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    Efficiency of biofilm removal by combination of water jet and cold plasma: an in-vitro study
    (London : BioMed Central, 2022) Matthes, Rutger; Jablonowski, Lukasz; Pitchika, Vinay; Holtfreter, Birte; Eberhard, Christian; Seifert, Leo; Gerling, Torsten; Vilardell Scholten, Laura; Schlüter, Rabea; Kocher, Thomas
    Background: Peri-implantitis therapy is a major problem in implantology. Because of challenging rough implant surface and implant geometry, microorganisms can hide and survive in implant microstructures and impede debridement. We developed a new water jet (WJ) device and a new cold atmospheric pressure plasma (CAP) device to overcome these problems and investigated aspects of efficacy in vitro and safety with the aim to create the prerequisites for a clinical pilot study with these medical devices. Methods: We compared the efficiency of a single treatment with a WJ or curette and cotton swab (CC) without or with adjunctive use of CAP (WJ + CAP, CC + CAP) to remove biofilm in vitro from rough titanium discs. Treatment efficacy was evaluated by measuring turbidity up to 72 h for bacterial re-growth or spreading of osteoblast-like cells (MG-63) after 5 days with scanning electron microscopy. With respect to application safety, the WJ and CAP instruments were examined according to basic regulations for medical devices. Results: After 96 h of incubation all WJ and CC treated disks were turbid but 67% of WJ + CAP and 46% CC + CAP treated specimens were still clear. The increase in turbidity after WJ treatment was delayed by about 20 h compared to CC treatment. In combination with CAP the cell coverage significantly increased to 82% (WJ + CAP) or 72% (CC + CAP), compared to single treatment 11% (WJ) or 10% (CC). Conclusion: The newly developed water jet device effectively removes biofilm from rough titanium surfaces in vitro and, in combination with the new CAP device, biologically acceptable surfaces allow osteoblasts to grow. WJ in combination with CAP leads to cleaner surfaces than the usage of curette and cotton swabs with or without subsequent plasma treatment. Our next step will be a clinical pilot study with these new devices to assess the clinical healing process.
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    Short- and long-term polystyrene nano- and microplastic exposure promotes oxidative stress and divergently affects skin cell architecture and Wnt/beta-catenin signaling
    (London : BioMed Central, 2023) Schmidt, Anke; da Silva Brito, Walison Augusto; Singer, Debora; Mühl, Melissa; Berner, Julia; Saadati, Fariba; Wolff, Christina; Miebach, Lea; Wende, Kristian; Bekeschus, Sander
    Nano- and microplastic particles (NMP) are strong environmental contaminants affecting marine ecosystems and human health. The negligible use of biodegradable plastics and the lack of knowledge about plastic uptake, accumulation, and functional consequences led us to investigate the short- and long-term effects in freshly isolated skin cells from mice. Using fluorescent NMP of several sizes (200 nm to 6 µm), efficient cellular uptake was observed, causing, however, only minor acute toxicity as metabolic activity and apoptosis data suggested, albeit changes in intracellular reactive species and thiol levels were observed. The internalized NMP induced an altered expression of various targets of the nuclear factor-2-related transcription factor 2 pathway and were accompanied by changed antioxidant and oxidative stress signaling responses, as suggested by altered heme oxygenase 1 and glutathione peroxide 2 levels. A highly increased beta-catenin expression under acute but not chronic NMP exposure was concomitant with a strong translocation from membrane to the nucleus and subsequent transcription activation of Wnt signaling target genes after both single-dose and chronic long-term NMP exposure. Moreover, fibroblast-to-myofibroblast transdifferentiation accompanied by an increase of α smooth muscle actin and collagen expression was observed. Together with several NMP-induced changes in junctional and adherence protein expression, our study for the first time elucidates the acute and chronic effects of NMP of different sizes in primary skin cells' signaling and functional biology, contributing to a better understanding of nano- and microplastic to health risks in higher vertebrates.
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    Consequences of nano and microplastic exposure in rodent models: the known and unknown
    (London : BioMed Central, 2022) da Silva Brito, Walison Augusto; Mutter, Fiona; Wende, Kristian; Cecchini, Alessandra Lourenco; Schmidt, Anke; Bekeschus, Sander
    The ubiquitous nature of micro- (MP) and nanoplastics (NP) is a growing environmental concern. However, their potential impact on human health remains unknown. Research increasingly focused on using rodent models to understand the effects of exposure to individual plastic polymers. In vivo data showed critical exposure effects depending on particle size, polymer, shape, charge, concentration, and exposure routes. Those effects included local inflammation, oxidative stress, and metabolic disruption, leading to gastrointestinal toxicity, hepatotoxicity, reproduction disorders, and neurotoxic effects. This review distillates the current knowledge regarding rodent models exposed to MP and NP with different experimental designs assessing biodistribution, bioaccumulation, and biological responses. Rodents exposed to MP and NP showed particle accumulation in several tissues. Critical responses included local inflammation and oxidative stress, leading to microbiota dysbiosis, metabolic, hepatic, and reproductive disorders, and diseases exacerbation. Most studies used MP and NP commercially provided and doses higher than found in environmental exposure. Hence, standardized sampling techniques and improved characterization of environmental MP and NP are needed and may help in toxicity assessments of relevant particle mixtures, filling knowledge gaps in the literature.
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    Detection of fractures of hand and forearm in whole-body CT for suspected polytrauma in intubated patients
    (London : BioMed Central, 2020) Münn, F.; Laun, R.A.; Asmus, A.; Bülow, R.; Bakir, S.; Haralambiev, L.; Eisenschenk, A.; Kim, S.
    Background: The aim of this study was to evaluate the potential of whole-body CT for diagnosis of hand and forearm fractures in intubated patients with suspected polytrauma. Methods: We performed a retrospective analysis on data collected from two trauma centres in Germany, including demographics, ISS, clinical symptoms, depiction in whole-body CT, and time to diagnosis. Results: Out of 426 patients included in the study, 66 (15.5%) suffered a hand or forearm fracture. The total number of fractures was 132, the whole-body CT report mentioned 98 (74.2%). 16 (12,1%) fractures of 12 patients were diagnosed later than 24 h after admission. Late diagnoses of fractures of the hand occurred more often if the hand was not fully included in the CT scan field. The sensitivity of whole-body CT for cases with fractures of hand and/or forearm with full inclusion of the corresponding area in the scan field was 80.2%. Conclusions: This study shows that whole-body CT is a valuable diagnostic tool for hand fractures in polytrauma patients. Hands should be evaluated regardless of clinical presentation in intubated patients after suspected polytrauma if they are included in the whole-body CT. © 2020 The Author(s).
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    Tissue Tolerable Plasma (TTP) induces apoptosis in pancreatic cancer cells in vitro and in vivo
    (London : BioMed Central, 2012) Partecke, L.I.; Evert, K.; Haugk, J.; Doering, F.; Normann, L.; Diedrich, S.; Weiss, F.-U.; Evert, M.; Huebner, N.O.; Guenther, C.; Heidecke, C.D.; Kramer, A.; Bussiahn, R.; Weltmann, K.-D.; Pati, O.; Bender, C.; von Bernstorff, W.
    Background: The rate of microscopic incomplete resections of gastrointestinal cancers including pancreatic cancer has not changed considerably over the past years. Future intra-operative applications of tissue tolerable plasmas (TTP) could help to address this problem. Plasma is generated by feeding energy, like electrical discharges, to gases. The development of non-thermal atmospheric plasmas displaying spectra of temperature within or just above physiological ranges allows biological or medical applications of plasmas.Methods: We have investigated the effects of tissue tolerable plasmas (TTP) on the human pancreatic cancer cell line Colo-357 and PaTu8988T and the murine cell line 6606PDA in vitro (Annexin-V-FITC/DAPI-Assay and propidium iodide DNA staining assay) as well as in the in vivo tumour chorio-allantoic membrane (TUM-CAM) assay using Colo-357.Results: TTP of 20 seconds (s) induced a mild elevation of an experimental surface temperature of 23.7 degree Celsius up to 26.63+/-0.40 degree Celsius. In vitro TTP significantly (p=0.0003) decreased cell viability showing the strongest effects after 20s TTP. Also, TTP effects increased over time levelling off after 72 hours (30.1+/-4.4% of dead cells (untreated control) versus 78.0+/-9.6% (20s TTP)). However, analyzing these cells for apoptosis 10s TTP revealed the largest proportion of apoptotic cells (34.8+/-7.2%, p=0.0009 versus 12.3+/-6.6%, 20s TTP) suggesting non-apoptotic cell death in the majority of cells after 20s TTP. Using solid Colo-357 tumours in the TUM-CAM model TUNEL-staining showed TTP-induced apoptosis up to a depth of tissue penetration (DETiP) of 48.8+/-12.3μm (20s TTP, p<0.0001). This was mirrored by a significant (p<0.0001) reduction of Ki-67+ proliferating cells (80.9+/-13.2% versus 37.7+/-14.6%, p<0.0001) in the top cell layers as well as typical changes on HE specimens. The bottom cell layers were not affected by TTP.Conclusions: Our data suggest possible future intra-operative applications of TTP to reduce microscopic residual disease in pancreatic cancer resections. Further promising applications include other malignancies (central liver/lung tumours) as well as synergistic effects combining TTP with chemotherapies. Yet, adaptations of plasma sources as well as of the composition of effective components of TTP are required to optimize their synergistic apoptotic actions.
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    Detection of missed fractures of hand and forearm in whole-body CT in a blinded reassessment
    (London : BioMed Central, 2021) Kim, S.; Goelz, L.; Münn, F.; Kim, D.; Millrose, M.; Eisenschenk, A.; Thelen, S.; Lautenbach, M.
    Background: We examined the visibility of fractures of hand and forearm in whole-body CT and its influence on delayed diagnosis. This study is based on a prior study on delayed diagnosis of fractures of hand and forearm in patients with suspected polytrauma. Methods: Two blinded radiologists examined CT-scans of patients with fractures of hand or forearm that were diagnosed later than 24 h after admission and control cases with unremarkable imaging of those areas. They were provided with clinical information that was documented in the admission report and were asked to examine forearm and hands. After unblinding, the visibility of fractures was determined. We examined if time of admission or slice thickness was a factor for late or missed diagnoses. Results: We included 72 known fractures in 36 cases. Of those 65 were visible. Sixteen visible fractures were diagnosed late during hospital stay. Eight more fractures were detected on revision by the radiologists. Both radiologists missed known fractures and found new fractures that were not reported by the other. Missed and late diagnoses of fractures occurred more often around 5 pm and 1 am. Slice thickness was not significantly different between fractures and cases with fractures found within 24 h and those found later. Conclusions: The number of late diagnosis or completely missed fractures of the hand and forearm may be reduced by a repeated survey of WBCT with focus on the extremities in patients with suspected polytrauma who are not conscious. Level of evidence: III © 2021, The Author(s).