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Most cancer patients ultimately die from the consequences of distant metastases. As metastasis formation consumes energy mitochondria play an important role during this process as they are the most important cellular organelle to synthesise the energy rich substrate ATP, which provides the necessary energy to enable distant metastasis formation. However, mitochondria are also important for the execution of apoptosis, a process which limits metastasis formation. We therefore wanted to investigate the mitochondrial content in ovarian cancer cells and link its presence to the patient's prognosis in order to analyse which of the two opposing functions of mitochondria dominates during the malignant progression of ovarian cancer. Monoclonal antibodies directed against different mitochondrial specific proteins, namely heat shock proteins 60 (HSP60), fumarase and succinic dehydrogenase, were used in immunohistochemistry in preliminary experiments to identify the antibody most suited to detect mitochondria in ovarian cancer cells in clinical tissue samples. The clearest staining pattern, which even delineated individual mitochondria, was seen with the anti-HSP60 antibody, which was used for the subsequent clinical study staining primary ovarian cancers (n = 155), borderline tumours (n = 24) and recurrent ovarian cancers (n = 26). The staining results were semi-quantitatively scored into three groups according to their mitochondrial content: low (n = 26), intermediate (n = 50) and high (n = 84). Survival analysis showed that high mitochondrial content correlated with a statistically significant overall reduced survival rate In addition to the clinical tissue samples, mitochondrial content was analysed in ovarian cancer cells grown in vitro (cell lines: OVCAR8, SKOV3, OVCAR3 and COV644) and in vivo in severe combined immunodeficiency (SCID) mice.In in vivo grown SKOV3 and OVCAR8 cells, the number of mitochondria positive cells was markedly down-regulated compared to the in vitro grown cells indicating that mitochondrial number is subject to regulatory processes. As high mitochondrial content is associated with a poor prognosis, the provision of high energy substrates by the mitochondria seems to be more important for metastasis formation than the inhibition of apoptotic cell death, which is also mediated by mitochondria. In vivo and in vitro grown human ovarian cancer cells showed that the mitochondrial content is highly adaptable to the growth condition of the cancer cells., (© 2024. The Author(s).)

Aims: TauroPace (Tauropharm, Bavaria Germany), a taurolidine solution for combating cardiac implantable electronic device (CIED) infection, was compared with a historical control of 3% hydrogen peroxide (H2O2) in a prospective observational study., Methods and Results: The device pocket was irrigated, and all hardware accessible within (leads, suture sleeves, pulse generator) was wiped with H2O2, TauroPace, or taurolidine in a galenic formulation during any invasive CIED procedure at the study centre. Only CIED procedures covered by TauroPace or H2O2 from 1 January 2017 to 28 February 2022 were included for analysis. Patients who underwent >1 procedure were censored for the last treatment group and reassigned at the next procedure. The primary endpoint was major CIED infection within 3 months. The secondary endpoints were CIED infection beyond 3 months, adverse events potentially related to the antimicrobial solutions, CIED system, procedure, and death, till the end of follow-up. TauroPace covered 654 procedures on 631 patients, and H2O2 covered 551 procedures on 532 patients. The TauroPace group had more patient risk factors for infection than the H2O2 group (P = 0.0058) but similar device and procedure-specific risk factors (P = 0.17). Cardiac implantable electronic device infection occurred in 0/654 (0%) of the TauroPace group and 6/551 (1.1%) of the H2O2 group (P = 0.0075). Death occurred in 23/654 (3.5%) of the TauroPace group and 14/551 (2.5%) of the H2O2 group (P = 0.33). Non-infection related adverse events were rarer in the TauroPace (3.8%) than the H2O2 (6.0%) group (P = 0.0802)., Conclusion: TauroPace is safe but more effective than H2O2 in reducing CIED infection., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05576194., Competing Interests: Conflict of interest: B.B.: consultant/advisor: Abbott, Bioline Supply, Crosstec GmbH, Kapamed, Kimal PLC, M3 Medical/Ecclipse Medical, Medival SRL, Philips/Spectranetics, Sintec SRL, Tauro-Implant GmbH, Tauropharm GmbH, Transcutan; the other authors declare no conflict of interest in relation to this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Hyaluronan (HA), a component of the extracellular matrix, is frequently increased under pathological conditions including cancer. Not only stroma cells but also cancer cells themselves synthesize HA, and the interaction of HA with its cognate receptors promotes malignant progression and metastasis., Methods: In the present study, HA deposition in tissue sections was analyzed by hyaluronan-binding protein (HABP) ligand histochemistry in 17 borderline tumors and 102 primary and 20 recurrent ovarian cancer samples. The intensity and, particularly, localization of the HA deposition were recorded: for the localization, the pericellular deposition around the ovarian cancer cells was distinguished from the deposition within the stromal compartment. These histochemical data were correlated with clinical and pathological parameters. Additionally, within a reduced subgroup of ovarian cancer samples ( n = 70), the RNA levels of several HA-associated genes were correlated with the HA localization and intensity., Results: Both stroma-localized and pericellular tumor-cell-associated HA deposition were observed. Cancer-cell pericellular HA deposition, irrespective of its staining intensity, was significantly associated with malignancy, and in the primary ovarian cancer cohort, it represents an independent unfavorable prognostic marker for overall survival. Furthermore, a significant association between high CD44, HAS2 and HAS3 mRNA levels and a cancer-cell pericellular HA-deposition pattern was noted. In contrast, stromal hyaluronan deposition had no impact on ovarian cancer prognosis., Conclusions: In conclusion, the site of HA deposition is of prognostic value, but the amount deposited is not. The significant association of only peritumoral cancer-cell HA deposition with high CD44 mRNA expression levels suggests a pivotal role of the CD44-HA signaling axis for malignant progression in ovarian cancer.

Applications for dexterous robot teleoperation and immersive virtual reality are growing. Haptic user input devices need to allow the user to intuitively command and seamlessly "feel" the environment they work in, whether virtual or a remote site through an avatar. We introduce the DLR Exodex Adam, a reconfigurable, dexterous, whole-hand haptic input device. The device comprises multiple modular, three degrees of freedom (3-DOF) robotic fingers, whose placement on the device can be adjusted to optimize manipulability for different user hand sizes. Additionally, the device is mounted on a 7-DOF robot arm to increase the user's workspace. Exodex Adam uses a front-facing interface, with robotic fingers coupled to two of the user's fingertips, the thumb, and two points on the palm. Including the palm, as opposed to only the fingertips as is common in existing devices, enables accurate tracking of the whole hand without additional sensors such as a data glove or motion capture. By providing "whole-hand" interaction with omnidirectional force-feedback at the attachment points, we enable the user to experience the environment with the complete hand instead of only the fingertips, thus realizing deeper immersion. Interaction using Exodex Adam can range from palpation of objects and surfaces to manipulation using both power and precision grasps, all while receiving haptic feedback. This article details the concept and design of the Exodex Adam, as well as use cases where it is deployed with different command modalities. These include mixed-media interaction in a virtual environment, gesture-based telemanipulation, and robotic hand-arm teleoperation using adaptive model-mediated teleoperation. Finally, we share the insights gained during our development process and use case deployments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lii, Pereira, Dietl, Stillfried, Schmidt, Beik-Mohammadi, Baker, Maier, Pleintinger, Chen, Elawad, Mentzer , Pineault, Reisich and Albu-Schäffer.)