Open Access

Background: There is an urgent need for effective follow-up treatments after acute electroconvulsive therapy (ECT) in depressed patients. Preliminary evidence suggests psychotherapeutic interventions to be a feasible and efficacious follow-up treatment. However, there is a need for research on the long-term usefulness of such psychotherapeutic offers in a naturalistic setting that is more representative of routine clinical practice. Therefore, the aim of the current pilot study was to investigate the effects of a half-open continuous group cognitive behavioral therapy (CBT) with cognitive behavioral analysis system of psychotherapy elements as a follow-up treatment for all ECT patients, regardless of response status after ECT, on reducing depressive symptoms and promoting psychosocial functioning. Method: Group CBT was designed to support patients during the often-difficult transition from inpatient to outpatient treatment. In a non-controlled pilot trial, patients were offered 15weekly sessions of manualized group CBT (called EffECTiv 2.0). The Montgomery-Åsberg Depression Rating Scale was assessed as primary outcome; the Beck Depression Inventory, WHO Quality of Life Questionnaire–BREF, and the Cognitive Emotion Regulation Questionnaire were assessed as secondary outcomes. Measurements took place before individual group start, after individual group end, and 6months after individual group end. Results: During group CBT, Post-ECT symptom reduction was not only maintained but there was a tendency toward a further decrease in depression severity. This reduction could be sustained 6months after end of the group, regardless of response status after ECT treatment. Aspects of quality of life and emotion regulation strategies improved during group CBT, and these improvements were maintained 6months after the end of the group. Conclusion: Even though the interpretability of the results is limited by the small sample and the non-controlled design, they indicate that manualized group CBT with cognitive behavioral analysis system of psychotherapy elements might pose a recommendable follow-up treatment option after acute ECT for depressed patients, regardless of response status after ECT. This approach might not only help to further reduce depressive symptoms and prevent relapse, but also promote long-term psychosocial functioning by improving emotion regulation strategies and psychological quality of life and thus could be considered as a valuable addition to clinical routine after future validation.

Background: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor functional outcome. It is suggested that physical fitness training may play a role in decreasing long-term inflammatory activity and supports tissue recovery. Aim: We investigated the dynamics of selected inflammatory markers in the subacute phase following stroke and determined if fluctuations are associated with functional recovery up to 6 months. Further, we examined whether exposure to aerobic physical fitness training in the subacute phase influenced serum inflammatory markers over time. Methods: This is an exploratory analysis of patients enrolled in the multicenter randomized-controlled PHYS-STROKE trial. Patients within 45 days of stroke onset were randomized to receive either four weeks of aerobic physical fitness training or relaxation sessions. Generalized estimating equation models were used to investigate the dynamics of inflammatory markers and the associations of exposure to fitness training with serum inflammatory markers over time. Multiple logistic regression models were used to explore associations between inflammatory marker levels at baseline and three months after stroke and outcome at 3- or 6-months. Results: Irrespective of the intervention group, high sensitive CRP (hs-CRP), IL-6, and fibrinogen (but not TNF-alpha) were significantly lower at follow-up visits when compared to baseline (p all ≤ 0.01). In our cohort, exposure to aerobic physical fitness training did not influence levels of inflammatory markers over time. In multivariate logistic regression analyses, increased baseline IL-6 and fibrinogen levels were inversely associated with worse outcome at 3 and 6 months. Increased levels of hs-CRP at 3 months after stroke were associated with impaired outcome at 6 months. We found no independent associations of TNF-alpha levels with investigated outcome parameters. Conclusion: Serum markers of inflammation were elevated after stroke and decreased within 6 months. In our cohort, exposure to aerobic physical fitness training did not modify the dynamics of inflammatory markers over time. Elevated IL-6 and fibrinogen levels in early subacute stroke were associated with worse outcome up to 6-months after stroke. Clinical Trial Registration: ClinicalTrials.gov, NCT01953549.

Introduction: Multiparametric MRI (mpMRI) and MRI targeted biopsies (MRtb) are a new standard in prostate cancer (PCa) screening and diagnosis. Guidelines already include this approach for patients at risk. We aimed to gather information from German urologists about their knowledge, routine use, and attitude toward mpMRI and consecutive biopsy methods. Materials and Methods: An anonymous online questionnaire was sent via Survey Monkey to the members of the German Society of Urology (DGU). Statistical analyses were performed using SPSS version 25.0. Results: 496 members with a median age of 48.6 years (±11.7) participated in the survey. The majority rated mpMRI of the prostate as a very useful diagnostic tool (72.7%). MRtb of the prostate was considered as very advantageous (71.5%). MpMRI was used by 95.9%, and 83.2% also recommended MRtb predominantly in clinical institutions. For targeted biopsy, MRI-ultrasound fusion biopsy was clearly favored (75.8%). MpMRI was mostly used in patients with previously negative biopsy (90.9%) and in patients under active surveillance (60.9%). Arguments against the use of prostate mpMRI are costs (84.9%) and/or lack of sufficient radiological infrastructure (17.4%). Conclusion: Our data illustrate the meanwhile high acceptance and clinical use of the prostate mpMRI and MRtb in Germany.

Die initiale Integration von Implantaten ist von hoher Bedeutung für die spätere Stabilität und Standzeit von beispielsweise Endoprothesen im Körper. Mit Hinblick auf die steigende Zahl von Patienten, die ein Implantat benötigen, ist es von großer Bedeutung unterschiedliche Implantatmaterialien und Oberflächenmodifizierungen bezüglich ihrer Eigenschaften und Interaktionen mit dem Implantatlager zu untersuchen, um diese verbessern zu können. Ziel der vorgestellten Arbeit war die Entwicklung und Etablierung eines Screeningmodells zur Analyse der Auswirkung von verschiedenen Metallimplantaten auf die Mikrozirkulation in unmittelbarer Nähe des Implantats. Dazu wurde ein neues in vivo Modell an der Chorioallantoismembran des Hühnerembryos entwickelt, angewendet und etabliert. Dieses stellt eine Modifikation des seit Jahrzehnten etablierten HET-CAM (Hühnereitest an der Chorioallantoismembran) dar und ermöglicht quantitative und qualitative intravitalmikroskopische Aussagen über die Funktionelle Gefäßdichte (FGD) und die Leukozyten-Endothel-Interaktion (LEI). Zunächst wurden im Zuge der Modellanwendung Nickel- und Titan-Implantate verglichen, um die mögliche Reaktionsbreite des Modells zu untersuchen. Es folgte eine Etablierung des Modells, indem die Oberfläche der Implantate kurz vor der Applikation mit kaltem Atmosphärendruckplasma (CAP) behandelt wurde. Die intravitalmikroskopische Untersuchung erfolgte jeweils 24 h nach Applikation. Die Chorioallantoismembran der mit Nickel-Implantaten behandelten Hühnerembryonen zeigte im Vergleich zur Titan- und der internen Kontrollgruppe eine signifikante Reduktion der FGD sowie eine signifikante Erhöhung der LEI gegenüber der Kontrollgruppe. Durch Vorbehandlung der Nickel-Implantate mit CAP konnte der Negativeffekt auf das Gefäßsystem signifikant reduziert werden. Für Titanimplantate konnte mit Hinblick auf die FGD kein zusätzlicher Effekt nach der Behandlung mit CAP detektiert werden. Die vorgestellte Arbeit zeigt, dass sich das neue Modell als Screeningmodell dazu eignet, neue Implantatmaterialien und Oberflächenmodifikationen an der Schwelle zwischen in vitro Zellkultur und in vivo Tiermodellen zu untersuchen. Somit könnte es dabei helfen, Tierversuche gezielter einzusetzen. Vorteile und Einschränkungen des Modells werden diskutiert.

Ebolaviruses are zoonotic pathogens causing severe hemorrhagic fevers in humans and non-human primates with high case fatality rates. In recent years, the number and scope of outbreaks has increased, highlighting the importance of better understanding the molecular aspects of ebolaviral infection and host cell interactions in order to be able to better control this virus. To facilitate virus genome replication, transcription and protein expression, ebolaviruses recruit and interact with specific host factors. These interactions play a key role in viral infection and influence virus survival and disease outcome. Based on a genome-wide siRNA screen, the three host factors CAD, NXF1 and UAP56 were recently identified to be involved in ebolavirus genome replication and/or transcription and/or mRNA-translation. However, mechanistical details of how these host factors affect the ebolavirus lifecycle remained elusive. In this thesis I analyzed the functional interactions between EBOV and these newly identified host proteins in order to better understand the virus-host interface. To this end I used siRNA knockdown as well as overexpression of these host proteins in combination with different reverse-genetics based lifecycle modelling assays to investigate the influence of CAD, NXF1 and UAP56 on individual aspects of the EBOV lifecycle. Using these systems in relation with a host factor knockdown I was able to show that the provision of pyrimidines by CAD plays an important role for both EBOV genome replication and transcription, whereas NXF1 is predominantly required for mRNA transport. I furthermore used immunofluorescence analysis to examine whether these host factors are recruited by one or more EBOV proteins to inclusion bodies, which represent physical sites of ebolavirus genome replication. During these experiments, I was able to show that CAD and NXF1, and possibly also UAP56, are recruited to EBOV inclusion bodies in order to fulfill their individual function for EBOV RNA synthesis or later steps in protein expression. Additionally, I was able to show that the uptake of NXF1 into NP-induced inclusion bodies is most likely mediated via the C-terminal domain of NP, and that the FG-repeat interaction domains of NXF1 are sufficient for recruitment. Further, my data indicate that RNA interaction of both NXF1 and NP is not required for this process, but rather important for exit of NXF1 from inclusion bodies. I therefore suggest that the viral mRNA is transferred in inclusionbodies from NP to NXF1, which leads to a rapid export of the NXF1 packed viral mRNA into the cytosol for mRNA translation. The exact mechanism of how these host factors are recruited into inclusion bodies and whether they have similar functions in the lifecycle of other negative-sense RNA viruses still needs to be investigated. Nevertheless, this study increases our understanding of virus-host interaction of ebolaviruses, and thus helps to identify targets for the development of novel therapeutics against these viruses.