SCOPE: This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects. METHODS AND RESULTS: An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques, namely proton nuclear magnetic resonance (1H NMR), next-generation sequencing (NGS), and liquid chromatography-mass spectrometry (LC-MS) was used to determine silymarin microbial metabolites over 24 h, overall metabolome, and microbiota composition. Silymarin at a low diet-relevant dose of 50 μg mL-1 significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study reveals age-related differences in silymarin catabolism. Healthy elderly donors (70-80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12-45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which is associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003. CONCLUSION: This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies, and advancing our understanding of dietary (poly)phenol metabolism.
- MeSH
- dítě MeSH
- dospělí MeSH
- feces mikrobiologie MeSH
- fermentace MeSH
- kolon * mikrobiologie metabolismus účinky léků MeSH
- kyseliny mastné těkavé metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- silymarin * farmakologie MeSH
- střevní mikroflóra * účinky léků fyziologie MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The deep fascia has recently been a current topic in many medical fields, including rehabilitation. Some research has already focused on assessing deep fascia, however results of individual authors differ in certain aspects. This study focuses on the inter-rater reliability of ultrasound (US) measurement of the thickness of deep fascia and loose connective tissue (LCT). The aim was to define the causes of any discrepancies in measurement that could contribute to the unification of management of evaluating fascia. METHODS: An observational study was performed including 20 healthy individuals in whom fascia lata of the anterior thigh was examined by US imaging and then measured in Image J software. Three raters participated in this study: the first with 6 years of US imaging experience, other two were newly trained. The measurement of fascial parameters was conducted in two phases with special consultation between them resulting in an agreement of the research team on the more precise way of measurement. RESULTS: Results revealed the value of inter-rater reliability ICC3,1 = 0.454 for deep fascia thickness and ICC3,1 = 0.265 for LCT thickness in the first phase and any significant difference in the second phase. This poor inter-rater reliability led to a search for possible causes of discrepancies, which authors subsequently highlighted. CONCLUSION: The findings of the study show the main pitfalls of deep fascia measurement that should contribute to the unification of evaluation.
- MeSH
- dospělí MeSH
- fascia lata diagnostické zobrazování anatomie a histologie MeSH
- fascie diagnostické zobrazování anatomie a histologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- odchylka pozorovatele * MeSH
- reprodukovatelnost výsledků MeSH
- stehno diagnostické zobrazování MeSH
- ultrasonografie * metody MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Platelet aggregation is a complicated process mediated by different signaling pathways. As the process is highly complex and apparently redundant, the relationships between these pathways are not yet fully known. The aim of this project was to study the interconnections among seven different aggregation pathways in a group of 53 generally healthy volunteers aged 20 to 66 years. Platelet aggregation was induced with thrombin receptor activating peptide 6 (TRAP), arachidonic acid (AA), platelet activating factor 16 (PAF), ADP, collagen, thromboxane A2 analogue U46619 or ristocetin (platelet agglutination) ex vivo in fasting blood samples according to standardized timetable protocol. Additionally, some samples were pre-treated with known clinically used antiplatelet drugs (vorapaxar, ticagrelor or acetylsalicylic acid (ASA)). Significant correlations among all used inducers were detected (Pearson correlation coefficients (rP): 0.3 to 0.85). Of all the triggers, AA showed to be the best predictor of the response to other inducers with rP ranging from 0.66 to 0.85. Interestingly, the antiplatelet response to ticagrelor strongly predicted the response to unrelated drug vorapaxar (rP = 0.71). Our results indicate that a response to one inducer can predict the response for other triggers or even to an antiplatelet drug. These data are useful for future testing but should be also confirmed in patients.
PURPOSE: The common protocol of full-field stimulus threshold (FST) testing recommends pupil dilation. The aim of this study is to investigate the difference between FST measurements with dilated and nondilated pupils in healthy subjects and patients with retinitis pigmentosa (RP). METHODS: Twenty healthy subjects and 20 RP patients were selected. One pupil of each subject was dilated; the other eye was measured in physiological width of the pupil. The FST was conducted using Diagnosys Espion E2/E3 with white, blue, and red stimuli. Statistical analysis was conducted with a mixed-model analysis of variance and a paired t-test. RESULTS: The statistical analysis revealed a significant difference between measurements of dilated and nondilated pupils with the following: blue stimuli for all subjects and groups except those with highly progressed RP; white stimuli for all tested subjects in total, for RP patients with better-preserved visual field (VF), and rod-mediated FST response; and red stimuli for RP patients with better-preserved VF and rod-mediated FST response. On average, the difference between the FST values for RP patients were -3.2 ± 3 dB for blue, -2.3 ± 2.9 dB for white, and -0.83 ± 3 dB for red stimuli. The correlation between the FST values of dilated and nondilated pupils with all three stimuli was linear. CONCLUSIONS: Current recommendations are to perform FST with dilated pupils. However, based on this study's findings, pupil dilation can be omitted for clinical diagnostics or rough follow-ups. TRANSLATIONAL RELEVANCE: Our data provide useful information for the clinical use of FST.
- MeSH
- lidé MeSH
- pupila * MeSH
- retinopathia pigmentosa * diagnóza MeSH
- výzkumný projekt MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- zraková pole MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging.
- MeSH
- krátkodobá paměť MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mapování mozku * metody MeSH
- mozek * diagnostické zobrazování MeSH
- nervové dráhy MeSH
- senioři MeSH
- stárnutí MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To investigate whether a headshake applied during galvanic vestibular stimulation (GVS) can enhance GVS-induced nystagmus in healthy subjects. METHODS: In nineteen healthy participants, we evaluated an average slow-phase velocity (aSPV) of nystagmus in a head-still and after the headshake conditions, with/out the bitemporal 2 mA GVS. The GVS was applied also with polarity congruent (supporting) or incongruent (suppressing) to any preexisting spontaneous nystagmus. RESULTS: The orientation of GVS-induced nystagmus depended on GVS polarity. In the head-still condition, the GVS-induced nystagmus in 14 subjects (74%) for congruent and in 12 subjects (63%) for incongruent GVS. During headshake, we recorded nystagmus in 16 subjects (84%) for congruent and 15 subjects (79%) for incongruent GVS. The aSPV of congruent GVS-induced nystagmus was higher (p = 0.0003) by 1.33 (SE 0.26) deg/s for headshake compared to head-still condition. The aSPV of incongruent GVS also induced higher nystagmus (p = 0.0014) by 1.24 (SE 0.28) deg/s for the headshake condition. CONCLUSION: Our study adds a new principle to the knowledge of the central processing of a GVS response in healthy subjects. The GVS-safety profile of current up to 2 mA was sufficient to elicit a significant GVS nystagmus response in a head-still position in 63% and after a headshake in 79%. Compared to the GVS head-still condition, a headshake enhanced the GVS-induced nystagmus more than twice. SIGNIFICANCE: The headshake helps to identify GVS-induced nystagmus, which can be weak or absent during the head-still condition.
- MeSH
- dospělí MeSH
- elektrická stimulace * metody MeSH
- fyziologický nystagmus * fyziologie MeSH
- hlava - pohyby fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- pohyby očí fyziologie MeSH
- vestibulární aparát * fyziologie MeSH
- vestibulookulární reflex fyziologie MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Inhibitory control plays a role in the behavior selection and detection of conflicts. Defects in inhibitory control are an integral part of many neuropsychiatric disorders and the possibilities of influencing it are the subject of active study. Studies have shown and confirmed the activation of the dorsolateral prefrontal cortex (DLPFC) during the Stroop task and other tests involving response inhibition. Non-invasive brain stimulation is an emerging and actively developing group of methods used in cognitive research. In the present study, we used non-invasive, painless, and delicate transcranial direct stimulation (tDCS) for the study of inhibitory control, and to explore the effect of impulsivity on response inhibition ability in young healthy participants. We conducted a cross-over study with cross-hemispheric application of 2 mA tDCS with electrodes placed on the right - cathode, and left - anode - DLPFC. Participants performed a classic Stroop test before and after stimulation. Impulsivity was measured via the personal impulsiveness questionnaire. There was no significant difference in interference score alteration between active and sham stimulations, anodal and sham tDCS both induced slight improvement in Stroop test results. Individual impulsivity in healthy participants showed no influence on their results. Our study adds to the picture and helps to deepen knowledge about the impact of different stimulation parameters on cognitive functions.
BACKGROUND AND OBJECTIVE: The dual orexin receptor antagonist daridorexant was approved in 2022 for the treatment of insomnia at doses up to 50 mg once per night. This study aimed at investigating the effect of daridorexant 50 mg at steady state on the pharmacokinetics of dabigatran, the active moiety of dabigatran etexilate, and rosuvastatin, sensitive substrates of P-glycoprotein and breast cancer resistance protein, respectively. METHODS: This single-center, open-label, fixed-sequence study enrolled 24 healthy male subjects who were dosed orally with dabigatran etexilate 75 mg on days 1 (Treatment A1) and 9 (Treatment C1) as well as rosuvastatin 10 mg on days 3 (Treatment A2) and 11 (Treatment C2). On days 7-14, daridorexant (50 mg once daily) was administered. Blood samples for the pharmacokinetics of both substrates and the pharmacodynamics of dabigatran, i.e., two coagulation tests, were collected and safety assessments performed. Noncompartmental pharmacokinetic parameters and pharmacodynamic variables were evaluated with geometric mean ratios and 90% confidence intervals of Treatment C1/C2 versus A1/A2. RESULTS: Geometric mean ratios (90% confidence interval) of dabigatran maximum plasma concentration and area under the plasma concentration-time curve were 1.3 (1.0-1.7) and 1.4 (1.1-1.9), respectively, whereas the time to maximum plasma concentration and terminal half-life were comparable between treatments. Pharmacodynamic variables showed a similar pattern as dabigatran pharmacokinetics in both treatments. Rosuvastatin pharmacokinetics were unchanged upon concomitant daridorexant administration. All treatments were well tolerated. CONCLUSIONS: A mild inhibition of P-glycoprotein was observed after administration of daridorexant (50 mg once daily) at steady state, whereas breast cancer resistance protein was not affected. CLINICAL TRIAL REGISTRATION: NCT05480475; date of registration: 29 July, 2022.
- MeSH
- ABC transportér z rodiny G, člen 2 MeSH
- benzimidazoly MeSH
- dabigatran * škodlivé účinky MeSH
- lidé MeSH
- nádorové proteiny MeSH
- nádory prsu * MeSH
- P-glykoprotein MeSH
- plocha pod křivkou MeSH
- pyridiny škodlivé účinky MeSH
- rosuvastatin kalcium farmakologie MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Primárním cílem studie bylo zjistit odezvu nitroočního tlaku (NOT) na rychlý příjem vody sycené vodíkem (HRW) ve srovnání s obyčejnou vodou (placebem) u zdravých osob. Dále byl sledován dopad příjmu HRW na centrální tloušťku rohovky (CCT). Subjekty a metodika: Do studie bylo zařazeno 24 zdravých dobrovolníků (5 mužů a 19 žen) ve věku od 20 do 33 let, u každého bylo měřeno vždy jen jedno oko. Jednalo se o prospektivní, randomizovanou, dvojitě zaslepenou studii s crossover designem. Každý proband podstoupil dvě části experimentu, náhodně rozdělené do dvou různých dnů. V každé z částí experimentu bylo každému účastníkovi během 15 minut podáno 1260 ml HRW nebo placeba ve třech dávkách. Před a po konzumaci vody byl všem účastníkům měřen NOT a CCT, a to po dobu 75 min od zahájení konzumace. Výsledky: HRW i placebo navodily signifikantní nárůst NOT. Maximální změna oproti výchozí hodnotě byla 2,7 mmHg ±2,0 mmHg v 25. minutě od zahájení experimentu při konzumaci HRW a 1,4 mmHg ±2,0 mmHg v 35. minutě u placeba. Statisticky signifikantní rozdíl mezi hodnotami NOT po vypití HRW a placeba nebyl zjištěn, avšak po vypití HRW se vyskytlo významně více klinicky významných individuálních odchylek (58 %) oproti placebu (25 %). V případě CCT nebyly během experimentu zjištěny žádné signifikantní změny. Závěr: Rychlý příjem 1260 ml HRW i obyčejné vody působí u zdravých jedinců statisticky významný nárůst NOT oproti výchozí hodnotě. V případě HRW byl tento nárůst u většiny subjektů významný i z klinického hlediska. Výsledky tak naznačují, že rychlý příjem HRW může z hlediska NOT představovat vyšší riziko než placebo. V případě rizikových skupin, jako jsou osoby s glaukomem, suspektním glaukomem nebo oční hypertenzí, je však nutné tento závěr ověřit dalšími studiemi.
Purposes: The primary aim of the study was to assess the response of intraocular pressure (IOP) to the acute ingestion of hydrogen-rich water (HRW) compared to hydrogen-free water (placebo) in healthy subjects. The effect of HRW intake on central corneal thickness (CCT) was also monitored. Subjects and Methods: Twenty-four healthy volunteers (5 men, 19 women) aged between 20 and 33 were included in the study, in which one eye of each subject was measured. The study was prospective, randomized and double-blind, with crossover design. Each subject underwent two parts of the experiment, each part on a different day and in random order. In each part of experiment, a total volume of 1260 ml of HRW or placebo was administered over 15 minutes in three doses. IOP and CCT were measured before and during the course of 75 minutes from the start of the HRW or placebo intake. Results: Administration of both HRW and the placebo caused a significant increase in IOP. The maximum IOP increase was 2.7 mmHg ±2.0 mmHg in minute 25 after the commencement of the experiment (HRW intake), and 1.4 mmHg ±2.0 mmHg in minute 35 (placebo intake). The values of IOP did not differ significantly between both parts, but there were significantly more clinically significant individual IOP increases after HRW intake (58%) compared to the placebo (25%). CCT did not change significantly during the experiment. Conclusion: The rapid intake of 1260 ml of both HRW and hydrogen-free water causes a statistically significant increase in IOP compared to the baseline in healthy individuals. In the case of HRW, the increase was also clinically significant in most of the subjects. Thus, the results indicate that acute intake of HRW may pose a higher risk than placebo intake in terms of IOP. However, in the case of risk groups such as subjects with glaucoma, ocular hypertension or suspected glaucoma, it is necessary to verify this conclusion by further studies.
- Klíčová slova
- vodíková voda,
- MeSH
- klinické křížové studie MeSH
- lidé MeSH
- mladý dospělý MeSH
- nitrooční tlak * MeSH
- pití * MeSH
- prospektivní studie MeSH
- rohovka MeSH
- voda MeSH
- vodík MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
