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OBJECTIVE: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years. RESULTS: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17). INTERPRETATION: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543.
BACKGROUND: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). OBJECTIVE: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. METHODS: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. RESULTS: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). CONCLUSIONS: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.
- MeSH
- alely MeSH
- Alzheimerova nemoc * genetika MeSH
- apolipoprotein E4 genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- jednonukleotidový polymorfismus * genetika MeSH
- kognitivní dysfunkce * genetika MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- neuropsychologické testy MeSH
- paměť fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The gold standard for serum neurofilament light chain (sNfL) determination is the single molecule array (SIMOA), the use of which is limited by availability and cost. The VEUS method is a fully automated, user-friendly diagnostic system requiring no sample preparation, with high reported sensitivity, multiplexing capability, and rapid diagnostics. The aim of this study was to compare the SIMOA and VEUS methods for determining sNfL levels in patients with multiple sclerosis (MS). METHODOLOGY: A single-centre cross-sectional study was conducted at the MS Centre of University Hospital Ostrava. Patients were enrolled in the study from January 18 to January 31, 2024. Inclusion criteria were: 1) diagnosis of MS according to the revised 2017 McDonald criteria, 2) age ≥18 years, and 3) signed informed consent. The NF-light V2 diagnostic kit (SIMOA, Quanterix) and the Singleplex Neurology assay kit (VEUDx, EZDiatech) were used to determine sNfL concentrations. The two methods were compared by use of Spearman correlation, Passing-Bablok regression, and Bland-Altman analysis. RESULTS: A total of 49 patients were included in the study, of whom 39 (79.6 %) were female. The median sNfL concentration was 7.73 (IQR 5.80-9.93) ng/L determined by SIMOA and 1.31 (IQR 1.18-1.65) ng/L by VEUS. We did not find a correlation between SIMOA and VEUS (rs = 0.025, p = 0.866). Passing-Bablok regression demonstrated a systematic and proportional difference between the two methods. A significant disagreement between them was also confirmed by the Bland-Altman plots. On average, sNfL values measured by SIMOA were 3.56 ng/L (95 % CI 0.78 to 6.34) higher than those measured by VEUS. CONCLUSION: Our investigation uncovered noteworthy disparities between the SIMOA and VEUS techniques in determining sNfL levels. Specifically, the VEUS technique systematically produces lower estimates of sNFL levels. This substantial variance emphasizes the importance of carefully evaluating assay methods when quantifying sNfL.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurofilamentové proteiny * krev MeSH
- průřezové studie MeSH
- roztroušená skleróza * krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Speech dysfunction represents one of the initial motor manifestations to develop in Parkinson's disease (PD) and is measurable through smartphone. OBJECTIVE: The aim was to develop a fully automated and noise-resistant smartphone-based system that can unobtrusively screen for prodromal parkinsonian speech disorder in subjects with isolated rapid eye movement sleep behavior disorder (iRBD) in a real-world scenario. METHODS: This cross-sectional study assessed regular, everyday voice call data from individuals with iRBD compared to early PD patients and healthy controls via a developed smartphone application. The participants also performed an active, regular reading of a short passage on their smartphone. Smartphone data were continuously collected for up to 3 months after the standard in-person assessments at the clinic. RESULTS: A total of 3525 calls that led to 5990 minutes of preprocessed speech were extracted from 72 participants, comprising 21 iRBD patients, 26 PD patients, and 25 controls. With a high area under the curve of 0.85 between iRBD patients and controls, the combination of passive and active smartphone data provided a comparable or even more sensitive evaluation than laboratory examination using a high-quality microphone. The most sensitive features to induce prodromal neurodegeneration in iRBD included imprecise vowel articulation during phone calls (P = 0.03) and monopitch in reading (P = 0.05). Eighteen minutes of speech corresponding to approximately nine calls was sufficient to obtain the best sensitivity for the screening. CONCLUSION: We consider the developed tool widely applicable to deep longitudinal digital phenotyping data with future applications in neuroprotective trials, deep brain stimulation optimization, neuropsychiatry, speech therapy, population screening, and beyond. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- biologické markery MeSH
- chytrý telefon * MeSH
- hlas fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * patofyziologie komplikace MeSH
- parkinsonské poruchy patofyziologie MeSH
- porucha chování v REM spánku * patofyziologie diagnóza MeSH
- poruchy řeči etiologie MeSH
- prodromální symptomy MeSH
- průřezové studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Kompletně decelularizované matrice jsou vysoce perspektivní v moderním tkáňovém inženýrství, a to pro jejich výrazně sníženou imunogenní aktivitu a obdobné mechanické vlastnosti, složení a 3D strukturu jako u přirozené extracelulární matrix. V tomto projektu proto hodláme využít decelularizovaný perikard a krevní cévy pro konstrukci cévních záplat a cévních náhrad o malém průměru. Kompletní decelularizace bude dosaženo v plně automatizovaném systému za definovaných podmínek, což umožní reprodukovatelnost výsledků a vytvoření netoxických matricí vhodných pro recelularizaci endotelovými buňkami (EB), která bude dále podpořena pokrytím decelularizovaných matricí heparinem a kyselinou hyaluronovou. Očekáváme, že tato „simulovaná glykokalyx“ bude mít rovněž antitrombogenní účinky. Recelularizace bude nejprve sledována in vitro ve statických a především v dynamických kultivačních systémech, kde budou EB a jejich prekursory vychytávány z cirkulujícího kultivačního média či heparinizované králičí krve. Nejslibnější vzorky budou vybrány pro preklinické testy in vivo na modelu králíka.; Completely decellularized matrices are promising in advanced tissue engineering, because they lose most of their immunogenicity and preserve similar mechanical properties, composition and 3D structure as the native extracellular matrix. Therefore, we intend to use decellularized pericardium and blood vessels for creating vascular patches and small-diameter vascular grafts, respectively. The decellularization will be carried out in a fully automated system under defined conditions, giving reproducible results and producing non-toxic matrices suitable for further recellularization with endothelial cells (EC), which will be supported by coating the matrices with heparin and hyaluronic acid. This “simulated glycocalyx” is also supposed to have antithrombogenic effects. The recellularization will be first tested in vitro in static and particularly dynamic cell culture systems, where the EC or their precursors will be captured from a circulating culture medium or heparinized blood. The most promising samples will be then selected for preclinical tests in vivo in a rabbit model.
- Klíčová slova
- kyselina hyaluronová, hyaluronic acid, perikard, krevní cévy, decelularizace, recelularizace, heparin, endotelové buňky, cévní záplaty, cévní náhrady, pericardium, blood vessels, decellularization, recellularization, heparin, endothelial cells, vascular patches, vascular grafts, králik in-vivo, rabbit in-vivo,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
BACKGROUND: During and after exercise, dynamic 31 P MR parameters are typically measured using an MR-compatible ergometer. Self-built equipment for local condition can be constructed where possible. PURPOSE: To develop a pedal resistance ergometer with rocker arm based on a system that combines electric weight displacement, visual self-monitoring, and exercise triggering. The repeatability and reproducibility were tested. METHODS: The hardware and software for the ergometer were constructed from commercial components in a home laboratory. Twelve volunteers participated in the testing of the ergometer. RESULTS: A fully automated ergometer system was developed, allowing the pedal resistance to be adjusted during the examination. The system includes a self-monitoring and triggering mechanism that enables both the operator and subject to monitor pedal frequency and force. The operator can modify the pedal resistance as desired during the exercise. This self-monitoring solution is simple and cost-effective, requiring only a commercial potentiometer, an Arduino converter, and a conventional video projector with a personal computer (PC). Additionally, all system components are located outside the magnetic resonance (MR) room, avoiding interference with the MR system. Results of several test of the reproducibility/repeatability of power at three pedal resistance values (15%, 24%, 25% maximal voluntary force) were expressed both as a coefficient of variation ranging from 6% to 3.1% and as an intraclass correlation of coefficient ranging from 0.96 to 0.99. Similar values were also found for other dynamic parameters of 31 P MR spectroscopy. These findings are similar to published data obtained on different types of ergometers. CONCLUSIONS: Based on more than 1 year of usage, the ergometer proved successful in handling stationary and variable loads, and can be easily operated by a single user.
This study aims to develop a fully automated imaging protocol independent system for pituitary adenoma segmentation from magnetic resonance imaging (MRI) scans that can work without user interaction and evaluate its accuracy and utility for clinical applications. We trained two independent artificial neural networks on MRI scans of 394 patients. The scans were acquired according to various imaging protocols over the course of 11 years on 1.5T and 3T MRI systems. The segmentation model assigned a class label to each input pixel (pituitary adenoma, internal carotid artery, normal pituitary gland, background). The slice segmentation model classified slices as clinically relevant (structures of interest in slice) or irrelevant (anterior or posterior to sella turcica). We used MRI data of another 99 patients to evaluate the performance of the model during training. We validated the model on a prospective cohort of 28 patients, Dice coefficients of 0.910, 0.719, and 0.240 for tumour, internal carotid artery, and normal gland labels, respectively, were achieved. The slice selection model achieved 82.5% accuracy, 88.7% sensitivity, 76.7% specificity, and an AUC of 0.904. A human expert rated 71.4% of the segmentation results as accurate, 21.4% as slightly inaccurate, and 7.1% as coarsely inaccurate. Our model achieved good results comparable with recent works of other authors on the largest dataset to date and generalized well for various imaging protocols. We discussed future clinical applications, and their considerations. Models and frameworks for clinical use have yet to be developed and evaluated.
- MeSH
- adenom * diagnostické zobrazování chirurgie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nádory hypofýzy * diagnostické zobrazování chirurgie MeSH
- neuronové sítě MeSH
- počítačové zpracování obrazu metody MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Hybridní uzavřené okruhy jsou v současné době nejúčinnější léčebnou technologickou metodou u pacientů s diabetes mellitus 1. typu. Okruh sestává ze senzoru ke kontinuální monitoraci glukózy, inzulínové pumpy a chytrého algoritmu vydávajícího inzulin částečně samostatně s úpravou podle aktuální koncentrace glukózy. Hybridní okruhy vyžadují spolupráci pacienta v podobě oznamování jídel pro aplikaci prandiálního bolusu a udržování funkčního místa vpichu senzoru/kanyly. Podle klinických studií je užívání certifikovaných hybridních okruhů jednoznačně bezpečné a účinné. V současnosti poskytují uzavřené okruhy jejich uživatelům komfortní způsob každodenní péče o svůj diabetes. Do budoucna lze očekávat příchod plně automatizovaných, na pacientovi nezávislých technologií či bihormonálních okruhů.
Hybrid closed-loop systems are currently the most effective treatment technologies for patients with type 1 diabetes mellitus. The system consists of a continuous glucose monitoring sensor, an insulin pump, and a smart algorithm that partially independently adjusts insulin dosage based on the current glucose concentration. Hybrid loops require patient's cooperation in terms of meal announcement for prandial bolus delivery and maintaining a functional injection site of the sensor/cannula. According to clinical studies, the use of certified hybrid loops is safe and effective. Currently, closed-loop systems provide users with a comfortable way to manage their diabetes on a daily basis. In the future, fully automated, patient-independent technologies or bihormonal loops, are expected.
- Klíčová slova
- hybridní uzavřené okruhy,
- MeSH
- diabetes mellitus 1. typu * farmakoterapie MeSH
- inzulinové infuzní systémy * MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
In this paper, we present the ImmunoDisk, a fully automated sample-to-answer centrifugal microfluidic cartridge, integrating a heterogeneous, wash-free, magnetic- and fluorescent bead-based immunoassay (bound-free phase detection immunoassay/BFPD-IA). The BFPD-IA allows the implementation of a simple fluidic structure, where the assay incubation, bead separation and detection are performed in the same chamber. The system was characterized using a C-reactive protein (CRP) competitive immunoassay. A parametric investigation on air drying of protein-coupled beads for pre-storage at room temperature is presented. The key parameters were buffer composition, drying temperature and duration. A protocol for drying two different types of protein-coupled beads with the same temperature and duration using different drying buffers is presented. The sample-to-answer workflow was demonstrated measuring CRP in 5 μL of human serum, without prior dilution, utilizing only one incubation step, in 20 min turnaround time, in the clinically relevant concentration range of 15-115 mg/L. A reproducibility assessment over three disk batches revealed an average signal coefficient of variation (CV) of 5.8 ± 1.3%. A CRP certified reference material was used for method verification with a concentration CV of 8.6%. Our results encourage future testing of the CRP-ImmunoDisk in clinical studies and its point-of-care implementation in many diagnostic applications.
- MeSH
- C-reaktivní protein * MeSH
- imunoanalýza metody MeSH
- indikátory a reagencie MeSH
- lidé MeSH
- mikrofluidika * MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH