OBJECTIVE: To assess the effect of overall, between- and within-day subjectively rated fluctuations in motor and non-motor symptoms in people with functional motor disorder (FMD) on the health-related quality of life (HRQoL). BACKGROUND: FMD is a complex condition characterized by fluctuating motor and non-motor symptoms that may negatively impact HRQoL. METHODS: Seventy-seven patients (54 females, mean age 45.4 ± 10.4 years) with a clinically established diagnosis of FMD, including weakness, completed symptom diaries, rating the severity of motor and non-motor symptoms (i.e., pain, fatigue, mood, cognitive difficulties) on a 10-point numerical scale three times daily for seven consecutive days. HRQoL was assessed using the SF-36 questionnaire. For the analysis, fluctuation magnitude was defined in terms of the variability in self-reported symptom scores. RESULTS: The mental component of SF-36 was jointly predicted by the overall severity scores (t(74) = -3.61, P < 0.001) and overall general fluctuations (t(74) = -2.98, P = 0.004). The physical SF-36 was found to be related only to the overall symptom severity scores (t(74) = -7.09, P < 0.001), but not to the overall fluctuations. The assessment of the impact of different components showed that the mental component of SF-36 was significantly influenced by the combined effect of average fatigue (t(73) = -3.86, P < 0.001), between-day cognitive symptoms fluctuations (t(73) = -3.22, P = 0.002), and within-day mood fluctuations (t(73) = -2.48, P = 0.015). CONCLUSIONS: This study demonstrated the impact of self-reported symptom fluctuations across multiple motor and non-motor domains on mental but not physical HRQoL in FMD and highlighted the importance of assessing and managing fluctuations in clinical practice.

• MeSH
• afekt fyziologie   MeSH
• bolest psychologie   patofyziologie   MeSH
• dospělí MeSH
• kvalita života * psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pohybové poruchy psychologie   patofyziologie   MeSH
• průzkumy a dotazníky MeSH
• stupeň závažnosti nemoci MeSH
• únava * psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD.

• MeSH
• deprese epidemiologie   patofyziologie   MeSH
• dospělí MeSH
• komorbidita * MeSH
• lidé středního věku MeSH
• lidé MeSH
• periodické pohyby končetinami ve spánku epidemiologie   patofyziologie   MeSH
• polysomnografie * MeSH
• poruchy nadměrné spavosti * epidemiologie   patofyziologie   MeSH
• poruchy spánku a bdění epidemiologie   patofyziologie   MeSH
• průzkumy a dotazníky MeSH
• somnolence MeSH
• spánková latence fyziologie   MeSH
• syndrom neklidných nohou patofyziologie   epidemiologie   MeSH
• únava patofyziologie   epidemiologie   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

OBJECTIVE: The role of inflammation and neuroimmune mechanisms, which have been documented in various neuropsychiatric disorders including the seizure subtype of functional neurological disorder, remains unclear in functional movement disorders (FMD). To explore these mechanisms, we analyzed selected inflammatory markers in cerebrospinal fluid (CSF) in patients with FMD. METHODS: We compared CSF markers in 26 patients with clinically established FMD (20 females; mean [SD] age = 43.3 [10.9], disease duration = 3.9 [3], range = 0.1-11 years; mean follow-up after lumbar puncture = 4.3 [2] years, range = 0.5-7 years) and 26 sex- and age-matched clinical controls with noninflammatory nonneurodegenerative neurological disorders, mostly sleep disorders. RESULTS: Sixty-five percent of FMD patients versus 15% of controls showed cytological abnormalities (i.e., increased white blood cells [WBC] count, signs of WBC activation, or both; odds ratio [OR] = 9.85, 95% confidence interval = 2.37-52.00, p < .01, corrected), with a significantly higher frequency of an isolated lymphocytic activation, 35% versus 0% (OR = ∞, 95% confidence interval = 2.53-∞, p < .05, corrected). There were no differences in CSF protein and albumin levels, quotient albumin, IgG index, and oligoclonal bands. CSF abnormalities were not associated with more severe motor symptoms or a higher frequency of depression in FMD. CONCLUSIONS: Our results suggest a possible involvement of immune mechanisms in the pathophysiology of (at least a subtype of) FMD that deserves further investigation.

