Hauptautor*innen: Finja Meyer

Co-Autor*innen: Cornelia Hinz, Vaishnavi Joshi, Matthias Lange, Torsten Plösch, Axel Heep

Abstract:

Hintergrund: Die intrauterine Entwicklung von Geruchswahrnehmungen beginnt bereits in der 28. Schwangerschaftswoche. Frühgeborene sind postnatal vielen Gerüchen ausgesetzt, die nicht dem natürlichen olfaktorischen Umfeld entsprechen. In einer kurzen Phase nach der Geburt und während des Stillens sind Neugeborene besonders empfänglich für olfaktorisches Lernen.

Projektidee: Analyse der Expression olfaktorischer Gene bei Neu- und Frühgeborenen aus Epithelzellen der Nasenschleimhaut.

Hypothese: Die Genexpression definierter olfaktorischer Gene bei Früh- und Neugeborenen ist entsprechend dem Gestationsalter unterschiedlich.

Methoden/ Studiendesign: Diese explorative Querschnittstudie untersucht die Genexpression von 13 Genen der Neuropeptid- und olfaktorischen Rezeptoren, olfaktorischen Signaltransduktion und Neurogenese mittels Real-Time-PCR. Die Auswahl der Zielgene basiert auf einer vorangegangenen Literaturrecherche. Als Material dienen Zellen des respiratorischen Epithels der Nase von einem nicht-invasiven Nasenabstrich aus beiden Nasenlöchern. Eine Pilotstudie soll zunächst die Eignung der Methode exemplarisch an 12 gesunden Erwachsenen (18 - 65 Jahre) und reifen Neugeborenen (37. - 41. Schwangerschaftswochen) zeigen.

Ausblick: Die unterschiedliche Umgebung während der Entwicklung des olfaktorischen Systems könnte zu einer veränderten Genexpression olfaktorischer Gene führen. In einer auf diesen Erkenntnissen aufbauenden Studie ist ein Vergleich zwischen Früh- und Neugeborenen geplant. Da der Geruchssinn eine erhebliche Rolle für die Eltern-Kind-Bindung spielt, ist ein langfristiges Ziel, postnatal positiv Einfluss auf diesen zu nehmen.

Hauptautor*innen: Sabeth Becker

Co-Autor*innen: Dana Behrens, Lena Dübbel, Eduard Malik, Meike Schild Suhren

Abstract:

Introduction: Vulvar dysplasia is typically diagnosed invasively by biopsy. It lacks clear guidelines for therapeutic management. The GynTect® assay identifies cervical dysplasia and has prognostic capability by measuring the methylation of six marker genes. This study aimed to transfer these methylation markers to vulvar tissue and investigate non-invasive diagnostics using vulvar smears.

Methods: 121 FFPE samples and 79 fresh tissue swabs with different VIN grades, vulvar carcinoma, and healthy controls were tested. After DNA isolation and bisulfite conversion, the methylation status of the six marker genes was determined by qRT-PCR.

Results: The six markers exhibited higher methylation in vulvar dysplasia tissue than in control samples. The diagnostic kit showed a sensitivity of 82.69% and a specificity of 71.05% for FFPE samples, and a sensitivity of 92.31% and a specificity of 88.1% for smears. The GynTect®scores of fresh frozen carcinomas matched those of the corresponding FFPE samples. Four markers showed a continuous increase in methylation across the dysplasia stages.

Discussion: Cervix-typical methylation markers can be detected in vulvar dysplasia. The GynTect®assay seems generally applicable to diagnosevulvar dysplasia. Non-invasive diagnostics using vulva smears are possible for the first time. Consideration should be given to downgrading ZNF671 and upgrading DLX1 in the score.

Hauptautor*innen: Dr. med. Naomi Giesers

Co-Autor*innen: PD Dr. Thomas Liman

Abstract:
Ein Drittel bis die Hälfte aller Schlaganfallpatienten leiden an neuropsychiatrischen Folgeerkrankungen. Diese Defizite sind unterdiagnostiziert, potenziell behandelbar und haben einen Einfluss auf die Lebensqualität. Die endovaskuläre Thrombektomie (EVT) hat die Behandlung großer Gefäßverschlüsse revolutioniert und verbessert die Prognose entscheidend, sodass etwa ein Drittel der Patienten keine oder moderate neurologische Defizite behalten. Kognitive und psychiatrische Outcomes waren nicht Teil der vorliegenden Zulassungsstudien für die EVT, diese Lücke soll mit dieser derzeit laufenden Studie geschlossen werden. Es handelt sich um eine Beobachtungsstudie mit Einschluss von Schlaganfallpatienten nach EVT und gutem funktionellen Outcome (Modified Ranking Scale ≤2), welche daher auch wieder in die häusliche Umgebung entlassen werden. In der neurovaskulären Studienambulanz der Universitätsklinik für Neurologie werden im Follow-Up nach drei Monaten die Prävalenz von Depression, Kognitiven Defiziten, Angststörungen und Fatigue untersucht.

Hauptautor*innen: Dr. med. Svenja Christine Schwichtenberg

Co-Autor*innen: Charlotte Becker, Julia Neubauer, Till Bömmer, Prof. Mandy Roheger, Prof. Karsten Witt

Abstract:

Der Locus coerulens (LC), eine Region im Hirnstamm, reguliert autonome Funktionen ebenso wie kognitiver Prozesse. Interessanterweise sind diese Prozesse gekoppelt, sodass eine kognitive Anstrengung zu einer erhöhten LC-Aktivität führt, die wiederum eine Erweiterung der Pupille (autonome Funktion) induziert. Da der LC schon früh im Krankheitsverlauf der Parkinsonkrankheit (PK) betroffen ist, ist das Studienziel diesen „Reflexbogen“ bei PK-Patient:innen zu untersuchen. Hierfür soll ein „Odd-Ball-Experiment“ genutzt werden, welches die Reaktion auf abweichende Reize untersucht. Es konnte bereits gezeigt werden, dass das Hören von akustischen Stimuli (wiederholt 5 gleiche Töne, xxxxx), bei seltener Darbietung eines devianten Stimulus (einzelner Ton in anderer Tonhöhe, xxxxY) eine LC-Reaktion auslöst, die mittels Pupillendilatation nachgewiesen werden kann. Im ersten Schritt soll gezeigt werden, dass die Pupillendilatation bei PK-Patient:innen kleiner ausfällt als in einer altersgleichen gesunden Vergleichsgruppe. Da auch unabhängig von der PK eine altersbedingte Degeneration des LC möglich scheint, soll ein potenzieller Unterschied in der Pupillendilatation auf die devianten Stimuli zwischen jüngeren und älteren gesunden Proband:innen untersucht werden. Die Ergebnisse dieser Grundlagenstudie können Erkenntnisse bzgl. der physiologischen Eigenschaden des LCs während des gesunden Alters und im Rahmen der PK liefern sowie für die Früherkennung der PK und einige ihrer therapeutischen Optionen (noradrenerge Behandlung, Vagusnervstimulation) wichtige Implikationen bieten.

