Aims: Cystic fibrosis is an autosomal recessive multisystem disease caused by a mutation of the CFTR gene. To date, more than 1900 mutations of this gene are known. Studies have shown that the most common mutation is delF508. In Bosnia and Herzegovina, the prevalence of individual mutations in the general population has not been thoroughly studied, so this study aimed to determine the prevalence of the mutation concerning the countries of the region and the rest of the world. Study Design: Retrospective study. Place and Duration of Study: Thirty-nine subjects with suspected Cystic fibrosis were referred to the Center for Genetics of the Medical Faculty in Sarajevo between 2018-2020. Methodology: 29 common CFTR gene mutations were analysed with the ELUCIGENE CF29 v2 kit (Elucigene Diagnostics, UK) using four multiplex PCR. Results: The most common mutation in our study was the F508 deletion, present in 14 subjects (73.68%). R347P and G542X mutations were confirmed in two subjects in the heterozygous state in combination with delF508 (M) 5.26% of each of these mutations. 621+1G>T was found in a homozygous state in one subject, while in another, it was in a heterozygous state in combination with delF508(M) mutation, 10.52%. Mutation 2184 delA was found in one subject in the homozygous state with a total frequency of 5.26%. Conclusion: Subjects with cystic fibrosis in Bosnia and Herzegovina are most often carriers of the delF508 mutation. Considering the existence of many mutations and that it is difficult to test them all, targeting the most common mutations in a clinical environment might help in approving therapy, and increasing patients’ quality of life.

Background: Thiomersal is used as a preservative of some vaccines or as a trace from the pathogen inactivation process in vaccine production. Prophylactic use of paracetamol upon vaccination is still common, even though paracetamol decreases immune response on some vaccines. Considering the cytotoxic and genotoxic potential of thiomersal and paracetamol and possible interaction in vivo, in vitro study was performed. Methods: The genotoxic and cytotoxic effects of thiomersal and paracetamol combination were examined on human lymphocyte cultures by using two methods: analysis of chromosomal aberrations and cytokinesis-block micronucleus cytome assay. Blood samples of three healthy donors were analyzed with the following concentrations of tested substances: thiomersal 1 µg/ml and 0.5 µg/ml, paracetamol 20 µg/ml, thiomersal 0.5 µg/ml with paracetamol 20 µg/ml and thiomersal 1.0 µg/ml with paracetamol 20 µg/ml. Results: The analysis of structural chromosomal aberrations was significantly increased in all treated cultures. In cells treated with the combination of thiomersal 1 µg/ml and 20 µg/ml of paracetamol, the number of aberrations was significantly decreased. Cytokinesis-block micronucleus cytome assay analyses showed significantly increased micronucleus frequency in lymphocytes cultivated with thiomersal 1 µg/ml compared to lymphocytes cultures exposed to thiomersal 0.5 µg/ml. Conclusions: Induction of structural chromosome aberrations and micronucleus is shown as a sign of genotoxicity for the examined concentrations of thiomersal and paracetamol. The suppressing effect of paracetamol on thiomersal genotoxicity in lymphocytes culture treated with thiomersal was shown to be indicative of further examination of paracetamol use in the prevention of genotoxicity.

Purpose Educational interventions have already been shown to positively affect awareness of clinical trials (CTs) among medical students. We aimed to explore basic knowledge and attitudes about CTs among medical students in terms of educational interventions that should be reflected in their further involvement in performing CTs and their role in raising awareness about CTs. Methods This cross-sectional, self-report anonymous online survey involved undergraduate medical students of the Medical Faculty University of Sarajevo enrolled in classes held within the Department of Pharmacology and Toxicology in the academic year 2015–2016. To include all accessible subjects for better representation of the whole population, consecutive sampling was applied. Results Among 142 students who completed questionnaire, 50% of them expressed partial or full agreement with the questionnaire statement that they were satisfied with the available information on CTs. Only 38% said they would participate in a CT, 21% would not, while 41% were not sure. Positive correlations were detected for composite subscale scores of agreement with questionnaire statements conveying the student’s knowledge about ethical and legal aspects of CTs and their perception about reliability/integrity and impact of CTs on medical practice. Conclusion Students have knowledge of the basic design and ethical aspects of CTs. Positive attitudes toward the impact of CTs on medical practice were shown in students of higher years of study, where educational intervention of additional knowledge of CTs was inserted and those students expressed better knowledge of CTs. However, no significant impact was detected between knowledge and willingness to participate in CTs, irrespective of years of study, reflecting the third of students that would participate in CTs. Changes in medical curricula led to the change in students’ knowledge and attitudes regarding CTs as well as their involvement in CTs.

Aim To determine the value of IFN (intzerferon)-α in the patients with systemic lupus erythematosus (SLE) and to correlate IFN-α with values of non-specific biochemical parameters of inflammation (C-reactive protein, leukocytes values, erythrocyte sedimentation rate, albumins and globulins). Methods Research included 55 patients with SLE diagnosis and a control group consisted of 25 healthy subjects (during period 2019-2020). IFN (Interferon)-α and non-specific biochemical parameters of inflammation were obtained using standard protocols. Results IFN-α values were independent of gender (p=0.95). The difference in serum IFN-α values in relation with the age in the SLE group was statistically significant (p=0.036). Only serum globulin was significantly higher (p=0.0023) in IFN-α positive compared to IFN-α negative SLE patients. A statistically significant correlation between the values of IFN-α and globulin was proved (r=0.315; p=0.019). No significant correlation was found between other non-specific biochemical parameters and IFN-α values. Conclusion Increased IFN-α values were observed in younger patients, and the correlation between IFN and globulin was proved.

Background: Thimerosal is an organomercury compound with high mercury content. Thimerosal is located in the market as an effective bacteriostatic in a series of pharmaceutical products, ophthalmic and nasal products, immunoglobulin preparations, and as a preservative in vaccines. Aims and Objectives: Since it is a compound with living content, this study aimed to examine the genotoxic and cytotoxic potential of thimerosal in human lymphocytes culture. Materials and Methods: We used chromosome aberration analysis and cytokinesis-block micronucleus cytome (CBMN-Cyt) assay to test its genotoxic and cytotoxic potential in human lymphocyte culture. Results: Results showed that the frequency of structural chromosome aberrations and CBMN-cyt assay was significantly increased in treated cultures (1 μg/ml and 0.5 μg/ml) compared to the negative control. Conclusion: Obtained results and statistical analysis show that thimerosal is genotoxic and cytotoxic in human lymphocytes in tested concentrations.

INTRODUCTION During the plateletpheresis procedure the number of thrombocytes in the donor's blood significantly decreases, and the levels of the hematocrit (HCT), hemoglobin (Hgb), and leukocyte (WBC) diminish as well. Influence of the cell separator is one of the factors that affects the levels of HCT, Hgb and WBC. In this study, the goal was to determine the value difference of HCT, Hgb, WBC, and platelets after the platelet pheresis process between performance on Fenwal AMICUS and on Fresenius Com Tec. DONORS AND METHODS The criteria for participation: male in the age range of 25-45. We have formed two groups: for both groups - 180 separations were performed on 60 participants were the values of hematocrits, concentration of hemoglobin and number of leukocytes were established before and after separation using the double-needle continuous flow cell separation (DN-CFCS) on two different devices, Fenwal AMICUS device and the Fresenius Com Tec. device. To confirm the statistical differences we have used Student t-test for independent or dependent samples, as well as Mann-Whitney U test as non-parametric alternative. To compare differences between the values of four parameters (P1-P2) from two groups (using two devices - Fenwal AMICUS and Fresenius Com Tec) The possibility of errors were accepted for α<0.05, and the difference between groups as statistical relevant were accepted for p<0.05. RESULTS Statistically significant lower values were noted for all researched parameters after separation on both devices. The statistically significant average values for Hct, Hgb and WBC obtained between two devices, were less than 0.05 (p=0.05). For the platelets (Plt) there was no statistical significant difference (p>0.05 - α=0.05), between average level obtained using either Fenwal AMICUS or Frazenius Com Tec. CONCLUSION The type of cell separator had the influence on the decrease value of the observed parameters.

Background: Multiple myeloma (MM) is a disease of B cell population with excessive secretion of immunoglobulins and presence of free light chains (FLCs) that are by products of immunoglobulin synthesis. Free light chains play crucial role in causing renal damage. Interleukine-6 (IL-6) supports the survival and/or expansion of MM cells by stimulating cells as well as by preventing programmed cell death. Aims and Objectives: The aim of this study was to evaluate serum and urine free light chains (FLC)measurement and compare with IL-6 levels in patients with different stages of Multiple Myeloma (MM) and control group of subjects and to determine their relevance in acute kidney injury occurrence. Materials and Methods: Recruitment of patients with MM (n=62) made the hematologist that followed clinical Solomon-Durie MM classification. Control group consisted of 20 healthy individuals. Results: Patients with MM and renal function injury had significantly higher concentration of urine κ chains compared to control group and group of MM without renal function injury (p<0.005), whereas this difference was not observed when the patients were divided into disease stages groups. Concentration of IL-6 was significantly higher in patients at MM steady stage compared to control group (p<0.001) and significant difference was also detected in patients with MM at relapse stage and control group (p<0.0005). Concentration of IL-6 in MM patients without renal function and with renal function injury was significantly higher compared to control group (p< 0.001; p<0.0005 respectively). Statistically significant correlation was determined between sera κ and urine κ chains (rho=0.437; p<0.01) as well as between urine λ and sera λ chains (rho=0.505; p<0.01) and between urine κ and urine λ chains (rho=0.364; p<0.01). Conclusion: Results showed that urine κ chains, sera κ chains and IL-6 are constructing a fine tuned net and point to conclusion that FLC and IL-6 are important for an early treatment response detection for patients with potentially reversible renal failure.

