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Research background: Man has been interfering in the environment with his action since ancient time. At the very begging, these were only small interventions, but with scientific and technical development, the interconnection of national economies and the growth of population and consumptions, these interventions are so significant that there is a risk of depletion of some non-renewable resources and degradation of the natural environment. Experts have agreed that these are problems with a global dimension and they have been pointing out the need to address these issues for decades. Purpose of the article: The paper is aimed at representatives of the Z generation in order to show how this generation perceives the current global environmental issues and what is their view on the application of the circular economy in practice. Methods: Survey analysis. Findings & Value added: There are many companies which are aware of the fact and they have started to apply the concept of the circular economy in order to eliminate the negative effects on the environment. This concept consists of using fewer resources in the production of new products through more efficient process and the prevention of waste trough reuse, repair treatment and recycling. All product and material flows will be reintegrated into their cycle after their use, where they will subsequently become resources for the production of the new products and services. Companies that put this concept into practice can gain a competitive advantage in the market by providing consumers with products which are more durable, innovative and mainly environmentally friendly.

Currently, the issues related to the global threats of the environment represent a special, increasingly more significant category of global issues. The main cause of the constantly changing conditions of the environment is the economic growth itself as it is closely connected to the growth of population, satisfaction of the man´s needs and a consequent increase in consumption. With the increase in consumption, there is an increase in the use of natural resources which we perceive as a usable resource that results in the transformation of raw materials into materials being used in the production of consumer goods. The energy used in the production, together with the reusable resources, is being later returned to the economic cycle in the form of waste. However, the way we currently use resources is not sustainable. To ensure sustainable development in the Slovak Republic, as well as in the whole European Union, we need to employ resources in a more inteligent, sustainable way. It is evident that the linear model of economic growth, that we relied on in the past, does not fullfill the needs of present, modern societies in the globalized world. The transition to a circular economy seems to be an appropriate system that can provide environmentally- and economically- sustainable use of available resources, and , thereby, being able to support the main objective within the Strategy for Smart, Sustainable and Inclusive Growth - Europe 2020.

Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.

Oxidative stress and inflammation contribute significantly to atherogenesis. We and others have demonstrated that mildly elevated serum bilirubin levels protect against coronary and peripheral atherosclerosis, most likely due to the antioxidant and anti-inflammatory activities of bilirubin. The aim of the present study was to assess serum bilirubin and the markers of oxidative stress and inflammation in both healthy subjects and patients with various forms of atherosclerosis. The study was performed in patients with premature myocardial infarction (n = 129), chronic ischemic heart disease (n = 43), peripheral artery disease (PAD, n = 69), and healthy subjects (n = 225). In all subjects, standard serum biochemistry, UGT1A1 genotypes, total antioxidant status (TAS), and concentrations of various pro- and anti-inflammatory chemokines were determined. Compared to controls, all atherosclerotic groups had significantly lower serum bilirubin and TAS, while having much higher serum high-sensitivity C-reactive protein (hsCRP) and most of the analyzed proinflammatory cytokines (p < 0.05 for all comparisons). Surprisingly, the highest inflammation, and the lowest antioxidant status, together with the lowest serum bilirubin, was observed in PAD patients, and not in premature atherosclerosis. In conclusion, elevated serum bilirubin is positively correlated with TAS, and negatively related to inflammatory markers. Compared to healthy subjects, patients with atherosclerosis have a much higher degree of oxidative stress and inflammation.

What Is Known and Objective: Fondaparinux exhibits a similar mechanism of action as LMWH. Since both of these drugs bind to antithrombin and increase its affinity to factor Xa, fondaparinux is not expected to be an effective alternative anticoagulant to LMWH in case of LMWH resistance., Case Summary: We report on a case of effective anticoagulation using fondaparinux following total unresponsiveness to high doses of nadroparin administered twice daily, as confirmed via repeated anti-Xa measurements. The antithrombin levels were within the normal range., What Is New and Conclusion: To the best of our knowledge, this is the first report of the effective use of fondaparinux in the case of unresponsiveness to LMWH., (© 2020 John Wiley & Sons Ltd.)

