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  • Open Access German
    Authors: 
    Selenz, Carolin;
    Country: Germany

    Lung cancer represents the most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Approximately 80 % of patients are non-small-cell lung cancer (NSCLC) cases. These can be further subcategorised depending on the histological and molecular composition of tumours. Oncogene-dependent NSCLC comprise a major subtype of NSCLC that harbours oncogenic driver mutations, for example in the epidermal growth factor receptor tyrosine kinase. These mutations induce aberrant activation of cell signalling, thus facilitating uncontrolled cell growth and tumorigenesis. Targeted therapy represents one essential treatment strategy that is well-established in the clinic for oncogene-driven NSCLC, for example in the form of tyrosine kinase inhibitors. Other therapy approaches, such as anti-angiogenic compounds, aim to modulate the tumour microenvironment (TME) to become less advantageous to tumour cells, thus inhibiting cancer progression. Unfortunately, highly adaptive tumour cells and the dynamic nature of the TME limit the benefits of targeted therapy due to the emergence of resistance mechanisms or suppression of immune response. Therefore, it is essential to elucidate the effects of targeted therapy on the TME to increase our understanding of the underlying mechanisms responsible for the escape of immunosurveillance and tumour progression. This thesis investigated the impact of targeted therapy on cancer cells and the TME in oncogene-driven NSCLC and evaluated the remaining difficulties associated with this therapy approach, which illustrate the need for optimisation of existing therapy options or development of alternative treatment strategies.

  • Open Access German
    Authors: 
    Thelen, Lavinia;
    Country: Germany

    Academic underachievement affects many adolescents and is defined as a notable discrepancy between actual and expected achievement, given the student's cognitive ability level. A significant percentage of adolescents suffer from both academic underachievement and mental disorders, putting them at risk for negative psychosocial development. However, there are few treatments available focussing on these adolescents. The present doctoral thesis evaluated the efficacy of the treatment program "SELBST – achievement problems" in a randomised controlled trial (RCT). Furthermore, the added benefit of a specifically designed smartphone app to improve therapy transfer was investigated. Methods: The psychometric properties of the primary outcome, the Academic Problems Checklist, were analysed. A clinically referred sample of n = 60 adolescents aged 11-18 years was randomised into either the experimental group, receiving weekly cognitive behavioural therapy based on the "SELBST – achievement problems" treatment manual including a therapy smartphone app or into the control group, receiving treatment as usual. Results: The revised version of the Academic Problems Checklist consists of a 17-item, semi�structured clinical interview for adolescents, parents, and teachers. The analysis of the psychometric properties of the APC showed it is a short, reliable, and valid instrument for assessing academic underachievement of adolescents with mental disorders using a multi�informant approach. The RCT showed for both groups clinically relevant improvements on the primary outcome of academic underachievement. For the teacher-rated academic underachievement, a statistical superiority of the treatment group compared to the control group was found during the follow-up phase. The treatment group showed significant improvements regarding their grade point average compared to the control group. Statistical superiority of the treatment group was found for the individual problemlist measuring individual academic underachievement problems with large effects in the adolescent and parent rating. Mental health problems improved in both groups, however, there was no statistical superiority of either group. These effects remained largely stable during the follow-up period. The smartphone app was well accepted by the adolescents, however, it showed no statistically significant additional benefit compared to the standard SELBST-treatment. Conclusion: In summary, improvements were found for academic underachievement and mental problems. The treatment satisfaction was high, but the smartphone app provided no significant additional benefit. The study's limitations included the small sample size, the substantial dropout rate in the experimental group, and the technical challenges encountered implementing a smartphone app

  • Open Access English
    Authors: 
    Kamga Kapchoup, Michelle Vanessa;
    Country: Germany

