Fluctuations and differential contraction during regeneration of Hydra vulgaris tissue toroids

We studied regenerating bilayered tissue toroids dissected from Hydra vulgaris polyps and relate our macroscopic observations to the dynamics of force-generating mesoscopic cytoskeletal structures. Tissue fragments undergo a specific toroid-spheroid folding process leading to complete regeneration towards a new organism. The time scale of folding is too fast for biochemical signalling or morphogenetic gradients which forced us to assume purely mechanical self-organization. The initial pattern selection dynamics was studied by embedding toroids into hydro-gels allowing us to observe the deformation modes over longer periods of time. We found increasing mechanical fluctuations which break the toroidal symmetry and discuss the evolution of their power spectra for various gel stiffnesses. Our observations are related to single cell studies which explain the mechanical feasibility of the folding process. In addition, we observed switching of cells from a tissue bound to a migrating state after folding failure as well as in tissue injury. We found a supra-cellular actin ring assembled along the toroid's inner edge. Its contraction can lead to the observed folding dynamics as we could confirm by finite element simulations. This actin ring in the inner cell layer is assembled by myosin- driven length fluctuations of supra-cellular {\alpha}-actin structures (myonemes) in the outer cell-layer.Comment: 19 pages and 8 figures, submitted to New Journal of Physic

Dimerization of inositol monophosphatase Mycobacterium tuberculosis SuhB is not constitutive, but induced by binding of the activator Mg2+

Background The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. Results We determined the crystal structure, to 2.6 Å resolution, of the IMPase M. tuberculosis SuhB in the apo form, and analysed self-assembly by analytical ultracentrifugation. Contrary to the paradigm of constitutive dimerization of IMPases, SuhB is predominantly monomeric in the absence of the physiological activator Mg2+, in spite of a conserved fold and apparent dimerization in the crystal. However, Mg2+ concentrations that result in enzymatic activation of SuhB decisively promote dimerization, with the inhibitor Li+ amplifying the effect of Mg2+, but failing to induce dimerization on its own. Conclusion The correlation of Mg2+-driven enzymatic activity with dimerization suggests that catalytic activity is linked to the dimer form. Current models of lithium inhibition of IMPases posit that Li+ competes for one of three catalytic Mg2+ sites in the active site, stabilized by a mobile loop at the dimer interface. Our data suggest that Mg2+/Li+-induced ordering of this loop may promote dimerization by expanding the dimer interface of SuhB. The dynamic nature of the monomer-dimer equilibrium may also explain the extended concentration range over which Mg2+ maintains SuhB activity

Focal Salvage MR Imaging–Guided Cryoablation for Localized Prostate Cancer Recurrence after Radiotherapy:12-Month Follow-up

Purpose: To evaluate safety, quality of life (QoL), and local cancer control after focal salvage MR imaging–guided cryoablation in patients with local recurrence of prostate cancer (PCa) after radiotherapy. Materials and Methods: A retrospective, single-center study was performed in 62 patients with radiorecurrent PCa who underwent MR imaging–guided cryoablation since May 2011 with a follow-up ≥12 months in December 2017. Rates and descriptions of adverse events were reported. Ablation complications were classified according to the Clavien and SIR systems. Validated questionnaires were used to observe functional outcomes and QoL before therapy and 6 and 12 months after therapy. Cancer control was defined as no biochemical failure according to Phoenix criteria and no other clinical evidence for local or metastatic disease. Results: All procedures were technically feasible. The number of complications requiring major therapy (Clavien grade 3b/4 or SIR grade D/E/F) was low (2 [3.2%] and 1 [1.6%], respectively). After 12 months, the International Consultation of Incontinence Questionnaire–Short Form (P < .001) and 5-item International Index of Erectile Function (P = .001) scores became significantly worse, indicating increased symptoms of incontinence and diminished erectile function, without compromising QoL. Six patients developed metastases within 6 months. After 12 months, 36 patients (63%) were disease-free. Conclusions: Focal salvage MR imaging–guided cryoablation is safe and is associated with a high technical success rate, preservation of QoL, and local PCa control. This treatment can be a reasonable alternative to salvage radical prostatectomy in properly selected patients with low morbidity and preservation of QoL; however, longer follow-up is needed

Role of multiparametric magnetic resonance imaging in early detection of prostate cancer.

UNLABELLED: Most prostate cancers (PC) are currently found on the basis of an elevated PSA, although this biomarker has only moderate accuracy. Histological confirmation is traditionally obtained by random transrectal ultrasound guided biopsy, but this approach may underestimate PC. It is generally accepted that a clinically significant PC requires treatment, but in case of an non-significant PC, deferment of treatment and inclusion in an active surveillance program is a valid option. The implementation of multiparametric magnetic resonance imaging (mpMRI) into a screening program may reduce the risk of overdetection of non-significant PC and improve the early detection of clinically significant PC. A mpMRI consists of T2-weighted images supplemented with diffusion-weighted imaging, dynamic contrast enhanced imaging, and/or magnetic resonance spectroscopic imaging and is preferably performed and reported according to the uniform quality standards of the Prostate Imaging Reporting and Data System (PIRADS). International guidelines currently recommend mpMRI in patients with persistently rising PSA and previous negative biopsies, but mpMRI may also be used before first biopsy to improve the biopsy yield by targeting suspicious lesions or to assist in the selection of low-risk patients in whom consideration could be given for surveillance. TEACHING POINTS: ? MpMRI may be used to detect or exclude significant prostate cancer. ? MpMRI can guide targeted rebiopsy in patients with previous negative biopsies. ? In patients with negative mpMRI consideration could be given for surveillance. ? MpMRI may add valuable information for the optimal treatment selection

Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1):a phase I trial towards adaptive, image-controlled treatment delivery

PURPOSE: Transarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 ((166)Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing (166)Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry. METHODS: Six patients were treated with (166)Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, (166)Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for (166)Ho TARE. RESULTS: Administration of (166)Ho microspheres within the MRI scanner was feasible in 9/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18/19 (95%) of treated tumours. Two CTCAE grade 3–4 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4/18 tumours exhibited signs of saturation, while in 14/18 tumours, the microsphere uptake patterns did not deviate from the linear trend. CONCLUSION: This study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization. REGISTRATION: Clinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-022-05902-w

Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies

Item does not contain fulltextOBJECTIVES: To evaluate the accuracy and speed of a novel robotic technique as an aid to perform magnetic resonance image (MRI)-guided prostate biopsies on patients with cancer suspicious regions. METHODS: A pneumatic controlled MR-compatible manipulator with 5 degrees of freedom was developed in-house to guide biopsies under real-time imaging. From 13 consecutive biopsy procedures, the targeting error, biopsy error and target displacement were calculated to evaluate the accuracy. The time was recorded to evaluate manipulation and procedure time. RESULTS: The robotic and manual techniques demonstrated comparable results regarding mean targeting error (5.7 vs 5.8 mm, respectively) and mean target displacement (6.6 vs 6.0 mm, respectively). The mean biopsy error was larger (6.5 vs 4.4 mm) when using the robotic technique, although not significant. Mean procedure and manipulation time were 76 min and 6 min, respectively using the robotic technique and 61 and 8 min with the manual technique. CONCLUSIONS: Although comparable results regarding accuracy and speed were found, the extended technical effort of the robotic technique make the manual technique - currently - more suitable to perform MRI-guided biopsies. Furthermore, this study provided a better insight in displacement of the target during in vivo biopsy procedures.01 februari 201

The Weddell Gyre, Southern Ocean: present knowledge and future challenges

The Weddell Gyre (WG) is one of the main oceanographic features of the Southern Ocean south of the Antarctic Circumpolar Current which plays an influential role in global ocean circulation as well as gas exchange with the atmosphere. We review the state‐of‐the art knowledge concerning the WG from an interdisciplinary perspective, uncovering critical aspects needed to understand this system's role in shaping the future evolution of oceanic heat and carbon uptake over the next decades. The main limitations in our knowledge are related to the conditions in this extreme and remote environment, where the polar night, very low air temperatures and presence of sea ice year‐round hamper field and remotely sensed measurements. We highlight the importance of winter and under‐ice conditions in the southern WG, the role that new technology will play to overcome present‐day sampling limitations, the importance of the WG connectivity to the low‐latitude oceans and atmosphere, and the expected intensification of the WG circulation as the westerly winds intensify. Greater international cooperation is needed to define key sampling locations that can be visited by any research vessel in the region. Existing transects sampled since the 1980s along the Prime Meridian and along an East‐West section at ~62°S should be maintained with regularity to provide answers to the relevant questions. This approach will provide long‐term data to determine trends and will improve representation of processes for regional, Antarctic‐wide and global modeling efforts – thereby enhancing predictions of the WG in global ocean circulation and climate