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Intravital diagnostics of neurodegenerative diseases
Baranová, Soňa ; Holada, Karel (advisor) ; Kaňovský, Petr (referee) ; Žáková, Dana (referee)
Prionopathies, also called transmissible spongiform encephalopathies (TSE) and synucleinopathies are neurodegenerative diseases that are associated with the accumulation of misfolded proteins (prion and α-synuclein) mostly in the central nervous system. To this day, early and definite diagnosis remains unavailable during the patient's lifetime, mainly due to the absence of reliable biomarker which makes clinical diagnosis more challenging. Therefore, the gold standard in diagnostics remains direct post-mortem evaluation of misfolded proteins within brain tissue by western blot and immunohistochemistry. In the recent years, seeding amplification assays (SAAs) like Real-Time Quacking-Induced Conversion (RT-QuIC) emerged for ultra-sensitive ante-mortem diagnosis of neurodegenerative diseases. SAAs exploit ability of pathological misfolded proteins present in patient's samples to change the conformation and initiate aggregation of native recombinant protein substrate by prion-like seeding mechanism. In the presented dissertation thesis, we exploited second-generation RT-QuIC assay (55řC, 700 rpm, cycles of 1 min double-orbital shaking and 1 min incubation) utilizing recombinant hamster shortened prion protein (rHAPrP90-231) to evaluate prion seeding activity in post-mortem TSE (n=38) and non-TSE (n=30)...
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The structure of minor alkaloids of the Amaryllidaceae family as inspiration for the synthesis of compounds with biological activity targeting Alzheimer's disease
Pidaný, Filip ; Cahlíková, Lucie (advisor) ; Drašar, Pavel (referee) ; Strnad, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Mgr. Filip Pidaný Supervisor: Prof. Ing. Lucie Cahlíková, Ph.D. Consultant: Assoc. Prof. Jan Korábečný, Ph.D. Title of Doctoral Thesis: The structure of minor alkaloids of the Amaryllidaceae family as inspiration for the synthesis of compounds with biological activity targeting Alzheimer's disease The theoretical part of this dissertation provides a basic overview of the Amaryllidaceae family known for its rich occurrence of structurally diverse alkaloids. These substances exhibit a wide range of pharmacological effects, with our studies focusing on their potential therapeutic use in the treatment of Alzheimer's disease (AD). It is the most common form of dementia, which is characterized by progressive neurodegeneration. As the life expectancy of the population increases, the global prevalence of AD is also rising. This trend presents not only economic but also social challenges for healthcare systems, and society as a whole. The thesis provides detailed descriptions of the most well-known hypotheses of AD development and the characteristics of clinically used medications. Attention is given to the decline in levels of acetylcholinesterase, the dominant enzyme in a healthy...
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Case Study of Physiotherapy Treatment of a Patient with Diagnosis of Multiple Sclerosis
Novotný, Ondřej ; Kučerová, Ilona (advisor) ; Nováková, Tereza (referee)
Title: Case study of physiotherapeutic treatment of patient with diagnosis of multiple sclerosis Author: Ondřej Novotný Head of the thesis: Mgr. Ilona Kučerová Objectives: The aim of this thesis is to elaboratethe theoretical part of the diagnosis of multiple sclerosis. Follow-up practical processing of the case study of patient diagnosed with multiple sclerosis Methods: This work was processed based on bachelor's and specialized internships. The case study was conducted on a patient diagnosed with multiple sclerosis at Agel Říčany a. s., with these internships taking place from January 8, 2024, to February 2, 2024. Specialized methods taught at the UK FTVS were used in the bachelor's degree program scope. Initialy, the patient's medical history was taken, followed by an initial kinesiological analysis. Based on the results of the initial kinesiological analysis, a shortterm and long-term therapeutic plan were established. A total of 17 therapeutic sessions were conducted. During the final session, an exit kinesiological analysis was performed, upon which the therapy's effectiveness was evaluated. The general section involved processing theoretical information related to multiple sclerosis. Results: As a result of the therapy, the patient experienced improvement, and most of the set goals were...
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Influence of parcellation atlas on quality of classification in patients with neurodegenerative dissease
Montilla, Michaela ; Lamoš, Martin (referee) ; Gajdoš, Martin (advisor)
The aim of the thesis is to define the dependency of the classification of patients affected by neurodegenerative diseases on the choice of the parcellation atlas. Part of this thesis is the application of the functional connectivity analysis and the calculation of graph metrics according to the method published by Olaf Sporns and Mikail Rubinov [1] on fMRI data measured at CEITEC MU. The application is preceded by the theoretical research of parcellation atlases for brain segmentation from fMRI frames and the research of mathematical methods for classification as well as classifiers of neurodegenerative diseases. The first chapters of the thesis brings a theoretical basis of knowledge from the field of magnetic and functional magnetic resonance imaging. The physical principles of the method, the conditions and the course of acquisition of image data are defined. The third chapter summarizes the graph metrics used in the diploma thesis for analyzing and classifying graphs. The paper presents a brief overview of the brain segmentation methods, with the focuse on the atlas-based segmentation. After a theoretical research of functional connectivity methods and mathematical classification methods, the findings were used for segmentation, calculation of graph metrics and for classification of fMRI images obtained from 96 subjects into the one of two classes using Binary classifications by support vector machines and linear discriminatory analysis. The data classified in this study was measured on patiens with Parkinson’s disease (PD), Alzheimer’s disease (AD), Mild cognitive impairment (MCI), a combination of PD and MCI and subjects belonging to the control group of healthy individuals. For pre-processing and analysis, the MATLAB environment, the SPM12 toolbox and The Brain Connectivity Toolbox were used.
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The role of a specific miRNAs in the regulation of apoptosis during physiological and pathophysiological processes in the CNS
Kaslová, Tereza ; Romanyuk, Natalyia (advisor) ; Klassen, Ruslan (referee)
MicroRNAs are small non-coding RNAs of 20 to 24 nucleotides in size that are able to post- transcriptionally regulate gene expression by binding to mRNA. This paper focuses on how these microRNAs are generated and how they are able to regulate at the level of proteins involved in programmed cell death - apoptosis. By what mechanisms apoptosis occurs, what proteins are involved and what changes the cell undergoes are further discussed in this thesis. The precise influence of this post-transcriptional regulation is presented by using selected microRNAs that influence apoptosis during the development of the central nervous system, as well as during and as a consequence of the neurodegenerative diseases and damage that can affect it. Finally, it will also introduce the use of microRNAs as potential biomarkers, due to changes in their levels associated with various diseases, and as direct therapeutic targets. Keywords Apoptosis, microRNA, cell death, central nervous system, neurodegenerative diseases, gene expression regulation
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Communication disorders of people with Alzheimer's disease
Bláhová, Natálie ; Korandová, Zuzana (advisor) ; Horynová, Jana (referee)
The topic of the thesis Communication disorders of people with Alzhiemer's disease is focused on the analysis of the manifestations of impaired communication ability of people with Alzheimer's disease. The bachelor thesis is divided into theoretical and practical part. The theoretical part consists of two chapters. In the firts chapter, entitled Theoretical Background, the term communication is discussed, as well as the concept of dementia. Other subsections discuss cognitive-communication disorders and manifestiations of impaired communication ability of people with dementia. Speech and language process deficits in individual language levels are also listed here. The second chapter deals with neurodegenerative disease. It is followed by a subchapter related to Alzheimer's disease and subsequently clarifies the topic of the burden placed on family caregivers. The practical part presents an analysis of a research investigation that was carried out in the Clementas home for the elderly in Janovice nad Úhlavou. A presentation of the Clementas Center is also included in the bachelor's thesis. The research sample consisted of tree clients of this home. The practical part was based on observing the participants, using indicative diagnostic tools and the clients' health documentation. Furthermore, the...
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Case Study of a Physiotherapy Treatment of a Patient with Amyotrophic Lateral Sclerosis
Pešková, Laura ; Novotná, Irena (advisor) ; Hamouzová, Dita (referee)
v Abstract Author: Laura Pešková Supervisor: Mgr. Irena Novotná Title: Case study of a physiotherapy treatment of a patient with amyotrophic lateral sclerosis Objectives: The aim of this bachelor thesis is to summarize the theoretical knowledge about the diagnosis of amyotrophic lateral sclerosis, about the possibilities of therapy and to elaborate a case study of physiotherapy treatment of a patient with this diagnosis. Methods: The thesis is divided into two parts - a general part and a special part. The general part is focused on the summary of theoretical knowledge about amyotrophic lateral sclerosis. This part includes chapters of neuroanatomy, general characteristics and clinical picture of the disease, possibilities of diagnostic and therapeutic procedures. The special part includes initial kinesiological examination, design of short-term and long-term physiotherapy plan, description of therapeutic units, output kinesiological examination and evaluation of the effect of therapy. Results: Positive outcomes of the physiotherapy intervention include increased range of motion, improved gait stability and training in independent verticalization. The therapy failed to affect muscle tone and spasticity. All results of the work are presented in the chapter on the effect of therapy. Conclusion: The above case...
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Ultrafine particles and their possible role in etiology and development of neurodegenerative diseases
Topinka, Jan ; Závodná, Táňa ; Rössnerová, Andrea ; Rössner ml., Pavel
Air pollutants have been shown to cause a vast amount of different adverse health effects. These effects include impairment of many respiratory (e.g. asthma, chronic obstructive pulmonary disease) and cardiovascular (ischemic heart disease, infarction, stroke) diseases. However, in recent years, the evidence showing effects beyond the lungs and circulatory system are becoming more evident. Neurological diseases, namely Alzheimer's disease (AD) has shown to be associated with living near traffic. However, reason for this has remained unresolved until today. Our new H2020 project TUBE aims on revealing the mechanisms of action of ultrafine particles involved in neurological diseases. The TUBE consortium includes experts in areas of aerosol technology, emission research, engine and fuel research, human clinical studies, epidemiology, emission inventories, inhalation toxicology, neurotoxicology and disease mechanism studies. This enables research of resolving the effects of nanoparticles from different traffic modes for both air quality and concomitant toxic effect of these air pollutants. We will investigate adverse effects of air pollutants using cell cultures, animal exposures and volunteered human exposures as well as the material from epidemiological cohort study. These are going to be compared according to inflammatory, cytotoxic and genotoxic changes and furthermore beyond the current state of the art to neurotoxic and brain health effects. With this approach, we are aiming to a comprehensive understanding of the adverse brain effects of nanoparticles from traffic.
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Biomarkers of neurodegeneration in serum and cerebrospinal fluid in patients with selected neurological diseases
Nosková, Libuše ; Fialová, Lenka (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Švarcová, Jana (referee)
Neurofilaments are the key structural component of the cytoskeleton of neurons, where they are essential for many functions. They consist of 3 subunits: light chain (NFL); medium chain (NfM) and heavy chain (NfH). Except neurofilament proteins there is also α-internexin in the central nervous system (CNS) or peripherin in the peripheral NS. Due to various pathophysiological processes, neurofilament proteins are released into the extracellular space, where they can interact with the components of the immune system. While the involvement of the immune system in the pathogenesis of neurodegenerative diseases is obvious, less knowledge about the antibody response to the neurofilament proteins is available. It is eligible to expand our knowledge in this area. Determination of free antibodies against neurofilaments together with their immune complexes with corresponding antigen provides us more detailed insight into the antibody immune response against neurofilaments. We have optimized the ELISA methods to determine free antibodies against light and heavy chain of neurofilaments together with their corresponding immunocomplexes in both serum and cerebrospinal fluid. Implementation of these methods is precondition for analysis of those parameters in serum and cerebrospinal fluid of patients with...
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Monitoring neurotoxinu \recke{beta}-N-methylamino-L-alaninu v povrchových vodách
PIXA, Jan
This bachelor thesis describes common information about cyanobacteria and cyanotoxins, environmental drivers of cyanobacterial blooms and summaries present knowledges of the occurrence of their secondary metabolite neurotoxin \recke{beta}-N-methylamin-L-alanin. The thesis includes a project proposal regarding monitoring of neurotoxin \recke{beta}-N-methylamin-L-alanin in fishponds and water reservoirs.
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