    Cardiovascular diseases can be congenital or acquired and represent the main cause of mortality worldwide. Long QT Syndrome 3 (LQTS3) and Brugada Syndrome (BrS) are congenital channelopathies mostly caused by SCN5A mutation. Both diseases have been associated with gain- and loss-of-function of the channel respectively. However, some mutations display an overlapping phenotype between the two diseases, rendering the diagnostic as well as the therapy of the diseases challenging. The use of disease-specific pluripotent stem cells to develop disease models has enabled the research of pathogenic pathways related to diseases and the search for new treatments. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a platform that has allowed advancement in personalized therapy circumventing the problem of genotype-phenotype differences existing between individuals. This study aimed to characterize both disease phenotypes at a cellular, molecular, and functional level. For this purpose, we used different stages of cardiomyocytes maturation to perform our experiments. The use of cardiomyocytes at distinct time points of maturation revealed that a certain threshold of CMs maturity is necessary for the evaluation of disease phenotypes during in-vitro experiments. At the cellular level, we observed that Cx43 distribution within the intercalated discs is not disturbed in disease models compared to the control. However, numerous genes coding for proteins involved in the mechanisms of ECC and cardiomyocytes' contractility were dysregulated. The molecular data as well as the patch-clamp analysis allow us to hypothesize that V240M mutation could be associated with a mixed phenotype between LQTS3 and BrS, and that the Q646Rfs*5 mutation is associated with BrS as described by prior studies. The calcium imaging showed that in the two disease models, the Ca2+ transient is impaired, and the time corresponding to 50% of Ca2+ extrusion is prolonged.

  • Open Access German
    Authors: 
    Gnade, Benjamin;
    Country: Germany

    Die Dissertation »Relative Chronologie der Rheinzaberner Reliefsigillata. Seriation, Punzen- und Stilanalyse« stand an der Universität zu Köln, Philosophische Fakultät – Archäologie der Römischen Provinzen, unter der Betreuung von Prof. Dr. Eckhard Deschler-Erb und wurde zum 14. Oktober 2020 eingereicht und am 27. Januar 2021 mündlich geprüft. Sowohl die Abfolge von H. Ricken als auch die bisherigen Computerseriationsergebnisse zur Rheinzaberner Relief-TS von H. Bernhard, F.-K. Bittner und A. Mees lassen sich im Wesentlichen bestätigen, da bei den letzteren drei Arbeiten die verwendeten Formeln von Yule und Jaccard auf der Mengenlehre beruhen und die Programme über die Punzenschnittmengen je nachdem die Nähe oder Distanz von den Waren-Punzensets anzeigen können. Im Rahmen einer manuell durchgeführten Seriation wurden Punzenlisten erstellt (Tab. 1-82), wonach die jeweiligen Punzenschnittmengen und Punzengruppen herleitbar waren. Diese Punzengruppen ließen sich in weiteren Arbeitsschritten vor allem über stilprägende Punzen im Rahmen der Stilanalyse sowie im Abgleich mit absolutchronologisch fassbaren Waren insbesondere aus Straten von Zerstörungshorizonten zu den Stilgruppen 1-5 mit insgesamt 11 Stilgruppen definieren und in Bezug zu den Filialen setzen (Beil. 1). Anm.: Die Punzenlisten (Tab. 1-82) sind als eigene Datei aus dem PDF extrahierbar. Mit dieser Datei bzw. den Einzeldateien lassen sich Seriationsarbeiten als »Rheinzabern gesamt«, nach einzelnen Stilgruppen (z. B. Stilgruppe 1 mit Tab. 1-16), Töpfern oder Waren/Serien mit entsprechenden Schlagworten wie beispielsweise »Cob« (Cobnertus) durchführen. Für einen beidseitigen Ausdruck der Arbeit mit üblicher Seitenzahlordnung ist die Leerseite – PDF S. 11 – zu entfernen.

  • Open Access German
    Authors: 
    Bresgen, Charlotte;
    Country: Germany

    Die Retina mit ihrer physiologischen Abgrenzung durch die Blut-Retina-Schranke bildet ein sogenanntes immunprivilegiertes Organ, dessen einzige Immunzellen die Mikroglia darstellen. Diese Mikrogliazellen nehmen daher eine entscheidende Rolle bei der Schädigung und Degeneration der Netzhaut durch inflammatorische Prozesse sowohl bei hereditären als auch bei erworbenen Erkrankungen der Retina ein. Hierbei steht der Übergang der physiologisch ramifizierten Mikroglia in eine aktivierte, sogenannte reaktive Form und die dadurch folgende fehlregulierte Immunantwort mit Hyperinflammation und neuronaler Degeneration im Vordergrund. Da dies über einen gewissen Zeitraum hin zu einer Sehstörung im Rahmen der unterschiedlichen Erkrankungen führt, rückt die Mikroglia als möglicher Therapieansatz immer weiter in den Fokus der Betrachtung. Ziel der aktuellen Forschung ist es, eine möglichst potente Substanz für diese Zielsetzung zu finden. In dieser Arbeit wurde Pomalidomid, welches bereits in der Therapie des multiplen Myeloms eine immunmodulatorische Wirkung in der Tumorumgebung zeigt, hinsichtlich seiner immunmodulatorischen Effekte auf die retinale Mikroglia untersucht. Hierzu erfolgte die Betrachtung der Toxizität, der Genexpression und der Veränderungen der Morphologie in BV-2 Mikrogliazellen unter Einsatz von Pomalidomid sowie dessen Einfluss auf deren Effektorfunktionen wie Phagozytoseverhalten, Migrationsverhalten und Veränderungen der NO- Produktion. Zusätzlich wurde der Einfluss von Pomalidomid mittels konditionierten Mediums aus BV-2 Mikrogliazellen auf die Genexpression sowie die Morphologie von ARPE-19 Pigmentepithelzellen und dessen Einfluss auf das Apoptoseverhalten von ARPE-19 Pigmentepithelzellen sowie 661W Photorezeptorzellen untersucht. Es konnte gezeigt werden, dass der immunmodulatorische Effekt von Pomalidomid, der für Makrophagen des peripheren Bluts eindeutig beschrieben wurde, in der retinalen Mikroglia kaum vorhanden ist. Ein signifikanter Effekt durch Pomalidomid konnte ausschließlich in der Morphologie und dem Migrationsverhalten der BV-2 Mikrogliazellen sowie in der Genexpression durch ARPE-19 Zellen gezeigt werden. in der Untersuchung der Phagozytoserate zeigte sich eine Tendenz zur Reduktion dieser durch Pomalidomid. In allen weiteren Experimenten zeigte Pomalidomid keinen Einfluss. Aufgrund der unzureichenden antiinflammatorisch-immunmodulatorischen Wirkung von Pomalidomid auf die retinale Mikroglia sowie der verhältnismäßig hohen Toxizität der Substanz ist diese für einen Einsatz in der Therapie retinal- degenerativer Erkrankungen nicht vielversprechend, sodass der Fokus zukünftiger Forschung auf der Untersuchung alternativer Substanzen liegen sollte.

  • Open Access English
    Authors: 
    Tulli, Susanna;
    Country: Germany
  • Open Access German
    Authors: 
    Lorenz, Laura;
    Country: Germany

    Background: Overweight and obesity are major health challenges and risk factors for subsequent diseases in both children and adults. There is an urgent need for effective preventive interventions and suitable settings in which they can be provided to a wide public. Research on perinatal programming indicates that maternal lifestyle during pregnancy influences the risks for pregnancy and birth complications, as well as the risks of obesity and chronic disease in children in the long term. There is evidence that lifestyle counseling interventions during pregnancy can be effective in improving maternal and infant health outcomes. In Germany, however, lifestyle topics are not consistently discussed during regular prenatal care. Methods: The GeMuKi intervention enhances prenatal care by embedding lifestyle counseling in routine checkup visits during pregnancy in different regions of the southern German state Baden-Württemberg. Supported by a novel shared telehealth platform, gynecologists and midwives provide lifestyle counseling to pregnant women using motivational interviewing (MI) techniques. Alongside the effectiveness trial, a process evaluation is conducted to identify factors that facilitate or inhibit the implementation of the intervention and to investigate the extent to which the intervention is implemented as intended. The cumulative dissertation addresses these objectives by providing three studies (Studies I-III) as well as supplementary data that analyzed the implementation process at different stages. Guided by different theoretical frameworks, a combination of quantitative and qualitative research methods is used to comprehensively understand and cover the implementation process from different perspectives. Different Questionnaires (n=401; n=46) and administrative data were analyzed using descriptive statistics, while semi-structured interviews with the GeMuKi recruiting staff (n=6), multiprofessional healthcare providers (n=13) and pregnant women (n=12) as well as other text material like observation protocols (n=29) and internal project documents (n=99) were analyzed using qualitative content analysis. Results: Check-up visits in routine prenatal care proved to be a suitable setting for focusing on lifestyle topics. Pregnant women as well as healthcare providers expressed a need to address lifestyle topics. Intrinsic motivation and personal interest in the topics of nutrition, exercise, and overweight/obesity acted as facilitators for the implementation as they were crucial for the active participation of healthcare providers. A flexible distribution of tasks between gynecologists and medical assistants also facilitated the implementation. Lack of time due to many other tasks related to routine care was a key barrier to the implementation. Not all intervention components were implemented as intended. For instance, while the selection of counseling topics and the combination of joint goal-setting, feedback discussions, and push notifications were well received, other measures such as the conversational approach MI were inconsistently implemented by healthcare providers. The evaluation revealed information gaps regarding gestational weight gain and demonstrated much room for improvement in the inter-professional cooperation between gynecologists and midwives. Conclusion: The results provide valuable guidance as to how healthcare services in prenatal care might be reorganized, with the aim of reducing the future burden of chronic diseases for both mothers and children. For a successful translation into routine care, adaptations of specific intervention components as well as strategies to improve inter-professional cooperation should be discussed. In light of the increasing need for preventive action to reduce risks of lifestyle-related diseases, the opportunities and high accessibility offered by routine check-ups in community-based settings should not be missed.

  • Publication . Doctoral thesis . 2022
    Open Access German
    Authors: 
    Schließauf, Henrik;
    Country: Germany

    Symplectic twist maps already appeared in the works of Poincaré. They emerge naturally as discretizations of certain low-dimensional Hamiltonian systems and offer a nice handle for studying their dynamics. The associated theory had experienced a tremendous boost from the discoveries made by Kolmogorow, Arnold and Moser in the 1960's, and by Aubry and Mather in the 1980's. In this thesis, we will substantiate the usefulness of studying twist maps also in non-periodic and low regularity settings, that is in situations where the classical results are not applicable. In particular, we will concentrate on perturbative methods for near-integrable systems. One typical feature of such systems is the existence of ``approximate first integrals'', so called adiabatic invariants, and their presence usually has strong consequences for the dynamics. Here, we derive growth rates for a large class of non-periodic twist maps depending on the regularity assumptions. As an application, the Fermi-Ulam ping-pong is considered, where the possible growth in velocity is linked to the number of bounded derivatives of the forcing function. Moreover, in systems with adiabatic invariants and almost periodic time-dependence the underlying compact structure enables one to use a generalization of Poincaré's recurrence theorem. By harnessing this fact, we prove that in such systems the set of initial condition leading to escaping orbits typically has measure zero. This is again demonstrated using the ping-pong model. Other applications are found in the Littlewood boundedness problem, where we consider a periodically forced piecewise linear oscillator together with its discontinuous limit case, and also a super-linear oscillator with an almost periodic forcing term. These systems are given by differential equations and thus the mentioned results imply also the Poisson stability of almost every solution. Even in the periodic case, these insights represent valuable contributions due to the low regularity assumptions necessary to obtain them.

  • Open Access
    Authors: 
    Speer, Lothar;
    Publisher: Böhlau Verlag
    Country: Germany

    „Die Entstehung der Ringpartnerschaft der Städte Esch-sur-Alzette, Lille, Lüttich, Köln, Rotterdam und Turin vom 3. Juli 1958. Im Rahmen des Citizen Science Projekts „KölnErforschen – Europa in Köln-Köln in Europa“ untersuchte der Autor die Entstehung der Ringpartnerschaft der Stadt Köln vom 3.7.1958 – bisher ein Desiderat in der historischen Forschung. Anfangs der 1950er Jahre lassen sich bilaterale Verbindungen Kölns zu Turin, Lüttich, Lille und Rotterdam feststellen. 1954 gingen von Lille erste Bemühungen aus, eine Ringpartnerschaft mit Lüttich, Köln und Turin zu begründen. Der Gedanke der Völkerverständigung bildete das Leitmotiv in diesem Prozess. Durch politische Veränderungen in Lille kam der Prozess zum Erliegen, nicht aber die bilateralen Beziehungen Kölns zu diesen Städten. Im Zusammenhang mit der Gründung der EWG griff die Stadt Lüttich die Idee der Ringpartnerschaft wieder auf und initiierte eine Partnerschaft mit je einer Stadt aus der neu gegründeten EWG. Der bisher angedachte Ring wurde erweitert um Rotterdam und Esch-sur-Alzette. Zum Auftakt des IV. Generalkongresses des Rates der Gemeinden Europas (RGE) wurde in Lüttich am 3.7.1958 der Verschwisterungseid unterzeichnet.

