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Real-time fMRT Neurofeedback als add-on Therapie bei Patienten mit Depressionen
Get PDFEs handelt sich um eine realtime fMRT Neurofeedback-Studie an Patienten mit Depressionen. Ziel war eine Erhöhung der Konnektivität zwischen Inselrinde und dorsolateralem präfrontalen Kortex. Es wurden die Ergebnisse zwischen einer depressiven Patienten- und einer gesunden Probandengruppe verglichen
Retrospektive Analyse klinischer Verläufe von pädiatrischen Infektionen mit dem Respiratorischen Synzytial-Virus (RSV)
Get PDFPräoperative Chemotherapie bei lokal fortgeschrittenen und grenzwertig resektablen Pankreastumoren
Get PDFGeschlechtsspezifische Auswirkungen von „low-carbohydrate-high-fat“ Diäten – Skelettmuskulatur, Triacylgyceridmetabolismus und Veränderungen der somatotropen Achse
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Zeit bis zur Therapieeinleitung und strukturierte Nachsorge als prognostische Variablen bei Patienten mit Pankreaskarzinom
Get PDFFunctional replacement of the T-cell receptor in primary human T cells for the treatment of refractory adenovirus infections
Get PDFAdenoviral (AdV) infections can cause life-threatening infections, especially in paediatric patients, following haematopoietic stem cell transplantations due to transient lacking T-cell immunity. AdV hexon-protein derived peptide LTDLGQNLLY (LTDL)-specific T cells have proven to induce cross-reactive protection, thus being highly attractive targets for adoptive T-cell transfer (ACT). The aim of this project was to redirect primary human T cells by replacing endogenous T-cell receptors (TCRs) with a LTDL-specific TCR using CRISPR/Cas9 technology. Simultaneous knock out (KO) of the complete endogenous TCR will prevent harmful TCR mispairing and alloreactivity.
Stable and highly efficient genetic KO of the endogenous TCR in primary human T cells was confirmed on protein as well as on genetic level. TCR-KO T cells are phenotypically very similar to unedited cells but fail to produce IFNγ upon stimulation, thereby functionally demonstrating TCR disruption. Whole-genome sequencing of CRISPR/Cas9-edited cells revealed no significant increase of mutations, although analysis of predicted gRNA-dependent off-target sites revealed two putative off-target mutations for the gRNA targeting TCR β chain. Functional analysis of two novel LTDL-specific TCRs revealed strong, target-specific effector functions for both of them. CRISPR/Cas9-mediated knock in (KI) using non-viral delivery of one protective LTDL-specific TCR rescued IFNγ production upon LTDL-specific stimulation and demonstrated LTDL-specific cytotoxic capacity, cytokine secretion and proliferation. The targeted and in-frame integration into the endogenous TCR α chain was combined with an additional KO of the β chain to prevent TCR mispairing and enables expression under the control of the endogenous promoter.
In conclusion, redirecting primary human T cells by replacing endogenous TCRs with a LTDL-specific TCR using CRISPR/Cas9 is feasible, resulting in target-specific cytotoxic T cells with strong effector functions. The combined TCR KO/KI procedure could outcompete transduction based conventional TCR editing strategies and therefore presents a safe and powerful tool for the treatment of refractory viral infections in the immunocompromised host
Structural and biomechanical analysis of articular cartilage of mouse genetic models via atomic force microscopy
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Working conditions as risk factors for depressive symptoms among spanish speaking au-pairs living in Germany
Get PDFBackground: The number of au-pairs in Germany has been increasing in the past years. In 2019, 15,000 au-pairs were registered in Germany, with Colombians being the largest group (9.2%). The lack of a working protection law due to immigration status (au-pairs’ visa) and the structural dependency of the employer/host family may contribute to au-pairs’ poor working conditions and poor mental health. Therefore, the main objective of this study was to assess the occurrence of depressive symptoms and its association with sociodemographic characteristics, working condi-tions, and violence at work overtime among Spanish speaking au-pairs (SSA) living in Germany.
Methods: We conducted a prospective cohort study. Data was collected from August 2018 to April 2020. A total of 409 participants fulfilled the inclusion criteria for the cross-sectional analysis and 189 participants for the follow-up analysis. Depressive symptoms were assessed by the de-pression module Patient Health Questionnaire. Poisson regression model and Generalized Esti-mating Equations were applied to estimate the association between predictors and depressive symptoms.
Results: Forty percent of SSA living in Germany were between 22 and 24 years old, 91% were female, and 48% came from Colombia. In the cross-sectional analysis, experienced au-pairs pre-sented a higher prevalence of depressive syndromes (30% vs. 16%; p <0.001) than newcomer au-pairs. Over time, working more than forty hours per week (OR: 3.47; 95% 95%CI: 1.46–8.28), suffering physical violence (OR: 4.95; 95% CI: 2.16–9.75), and struggling to adapt au-pairs schedules to social and family activities were associated with depressive symptoms.
Conclusion: Poor working conditions were associated with higher prevalence of depressive symptoms among SSA living in Germany. These results may be used to create awareness among policy makers and au-pairs’ agencies as well as to develop interventions on working con-ditions to prevent poor mental health