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Zwischen Elternrolle und Gesundheit: Lebensbereiche von Eltern mit vs. ohne behinderte Kinder in Deutschland
No full textAnti-inflammatory Effects of alpha1-Antitrypsin via Neutralization of Heme Toxicity in Human Endothelial Cells and Neutrophils
Full text linkAcquisition of innate B cell properties and generation of autoreactive IgA antibodies by follicular B cells during homeostatic proliferation
Full text linkThe physiologic process of homeostatic proliferation serves to restore the pool of peripheral lymphocytes in response to lymphopenia. However, functional changes in B cell responses during homeostatic proliferation are still only insufficiently characterized. Mature peripheral B cells consist of functionally distinct B cell subsets, such as adaptive follicular B cells (FoBs) and the innate B cell subsets, marginal zone B cells (MZBs) and B1a B cells. During homeostatic proliferation, B cells undergo antigen-independent clonal expansion and differentiation into antibody-producing plasma cells (PCs). However, it is still largely unknown which B cell lineages are involved in the formation of antibodies in response to lymphopenia and what functional properties these antibodies have. Employing adoptive transfer of different mature B cell subsets into lymphopenic Rag2-/- hosts, we here show that not only innate B cells - MZBs and B1a cells - but also adaptive FoBs were capable to differentiate into PCs and to produce IgM and class-switched IgA serum antibodies in a T cell-independent fashion during homeostatic proliferation. In light of the poor reactivity of FoBs to innate stimulation in vitro, the observed high expansion capacity of FoBs, their sustained repopulation of lymphoid and intestinal organs and their particularly prominent ability to induce class-switched auto-/polyreactive IgA antibodies in this antigen- and T cell-independent system was rather unexpected. These properties, which are more typical for innate B cells, were associated with a striking plasticity of FoBs that transdifferentiate into MZB-like cells under lymphopenic conditions. Together, our study indicates that the reconstitution of antibodies in response to lymphopenia-induced homeostatic B cell proliferation is mainly elicited by innate MZB-like B cell responses via antigen- and T cell-independent pathways resulting in the selection of autoreactive IgA antibodies. In addition, our data point to the pathogenic potential of the conversion of conventional adaptive B cells, which are the most common population of mature B cells, into innate-like B cells and the production of autoreactive IgA antibodies during homeostatic proliferation. This process could also manifest as clinical complication of therapy-induced lymphopenia in the context of transplantation and cancer in human patients
DFG Abschlussbericht zur Projektnummer 250170148
No full textZusammenfassung: Polytrauma, das gleichzeitige Auftreten schwerer Verletzungen an verschiedenen Körperstellen, führt im Durchschnitt zu einem Verlust von 32 Lebensjahren und ist die Haupttodesursache für Menschen unter 50 Jahren. Überlebende leiden oft langfristig unter Behinderungen, wobei nur etwa die Hälfte nach zwei Jahren wieder arbeitsfähig ist. Frakturen und Trauma-Hämorrhagie (TH) treten häufig gemeinsam auf, wobei unkontrollierter Blutverlust die zweithäufigste Todesursache darstellt. Herausforderungen für PolytraumapatientInnen manifestieren sich in gestörter Frakturheilung aufgrund von Gewebsminderperfusion und einer beeinträchtigten inflammatorischen Frakturheilungs-phase. Besonders relevant ist der Einfluss von Trauma-Hämorrhagie auf die Frakturheilung bei über 70-Jährigen, die oft durch Stürze lange Röhrenknochen brechen. Osteoporose erhöht das Pseudarthroserisiko, was mit erhöhter Morbidität und Mortalität verbunden ist. In der ersten Förderphase wurden die Auswirkungen von schwerem Blutverlust auf die Frakturheilung und die zugrundeliegenden Signalwege untersucht. Ergebnisse zeigten, dass die Frakturheilung nach TH und Fraktur beeinträchtigt war, manifestiert in biomechanischen, histologischen und Signalwegänderungen. In der zweiten Förderphase wurde der Einfluss von Alter und Alkoholintoxikation auf die Frakturheilung und das regenerative Potenzial untersucht. Mäuse wurden in verschiedene Alters- und Behandlungsgruppen aufgeteilt. Fortgeschrittenes Alter führte zu geringerer Knochenmineralisierung und reduzierter Osteoklastenanzahl im Frakturspalt. Ältere Mäuse zeigten erhöhte Anfälligkeit für Organschäden in Leber und Lunge nach Trauma. Alkohol hatte entzündungshemmende Effekte, besonders bei jungen Mäusen, wobei diverse molekulare Mechanismen beeinflusst wurden. Altersabhängige Veränderungen der Immunantwort und verstärkte Entzündungsreaktionen wurden beobachtet. Signalweganalysen zeigten, dass NF-kappaB und Wnt/β-Catenin in Leber und Lunge durch Alkohol beeinflusst wurden. Reduzierte Aktivität von zirkulierenden Neutrophilen nach Alkoholexposition könnte die Heilung beeinträchtigen. Die Ergebnisse bieten Einblicke in die komplexen Wechselwirkungen zwischen Trauma, Hämorrhagie, Alter und Alkohol auf die Frakturheilung, Organregeneration und die zugrundeliegenden Mechanismen auf zellulärer und molekularer Ebene.Summary: Polytrauma, the simultaneous occurrence of severe injuries at different body sites, on average leads to a loss of 32 life years and is the primary cause of death for individuals under 50 years of age. Survivors often suffer long-term disabilities, with only about half being able to return to work after two years. Fractures and trauma-hemorrhage (TH) frequently occur together, with uncontrolled blood loss being the second most common cause of death. Challenges for polytrauma patients manifest in disrupted fracture healing due to tissue hypoperfusion and impaired inflammatory phase of fracture healing. The influence of trauma-hemorrhage on fracture healing is particularly relevant in individuals over 70 years old, who often experience long bone fractures from falls. Osteoporosis increases the risk of pseudarthrosis, associated with higher morbidity and mortality. The project investigates the impact of TH on fracture healing in young and old mice with and without alcohol intoxication. In the first funding phase, the effects of severe blood loss on fracture healing and underlying signaling pathways were examined. Results indicated impaired fracture healing after TH and fracture in male mice, manifested in biomechanical, histological, and signaling changes. In the second funding phase, the influence of age and alcohol intoxication on fracture healing and regenerative potential was explored. Mice were divided into different age and treatment groups. Advanced age led to lower bone mineralization and a reduced number of osteoclasts in the fracture gap. Older mice exhibited increased susceptibility to organ damage in the liver and lungs after trauma. Alcohol had anti-inflammatory effects, especially in young mice, influencing various molecular mechanisms. Age-dependent changes in immune response and heightened inflammatory reactions were observed. Pathway analyses revealed that NF-kappaB and Wnt/β-Catenin in the liver and lungs were influenced by alcohol. Reduced activity of circulating neutrophils and monocytes after alcohol exposure could impact healing. The results provide comprehensive insights into the complex interactions among trauma, hemorrhage, age, and alcohol on fracture healing, organ regeneration, and the underlying mechanisms at the cellular and molecular levels
Einhaltung der Antibiotikaleitlinien in vier Krankenhäusern der Grund- und Regelversorgung in Deutschland
Full text linkUnerwünschte Arzneimittelwirkungen in der Gerontopsychiatrie: eine retrospektive Kohortenstudie über einen Zeitraum von 6 Jahren
Full text linkDie Enquete - Rückblick und kritische Reflexion auf die zurückliegenden 50 Jahre: Referat von Hermann Elgeti auf dem Fachtag des Paritätischen Hessen zu 50 Jahren Psychiatrie-Enquete am 21.10.2025 in Frankfurt am Main
Full text linkDisconnect between advanced diabetes technology and psychological well-being among young people: a cross-sectional analysis
Full text linkIntroduction Diabetes technologies may improve glycemic control and psychological well-being among adolescents and young adults (AYA) with type 1 diabetes. This cross-sectional study examines perceptions of automated insulin dosing (AID) systems and their association with glycemic and psychological outcomes compared with multiple daily insulin injections (MDI) and continuous subcutaneous insulin infusion (CSII). Research design and methods Participants were recruited from the largest diabetes camp for AYA in Germany. A total of 151 participants (70% female, mean age 20.7±2.9 years, 33% AID users) completed a questionnaire that included self-reported glycated hemoglobin A1c (HbA1c), global health status, emotional well-being (WHO-5), Generalized anxiety (GAD-7) and diabetes distress (PAID-5). AID users also rated their experiences with the system. Results AID users reported significantly lower HbA1c levels (7.3±1.0%) than CSII users (7.5±1.1%) and MDI users (8.4±2.0%, p=0.003). Approximately 75% of AID users viewed their current system as an improvement over previous therapy, reporting greater ease (84%), comfort (82%) and safety (80%). They reported higher treatment satisfaction than CSII users (p=0.044) and lower diabetes burden than MDI users (p=0.044) after controlling for age and gender. Treatment groups did not differ in well-being or anxiety. Better global health status was associated with the absence of other chronic health conditions (p=0.024), greater well-being (WHO-5; p<0.001), lower HbA1c (p=0.038) and fewer anxiety symptoms (GAD-7, p=0.007). Despite these positive indicators, a substantial proportion of participants reported symptoms of depression (18%), anxiety (30%), and diabetes distress (39%). Conclusions AID systems were associated with improved glycemic control and high satisfaction among AYA. However, psychological distress remained prevalent across all treatment modalities, underscoring a discrepancy between metabolic benefits and persistent mental health challenges. These findings highlight the need to integrate psychological support alongside technological advances in the care of AYA living with diabetes