BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.

• MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• modafinil * farmakologie   aplikace a dávkování   MeSH
• mozeček * účinky léků   diagnostické zobrazování   metabolismus   MeSH
• neokortex účinky léků   metabolismus   diagnostické zobrazování   MeSH
• nervové dráhy účinky léků   metabolismus   MeSH
• stimulancia farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.

• MeSH
• dospělí MeSH
• kosterní svaly * diagnostické zobrazování   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• počítačová rentgenová tomografie * metody   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• sarkopenie etiologie   metabolismus   MeSH
• senioři MeSH
• transplantace jater * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

• MeSH
• dospělí MeSH
• interocepce * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mladý dospělý MeSH
• mozek * patofyziologie   diagnostické zobrazování   MeSH
• nemoci nervového systému * patofyziologie   diagnostické zobrazování   MeSH
• pozornost fyziologie   MeSH
• srdeční frekvence fyziologie   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

BACKGROUND: Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. OBJECTIVES: To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. METHODS: 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. RESULTS: While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. CONCLUSIONS: Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.

• MeSH
• akcelerometrie přístrojové vybavení   metody   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• dystonie diagnóza   patofyziologie   MeSH
• esenciální tremor * diagnóza   patofyziologie   MeSH
• hlava * patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• paže * patofyziologie   MeSH
• postura těla fyziologie   MeSH
• senioři MeSH
• tortikolis diagnóza   patofyziologie   MeSH
• tremor * diagnóza   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.

• MeSH
• dospělí MeSH
• kognitivní dysfunkce etiologie   patofyziologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• průřezové studie MeSH
• roztroušená skleróza * komplikace   diagnostické zobrazování   patofyziologie   MeSH
• rychlost zpracování MeSH
• únava * patofyziologie   etiologie   diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Accelerated epigenetic aging has been associated with changes in cognition. However, due to the lack of neuroimaging epigenetics studies, it is still unclear whether accelerated epigenetic. Aging in young adulthood might underlie the relationship between altered brain dynamics and cognitive functioning. We conducted neuroimaging epigenetics follow-up of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort in young adulthood and tested the possible mediatory role of accelerated epigenetic aging in the relationship between dynamic functional connectivity (DFC) and worse cognition. A total of 240 young adults (51% men; 28-30 years, all of European ancestry) participated in the neuroimaging epigenetics follow-up. Buccal swabs were collected to assess DNA methylation and calculate epigenetic aging using Horvath's epigenetic clock. Full-scale IQ was assessed using the Wechsler adult intelligence scale (WAIS). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired using a 3T Siemens Prisma MRI scanner, and DFC was assessed using mixture factor analysis, revealing information about the coverage of different DFC states. In women (but not men), lower coverage of DFC state 4 and thus lower frequency of epochs with high connectivity within the default mode network and between default mode, fronto-parietal, and visual networks was associated with lower full-scale IQ (AdjR2 = 0.05, std. beta = 0.245, p = 0.008). This relationship was mediated by accelerated epigenetic aging (ab = 7.660, SE = 4.829, 95% CI [0.473, 19.264]). In women, accelerated epigenetic aging in young adulthood mediates the relationship between altered brain dynamics and cognitive functioning. Prevention of cognitive decline should target women already in young adulthood.

• MeSH
• default mode network * diagnostické zobrazování   fyziologie   MeSH
• dospělí MeSH
• epigeneze genetická * fyziologie   MeSH
• inteligence * fyziologie   MeSH
• kognice * fyziologie   MeSH
• konektom * MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• metylace DNA MeSH
• mladý dospělý MeSH
• mozek * diagnostické zobrazování   fyziologie   MeSH
• nervová síť * diagnostické zobrazování   fyziologie   MeSH
• stárnutí * fyziologie   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The outcomes of alpha-mannosidosis after hematopoietic stem cell transplantation (HSCT) are incompletely described. This retrospective multi-center study evaluated the outcomes of patients who underwent HSCT for their alpha-mannosidosis after 2010. Twenty-one children (11 females) with enzymatically and/or genetically confirmed alpha-mannosidosis, diagnosed at a mean age of 14 months (0-60 months), were included. The median age at HSCT was 3.9 years (10 months to 13.3 years) with a median follow-up of 2.3 years (0.3-14.1 years). Seventy-four percent (14/19) of patients received an unrelated graft while the rest had a matched sibling donor. Primary engraftment was reached in 17 of 21 patients; four patients required a second HSCT with successful subsequent engraftment. Nine patients had severe post-HSCT infections, five patients developed acute graft-versus-host disease (GvHD) (> = grade II), and one patient had chronic GvHD. No patient died during follow-up. Seven out of ten patients received enzyme replacement therapy both pre- and post-HSCT. Among children with clinical symptoms, improvement was documented in hepatomegaly (40% of patients before HSCT, down to 10% after), recurrent infections (62%/30%), and hearing disorder (85%/65%). In 13 patients with developmental data, outcomes after HSCT suggested at least mild delays persisted post-HSCT in the majority (85%), with some trends of higher functioning with earlier treatment. Findings suggest HSCT has shown notable improvements in safety and is associated with clinical benefit in alpha-mannosidosis. Neurodevelopmental findings require longer-term study to account for phenotypic diversity.

• MeSH
• alfa-mannosidóza * terapie   diagnóza   komplikace   MeSH
• dítě MeSH
• enzymová substituční terapie MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• nemoc štěpu proti hostiteli etiologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Twenty-eight endurance-trained males aged 31.1 ± 10.2 years (body mass [BM] 81.9 ± 9.0 kg) completed this randomized double-blind placebo (PLA)-controlled crossover study investigating the effect of 12-week Colostrum Bovinum (COL) supplementation (25gCOL·day-1) on aerobic fitness and capacity, time to exhaustion, BM and body composition (BC), and blood lactate concentration. There were four main-before/after supplementation study visits (COLPRE and COLPOST; PLAPRE, and PLAPOST). During study visits, BM and BC evaluation, incremental rowing test (IRT) to exhaustion, and evaluation of resting (REST) and post-exercise (POST-IRT) blood lactate concentration were performed. COL, but not PLA supplementation, significantly increased (p < 0.05) time to ventilatory threshold (TVT). Moreover, the implemented treatments had large (mL·min-1) and moderate (mL·min-1·kg-1) effects on oxygen uptake at VT (VO2VT), as well as moderate effect on power output at VT (PVT; W·kg-1) with the highest values observed at COLPOST visit. Neither significant influence of COL supplementation on time to exhaustion (TEXH) in IRT, BM, and BC on blood lactate was observed. Importantly, there were significantly (p < 0.05) higher increases in VO2VT (mL·min-1 and mL·min-1·kg-1) after COL compared to PLA supplementation. In summary, COL supplementation resulted in a favorable increase in TVT, and tended to improve some of the evaluated threshold indicators, namely VO2VT and PVT in endurance-trained male athletes during IRT. Therefore, COL supplementation may be considered as a support to improve aerobic fitness and capacity in endurance-trained males; however, supplementation strategy must be personalized and properly incorporated into the individual training. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov (NCT06390670).

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fyzická vytrvalost * MeSH
• klinické křížové studie MeSH
• kolostrum * MeSH
• kyselina mléčná krev   MeSH
• lidé MeSH
• mladý dospělý MeSH
• potravní doplňky * MeSH
• složení těla * MeSH
• spotřeba kyslíku MeSH
• vytrvalostní trénink * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Background: The surgical procedure of feminizing genitoplasty aims at restoration of normal anatomy and function in various cases of disorders of sexual development with ambiguous genitalia. Material and methods: Between April 2021 and May 2023, 23 patients underwent a single stage feminizing genitoplasty procedure at the department of plastic and reconstructive surgery. All the patients underwent clitoroplasty with partial glans preservation, omega flap vaginoplasty and labioplasty. Cases with only clitoroplasty were excluded from the study. Of these 23 patients, 17 had congenital adrenal hyperplasia and the rest 6 had varying degrees of androgen insensitivity syndrome. The age of the patients ranged from 4 to 23 years and all were raised as females. The mean operating time was around 120 to 150 minutes and average hospitalization period was 7 to 8 days. At follow-up evaluation, no major complications were observed. In all cases the vaginal introitus was located in the physiological position and was of varying size and elastic. Conclusion: This procedure of single stage feminizing genitoplasty enables reconstruction with good cosmetic and functional results not only in children but also in adults presenting with ambiguous genitalia.

Major depressive disorder, particularly its treatment-resistant form (TRD), poses significant treatment challenges. Ketamine, an N-methyl-d-aspartate receptor antagonist, has shown promise in rapidly alleviating depressive symptoms by influencing neuroplasticity and glutamatergic modulation, which are thought to influence brain activity complexity. In this placebo-controlled study, we examined the effects of subanesthetic doses of intravenous ketamine on EEG signal complexity in 24 MDD patients, 21 of whom had TRD. Treatment response was defined by a ≥ 33 % reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) after ketamine administration. Patients underwent eyes-closed resting state EEG recording pre-, start-, end- and 24 h post-infusion, analyzed for temporospatial and spatiotemporal Lempel-Ziv complexity (LZCT and LZCS). Results indicated that ketamine significantly increased whole-brain LZCT during infusion compared to placebo (sodium chloride 0.9 %) (16.90 % vs. -4.84 %, 95 % CI 4.29 to 39.18, p = 0.017). Elevated LZCT at end-pre was associated with less short-term symptom improvement the following day. Conversely, lower pretreatment occipital LZCT (0.33 vs. 0.46, 95 % CI 0.007 to 0.26, p = 0.040) predicted a favorable response to ketamine, supported by a logistic regression model with an ROC area of 0.75. No significant changes were observed in LZCS, suggesting limited utility as a biomarker. In conclusion, occipital LZCT could serve as an effective predictive biomarker for ketamine's therapeutic effects in MDD, with implications for patients with TRD. This underscores the potential of EEG complexity measures in stratifying treatment and enhancing our understanding of the neural impacts of ketamine in depressive disorders.

• MeSH
• antagonisté excitačních aminokyselin * aplikace a dávkování   farmakologie   MeSH
• deprese nereagující na léčbu * farmakoterapie   patofyziologie   MeSH
• depresivní porucha unipolární * farmakoterapie   patofyziologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• elektroencefalografie * účinky léků   MeSH
• ketamin * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek * účinky léků   patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH