Abstract The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. Among them, CYP2C9 and CYP2C19 are clinically important, as they can mediate severe toxicity, therapy failure, and increased susceptibility to cancer and other diseases caused by chemicals. The aim of this study was to determine the prevalence of pharmacologically most important allelic variants of the CYP2C9 and CYP2C19 genes in the general population of the Republic of Srpska (Bosnia and Herzegovina) and to compare them with other populations. For this purpose we determined the genotype profile and allele frequency of 216 randomly selected healthy volunteers using real-time polymerase chain reaction (RT-PCR). The prevalence of the CYP2C9 *2 and *3 alleles was 13.6 and 7.4 %, respectively. Based on these frequencies, of the 216 participants four (1.86 %) were predicted to be poor metabolisers, 78 (36.11 %) intermediate, and the remaining 134 (62.03 %) normal metabolisers. Based on the prevalence of CYP2C19 *2 and *17 variants – 16.2 and 20.4 %, respectively – nine (4.17 %) were predicted to be poor, 57 (26.39 %) rapid, and nine (4.17 %) ultra-rapid metabolisers. We found no significant differences in allele frequencies in our population and populations from other European countries. These findings suggest that genetically determined phenotypes of CYP2C9 and CYP2C19 should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.

SUMMARY The aim of this cross-sectional study was to investigate the occurrence of chromosomal abnormalities through the frequency of micronuclei and other genomic damage markers in patients with chronic generalized periodontitis and without periodontal disease. Micronucleus assay was performed in exfoliated gingival epithelial cells of 35 patients with generalized chronic periodontitis and 30 control subjects with healthy periodontium. Full mouth clinical examination was performed to define periodontal condition. The mean number of cells with micronuclei observed in chronic periodontitis and control groups was 1.8 (±1.49) and 2.0 (±1.34), respectively. Differences between the groups were not significant (p=0.574). Compared to control subjects, patients with chronic periodontitis showed a significant increase in the number of binucleated cells (p≤0.001) and number of cells with nucleoplasmic bridges (p=0.042). Study results indicated that chronic periodontitis was not associated with higher occurrence of chromosomal damage in gingival cells compared to individuals with healthy periodontium.

Abstract At the end of December 2019, first identified cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started emerging. Ever since the emergence of the first case of infection with SARS-CoV-2 or COVID-19, it became the hottest research topic of numerous studies, in which scientists are trying to understand the path of infection, transmission, replication and viral action, all in order of finding a potential cure or vaccine applying various fundamental principles and methodologies. Using in silico method via AutoDock Vina 1.1.2., we analysed the binding affinity of six selected compounds from grapefruit seed extract (GSE) (narirutin, naringin, naringenin, limonin, ascorbic acid and citric acid) to SARS-CoV-2 main protease Mpro (PDB ID: 6Y84), using acetoside, remdesivir and gallic acid as a positive controls of binding affinity. Results showed highest affinity (rmsd l.b. 0.000; rmsd u.b. 0.000) for narirutin (-10.5), then for naringin (-10.1), acetoside (-10.0), limonin (-9.9), remdesivir (-9.6), naringenin (-8.2), ascorbic acid (-6.7), citric acid (-6.4) and gallic acid (-6.4), all expressed in kcal/mol. Our findings suggest that selected compounds from grapefruit seed extract represent potential inhibitors of SARS-CoV-2 Mpro, but further research is needed as well as preclinical and clinical trials for final confirmation of inhibitory functionality of these compounds.

Possibilities to use unmanned aerial vehicles (UAVs) are rapidly growing. With the development of battery technologies, communication, navigation, surveillance, and autonomous systems in general, many UAVs are expected to operate at relatively low altitudes. Thus, the problem of UAV noise impact on human health and well-being will be more pronounced. In this paper, we conducted noise measurements of two UAVs of different performance (quadrotor and hexarotor) in flying up and down, hovering, and overflight procedures. Respondents of good hearing who were confirmed by audiogram measurement and had participated in the survey during UAV noise measurement gave their subjective assessments on the UAV noise perception. UAV noise measurements and subjective respondents’ assessments were analysed and related. UAV noise analysis showed that the parameters measured at the same measurement point for the hexarotor were higher than those for the quadrotor in flying up and down and flying-over procedures. Low frequency noise was present in the noise spectrum of both drones. Participants were able to distinguish between the noise of UAVs and had a generally more negative experience with the hexarotor. Regardless of the noise perception, more than 80% of the respondents believe there are more pros than cons for UAV introduction into everyday life.

