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Background: Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in UGT1A1 gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of UGT1A1 TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse. Methods: Genetic testing of UGT1A1 TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging. Results: UGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p= 0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of U G T1A1*28 genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of U G T1A 1*28 genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of U G T1A 1*28 genotype in CHC patients with severe liver injury. Conclusions: Frequencies of U G T1A 1*28 genotype are high in both Serbian CHC patients and healthy subjects. The presence of U G T1A 1*28 genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

Introduction: Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema after sudden raise of intracranial pressure. NPE is the result of release of catecholamines into the circulation immediately after intracranial hemorrhage. The aim of this study is to investigate a possible correlation between the values of cardiac biomarkers on admission and incidence of NPE in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods: Prospective study includes 262 patients with SAH (162 females). Clinical characteristics, serum cardiac and inflammatory biomarkers were measured on admission and on the day of development of NPE. These data were analysed by tests of statistical significance and binary logistic regression analysis in order to predict the development of NPE. Results: 19 patients (7.25%) developed NPE. Statistical analysis revealed that patients who subsequently developed NPE experienced more severe SAH. Cardiac damage was more severe in these patients, as represented by significantly higher number of patients with elevated values of all examined cardiac biomarkers (P from < 0.001 to 0.004). Multivariate regression analysis revealed that elevated troponin I (OR 4.980; 95% CI 1.27-19.49, P = 0.021) and white blood cells count (OR 22.195; 95% CI 3.99-123.50, P < 0.001) were predictors of NPE. Conclusion: Significantly higher number of patients with elevated values of cardiac biomarkers had SAH complicated with NPE. Elevated values of cardiac biomarkers might play an active role in prediction of NPE, although white blood cells count may be involved in the prediction of NPE.

Background/Aim. It is estimated that about 230 million refugees and asylum seekers circulates worldwide. Parasitosis are diagnosed in recent years with increasing frequency both in Europe and other developed countries. International migration of population, as an inalienable part and a result of the process of globalization, has an increasing impact on health of the population of countries through which migrants pass or settle. The aim of this study was to determine the incidence of intestinal parasitic diseases in asylum seekers on the territory of Belgrade. Methods. The study group included 97 asylum seekers from the Centre for Asylum seekers in Obrenovac, in the period December 2013– January 2014. Stool samples were taken less than seven days after arriving to the Center and sent to the Laboratory for Parasitological Diagnosis of the Public Health Institute of Belgrade. Detection of parasites in stool samples was performed by a direct native slide made of fresh sample and direct slide made after stool concentration applying "Mini Parasep" technique. Statistical analysis included application of χ2-test of matching and χ2-test of independence. Results. The study showed that the parasites were detected in 9.3% of cases, in the group of 15–24 years of age. Protozoa were found in 6.2% and helminthes in 3.1% of the samples. Conclusion. Most intestinal parasitosis were found in asylum seekers from Bangladesh. All parasitosis were found in males and the most frequently detected parasite was Giardia lamblia.

Background/Aim. Bronchiolitis in early childhood caused by respiratory syncytial virus (RSV) is considered to be important risk factor of the recurrent wheezing and asthma development. The aim of this study was to examine the frequency of RSV infection and atopy in children up to two years of age and to determine their correlation with bronchial hyperreactivity. Methods. The study included 175 children aged 5-24 months. The presence of RSV infection was identified by serum levels of IgA and IgG determined by ELISA. Bronchial hyperreactivity (BHR) has been defined as the existence of chronic bronchial disease and/or three or more previous suspected diagnosis of acute bronchial disease. Atopy was confirmed by detection of the specific serum IgE using quantitative multitest Phadiatop infant (cut off ≥ 0.35 kUA/L). Results. The children with atopy were more frequently infected with RSV (43.3%) than those without atopy (22.8%; p = 0.02). The higher frequency of RSV infection was found in children with BHR in comparison with those without it but only in the group who also had atopy (77.8% vs 28.6%, p = 0.018). In the female children, BHR and RSV infection were associated in 62.5% of cases, regardless the atopy. In the male children with atopy, RSV infection was associated with BHR in 83.3% of the cases, while in those without atopy, RSV infection with BHR was found in only 17.4% of the cases. Conclusion. Children up to two years of age with atopy are more frequently infected with RSV (43.3%) than non-atopic children. Every third child with atopy develops BHR and 77.8% of them also have RSV infection. Atopic children are at higher risk for development of BHR when infected with RSV also.

Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LM P1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LM P1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p= 0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LM P1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LM P1, and EBNA1 polymorphisms, deleted LM PI/P-thr and non-deleted LMp1/P-ala, as well as genotype 1/ 4 .5 33-bp LM P1 repeats or genotype 2 / 4 .5 33-bp LM P1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers.

Structural sandwich is a unique form of the composite structure, and it finds a widespread use in the aerospace industry, where weight saving is a primary concern. The major difference between analysis procedures for sandwich construction and those for homogeneous structural elements is the inclusion of core shear effects on deflection, buckling and stress. The design procedure given in this article is intended to guide the designer in sizing the sandwich parts for primary loading properly. These procedures are usually iterative, and optimum design may require the design of several face-core combinations. Comparing the results obtained through the analytical procedure and Finite Element Analysis (FEA) one can conclude their good agreement. Differences for most of the results are from 10% to 15%, which is quite satisfactory, taking into account that the analytical models are formed on the basis of a number of assumptions and approximations.

Failure of an aircraft structural component can have catastrophic consequences, with a resultant loss of life and of the aircraft. The investigation of defects and failures in aircraft structures is, thus, of the vital importance in preventing further incidents. This review discusses the common failure modes observed in aircraft structures, with examples drawn from case histories. A review has given three notable aircraft and aeroengine service failures investigated by the National Aerospace Laboratory NLR in the Netherlands. All three failures were initiated by a corrosion.

Human polyomaviruses, BK virus (BKV) and JC virus (JCV), are world widely distributed in human population. After primary infection, BKV and JCV establish latency in kidneys and upper part of urinary tract. In seropositive healthy individuals asymptomatic reactivation of both viruses occurs in in 0.5-20%. On the other hand, reactivation of these viruses in imunosuppressed patients, primarily in patients with T cell immunodeficiency, can lead to development of polyomavirus-associated diseases. Some of these diseases such as progressive multifocal leukoencephalopathy (PML), polyomavirus-induced nephropathy (PVN), hemorrhagic cystitis (HC) are life-threatening diseases with high mortality and morbidity rate. However, they do not affect all immunosuppressed patients, suggesting that other factors, such as genetic variability of BKV and JCV, can contribute to their occurrence. Immunosuppression leads to increased levels of replication of both viruses. Increased levels of replication are associated with higher incidence of mutations in the VP1 gene. Mutations, especially those located in outer loops, may lead to changed tropism and generation of more aggressive variants of BKV and JCV. This review is focused on clinical significance of BK and JC virus infection in immunosuppressed patients, especially in HIV-infected, and sequence changes in the VP1 gene that can contribute to selection of more virulent variants of BKV and JCV via adaptive evolution.

The data on forests shown in this paper which are general useful functions determine the main way of managing, because these forests are marked as water protective and especially significant for the water supply of the Vrnjačka Banja area from 1985. These are forests of beech and beech mixed with fir of the highest quality located in the river Zagrža basin on mountain Goč and they represent more than 85 % of the basin and provide the hydrological and water protective functions at the highest level. For that reason, they have a special protective status. In the river Zagrža basin, there is the management unit "Selište" of particular importance and the accumulation Selište was built there with about 380 000 m3 volume and its primary task is water supply of the Vrnjačka Banja area during critical months without water. The aim of this scientific paper is to emphasize the need of increasing and protecting the water potential using adequate ways of forest vegetation management, which means overall basin organization. The final result should be related to the optimal use of natural sources in that area.

