The first nationwide multicenter study ofAcinetobacter baumanniirecovered in Serbia: emergence of OXA-72, OXA-23 and NDM-1-producing isolates

Background The worldwide emergence and clonal spread of carbapenem-resistantAcinetobacter baumannii(CRAB) is of great concern. The aim of this nationwide study was to investigate the prevalence of CRAB isolates in Serbia and to characterize underlying resistance mechanisms and their genetic relatedness. Methods Non-redundant clinical samples obtained from hospitalized patients throughout Serbia were included in the prospective, observational, multicenter study conducted from January to June 2018. Samples were initially screened for the presence ofAcinetobacter baumannii-calcoaceticus(Acb) complex using conventional bacteriological techniques. Acb complexes recovered from clinical samples obtained from inpatients with confirmed bacterial infections were further evaluated for the presence ofA. baumannii. Identification to the species level was done by the detection of thebla(OXA-51)gene andrpoBgene sequence analysis. Susceptibility testing was done by disk diffusion and broth microdilution method. CRAB isolates were tested for the presence of acquired carbapenemases(bla(OXA-24-like),bla(OXA-23-like,)bla(OXA-58-like),bla(OXA-143-like),bla(IMP),bla(VIM),bla(GIM),bla(SPM),bla(SIM),bla(NDM)) by PCR. Clonal relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results Acb complex was isolated in 280 out of 2401 clinical samples (11.6%). Overall,A. baumanniiwas identified in 237 out of 280 Acb complex (84.6%). CRAB prevalence was found to be 93.7% (237/222). The MIC50/MIC(90)for imipenem and meropenem were 8/ gt 32 mu g/mL and 16/ gt 32 mu g/mL, respectively. Although susceptibility was high for colistin (95.7%;n = 227) and tigecycline (75.1%;n = 178), ten isolates (4.3%) were classified as pandrug-resistant. The following carbapenemases-encoding genes were found: 98 (44.2%)bla(OXA-24-like), 76 (34.5%)bla(OXA-23-like), and 7 (3.2%)bla(NDM-1). PFGE analysis revealed six different clusters. MLST analysis identified three STs: ST2 (n = 13), ST492 (n = 14), and ST636 (n = 10). Obtained results evaluated that circulating CRAB clones in Serbia were as follows:bla(OXA66)/bla(OXA23)/ST2 (32.4%),bla(OXA66)/bla(OXA23)/bla(OXA72)/ST2 (2.7%),bla(OXA66)/bla(OXA72)/ST492 (37.8%), andbla(OXA66)/bla(OXA72)/ST636 (27.1%). Conclusion This study revealed extremely high proportions of carbapenem resistance amongA. baumanniiclinical isolates due to the emergence ofbla(OXA-72),bla(OXA-23), andbla(NDM-1)genes among CRAB isolates in Serbia and their clonal propagation

Quality Parameters and Antioxidant Activity of Three Clover Species in Relation to the Livestock Diet

Products of metabolism that are directly involved in growth, development and reproduction and also secondary products of metabolism were studied in 16 natural populations of three species of the genus Trifolium (T. repens - four populations, T. alpestre - three populations, T. pannonicum - nine populations), collected from the central Balkans region, i.e. territory of Serbia. Statistical analysis showed the presence of variability in all species of the test material. The best quality of dry matter, estimated by the ratio of crude protein and crude fiber, was achieved in the populations of white clover. In this species, average protein content was 216.4 g kg(-1) while the average content of crude fiber was 222.4 g kg(-1). The highest average content of total phenols (77.9 mg GA g(-1)), flavonoids (159.7 mg Ru g(-1)) and antioxidant activity (70.2 mu g ml(-1)) was measured in populations of T. pannonicum by phytochemical analysis of aerial parts of plants. The content of secondary metabolites and antioxidant activity in other species were extremely low. Populations of T. pannonicum were notable for fodder quality and antioxidant activity: CS091 with 186.2 g kg(-1) of crude protein and antioxidant activity of 55 mu g ml(-1); RA123 with 175.6 g kg(-1) of crude protein and a high level of antioxidant activity of 44.8 mu g ml(-1). It can be concluded that the selection of these populations may lead to creation of different varieties of fodder crops that could give safe animal feed and would be suitable for growing under adverse conditions of mountainous climate

Quality Parameters and Antioxidant Activity of Three Clover Species in Relation to the Livestock Diet

Products of metabolism that are directly involved in growth, development and reproduction and also secondary products of metabolism were studied in 16 natural populations of three species of the genus Trifolium (T. repens – four populations, T. alpestre – three populations, T. pannonicum – nine populations), collected from the central Balkans region, i.e. territory of Serbia. Statistical analysis showed the presence of variability in all species of the test material. The best quality of dry matter, estimated by the ratio of crude protein and crude fiber, was achieved in the populations of white clover. In this species, average protein content was 216.4 g kg-1 while the average content of crude fiber was 222.4 g kg-1. The highest average content of total phenols (77.9 mg GA g-1), flavonoids (159.7 mg Ru g-1) and antioxidant activity (70.2 μg ml-1) was measured in populations of T. pannonicum by phytochemical analysis of aerial parts of plants. The content of secondary metabolites and antioxidant activity in other species were extremely low. Populations of T. pannonicum were notable for fodder quality and antioxidant activity: CS091 with 186.2 g kg-1 of crude protein and antioxidant activity of 55 μg ml-1; RA123 with 175.6 g kg-1 of crude protein and a high level of antioxidant activity of 44.8 μg ml-1. It can be concluded that the selection of these populations may lead to creation of different varieties of fodder crops that could give safe animal feed and would be suitable for growing under adverse conditions of mountainous climate

Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(μ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(μ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(μ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(μ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1–C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV–Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1–C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo

Economics of Digital Transformation

The papers published in this monograph present best papers presented at the first conference of the Faculty of Economics and Bussiness of University of Rijeka organized on the topic of “Economics of digital transformation” from 2nd to 4th of May, 2018 in Opatija, Croatia (www.edt- conference.com). During the three days of the conference more than 50 researchers from European region contributed with their presentations. We are particularly proud on the results of our doctoral workshop where nine young researchers presented their research while five papers were published in the monograph. In this way we are building our future research capacities and expose young researchers to rigorous scientific challenge

Economics of Digital Transformation

The papers published in this monograph present best papers presented at the first conference of the Faculty of Economics and Bussiness of University of Rijeka organized on the topic of “Economics of digital transformation” from 2nd to 4th of May, 2018 in Opatija, Croatia (www.edt- conference.com). During the three days of the conference more than 50 researchers from European region contributed with their presentations. We are particularly proud on the results of our doctoral workshop where nine young researchers presented their research while five papers were published in the monograph. In this way we are building our future research capacities and expose young researchers to rigorous scientific challenge