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The paper introduces results of computational fluid dynamics (CFD) simulations of water flow at the reactor pressure vessel (RPV) outlet and under the RPV head. Several CFD calculations of the steady-state and dynamic processes involving forced and natural circulation of coolant are presented in the paper. In the steady state regime, several calculations were performed for various number of the reactor coolant system (RCS) loops connected to the reactor and the results have been used to analyse the effect of the RCS configuration to the coolant flow at the reactor outlet and under the reactor vessel head. General flow patterns are described in the outlet part of the reactor and under the reactor vessel head and, also, the influence of a lower flow rate through the reactor on thermal homogeneity of coolant under the vessel head. Simultaneously, we discuss the influence of the coolant flow rate at the core outlet on the heat transfer from the under-head space. Unsteady calculation was also done for a reactor cool-down in the regime of natural circulation. The calculation conditions correspond with the data obtained from the experiments led in the frame of the cool-down process of VVER440 reactor at Mochovce nuclear power plant in 2003. In the calculations, the main attention was applied to establishing the basic trends in the cool-down of water content at the outlet part of the reactor and under the head of the reactor vessel.

The round goby Neogobius melanostomus (Pallas, 1814) is one of the most problematic invasive fish species in recent years in Europe. It has proliferated from its native Ponto-Caspian region to several European river systems including their mouths and coastal brackish waters and was also introduced to and became widely established in the Great Lakes in North America. Despite recent reports about further invasions of round goby in the Odra and Vistula Rivers, including penetration of Baltic and North Seas, in the Elbe River this species was only recorded near its mouth close to Hamburg. Here we report the occurrence of round goby 622 km upstream from the previous record in Geesthacht (Germany) in the upper part of the Elbe River in Usti nad Labem (Czech Republic). This report illustrates the fast spread of round goby through several possible pathways, but the most certain is an introduction in ballast water.

Methamphetamine (MEA) is commonly detected in municipal wastewater. It causes imbalances in the system of neurotransmitters as well as several other adverse effects on human health. The aim of this study was to investigate bioconcentration and depuration rates at an environmentally relevant concentration of 1 µg·L -1 in Aeshna cyanea nymphs exposed to MEA for six days followed by three days of depuration. The metabolomes of nymphs sampled during exposure and depuration were compared using non-targeted screening. Concurrently, a behavioural experiment was run to evaluate the effect of MEA on movement. Since most samples were below the limits of quantification (LOQs) - MEA was quantified in only four out of the 87 samples and only during the first 24 h of exposure at concentrations at LOQ level - we estimated maximal possible bioconcentration factor (BCF) on 0.63 using the LOQ. An MEA metabolite - amphetamine - was not detected in any sample at levels above their LOQs. From 247 up to 1458 significant down- and up-regulated metabolite signals (p ≤ 0.05) were detected by non-targeted screening during initial times of exposure and depuration. Numbers of significant down- and/or up-regulated signals in metabolomes (p ≤ 0.05) calculated for particular sampling times possibly correlated with the size of the effect on movement recorded at the same times. In the MEA treatment, movement was not significantly greater during exposure (p > 0.05) but was significantly lower during depuration (p < 0.05). This study shows how MEA acts on dragonfly nymphs, an ecologically important group of aquatic insects with a high trophic level., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.

Using stable carbon and nitrogen isotope analysis (δ 13 C and δ 15 N) to assess trophic interactions in freshwater ecosystems is a well established method, providing insight into ecosystem functioning. However, the spatial and temporal variability of isotope values, driven by environmental fluctuation is poorly understood and can complicate interpretations. We investigated how the temporal variation of stable isotopes in consumers (fish, crayfish and macrozoobenthos) of a canyon-shaped oligotrophic reservoir is associated with environmental factors such as water temperature, transparency, flooded area, and water quality measures. Consumers and their putative food sources were sampled and analyzed for carbon and nitrogen stable isotopes annually, and environmental parameters were measured monthly from 2014 to 2016. Results revealed significant differences in δ 13 C and δ 15 N values in each consumer among studied years. Over the years, fish and crayfish expressed differences in δ 13 C between 3 and 5‰, whereas in zoobenthos differences were 12‰. Variability in δ 15 N was similar across all consumers (2-4‰). Moreover, results suggest that the flooded area of the reservoir was a major driver of δ 13 C stable isotope values variation in consumers, while variation in δ 15 N was not linked to any of the studied environmental factors. Bayesian mixing models further showed significant changes in the origin of detritivorous zoobenthos carbon sources (reversal shift from terrestrial detritus to algae origin) between years with low water level to years with the standard water level. Other species showed only slight differences in food source utilization among years. Our study highlights the importance of environmental factors as sources of variation in consumer's stable isotope values which should be considered especially when studied ecosystem strongly fluctuate in some environmental factor., (© 2023. The Author(s).)

