Údolní nádrž Seč slouží jako retenční prostor při povodních, dále jako zdroj pitné vody a v posledních desetiletích i jako významná rekreační oblast. Z důvodu eutrofizace i zde opakovaně docházelo k výskytu sinicového vodního květu. V červenci roku 2024 došlo ke zcela výjimečné události, kdy po vydatných deštích proniklo do nádrže extrémní množství prvoků ze skupiny obrněnek (Dinophyta). Ty pak vytvořily povlak postupující s proudem vody po nádrži. Jev byl pozorován zhruba měsíc. Doposud nebyly zjištěny sladkovodní obrněnky (na rozdíl od mořských), které by produkovaly toxiny nebezpečné pro lidský organismus, a tak k přímému ohrožení zdraví koupajících se osob nedošlo. Ohrožena nebyla ani výroba pitné vody z nádrže.
The Seč valley reservoir serves as a retention area during floods, as a source of drinking water and in recent decades as an important recreational area. Due to eutrophication, cyanobacterial blooms have repeatedly occurred here. In July 2024, a highly exceptional event occurred when, after heavy rains, an extreme amount of protozoa from the group of giant nematodes (Dinophyta) entered the reservoir. They then formed a coating that progressed with the flow of water through the reservoir. The phenomenon was observed for about a month. So far, freshwater Dinoflagellates (as opposed to marine Dinoflagellates) have not been found to produce toxins dangerous to the human body, so there has been no direct threat to the health of bathers. Nor has the production of drinking water from the reservoir been compromised.
Tento příspěvek se snaží poukázat na šíři problematiky legionel a přispět k jejímu porozumění. Vysvětluje nutnost jejího chápání v širších souvislostech a účel použití ukazatelů Legionella spp. a Legionella pneumophila, které nelze náhodně ani stabilně zaměnit jeden za druhý, protože oba mají odlišnou funkci. Jakákoliv šetření (ať už se jedná o posouzení rizik vnitřního vodovodu, o epidemiologické šetření nebo o výzkumnou studii) a hodnocení se musí provádět s jasně daným cílem a vhodně zvolenými analytickými metodami.
This paper seeks to highlight the scope of the Legionella issue and contribute to its better understanding. It explains the necessity of perceiving it in a broader context and the purpose of using the indicators Legionella spp. and Legionella pneumophila, which cannot be randomly confused or stably substituted for each other, as both have different functions. Any investigation (whether it is domestic distribution system risk assessment, an epidemiological investigation or a research study) and evaluation must be carried out with a clear objective and using analytical methods appropriately chosen for that purpose.
INTRODUCTION: Neonatal hypoglycaemia is the most common metabolic disorder of various causes, relatively rare being MODY (Maturity Onset Diabetes of the Young). CONTENT: Data search of relevant articles focused on hypoglycaemia in carriers of selected MODY gene mutations published from 2007 to 2022 was performed in databases Medline, PubMed, Cochrane and UptoDate based on key words: 'hyperinsulinemic hypoglycaemia', 'congenital hyperinsulinism', 'MODY', 'HNF4A mutation', 'HNF1A mutation'. SUMMARY: Loss of function of HNF4A and HNF1A genes comprises approximately to 5.9 % of diazoxide responsive hyperinsulinemic hypoglycaemia, which may appear in 15 % HNF4A mutation carriers. A typical finding of HNF4A mutation carriers with neonatal hypoglycaemia was a birth weight above 4000 g or above 97th percentile. OUTLOOK: Although mutations in MODY genes represent a rare cause of neonatal hypoglycaemia, they should be considered in the differential diagnosis, particularly in cases of persistent hypoglycaemia requiring intensive care.
- MeSH
- diabetes mellitus 2. typu * genetika komplikace MeSH
- hepatocytární jaderný faktor 1-alfa genetika MeSH
- hepatocytární jaderný faktor 4 * genetika MeSH
- hypoglykemie * genetika etiologie patologie MeSH
- lidé MeSH
- mutace * MeSH
- nemoci novorozenců * genetika MeSH
- novorozenec MeSH
- rodiče MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non-gBRCAm) who had platinum-sensitive relapsed ovarian cancer in the phase IIIb, open-label, single-arm, non-comparator, international OPINION trial (NCT03402841). We report final overall survival (OS; secondary endpoint), prespecified secondary endpoint updates and ad hoc OS analysis by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. METHODS: Patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, ≥2 prior lines of platinum-based chemotherapy, and in response following their last platinum-based chemotherapy received 300 mg olaparib tablets twice daily until disease progression or unacceptable toxicity. RESULTS: 279 patients were enrolled and treated. With a median follow-up in patients censored for OS of 33.1 months (data cut-off September 17, 2021), median OS was 32.7 months (95 % CI 29.5-35.3); the 24-month OS rate was 65.8 %. In ad hoc subgroup analyses, OS rates tended to be higher in patients with HRD-positive tumors; 24-month OS rates were 81.5 %, 74.2 %, 72.0 % and 55.8 % in the sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative subgroups, respectively. Grade ≥ 3 treatment-emergent adverse events were reported in 82 patients (29.4 %), most commonly anemia (13.6 %). Overall, two cases of myelodysplastic syndrome were reported (no new cases since the primary analysis). CONCLUSION: These data provide additional evidence of olaparib as maintenance therapy in patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, with longer OS observed in those with HRD-positive tumors. The safety profile was consistent with the primary analysis and known safety profile of olaparib, with no new safety findings.
- MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- epiteliální ovariální karcinom * farmakoterapie genetika mortalita MeSH
- ftalaziny * škodlivé účinky aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * farmakoterapie genetika MeSH
- nádory vaječníků * farmakoterapie genetika mortalita MeSH
- PARP inhibitory * škodlivé účinky aplikace a dávkování terapeutické užití MeSH
- piperaziny * škodlivé účinky aplikace a dávkování terapeutické užití MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- senioři MeSH
- udržovací chemoterapie MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
Many photosensitive substances suitable for photodynamic therapy (PDT) have limited applications due to their insufficient solubility in polar solvents. Our research overcomes this challenge by means of nanotechnology in order to transform hydrophobic compounds into stable aqueous solutions, enabling them to use their full potential and unique properties in cancer therapy. In this study, the novel nano-composite cGQDs-PEG-curcumin was developed to overcome the insolubility of curcumin in water and its extraordinary efficacy in PDT was evaluated. Complex characterization was performed using high-resolution transmission electron microscopy (HR-TEM), FTIR, and UV-Vis spectroscopy. Further analysis involved fluorescence lifetime imaging (FLIM), and its cellular localization was mapped with confocal microscopy. In order to evaluate PDT effectiveness, cells treated with cGQDs-PEG-curcumin were irradiated with 5 J/cm2 of 414 nm light. After irradiation, cell viability assay, scanning electron microscopy (SEM), reactive oxygen species (ROS) detection, comet assay, and γH2AX-based DNA double-strand breaks (DSBs) detection were assessed and revealed a remarkable ability of the nano-composite to induce DNA damage after irradiation without ROS production. Our findings highlight the potential of cGQDs-PEG-curcumin as a cutting-edge PDT agent, capable of disrupting cell membrane and nucleolar integrity and impairing ribosomal synthesis, which is crucial for proliferating tumour cells.
- MeSH
- buněčné jadérko * účinky léků metabolismus MeSH
- dvouřetězcové zlomy DNA účinky léků MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky * farmakologie MeSH
- grafit * chemie farmakologie MeSH
- kurkumin * farmakologie chemie MeSH
- kvantové tečky * chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory * farmakoterapie MeSH
- polyethylenglykoly * chemie farmakologie MeSH
- poškození DNA * účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Flow cytometry immunophenotyping is critical for the diagnostic classification of mature/peripheral B-cell neoplasms/B-cell chronic lymphoproliferative disorders (B-CLPD). Quantitative driven classification approaches applied to multiparameter flow cytometry immunophenotypic data can be used to extract maximum information from a multidimensional space created by individual parameters (e.g., immunophenotypic markers), for highly accurate and automated classification of individual patient (sample) data. Here, we developed and compared five diagnostic classification algorithms, based on a large set of EuroFlow multicentric flow cytometry data files from a cohort 659 B-CLPD patients. These included automatic population separators based on Principal Component Analysis (PCA), Canonical Variate Analysis (CVA), Neighbourhood Component Analysis (NCA), Support Vector Machine algorithms (SVM) and a variant of the CA(Canonical Analysis) algorithm, in which the number of SDs (Standard Deviations) varied for each of the comparisons of different pairs of diseases (CA-vSD). All five classification approaches are based on direct prospective interrogation of individual B-CLPD patients against the EuroFlow flow cytometry B-CLPD database composed of tumor B-cells of 659 individual patients stained in an identical way and classified a priori by the World Health Organization (WHO) criteria into nine diagnostic categories. Each classification approach was evaluated in parallel in terms of accuracy (% properly classified cases), precision (multiple or single diagnosis/case) and coverage (% cases with a proposed diagnosis). Overall, average rates of correct diagnosis (for the nine B-CLPD diagnostic entities) of between 58.9 % and 90.6 % were obtained with the five algorithms, with variable percentages of cases being either misclassified (4.1 %-14.0 %) or unclassifiable (0.3 %-37.0 %). Automatic population separators based on CA, SVM and PCA showed a high average level of correctness (90.6 %, 86.8 %, and 86.0 %, respectively). Nevertheless, this was at the expense of proposing a considerable number of multiple diagnoses for a significant proportion of the test cases (54.5 %, 53.5 %, and 49.6 %, respectively). The CA-vSD algorithm generated the smaller average misclassification rate (4.1 %), but with 37.0 % of cases for which no diagnosis was proposed. In contrast, the NCA algorithm left only 2.7 % of cases without an associated diagnosis but misclassified 14.0 %. Among correctly classified cases (83.3 % of total), 91.2 % had a single proposed diagnosis, 8.6 % had two possible diagnoses, and 0.2 % had three. We demonstrate that the proposed AI algorithms provide an acceptable level of accuracy for the diagnostic classification of B-CLPD patients and, in general, surpass other algorithms reported in the literature.
- MeSH
- algoritmy MeSH
- B-lymfocyty * patologie MeSH
- imunofenotypizace * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfoproliferativní nemoci * diagnóza klasifikace MeSH
- průtoková cytometrie * metody MeSH
- senioři MeSH
- support vector machine MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
