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JLUpub bietet Mitgliedern und Angehörigen der Universität die Möglichkeit neben wissenschaftlichen Dokumenten auch Forschungsdaten elektronisch zu veröffentlichen und dauerhaft zugänglich zu machen. Alle Veröffentlichungen erhalten einen Digital Object Identifier (DOI) und werden über nationale und internationale Bibliothekskataloge sowie Suchmaschinen nachgewiesen und auffindbar.
Neue Veröffentlichungen:
Predominant transmission of KPC-2 carbapenemase in Germany by a unique IncN plasmid variant harboring a novel non-transposable element (NTE KPC -Y)
(2024) Yao, Yancheng; Falgenhauer, Linda; Rezazadeh, Yalda; Falgenhauer, Jane; Imirzalioglu, Can; Chakraborty, Trinad
Carbapenemase-producing Enterobacterales (CPE) pose a major public health threat. Despite active infection prevention efforts, the incidence of KPC-2 carbapenemase-producing Enterobacterales (KPC2-CPE) continues to increase worldwide. In this study, we performed genome sequencing of 135 KPC2-CPE isolates obtained from multiple sources (clinical, hospital environments, and surface water) in Germany between 2013 and 2019 and analyzed them for epidemiological clues regarding transmission. For 92% (124/135) of all isolates, which comprised 14 different species such as Klebsiella, Escherichia, Citrobacter, Enterobacter, Raoultella, and Serratia, KPC-2 was present on an IncN[pMLST15] plasmid. All plasmids carried a novel non-Tn4401-element harboring an aac (3)-IId-bla TEM-1B-bla KPC-2–cassette (designated NTE KPC -Y) that was co-transferred with an adjacent region carrying 12 further antibiotic resistance genes. Identical plasmids were also detected in KPC2-CPE isolates from environmental samples. These plasmids were remarkably stable and were maintained in individual patients colonized with KPC-2 CPEs over a long-term period (>1 year). Thus, a predominant broad host range signature IncN[pMLST15] plasmid mediates transmission of both KPC-2 and associated multiple antimicrobial drug resistance genes in Germany. These data underline the need for in-depth characterization of plasmid carriers of CPE in surveillance and outbreak studies as well as in microbiomes from patients and the environment to identify hidden transmission reservoirs. This information will be essential for the development and implementation of effective infection control and prevention measures to disrupt dissemination of KPC2- CPEs in healthcare and associated environmental settings.
Patient-Reported Postoperative Neuropsychological Deterioration After Heart Valve Replacement and Coronary Artery Bypass Grafting
(2024) Butz, Marius; El-Shazly, Jasmin; Gerriets, Tibo; Meyer, Rolf; Tschernatsch, Marlene; Braun, Tobias; Schramm, Patrick; Doeppner, Thorsten R.; Gerner, Stefan T.; Boening, Andreas; Choi, Yeong-Hoon; Schoenburg, Markus; Juenemann, Martin
Background: Postoperative cognitive decline (POCD) after cardiosurgical interventions are well described through objective psychometric tests. However, a patient’s subjective perception is essential to clinical assessment and quality of life. This study systematically evaluated patient-reported POCD between subjects undergoing coronary artery bypass grafting and heart valve replacement.
Methods: This study was a multicentre, prospective questionnaire survey conducted at the cardiac surgery departments at the Kerckhoff Clinic in Bad Nauheim and the University Hospital in Giessen, Germany. We included patients undergoing elective coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral valve replacement or reconstruction (MVR), and combined surgery (CABG + valve replacement [VR]) with extracorporeal circulation. The Hospital Anxiety and Depression Scale, the Cognitive Failures Questionnaire (CFQ) for Self-assessment (CFQ-S), and the external assessment (CFQ-foreign [F]) were completed preoperatively, as well as at 3 and 12 months postoperatively.
Results: A total of 491 patients were available for analyses (CABG = 182, AVR = 134, MVR = 93, CABG + VR = 82). POCD and postoperative depression increase (PODI) were observed for each surgical procedure. (At the 3-month follow-up: CFQ-S [CABG = 7.1%, AVR = 3.7%, MVR = 9.7%, CABG + VR = 9.8%]; CFQ-F [CABG = 9.9%, AVR = 9.7%, MVR = 9.7%, CABG + VR = 15.9%]; PODI [CABG = 7.7%, AVR = 9.7%, MVR = 6.5%, CABG + VR = 8.5%]. At the 12-month follow-up: CFQ-S [CABG = 6.6%, AVR = 7.5%, MVR = 15.1%, CABG + VR = 7.3%]; CFQ-F [CABG = 7.1%, AVR = 14.9%, MVR = 10.8%, CABG + VR = 9.8%]; PODI [CABG = 10.4%, AVR = 11.2%, MVR = 6.5%, CABG + VR = 4.9%]). No significant between-group effects were observed for the CFQ-S, CFQ-F, or the Hospital Anxiety and Depression Scale.
Conclusions: For clinicians, paying attention to patients' self-reported experiences of reduced cognitive function and symptoms of depression following cardiac surgery is important. Such reporting is an indication that interventions such as cognitive training or psychotherapy should be considered.
Rhodopsin orphan GPCR20 interacts with neuropeptides and directs growth, sexual differentiation, and egg production in female Schistosoma mansoni
(2024) Li, Xuesong; Weth, Oliver; Haimann, Martin; Möscheid, Max F.; Huber, Theresa S.; Grevelding, Christoph G.
Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease of worldwide importance. Since standard treatment of schistosomiasis relies on a single drug, praziquantel, alternative drugs are needed. G protein-coupled receptors (GPCRs) represent promising targets for new anthelmintics. Although GPCRs represent a prominent receptor class in schistosomes, functional studies are limited just as knowledge about their ligands. Candidate ligands are neuropeptides acting as neurotransmitters, neuromodulators, or hormones in the nervous system. Transcriptomics studies in Schistosoma mansoni indicated that nearly all neuropeptide genes (Sm_npps) and a subgroup of GPCRs exhibited a sex- and pairing-dependent expression profile. Among these was the rhodopsin orphan GPCR20 (SmGPCR20), which we characterized in our study. Using a yeast two-hybrid-based approach, we identified specific interactions between SmGPCR20 and two neuropeptides SmNPP26 and SmNPP40. As analyzed by qRT-PCR, Smgpcr20, Smnpp26, and Smnpp40 showed sex- and/or pairing-influenced expression. Whole-mount in situ hybridization exhibited transcripts of these genes in neuronal cells, subtegumental area, and parenchyma of both sexes. Furthermore, we received indication for co-localization of transcripts of these genes in the anterior “head” region of single-sex females and in particular patterns along the worm body indicating neuronal expression. RNA interference (RNAi) with combinations of double-stranded RNAs against the three genes resulted in reduced egg production. Confocal microscopy revealed morphologic changes in the female gonads. Furthermore, RNAi in first-time paired females caused a reduced length of females after double knockdown of SmGPCR20 and SmNPP26 and changes in the ovary. In addition, we found reduced transcript levels of egg formation-associated and gonad-specifically transcribed genes and the stem-cell marker nanos-1. The obtained results suggest that SmNPP26 and SmNPP40 are potential ligands of SmGPCR20 and that this GPCR in combination with both neuropeptides affects egg production, oogenesis, and growth of S. mansoni females.
Schistosoma mansoni–Induced Oxidative Stress Triggers Hepatocellular Proliferation
(2024) von Bülow, Verena; Schneider, Maryam; Dreizler, Dorothee; Russ, Lena; Baier, Anne; Buss, Nicola; Lichtenberger, Jakob; Härle, Lukas; Müller, Heike; Tschuschner, Annette; Schramm, Gabriele; Pons-Kühnemann, Jörn; Grevelding, Christoph G.; Roeb, Elke; Roderfeld, Martin
Background & Aims: Schistosomiasis is one of the most prominent parasite-induced infectious diseases, affecting more than 250 million people. Schistosoma mansoni causes metabolic exhaustion and a strong redox imbalance in the liver, causing parenchymal damage, and may predispose for cancer. We investigated whether oxidative stress provokes hepatocellular proliferation upon S. mansoni infection.
Methods: The cell cycle, replication stress response, and proliferation were analyzed on transcriptional and protein levels in the livers of S. mansoni–infected hamsters and by mechanistic gain- and loss-of-function experiments in human hepatoma cells. Major results were validated in human biopsy specimens of S. mansoni–infected patients.
Results: S. mansoni infection induced licensing factors of DNA replication and cell-cycle checkpoint cyclins in parallel with a DNA damage response in hamster hepatocytes. Moreover, even unisexual infection without egg effects, as a reflection of a chronic inflammatory process, resulted in a moderate activation of several cell-cycle markers. S. mansoni soluble egg antigens induced proliferation of human hepatoma cells that could be abolished by reduced glutathione.
Conclusions: Our data suggest that hepatocellular proliferation is triggered by S. mansoni egg-induced oxidative stress.
Periodontal pathogens and cancer development
(2024) Zhou, Yuxi; Meyle, Joerg; Groeger, Sabine
Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.