Background: Contemporary continuous-flow left ventricular assist devices (CF-LVADs) are associated with degradation of von Willebrand factor (vWF) high-molecular-weight multimers (HMWMs), a critical factor supporting platelet function. We hypothesized that the HeartMate 3 fully magnetically levitated LVAD, designed to reduce circulatory shear stress, favorably influences these hemostatic parameters., Methods: Fifteen consecutive HeartMate 3 LVAD patients were compared with 11 consecutive HeartMate II controls. Serial plasma samples were collected pre-implant and on Days 2, 7, 30 and 45 post-operatively. Changes in vWF HMWMs were evaluated by 2 independent, study-blind hematologists and confirmed using densitometry-based computerized software. Ristocetin cofactor (RiCO) and vWF antigen (vWF Ag) were measured using standard protocols with enzyme-linked immunosorbent assay., Results: HeartMate 3 patients and HeartMate II controls had a mean age of 67.3 ± 1.4 and 52.8 ± 2.5 years, respectively (INTERMACS Profiles 2 to 4 in 93.3% and 91%, respectively). HeartMate 3 group demonstrated a significantly greater preservation of HMWMs compared with the HeartMate II group, with the most prominent decrease occurring by Day 2 post-operatively and sustained through 45 days (71.94% vs 31.16%, p = 0.001). Laboratory values (normalized to baseline) for RiCO activity, vWF Ag and RiCO:vWF Ag ratio remained in the functional range with no statistically significant differences observed between groups., Conclusion: The HeartMate 3 LVAD is associated with enhanced hemocompatibility compared with the HeartMate II LVAD, as demonstrated by the improved preservation of vWF HMWMs, In contrast, effects on HMWM degradation appeared to be dissociated from functional attributes. Further confirmation of these findings in randomized clinical trials is warranted., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

There are presently new oral anticoagulants (NOAC) for prevention and the treatment of thromboembolic diseases and they are registered in CZ. It concerns of orally direct inhibitors of thrombin (dabigatran etexilate), inhibitors of factor Xa (apixaban, rivaroxaban), respectively, with advantage of some properties not being seen in "classical" anticoagulants. In the use of new anticoagulants, however, are some problems - such as laboratory monitoring in urgent situations of effective treatment and the absence of specific antidote - resolved. The text below brings indications, dosage of the drugs, their elimination, follow-up of efficacy of the treatment or risk of the bleeding as well as the therapy of bleeding complications.Key words: apixaban - dabigatran etexilate - NOAC - rivaroxaban.

This paper details our further experiments pertaining to the influence of low frequency electromagnetic fields (LF EMF) on the growth dynamics of two wild-type Saccharomyces cerevisiae strands. We opted to explore frequencies beyond the usual 50-60 Hz range, motivated by the ion parametric resonance theory and several studies which discovered and recorded endogenous biosignals in various Saccharomyces cerevisiae strands in the 0.4-2.0 kHz frequency range, most probably stemming from microtubules. Both yeast strands used in our experiments have been subjected to continuous 66-hour session of LF EMF exposure (frequencies 1.2, 1.4, 1.6, 1.8, and 2.0 kHz; average magnetic flux density 2.43 mT) under identical ambient conditions. Experiment results indicate a frequency-dependent proliferative response of both yeast strands.

The objective of our study was to examine the changes in coagulation parameters and inflammatory reaction over the course of 15 days in patients with severe sepsis. We tried to identify mechanisms by which sepsis-induced pathophysiological changes may influence the effectiveness of subcutaneously (SC) administered enoxaparin 40 mg once daily. A total of 16 patients (8 men, 8 women; age 35-83 years) meeting the inclusion criteria of severe sepsis were enrolled in this study. The follow-up was performed on days 1, 2, 3, 6, 9, 12, and 15 of hospitalization at the intensive care unit (ICU). Blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen, antithrombin (AT), protein C [PC], D-dimer, fragment 1.2 [F1.2], factor Xa [FXa] inhibition) and inflammatory reactants (interleukin 6 [IL-6], C-reactive protein [CRP], orosomucoid, alpha-1-antitrypsin) were tested. The mean FXa inhibition was 0.17 (+ or - 0.17) IU/mL. The arbitrarily established range of FXa inhibition for prophylaxis, 0.2 to 0.4 IU/mL, was reached in 22 cases (20%), while in 74 cases (68%), it was below and in 13 cases (12%) above the aforementioned range. Factor Xa inhibition positively correlated with AT (r = .42; P < .001) and PC (r = .45; P < .001) activities. A negative correlation was found between the FXa inhibition and alpha-1-antitrypsin concentrations (r = -.33; P = .01) but only in the subgroup with alpha-1-antitrypsin concentrations > or = 2.2 g/L. We confirmed that in most patients with sepsis, the prophylaxis with enoxaparin did not lead to the required FXa inhibition. The inhibition of FXa by enoxaparin depends mainly on the AT and PC activities.

Hip trauma and surgery are associated with systemic inflammatory reaction. However, little evidence exists about the role of IL-6. In order to assess the inflammatory response, we evaluated white blood cell (WBC) count, C-reactive protein (CRP) and IL-6 dynamics in sequential pre- and postsurgical samples collected from 125 elderly patients (mean age 78+/-9 years) undergoing osteosynthesis (OS) for extracapsular hip fractures (n=69), hemiarthroplasty (HA) or urgent total hip arthroplasty for intracapsular fractures (UA) (n=35), and elective total hip arthroplasty for osteoarthrosis (OA) (n=21). Both preoperative CRP and IL-6 levels were higher in patients with intracapsular fractures. IL-6 levels reached peak values immediately after the surgery, while CRP peak levels were reached 48 h after the surgery. The overall inflammatory reaction was more intense in HA patients compared to the other subgroups. Independent of each other, older age and the hip fracture type affected the IL-6 response, while the CRP response depended only on the type of surgery. The abrupt increase in IL-6 immediately after the procedure suggests its involvement in the early stages of the postoperative inflammatory reaction after hip surgery. This reaction is particularly pronounced in elderly patients receiving HA., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Twenty-three patients with fondaparinux prophylaxis over 75 years of age who underwent hip fracture surgery were enrolled in the study. Fondaparinux sodium (2.5 mg) was administered subcutaneously 6 h postoperatively and then every 24 h for 28 days. Coagulation and inflammatory parameters were measured preoperatively, then 10 h, 2, 7, and 28 days postoperatively. Increased D-dimers, positive acute phase proteins, and IL-6, and decreased negative acute phase proteins were observed preoperatively (P < 0.05). Maximum values were reached 10 h postoperatively for IL-6 and D-dimer, and on postoperative days 2 and 7 for positive acute phase proteins (P < 0.05). Transferrin, prealbumin and antithrombin levels were lowest 10 h postoperatively and on postoperative day 2 (P < 0.05). Increased D-dimers, IL-6, and positive acute phase proteins, and decreased negative acute phase proteins persisted until postoperative day 28 (P < 0.05). Prothrombin fragments (F1 + 2) reached peak levels preoperatively and decreased gradually until postoperative day 28. Fondaparinux promoted the inhibition of thrombin generation, as documented by negative correlation between F1 + 2 and FXa inhibition (r = -0.46; P < 0.001). Fondaparinux-induced FXa inhibition increased gradually until postoperative day 28. This increase correlated positively with antithrombin activity (r = 0.4; P < 0.05). Fondaparinux prophylaxis counteracted pro-thrombogenic effect associated with hip fracture and subsequent surgery without severe bleeding complications.

Objective: The capacity of mononuclear blood cells to form autoreactive cytotoxic T lymphocytes was investigated in order to elucidate the mechanism of successful immunosuppressive therapy in some myelodysplastic syndrome (MDS) patients (autoreactivity studies). The failure in autoreactivity studies raised the question of alloreactive cytotoxic T lymphocyte formation in MDS (alloreactivity studies)., Materials and Methods: Sixteen MDS patients and relevant controls were examined. Autoreactive lymphocytes directed against autologous bone marrow mononuclear cells and alloreactive lymphocytes directed against unrelated third-party cells were tested using cytotoxicity assay. In addition, we used one-way mixed lymphocyte reaction, human androgen receptor test for clonality detection, and enzyme-linked immunosorbent assay kits for tumor necrosis factor and interferon-gamma testing., Results: We did not confirm the presence of autoreactive T cells in eight of nine MDS patients tested. The response to allogeneic cells was impaired in 11 of 16 MDS patients, more often in refractory anemia (RA; 80%) than in RA with ring sideroblasts (40%). Interestingly, the response to allogeneic cells in mixed lymphocyte reaction was normal in all MDS patients. T lymphocytes were polyclonal in all but one patient. Tumor necrosis factor and interferon-gamma level in supernatants of mononuclear cells was significantly reduced in RA., Conclusion: The presumed autoaggressive T cells were not confirmed in MDS in our experimental arrangement. Alloreactivity studies demonstrated the impairment of effector cytotoxic phase of cell-mediated immunological reaction in MDS, namely in RA. The significance of our finding of defective cytotoxicity for pathogenesis, clinical course, and even for therapy is discussed together with other immunological defects reported so far.

Patients with severe sepsis are at increased risk for developing thrombembolic phenomena. This article aims to clarify the association between systemic inflammation activation and coagulation, pathogenesis of coagulation abnormalities during severe sepsis. The article reviews incidence and deep venous thrombosis risk factors among these patients and summarizes recent evidence-based guidelines for deep venous thrombosis prophylaxis.

Background: Successful therapy with ATG and cyclosporine A in some myelodysplastic syndrome (MDS) patients led us to study the existence of T cells attacking autologous hemopoietic cells. In our study, we attempted to give the direct prove of autoreactive T cells in MDS (autoreactivity analysis). Simultaneously, we analysed the capacity of MDS patients to respond to allogeneic cells from unrelated individuals (alloreactivity analysis)., Methods and Results: Autoreactive lymphocytes directed against own bone marrow mononuclear cells were analysed using the modification of cell mediated cytotoxic reaction. With one exception we did not confirm the presence of autoreactive T cells among 10 patients examined. Analysis of alloreactivity was performed by means of standard cell mediated cytotoxic reaction and mixed lymphocyte reaction. Surprisingly, the cytotoxic response to allogeneic cells was negative in 11 MDS patients from 16 analysed. When comparing refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RARS) patients, the proportion of negative results was higher in RA (78 %) than in RARS (40 %). In mixed lymphocyte reaction, the response of MDS cells to allogeneic cells of unrelated individual was positive in all tested patients. The preliminary testing of TNF and IFNgamma secretion examined in supernatants of effector cells showed impaired levels of both cytokines in RA and normal levels in RARS in accordance with the findings achieved in alloreactivity analysis., Conclusions: Autoreactive T cells were not found in MDS patients using our experimental arrangement. Analysis of alloreactivity showed the defect in effector--cytotoxic--phase of cell mediated cytotoxic reaction in the majority of MDS patients. The initial phase of this reaction represented in vitro by mixed lymphocyte reaction gave normal results. The possible reasons of disturbed alloreactivity and its relevance to immunity in MDS are commented in discussion.

Disseminated intravascular coagulation (DIC) is characterized by systemic activation of the haemostasis. In many instances the release of inflammatory cytokines and tissue factor trigger the system in septic or traumatic conditions. Initially, the increased activation of haemostasis can be compensated by natural inhibitor systems. As release of the triggers persists, inhibitors (e.g. antithrombin and protein C) will be consumed leading to intravascular clotting. In this process many coagulation factors, most notably fibrinogen and platelets are consumed too, resulting in a failure of haemostasis system and in a diffuse bleeding (decompensated DIC). Fresh frozen plasma, blood transfusion, and fibrinogen concentrate correct the bleeding, if needed, in the case of traumatic (obstetric) DIC. Arrest of the activated haemostasis by heparin and natural anticoagulants (antithrombin or/and protein C) is recommended, mainly in septic conditions with systemic inflammatory reactions. A case of stercoral sepsis usefully treated by recombinant human activated protein C is reported.