Extrapyramídové ochorenia predstavujú heterogénnu skupinu ochorení, v mnohých prípadoch monogénne podmienenú. Najmä zásluhou technologického pokroku v oblasti sekvenovania došlo v posledných rokoch k významnému posunu diagnostických algoritmov pre túto skupinu ochorení, kde sa čoraz viac využívajú metodiky "next-generation sequencing". V prehľadovom článku je prezentovaný súčasný pohľad na genetickú diagnostiku extrapyramídových ochorení, súčasné možnosti testovania a prichádzajúce trendy so zameraním najmä na priblíženie pragmatických algoritmov testovania.

Movement disorders represent a heterogeneous group of diseases, often with a monogenic background. Especially thanks to technological progress in the field of sequen­cing, there has been a significant shift in diagnostic algorithms for this group of diseases in recent years, where "next-generation sequencing" methodologies are increasingly being used. The review article presents a current view of the genetic diagnostics of movement disorders, current testing options and upcoming trends, with a particular focus on pragmatic testing algorithms.

• MeSH
• Diagnosis, Differential MeSH
• Dystonia diagnosis   genetics   classification   MeSH
• Genetic Testing methods   MeSH
• Attention Deficit Disorder with Hyperactivity diagnosis   genetics   classification   MeSH
• Humans MeSH
• Basal Ganglia Diseases * diagnosis   genetics   classification   MeSH
• Parkinsonian Disorders diagnosis   genetics   classification   MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Public transport represents a potential site for the transmission of resistant pathogens due to the rapid movement of large numbers of people. This study aimed to investigate the bacterial contamination of frequently touched surfaces in the public transport system operating in the proximity of the biggest Czech hospital during the coronavirus pandemic despite extensive cleaning and disinfection efforts. In June and September 2020, samples from the metro trains, ground transport and stationary objects were collected, enriched and cultured. The antimicrobial susceptibility was tested by broth microdilution. Staphylococcus aureus isolates exhibiting inconclusive results of vancomycin susceptibility testing were retested by broth macrodilution and subjected to whole genome sequencing. All S. aureus isolates were tested for vancomycin heteroresistance (hVISA). A total of 513/542 (94.6 %) samples were culture-positive with higher frequency in September (p = 0.004). S. aureus was the most frequent opportunistic bacterial pathogen found (3.7 %, 20/542) followed by Enterobacterales spp. (1.8 %, 10/542). No methicillin-resistant S. aureus (MRSA), extended-spectrum beta-lactamase producers (ESBL) or carbapenemase-producing bacteria were detected. Resistance to clinically relevant drugs was rare except for resistance to ampicillin (67 %, 8/12), cefuroxime (42 %, 5/12) in Enterobacterales and chloramphenicol (90 %, 18/20), penicillin (45 %, 9/20), and erythromycin (20 %, 4/20) in S. aureus. One S. aureus isolate was shown to be resistant to vancomycin (8 mg/L) by forming large visible cell aggregates. Population analysis profile-area under the curve ratio (PAP-AUC) testing did not confirm the hVISA phenotype, but mutations in the hVISA phenotype-related gene vraR and other genes related to cell wall synthesis (fmtB) and intercellular adhesion (sasC) were found. Our study shows that in the COVID-19 pandemic, despite the intensive use of disinfectants, public transport was a source of opportunistic bacterial pathogens including S. aureus with unusual vancomycin resistance phenotype that could be easily missed by standard susceptibility testing.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• COVID-19 * MeSH
• Transportation MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Pandemics MeSH
• Vancomycin Resistance MeSH
• SARS-CoV-2 * MeSH
• Staphylococcus aureus * drug effects   genetics   MeSH
• Vancomycin * pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia. OBJECTIVE: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia. METHODS: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation. RESULTS: This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small. CONCLUSIONS: Moderate single-nucleotide polymorphism-based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• MeSH
• Genome-Wide Association Study * MeSH
• Adult MeSH
• Dystonic Disorders genetics   MeSH
• Dystonia * genetics   MeSH
• Genetic Predisposition to Disease * genetics   MeSH
• Polymorphism, Single Nucleotide * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Risk Factors MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Východiska: N-myc downstream-regulovaný gen 1 (NDRG1) má významnou funkci při progresi nádorů. U karcinomu prostaty (prostate cancer – PCa) však regulační mechanizmus NDRG1 zůstává nejasný. Materiál a metody: Hladiny exprese miR-96-5p a NDRG1 byly hodnoceny v buněčných liniích PCa a v tkáních prostaty a validovány ve veřejných databázích pomocí polymerázové řetězové reakce v reálném čase, analýzy western blot a imunohistochemie. Funkce miR-96-5p a NDRG1 byla zkoumána pomocí testů hojení ran a transwell testů in vitro a testu myšího xenoimplantátu in vivo. Dráha regulovaná pomocí NDRG1 byla testována technikou sekvenování nové generace. K detekci vztahu mezi miR-96-5p, NDRG1 a NF-kB dráhou byl použit imunofluorescenční test a test s luciferázou. Výsledky: Nadměrná exprese NDRG1 potlačuje migraci, invazi a epiteliálně-mezenchymální přechod (EMT) in vitro a inhibuje metastázy in vivo. Navíc miR-96-5p přispívá k deficitu NDRG1 a podporuje migraci a invazi buněk PCa. Kromě toho ztráta NDRG1 aktivuje dráhu NF-kB, která stimuluje fosforylaci p65 a IKBa a indukuje EMT v PCa. Závěr: MiR-96-5p podporuje migraci a invazi PCa tím, že cílí na NDRG1 a reguluje dráhu NF-kB.

