Introduction: Over the past 15 years, direct oral anticoagulant (DOAC) drugs have replaced vitamin K antagonists in a number of indications requiring oral anticoagulant therapy. Review work: The article written is an overview of the most important information related to the use of DOAC drugs in the secondary prevention of venous thromboembolism (VTE). The first randomized studies with dabigatran, rivaroxaban and apixaban are presented, which introduced these drugs into clinical practice in the first step, and then enabled the prolonged safe use of these drugs in the secondary prevention of VTE. Studies have also been described as current attitudes for the use of DOAC in patients with VTE associated with malignancy and antiphospholipid syndrome. An assessment of the risk of bleeding in patients with DOAC is also presented. Finally, we briefly presented the results of the use of DOAC in the treatment of pulmonary embolism in a group of patients from the regional PE registry.

Behavioral economics suggests that people do not always decide rationally but are even predictably irrational. This gives rise to the concept of nudge, which creates an architecture of choices that encourages people to behave as they wish. Loss aversion is one of the best-known phenomena in behavioral economics and a central notion of the prospect theory. The main idea behind this phenomenon is that losses hurt more than gains feel good. The framing effect is a bias where people choose some options differently, depending on whether they are presented as a gain or a loss. In this quasi-experimental study, the authors examine the role of loss aversion and framing effects on students' engagement and academic success. This study aims to test the hypothesis that students will have a stronger reaction to the reduction of awarded points, as opposed to an increase of awarded points, as they progress through the course. This will motivate them to work harder and achieve better academic success. The results show significant differences between the two groups in favor of the group being graded using the point reduction grading scheme. This suggests that the power of loss aversion can be exploited to increase students' engagement and academic success. The existence of framing effect in this case has been demonstrated, which shows it might be possible to use the choice architecture to improve the student results.

Background/Aim: Sulphur mineral water is widely used in the treatment of musculoskeletal diseases. Hydrogen sulphide is an important regulator of bone metabolism and its application in the treatment of osteoporosis is intensively researched. The aim of this study was to analyse biochemical and histological effects of H2S containing mineral water of "Mlječanica" spring on ovariectomy-induced experimental osteoporosis in rats. Methods: In this experiment a 14-week-old Wistar female rats were used. The animals undergone bilateral ovariectomy (OVX groups) as an experimental model for oestrogen-deficient osteoporosis. After six weeks, animals were divided into control and the experimental group. Rats from the experimental group treated with H2S (SW group) containing mineral water ad libitum during five weeks. Biochemical parameters for monitoring sulphur water effects were concentration in serum of osteocalcin, alkaline phosphatase, calcium and phosphorus. Histological analyses of the left tibia coloured with haematoxylin-eosin were carried out. Results: Regarding the biochemical parameters, a statistically significant increase was observed in the OVX group for osteocalcin, alkaline phosphatase calcium and phosphorus compared to the sham-operated (CNT) group (p < 0.01). In SW + OVX, alkaline phosphatase was statistically significantly decreased (p < 0.01) and serum osteocalcin and phosphorus increased (p < 0.01). Calcium values were increased without significance. In the OVX + SW group, histological analyses showed numerous osteoblasts along the trabecular endosteum and the growth of young chondrocytes in the central bone zone and their migration to the peripheral parts. Conclusion: Drinking the H2S containing "Mlječanica" mineral water has led to decreased alkaline phosphatase, increased osteocalcin and phosphorus concentration in serum and stimulated the bone reparation in osteoporotic rats.

Plant extracts are widely used as biofungicides and medical bioproducts because of their eco-friendly nature and cost effectiveness. The present investigation focuses on the activity of a solvent based on industrial hemp extracts against two phytopathogenic fungi and five human pathogenic bacteria. The present study suggests the potential of the industrial hemp extracts for the development of novel broad spectrum herbal formulations used in plant protection and medicine.

Background/Aim: With the adoption of legislation over the Austro-Hungarian rule (1878-1918) apothecary in Bosnia and Herzegovina (B&H) became a regulated profession, which enabled the arrival of graduated pharmacists. The aim of the paper was to present in which towns on the B&H territory public pharmacies were opened over this period and their owners. Methods: A retrospective and descriptive research was conducted at the Archives of the Republic of Srpska, the Museum of the Republic of Srpska and the Archives of Bosnia and Herzegovina. The method of the qualitative secondary data analysis was applied. Results: With the arrival of Masters of Pharmacy from all parts of the Austro-Hungary, an increasing number of public pharmacies began to open. Concessions for the opening pharmacies were initially granted to foreigners and among the settlers, pharmacists there were mostly Czechs, Croats, Poles, Hungarians, Slovaks, who completed pharmacy studies at universities in Vienna, Zagreb, Prague, Lviv, Graz, Innsbruck, Krakow. In the beginning, there were no locally educated pharmacists and the first appeared at the end of the 19th and the beginning of the 20th century. During this period at least one pharmacy was opened in many towns, two worked in Banja Luka, Mostar, Tuzla and Bijeljina and seven in Sarajevo. In the first years, each pharmacy was staffed by only one pharmacist and over time there were more pharmacy staff in the pharmacies. Twenty years after the occupation, public pharmacies owned by Masters of Pharmacy were opened in thirty three towns around B&H and in 1918 there were forty eight public pharmacies in thirty eight towns. Conclusion: The number of public pharmacies and qualified pharmacy staff in B&H increased over the Austro-Hungarian rule from 1878 to 1918, which contributed to the improvement of the profession, health and social conditions in the country during this period.

Background / Aim: Up until ten years ago stage four melanoma was considered a disease with extremely poor prognosis. Standard therapy during this period of time was dacarbazine chemotherapy. Patients with better performance status were treated with immunotherapy cytokine IL-2. In the last ten years eight medications have been approved by the FDA for the therapy of melanoma. The goal of this study was to determine objective response rate (ORR), median overall survival (OS), median progression free survival (PFS) and safety in patients with advanced and metastatic cutaneous melanoma treated with targeted therapy and immunotherapy at the University Clinical Centre of the Republic of Srpska (Centre). Methods: A non-randomised observational retrospective/prospective trial was conducted to investigate first experiences with the use of targeted therapy and immunotherapy at the Centre and compare the results with the literature data. A total of 23 patients received BRAF targeted therapy for the treatment of metastatic cutaneous melanoma in the first line of treatment. Nine patients received vemurafenib, fourteen patients received a combination of BRAF/MEK inhibitor. Nine patients were treated with pembrolizumab immunotherapy. The trial was performed in a period from May 2017 until December 2020. Results: In patients receiving vemurafenib ORR was 44.4 %, median PFS was 5 months (95 % CI, 1 to 11) and the median OS was 9 months (95 % CI, 2 to 17). In the vemurafenib/cobimetinib group ORR was 71.4 %. Median PFS was 9 months and median OS was 12 months. ORR in patients receiving pembrolizumab was 22.9 %, median PFS was 3 months (95 % CI, 1 to 11) and the median OS was 4.5 months (95 % CI, 2 to 12). Results in all three groups were inferior compared to the results from the literature except for ORR in patients receiving vemurafenib and vemurafenib/cobimetinib. Adverse events were tolerable and manageable and were similar to those described in the literature. Conclusion: Based on the experience with the targeted and immunotherapy in the Centre, which was presented in this study, it was concluded that in conditions when there is limited access to drugs, the greatest benefit have the patients who meet the inclusion criteria in clinical trials.

Technical problems have accrued and we were not able to place abstract here in it's full length. Abstract can we found in the pdf version of the paper attached down below.

Background/Aim: Optimal intake of magnesium minerals is essential in maintaining the coordinated physiological functions of cells, tissues and organs. The importance of this element is reflected in the fact that it is the fourth most abundant cation in the human body, participating as a cofactor in more than three hundred enzymatic reactions. Its presence is necessary for the proper functioning of a number of vital functions, such as glycaemic control, the work of the heart and the vascular system and it can potentially play a role in the regulation of body weight. Aim of this study was to investigate the effects of subchronic intake of magnesium hydrocarbonate-rich water on changes in body weight, organ weight and cardiovascular variables in rats with streptozotocin-induced diabetes. Methods: Wistar rats (n = 28) were divided into 4 groups: two control groups, on tap water (TW-C, n = 7) and magnesium hydrocarbonate-rich water (MW-C, n = 7); and two experimental groups with streptozotocin-induced diabetes, on tap water (TW-DM, n = 7) and magnesium hydrocarbonate-rich water (MW-DM, n = 7). The values of body weight, organ weight and cardiovascular parameters were compared after 6 weeks between control groups of rats on subchronic treatment with tap water (TW-C) and magnesium hydrocarbonate-rich water (MW-C) and between groups with streptozotocin-induced diabetes on tap water (TW-DM) and with magnesium hydrocarbonate-rich water (MW-DM). Results: By comparing the values of cardiovascular parameters between groups, significant (p < 0.05) positive effects of magnesium hydrocarbonate-rich water were registered on the values of systolic and pulse blood pressure in diabetic rats fed with magnesium hydrocarbonate-rich water (MW-DM) compared to those fed with tap water (TW-DM). In contrast, no significant effect of magnesium hydrocarbonate on changes in body weight and organ weight was observed. Conclusion: Based on the results, the beneficial effects of magnesium hydrocarbonate-rich water in the regulation of blood pressure can be clearly observed. Potential effects on other cardiovascular variables and body weight and organ weight should be further investigated.

Background/Aim: Type 2 diabetes is a common comorbidity in patients with knee osteoarthritis. Bearing in mind that obesity and insulin resistance are risk factors for the development of knee osteoarthritis, physical therapy and balneotherapy containing hydrogen sulphide (H2S) has a positive effect on the functional and metabolic status of these patients. This work was aimed to investigate the effect of sulphate-sulphide-rich mineral baths containing H2S on the level of serum glucose in patients with knee osteoarthritis. Methods: An open prospective randomised clinical trial included patients suffering from stage I and II of the knee osteoarthritis. Patients were divided into two groups of 40 subjects each: control group and experimental group. All subjects underwent inpatient physical treatment consisting of kinesitherapy and transcutaneous electrical nerve stimulation (TENS) 6 days a week. Patients from experimental group, in addition to all the mentioned treatments, also took sulphate-sulphide mineral water baths once a day for 30 minutes for 7 days, unlike the patients from control group who took tap water baths, according to the same schedule. The level of serum glucose was monitored in all patients on admission, after discharge and 6 months after the treatment. The Student t-test was used for statistical data processing and p < 0.05 was considered as statistically significant. Results: Study included 80 patients of both sexes, with an average age of 67.00 ± 5.75 years. All patients had elevated serum glucose values on admission. The initial levels of glycaemia in the control and experimental groups were not significantly different (6.99 ± 1.95 and 7.88 ± 1.90 mmol/L, respectively). At discharge, patients who performed balneotherapy had a statistically significant decrease in serum glucose values compared to patients from the control group (by 1.84 vs 0.26 mmol/L, p < 0.001). This effect did not persist six months after the end of the treatment (p > 0.05). Conclusion: The application of balneotherapy with sulphate-sulphide mineral baths containing H2S as a potent gas transmitter significantly reduces serum glucose levels in patients with knee osteoarthritis.

Background/Aim: Hypomagnesaemia is one of the most detected electrolyte abnormalities in diabetics. Modulation of numerous cardiovascular pathophysiological processes is a potential goal for anti-diabetic therapy. Magnesium supplementation prevents subclinical tissue magnesium deficiency, thus delaying the onset of metabolic imbalance in diabetes, but long-term effects of magnesium supplementation in chronic diabetes and numerous pathophysiological processes remain unknown. Aim of this study was to determine the effects of subchronic intake of magnesium hydrocarbonate-rich mineral water on cardiometabolic markers and electrolytes in rats with streptozotocin-induced diabetes. Methods: A total of 28 Wistar, male rats, body weight 160 g at start, were divided into four groups of 7 each: two controls, group that drank tap water and received a single ip injection of saline (0.9 % NaCl) (TW-C), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of saline (0.9 % NaCl) (MW-C); and two experimental groups with streptozotocin-induced diabetes, group that drank tap water and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (TW-DM), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (MW-DM). Results: Regarding the biochemical parameters, a decrease was observed in the MW-C group for vitamin B12 and proteins, while triglycerides were higher compared to the TW-C group. By comparing the haemostatic biomarkers between TW-C and MW-C groups, a statistically significant decrease was found for fibrinogen, while the electrolyte analysis showed an increase in phosphates for the MW-C group. Biochemical value comparison between TW-DM and MWDM groups showed that magnesium hydrocarbonate usage in diabetic rats did not significantly reduce glycaemia although the average glycaemic values were lower in the group treated with magnesium hydrocarbonate. Regarding the electrolyte values, a statistically significant decrease was observed for sodium, potassium and phosphate in the MW-DM group. The MW-DM group also showed a significant increase in iron value compared to TW-DM group. Conclusion: Subchronic intake of magnesium hydrocarbonate-rich mineral water, as a form of magnesium supplementation, did not cause a significant improvement in glycaemia or normalisation of diabetes-induced dyslipidaemia. This study showed the reduction of fibrinogen value, thus indicating the possibility of usage of this form of magnesium supplementation in different pro-thrombogenic conditions.

Using natural and modified Ca-bentonite as an adsorbent to observe a satisfactory trend in the removal of heavy metal ions As(V) and Hg(II) from simulated wastewaters. In this original scientific paper, Ca-bentonite was modified in two ways, thermally activated at a temperature of 300 °C for 3 hours and acid activated with HCl and H2SO4, molar concentrations 0,4 mol/L. Ca-bentonite used in this original scientific work was used from the Shipovo mine (Šipovo mine), Bosnia and Herzegovina and proved to be an excellent bioadsorbent for the removal of present ions from simulated wastewaters. Also this is eco-friendly adsorbent and low costed compared to other expensive adsorbents. Due to its chemical composition in which two oxides predominate, namely SiO2 (48.28 mass %) and Al2O3 (23.04 mass%), it can be concluded that Ca-bentonite from the Shipovo mine (Šipovo mine), Bosnia and Herzegovina belongs to the group of refractory materials. The highest removal efficiency of As(V) ions expressed in % was 75.11 at the initial concentration of 1.5 mg/L and was recorded using HCl acid-activated Ca-bentonite. The efficiency of Hg(II) ion removal was the highest using thermally activated Ca-bentonite and this value was 99.66% at an initial concentration of 1 mg/L.