Background/Aim. Norovirus (NoV), formerly Norwalk-like virus is the most common cause of acute gastroenteritis in humans of all ages. It is known that 90% of viral gastroenteritis and about 60-85% of all outbreaks of gastroenteritis, especially in the territory of United States of America, Europe and Japan are caused by this virus. For the countries of the northern hemisphere, individual cases and outbreaks of acute NoV gastroenteritis appear in seasonal pattern, mainly during the winter months. The aim of this study was to describe characteristics of acute gastroenteritis with the established NoV etiology in Serbia. Methods. The study group included 88 patients with the symptoms of acute gastroenteritis, throughout the year 2010 and 2011. From all the patients, stool samples were taken less than three days from the onset of symptoms. Detection of NoV in stool samples was performed by commercial qualitative immuno-chromatography assay. Statistical analysis included application of χ2 test, Mann-Whitney U-test, Kruskal-Wallis's test, Spearman’s rank correlation test and logistic regression analysis. Results. Outbreaks of acute gastroenteritis caused by NoV were recorded to be the most common in children with the incidence of infection of 50% in the age group 0-15 years. Analysis of individual symptoms in the NoV proven infection, showed that diarrhea was the most common symptom, followed by vomiting especially in small children, while abdominal pain was most common in elderly (≥ 65 years). The presence of frequent vomiting, more than 4 times/day, indicated NoV infection in the women, while for men the infection was always presented with diarrhea. Conclusion. The obtained results confirmed that small children and elderly are the most susceptible to NoV infection and that out-breaks are more frequent in the winter months. Those who consumed food in restaurants and other public facilities were not at higher risk for NoV infection.

Macrolide resistance in Streptococcus pneumoniae and in group A streptococci (GAS) is a significant problem worldwide. In Serbia, data on the mechanisms of resistance and the corresponding resistance genes in streptococci are largely lacking. Therefore, we analyzed the distribution of macrolide resistance phenotypes and genotypes in 44 macrolideresistant GAS (MRGAS) and 50 macrolide-resistant S. pneumoniae (MRSP) isolates collected in the same period. The double disk diffusion test and PCR were used to analyze resistance phenotypes and resistance genes, respectively. Among MRSP, the MLSB phenotype dominated, whereas the M phenotype was the most prevalent among MRGAS isolates. Consequently, in MRSP, the ermB gene was the most common (n=40, 80%), followed by the mefA gene (n=7,14%). In MRGAS strains, mefA dominated (n=27,61%), followed by ermA (n=15, 33%) and ermB (n=3, 7%). In 3 MRSP isolates no resistance genes were detected, while one MRGAS strain with iMLSB phenotype harbored both ermA and mefA genes.

BK virus (BKV) and JC virus (JCV) persist as latent infection in the kidneys. Reactivation of both viruses may be linked to immunodeficiency. The aims of this study were to determine the prevalence of BKV and JCV viruria and to evaluate the relationship between immunodeficiency and viruria in a cohort of HIV-infected patients. Urine samples from 93 HIV-infected patients were collected and tested for the presence of BKV and JCV DNA by PCR. The overall prevalence of polyomavirus DNA in urine was 74.2%. BKV DNA was detected in 30.1% urine samples and JCV DNA in 23.7% samples. Both BKV and JCV DNA were detected in 20.4% samples. There was no association between BKV/JCV urinary shedding and the degree of immunosuppression measured by CD4+ cell count. However, taking into account the severity of disease resulting from reactivation of BKV and JCV, patients with HIV/polyomavirus co-infection should be kept under frequent and regular supervision. [Projekat Ministarstva nauke Republike Srbije, br. 175073]