The aim of this research was to examine the impact of aircraft noise on communities near the Belgrade Airport by conducting short-term noise measurements. Apart from the noise abatement procedure published in the Aeronautical Information Publication for Belgrade Airport, there are still neither publicly available reports of the actual efforts made towards the aircraft noise reduction nor the description of the current noise situation. In order to estimate the current noise situation, eighteen aircraft overflight noise measurements were taken in two settlements in specific sound-sensitive community areas around the Belgrade Airport. The results showed that level differences between background noise and aircraft overflights were higher than 10 dB for each measurement and could be considered significant. Furthermore, preliminary compatibility analysis with acoustic zoning was performed. Average daily noise levels were estimated from these short-term measurements and were compared to legal noise limits for different acoustic zones. The results indicate that in some cases noise levels exceed the legal threshold, which should encourage land use planners to include the issue of Belgrade acoustic zoning on the agenda, but also prompt Belgrade Airport to implement continuous noise and flight tracks monitoring.

Abstract Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms – direct or via transcription factors such as NRF2 and NF-κB – and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening.

Bosnia and Herzegovina represents a very suitable experimental space for the analysis of integrative policy in the conditions, war and long-lasting crisis, of a devastated society which, due to the challenges of history, is deeply divided. In such a space, applying the analytical model designed and used by Seymour Lipset and Stein Rokan, the paper deals with the detection of social divisions that underlie party preferences in the 1990 elections for the Assembly of the Socialist Republic of Bosnia and Herzegovina. Analyzes of pre-election and post-election activities of political entities show the existence of an important link between ethno-confessional characteristics and attitudes on political issues and party preferences, which in accordance with the used theoretical model creates preconditions for talking about social divisions that have turned into party divisions. It can be determined that they are bh. political parties formed, with all their specifics, on the basic lines of Bosnia and Herzegovina social divisions. In the analysis of the relationship between social and political space and the influence of the structure of society on political relations and divisions, it is possible to determine that party divisions and divisions, their segmentation and polarization are conditioned, above all, by the depth and dynamics of fundamental Bosnia and Herzegovina social divisions. The divisions that emerged in the pre-election period of 1990 (we can conditionally define them as divisions communism vs anti-communism) were pushed into the background in the first post-election year and priority was given to the split that S. Lipset and S. Rokan defined as the center-periphery split. (or the territorial-cultural split as, after adaptation, Professor Nenad Zakošek called it). The second part of the paper presents an overview of the most important political parties in the 1990 elections and continues to examine the applicability of S. Lipset and S. Rokan's theory of turning social divisions into party divisions, this time in the first year of ethno-confessional parties in Bosnia and Herzegovina. Analyzing the basic lines of historical ethnic and confessional divisions in Bosnia and Herzegovina society and in the sphere of political (sub) system through indicators such as: predominant (ethnic, confessional, linguistic, cultural and regional) identifications, the relationship between ethno-confessional and civil, the relationship to the rights and freedoms guaranteed in Bosnia and Herzegovina. According to the Constitution, the attitude towards different solutions to the state question (remaining in the common state of Yugoslavia vs. the independent Republic of Bosnia and Herzegovina) tested the hypothesis that historical lines of ethno-confessional splits represent the basic determinant of political goals. It can be seen that the territorial-cultural divide (primarily in the form of center-periphery conflict) is actually a kind of complete split, given that it is a split that involves conflict between stable social groups (residents of the center and periphery but also members of different ethnic and confessional communities). In the Bosnia and Herzegovina case, these are (ethnic and confessional) communities that have different views on the most important issues of the social organization of the common state, which results in open conflict on the political scene in the form of voting for different political options, which can be transformed by ethnopolitical elites. (very easily) into various forms of violence against others and different in the territory that is under their political (and police) control.

Introduction: Dental implantology is the branch of dentistry that is gaining greater significance because a larger number of patients come with requests of implant placements. During dental implant placements, with patients with whom operation is carried out in the mandible, very frequently nervus alveolaris inferior can be injured. The nerve injury may occur during the implant placement, but the nerve may also be injured in case of harvesting of intraoral bone graft. During the bone graft harvesting, but also during any other procedure in the dentistry that entails working on vestibular side of corpus of the mandible, in order not to injure the nervus alveolaris inferior, it is important to familiarize oneself with the distance of the nerve from the outer vestibular cortex of the mandible. The objective of the study was to assess the vestibular bone thickness of the mandible in relation to the mandibular canal with the help of analysis of cone-beam computed tomography (CBCT) images.Methods: It was accessed the database of CBCT images taken at the School of Dental Medicine at the University of Sarajevo, where out of 700 reviewed CBCT images, an analysis of 322 CBCT images was conducted that satisfied inclusion criteria of the study. CBCT images were taken using of ORTHOPHOS SLX imaging unit. The measurement was conducted by Sidexis program on cross-section of CBCT image. The measurement of vestibular bone thickness was performed, by measuring the distance from the lateral wall of the mandibular canal to buccal mandibular compact bone, in the region of the second premolar, of the first and the second molar.Results: There were statistically significant differences in vestibular bone thickness between men and women on both sides in the region of the second premolar (p < 0.001) and first molar (p = 0.016 right, p = 0.018 left). T-test demonstrated no statistically significant difference in the vestibular bone thickens between men and women on either side in the case of vestibular bone thickness of the center of the second molar (p = 0.397 right, p = 0.743 left).Conclusion: Values of vestibular thickness of the mandible are larger with men than with women in all measuring points; however, statistically more significant differences between genders have been detected in the second premolar and center of the first molar.

The task of every government, especially during the Covid-19 pandemic, is to provide services and goods for citizens and to maintain economic order. Therefore, the combination of legislation, the judiciary and administration is inevitable. Moreover, public administrations must transform the way they function by using more information and communication technology in order to remain responsive and efficient. This challenge was further revealed during lockdowns in individual countries, which affected their social and economic development. The solution to that challenge is the implementation of e-government in the public sector. It also increases innovation in governance processes as well as efficiency and effectiveness by offering more participative opportunities to citizens. Hence, a mature level of e-government development also arises. Nevertheless, there are significant differences among the levels of e-government development in the EU-28. The aim of this article is to assess the influence of e-government maturity on government effectiveness and efficiency in the EU-28. In order to obtain empirical results, a two-stage least square regression (2SLS) was applied. The empirical results show that e-government maturity positively and significantly contributes to enhancing government effectiveness and efficiency in the EU-28. In addition, the rule of law plays an important role in each stage regression model. Based on the empirical results, we can conclude that e-government is inevitable and should ensure the proper functioning of public administration during the Covid-19 pandemic.  

Recent research in AI ethics has put forth explainability as an essential principle for AI algorithms. However, it is still unclear how this is to be implemented in practice for specific classes of algorithms—such as motion planners. In this paper we unpack the concept of explanation in the context of motion planning, introducing a new taxonomy of kinds and purposes of explanations in this context. We focus not only on explanations of failure (previously addressed in motion planning literature) but also on contrastive explanations—which explain why a trajectory A was returned by a planner, instead of a different trajectory B expected by the user. We develop two explainable motion planners, one based on optimization, the other on sampling, which are capable of answering failure and constrastive questions. We use simulation experiments and a user study to motivate a technical and social research agenda.

Cadmium (Cd2+) is toxic metal and environmental pollutant. Accumulation of cadmium in the kidney results initially in proximal tubule dysfunction. Although Cd2+ toxicity is well documented, all mechanisms that are involved in the early stages of nephrotoxicity, especially considering low micromolar concentrations of Cd2+ ions are still unknown. The Aim of this study was to investigate the effects acute exposure to different peritubular micromolar concentrations of cadmium (0.25, 0.50, 1.0, 2.0, 3.0, 5.0 μmol/L) on the peritubular cell membrane potential in proximal tubular cells of frog kidney. The experiments were performed on isolated, doubly perfused kidneys of Rana esculenta of both sexes. Aortic and portal vein were cannulated in order to perfusate luminal and peritubular cell membraine. In controled conditions, Ringer solution was simultaneously used to perfusate both cell membraines. Cadmium chloride (different concentrations: 0.25, 0.50, 1.0, 2.0, 3.0, 5.0 μmol/L) were added to the peritubular perfusate separately, by switching the peritubular perfusate from the control Ringer solution to Ringer solution with addition of cadmium ions. Peritubular cell membrane potentials (PD) were measured with conventional 3 mol/L KCl microelectrodes. The peritubular application of different micromolar Cd2+ concentrations led to a rapid, sustained, reversible hyperpolarization of the peritubular cell membrane: 0.25 µmol/L, by −3.3±0.4 mV (n=8, p<0.001); 0.50 µmol/L, by −3.0±0.5 mV (n=11, p<0.001); 1.0 µmol/L, by −2.9±0.6 mV (n=8, p<0.01); 2.0 µmol/L, by −4.2±0.4 mV (n=13, p<0.01); 3.0 µmol/L, by −3.4±0.3 mV (n=14, p<0.001); 5.0 µmol/L, by −3.0±0.4 mV (n=10, p<0.001). After switching the perfusion from Ringer solution with addition of cadmium ions to control Ringer, the peritubular membraine potential returned to the average values that were maintained before the peritubular Cd2+ application (p>0.05). Comparing the effect of different Cd2+ concentrations, there was no difference in the hyperpolarization of the peritubular cell membrane (p>0.05).Each cell served as its own control. Different low micromolar concentrations of Cd2+ provoked rapid and sustained hyperpolarization of peritubular membrane potential that did not show concentration-dependent response.

Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications. A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs. At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p<0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p<0.05), P04 (p<0.001), CRP (p<0.011), SBP and DBP (p<0.05). HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.