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Background: Grammatical deficits in aphasia have been the subject of research in many languages. It is stated that the symptoms vary depending on morphological-syntactic properties of a studied language. Only a few studies have mapped the symptoms of the grammatical impairment in inflective languages, but the Slovak language has not been studied so far. Aims: The primary aim of our study was to map grammatical deficits in aphasic patients speaking Slovak by analysing some aspects of morphology and syntax. We studied the influence of the type of aphasia, the degree of non-fluent aphasia, and the method eliciting speech on the fluency of patients' production. Methods & Procedures: We analysed production in 7 patients with anomic and 4 patients with non-fluent (Broca's) aphasia. Patients with Broca's aphasia were divided into 2 groups according to the fluency of their production. The speech of patients with a more severe degree of aphasia consisted of content words separated with long pauses. Production of patients with a mild degree of Broca's aphasia was non-fluent sometimes full of perseverations, repairs and false starts but with some syntactic organisation. The samples of spontaneous speech were obtained with two methods: interview and picture description. The speech production of patients was tape-recorded, transcribed, and analysed. The analysis included various aspects of morphology and syntax. Outcomes & Results: According to our results, patients with anomic aphasia did not have apparent problems with any aspect of morphology, but errors occurred on the level of complex syntactic constructions. The speech production of patients with Broca's aphasia was deficient and some symptoms (the use of grammatical morphemes, contextually disallowed verbal ellipses) varied depending on the degree of aphasia. Conclusions: This analysis revealed morphological-syntactic deficits in Slovak-speaking aphasic patients. The results indicate that the symptoms depend not only on the type of aphasia but also on the degree of Broca's aphasia. We compared these results with studies carried out in other languages (for example, Czech, Polish, Serbo-Croatian, Hungarian, Turkish). [ABSTRACT FROM AUTHOR]

The paper is focused on the deterioration of industrial reinforced concrete chimneys caused by carbonation. It is considered that a chimney has to be repaired when more than 30% of its surface is affected by visible corrosion-induced cracks. An optimal maintenance strategy aims at the postponement of this state beyond the intended service life of the chimney with minimum maintenance costs.

The contribution is focused on reliability of balcony girders of a Czech national heritage monument. As preliminary reliability assessment suggests insufficient resistance, a series of nondestructive tests supplemented by a single tensile test are performed and evaluated by the statistical methods. Values of material properties, recommended in standards for historic materials, seem to be overly conservative and it is advised to specify properties of historic metallic materials by tests.

The contribution is focused on quantifying model uncertainty of crack width estimates for reinforced concrete beams. Predictions obtained by the model provided by the fib Model Code 2010 are compared with results of tests of beams having different longitudinal and shear reinforcement ratios and concrete cover. Trends of model uncertainty with basic variables are investigated.

Presently the new generation of Eurocodes is under development. It is expected that the basis of structural design given in current EN 1990 will be considerably revised including the format for load combinations in the Ultimate Limit States and new categorisation of consequence classes for construction works. It is expected that the partial factors for self-weight of structural members could be reduced and factors for variable loads more differentiated. Calibration of partial factors should be performed for actions and materials including also structural glass and FRP polymers.

The assessment of existing components of power producing facilities is based on probabilistic methods of the theory of reliability provided in Eurocodes and ISO standards. An example of quickclosing valves in a selected hydroelectric power plant indicates the assessment of reliability and the prediction of the remaining working life of a structural component for the considered model of corrosion.

The article deals with two wells in the country of Brno-district (Brčálka well and Well Olšová). The aim of work was monitoring of elementary parameters of water at regular monthly intervals to measure: water temperature, pH values, solubility oxygen and spring yield. According to the client's requirements (Lesy města Brno) laboratory analyzes of selected parameters were done twice a year and their results were compared with Ministry of Health Decree no. 252/2004 Coll.. These parameters: nitrate, chemical oxygen demand (COD), calcium and magnesium and its values are presented in graphs, for ammonium ions and nitrite in the table. Graphical interpretation of spring yields dependence on the monthly total rainfall and dependence of water temperature on ambient temperature was utilized. The most important features of wells include a water source, a landmark in the landscape, aesthetic element or resting and relaxing place. Maintaining wells is important in terms of future generations.

A 62-year-old woman presented with loss of memory and a mild hemiparesis. Neuroradiology demonstrated a left frontoparietal tumour. Biopsy specimens of this lesion revealed intracerebral Hodgkin's lymphoma, a diagnosis supported by immunohistochemical reactions of the tumour cells for the CD30 antigen. Additional cell cycle studies revealed a high proliferative activity of the tumour cells in association with absence of apoptosis. There was no evidence that overexpression of bcl-2 or Epstein-Barr virus infection was involved in the pathogenesis of this neoplasm. Lymphomas in the lung were detected 3 months later. Following neurosurgical excision, radiotherapy, and chemotherapy, the patient had no evidence of Hodgkin's disease after 13 months of follow-up. [ABSTRACT FROM AUTHOR]

Cultures of microorganisms were isolated from endosphere of Lake Baikal littoral zone plants: Veronica chamaedrys L., Alchemilla subscrenata Buser, Achillea asiatica Serg., Taraxacum officinale Wigg., Plantago major L. Morphology and biochemical properties of isolated bacteria were studied. For the majority of the endophytic bacterial cultures cellulolitic and proteolytic activity has been shown, which necessary for the effective colonization of plant tissue. For many cultures revealed ability in varying degrees to form a biofilm to improve survival in a vegetative organism. Their potencial role in adaptation of plant-hosts under conditions of climat Baikal region was shown. In particular, 9 of cultures demonstrated ability to act as nitrogen retainer. The vast majority of bacterial cultures did not have phytotoxicity or demonstrated its low level, reflecting and minimum negative effects of them on plant. Moreover, culture with encryption P3, isolated from Plantago major in August, showed a stimulatory effect in experiments on phytotoxicity. This same culture possessed the highest ability to secrete sugars as at +26°С and at +4°С.

Ornamental aquaculture is known to be one of the main sources of non-native species and Indonesia has been identified as one of the leading suppliers of these organisms worldwide. Released or escaped ornamental aquatic animals can establish new populations and become invasive. On the other hand, some invasive species can be also endangered in their native range, which is called the “Biodiversity Conservation Paradox”. This is true for Arapaima gigas, one of the popular ornamental creatures and the largest bony fish of all, which is threatened in its native range in parts of Amazonia and which has been found to occur in various localities in Java and Sumatra in Indonesia. Based on climate matching we found the vast majority of Indonesian territory to be suitable for this species establishment. Keeping in mind the size and predatory behaviour of A. gigas, we discussed possible consequences of its spread and impacts on native biota in Indonesia.

The target reliability levels recommended in national and international documents vary within a broad range, while the reference to relevant costs and failure consequences is mentioned only very vaguely. In some documents the target reliability index is indicated for one or two reference periods (1 year, 50 years or life-time) without providing appropriate links to the design working life. This contribution attempts to clarify the relationship between the target reliability levels, costs of safety measures, failure consequences, reference periods and the design working life

The article concerns the monitoring of selected sources (monitored a total of 10 springs, presented the results of 5 springs) administered by the Forests of the city of Brno in the northern district of Brno-county, describing their current state, including the evaluation of selected water quality parameters. The basis of the study was to measure basic water quality parameters (water temperature, pH, oxygen and measuring the rate of flow of water in springs) and sampling for laboratory analysis. The values obtained were tabulated and graphically evaluated and compared with values in accordance with Decree no. 252/2004 Coll., which lay down the hygienic requirements for drinking water. Based on the measured values charts and graphs were compiled, and the water quality of the individual strands were assessed. The overall condition of wells and their surroundings is described in detail and assessed.

Purpose: Parasites of genus Encephalitozoon are well known pathogens of domestic animals however less attention was paid to its spread among wildlife that can play an important role of reservoir of infection. The aim of the study was to conduct molecular detection and genotype characterization of Encephalitozoon spp. in wild small mammals trapped in localities both near to and at a large distance from residential areas., Methods: In total, 300 wild small mammals (274 Rodentia and 26 Eulipotyphla) were trapped in 41 localities of the Czech Republic and tested by nested PCR for Encephalitozoon spp., Results: The DNA of Encephalitozoon spp. was proved in tissues (brain or liver) of 11% (32/300) of animals. There was a statistically significant difference (p < 0.001) in positivity among animal species with the most infected species Micromys minutus (50%, 4/8) and Myodes glareolus (17%, 9/53). There was also statistically significant difference (p < 0.001) between localities with the higher positivity (29%, 12/42) in localities near to residential areas, compared to localities with a large distance from residential areas (8%, 20/258). Sex and age of wild small mammals did not have effect on their positivity. Genotyping analysis revealed E. cuniculi genotype II in 22 samples and E. hellem genotype 1 A in one sample., Conclusion: This study brings new information on the molecular characterization of Encephalitozoon spp. isolated from wild small mammals trapped in two different areas (localities in near to residential areas and localities with a large distance from residential areas)., Competing Interests: Declarations. Ethical Approval Statement: The trapping of animals and the sampling were conducted according to the experimental projects approved by the Administration of the Poodří Protected Landscape Area, by the Administration of the Moravian Karst, and by the Ministry of the Environment of the Czech Republic (projects no. 41/2015, no. 8/2016, and no. 42/2015). Competing Interests: The authors declare no competing interests. Conflict of Interest: None of the authors have any financial or personal relationships that could inappropriately influence or bias the content of the paper., (© 2024. The Author(s).)

Background: Several studies have proven the presence of cohesion difficulties in neurogenic communication disorders. However, we still have very little information about discourse cohesion in the intact adult population and the factors that influence it. The aim of the present study is to provide additional information on this topic and to assess the effect of age and education on discourse cohesion., Methods: One hundred and eighty-two healthy Slovak-speaking adult participants were divided into three age groups and three education groups were asked to tell Cinderella's story. The cohesion of the obtained discourse samples was evaluated., Results: Our study indicates no significant effect of age. However, an increasing tendency of the occurrence of cohesive tie errors with increasing age was described. Education, on the other hand, turned out to be a statistically significant factor and had an impact on the overall use of cohesive ties as well as the use of referential pronouns., Conclusion: Our findings suggest that monitoring the influence of education when creating normative data for discourse cohesion is more important than monitoring the effect of age.

Somatic JAK2 mutations are the main molecular cause of the vast majority of polycythemia vera (PV) cases. According to a recent structural model, the prevalent acquired V617F mutation improves the stability of the JAK2 dimer, thereby enhancing the constitutive JAK2 kinase activity. Germline JAK2 mutations usually do not largely alter JAK2 signaling, although they may modulate the impact of V617F. We found an unusual germline JAK2 mutation L604F in homozygous form in a young PV patient, along with a low allele burden JAK2 V617F mutation, and in her apparently healthy sister. Their father with a PV-like disease had L604F in a heterozygous state, without V617F. The functional consequences of JAK2 L604Fmutation were compared with those induced by V617F in two different in vitro model systems: (i) HEK293T cells were transfected with plasmids for exogenous JAK2-GFP expression, and (ii) endogenous JAK2 modifications were introduced into HeLa cells using CRISPR/Cas9. Both mutations significantly increased JAK2 constitutive activity in transfected HEK293T cells. In the second model, JAK2 modification resulted in reduced total JAK2 protein levels. An important difference was also detected: as described previously, the effect of V617F on JAK2 kinase activity was abrogated in the absence of the aromatic residue F595. In contrast, JAK2 hyperactivation by L604F was only partially inhibited by the F595 change to alanine. We propose that the L604F mutation increases the probability of spontaneous JAK2 dimer formation, which is physiologically mediated by F595. In addition, L604F may contribute to dimer stabilization similarly to V617F., (© 2023. The Author(s).)

Caseous lymphadenitis (CL) is a chronic contagious disease that affects small ruminants and is characterized by the formation of pyogranulomas in lymph nodes and other organs. However, the pathogenesis of this disease and the response of the host genome to infection are not yet fully understood. This study aimed to investigate the whole blood transcriptome and evaluate differential gene expression during the later stages of CL in naturally infected ewes. The study included diseased, serologically positive (EP), exposed, serologically negative (EN) ewes from the same infected flock and healthy ewes (CN) from a different flock. RNA sequencing was performed using the Illumina NextSeq system, and differential gene expression was estimated using DESeq2 and Edge R approaches. The analysis identified 191 annotated differentially expressed genes (DEGs) in the EP group (102 upregulated and 89 downregulated) and 256 DEGs in the EN group (106 upregulated and 150 downregulated) compared to the CN group. Numerous immunoregulatory interactions between lymphoid and nonlymphoid cells were influenced in both EP and EN ewes. Immune DEGs were preferentially assigned to antigen presentation through the MHC complex, T lymphocyte-mediated immunity, and extracellular matrix interactions. Furthermore, the EP group showed altered regulation of cytokine and chemokine signaling and activation and recombination of B-cell receptors. Conversely, NF-kappa B signaling, apoptosis, and stress response were the main processes influenced in the EN group. In addition, statistically significant enrichment of the essential immune pathways of binding and uptake of ligands by scavenger receptors in EP and p53 signaling in the EN group was found. In conclusion, this study provides new insights into the disease course and host-pathogen interaction in naturally CL-infected sheep by investigating the blood transcriptome.

Bats may carry various viruses and bacteria which can be harmful to humans, but little is known about their role as a parasitic source with zoonotic potential. The aim of this study was to test wild bats for the presence of selected parasites: Toxoplasma gondii , Neospora caninum and microsporidia Encephalitozoon spp. In total, brain and small intestine tissues of 100 bats (52 Myotis myotis , 43 Nyctalus noctula and 5 Vespertilio murinus ) were used for the DNA isolation and PCR detection of the abovementioned agents. Toxoplasma gondii DNA was detected by real-time PCR in 1% of bats (in one male of M. myotis ), while all bats were negative for N. caninum DNA. Encephalitozoon spp. DNA was detected by nested PCR in 25% of bats, including three species (twenty-two M. myotis , two N. noctula and one V. murinus ). Positive samples were sequenced and showed homology with the genotypes Encephalitozoon cuniculi II and Encephalitozoon hellem 2C. This is the first study on wild vespertilionid bats from Central Europe and worldwide, with a relatively high positivity of Encephalitozoon spp. detected in bats.

The immune system is important for elimination of residual leukemic cells during acute myeloid leukemia (AML) therapy. Anti-leukemia immune response can be inhibited by various mechanisms leading to immune evasion and disease relapse. Selected markers of immune escape were analyzed on AML cells from leukapheresis at diagnosis (N = 53). Hierarchical clustering of AML immunophenotypes yielded distinct genetic clusters. In the absence of DNMT3A mutation, NPM1 mutation was associated with decreased HLA expression and low levels of other markers (CLIP, PD-L1, TIM-3). Analysis of an independent cohort confirmed decreased levels of HLA transcripts in patients with NPM1 mutation. Samples with combined NPM1 and DNMT3A mutations had high CLIP surface amount suggesting reduced antigen presentation. TIM-3 transcript correlated not only with TIM-3 surface protein but also with CLIP and PD-L1. In our cohort, high levels of TIM-3/PD-L1/CLIP were associated with lower survival. Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment., Competing Interests: The authors report there are no competing interests to declare., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Wild small mammals and ticks play an important role in maintaining and spreading zoonoses in nature, as well as in captive animals. The aim of this study was to monitor selected agents with zoonotic potential in their reservoirs and vectors in a zoo, and to draw attention to the risk of possible contact with these pathogens. In total, 117 wild small mammals (rodents) and 166 ticks were collected in the area of Brno Zoo. Antibodies to the bacteria Coxiella burnetii , Francisella tularensis , and Borrelia burgdorferi s.l. were detected by a modified enzyme-linked immunosorbent assay in 19% (19/99), 4% (4/99), and 15% (15/99) of rodents, respectively. Antibodies to Leptospira spp. bacteria were detected by the microscopic agglutination test in 6% (4/63) of rodents. Coinfection (antibodies to more than two agents) were proved in 14.5% (15/97) of animals. The prevalence of C. burnetii statistically differed according to the years of trapping ( p = 0.0241). The DNAs of B. burgdorferi s.l., Rickettsia sp., and Anaplasma phagocytophilum were detected by PCR in 16%, 6%, and 1% of ticks, respectively, without coinfection and without effect of life stage and sex of ticks on positivity. Sequencing showed homology with R. helvetica and A. phagocytophilum in four and one positive samples, respectively. The results of our study show that wild small mammals and ticks in a zoo could serve as reservoirs and vectors of infectious agents with zoonotic potential and thus present a risk of infection to zoo animals and also to keepers and visitors to a zoo.

