INTRODUCTION Hepatitis C Virus (HCV) is the leading cause of chronic liver disease and is a serious global health problem. Hepatitis C infection is highly prevalent in patients with end stage renal disease (ESRD), due to frequent exposure to blood and blood products, nosocomial transmission of HCV, and prolong hemodialysis duration. The aim of the study was to evaluate the influence of IL-33/ST2 signaling pathway on severity of the liver disease in ESRD HCV+ patients. METHODOLOGY Blood samples from patients with end stage renal disease (ESRD) and hepatitis C infection (HCV), 20 patients with HCV infection, 20 patients with ESRD and 20 healthy control donor patients were taken for the examination of biochemical parameters, for the determination of the serum cytokine concentration, and for the molecular diagnostics of HCV. RESULTS Systemic sST2 positively correlated with serum level of urea and creatinine, respectively. Serum sST2 was significantly increased in ESRD HCV+ patients in comparison to HCV+ group. sST2/IL-1, sST2/IL-4 and sST2/IL-23 ratios were significantly increased in serum of ESRD HCV+ patients in comparison to HCV+ patients. Significantly higher systemic level of sST2 and sST2/IL-1 and sST2/IL-4 ratios were measured in ESRD patients compared to non-ESRD patients. CONCLUSION These results suggested that elevated level sST2, as the consequence of renal failure, causes less destruction of liver in HCV infection.

Introduction. Cellulose nanocrystals (CNCs) as attractive natural materials,have numerous applications in the biomedical field. Their unique biomechanicalcharacteristics, surface chemistry, low cost and sustainable naturemake them an engaging alternative to conventional materials and potentiatetheir use as progressive material. Therefore, it is critical to evaluate thecytocompatibility and immunomodulatory properties of nCNCs, which havenot been completely explored. The objective of this study was to examinea dose-dependent effect of native (n)CNCs on cytotoxicity and proliferativeactivity of human peripheral blood mononuclear cells (PBMNCs) in vitro.Methods. PBMNCs, obtained from the healthy blood donors, were cultivatedwith nCNCs. Cell viability was analyzed by flow cytometry assay, whileproliferative activity was determined by MTT, [3H]-thymidine uptake assayand detection of IL-2 production.Results. The cytotoxicity results suggested that no concentration of nCNCs(50-400 μg/ml) affected necrosis of PBMNCs, whereas apoptosis was inducedby the highest concentration of nCNCs compared to control (p<0.05).Unexpectedly, the highest concentration of nCNCs increased the metabolicactivity of PHA-stimulated cells compared to control (p<0.05). In contrastto these findings, lower concentrations of nCNCs (50 μg/ml and 100 μg/ml)stimulated proliferation of PBMNCs (p<0.05 and p<0.001). It was followedby increased production of IL-2 (100 μg/ml) (p<0.001).Conclusion. The results suggest that non-cytotoxic concentrations of nCNCsmodulate the proliferative activity of human PBMNCs, a phenomenon whichhas not been published up to now and which is relevant for further studies.

Introduction. Human monocytes are heterogeneous and plastic cell population with the ability to undergo phenotypic and functional changes as a response to a stimulus from a local microenvironment. Our aim was to determine the potential of human monocytes to differentiate into different cell populations depending on two different cytokines (IL-4 and IL-6) added to cultures as well as to compare their phenotypical and functional characteristics. Methods. Peripheral blood mononuclear cells (PBMNC) were isolated from buffy coats of healthy donors. Monocytes, which were separated from PBMNC by plastic adherence, had been cultivated in Dendritic cell (DC), serum free medium for 5 days, either with granulocyte/macrophage colony-stimulating factor (GM-CSF) alone or with GM-CSF, with addition of interleukin 4 (IL-4) or interleukin 6 (IL-6), respectively. After cultivation, phenotypic characteristics of these cells were analyzed by flow cytometry, whereas the levels of produced cytokines in culture supernatants were quantified by ELISA. The potential of differentiated cells to modulate the proliferation of allogeneic T cells was examined by co-cultivation of these cells with PBMNC. Results. GM-CSF differentiated monocytes into M0/M1 macrophages (MØ). The combination of GM-CSF and IL-4 favoured differentiation of immature DC, whereas GM-CSF and IL-6 transformed monocytes into monocytic myeloid derived suppressor cells (M-MDSC). All cell populations expressed typical monocyte/macrophage markers such as CD14, CD11b, CD16 and CD33, HLA-DR, CD209 and CD86, a co-stimulatory marker. DC and M-MDSC expressed CD1a and CD11c, in contrast to M0/M1 MØ. The expression of HLA-DR, CD1a, CD209 and CD86 was highest on DC. The expression of CD33 and CD16 was highest on M-MDSC, followed by lowest expression of HLA-DR. The potential of promoting T-cell proliferation was highest in cultures of PBMNC with DC, whereas M-MDSC had the opposite, suppressive, effect. These differences correlated with highest production of immunosuppressive cytokines such as IL-10, IL-27 and TGF-b by M-MDSC. Conclusion. This study confirmed the differentiation plasticity of human monocytes, which are influenced by cytokines added in cultures. Phenotypic characteristics of these cells correlated with the production of cytokines involved in modulation of T-cell proliferation.

Progress in diagnosis and treatment has led to a significant improvement in the fate of children born with tetralogy of Fallot, with the perioperative mortality of 2-3% and a 30-year survival rate of 90%. However, the majority of these patients have residual postoperative morphological and hemodynamic disorders, as well as heart rhythm disorders, primarily due to the volume loading of the right ventricle caused by chronic pulmonary regurgitation. Improved surgical techniques have reduced early mortality to less than 3%, but the annual mortality rate has increased 20-30 years after initial surgical remediation, mainly due to unwanted cardiac events. In longitudinal monitoring of patients after repair of tetralogy of Fallot, early detection of morphological and hemodynamic residual disorders both in asymptomatic and symptomatic patients is of great importance. The purpose of this is a timely identification of new therapeutic measures (e.g. pulmonary valve replacement) in order to improve the course and outcome of treatment. Cardiovascular magnetic resonance imaging is a diagnostic method that provides the most precise and accurate estimation of individual parameters of cardiac dysfunction and poor outcomes. Furthermore, it plays a significant role in defining the predictive ability of individual parameters. Previous research has shown that the increase in mortality risk coincides with progressive dilation and right ventricular dysfunction, by means of ventriculo-ventricular interaction and left ventricular dysfunction. Identification of parameters that can predict the high-risk patients for future unwanted cardiac events such as ventricular tachycardia and cardiac insufficiency can assist the customization of a therapeutic approach leading to improvement in quality of life and patient's survival rate.

Myeloid-derived suppressor cells (MDSC) emerged as major factors driving the tumor progression due to numerous immunosuppressive mechanisms they possess. Prostaglandin (PG)E2 is shown critical for the induction of MDSC and their suppressive functions in vivo, but it is poorly understood how it affects the capacity of MDSC to induce different subsets of regulatory T cells (Treg). By using a novel protocol for the generation of mononuclear (M)-MDSC, we showed that PGE2 potentiates the GM-CSF/IL-6-dependent induction of CD33+CD11b+HLA-DR−CD14+ M-MDSC in vitro. PGE2 diminished the capacity of GM-CSF/IL-6 M-MDSC to produce proinflammatory cytokines upon activation and augmented their capacity to produce IL-27, IL-33, and TGF-β. These results correlated with an increased potential of GM-CSF/IL-6/PGE2 M-MDSC to suppress T cell proliferation, expand alloreactive Th2 cells, and reduce the development of alloreactive Th17 and cytotoxic T cells. Interestingly, GM-CSF/IL-6/PGE2 M-MDSC displayed a lower capacity to induce TGF-β-producing FoxP3+ regulatory Treg compared to GM-CSF/IL-6 M-MDSC, as a consequence of reduced IDO-1 expression. In contrast, GM-CSF/IL-6/PGE2 M-MDSC potentiated IL-10 production by CD8+T, Th2, and particularly CD4+FoxP3− type 1 Treg, the latter of which depended on ILT3 and ILT4 expression. Cumulatively, PGE2 potentiated the suppressive phenotype and functions of GM-CSF/IL-6-induced M-MDSC and changed the mechanisms involved in Treg induction, which could be important for investigating new therapeutic strategies focused on MDSC-related effects in tumors and autoimmune diseases.

In 2012, alcohol liver disease resulted in 3.3 million—5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey (per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper–zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Paper description: Ethanol in alcoholic drinks causes liver injury. Cow whey and pumpkin seed oil have shown hepatoprotective effects in many studies. The effects of whey and pumpkin oil supplementation on the blood biochemical parameters of liver function in male Wistar rats subjected to chronic daily intake of 12% ethanol ad libitum were examined. Ethanol consummation in small doses for 6 weeks changed lipid metabolism, but did not induce extensive liver damage. Both whey and pumpkin seed oil showed some protective potential, but pumpkin seed oil and whey together with ethanol elevated lactate dehydrogenase. Abstract: We studied the effects of whey and pumpkin seed oil supplementation on the biochemical parameters in blood serum of male rats after chronic ad libitum alcohol consumption. The levels of AST, ALT, total bilirubin, ALP, LDH, triglycerides, total cholesterol, HDL, LDL, VLDL, triglyceride/HDL ratio, total cholesterol/HDL ratio (cholesterol ratio) and LDL/HDL ratio (index of atherosclerosis) were determined in rats after six weeks of treatment with: (i) ethanol (12% ethanol, ad libitum ), (ii) whey (2 g/kg per day), (iii) pumpkin seed oil (2 mL/kg per day), (iv) both ethanol and whey, and (v) both ethanol and pumpkin seed oil. The results showed no changes in the levels of AST, ALT, total bilirubin, ALP, total cholesterol, HDL and VLDL in alcoholic rats when compared to the controls (fed with a standard laboratory diet ad libitum ) and rats supplemented with whey and pumpkin seed oil. Our results suggest that alcohol consumption in small doses for 6 weeks changes lipid metabolism and significantly elevates the LDL/HDL ratio (index of atherosclerosis) but does not induce extensive liver damage. Ethanol consumption in our experimental conditions lowered the triglyceride level as well as the triglyceride/HDL ratio, suggesting lipid redistribution and the induction of some cardio-protective effect. However, ethanol induced a higher index of atherosclerosis. Pumpkin seed oil showed some protective potential in alcoholic rats by lowering the total cholesterol/HDL ratio, but it elevated the LDH. Whey consumption prevented elevation of the atherosclerosis index, pointing to its protective role, probably through the redistribution of lipids. However, whey in combination with ethanol elevated LDH. https://doi.org/10.2298/ABS180320014R Received: March 20, 2018; Revised: March 30, 2018; Accepted: March 30, 2018; Published online: April 17, 2018 How to cite this article: Radic I, Nestorovic V, Mijovic M, Tatalovic N, Joksimovic B, Lukic V, Mitic M, Adžic M, Blagojevic D, Velickovic S, Bulajic S, Đerkovic B, Miric M, Janicijevic-Hudomal S. The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol. Arch Biol Sci. 2017;70(3):…

OBJECTIVES Interprofessional teamwork is best attained through education that promotes mutual trust and effective communication. The primary aim of the study was to evaluate the impact of interprofessional learning on knowledge about diabetes. METHODS The cross-sectional study included students of medicine, dentistry and nursing at the Faculty of Medicine Foča, Bosnia and Herzegovina. The students were randomly allocated into one of two groups. Group 1 attended an interprofessional course on diabetes while group 2 was divided into three subgroups and each of the subgroups attended an uniprofessional diabetes course. The measuring instrument used in the course in order to assess the participants' knowledge about diabetic care was a test containing multiple-choice questions about diabetes. The Interprofessional Questionnaire was used to explore the attitudes, views, values and beliefs of students regarding interprofessional education (IPE). RESULTS No statistically significant difference in total score on the test was found between the groups at baseline, but at follow-up the difference was highly statistically significant (F=10.87; p=0.002). The students from Group 1 had better results (21.82 points), compared to Group 2 (18.77 points). The statistically significant difference was observed in mean values (t=-3.997; p=0.001), between Groups 1 and 2; the students from Group 1 obtained 20.42 points, which is considered to indicate a respectively positive self-assessment of communication and teamwork skills. However, Group 2 indicated a negative self-assessment of communication and teamwork skills. CONCLUSION The findings suggest that IPE activities may provide health profession students with valuable collaborative learning opportunities.

Abstract Introduction The purpose of the present study was to examine self-perceived stress of health professions students at the Faculty of Medicine Foča, and to explore its association with anxiety, depression and health-related quality of life. Methods The cross-sectional study enrolled 451 students at the Faculty of Medicine (medicine, dentistry, nursing and speech therapy). Survey instruments were distributed at the conclusion of the spring semester during the last required lecture for each year and study programme class. Perceived stress was assessed using the 14-item Perceived Stress Scale. The students were evaluated for symptoms of depression and anxiety, using Zung’s self-assessment inventory for depression and the Spielberger State-Trait Anxiety Inventory (STAI). European Quality of Life-5 dimensions were used for describing and evaluating health. Multivariate analyses were carried out using logistic regression to examine the relationship between the outcome variable and selected determinant factors. Results A high degree of stress was reported by 1.6% of students, while the majority of students had either moderate (70.6%) or low degree (27.5%) of stress. The significant independent factors associated with perceived stress were anxiety score (OR, 0.339; CI 95%, 0.276-0.403) and EQ-5D score (OR, 0.044; CI 95%, 0.033-0.085). A high degree of perceived stress (OR, 0.624; CI 95%, 0.507-0.704), the presence of depression (OR, 0.800; CI 95%, 0.513-1.087), and low quality of life were associated with anxiety (OR, 0.073; CI 95%, 0.018-0.128). Conclusion Higher levels of perceived stress predispose health professions students for anxiety and lower quality of life. The study programme was not a significant determinant of perceived stress sore.

Introduction. Orthodontic treatment is a common dental procedure in developed countries. Assessment of orthodontic treatment need is important for health services planning and population trends monitoring. The aim of this study was to assess the need for orthodontic treatment among children in Foca, Bosnia and Herzegovina. Methods. The study involved 81 students of two primary schools in the municipality of Foca, aged 11-13 years. The subjects underwent clinical examinations, the dental impressions were taken, study models were made and analyzed, and digital photographs of anterior dentition were taken too. Index of Complexity, Outcome and Need (ICON) was used to assess the need for orthodontic treatment. The number of orthodontists, which would be sufficient to meet the needs of this population of children, was estimated. Results. ICON index results showed that 56.8% of children needed orthodontic treatment. There was no statistical significance in the need for orthodontic treatment between the subjects of different gender and age. The study showed that 22.2% of boys and 34.6% of girls needed orthodontic treatment. In relation to age, 21% of eleven- and 21% of twelve-year-olds needed orthodontic treatment and 14.8% of thirteen-year-olds. The incidence of crowding was 80.2%. Crossbite was present in 23.5% of examined students, open bite in 2.5%, deep bite in 29.6% and irregular dental esthetics anterior teeth in 28.4%. Class II/1 malocclusion was found in 39.5% of children, II/2 class in 9.9%, class I in 38.3%, while class III malocclusion was found in 9.9% of examined children. Conclusion. The study shows that a large percentage of children in Foca need orthodontic treatment. Percentage of the need for orthodontic treatment is higher in comparison to most of the countries in Europe and the world. The development of prevention programs and early caries therapy can greatly reduce the need for orthodontic treatment.

Abstract Background: Despite considerable efforts to promote and support clinical practice guidelines (CPGs) use, adherence has often been suboptimal universally. Objectives: The aim of this study was to assess to which extent family physicians (FPs) in Republic of Srpska (RS), Bosnia and Herzegovina (BiH) accept or reject the concept and practice of CPGs and evidence-based medicine (EBM). Methods: A cross-sectional survey was conducted among FPs from the RS, BiH in the period between January and March 2014. Recruitment of FPs was performed combining two different strategies, in-person recruitment at family medicine conferences and mailed invitations. The Questionnaire included19 questions from the existing Healthcare Monitor Questionnaire, divided into four thematic blocks and 11 self-designed questions. Results: Seventy-seven per cent of 131 interviewed physicians reported already using guidelines in the treatment of patients, while 22.9% of them are undecided or disagree. As the reason for rejecting guidelines, 13.0% of the physicians stated they did not support their content, 12.2% found that limited knowledge about guidelines prevented their application, and another 12.2% reported that the current guidelines were not practical enough. All groups would rather not use guidelines developed by a governmental institution. Conclusion: Most physicians in the RS, BiH accept and declare application of CPG. However, a substantial percentage remains sceptical, using CPGs only as an exception, or rejecting them due to their content or impracticability. Key Messages Most physicians declare application of clinical practice guidelines. Substantial percentage of physicians remains sceptical, using CPGs only exceptionally. Further studies are needed to promote the use of CPG and the concept of EBM.

BACKGROUND Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. AIM To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. PATIENTS AND METHODS Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. RESULTS In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. CONCLUSIONS Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.