  • Publication . Other literature type . 2022
    Open Access English
    Authors: 
    Borgmann, Diba;
    Country: Germany
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  • Open Access German
    Authors: 
    Selenz, Carolin;
    Country: Germany

    Lung cancer represents the most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Approximately 80 % of patients are non-small-cell lung cancer (NSCLC) cases. These can be further subcategorised depending on the histological and molecular composition of tumours. Oncogene-dependent NSCLC comprise a major subtype of NSCLC that harbours oncogenic driver mutations, for example in the epidermal growth factor receptor tyrosine kinase. These mutations induce aberrant activation of cell signalling, thus facilitating uncontrolled cell growth and tumorigenesis. Targeted therapy represents one essential treatment strategy that is well-established in the clinic for oncogene-driven NSCLC, for example in the form of tyrosine kinase inhibitors. Other therapy approaches, such as anti-angiogenic compounds, aim to modulate the tumour microenvironment (TME) to become less advantageous to tumour cells, thus inhibiting cancer progression. Unfortunately, highly adaptive tumour cells and the dynamic nature of the TME limit the benefits of targeted therapy due to the emergence of resistance mechanisms or suppression of immune response. Therefore, it is essential to elucidate the effects of targeted therapy on the TME to increase our understanding of the underlying mechanisms responsible for the escape of immunosurveillance and tumour progression. This thesis investigated the impact of targeted therapy on cancer cells and the TME in oncogene-driven NSCLC and evaluated the remaining difficulties associated with this therapy approach, which illustrate the need for optimisation of existing therapy options or development of alternative treatment strategies.

  • Open Access German
    Authors: 
    Thelen, Lavinia;
    Country: Germany

    Academic underachievement affects many adolescents and is defined as a notable discrepancy between actual and expected achievement, given the student's cognitive ability level. A significant percentage of adolescents suffer from both academic underachievement and mental disorders, putting them at risk for negative psychosocial development. However, there are few treatments available focussing on these adolescents. The present doctoral thesis evaluated the efficacy of the treatment program "SELBST – achievement problems" in a randomised controlled trial (RCT). Furthermore, the added benefit of a specifically designed smartphone app to improve therapy transfer was investigated. Methods: The psychometric properties of the primary outcome, the Academic Problems Checklist, were analysed. A clinically referred sample of n = 60 adolescents aged 11-18 years was randomised into either the experimental group, receiving weekly cognitive behavioural therapy based on the "SELBST – achievement problems" treatment manual including a therapy smartphone app or into the control group, receiving treatment as usual. Results: The revised version of the Academic Problems Checklist consists of a 17-item, semi�structured clinical interview for adolescents, parents, and teachers. The analysis of the psychometric properties of the APC showed it is a short, reliable, and valid instrument for assessing academic underachievement of adolescents with mental disorders using a multi�informant approach. The RCT showed for both groups clinically relevant improvements on the primary outcome of academic underachievement. For the teacher-rated academic underachievement, a statistical superiority of the treatment group compared to the control group was found during the follow-up phase. The treatment group showed significant improvements regarding their grade point average compared to the control group. Statistical superiority of the treatment group was found for the individual problemlist measuring individual academic underachievement problems with large effects in the adolescent and parent rating. Mental health problems improved in both groups, however, there was no statistical superiority of either group. These effects remained largely stable during the follow-up period. The smartphone app was well accepted by the adolescents, however, it showed no statistically significant additional benefit compared to the standard SELBST-treatment. Conclusion: In summary, improvements were found for academic underachievement and mental problems. The treatment satisfaction was high, but the smartphone app provided no significant additional benefit. The study's limitations included the small sample size, the substantial dropout rate in the experimental group, and the technical challenges encountered implementing a smartphone app

  • Open Access English
    Authors: 
    Kamga Kapchoup, Michelle Vanessa;
    Country: Germany

    Cardiovascular diseases can be congenital or acquired and represent the main cause of mortality worldwide. Long QT Syndrome 3 (LQTS3) and Brugada Syndrome (BrS) are congenital channelopathies mostly caused by SCN5A mutation. Both diseases have been associated with gain- and loss-of-function of the channel respectively. However, some mutations display an overlapping phenotype between the two diseases, rendering the diagnostic as well as the therapy of the diseases challenging. The use of disease-specific pluripotent stem cells to develop disease models has enabled the research of pathogenic pathways related to diseases and the search for new treatments. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a platform that has allowed advancement in personalized therapy circumventing the problem of genotype-phenotype differences existing between individuals. This study aimed to characterize both disease phenotypes at a cellular, molecular, and functional level. For this purpose, we used different stages of cardiomyocytes maturation to perform our experiments. The use of cardiomyocytes at distinct time points of maturation revealed that a certain threshold of CMs maturity is necessary for the evaluation of disease phenotypes during in-vitro experiments. At the cellular level, we observed that Cx43 distribution within the intercalated discs is not disturbed in disease models compared to the control. However, numerous genes coding for proteins involved in the mechanisms of ECC and cardiomyocytes' contractility were dysregulated. The molecular data as well as the patch-clamp analysis allow us to hypothesize that V240M mutation could be associated with a mixed phenotype between LQTS3 and BrS, and that the Q646Rfs*5 mutation is associated with BrS as described by prior studies. The calcium imaging showed that in the two disease models, the Ca2+ transient is impaired, and the time corresponding to 50% of Ca2+ extrusion is prolonged.

  • Open Access German
    Authors: 
    Gnade, Benjamin;
    Country: Germany

    Die Dissertation »Relative Chronologie der Rheinzaberner Reliefsigillata. Seriation, Punzen- und Stilanalyse« stand an der Universität zu Köln, Philosophische Fakultät – Archäologie der Römischen Provinzen, unter der Betreuung von Prof. Dr. Eckhard Deschler-Erb und wurde zum 14. Oktober 2020 eingereicht und am 27. Januar 2021 mündlich geprüft. Sowohl die Abfolge von H. Ricken als auch die bisherigen Computerseriationsergebnisse zur Rheinzaberner Relief-TS von H. Bernhard, F.-K. Bittner und A. Mees lassen sich im Wesentlichen bestätigen, da bei den letzteren drei Arbeiten die verwendeten Formeln von Yule und Jaccard auf der Mengenlehre beruhen und die Programme über die Punzenschnittmengen je nachdem die Nähe oder Distanz von den Waren-Punzensets anzeigen können. Im Rahmen einer manuell durchgeführten Seriation wurden Punzenlisten erstellt (Tab. 1-82), wonach die jeweiligen Punzenschnittmengen und Punzengruppen herleitbar waren. Diese Punzengruppen ließen sich in weiteren Arbeitsschritten vor allem über stilprägende Punzen im Rahmen der Stilanalyse sowie im Abgleich mit absolutchronologisch fassbaren Waren insbesondere aus Straten von Zerstörungshorizonten zu den Stilgruppen 1-5 mit insgesamt 11 Stilgruppen definieren und in Bezug zu den Filialen setzen (Beil. 1). Anm.: Die Punzenlisten (Tab. 1-82) sind als eigene Datei aus dem PDF extrahierbar. Mit dieser Datei bzw. den Einzeldateien lassen sich Seriationsarbeiten als »Rheinzabern gesamt«, nach einzelnen Stilgruppen (z. B. Stilgruppe 1 mit Tab. 1-16), Töpfern oder Waren/Serien mit entsprechenden Schlagworten wie beispielsweise »Cob« (Cobnertus) durchführen. Für einen beidseitigen Ausdruck der Arbeit mit üblicher Seitenzahlordnung ist die Leerseite – PDF S. 11 – zu entfernen.