Gene polymorphisms result from evolutionary processes representing mutations that survive in the population with a frequency higher than 1%. The most investigated type of gene polymorphisms are single nucleotide polymorphisms (SNPs). The SNPs of IL-12B (rs 3212227) A/C among a population of kidney graft CMV-seropositive recipients have an impact on a clinical events in cytomegalovirus (CMV) disease. Constitutive -308 G/A TNF-α polymorphism (rs1800629) is related to the susceptibility of HR-HPV-associated cervical dysplasia and cancer. SNP located 3 kb upstream of the IL- 28B gene (rs12979860) seems to be the strongest host genetic predictor of sustained virologic response (SVR) in hepatitis C genotype 1 patients. It is very important to identify viral and host genetic markers that may facilitate the risk of developing viral disease or some viral-associated cancers. In addition, these markers could be useful in the choice of effective treatments and preventive strategies against virally induced infection. [Projekat Ministarstva nauke Republike Srbije, br. 175073 i br. 175038]

This study aimed to determine the prevalence and mutational patterns of lamivudine-resistant hepatitis B virus (HBV) strains in chronically infected Serbian patients. The study included 154 patients on long-term lamivudine monotherapy. Resistance-associated mutations were identified by direct sequencing of the S/P gene. The genotypic resistance to lamivudine was confirmed in 54.5% of patients. Three primary resistance-associated mutations were found: rtM204V (55.9%), rtM204I (40.5%), rtA181T (3.6%) and two compensatory mutations rtV173L (17.8%) and rtL180M (67.8%). Seven mutational patterns were discovered with rtL180M+rtM204V being dominant (41.6%). The presence of resistance associated mutations was correlated to the older age of patients, the presence of clinically relevant HBsAg mutations and higher values of viral load. No correlation with HBV genotypes, subgenotypes or HBsAg subtypes was observed. High prevalence of resistance supports the use of genotypic testing in monitoring patients on lamivudine therapy and selecting those who would benefit from therapy with newly developed nucleos(t)ide analogs. [Projekat Ministarstva nauke Republike Srbije, br. 175073]

The development of nasopharyngeal carcinoma (NPC) is the result of interaction between Epstein-Barr Virus (EBV) and many non-viral factors. The aims of this study were to determine the prevalence of EBV in NPC biopsies from Serbian patients and to investigate the correlation between EBV presence and demographic, anamnestic and clinical data. Ninety-three tissue blocks were included. For detection of EBV DNA, the C terminus of the LMP1 gene was amplified by nested-PCR. Twenty-eight biopsies were EBV-DNA-positive (30.1%), with a statistically significant difference in EBV DNA presence between geographical regions (p=0.02) and between the stages of tumor-node-metastasis (TNM) (p=0.02). A correlation was also found with the presence of EBV DNA and smoking (p=0.02). The correlation of EBV DNA presence, with or without smoking and the promising outcome of the disease was statistically significant (p=0.02; p=0.01). The EBV DNA findings from this study confirm the role of EBV in NPC carcinogenesis, and show the different distribution among TNM stages and correlation between the virus and outcome of disease. [Projekat Ministarstva nauke Republike Srbije, br. 175073]

The aim of this study was to implement the progesterone EIA test, developed in our laboratory by using an anti-progesterone antibody (Yamaguchi University, Japan), in order to determine the optimal moment for artificial insemination (AI) and to detect pregnancy in Holstein-Friesian cows according to the progesterone concentration in the whole milk. Also, the influence of β-carotene, applied at the day of insemination and human chorionic gonadotrophin applied on day 7 after AI on the progesterone level and the pregnancy rate were evaluated.For the accuracy of oestrus detection, the milk samples from 70 cows were collected on the day of insemination. Milk samples from 148 cows were collected 19-22 days following insemination for pregnancy check.After detection of naturally occurring oestrus (day 0) and AI, cows were divided into the following groups: group A (n = 19) was treated with 200 mg β-carotene (20 ml Carofertin® i.m. Alvetra u. Werfft Gmbh, Austria), group B (n = 17) was treated with 1 500 IU hCG i.m. (Schering-Plough, the Netherlands) and control (non treated) group C (n = 18). The milk samples for EIA progesterone concentration analysis were collected on the day of AI, the 14th and the 20th day of the oestrus cycle. Oestrus detection errors and inappropriate moments of insemination according to the progesterone concentration were detected in 22.86% animals (16/70). The test accuracy for non-pregnant cows was 90.48% (76/84). The accuracy of the progesterone test in pregnant cows was 75% (48/64). False positive results (high progesterone level, but the cows were not pregnant) was detected in 25% of cows (16/64) as a result of a prolonged oestrus cycles, embrional mortality and endomethritis (10/16 cases). The treatment of cows with 1500 IU of hCG, on the day 7 of the oestrus cycle, resulted in statistically significant increase of progesterone concentration in the dioestrus (P < 0.01). The most successful insemination was in the group of cows that was treated with hCG (47.05%; 8/17), then in the control group (38.88%; 7/18) and the least in the Carofertin group - 36.84% (7/19). These differences were only numerical (p>0.05).The EIA test developed in our laboratory could be used for accurate progesterone determination in the whole milk during implementation of different methods for control of bovine reproduction.