Monitoring of infectious diseases is one of the most important pillars of preventive medicine in zoos. Screening for parasitic and bacterial infections is important to keep animals and equipment safe from pathogens that may pose a risk to animal and human health. Zoos usually contain many different animal species living in proximity with people and wild animals. As an epidemiological probe, 188 animals (122 mammals, 65 birds, and one reptile) from a zoo in Slovenia were examined for selected pathogens. Antibodies to Toxoplasma gondii and Neospora caninum were detected by ELISA in 38% (46/122) and 3% (4/122) of mammals, and in 0% (0/64) and 2% (1/57) of birds, respectively; the reptile (0/1) was negative. A statistically significant difference in T. gondii prevalence was found in Carnivora compared to Cetartiodactyla and primate antibodies to Encephalitozoon cuniculi were detected by IFAT in 44% (52/118) of mammals and 20% (11/56) of birds, respectively; the reptile (0/1) was negative. Herbivores had a higher chance of being infected with E. cuniculi compared to omnivores. Antibodies to Chlamydia abortus and Coxiella burnetii were not detected in any of the 74 tested zoo animals. The sera of 39 wild rodents found in the zoo were also examined; they were negative for all three parasites. The parasite T. gondii was detected by PCR in the tissue of two mute swans ( Cygnus olor ), three eastern house mice ( Mus musculus ), one yellow-necked field mouse (Apodemus flavicollis ), and one striped field mouse ( A. agrarius ). Positive samples were genotyped by a single multiplex PCR assay using 15 microsatellite markers; one sample from a mute swan was characterized as type II. This micro-epidemiological study offers a better understanding of pathogens in zoo animals and an understanding of the role of zoos in biosurveillance.

Objectives: Interaction of leukemia cells with the bone marrow extracellular matrix promotes cell survival and resistance to chemotherapy. In this work, we analyzed integrin expression and adhesivity to fibronectin in primary cells from patients with acute myeloid leukemia., Methods: Surface expression of integrins β1 and αVβ3 on primary leukemia cells (N = 46) was correlated with the stem cell marker CD34, as well as with cell adhesivity to fibronectin. The results were analyzed with regard to the mutational status of NPM1 and FLT3 genes., Results: The integrin β1 was omnipresent, whereas αVβ3 was often more expressed on CD34-positive cells. In particular, higher αVβ3 expression on CD34+ cells was associated with NPM1 mutation (P = .0018). Monocytic leukemias had significantly higher αVβ3 expression compared to less maturated cases (P = .0008). Cells from patients with internal tandem duplications in FLT3 (FLT3-ITD) had lower adhesivity to fibronectin compared to cells with wild-type FLT3 (P = .031), specifically in less differentiated myeloblasts. Inhibition of a putative FLT3-ITD target, EZH2, increased cell adhesivity in MV4-11 cell line (P = .024)., Conclusions: The integrin αVβ3 is expressed in particular on CD34+ cells with NPM1 mutation and might have a prognostic value in patients with mutated NPM1. FLT3-ITD is associated with lower cell adhesivity, especially in patients with less differentiated leukemias., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A novel series of aromatic esters (1a-1m) related to the Amaryllidaceae alkaloid (AA) haemanthamine were designed, synthesized and tested in vitro with particular emphasis on the treatment of neurodegenerative diseases. Some of the synthesized compounds revealed promising acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory profile. Significant human AChE (hAChE) inhibition was demonstrated by 11-O-(3-nitrobenzoyl)haemanthamine (1j) with IC 50 value of 4.0 ± 0.3 µM. The strongest human BuChE (hBuChE) inhibition generated 1-O-(2-methoxybenzoyl)haemanthamine (1g) with IC 50 value 3.3 ± 0.4 µM. Moreover, 11-O-(2-chlorbenzoyl)haemanthamine (1m) was able to inhibit both enzymes in dose-dependent manner. The mode of hAChE and hBuChE inhibition was minutely inspected using enzyme kinetic analysis in tandem with in silico experiments, the latter elucidating crucial interaction in 1j-, 1m-hAChE and 1g-, 1m-hBuChE complexes. The blood-brain barrier (BBB) permeability was investigated applying the parallel artificial membrane permeation assay (PAMPA) to predict the CNS availability of the compounds., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction : Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of relapsed/refractory Hodgkin lymphoma (R/R HL). In this study, we report on outcomes with BV in a real-world setting using data collected in clinics in the Czech Republic and Slovakia. Patients and Methods : Clinical and epidemiological data for patients with R/R HL who received treatment with BV at eight centers across the Czech Republic and Slovakia were examined. Data were amalgamated and analyzed retrospectively. Results : Clinical data for 58 patients (median age: 30.5 years) with R/R HL who received BV during the course of their treatment were collected and analyzed. Patients had received a median of 3 prior treatment regimens and most (91%) were treated with BV after relapse following autologous stem cell transplantation. Therapeutic responses after BV included 19 (33%) complete responses (CRs) and 8 (14%) partial responses. CRs occurred more frequently in patients who had received fewer prior treatment regimens. The 1-, 2-, and 3-year overall survival (OS) rates from initiation of BV were 78%, 62%, and 41%, respectively. Conclusion : Response rates and OS in this analysis of BV in real-world settings in the Czech Republic and Slovakia were consistent with those reported for pivotal clinical trials and from previous studies outside the clinical trial setting. The results support the efficacy of BV for treatment of R/R HL in real-life clinical practice., Competing Interests: Competing Interests: Zdeněk Král, MD, consultancy/advisory board member: Takeda, speaker for: Amgen, Teva, research support from: no, stock options with: no, consultancy for: Takeda. Jozef Michalka, MD, consultancy/advisory board member: no, speaker for: no, research support from: no, stock options with: no, consultancy for: no. Heidi Móciková, MD, consultancy/advisory board member: no, speaker for: no, research support from: no, stock options with: no, consultancy for: no. Jana Marková, MD, consultancy/advisory board member: no, speaker for: no, research support from: no, stock options with: no, consultancy for: no. Alice Sýkorová, MD, consultancy/advisory board member: no, speaker for: Bristol-Myers Squibb, Roche, Takeda research support from: no, stock options with: no, consultancy for: no. David Belada, MD, consultancy/advisory board member: Takeda, speaker for: Takeda, research support from: Takeda, stock options with: no, consultancy for: no. Alexandra Jungová, MD, consultancy/advisory board member: no, speaker for: no, research support from: no, stock options with: no, consultancy for: no. Samuel Vokurka, MD, consultancy/advisory board member: Takeda, speaker for: no, research support from: no, stock options with: no, consultancy for: Novartis, Roche, Teva. Marie Lukášová, MD, consultancy/advisory board member: no, speaker for: Bristol-Myers Squibb, research support from: no, stock options with: no, consultancy for: no. Vít Procházka, MD, consultancy/advisory board member: Bristol-Myers Squibb, Takeda, speaker for: Gilead, Servier, research support from: Takeda, stock options with: no, consultancy for: no. Juraj Ďuraš, MD, consultancy/advisory board member: Roche, speaker for: no, research support from: no, stock options with: no, consultancy for: no. Roman Hájek, MD, consultancy/advisory board member: Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Takeda, speaker for: no, research support from: Janssen-Cilag, Takeda, stock options with: no, consultancy for: Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Takeda, honoraria from: Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag and Takeda. Ladislav Dušek MD, consultancy/advisory board member: no; speaker for: no, research support from: no, stock options with: no, consultancy for: no. Ľuboš Drgoňa MD, consultancy/advisory board member: AbbVie, Bristol-Myers Squibb, Celgene, Gilead, JnJ/Janssen, Pfizer, Roche/Genentech, Servier, Takeda; speaker for: Celgene, Pfizer, Roche/Genentech, Servier, Teva, research support from: no, stock options with: no, consultancy for: no. Miriam Ladická MD, consultancy/advisory board member Celgene, Roche/Genentech, Servier, Takeda, speaker for: Celgene, Roche/Genentech, Servier, Takeda, research support from: no, stock options with: no, consultancy for: no. Veronika Ballová MD, consultancy/advisory board member -no; speaker for: -no, research support from: -no, stock options with: no, consultancy for: no. Andrej Vranovský MD, consultancy/advisory board member of: Celgene, Gilead, Janssen, Roche, Takeda, speaker for: Roche, research support from: Celgene, stock options with: no, consultancy for: no., (© The author(s).)

Subsequent to EMA approval of tetrahydrocannabinol (THC): cannabidiol (CBD) oromucosal spray based on results of various studies, including an enriched-design clinical trial, two newer postapproval randomized trials have confirmed its efficacy and safety for treating resistant multiple sclerosis spasticity, while simultaneously addressing specific authorities' concerns. A double-blind, placebo-controlled, Phase IV trial, conducted as part of the EMA's risk management plan, found no effect of THC:CBD spray on cognition and mood after 50 weeks of treatment. In the Sativex ® as add-on therapy versus further optimized first-line ANTispastics (SAVANT)  study, add-on THC:CBD spray was significantly more effective than readjusting standard antispasticity therapy and provided new evidence of efficacy as requested by German authorities. SAVANT results support practical recommendations for treating resistant multiple sclerosis spasticity in daily practice.

The aim of this study was to determine the seroprevalence of antibodies to B. burgdorferi s.l. in wild small mammals in the Czech Republic and compare sensitivity of PCR and cultivaton. Wild small mammals (n = 691) were trapped in years 2010-2014 in three localities of the Czech Republic. Heart rinses (n = 340) and sera (n = 351) were examined by modified indirect ELISA. Seventy animals were randomly selected for comparison of results of cultivation and PCR. Mean annual antiborelian positivity was 12% with statistical difference (p < 0.05) between Bank Vole (Clethrionomys glareolus) and other six animal species, while there was no statistical difference (p > 0.05) between rodentia and insectivora, gender and localities. The cultivation revealed one positive sample (1.4%), negative in both PCR and ELISA. Method PCR revealed seven positive samples (10%); two of them were simultaneously dubious in ELISA. Eleven animals, negative in cultivation and PCR, had antibodies in ELISA. Method of PCR compared to cultivation seems to be more sensitive for detection of Borrelia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The majority of patients with Hodgkin Lymphoma (HL) can be cured with stage and risk adapted treatment today. Therefore, current research focuses on reducing long-term sequelae of treatment. Osteonecrosis (ON) is a severe long-term complication of HL treatment which has so far not been systematically evaluated. Hence, we investigated incidence, risk factors and timing of symptomatic ON in HL patients. Further endpoints included localization, intervention and outcome of ON. We included all qualified HL patients of the randomized German Hodgkin Study Group trials HD10-15 and HD18, recruited between 05/1998 and 07/2014 and aged from 16 to 60 years. Among 11 330 patients, 66 developed symptomatic ON after first-line treatment, 83.3% within three years. The incidence of symptomatic ON was 0.2% in early-stage HL and 1.0% in advanced-stage HL. Logistic regression revealed the total cumulative corticosteroid dose to be a strong risk factor interacting with younger age. Male sex additionally increased the risk of symptomatic ON. The prognostic value of the corresponding logistic regression model was rather high (AUC = 0.78). Other tested potential risk factors including obesity, IPS and radiotherapy did not further increase the risk of ON. Further development of current treatment protocols should aim to reduce the cumulative corticosteroid dose.

Toxoplasma gondii, Neospora caninum, and Encephalitozoon cuniculi are important infectious agents, with T. gondii and E. cuniculi having zoonotic potential. There are two main clonal lineages (types I and II) of T. gondii in Europe, but little is known about genotypes of T. gondii in wild animals. The aim of our study was molecular detection of these three pathogens in tissues of wild red foxes ( Vulpes vulpes) from the Czech Republic. Using PCR (B1 gene), we detected T. gondii in 10% of the animals that we tested ( n=100); N. caninum and E. cuniculi were not detected. The T. gondii samples were genotyped by single multiplex PCR assay with 15 microsatellite markers. Five samples were successfully genotyped as genotype II, a unique finding for T. gondii isolated from red foxes from the Czech Republic.

Background: According to some studies, sentence comprehension is diminished in Alzheimer's disease (AD) patients, but they differ on what underlies the sentence comprehension impairment. Sentence comprehension in AD patients has been studied mainly in the English language. It is less clear how patients with AD speaking a morphologically rich language with grammatical morphemes indicating case and through it even thematic roles process reversible sentences., Aims: To compare the comprehension of various syntactic constructions in Slovak-speaking AD patients and cognitively intact elderly people. We were concerned with the influence of the following aspects on sentence comprehension: its length, the order of thematic roles and the presence of a morphological cue placed on the first noun (or at the beginning of a sentence)., Methods & Procedures: We used our own Slovak test of sentence comprehension based on matching pictures to spoken sentences. These sentences contain transitive verbs and two nouns (person/animal), one functioning as a subject and the other as an object, which both can perform the action expressed by the verb. We assessed 62 healthy elderly people and two groups of AD patients. The first group consisted of 34 participants with a mild degree of AD and the other group of 43 participants with a moderate degree of AD., Outcome & Results: Statistical comparisons showed that the elderly controls were significantly better in the comprehension of simple active OVS (object-verb-subject word order) sentences and complex EO sentences (a centre-embedded relative clause with a relative pronoun substituting for an object) than patients with a mild degree of AD. In patients with a moderate degree of AD, comprehension of all tested sentence types was worse than in healthy elderly people. The results also indicated that even mild AD patients have more serious problems with processing sentences with non-canonical order of thematic roles regardless of a morphological cue at the beginning of a sentence., Conclusion & Implications: The results point to diminished sentence comprehension in patients with AD. In the group of mild AD patients, the order of thematic roles played a significant role in their sentence comprehension. Even though the grammatical morphemes clearly code the functions of words in the Slovak language, mild AD patients do not process them in sentences with a non-canonical order of thematic roles at the same level as the healthy controls. Patients with moderate AD have significant problems even with the comprehension of sentences with a canonical order of thematic roles. These difficulties seem to be a consequence of insufficient resources for language processing., (© 2016 Royal College of Speech and Language Therapists.)

Background: Cognitive impairment (impairment of memory, attention, or concentration) is documented in 17-75% of patients with various malignancies treated with chemotherapeutic agents that worsen quality of life. CRCI affects patients of all ages. The impairment of cognitive function in connection with chemotherapy is usually mild, but an event. relationship with dementia remains to be confirmed. Chemotherapy in combination with radiotherapy in Hodgkin lymphoma can cure 80-90% of patients., Aim: This review summarizes the most frequently observed changes in cognitive function in patients suffering from CRCI. The article further describes the possible pathophysiological mechanisms behind these changes and the risk factors that can increase the likelihood of cognitive functional impairment after chemotherapy of malignant tumors. Special attention is given to how this relates to Hodgkins lymphoma. We also discuss the neuroprotective factors involved in chemotherapy-related cognitive impairment and its treatment options., Conclusion: Changes occur mainly in the ability to learn and remember, in the speed of reactions, and in attention and executive functions. Although CRCI pathophysiological mechanisms are complex and not yet fully understood, the involvement of neurotoxicity, such as that induced by treatment, anemia, higher levels of oxidative stress and inflammatory responses, genetic factors, and reduced brain connectivity is discussed. CRCI is further modified by comorbidities and patient age. Pharmacological and nonpharmacological treatment options for CRCI are outlined.Key words: Hodgkin lymphoma - chemotherapy - cognitive impairment - risk factors The project was supported by the grant of the Agency for the Czech Republic Health Research of the Ministry of Health of the Czech Republic 16-29857A and by the project Sustainability for the National Institute of Mental Health No. LO1611 with a financial support of the Ministry of Education, Youth and Sports of the Czech Republic in the frame of the National Sustainability Programme I. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 9. 2016Accepted: 12. 2. 2017.

High-dose chemotherapy with autologous stem cell transplantation remains the current standard of treatment for young patients with Hodgkin lymphoma in first relapse or in those who are refractory to first-line treatment. The most important prognostic factors in relapses are clinical stage IV, poor performance status, bulky mass, and less than partial remission after salvage chemotherapy. Standard salvage chemotherapy in relapse before autologous transplantation has not been defined; however, DHAP and ICE are most frequently used in this setting. A standard conditioning regimen before autologous transplantation is BEAM. Tandem autologous transplantation has been investigated in high-risk patients. Brentuximab vedotin is recommended as a consolidation treatment in patients with a high risk of relapse after autologous transplantation. Brentuximab vedotin is the standard of treatment for relapse after autologous transplantation, and subsequent allogeneic stem cell transplantation should be considered in young patients. Bretuximab vedotin in combination with bendamustine, nivolumab, and pembrolizumab, and combinations thereof with other drugs, were investigated in clinical trials in relapsed or refractory patients with Hodgkin lymphoma.Key words: Hodgkin lymphoma - autologous stem cell transplantation - brentuximab vedotin - nivolumabThis work was supported by grant awarded by AZV 16-29857, Ministry of Health in Czech Republic, Research project P 27/2012 awarded by Charles University in Prague, 3rd Faculty of Medicine, Prague.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 6. 2016Accepted: 24. 8. 2016.

Introduction and Objectives: Encephalitozoon cuniculi is an obligate intracellular parasite infecting especially domestic rabbits; however, spontaneous infections have been documented in other mammalian species such as dogs, cats, rabbits, horses, cows and sheep all over the world. Encephalitozoonosis is a chronic and latent disease leading to renal failure, encephalitis, disorders of brain and urinary tract, and may lead to death. There are limited reports on encephalitozoonosis in wildlife, which is why the aim of this study was to detect the prevalence of antibodies to E. cuniculi in European hares., Materials and Methods: Samples of blood sera from 701 wild hares from the Czech Republic (n = 245), the Slovak Republic (n = 211) and Austria (n = 245) were examined by indirect immunofluorescence antibody test (IFAT); samples with titer ≥ 40 were marked as positive., Results: The total seroprevalence of E. cuniculi antibodies was 1.42% with titres in the range 40-640. Antibodies to E. cuniculi were detected in 2.9% (7/245), 0.8% (2/245) and 0.47% (1/211) hares from the Czech Republic, Austria and the Slovak Republic, respectively., Conclusions: This is the first detection of antibodies to E. cuniculi in hares from Europe showing that hares could be exposed to E. cuniculi infection, however with a low rate.

Background: Studying DNA methylation changes in the context of structural rearrangements and point mutations as well as gene expression changes enables the identification of genes that are important for disease onset and progression in different subtypes of acute myeloid leukemia (AML) patients. The aim of this study was to identify differentially methylated genes with potential impact on AML pathogenesis based on the correlation of methylation and expression data., Methods: The primary method of studying DNA methylation changes was targeted bisulfite sequencing capturing approximately 84 megabases (Mb) of the genome in 14 diagnostic AML patients and a healthy donors' CD34+ pool. Subsequently, selected DNA methylation changes were confirmed by 454 bisulfite pyrosequencing in a larger cohort of samples. Furthermore, we addressed gene expression by microarray profiling and correlated methylation of regions adjacent to transcription start sites with expression of corresponding genes., Results: Here, we report a novel hypomethylation pattern, specific to CBFB-MYH11 fusion resulting from inv(16) rearrangement that is associated with genes previously described as upregulated in inv(16) AML. We assume that this hypomethylation and corresponding overexpresion occurs in the genes whose function is important in inv(16) leukemogenesis. Further, by comparing all targeted methylation and microarray expression data, PBX3 differential methylation was found to correlate with its gene expression. PBX3 has been recently shown to be a key interaction partner of HOX genes during leukemogenesis and we revealed higher incidence of relapses in PBX3-overexpressing patients., Conclusions: We discovered new genomic regions with aberrant DNA methylation that are associated with expression of genes involved in leukemogenesis. Our results demonstrate the potential of the targeted approach for DNA methylation studies to reveal new regulatory regions.

Background: Relapses occur in 20-30% of patients with Hodgkin lymphoma (HL). Currently, there is no widely accepted standard treatment strategy in relapsed/refractory HL patients ineligible for autologous stem cell transplantation (ASCT). This article retrospectively evaluates survival and prognosis of patients with relapsed/refractory HL who were not suitable for high-dose chemotherapy and ASCT. New drugs and their efficacy in this indication are also disscussed., Patients and Methods: A total of 17 patients treated with at least three lines of standard chemotherapy ± radiotherapy were analysed. High-dose chemotherapy and ASCT was not indicated due to advanced age (seven patients), chemorefractory disease (seven patients), cardiotoxicity (two patients) and insufficient stem cell collection of CD34+ cells (one patient)., Results: Median follow-up of the whole group after establishing the diagnosis was 3.48 years. Overall response to the second-line treatment was achieved in eight patients (47.0%). Four patients (23,5%) were classified as primary refractory after the first-line treatment and three more chemorefractory patients (17,6%) were detected after the second-line treatment. Out of 17 patients four are still alive (23,5%) in remission and 13 have died (eight due to HL progressions, four due to toxicity of the treatment and one patient with unknown cause of death). The estimated 5-year overall survival from the time of initial diagnosis was 46.3% and 30.8% when counted from the diagnosis of the first relapse. The estimated 5-year overall survival of four primary chemorefractory patients was significantly worse when compared to the group of 13 relapsed patients: 0 vs. 60.6%, p < 0,001., Conclusion: Prognosis of relapsed/refractory HL patients ineligible for ASCT and treated with several lines of standard chemotherapy ± radiotherapy is poor. Brentuximab vedotin is indicated in primary refractory patients in the second-line settings and in other relapsed patients in the third-line treatment. This strategy would help to increase the number of remissions, hence achieving a higher survival rate.

Background: Indication of radiotherapy in lymphoma treatment is an important strategic decision requiring comprehensive expertise. It also calls for a better definition of the position of radiotherapy in clinical practice., Design: This position paper represents a consensus between hematooncologists and radiation oncologists on the role of RT in treatment of different histological types and stages of malignant lymphomas. The discussion was underway within professional societies of both specializations (Czech Lymphoma Study Group for the hematooncologists and the Society of Radiation Oncology, Biology and Physics for the radiation oncologists)., Results: The consensus presented here was reached in early 2012 and draws on evidence-based medicine and clinical practice. Besides defining the role of radiotherapy in lymphoma treatment, this paper also gives specific recommendations on total doses of radiotherapy in lymphoma treatment., Conclusion: These recommendations will supplement 7th edition of "Diagnostic and treatment guidelines in patients with malignant lymphoma" scheduled for publication in 2013.

We examined 79 acute myeloid leukemia (AML) patients for DNA methylation of 12 tumor suppressor genes (TSG) and 24 homeobox domain (Hox) genes, and additionally for mutations in DNMT3A gene. We observed lower levels of DNA methylation (P<0.0001) as well as smaller numbers of concurrently hypermethylated genes (P<0.0001) in patients with DNMT3A mutations. Our study of the impact of DNA methylation on prognosis in intermediate and high risk AML patients revealed a relation between higher DNA methylation and better patients' outcome. Lower DNA methylation was linked with higher relapse rates and an inferior overall survival., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Recently, mutations in DNMT3A gene have been described in about 25% acute myeloid leukemia (AML) cases, preferentially in monocytic AML. They were found to predict worse overall survival (OS) of mutated patients., Patients and Methods: RT-PCR followed by direct sequencing was used to test the presence of DNMT3A mutations in 226 AML patients with an intermediate-risk (IR) cytogenetics., Results: Sixty-seven patients of 226 (29.6%) carried a mutation in the DNMT3A gene. Occurrence of DNMT3A mutations was associated with female sex (P = 0.027) and with the presence of FLT3/ITD (P = 0.003), but not with particular FAB subtypes. Patients with DNMT3A mutation had higher initial WBC counts than those without it (P = 0.064) only because of higher incidence of FLT3/ITD within these cases. There was no difference between mutated and wild-type groups in reaching complete remission (CR) (P = 0.380). OS was not affected by DNMT3A mutation (P = 0.251), but OS of patients who reached CR was longer in DNMT3A negative cases (P = 0.025). Patients with DNMT3A mutation had a higher relapse rate (P = 0.007). Patients carrying both the DNMT3A mutation and FLT3/ITD relapsed more often than either patients with single DNMT3A mutation (P = 0.044) or patients with FLT3/ITD only (P = 0.058). DNMT3A mutations were associated with higher relapse rate even within the FLT3/ITD-negative group (P = 0.072). After reaching CR, these two genetic factors were independent predictors of relapse at multivariate analysis (P < 0.001). Only three of 30 'double-mutated' (FLT3/ITD+, DNMT3A+) patients are still alive, all of them having undergone hematopoietic stem cell transplant., Conclusions: We have confirmed the high incidence of DNMT3A mutations in patients with AML with IR cytogenetics. Patients with DNMT3A mutations relapse more often and have inferior OS when only patients achieving CR are analyzed. 'Double-mutated' patients have a very poor prognosis., (© 2011 John Wiley & Sons A/S.)

To date, approximately one half of acute myeloid leukaemia (AML) patients do not have a suitable specific molecular marker for monitoring minimal residual disease (MRD). The Wilm's tumour gene (WT1) has been suggested as a possible molecular marker of MRD in AML. The expression of WT1 in peripheral blood (PB) was measured using quantitative real-time reverse transcription-polymerase chain reaction in peripheral leukocytes from 151 patients with AML at diagnosis. WT1 expression was significantly elevated, i.e. up to 3 orders of magnitude in the majority (80%) of AML patients at diagnosis compared to the PB of healthy donors. Sequence samples of the long-term followed-up AML patients treated with chemotherapy and/or allogeneic bone marrow transplantation were analysed for WT1 expression. The results revealed that the hematological relapses were preceded (median, 1.8 months) by an increase in WT1 gene expression. For the practical utility of this gene as a molecular marker of relapse, it was necessary to determine an upper remission limit, crossing which would signal hematological relapse. The upper remission limit was determined in our set of patients to be 0.02 WT1/ABL. The AML patients who consequently relapsed crossed this upper remission limit; however, those in permanent remission did not. Therefore, this upper remission limit could be taken as the border of molecular relapse of AML patients. Moreover, insufficient decline of WT1 expression under the upper remission limit following induction and/or consolidation therapy was associated with markedly high risk of relapse. The results show that our upper remission limit can be taken as the border of molecular relapse of AML patients and WT1 levels following initial therapy as a beneficial prognostic marker.

Backgrounds: This retrospective study evaluated treatment outcomes in patients undergoing autologous stem cell transplantation (ASCT) for relapsed/refractory Hodgkin lymphoma (HL)., Patients and Methods: Overall, 194 HL patients treated with ASCT between 2000 and 2009 were analyzed. Survival was calculated using Kaplan-Meier method and differences in survival between subgroups with log-rank test., Results: Best responses observed after ASCT: 124 complete and 35 partial remissions, 2 patients with stable disease and 33 relapses/progressions. During a median follow-up of 44 months, seventy patients after ASCT progressed/relapsed. Thirty-seven patients received salvage chemotherapy only with or without radiotherapy, 25 underwent allogeneic stem cell transplantation (SCT), 4 the second ASCT and 4 refused treatment. 5-year overall survival after ASCT was 71% and progression-free survival 54%. Median survival of the 70 patients relapsing after ASCT was 16.9 months. Median survival in patients after allogeneic SCT was 31.8 months and 12.4 months in patients treated with other modalities (p = 0.21). Overall mortality was 26.3% (51/194 patients): 13.4% progressions/relapses of HL and 12.9% non-relapse mortality., Conclusion: Efficacy of ASCT was confirmed in 54% progression-free survivors. Median survival after ASCT failure is relatively short. There is a slightly longer overall survival after allogeneic SCT, although not statistically significant when compared to other approaches.