Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases

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    Belastungserleben und Selbstfürsorge im Berufsalltag von Lehrkräften für Sonderpädagogik im Förderschwerpunkt Hören und Kommunikation: Eine Interview-Studie zum Umgang mit sich selbst in emotional herausfordernden Situationen

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    Abstract Der Lehrberuf ist mit vielfältigen Anforderungen verbunden, die neben fachlichen Aufgaben auch kommunikative, emotionale und organisatorische Aspekte umfassen. Lehrkräfte sind dabei regelmäßig hohen Belastungen ausgesetzt, deren Bewältigung individuelle Ressourcen erfordert (Gehrmann, 2013; Semmer & Meier, 2019). Im sonderpädagogischen Bereich, insbesondere im Förderschwerpunkt Hören und Kommunikation, liegen bislang nur wenige Erkenntnisse zu spezifischen Belastungsfaktoren und Bewältigungsstrategien von Lehrkräften vor (Neugebauer & Wilbert, 2010; Shyman, 2011). Die Anforderungen der Inklusion sowie die Heterogenität der Schülerschaft stellen zusätzliche Herausforderungen dar (Hintermair et al., 2014). Die Forschung hebt die Bedeutung von Selbstregulation und Selbstwirksamkeitserwartungen als zentrale psychosoziale Schutzfaktoren hervor (Baumert & Kunter, 2006; Klusmann & Waschke, 2018). In den letzten Jahren rückte zudem das Konzept des Selbstmitgefühls (Self-Compassion) verstärkt in den Fokus, da es nachweislich mit reduziertem Stresserleben und erhöhter Resilienz assoziiert ist (Ne^, 2003a; Gumley & MacBeth, 2012). Auch im Kontext der Hörgeschädigtenpädagogik konnte gezeigt werden, dass ein ausgeprägtes Selbstmitgefühl mit einer geringeren Neigung zu perfektionistischem Arbeitsverhalten und einer verbesserten Bewältigung emotionaler Anforderungen korreliert (Vogt et al., 2021). Die vorliegende Studie untersucht subjektive Belastungserlebnisse, hiermit verbundene gedankliche und emotionale Wahrnehmungsmuster sowie selbstunterstützende Bewältigungsstrategien von Lehrkräften im Förderschwerpunkt Hören und Kommunikation anhand problemzentrierter Interviews (Witzel, 1985). Die Ergebnisse verdeutlichen, dass eine differenzierte Selbstwahrnehmung, die Fähigkeit zur Distanzierung und lösungsorientierten Selbstreflexion, Kompetenzen der Selbstregulation sowie das ausdrückliche Formulieren von Bedürfnissen, das Erleben und aktive Gestalten von Verbundenheit und Wertschätzung sowie der kollegiale Austausch als selbstunterstützende Ressourcen bei der Bewältigung emotionaler Belastungssituationen wahrgenommen werden. Diese Faktoren tragen wesentlich zur Förderung von Selbstfürsorge und Selbstmitgefühl bei und unterstützen die Entwicklung von Resilienz im schulischen Alltag

    Non-invasive imaging of neuronal activity using PET

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    Measuring neuronal activity in vivo is still a challenging approach, although it might have a huge impact on science and clinical therapy. cfos, an immediate early gene, is expressed in most brain regions in neurons and has low expression at the basal level, but it is activated rapidly in response to various stimuli, including neuronal activity. It is used in science as a marker for evaluating neuronal activation in vivo. However, it hasn’t been yet possible to measure brain cfos activation in vivo. The 18F-FHBG/PET system is extensively used in both science and clinics to measure the expression of Herpes Simplex Virus 1 thymidine kinase (HSV1-TK) in vivo. HSV1-TK is an enzyme that phosphorylates 18F-FHBG to trap it in the cell, and using the PET system, helps to visualize the cells expressing HSV1-TK. When HSV1-TK expression is controlled by the cfos promoter, we are able to indirectly measure cfos in vivo using PET. However, the 18F-FHBG/PET technique has its limitations for measuring HSV1-TK expression in the brain due to the lack of transporters and the presence of the blood-brain barrier (BBB). SLC43A3 is a purine nucleobase transporter reported to work as a transporter for adenosine and guanosine analogs, including 18F- FHBG. In this project, we aimed to develop a non-invasive PET imaging system to assess neuronal activity in vivo using the 18F-FHBG/PET system. To this end, a cfos-BAC was modified such that a FLEx HSV1-TK cDNA together with a PGK promoter-driven SLC43A3 transporter was inserted into the second exon of the cfos gene via CRISPR/CAS9 Red/ET recombination. The linearized cfos-fl-HSV1-TK:PGK-SLC43A3 BAC was used in pronuclear injection experiments to generate founder lines. To identify the best founder line, mouse embryonic fibroblasts (MEFs) were generated and tested in ex vivo experiments. These tests showed that HTNCre activation triggered HSV1-TK expression under cfos control. Thus, founder mice were crossed with Cre deleter mice to activate cfos-HSV1-TK in all cells to investigate our PET system in vivo. However, although HSV1-TK expression was controlled by the cfos promoter, the 18F-FHBG failed to enter the brain since SLC43A3 was not expressed in lectin-positive BBB. To overcome this limitation, several AAVs were constructed with a strong CAG promoter driving SLC43A3 expression. However, this also failed to be su�ciently expressed in the BBB. The inability to express SLC43A3 in the whole brain, especially in endothelial cells of the blood vessels, might be a potential reason why SLC43A3 doesn’t facilitate 18F-FHBG entrance into the brain. However, we also attempted to reproduce the published data regarding ganciclovir (GCV) tritium or 18F-FHBG uptake in SLC43A3-expressing cells. Surprisingly, these experiments revealed that SLC43A3 neither transports 3H-GCV nor 18F- FHBG, indicating that finding a new transporter for 18F-FHBG to facilitate its entry into the brain without damaging the BBB is a precondition for measuring neuronal activity non-invasively in vivo with great precision

    Employees’ Psychological Wellbeing - Quantitative Analyses on the Relationship between Employees’ Psychological Wellbeing and Individual, Interpersonal, and Organizational Factors

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    In Germany, mental health issues are a major cause of sick leave, and the number of workdays lost due to mental illnesses is increasing. Furthermore, the psychological wellbeing of employees can affect both individuals and employers. This doctoral thesis aims to explore three research questions based on well-established models and the current state of research: 1. What is the role of employees’ psychological wellbeing as antecedent and consequence in a worksite healthcare management program for employees with first minor musculoskeletal disorders? 2. Is there a reciprocal relationship between transformational leadership and employees’ psychological wellbeing? 3. What influence do organizational health literacy and health supporting leadership have on the association between individual health literacy and employees’ psychological wellbeing? To address these questions, three studies were conducted using employee surveys, which were available in both online and paper-based formats. The participants worked in various sectors throughout Germany and represented companies of different sizes. While the first two studies were based on longitudinal data, cross-sectional data was analyzed in the third study. The results for the first research question indicated that employees’ psychological wellbeing improved following a worksite healthcare management program. Those with lower psychological wellbeing exhibited higher pain intensity and disability scores compared to those with higher psychological wellbeing. Changes in disability scores over time completely mediated the impact of changes in pain intensity over time on psychological wellbeing after the intervention. The differences over time in disability scores totally mediates the impact of the differences over time in pain intensity on psychological wellbeing after a worksite healthcare management program. The more psychological wellbeing increased over time, the better the disability score was after a worksite healthcare management program. For the second research question, the findings revealed that the change in perceived transformational leadership over time did not significantly impact employees’ psychological wellbeing, nor did changes in employees’ psychological wellbeing significantly impact transformational leadership. Regarding the third research question, the analysis revealed that the relationship between individual health literacy and employees’ psychological wellbeing is partially mediated by organizational health literacy and health supporting leadership. Overall, the results of this doctoral thesis highlight the importance of focusing on individual, interpersonal, and organizational aspects in relation to employees’ psychological wellbeing while also considering potential reciprocal relationships. The comprehensive metamodel presented in this doctoral thesis could serve as a valuable foundation for future practice and research by integrating relevant elements from various models

    Qualitative Studie zu Herausforderungen, Bewältigungsstrategien und Bedürfnissen von jungen Erwachsenen mit Krebs mit Fokus auf die Lebensbedrohlichkeit der Erkrankung

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    Junge Erwachsene mit Krebs (18 bis 39 Jahre bei Erstdiagnose) sind durch die Erkrankung, deren Therapie und die plötzliche Lebensbedrohung stark herausgefordert. Es wurden 15 Betroffene 2-5 Jahre nach der Erstdiagnose zu ihren Herausforderungen, Bewältigungsstrategien und ihrem Unterstützungsbedarf während des gesamten Krankheitsverlaufs interviewt. Ein Fokus wurde hierbei auf die Lebensbedrohlichkeit, mit welcher die Erkrankung einhergeht, gelegt. Die Ergebnisse dieser qualitativen Studie sind in zwei Publikationen veröffentlicht, welche Teil dieser kumulativen Dissertation sind

    Survey-Guided Policy Design: An Economic Approach to Student Aid and Beyond

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    In this dissertation, I use research-guided surveys to systematically analyze the problems or barriers that prevent individuals from acting in line with a policy goal. Based on this evidence, I design policy interventions that address these problems to achieve behavioral change. These interventions are tested in randomized controlled trials to evaluate their effectiveness. By using survey methods to identify problems and design interventions before evaluating their effectiveness, I show how survey evidence can help to inform policy ex-ante. In Chapter 2, I provide a general, parsimonious survey tool to predict intervention effectiveness and design effective intervention accordingly. Then, I turn to the applied case of student aid non-take-up with a special focus on misperceptions in Chapter 3, and evaluate an information intervention to resolve misperceptions and increase take-up of student aid in Chapter 4

    Synthesis, Characterization, and Functionalization of Bis-Thiosemicarbazones: Applications in Metal Binding, Catalysis and As Single-Source Precursor

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    Pentadentate Bis-thiosemicarbazones (BTSC) of class S^N^N^N^S binding sites have been known for their therapeutic activities. Thus, investigation of pentadentate BTSC in other fields besides biological activities is often scarce or lacking. Pentadentate BTSC ligand of type S^N^N^N^S comprises a dicarbonyl backbone, N^S core and a diamine tail. Pentadentate BTSC is appealing because the dicarbonyl backbone and the diamine tail can be derivatized, functionalized and conjugated with a nanoparticle (NP) or other molecules, thus potentially expanding the applications of pentadentate BTSC. Thus, the study commenced with the synthesis of various pentadentate BTSC ligands and their metal complexes to expand the library of BTSC. Single crystal XRD showed that Pd2+ and Zn2+ conform to a distorted square planar geometry. Pd2+ bind through Sthiol^Nimine^Npyridinic^Namide, exhibiting a thione/thiol character. Zn2+ is coordinated through Sthiol^Nimine^Nimine^Sthiol showing only thiol characters. Cu2+ coordinate through Sthiol^Nimine^Npyridinic^Nimine^Sthiol, resulting in a bipyramidal geometry. The reaction between pentadentate BTSC and the linkers (dopamine hydrochloride and (3-aminopropyl)-triethoxysilane) was first carried out and to establish a new route to conjugate BTSC with NPs. 1H NMR spectroscopy revealed the new amide bond, confirming the successful conjugation of BTSC with (3-aminopropyl)-triethoxysilane) or dopamine. Magnetic Fe3O4 conjugate of BTSC was first synthesized using the well-established NHS/EDC coupling route. The Fe3O4 was first coated with SiO2, followed by the deposition of (3-aminopropyl)-triethoxysilane to afford amine functionalized Fe3O4 (Fe3O4@SiO2–APTES) and subsequent conjugation with BTSC (Fe3O4@SiO2–APTES–BTSC). The magnetic material (Fe3O4@SiO2–APTES–BTSC) exhibit a high adsorption capacity for binding Pd2+. The unusual high uptake of Pd2+ was attributed to different adsorbed species contributing to the uptake of Pd2+ ions, as revealed by different characterization techniques, including DFT calculations. The newly developed route was employed to conjugate BTSC with different NP (SiO2 and Fe2O3). SiO2 was conjugated with BTSC at the dicarbonyl backbone, and Fe2O3 was conjugated with BTSC at the diamine tail part of the BTSC. SiO2 was initially pre-functionalized with (3-aminopropyl)-triethoxysilane, and Fe2O3 was pre-functionalized with dopamine, and the subsequent reaction with BTSC at room temperature affords SiO2@APTES–BTSC or Fe2O3–Dopamine–BTSC. SiO2@APTES–BTSC was further coordinated with Pd2+ ions and employed as a heterogeneous catalyst in the - 6 - Suzuki-Miyaura cross-coupling reaction. X-ray Photoelectron Spectroscopy investigation of SiO2@APTES–BTSC–Pd revealed that palladium is predominantly Pd0, thus, an invaluable catalyst for coupling aryl compounds. Metal complexes of pentadentate BTSC were also used as single-source precursors for synthesizing metal sulfides NPs. The metal sulfide NP particles were obtained by microwave-assisted decomposition of metal complexes of pentadentate BTSC. Thus, pure Cu7.2S4, Pd16S7, and ZnS metal sulfides NPs were synthesized

    Skin Picking Disorder: Diagnostics, Trigger and Treatment

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    Manipulating one’s skin is a natural behavior observed in both animals and humans – often serving as a stress-relieving and/or hygienic act (Feusner et al., 2009). However, for some individuals, this behavior escalates into a compulsion they find difficult to resist. This can result in excessive manipulation of the integumentary system (skin, hair, nails), which may cause skin damage, lesions, or hair loss (International Classification of Diseases [ICD-11], World Health Organization [WHO], 2024). The description of such behaviors has historical root. Hippocrates mentioned them as early as 400 BCE: „Next, we must note whether he plucks his hair, scratches or weeps “(Lloyd 1983, p. 100). Compared to well-established mental disorders like anxiety, classified in one of the first versions of ICD-10 (ICD-10-SGB-V Version 1.1; WHO, 1995) and Diagnostic and Statistical Manual of Mental Disorders (DSM-III; American Psychiatric Association [APA], 1980), body-focused repetitive behaviors (BFRBs) such as dermatillomania (skin picking disorder [SPD], excoriation disorder; DSM-5; APA, 2013) and onychophagia (nail biting; DSM-5, APA, 2013) have only recently been formally recognized in diagnostic manuals. An exception to this is trichotillomania (hair pulling disorder), which was acknowledged as early as DSM-III (APA, 1980). Interest in BFRBs has grown significantly in recent years, as reflected by an increase in research publications (see table 1). Despite this progress, public and professional awareness about BFRBs and their treatment options remain limited (Gallinat et al., 2019; Loftus et al., 2024). More than half of the participants in two studies reported not seeking help for their SPD, citing reasons such as doubts about severity, uncertainty about whom to approach, and concerns over whether medical professionals possess adequate expertise in this area (Gallinat et al., 2019; Tucker et al., 2011). Addressing this gap in professional knowledge and promoting evidence-based treatment strategies represent critical efforts undertaken in this dissertation

    Einfluss unterschiedlicher Reinigungsstrategien auf die Geometrie, Lichttransmission, Oberflächenparameter und Biegefestigkeit 3-D- gedruckter Zirkondioxidkeramik

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    Additiv hergestelltes Zirkondioxid (LithaCon 3Y 210®, Lithoz, Wien, Österreich) muss nach dem 3-D-Druckprozess (CeraFab 7500, Lithoz, Wien, Österreich; vor dem Entbinderungs- und Sinterbrand) gereinigt werden. Dadurch werden anhaftende Harzüberschüsse entfernt. Ziel der vorliegenden Untersuchung war es, den Einfluss verschiedener Reinigungsstrategien auf die Geometrie, Lichttransmission, Oberflächenbeschaffenheit und biaxiale Biegefestigkeit 3-D-gedruckter Zirkondioxidkeramik zu untersuchen. Zylindrische Prüfkörper (N = 115; r = 6,2 mm, b = 1,2 mm) wurden aus 3 mol% Yttriumoxid-stabilisiertem Zirkondioxid (LithaCon 3Y 210®, Lithoz, Wien, Österreich) 3-D-gedruckt und durch fünf verschiedene Methoden gereinigt (n = 23): (A) „Airbrushing“-Methode (25 Sek.) mit spezieller Reinigungslösung (Lithasol30®, Lithoz, Wien, Österreich) und einwöchiger Lagerung in einem Trockenofen (40°C); (B) „Airbrushing“ (25 Sek., Lithasol30®) ohne Lagerung im Trockenofen; (C) Ultraschallbad kurz (US, 30 Sek.) gefüllt mit Lithasol30®; (D) US lang (300 Sek.) gefüllt mit Lithasol30®; (E) US kurz (30 Sek.) gefüllt mit Lithasol30® gefolgt von „Airbrushing“ (40 Sek., Lithasol30®). Im Anschluss an das „Post-Printing Cleaning“ folgte der Entbinderungs- und Sinterbrand. Ohne weitere Veränderung der Oberflächen wurden Geometrie, Lichttransmission, Oberflächenbeschaffenheit und biaxiale Biegefestigkeit (BFS) sowie charakteristische Festigkeit σθ und Weibull- Parameter m mittels Kolmogorov-Smirnov-, t-, Kruskal-Wallis- und Mann-Whitney-U- Test untersucht (α < 0,05). Die Prüfkörper der PPC-Methode C (US kurz) wiesen die größte mittlere Dicke und den größten Durchmesser auf. Die höchste Lichttransmission wurde für US kurz in Kombination mit „Airbrushing“ gefunden (Methode E, p ≤ 0,004), gefolgt von Methoden D und B (p = 0,070). Die niedrigste Oberflächenrauigkeit konnte durch das US kurz kombiniert mit „Airbrushing“ (Methode E, p ≤ 0,039), gefolgt von Methoden A und B (p = 0,172) festgestellt werden. Die Methoden A (σθ = 1030 MPa, m = 8,2), B (σθ = 1165 MPa, m = 9,8) und E (σθ = 1146 MPa, m = 8,3) zeigten signifikant höhere Biegefestigkeiten (p < 0,001) sowie eine größere Zuverlässigkeit als C (σθ = 480 MPa, m = 1,9) und D (σθ = 486 MPa, m = 2,1). Das „Post-Printing Cleaning“ beeinflusst die Materialeigenschaften 3-D-gedruckten Zirkondioxids. „Airbrushing“ (B) und kurzes US in Kombination mit „Airbrushing“ (E) waren vor allem hinsichtlich Oberflächenrauigkeit und biaxialer Biegefestigkeit vorteilhaft. Die alleinige Ultraschallreinigung war unwirksam (C) oder nachteilig (D). Für die Reinigung hohler oder poröser Strukturen könnte Methode E vielversprechend sein

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