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Marija Milić, J. Dotlic, G. Rachor, G. Asmundson, B. Joksimović, J. Stevanović, D. Lazic, Zorica Stanojevic Ristic et al.

This study aimed to generate a linguistic equivalent of the COVID Stress Scales (CSS) in the Serbian language and examine its psychometric characteristics. Data were collected from September to December 2020 among the general population of three cities in Republic of Serbia and Republic of Srpska, countries where the Serbian language is spoken. Participants completed a socio-demographic questionnaire, followed by the CSS and Perceived Stress Scale (PSS). The CSS was validated using the standard methodology (i.e., forward and backward translations, pilot testing). The reliability of the Serbian CSS was assessed using Cronbach’s alpha and McDonald’s omega coefficients and convergent validity was evaluated by correlating the CSS with PSS. Confirmatory factor analysis was performed to examine the construct validity of the Serbian CSS. This study included 961 persons (52.8% males and 47.2% females). The Cronbach’s alpha coefficient of the Serbian CSS was 0.964 and McDonald’s omega was 0.964. The Serbian CSS with 36 items and a six-factorial structure showed a measurement model with a satisfactory fit for our population (CMIN/DF = 4.391; GFI = 0.991; RMSEA = 0.025). The CSS total and all domain scores significantly positively correlated with PSS total score. The Serbian version of the CSS is a valid and reliable questionnaire that can be used in assessing COVID-19-related distress experienced by Serbian speaking people during the COVID-19 pandemic as well as future epidemics and pandemics.

B. Joksimović, Milica Radović, B. Mitrović, Sasa S. Pancevacki, V. Samardzic, M. Lačković, M. Obradović, E. Isenovic et al.

B. Mijovic, B. Joksimović, Z. Maksimović, Slobodan Stanić, Milena Božinović, Radmila Balaban, Biljana Čančar

Introduction. Inhalation of coal dust during blasting in brown coal mines has been shown to lead to a lung disease called pneumoconiosis. There is very little data in the literature on the direct impact of coal on the quality of life of people who work in coal mines as well as the body's immune response to the effects of coal dust. The aim was to examine the immune response to exposure to coal dust in miners in a brown coal mine and whether mine workers have poorer quality of life compared to those not exposed to coal dust. Methods. This is a cross-sectional study among 100 employees in the Brown Coal Mine in Ugljevik, of which 50 of them are exposed to coal dust on a daily basis. Blood samples were taken from all subjects to test for the presence of cytokines IL-2, 4, 5, 9, 10, 13, 17A, 17F, 21, 22, IFN-g and TNF-a. The quality of life of employees was measured using a questionnaire for self-assessment of physical and mental health (36-item Short-Form Health Survey, SF-36). Results. Group of miners had a significantly (p<0.05) higher concentrations of pro-inflammatory cytokines IL-6, IFN-g, IL-17A and IL-22 when compared to the control group. Subjects from the control group had significantly (p<0.05) higher concentrations of anti-inflammatory cytokines IL-4 and IL-10 when compared to the group of miners. The quality of life was significantly (p<0.05) better in the control group when compared to the group of miners. Conclusion. Physical functioning, general health, mental health and Physical component summary were significantly poorer in the group of miners. Exposition to coal dust led to a significant increase in the production of pro-inflammatory cytokines and a decrease in the production of anti-inflammatory cytokines.

B. Joksimović, B. Mijovic, Biljana Čančar, Milena Božinović, Z. Maksimović, Slobodan Stanić, Djordje Jevtic

Pneumoconiosis of workers in brown coal mines is an occupational disease, a global public health problem and a serious disease of the lung parenchyma. If it is not prevented, it leads to irreversible changes in the lungs with complications. The disorder occurs after prolonged exposure to coal dust containing high concentration of free crystalline silica. Data in literature regarding its health impact on people working in coal mines are relatively scarce. Recently, there has been an increase in miners’ pneumoconiosis, which requires a stricter policy to protect workers in the mines. There are two classical types of CWP: simple and complicated. The main diagnostic method of CWP is based on a specific X-ray finding, and the auxiliary method of choice is spirometry. The pathophysiological mechanism of CWP formation is not fully known, although it has been shown that damage to the lung parenchyma goes through three phases caused by effect of lung cells exposure to coal dust. Studies show that cytokines play an important role in inflammation and the immune response as mediators of toxic and pathogenic effects in CWP. A link between exposure to coal dust in brown coal mines and the development of CWP has also been demonstrated, with a consequent reduction in the physical and psychological quality of life of workers in the mines.

Lj. Krsmanović, Siniša Šolaja, N. Arsovic, B. Joksimović, Z. Dudvarski, Gabrijela Šolaja

Introduction. Tinnitus is a perception of a sound in the ears in the absence of acoustic stimulation whose pathophysiological mechanisms have not been evaluated yet. Approximately, 1-2% of people report distress which can negatively affect their daily performance. Our study aimed to assess the incidence of anxiety in patients with tinnitus. Methods. The study was designed as a cross-sectional study. The participants were divided into two groups: a group of 73 patients with tinnitus (with two subgroups in relation to the duration of tinnitus-less than one year and more than one year) and a control group of 43 patients without tinnitus. We examined the presence of anxiety in all patients using the Burns Anxiety Inventory (BAI). The quality of life of all patients was estimated by Tinnitus Handicap Inventory (THI). Results. In the group of patients with tinnitus, 56.2% of them had mild and 24.7% moderate hearing loss, while 27.7% of respondents from control group had mild and 8.5% moderate levels of hearing impairment. THI results showed that patients with tinnitus less than 1 year had a significantly (p= 0.002) higher level of disorders in daily life, compared with the group who had tinnitus for more than 1 year. The 30.8% of respondents had minimal anxiety, 26.7% borderline anxiety, 17.5% mild anxiety, the same percentage of respondents moderate, 5% severe, while 2.5% had extreme anxiety based on BAI. Conclusion. Anxiety can be considered as potentially significant modulators of changes in brain structures observed in people with tinnitus.

Slađana Đorem, G. Odovic, A. Lukić, Jelena Milic, B. Joksimović, Milena Božinović

Introduction. Higher level of knowledge and frequent contacts with peers with disabilities can influence the emergence of more positive attitudes of students towards peers with disabilities. In regard to that, our aim was to test the importance of knowledge, contact frequency and other possible factors influencing attitudes of students toward disabled peers. Methods. The study included 140 students of 4th and 5th grade of primary schools. The research was conducted in the period from December 2020 to March 2021 in two primary schools. The Chedoke McMaster scale was used to examine students' attitudes toward peers with disabilities, while Contact with Disabled Persons Scale and the Children's Knowledge about Handicapped Persons Scale were used to assess frequency of contact and knowledge about disabilities. Results. Girls showed a significantly higher level (25.21±6.21) of frequency of contacts with students with disabilities compared to boys (19.66±7.30) (p=0.043) and higher level of knowledge (27.88±5.88) about disabilities compared to boys (25.50±4.69) (p=0.009). Respondents who attended school together with children with disabilities (31.07 ± 8.41) showed a significantly higher level of frequency of contacts with students with disabilities compared to respondents who did not attend school with peers with disabilities (13.72±6.32) (p=0.001). Conclusion. Higher level of knowledge and frequent contacts with peers with disabilities does not have influence on the emergence of more positive attitudes of students towards peers with disabilities.

R. Lukić, M. Ćupić, N. Gajović, M. Jurišević, Željko Mijailović, Bojana Davidovic, B. Kujundžić, B. Joksimović et al.

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.

M. Vasiljević, S. Tomić, M. Bekić, B. Joksimović, D. Vučević, M. Čolić

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.

B. Joksimović, S. Tomić, M. Bekić, M. Vasiljević, D. Vučević, M. Čolić

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.

M. Račić, A. Virijević, N. Ivković, B. Joksimović, Vedrana R Joksimović, B. Mijovic

Aims. The aim of this study was to examine self-perceived compassion fatigue and compassion satisfaction among family physicians in Bosnia and Herzegovina and describe potential contributing factors. Methods. The cross-sectional study enrolled 120 family physicians. Professional quality of life compassion satisfaction and fatigue version 5 (ProQOL5) was used to assess compassion satisfaction and two components of compassion fatigue, secondary traumatic stress and burnout. The symptoms of chronic fatigue were evaluated using the Chalder fatigue scale. Results. The majority of family physicians had moderate levels of compassion satisfaction (70%), burnout (75%) and secondary traumatic stress (55.8%). Family physicians with higher levels of secondary traumatic stress reported chronic fatigue (p = 0.001), longer length of service (p = 0.024) and residency training (p = 0.041). Chronic fatigue (p = 0.001), living in a rural environment (p = 0.033), larger size of practice (p = 0.006) and high number of patients with chronic disease (p = 0.001) were associated with a higher risk of burnout. Conclusion. Family physicians with large practices, long years of experience, a high number of chronically ill patients and experiencing chronic fatigue are at risk of developing compassion fatigue. A systematic exploration of compassion fatigue in relation to working conditions might provide an appropriate starting point for the development of preventive interventions.

S. Tomić, B. Joksimović, M. Bekić, M. Vasiljević, M. Milanović, M. Čolić, D. Vučević

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.

I. Radic, M. Mijović, N. Tatalović, M. Mitić, V. Lukić, B. Joksimović, Z. Petrovic, S. Ristic et al.

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.

I. Radic, V. Nestorovic, M. Mijović, N. Tatalović, B. Joksimović, V. Lukić, M. Mitić, M. Adzic et al.

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):…

M. Račić, B. Joksimović, Smiljka Cicmil, S. Kusmuk, N. Ivković, N. Hadživuković, Milan Kulić, B. Mijovic et al.

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.

M. Račić, Radica Todorovic, N. Ivković, S. Mašić, B. Joksimović, Milan Kulić

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.

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