Although the genotype and subgenotype distribution of HBV isolates from Serbia has previously been reported, data about whole genome sequences from this area are scarce. This study included plasma samples from 5 chronically infected patients. Full genome amplification of the HBV isolates was performed by nested-PCR using 7 primer pairs, and the whole genome nucleotide sequences were obtained by direct sequencing. Two complete genome sequences belonged to D2 subgenotype (ayw3 HBsAg subtype), one to D1 (ayw2) and two to A2 (adw2). All 5 Serbian isolates clustered with sequences from the expected geographic regions and had nucleotide and coded protein length in accordance to their assigned genotypes, except for one HBeAg-negative isolate displaying G1896A mutation leading to a premature stop codon in the Pre-C region. The first complete genome sequences of HBV D1, D2 and A2 subgenotypes from Serbian patients showed characteristics similar to the nucleotide sequences of HBV isolates from other European and Middle East countries. [Projekat Ministarstva nauke Republike Srbije, br. 175073]

The BK (BKV) and JC viruses (JCV) are human polyomaviruses. After primary infection, they persist as latent infection in the kidneys. Immunosuppression leads to their reactivation, which is associated with life-threatening diseases such as polyomavirus-induced nephropathy and progressive multifocal leukoencephalopathy. However, the behavior of these viruses in immunocompetent individuals is still an open question with no right answer. The aim of this study was to determine the prevalence of BKV and JCV shedding in the urine of immunocompetent individuals from the Serbian population. Sixty-five urine samples were collected and tested for the presence of BKV and JCV DNA by PCR. JCV DNA was detected in 19/65 (29.2%) and BKV DNA in 3/65 (4.6%) of the urine samples. Forty-three (66.2%) urine samples of the immunocompetent donors were negative for both viruses. The present study provides the first results of urinary excretion of human polyomaviruses in the Serbian population. [Projekat Ministarstva nauke Republike Srbije, br. 175073]

Viruses are the main cause of opportunistic infections after kidney transplantation. The aim of this study was to determine the prevalence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), B. K. virus (BKV) and John Cunningham virus (JCV) infections in renal transplant recipients (RTR). This retrospective study of 112 RTR investigated the presence of CMV, EBV and polyomaviruses DNA in plasma and/or urine by PCR. The visualization of PCR products was performed by electrophoresis on 2% agarose gel stained with ethidium bromide and photographed under a UV light. The chi-square test was used for statistical analysis. CMV DNA was detected in 14/112 (12.5%), EBV DNA in 4/49 (8.16%), BKV DNA in 10/31 (32.26%) and JCV DNA in 3/31 (9.68%) RTR. These results show that CMV infection is more often present in RTR compared to other investigated viral infections. In the light of these results, molecular testing could be useful in identifying recipients at high risk of symptomatic post-transplant viral infection. [Projekat Ministarstva nauke Republike Srbije, br. 175073, br. 175038 and br. 175089]

Oncogenic viruses trigger persistent infections, which can stimulate uncontrolled cell growth by inducing cell transformation. Different oncogenic viruses use different mechanisms for infecting cells. Most oncogenic DNA viruses integrate transforming sets of genes into the host chromosome and encode proteins that bind and inactivate cell growth regulatory proteins, such as p53 and retinoblastoma gene product. Tumorous RNA viruses use different oncogenic mechanisms. Some of them encode oncogenic proteins that are almost identical to the cellular proteins involved in the control of cellular growth. The overproduction or altered function of these oncogenic materials stimulates cell growth. These RNA viruses can cause tumors rapidly. The second group of oncoviruses integrates their promoter sequences and viral enhancers near to the cellular growth-stimulating gene, initiating the transformation of the cell. The third group of RNA tumor viruses encodes a protein tax that transactivates the expression of cellular genes. Virus-induced malignant transformation of the cell represents the first step in the complex process of oncogenesis.

During chronic hepatitis B virus (HBV) infection, the seroclearance of hepatitis B e antigen (HBeAg) is an important event and a significant surrogate endpoint of all current therapeutic strategies. The prediction of HBeAg seroclearance can help assess the benefits of therapy in patients during or before therapy initiation. The quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker for solving multiple diagnostic dilemmas. A systematic review and meta-analysis of studies that measured qAnti-HBc in patients who achieved HBeAg seroclearance were performed through PubMed, Web of Science (WoS) and SCOPUS electronic database searches. Nineteen articles were included in the systematic review, comprising 3434 chronically infected patients (1014 with and 2420 without HBeAg seroclearance). Sixteen publications with data regarding qAnti-HBc levels were included in the meta-analysis. The baseline level of qAnti-HBc antibodies was significantly higher in patients with than without HBeAg seroclearance (SMD = 0.88, 95%CI SMD = 0.56-1.2, p < 0.001). The same conclusion was reached for patients originating from Asia (SMD = 0.94, 95%CI SMD = 0.55-1.33) and for the qAnti-HBc antibodies among adult HBV patients with therapy-induced HBeAg seroclearance (SMD = 0.90, 95%CI SMD = 0.54-1.25, p < 0.001). The systematic review and meta-analysis provide evidence of the role of qAnti-HBc as a promising biomarker for predicting HBeAg seroclearance in chronically infected patients.

The hepatitis B surface antigen (HBsAg) is a multifunctional glycoprotein composed of large (LHB), middle (MHB), and small (SHB) subunits. HBsAg isoforms have numerous biological functions during HBV infection-from initial and specific viral attachment to the hepatocytes to initiating chronic infection with their immunomodulatory properties. The genetic variability of HBsAg isoforms may play a role in several HBV-related liver phases and clinical manifestations, from occult hepatitis and viral reactivation upon immunosuppression to fulminant hepatitis and hepatocellular carcinoma (HCC). Their immunogenic properties make them a major target for developing HBV vaccines, and in recent years they have been recognised as valuable targets for new therapeutic approaches. Initial research has already shown promising results in utilising HBsAg isoforms instead of quantitative HBsAg for correctly evaluating chronic infection phases and predicting functional cures. The ratio between surface components was shown to indicate specific outcomes of HBV and HDV infections. Thus, besides traditional HBsAg detection and quantitation, HBsAg isoform quantitation can become a useful non-invasive biomarker for assessing chronically infected patients. This review summarises the current knowledge of HBsAg isoforms, their potential usefulness and aspects deserving further research.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated., Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients., Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported., Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Banko, Cirkovic, Miskovic, Jeremic, Grk, Basaric, Lazarevic, Raskovic, Despotovic and Miljanovic.)

Epstein-Barr virus (EBV) infection has been shown as a potential risk factor for the development of rheumatoid arthritis (RA). This prospective research aimed to investigate whether EBV infection markers changed during the six-month follow-up period in 133 RA patients (80 newly diagnosed on methotrexate (MTX)-RA-A, and 53 on biologic therapy-RA-B) and whether it was related to a disease outcome. Reduction of disease activity and inflammation was obtained. A significant decline in seroprevalence and titer for anti-VCA-IgM ( p = 0.022 and p = 0.026) and anti-EA(D)-IgM ( p = 0.022 and p = 0.006) in RA-A, and in seroprevalence and titer of anti-EA(D)-IgG in the RA-B subgroup ( p = 0.021 and p = 0.006) were detected after the follow-up. A lower titer of anti-EBNA1-IgG could be considered a significant marker of RA remission in all RA patients regardless of age and gender (OR = 0.99, 95% CI OR = 0.98-0.99, p = 0.038), and also in RA-B patients separately (OR = 0.988, 95% CI OR = 0.98-0.99, p = 0.041). This study supported the basic hypothesis that the immune response to EBV infection is involved in the RA pathogenesis, at the beginning of the disease or during the RA evolution. Moreover, the potential influence of MTX or TNF-alpha inhibitors on the impairment of the host to control EBV infection was indirectly refuted.

Although the connection between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 (Epstein-Barr nuclear antigen 1-EBNA1) variants and clinical parameters of RA patients. This prospective cohort study included 133 RA patients and 50 healthy controls. Active/recent EBV infection was more prevalent in RA patients than in controls (42% vs. 16%, p < 0.001). RA patients had higher titers of anti-EBV-CA-IgM (capsid antigen-CA) and anti-EBV-EA(D)-IgG (early antigen-EA) antibodies than controls ( p = 0.003 and p = 0.023, respectively). Lower levels of anti-EBNA1-IgG and anti-EBV-CA-IgG were observed in RA patients who received methotrexate (anti-EBNA1 IgG p < 0.001; anti-EBV-CA IgG p < 0.001). Based on amino acid residue on position 487, two EBNA1 prototypes were detected: P-Thr and P-Ala. Patients with active/recent EBV infection had a five times more chance of having RA and a nearly six times more chance of getting RA. Also, EBV active/recent infection is twice more likely in newly diagnosed than in methotrexate-treated patients. Further studies are needed to clarify "who is the chicken and who is the egg" in this EBV-RA relationship.

Systemic lupus erythematosus (SLE) is characterized by an imbalance between proinflammatory and anti-inflammatory mediators. Single-nucleotide polymorphisms (SNPs) in genes coding IL10RA , IL10RB , and IL22RA could affect their expression or function and disrupt immune homeostasis. We aimed to analyze the associations of IL10RA , IL10RB , and IL22RA polymorphisms/haplotypes with patients' susceptibility to and clinical manifestations of SLE. Our study included 103 SLE patients and 99 healthy controls. The genotypes of the selected polymorphisms within IL10RA (rs10892202, rs4252270, rs3135932, rs2228055, rs2229113, and rs9610), IL10RB (rs999788, rs2834167, and rs1058867), and IL22RA (rs3795299 and rs16829204) genes were determined by TaqMan ® Assays. IL10RB rs1058867 G allele carriers were significantly more frequent among the controls than among the SLE patients (76.8% vs. 61.2%; p = 0.017, OR = 0.477, 95% CI: 0.258-0.879). The IL10RB CAA haplotype was more frequent among the SLE patients than in the control group (42.7% vs. 30.7%; p = 0.027). The IL22RA rs3795299 C allele and rs16829204 CC genotype were associated with Hashimoto thyroiditis in the SLE patients (n = 103; p = 0.002 and p = 0.026, respectively), and in all the included participants (n = 202, p < 0.000 and p = 0.007, respectively), and the IL22RA CC haplotype was more frequent in the SLE patients with Hashimoto thyroiditis ( p = 0.047) and in the overall participants with Hashimoto thyroiditis (n = 32, p = 0.004). The IL10RA , IL10RB , and IL22RA polymorphisms/haplotypes could be associated with SLE susceptibility and various clinical manifestations, and the IL22RA CC haplotype could be associated with Hashimoto thyroiditis.