Hauptautor*innen: Nicola Brandt

Co-Autor*innen: Jan Baumgart, Axel Heep, Anja U. Bräuer

Abstract:

A proper functional architecture of the cerebral neocortex is central to normal neuronal abilities. This architecture is established during embryonic development and requires well-coordinated processes, including neurogenesis, migration, and differentiation, leading to six layers of the cortex that have distinct morphological and functional identities. The correct establishment of these layers is tightly controlled by extracellular and intracellular signals. Perturbances in these processes lead to severe brain malformations. The molecular mechanisms are poorly understood. A promising external cue is the bioactive phospholipid lysophosphatidic acid (LPA), which plays important roles in several aspects of brain development, including neuronal migration. The downstream signal transduction of LPA is mediated by LPA receptors (LPA1- 6). Inactivation of LPA signalling is controlled by the degradation of LPA via Lipid phosphate phosphatase 1 (LPP1). In preliminary experiments, we found that LPP1/1a is involved in the migration process in the developing cortex. We aim to investigate how exactly LPP1/1a intervenes in the developmental processes and the fundamental principles of layer-specific development using in utero electroporation in mice. This will accelerate our understanding of neocortex formation and the aetiology of neurodevelopmental disorders and is key to designing novel therapeutic strategies.

Hauptautor*innen: Laura Gieldon

Co-Autor*innen: Gregor Dombrowsky, Enrique Audain, Andreas Niederprüm, Amilcar Perez-Riverol, Christina Lißewski, Ann-Kathrin Bauer, Christoph Geier, Marlene Kullik, Andreas Rump, Marc-Phillip Hitz

Abstract:

Cancer is the leading cause of death, accounting for ten million fatalities annually. Up to 10 % of cancers are caused by pathogenic germline variants that can be passed on over generations. Identification of such cancer predisposing genetic alterations impacts both patients and their family members. Moreover, in precision oncology, targeted treatments are based on germline genetic variants, adding an urgent clinical perspective to the field of cancer predisposition research. Standard diagnostic approaches for genetic tumor predisposition currently focus on target regions of interest (gene panels) using short read Next Generation Sequencing (NGS). However, using this approach the underlying causes for many familial cancers remain unresolved, with detection rates for hereditary tumor predisposition ranging significantly under 50% for most tumor entities. Within this project, we currently subject unsolved patient cases with fulfilled clinical diagnostic criteria for hereditary cancer predisposition to non-targeted (whole-genome) short-read NGS and 3rd generation genome (DNA) and transcriptome (RNA) Nanopore sequencing, broadening the diagnostic spectrum to non-coding genetic variants and copy number variants. Nanopore sequencing additionally allows for analysis of a range of previously undetectable aberrations, including structural variants and epigenetic modifications. Here, we will present the current status and preliminary results generated within this project.

Hauptautor*innen: Sabrina Schröder

Co-Autor*innen: Sebastian Fudickar, Navid Tabriz, Dirk Weyhe, Verena Uslar

Abstract:

Zweck, Ziel: Die Entwicklung von LAOLA profitiert von einem interprofessionellen Team der Disziplinen Logopädie, Public Health und Medizininformatik: Künftig können LogopädInnen individuelle Hausaufgaben für ihre erwachsenen Stimm-PatientInnen auswählen, indem sie ihnen an ihre Smartphones vorproduzierte Übungsvideos senden. Während der Nutzung erhalten diese ein direktes Feedback zu ihrer Leistung, basierend auf visuellen und verbalen Informationen, das über einen Machine-Learning-Algorithmus erfolgt.

Vorgehen: In Interviews und Fokusgruppen wurde das Erfahrungswissen von LogopädInnen und PatientInnen ermittelt. Es wurde nach der qualitativen Inhaltsanalyse nach Kuckartz und Rädicker (2018) ausgewertet.

Ergebnis: 29 LogopädInnen und sechs Patientinnen wurden befragt: Die Motivation, LAOLA im Alltag zu nutzen, ist bei allen hoch. Gefördert werden die Motivation und Praktikabilität, indem die App ansprechend designt und intuitiv zu nutzen sein soll. Weiter sind u.a. individuell einstellbare Erinnerungsfunktionen, Informationstexte sowie die Inklusion von Gamification von Bedeutung. Schlussfolgerung: LAOLA soll die Präsenztherapie nicht ersetzen und PatientInnen wollen sich bei der LAOLA-Nutzung nicht kontrolliert oder unter Druck stehend fühlen. “Motivation” hat hohe Priorität und wird daher stark in der Entwicklung berücksichtigt. Angesichts des Fachkräftemangels und der zunehmenden Digitalisierung im Gesundheitswesen hat die innovative App Potenzial, die Arbeit von TherapeutInnen zu vereinfachen und die Effektivität des Patiententrainings zu erhöhen.

Hauptautor*innen: Franziska Köper

Co-Autor*innen: Danara Vonk; Malte W. Dirksen; Axel Heep; Thorsten Plösch; Mark Hipp; Anja U. Bräuer

Abstract:

Plasticity related gene 5 (PRG5) is a membrane protein predominantly found in neurons that is involved in cellular processes such as growth cone guidance, migration, and spine formation. Overexpression of PRG5 induces filopodia in non-neuronal cell lines, contributes to the induction of spines in immature neurons, and regulates spine density and morphology in mature neurons. Understanding the formation of spines is curtail, as disruptions in spine appearance are associated with neurological disorders. Although the importance of PRG5 in neuronal function is evident, the precise mechanisms through which it induces membrane protrusions and orchestrates cellular responses remain unresolved. We hypothesise that multimerization of PRG5 is required for its functionality. By using in vitro biochemical assays, we demonstrate PRG5 homodimerization. This was further confirmed in living cells, where we detected PRG5 multimerization at the plasma membrane, in particular at the tips of the filopodial protrusions using Fluorescence Lifetime Imaging - Förster Resonance Energy Transfer (FLIM-FRET). Notably, this effect is observed in non-neuronal cells and primary hippocampal neurons, with a primary localization of PRG5 multimers within small neuronal protrusions. Unravelling the complexities of the role of PRG5 in membrane protrusion formation is crucial for advancing our understanding of neuronal development.

Hauptautor*innen: Danara Vonk

Co-Autor*innen: Isabel Gross, Nicola Brandt, Hong Yan, Martina Schmidt, Anja U. Bräuer, Mark S. Hipp

Abstract:

The family of Plasticity Related Genes is a group of transmembrane proteins that are part of the Lipid Phosphate Phosphatase superfamily. PRGs are involved in multiple processes in neuronal development, and knockout or downregulation of PRGs leads to an increased sensitivity to seizures and epilepsy, whereas overexpression of PRG2, PRG3 and PRG5 promotes the formation of protrusions at the membranes of both non-neuronal and neuronal cells. These results suggest a role for the PRGs in regulating neuronal development and suggest a role in diseases where neuronal development, specifically neurodifferentiation of the dendritic tree, is impaired. However, it is not yet clear how PRGs regulate these processes and which signaling pathways are involved. Here, I will present the results obtained from two experimental approaches designed to identify the signaling pathways involved. We performed mass spectrometry after pulldown of PRG5 from different brain areas to identify possible interaction partners. Additionally we tested for effects on PRG5-mediated protrusion formation of pharmacologic inhibition of kinases involved in pathways known to be involved in morphological changes.

