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Background and Aims: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH., Methods: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well., Results: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment., Conclusion: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients., (© 2023. The Author(s).)

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).)

Introduction: Familial hypercholesterolemia (FH) is an autosomal codominant lipid metabolism disorder. It results in lifelong elevation of plasmatic low-density lipoprotein cholesterol (LDL-C) levels, followed by premature atherosclerosis. In women, pregnancy and lactation represent an additional risk due to association of physiological changes, pre-existing dyslipidemia, and limited therapeutic possibilities and experiences. Methods of extracorporeal LDL-apheresis represent a suitable therapeutic approach., Case Series: We present our experience in case reports of six HoFH women and their 13 pregnancies (nine successful, three abortions, and one interruption). One patient experienced a lethal complication of her pregnancy. Of the nine successful pregnancies, two cases were treated by LDL-apheresis., Conclusion: Pregnancy in HoFH women represents substantial risk; however, patients without signs of decompensated cardiovascular disease can have a good prognosis. LDL-apheresis plays an important role in the management of pregnancy in HoFH., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

Purpose: Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD)., Materials and Methods: The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5-2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters., Results: Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with an steaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings., Conclusion: We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.

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.

Nanocomposites of graphene materials and conducting polymers have been extensively studied as promising materials for electrodes of supercapacitors. Here, we present a graphene/polyaniline heterostructure consisting of a CVD-graphene and polyaniline monolayer and its electrochemical operation in a supercapacitor. The synthesis employs functionalization of graphene by p -phenylene sulfonic groups and oxidative polymerization of anilinium by ammonium persulfate under reaction conditions, providing no bulk polyaniline. Scanning electron microscopy, atomic force microscopy, and Raman spectroscopy showed the selective formation of polyaniline on the graphene. In situ Raman spectroelectrochemistry and cyclic voltammetry (both in a microdroplet setup) confirm the reversibility of polyaniline redox transitions and graphene electrochemical doping. After an increase within the initial 200 cycles due to the formation of benzoquinone-hydroquinone defects in polyaniline, the specific areal capacitance remained for 2400 cycles with ±1% retention at 21.2 μF cm -2 , one order of magnitude higher than the capacitance of pristine graphene.

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.)

The phylogeny of European crayfish fauna, especially with respect to Eastern European species, is still far from being completely resolved. To fill this gap, we analyzed most of the European crayfish species focusing on the phylogenetic position of the endemic crayfish Astacus colchicus, inhabiting Georgia. Three mitochondrial and one nuclear marker were used to study evolutionary relationships among European crayfish species, resulting in the unique phylogenetic position of A. colchicus indicating independent species status to A. astacus. Phylogenetic analyses revealed a deep molecular divergence of A. colchicus in comparison to A. astacus (6.5-10.9% in mtDNA and 1.1% in nDNA) as well as to Pontastacus leptodactylus and P. pachypus (5.5-10.0% in mtDNA and 1.4-2.4% in nDNA). Absent ventral process on second male pleopod and abdominal somites II and III with pleura rounded lacking prominent spines clearly indicate taxonomic assignment to the genus Astacus; however, the species is distributed almost in the middle of Ponto-Caspian area typical by occurrence of the genus Pontastacus. Several morphological indices linked to head length, carapace, and total body length and width were found to demonstrate apparent differences between A. colchicus and A. astacus. Although this study provides a novel insight into European crayfish phylogeography, we also point out the gaps in comprehensive study of the P. leptodactylus species complex, which could reveal details about the potential species status of particular species and subspecies within this genus., (© 2020 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

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.)

Metal-organic frameworks (MOFs) represent a class of porous materials whose properties can be altered by doping with redox-active molecules. Despite advanced properties such as enhanced electrical conduction that doped MOFs exhibit, understanding physical mechanisms remains challenging because of their heterogeneous nature hindering experimental observations of host-guest interactions. Here, we show a study of charge transfer between Mn-MOF-74 and electron acceptors, 7,7,8,8-tetracyanoquinodimethane (TCNQ) and XeF 2 , employing selective enhancement of Raman scattering of different moieties under various optical-resonance conditions. We identify Raman modes of molecular components and elucidate that TCNQ gets oxidized into dicyano- p -toluoyl cyanide (DCTC - ) while XeF 2 fluorinates the MOF upon infiltration. The framework's linker in both cases acts as an electron donor as deduced from blue shifts of the C-O stretching mode accompanied by the emergence of a quinone-like mode. This work demonstrates a generally applicable methodology for investigating charge transfer in various donor-acceptor systems by means of resonance Raman spectroscopy., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

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.

Polyaniline is a conducting polymer with an application potential in the field of biomedical engineering. By employing FTIR spectroscopy and conductivity measurements, it has been shown that the oxidation at stoichiometric peroxydisulfate-to-aniline mole ratio 1.25 in the solutions of formic acid in the range 0-10 M provides samples of a moderate conductivity of the orders 0.01-0.1 S cm -1 . They consist of polyaniline and aniline oligomers as typical of the aniline oxidation in weak acids. The detailed investigation of the infrared spectra indicates a partial ring-carboxylation of polyaniline at high acid concentrations. The extent of structural defects is higher for a series prepared at over-stoichiometric peroxydisulfate-to-aniline mole ratio 2.5, which provided only non-conducting samples. The reference sample series represented by poly(aniline-co-o-aminobenzoic acid) was also prepared and is used in the discussion of the infrared spectra., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The growth of cyanobacteria (blue-green algae) is a typical phenomenon in water bodies worldwide. The use of silver carp (Hypophthalmichthys molitrix) to reduce excessive phytoplankton development is controversial. In the case of cyanobacteria, many of which are toxic, understanding their possible digestion mechanism by fish is particularly desirable. A unique methodical approach, which consists of applying intestinal contents or extracts to a cyanobacteria culture, was used. Unicellular cyanobacteria (Cyanothece) were incubated in vitro with bile, contents of different parts of the intestinal tract, and cytosolic and microsomal extracts of the intestinal tissue of silver carp. The abundance of cyanobacteria decreased in all treatments containing either exclusively bile or its combination with intestinal contents. This research provides the first evidence of non-mechanical digestion of cyanobacteria by silver carp. Cyanobacteria incubated with intestinal contents or extracts reached mostly higher abundances than those incubated with the nutrient medium. The existence of non-mechanical digestion mediated via intestinal contents and extracts or its compensation connected with organic substance uptake is discussed.

Introduction: Colorectal cancer (CRC) is the third most common malignant disease worldwide. The stage of the disease at the time of diagnosis and the capture of an early recurrence have a direct impact on long-term survival. Existing control screening methods often do not reflect real-time metastatic disease. In patients with detectable circulating tumor DNA (ctDNA), liquid biopsy can be an effective monitoring tool., Case Report: In 2012, we performed sigmoid resection in a 57 years old patient for advanced CRC. The follow-up assessments included: blood samples for CA 19-9 and CEA, endoscopy and imaging methods. We also sampled peripheral blood to determine the level of ctDNA. Its value corresponded to the development of the disease throughout the period. Twice it outperformed imaging methods. CEA showed some degree of unreliability, especially after prolonged illness. CA 19-9 was in the normal range at all times., Conclusion: Circulating tumor DNA is an effective tool in the diagnosis of recurrent metastatic CRC. In patients with detectable ctDNA, its level correlates with the tumoral mass in real time. It has a predictive value in monitoring the treatment response. Its implementation in the follow-up of patients with CRC may have an impact on the choice of treatment strategy and consequently on patient survival.

Purpose: The present study evaluates the safety and efficacy of double-plasma filtration (PF) to remove the exceeding pegylated liposomal doxorubicin (PLD) in circulation, thus reducing mucocutaneous toxicity., Methods: A total of 16 patients with platinum-resistant ovarian cancer were treated with 50 mg/m 2 PLD applied in 1-h IV infusion every 28 days. PF was scheduled at 44-46 h post-infusion. The concentration of plasma PLD and non-liposomal doxorubicin (NLD) was monitored with high-performance liquid chromatography at 116 h post-infusion. A non-linear method for mixed-effects was used in the population pharmacokinetic model. The dose fraction of PLD eliminated by the patient prior to PF was compared with the fraction removed by PF. PLD-related toxicity was recorded according to CTCAE v4.0 criteria and compared to historical data. Anticancer effects were evaluated according to RECIST 1.1 criteria., Results: The patients received a median of 3 (2-6) chemotherapy cycles. A total of 53 cycles with PF were evaluated, which removed 31% (10) of the dose; on the other hand, the fraction eliminated prior to PF was of 34% (7). Exposure to NLD reached only 10% of exposure to the parent PLD. PLD-related toxicity was low, finding only one case of grade 3 hand-foot syndrome (6.7%) and grade 1 mucositis (6.7%). Other adverse effects were also mild (grade 1-2). PF-related adverse effects were low (7%). Median progression-free survival (PFS) and overall survival (OS) was of 3.6 (1.5-8.1) and 7.5 (1.7-26.7) months, respectively. Furthermore, 33% of the patients achieved stable disease (SD), whereas that 67% progressed., Conclusion: PF can be considered as safe and effective for the extracorporeal removal of PLD, resulting in a lower incidence of mucocutaneous toxicity.

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.

Although pharmaceuticals are recognized as a major threat to aquatic ecosystems worldwide, little is known about their ecological effect on aquatic biota and ecosystems. Drug-induced behaviour changes could have a substantial impact on consumer-resource interactions influencing stability of the community and ecosystem. We combined laboratory experiments and functional response modelling to investigate effects of real wastewater treatment plant (WWTP) effluent, as well as environmentally relevant concentrations of the antidepressants citalopram and opioid pain medication tramadol, on trophic interactions. Our biological system consisted of dragonfly Aeshna cyanea larvae as predator of common carp Cyprinus carpio fry. Exposure to WWTP effluent significantly increased A. cyanea maximum feeding rate, while those parameters in tramadol and citalopram-exposed larvae were significantly lower from unexposed control group. This suggested the potential of all tested pollutants to have an effect on consumer-resource equilibrium in aquatic ecosystems. While WWTP effluent strengthened interaction strength (IS) of consumer-resource interaction dynamics making the food web more vulnerable to fluctuation and destabilization, tramadol and citalopram could inhibit the potential oscillations of the consumer-resource system by weakening the IS. Similar studies to reveal the potential of pervasive pharmaceuticals to change of consumer-resource interactions dynamics are needed, especially when real WWTP effluent consisting of mixture of various pharmaceuticals displayed very different effect from single compounds tested., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

Background: Weight concerns are prevalent in smokers and may reduce the success rate of quitting. This concept has been primarily studied on US populations and it is unknown how weight concerns may differ cross-culturally. This study examined the role of weight concern in European smokers wishing to stop smoking., Methods: A sample of 593 smokers (299 men and 294 women, mean age 38 years) utilizing the Centre for Tobacco-Dependent in Prague, Czech Republic, between 2010 and 2013 were studied. Weight concerns were assessed at baseline prior to treatment by evidence-based stop smoking methods. Abstinence was evaluated at 12 months post baseline., Results: Approximately 34% of all patients (204/593) were classified as weight concerned (by indicating on the Weight Concern Scale that they would return to smoking after any weight gain) at the time they sought treatment. Among all men, 19.4% (58/299) were weight concerned and among all women, 49.7% (146/294) were weight concerned. Among females, weight-concerned smokers were of similar weight, but younger (p < .001), and had been smoking cigarettes for fewer years (p = .002) compared with those without weight concerns, whereas the male weight-concerned smokers were significantly (p = .030) heavier than those without weight concerns. Although the presence of weight concern was associated with a delay in setting a quit date (log-rank test p = .019), it was not associated with abstinence at one year., Conclusion: The quit success rate of weight-concerned smokers in Czech Republic did not differ from those without weight concern when utilizing an individualized smoking cessation treatment program. Individually tailored tobacco dependence treatment could help to prevent weight concern from affecting successful quitting., Implications: This study adds the new cross-cultural aspect of post-cessation weight concern. Weight concern has been studied primarily on US populations and our sample consists of European sample of smokers. Additionally, we have found that the presence of weight concern lead to delay in setting a quit date, but the success rate of those weight concerned did not differ from those without weight concern. Thus, it is possible, that this individualized evidence-based tobacco treatment program was able to prevent weight concern impact towards successful quitting., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cherax acherontis n. sp., is a crayfish endemic to the submerged river Yumugima in Hagepma/Jugurama cave in the New Guinea Highlands, Jayawijaya Regency, Papua Province, Indonesia. This species is the first cave crayfish from the Southern Hemisphere. The new species is most similar to Cherax monticola. Both species can be easily distinguished by certain morphological characteristics, which easily demonstrate C. acherontis n. sp. is a valid species.

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.

In 1984, we started using therapeutic plasmapheresis (plasma exchange) as a method of extracorporeal lipoprotein elimination for the treatment of hypercholesterolemic patients. We evaluated the results of long-term therapy in 14 patients, 8 men and 6 women. The average age was 55.6+/-13.2 (range 28-70), median 59.5 years. 14 patients were diagnosed with familial hypercholesterolemia (FH): 5 homozygous, 9 heterozygous. Ten patients in the group were treated using immunoadsorption lipoprotein apheresis and 4 using hemorheopheresis. Immunoapheretic interventions decreased LDL-cholesterol (82+/-1 %), ApoB (73+/-13 %) and even Lp(a) by 82+/-19 %, respectively. Selected non-invasive methods are important for long-term and repeated follow-up. Carotid intima-media thickness showed improvement or stagnation in 75 % of the patients. Biomarkers of endothelial dysfunction such as endoglin (in the control group: 3.85+/-1.25 microg/l, in lipoprotein apheresis-treated hypercholesterolemic individuals 5.74+/-1.47 microg/l), CD40 ligand (before lipoprotein apheresis: 6498+/-2529 ng/l, after lipoprotein apheresis: 4057+/-2560 ng/l) and neopterin (before lipoprotein apheresis: 5.7+/-1.1 nmol/l, after lipoprotein apheresis: 5.5+/-1.3 nmol/l) related to the course of atherosclerosis, but did not reflect the actual activity of the disease nor facilitate the prediction or planning of therapy. Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other microcirculation disorders via significantly decreased activity of thrombomodulin (p<0.0001), tissue factor (p<0.0001), aggregation of thrombocytes (p<0.0001) and plasma and whole blood viscosity (p<0.0001). In conclusion, lipoprotein apheresis and hemorheopheresis substantially lowered LDL-cholesterol in severe hypercholesterolemia. Our experience with long-term therapy also shows good tolerance and a small number of complications (6.26 % non-serious clinical complications).

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.

The phylogenetic relationships among imported ornamental crayfish belonging to the genus Cherax were inferred from a combined dataset of 3 mitochondrial genes (COI, 16S and 12S) and by comparison with available GenBank sequences of 14 Cherax species. Furthermore, the concordance of previously described species obtained from a wholesaler (Cherax boesemani, C. holthuisi and C. peknyi) with available GenBank sequences was verified based on COI with special respect to comparison with sequences assigned as Cherax species. Recently described species C. gherardiae, C. pulcher and C. subterigneus belong to the northern group of Cherax species. Comparison and analysis with other GenBank COI sequences show previously unreported diversity of New Guinean species, suggesting 5 putative new species. Surprisingly, species assigned to the subgenus Astaconephrops do not form a monophyletic clade; this subgenus should be reappraised relative to the purported typical morphological characteristic of the uncalcified patch on male chelae. Increasing importation of crayfish underscores the importance of accurate species identification. Use of basic molecular methods is a necessary requisite for documenting occurrence, abundance and population trends of target species. Consequently, it helps to support eventual conservation decision-making by stakeholders., (© 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

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.

Introduction: Improvement in any human activity is preconditioned by inspection of results and providing feedback used for modification of the processes applied. Comparison of experts experience in the given field is another indispensable part leading to optimisation and improvement of processes, and optimally to implementation of standards. For the purpose of objective comparison and assessment of the processes, it is always necessary to describe the processes in a parametric way, to obtain representative data, to assess the achieved results, and to provide unquestionable and data-driven feedback based on such analysis. This may lead to a consensus on the definition of standards in the given area of health care., Method: Total mesorectal excision (TME) is a standard procedure of rectal cancer (C20) surgical treatment. However, the quality of performed procedures varies in different health care facilities, which is given, among others, by internal processes and surgeons experience. Assessment of surgical treatment results is therefore of key importance. A pathologist who assesses the resected tissue can provide valuable feedback in this respect., Results: An information system for the parametric assessment of TME performance is described in our article, including technical background in the form of a multicentre clinical registry and the structure of observed parameters., Conclusion: We consider the proposed system of TME parametric assessment as significant for improvement of TME performance, aimed at reducing local recurrences and at improving the overall prognosis of patients., Key Words: rectal cancer total mesorectal excision parametric data clinical registries TME registry.

Introduction: Tumour size and the quality of its complete surgical removal are the main prognostic factors in rectal cancer treatment. The number of postoperative local recurrences depends on whether the mesorectum has been completely removed - total mesorectal excision (TME) - and whether tumour-free resection margins have been achieved. The surgery itself and its quality depend on the accuracy of preoperative diagnosis and detection of risk areas in the rectum and mesorectum, on the surgeons skills, and finally on pathological assessment evaluating whether complete tumour excision has been accomplished including circumferential margins of the tumour, and whether mesorectal excision is complete. The aim of our study was to implement and standardize a new method of evaluation of the quality of the surgical procedure - TME - in rectal cancer treatment using an assessment of its circumferential margins (CRO) and completeness of the excision., Methods: The study consisted of two parts. The first, multi-centre retrospective phase with 288 patients analysed individual partial parameters of the diagnosis, operations and histological examinations of the rectal cancer. Critical points were identified and a unified follow-up protocol was prepared. In the second, prospective part of this study 600 patients were monitored parametrically focusing on the quality of the TME and its effect on the oncological treatment results., Results: The proportion of patients with restaging following neoadjuvant therapy increased from 60.0% to 81.7% based on preoperative diagnosis. The number of specimens missing an assessment of the mesorectal excision quality decreased from 52.9% in the retrospective part of to the study to 22.8% in the prospective part. The proportion of actually complete TMEs rose from 22.6% to 26.0%, and that of nearly complete TMEs from 10.1% to 24.0%., Conclusion: The introduction of parametric monitoring into routine clinical practice improved the quality of pre-treatment and preoperative diagnosis, examination of the tissue specimen, and consequently improved quality of the surgical procedure was achieved., Key Words: rectal cancer TME - parametric monitoring - quality control.