Introduction : Multiple Myeloma (MM) is a malignant disease of the hematopoietic system, which is classified as malignant tumor of mature B-lymphocytes according to the classification of WHO. Multiple Myeloma is characterized by an uncontrollable monoclonal proliferation of bone marrow plasma cells. The main goal of this study was to present the importance of determining κ and λ chains in serum and urine, as well as their ratio in patients with Multiple Myeloma according to various stages of disease and to compare them with the control group. Methods: The research was conducted at the Clinic for Hematology, University Clinical Center Sarajevo (UKCS). The study included 82 patients of both genders (41 male, 41 female). The control group included 20 healthy volunteers, both genders. The conducted research was a clinical, cross-sectional, descriptive study.Methods of work were Immunoelectrophoresis - for determining Bence-Jones proteins in urine. Determining the concentrations of free light chains in patients with Multiple Myeloma was done using the nephelometric method in serum and urine. Results :Patients with Multiple Myeloma had a statistically significantly higher ratio value of κ/λ chains in serum 3,9 (0,57-22,48) when compared to the control group 1,35 (1,15-1,79) (p=0,025), as well as, significantly higher ratio value of λ chains in urine 0,007 (0,003-0,003) in comparison with the control group 0,0 (0,0-0,0) (p<0,001). Patients with Multiple Myeloma had a statistically significantly higher ratio value of κ/λ chains in urine 18,49 (0,27-73,29) in comparison with the control group  of volunteers 0 (0-0) (p<0.001). Conclusions : The results of our research have shown that the ratio of κ/λ chains in the serum of patients with MM had a significantly higher value 3,9 (0,57-22,48) in comparison with the κ/λ chains in the serum of the control group of volunteers 1,35 (1,15-1,79) (p=0,025). Key words : Multiple Myeloma, light chains, heavy chains, Immunoelectrophoresis

The aim of this study was to determine the values of micronuclei (MN) and structural chromosomal aberrations (CA) in peripheral blood lymphocytes from 200 healthy participants of both genders from general population of FBH and of the age in both genders. Frequency distribution of CTAs and CSAs between male and female groups showed predominance of CTAs over CSAs, independently of gender. The results of this study will be incorporated into reference data base for comparative research in future.

Aim: The aim of this study was to investigate which is the most acceptable model for body mass index evaluation by a standard general pattern, since the one of the oldest bioantropological issues is what is the mass that a person should have, with a certain height, constitution, gender, age and other important determinants. Methods: This prospective study included 78 patients, male gender, divided into two groups: PTSD - group (44 patients) and control group (34 patients). Those were heterogeneous groups according to age and educational structure, where the 30's and 40's are dominant for age and high school education is dominant for education. Calculations of body mass index were performed using standard general pattern, applying different methodologies to obtain the theoretical mass values (Broca's, Azerad's, American insurance company's, Demelov's) Results: There are significant differences between the average values of body mass index calculated by the general standard pattern, depending on the different kind of calculation of theoretical mass used within the PTSD group  and control group.  Conclusion: The correlation coefficient indicates that nutritional index obtained by standard general pattern by use of different methodologies for determining a theoretical body mass is very similar for measurment and calculation of nutitinal state within the PTSD and control group. However, compared to correlation matrix we obtained within the PTSD group the coefficients of correlation  levels were slightly lower within the control group Kayword: body mass index, theoretical mass, PTSD

The aim of this study was to determine the value of micronuclei test (MN) on peripheral blood lymphocytes from 200 healthy participants of both gender from general population of FB&H, as well as to determine if the gender, age or smoking habit have influence on MN frequency. Standard protocol for MN test cultivating and micronuclei analyzing from peripheral blood binuclear lymphocytes have been applied. Results have presented that range of singe values are from 0 to 8 MN in 1000 binuclear cells. It has been determined that gender, age and smoking habit do have influence on MN frequency, especially on 2 MN frequencies. Females on average do have higher values of all variables of MN test than men. It has been proven that smoking habit do have influence on increased number of cells with 2MN, as well. The results of this study will help to form data base as start for comparative research in

Introduction: The met-enkephalin (1-5 Adrenorphin) and tridecactide (alpha-corticotropin 1-13) combination is used in the multiple sclerosis (MS) immuno-modulatory treatment. A testing of cytogenetic effects of met-enkephalin resulted in reductions of lymphocytic aberrations in the in the lymphocytes of the peripheral blood (PBL) of patients with immune-mediated diseases. The aim of this research is to evaluate the in vitro effects of the combination of the met-enkephalin and tridecactide on the number and the type of chromosome aberrations in PBL of the MS patients. Methods: We used blood samples from seven female patients with the diagnosis multiple sclerosis based on a McDonald Diagnostic Criteria. The tested combination, met-enkephalin and alpha-ACTH 1-13 was added at three different concentrations and constant volume. Results: Results showed that the combination of tested substances did not reduce the number of structural aberrations, although the treatment did not result in severe aberrations such as ring, fragmented, and dicentric chromosomes. Furthermore, it elicited an increase in the number of numerical aberrations and aneuploidy after the treatment with the test combo. Conclusion: As the changes in ploidy significantly change the DNA as well as the biochemical cell phenotype, we concluded that more research in this field should be conducted, including both toxicological as well as the pharmacodynamic considerations.