BACKGROUND AND OBJECTIVES: Given the paucity of high-quality safety/efficacy data on acute stroke therapies in patients with premorbid disability, they risk being routinely excluded from such therapies. We examined utilization of endovascular thrombectomy (EVT), associated workflow, and poststroke outcomes among patients with vs without premorbid disability. METHODS: We used national registry data on thrombolysis/EVT for the Czech Republic from 1 January 2016 to 31 December 2020. Premorbid disability was defined as prestroke modified Rankin Scale score (mRS) ≥3. We compared proportions of patients with vs without premorbid disability who received EVT and examined workflow times. We compared ΔmRS-change in mRS from prestroke to 3 months-in patients with vs without premorbid disability, in addition to intracerebral hemorrhage (ICH), mortality, and discharge NIHSS (National Institutes of Health Stroke Scale score), adjusting for age, sex, baseline NIHSS, and comorbidities, and verified using propensity score weighting (PSW) and matching for differences in treatment assignment. We stratified by age group (<65, 65-74, 75-84, ≥85 years) to explore outcome heterogeneity with vs without premorbid disability. RESULTS: Among 22,405 patients with ischemic stroke who received thrombolysis/EVT/both, 1,712 (7.6%) had prestroke mRS ≥ 3. Patients with prestroke disability were less likely to receive EVT vs those without (10.1% vs 20.7%, aOR: 0.30, 95% CI 0.24-0.36). When treated, they had longer door-to-arterial puncture times (median: 75 minutes, IQR: 58-100 vs 54, IQR: 27-77, adjusted difference: 12.5, 95% CI 2.68-22.3). Patients with prestroke disability receiving thrombolysis/EVT/both had worse ΔmRS (adjusted rate ratio, aIRR on PSW: 1.57, 95% CI 1.43-1.72), rates of 3-month mRS 5-6, discharge NIHSS, and mortality (aOR-PSW [mortality]: 2.54, 95% CI 1.92-3.34), while ICH did not significantly differ. 32.1% of patients with prestroke disability receiving thrombolysis/EVT/both successfully returned to prestroke state, but this proportion ranged from 19.6% for those older than 85 years to 66.0% for those younger than 65 years. Regardless of premorbid disability, EVT was associated with better outcomes including lower ΔmRS (aIRR-PSW: 0.87, 95% CI 0.83-0.91) and mortality, with no interaction of treatment effect by premorbid disability status (e.g., mortality pinteraction = 0.73). EVT recipients with premorbid disability did not differ significantly for several outcomes including ΔmRS (aIRR: 0.99, 95% CI 0.84-1.17) but were more likely to have 3-month mRS 5-6 (70.1% vs 39.5% without premorbid disability, aOR: 1.85, 95% CI 1.12-3.04). DISCUSSION: Patients with premorbid disability were less likely to receive EVT, had slower treatment times, and had worse outcomes compared with patients without premorbid disability. However, regardless of premorbid disability, patients fared better with EVT vs medical management and one-third with prestroke disability returned to their prestroke status.

• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage (ICH) is a serious medical condition with high mortality. However, factors leading to long-term mortality after ICH are largely unclear. The aim of this community-based study is to assess predictors of long-term mortality after spontaneous ICH. METHODS: We identified all patients admitted with spontaneous ICH to hospitals with a certified stroke unit in Brno, the second largest city in the Czech Republic (CR), in 2011, the year of the Czech Population and Housing Census. We reviewed their medical records for risk factors, radiographic parameters, and measures of post-stroke neurological deficit [National Institutes of Health Stroke Scale (NIHSS)]. Using the dates of death from the Czech National Mortality Register, we calculated mortality at 30 days, six months, one year, and three years after the ICH. Multivariate analysis with forward stepwise logistic regression was performed to determine independent predictors of mortality (p < 0.05). RESULTS: In 2011, 1086 patients with stroke were admitted to the four stroke-certified hospitals in Brno, CR. Of these, 134 had spontaneous ICH, with complete data available in 93 of them entering the final analysis. The mortality at 30 days, 6 months, 1 year, and 3 years post-ICH was 34%, 47%, 51%, and 63%, respectively. The mortality was highest in the first few days post-event, with 50% of patients dying in 255 days and average survival being 884 ± 90 days. Both NIHSS and modified ICH (MICH) score showed to be strong and reliable predictors of short- as well as long-term mortality; the risk of death post-ICH increased with older age and size of ICH. Other risk factors contributing to higher, primarily shorter-term mortality included history of cardiac failure, myocardial infarction, or atrial fibrillation. CONCLUSIONS: In our community-based study, we found that severity of neurological deficit at admission (NIHSS), combined with age and size of ICH, well predicted short- as well as long-term mortality after spontaneous ICH. A history of cardiac failure, myocardial infarction, or atrial fibrillation at presentation were also predictors of mortality, underscoring the need for optimal cardiac management in patients with ICH.

