant factors in conjunctival papilloma occurrence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    British Journal of Ophthalmology 12/2014; · 2.81 Impact Factor
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    ABSTRACT: Abstract Background: HIV-1 subtype CRF01_AE originated in Africa and then passed to Thailand where it established a major epidemic. Despite the global presence of CRF01_AE little is known about its subsequent dispersal pattern. Methods: We assembled a global dataset of 2,736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns using statistical phylogeography run over bootstrap trees estimated by the maximum likelihood (ML) method. Results: We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 out of 20 sampled countries in Europe. Japan, Singapore, Vietnam and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported infections from neighbouring Asian countries, North America and Africa without any significant exporting transmissions. Discussion: The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sexual tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade for which its global dispersal was not originated in Africa.
    The Journal of infectious diseases. 12/2014;
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    ABSTRACT: In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. During follow-up only limited selection of additional polymorphisms was observed (median: 1). We demonstrate limited in vivo evolution of protease and RT harbouring frequently observed TDRM in the plasma. This is in line with the high in vitro replication capacity of patient-derived viruses harbouring TDRM compared to site-directed mutant viruses harbouring TDRM. As site-directed mutant viruses have a lower replication capacity than the patient-derived viruses with similar mutational patterns, we propose that (baseline) polymorphisms function as compensatory mutations improving viral replication capacity.
    Retrovirology 11/2014; 11(1):105. · 4.77 Impact Factor
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    ABSTRACT: Background Betapapillomaviruses (β-PV) are etiologically associated with epidermodysplasia verruciformis and a proportion of skin precancerous lesions and cancer, mainly in immunocompromised individuals. Objectives The prevalence and persistence of anal β-PV infection and β-PV type distribution were determined in a cohort of men who have sex with men (MSM). A correlation with HIV-1 infection status and selected demographic and behavioral risk factors were additionally established. Study design A total of 181 anal swabs (135 initial and 46 follow-up swabs) obtained from 135 Slovenian MSMs (17.0% HIV-1 positive) were tested for the presence of 25 different β-PV types using Diassay RHA Kit Skin (beta) HPV assay and, if negative, with an in-house nested Ma/Ha PCR. Results β-PVs were detected in 88/135 (65.2%) initial anal swabs. Infection with multiple β-PV types was found in 26 samples; the number of β-PVs ranged from 2 to 9. A total of 29 distinct β-PVs were detected: HPV-36 and HPV-38 were the most prevalent, followed by HPV-23, HPV-24, and HPV-93. HIV-1 positive status, promiscuity and use of alkyl nitrites were significantly associated with a higher prevalence of anal β-PV infection. Three partial DNA sequences suggesting putative new HPV types were identified. Conclusion To the best of our knowledge, this is the first study to investigate and characterize β-PV infections in the anal region. We showed that anal β-PV infection is highly prevalent in the MSM population and that β-PVs can establish persistent infection in the anal region for up to 4.8 years.
    BMC Infectious Diseases 10/2014; · 2.56 Impact Factor
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    ABSTRACT: Several studies have been performed investigating the role of a real-time multiplex polymerase chain reaction assay LightCycler SeptiFast with inconsistent results. In prospective evaluation of adult patients with severe sepsis or septic shock SeptiFast assay and blood culture results were compared regarding concordance, the impact of SeptiFast assay on antimicrobial therapy adjustment, time to results and the role of SeptiFast assay as a marker of disease severity. 63 blood sample sets were collected from 57 patients. 51 (80.9%) results were concordant negative and 7 (11.1%) concordant posi- tive. In one (1.6%) sample set blood culture was positive and SeptiFast assay negative, in three (4.8%) sample sets with negative blood cultures pathogens were detected by SeptiFast assay and in one (1.6%)patient an additional pathogen was detected by SeptiFast assay. If blood culture is considered as "gold standard", 1 (1.6%) SeptiFast false negative and 4 (6.3%) false positive results were identified (sensitivity 87.5%, specificity 92.6%, negative predictive value 97.8%). Antibiotic treatment was adjusted according to SeptiFast assay in 4 (6.3%) cases. Time to final results was significantly shorter with SeptiFast assay (32 +/- 23 h vs. 97 +/- 28 h, p < 0.0001). Positive SeptiFast assay was not associated with higher mortality, C-reactive protein orprocalcitonin (p = 0.74, p = 0.44 and p = 0.12, respectively). According to our results SeptiFast assay can be used as a valuable add-on to blood culture in diagnostic workup ofpatients with severe sepsis and septic shock but it cannot replace the blood culture.
    Collegium antropologicum 09/2014; 38(3):829-33. · 0.61 Impact Factor
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    ABSTRACT: Traditional cardiovascular (CVD) risk assessment algorithms such as the Framingham Risk Score (FRS), Systematic Coronary Risk Evaluation (SCORE) and Prospective Cardiovascular Munster (PROCAM) were developed for general populations, their usefulness in HIV-infected population has not been confirmed. DAD algorithm was developed specifically for HIV-infected patients. The aim of our study was to evaluate the performance of risk assessment algorithms in HIV-infected population.
    Acta dermatovenerologica Alpina, Panonica, et Adriatica 09/2014; 23(3):43-7.
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    ABSTRACT: HPV-52 is one of the most frequent human papillomavirus (HPV) genotypes causing significant cervical pathology. The most widely used HPV genotyping assay, the Roche Linear Array HPV Genotyping Test (Linear Array), is unable to identify HPV-52 status in samples containing HPV-33, HPV-35, and/or HPV-58.
    Acta dermatovenerologica Alpina, Panonica, et Adriatica 09/2014; 23(3):53-6.
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    ABSTRACT: Antiretroviral therapy in HIV-infected patients appears to be associated with increased incidence of cardiovascular disease (CVD).The aim of our study was to investigate the differences in markers of inflammation, endothelial dysfunction and prothrombotic state between treated and untreated HIV-infected patients with or without subclinical atherosclerosis.
    Acta dermatovenerologica Alpina, Panonica, et Adriatica 09/2014; 23(3):49-52.
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    ABSTRACT: The aims of our study were to determine the prevalence of the babA2 gene within Helicobacter pylori strains circulating in the Slovenian pediatric population, to further clarify its significance in causing inflammation of gastric mucosa in children and to verify whether cagA, vacA, iceA and babA genes work independently or synergistically in causing gastritis. A total of 163 H. pylori isolates obtained from the same number of children were tested for the presence of cagA, vacA and iceA genes using previously established methods, while the babA2 gene was determined using novel polymerase chain reaction assay targeting a 139-bp fragment of the central region of babA2. The babA2 gene was detected in 47.9 % of H. pylori samples. The presence of the babA2 gene was strongly associated with cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with bacterial density score, activity of inflammation and chronic inflammation of gastric mucosa. No significant correlation was found between the babA2 status and the presence of atrophy or intestinal metaplasia. In addition, the activity of gastric inflammation and density score were significantly associated with the coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which included the largest number of pediatric H. pylori samples to date, confirmed that babA2 gene plays an important role in the pathogenesis of H. pylori gastritis in children. Furthermore, our results suggest that babA2, cagA and vacA s1 and m1 gene products may work synergistically in worsening the inflammation of gastric mucosa.
    Antonie van Leeuwenhoek 07/2014; · 2.07 Impact Factor
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    ABSTRACT: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.
    BMC Infectious Diseases 07/2014; 14(1):407. · 2.56 Impact Factor
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    ABSTRACT: It has been shown for hepatitis C virus (HCV) infection that host miRNAs contribute to the replication of the viral RNA genome. However, the clinical impact of these and many other cellular miRNAs on HCV in humans is still largely unclear. We therefore analysed the expression of miR-122, miR-126, miR-181a and miR-136 in HCV-infected patients. The study included liver biopsies of 65 patients infected with HCV of different genotypes (gt 1, gt 1a, gt 1b, gt 3 and gt 4) and nine noninfected individuals. Expression analysis of miRNAs was performed by qPCR, and they were analysed for differences between patient gender and age, genotypes, stage of fibrosis, grade of inflammation, serum level of liver enzymes, serum viral load, the presence of steatosis and mode of transmission. Different target prediction algorithms were used to search for targets of analyzed miRNAs. Statistical analysis revealed significant up-regulation of miR-136 and down-regulation of miR-126 and miR-181a in patients infected with HCV of different genotypes compared with noninfected individuals. The same expression pattern was observed in different stages and grades of liver disease. miR-122 was up-regulated in women relative to men and associated to portal inflammation, miR-122 and miR-126 correlated with serum HCV load and miR-136 and miR-122 correlated with the presence of steatosis. miR-126 and miR-136 were differentially expressed between different modes of HCV transmission. There were approximately 2000 different targets predicted for all four miRNAs and each of the analyzed miRNAs could be involved in more than a 100 different biochemical pathways. miR-122, miR-126, miR-136 and miR-181a have been shown to be involved in HCV infection with different genotypes. Their expression has been associated with the gender, stage and grade of liver disease, mode of transmission, serum HCV load and the presence of steatosis. Numerous target genes and biochemical pathways are predicted for each of the analyzed miRNAs. All these results suggest their role in HCV-infected liver disease.
    Journal of Viral Hepatitis 07/2014; · 3.08 Impact Factor
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    ABSTRACT: Cervical infections with non-high-risk human papillomavirus (non-HR-HPV) types have been associated with genital warts and a fraction of atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The pre-vaccination prevalence of cervical infections with 25 non-HR-HPV types has been estimated, regardless of and without the coexistence of infection with HR-HPV types among Slovenian women 20-64 years old in cervical cancer screening, overall and according to age and cytology result. One thousand cervical specimens selected randomly from 4,455 specimens collected in 2010 in the Slovenian HPV prevalence survey were tested with Linear Array HPV Genotyping Test. Prevalence of cervical infections with any of the 25 non-HR-HPV types was 10.0% (95% CI: 8.1-11.9%) and with exclusively non-HR-HPV types 4.5% (95% CI: 3.2-5.8%). Prevalence of infections with any non-HR-HPV types among women with normal cytology was 8.8%, with atypical squamous cells of undetermined significance 30.4%, with low-grade squamous intraepithelial lesions 60.0%, and with high-grade squamous intraepithelial lesions 7.7%. Non-HR-HPV types without coexisting HR-HPV types were found in 4.0% of women with normal cytology, 26.1% with atypical squamous cells of undetermined significance, 6.7% with low-grade squamous intraepithelial lesions, and none with high-grade squamous intraepithelial lesion. Non-HR-HPV type cervical infections without coexisting HR-HPV infections were common among Slovenian women in cervical cancer screening with atypical squamous cells of undetermined significance, while rare in those with low-grade squamous intraepithelial lesions or worse. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2014; 86(10). · 2.22 Impact Factor
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    ABSTRACT: In the case of an aggressive course of recurrent respiratory papillomatosis (RRP), adjuvant therapy can be used besides surgery. The aim of the study was to investigate the influence of vaccination with a quadrivalent vaccine against human papilloma viruses (HPV) types 6, 11, 16 and 18 on the course of RRP. Eleven subjects aged 13-46 years with a rapid growth of laryngeal papillomas were included in the study. They were vaccinated with three doses of the quadrivalent prophylactic HPV vaccine (Silgard(®), MSD) and followed up for 12-52 months. The intervals between the successive surgical procedures, the extension of the disease (Derkay score) at each surgery, and the number of surgical procedures per year before vaccination and after its completion were compared. The mean interval between the surgical procedures was 271.2 days before the vaccination and 537.4 days after it (p = 0.034). The mean number of surgeries per year was 2.16 before the vaccination and 0.93 after it (p = 0.022). The Derkay score did not change significantly after vaccination. Complete remission of the disease was observed in one patient, partial response to the vaccination was observed in seven patients and no response was observed in three patients. In conclusion, vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with the rapid growth of the papillomas. It significantly prolongs the intervals between the surgical procedures and reduces the number of procedures needed in the majority of patients. The present investigation can serve as a pilot study for further research. For a final conclusion a longer follow-up and studies on more patients are necessary.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 06/2014; 271(12). · 1.61 Impact Factor
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    ABSTRACT: Introduction: Since the introduction of highly active antiretroviral therapy, chronic hepatitis C has become one of the leading causes of non-AIDS-related morbidity and mortality in patients with HIV infection. Two previous Slovenian nationwide studies published in 2002 and 2009 showed a very low prevalence of hepatitis C virus (HCV) infection among Slovenian HIV-infected individuals (14.5% and 10.7%, respectively). Methods and results: The presence of HCV infection was tested in 579/639 (90.6%) patients that were confirmed as HIV-positive in Slovenia by the end of 2013. Among them, 7.6% (44/579) of HIV-infected individuals were anti-HCV-positive, and 33/44 (75%) anti-HCV-positive patients were also HCV RNA-positive. HCV genotype 1 was most prevalent among HIV-infected patients (68%), followed by genotype 3 (20%), genotype 4 (8%), and genotype 2 (4%). Anti-HCV positivity was significantly higher in those that acquired HIV by the parenteral route (91.8%) than in those that acquired HIV by the sexual route (2.8%). Discussion: Slovenia remains among the countries with the lowest prevalence of HCV infection in HIV-infected individuals. Because the burden of HIV among men who have sex with men in Slovenia is disproportionately high and increasing rapidly, the current favorable situation could change quickly and should be therefore monitored regularly.
    Acta dermatovenerologica Alpina, Panonica, et Adriatica 06/2014; 23(2):25-6.
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    ABSTRACT: Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer dataset. HPV DNA was detected in 88.3% of anal cancers (95%CI: 85.1-91.0%) and in 95.3% of AIN 2/3 (95%CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA positive anal cancers. In view of HPV DNA results and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2014; · 6.20 Impact Factor
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    M. Poljak, R. Norrby
    Clinical Microbiology and Infection 05/2014; 20(s5). · 4.58 Impact Factor
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    ABSTRACT: Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated global genomic diversity of HPV6 on 724 isolates and 190 complete genomes from six continents and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease and gender. Initially, a 2,800 bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6 positive samples collected for this study. Out of them, 130 exhibited at least one single nucleotide polymorphisms (SNP), indel or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full-length. A global alignment and maximum likelihood tree of 190 HPV6 complete genomes (130 fully sequenced in this study and 60 from sequence repositories) revealed two variant lineages: A and B, and five B sublineages: B1, B2, B3, B4 and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America and lineage A in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender and/or disease predilection in their distribution. This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new HPV6 complete genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease and/or gender. We additionally identified several HPV6 lineage and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within L2 gene suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination and molecular assay development studies.
    Journal of Virology 04/2014; · 4.65 Impact Factor
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Publication Stats

2k Citations
584.85 Total Impact Points

Institutions

  • 1997–2014
    • University of Ljubljana
      • • Institute of Microbiology and Immunology
      • • Institute of Pathology
      Lubliano, Ljubljana, Slovenia
  • 2013
    • Slovenia Medical
      Maribor, Maribor, Slovenia
    • University of Latvia
      • Faculty of Medicine
      Riga, Riga, Latvia
    • Statens folkhälsoinstitut
      Östersund, Jämtland, Sweden
  • 2011
    • Albert Einstein College of Medicine
      New York City, New York, United States
    • National Forensic Laboratory Slovenia
      Lubliano, Ljubljana, Slovenia
  • 1996–2011
    • Ljubljana University Medical Centre
      • • Clinic of Otorhinolaryngology and Cervicofacial Surgery
      • • Department of Maxillofacial and Oral Surgery
      Lubliano, Ljubljana, Slovenia
  • 2007–2009
    • Zagreb University Hospital for Infectious Diseases
      Zagrabia, Grad Zagreb, Croatia