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Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To assess changes in the relative distribution of interictal epileptiform discharges (IEDs) and interictal EEG prognostic value in terms of surgical outcome between periods with full medication (FMP) and reduced medication (RMP) in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS). Methods: Interictal scalp EEGs of 43 patients were evaluated for the presence of IEDs separately in a waking state (WS) and sleeping state (SS) during FMP and RMP. In each period, patients were categorized as having unitemporal or bitemporal IEDs. Surgical outcome was classified as Engel I or Engel II–IV; and alternatively as completely seizure-free (CSF) or not seizure-free (NSF). Results: There were significant changes in relative IED distribution between FMP and RMP during SS. The representation of patients with unitemporal IEDs declined from 37 (86%) in FMP during SS to 25 (58%) in RMP during SS (p=0.003). The relative IED distribution is a predictive factor for surgical outcome defined as Engel I or Engel II-IV in FMP during SS (p =0.020). The relative IED distribution could be a predictor for surgical outcome defined as CSF or NSF in both FMP during WS (p =0.043) and FMP during SS (p =0.015). When stepwise logistic analysis was applied, only FMP during SS was found to be an independent predictor for surgical outcome defined as Engel I or Engel II–IV (p =0.017), as CSF or NSF (p =0.018). Conclusion: The predictive value of relative IED distribution with respect to surgical outcome in interictal EEG is present only during FMP; the predictive value decreases with the reduction of AEDs caused by the change of relative IED distribution. [ABSTRACT FROM AUTHOR]

Background: Modern trends in reconstructive surgery involve the use of free perforator flaps to reduce the donor site morbidity. The course of perforator vessels has a great anatomic variability and demands a careful knowledge of the anatomical relationships and the variability of the course of the perforators. The numerous modifications of perforator nomenclature were proposed by many authors and brought confusion rather than a simplification. In our study we focused on a hypothesis, that septocutaneous perforator passes from the given source vessel to the deep fascia adherent to, but not to within the septum itself., Methods: 69 septocutaneous perforators from three different limb donor sites (Lateral Arm Flap, Anterolateral Thigh Flap, Radial Forearm Free Flap) were collected from gross pathology specimens of 14 fresh cadavers. The gross picture and the cross sections with the histological cross sections on different levels were examined to determine the position of vessel to the septal tissue., Results: Of the observed 69 septal perforators, 61 (88,5%) perforators were adherent to but not within the septum. Remaining eight (12,5%) perforators passed through the septum. All these eight perforators were found in multiple different cross section levels. (two of 19 in Lateral Arm Flap, three of 27 in Anterolateral Thigh Flap, three of 23 in Radial Forearm Free Flap)., Conclusion: Although macroscopically identical septocutaneous vessels, microscopically we observe two types of vessels - with paraseptal and intraseptal pathways. The majority are merely adherent to the septum having a paraseptal pathway. A minority are within the septum, and are "true" septocutaneous perforators. It is advisable to dissect with a piece of the septum in order to avoid damage any injury of perforator., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Collagen fiber arrangement is decisive for constitutive description of anisotropic mechanical response of arterial wall. In this study, their orientation in human common carotid artery was investigated using polarized light microscopy and an automated algorithm giving more than 4·10 6 fiber angles per slice. In total 113 slices acquired from 18 arteries taken from 14 cadavers were used for fiber orientation in the circumferential-axial plane. All histograms were approximated with unimodal von Mises distribution to evaluate dominant direction of fibers and their concentration parameter. 10 specimens were analyzed also in circumferential-radial and axial-radial planes (2-4 slices per specimen in each plane); the portion of radially oriented fibers was found insignificant. In the circumferential-axial plane, most specimens showed a pronounced unimodal distribution with angle to circumferential direction μ = 0.7° ± 9.4° and concentration parameter b = 3.4 ± 1.9. Suitability of the unimodal fit was confirmed by high values of coefficient of determination (mean R 2  = 0.97, median R 2  = 0.99). Differences between media and adventitia layers were not found statistically significant. The results are directly applicable as structural parameters in the GOH constitutive model of arterial wall if the postulated two fiber families are unified into one with circumferential orientation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Histiocytoses are rare disorders characterized by the accumulation of macrophages, dendritic cells, or monocyte-derived cells in various tissues and organs of children and adults, with a wide range of clinical manifestations, presentations, and histology. The histiocytoses are classified according to the WHO Classification, the last version of which was published in 2022, or according to the Histiocyte Society Classification, with the last version published in 2016., Purpose: This text provides an overview of histiocytoses as described in the WHO Classification 2022.

The current WHO classification of digestive system tumours (2019) has presented the concept of diagnostics of intraductal and cystic neoplasms of the pancreas mostly based on integrated molecular data and evaluations of their malignant potential. Intraductal pancreatic neoplasms with ductal phenotype include microscopic precursor lesions of pancreatic ductal adenocarcinoma - the pancreatic intraepithelial neoplasia and macroscopic precursor lesions of pancreatic cancer, where intraductal papillary mucinous neoplasm represents the most common neoplasm of the pancreas with cystic appearance. Both intraductal oncocytic papillary neoplasm and intraductal tubulopapillary neoplasm are now classified as separate entities associated with less aggressive subtypes of pancreatic carcinoma and better prognosis. Clinical significance of microscopic pancreatic intraepithelial neoplasias is limited, in contrast to other intraductal neoplasms, which are presented as cystic and/or solid tumours by imaging methods with important consequences for further treatment and indication of surgical therapy (resection versus "watch and wait" strategies). Neoplasms of nonductal origin, such as acinar cell carcinomas and neuroendocrine neoplasms, can uncommonly display an intraductal growth and their correct classification has a great clinical importance. Moreover, differential diagnostics of cystic pancreatic lesions include not only cystic and pseudocystically transformed neoplasms, but also a large spectrum of reactive, inflammatory and dysontogenetic cystic lesions.

Most frequently used structure-based constitutive models of arterial wall apply assumptions on two symmetric helical (and dispersed) fibre families which, however, are not well supported with histological findings where two collagen fibre families are seldom found. Moreover, bimodal distributions of fibre directions may originate also from their waviness combined with ignoring differences between local and global fibre orientations. In contrast, if the model parameters are identified without histological information on collagen fibre directions, the resulting mean angles of both fibre families are close to ±45°, which contradicts nearly all histologic findings. The presented study exploited automated polarized light microscopy for detection of collagen fibre directions in porcine aorta under different biaxial extensions and approximated the resulting histograms with unimodal and bimodal von Mises distributions. Their comparison showed dominantly circumferential orientation of collagen fibres. Their concentration parameter for unimodal distributions increased with circumferential load, no matter if acting uniaxially or equibiaxially. For bimodal distributions, the angle between both dominant fibre directions (chosen as measure of fibre alignment) decreased similarly for both uniaxial and equibiaxial loads. These results indicate the existence of a single family of wavy circumferential collagen fibres in all layers of the aortic wall. Bimodal distributions of fibre directions presented sometimes in literature may come rather from waviness of circumferentially arranged fibres than from two symmetric families of helical fibres. To obtain a final evidence, the fibre orientation should be analysed together with their waviness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy., Methods: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center., Results: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years., Significance: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The study compares stresses and strains in the aortic wall derived using different constitutive models for various stress-strain conditions. Structure-based constitutive models with two fibre families with (GOH) and without (HGO) dispersion of collagen fibres are compared. The constitutive models were fitted to data from equibiaxial tension tests of two separated layers of the porcine aortic wall. The initial fit was evaluated with unrestricted parameters and subsequently, the mean angles of the fibre families and the angular dispersion were fixed to the values obtained from histology. Surprisingly, none of the tested models was capable to provide a good quality fit with histologically obtained structural parameters. Fitting the HGO model to experimental data resulted in two fibre families under angles close to ±45°, while the GOH model resulted in a nearly isotropic fibre distribution. These results indicate that both of these models suffer from the absence of isotropic strain stiffening. After having modified both models with corresponding additional members based on the Yeoh model of matrix, we obtained a perfect fit to the measured data while keeping the structural histology-based parameters. Finally, significant differences in compliance and resulting stresses and strains between different models are shown by means of simulations of uniaxial tension test, equibiaxial tension tests and inflation of the aorta., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Drug efficacy determined in preclinical research is difficult to transfer to clinical practice. This is mainly due to the use of oversimplified models omitting the effect of the tumor microenvironment and the presence of various cell types participating in the formation of tumors in vivo. In this study, we used robust three-dimensional models including spheroids grown from colon cancer cell lines and organotypic cultures prepared from the colorectal carcinoma tissue to test novel therapeutic strategies. We developed a multi-modal approach combining brightfield and fluorescence microscopy for evaluating drug effects on organotypic cultures. Combined treatment with 5-fluorouracil and disulfiram/copper efficiently eliminated cancer cells in these 3D models. Moreover, disulfiram/copper down-regulated the expression of markers associated with 5-fluorouracil resistance, such as thymidylate synthase and CD133/CD44. Thus, we propose combined therapy of 5-fluorouracil and disulfiram/copper for further testing as a treatment for colorectal carcinoma. In addition, we show that organotypic cultures are suitable models for anti-cancer drug testing., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The aim of the presented communication is to clearly inform the general professional public about the newly approved modifications in this classification, including the newly approved types of tumours. A significant change is the new grading system for these tumours, including the innovative involvement of tumour profiling at the molecular level in the system for determining the degree of tumour differentiation and the application of the principle of integrated diagnostics, i. e. the synthesis of available histopathological and molecular findings in CNS tumors.

Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS., Methods: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology., Results: Upregulation of IL-1β (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p < 0.001), and CCL4 (p < 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures., Conclusion: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis., (Copyright © 2022. Published by Elsevier B.V.)

A novel method for semiautomated assessment of directions of collagen fibers in soft tissues using histological image analysis is presented. It is based on multiple rotated images obtained via polarized light microscopy without any additional components, i.e., with just two polarizers being either perpendicular or nonperpendicular (rotated). This arrangement breaks the limitation of 90° periodicity of polarized light intensity and evaluates the in-plane fiber orientation over the whole 180° range accurately and quickly. After having verified the method, we used histological specimens of porcine Achilles tendon and aorta to validate the proposed algorithm and to lower the number of rotated images needed for evaluation. Our algorithm is capable to analyze 5·10 5 pixels in one micrograph in a few seconds and is thus a powerful and cheap tool promising a broad application in detection of collagen fiber distribution in soft tissues., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Michaela Turčanová et al.)

Recently, the World Health Organization (WHO) classification of tumours of the central nervous system (CNS) has brought essential changes. The currently valid revised WHO 2016 classification of CNS tumours introduced the concept of integrated dia-gnostics, which incorporated not only histopathological morphological finding and immunophenotype but also molecular-genetic characteristics of the tumour. Thus, the final integrated dia-gnosis comprises the traditional morphological and growth pattern characteristics of a tumour including histopathological grade and also specific molecular bio-markers. The classification of tumour based on a combination of both tumour phenotype and genotype enables more precise prognostic stratification, increases the objectivity of dia-gnostics and prediction of response to treatment. In 2017, an international platform, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy - not official WHO (cIMPACT-NOW), was established to create and formulate practical recommendations for integrated dia-gnostics of CNS tumours and upcoming WHO classification. The incorporation of molecular bio-markers into the integrated dia-gnostics radically changed the classification of diffuse gliomas, which include entities with different morphological characteristics, genetic alterations and bio-logical behaviour. This review article summarizes essential morphological, immunophenotypical and molecular genetic characteristics of diffuse gliomas within the scope of integrated dia-gnostics according to the valid WHO classification of tumours of the CNS and subsequent recommendations of dia-gnostic approaches. This work was supported by grant of the Ministry of Health of the Czech Republic - Conceptual Development of a Research Organization (MMCI 00209805) and Grant Agency of Masaryk University (MUNI/A/1562/2018). 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.

Objective: The main aim of this study was to investigate the potential differences in terms of interictal high frequency oscillations (HFOs) between both hippocampi in unilateral (U-MTLE) and bilateral mesial temporal lobe epilepsy (B-MTLE)., Methods: Sixteen patients with MTLE underwent bilateral hippocampal depth electrode implantation as part of epilepsy surgery evaluation. Interictal HFOs were detected automatically. The analyses entail comparisons of the rates and spatial distributions of ripples and fast ripples (FR) in hippocampi and amygdalae, with respect to the eventual finding of hippocampal sclerosis (HS)., Results: In U-MTLE, higher ripple and FR rates were found in the hippocampi ipsilateral to the seizure onset than in the contralateral hippocampi. Non-epileptic hippocampi in U-MTLE were distinguished by significantly lower ripple rate than in the remaining analyzed hippocampi. There were not differences between the hippocampi in B-MTLE. In the hippocampi with proven HS, higher FR rates were observed in the ventral than in the dorsal parts., Conclusions: Non-epileptic hippocampi in U-MTLE demonstrated significantly lower ripple rates than those epileptic in U-MTLE and B-MTLE., Significance: Low interictal HFO occurrence might be considered as a marker of the non-epileptic hippocampi in MTLE., (Copyright © 2019. Published by Elsevier B.V.)

Background: The incidence of oropharyngeal carcinomas associated with human papillomavirus (HPV) is continuously increasing. HPV-positive and -negative oropharyngeal carcinomas have different epidemiological, clinical, and molecular features, with HPV-positive tumors having a better response to treatment and better prognosis. An adequate staging system for HPV-related oropharyngeal carcinomas is needed, as the American Joint Committee on Cancer 7th Edition did not consider their unique biological behavior. At present, oropharyngeal carcinomas are subdivided into p16 positive and p16 negative tumors, based on their expression of p16, a surrogate marker of high-risk HPV., Purpose: This review summarizes current knowledge of HPV-associated oropharyngeal carcinomas with emphasis on their molecular features and histopathology, as well as summarizes and compares HPV detection methods and genotyping techniques. This review also describes the prognostic significance of p16 expression in these tumors and significant changes in the staging of oropharyngeal carcinomas based on p16 expression, together with the justifications for these changes. Finally, this review reports the recommendations of the College of American Pathologists for testing HPV in head and neck cancers, supported by the American Society of Clinical Oncology. This work was supported by the Ministry of Health of the Czech Republic, grant No. 15-31627A. All rights reserved. Auto&#345;i deklarují, &#382;e v souvislosti s p&#345;edm&#283;tem studie nemají &#382;ádné komer&#269;ní zájmy. Redak&#269;ní rada potvrzuje, &#382;e rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských &#269;asopis&#367;. Submitted: 18. 2. 2019 Accepted: 30. 5. 2019.

