Neurodegenerative pathologies as Parkinson's Disease (PD) show important distortions in speech, affecting fluency, prosody, articulation and phonation. Classically, measurements based on articulation gestures altering formant positions, as the Vocal Space Area (VSA) or the Formant Centralization Ratio (FCR) have been proposed to measure speech distortion, but these markers are based mainly on static positions of sustained vowels. The present study introduces a measurement based on the mutual information distance among probability density functions of kinematic correlates derived from formant dynamics. An absolute kinematic velocity associated to the position of the jaw and tongue articulation gestures is estimated and modeled statistically. The distribution of this feature may differentiate PD patients from normative speakers during sustained vowel emission. The study is based on a limited database of 53 male PD patients, contrasted to a very selected and stable set of eight normative speakers. In this sense, distances based on Kullback-Leibler divergence seem to be sensitive to PD articulation instability. Correlation studies show statistically relevant relationship between information contents based on articulation instability to certain motor and nonmotor clinical scores, such as freezing of gait, or sleep disorders. Remarkably, one of the statistically relevant correlations point out to the time interval passed since the first diagnostic. These results stress the need of defining scoring scales specifically designed for speech disability estimation and monitoring methodologies in degenerative diseases of neuromotor origin.
- MeSH
- biomechanika fyziologie MeSH
- čelisti patofyziologie MeSH
- datové soubory jako téma MeSH
- dysartrie etiologie patofyziologie MeSH
- jazyk patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc komplikace diagnóza MeSH
- poruchy artikulace etiologie patofyziologie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Získaná hemofilie je vzácné autoimunitní onemocnění, které se může vyvinout v průběhu života a svou náhlou manifestací skončit i fatálně. Autoři popisují případ pacientky, u které se toto onemocnění projevilo hematomem a otokem spodiny ústní dutiny. Klíčová slova: získaná hemofilie, edém, hematom, spodina ústní dutiny
Acquired haemophilia is a rare autoimmune disease, which can develop in the course of life and with its sudden manifestation can lead to a fatal end. In this case report, we present a patient with this disease, which was manifested by hematoma and swelling of the floor of the mouth.
- Klíčová slova
- získaná hemofílie, spodina ústní dutiny,
- MeSH
- autoimunitní nemoci diagnóza terapie MeSH
- diagnostické techniky a postupy MeSH
- edém * etiologie terapie MeSH
- hematom * etiologie terapie MeSH
- hemofilie A * diagnóza terapie MeSH
- jazyk patofyziologie MeSH
- klinické laboratorní techniky metody MeSH
- lidé MeSH
- prednison terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Large animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. OBJECTIVE: The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping minipigs transgenic for Huntington's disease (tgHD) and whether tgHD minipigs reveal changes in this domain compared to wildtype (wt) minipigs. METHODS: While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt minipigs. RESULTS: Vocalisation can easily be documented during phenotyping assessments of minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. CONCLUSION: Vocalisation may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.
- MeSH
- časové faktory MeSH
- diskriminace (psychologie) MeSH
- fenotyp * MeSH
- geneticky modifikovaná zvířata * MeSH
- Huntingtonova nemoc * patofyziologie psychologie MeSH
- jazyk patofyziologie MeSH
- lidé MeSH
- longitudinální studie MeSH
- miniaturní prasata * MeSH
- modely nemocí na zvířatech * MeSH
- motorické dovednosti MeSH
- prasata MeSH
- protein huntingtin genetika metabolismus MeSH
- reverzní učení MeSH
- vnímání barev MeSH
- vokalizace zvířat * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioral phenotype of a transgenic (tg) HD minipig model. NEW METHODS: A group of tgHD and wildtype (wt) Libechov minipigs (n=36) was available for assessment with (1) a gait test using the GAITRite(®) automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a color discrimination test, (5) a startbox back and forth test and (6) a dominance test. Performance of all tests and definition of measures obtained is presented. RESULTS: Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt minipigs assessed, but low variability within and between groups. COMPARISON WITH EXISTING METHOD(S): So far there are no established or validated assessments to test minipigs in the domains described. CONCLUSIONS: The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioral features of tg and wt minipigs.
