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Honey is a product of high nutritional value, used as a raw material for obtaining mead. However, adding fruit juices, including chokeberry juice, can improve mead quality. This paper aims to assess the effects that adding different quantities of chokeberry juice, with the variation of 3 amounts of inoculated yeast, has on the fermentation and physicochemical, antioxidant, and antimicrobial properties of mead. The parameters analyzed are the dry matter content, pH value, and content of volatile acids, ethanol and methanol, total phenols and flavonoids, FRAP, DPPH, and ABTS tests, and antimicrobial properties. The results obtained in this paper show that adding chokeberry juice improves the antioxidant properties of the final product and positively affects the course of mead fermentation, i.e., it has led to an increase in the maximum concentration of ethanol. Regarding the chemical composition of mead, there is no significant difference, except in the obtained ethanol content, which is the highest in samples with 10% of added chokeberry juice. Furthermore, the control sample showed the best antimicrobial activity, while the sample with 5% added chokeberry juice showed the weakest effect. Finally, the strongest effect was seen in the sample with 20% of added chokeberry juice.

Introduction. The myelodysplastic syndromes are a group of clonal haematopoietic stem cell disorders characterized by cytopenia, dysplasia, ineffective hematopiesis, recurrent genetic abnormalities, and increased risk of developing acute myeloid leukemia. In this paper, we present the review and recommendations for treatment of high risk myelodysplastic syndromes on behalf of the Serbian myelodysplastic syndromes group. Material and Methods. A literature review was conducted using the following bibliographic databases: Google Scholar, MEDLINE and Kobson. The recommendations treatment of high risk myelodysplastic syndromes are based on expert opinion based on review of literature and contemporary recommendations for treatment of high risk for myelodysplastic syndromes. Recommendations. Higher-risk myelodysplastic syndromes should be defined in patients risk group with > 3.5 IPSS-R score. Allo- HSCT is recommended in fit higher-risk patients with IPSS-R > 3.5 as well as in fit lower-risk patients with poor risk features according to EBMT/ELN International expert panel and myelodysplastic syndromes right group. Acute myeloid leukemia like or hypomethylation treatment before Allo-HSCT is indicated in patients with myelodysplastic syndromes with ? 10% of blasts. Azacitidine is recommended in intermediate-2 and high risk IPSS patients who are not eligible for transplantation with minimal number of six cycles to define response. Acute myeloid leukemia like treatment is recommended in fit higher-risk for patients with myelodysplastic syndromes with excess of blasts, good performance status, without substantial comorbidities, and with no poor/very poor cytogenetics/genetics. Conclusion. The treatment of fit higher-risk patients should be based on allo-SCT. In patients who are not candidates for transplant hypomethylation treatment is indicated as well as acute myeloid leukemia like treatment in selected patients.

Introduction. We present the recommendations for treatment of the lower-risk myelodysplastic syndromes on behalf of the Serbian myelodysplastic syndromes group. Material and Methods. A literature review was conducted using the following bibliographic databases: Google Scholar, MEDLINE and Kobson. The recommendations for treatment of lower-risk myelodysplastic syndromes are based on expert opinion based on review of the literature and contemporary recommendations for treatment of lower risk myelodysplastic syndromes. Recommendations. Anemia is the most relevant cytopenia in terms of frequency and symptoms in lower-risk myelodysplastic syndromes, and may be treated successfully with erythropoietic stimulating agents, with or without granulocyte growth factor, provided a careful selection is performed on the basis of Revised International Prognostic Scoring System, endogenous erythropoietin levels, and transfusion independence. In case a patient fails erythropoietic stimulating agents treatment, the available options may include lenalidomide, hypomethylating agents, and a rather large number of experimental agents. Chelation therapy is recommended in patients who have received or are anticipated to receive > 20 red blood cell transfusions and those with serum ferritin levels > 2500 ng/mL. Specific therapy for thrombocytopenia has been proposed in experimental clinical trials with thrombomimetic agents that have shown good efficacy, but raised some safety concern. Severe neutropenia is targeted symptomatically with growth factor supportive care. The immunosuppressive treatments are indicated mainly for pancytopenia, hypoplastic lowerrisk myelodysplastic syndromes. Finally, hematopoietic stem cell transplantation is the curative option for younger, good performance (fit) lower-risk patient with poor risk features, according to European Blood and Marrow Transplantation/European Leukemia Net International expert panel and myelodysplastic syndrome-RIGHT group. Conclusion. Treatment of myelodysplastic syndromes is mainly based on resolution of symptoms due to particular cytopenia(s).

Background/Aim. The treatment of chronic myeloid leukemia (CML) has changed dramatically with the advent of targeted therapies. This study aimed to assess the efficacy of generic imatinib in CML patients treated in our center. Methods. The study was retrospective. It included 101 patients diagnosed with CML ? chronic phase (CP). The patients were divided into two groups. Group 1 included 55 patients initially treated with branded imatinib and then switched to generic imatinib. Group 2 consisted of 46 newly diagnosed patients who received only generic imatinib from the beginning of therapy. Results. The patients were treated with branded imatinib for the mean of 42 months (range 6?132 months) before switching to generic imatinib. Treatment with generic imatinib lasted for 25 months on average (range 3?66 months). A quarter of the patients from the group 1 lost their cytogenetic reponse after being switched to generic imatinib, but with-out signs of transformation to acute leukemia. The patients treated with branded imatinib had a significantly longer event-free survival (EFS) and failure-free survival (FFS) (log-rank p = 0.01 and p = 0.03, respectively). These results could have been influenced by frequent changes of the brand and dosage formulation of generic imatinib. Conclusions. Our study showed a significantly longer EFS and FFS in the patients who were initially treated with branded imatinib, compared to those treated with generic imatinib only. These results provide useful information, but have to be interpreted within the context of the crossover study.

Introduction. Bacterial blood infections during febrile neutropenia episodes are urgent medical conditions which were and still are the main cause of morbidity and mortality among patients with hematologic malignancies. The aim of this study was to determine the incidence and clinical characteristics of bacteremia, infectious agents, presence and incidence of antibiotic resistance, as well as the treatment outcome of bloodstream infections in patients with hematologic malignancies. Material and Methods. A three-year retrospective study included 107 patients with hematologic malignancies and positive blood culture results during febrile neutropenia. Results. The most common isolates were Gram-negative bacteria (58.5%), with Escherichia coli being the most frequent pathogen. The Gram-negative microorganisms were mostly sensitive to carbapenems in 70.7%, whereas sensitivity to other antibiotics was as follows: piperacillin/ tazobactam 62%, amikacin 58.5%, and third-generation cephalosporins 50.5%. Acinetobacter spp. was sensitive only to colistin (94.1%). The antibiotic sensitivity among Gram-positive bacteria was highest to linezolid (97.1%), followed by teicoplanin (81.4%) and vancomycin (81.4%). In our patients, the mortality rate during the first 28 days from the moment of positive isolates was high (37.4%). Most patients died within the first seven days. Bacterial blood infections caused by Gram-negative bacteria were associated with significantly higher mortality (?2 = 4.92, p = 0.026). Acinetobacter spp. was isolated in almost half of the patients with fatal outcome, of whom 62.5% died in the first 24 hours. Conclusion. Bacterial bloodstream infections are severe complications with a high rate of mortality in febrile neutropenic hematological patients. Gram-negative bacteria were the most common isolates in our Clinic, with high mortality. It is of utmost importance to constantly monitor the resistance of bacteria to antibiotics, as well as to prevent and control the spread of resistant strains. Antibiotics resistance patterns should regularly be followed.

Introduction. The development of inflammatory bowel disease during the treatment with tumor necrosis factor-? inhibitors is seen in patients with ankylosing spondylitis. Crohn?s disease is the mainly developing form, and etanercept is the most frequently associated agent. Although thrombocytosis in patients with ankylosing spondylitis and inflammatory bowel diseases is often seen due to chronic inflammation, iron deficiency anemia or drug administration, presence of essential thrombocythemia is not common. To our knowledge, there is no published data of coexistence of these three diseases in one patient. Case report. We reported a 35-year-patient with simultaneous presentation of ankylosing spondylitis and essential thrombocythemia. Due to hepatotoxicity of initial treatment with sulfasalazine and metotrexate, tumor necrosis factor-? inhibitor (etanercept) was introduced. Both diseases were well controlled until Crohn?s disease emerged. Two years after switching from etanercept to adalimumab all three coexisting diseases were in remission. Conclusion. Treatment with tumor necrosis factor-? inhibitors significantly improved clinical outcome of patients with chronic inflammatory diseases. However, the appearance of adverse effects may cause a discontinuation or change of a drug. The existence of comorbidities additionally complicates the treatment of such patients.

Evidence on long-term effectiveness and cost effectiveness of treatment sequences for multiple myeloma (MM) is sparse. We used published data and country-specific data to assess the cost effectiveness of four-line treatment sequences for elderly transplant-ineligible patients with MM in Serbia.We developed a Markov cohort model to compare long-term effectiveness and cost effectiveness of five sequential MM treatment alternatives from the perspective of the national healthcare provider. Effectiveness parameters on progression, mortality and adverse events were extracted from published clinical trials. Costs were based on price lists of the National Health Insurance Fund. We compared life expectancy, costs, and incremental cost-effectiveness ratios among alternative courses of action. The model was analyzed over a lifelong time horizon applying a 3% annual discount rate for effectiveness outcomes and costs. Robustness of the model was tested in multiple deterministic sensitivity analyses.The sequences were defined by the frontline treatment: MPT (melphalan-prednisone-thalidomide), MPV (melphalanprednisone-bortezomib), CTD (cyclophosphamide-thalidomide-dexamethasone), VCD (bortezomib-cyclophosphamidedexamethasone) and BP (bendamustine-prednisone). MPV sequence resulted in the highest remaining life expectancy (4.76 life years). Cost-effectiveness analysis resulted in three non-dominated strategies: MPT, VCD, and MPV sequences, with an incremental cost-effectiveness ratio of EUR 35,300 per life-year gained (LYG) for VCD and EUR 47,200/LYG for MPV relative to MPT.MPV sequence was the most effective in terms of life expectancy for elderly transplant-ineligible MM patients in Serbia. Bortezomib-based strategies would be recommended for the frontline treatment of patients with MM in Serbia if the willingness-to-pay threshold is around EUR 35,000-60,000/LYG.O dolgoročni uspešnosti in stroškovni učinkovitosti zaporedij zdravljenja multiplega mieloma (MM) ni veliko dokazov. Na podlagi objavljenih podatkov in podatkov za posamezne države smo ocenili stroškovno učinkovitost štirih zaporedij zdravljenja starejših bolnikov z MM, ki niso primerni za presaditev, v Srbiji.Za primerjanje dolgoročne uspešnosti in stroškovne učinkovitosti petih alternativ zaporednega zdravljenja MM z vidika nacionalnega izvajalca zdravstvenega varstva smo razvili kohortni model Markova. Parametre uspešnosti glede napredovanja, umrljivosti in neželenih dogodkov smo pridobili iz objavljenih kliničnih preskušanj. Stroški temeljijo na cenikih nacionalnega sklada za zdravstveno zavarovanje. Med različnimi ukrepi smo primerjali pričakovano življenjsko dobo, stroške in mejno razmerje stroškovne učinkovitosti. Model smo analizirali v vseživljenjskem časovnem okviru, pri čemer smo za rezultate uspešnosti in stroške uporabili 3-odstotno letno diskontno stopnjo. Robustnost modela smo preizkusili z več determinističnimi analizami občutljivosti.Zaporedja so bila opredeljena z zdravljenjem v prvi liniji: MPT (melfalan-prednizon-talidomid), MPV (melfalanprednizon-bortezomib), CTD (ciklofosfamid-talidomid-deksametazon), VCD (bortezomib-ciklofosfamid-deksametazon) in BP (bendamustin-prednizon). Pri zaporedju MPV je bila pričakovana preostala življenjska doba najdaljša (4,76 leta življenja). Pri analizi stroškovne učinkovitosti so bile ugotovljene tri neprevladujoče strategije: zaporedja MPT, VCD in MPV z mejnim razmerjem stroškovne učinkovitosti 35.300 EUR na pridobljeno leto življenja (LYG) za VCD in 47.200 EUR/LYG za MPV glede na MPT.Zaporedje MPV je bilo najuspešnejše v smislu pričakovane življenjske dobe starejših bolnikov z MM, ki niso primerni za presaditev, v Srbiji. Strategije, ki temeljijo na bortezomibu, bi bile priporočljive za zdravljenje bolnikov z MM v prvi liniji v Srbiji, če je prag pripravljenosti na plačilo približno 35.000–60.000 EUR/LYG.

A broadband permittivity extraction method for fluids by means of electrically small impedance sensors is reported. It relies on an equivalent circuit model of the sensors, which takes into account the most significant parasitic effects. It assumes the sensor’s intrinsic susceptance and conductance to depend linearly on the real and the imaginary part of the permittivity, respectively. The simplicity of the approach eases calibration. Besides conventional thru-reflect-line standards, which define the reference plane, only air and a single reference liquid are needed. The method is applied to three different devices, namely, a common open-ended coaxial line, a compact printed circuit board design, and an integrated microchip sensor for (milli-)liter, microliter, and picoliter sample volumes, respectively. It is shown how the frequency limits can be determined, and how the sensitivity can be maximized in terms of the model parameters. The method is shown to be robust against production tolerances.

Utilization possibilities of solidified fractions of industrial hazardous waste obtained by mixing with inert materials in construction were investigated. Waste mineral oils, water-hydrocarbon emulsions mixture, and waste filter cakes from the physico-chemical treatment of wastewater generated by washing of patterned rollers for a printing machine, were used as models of industrial hazardous waste in the solidification process. Investigation comprised preparation of concrete and asphalt mixtures for further testing. The solidified powder was analyzed regarding the granulometric composition, while the obtained concrete samples were further subjected to compressive strength determination, whereas the asphalt mixtures were tested in the context of potential waterproofing materials. According to the obtained leaching test results, all the samples met the required conditions for further application. Compressive strength test results were in the range of 8.7 - 22.6 MPa. Still, the measured compressive strength values were lower than expected, which is explained using solidified powder fractions of smaller grain size. According to the results, it can be concluded that the investigated mixtures cannot be used for structural building elements, but their usage is recommended for elements such as pavements, roadside, path cubes, concrete haberdashery, etc. Asphalt mixtures showed acceptable properties in terms of mechanical, durability, and waterproofing tests.

In the era of smart grid and advanced technological development, including artificial intelligence, there is a possibility to expand the horizons when it comes to overall energy production, distribution and consumption. The current practice of having independent analysis and control of electrical, gas and heat networks should be abandoned for multi-carrier energy system analysis. Multi-carrier energy systems have coupling points in gas power plants, CHP and gas-CHP power plants, as well as at the consumption end. Smart homes and net metering enable consumers to control their energy demand and make decisions between electrical, gas or heat energy consumption, consequently affecting all three energy grids. A simplified coupled multi-carrier energy system is the combination of district heating and electricity networks. Combined Heat and Power (CHP) units, heat pumps and electric boilers create linkages between electricity and heat networks. This paper shows decomposed electrical-hydraulic-thermal calculation technique for multi-carrier energy system analysis.

Due to wake effect, the construction of a wind farm requires a wide area of land. One of the main issues when planning a wind farm is the optimal wind farm layout design. This paper presents a new approach to the optimization of the wind farm layout, taking wake effect into consideration. The optimization problem is modelled with two objective functions, which are simultaneously optimized. The result of the optimization, considering wake effect, leads to the dependence between the wind farm Annual Energy Production (AEP) and the occupied area of the wind farm. The proposed procedure is verified using realistic measurement data of wind speed. The obtained results show that the suggested procedure can be successfully applied to the optimal wind farm layout design.

Introduction. Multiple myeloma is an incurable plasma-cell pro?liferation mainly affecting the elderly population. The aim of this study was to analyze treatment patterns, utilization of health resources and treatment costs of multiple myeloma in the elderly patients ineligible for autologous hematopoietic stem cell transplantation in Serbia. Material and Methods. The analysis of the health?care costs, from the perspective of the Serbian healthcare system, took into account the costs of medications, diagnostic procedures, inpatient and outpatient care, as well as the costs of drug administration and management of drug adverse effects. Results. Thalidomide based regimens were less costly than bortezomib-based regimens (average per-protocol costs 6,000 ? vs. 64,700 ?, respectively). The most expensive treatment regimen was lenalidomide-dexamethasone (average per-protocol costs 145,200 ?). The sequential (four-line therapy) treatment costs varied from 85,800 ?, starting with melphalan-prednisone-thalidomide to 153,800 ?, starting with melphalan-prednisone-bortezomib. The estimated costs did not significantly differ during variation of the parameters in the sensitivity analysis. Conclusion. The costs of multiple myeloma treatment in the Republic of Serbia are mainly driven by the cost of antimyeloma drugs. The most expensive treatment sequence was starting with melpha1an-prednisone-bortezomib treatment protocol.

The broad purpose of this essay is to demonstrate how scholarly readings of medieval hagiography might benefit from a theoretical-methodological shift towards space as the principal focal point of analysis. More specifically, it aims to put forward a new, spatial interpretation of two well-known miracle episodes from the Lives of St Sava of Serbia, both of which are said to have transpired on the high seas.

Parallel plate capacitor configurations are common for permittivity measurements. Depending on the exact geometry of the plates, the contribution of the usually unwanted fringing fields can be significant. At low frequencies, this effect can be simply avoided by means of properly driven guard electrodes. This way, only the approximately homogeneous field beneath the main electrode is measured. This paper proposes a microwave implementation of such a sensor and a simple method based on scattering parameter measurements for permittivity extraction. The intended application is the size independent assessment of biological cell properties in a microfluidic setup. The paper presents simulation results for a parallel plate cell sensor without and with a guard electrode. Experimental verification is provided with a scaled version realized in printed circuit board technology. The measurements are performed on a dielectric slab at different positions.

Available evidence suggests that in most patients with LR-MDS the risk of death is not related to disease progression but is mainly attributable to non-leukemic death. 2,17 In addition, a proportion of these patients have prolonged survival that precludes the design of clinical trials adopting OS as a primary endpoint. These challenges have resulted in potentially biased assessment of the effectiveness and appropriate use of the available interventions in this patient population. The EUMDS Registry has identified novel meaningful outcome indicators and clinical endpoints, and reliable measures of response to HCI (Figure 4). The results of our analysis indicate that RBCT density is strongly associated with a decreased OS, even at relatively low dose densities. In addition, we observed that an early decrease in platelet count is an independent adverse prognostic indicator in LR-MDS, and combining relative platelet drop and transfusion dependency allows early identification of patients at risk of rapid progression, and may guide early therapeutic interventions, including allogeneic hematopoietic stem cell transplantation or experimental interventions. Taken together, these results indicate that regular RBCT requirement, early platelet count kinetics, and restriction in HRQoL are early independent and meaningful outcome indicators, and reliable measures of effectiveness of therapeutic interventions, evaluated in this set of studies. These findings support the integration of RBCT requirement and HRQoL in the general core outcome sets and in response criteria in patients with LR-MDS, and have important implications for clinical practice and the design of clinical endpoints. Our results strongly support the adoption of freedom from transfusion as a meaningful clinical endpoint in patients with LR-MDS. Anemia is the main determinant of therapeutic intervention in patients with LR-MDS, and ESA are recommended as first-line treatment for patients with symptomatic anemia. 10 The observational studies within the EUMDS Registry showed that the response rate, as well as the capacity of these agents to delay the onset of a regular RBCT need, is most pronounced in RBCT-naïve patients. These results identified early initiation of treatment with ESA as a major treatment response indicator, and indicate that ESA should be recommended in LR-MDS patients with symptomatic anemia before starting regular RBCT. After the onset of RBCT dependency, patients with LR-MDS are prone to long-term accumulation of iron. 1,43 The EUMDS Registry studies provided evidence that elevated LPI levels are associated with reduced survival in RBCT dependent patients, whereas iron chelation therapy normalizes LPI levels. These findings suggest that NTBI and LPI may serve as early indicators of iron toxicity and a means to measure the effectiveness of iron chelation therapy in patients with LR-MDS. However, qualified NTBI and LPI are only currently available in specialized laboratories. 44 Large observational cohorts with detailed clinical and laboratory data, like the EUMDS cohort, are the ideal framework in which to identify well defined MDS subtypes that may benefit from novel targeted treatments. An example of such a subtype is MDS with loss of parts of chromosome 5, namely del5q; these patients have a relatively favorable outcome on lenalidomide treatment. In order to identify homogeneous subsets of patients within MDS, preliminary evidence has suggested that recently identified mutations in splicing factors may recognize distinct disease entities within myeloid neoplasms. 45 Splicing modulators are now in pre-clinical testing, and are very likely to lead to the introduction of effective drugs for specific groups of MDS patients. Luspatercept, a specific inhibitor of growth and differentiation factor-11, a member of the transforming growth factor β superfamily, induced substantial improvement of anemia, especially in patients with ring sideroblasts. 46 Characterization of individual cases by new genetic markers (one of the main objectives of the MDS-RIGHT project) will allow refined classification of patients into biological subgroups that are expected to respond differently to therapeutic interventions to guide discontinuation of those interventions that are less effective or less cost-effective. The main question is whether RCT data and retrospective cohort data in selected tertiary care centers are representative of the 'real world' data of the older patients with LR-MDS in the general population. A careful comparison of the 'real world' data and the RCT data will be needed in order to provide a clear answer to these questions. Meanwhile, the current analyses of data collected over 10 years in the EUMDS Registry provides relevant and important information which could help assess prognosis and response to standard interventions in this older patient group.

Iron overload due to red blood cell transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome patients. Many studies suggested improved survival after iron chelation therapy, but valid data are limited. The aim of this study was to assess the effect of iron chelation on overall survival and hematological improvement in lower-risk myelodysplastic syndrome patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival, treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for overall survival for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative red blood cell transfusions, IPSS-R, and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, red blood cell transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R and additionally corrected for cumulative red blood cell transfusions and presence of ringed sideroblasts, demonstrated a significantly improved overall survival for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve overall survival and hematopoiesis in transfused lower-risk myelodysplastic syndrome patients. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoiesis-stimulating agents, lenalidomide and/or iron chelators. In conclusion, the negative effect of transfusion treatment on PFS already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior PFS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

In this paper we will investigate the problem of finding the open-locating-dominating number for some classes of planar graphs - convex polytopes. We considered Dn, Tn, Bn, Cn, En and Rn classes of convex polytopes known from the literature. The exact values of open-locating-dominating number for Dn and Rn polytopes are presented, along with the upper bounds for Tn, Bn, Cn, and En polytopes.

Introduction. Acute myeloid leukemia is a malignant, clonal disease of a hematopoietic stem/progenitor cell, characterized by accumulation of acquired somatic genetic and epigenetic alterations. Acute myeloid leukemia is, basically, highly heterogeneous disease, so individual treatment approach is needed. With the use of high-throughput genome sequencing technologies, a full spectrum of recurrent gene mutations in acute myeloid leukemia has been discovered, which has also provided deeper insight into leukemogenesis and acute myeloid leukemia ontogeny. This review focuses on molecular markers with proven prognostic significance, which form, together with standard cytogenetics, basis for current acute myeloid leukemia risk stratification. Even in the era of molecular markers, standard prognostic factors (pre-treatment and postinduction factors) have a strong influence on the choice of postremission therapy. Conclusion. Evaluation of molecular markers and their impact on prognosis in acute myeloid leukemia should be interpreted in the context of complex gene interactions. Only comprehensive understanding of acute myeloid leukemia biology and integration of all prognostic markers enable us to timely plan risk adapted treatment.

Introduction. Autologous stem cell transplantation combined with high dose chemotherapy is an effective and safe approach in the treatment of different hematological malignancies. Nowadays, autologous stem cell transplantation represents a standard therapeutic option in the treatment of multiple myeloma, lymphomas and other hematological malignancies. Aim is to analyze the available medical data of patients with multiple myeloma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma acute myeloid and lymphoblastic leukemia, who underwent autologous stem cell transplantation, and to compare the results with published data from other similar studies. Material and Methods. A retrospective study included 90 patients with multiple myeloma, acute myeloid and lymphoblastic leukemia, non-Hodgkin’s and Hodgkin’s lymphoma who underwent autologous stem cell transplantation in the period from 2004 to August 2017. Results. In relation to the underlying disease, the distribution of the respondents was as follows: 39 patients had multiple myeloma, 25 non-Hodgkin’s lymphoma, 20 Hodgkin’s lymphoma and 6 had acute leukemia. 75 patients (89.3%) had the large volume apheresis procedure, while 9 patients (10.7%) had the conventional two-day apheresis procedure. The average number of the mononuclear cells in the apheresis product was 7,8x108/kg, and the number of the CD34 + cells was about 12,11x106 kg. After applying the conditioning regimen, depending on the underlying disease, neutrophils engraftment mainly occurred on the 11th while the platelet engraftment occurred on the 14th post-transplant day. Transplant-related mortality was low, and the mortality rate was 3.57%. Conclusion. Autologous stem cell transplantation is an efficient method of treatment for patients with he­matological malignancies. It is associated with a low rate of complications as well as low rate of transplant-related mortality.

Introduction. Allogenic hematopoietic stem cell transplantation is the best therapeutic option for the treatment of some inherited and acquired diseases of the hematopoietic system as well as various hematological malignancies. Material and Methods. The study was conducted as a retrospective analysis of 35 patients who underwent allogenic hematopoietic stem cell transplantation at the Clinic of Hematology, Clinical Center of Vojvodina. Results. In a group of 35 patients with median age 33 years, 13 patients had acute myeloid leukemia, one patient had acute lymphoblastic leukemia, nine had chronic myeloid leukemia, five had aplastic anemia, five myelodysplastic syndrome, one had multiple myeloma and one had Ewing sarcoma. Nine patients (26%) had an advanced, resistant disease at the time of transplantation. The majority of patients had a matched related transplantation - 89% (31/35) - three patients had syngeneic transplantation, and one patient had a haploidentical transplantation. Out of 35 patients, 16 (45.7%) are alive. The European Bone Marrow Transplantation score ?3 and the presence of advanced disease at the time of transplant were unfavourable prognostic factors for survival (p

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.

The paper proposes a new method for optimal allocation of shunt capacitors in distribution network with renewable distributed generation units such as wind turbines and/or solar power plants. The proposed method, based on application of the Monte Carlo simulation methods, respects the uncertainties associated with load demand and renewable sources power production. The optimisation problem is modelled by two criterion functions with the aim of improving voltage profile in a network by optimal selection of the locations and installed powers of the shunt capacitors. The suggested criterion functions have been optimised simultaneously by applying the non-dominated sorting genetic algorithm. On the basis of the measured data on wind speed and solar radiation, the method has been tested by the example of a real distribution network.

Introduction. A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory rheumatic disease affecting the spine and sometimes peripheral joints in which reactive mild to moderate thrombocytosis is a common finding. There have been no previously reported cases of essential thrombocythemia associated with ankylosing spondylitis. Case Outline. We report a case of a 32-year-old man with human leukocyte antigen B27-positive ankylosing spondylitis and Janus kinase 2-positive essential thrombocythemia who was treated first with a combination of anagrelide and disease-modifying antirheumatic drugs and, after liver toxicity, with a combination of anagrelide and etanercept (TNF-? antagonist). Both diseases were gradually brought under control. Conclusion. Our case of ankylosing spondylitis and essential thrombocythemia suggests that concomitant etanercept and anagrelide therapy is safe, as well as effective.

SummaryBackground Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improve the treatment of bleeds in hemophilia patients with inhibitors, differs from native FVIIa by three amino acid substitutions. In a randomized, double-blind, crossover, confirmatory phase III trial (adept™2), 8/72 (11%) hemophilia A or B patients with inhibitors treated for acute bleeds developed anti-drug antibodies (ADAs) to vatreptacog alfa. Objectives To characterize the formation of anti-vatreptacog alfa ADAs in hemophilia patients with inhibitors. Methods/patients This was a post hoc analysis of adept™2. Immunoglobulin isotype determination, specificity analysis of rFVIIa cross-reactive antibodies, epitope mapping of rFVIIa single mutant analogs and pharmacokinetic (PK) profiling were performed to characterize the ADAs. Results Immunoglobulin isotyping indicated that the ADAs were of the immunoglobulin G subtype. In epitope mapping, none of the rFVIIa single mutant analogs (V158D, E296V or M298Q) contained the complete antibody epitope, confirming that the antibodies were specific for vatreptacog alfa. In two patients, for whom PK profiling was performed both before and after the development of ADAs, vatreptacog alfa showed a prolonged elimination phase following ADA development. During the follow-up evaluation, the rFVIIa cross-reactivity disappeared after the last vatreptacog alfa exposure, despite continued exposure to rFVIIa as part of standard care. Conclusions Results from the vatreptacog alfa phase III trial demonstrate that the specific changes made, albeit relatively small, to the FVIIa molecule alter its clinical immunogenicity.