• Klíčová slova
• Community-based study, Czech Republic, Intracerebral hemorrhage, Mortality,
• MeSH
• cerebrální krvácení * mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Two principal growth regulators, cytokinins and ethylene, are known to interact in the regulation of plant growth. However, information about the underlying molecular mechanism and positional specificity of cytokinin/ethylene crosstalk in the control of root growth is scarce. We have identified the spatial specificity of cytokinin-regulated root elongation and root apical meristem (RAM) size, both of which we demonstrate to be dependent on ethylene biosynthesis. Upregulation of the cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE (IPT) in proximal and peripheral tissues leads to both root and RAM shortening. By contrast, IPT activation in distal and inner tissues reduces RAM size while leaving the root length comparable to that of mock-treated controls. We show that cytokinins regulate two steps specific to ethylene biosynthesis: production of the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC) by ACC SYNTHASEs (ACSs) and its conversion to ethylene by ACC OXIDASEs (ACOs). We describe cytokinin- and ethylene-specific regulation controlling the activity of ACSs and ACOs that are spatially discrete along both proximo/distal and radial root axes. Using direct ethylene measurements, we identify ACO2, ACO3, and ACO4 as being responsible for ethylene biosynthesis and ethylene-regulated root and RAM shortening in cytokinin-treated Arabidopsis. Direct interaction between ARABIDOPSIS RESPONSE REGULATOR 2 (ARR2), a member of the multistep phosphorelay cascade, and the C-terminal portion of ETHYLENE INSENSITIVE 2 (EIN2-C), a key regulator of canonical ethylene signaling, is involved in the cytokinin-induced, ethylene-mediated control of ACO4. We propose tight cooperation between cytokinin and ethylene signaling in the spatially specific regulation of ethylene biosynthesis as a key aspect of the hormonal control of root growth.

• Klíčová slova
• ACC OXIDASE, ACC SYNTHASE, Arabidopsis, cytokinin, ethylene, multistep phosphorelay,
• MeSH
• Arabidopsis * genetika   růst a vývoj   metabolismus   MeSH
• cytokininy * metabolismus   MeSH
• ethyleny * metabolismus   biosyntéza   MeSH
• kořeny rostlin * růst a vývoj   genetika   metabolismus   MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• regulace genové exprese u rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokininy * MeSH
• ethylene MeSH Prohlížeč
• ethyleny * MeSH
• proteiny huseníčku MeSH

Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.

• Klíčová slova
• COVID-19, Hematology malignancy, SARS-CoV-2, Tixagevimab/cilgavimab,
• MeSH
• COVID-19 * MeSH
• dospělí MeSH
• hematologické nádory * komplikace   farmakoterapie   epidemiologie   MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• preexpoziční profylaxe * MeSH
• retrospektivní studie MeSH
• SARS-CoV-2 MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cilgavimab MeSH Prohlížeč
• monoklonální protilátky MeSH
• tixagevimab MeSH Prohlížeč

The ability for plant regeneration from dedifferentiated cells opens up the possibility for molecular bioengineering to produce crops with desirable traits. Developmental and environmental signals that control cell totipotency are regulated by gene expression via dynamic chromatin remodeling. Using a mass spectrometry-based approach, we investigated epigenetic changes to the histone proteins during callus formation from roots and shoots of Arabidopsis thaliana seedlings. Increased levels of the histone H3.3 variant were found to be the major and most prominent feature of 20-day calli, associated with chromatin relaxation. The methylation status in root- and shoot-derived calli reached the same level during long-term propagation, whereas differences in acetylation levels provided a long-lasting imprint of root and shoot origin. On the other hand, epigenetic signs of origin completely disappeared during 20 days of calli propagation in the presence of histone deacetylase inhibitors (HDACi), sodium butyrate, and trichostatin A. Each HDACi affected the state of post-translational histone modifications in a specific manner; NaB-treated calli were epigenetically more similar to root-derived calli, and TSA-treated calli resembled shoot-derived calli.