Hauptautor*innen: Dr. Jens Hausmann

Co-Autor*innen: Supreet Arabi, Jennifer Sevecke-Rave, Dr. Nicola Brandt, Dr. Alexander Scholten, Prof. Dr. Karl-Wilhelm Koch, Prof Dr. Anja Bräuer

Abstract:

Niemann-Pick disease type C (NPC) is a devastating deadly rare disease belonging to the class of lysosomal storage diseases. NPC1 is a lysosomal transmembrane protein, that mediates the efflux of cholesterol and phospholipids from lysosomes. NPC1 loss of function mutation leads to an accumulation of cholesterol and phospholipids in lysosomes, finally leading to cellular death. The first clinical symptom of NPC is a hepatosplenomegaly, and neurodegeneration becomes more evident with ongoing disease progression. An important player in neurodegeneration is the ATX-LPA signaling axis. This signaling axis comprises autotaxin (ATX), its catalytic product lysophosphatidic acid (LPA), and six specific G-protein coupled receptors (LPA1-6). ATX converts lysophosphatidylcholine (LPC) into LPA. LPA is a potent lipid mediator that triggers many essential cellular processes. Here, we investigate the so far uncharacterized role of ATX-LPA signalling axis in NPC. Therefore, we isolate bone-marrow-derived macrophages from Npc1-/- mice and wild-type litter mates and demonstrate a cellular uptake of exogenous applied ATX. Internalized ATX show a co-localization with lysosomes in confocal microscopy. qRT-PCR verified a differential up-regulation of the murine ATX gene Enpp2 and Cd36 in our disease model. Thus, from our study, we conclude that ATX is an important player in lipid homeostasis in NPC.

Hauptautor*innen: Esther C Maier

Co-Autor*innen: Veysel Ödemis, Anja Bräuer, Verena Uslar, Ricarda Stauss, Peter Haddawy, Metasit Getrak, Myat Su Yin Maung, Paphon Sangasoongsong

Abstract:

Qualitative and in-depth anatomical education is fundamental in training competent medical students. The “golden standard” for acquiring anatomical knowledge relies on hands-on experiences in dissection rooms, which is essential for students to develop a profound understanding of anatomy in a 3D space. Cadaveric dissection in Oldenburg is currently only possibly in collaboration with the UCM Groningen. Augmented-reality based learning scenarios using head mounted displays (HMDs) have become more prevalent in medical education. They have the advantage that they can be made available in Oldenburg to provide hands-on-tools for students to recapitulate and reactivate anatomical knowledge and concepts. In the present study, we developed a "Virtual Seminar-Anatomy and Orthopaedics" (VS-AaO), a digital AR learning environment developed to teach anatomy with relevance for orthopaedic clinical training and patient assessment. The qualitative pilot phase of the concept involves testing in groups from different universities, allowing students to interact in a virtual classroom. The objectives of this pilot study fall in two categories: first, we were interested to investigate the technical feasibility of creating an immersive teaching environment. Second, we also examined the views of students and educators/teachers on the potential and drawbacks of AR technology, particularly in relation to group teaching

Hauptautor*innen: Emely Reyentanz

Co-Autor*innen: Prof. Dr. Yulia Golub

Abstract:

Regulatory disorders in early childhood include, for example, excessive crying, sleeping or feeding disorders. They are described by a symptom triad which, in addition to the child’s behavioral symptoms, includes parental psychopathology and a dysfunctional parent-child interaction. Regulatory disorders are associated with an increased risk of psychiatric disorders over the entire lifespan. Prenatal risks, such as maternal stress or substance use, are related to a higher risk of regulatory disorders. However, there is still a lack of diagnostic tools to assess prenatal risks and regulatory disorders. In addition, an intervention program for the treatment of early childhood regulatory disorders that also considers parental psychopathology and parent-child interaction is still lacking in German-speaking countries. The Pro_Mini project aims to fill this gap by developing and validating a Prenatal Risk Index for the comprehensive assessment of prenatal risks and a Regulation Index for the assessment of regulatory problems in young children. In addition, we will develop and evaluate an attachment-based parent-child group program for the treatment of regulatory disorders in early childhood. The systematic assessment of prenatal risks and regulatory problems in young children offers the opportunity for early interventions in order to promote the healthy psychological development of children.

Hauptautor*innen: Drs. Francine Vos

Co-Autor*innen: Sophie Polman, Dr. Ben Saleem, Prof. Dr. Paul M. N. Werker, Dr. Luz Angela Torres-de La Roche, Prof. Dr. Dr. med. Rudy Leon De Wilde

Abstract:

Early and late surgical site infections (SSI) are amongst the most devastating complications following Breast Implants (BI) and vascular reconstructions using grafts or endografts (VGE), since this may lead to the loss of the implant in case of a breast implant infection (BII) and since it is associated with a high mortality in vascular graft or endograft infection (VGEI) cases. It has been shown that the overall incidence of infection is lower in Germany (DE) than in The Netherlands (NL), but the incidence of antibiotic resistance is much higher in DE than in NL. However, it is not known if these differences affect the incidence of early and or late SSI following BI and VGE surgery. Furthermore, little is known about the involved micro-organisms or their antibiotic resistance pattern. Finally, standards operating procedures (SOPs) for BI or VGE surgery and compliance to the protocols vary between DE and NL, but it is unknown to what extent and what additions they can offer each other.

Hauptautor*innen: Eyad Alsaedi

Co-Autor*innen: Eyad Alsaedi, Nadine Mykicki, Nivedha Srinivasan, Andre Hildebrand, Sven Meuth, Karin Loser

Abstract:

In experimental autoimmune encephalomyelitis (EAE), a mouse model partially mimicking human multiple sclerosis, the dysfunction of the blood-brain barrier (BBB), is an important prerequisite for the infiltration of pathogenic immune cells into the central nervous system. The increased permeability between endothelial cells (EC), the main component of the BBB, is caused by the downregulation of Tight Junctions (TJ), which allow the infiltration of immune cells. Previously, we demonstrated that the neuropeptide derivative Nle4-D-Phe7–alpha-melanocyte-stimulating hormone (NDP-MSH) ameliorates EAE by reducing immune cell infiltration via MC1R receptor binding. To explore if NDP-MSH also improves BBB integrity, we conducted Trans-Endothelial Electrical Resistance (TEER) assays on EC stimulated with IFNy and TNF. NDP-MSH treatment significantly increased EC electrical resistance, indicating improved monolayer integrity. Surprisingly, this effect of NDP-MSH was abrogated in EC isolated from mice having a defective MC1R receptor (MC1Re/e). Immunofluorescence staining of EAE brain sections revealed increased expression of TJ proteins Zonula occludens-1 (ZO-1) and claudin-5 in NDP-MSH-treated mice, but not of MC1Re/e. Real-time PCR confirmed elevated mRNA expression of claudin-5 and ZO-1 in the brain of NDP-MSH-treated EAE B57BL/6 mice. Altogether, these data indicate that NDP-MSH enhanced the BBB integrity by upregulating TJ proteins, such as ZO-1 and claudin-5.