We present a novel dual redox labeling approach enabling a facile relative evaluation of protein-DNA interactions based on immunoprecipitation at magnetic beads (MBIP) with subsequent electrochemical detection. DNA probes labeled with two different electroactive markers, benzofurazane and nitrobenzene, which yield reduction peaks at distinct potentials, were synthesized using primer extension (PEX) reaction. We show that using the labeled DNA probes, specific and non-specific binding of the p53 protein can be distinguished in a simple competition binding experiment, as a strong preference of the p53 protein was observed towards DNA probes bearing a specific p53 binding site (p53CON), which is in agreement with known binding properties of the p53 protein. The p53 binding to the individual DNA probes can be modulated by specific monoclonal antibodies used for the immunoprecipitation. This approach can potentially be applied, after selection of appropriate DNA probes and monoclonal antibodies, for investigations of DNA-binding properties of other proteins and thus represents a versatile tool for studies of any DNA-binding proteins., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) represents a serious challenge for oncologists due to high incidence and large heterogeneity. Prognostic factors are needed to stratify patients according to risk of disease progression. In this study, we report that high expression of c-Myb protein, determined by immunohistochemistry (IHC), associates with better overall and disease-free survival (OS, DFS) in a cohort of 103 patients. Although MYB has been previously considered to act as oncogene in CRC, our further analysis of datasets deposited in PrognoScan and SurvExpress databases confirmed that high MYB expression largely associates with good prognosis in CRC. As therapies targeting c-Myb have been developed and tested in preclinical studies, we believe that further studies are needed for detailed understanding of c-Myb function in CRC, before the c-Myb-targeted therapy enters clinical trials., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Oropharyngeal squamous cell tumors associated with human papillomavirus infection (p16 positive tumors) have better prognosis than p16 negative tumors regardless of the more advanced stage of the disease. Tumor volume (GTVt+n) is generally an important factor affecting treatment results of ionizing radiation. The aim of this prospective non-randomized study is to evaluate the effect of tumor volume on the (chemo)radiation treatment results in a group of patients with p16 negative and p16 positive oropharyngeal tumors., Patients and Methods: Patients with confirmed squamous cell tumor of the oropharynx of stages III and IV, according to the 7th version of the TNM (tumor-nodes-metastases) classification, were eligible for this study. The main exclusion criteria were palliative treatment, neoadjuvant chemotherapy or planned concomitant therapy with cetuximab. Patients were treated according to standardized protocols with curative intent. Primary tumor volume (GTVt) and involved nodes volume (GTVn) were obtained from radiotherapy planning system for further statistical analysis. The differences in tumor volumes between the groups according to p16 expression were assessed with subsequent testing of probability to achieve complete remission (CR) of the disease in both groups., Results: In total, 49 patients - 84% men, median age 60.5 years, 25 (51%) patients p16 positive, 40 (82%) underwent concomitant chemoradiotherapy. Median of GTVt in the whole patients group is 40.2 ccm, GTVn 11.78 ccm and median volume of the whole tumor burden (GTVt+n) 70.21 ccm (range 11.05-249). Median of GTVn was greater in the p16 positive cohort (p = 0.041). In the entire group, the median time to reach CR was 91 days (95% CI 86-107 days) from the end of radiotherapy. In the group of p16 negative patients, 14 achieved CR (61%) out of 23 patients, in p16 positive group 20 (80%) out of 25 patients (p = 0.111). P16 negative patients had a longer time to CR (p = 0.196, HR 1.58, 95% CI 0.79-3.18). None of the independently assessed volumetric parameters of the tumor (GTVt, GTVn, GTVt+n) affected CR in the p16 positive patients group, while there was a significant impact of the whole tumor burden (GTVt+n) in the p16 negative cohort (median 58.1 ccm in CR patients vs. 101.9 ccm, p = 0.018)., Conclusion: We have showed less GTVt+n dependence to achieve CR in p16 positive tumors in comparison with p16 negative tumors. Thus, p16 positive oropharyngeal squamous cell cancers should not be withdrawn from the curative treatment intent based on the greater GTVt+n. Key words oropharyngeal neoplasms - p16 status - treatment outcome - tumor burden - complete remission This work was supported by grant of the Ministry of Health of the Czech Republic AZV 15-31627A and by grant of the Ministry of Health of the Czech Republic - Conceptual development of a research organization (MMCI 00209805). 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: 2. 11. 2018 Accepted: 11. 11. 2018.

Metastasis accounts for most of cancer-related deaths. Paracrine signaling between tumor cells and the stroma induces changes in the tumor microenvironment required for metastasis. Transcription factor c-Myb was associated with breast cancer (BC) progression but its role in metastasis remains unclear. Here we show that increased c-Myb expression in BC cells inhibits spontaneous lung metastasis through impaired tumor cell extravasation. On contrary, BC cells with increased lung metastatic capacity exhibited low c-Myb levels. We identified a specific inflammatory signature, including Ccl2 chemokine, that was expressed in lung metastatic cells but was suppressed in tumor cells with higher c-Myb levels. Tumor cell-derived Ccl2 expression facilitated lung metastasis and rescued trans-endothelial migration of c-Myb overexpressing cells. Clinical data show that the identified inflammatory signature, together with a MYB expression, predicts lung metastasis relapse in BC patients. These results demonstrate that the c-Myb-regulated transcriptional program in BCs results in a blunted inflammatory response and consequently suppresses lung metastasis.

Objective: This study was designed to use statistical parametric mapping of interictal positron-emission tomography using [ 18 F]Fluorodeoxyglucose (FDG-PET) to compare the brain metabolisms of patients with mesial temporal lobe epilepsy (MTLE)/hippocampal sclerosis and controls. Another aim of this study was to analyze the potential differences among patients in terms of epilepsy duration, side of hippocampal sclerosis, histopathological findings, insult in their history, and postoperative outcomes., Methods: We analyzed FDG-PET scans from 49 patients with MTLE/hippocampal sclerosis and 24 control subjects. We analyzed the differences in regional glucose metabolism between the patients and the control group and within the patient group using multiple variables., Results: We observed widespread hypometabolism in the patient group in comparison with the control group in temporal and extratemporal areas on the epileptogenic side (ES). On the nonepileptogenic side (NES), we observed the most hypometabolism in the thalamus and the anterior and middle cingulate gyrus. In the group of patients with more severe hippocampal sclerosis, we observed statistically significant hypometabolism in the insula on the ES. In patients with poor postoperative outcomes, we found statistically significant hypometabolism in the insula on the ES and the temporal pole (TP) on the NES. Patients with any insult in their history showed hypermetabolism in the TP on both sides., Conclusion: Our study showed that there are widespread changes in metabolism in patients with MTLE in comparison to controls, either inside or outside the temporal lobe. There are significant differences among these patients in terms of postoperative outcomes, degree of hippocampal sclerosis, and insults in their history., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population., Methods: Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated., Results: We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p=0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8years of age [median; min-max 0.5-17] in left-handers versus 15years of age [median; min-max 3-30] in right-handers (p<0.001)., Conclusions: Left-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG)., Methods: According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology., Results: Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found., Conclusions: According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The MYB gene codes for the c-Myb transcription factor maintaining proliferation of colon epithelial progenitors, thus controlling colon development and homeostasis. This gene is overexpressed in early phases of colorectal cancer (CRC) tumorigenesis. The aim of this study was to examine the expression of c-Myb in CRC tissue samples both at the messenger RNA (mRNA) and protein levels and to evaluate their associations with clinicopathological characteristics in a group of 108 CRC patients. Statistically significant negative association was found between the frequency of the c-Myb-positive tumor cells assessed by immunohistochemistry and the presence of distant metastases (p < 0.01) but not tumor differentiation, tumor stage, lymph node involvement, vascular invasion, tumor localization, age, and gender of the patients. Although the c-Myb protein level in the tumor tissue correlated with its mRNA level, no significant association between MYB mRNA and any clinicopathological characteristics was observed. We conclude that albeit overexpression of c-Myb is considered as an important factor contributing to early phases of CRC tumorigenesis, it may later have negative effect on tumor cell dissemination as observed recently in breast cancer as well. Further studies are required to explain the role of c-Myb during formation of CRC distant metastases.

Objective: The main purpose of the study was to analyze the long-term outcomes and therapeutic approaches for patients with seizures within the first year after surgery. The secondary aim of the study was to evaluate the relationship between 1-year outcome and long-term outcome and choice of therapy., Methods: Our study was a retrospective investigation of the long-term outcomes of 95 patients (33.5% of all surgically treated patients) with seizure recurrence in the first year after surgery. The patients had follow-up visits for >5 years., Results: At the 5-year follow-up visit (FU5), 28 (29.5%) of the 95 patients were completely seizure-free (International League Against Epilepsy (ILAE) class 1), 17 (17.9%) had auras only (ILAE class 2), and 21 (22.1%) were unimproved (ILAE classes 5 and 6). Statistically significant factors for these long-term outcomes were the focus localization of the epilepsy, preoperative MRI findings, and postoperative follow-up results in the first year. The patients with <3 seizure days in the first postoperative year (ILAE 3) represented 53.6% of the seizure-free patients at FU5; the patients with auras in the first year constituted 64.7% of the patients with only auras at FU5; and the patients unimproved in the first year represented 76.2% of the unimproved patients at FU5., Significance: Postoperative outcome depends to a certain extent on the outcome achieved in the first postoperative year. More than one third of the patients with postoperative seizures reached a long-term seizure-free outcome, and more than half of them did not experience disabling seizures in the last outcome year. The most therapeutic options were used in patients who were minimally influenced by the operation; the majority of patients with considerable improvement because of the operation do not use any other add-on antiepileptic drugs or other kinds of therapy., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Perigraft seroma is quite a rare complication that may occur after implantation of Dacron or expanded polytetrafluoroethylene (ePTFE) vascular grafts. We report a case of a 54-year-old patient with perigraft seroma around an axillofemoral bypass (ePTFE graft). Definitive treatment involved the explantation of this extraanatomic bypass with perigraft seroma and the implantation of an aortobiiliac bypass using vascular prosthesis made of a different material. Based on published studies, therapeutic options for this complication are discussed. No guidelines or recommendations are available. In conclusion, the approach to perigraft seroma treatment remains strictly individual. Vascular graft replacement using grafts made of different material seems to be the best option in the case of recurring perigraft seroma, where less invasive procedures were not successful.

Objective: To assess changes in the relative lateralization of interictal epileptiform discharges (IEDs) and interictal EEG prognostic value in terms of surgical outcome between periods with full medication (FMP) and reduced medication (RMP) in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS)., Methods: Interictal scalp EEGs of 43 patients were evaluated for the presence of IEDs separately in a waking state (WS) and sleeping state (SS) during FMP and RMP. In each period, patients were categorized as having unitemporal or bitemporal IEDs. Surgical outcome was classified at year 1 after surgery and at last follow-up visit as Engel I or Engel II-IV; and alternatively as completely seizure-free or not seizure-free., Results: There were significant changes in relative IED lateralization between FMP and RMP during SS. The representation of patients with unitemporal IEDs declined from 37 (86%) in FMP during SS to 25 (58%) in RMP during SS (p=0.003). At year 1 after surgery, the relative IED lateralization is a predictive factor for surgical outcome defined as Engel I vs. Engel II-IV in both FMP during WS (p=0.037) and during SS (p=0.007), and for surgical outcome defined as completely seizure-free vs. not seizure-free in FMP during SS (p=0.042). At last follow up visit, the relative IED lateralization is a predictor for outcome defined as Engel I vs. Engel II-IV in FMP during SS (p=0.020), and for outcome defined as completely seizure-free vs. not seizure-free in both FMP during WS (p=0.043) and in FMP during SS (p=0.015). When stepwise logistic regression analysis was applied, only FMP during SS was found to be an independent predictor for surgical outcome at year 1 after surgery (completely seizure-free vs. not seizure-free p=0.032, Engel I vs. Engel II-IV p=0.006) and at last follow-up visit (completely seizure-free vs. not seizure-free p=0.024, Engel I vs. Engel II-IV p=0.017). Gender was found to be independent predictor for surgical efficacy at year 1 if the outcome was defined as completely seizure-free vs. not seizure-free (p=0.036)., Conclusion: The predictive value of relative IED lateralization with respect to surgical outcome in interictal EEG is present only during FMP; the predictive value decreases with the reduction of AEDs caused by the change of relative IED lateralization., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes., Methods: PCR-sequencing analysis; sequence capture and targeted resequencing., Results: Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in this gene were identified in 71 patients in a set of 218 Czech probands with a suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have been described only in Czech LGMD2A patients. The mutation c.550delA is the most frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71 probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4% for LGMD2L (3 probands).Further, we present the first results of a new approach established in the Czech Republic for diagnosis of neuromuscular diseases: sequence capture and targeted resequencing. Using this approach, we identified patients with mutations in the DYSF and SGCB genes., Conclusions: We characterised a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes associated with the most common forms of LGMD2 in the European population and subsequently compared the occurrence of particular forms of LGMD2 among countries on the basis of our results and published studies.

Purpose: We analyzed the long-term postoperative outcome and possible predictive factors of the outcome in surgically treated patients with refractory extratemporal epilepsy., Methods: We retrospectively analyzed 73 patients who had undergone resective surgery at the Epilepsy Center Brno between 1995 and 2010 and who had reached at least 1 year outcome after the surgery. The average age at surgery was 28.3±11.4 years. Magnetic resonance imaging (MRI) did not reveal any lesion in 24 patients (32.9%). Surgical outcome was assessed annually using Engel's modified classification until 5 years after surgery and at the latest follow-up visit., Results: Following the surgery, Engel Class I outcome was found in 52.1% of patients after 1 year, in 55.0% after 5 years, and in 50.7% at the last follow-up visit (average 6.15±3.84 years). Of the patients who reached the 5-year follow-up visit (average of the last follow-up 9.23 years), 37.5% were classified as Engel IA at each follow-up visit. Tumorous etiology and lesions seen in preoperative MRI were associated with significantly better outcome (p=0.035; p<0.01). Postoperatively, 9.6% patients had permanent neurological deficits., Conclusion: Surgical treatment of refractory extratemporal epilepsy is an effective procedure. The presence of a visible MRI-detected lesion and tumorous etiology is associated with significantly better outcome than the absence of MRI-detected lesion or other etiology., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)