One of the less studied in vitro biological activities in the aquatic environment are thyroid hormone receptor beta (TRβ)-mediated agonistic and antagonistic activities and transthyretin (TTR) binding activity. They were measured mostly using active sampling methods, but rarely found. It is unclear if these activities co-occur, and the drivers of the (anti-)TRβ activity are mostly unknown. Therefore, the main aim of the study was to determine (anti-)TRβ activities as well as transthyretin (TTR) binding activity in passive samplers from Czech surface waters in combination with the search for the effect drivers based on liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis by applying suspect screening. Passive samplers (polar organic chemical integrative samplers, POCIS) were deployed at twenty-one sites (all ends of watersheds and other important sites in Elbe River) in the Czech rivers. The (anti-)TRβ and TTR binding activity were measured using (anti-)TRβ-CALUX and TTR-TRβ-CALUX bioassays. Anti-TRβ activity was found at eight sites, and TTR binding activity co-occurred there at six of these sites. The co-occurrence of TRβ-mediated antagonistic activity and TTR binding indicate that they may have common effect drivers. No sample exhibited TRβ agonistic activity. The extract from the site Bílina River, the most burdened with anti-TRβ activity, was further successfully fractionated, and this activity was revealed in the fraction, where mid-polar compounds prevailed. However, the suspect LC-HRMS analysis did not reveal the chemical effect drivers. Our results showed that anti-TRβ activity can be found in surface waters by employing passive sampling and frequently co-occurs with TTR binding activity. Overall, the fractionation procedure and non-target data acquisition used in this study can serve as a basis for searching the effect drivers in future research.

• Klíčová slova
• Concentration addition, Effect-directed analysis, Fractionation, Thyroid hormone, Transporter protein,
• MeSH
• chemické látky znečišťující vodu analýza   MeSH
• chromatografie kapalinová metody   MeSH
• hmotnostní spektrometrie metody   MeSH
• monitorování životního prostředí * metody   MeSH
• prealbumin * metabolismus   MeSH
• receptory thyreoidních hormonů metabolismus   MeSH
• řeky * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• prealbumin * MeSH
• receptory thyreoidních hormonů MeSH

The occurrence, environmental risks and contribution of organic UV filters to detected (anti-)progestogenic activities were examined in samples of wastewater treatment plant influents and effluents, various surface waters and fish from the Czech Republic. Of the 20 targeted UV filters, 15 were detected in the WWTP influent samples, 11 in the effluents, and 13 in the surface water samples. Benzophenone-3, benzophenone-4, and phenyl benzimidazole sulfonic acid (PBSA) were found in all water samples. Octocrylene, UV-327 and 4-methylbenzylidene camphor exceeded the risk quotient of 1 at some sites. In the anti-progestogenic CALUX assay, 10 out of the 20 targeted UV filters were active. Anti-progestogenic activities reaching up to 7.7 ng/L, 3.8 ng/L, and 4.5 ng/L mifepristone equivalents were detected in influents, effluents, and surface waters, respectively. UV filters were responsible for up to 37 % of anti-progestogenic activities in influents. Anti-progestogenic activities were also measured in fish tissues from the control pond and Podroužek (pond with the highest number of detected UV filters) and ranged from 2.2 to 9.5 and 1.9 to 8.6 ng/g dw mifepristone equivalents, respectively. However, only benzophenone was found in fish, but it does not display anti-progestogenic activity and thus could not explain the observed activities.

• Klíčová slova
• Chemical analysis, Organic micropollutants, Pollution, Solid-phase extraction, in vitro bioassays,
• MeSH
• chemické látky znečišťující vodu * analýza   toxicita   MeSH
• hodnocení rizik MeSH
• monitorování životního prostředí MeSH
• odpadní voda MeSH
• přípravky chránící proti slunci * analýza   toxicita   MeSH
• progestiny analýza   MeSH
• ryby * metabolismus   MeSH
• ultrafialové záření MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• chemické látky znečišťující vodu * MeSH
• odpadní voda MeSH
• přípravky chránící proti slunci * MeSH
• progestiny MeSH

Concerns are growing about adverse effects of progestins on biota, even at ultra-trace concentrations. The enrichment factor (EF) from extraction of analytes in environmental samples that is needed for sample pre-concentration can affect not only performance of the analytical method but also the matrix effect. Therefore, the present study aimed to assess the influence of high sample EF on performance of the high-performance liquid chromatography with atmospheric pressure chemical ionization and photoionization coupled with high-resolution mass spectrometry (HPLC-APCI/APPI-HRMS) method for analysis of progestins in waste water treatment plant (WWTP) effluents and surface waters and analysis of (anti-)progestogenic activities measured by (anti-)PR-CALUX bioassays. The results showed that HPLC-APCI/APPI-HRMS coupled with solid-phase extraction and a high EF (33,333 Lwater/Lextract) enabled the detection of more compounds compared to samples with lower sample EF (10,000 Lwater/Lextract). The matrix effect did not increase proportionally compared to lower EFs (10,000 and 16,666 Lwater/Lextract), and lower limits of quantification were achieved in WWTP effluents and surface waters. The results of bioassays have shown that relative EF of 25 Lwater/Lbioassay appears high enough to detect progestogenic activity in treated waste water. Our study is one of the first to provide insights into sample pre-concentration in analysis of progestins and progestogenicity in aquatic environments.

• Klíčová slova
• Contamination, Contraceptives, In vitro bioassays, Mass spectrometry, Organic micropollutants, Pollutants, Progestogens,
• Publikační typ
• časopisecké články MeSH

Monitoring methodologies reflecting the long-term quality and contamination of surface waters are needed to obtain a representative picture of pollution and identify risk drivers. This study sets a baseline for characterizing chemical pollution in the Danube River using an innovative approach, combining continuous three-months use of passive sampling technology with comprehensive chemical (747 chemicals) and bioanalytical (seven in vitro bioassays) assessment during the Joint Danube Survey (JDS4). This is one of the world's largest investigative surface-water monitoring efforts in the longest river in the European Union, which water after riverbank filtration is broadly used for drinking water production. Two types of passive samplers, silicone rubber (SR) sheets for hydrophobic compounds and AttractSPETM HLB disks for hydrophilic compounds, were deployed at nine sites for approximately 100 days. The Danube River pollution was dominated by industrial compounds in SR samplers and by industrial compounds together with pharmaceuticals and personal care products in HLB samplers. Comparison of the Estimated Environmental Concentrations with Predicted No-Effect Concentrations revealed that at the studied sites, at least one (SR) and 4-7 (HLB) compound(s) exceeded the risk quotient of 1. We also detected AhR-mediated activity, oxidative stress response, peroxisome proliferator-activated receptor gamma-mediated activity, estrogenic, androgenic, and anti-androgenic activities using in vitro bioassays. A significant portion of the AhR-mediated and estrogenic activities could be explained by detected analytes at several sites, while for the other bioassays and other sites, much of the activity remained unexplained. The effect-based trigger values for estrogenic and anti-androgenic activities were exceeded at some sites. The identified drivers of mixture in vitro effects deserve further attention in ecotoxicological and environmental pollution research. This novel approach using long-term passive sampling provides a representative benchmark of pollution and effect potentials of chemical mixtures for future water quality monitoring of the Danube River and other large water bodies.

• Klíčová slova
• Bioanalytical equivalent, Concentration addition, Iceberg modelling, Mixture effects, Passive sampling, Risk prioritization,
• MeSH
• antagonisté androgenů MeSH
• chemické látky znečišťující vodu * toxicita   analýza   MeSH
• ekotoxikologie MeSH
• estron MeSH
• kvalita vody * MeSH
• monitorování životního prostředí metody   MeSH
• řeky chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté androgenů MeSH
• chemické látky znečišťující vodu * MeSH
• estron MeSH

Many reports on anti-progestogenic activities in aquatic environments have been published in the past decade. These are monitored mainly by in vitro reporter gene bioassays based upon the human progesterone receptor (PR). However, results obtained by some human in vitro bioassays may not be relevant for aquatic animals, especially fish. The present work aimed to detect fish (anti-)PR activity in waste- and receiving surface waters. In parallel, human (anti-)PR activity was analysed to determine if there was any connection between human and fish (anti-)PR activities. Finally, (anti-)PR activities were linked to the occurrence of progestins in water samples. Human PR agonistic activity was detected in all wastewater and most receiving surface water samples. Nevertheless, zebrafish PR (zfPR) agonistic activity was found in only two influent wastewater samples (max. 117 ng/L 17α,20β-dihydroxy-4-pregnen-3-one [DHP] equivalents). Analysed synthetic progestins and progesterone accounted for 14 % to 161 % of detected human PR (hPR) agonistic activity in water samples. Progesterone also contributed significantly to zfPR agonistic activity (up to 10 %) in raw wastewater. The anti-hPR activity was detected also in most wastewater and some surface water samples, but synthetic progestins did not trigger anti-zfPR activity in excess of LOQ values. In addition, altrenogest, dienogest, and ulipristal acetate were tested for their potency to zfPR for the first time. The activity analyses of both pure substances and environmental samples showed that human and zebrafish progesterone receptors are differentially activated. Therefore, results based on human PR in vitro bioassays could not predict fish PR activities in the environment.

• Klíčová slova
• Human, In vitro bioassay, Progesterone receptor, Progestin, Wastewater, Zebrafish,
• MeSH
• dánio pruhované * MeSH
• lidé MeSH
• odpadní voda MeSH
• progesteron MeSH
• progestiny analýza   MeSH
• receptory progesteronu * MeSH
• voda analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• odpadní voda MeSH
• progesteron MeSH
• progestiny MeSH
• receptory progesteronu * MeSH
• voda MeSH

Ultraviolet filters are commonly used in various cosmetic products. Due to their huge consumption ultraviolet filters become a part of the environment. Octinoxate is a commonly used ultraviolet filter that is widely detected in the aquatic environment. In our study, we investigated whether this ultraviolet filter is able to disrupt thyroid hormone regulation after six weeks of exposure in rainbow trout (Oncorhynchus mykiss). Thyroid hormones play crucial role in development and regulation of the organism and its disruption could cause the whole-body imbalance. Our study includes a compilation of in vivo and in vitro tests. The results of the in vivo experiment revealed a significant increase in thyroxine hormone in plasma for the highest tested dose of octinoxate (i.e. 395.6 μg/kg). We examined selected tissues (liver and cranial kidney) to determine the mRNA expression of genes involved in thyroid hormones regulation. The analysis confirmed downregulation of deiodinase 2 mRNA expression for the highest tested dose (i.e. 395.6 μg/kg) and downregulation of paired box 8 mRNA for medium (96 μg/kg) and the highest octinoxate dose (395.6 μg/kg.) only in cranial kidney. In vitro analysis indicated that octinoxate does not elicit (anti-)thyroid activity via thrβ and does not behave as a transthyretin ligand. Based on our results, octinoxate has a potential to act as a thyroid hormone disruptor, but further research required to better understand the entire regulatory mechanism.

• Klíčová slova
• Fish, Gene expression, Oncorhynchus mykiss, Thyroxine, UV filter,
• MeSH
• hormony štítné žlázy * MeSH
• messenger RNA metabolismus   MeSH
• Oncorhynchus mykiss * metabolismus   MeSH
• thyroxin MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormony štítné žlázy * MeSH
• messenger RNA MeSH
• octylmethoxycinnamate MeSH Prohlížeč
• thyroxin MeSH

Vaccination is an important tool in the fight against the COVID-19 pandemic in patients with haematologic malignancies. The paper provides an analysis of the course of breakthrough SARS-CoV-2 infection in a group of vaccinated patients with haematological malignancy and a comparison with a historical cohort of 96 non-vaccinated patients with haematologic malignancies and bone marrow failure syndromes (two patients) in the treatment of COVID-19. A severe or critical course of COVID-19 was significantly less frequent in the group of vaccinated patients (10.2% vs. 31.4%, p = 0.003). The need for hospitalisation due to COVID-19 was significantly lower in vaccinated patients (27.1% vs. 72.6%, p < 0.0001) and the duration of hospitalisation was significantly shorter (10 vs. 14 days, p = 0.045). Vaccinated patients were insignificantly less likely to require oxygen therapy during infection. COVID-19 mortality was significantly higher in non-vaccinated patients (15.6% vs. 5.1%, p = 0.047). The paper demonstrated a significant positive effect of vaccination against COVID-19 on a less severe clinical course of infection, lower need for hospitalisation and mortality. However, the results need to be evaluated even in the context of new antivirals and monoclonal antibodies against SARS-CoV-2 or virus mutations with different biological behaviour.

• Klíčová slova
• COVID-19, SARS-CoV-2, haematological malignancy, monoclonal antibodies, mortality, vaccination,
• Publikační typ
• časopisecké články MeSH

Background and Objectives: Given the limited knowledge of antibody responses to COVID-19 and their determinants, we analyzed the relationship between the occurrence of acute-phase symptoms and infection-induced immunoglobulin (Ig) G seropositivity up to 8 months post-symptom onset. Materials and Methods: In this cross-sectional study, 661 middle-aged unvaccinated healthcare workers (HCWs) were interviewed about the presence of symptoms during the acute phase of their previously confirmed COVID-19 and were tested for specific IgG, targeting the spike protein (S1 and S2). The dependence of seropositivity on the symptom occurrence was explored through multiple logistic regression, adjusted for the interval between symptom onset and serology testing, and through classification and regression trees. Results: A total of 551 (83.4%) HCWs showed seropositivity and, inversely, 110 (16.6%) HCWs were seronegative. The chance of IgG seropositivity was increased by dyspnea (odds ratio (OR) 1.48, p < 0.001) and anosmia (OR 1.52, p = 0.021). Fever in HCWs with dyspnea resulted in the highest detected seropositivity rate, and anosmia in HCWs without dyspnea significantly increased the proportion of seropositivity. Conclusion: Clinical manifestation of the acute phase of COVID-19 predisposes to the development of infection-induced antibody responses. The findings can be applied for assessing the long-term protection by IgG, and thus, for creating effective surveillance strategies.

• Klíčová slova
• COVID-19, anosmia, dyspnea, seropositivity, symptom,
• MeSH
• anosmie MeSH
• COVID-19 * komplikace   MeSH
• dyspnoe MeSH
• imunoglobulin G MeSH
• lidé středního věku MeSH
• lidé MeSH
• protilátky virové MeSH
• průřezové studie MeSH
• zdravotnický personál MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin G MeSH
• protilátky virové MeSH

All renal transplant recipients should undergo a regular screening for BK viral (BKV) viremia. Gradual reduction of immunosuppression is recommended in patients with persistent plasma BKV viremia for 3 weeks after the first detection, reflecting the presence of probable or suspected BKV-associated nephropathy. Reduction of immunosuppression is also a primary intervention in biopsy proven nephropathy associated with BKV (BKVN). Thus, allograft biopsy is not required to treat patients with BKV viremia with stabilized graft function. There is a lack of proper randomised clinical trials recommending treatment in the form of switching from tacrolimus to cyclosporin-A, from mycophenolate to mTOR inhibitors or leflunomide, or the additive use of intravenous immunoglobulins, leflunomide or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. There are on-going studies to evaluate the possibility of using a multi-epitope anti-BKV vaccine, administration of BKV-specific T cell immunotherapy, BKV-specific human monoclonal antibody and RNA antisense oligonucleotides. Retransplantation after allograft loss due to BKVN can be successful if BKV viremia is definitively removed, regardless of allograft nephrectomy.

• Klíčová slova
• BK virus nephropathy, BK virus vaccine, BK virus-specific T-cell immunotherapy, RNA antisense oligonucleotides, immunosuppressive therapy, kidney transplantation, monoclonal anti-BK virus antibodies,
• MeSH
• imunosupresiva terapeutické užití   MeSH
• leflunomid terapeutické užití   MeSH
• lidé MeSH
• nemoci ledvin * farmakoterapie   MeSH
• polyomavirové infekce * diagnóza   farmakoterapie   MeSH
• transplantace ledvin * MeSH
• viremie diagnóza   farmakoterapie   MeSH
• virus BK * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunosupresiva MeSH
• leflunomid MeSH

BACKGROUND AND AIMS: COVID-19 pandemic has impacted on all endoscopy centers in the Czech Republic, that belongs to the most affected countries in the world. The aim of our study was to analyze all procedures following routine RT-PCR testing in our tertiary center during the peak of the pandemic. METHODS: We retrospectively analyzed all procedures performed from October 2020 to January 2021 after a new RT-PCR center had been set up. Main outcomes were type of scheduled procedure, indication, rate of therapeutic interventions and rate of new relevant and malignant findings. Comparison to the same period before the pandemic and SARS-CoV-2 infection in endoscopy staff are also reported. RESULTS: A total of 1,953 procedures were performed. 624 patients were referred with a negative RT-PCR test and the remaining 1,346 patients were tested in the new center. 1,293 negative tests led to 1,329 procedures. A new relevant finding was reported in 589 (44.3%), including new malignancy in 56 (4.2%). 53 patients tested positive (3.9%). There was a reduction by 9% in the number of all procedures compared to the same period before the pandemic and an increase in the number of screening colonoscopies and ERCP procedures. In the study period, 9 of 54 staff members contracted SARS-CoV-2 infection. CONCLUSIONS: Routine RT-PCR testing of patients scheduled for elective endoscopy during the peak of COVID-19 pandemic enabled us to essentially maintain our unit productivity, including activities such as screening colonoscopy, endoscopic resection and pancreatobiliary endoscopy.

• Klíčová slova
• coronavirus disease 2019 (COVID-19), digestive endoscopy, reverse transcription polymerase chain reaction (RT-PCR), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
• MeSH
• centra terciární péče MeSH
• COVID-19 * diagnóza   MeSH
• diagnostické testy rutinní MeSH
• gastrointestinální endoskopie * MeSH
• lidé MeSH
• pandemie * MeSH
• polymerázová řetězová reakce s reverzní transkripcí * MeSH
• retrospektivní studie MeSH
• testování na COVID-19 průkazem nukleové kyseliny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH