OBJECTIVE: The pre-surgical evaluation of epilepsy relies on the electrophysiological recordings of spontaneous seizures. During this period drug dose decreases increase the likelihood of seizures transitioning the brain from a low to high seizure likelihood state, so-called pro-ictal state. This study aimed to identify the dynamic brain changes characteristic of this transition from 386 ten-minute segments of intracranial EEG recordings of 29 patients with drug-refractory temporal lobe epilepsy. METHODS: We studied brain dynamics through mean phase locking value and relative power in gamma band, and autocorrelation function width. We further explored interactions with pro-ictal factors, such as rate of interictal spikes and high frequency oscillations, circadian and multi-day cycles, and clinical outcomes. RESULTS: We observed significant increases in gamma power in the epileptogenic zone, and critical slowing in both the epileptogenic zone and presumably healthy cortex. These changes were linked with increases in spike and high frequency oscillations rate. CONCLUSIONS: Brain dynamics changed on the slow time scale - from the beginning to the end of the multi-day interval - but did not change in the short-term during the pre-ictal interval, thus could reflect pro-ictal changes. SIGNIFICANCE: We highlight gamma power and critical slowing indices as markers of pro-ictal brain states, as well as their potential to track the seizure-related brain mechanisms during the presurgical evaluation of epilepsy patients.

• MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• elektrokortikografie metody   MeSH
• epilepsie temporálního laloku * patofyziologie   diagnóza   MeSH
• gama rytmus EEG * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek * patofyziologie   MeSH
• refrakterní epilepsie * patofyziologie   MeSH
• záchvaty * patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Epilepsy is a neurological disease characterized by epileptic seizures, which commonly manifest with pronounced frequency and amplitude changes in the EEG signal. In the case of focal seizures, initially localized pathological activity spreads from a so-called "onset zone" to a wider network of brain areas. Chimeras, defined as states of simultaneously occurring coherent and incoherent dynamics in symmetrically coupled networks are increasingly invoked for characterization of seizures. In particular, chimera-like states have been observed during the transition from a normal (asynchronous) to a seizure (synchronous) network state. However, chimeras in epilepsy have only been investigated with respect to the varying phases of oscillators. We propose a novel method to capture the characteristic pronounced changes in the recorded EEG amplitude during seizures by estimating chimera-like states directly from the signals in a frequency- and time-resolved manner. We test the method on a publicly available intracranial EEG dataset of 16 patients with focal epilepsy. We show that the proposed measure, titled Amplitude Entropy, is sensitive to the altered brain dynamics during seizure, demonstrating its significant increases during seizure as compared to before and after seizure. This finding is robust across patients, their seizures, and different frequency bands. In the future, Amplitude Entropy could serve not only as a feature for seizure detection, but also help in characterizing amplitude chimeras in other networked systems with characteristic amplitude dynamics.

• MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• entropie MeSH
• epilepsie parciální * patofyziologie   MeSH
• lidé MeSH
• mozek * patofyziologie   MeSH
• záchvaty * patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.

• MeSH
• akční potenciály * fyziologie   MeSH
• draslík * krev   metabolismus   MeSH
• ischemická choroba srdeční * patofyziologie   krev   metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu krev   patofyziologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Vestibulární schwannom (VS) je intrakraniální benigní tumor vycházející ze Schwannových buněk vestibulární porce vestibulokochleárního nervu. Tento nádor tvoří 85 % tumorů mostomozečkového koutu. Vyrůstá v tzv. přechodové zóně vnitřního zvukovodu, odkud roste směrem k mozkovému kmeni a mozečku. Z toho lze vyvodit posloupnost příznaků, které se u pacienta rozvinou. Mezi jeho nejčastější projevy patří jednostranná porucha sluchu, ušní šelesty a poruchy rovnováhy. Ve většině případů je jeho růst pomalý. V naprosté většině případů (95 %) se jedná o sporadický typ nádoru, ve zbylých 5 % se pak jedná o dědičnou, autozomálně dominantní formu nádoru, která se vyskytuje především u neurofibromatózy 2. typu (NF2).

Vestibular schwannoma (VS) is a benign intracranial tumor derived from myelinating Schwann cells of the vestibular division of the vestibulocochlear nerve. Vestibular schwannomas account for approximately 85 % of cerebellopontine angle tumors. It grows in the so-called transition zone of the internal auditory canal, from which it extends toward the brainstem and cerebellum. From this knowledge, the sequence of symptoms the patient develops can be deduced. The most common manifestations include unilateral hearing loss, tinnitus, and balance disorders. In most cases, VS growth is slow. The vast majority of VS (95 %) occur as sporadic tumors, with the remaining 5 % occurring as part of an inherited, autosomal dominant form of VS, mainly found in patients with neurofibromatosis type 2 (NF2).

