The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer's protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P=0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR)=6.620, 95% confidence interval (CI): 2.214-19.791, P=0.001]. DNMT1 rs2228612 was also associated with ulceration (P=0.045), nodal status (P=0.030), progression (P=0. 007), and stage of disease (P=0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR=0.323, 95% CI: 0.127-0.855, P=0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P=0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR=12.126, 95% CI: 2.345-62.715, P=0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR=37.888, 95% CI: 3.615-397.062, P=0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.

Abstract Background: Many destructive and immunotherapeutic modalities have been used for the management of plantar warts; however, an optimal treatment with high efficacy and absent or low recurrence has not been explored to date. Tuberculin purified protein derivative (PPD) shown promising results for treatment of viral warts without ablation. Aim of Study: To evaluate the efficacy and safety of intralesional (IL) PPD in the treatment of plantar warts. Patients and Methods: Twenty patients with plantar warts were included in this study and divided into two equal groups; group I was treated using IL tuberculin PPD every 2 weeks, group II was treated with IL saline every 2 weeks, till complete clearance or for a maximum of 3 sessions. The patients were followed-up for a period of 6 months. Results: There was a statistically highly significant im-provement in the therapeutic group compared with control group. This modality was well tolerated, with no remarkable side effects and no recurrence in cured patients during follow up period. A significant positive correlation existed between the number of sessions and treatment response. There was a significant negative correlation between the number of lesions and response to treatment. Conclusion: Intralesional PPD is safe and effective treat-ment alternative for the treatment of plantar warts even if they are recalcitrant or multiple, with no post-procedural downtime and better results and patient satisfaction.

Background Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. Methods A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Methylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non-malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver-operating characteristics (ROC) analysis and statistical tests of hypothesis. Results Methylation level of tested genes is generally low but significantly decreased in tumor tissues (ASC/TMS1/PYCARD, P<0.0001; MyD88, P<0.0002), which correlates with increased protein expression. Three CpG sites were identified as promising diagnostic marker candidates; CpG11 (-63 position) in ASC/TMS1/PYCARD and CpG1 (-253 position) and 2 (-265 position) in MyD88. The association study showed that the methylation status of the ASC/TMS1 CpG4 site (-34 position) in malignant and non-malignant tissues is associated with the overall survival (P=0.019) and the methylation status of CpG8 site (-92 position) is associated with TNM-stage (P=0.011). Conclusions The methylation status of the ASC/TMS1/PYCARD and MyD88 promoters are promising prognostic biomarker candidates. However, presented results should be considered as a preliminary and should be confirmed on the larger number of the samples.

We propose a novel strategy to construct optimal controllers for continuous-time nonlinear systems by means of linear-like techniques, provided that the optimal value function is differentiable and quadratic-like. This assumption covers a wide range of cases and holds locally in general. The proposed strategy avoids solving the Hamilton-Jacobi-Bellman (HJB) equation, that is a nonlinear partial differential equation, which is known to be hard or impossible to solve. Instead, the HJB equation is replaced with an easy-solvable state- dependent Lyapunov matrix equation without introducing any approximation. We achieve this exploiting a linear-factorization of the underlying nonlinear system and a policy-iteration algorithm (PI) to yield a linear-like PI for nonlinear systems. The proposed control strategy solves optimal nonlinear control problems in an exact, yet still linear-like manner. We prove optimality of the resulting solution and illustrate the results via two examples.

OBJECTIVE The purpose of this study was to evaluate the efficiency of the anticholinergic therapy with oxybutynin and the effects of daily transcutaneous tibial nerve stimulation (TTNS) on the quality of life of patients with an overactive bladder (OAB) and multiple sclerosis (MS). PATIENTS AND METHODS The study was designed as a randomized controlled trial. The patients who suffer from MS underwent urodynamic tests which showed that they had an OAB. The tests used to assess symptoms and quality of life were Overactive Bladder Questionnaires (OAB-q) SF. Patients were divided into 2 groups of 30 patients each. The first group received a 5 mg oxybutynin tablet twice a day for 3 months and the second group had TTNS every day for 3 months. RESULTS The anticholinergic therapy showed a statistically significant improvement in all symptoms and quality of life (P<0.001). Side effects such as dry mouth were observed in about 35% of patients. The results of the study TTNS daily therapy showed good performance in the reduction all clin ical symptoms of the bladder and improved quality of life, with statistical significance (P<0.05) and with no side effects. It was found that the improved quality of life parameters and the reduced symptoms were more statistically significant in the treatment with oxybutynin tablets than TTNS therapy (P<0.001). CONLCUSION Our recommendation for the treatment of OAB is oxybutynin in doses of 2x5 mg. If a patient can not tolerate anticholinergic drugs, daily TTNS is recommended to reduce OAB symptoms and improve quality of life, without side effects.

Introduction: Although sense of security in mothers is not clearly specified in literature, most important factors that make it up in women that do not have issues in pregnancy are social support, prenatal health care and partner’s support. Psychological factors play a key role in recognizing fear of childbirth, distinguishing anxiety from clinical depression. Recognizing risk factors and adequate intervention support would significantly reduce fear. Aim: to analyze development of mother’s sense of security during the postnatal period and establish the differences between two study groups. Methods: The Cross section study was conducted in 2017 in the Public Institute for Health care Protection of Women and Maternity in Canton Sarajevo. Using random method in the study were included 395 mothers. The research instrument was PPSS-instrument and modified questionnaire. Results: Postnatal sense of security in n=395 of the mothers on average was 49, 61±7, 6. Mothers’ sense of security during the first week after their child’s birth differed significantly (p=0.004) between mothers whose husband actively participated in psychophysical preparation for childbirth. Development of parents sense of security is in direct connection with psycho-physical preparations of pregnant women for labor only when both partners took active part in preparations for labor. Conclusion: Postnatal sense of security in parents is a term that has not been researched enough and it requires further studies. Bachelor degree in health care/graduated nurse/midwife, especially in primary health care field, according to her competencies would be able to independently create and work on promoting prevention programs through holistic approach with individuals and families.

Objectives: To assess the prognostic value of pentraxin 3 (PTX3) in patients with ST-elevation myocardial infarction (STEMI) after bare-metal stent (BMS) implantation. Methods: In this prospective study, PTX3, interleukin (IL-6), IL-10, high-sensitivity c-reactive protein (hsCRP), and cardiac troponin I (cTnI) plasma values were determined before and 24hours after BMS implantation in 97 consecutively enrolled patients with STEMI who were admitted to University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina between February 2016 and February 2017. Patients were followed for 24 months to assess major adverse cardiovascular events (MACEs). Results: At 24 hours after percutaneous coronary intervention (PCI), plasma values of PTX3, IL-6, hsCRP, and cTnI were significantly increased; and IL-10 levels were significantly decreased compared with the values determined before PCI. Patients with MACEs had significantly higher plasma PTX3 levels at 24 hours after BMS-PCI than in patients without MACEs. Patients with PTX3 plasma values ≥5042 ng/ml had a significantly higher risk of MACEs than patients with PTX3 levels <5.042 ng/mL. Pentraxin 3 levels exhibited strong and significant correlations with IL-6 and IL-10 levels. Pentraxin 3, cTnI, and IL-6, but not hsCRP levels have showed independent association with MACEs, according to the multivariate Cox regression analysis. Conclusion: Pentraxin 3 might be better serum prognostic marker than IL-6, IL-10 or high sensitivity CRP for MACEs after BMS-PCI. It might help to make better risk stratification of those patients who are undergoing BMS-PCI.

Introduction: Colorectal cancer is the third most common cancer in the male and female population. Surgical treatment of colorectal cancer is based on tumor resection and removal of associated lymph glands. Aim: The aim of the paper is to present data from a five-year retrospective study of the surgical treatment of colorectal cancer at the Clinic for General and Abdominal Surgery at the Clinical Center of the University of Sarajevo. Methods: This is a retrospective five-year clinical trial (2014-2018) of patients with and surgically treated for colorectal cancer at the Clinic for General and Abdominal Surgery at the Clinical Center of Sarajevo University. Results: In the 2014-2018 period, n = 11 172 patients were hospitalized at the Clinic, of which n = 732 were surgically treated for colorectal cancer. 69.80% were operated in an elective program. 30.20% were made as emergencies. 51.09% were male patients and 48.36% were female patients. 97.20% were made by open technique. 2.10% operated by minimally invasive procedure. the most common type of colon tumor is Adenocarcinomas are the most common with 79%. Conclusions: Better prevention and early detection are required to reduce the incidence of patients, which ultimately leads to more effective treatment and longer survival of colon cancer patients. Operative surgical principles must be adapted to modern trends, minimally invasive procedures (laparoscopic surgery, robotic surgery).

Summary The apple (Malus domestica Borkh.) possesses a number of health-promoting properties. The main beneficial effects of apple fruits on human health are associated with the antioxidant properties of components synthesising in apple fruits during their growth and development. Phenolic compounds and flavonoids are such components that contribute significantly to the antioxidant capacity of fruits, thus enhancing their health properties. The purpose of this study is to compare the antioxidant properties (namely antioxidant capacity, ascorbic acid, total phenolic and flavonoid contents) of the ‘Idared’ and ‘Braeburn’ apple cultivars, grown under optimal growing conditions in the Goražde area. Ascorbic acid contents were estimated using the 2.6-dichlorophenolindophenol titration method, whereas total phenolics were determined using the Folin-Ciocalteu method. Furthermore, total flavonoids were determined using the aluminium chloride colorimetric assay, whereas the ferric reducing/antioxidant power assay was used to determine the total antioxidant capacity of the apple fruits examined. The average values of the ascorbic acid, the total phenolic and flavonoids contents, and the total antioxidant capacity of the ‘Idared’ apples under consideration were 8.09 mg 100 g−1, 34.56 mg gallic acid equivalents 100 g−1, 12.62 mg catechin equivalents 100 g−1 and 323.28 μmol Fe2+ 100 g−1of fresh weight, respectively. The average values of the total phenolic and flavonoids contents, as well as the antioxidant capacity of the ‘Braeburn’ apples examined were as follows: 8.89 mg 100 g−1, 33.4 mg gallic acid equivalents 100 g−1, 13.56 mg catechin equivalents 100 g−1 and 367.01 μmol Fe2+ 100 g−1 of fresh weight, respectively. The analyses performed indicate that the differences recorded in the parameter values between the apple cultivars ‘Idared’ and ‘Braeburn’ were statistically non-significant. A correlation data analysis confirmed that phenolic compounds are the carriers of the antioxidant activity of apples.

Abstract The aim of this paper is to examine performance of pension funds in Croatia, or more precisely, to measure the technical efficiency of mandatory pension funds. The main role of the pension funds is to collect and invest the money contributed by the employer or the employee during working years until retirement. Therefore, development of pension funds as institutional investors is especially important for capital markets as well as for the whole economy. By applying the methodology of data envelopment analysis on a sample of 12 DMUs, i.e. four mandatory pension funds divided into three categories (A, B or C) for 2015-2018 period, we provide further evidence on their efficiency level. The results have shown very small differences among relative inefficient pension funds.