TY - JOUR A1 - Raulien, Nora A1 - Friedrich, Kathleen A1 - Strobel, Sarah A1 - Raps, Stefanie A1 - Hecker, Friederike A1 - Pierer, Matthias A1 - Schilling, Erik A1 - Lainka, Elke A1 - Kallinich, Tilmann A1 - Baumann, Sven A1 - Fritz-Wallace, Katarina A1 - Rolle-Kampczyk, Ulrike A1 - Bergen, Martin von A1 - Aigner, Achim A1 - Ewe, Alexander A1 - Schett, Georg A1 - Cross, Michael A1 - Rossol, Manuela A1 - Wagner, Ulf T1 - Glucose-oxygen deprivation constrains HMGCR function and Rac1 prenylation and activates the NLRP3 inflammasome in human monocytes JF - Science Signaling N2 - Hypoxia and low glucose abundance often occur simultaneously at sites of inflammation. In monocytes and macrophages, glucose-oxygen deprivation stimulates the assembly of the NLRP3 inflammasome to generate the proinflammatory cytokine IL-1β. We found that concomitant glucose deprivation and hypoxia activated the NLRP3 inflammasome by constraining the function of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate kinase pathway. HMGCR is involved in the synthesis of geranylgeranyl pyrophosphate (GGPP), which is required for the prenylation and lipid membrane integration of proteins. Under glucose-oxygen deprivation, GGPP synthesis was decreased, leading to reduced prenylation of the small GTPase Rac1, increased binding of nonprenylated Rac1 to the scaffolding protein IQGAP1, and enhanced activation of the NLRP3 inflammasome. In response to restricted oxygen and glucose supply, patient monocytes with a compromised mevalonate pathway due to mevalonate kinase deficiency or Muckle-Wells syndrome released more IL-1β than did control monocytes. Thus, reduced GGPP synthesis due to inhibition of HMGCR under glucose-oxygen deprivation results in proinflammatory innate responses, which are normally kept in check by the prenylation of Rac1. We suggest that this mechanism is also active in inflammatory autoimmune conditions. Y1 - 2024 U6 - https://doi.org/10.1126/scisignal.add8913 SN - 1945-0877 VL - 17 IS - 845 PB - American Association for the Advancement of Science (AAAS) ER - TY - GEN A1 - Jahnke, Sonja A1 - Cruysen, Caren A1 - Prill, Robert A1 - Kittmann, Fabian A1 - Pflug, Nicola A1 - Albert, Justin Amadeus A1 - Camargo, Tibor de A1 - Arnrich, Bert A1 - Krolikowska, Aleksandra A1 - Kolcz, Anna A1 - Reichert, Pawel A1 - Oleksy, Lukasz A1 - Michel, Sven A1 - Kopf, Sebastian A1 - Wagner, Michael A1 - Scheffler, Sven A1 - Becker, Roland T1 - Protocol for a Randomized Crossover Trial to Evaluate the Effect of Soft Brace and Rigid Orthosis on Performance and Readiness to Return to Sport Six Months Post‑ACL‑Reconstruction T2 - Healthcare N2 - A randomized crossover trial was designed to investigate the influence of muscle activation and strength on functional stability/control of the knee joint, to determine whether bilateral imbalances still occur six months after successful anterior cruciate ligament reconstruction (ACLR), and to analyze whether the use of orthotic devices changes the activity onset of these muscles. Furthermore, conclusions on the feedforward and feedback mechanisms are highlighted. Therefore, twenty‑eight patients will take part in a modified Back in Action (BIA) test battery at an average of six months after a primary unilateral ACLR, which used an autologous ipsilateral semitendinosus tendon graft. This includes double‑leg and single‑leg stability tests, double‑leg and single‑leg countermovement jumps, double‑leg and single‑leg drop jumps, a speedy jump test, and a quick feet test. During the tests, gluteus medius and semitendinosus muscle activity are analyzed using surface electromyography (sEMG). Motion analysis is conducted using Microsoft Azure DK and 3D force plates. The tests are performed while wearing knee rigid orthosis, soft brace, and with no aid, in random order. Additionally, the range of hip and knee motion and hip abductor muscle strength under isometric conditions are measured. Furthermore, patient‑rated outcomes will be assessed. Y1 - 2023 U6 - https://doi.org/10.3390/healthcare11040513 SN - 2227-9032 VL - 11 IS - 4 ER - TY - GEN A1 - Dropco, Ivor A1 - Kaiser, Ulrich A1 - Wagner, Lola A1 - Brunner, Stefan M. A1 - Schlitt, Hans Jürgen A1 - Stroszczynski, Christian A1 - Jung, Friedrich A1 - Yi, Dong A1 - Herr, Wolfgang A1 - Jung, Ernst Michael T1 - Color mapping using ultrasound system-integrated perfusion software for evaluation of focal liver lesions: a possible first step for more independent reading T2 - Journal of Gastrointestinal and Liver Diseases N2 - Aims To assess the value of using integrated parametric ultrasound software for contrast-enhanced ultrasonography (CEUS) of liver tumors. Methods 107 patients with liver tumors were studied. CEUS were performed to detect focal lesions. Parametric images were based on continuous CINE LOOPs, from the early-arterial phase (15 s) to the portal-venous phase (1 min) generated by perfusion software. The evaluations of the parametric images and their dignity for liver lesions were performed independently by an experienced and a less-experienced investigator. Computed tomography, magnetic resonance imaging scans or histological analysis were used as references. Results High parametric image quality were obtained in all patients. Among the patients, 44% lesions were benign, 56% were malignant. The experienced investigator correctly classified 46 of 47 (98%) as benign, and 60 of 60 (100%) as malignant tumors based on the parametric images. The less-experienced investigator correctly classified 39 of 47 (83%) as benign, and 49 of 60 (82%) malignant tumors, acheaving a high statistical accuracy of 98% with this type of diagnostic. Conclusion Parametric imaging for grading the malignant degree of tumor may be a good complement to existing ultrasound techniques and was particularly helpful for improving the assessments of the less-experienced examiner. KW - CEUS KW - parametric imaging KW - dynamic vascularization KW - liver malignancies Y1 - 2023 UR - https://europepmc.org/article/med/38147619 U6 - https://doi.org/10.15403/jgld-4997 SN - 1842-1121 VL - 32 IS - 4 SP - 479 EP - 487 ER - TY - GEN A1 - Lützner, Jörg A1 - Lange, Toni A1 - Schmitt, Jochen A1 - Kopkow, Christian A1 - Dreinhöfer, Karsten E A1 - Friederich, Niklaus F. A1 - Gravius, Sascha A1 - Heller, Karl-Dieter A1 - Hube, Robert A1 - Gromnica-Ihle, Erika A1 - Kirschner, Stephan A1 - Kladny, Bernd A1 - Kremer, Michael A1 - Linke, Maike A1 - Malzahn, Jürgen A1 - Sabatowski, Rainer A1 - Scharf, Hanns-Peter A1 - Stöve, Johannes A1 - Wagner, Richard A1 - Günther, Klaus-Peter T1 - [The S2k guideline: Indications for knee endoprosthesis : Evidence and consent-based indications for total knee arthroplasty] T2 - Der Orthopäde Y1 - 2018 U6 - https://doi.org/10.1007/s00132-018-3612-x SN - 1433-0431 SN - 0085-4530 VL - 47 IS - 9 SP - 777 EP - 781 ER -