Background: The N-myc downstream-regulated gene 1 (NDRG1) has been discovered as a significant gene in the progression of cancers. However, the regulatory mechanism of NDRG1 remained obscure in prostate cancer (PCa). Methods: The miR-96-5p and NDRG1 expression levels were evaluated in PCa cell lines, and prostate tissues, and validated in public databases by real-time polymerase chain reaction, western blot analysis, and immunohistochemistry. The function of miR-96-5p and NDRG1 were investigated by scratch assay and transwell assays in vitro, and mouse xenograft assay in vivo. The candidate pathway regulated by NDRG1 was conducted by the next-generation gene sequencing technique. Immunofluorescence and luciferase assays were used to detect the relation between miR-96-5p, NDRG1, and NF-kB pathway. Results: Overexpressing NDRG1 suppresses the migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, and inhibits metastasis in vivo. Moreover, miR-96-5p contributes to NDRG1 deficiency and promotes PCa cell migration and invasion. Furthermore, NDRG1 loss activates the NF-kB pathway, which stimulates p65 and IKBa phosphorylation and induces EMT in PCa. Conclusions: MiR-96-5p promotes the migration and invasion of PCa by targeting NDRG1 and regulating the NF-kB pathway.

• Keywords
• NDRG1, miR-96-5p,
• MeSH
• Epithelial-Mesenchymal Transition MeSH
• Genetic Techniques MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms * genetics   physiopathology   MeSH
• NF-kappa B * MeSH
• Cell Movement MeSH
• Polymerase Chain Reaction methods   MeSH
• Sequence Analysis MeSH
• Signal Transduction MeSH
• Transfection methods   MeSH
• Blotting, Western methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Study MeSH

The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-κB activity and disease expansion. We found that IκBε loss leads to NF-κB pathway activation and promotes both migration and proliferation of CLL cells in a dose-dependent manner. Importantly, NFKBIE inactivation was sufficient to induce a more rapid expansion of the CLL clone in lymphoid organs and contributed to the development of an aggressive disease with a shortened survival in both xenografts and genetically modified mice. IκBε deficiency was associated with an alteration of the MAPK pathway, also confirmed by RNA-sequencing in NFKBIE-mutated patient samples, and resistance to the BTK inhibitor ibrutinib. In summary, our work underscores the multimodal relevance of the NF-κB pathway in CLL and paves the way to translate these findings into novel therapeutic options.

• MeSH
• Adenine analogs & derivatives   pharmacology   MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell * genetics   pathology   metabolism   drug therapy   MeSH
• Humans MeSH
• Mice MeSH
• NF-kappa B * metabolism   MeSH
• Piperidines pharmacology   MeSH
• Cell Movement MeSH
• Cell Proliferation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND OBJECTIVES: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. METHODS: We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details. RESULTS: We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death. DISCUSSION: We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.

• MeSH
• Child MeSH
• Ether-A-Go-Go Potassium Channels * genetics   MeSH
• Epilepsy, Generalized * genetics   MeSH
• Epilepsy * genetics   MeSH
• Phenotype MeSH
• Humans MeSH
• Mutation MeSH
• Infant, Newborn MeSH
• Seizures genetics   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

The classical hypothesis proposes that the lack of recombination on sex chromosomes arises due to selection for linkage between a sex-determining locus and sexually antagonistic loci, primarily facilitated by inversions. However, cessation of recombination on sex chromosomes could be attributed also to neutral processes, connected with other chromosome rearrangements or can reflect sex-specific recombination patterns existing already before sex chromosome differentiation. Three Coleonyx gecko species share a complex X1X1X2X2/X1X2Y system of sex chromosomes evolved via a fusion of the Y chromosome with an autosome. We analyzed synaptonemal complexes and sequenced flow-sorted sex chromosomes to investigate the effect of chromosomal rearrangement on recombination and differentiation of these sex chromosomes. The gecko sex chromosomes evolved from syntenic regions that were also co-opted also for sex chromosomes in other reptiles. We showed that in male geckos, recombination is less prevalent in the proximal regions of chromosomes and is even further drastically reduced around the centromere of the neo-Y chromosome. We highlight that pre-existing recombination patterns and Robertsonian fusions can be responsible for the cessation of recombination on sex chromosomes and that such processes can be largely neutral.

• MeSH
• Y Chromosome genetics   MeSH
• Lizards * genetics   MeSH
• Sex Chromosomes genetics   MeSH
• Cell Movement MeSH
• Recombination, Genetic MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: In severe conditions of limited motor abilities, frequent position changes for work or passive and active rest are essential bedside activities to prevent further health complications. We aimed to develop a system using eye movements for bed positioning and to verify its functionality in a control group and a group of patients with significant motor limitation caused by multiple sclerosis. METHODS: The eye-tracking system utilized an innovative digital-to-analog converter module to control the positioning bed via a novel graphical user interface. We verified the ergonomics and usability of the system by performing a fixed sequence of positioning tasks, in which the leg and head support was repeatedly raised and then lowered. Fifteen women and eleven men aged 42.7 ± 15.9 years in the control group and nine women and eight men aged 60.3 ± 9.14 years in the patient group participated in the experiment. The degree of disability, according to the Expanded Disability Status Scale (EDSS), ranged from 7 to 9.5 points in the patients. We assessed the speed and efficiency of the bed control and the improvement during testing. In a questionnaire, we evaluated satisfaction with the system. RESULTS: The control group mastered the task in 40.2 s (median) with an interquartile interval from 34.5 to 45.5 s, and patients mastered the task in in 56.5 (median) with an interquartile interval from 46.5 to 64.9 s. The efficiency of solving the task (100% corresponds to an optimal performance) was 86.3 (81.6; 91.0) % for the control group and 72.1 (63.0; 75.2) % for the patient group. Throughout testing, the patients learned to communicate with the system, and their efficiency and task time improved. A correlation analysis showed a negative relationship (rho = - 0.587) between efficiency improvement and the degree of impairment (EDSS). In the control group, the learning was not significant. On the questionnaire survey, sixteen patients reported gaining confidence in bed control. Seven patients preferred the offered form of bed control, and in six cases, they would choose another form of interface. CONCLUSIONS: The proposed system and communication through eye movements are reliable for positioning the bed in people affected by advanced multiple sclerosis. Seven of 17 patients indicated that they would choose this system for bed control and wished to extend it for another application.

• MeSH
• Humans MeSH
• Eye Movements MeSH
• Persons with Disabilities * MeSH
• Surveys and Questionnaires MeSH
• Multiple Sclerosis * MeSH
• Eye-Tracking Technology MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Článek si klade za cíl popsat objevování obrazů v lidském těle jakožto nositele nového a zdravého přístupu k pohybu. Nahlíží na problematiku skrze principy, cvičení a mentální obrazy Franklinovy metody (F-M), které simulují pohyb určité tělesné struktury, její pohybovou kvalitu a dynamiku. Metoda využívá specifických cvičení pro přípravu na fyzický výkon či pro regeneraci a rehabilitaci organizmu. Na konkrétních příkladech nastíním, jak lze představy a cvičení uchopit a jak s nimi dále a kreativně pracovat v rámci určité pohybové sekvence. Čerpám nejen z profesionální taneční praxe, vzdělávacích programů a výuky F-M v tanečním prostředí i mimo něj, ale opírám se také o poznatky, studie a literaturu na poli F-M, dynamické neurokognitivní imaginace a ideokineze. Dlouhodobá praxe s technikami F-M vede k porozumění pohybu a funkcím našeho těla, k šetrnějšímu zacházení s tělem, k celkovému zlepšení koordinace, a tím k optimalizaci fyzického výkonu.

The article aims to describe the discovery of images in the human body as a bearer of a new and healthy approach to movement. It looks at the issue through the principles, exercises and mental images of the Franklin Method (F-M), which simulate the movement of certain body structure, its movement quality and dynamics. The method uses specific exercises to prepare for physical performance or to regenerate and rehabilitate the body. By means of specific examples, I will outline how ideas and exercises can be grasped and how to work with them further and creatively within a certain movement sequence. I draw not only from professional dance practice, educational programs, and teaching F-M in the dance and outside the dance environment, but I also rely on knowledge, studies, and literature in the field of F-M, dynamic neuro-cognitive imagery and ideokinesis. Long-term practice with F-M techniques leads to understanding of the movement and functions of our body, in order to treat the body more gently, improve overall coordination, and, thus, optimize physical performance.

• Keywords
• Franklinova metoda,
• MeSH
• Imagination MeSH
• Humans MeSH
• Motor Activity MeSH
• Mind-Body Therapies * methods   MeSH
• Rehabilitation MeSH
• Awareness MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Based on our previously developed mono-color video-ophthalmoscope a multi-color video-ophthalmoscope was developed. Using narrow band transmission filters, this instrument allows to measure the pulsatile cardiac cycle induced blood volume changes in the human retina for any wavelength in the sensitivity range of the used CMOS-camera. In this key experiment, video sequences (8 s, 25 fps, 200 frames) of the optic nerve head (ONH) were acquire for seven wavelengths between 475 nm and 677 nm one after the other. After image registration of all frames of each video sequence (to compensate for eye movements) and trend correction (to compensate for slow intensity changes), the amplitude of the cardiac cycle induced light intensity changes (pulsatile absorption amplitude PAA) can be calculated for all seven wavelengths. The results confirmed that the spectral distribution of PAA (λ) follows the distribution of the light absorption of blood. The measured values correspond to the absorption of a thin blood layer of about 0.5 μm thickness.

• Publication type
• Journal Article MeSH