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Primärstabilität von PEEK Fadenankern bei Bankart-Läsionen im Primär- und Revisionsfall nach Überbohrung und Implantation eines Fadenankers eines größeren Durchmessers
Get PDFDie Rolle des NLRP3-Inflammasoms in der T-Zell-Differenzierung in einem T-Zell-basierten Transferkolitismodell
Get PDFPsychosoziale Versorgung in der frühen Kindheit
Get PDFDie Coronapandemie hat dazu geführt, dass das Wohlbefinden und die Gesundheit von Kindern und Familien vermehrt als wertvolle und nicht selbstverständliche Güter diskutiert wurden. Wenngleich die Bedürfnisse von Kindern und ihren Familien erst spät in der Pandemie stärker in den Fokus gerückt sind, hat die Bedeutung psychischer und psychosozialer Belastungen sowie geeigneter Versorgungsangebote neue Brisanz erlangt. Bereits vor den pandemischen Bedingungen wurden im Kontext der Frühen Hilfen die psychosoziale Gesundheit und Versorgung in der frühen Kindheit gefördert und erforscht. Der Schwerpunkt der Arbeit liegt auf den Herausforderungen und Problemlagen, in denen sich Familien befinden können, und auf der Möglichkeit, von (Frühen) Hilfen Gebrauch zu machen
Signaling mechanisms in the regulation of cardiomyocyte cohesion in arrhythmogenic cardiomyopathy
Get PDFArrhythmogenic cardiomyopathy (AC) is a genetic disease, leading to fibro-fatty replacement of the myocardium, which untreated can lead to sudden cardiac death. One of the underlying mechanisms of AC is loss of cardiomyocyte cohesion due to mutations in genes coding for proteins of the intercalated disc (ICD), such as plakoglobin (PG), desmoplakin (DP), plakophilin 2 (PKP2) or desmoglein 2 (DSG2). In this work, several, in part interdependent mechanisms that stabilize cardiomyocyte cohesion were investigated. The Jup-/- murine AC model (Jup being the gene coding for PG), which shows arrhythmia and fibrosis was used in this work. Jup-/- mice had increased epidermal growth factor receptor (EGFR) levels and p38 mitogen activated protein kinase (p38MAPK) activation. EGFR levels were also increased in heart lysates obtained from Pkp2-/- mice, representing another AC model. Furthermore, EGFR levels were increased in AC patients’ hearts compared to dilated cardiomyopathy hearts, and EGFR localization at the ICD was found in AC patients’ hearts.
Adrenergic signaling, protein kinase C (PKC) activation, p38MAPK, EGFR, SRC or A Disintegrin and Metalloprotease 17 (ADAM17) inhibition led to positive adhesiotropy in HL-1 cardiomyocytes and wildtype mice, and (apart from adrenergic signaling) also in Jup-/- mice.
Positive adhesiotropy in HL-1 cardiomyocytes upon adrenergic signaling, PKC activation or p38MAPK inhibition was extracellular signal regulated kinase 1/2 (ERK1/2)-dependent under basal conditions but not upon hyperadhesion. In all cases but PKC activation, positive adhesiotropy in HL-1 cardiomyocytes was paralleled by an ERK1/2-dependent enhanced DSG2 localization at the membrane. DP localization at the membrane was enhanced upon inhibition of EGFR, SRC or ADAM17. In wildtype hearts, enhanced DSG2 and DP staining width at the ICD upon EGFR or SRC inhibition was observed, whereas in Jup-/- hearts, only DSG2 was enhanced at the ICD upon EGFR or SRC inhibition. Adrenergic signaling, PKC activation or p38MAPK inhibition-mediated positive adhesiotropy was dependent on the expression of PG, DP and DSG2 as well as ERK1/2 activity. Positive adhesiotropy upon EGFR or SRC inhibition was dependent on the expression of DP, but still effective upon Dsg2 knockdown. In contrast, positive adhesiotropy upon ADAM17 inhibition was dependent on the expression of Dsg2. EGFR inhibition activated the Rho associated kinase (ROCK), and positive adhesiotropy upon EGFR inhibition was achieved through ROCK-mediated enhanced desmosomal assembly.
Together, these findings might not only pave the way to find new treatment options for AC by stabilizing cardiomyocyte cohesion, but could also be suited for other diseases with dysfunctional desmosomes
Retrospektive Analyse der MRT-geführten Vakuumbiopsien der Brust im Zeitraum 2013-2016 an einem universitären Brustzentrum
Get PDFAdding a piece to the puzzle of Latin American blood donors and the potential risk of Trypanosoma cruzi transmission in Germany
Get PDFIntroduction: Chagas disease (CD) is caused by the Trypanosoma cruzi (T. cruzi) infection and has become a global health concern due to population mobility, as well as non-vectorial transmission routes. Several countries outside Latin America (LA) have reported transfusion-associated transmission, but equivalent studies in Germany are lacking. This study aims to collect first data on the risk of transfusion associated transmission as well as LA blood donors originating from CD endemic countries in Germany.
Materials and methods: A total of 305 blood donors who were assumed to be at risk for T. cruzi infection were retrospectively (267) as well as prospectively (38) selected at German blood donation sites in Bavaria and Berlin, and all retrospectively as well as 27 prospectively selected were serologically screened. Prospective study subjects additionally filled out a questionnaire.
Results: All samples tested seronegative for T. cuzi specific antibodies. Prospectively enrolled study subjects all had high socio-economic status including good education. Knowledge regarding CD was limited but willingness to donate frequently was high. Blood donation rates from donors born in LA countries seem to increase from 2015.
Discussion: Although no transfusion associated T. cruzi infection has been documented in Germany, it has likely already happened unnoticed, or will do in the near future. Performing risk-adapted serology-based blood donor screenings in Germany could avoid transfusion-associated transmission events as well as contribute to active case detection. Moreover, larger, and ongoing studies are needed to increase the evidence base as well as end the neglect of CD in Germany