- MeSH
- chování zvířat * MeSH
- chůze (způsob) fyziologie MeSH
- design vybavení MeSH
- diskriminace (psychologie) fyziologie MeSH
- fenotyp MeSH
- geneticky modifikovaná zvířata * MeSH
- Huntingtonova nemoc genetika MeSH
- jazyk patofyziologie MeSH
- lidé MeSH
- miniaturní prasata genetika fyziologie psychologie MeSH
- modely nemocí na zvířatech * MeSH
- neuropsychologické testy MeSH
- pohybová aktivita fyziologie MeSH
- prasata MeSH
- protein huntingtin genetika metabolismus MeSH
- studie proveditelnosti MeSH
- učení fyziologie MeSH
- vidění barevné fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- biopsie MeSH
- imunoglobuliny farmakologie terapeutické užití MeSH
- imunologické testy MeSH
- imunosupresivní léčba metody MeSH
- injekce intramuskulární MeSH
- jazyk patofyziologie MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- methotrexát farmakologie terapeutické užití MeSH
- nemoci jazyka diagnóza MeSH
- pemfigus * diagnóza farmakoterapie MeSH
- prednison farmakologie terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- abnormality čelisti * genetika chirurgie MeSH
- dítě MeSH
- jazyk * chirurgie patofyziologie MeSH
- kojenec MeSH
- lidé MeSH
- mikrognacie genetika komplikace MeSH
- obstrukce dýchacích cest * etiologie genetika chirurgie MeSH
- Pierre Robinův syndrom * genetika chirurgie MeSH
- rozštěp patra genetika MeSH
- ústa * chirurgie patofyziologie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The epidermis is a stratified tissue composed of different keratinocyte layers that create a barrier protecting the body from external influences, pathogens, and dehydration. The barrier function is mainly achieved by its outermost layer, the stratum corneum. To create a mouse model to study pathophysiological processes in the outermost layers of the epidermis in vivo and in vitro we prepared a construct containing red fluorescent td-Tomato reporter sequence under the control of involucrin promoter and its first intron. Transgenic mice were generated by pronuclear injection and the expression and regulation of the transgene was determined by in vivo imaging and fluorescent microscopy. The promoter targeted the transgene efficiently and specifically into the outermost epidermal layers although weak expression was also found in epithelia of tongue and bladder. The regulation of expression in the epidermis, i.e. fluorescence intensity of the reporter, could be easily followed during wound healing and dermatitis. Thus, these transgenic mice carrying the tdTomato reporter could be used as a valuable tool to study impact of various genes dysregulating the epidermal barrier and to follow effects of therapeutic agents for treatment of skin diseases in vivo.
- MeSH
- buněčná diferenciace MeSH
- dermatitida metabolismus patofyziologie MeSH
- epidermis metabolismus patofyziologie MeSH
- epitel metabolismus patofyziologie MeSH
- fluorescenční mikroskopie MeSH
- genový targeting metody MeSH
- hojení ran MeSH
- imunohistochemie MeSH
- introny MeSH
- jazyk metabolismus patofyziologie MeSH
- luminescentní proteiny metabolismus MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- promotorové oblasti (genetika) MeSH
- proteinové prekurzory genetika MeSH
- regulace genové exprese MeSH
- reportérové geny MeSH
- Solanum lycopersicum genetika MeSH
- transgeny MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- faryngitida komplikace MeSH
- jazyk patofyziologie MeSH
- lidé MeSH
- mladiství MeSH
- nemoci jazyka diagnóza etiologie MeSH
- paréza diagnóza etiologie MeSH
- periferní nervy patofyziologie MeSH
- tonzilitida komplikace MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
