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Introduction/Objective. The main aim of this study was to assess COVID-19 vaccination effectiveness (VE) of BBIBP-CorV, Gam-COVID-Vac, BNT162b2, and ChAdOx1-nCoV-19 in Serbia during the first three months of rollout. Methods. The data from the Serbian National Immunization Registry, the Primary Health Centre Report, and the University Clinical Centre Report for Kragujevac, Serbia, for the period from January 1 to March 31, 2021 were used to compare COVID-19 vaccinated population to unvaccinated individuals in terms of laboratory confirmed SARS-CoV-2 infection, COVID-19-related hospitalization and intensive care unit (ICU) admission due to COVID-19. VE was estimated based on the incidence rate ratio, adjusted for age and sex. Results. Overall VE after the first dose reached 20.6%, 28.2%, and 56.1%, and 55.7%, 63.9%, and 79.8%, after the second dose for SARS-CoV-2 infection, COVID-19-related hospitalization, and ICU admission, respectively. BNT162b2 exhibited 96.7% VE against infection and no hospitalization after the second dose. Complete vaccination with BBIBP-CorV and Gam-COVID-Vac demonstrated VE of 43.2% and 78.6% against infection, 56.9% and 85.3% against hospitalization, and 82.3% and 52.7% against ICU admission, respectively. ChAdOx1-nCoV-19 after the first received dose showed VE of 10.3% and 74.7% against infection and hospitalization, with no ICU admission. Conclusion. COVID-19 vaccination in general, as well as each of the four studied vaccines, reduces the risk of SARS-CoV-2 infection, hospitalization due to COVID-19, and COVID-19-related ICU admission. Vaccine effectiveness significantly increases with the second received dose for all study outcomes.

Introduction/Objective. The duration of vaccine-induced protection against SARS-CoV-2 is shown to be limited. The aim of this study was to assess vaccine effectiveness (VE) of a third dose of four different COVID-19 vaccines during Delta variant predominance in Serbia. Methods. The data for the period from August 18, to October 1, 2021 were used to estimate the incidence rates (IR) of the SARS-CoV-2 infection, COVID-19-related hospitalization, and intensive care unit (ICU) admission. The study included 41,186 fully vaccinated subjects, of which 13,589 had received the third dose. VE was estimated based on the IR ratio following vaccination with three vs. two doses. Results. We found that a third dose of all investigated vaccines reduces the incidence of both SARS-CoV-2 infection and severe illness that requires hospitalization or ICU admission. The highest VE against infection demonstrated BNT162b2, followed by Gam-COVID-Vac and BBIBP-CorV. Third dose vaccination reduced the risk of hospitalization (IR = 0 for Gam-COVID-Vac and BBIBP-CorV), and ICU admission (IR = 0 for all vaccines). The hazard distributions for SARS-CoV-2 infection and hospitalization following vaccination with three versus two doses were significantly different. Conclusion. These findings indicate that an additional, third dose of studied vaccine boosters protection against all investigated outcomes.

As cancer remains a significant global health challenge, there is an increasing need for novel therapeutic approaches. We investigated the antitumor potential of Juniperus communis berry essential oil on cervical cancer HeLa and colorectal HCT 116 cells. Cytotoxicity was evaluated through the MTT assay, revealing concentration-dependent reductions in cell viability. A clonogenic assay demonstrated long-term cytotoxic effects. Apoptosis markers were assessed via flow cytometric analysis and showed an induction of the intrinsic pathway in both cell lines, demonstrated by the elevated levels of cleaved caspase-3, Bax/Bcl-2 ratio, JC-10 monomer formation, and cytochrome C migration to the cytosol. The treatment inhibited cell-survival pathways in HCT 116 cells and arrested HeLa cells in the S phase. An extensive molecular docking screening provided insight into the binding affinity and interaction patterns of the essential oil components with NADH ubiquinone oxidoreductase and superoxide dismutase enzymes, further confirming the induction of the intrinsic pathway of apoptosis. The obtained in silico and in vitro results indicated the anticancer potential of J. communis berry essential oil as it interferes with cancer cell molecular mechanisms. Our findings highlight J. communis berry essential oil as a promising natural agent with anticancer potential. [ABSTRACT FROM AUTHOR]

A dicarboxylato-diamide-type compound 2,2'-[(1,2-dioxoethane-1,2- -diyl)diimino]dibenzoic acid (H4obbz) (1) was synthesized and characterized. The crystal structure of K2H2obbz·2H2O (2) was determined by X-ray diffracttion analysis. The cytotoxic activities of the compounds were tested against four different cancer cell lines MCF-7, A549, HT-29, HeLa and a human normal cell line MRC-5. The results indicate reasonable dose-dependent cytotoxicity of the ligands that show selectivity against the tested carcinoma and healthy cell lines. Flow cytometric analysis and fluorescence microscopy showed that the most active compound, H4obbz, induced apoptosis and G0/G1 cell cycle arrest, indicating blockage of DNA synthesis as a possible mechanism that triggers apoptosis. Docking and molecular dynamics simulations gave similar responses regarding interactions (binding) between their ligands and chaperon Grp78. The MMGBSA determined ΔG binding energies were in the range from –104 to –140 kJ mol-1.

Background/Aim. Bacterial vaginosis (BV) is a common cause of vaginal discomfort in women. The aim of this study was to compare Nugent’s scoring system and novel microscopy method, introduced in our laboratory and used in BV diagnosis. Methods. This study included 705 pregnant and asymptomatic women between 24 and 28 weeks of pregnancy. The degree of agreement between methods was determined by the kappa (κ) index. The sensitivity, specificity, positive and negative predictive value of the novel microscopy method was compared to Nugent’s score as standard. Results. Based on the scoring system of both methods, Nugent’s and novel microscopy method, BV was diagnosed in 21% and 25% of women, respectively. Despite the disparities among diagnostic criteria, which mainly concerned classification of intermediary samples, the degree of agreement between categories, determined by κ index, was satisfactory: Nugent’s vs. novel microscopy method (κ = 0.68; good agreement), and Nugent’s vs. novel microscopy method without intermediary results (κ = 0.83; very good agreement). We also demonstrated that compared to Nugent’s method, as the golden standard, the novel microscopy method had high sensitivity and specificity (ranging from 75%–99.3%) and positive and negative predictive values (ranging from 88.8%–99.5%). Our method is based on a relative number of bacterial morphotypes, either rod forms (˃ 1.5 μm, lactobacilli) or non-rod forms (< 1.5 μm, bacterial vaginosis associated bacteria) under 200× magnification, which extends the surface of examined preparation, but without prolongation of observer’s working time. Conclusion. The novel microscopy method in diagnosing BV corresponded well with Nugent’s scoring system which allows it to be an alternative method in diagnosing BV. Further-more, the novel microscopy method is based on a relative number of bacterial morphotypes that appeared to be flexible and can be reorganized in the way to categorize findings into only two groups: normal and BV, which makes it comparable to dichotomous Amsel’s clinical criterion.

Introduction/Objective. The increasing resistance to macrolides and lincosamides among staphylococci and streptococci is becoming a global problem. The aim of this study was to investigate the prevalence of macrolide-lincosamide-streptogramin (MLS) resistance phenotypes in staphylococcal and streptococcal isolates in southeast Serbia. Methods. The MLS phenotypes were determined by the double-disk diffusion method in 2,121 inpatient and outpatient staphylococcal and streptococcal isolates collected during a one-year period at the Center for Microbiology. Results. The methicillin-resistant staphylococci isolates were significantly more resistant to penicillin, erythromycin, clindamycin, gentamicin, and ciprofloxacin (100%, 100%, 29.2%, 65.6%, and 53.1%, respectively) than the methicillin-sensitive ones (93.6%, 64.9%, 12%, 28.9%, and 11.7%, respectively). The inducible clindamycin resistance phenotype was dominant in S. aureus and coagulase-negative staphylococci isolates. S. pneumoniae, S. pyogenes, and S. agalactiae isolates showed very high resistance to erythromycin (77.8%, 46.2%, and 32.4%, respectively). All staphylococci and streptococci isolates were sensitive to vancomycin and linezolid, and all beta-hemolytic streptococci isolates to penicillin and ceftriaxone. Conclusion. The phenotypic triage of staphylococci is necessary in order to separate inducible resistant and truly clindamycin-sensitive isolates. Macrolides should not be recommended for empirical therapy of streptococcal infections. Penicillins remain the drug of choice for treatment of streptococcal infections in our local area. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41010]

Introduction/Objective. Bacterial vaginosis (BV) is defined as disequilibrium of vaginal microbiota due to proliferation of Gram-negative/variable anaerobes and reduction/depletion of vaginal lactobacilli. Difficulties in interpreting microscopically categorized findings in diagnosis of BV need a molecular analysis of bacteria present in vaginal discharge of patients. In this regard, we performed real-time qPCR analysis of vaginal discharge samples with the goal to explore in which extent prevalence and amount of anaerobes, Gardnerella vaginalis and Atopobium vaginae, are related to findings obtained by microscopy. Methods. This study enrolled 111 asymptomatic pregnant women between 24 and 28 weeks of pregnancy. Gram-stained vaginal smears were evaluated microscopically. Afterwards, DNA of bacteria was extracted from Gram slides and real-time qPCR was performed with the aim to detect and quantify G. vaginalis and A. vaginae. Results. The data of our study showed that 53.2% of patients had normal results, while 20.7% and 26.1% of patients had intermediary (IMD) and BV results, respectively. G. vaginalis and A. vaginae were more frequently found in IMD and BV than in healthy patients; also, the average bacterial number of G. vaginalis and A. vaginae were significantly higher in BV and IMD than in the group with normal findings (p = 0.000). Comparing mutual relation of G. vaginalis and A. vaginae, the prevalence and number of G. vaginalis were in all groups significantly higher than A. vaginae. Conclusion. The data of our study have shown that in distinguishing normal from BV findings, quantification of bacteria may be more important than just molecular detection of bacteria. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41010]

Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV) infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010]

This paper presents the synthesis and structural characterization of a series of new ruthenium(II) complexes 1–7, with the general formula mer-[RuL3(N–N)Cl]Cl, where L is 2,2′:6′,2′′-terpyridine (tpy) or 4′-(4-chlorophenyl)-2,2′:6′,2′′-terpyridine (Cl-Ph-tpy) and N–N is o-benzoquinonediimine (o-bqdi), 2,3-naphthoquinonediimine (nqdi), 4,4′-dimethyl-2,2′-bipyridine (dmbpy) or 2,2′-bipyridine-4,4′-dicarboxylic acid (dcbpy). The kinetic results showed that the ligand substitution reactions of new Ru(II)-polypyridyl complexes with biomolecules were affected by different substituents and the aromaticity of meridional tridentate and bidentate spectator ligands as well as by the nature of the entering nucleophile. The reactivity of the complexes increases in the order: dmbpy < dcbipy < nqdi < o-bqdi. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data. Furthermore, combining ethidium bromide (EB) and Hoechst 33258 (2-(4-hydroxyphenyl)-5-[5-(4-methylpiperazine-1-yl)benzimidazo-2-yl]-benzimidazole) fluorescence assay results implied that 1–7 might interact with calf thymus DNA through partial intercalation and/or minor groove binding. The human serum albumin (HAS)-fluorescence binding studies involving the site markers, eosin Y, as a marker for site I of subdomain IIA, and ibuprofen, as a marker for site II of subdomain IIIA, showed that Ru(II) compounds bind to both sites with moderately strong affinity (Kb = 104–106 M−1). Moreover, these DNA/HSA experimental results were confirmed by molecular docking. Complexes 2, 5 and 6 exerted good to strong and highly selective cytotoxic activity against breast adenocarcinoma (MDA-MB 231), colorectal carcinoma (HCT116) and cervix adenocarcinoma (HeLa). Depending on their structure and cell line, the complexes acted differently in terms of their influence on autophagy, the cell cycle and the engaged apoptotic pathway. [ABSTRACT FROM AUTHOR]

Background/Aim. Atopic diseases such as atopic dermatitis, allergic rhinitis and asthma have had increased prevalence during the past decade and nowadays occur in every third child in developed countries. The aim of the study was to determine frequency and type of atopic diseases at the age of two, as well as the importance the total IgE antibodies concentrations have in diagnosis and prognosis of the disease. Methods. The study involved 175 children up to two years of age. Allergy-like symptoms were found after surveying their parents and pediatric medical records. Using the fluorescence immunossay (FIA) method, total IgE antibodies concentrations and specific IgE antibodies (Phadiatop infant) were determined on an Immunocap 100 Dyagnostic System. Results. One or more allergy-like symptoms accounted for 57.7% of findings in children under the age of two, whilst in 19.4% the existence of IgE-related allergic diseases was found. Atopic diseases usually have clinical manifestations of atopic dermatitis (11.4%), IgE-bound wheezing/asthma (10.8%) and food allergies (7.4%), and to much lesser extent those of allergic rhinitis (3.4%) and urticaria (1.7%). The significantly higher total IgE antibodies concentrations were found in children with allergy-like symptoms (p < 0.0005) (cut-off 15.15 kU/L, sensitivity 76.5% specificity 71.6%). Conclusion. Almost 20% of two-year-old children have any of clinically manifested allergic diseases, with atopic dermatitis and IgE wheeze/asthma being predominant. The higher total IgE antibodies concentration is a good marker for sensitization in children with allergy-like symptoms.

Introduction. Non-small cell lung cancer (NSCLC) accounts for about 70-80% of all lung cancers. In comparison with small cell lung cancer, NSCLC has relatively low therapy response. Discovery of neuroendocrine markers within the NSCLC group (10-30%) has initiated the issue of their importance in the therapy and prognosis. Objective. The aim of this study was to determine the influence of neuroendocrine differentiation on treatment response and survival in patients with advanced NSCLC. Methods. A clinical trial included 236 patients (73.7% males), with diagnosis of NSCLC, determined by histological verification. These patients were treated by combined chemo- and X-ray therapy at stage III (without pleural effusion) or chemotherapy only at stage III (with pleural effusion) and stage IV of NSCLC. When the progression had been noted at the stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron-specific enolase (NSE), chromogranin A (ChrA) as well as synapthophysin (SYN) expression in tissue examples was determined by immunohistochemical analysis with monoclonal mouse anti human bodies (DAKO Comp, Denmark). The treatment was conducted during 4 to 6 chemotherapeutic cycles. The efficacy was assessed after the therapy regimen; median survival time was assessed after the randomization. Results. NSE, ChrA and SYN expression were noted in 56 (23.7%), 33 (13.9%) and 39 (16.5%) patients, respectively. Better therapeutic response was significantly higher in patients with expression of NSE, ChrA and SYN (p

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