• Klíčová slova
• Arabidopsis thaliana, callus formation, epigenetics, histone posttranslational modifications, mass spectrometry, sodium butyrate, trichostatin A,
• Publikační typ
• časopisecké články MeSH

PURPOSE: To investigate the safety and efficacy of baseline antiplatelet treatment in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: Baseline use of antiplatelet medication before MT for (AIS) may provide benefit on reperfusion and clinical outcome but could also carry an increased risk of intracranial hemorrhage (ICH). All consecutive patients with AIS and treated with MT with and without intravenous thrombolysis (IVT) between January 2012 and December 2019 in all centers performing MT nationwide were reviewed. Data were prospectively collected in national registries (eg, SITS-TBY and RES-Q). Primary outcome was functional independence (modified Rankin Scale 0-2) at 3 months; secondary outcome was ICH. RESULTS: Of the 4,351 patients who underwent MT, 1,750 (40%) and 666 (15%) were excluded owing to missing data from the functional independence and ICH outcome cohorts, respectively. In the functional independence cohort (n = 2,601), 771 (30%) patients received antiplatelets before MT. Favorable outcome did not differ in any antiplatelet, aspirin, and clopidogrel groups when compared with that in the no-antiplatelet group: odds ratio (OR), 1.00 (95% CI, 0.84-1.20); OR, 1.05 (95% CI, 0.86-1.27); and OR, 0.88 (95% CI, 0.55-1.41), respectively. In the ICH cohort (n = 3,685), 1095 (30%) patients received antiplatelets before MT. The rates of ICH did not increase in any treatment options (any antiplatelet, aspirin, clopidogrel, and dual antiplatelet groups) when compared with those in the no-antiplatelet group: OR, 1.03 (95% CI, 0.87-1.21); OR, 0.99 (95% CI, 0.83-1.18); OR, 1.10 (95% CI, 0.82-1.47); and OR, 1.43 (95% CI, 0.87-2.33), respectively. CONCLUSIONS: Antiplatelet monotherapy before MT did not improve functional independence or increase the risk of ICH.

• MeSH
• Aspirin škodlivé účinky   MeSH
• cévní mozková příhoda * diagnostické zobrazování   terapie   MeSH
• intrakraniální krvácení chemicky indukované   MeSH
• ischemická cévní mozková příhoda * diagnostické zobrazování   terapie   MeSH
• ischemie mozku * diagnostické zobrazování   terapie   MeSH
• klopidogrel škodlivé účinky   MeSH
• lidé MeSH
• mechanická trombolýza * škodlivé účinky   MeSH
• trombektomie škodlivé účinky   MeSH
• trombolytická terapie škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Aspirin MeSH
• klopidogrel MeSH

Seedling de-etiolation is one of the key stages of the plant life cycle, characterized by a strong rearrangement of the plant development and metabolism. The conversion of dark accumulated protochlorophyllide to chlorophyll in etioplasts of de-etiolating plants is taking place in order of ns to µs after seedlings illumination, leading to detectable increase of chlorophyll levels in order of minutes after de-etiolation initiation. The highly complex chlorophyll biosynthesis integrates number of regulatory events including light and hormonal signaling, thus making de-etiolation an ideal model to study the underlying molecular mechanisms. Here we introduce the iReenCAM, a novel tool designed for non-invasive fluorescence-based quantitation of early stages of chlorophyll biosynthesis during de-etiolation with high spatial and temporal resolution. iReenCAM comprises customized HW configuration and optimized SW packages, allowing synchronized automated measurement and analysis of the acquired fluorescence image data. Using the system and carefully optimized protocol, we show tight correlation between the iReenCAM monitored fluorescence and HPLC measured chlorophyll accumulation during first 4h of seedling de-etiolation in wild type Arabidopsis and mutants with disturbed chlorophyll biosynthesis. Using the approach, we demonstrate negative effect of exogenously applied cytokinins and ethylene on chlorophyll biosynthesis during early de-etiolation. Accordingly, we identify type-B response regulators, the cytokinin-responsive transcriptional activators ARR1 and ARR12 as negative regulators of early chlorophyll biosynthesis, while contrasting response was observed in case of EIN2 and EIN3, the components of canonical ethylene signaling cascade. Knowing that, we propose the use of iReenCAM as a new phenotyping tool, suitable for quantitative and robust characterization of the highly dynamic response of seedling de-etiolation.

