Uterine sarcomas with KAT6B/A::KANSL1 fusion represent a new entity characterized by bland morphology, commonly with hybrid features of low-grade endometrial stromal sarcoma (LG-ESS) and tumors with smooth muscle differentiation. In our study, we performed a detailed morphological, immunohistochemical, and molecular analysis of 9 cases of these tumors. Six of those had been originally diagnosed as LG-ESS, one as leiomyoma, one as leiomyosarcoma, and the remaining case as sarcoma with the KAT6B/A::KANSL1 fusion. Seven cases showed overlapping features between endometrial stromal and smooth muscle tumors, one case resembled cellular leiomyoma, and one case resembled high-grade endometrial stromal sarcoma. Immunohistochemically, the tumors showed a common expression of smooth muscle markers and endometrial stromal markers. Molecular findings showed the KAT6B/A::KANSL1 fusion in all cases (by NGS and FISH). In addition, mutations affecting genes such as TP53, PDGFRB, NF1, RB1, PTEN, ATM, RB1, FANCD2, and TSC1 were present in all 5 cases with aggressive behavior. One patient with no evidence of disease showed no additional mutations, while another harbored a mutation of a single gene (ERCC3). Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

• MeSH
• dospělí MeSH
• endometriální stromální sarkom genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• histonacetyltransferasy genetika   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory dělohy * patologie   genetika   MeSH
• sarkom genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.

• MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• hepatolentikulární degenerace * patologie   diagnostické zobrazování   MeSH
• játra patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• studie případů a kontrol 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

The pertinent literature widely describes ultrasound-guided procedures targeting the retrocalcaneal bursa and the tendon tissue to manage insertional Achilles tendinopathy. Synovial bursae and cutaneous nerves of the superficial retrocalcaneal pad are often overlooked pain generators and are poorly considered by clinicians and surgeons. A layer-by-layer dissection of the superficial soft tissues in the retrocalcaneal region of two fresh frozen cadavers was matched with historical anatomical tables of the textbook Traite d'Anatomie Topographique Avec Applications Médico-Chirurgicales (1909 by Testut and Jacob). An accurate and detailed description of the superficial retrocalcaneal pad with its synovial bursae and cutaneous nerves was provided. Cadaveric dissections confirmed the compartmentalized architecture of the superficial retrocalcaneal fat pad and its histological continuum with the superficial lamina of the crural fascia. Superficial synovial tissue islands have been demonstrated on the posterior aspect of the Achilles tendon in one cadaver and on the posterolateral surface of the tendon in the other one. Digitalization of the original anatomical tables of the textbook Traite d'Anatomie Topographique Avec Applications Médico-Chirurgicales (1909 by Testut and Jacob) showed five potential locations of the superficial calcaneal bursa and a superficial retrocalcaneal nerve plexus within the Achilles tendon-fat pad interface. In clinical practice, in addition to the previously described interventions regarding the retrocalcaneal bursa and the tendon tissue, ultrasound-guided procedures targeting the synovial and neural tissues of the superficial retrocalcaneal pad should be considered to optimize the management of insertional Achilles tendinopathy.

• MeSH
• Achillova šlacha * anatomie a histologie   diagnostické zobrazování   MeSH
• bursa synovialis * anatomie a histologie   diagnostické zobrazování   MeSH
• intervenční ultrasonografie metody   MeSH
• lidé MeSH
• mrtvola * MeSH
• patní kost * anatomie a histologie   inervace   diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVES: The impact of dopaminergic medication on language in Parkinson's disease (PD) remains poorly understood. This observational, naturalistic study aimed to investigate the effects of long-term dopaminergic therapy on language performance in patients with de-novo PD based on a high-level linguistic analysis of natural spontaneous discourse. METHODS: A fairy-tale narration was recorded at baseline and a 12-month follow-up. The speech samples were automatically analyzed using six representative lexical and syntactic features based on automatic speech recognition and natural language processing. RESULTS: We enrolled 109 de-novo PD patients compared to 68 healthy controls. All subjects completed the 12-month follow-up; 92 PD patients were on stable dopaminergic medication (PD-treated), while 17 PD patients remained without medication (PD-untreated). At baseline, the PD-treated group exhibited abnormalities in syntactic domains, particularly in sentence length (p = 0.018) and sentence development (p = 0.042) compared to healthy controls. After 12 months of dopaminergic therapy, PD-treated showed improvements in the syntactic domain, including sentence length (p = 0.012) and sentence development (p = 0.030). Of all PD-treated patients, 37 were on monotherapy with dopamine agonists and manifested improvement in sentence length (p = 0.048), while 32 were on monotherapy with levodopa and had no language amelioration. No changes in language parameters over time were seen in both the PD-untreated group and healthy controls. DISCUSSION: Initiation of dopaminergic therapy improved high-language syntactic deficits in de-novo PD, confirming the role of dopamine in cognitive-linguistic processing. Automated linguistic analysis of spontaneous speech via natural language processing can assist in improving the prediction and management of language deficits in PD.

• MeSH
• agonisté dopaminu * terapeutické užití   MeSH
• antiparkinsonika * terapeutické užití   MeSH
• dopaminové látky * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• Parkinsonova nemoc * farmakoterapie   komplikace   MeSH
• řeč * účinky léků   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

AIM: To determine whether people with type 1 diabetes (T1D) initiating glucose sensor monitoring experience greater improvements in HbA1c when provided with education on carbohydrate counting and flexible insulin dosing than those who do not receive nutrition education. MATERIALS AND METHODS: Our retrospective observational study included 329 people with T1D initiating glucose sensor monitoring between 2015 and 2021. The participants were divided into two groups: one group attended at least one structured educational session with a registered dietitian (n = 126), while the other group did not receive structured education (n = 203). After 12 months of glucose sensor initiation, we compared glycaemic outcomes and CGM metrics between the two groups. RESULTS: At glucose sensor initiation, both groups with and without education had similar HbA1c levels (7.64% [60.0 mmol/mol] vs. 7.66% [60.2 mmol/mol]). After twelve months, the education group demonstrated greater improvement in glycemic outcomes (HbA1c 7.17% [54.9mmol/mol] vs. 7.37% [57.1 mmol/mol], p < 0.05) and spent significantly more time in the target range than did the group without structured education (68.8% vs. 64.1%, p < 0.05). We observed an inverse correlation between the number of completed educational sessions and HbA1c after 12 months, as well as between the number of educational sessions and the change in HbA1c. CONCLUSIONS: People with T1D who initiated glucose sensor monitoring alongside nutrition education showed greater improvements in HbA1c and increased time spent in the target glucose range compared to individuals who did not receive structured education. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT06264271.

• MeSH
• diabetes mellitus 1. typu * krev   MeSH
• dospělí MeSH
• glykovaný hemoglobin * analýza   metabolismus   MeSH
• hypoglykemika aplikace a dávkování   MeSH
• inzulin aplikace a dávkování   MeSH
• krevní glukóza * analýza   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• regulace glykemie MeSH
• retrospektivní studie MeSH
• selfmonitoring glykemie * MeSH
• vzdělávání pacientů jako téma * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

The neurotoxicity of phosphorylated tau protein (P-tau) and mitochondrial dysfunction play a significant role in the pathophysiology of Alzheimer's disease (AD). In vitro studies of the effects of P-tau oligomers on mitochondrial bioenergetics and reactive oxygen species production will allow us to evaluate the direct influence of P-tau on mitochondrial function. We measured the in vitro effect of P-tau oligomers on oxygen consumption and hydrogen peroxide production in isolated brain mitochondria. An appropriate combination of specific substrates and inhibitors of the phosphorylation pathway enabled the measurement and functional analysis of the effect of P-tau on mitochondrial respiration in defined coupling control states achieved in complex I-, II-, and I&II-linked electron transfer pathways. At submicromolar P-tau concentrations, we found no significant effect of P-tau on either mitochondrial respiration or hydrogen peroxide production in different respiratory states. The titration of P-tau showed a nonsignificant dose-dependent decrease in hydrogen peroxide production for complex I- and I&II-linked pathways. An insignificant in vitro effect of P-tau oligomers on both mitochondrial respiration and hydrogen peroxide production indicates that P-tau-induced mitochondrial dysfunction in AD is not due to direct effects of P-tau on the efficiency of the electron transport chain and on the production of reactive oxygen species.

• MeSH
• buněčné dýchání MeSH
• fosforylace MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mitochondrie * metabolismus   MeSH
• mozek metabolismus   MeSH
• peroxid vodíku * metabolismus   MeSH
• proteiny tau * metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• spotřeba kyslíku MeSH
• transport elektronů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Corneal dystrophies are a group of predominantly rare inherited disorders. They are by definition bilateral, relatively symmetrical, and without systemic involvement, affecting corneal transparency and/or refraction. Traditional classification of corneal dystrophies is based on slit-lamp appearance, affected corneal layer and histological features. Molecular genetics has provided ultimate proof for the existence of distinct corneal dystrophies and discarded duplicates in their terminology. Currently, there are at least 16 genes with identified pathogenic variants implicated in corneal dystrophies. Herein, we summarise contemporary knowledge on genotype-phenotype correlations of corneal dystrophies, including a critical review of some reported variants, along with the understanding of the underlying pathogenic dystrophic process; essential knowledge for the development of targeted therapies.

• MeSH
• dědičné dystrofie rohovky * genetika   terapie   MeSH
• fenotyp MeSH
• genetické asociační studie * MeSH
• genotyp MeSH
• lidé MeSH
• molekulární biologie MeSH
• mutace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Ageing is a complex phenomenon affecting a wide range of coexisting biological processes. The homogeneity of the studied population is an essential parameter for valid interpretations of outcomes. The presented study capitalises on the MRI data available in the Human Connectome Project-Aging (HCP-A) and, within individuals over 55 years of age who passed the HCP-A section criteria, compares a subgroup of 37 apparently neurocognitively healthy individuals selected based on stringent criteria with 37 age and sex-matched individuals still representative of typical ageing but who did not pass the stringent definition of neurocognitively healthy. Specifically, structural scans, diffusion weighted imaging and T1w/T2w ratio were utilised. Furthermore, data of 26 HCP-A participants older than 90 years as notional 'super-agers' were analysed. The relationship of age and several microstructural MRI metrics (T1w/T2w ratio, mean diffusivity, intracellular volume fraction and free water volume fraction) differed significantly between typical and healthy ageing cohort in areas highly relevant for ageing such as hippocampus, prefrontal and temporal cortex and cerebellum. However, the trajectories of the healthy ageing population did not show substantially better overlap with the findings in people older than 90 than those of the typical population. Therefore, caution must be exercised in the choice of adequate study group characteristics relevant for respective ageing-related hypotheses. Contrary to typical ageing group, the healthy ageing cohort may show generally stable levels of several MRI metrics of interest.

• MeSH
• kognice * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• šedá hmota * diagnostické zobrazování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí * fyziologie   MeSH
• zdravé stárnutí fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND AND OBJECTIVES: Patients with synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease (PD) frequently display speech and language abnormalities. We explore the diagnostic potential of automated linguistic analysis of natural spontaneous speech to differentiate MSA and PD. METHODS: Spontaneous speech of 39 participants with MSA compared to 39 drug-naive PD and 39 healthy controls matched for age and sex was transcribed and linguistically annotated using automatic speech recognition and natural language processing. A quantitative analysis was performed using 6 lexical and syntactic and 2 acoustic features. Results were compared with human-controlled analysis to assess the robustness of the approach. Diagnostic accuracy was evaluated using sensitivity analysis. RESULTS: Despite similar disease duration, linguistic abnormalities were generally more severe in MSA than in PD, leading to high diagnostic accuracy with an area under the curve of 0.81. Compared to controls, MSA showed decreased grammatical component usage, more repetitive phrases, shorter sentences, reduced sentence development, slower articulation rate, and increased duration of pauses, whereas PD had only shorter sentences, reduced sentence development, and longer pauses. Only slower articulation rate was distinctive for MSA while unchanged for PD relative to controls. The highest correlation was found between bulbar/pseudobulbar clinical score and sentence length (r = -0.49, p = 0.002). Despite the relatively high severity of dysarthria in MSA, a strong agreement between manually and automatically computed results was achieved. DISCUSSION: Automated linguistic analysis may offer an objective, cost-effective, and widely applicable biomarker to differentiate synucleinopathies with similar clinical manifestations.

• MeSH
• diferenciální diagnóza MeSH
• lidé středního věku MeSH
• lidé MeSH
• multisystémová atrofie * diagnóza   patofyziologie   komplikace   MeSH
• Parkinsonova nemoc * diagnóza   komplikace   patofyziologie   MeSH
• řeč fyziologie   MeSH
• senioři MeSH
• zpracování přirozeného jazyka MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16). RESULTS: Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q. CONCLUSION: Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.

• Publikační typ
• časopisecké články MeSH