• MeSH
• biologické markery mozkomíšní mok   MeSH
• cytologie MeSH
• dospělí MeSH
• konverzní poruchy mozkomíšní mok   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet leukocytů MeSH
• pohybové poruchy * mozkomíšní mok   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

• MeSH
• bazální ganglia MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   MeSH
• Parkinsonova nemoc * diagnostické zobrazování   MeSH
• pohyb fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort. METHODS: One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL. RESULTS: Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups. CONCLUSIONS: We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of 'functional' symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

• MeSH
• konverzní poruchy * MeSH
• kvalita života * psychologie   MeSH
• lidé MeSH
• syndrom MeSH
• úzkost diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Akutní lymfoblastická leukémie (ALL) je nejčastějším maligním onemocněním u dětí. Prognóza těchto pacientů se neustále zlepšuje i díky přesnější diagnostice a sledování minimální reziduální nemoci (MRN) pomocí průtokové cytometrie. V předkládaném projektu vyvineme automatické nástroje na analýzu velkého počtu multidimenzionálních cytometrických dat, které umožní kategorizaci leukémií dle jejich imunofenotypu s ohledem na přežití a další klinické charakteristiky pacientů. Popis vývoje imunofenotypu leukémií v průběhu léčby umožní optimalizaci detekce MRN. Imunofenotyp leukémií dále zkombinujeme s celogenomovými daty, abychom stanovili relevanci genetických aberací a jejich vliv na fenotyp. Tato integrální analýza povede ke zlepšení diagnostiky specifických maligních onemocnění, predikce prognózy dětských pacientů s ALL i k racionalizaci nákladů zahrnutých metod.; Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children. Its improving outcome depends on accurate diagnosis and minimal residual disease (MRD) monitoring as done by flow cytometry. In proposed project we will develop automatic tools usable in clinical setting to analyse large numbers of multidimensional flow cytometry datasets. This will allow for clinical relevant categorisation of leukemias based on their immunophenotypes (LAIPs) with respect to outcome and other clinical features. Likewise better description of LAIPs dynamics and changes under treatment will allow for optimisation of MRD detection. Moreover, we will use whole genome data to associate genetic traits to immunophenotypes. Such integrative analysis will provide insights into relevance of genetic aberrations and their propagation into phenotype. Thus ultimately the combined analysis will lead to improvement of diagnostic of specific cancer subtypes and to better prediction of treatment outcome as well as rationalisation of costs of involved methods.

• MeSH
• akutní lymfatická leukemie MeSH
• fenomika MeSH
• genomika MeSH
• průtoková cytometrie MeSH
• reziduální nádor MeSH
• sekvenování celého genomu MeSH
• sekvenování transkriptomu MeSH

• Konspekt
• Pediatrie
• NLK Obory
• pediatrie
• onkologie
• genetika, lékařská genetika
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

OBJECTIVE: Pathophysiology explanations for functional movement disorders often assume a role for emotional hyperarousal. Pupillometry is a validated method for evaluation of emotional arousal by detecting changes in pupil size in response to emotional stimuli. In a case-control study design, we aimed to study objective and subjective emotional arousal using pupillometry and affective ratings. To assess attentional engagement by affective stimuli, we used videooculographic tracking of eye movement patterns (scanpath). METHODS: Twenty-five female patients with functional movement disorders (mean age: 40.9 [SD 12.7] years) and 23 age matched healthy female controls participated in the study. Using infrared high-resolution eye-tracker, both pupil size and eye movement pattern in response to emotionally charged erotic, adventure, threat, victim, and neutral pictures were recorded along with subjective ratings of emotional valence and arousal of the presented pictures. RESULTS: A between-group comparison showed significantly smaller pupil dilation to adventure stimuli compared to neutral stimuli in patients compared to controls (P < 0.004, bootstrap, uncorr., adj. η2 = 0.00). No significant difference in pupillary response to other stimuli and scanpath parameters was found between the groups. Patients rated significantly lower emotional arousal to erotic pictures than controls (P < 0.001, bootstrap, uncorr., adj. η2 = 0.09). CONCLUSION: This study did not find evidence of autonomous or subjective emotional hyperarousal. The mismatch between objective autonomic measures and subjective arousal ratings in patients is of pathophysiological interest and in line with recent findings of impaired interoception in functional movement disorders.

• MeSH
• arousal * fyziologie   MeSH
• dospělí MeSH
• emoce fyziologie   MeSH
• konverzní poruchy * MeSH
• lidé MeSH
• pozornost MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March-October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.

• MeSH
• COVID-19 epidemiologie   patologie   terapie   MeSH
• dospělí MeSH
• farmakoterapie COVID-19 MeSH
• hospitalizace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci * MeSH
• senioři MeSH
• statistické modely MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. OBJECTIVES: Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. METHODS: Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. RESULTS: The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. CONCLUSIONS: Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration.

• MeSH
• algoritmy MeSH
• artefakty MeSH
• elektrokardiografie MeSH
• esenciální tremor * MeSH
• lidé MeSH
• rozhraní mozek-počítač * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes.

• MeSH
• buněčná diferenciace MeSH
• buněčné linie MeSH
• exprese genu MeSH
• komplex proteinů jaderného póru metabolismus   MeSH
• kosterní svalová vlákna * cytologie   metabolismus   MeSH
• myoblasty kosterní * cytologie   metabolismus   MeSH
• myši MeSH
• protoonkogenní proteiny metabolismus   MeSH
• regulace genové exprese MeSH
• těžké řetězce myosinu metabolismus   MeSH
• vývoj svalů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH