The human cytomegalovirus (HCMV) encoded chemokine receptor US28 promotes tumorigenesis through activation of various proliferative and angiogenic signaling pathways. Upon infection, US28 displays constitutive activity and signals in a G protein-dependent manner, hijacking the host's cellular machinery. In tumor cells, the hypoxia inducible factor-1α/pyruvate kinase M2 (HIF-1α/PKM2) axis plays an important role by supporting proliferation, angiogenesis and reprogramming of energy metabolism. In this study we show that US28 signaling results in activation of the HIF-1α/PKM2 feedforward loop in fibroblasts and glioblastoma cells. The constitutive activity of US28 increases HIF-1 protein stability through a Gαq-, CaMKII- and Akt/mTOR-dependent mechanism. Furthermore, we found that VEGF and lactate secretion are increased and HIF-1 target genes, glucose transporter type 1 (GLUT1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), involved in glucose metabolism, are upregulated in US28 expressing cells. In addition, PKM2 is phosphorylated and found to be in a tumor-associated dimeric state upon US28 expression. Also in HCMV-infected cells HIF-1 activity is enhanced, which in part is US28-dependent. Finally, increased proliferation of cells expressing US28 is abolished upon inhibition of the HIF-1α/PKM2 cascade. These data highlight the importance of HIF-1α and PKM2 in US28-induced proliferation, angiogenesis and metabolic reprogramming.

The focus of this study was on genetic diversity of TB horse population raised in B&H. Genomic DNA was genotyped by using 17 microsatellite markers. A total of 103 alleles were detected. The average number of alleles per locus was 6.059 and effective number of alleles was 3.293. Means of observed and expected heterozygosity were calculated 0.645 and 0.696, respectively. The average PIC values was 0.649 and inbreeding coefficient was 0.090. Based on all observed parameters, ASB2 locus showed the highest genetic diversity while locus HMS2 was the least diverse. These results suggest that the population of TB horses from B&H is not affected by substantial loss of genetic diversity, indicating the presence of reasonably high level of genetic variability.

Aim To assess prevention and reduction of trismus after surgically extracted impacted mandibular third molars with individual and combined therapy with corticosteroids and anti-inflammatory analgesics. Methods The research included 60 randomly selected patients (3 groups) attended to the Dental Oral Surgery of the Public Institution Healthcare Center Zenica during the period January-December 2008. Patients of both genders, 18-45 years of age, were presented without pain and other inflammatory symptoms at the time of surgery. According to a scheme established in the research protocol, two medications were administered orally: methylprednisolone(corticosteroid) 32 mg and meloxicam (non-steroidal anti-inflammatory analgesic, NSAID) 15 mg as a single drug, or a combination of both drugs. The level of trismus is assessed on the basis of differences of preoperative and postoperative values of interincisal spaces when fully opening the mouth on the second and the seventh post-operative day. The differences between groups of patients were evaluated by means of Tukey's HSD test. Results On the second and on the seventh post-operative day significantly better results were registered in the group that received only corticosteroids and in the group that received both, corticosteroids and NSAIDs compared to the group that received only NSAIDs. A tendency of trismus reduction was present in all patient groups for the second and seventh day after surgery. Conclusion Prevention and control of postoperative trismus after surgical extraction of impacted mandibular third molars with combined therapy is effective and superior comparing to individual therapy with meloxicam-or methylprednisolone alone.

BackgroundAlthough the costs of treating inflammatory bowel disease (IBD) in developed countries are well established, they remain largely unknown in countries with recent histories of socio-economic transition including Serbia.ObjectiveTo estimate the costs of treatment including the resources used by patients with IBD in Serbia from a societal perspective. This includes both Crohn’s disease and ulcerative colitis.MethodsThis cost-of-illness study was conducted to identify direct, indirect and out-of-pocket costs of treating patients with IBD in Serbia. Patients with IBD (n = 112) completed a semi-structured questionnaire with data concerning their utilisation of heath-care resources and illness-related expenditures. All costs were calculated in Republic of Serbia dinars (RSD) at a 1-year level (2014) and subsequently converted to Euros. Median values and ranges were reported to avoid potential distortions associated with mean costs.ResultsMedian total direct costs and total indirect costs per patient per year in patients with Crohn’s disease were 192,614.32RSD (€1602.97) and 28,014.00RSD (€233.13) and 142,267.15RSD (€1183.97) and 21,436.00RSD (€178.39), respectively, in patients with ulcerative colitis. In both groups, the greatest component of direct costs was hospitalisation.ConclusionsCosts of IBD in Serbia are lower than in more developed countries for two reasons. These include the fact that expensive biological therapy is currently under-utilised in Serbia and prices of health services are largely controlled by the State at a low level. The under-utilisation of biologicals may change with the advent of biosimilars at increasingly lower prices.

Background/Aim Delirium is an acute or subacute, and most frequently reversible syndrome of higher cortical functions disturbances that is manifested as generalized disorder. If not prevented, it is associated with various adverse outcomes. The aim of this study was to determine the connection between the markers of inflammation and lethal outcome in patients diagnosed with delirium, hospitalized in the psychiatric intensive care unit. Methods This retrospective study included 120 patients hospitalized in the psychiatric intensive care unit in whom examination of differences in inflammation markers was done. The examinees have been divided into two groups: the case group of 40 patients who died during the hospitalization, and the control group of 80 examinees who were discharged with the diagnosis Post delirium status. The following variables were taken into account: age, gender, clinical diagnosis of infection (pneumonia and urinary tract infection), laboratory parameters (total of white blood cells, granulocytes, monocytes, C-reactive protein − CRP) and type of delirium (withdrawal or organic). Results The average age of patients was 50.3 ± 13.1 years. The patients who survived delirium, were on the average 10.5 years younger than the deceased (p < 0.001). More than half (57.5%) of the deceased had pneumonia. There was a statistically significant correlation between pneumonia and lethal outcome in the patients with delirium (p < 0.001). The examinees with lethal outcome had significantly higher median CRP levels than the group of examinees who survived (75.6% ± 54.0 vs 30.3 ± 42.5 ng/L, p < 0.001). Conclusion Aiming to better and more precise diagnostics of this complicated and still unclear neuropsychiatric syndrome it would be useful to consider introduction of more precise diagnostic algorithms in every unit of intensive care. That would significantly reduce the number of delirium diagnosis overlook, decrease complication of clinical features and would also reduce the unfavorable outcome rate, therefore the total cost of treatment.

Summary The aim of the paper was to determine the factors related to the initial therapy that may contribute to death from severe necrotizing acute pancreatitis and to analyze their clinical importance as well as possible additive effects. A retrospective case-control study included all adult patients treated for severe necrotizing acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the five-year period (2006-2010.). The cases (n = 41) were patients who died, while the controls (n = 69) were participants who survived. In order to estimate the relationship between potential risk factors and observed outcome, crude and adjusted odds ratios (OR) with 95 % confidence intervals (CI) were calculated in logistic regression models. Significant association with observed outcome was shown for the use of gelatin and/or hydroxyethyl starch (adjusted OR 12.555; 95 % CI 1.150-137.005), use of albumin (adjusted OR 27.973; 95 % CI 1.741-449.373), use of octreotide (adjusted OR 16.069; 95 % CI 1.072-240.821) and avoiding of enteral feeding (adjusted OR 3.933; 95 % CI 1.118-13.829), while the use of nonsteroidal anti-inflammatory drugs had protective role (adjusted OR 0.057; 95 % CI 0.004-0.805). The risk of death in patients with predicted severe necrotizing acute pancreatitis could be reduced with avoidance of treatment with colloid solutions, albumin and octreotide, as well as with an early introduction of oral/enteral nutrition and use of nonsteroidal anti-inflammatory drugs.