  • Open Access German
    Authors: 
    Bresgen, Charlotte;
    Country: Germany

    Die Retina mit ihrer physiologischen Abgrenzung durch die Blut-Retina-Schranke bildet ein sogenanntes immunprivilegiertes Organ, dessen einzige Immunzellen die Mikroglia darstellen. Diese Mikrogliazellen nehmen daher eine entscheidende Rolle bei der Schädigung und Degeneration der Netzhaut durch inflammatorische Prozesse sowohl bei hereditären als auch bei erworbenen Erkrankungen der Retina ein. Hierbei steht der Übergang der physiologisch ramifizierten Mikroglia in eine aktivierte, sogenannte reaktive Form und die dadurch folgende fehlregulierte Immunantwort mit Hyperinflammation und neuronaler Degeneration im Vordergrund. Da dies über einen gewissen Zeitraum hin zu einer Sehstörung im Rahmen der unterschiedlichen Erkrankungen führt, rückt die Mikroglia als möglicher Therapieansatz immer weiter in den Fokus der Betrachtung. Ziel der aktuellen Forschung ist es, eine möglichst potente Substanz für diese Zielsetzung zu finden. In dieser Arbeit wurde Pomalidomid, welches bereits in der Therapie des multiplen Myeloms eine immunmodulatorische Wirkung in der Tumorumgebung zeigt, hinsichtlich seiner immunmodulatorischen Effekte auf die retinale Mikroglia untersucht. Hierzu erfolgte die Betrachtung der Toxizität, der Genexpression und der Veränderungen der Morphologie in BV-2 Mikrogliazellen unter Einsatz von Pomalidomid sowie dessen Einfluss auf deren Effektorfunktionen wie Phagozytoseverhalten, Migrationsverhalten und Veränderungen der NO- Produktion. Zusätzlich wurde der Einfluss von Pomalidomid mittels konditionierten Mediums aus BV-2 Mikrogliazellen auf die Genexpression sowie die Morphologie von ARPE-19 Pigmentepithelzellen und dessen Einfluss auf das Apoptoseverhalten von ARPE-19 Pigmentepithelzellen sowie 661W Photorezeptorzellen untersucht. Es konnte gezeigt werden, dass der immunmodulatorische Effekt von Pomalidomid, der für Makrophagen des peripheren Bluts eindeutig beschrieben wurde, in der retinalen Mikroglia kaum vorhanden ist. Ein signifikanter Effekt durch Pomalidomid konnte ausschließlich in der Morphologie und dem Migrationsverhalten der BV-2 Mikrogliazellen sowie in der Genexpression durch ARPE-19 Zellen gezeigt werden. in der Untersuchung der Phagozytoserate zeigte sich eine Tendenz zur Reduktion dieser durch Pomalidomid. In allen weiteren Experimenten zeigte Pomalidomid keinen Einfluss. Aufgrund der unzureichenden antiinflammatorisch-immunmodulatorischen Wirkung von Pomalidomid auf die retinale Mikroglia sowie der verhältnismäßig hohen Toxizität der Substanz ist diese für einen Einsatz in der Therapie retinal- degenerativer Erkrankungen nicht vielversprechend, sodass der Fokus zukünftiger Forschung auf der Untersuchung alternativer Substanzen liegen sollte.

  • Open Access English
    Authors: 
    Tulli, Susanna;
    Country: Germany
  • Open Access German
    Authors: 
    Lorenz, Laura;
    Country: Germany

    Background: Overweight and obesity are major health challenges and risk factors for subsequent diseases in both children and adults. There is an urgent need for effective preventive interventions and suitable settings in which they can be provided to a wide public. Research on perinatal programming indicates that maternal lifestyle during pregnancy influences the risks for pregnancy and birth complications, as well as the risks of obesity and chronic disease in children in the long term. There is evidence that lifestyle counseling interventions during pregnancy can be effective in improving maternal and infant health outcomes. In Germany, however, lifestyle topics are not consistently discussed during regular prenatal care. Methods: The GeMuKi intervention enhances prenatal care by embedding lifestyle counseling in routine checkup visits during pregnancy in different regions of the southern German state Baden-Württemberg. Supported by a novel shared telehealth platform, gynecologists and midwives provide lifestyle counseling to pregnant women using motivational interviewing (MI) techniques. Alongside the effectiveness trial, a process evaluation is conducted to identify factors that facilitate or inhibit the implementation of the intervention and to investigate the extent to which the intervention is implemented as intended. The cumulative dissertation addresses these objectives by providing three studies (Studies I-III) as well as supplementary data that analyzed the implementation process at different stages. Guided by different theoretical frameworks, a combination of quantitative and qualitative research methods is used to comprehensively understand and cover the implementation process from different perspectives. Different Questionnaires (n=401; n=46) and administrative data were analyzed using descriptive statistics, while semi-structured interviews with the GeMuKi recruiting staff (n=6), multiprofessional healthcare providers (n=13) and pregnant women (n=12) as well as other text material like observation protocols (n=29) and internal project documents (n=99) were analyzed using qualitative content analysis. Results: Check-up visits in routine prenatal care proved to be a suitable setting for focusing on lifestyle topics. Pregnant women as well as healthcare providers expressed a need to address lifestyle topics. Intrinsic motivation and personal interest in the topics of nutrition, exercise, and overweight/obesity acted as facilitators for the implementation as they were crucial for the active participation of healthcare providers. A flexible distribution of tasks between gynecologists and medical assistants also facilitated the implementation. Lack of time due to many other tasks related to routine care was a key barrier to the implementation. Not all intervention components were implemented as intended. For instance, while the selection of counseling topics and the combination of joint goal-setting, feedback discussions, and push notifications were well received, other measures such as the conversational approach MI were inconsistently implemented by healthcare providers. The evaluation revealed information gaps regarding gestational weight gain and demonstrated much room for improvement in the inter-professional cooperation between gynecologists and midwives. Conclusion: The results provide valuable guidance as to how healthcare services in prenatal care might be reorganized, with the aim of reducing the future burden of chronic diseases for both mothers and children. For a successful translation into routine care, adaptations of specific intervention components as well as strategies to improve inter-professional cooperation should be discussed. In light of the increasing need for preventive action to reduce risks of lifestyle-related diseases, the opportunities and high accessibility offered by routine check-ups in community-based settings should not be missed.

  • Publication . Doctoral thesis . 2022
    Open Access German
    Authors: 
    Schließauf, Henrik;
    Country: Germany

    Symplectic twist maps already appeared in the works of Poincaré. They emerge naturally as discretizations of certain low-dimensional Hamiltonian systems and offer a nice handle for studying their dynamics. The associated theory had experienced a tremendous boost from the discoveries made by Kolmogorow, Arnold and Moser in the 1960's, and by Aubry and Mather in the 1980's. In this thesis, we will substantiate the usefulness of studying twist maps also in non-periodic and low regularity settings, that is in situations where the classical results are not applicable. In particular, we will concentrate on perturbative methods for near-integrable systems. One typical feature of such systems is the existence of ``approximate first integrals'', so called adiabatic invariants, and their presence usually has strong consequences for the dynamics. Here, we derive growth rates for a large class of non-periodic twist maps depending on the regularity assumptions. As an application, the Fermi-Ulam ping-pong is considered, where the possible growth in velocity is linked to the number of bounded derivatives of the forcing function. Moreover, in systems with adiabatic invariants and almost periodic time-dependence the underlying compact structure enables one to use a generalization of Poincaré's recurrence theorem. By harnessing this fact, we prove that in such systems the set of initial condition leading to escaping orbits typically has measure zero. This is again demonstrated using the ping-pong model. Other applications are found in the Littlewood boundedness problem, where we consider a periodically forced piecewise linear oscillator together with its discontinuous limit case, and also a super-linear oscillator with an almost periodic forcing term. These systems are given by differential equations and thus the mentioned results imply also the Poisson stability of almost every solution. Even in the periodic case, these insights represent valuable contributions due to the low regularity assumptions necessary to obtain them.

  • Open Access
    Authors: 
    Speer, Lothar;
    Publisher: Böhlau Verlag
    Country: Germany

    „Die Entstehung der Ringpartnerschaft der Städte Esch-sur-Alzette, Lille, Lüttich, Köln, Rotterdam und Turin vom 3. Juli 1958. Im Rahmen des Citizen Science Projekts „KölnErforschen – Europa in Köln-Köln in Europa“ untersuchte der Autor die Entstehung der Ringpartnerschaft der Stadt Köln vom 3.7.1958 – bisher ein Desiderat in der historischen Forschung. Anfangs der 1950er Jahre lassen sich bilaterale Verbindungen Kölns zu Turin, Lüttich, Lille und Rotterdam feststellen. 1954 gingen von Lille erste Bemühungen aus, eine Ringpartnerschaft mit Lüttich, Köln und Turin zu begründen. Der Gedanke der Völkerverständigung bildete das Leitmotiv in diesem Prozess. Durch politische Veränderungen in Lille kam der Prozess zum Erliegen, nicht aber die bilateralen Beziehungen Kölns zu diesen Städten. Im Zusammenhang mit der Gründung der EWG griff die Stadt Lüttich die Idee der Ringpartnerschaft wieder auf und initiierte eine Partnerschaft mit je einer Stadt aus der neu gegründeten EWG. Der bisher angedachte Ring wurde erweitert um Rotterdam und Esch-sur-Alzette. Zum Auftakt des IV. Generalkongresses des Rates der Gemeinden Europas (RGE) wurde in Lüttich am 3.7.1958 der Verschwisterungseid unterzeichnet.

  • Publication . Other literature type . 2022
    Open Access English
    Authors: 
    Borgmann, Diba;
    Country: Germany
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