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Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.
- MeSH
- dítě MeSH
- elektroencefalografie * metody MeSH
- epilepsie * terapie patofyziologie MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- refrakterní epilepsie * terapie patofyziologie MeSH
- skalp MeSH
- vagová stimulace * metody MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.
- MeSH
- dospělí MeSH
- glukokortikoidy terapeutické užití MeSH
- Gravesova oftalmopatie * farmakoterapie krev MeSH
- imunoglobuliny stimulující tyreoideu krev MeSH
- imunologické faktory terapeutické užití MeSH
- léková rezistence * MeSH
- lidé středního věku MeSH
- lidé MeSH
- retrospektivní studie MeSH
- rituximab * terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes. METHODS: From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0 weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients. RESULTS: We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33. CONCLUSIONS: External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes.
- MeSH
- alfa-fetoproteiny * analýza metabolismus MeSH
- amniocentéza metody MeSH
- chorioamnionitida * diagnóza MeSH
- dospělí MeSH
- hodnocení rizik metody MeSH
- interleukin-6 * analýza krev metabolismus MeSH
- lidé MeSH
- plodová voda * metabolismus chemie MeSH
- point of care testing MeSH
- předčasná porodní činnost * diagnóza MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- vagina metabolismus MeSH
- vyšetření u lůžka MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
The precise measurement of cell temperature and an in-depth understanding of thermogenic processes are critical in unraveling the complexities of cellular metabolism and its implications for health and disease. This review focuses on the mechanisms of local temperature generation within cells and the array of methods developed for accurate temperature assessment. The contact and noncontact techniques are introduced, including infrared thermography, fluorescence thermometry, and other innovative approaches to localized temperature measurement. The role of thermogenesis in cellular metabolism, highlighting the integral function of temperature regulation in cellular processes, environmental adaptation, and the implications of thermogenic dysregulation in diseases such as metabolic disorders and cancer are further discussed. The challenges and limitations in this field are critically analyzed while technological advancements and future directions are proposed to overcome these barriers. This review aims to provide a consolidated resource for current methodologies, stimulate discussion on the limitations and challenges, and inspire future innovations in the study of cellular thermodynamics.
- MeSH
- lidé MeSH
- teplota MeSH
- termogeneze * fyziologie MeSH
- termografie * metody MeSH
- termometrie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h. Gene expression was assessed using 3'-mRNA sequencing and modelled using negative binomial models. Incubation with ETI resulted in a significant upregulation of several biological processes: mostly related to chemokines and signalling, chemotaxis, and tissue development processes. No changes were observed in abundance of the CFTR transcripts or in CFTR-related gene sets and pathways. The genes and pathways associated with ETI did not overlap with those whose expression changed with time only. PDIOs with a high FIS response did not significantly differ in any interpretable gene from the FIS-low organoids. The changes in the PDIOs gene expression upon the exposure to ETI cannot explain differences in the magnitude of PDIOs FIS-measured response to ETI. In conclusion, on incubation with ETI, genes of the CFTR-related pathways do not change their transcriptional activity; instead, overexpression was observed in genes of inflammatory-like cytokine response and receptor activation pathways.
- MeSH
- aktivátory chloridových kanálů terapeutické užití farmakologie MeSH
- aminofenoly * terapeutické užití farmakologie MeSH
- benzodioxoly * terapeutické užití farmakologie MeSH
- chinolony * farmakologie terapeutické užití MeSH
- cystická fibróza * genetika farmakoterapie MeSH
- fixní kombinace léků MeSH
- indoly * farmakologie MeSH
- lidé MeSH
- organoidy * metabolismus MeSH
- protein CFTR genetika MeSH
- pyrazoly * farmakologie MeSH
- pyridiny farmakologie MeSH
- pyrrolidiny farmakologie MeSH
- pyrroly farmakologie MeSH
- stanovení celkové genové exprese metody MeSH
- střeva účinky léků MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.
INTRODUCTION: The aim of our study was to study the association between end-of-surgery facial nerve stimulation threshold and extent of tumor resection in case of grade IV vestibular schwannomas. MATERIALS AND METHODS: Grade IV VSs represent a surgical challenge as a risk/benefit ratio must be considered in balancing a satisfactory extent of resection against a good postoperative functional outcome. We reviewed a cumulative series of 57 patients with large/giant VSs who were operated on by retrosigmoid approach in the period from 2008 to 2018 in two European centers, namely San Filippo Neri Hospital, Rome, Italy and Masaryk Hospital, Usti nad Labem, Czech Republic. Extent of resection, intraoperative direct electrical stimulation threshold of facial nerve and postoperative facial outcome were examined. RESULTS: Total or near-total resection was accomplished in 40 (75.5%) cases. Two groups were compared: total or near-total resection (T + NT) and subtotal resection (ST); the end-of-surgery facial nerve stimulation threshold significantly differed (T + NT: 0.24 mA, ST: 0.44 mA, p = 0.036). A critical cutoff was found at 0.2mA; values similar or inferior to this correctly predicted total or near-total resection in 86.7% of cases. Thirty (56.6%) patients had a normal postoperative facial outcome (HB1). Among the 40 patients in T + NT group, 32 (80%) retained an acceptable facial function (HB1-2). CONCLUSIONS: Lower facial nerve stimulation thresholds positively predict a broader extent of resection and total or -near total resection should be accomplished in such cases. Judicious (subtotal) resection is preferred if threshold values increase while dissecting firmly adherent tumors.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervus facialis patofyziologie MeSH
- neurochirurgické výkony * metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- stupeň nádoru MeSH
- vestibulární schwannom * chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVE: Resection of the vestibular schwannoma causes acute peripheral vestibular loss. The process of central compensation starts immediately afterward. The rehabilitation goal is to support this process and restore the quality of life. MATERIALS AND METHODS: In this prospective single-center study, 67 consecutive patients underwent vestibular schwannoma resection (40 females, mean age 52 ± 12 years). The patients were divided into three groups: the prehabilitation with intratympanic gentamicin group, the virtual reality group (optokinetic stimulation via virtual reality goggles in the first ten days after the surgery), and the control group. All patients were examined with objective methods and completed questionnaires before the prehabilitation, before the surgery, at the hospital discharge, and after three months. RESULTS: Intratympanic gentamicin prehabilitation leads ipsilaterally to a significant aVOR reduction in all semicircular canals (p < 0.050), the increase of the unilateral weakness in air calorics (p = 0.026), and loss of cVEMPs responses (p = 0.017). Prehabilitation and postoperative exposure to virtual reality scenes improved the patient's perception of vertigo problems according to Dizziness Handicap Inventory (p = 0.039 and p = 0.076, respectively). These findings conform with the optokinetic testing results, which showed higher slow phase velocities at higher speeds (40 deg/s) in both targeted groups compared to the control group. CONCLUSION: Preoperative intratympanic gentamicin positively affects peripheral vestibular function, influencing balance perception after VS resection. In long-term follow-up, prehabilitation and postoperative exposure to virtual reality improve patients' quality of life in the field of vertigo problems.
- MeSH
- antibakteriální látky aplikace a dávkování MeSH
- dospělí MeSH
- gentamiciny * aplikace a dávkování MeSH
- intratympanická injekce MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- pooperační péče metody MeSH
- předoperační péče metody MeSH
- prospektivní studie MeSH
- senioři MeSH
- terapie pomocí virtuální reality metody MeSH
- vestibulární funkční testy MeSH
- vestibulární schwannom * chirurgie MeSH
- virtuální realita MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Kliešťová encefalitída (KE) je opomínaná neuroinvazívna antropozoonóza. Väčšina prípadov KE má mierny priebeh, ale u niektorých pacientov s encefalitídou sa vyvinú dlhodobé neurologické alebo neuropsychické následky. Uvádzame fatálny prípad KE z endemickej oblasti. Prípad sa vyskytol u muža v strednom veku bez epidemiologických dôkazov o uhryznutí kliešťom alebo konzumácii surových mliečnych výrobkov a ktorý nebol očkovaný proti KE. Cieľom tohto príspevku je upozorniť na potrebu lepšej znalosti rizikových faktorov spojených s kliešťovou encefalitídou s dlhodobými následkami, zlepšiť manažment prípadov a podnietiť vývoj nových vakcinačných stratégií. Podľa našich vedomostí ide o prvý hlásený prípad zriedkavej fatálnej KE u muža stredného veku bez závažných komorbidít na Slovensku.
Tick-borne encephalitis (TBE) is a neglected zoonotic neuroinvasive disease. Most cases of TBE have a mild course, but some patients with encephalitis develop long-term neurological or neuropsychic sequelae. We report a fatal case of TBE in a patient living in an endemic area. The case occurred in a middle-aged man with no epidemiological evidence of tick bites, no consumption of raw dairy products, and who was not vaccinated against TBE. The aim of this paper is to draw attention to the need for better information of the risk factors associated with TBE with the long-term sequelae, to improve case management and to stimulate the development of new vaccination strategies. To our knowledge, this is the first reported case of rare fatal TBE in a middle-aged man with no severe comorbidities in Slovakia.
Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.
- MeSH
- fenotyp * MeSH
- glioblastom * patologie genetika metabolismus MeSH
- invazivní růst nádoru * genetika MeSH
- lidé MeSH
- membránové proteiny MeSH
- mikrotubuly metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory mozku * patologie genetika metabolismus MeSH
- pohyb buněk genetika fyziologie MeSH
- proteiny nervové tkáně metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