Hauptautor*innen: Srushti Borkar

Co-Autor*innen: F. Griesinger, J. Roeper, T. Overbeck, K. Willborn, F. Markus, P. Weist, E.M. Willing, L.C. Heukamp

Abstract:

With over 55,000 new diagnoses per year in Germany, lung carcinoma is one of the most common cancers. Due to high treatment costs, efficient patient stratification before and monitoring during therapy are essential. Disease monitoring using cell-free tumor DNA (ctDNA) from blood-based liquid biopsy (LB) has the potential to inform optimal therapy in the metastatic and the non-metastatic curative setting. It has recently been shown in neuroblas-toma that somatic breakpoints of frequent chromosomal rearrangements can be used as biomarkers to monitor disease over the course of treatment, by generating patient-specific ddPCR assays for these breakpoint regions. The current study plans apply the same concept to NSCLC, and to investigate the application of invidualized, breakpoint-specific ddPCR assay in 40 NSCLC IV patients treated in the palliative setting with ICI +/- chemotherapy for disease monitoring purposes. The assay will be used at 3 different time points over the course of 1st line treat-ment, i.e. prior to systemic therapy, at 6 and 9 weeks on therapy and at progression. Correlation of ddPCR MRD monitoring results will be done for ORR, PFS, and OS within the TheraSure CNI-Monitor Trial conducted by the CCC-N.

Hauptautor*innen: Esin Aysel Kandemir

Co-Autor*innen: Julia Roeper, Frank Griesinger

Abstract:

Introduction: Multidisciplinary tumor boards (MTBs) intend to increase the quality of cancer patients receive. This study aims to determine the effects of adherence to MTB recommendations on survival time.

Methods: This is a retrospective, observational study including colorectal cancer patients diagnosed between 2014-2018 at the Klinikum Oldenburg. Primary outcome is disease-free survival (DFS) and Kaplan-Meier analysis was done by R version 11.

Results: In total 268 colon cancer (mean age: 68.08 ± 12.25) and 190 rectum cancer patients (mean age: 63.14 ± 12) were included in the study. Median follow-up time was 54 months (47, 62; 95% CI) for colon cancer patients and 64 months (59, 69; 95% CI) for rectum cancer patients. In total 87.3% of the included cases treatment recommendations from MTBs were fully implemented (complete adherence, n=400) The most common reason for deviation was patient wish (n=23). Kaplan-Meier survival analysis is resulted in a significant DFS difference between adherence groups in colon cancer (log-rank test, p=0.006), rectum cancer (log-rank test, p=0.003), and in all patients (log-rank test, p=0.0002).

Conclusion: MTBs are able to increase survival time of colorectal cancer patients. Further studies should choose survival time as a primary endpoint to confirm our results.

Hauptautor*innen: Bastian Schrader

Co-Autor*innen: Armin Weers

Abstract:

Die Lebenserwartung entwickelt sich in Deutschland weiterhin schlechter als in allen andere Westeuropäischen Ländern, obwohl Deutschland das teuerste Gesundheitssystem hat. Den größten Anteil daran haben kardiovaskuläre Erkrankungen. Der Norden Deutschlands insbesondere auch ländliche Regionen stehen im deutschlandweiten Vergleich schlecht dar. Es braucht innovative Projekte zur niederschwelligen Gesundheitsvorsorge. 3F (Fit& fun mit Fußball) verbindet Vereinsinfrastruktur mit evidenzbasierter Herz-Prävention. Eine gesundheitsorientierte Fußballvariante konnte an Bluthochdruck- Patienten und in einer gerade frisch abgeschlossenen kontrollierten Studie an Herzinfarkt Patienten signifikante Effekte durch 1x wöchentliches 3F Training über ein Jahr nachweisen. Verglichen wurde mit einer Kontrollgruppe, die Routine Präventionsempfehlungen erhalten hat. Die Herzinfarkt Studie wird hier präsentiert. Der Blutdruck ( Fußballgruppe, n=100 (FG) von 132,3/80,7 mmHg auf 125/76,2mmHg, p<0,001); Kontrollgruppe n= 100 (KG) von 137/81,6 auf 136/82mmHg n.s.) , das Gewicht (FG von 98,2 auf 96,5kg, KG von 94,5 auf 96,2kg p<0,001) und die Fitness (FG 17,89 ml/min/kg auf 20,01 ml/min/kg, p<0,001; KG 19,37 auf 18,85 p=0,291) haben sich in der Fußballgruppe nicht aber in der Kontrollgruppe signifikant verbessert. Die KG brauchte signifikant häufiger mehr Blutdruck und lipidsenkende Medikamente. 3F hat das Potenzial mit Spaß Frauen und Männer mit und ohne Vorerkrankungen wieder zu körperlicher Aktivität zu motivieren und Herzerkrankungen so effektiv zu verhindern.

Hauptautor*innen: Daniel Rosenkranz

Co-Autor*innen: Kathrin Budde, Ann-Kristin Henning, Gunnar Brandhorst, Sarah Schäfer, Karen Friederike Gauß, Nele Friedrich, Astrid Petersmann, Matthias Nauck

Abstract:

Reference intervals are crucial for the interpretation of numerical laboratory results. They are essential for diagnosing diseases, monitoring patient health, and guiding treatment decisions. Usually, the limits are derived from the central 95% range in apparently healthy subjects and separately for each analyte. The establishment for multi-measurand determinations, such as those obtained from NMR spectra, remains complex and underdeveloped. This study aims to establish reference intervals for NMR spectra in human plasma. Utilizing a 600 MHz NMR spectrometer, we analyzed 3350 human plasma samples from the Study of Health in Pomerania (SHIP). To address spectral variations due to instrumental drifts, data normalization was performed using the ERETIC method. Percentile curves (2.5%, 10%, 25%, 50%, 75%, 90%, 97.5%) were calculated, and modified z-scores were calculated to identify abnormal signals, with z-scores above or below ±3.5 indicating significant deviations. Normalized peak integrals provided result quotients for quantitative comparisons. This comprehensive approach facilitates the generation of reference spectra, enhancing the medical value of NMR technology for both targeted and untargeted metabolomics in healthcare. The establishment of these reference intervals is pivotal for measurand quantification and biomarker identification, improving the clinical utility of NMR spectroscopy in human plasma analysis.

Hauptautor*innen: Prof. Dr. med. Astrid Petersmann

Co-Autor*innen: Stephanie Lüthke, Corinna, Feeken, Heike Adam, Marc Wilken, Felix Kempa, Volker Thiemann, Christoph Wilken, Hauke Fischer

Abstract:

The University Medicine Oldenburg (UMO) includes four hospitals under different ownership, including one municipal, one private, and two distinct church-affiliated hospitals, each with its own ecclesiastical law, together with the Medical Faculty Oldenburg. This legally and organizationally complex structure represents a challenge for establishing a participative biobank structure. The Biobank Structure Oldenburg (BSO) as a Core Facility is designed to be accessible to all participating hospitals, the faculty and cooperating institutions. The BSO employs digitalized workflows to facilitate standardized and quality-assured biosample collection, processing, storage, and distribution. The BSO provides various utilization opportunities, including consultation on sample management, support for collection and processing, and the legal transfer of well-characterized biosamples to the faculty after project completion. It allows targeted sample collection under a Broad Informed Consent. The reuse of biosamples from completed projects and compatibility with national and international research infrastructures underscore its comprehensive approach. The infrastructure of the biobank relies on a central IT system (CentraXX, Kairos) for sample management and workflow provision, with decentralized web-based access. Centralized and decentralized storage capacities, process-oriented sample management, quality assurance, and documentation of clinical data further enhance the facility's efficiency.The governance structurecomprises a user council, a Core Facility leadership, and staff.

Hauptautor*innen: Linea Katharina Muhsal

Co-Autor*innen: Cansu Cimen, Axel Hamprecht

Abstract:

The worldwide spread of carbapenemase-producing Enterobacterales (CPE) poses a severe threat to global health. Carbapenems are effective antibiotic agents conventionally reserved to treat infections with multi-resistant bacteria. In 2022, the ECDC reported an EU average of 10.9 % carbapenem-resistant K. pneumoniae strains, as well as resistant E. coli, P. aeruginosa and Acinetobacter strains. Early detection of CPE is essential for appropriate treatment of infections and prevention of further spread. Existing algorithms are often customized to the data set on which they are based, making them less specific and sensitive when applied to user data and thus ineffective. Here we present Carba-Detector, a web app that uses a random forest model to accurately predict carbapenemase production of Enterobacterales based on the disk diffusion diameters and species of the focal strain. When tested with a data set provided by a collaborating laboratory (n = 518), sensitivity was 92.3 % (CI 89.1-94.8 %) and specificity was 91.6 % (CI 86.0-95.4 %). The use of Carba-Detector could significantly reduce both the cost and time required to detect CPE, leading to improved treatment and prevention of the spread of CPE.

Hauptautor*innen: Kelly Mieck

Co-Autor*innen: Volker Kinast

Abstract:

Retrotransposable elements (RTE) are genetic components that are capable to change their genomic location by a copy and paste mechanism. Inhibitors of RTE activity are critical to prevent harmful mutagenesis potentially resulting neurological and age-related disorders. Notably, several endogenous RTE inhibitors are members of the family of interferon-stimulated genes (ISGs). The ISG Shiftless (SHFL) was recently reported to restrict multiple viruses including human immunodeficiency virus 1 (HIV-1) and hepatitis C virus (HCV) but its role in restricting RTE remains elusive.

Hauptautor*innen: Olinda Pinto Veiga

Co-Autor*innen: Sarah Schlienkamp, Eleftherios Michailidis, Yannick Brüggemann, Axel Hamprecht, Finn Grey, Charles M Rice, Eike Steinmann, Volker Kinast

Abstract:

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in humans worldwide. The infection is usually self-limiting but can cause fulminant hepatitis and lead to liver cirrhosis and liver failure. Interferon-stimulated genes (ISGs), as part of the innate immune response, provide a robust first line of defense against many viruses, but for HEV it remains unknown which ISGs contribute to the viral restriction. We took advantage of arrayed ISG libraries from different species to identify ISGs that play a role in the control of HEV infections and focus on the characterization of their molecular mechanism underlying their restriction capacity. ISGs with a strong anti-HEV phenotype were identified, including well-known factors (TRIM25, MDA5, IRF proteins) but also uncharted proteins such as the glutamate transporter SLC1A1 and the hydrolase TMEM62. HEV infection experiments revealed a 5-fold reduction of HEV-infected cells in the presence of SLC1A1 and TMEM62 respectively. Transfection of subgenomic HEV reporter replicons, enabling us to bypass the process of viral entry, showed that HEV RNA replication was similar in the presence or absence of the ISGs, suggesting that both SLC1A1 and TMEM62 restrict the entry process of HEV.

Hauptautor*innen: Cansu Cimen

Co-Autor*innen: Philipp Siemer, Andreas Voss, Matthijs Berends, Axel Hamprecht

Abstract:

OXA-48-like are the most prevalent carbapenemases in western Europe. They are challenging to detect, as many isolates have low minimal inhibitory concentrations (MIC) values for carbapenems. We determined carbapenem MICs in OXA-48-like carbapenemase producing Enterobacterales (CPE) isolates and controls by broth microdilution (BMD) and assessed the performance of three derivative antibiotic susceptibility testing (AST) methods.
Susceptibility was assessed by BMD, disk diffusion (DD), gradient test (ETEST®), and VITEK®2 with N223, N428, N432 cards. The challenge collection included 108 OXA-48-like isolates and 150 non-CPE strains,all previously characterized by whole genome sequencing. All assays were performed using the same inoculum.The highest rate of resistance was observed for ertapenem (87% by BMD), compared to 12.0% for imipenem and 11.1% for meropenem. The categorical agreement (CA) with BMD as the reference methods varied among different antibiotics and methods. Ertapenem consistently showed higher agreement (89.8%-99.1%) across all methods compared to imipenem (56.0%- 91.7%) and meropenem (78.3%-95.4%). DD exhibited a generally lower agreement, particularly notable for imipenem and in OXA-48-like CPEs. Gradient tests consistently performed well for all antibiotics tested, with high agreement to the reference method. The different VITEK®2 AST cards performed similarly but with lower agreement compared to gradient tests.

Hauptautor*innen: PD Klein

Co-Autor*innen: SOA Helgers, P Dömer, C Klüner, A Wijaya, F Meinert, B Zimmermann, C Mathys, J Woitzik

Abstract:

Glioblastome sind die häufigsten primär malignen Hirntumore und gehen üblicherweise mit einer schlechten Prognose einher. Die wichtigste Therapiesäule zur Verlängerung des Gesamtüberlebens stellt die Totalresektion dar. Da das Tumorgewebe insbesondere im Randbereich schwer von vitalem Hirngewebe zu differenzieren ist, kommen im Operationsverlauf vielfältige Techniken zum Einsatz, etwa die fluoreszenzgestützte Chirurgie mit Gliolan oder Fluoreszein, oder das intraoperative MRT (iMRT). Das iMRT ist aus sozioökonomischen Gründen nur an wenigen, hochspezialisierten Zentren verfügbar. Mit den beiden genannten Techniken können Totalresektionsraten von 78% (Gliolan), bzw. 81% (iMRT) erzielt werden. In unserer Studie wurde das DoubleVision-Protokoll entwickelt. Dabei wird, analog zu nichtmedizinischen Hochsicherheitsszenarien, das Vier-Augen-Prinzip angewandt. Dabei erfolgt eine abschließende, intraoperative Resektionskontrolle durch einen zweiten, erfahrenen Neurochirurgen. Hierdurch soll das Resektionsvolumen größtmöglich gesteigert werden, unter Aussparung des vitalen Hirngewebes. Die intraoperative Orientierung erfolgt dabei auch fluoreszenzgestützt mit Gliolan und Fluoreszein. Die Auswertung erfolgt anhand postoperativer MRT-Datensätze, der Operationszeit, sowie allgemeinen Patientendaten bezüglich des Outcomes. In einer präliminären Auswertung zeigten sich eine Totalresektionsrate von 100% bei geringerer Operationsdauer im Vergleich zu publizierten Vergleichsgruppen. Gleichzeitig zeigte sich keine Verschlechterung der postoperativen klinischen Parameter. Im Hinblick auf die positiven ersten Teilergebnisse der DoubleVision-Studie liegt der Fokus derzeit auf einer Fallzahlerhöhung und der Einbeziehung zusätzlicher klinischer Parameter.

Hauptautor*innen: Marc Rosenkranz

Co-Autor*innen: Thorge Haupt, Manuela Jaeger, Verena N. Uslar, Dirk Weyhe, Martin G. Bleichner

Abstract:

The soundscape in the operating room can be a burden for personnel. While this issue has long been identified, the exact effects are difficult to quantify. Surgeons often find the soundscape disturbing, yet this is not immediately reflected in diminished surgical performance, suggesting that performance is not sufficient for measuring the individual burden of noise. To address this gap, we explore the possibility to use mobile electroencephalography (EEG) to capture sound processing continuously and non-intrusively during surgical procedures to understand when sound becomes a burden. We gradually developed our empirical approach to study medical staff in the operating room. Frist, to establish that meaningful data could be obtained in dynamic, activity-rich environments, we used a complex audio-visual-motor task (3D Tetris) to investigate the perception of realistic operating room soundscapes. Second, participants performed short laparoscopic tasks on a surgical simulator while exposed to complex soundscapes under two different workload conditions. While participants experienced the high workload condition as more demanding than the low workload condition, this was not reflected in the EEG measures. Taken together, we made important steps towards using mobile EEG as a tool to study individual sound perception in the operating room and other workplaces.

Hauptautor*innen: Dr. Julia Gockel

Co-Autor*innen: Anne Dehlfing, Katrin Wüstenbecker, Vito Olschewski, Heiko Klaassen, Timo Ulferts, Martin Faqeri, Silvia Sommer, Frederick Dettmann, Kirsten Habbinga

Abstract:

Interprofessional collaboration in healthcare is crucial for safe and effective patient care, especially in acute emergency situations. To train these skills, three ‘interprofessional emergency simulation’ sessions were piloted and evaluated in Oldenburg with participants from human medicine, emergency paramedic, and advanced emergency care training, aiming for permanent curriculum integration. The simulations realistically depicted the entire rescue chain, from pre-hospital scenes to ambulance care and treatment in an Oldenburg hospital’s ZNA. Evaluations were conducted using questionnaires, focus group interviews, and structured reflection discussions with instructors. Participants rated the training positively, considering it a useful addition to their programmes. Over time, more emphasis was placed on introductions and role clarification. To enhance realism, the clinical part of the simulation was moved from the university to a hospital, with a future reduction of preclinical work in favor of clinical care. Future improvements should incorporate more prior knowledge and understanding of each professional group's roles. Expanding the simulation beyond emergency care contexts is also advisable. The greatest challenge remains integrating these simulations into the existing lesson plans of the respective training programmes.

Hauptautor*innen: Maryam Kheyrollah

Co-Autor*innen: Nicola Brandt, Anja U. Bräuer, Stefan Schrader, Sonja Mertsch

Abstract:

Purpose: Corneal nerve damage is the main cause of the degenerative disease Neurotrophic Keratopathy (NK), which in severe cases can result in vision loss due to limited curative treatments. Despite the regenerative ability of the peripheral nerve system, the regeneration of corneal nerves is often incomplete and the underlying mechanisms are still unknown. This study aims to investigate the effect of Lysophosphatidic acid (LPA) on corneal nerve regeneration, which is known for its influence on the central nervous system.

Methods: Dorsal root ganglion cells of male C57BL/6 mice were isolated. The fiber length and the regeneration of injured neurons were measured with/without LPA. Additionally, siRNA experiments were performed to identify the specific LPA receptor (Lpar). Furthermore, underlying signaling pathways were investigated by qrt-PCR.

Results: The single-cell assay demonstrated a significant decrease in fiber length in the LPA-treated group after 48h. However, the neuronal fiber length of LPA-treated neurons after Lpar2 knockdown increased at 48h. The wound healing assay exhibited comparable results. Ngf and Gdnf were upregulated in injured neurons after LPA treatment.

Conclusion: This study elucidates the inhibitory effects of LPA on fiber outgrowth of neurons. Furthermore, Lpar2 is the responsible receptor for this inhibitory effect of LPA.

Hauptautor*innen: Nils Becker

Co-Autor*innen: PD Dr. med. Peter Savov, Prof. Dr. med. Max Ettinger, Dr. med. Ricarda Stauß, Dr. Dr. rer. medic. Gesine H. Seeber

Abstract:

Background: Short stem prostheses (ShS) were introduced as an alternative to conventional straight stem prostheses (CS), offering benefits like minimally invasive approaches, tissue and bone preservation, and physiological load transfer to the metaphysis. However, data on postoperative complication rates and implant survival are scarce.

Methods: A retrospective analysis of 1327 patients undergoing primary total hip arthroplasty (THA) using the Metha® ShS between 2006 and 2023 was conducted. Complication and revision rates were assessed for intraoperative, immediate postoperative, and follow-up periods. Implant survival was evaluated with the endpoint being all-cause stem revision.

Results: Intraoperative complications occurred in 3.77% of cases. The immediate postoperative complication rate was 2.44%, including 11 revision procedures (0.84%). The mean follow-up period was 7 years (range 1–17). During follow-up, 60 femoral component revisions were performed, with aseptic loosening and stem subsidence accounting for 80% of these cases. Implant survival was 95.66% and 95.50% at 5 vears and 15 years, respectively.

Conclusions: This study provides a comprehensive analysis of postoperative complications and revision rates in patients undergoing primary short stem THA. The results show favourable postoperative complication rates and long-term implant survival rates comparable to CS, suggesting that ShS are a viable option for younger patients.

Hauptautor*innen: Merle Marek

Co-Autor*innen: Dieter Wolke, Christian Sorg, Jil Wendt, Aurore Menegaux, Dennis Hedderich, Peter Bartmann, Micha Burkhardt, Andrea Hildebrandt, Axel Heep

Abstract:

In this study, we investigated the long-term consequences of very preterm (PT) birth (<32 weeks of gestation) or very low birth weight (<1500 g) on cognitive control and brain network topology using a multimodal approach. The study is based on a dataset of NPT = 63 PT and NFT = 80 full term (FT) 26-year old individuals that was acquired as part of the Bavarian Longitudinal Study (BLS, www.bayerische-entwicklungsstudie.de/). Results showed lower cognitive control performance in the PT group, with a 0.727 SD reduction in latent speed (p = .001) and a 1.143 SD reduction in latent sustained attention (p = .047). Contrary to our expectations, the PT group exhibited higher network integration and lower segregation in the cognitive control structural brain network, suggesting compensatory developmental processes. However, these network characteristics did not predict cognitive control outcomes. These findings highlight persistent cognitive control deficits in PT individuals and indicate potentially adaptive changes in brain network topology that do not directly translate to improved cognitive performance. This research underscores the importance of continued monitoring and support for individuals born very preterm as they transition into adulthood.

Hauptautor*innen: Akshay Anilkumar

Co-Autor*innen: Diana Faist, Praphulla Shukla, Gregor Theilmeier

Abstract:

Background: Foam cell formation by uptake of oxidized-LDL (oxLDL) in macrophages (Mϕ) marks the onset and progression of atherosclerosis and ultimately plaque destabilization. G-Protein Coupled Receptors (GPCR) and Regulator of G-protein signalling 5 (RGS5) drive atherogenic signalling. Lysophosphatidic acid receptors (LPA-R) and C-X-C chemokine receptor type 4 (CXCR4) could be regulated by RGS5. Objective: To examine RGS5’s role in oxLDL-uptake by Mϕ-derived foam cells in vitro

Methods: PMA-differentiated THP-1-Mϕ were transfected using RGS5 siRNA. RGS5 knockdown efficiency was evaluated by RTqPCR. Mϕ were incubated with Copper-oxidized human LDL (oxLDL, 10µg/ml) and Farnesyl monophosphate (FMP, 0.5 µM, LPA-R-inhibitor) or Plerixafor (0.01 µM, CXCR4-inhibitor). Oil-red-O staining was carried out on Mϕ followed by photometric analysis. Data were analyzed by Wilcoxon test using R.

Results: RGS5 knockdown was successful (ΔΔCT RGS5: 0.1892±0.042, n=5, p<0.01). Mϕ oxLDL-uptake (Absorbance Units: 1.403±0.238, n=5, p<0.01) was reduced by RGS5 knockdown (1.085±0.149, n=5, p<0.05). FMP decreased oxLDL-uptake (0.054±0.035, n=5/6, p<0.05), which was reversed by RGS5-kd (0.221±0.066, n=5/6, p<0.01). Plerixafor had no effect (0.127±0.089) even with RGS5-kd (0.168±0.126). Conclusion: oxLDL-uptake in Mϕ depends in part on RGS5 that affects LPA-R- but not CXCR4-mediated oxLDL-uptake. Further research could deliver potential RGS5-targeted therapeutic strategies to prevent atherosclerosis-related cardiovascular accidents.

Hauptautor*innen: Diana Faist

Co-Autor*innen: Akshay Anilkumar, Praphulla Shukla, Gregor Theilmeier

Abstract:

Background: G Protein Coupled Receptors and regulators of G-protein signaling 5 (RGS5) drive atherogenic signaling processes. Atherosclerotic plaque development involves foam cell formation from macrophages (Mϕ) and vascular smooth muscle cells (VSMCs) by oxLDL uptake.

Objective: To examine RGS5’s role for plaque composition and foam cell origin Methods: ApoE-/-RGS5+/+ (controls) and ApoE-/-RGS5-/- (RGS5-/-) mice were fed a 14w-high-fat-diet. Aortic valve lesions were quantified on H&E staining. Plaque composition was examined by Oil Red O, collagen, CD45, CD68, and alphaSMA staining. CD45 combined with pro- and anti-inflammatory markers was stained and co-localization analyzed.

Results: Lesion size and complexity were significantly reduced in RGS5-deficient mice. Oil Red O and collagen levels were unchanged. CD45-positive area increased significantly by 30.8%, whereas CD68 area decreased by 10.3% in RGS5-/- (both p<0.05). Mϕ-derived foam cells decreased by 23% (p<0.05), VSMC-derived foam cells increased by 5.8%. Pro-inflammatory Mϕ numbers increased, with no change in anti-inflammatory Mϕ numbers in RGS5-/- compared to controls.

Conclusion: RGS5 promotes plaque formation, increases Mϕ-derived foam cell numbers and reduces pro-inflammatory Mϕ. No difference in anti-inflammatory Mϕ indicate RGS5 inhibits VSMCs transition to foam cells, decreasing CD68-positive cells. Further study is required to assess therapeutic potential of RGS5 signaling.

Hauptautor*innen: Marie-Carlotta Müller

Co-Autor*innen: Prof. Dr. Bernhard Rauch

Abstract:

Colon cancer is currently the second most common tumor disease in Germany, although an increase in numbers is expected due to demographic change. Therefore, it is important to focus on optimized therapy and therefore develop efficient and appropriate test models to obtain information for possible future treatments. 3D organoids from malignant and healthy tissue of colorectal cancer patients help to illustrate the complex structure and interactions of the tumor and its surroundings in vitro. The aim of this study is to establish the culture of primary cells and the subsequent generation of organoids from patient samples. The focus then will be on investigating the influence of cytostatic drugs and the bioactive signaling lipid sphingosine-1-phosphate (S1P) on tumor cell growth in the 3D model compared to classic 2D cell culture. S1P has been shown to have an impact on various types of cancer, but there is still no evidence that these results can be extrapolated to patients with colorectal cancer, which might justify additional therapy with S1P receptor antagonists. This makes it interesting to study the influence of platelet-derived S1P on growth and sensitivity of organoids to cytotoxic drugs to prospectively provide estimates for patients with colorectal cancer.

Hauptautor*innen: Dipl.-Pharm. Christian Baume

Co-Autor*innen: Prof. Dr. Bernhard Rauch

Abstract:

Bioactive lipids such as the phospholipids sphingosine-1-phosphate, various derivatives from the group of lysophosphatidylcholines and lysophosphatidic acids mediate the activation of different signaling cascades of cell migration, apoptosis and metastasis, e.g. via membrane-bound G-protein coupled receptors. Deviations from the physiological concentrations of this phospholipids has been associated with the occurrence and progression of some diseases, including multiple sclerosis, gastrointestinal tumors and hematological neoplasms. We developed and validated a method for detection and quantification of selected phospholipids by HPLC-MS/MS in plasma and serum samples of humans and mice to understand the influence of bioactive lipids on the process of various diseases.

Hauptautor*innen: Chunjian Wang

Co-Autor*innen: Christian Keine, Go Ashida, Tamara Radulovic,Ivan Milenkovic

Abstract:

Globular bushy cells (GBCs) in the cochlear nucleus encode temporal information of sounds critical for sound source localization. Excitatory inputs to GBC arise from auditory nerve fibers (ANFs) which form large axosomatic synaptic terminals called endbulbs of Held. Each GBC is contacted by 5-12 endbulbs of largely varying size. This morphological variation in input size suggests a similar variation in synaptic input strength but it remains elusive how input variation influences the encoding of sounds. Here, we simulated ANF responses to sounds and tested how variation in input strength impacts responses in GBCs of the Mongolian Gerbil. While input variability increased spontaneous and sustained firing rates, it had little effect on the onset firing rate. Temporal precision of GBC responses, measured as phase-locking, decreased with input variability at low-frequency sounds without affecting responses to mid- and high-frequency sounds. For amplitude-modulated tones, commonly present in environmental sounds, increased input variability improved the neuronal reproduction of the stimulus at the expense of phase-locking accuracy. These findings suggest that changes in input variability in GBC can shift the emphasis from time-coding to level-coding and thus may play a role in enhancing GBCs’ ability to encode multiple features of complex acoustic signals.

Hauptautor*innen: Jin-Rong He

Co-Autor*innen: Tamara Radulovic, Nicole Ahrens, Anna-Maria Hartmann, Christian Keine, Ivan Milenkovic

Abstract:

The principal neurons in the lateral superior olive (LSO) compute interaural level differences by integrating excitatory inputs from the ipsilateral ear with inhibitory inputs from the contralateral ear. The lateral olivocochlear (LOC) neurons, also located in the LSO, receive the sound information from the ipsilateral ear and provide a feedback by regulating excitability of auditory nerve fibers beneath the inner hair cells on the same side. In a mouse model with KCC2 Thr934Ala/Ser937Asp double mutation, LSO neurons show premature onset of hyperpolarizing inhibition (P3) due to KCC2 activity. In the present study we use this mouse model to investigate the development of LSO and LOC neurons with patch-clamp recordings in acute slices. The LSO neurons in KCC2 Thr934Ala/Ser937Asp mice show higher action potential threshold compared to control. The LOC neurons of KCC2 Thr934Ala/Ser937Asp mice show lower input resistance than the control. These data indicate changes in the development of biophysical properties. The data are complemented by morphological analysis of synaptic inputs to LSO and LOC neurons.

Hauptautor*innen: Tamara Radulovic

Co-Autor*innen: Lena Ebbers, Michael Winklhofer, Hans Gerd Nothwang, Ivan Milenkovic, and Anna-Maria Hartmann

Abstract:

The potassium chloride cotransporter KCC2 is crucial for Cl- extrusion from mature neurons and thus key to hyperpolarizing inhibition. Auditory brainstem circuits contain well-understood inhibitory projections and provide a potent model to study the regulation of synaptic inhibition. Two peculiarities of the auditory brainstem are (i) posttranslational activation of KCC2 during development and (ii) extremely negative reversal potentials in specific circuits. To investigate the role of the potent phospho-site serine 937 therein, we generated a KCC2 Thr934Ala/Ser937Asp double mutation, in which Ser937 is replaced by aspartate mimicking the phosphorylated state, and the neighbouring Thr934 arrested in the dephosphorylated state. This double mutant showed a twofold increased transport activity in HEK293 cells, raising the hypothesis that auditory brainstem neurons show lower [Cl−]i. and increased glycinergic inhibition. This was tested in a mouse model carrying the same KCC2 Thr934Ala/Ser937Asp mutation by the use of the CRISPR/Cas9 technology. Homozygous KCC2 Thr934Ala/Ser937Asp mice showed an earlier developmental onset of hyperpolarisation in the auditory brainstem. Mature neurons displayed stronger glycinergic inhibition due to hyperpolarized ECl−. These data demonstrate that phospho-regulation of KCC2 Ser937 is a potent way to interfere with the excitation-inhibition balance in neural circuits.

Hauptautor*innen: Jella Voelter

Co-Autor*innen: René Hurlemann, Dirk Scheele

Abstract:

Patients with Borderline Personality Disorder (BPD) suffer from severe social impairments and interpersonal problems. Social touch facilitates the maintenance of social bonds and preliminary evidence indicates a negative evaluation of social touch in BPD patients. Skin-mediated signals are conceptualized as an interoceptive domain and BPD is associated with altered interpretation of inner bodily signals. However, the neural mechanisms underlying aberrant touch and interoceptive attention processing in BPD remain unclear. We recruited 55 BPD patients and 31 Healthy Controls (HC) and used functional magnetic resonance (fMRI) imaging to probe neural responses to slow (C-tactile (CT)-optimal) and fast (CT-suboptimal) touch before and after four weeks of inpatient Dialectical Behavior Therapy (DBT). Additionally, BPD patients underwent an fMRI paradigm to evaluate their interoceptive attention by focusing on either their heart or stomach. Results revealed a negative bias towards social touch in BPD patients, evident in a more negative attitude towards and reduced comfort zones of social touch. Despite significant improvements in overall BPD symptom load, dysfunctional social touch processing persisted after four weeks of DBT. Neural findings suggest that impairments in the insula-mediated integration of sensory and affective components of CT-optimal touch may constitute a biological signature of interpersonal problems in BPD.

Hauptautor*innen: Danilo Postin

Co-Autor*innen: Prof. Dr. Dr. René Hurlemann

Abstract:

Even after successful treatment of the psychotic symptoms, most patients with schizophrenia suffer from persistent impairments in cognitive, occupational and social domains. These impairments compromise participation in everyday life and are often accompanied by increasing social isolation and loneliness. Subtle changes in social behaviours, including social withdrawal, can already be observed in the prodromal phase of schizophrenia (at-risk mental state) and play a crucial role in the chronic course of the disease. While previous studies have demonstrated behavioural deficits in various social-cognitive domains in patients with schizophrenia, little is known about disease-related changes in the neural processing of basic stimuli of the social world such as touch. The present study therefore aimed to investigate differences in the neural and behavioural correlates of social touch between patients with schizophrenia and a healthy control group without a family history of psychotic illness. Both groups underwent task-based functional magnetic resonance imaging (fMRI) to examine the neural correlates of social and non-social touch. To further characterize potential biases related to social touch, additional physical touch "permission maps" were measured. The present study may inform future strategies in the development of personalized treatment approaches for schizophrenia.

Hauptautor*innen: Christina Müller

Co-Autor*innen: Carsten Gießing, René Hurlemann, Sahib Khalsa

Abstract:

Urbach-Wiethe Disease (UWD) is a very rare genetic disorder often accompanied by bilateral amygdala damage. Previous behavioral studies showed amygdala damage is associated with altered processing of interoceptive stimuli, but the underlying neural mechanisms are still unclear. In this study, one patient with UWD and 51 healthy controls (HCs) participated in a functional magnetic resonance imaging experiment (fMRI) with an interoceptive perturbation task. Participants were administered isoproterenol leading to fast and transient increase in heart rate. Our results demonstrated marked differences in the shape of the heart rate. In a subsequent network analysis, we constructed networks separate for the peak phase (80 – 120 seconds) and early recovery phase (120 – 180 seconds) and selected edges showing granger causal relationship between heart rate and dynamic functional connectivity. During peak phase, strongest differences in connectivity were between the right anterior insula and the dorsal anterior cingulate cortex (dACC). During early recovery phase, most striking dissimilarities were observable between dACC and ventromedial prefrontal cortex. The alterations in the network configuration could indicate adaptive reconstruction of the interoceptive network in UWD patient to compensate for the loss of amygdala function.