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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.