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Item type: Item , Feline malignant lymphoma in an uncommon location as a differential diagnosis for neurological disease(2025) Lépine, Maximilien; Schmitz, Sarah; Körber, Svenja; Köhler, KerntItem type: Item , Rates and predictors for sustained ventricular tachycardia in patients with cardiac sarcoidosis and AV block as first cardiac presentation: Implications for device implantation(2025) Dinov, Borislav; Henfling, Carsten; Ebbinghaus, Hans; Latuscynski, Konrad; Paetsch, Ingo; Jahnke, Cosima; Sossalla, Samuel; Laufs, Ulrich; Ueberham, LauraBackground: Atrioventricular block (AVB) is a frequent initial presentation of cardiac sarcoidosis (CS), but dangerous ventricular arrhythmias (VA) can occur. Despite the scarcity of data, guidelines recommend implantable cardioverter-defibrillator (ICD) rather than a pacemaker implantation whenever a device is needed. Objective: In this study, we aimed to establish predictors for sustained VA in patients with CS presenting with pacing indication because of an AVB. Methods: We prospectively enrolled 112 patients with CS. Excluding those with VA, 82 patients remained and were divided into 2 groups: 34 individuals with AVB as initial presentation and 48 with other symptoms as first presentation (OSF). Both groups were compared for clinical characteristics, rates of VA, left ventricular assist device (LVAD) implantation, heart transplantation, and mortality. Results: During follow-up, VA was detected in 50% in the AVB and 10.4% in the OSF group (P = .001). Death, LVAD implantation, and heart transplantation occurred in 11.8% in AVB group vs 10.4% in the OSF group (P = .847). Late gadolinium enhancement (LGE) was equally observed in both groups: 70% vs 70.5% (P = .966), whereas more patients in the AVB group exhibited abnormal positron emission tomography (PET) uptake: 86.2% vs 54.3% (P = .007). In multivariate analysis, AVB (hazard ratio [HR], 25.15), right ventricular (RV) LGE in cardiovascular magnetic resonance (CMR) (HR, 7.39) were predictors for VA occurrence, whereas the use of immunosuppressive therapy was associated with less VA (HR, 0.26). Conclusions: Patients with CS presenting with AVB have a high risk of sustained VA. Although immunosuppressive drugs may reduce the occurrence of VA, ICD implantation is reasonable, especially in case of RV LGE.Item type: Item , Very pronounced bowel sparing during radiation therapy for anal carcinoma using a natural spacer (Myoma) – a case report(2024) Hoeng, L.; Exeli, A. K.; Krombach, G. A.; Schwandner, T.; Agolli, L.; Habermehl, D.Background: Using dose-painted intensity-modulated radiation therapy, specific dose volume constraints or implantation of tissue expanders prior to radiotherapy are validated options for reducing radiation dose on the bowel and therefore minimizing acute gastrointestinal toxicity during chemoradiation for anorectal malignancies. We describe the rare case of a female patient with a locally advanced anal carcinoma where a large myomatous uterus served as a natural spacer to protect the bowel during radiation therapy. Case presentation: Initially the patient presented with anal pain, proctoscopy followed by an excisional biopsy confirmed the diagnosis of a squamous cell carcinoma of the anus. Imaging examination showed a locally advanced tumor and in addition a large uterus with typical leiomyomas up to 11.5 cm in diameter. The patient underwent chemoradiation; because of the large leiomyomas there was almost no dose burden for the small intestine and therefore practically no gastrointestinal toxicity. Conclusion: As we know, this report describes the situation that a large myomatous uterus served as a natural spacer during radiation therapy in a way that is unique to date.Item type: Item , Toxoplasma gondii infection induces early host cell cycle arrest and DNA damage in primary human host cells by a MYR1-dependent mechanism(2024) Velásquez, Zahady D.; Rojas-Baron, Lisbeth; Conejeros, Iván; Hermosilla, Carlos; Taubert, AnjaToxoplasma gondii, an obligate intracellular parasite, control its host cell cycle through mechanisms that are not fully understood. Key effector molecules, including MYR1 and HCE1, play roles in translocating parasite proteins and inducing host cellular cyclin E1 overexpression, respectively. We investigated the early role of MYR1- and HCE1-driven host cell cycle arrest and DNA damage (up to 3 h p.i.). Our findings showed that T. gondii-infected cells experienced S-phase arrest and displayed double-strand DNA breaks as soon as 15 min p.i. This condition persisted until 3 h p.i., at which point we also observed increased host cell binucleation and micronuclei formation, both hallmarks of genomic instability. Furthermore, host cells responded to DNA damage by activating the ATM branch of the homologous recombination repair pathway. MYR1 was shown to be crucial, as TgΔmyr1 tachyzoites failed to induce S-phase arrest and DNA damage foci. In contrast, the absence of HCE1 did not produce these effects, suggesting that cyclin E1 expression was not involved. Also, DNA damage was demonstrated to be ROS-independent, suggesting that ROS did not trigger DNA damage. Our results suggest that T. gondii compromises host cellular DNA integrity depending on MYR1 shortly after infection, maintaining it over time.Item type: Item , Molecular composition of skeletal muscle in infants and adults: a comparative proteomic and transcriptomic study(2024) Schaiter, Alexander; Hentschel, Andreas; Kleefeld, Felix; Schuld, Julia; Umathum, Vincent; Procida-Kowalski, Tara; Nelke, Christopher; Roth, Angela; Hahn, Andreas; Krämer, Heidrun H.; Ruck, Tobias; Horvath, Rita; van der Ven, Peter F. M.; Bartkuhn, Marek; Roos, Andreas; Schänzer, AnneTo gain a deeper understanding of skeletal muscle function in younger age and aging in elderly, identification of molecular signatures regulating these functions under physiological conditions is needed. Although molecular studies of healthy muscle have been conducted on adults and older subjects, there is a lack of research on infant muscle in terms of combined morphological, transcriptomic and proteomic profiles. To address this gap of knowledge, we performed RNA sequencing (RNA-seq), tandem mass spectrometry (LC–MS/MS), morphometric analysis and assays for mitochondrial maintenance in skeletal muscle biopsies from both, infants aged 4–28 months and adults aged 19–65 years. We identified differently expressed genes (DEGs) and differentially expressed proteins (DEPs) in adults compared to infants. The down-regulated genes in adults were associated with functional terms primarily related to sarcomeres, cellular maintenance, and metabolic, immunological and developmental processes. Thus, our study indicates age-related differences in the molecular signatures and associated functions of healthy skeletal muscle. Moreover, the findings assert that processes previously associated solely with aging are indeed part of development and healthy aging. Hence, combined findings of this study also indicate that age-dependent controls are crucial in muscle disease studies, as otherwise the comparative results may not be reliable.