• MeSH
• centrální poruchy sluchu MeSH
• diagnostické techniky otologické MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mikrochirurgie metody   MeSH
• nervus facialis MeSH
• radiochirurgie MeSH
• rehabilitace MeSH
• sluchové kmenové evokované potenciály MeSH
• vestibulární schwannom * diagnóza   komplikace   terapie   MeSH
• Check Tag
• lidé MeSH

INTRODUCTION: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity. METHODS: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro. RESULTS: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes. CONCLUSION: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.

• MeSH
• chondrocyty * metabolismus   patologie   MeSH
• dospělí MeSH
• ELISA MeSH
• fenotyp MeSH
• imunohistochemie MeSH
• interleukiny * metabolismus   MeSH
• kloubní chrupavka metabolismus   patologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoartróza * metabolismus   patologie   MeSH
• senioři MeSH
• synoviální tekutina * metabolismus   MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: RTX, an anti-CD20 monoclonal antibody, added to chemotherapy has proven to be effective in children and adolescents with high-grade, high-risk and matured non-Hodgkin lymphoma. RTX leads to prompt CD19+ B lymphocyte depletion. However, despite preserved immunoglobulin production by long-lived plasmablasts after treatment, patients remain at risk of prolonged hypogammaglobulinemia. Further, there are few general guidelines for immunology laboratories and clinical feature monitoring after B cell-targeted therapies. The aim of this paper is to describe B cell reconstitution and immunoglobulin levels after pediatric B-NHL protocols, that included a single RTX dose and to review the literature. METHODS: A retrospective single-center study on the impact of a single RTX dose included in a chemotherapeutic pediatric B Non-Hodgkin Lymphoma (B-NHL) treatment protocols. Immunology laboratory and clinical features were evaluated over an eight hundred days follow-up (FU) period, after completing B-NHL treatment. RESULTS: Nineteen patients (fifteen Burkitt lymphoma, three Diffuse large B cell lymphoma, and one Marginal zone B cell lymphoma) fulfilled the inclusion criteria. Initiation of B cell subset reconstitution occurred a median of three months after B-NHL treatment. Naïve and transitional B cells declined over the FU in contrast to the marginal zone and the switched memory B cell increase. The percentage of patients with IgG, IgA, and IgM hypogammaglobulinemia declined consistently over the FU. Prolonged IgG hypogammaglobulinemia was detectable in 9%, IgM in 13%, and IgA in 25%. All revaccinated patients responded to protein-based vaccines by specific IgG antibody production increase. Following antibiotic prophylaxes, none of the patients with hypogammaglobulinemia manifested with either a severe or opportunistic infection course. CONCLUSION: The addition of a single RTX dose to the chemotherapeutic treatment protocols was not shown to increase the risk of developing secondary antibody deficiency in B-NHL pediatric patients. Observed prolonged hypogammaglobulinemia remained clinically silent. However interdisciplinary agreement on regular long-term immunology FU after anti-CD20 agent treatment is required.

• MeSH
• B-buněčný lymfom farmakoterapie   imunologie   MeSH
• dítě MeSH
• imunoglobuliny aplikace a dávkování   MeSH
• lidé MeSH
• mladiství MeSH
• nehodgkinský lymfom farmakoterapie   imunologie   MeSH
• podskupiny B-lymfocytů imunologie   účinky léků   MeSH
• předškolní dítě MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Treating oral diseases remains challenging as API is quickly washed out of the application site by saliva turnover and mouth movements. In situ gels are a class of application forms that present sol-gel transition's ability as a response to stimuli. Their tunable properties are provided using smart polymers responsible for stimuli sensitivity, often providing mucoadhesivity. In this study, antimicrobial in situ gels of thermosensitive and pH-sensitive polymers loaded with silver nanoparticles were prepared and evaluated. The nanoparticles were prepared by green synthesis using Agrimonia eupatoria L. extract. According to the data analysis, the in situ gel with the most promising profile contained 15 % of Pluronic® F-127, 0.25 % of methylcellulose, and 0.1 % of Noveon® AA-1. Pluronic® F-127 and methylcellulose significantly increased the viscosity of in situ gels at 37 °C and shear rates similar to speaking and swallowing. At 20 °C, a behavior close to a Newtonian fluid was observed while being easily injectable (injection force 13.455 ± 1.973 N). The viscosity of the formulation increased with temperature and reached 2962.77 ± 63.37 mPa·s (37 °C). A temperature increase led to increased adhesiveness and rigidity of the formulation. The critical sol-gel transition temperature at physiological pH was 32.65 ± 0.35 °C. 96.77 ± 3.26 % of Ag NPs were released by erosion and dissolution of the gel after 40 min. The determination of MIC showed effect against E. coli and S. aureus (0.0625 mM and 0.5000 mM, respectively). The relative inhibition zone diameter of the in situ gel was 73.32 ± 11.06 % compared to gentamicin sulfate. This work discusses the optimization of the formulation of novel antibacterial in situ gel for oromucosal delivery, analyses the impact of the concentration of excipients on the dependent variables, and suggests appropriate evaluation of the formulation in terms of its indication. This study offers a promising dosage form for local treatment of oral diseases.

• MeSH
• Escherichia coli MeSH
• gely chemie   MeSH
• kovové nanočástice * MeSH
• methylcelulosa MeSH
• poloxamer * chemie   MeSH
• Staphylococcus aureus MeSH
• stříbro MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH

Primary cilia are cellular surface projections enriched in receptors and signaling molecules, acting as signaling hubs that respond to stimuli. Malfunctions in primary cilia have been linked to human diseases, including retinopathies and ocular defects. Here, we focus on TMEM107, a protein localized to the transition zone of primary cilia. TMEM107 mutations were found in patients with Joubert and Meckel-Gruber syndromes. A mouse model lacking Tmem107 exhibited eye defects such as anophthalmia and microphthalmia, affecting retina differentiation. Tmem107 expression during prenatal mouse development correlated with phenotype occurrence, with enhanced expression in differentiating retina and optic stalk. TMEM107 deficiency in retinal organoids resulted in the loss of primary cilia, down-regulation of retina-specific genes, and cyst formation. Knocking out TMEM107 in human ARPE-19 cells prevented primary cilia formation and impaired response to Smoothened agonist treatment because of ectopic activation of the SHH pathway. Our data suggest TMEM107 plays a crucial role in early vertebrate eye development and ciliogenesis in the differentiating retina.

• MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• myši MeSH
• polycystická choroba ledvin * genetika   MeSH
• poruchy ciliární motility * genetika   metabolismus   MeSH
• retina metabolismus   MeSH
• retinopathia pigmentosa * metabolismus   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Inflamatorní kloakogenní polyp je vzácnou lézí vznikající v zona transitionalis analis. Většinou se chová benigně, ale jsou známy i vzácné případy maligní transformace. Nejčastěji se objevuje u dospělé populace mezi čtvrtou a šestou dekádou, nicméně jej můžeme nalézt i u dětí a adolescentů. Mezi nejčastější příznaky patří krvácení z konečníku a změna defekačního stereotypu, ale část pacientů může být i asymptomatická. Léčba spočívá v odstranění metodou transanální endoskopické mikrochirurgie s následnou péčí o měkkou stolici. Předkládáme popis případu 14letého pacienta s intermitentním krvácením z konečníku, u nějž byla nalezena polypózní léze při vyšetření per rectum. Suspektní léze byla při rektosigmoideoskopii odstraněna metodou transanální endoskopické mikrochirurgie a histologicky byla stanovena diagnóza inflamatorního kloakogenního polypu. V dalším období byl pacient již bez obtíží. Sdělením chceme upozornit na tuto vzácnou nosologickou jednotku a zdůraznit, že v diferenciální diagnostice krvácení z rekta u všech věkových kategorií by měl být inflamatorní kloakogenní polyp brán v potaz.

Inflammatory cloacogenic polyp is a rare lesion arising in the anal transitional zone. It is usually benign, but rare cases of malignant transformation are known. It is most commonly seen in the adult population from the fourth to the sixth decade of life, but it can be found among children and adolescents as well. The most common clinical symptoms include rectal bleeding and altered bowel habits, although some patients may be asymptomatic. Treatment involves transanal endoscopic microsurgery followed by a bowel regimen with stool softeners. We present the case report of a 14-year-old boy presenting with intermittent rectal bleeding in whom a polypoid lesion was found during digital rectal examination. The patient underwent proctosigmoidoscopy during which the suspicious lesion was removed by transanal endoscopic microsurgery and the histological diagnosis of inflammatory cloacogenic polyp was established. In the postoperative period, the patient was without any further problems. In this case report, we want to raise awareness of this rare diagnosis and emphasize its place in the differential diagnosis of rectal bleeding across all age groups.

• MeSH
• gastrointestinální krvácení etiologie   MeSH
• lidé MeSH
• mladiství MeSH
• nádory anu * chirurgie   diagnóza   patologie   MeSH
• polypy střeva * chirurgie   diagnóza   patologie   MeSH
• transanální mikroskopická chirurgie škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH