Although impacts of extremely cold temperatures on human health have been widely studied, adverse effects of other extreme weather phenomena have so far received much less attention. We employed a high-quality long-term mortality time series (1982-2017) to evaluate impacts of extreme winter weather in the Czech Republic. We aimed to clarify whether compound events of extreme weather cause larger impacts on mortality than do each type of extreme if evaluated individually. Using daily data from the E-OBS and ERA5 datasets, we analyzed 9 types of extreme events: extreme wind gust, precipitation, snowfall, and sudden temperature and pressure changes. Relative mortality deviations from the adjusted baseline were used to estimate the immediate effect of the selected extreme events on excess mortality. The impact was adjusted for the effect of extreme cold. Extreme events associated with sudden rise of minimum temperature and pressure drops had generally significant impact on excess mortality (3.7% and 1.4% increase). The impacts were even more pronounced if these events occurred simultaneously or were compounded with other types of extremes, such as heavy precipitation, snowfall, maximum temperature rise, and their combinations (increase as great as 14.4%). Effects of some compound events were significant even for combinations of extremes having no significant impact on mortality when evaluated separately. On the other hand, a "protective" effect of pressure increases reduced the risk for its compound events. Meteorological patterns during extreme events linked to excess mortality indicate passage of a low-pressure system northerly from the study domain. We identified extreme winter weather events other than cold temperatures with significant impact on excess mortality. Our results suggest that occurrence of compound extreme events strengthen the impacts on mortality and therefore analysis of multiple meteorological parameters is a useful approach in defining adverse weather conditions.

• Klíčová slova
• Central Europe, Compound event, Extreme winter weather, Mortality, Sudden change,
• MeSH
• lidé MeSH
• mortalita MeSH
• nízká teplota * MeSH
• počasí * MeSH
• roční období MeSH
• teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

BACKGROUND: Plants, like all living organisms, metamorphose their bodies during their lifetime. All the developmental and growth events in a plant's life are connected to specific points in time, be it seed germination, seedling emergence, the appearance of the first leaf, heading, flowering, fruit ripening, wilting, or death. The onset of automated phenotyping methods has brought an explosion of such time-to-event data. Unfortunately, it has not been matched by an explosion of adequate data analysis methods. RESULTS AND DISCUSSION: In this paper, we introduce the Bayesian approach towards time-to-event data in plant biology. As a model example, we use seedling emergence data of maize under control and stress conditions but the Bayesian approach is suitable for any time-to-event data (see the examples above). In the proposed framework, we are able to answer key questions regarding plant emergence such as these: (1) Do seedlings treated with compound A emerge earlier than the control seedlings? (2) What is the probability of compound A increasing seedling emergence by at least 5 percent? CONCLUSION: Proper data analysis is a fundamental task of general interest in life sciences. Here, we present a novel method for the analysis of time-to-event data which is applicable to many plant developmental parameters measured in field or in laboratory conditions. In contrast to recent and classical approaches, our Bayesian computational method properly handles uncertainty in time-to-event data and it is capable to reliably answer questions that are difficult to address by classical methods.

• Klíčová slova
• Bayesian inference, Data analysis, Plant development, Plant phenotyping, Statistics, Survival analysis, Time-to-event data, Uncertainty,
• Publikační typ
• časopisecké články MeSH

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.

• Klíčová slova
• Adverse events, Ixazomib, Maintenance therapy, Multiple myeloma, Safety,
• MeSH
• autologní štěp MeSH
• glycin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mnohočetný myelom * mortalita   terapie   MeSH
• následné studie MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• silikáty aplikace a dávkování   škodlivé účinky   MeSH
• sloučeniny boru aplikace a dávkování   škodlivé účinky   MeSH
• transplantace kmenových buněk * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• glycin MeSH
• ixazomib MeSH Prohlížeč
• silikáty MeSH
• sloučeniny boru MeSH
• tourmaline MeSH Prohlížeč

Lake ecosystems process and cycle organic substrates, thus serving as important bioreactors in the global carbon cycle. Climate change is predicted to increase extreme weather and precipitation events that can flush nutrients and organic matter from soils to streams and lakes. Here we report changes in stable isotopes (δ2H, δ13C, δ15N, or δ18O) of water, dissolved organic matter (DOM), seston, and zooplankton in a subalpine lake at short time resolution following an extreme precipitation event between early July to mid-August 2021. Water from excess precipitation and runoff remained in the lake epilimnion and coincided with increasing δ13C values of seston (-30 ‰ to -20 ‰), due to the input of carbonates and terrestrial organic matter. Particles settled into deeper lake layers after two days and contributed to the uncoupling of C and N cycling as the lake responded to this extreme precipitation event. Following the event, there was an increase in bulk δ13C values of zooplankton (from -35 ‰ to -32 ‰). Throughout this study, δ13C values of DOM remained stable throughout the water column (-29 ‰ to -28 ‰), while large isotopic fluctuations in DOM δ2H (-140 ‰ to -115 ‰) and δ18O (+9 ‰ to +15 ‰) values suggested DOM relocation and turnover. Integrating isotope hydrology, ecosystem ecology, and organic geochemistry offers an element-specific, detailed approach to investigating the impact of extreme precipitation events on freshwater ecosystems and particularly aquatic food webs.

• Klíčová slova
• Basal aquatic resources, Deuterium, Organic matter cycling, Plankton food web,
• MeSH
• ekosystém MeSH
• izotopy uhlíku analýza   MeSH
• jezera * MeSH
• rozpuštěná organická hmota MeSH
• voda MeSH
• zooplankton * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• izotopy uhlíku MeSH
• rozpuštěná organická hmota MeSH
• voda MeSH

In the course of this study 37 sediment samples were analyzed. They were taken after the flooding in September 2002 along the Elbe and at the mouths of its major tributaries. The sampling program covered the entire river stretch that was affected by the floods, from Obristvi (Czech Republic) to the Elbe estuary (North Sea) on the German coast. Analyses were performed for dioxins, nonylphenols, nonylphenol ethoxylates, bisphenol A, DEHP, musk fragrances, polybrominated diphenylethers, chloroalkylphosphates, organochlorine compounds, PAH, and organotin compounds. The results show that only a few weeks after the flood, contaminant concentrations in solid matter were comparable to those prevailing beforehand. Significant sources of contaminant input proved to be the tributaries Vltava (Moldau), Bilina (both in the Czech Republic), and the Mulde (Germany), as well as industrial and municipal sewage treatment works (STW) located along the Elbe. Further point sources are to be found in still water zones such as harbors and abandoned channels. These sources are activated when erosive action stirs up older sediments. Statistical analyses of the congener distribution of the dioxins provided evidence on the sources of these contaminants and freight levels in different river sections. The chemical analyses were complemented by results of ecotoxicological investigations with two sediment organisms (Chironomus riparius and Potamopyrgus antipodarum).

• MeSH
• chemické látky znečišťující vodu analýza   toxicita   MeSH
• Chironomidae MeSH
• geologické sedimenty chemie   MeSH
• katastrofy * MeSH
• měkkýši MeSH
• monitorování životního prostředí MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Severní moře MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH

Here we report for the first time the development of a compact, closed bipolar electrochemistry (BPE) device for the determination of antioxidant capacity in real-world samples by recording the onset driving voltage at which an eye-visible reporting event at the cathode pole of bipolar electrode (BE) occurs. The BPE cell consists of two distinct anode and cathode compartments that are electrically connected through a platinum wire BE. The anode pole of the BE is covered by a cellulose acetate thin film to prevent the fouling of the surface, while the cathode pole is embedded into an agarose hydrogel containing phenolphthalein, i.e., an acid-base indicator. The method relies on the oxidation of the reducing compounds in the sample by a fixed amount of H2O2 and the electro oxidation of the remaining H2O2 in the anode pole of the BE. This reaction triggers the reduction of water at the cathodic pole accompanied by the production of hydroxyl ions at different, H2O2 concentration-dependent onset driving voltages. The resulting increase of pH at the cathode pole results in the formation of a pink spot (reporting event), which is visible by the unaided eye. The applicability of the BPE device for the determination of antioxidant capacity in fruit juices and sodas is demonstrated. The analytical results, expressed as Trolox (TEAC) or Vitamin C (CVEAC) equivalent antioxidant capacity, correlate well with those obtained by the CUPRAC method.

• Klíčová slova
• Agarose hydrogel, Antioxidant capacity, Bipolar electrochemistry, Eye visual detection, Phenolphthalein, Portable analytical device,
• Publikační typ
• časopisecké články MeSH

• MeSH
• evokované potenciály účinky léků   MeSH
• insekticidy toxicita   MeSH
• krysa rodu Rattus MeSH
• nervový systém účinky léků   patofyziologie   MeSH
• organofosforové sloučeniny * MeSH
• potkani Wistar MeSH
• těžké kovy toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• insekticidy MeSH
• organofosforové sloučeniny * MeSH
• těžké kovy MeSH

The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.

• Klíčová slova
• DNA methylation patterns, cancer, epigenetic modulations, oncogenes, phytochemicals, plant-based foods, tumor suppressor genes,
• MeSH
• epigeneze genetická genetika   MeSH
• fytonutrienty farmakologie   MeSH
• lidé MeSH
• metylace DNA účinky léků   MeSH
• nádory genetika   MeSH
• protinádorové látky farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fytonutrienty MeSH
• protinádorové látky MeSH

Epileptic seizures activate not only excitatory but also inhibitory systems what results in an arrest of seizures. Our recent data indicate that GABAergic inhibition plays an important role in this process in cortically elicited seizures. We started to study the role of GABA-B receptors in cortical epileptic afterdischarges (ADs) in immature rats 12, 18 and 25 days old with implanted electrodes. Low-frequency stimulation of sensorimotor cortical area was repeated with increasing intensities of stimulation current. Thresholds for movements directly elicited by stimulation, for spike-and-wave type of AD, for clonic seizures accompanying this type of ADs and for transition into limbic type of AD were decreased by the 200mg/kg dose of a GABA-B receptor antagonist CGP35348 in all three age groups. Duration of ADs was markedly increased by 50, 100 as well as 200mg/kg dose of CGP35348. The effects were best expressed in 18-day-old rats. To conclude, GABA-B receptors play an important role in generation and especially in arrest of cortical seizures in immature rats.

• MeSH
• analýza rozptylu MeSH
• biofyzika metody   MeSH
• elektrická stimulace škodlivé účinky   MeSH
• elektroencefalografie metody   MeSH
• epilepsie etiologie   patologie   patofyziologie   prevence a kontrola   MeSH
• evokované potenciály účinky léků   MeSH
• GABA antagonisté farmakologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra účinky léků   patofyziologie   MeSH
• novorozená zvířata MeSH
• organofosforové sloučeniny farmakologie   MeSH
• potkani Wistar MeSH
• stárnutí fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CGP 35348 MeSH Prohlížeč
• GABA antagonisté MeSH
• organofosforové sloučeniny MeSH

The mode of action of membrane-active molecules, such as antimicrobial, anticancer, cell penetrating, and fusion peptides and their synthetic mimics, transfection agents, drug permeation enhancers, and biological signaling molecules (e.g., quorum sensing), involves either the general or local destabilization of the target membrane or the formation of defined, rather stable pores. Some effects aim at killing the cell, while others need to be limited in space and time to avoid serious damage. Biological tests reveal translocation of compounds and cell death but do not provide a detailed, mechanistic, and quantitative understanding of the modes of action and their molecular basis. Model membrane studies of membrane leakage have been used for decades to tackle this issue, but their interpretation in terms of biology has remained challenging and often quite limited. Here we compare two recent, powerful protocols to study model membrane leakage: the microscopic detection of dye influx into giant liposomes and time-correlated single photon counting experiments to characterize dye efflux from large unilamellar vesicles. A statistical treatment of both data sets does not only harmonize apparent discrepancies but also makes us aware of principal issues that have been confusing the interpretation of model membrane leakage data so far. Moreover, our study reveals a fundamental difference between nano- and microscale systems that needs to be taken into account when conclusions about microscale objects, such as cells, are drawn from nanoscale models.

• Klíčová slova
• antimicrobial compound, dye release, fluorescence lifetime, fluorescence microscopy, leakage, lipid membrane, lipid vesicle, pore,
• MeSH
• fluoresceiny metabolismus   MeSH
• fluorescenční barviva metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• fluorescenční spektrometrie MeSH
• liposomy metabolismus   MeSH
• permeabilita buněčné membrány MeSH
• permeabilita MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluoresceiny MeSH
• fluorescenční barviva MeSH
• fluorexon MeSH Prohlížeč
• liposomy MeSH