Ornamental aquaculture and the related pet industry are known to be important sources of non-native species worldwide. In the temperate zone, thermal waterbodies are attractive places for irresponsible owners to release unwanted freshwater pets including decapod crustaceans. Several non-native ornamental species have been reported in the thermal locality of Miskolctapolca (a suburb of Miskolc, Hungary). So we surveyed this site in March 2019-November 2021 to update local occurrence records and detect potentially newly released species. A well-established population of Neocaridina denticulata and the occurrence of Caridina cf. babaulti had previously been noted. However, for the first time at this site, we found the shrimps Atyopsis moluccensis, Caridina gracilirostris and C. multidentata, as well as the crayfish Procambarus virginalis, P. clarkii, Cherax quadricarinatus, C. boesemani and C. snowden, and several formally undescribed Cherax species originating from New Guinea. Furthermore, in most species, gravid females carrying eggs were also noticed. Three shrimps, A. moluccensis, C. gracilirostris and C. multidentata, were recorded for the first time in European wild. Further monitoring of this locality and better education of the general public regarding the risks associated with the release of non-native species are strongly recommended., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abundances of EPT larvae sampled in a Central European locality affected by mining and smelting, as well as by the continual inflow of treated communal wastewaters (WWs), were recorded. High concentrations of trace metals in water (maximum 1200 µg·L -1 for zinc) and sediments (maximum 140,000 mg·kg -1 in dry weight for lead) were found at the most contaminated sites. The highest loads of pesticides, pharmaceuticals, and illegal drugs were found under the WW effluent. Other associated factors such as the physicochemical parameters of the water and alterations to microhabitats were also evaluated and taken into account. Although EPT richness was lower at affected sites, abundances did not fall. Stoneflies were dominant at unaffected sites, while caddisflies dominated at affected sites. Only baetid mayflies were detected at the sites contaminated by trace metals and WWs; ephemerellid, heptageniid, and leptophlebiid mayflies were absent from these sites. The site contaminated by trace metals was also inhabited by numerous limnephilid caddisflies, in which limb malformations were detected in up to 11.8% of all specimens of a single taxon. Downstream from the entrance of the WWs, the locality was dominated by hydropsychid caddisflies. The increasing prevalence of predator or passive filter-feeding strategies in these EPT communities was significantly related to increasing water conductivity and acute ecosystemic exposure to 'poorly treated' WWs.

The zebrafish ( Danio rerio ) genome contains a single gene fads2 encoding a desaturase (FADS2) with both Δ6 and Δ5 activities, the key player in the endogenous biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which serve essential functions as membrane components, sources of energy and signaling molecules. LC-PUFAs include the precursors of eicosanoids and are thus predicted to be indispensable molecules for reproductive health in virtually all vertebrates. In mice, an amniotic vertebrate, fads2 deletion mutants, both males and females, have been confirmed to be sterile. In anamniotic vertebrates, such as fish, there is still no information available on the reproductive (in)ability of fads2 mutants, although zebrafish have become an increasingly important model of lipid metabolism, including some aspects of the generation of germ cells and early embryonic development. In the present study, we apply the CRISPR/Cas9 genome editing system to induce mutations in the zebrafish genome and create crispants displaying a degree of fads2 gene editing within the range of 50-80%. Focusing on adult G 0 crispant females, we investigated the LC-PUFA profiles of eggs. Our data suggest an impaired pathway of the LC-PUFA biosynthesis of the ω6 and ω3 series in the first-rate limiting steps of the conversion of linoleic acid (LA) into γ-linolenic acid (GLA), and α-linolenic acid (ALA) into stearidonic acid (SDA), respectively, finally resulting in bad-quality eggs. Our data suggest the existence of an alternative Δ8 pathway, which bypasses the first endogenous LC-PUFA biosynthetic step in zebrafish in vivo, and suggest that the zebrafish bifunctional FADS2 enzyme is actually a trifunctional Δ6/Δ5/Δ8 desaturase.

Reliable quantification of aortic regurgitation (AR) severity is essential for clinical management. We aimed to compare quantitative and indirect echo-Doppler indices to quantitative cardiac magnetic resonance (CMR) parameters in asymptomatic chronic severe AR. Methods and Results: We evaluated 104 consecutive patients using echocardiography and CMR. A comprehensive 2D, 3D, and Doppler echocardiography was performed. The CMR was used to quantify regurgitation fraction (RF) and volume (RV) using the phase-contrast velocity mapping technique. Concordant grading of AR severity with both techniques was observed in 77 (74%) patients. Correlation between RV and RF as assessed by echocardiography and CMR was relatively good (r s = 0.50 for RV, r s = 0.40 for RF, p < 0.0001). The best correlation between indirect echo-Doppler and CMR parameters was found for diastolic flow reversal (DFR) velocity in descending aorta (r s = 0.62 for RV, r s = 0.50 for RF, p < 0.0001) and 3D vena contracta area (VCA) (r s = 0.48 for RV, r s = 0.38 for RF, p < 0.0001). Using receiver operating characteristic analysis, the largest area under curve (AUC) to predict severe AR by CMR RV was observed for DFR velocity (AUC = 0.79). DFR velocity of 19.5 cm/s provided 78% sensitivity and 80% specificity. The AUC for 3D VCA to predict severe AR by CMR RV was 0.73, with optimal cut-off of 26 mm 2 (sensitivity 80% and specificity 66%). Conclusions: Out of the indirect echo-Doppler indices of AR severity, DFR velocity in descending aorta and 3D vena contracta area showed the best correlation with CMR-derived RV and RF in patients with chronic severe AR.

Biological invasions are increasingly recognized ecological and economic threats to biodiversity and are projected to increase in the future. Introduced freshwater crayfish in particular are protruding invaders, exerting tremendous impacts on native biodiversity and ecosystem functioning, as exemplified by the North American spiny-cheek, signal and red swamp crayfish as well as the Australian common yabby. The marbled crayfish is among the most outstanding freshwater crayfish invaders due to its parthenogenetic reproduction combined with early maturation and high fecundity. As their introduced ranges expand, their sympatric populations become more frequent. The question of which species and under what circumstances will dominate in their introduced communities is of great interest to biodiversity conservation as it can offer valuable insights for understanding and prioritization of management efforts. In order to examine which of the aforementioned species may be more successful as an invader, we conducted a set of independent trials evaluating survival, growth, claw injury, and reproduction using single-species stocks (intraspecific interactions) and mixed stocks (interspecific interactions) of marbled crayfish vs. other crayfish invaders since the onset of exogenous feeding. In both single and mixed stocks, red swamp crayfish and yabby grew faster than marbled crayfish, while marbled crayfish were superior to both spiny-cheek and signal crayfish in terms of growth. With the exception of signal crayfish, the faster-growing species consistently reached a higher survival rate. The faster-growing species tended to negatively impair smaller counterparts by greater claw injury, delayed maturation, and reduced fecundity. Only marbled crayfish laid eggs as early as 14 weeks in this study, which is earlier than previously reported in the literature. Thus, the success of marbled crayfish among invasive crayfish is significantly driven by relatively fast growth as well as an early and frequent reproduction. These results shed light on how interactions between invasive populations can unfold when their expansion ranges overlap in the wild, thereby contributing to the knowledge base on the complex population dynamics between existing and emerging invasive species.

Despite their low concentrations in many aquatic environments, evidence exists to suggest that herbicides do affect non-target organisms. Given that burrowing is a primary life-history trait in crayfish, herbicides could potentially have serious negative effects on these ecologically important freshwater macroinvertebrates. In this study, we exposed the red swamp crayfish Procambarus clarkii to terbuthylazine (a triazine) and metazachlor (a chloroacetanilide) at an environmental concentration of 2.0 μg/L for 28 days, and then observed their burrowing behaviour for two days. The metazachlor-exposed males excavated a greater number of burrows than the other tested groups, with comparable depths and volumes relative to individual specimen weight. The relative depth and volume of female burrows were identical in all groups. The natural habit of female crayfish of constructing deeper burrows than males was marginally significant in the control and META groups but was not significant for relative volume. The hypothesized adverse effects of chronic exposure to real environmental concentrations of herbicides were not documented in terms of either relative depth or volume. However, the increased number of burrows in metazachlor-exposed animals may mean that this invasive species will cause greater damage to embankments and river banks. The mechanisms behind these effects require closer study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

With increasing demand for aquaculture products, water reuse is likely to increase for aquaculture operations around the world. Herein, wastewater stabilization ponds (WSP) represents low cost and sustainable treatment technologies to reduce nutrients and various contaminants of emerging concern from effluent. In the present study, we examined bioaccumulation of selected pharmaceuticals from several therapeutic classes by two important fish species in aquaculture with different feeding preferences (Cyprinus carpio and Sander lucioperca) and their common prey to test whether species specific accumulation occurs. Forty and nineteen from 66 selected pharmaceuticals and their metabolites were positively found in water and sediment samples, respectively from the representative WSP. After a six-month study, which corresponds to aquaculture operations, fourteen pharmaceuticals and their metabolites were detected (at a frequency of higher than 50% of samples) in at least one fish tissue collected from the WSP. We observed striking differences for species and organ specific BAFs among study compounds. Though muscle tissues consistently accumulated lower levels of the target analytes, several substances were elevated in brain, liver and kidney tissues (e.g., sertraline) of both species. Low residual concentrations of these target analytes in aquaculture products (fish fillets) suggest WSPs are promising to support the water-food nexus in aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cancer treatment has been greatly improved by the combined use of targeted therapies and novel biotechnological methods. Regarding the former, pegylated liposomal doxorubicin (PLD) has a preferential accumulation within cancer tumors, thus having lower toxicity on healthy cells. PLD has been implemented in the targeted treatment of sarcoma, ovarian, breast, and lung cancer. In comparison with conventional doxorubicin, PLD has lower cardiotoxicity and hematotoxicity; however, PLD can induce mucositis and palmo-plantar erythrodysesthesia (PPE, hand-foot syndrome), which limits its use. Therapeutical apheresis is a clinically proven solution against early PLD toxicity without hindering the efficacy of the treatment. The present review summarizes the pharmacokinetics and pharmacodynamics of PLD and the beneficial effects of extracorporeal apheresis on the incidence of PPE during chemoradiotherapy in cancer patients.

Background: Determining the value of new imaging markers to predict aortic valve (AV) surgery in asymptomatic patients with severe aortic regurgitation (AR) in a prospective, observational, multicenter study. Methods: Consecutive patients with chronic severe AR were enrolled between 2015-2018. Baseline examination included echocardiography (ECHO) with 2- and 3-dimensional (2D and 3D) vena contracta area (VCA), and magnetic resonance imaging (MRI) with regurgitant volume (RV) and fraction (RF) analyzed in CoreLab. Results: The mean follow-up was 587 days (interquartile range (IQR) 296-901) in a total of 104 patients. Twenty patients underwent AV surgery. Baseline clinical and laboratory data did not differ between surgically and medically treated patients. Surgically treated patients had larger left ventricular (LV) dimension, end-diastolic volume (all p < 0.05), and the LV ejection fraction was similar. The surgical group showed higher prevalence of severe AR (70% vs. 40%, p = 0.02). Out of all imaging markers 3D VCA, MRI-derived RV and RF were identified as the strongest independent predictors of AV surgery (all p < 0.001). Conclusions: Parameters related to LV morphology and function showed moderate accuracy to identify patients in need of early AV surgery at the early stage of the disease. 3D ECHO-derived VCA and MRI-derived RV and RF showed high accuracy and excellent sensitivity to identify patients in need of early surgery.

Polyaniline (PANI) and 2,5-dianilino- p -benzoquinone both are formed by oxidation of aniline in an acidic aqueous environment. The aim of this study is to understand the impact of addition of p -benzoquinone on the structure of PANI prepared by the oxidation of aniline hydrochloride with ammonium peroxydisulfate and to elucidate the formation of low-molecular-weight byproducts. An increasing yield and size-exclusion chromatography, Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy, and nuclear magnetic resonance analyses of the products show that p -benzoquinone does not act as a terminating agent in the synthesis of PANI and the content of 2,5-dianilino- p -benzoquinone increases with the increasing molar concentration of p -benzoquinone in the reaction mixture, [BzQ]. Regarding the structure of PANI, Raman and UV-visible spectra show that the doping level and the charge delocalization both decrease with the increase of [BzQ], and the FTIR spectra of the PANI bases indicate an increased concentration of benzenoid units at higher [BzQ]. We explain these observations by an increasing concentration of structural defects in PANI chains and propose a 2,5-dianilino- p -benzoquinone-like structure of these defects present as pendant groups. The bands typical of 2,5-dianilino- p -benzoquinone-like moiety are observed even in the vibrational spectra of the sample prepared without addition of p -benzoquinone. This confirms in situ oxidation of aniline to p -benzoquinone within the course of the oxidation of aniline hydrochloride to PANI., Competing Interests: The authors declare no competing financial interest.

Identification of animals is often hindered by decoupling of phenotypic and molecular evolutionary rates. The Acanthocyclops vernalis (Fischer, 1853) complex is arguably the most problematic group of cyclopoids and possibly of all copepods, with diversity estimates based on morphology ranging from 2 to 34 taxa. We reconstructed their phylogeny based on one nuclear and three mitochondrial markers, revealing only four species in the Holarctic and always the following sister-species pairs: vernalis-europensis sp. nov. and robustus-americanus. Landmarks for quantitative shape analyses were collected from 147 specimens on five structures commonly used to delineate cyclopoids. Procrustes ANOVA showed small directional asymmetry in all datasets, but large sexual dimorphism in shape and size. Allometry was also highly significant. Principal component analyses of size-corrected data almost completely separated species in morphospace based on the last exopodal and endopodal segments of the fourth leg. These two structures showed the highest amount of covariation, while modularity could not be proven and a phylogenetic signal was only observed in one structure. Spinules and sensilla have a limited use in delineating species here. Calculating mean shapes and the extent of inter and intraspecific phenotypic variability opens new horizons for modern taxonomy.

The blue thin polyaniline base film changes its color to green after immersion of the film into dibutyl phosphonate. The green color of the film converts to a greenish-blue after heating to 200 °C in air, which is characteristic for the protonated conducting form of polyaniline. This is in contrast to the "standard" polyaniline hydrochloride, which is transformed into a cross-linked polyaniline base under such conditions. To explain this unexpected observation, the interaction of polyaniline base with dibutyl phosphonate at ambient conditions and after heating to 200 °C was studied using UV-visible, FTIR and Raman spectroscopies. On the basis of these studies, we propose that the dibutyl phosphite tautomeric form of dibutyl phosphonate, which interacts with polyaniline base at 20 °C, converts to the oxidized form, dibutyl phosphate, at 200 °C and subsequently protonates the film. Quantum-chemical modeling of the interaction of polyaniline base with dibutyl phosphite and dibutyl phosphate supports this explanation.

Backround: Only few therapeutic options exist for patients with refractory sudden idiopathic sensorineural hearing loss (SISHL). Little is known about the efficacy of second-line therapies. Rheopheresis seems to be an effective therapeutic possibility., Methods: Between 2012 and 2015, 106 patients with SISHL were enrolled in the study, of whom 52 were refractory to initial treatment. As salvage therapy, these patients were offered either 3 sessions of rheopheresis (33 pts) or intratympanic steroid treatment through MicroWick application (19 pts). Pure tone audiometry was performed at diagnosis, at the 1st month and the 1st year during the follow-up., Results: Patients in the rheopheretic arm had higher hearing loss than in the MicroWick arm (81% vs. 52%, p = 0.04). In spite of this, there was a significant improvement for patients in the rheopheretic arm (27% of hearing loss reduction, p < 0.001) after the 1st month and this remained unchanged during the 1st year, while no improvement was seen in the MicroWick arm (0% of hearing loss reduction, p = 0.424). We found no predictive factor for steroid-failure in first-line therapy. Older age (p = 0.003), presence of vertigo (p = 0.006) and more profound initial hearing loss (p < 0.001) were identified as negative prognostic markers., Conclusion: Rheopheresis can be used as a potentially effective and safe salvage therapy for patients with cortico-refractory SISHL.

Background: Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients., Objective: The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR)., Methods: We examined 46 subjects (19 with AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry., Results: The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample., Conclusions: An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.

Invertebrates are a very diverse group of animals, showing a wide spectrum of life strategies and adaptations. They often exhibit very complex behavioural and social patterns. In crayfish, the largest freshwater invertebrates, we found a new behavioural pattern, burying their own exuviae after moulting. Such a pattern may be an as yet unrecognized type of hoarding or caching. The buried exuvia is exhumed after 2 or 3 days (when the crayfish body is no longer as soft) and consumed. This behaviour is probably self-protective (hiding the mark of a helpless prey), as well as having mineral storage reasons. Such complex behavioural patterns in invertebrates present new challenges for future research.

In recent years, the keeping of ornamental freshwater animals and plants in garden ponds has been growing in popularity. Water hyacinth (Eichhornia crassipes) is one of the preferred macrophytes seasonally imported mainly from South-eastern Asia throughout the world. This constitutes a secondary introduction inasmuch as the species is native to South America. Although many assemblages of aquatic invertebrates have been described as associated with this plant in the wild, there has been no research focused on their potential introduction via the international plant trade. We examined 216 specimens of water hyacinths imported for ornamental purposes from Indonesia into the Czech Republic. Numerous meio- and macroinvertebrates belonging to at least 39 species were captured. On the total number of individuals, the highest prevalence was of Tubulinea and Rotifera. Most of these were still alive and vital, including a caterpillar of the Indo-Australian invasive moth Spodoptera litura. Water hyacinths are usually placed into outdoor ponds immediately after import, which facilitates the release of non-target alien species. The present paper aims to draw attention to "hitchhikers" associated with the ornamental trade.

One of the generally recognized factors contributing to the initiation and maintenance of atrial fibrillation (AF) is structural remodeling of the myocardium that affects both atrial cardiomyocytes as well as interstitium. The goal of this study was to characterize morphologically and functionally interstitium of atria in patients with AF or in sinus rhythm (SR) who were indicated to heart surgery. Patient population consisted of 46 subjects (19 with long-term persistent AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atria were examined using immunohistochemistry to visualize and quantify collagen I, collagen III, elastin, desmin, smooth muscle actin, endothelium and Vascular Endothelial Growth Factor (VEGF). The content of interstitial elastin, collagen I, and collagen III in atrial tissue was similar in AF and SR groups. However, the right atrium was more than twofold more abundant in elastin as compared with the left atrium and similar difference was found for collagen I and III. The right atrium showed also higher VEGF expression and lower microvascular density as compared to the left atrium. No significant changes in atrial extracellular matrix fiber content, microvascular density and angiogenic signaling, attributable to AF, were found in this cohort of patients with structural heart disease. This finding suggests that interstitial fibrosis and other morphological changes in atrial tissue are rather linked to structural heart disease than to AF per se. Significant regional differences in interstitial structure between right and left atrium is a novel observation that deserves further investigation.

Aim. To evaluate the long-term effect of rheohemapheresis (RHF) treatment of age-related macular degeneration (AMD) on photoreceptor IS/OS junction status. Methods. In our study, we followed 24 patients with dry AMD and drusenoid retinal pigment epithelium detachment (DPED) for a period of more than 2.5 years. Twelve patients (22 eyes) were treated by RHF and 12 controls (18 eyes) were randomized. The treated group underwent 8 RHF standardized procedures. We evaluated best-corrected visual acuity, IS/OS junction status (SD OCT), and macular function (multifocal electroretinography) at baseline and at 2.5-year follow-up. Results. RHF caused a decrease of whole-blood viscosity/plasma viscosity at about 15/12%. BCVA of treated patients increased insignificantly (P = 0.187) from median 74.0 letters (56.2 to 81.3 letters) to median 79.0 letters (57.3 to 83.4 letters), but it decreased significantly from 74.0 letters (25.2 to 82.6 letters) to 72.5 letters (23.4 to 83.1 letters) in the control group (P = 0.041). The mfERG responses in the region of eccentricity between 1.8° and 7° were significantly higher in treated patients (P = 0.04). Conclusions. RHF contributed to sparing of photoreceptor IS/OS junction integrity in the fovea, which is assumed to be a predictive factor for preservation of visual acuity.

Ovarian cancer is the fifth most common malignancy in the world's female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits.

Lipid apheresis (extracorporeal lipoprotein elimination) is administered to patients with familial hypercholesterolemia who fail to respond to standard therapy. The nature of the treatment process raises the suspicion that it decreases not only cholesterol but also antioxidants. A group of 12 patients (average age 47±17 y, 4 homozygous and 8 heterozygous individuals) with familial hypercholesterolemia treated by LDL-apheresis or rheohaemapheresis for 3-12 y was included in the study. In addition to cholesterol and triacylglycerol levels, vitamin E and vitamin A and also other markers of antioxidant activity were investigated. Nevertheless, the most important determined parameter was the vitamin E/cholesterol ratio in serum and lipoproteins. The results indicate that both extracorporeal elimination methods are effective and suitable ways to treat severe familial hypercholesterolemia, as the LDL fraction of cholesterol decreased by approximately 77% and 66% following LDL-apheresis and rheohaemapheresis, respectively. In addition, the serum vitamin E decreased by 54% and 57% and the decrease of the serum vitamin A was approximately 20%. However, the main marker of antioxidant capacity, vitamin E/cholesterol ratio, in the serum, VLDL and LDL significantly increased. The increase of vitamin E levels in the erythrocyte membranes of 2% following LDL-apheresis and a significant increase of 4% following rheohaemapheresis were confirmed. The presented results indicate that LDL-apheresis and rheohaemapheresis can be considered to be safe procedures according to the antioxidant capacity of the serum, VLDL and LDL lipoprotein fractions and the erythrocyte membrane.

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

Background: Rheohemapheresis (RHF) is a method that can stop the activity of the dry form of age-related macular degeneration (AMD). The pathophysiologic mechanisms are not well understood, and the effects of the RHF procedures extend beyond the time of the individual procedures., Patients and Methods: We present the data for 46 patients with AMD treated with a series of 8 rheohemapheretic procedures. Blood count parameters were measured before the first and the last procedures. The clinical effect was judged by changes in the drusenoid pigment epithelium detachment (DPED) area before and after the rheopheretic sessions., Results: Rheopheresis caused a decrease in hemoglobin (P<0.001), a decrease in leukocytes (P<0.034), and an increase in platelets (P<0.005). We found a negative correlation between the amount of platelets and their volume (P<0.001, Pearson correlation coefficient: -0.509). We identified the platelet/MPV ratio as a good predictor of the clinical outcome. Patients with a platelet/MPV ratio greater than 21.5 (before the last rheopheresis) had a significantly better outcome (P=0.003, sensitivity of 76.9% and specificity of 80%)., Conclusion: Several basic blood count parameters after RHF can be concluded to significantly change, with some of those changes correlating with the clinical results (reduction of the DPED area).

Czech cancer screening programmes feature a comprehensive multimodal information system which covers all the levels of assessment needed - population-based monitoring (Czech National Cancer Registry), monitoring of results in the diagnostic databases of centres, as well as the quantification of coverage and outputs of primary care according to the administrative data of health care payers. A system of personalised invitations to cancer screening programmes was launched in 2014, based on a stand-alone component of the information system which makes it possible to identify eligible clients in health care payers databases. The system was fully standardised and uniformly implemented in all health insurance companies; its functionalities also involve both continuous and retrospective assessment of the results of personalised invitation. The legislative framework in force will have to be applied and implemented for a more comprehensive and integrated employment of all involved data sources, i.e. cancer registries, screening registries, and administrative data. The system must be able to analyse de-identified individual records on clients participation in screening programmes, and thus to ensure an adequate analysis of performance indicators in compliance with international recommendations.

Background: As a part of the development of a new prospective payment model for radiotherapy we analyzed data on costs of care provided by three comprehensive cancer centers in the Czech Republic. Our aim was to find a combination of variables (predictors) which could be used to sort hospitalization cases into groups according to their costs, with each group having the same reimbursement rate. We tested four variables as possible predictors -  number of fractions, stage of disease, radiotherapy technique and diagnostic group., Methods: We analyzed 7,440 hospitalization cases treated in three comprehensive cancer centers from 2007 to 2011. We acquired data from the I COP database developed by Institute of Biostatistics and Analyses of Masaryk University in cooperation with oncology centers that contains records from the National Oncological Registry along with data supplied by healthcare providers to insurance companies for the purpose of retrospective reimbursement., Results: When comparing the four variables mentioned above we found that number of fractions and radiotherapy technique were much stronger predictors than the other two variables. Stage of disease did not prove to be a relevant indicator of cost distinction. There were significant differences in costs among diagnostic groups but these were mostly driven by the technique of radiotherapy and the number of fractions. Within the diagnostic groups, the distribution of costs was too heterogeneous for the purpose of the new payment model., Conclusion: The combination of number of fractions and radiotherapy technique appears to be the most appropriate cost predictors to be involved in the prospective payment model proposal. Further analysis is planned to test the predictive value of intention of radiotherapy in order to determine differences in costs between palliative and curative treatment.

Purpose. Determining long-term effects of rheohaemapheresis on the dry form of age-related macular degeneration. Methods. This study evaluates 19 patients, average age of 67.6 years, treated with rheohaemapheresis and 18 patients, average age of 72.8 years, comprising the control group. Minimum follow up period was 3.5 years. Each treated patient received a series of 8 sessions of rheohaemapheresis of 1.5 plasma volumes within 10 weeks. We measured the drusenoid pigment epithelium detachment (DPED), best-corrected visual acuity (BCVA), electroretinography (ERG), and rheological parameters. Results. In the treatment group, the baseline BCVA was 0.74 (0.36-1.0) 95% CI and BCVA after 3.5 years was 0.79 (0.41-1.0) 95% CI (P = 0.726). In the control group, the baseline BCVA was 0.71 (0.15-1.0) 95% CI and BCVA after 3.5 years decreased to 0.7 (0.32-0.87) 95% CI (P = 0.031). Baseline DPED was 6.78 ± 3.79 mm(2); after 3.5 years, it decreased to 4.13 ± 3.84 mm(2) (P < 0.001). In the control group, the baseline DPED was 4.09 ± 3.48 mm(2); after 3.5 years, it increased to 6.69 ± 4.2 mm(2) (P = 0.001). We noted increasing levels of positive wave peaking at 50 milliseconds (P50) after treatment (P = 0.022) and a stable amplitude of photopic responses of treated patients. Conclusion. Over the long term, rheohaemapheresis reduced the DPED, improved the function of photoreceptors, and prevented the decline of BCVA.

Introduction: Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department., Patients and Methods: We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant., Results: Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome., Conclusion: Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.

Background: The aim of our study was to compare healthcare-related costs of treatment with XELOX and FOLFOX4 chemotherapeutic regimens in patients with colorectal cancer. We have evaluated costs claimed to the health insurance by the hospital administering these cancer therapies. This study is a pilot project utilising the new I-COP database developed by the Institute of Biostatistics and Analyses of the Masaryk University in Brno, Czech Republic., Patients and Methods: First, we estimated the costs based on current prices of procedures, medication, and materials from public sources. Using the I-COP database, we then carried out a matched-pair comparison of 26 patients treated with FOLFOX4 or XELOX for colorectal cancer. We evaluated a period of three months of therapy (i.e. 6 cycles of FOLFOX4 or 4 cycles of XELOX). Statistical analysis was done using the Wilcoxon matched pairs test., Results: The estimated cost for three months of therapy was 148,288 Czech crowns (CZK) for FOLFOX4 (including CZK 101,064 for chemotherapy drugs) and CZK 123,756 for XELOX. The overall costs claimed to the insurance companies were CZK 160,158 and CZK 151,176 for FOLFOX4 and XELOX, respectively (p = 0.221). The XELOX regimen had significantly higher costs for chemotherapy drugs (CZK 131,705 versus 114,531, p = 0.023) whereas other costs were lower than those for FOLFOX4., Conclusions: FOLFOX4 and XELOX regimens can be considered as equivalent in terms of costs claimed by the hospital administering cancer treatment.

Background: The current treatment of hereditary hemochromatosis (HH) consists of performing periodic whole blood phlebotomies. Erythrocytapheresis (EA) can remove up to three times more red blood cells per single procedure and could thus have a clinical benefit. A prospective study of 30 consecutive cases of HH were included in a periodic EA program., Methods and Patients: EA were performed using a discontinuous flow cell separators. The protocol consisted of a bimonthly EA until normalization of the serum ferritin was reached. The aim was to reduce the total erythrocyte volume by 25-35%, eventually, to adjust the amount so that hematocrit would not drop below 0.25., Results: 530 +/- 101 ml of erythrocytes were removed (median 517, range 116-761 ml). Iron depletion (ferritin < 20 microg/l) was achieved in all patients after a mean 6.9 +/- 7.6 months, median 5 months, range 1-36 months and a mean 14 EA sessions. The procedures were well tolerated and there were no severe side-effects., Conclusions: We conclude that HH patients treated with EA achieved iron depletion quickly under good conditions of tolerance. The efficacy, speed, tolerability, and more favorable schedule of an EA program facilitate treatment of HH.

Purpose: To evaluate the influence of haemorheopheresis on anatomical and functional findings in patients with soft-drusen maculopathy., Methods: We investigated 29 eyes (16 patients) and randomized 25 eyes (16 controls) with soft-drusen maculopathy [soft, confluent and reticular drusen, drusenoid retinal pigment epithelium detachment (RPED)]. Each patient received a series of eight haemorheophereses (cascade filtration of 1.5 plasma volume) within 10 weeks. The patients were followed up using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, optical coherence tomography, fluorescein angiography, electroretinography and measurements of pulsed ocular blood flow., Results: After the procedures, there was a substantial reduction in rheologically active substances [lipoproteins, α2-macroglobulin, immunoglobulin M (IgM), fibrinogen], plasma and blood viscosity. At the 1.5-year follow-up, we noticed soft drusen absorption; reattachment of drusenoid RPED and stabilization or improvement of visual acuity occurred in 72% of patients in comparison to only 39% of patients in the control group. Full-field electroretinograms showed significantly higher scotopic activity of treated patients in comparison with the control group, and mainly insignificant differences in photopic activity between both groups. Despite the significant increase of activity in the paramacular retina in treated patients, the differences in amplitudes of multifocal electroretinography (mfERG) average responses were insignificant between groups., Conclusion: Haemorheopheresis seems to be capable of changing the activity of promoters of the natural course of soft-drusen maculopathy, its development and progression. Visual acuity and electrical activity of the retina can be stabilized or even improved. The therapy has been shown to be effective and safe., (© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.)

The extracorporeal elimination of LDL-cholesterol could be performed using the classic non-selective centrifuge or membrane plasmapheresis. The modern methods are more selective and effective. The atherogenic particules are removed from plasma by active colon or capsula. The methods include: cascade filtration, imunoadsorbtion, heparin-induced precipitation of LDL, thermofiltration, dextran-induced precipitation of LDL and direct adsorption of lipids (DALI). The regular LDL-apheresis is the life-saving technique in the treatment of homozygous familial hypercholesterolaemia. It is used in heterozygous familial hypercholesterolaemia when the patients do not respond to diet and drugs therapy, too. The regular LDL-apheresis treatment may be followed by the decreased frequency of angina pain episodes, the reduction of ECG changes during the bicycle ergometry and significant disappearance of tendinous xantomas. Some prospective randomised studies has shown even in this group of patients, resistant to conventional treatment, a significant regression of atherosclerotic changes.

Recovery from radiation-induced bone marrow aplasia depends on appropriate cytokine support. The aim of our work was to find a cytokine combination allowing in vitro gamma-irradiated (2.5 Gy) CD34+/AC133+ haematopoietic stem cells to evade radiation-induced apoptosis and to enhance damage reparation, which should enable proliferation and ex vivo expansion of cells. Cells were isolated using separation in a Cobe separator followed by immunomagnetic selection by antibody against the AC133 antigen. Thus isolated cells were 80% AC133+/CD34+ and 10% of them expressed the CD33+ antigen. Ten thousand of AC133+ cells formed 1146 CFU-GM and 304 BFU-E. We proved a high expansion efficiency of cytokine combination SCF + IL-3 + FLT3L in comparison with the combination SCF + IL-3 + IL-11 in both, non-irradiated cells and cells irradiated with a dose of 2.5 Gy. The D0 value for AC133+ cells was determined by the clonogeneity test. The D0 value for CFU-GM was estimated to be 1.08 Gy and for BFU-E 0.95 Gy. The results of DNA analysis showed that the majority of isolated AC133+ cells were in G0/G1 phase of the cell cycle. We proved that the dose of 2.5 Gy induced massive apoptosis (80%) of these cells without progression through the cell cycle, which indicates interphase cell death. Under the influence of cytokine combination (SCF + IL-3 + FLT3L), the surviving 20% of cells entered the cell cycle and, similarly to non-irradiated control cells, on 7th day 35% of cells were in S phase.

The treatment of two cases of toxic epidermal necrolysis (Lyell's syndrome) is described. Although some features were common for both ones (young men practically of the same age, reaction after using the same drug) the clinical course of illness was very different. Spontaneous epithelisation of partial-thickness lesions and definitive healing under the xenografts in one patient and full-thickness skin-loss on 12% of body surface with severe septic complications requiring application of cultured keratinocytes and/or skin autografting in the other patient were the main differences. The interdisciplinary approach using a burns treatment protocol in non-burned patient including the close co-operation with the tissue bank in preparing different types of biological covers has been applied.