Effect-based methods including cell-based bioassays, reporter gene assays and whole-organism assays have been applied for decades in water quality monitoring and testing of enriched solid-phase extracts. There is no common EU-wide agreement on what level of bioassay response in water extracts is acceptable. At present, bioassay results are only benchmarked against each other but not against a consented measure of chemical water quality. The EU environmental quality standards (EQS) differentiate between acceptable and unacceptable surface water concentrations for individual chemicals but cannot capture the thousands of chemicals in water and their biological action as mixtures. We developed a method that reads across from existing EQS and includes additional mixture considerations with the goal that the derived effect-based trigger values (EBT) indicate acceptable risk for complex mixtures as they occur in surface water. Advantages and limitations of various approaches to read across from EQS are discussed and distilled to an algorithm that translates EQS into their corresponding bioanalytical equivalent concentrations (BEQ). The proposed EBT derivation method was applied to 48 in vitro bioassays with 32 of them having sufficient information to yield preliminary EBTs. To assess the practicability and robustness of the proposed approach, we compared the tentative EBTs with observed environmental effects. The proposed method only gives guidance on how to derive EBTs but does not propose final EBTs for implementation. The EBTs for some bioassays such as those for estrogenicity are already mature and could be implemented into regulation in the near future, while for others it will still take a few iterations until we can be confident of the power of the proposed EBTs to differentiate good from poor water quality with respect to chemical contamination.

• Klíčová slova
• Bioassay, Effect-based methods, Effect-based trigger value, Environmental quality standard, Mixture toxicity, Reporter gene assay, Water quality monitoring,
• Publikační typ
• časopisecké články MeSH

Background and Objectives Automatic detection of breathing disorders plays an important role in the early signalization of respiratory diseases. Measuring methods can be based on electrocardiogram (ECG), sound, oximetry, or respiratory analysis. However, these approaches require devices placed on the human body or they are prone to disturbance by environmental influences. To solve these problems, we proposed a heart contraction mechanical trigger for unobtrusive detection of respiratory disorders from the mechanical measurement of cardiac contractions. We designed a novel method to calculate this mechanical trigger purely from measured mechanical signals without the use of ECG. Methods The approach is a built-on calculation of the so-called euclidean arc length from the signals. In comparison to previous researches, this system does not require any equipment attached to a person. This is achieved by locating the tensometers on the bed. Data from sensors are fused by the Cartan curvatures method to beat-to-beat vector input for the Convolutional neural network (CNN) classifier. Results In sum, 2281 disordered and 5130 normal breathing samples was collected for analysis. The experiments with use of 10-fold cross validation show that accuracy, sensitivity, and specificity reach values of 96.37%, 92.46%, and 98.11% respectively. Conclusions By the approach for detection, the system offers a novel way for a completely unobtrusive diagnosis of breathing-related health problems. The proposed solution can effectively be deployed in all clinical or home environments.

• Klíčová slova
• Ballistocardiography, Cartan curvature, Convolutional neural networks, Disordered breathing, Euclidean arc length, Mechanical trigger, Tensometers,
• MeSH
• algoritmy MeSH
• elektrokardiografie * MeSH
• lidé MeSH
• nemoci dýchací soustavy * MeSH
• neuronové sítě MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A core evaluation framework that captures the health care and societal benefits of value added medicines (VAMs, also often called repurposed medicines) was proposed in Report 1, aiming to reduce the heterogeneity in value assessment processes across countries and to create incentives for manufacturers to invest into incremental innovation. However, this can be impactful only if the framework can be adapted to heterogeneous health care financing systems in different jurisdictions, and the cost of evidence generation necessitated by the framework takes into account the anticipated benefits for the health care system and rewards for the developers. AREAS COVERED: The framework could potentially improve the pricing and reimbursement decisions of VAMs by adapting it to different country specific decision-contexts such as deliberative processes, augmented cost-effectiveness frameworks or formal multi-criteria decision analysis (MCDA); alternatively, some of its domains may be added to current general evaluation frameworks of medicines. The proposed evaluation framework may provide a starting point for practices based on which VAMs can be exempted from generic pricing mechanisms or can be integrated into the reimbursement and procurement system, allowing for price differentiation according to their added value. Besides evidence from RCTs, pricing and reimbursement decision processes of VAMs should allow for ex-ante non-RCT evidence for certain domains. Alternatively, relying on ex-post evidence agreements-such as outcome guarantee or coverage with evidence development-can also reduce decision uncertainty. CONCLUSIONS: The core evaluation framework for VAMs could trigger changes in the existing pricing, reimbursement and procurement practices by improving the appraisal of the added value created by incremental innovation.

• Klíčová slova
• Drug repurposing, Evidence, Generic reference pricing, Incremental innovation, Multi-criteria decision analysis, Value assessment framework, Value-added medicines,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Water contamination by micropollutants is a global issue, yet there is limited information from low-income regions. To address this, we evaluated surface water quality in rapidly growing Sub-Saharan area of Malawi lacking wastewater treatment. Integrated assessment of passive sample extracts representing wet and dry seasons combined effect-based approach with in vitro bioassays, target and non-target chemical analyses (NTS). It revealed specific contamination profiles characterized by high concentrations of numerous pollutants, frequent exceedances of Predicted No-Effect Concentrations, and concerning levels of certain insecticides (chlorpyrifos, pirimiphos-methyl) and pharmaceuticals (sulfamethoxazole, trimethoprim, diclofenac). Proposed threshold values were exceeded for estrogenicity, androgenicity, aryl hydrocarbon receptor-mediated activity, thyroid hormone receptor agonism, and transthyretin (TTR) binding inhibition (highest effect-based trigger value exceedance, over 600-fold), which indicates risks to aquatic life. The combination of TTR pull-down assay, NTS, and bioassays enabled the isolation and identification of active compounds, including previously unreported TTR ligands 4-hydroxychlorothalonil (pesticide metabolite) and chlorothiazide (diuretic). Linear alkylbenzene sulfonates and related features contributed most significantly to TTR binding inhibition. This study introduces novel analytical approaches to address challenging groups of surfactants occurring in technical mixtures containing multiple branched isomers. The results underscore the added value of implementing effect-based assessment in understudied regions and the challenges posed by transformation products and technical mixtures lacking standards and reference spectra in NTS libraries. Our findings emphasize the need to expand MS/MS spectral libraries by incorporating metabolites and transformation products. The study highlights the impacts and risks of untreated wastewater discharges in regions affected by climatic and socio-economic pressures.

• Klíčová slova
• Bioassays, Endocrine disruption, Linear alkylbenzene sulfonates, Malawi, Pull-down assay, Transthyretin,
• Publikační typ
• časopisecké články MeSH

Water is a vital resource for natural ecosystems and human life, and assuring a high quality of water and protecting it from chemical contamination is a major societal goal in the European Union. The Water Framework Directive (WFD) and its daughter directives are the major body of legislation for the protection and sustainable use of European freshwater resources. The practical implementation of the WFD with regard to chemical pollution has faced some challenges. In support of the upcoming WFD review in 2019 the research project SOLUTIONS and the European monitoring network NORMAN has analyzed these challenges, evaluated the state-of-the-art of the science and suggested possible solutions. We give 10 recommendations to improve monitoring and to strengthen comprehensive prioritization, to foster consistent assessment and to support solution-oriented management of surface waters. The integration of effect-based tools, the application of passive sampling for bioaccumulative chemicals and an integrated strategy for prioritization of contaminants, accounting for knowledge gaps, are seen as important approaches to advance monitoring. Including all relevant chemical contaminants in more holistic "chemical status" assessment, using effect-based trigger values to address priority mixtures of chemicals, to better consider historical burdens accumulated in sediments and to use models to fill data gaps are recommended for a consistent assessment of contamination. Solution-oriented management should apply a tiered approach in investigative monitoring to identify toxicity drivers, strengthen consistent legislative frameworks and apply solutions-oriented approaches that explore risk reduction scenarios before and along with risk assessment.

• Klíčová slova
• Chemical legislation, Effect-based tools, Passive sampling, Prioritization of contaminants, Solution-oriented management, Water Framework Directive review,
• Publikační typ
• časopisecké články MeSH

Aerobic composting and anaerobic digestion plays an important role in reduction of organic waste by transforming the waste into humus, which is an excellent soil conditioner. However, applications of chemical-contaminated composts on soils may have unwanted consequences such as accumulation of persistent compounds and their transfer into food chains. The present study investigated burden of composts and digestates collected in 16 European countries (88 samples) by the compounds causing dioxin-like effects as determined by use of an in vitro transactivation assay to quantify total concentrations of aryl hydrocarbon receptor-(AhR) mediated potency. Measured concentrations of 2,3,7,8-Tetrachlorodibeno-p-dioxin (2,3,7,8-TCDD) equivalents (TEQbio) were compared to concentrations of polycyclic aromatic hydrocarbons (PAHs) and selected chlorinated compounds, including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), co-planar polychlorinated biphenyls (PCBs), indicator PCB congeners and organochlorine pesticides (OCPs). Median concentrations of TEQbio (dioxin-like compounds) determined by the in vitro assay in crude extracts of various types of composts ranged from 0.05 to 1.2 with a maximum 8.22μg (TEQbio)kg(-1) dry mass. Potencies were mostly associated with less persistent compounds such as PAHs because treatment with sulfuric acid removed bioactivity from most samples. The pan-European investigation of contamination by organic contaminants showed generally good quality of the composts, the majority of which were in compliance with conservative limits applied in some countries. Results demonstrate performance and added value of rapid, inexpensive, effect-based monitoring, and points out the need to derive corresponding effect-based trigger values for the risk assessment of complex contaminated matrices such as composts.

• Klíčová slova
• Biodetection tools, Compost, Digestate, Dioxin, Effect-based monitoring, PAHs,
• MeSH
• biotest MeSH
• chlorované uhlovodíky analýza   farmakologie   MeSH
• dioxiny analýza   farmakologie   MeSH
• hodnocení rizik MeSH
• krysa rodu Rattus MeSH
• látky znečišťující půdu analýza   farmakologie   MeSH
• nádorové buněčné linie MeSH
• polycyklické aromatické uhlovodíky analýza   farmakologie   MeSH
• půda chemie   MeSH
• receptory aromatických uhlovodíků metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• chlorované uhlovodíky MeSH
• dioxiny MeSH
• látky znečišťující půdu MeSH
• polycyklické aromatické uhlovodíky MeSH
• půda MeSH
• receptory aromatických uhlovodíků MeSH

A series of potassium isothiocyanato-(N-salicylidene-aminoacidato) cuprates (1-5) with the general formula of the monomeric unit K[Cu(sal-aa)(NCS)] ⋅ xH2O (x=0 or 2), containing a Schiff-base ligand (H2sal-aa) derived from natural amino acids such as glycine, DL-α-alanine, DL-valine, DL-phenylalanine and β-alanine, and salicylaldehyde, was screened for in vitro antiradical and major cellular effects against selected cancerous and normal cells. The complexes exhibited strong antioxidant properties against superoxide in vitro and a protective effect on DNA under Fenton-like reaction conditions. Screening of their cellular effects revealed moderate in vitro cytotoxicity against human cancer cell lines (A2780, A2780R and MCF-7), with IC50 values of 25-35 μM, and relatively low toxicity to normal fibroblast MRC-5 cells (with IC50 values>50 μM). Additional experiments performed on A2780 cells revealed that the most potent complex 5 significantly increased the number of A2780 cells arrested in the G2/M phase of the cell cycle and triggered intracellular oxidative stress. The selected flow cytometry experiments (detection of apoptosis/autophagy and activation of caspases 3/7 and depletion of mitochondrial membrane potential) did not reveal the dominant mechanism underlying the cytotoxicity of the complexes but clearly differentiated their molecular effects from those of the reference drug cisplatin. All the complexes exerted anti-inflammatory effects by modulating the levels of the proinflammatory cytokines TNF-α and IL-1β in LPS-activated THP-1 macrophage-like cells. Complex 5 also slightly influenced the activity of the upstream NF-κB transcription factor, while no effect on PPARγ activation was detected.

• Klíčová slova
• Cellular effects, Copper complex, Cytotoxicity, Inflammation, Schiff base,
• MeSH
• antiflogistika nesteroidní farmakologie   chemie   chemická syntéza   MeSH
• antiflogistika farmakologie   chemie   chemická syntéza   MeSH
• antioxidancia farmakologie   chemie   chemická syntéza   MeSH
• apoptóza účinky léků   MeSH
• kationty chemie   farmakologie   MeSH
• komplexní sloučeniny * farmakologie   chemie   chemická syntéza   MeSH
• lidé MeSH
• měď * chemie   farmakologie   MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• proliferace buněk * účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• Schiffovy báze * chemie   farmakologie   chemická syntéza   MeSH
• screeningové testy protinádorových léčiv * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• antiflogistika MeSH
• antioxidancia MeSH
• kationty MeSH
• komplexní sloučeniny * MeSH
• měď * MeSH
• protinádorové látky * MeSH
• Schiffovy báze * MeSH

INTRODUCTION: The exposures to hazardous antineoplastic drugs (AD) represent serious risks for health care personnel but the exposure limits are not commonly established because of the no-threshold effects (genotoxic action, carcinogenicity) of many ADs. In this study, we discussed and derived practically applicable technical guidance values (TGV) suitable for management of AD risks. METHODS: The long-term monitoring of surface contamination by eight ADs was performed in pharmacies and hospitals in the Czech Republic and Slovak Republic in 2008-2021; in total 2,223 unique samples were collected repeatedly in 48 facilities. AD contamination was studied by LC-MS/MS for cyclophosphamide, ifosfamide, methotrexate, irinotecan, paclitaxel, 5-fluorouracil and gemcitabine and by ICP-MS for total Pt as a marker of platinum-based ADs. RESULTS: The study highlighted importance of exposure biomarkers like 5-fluorouracil and especially carcinogenic and persistent cyclophosphamide, which should be by default included in monitoring along with other ADs. Highly contaminated spots like interiors of laminar biological safety cabinets represent a specific issue, where monitoring of contamination does not bring much added value, and prevention of staff and separated cleaning procedures should be priority. Rooms and surfaces in health care facilities that should be virtually free of ADs (e.g., offices, kitchenettes, daily rooms) were contaminated with lower frequency and concentrations but any contamination in these areas should be carefully examined. DISCUSSION AND CONCLUSIONS: For all other working places, i.e., majority of areas in pharmacies and hospitals, where ADs are being prepared, packaged, stored, transported, or administered to patients, the study proposes a generic TGV of 100 pg/cm2. The analysis of long-term monitoring data of multiple ADs showed that the exceedance of one TGV can serve as an indicator and trigger for improvement of working practices contributing thus to minimizing of unintended exposures and creating a safe work environment.

• Klíčová slova
• antineoplastic drugs, hazardous drugs, monitoring, surface contamination, technical guidance values,
• MeSH
• chromatografie kapalinová MeSH
• cyklofosfamid analýza   MeSH
• fluoruracil analýza   MeSH
• lékárny * MeSH
• lidé MeSH
• nemocnice MeSH
• pracovní expozice * analýza   MeSH
• protinádorové látky * MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• cyklofosfamid MeSH
• fluoruracil MeSH
• protinádorové látky * MeSH

BACKGROUND: During and after exercise, dynamic 31 P MR parameters are typically measured using an MR-compatible ergometer. Self-built equipment for local condition can be constructed where possible. PURPOSE: To develop a pedal resistance ergometer with rocker arm based on a system that combines electric weight displacement, visual self-monitoring, and exercise triggering. The repeatability and reproducibility were tested. METHODS: The hardware and software for the ergometer were constructed from commercial components in a home laboratory. Twelve volunteers participated in the testing of the ergometer. RESULTS: A fully automated ergometer system was developed, allowing the pedal resistance to be adjusted during the examination. The system includes a self-monitoring and triggering mechanism that enables both the operator and subject to monitor pedal frequency and force. The operator can modify the pedal resistance as desired during the exercise. This self-monitoring solution is simple and cost-effective, requiring only a commercial potentiometer, an Arduino converter, and a conventional video projector with a personal computer (PC). Additionally, all system components are located outside the magnetic resonance (MR) room, avoiding interference with the MR system. Results of several test of the reproducibility/repeatability of power at three pedal resistance values (15%, 24%, 25% maximal voluntary force) were expressed both as a coefficient of variation ranging from 6% to 3.1% and as an intraclass correlation of coefficient ranging from 0.96 to 0.99. Similar values were also found for other dynamic parameters of 31 P MR spectroscopy. These findings are similar to published data obtained on different types of ergometers. CONCLUSIONS: Based on more than 1 year of usage, the ergometer proved successful in handling stationary and variable loads, and can be easily operated by a single user.

• Klíčová slova
• MR compatible ergometer, construction, dynamic 31P MR spectroscopy, self-monitoring,
• MeSH
• cvičení MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• magnetická rezonanční tomografie * MeSH
• reprodukovatelnost výsledků MeSH
• senzorická zpětná vazba * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

In environmental and agronomic settings, even minor imbalances can trigger a range of unpredicted responses. Despite the widespread use of metal-based nanoparticles (NPs) and new bio-nanofertilizers, their impact on crop production is absent in the literature. Therefore, our research is focused on the agronomic effect of spray application of gold nanoparticles anchored to SiO2 mesoporous silica (AuSi-NPs), zinc oxide nanoparticles (ZnO-NPs), and iron oxide nanoparticles (Fe3O4-NPs) on sunflowers under real-world environments. Our findings revealed that the biosynthetically prepared AuSi-NPs and ZnO-NPs were highly effective in enhancing sunflower seasonal physiology, e.g., the value of the NDVI index increased from 0.012 to 0.025 after AuSi-NPs application. The distribution of leaf trichomes improved and the grain yield increased from 2.47 t ha-1 to 3.29 t ha-1 after ZnO-NPs application. AuSi-NPs treatment resulted in a higher content of essential linoleic acid (54.37%) when compared to the NPs-free control (51.57%), which had a higher determined oleic acid. No NPs or residual translocated metals were detected in the fully ripe sunflower seeds, except for slightly higher silica content after the AuSi-NPs treatment. Additionally, AuSi-NPs and NPs-free control showed wide insect biodiversity while ZnO-NPs treatment had the lowest value of phosphorus as anti-nutrient. Contradictory but insignificant effect on physiology, yield, and insect biodiversity was observed in Fe3O4-NPs treatment. Therefore, further studies are needed to fully understand the long-term environmental and agricultural sustainability of NPs applications.

• Klíčová slova
• foliar application, gold, insect biodiversity assessment, iron oxide, nanofertilizers, plant physiology, seeds quality, silica, sunflower yield, zinc,
• Publikační typ
• časopisecké články MeSH