14043 research outputs found
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Investigating CAG repeat instability and single nucleotide polymorphisms as modifiers in Huntington’s Disease
No full textDie Chorea Huntington (HD) ist eine tödliche Erkrankung, verursacht durch eine pathologisch verlängerte CAG-Wiederholung im HTT-Gen. Obwohl das Erkrankungsalter (AO) v.a. durch die CAG-Länge bestimmt wird, bedingen genetische Faktoren eine signifikante Variabilität. Die sog. somatische Expansion (SE) der CAG-Wiederholung gilt als möglicher Treiber der Zelltoxizität. Diese Studie untersucht SNPs aus DNA-Reparaturgenen (DDR) aus genomweiten Assoziationsstudien in Bezug auf AO und SE im Blut von HD-Patienten. Zudem wurde die SE im Blut als möglicher Biomarker mittels Indexberechnungen ausgewertet. In >500 Proben wurden neun SNPs analysiert. Die SNPs zeigten eine signifikante AO-modifizierende Wirkung, während einige mit SE und geschlechtsabhängigen Effekten assoziiert waren. Die Ergebnisse geben Hinweise dafür, dass SNPs auf DDR-Genen das AO über eine Modifikation der SE beeinflussen, was neue Therapieansätze ermöglicht. Zudem könnte die SE im Blut als zukünftiger Biomarker bei HD dienen
Bedeutung der Magnetresonanztomographie (MRT) bei der Differenzierung zwischen rheumatoider Arthritis der Hand und Fingergelenkspolyarthrose
No full textDas Hauptziel der Arbeit war es, die durch MRT sichtbaren Veränderungen bei RA und FPA zu vergleichen und deren Zuverlässigkeit bei der Differenzierung der beiden Krankheiten zu untersuchen. In der Studie wurden 200 Patienten (100 RA, 100 FPA) untersucht mithilfe des MRT-Scores RAMRIS. Dabei wurden Synovitis, Erosionen, Knochenmarködeme und Tenosynovitis untersucht und bewertet. Ergänzend wurden Entzündungsparameter, Autoantikörper sowie klinische Parameter analysiert.
Die Synovitis ist das Hauptmerkmal, das die RA von der FPA unterscheidet, und die MRT ist ein geeignetes und präzises bildgebendes Verfahren. MRT-basierte Entzündungsbefunde sind entscheidender als strukturelle Veränderungen für die Differenzierung von RA und FPA in Bezug auf den RAMRIS-Score
Tuning of functional ferroelectric oxides
No full textIn den letzten 100 Jahren hat sich das enorme technologische Potenzial von ferroelektrischen Materialien durch ihre spontanen und schaltbaren Polarisation gezeigt. Insbesondere ferroelektrische Perowskit-Oxide sind wegen ihrer anpassungsfähigen ABO3-Kristallstruktur und der Möglichkeit, ihre Eigenschaften durch chemische Substitution und in Kompositen einzustellen, von großem Forschungsinteresse. Obwohl die funktionellen Eigenschaften bekanntermaßen von der Domänenstruktur und Domänenwanddynamik abhängen, ist der Einfluss von Defekten und lokalen Inhomogenitäten auf diese noch unklar. Diese Dissertation nutzt ab-initio-basierte grobkörnige Molekulardynamiksimulationen, um zu untersuchen, wie Defekte und lokale Inhomogenitäten die Phasenstabilität, funktionellen Reaktionen und den Domänenwechsel in prototypischen BaTiO3-Materialien beeinflussen. Die Ergebnisse liefern zudem neue Einblicke in die Kopplungsmechanismen zwischen Defekten und Domänenwanddynamik.Over the past 100 years, ferroelectric materials have demonstrated tremendous technological potential due to their spontaneous and switchable polarization. Particularly, ferroelectric perovskite oxides have attracted significant research interest due to their adaptable ABO3 crystal structure and the ability to tailor their properties by chemical substitution and composites. Although it is widely accepted that functional properties depend on Domain structure and domain wall dynamics, the impact of defects and local inhomogeneities on these structures and dynamics remains unclear. Therefore, this cumulative thesis uses ab initio derived coarse-grained molecular dynamics simulations to systematically investigate how defects and local inhomogeneities affect phase stability, functional responses, and domain switching in prototypical BaTiO3-based materials. Furthermore, the results provide new insights into the coupling mechanisms between defects and domain wall dynamics
Eine modellbasierte Methode zur Entwicklung der informationsverarbeitenden Komponente von Systemen auf Grundlage von tiefem bestärkendem Lernen
No full textKlassische, regelbasierte Entwicklungsansätze stoßen bei komplexen Aufgaben an Grenzen. Als Alternative bietet sich das tiefe bestärkende Lernen an: Es lässt Systeme durch Interaktion aufgabenlösende Verhaltensweisen für komplexe Aufgaben selbst erlernen, bringt jedoch zugleich Herausforderungen bei Nachvollziehbarkeit, Reproduzierbarkeit und Dokumentation mit sich. Die Arbeit stellt eine strukturierte, modellbasierte Methode zur Entwicklung informationsverarbeitender Komponenten vor, um diese Herausforderungen zu adressieren. Sie umfasst fünf an das V-Modell angelehnte Phasen: Definition, Lernkonfiguration, Simulation, Training und Transfer. Ein kontinuierliches Modell auf Basis der Systemmodellierungssprache SysML unterstützt dabei den Entwicklungsprozess. Der Neuheitsgrad liegt in der systematischen Verwendung von bewährten Prinzipien des Maschinenbaus für das tiefe bestärkende Lernen. Mehrere Anwendungsfälle belegen Übertragbarkeit und effiziente Anpassbarkeit
Reducing the urge to be physically active in patients with anorexia nervosa through virtual reality
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Weight restoration is a primary goal in anorexia nervosa (AN) treatment. Recent studies suggest that addressing physical activity urges in patients with AN is a promising target to facilitate weight restoration. This trial will evaluate the feasibility of a virtual reality (VR)-based intervention as an add-on treatment to psychotherapy to improve activity urges and, consequently, initial treatment responses on core outcomes as targeted per AN treatment guidelines.
This single-centre feasibility trial adopts the single-blind, two-arm design and outcome measures of an intended full-scale randomised controlled trial (RCT) in order to establish that all necessary trial components work together as intended. It will evaluate feasibility as the primary endpoint and compare changes in ratings of the urge to be active between patients with AN randomly assigned to receiving VR intervention sessions and patients with AN in a control procedure. The feasibility of the full-scale RCT will depend on whether patients (1) will evaluate the experience as acceptable, (2) tolerate VR side effects and (3) will adhere to the intended intervention schedule. We define a set of three-tiered, formal progression criteria and employ a ‘traffic light system’ demarcating go (green), amend (amber) and stop (red) signals for advancing to the full-scale RCT.
The study was approved by the ethics committee of the Ruhr University Bochum’s Medical Faculty at Campus East-Westphalia (AZ 2024-1296, 9 December 2024). Patients have to provide written consent before taking part in the study. The findings will be published with open access
Relevance of pressure recovery in a young patient with aortic stenosis and small-caliber aorta
No full textThe case concerns a 20-year-old patient with Canadian Cardiovascular Society class II angina who was initially referred for aortic valve replacement because of a suspected high-grade aortic valve stenosis with increased transvalvular gradients (max/mean: 70/40 mm Hg) measured by Doppler echocardiography. Examinations using transesophageal echocardiography and computed tomography showed a sufficiently opening bicuspid aortic valve, excluded supra- and subvalvular stenoses, and measured a narrow aorta (diameter: 2 cm). The explanation for the highly increased gradients across the aortic valve was the pressure recovery (PR) phenomenon, which cannot be detected by Doppler gradients. Distal to a stenosis kinetic energy is converted back into potential energy, most effectively in small aortas (area: <3 cm). This reduces the actual transvalvular pressure gradient, which can directly be determined with cardiac catheterization. Accordingly, invasive measurements showed a moderate aortic stenosis (mean transvalvular pressure: 19 mm Hg), almost identical to the PR-corrected Doppler measurements. A high-grade stenosis of the proximal left anterior descending artery was treated interventionally, which could explain the angina symptoms
AVATAR Virtual Reality Social therapy (AVATAR_VRSocial) for distressing voices and their interference in social everyday life in early psychosis
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Around 70% of people with psychosis experience auditory verbal hallucinations (AVHs), which can cause distress and impair the social functioning of the individual. AVATAR therapy works by facilitating a "face-to-face" dialogue between the person and a digital representation (avatar) of their persecutory voice. Although there is cumulative evidence of this way of working with voices, enhancing the therapeutic focus on improved confidence and sense of control of the voices in social situations represents a promising way to boost generalisation of therapy gains into social contexts. We aim to enhance AVATAR therapy by incorporating immersive Virtual Reality (VR) social environments aiming to help the person to deal better with their voices in daily situations.
A randomised controlled feasibility trial will be conducted. 40 patients aged 18 or above who are at early stages of psychosis (first episode of psychosis in the last five years) and report distressing and interfering voices will be recruited. Participants will be randomised to receive either a novel, enhanced version of AVATAR therapy (AVATAR_VRSocial) in addition to usual care or usual care alone. Assessor-blinded assessments will be conducted at baseline, 3 months (post-intervention) and 6 months (follow-up). Key therapeutic targets of AVATAR_VRSocial will be those established by the previous evidence of this approach (ie, power and control, self-esteem and future focus), while introducing exposure and management of distressing voices during social interactions. Analyses will focus on feasibility outcomes (recruitment, retention and completion rates) and preliminary estimates of intervention effects. Qualitative interviews will be carried out with participants allocated to AVATAR_VRSocial to gain a comprehensive understanding of participants’ views on the acceptability of the intervention and research procedures. Thematic analysis of the qualitative interviews will assess the acceptability of the intervention, trial procedures and the new VR technology and software involved.
The study has received ethical approval from the Ethics Commission at the Faculty of Psychology (Ruhr-Universität Bochum), and there is an independent Trial Steering Committee and Lived Experience Advisory Panel also supporting it. Findings will be disseminated through peer-reviewed publications, conference presentations and science dissemination events
Should I stay or should I go
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This article explores the psychological burden experienced by medical assistants (MAs) in General Practices during the Covid-19 pandemic (Corona virus disease 2019 (SARS-CoV-2)) in Germany. The study aims on demanding patient behavior, increased workload, and the perceived lack of appreciation and discuss their potential impact on the MAs´ well-being and career decisions.
A qualitative approach was utilized. MAs were included via a regional practice network as well as professional associations and newsletters. In total, 21 interviews with MAs from various federal states in Germany were conducted between April and September 2021. The semi-structured interview guideline focused on daily work challenges during the pandemic and its consequences. Interviews were recorded, transcribed, and analyzed using qualitative content analysis according to Kuckartz.
The findings highlight core challenges, including demanding communication with patients, lack of appreciation in the media, a high workload, resilience versus career migration, and the needs and wishes of MAs in their everyday work. Abusive language, insults, and theft of materials by patients added significant stress. The interviews reveal how important teamwork and a supportive working environment are for overcoming these challenges.
The study underlines the urgent need for societal and political awareness regarding the challenges faced by MAs, especially during public health crises. The perceived social egoism in patient behavior, coupled with a lack of recognition and appreciation, contributed to a challenging work atmosphere and potential burnout risk. Recommendations include enhancing support for MAs, recognizing their contributions in the media, and fostering collaborative efforts between practitioners and policymakers to address the unique challenges in general practices
Duchenne muscular dystrophy patient iPSCs
No full textBackground: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle stem cells that play an important role in adult muscle maintenance and regeneration. The absence or mutation of dystrophin in DMD is hypothesized to impair SC asymmetric division, leading to cell cycle arrest. Methods: To overcome the limited availability of biopsies from DMD patients, we used our 3D skeletal muscle organoid (SMO) system, which delivers a stable population of myogenic progenitors (MPs) in dormant, activated, and committed stages, to perform SMO cultures using three DMD patient-derived iPSC lines. Results: The results of scRNA-seq analysis of three DMD SMO cultures versus two healthy, non-isogenic, SMO cultures indicate reduced MP populations with constant activation and differentiation, trending toward embryonic and immature myotubes. Mapping our data onto the human myogenic reference atlas, together with primary SC scRNA-seq data, indicated a more immature developmental stage of DMD organoid-derived MPs. DMD fibro-adipogenic progenitors (FAPs) appear to be activated in SMOs. Conclusions: Our organoid system provides a promising model for studying muscular dystrophies in vitro, especially in the case of early developmental onset, and a methodology for overcoming the bottleneck of limited patient material for skeletal muscle disease modeling