RepoMed (Medizinische Hochschule Hannover)
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Short- and long-term changes in neurological, behavioural, and blood biomarkers following repeated mild traumatic brain injury in rats-potential biological sex-dependent effects
Full text linkIntroduction Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease resulting from repeated mild traumatic brain injuries (rmTBI). The necessity for diagnosis of CTE, which can so far only be confirmed after post-mortem, is a pressing need. New approaches to early diagnose this disease are crucial to facilitate the translation of novel treatment strategies to the clinic. Several studies have found suitable candidate biomarkers, but the results are not straightforward. As biological sex is suggested to be a major confounding factor, we explored how sex influences behavioural and candidate blood biomarkers during CTE-like progression following experimental rmTBI. Methods To induce CTE-like development, we subjected male and female rats to three mTBIs at a 5-day interval. We then monitored and analysed differences in neurological, behavioural, and physiological parameters up to 12 weeks after the injuries-both by sex and grouped-and underwent further analysis using generalised estimated equation (GEE). To determine long-term changes in tau aggregation as a hallmark of CTE, we used [18F]-florzolotau (florzolotau) autoradiography in brain slices. Results Both short-term weight gain and time-to-right after rmTBI were increased in grouped animals, with male rats showing more prominent changes. The neurological state was impaired after each mTBI and still 12 weeks later, independent of the sex. A protracted anhedonic-like behaviour due to rmTBI was found at the group level only at week 2 but remained continuously present in male rats. While spatial memory was not impaired, male rats showed increased anxiety-like behaviour. Moreover, neuron-specific enolase (NSE) was elevated in the blood 1 day after rmTBI, but only in females. On the contrary, blood p-tau was increased 3 days after rmTBI only in males. In addition, male rats showed significantly increased florzolotau binding in the brain after 12 weeks, suggesting brain contusion causes increased tau aggregation. Interestingly, brain neurofibrillary tangles (NFTs) at 12 weeks after rmTBI showed a strong correlation with the neurological state at 1 day after rmTBI. Discussion Taken together, our findings suggest that male rats may be more susceptible to short-and long-term consequences of rmTBI in the applied model. These sex differences should be considered when translating preclinical biomarker candidates to the clinic. Understanding these differences could guide the diagnosis and treatment of CTE in a personalized manner, offering hope for more effective treatments in the future
Skull stripping tools in pediatric T2-weighted MRI scans: a retrospective evaluation of segmentation performance
Full text linkIntroduction For brain maturity assessment of infants aged above 6 months, T2-weighted MRI scans are recommended. Prior to automated brain tissue analysis, skull stripping is typically applied. However, most skull stripping tools neither focus on T2-weighted scans nor on pediatric cohorts. Here, we present the evaluation results of seven common skull stripping tools in a comparably large pediatric cohort. Methods This study is based on 199 T2-weighted scans of children under the age of 5 years retrospectively acquired from the clinical routine at Hannover Medical School. We established a manually labeled ground truth under quality control of a senior neuroradiologist specialized in pediatric neuroradiology and evaluated seven skull stripping tools (BET, ROBEX, HD-BET, HD-BET-fast, SynthStrip, SynthStrip-noCSF and d-SynthStrip). Segmentation performance (Dice score, 95th percentile Hausdorff distance, sensitivity, specificity) and computation time were assessed on non-preprocessed and preprocessed scans (zero padding, contrast enhancement, artifact removal and normalization) as well as in different brain regions. For the best performing model, we manually assessed the top and bottom quartile of segmentations with respect to the integrity of different anatomical brain structures. Results Only BET, HD-BET, HD-BET-fast profited from data preprocessing. Considering this, all models had median Dice scores between 0.88 and 0.96, with SynthStrip performing best. All models segmented most accurately in the middle axial slices of the brain. Resampling lowered the performance of all models, except ROBEX. Mean computing times ranged from 2 s (BET) to 132 s (HD-BET) with SynthStrip requiring 7 s. per scan. SynthStrip was prone to not entirely including the Sinus sagittalis superior, the upper Cerebrum, the temporal pole, the Cerebellum and the Chiasma opticum/pituitary gland. In contrast, the petrous bone and the skull in the middle axial slices have often been partly included. Discussion Due to its robustness and quick computation time, we recommend SynthStrip for skull stripping of pediatric T2-weighted MRI scans. We attribute the observed segmentation errors to the partial volume effect, which should be addressed in future research. Limitations of our study include the monocentric setting, the exclusion of pathological cases and the skewed age distribution in our cohort
Verbesserung der Arbeitsfähigkeit nach bariatrischen Operationen: Ergebnisse einer longitudinalen Studie vier Jahre postoperativ
Full text linkFrom evidence to action: Gender-sensitive cardiovascular care - a quantitative survey with physicians working in cardiology departments
No full textDie Daten stammen aus einer anonymen Online-Querschnittsbefragung (LimeSurvey), die von Mai 2024 bis Februar 2025 unter Ärztinnen und Ärzten in kardiologischen Krankenhausabteilungen in Deutschland durchgeführt wurde. Die Daten wurden erhoben im Rahmen des Innovationsfonds HeartGap-Projekts. Erfasst wurden (1) soziodemografische und berufliche Merkmale, (2) Geschlechtersensibilität, gemessen mit der validierten Gender Sensitivity-Subskala der Nijmegen Gender Awareness in Medicine Scale (N-GAMS), und (3) Wissen zu geschlechts- und genderspezifischen kardiovaskulären Aspekten, operationalisiert über 17 dichotome Items. Diese Wissensitems basieren auf einer systematischen Auswertung einschlägiger kardiologischer Leitlinien (ESC, DGK, AWMF). Die Daten liegen im CSV-Format vor und umfassen metrische Variablen (z. B. Alter in Jahren), kategoriale Variablen (z. B. Geschlecht, Krankenhaustyp), ordinalskalierte Likert-Items (1–5, N-GAMS) sowie dichotome Wissensvariablen (0/1). Alle Angaben sind vollständig anonymisiert. Die Studie wurde von der Ethikkommission der MHH genehmigt (10745_BO_K_2023)
PIL012_Auswertung_Schmerzevaluierung_Piritramid_LZ_05-2024.xlsx
No full textData concerning the following project/manuscript: Oral Self-Administration of Piritramide in C57BL/6JRj Mice Following Laparotomy: Cage-Side Pain Assessment Evaluation Lena Zachhuber, Claudia Kuntner, Thomas Wanek, Aylina Glasenapp, Marion Bankstahl Despite its clinical use, there is a lack of comprehensive data on the analgesic potential of piritramide for post-surgical pain management in laboratory animals. Therefore, this study investigated the potential of a combined therapy of orally administered piritramide and subcutaneously injected buprenorphine for post-surgical pain in C57BL/6JRj mice after laparotomy. Male and female mice received a preoperative buprenorphine injection, followed by oral self-administration of piritramide in drinking water for four days post-surgery. Physiological and behavioral parameters i.e., water and food intake, nesting behavior, voluntary wheel running activity, body weight, and clinical score, were monitored. Results indicated no significant decrease in water intake in female mice, whereas male mice had a significant reduction 4-7 hours after surgery (p = 0.0229). Dry food intake remained below baseline consumption, but a higher intake of wet food compensated for this. Nesting behavior, wheel running time and distance showed no significant impairment. However, male mice exhibited increased running velocity at 104 hours post-surgery (p = 0.0113). Minimal weight loss and mild increased clinical scores were observed. These findings suggest that piritramide, in combination with preoperative buprenorphine, exhibits analgesic potential and was well-tolerated, supporting its applicability for management of laparotomy-induced pain in laboratory mice. Data were aquired at Medical University of Vienna, by Lena Zachhuber et al
Anti-FAP CAR-NK cells as a novel targeted therapy against cervical cancer and cancer-associated fibroblasts.
Full text linkThe tumor microenvironment (TME) has a central role in many cancers, particularly by fostering an immunosuppressive milieu. Chimeric antigen receptor (CAR)-based immunotherapy displays a promising strategy to re-direct immune cells toward specific antigens, thereby inducing targeted cytotoxicity. The fibroblast activation protein (FAP) is overexpressed in various cancer types and has shown promise in CAR-based therapies. However, its application in gynecological cancers remains unexplored. This study evaluates the efficacy of anti-FAP CAR-NK cells as a targeted immunotherapy for cervical cancer and cancer-associated fibroblasts (CAFs). FAP expression was quantified on cervical cancer cell lines, primary cervical cancer tissues, and cells isolated from these tissues. Alpharetroviral SIN vectors were used to transduce NK-92 cells and primary cord blood-derived NK cells with 3rd-generation anti-FAP CARs. Immunohistochemistry and flow cytometry revealed high FAP expression on CaSki cells, cervical cancer tissues, and primary cervical CAFs. In 2D co-cultures with FAP-positive target cells, anti-FAP CAR-NK cells exhibited significantly enhanced cytotoxicity and elevated degranulation compared to control NK cells, with no observed effects against FAP-negative target cells. Primary NK cells revealed high cytotoxicity against cervical cancer cells with a high release of cytolytic enzymes. Anti-FAP CAR-NK cells also showed efficient elimination of cervical cancer cells and CAFs in 3D tumor spheroid models. These findings underscore the potential of anti-FAP CAR-NK cells as a potent therapeutic approach for cervical cancer and suggest broader applicability in diseases characterized by high FAP expression