• Klíčová slova
• Arabidopsis, chlorophyll biosynthesis, cytokinins, de-etiolation, ethylene, fluorescence, iReenCAM,
• Publikační typ
• časopisecké články MeSH

Although the link between microbial infections and Alzheimer's disease (AD) has been demonstrated in multiple studies, the involvement of pathogens in the development of AD remains unclear. Here, we investigated the frequency of the 10 most commonly cited viral (HSV-1, EBV, HHV-6, HHV-7, and CMV) and bacterial (Chlamydia pneumoniae, Helicobacter pylori, Borrelia burgdorferi, Porphyromonas gingivalis, and Treponema spp.) pathogens in serum, cerebrospinal fluid (CSF) and brain tissues of AD patients. We have used an in-house multiplex PCR kit for simultaneous detection of five bacterial and five viral pathogens in serum and CSF samples from 50 AD patients and 53 healthy controls (CTRL). We observed a significantly higher frequency rate of AD patients who tested positive for Treponema spp. compared to controls (AD: 62.2 %; CTRL: 30.3 %; p-value = 0.007). Furthermore, we confirmed a significantly higher occurrence of cases with two or more simultaneous infections in AD patients compared to controls (AD: 24 %; CTRL 7.5 %; p-value = 0.029). The studied pathogens were detected with comparable frequency in serum and CSF. In contrast, Borrelia burgdorferi, human herpesvirus 7, and human cytomegalovirus were not detected in any of the studied samples. This study provides further evidence of the association between microbial infections and AD and shows that paralleled analysis of multiple sample specimens provides complementary information and is advisable for future studies.

• Klíčová slova
• Alzheimer's disease, Microbial infection, PCR, Pathogen, Serum, Treponema spp.,
• MeSH
• Alzheimerova nemoc * epidemiologie   mikrobiologie   MeSH
• infekce bakteriemi rodu Treponema * epidemiologie   MeSH
• lidé MeSH
• lidský herpesvirus 6 MeSH
• studie případů a kontrol MeSH
• Treponema * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bradykinin analogy a deriváty   terapeutické užití   MeSH
• hereditární angioedémy * diagnóza   farmakoterapie   MeSH
• inhibiční protein komplementu C1 genetika   terapeutické užití   MeSH
• lidé MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• bradykinin MeSH
• icatibant MeSH Prohlížeč
• inhibiční protein komplementu C1 MeSH

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disease which causes health problem that affects more patients in the past few years. To be able to offer appropriate care, epidemiological analyses are crucial at the national level and its comparison with the international situation. AIM: The demographic description of reported patients with parkinsonism (including Parkinson's disease and atypical parkinsonian syndromes) according to the International Classification of Diseases (ICD-10) from the national health registries. METHODS: Retrospective analysis of data available from the National Health Information System-NHIS and the National Registry of Reimbursed Health Services (NRRHS). Analyzed epidemiological data are intending to determine the regional and specific prevalence of Parkinsonism in the Czech Republic. The International Classification of Diseases diagnoses (ICD-10) of G20 (Parkinson's disease-PD) and G23.1, G23.2, G23.3 (other degenerative disorders of basal ganglia), and G31.8 (another degenerative disease of basal ganglia) from the period of 2012 to 2018 were included into the analysis. RESULTS: We identified 78 453 unique patients from national registries in the period 2012 to 2018. Diagnoses of G20, G23.1, G23.2, and G31.8 were registered as the principal diagnoses in 76.6% of all individual patients. CONCLUSION: We have found a growing number of patients coded with ICD-10 of dg. G20, G23.1, G23.2, G23.3, or G31.8 (N = 27 891 in 2012, and N = 30 612 in 2018). We have proven regional differences in the prevalence of Parkinson´s diagnoses. Therefore we assume most likely also differences in the care of patients with PD based on the availability of specialty care centers.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurodegenerativní nemoci epidemiologie   MeSH
• Parkinsonova nemoc diagnóza   epidemiologie   MeSH
• parkinsonské poruchy diagnóza   epidemiologie   MeSH
• prevalence MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH