Recent Developments in Speeding up Prostate MRI

The increasing incidence of prostate cancer cases worldwide has led to a tremendous demand for multiparametric MRI (mpMRI). In order to relieve the pressure on healthcare, reducing mpMRI scan time is necessary. This review focuses on recent techniques proposed for faster mpMRI acquisition, specifically shortening T2W and DWI sequences while adhering to the PI-RADS (Prostate Imaging Reporting and Data System) guidelines. Speeding up techniques in the reviewed studies rely on more efficient sampling of data, ranging from the acquisition of fewer averages or b-values to adjustment of the pulse sequence. Novel acquisition methods based on undersampling techniques are often followed by suitable reconstruction methods typically incorporating synthetic priori information. These reconstruction methods often use artificial intelligence for various tasks such as denoising, artifact correction, improvement of image quality, and in the case of DWI, for the generation of synthetic high b-value images or apparent diffusion coefficient maps. Reduction of mpMRI scan time is possible, but it is crucial to maintain diagnostic quality, confirmed through radiological evaluation, to integrate the proposed methods into the standard mpMRI protocol. Additionally, before clinical integration, prospective studies are recommended to validate undersampling techniques to avoid potentially inaccurate results demonstrated by retrospective analysis. This review provides an overview of recently proposed techniques, discussing their implementation, advantages, disadvantages, and diagnostic performance according to PI-RADS guidelines compared to conventional methods. Level of Evidence: 3. Technical Efficacy: Stage 3.</p

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

Short ORF-Dependent Ribosome Shunting Operates in an RNA Picorna-Like Virus and a DNA Pararetrovirus that Cause Rice Tungro Disease

Rice tungro disease is caused by synergistic interaction of an RNA picorna-like virus Rice tungro spherical virus (RTSV) and a DNA pararetrovirus Rice tungro bacilliform virus (RTBV). It is spread by insects owing to an RTSV-encoded transmission factor. RTBV has evolved a ribosome shunt mechanism to initiate translation of its pregenomic RNA having a long and highly structured leader. We found that a long leader of RTSV genomic RNA remarkably resembles the RTBV leader: both contain several short ORFs (sORFs) and potentially fold into a large stem-loop structure with the first sORF terminating in front of the stem basal helix. Using translation assays in rice protoplasts and wheat germ extracts, we show that, like in RTBV, both initiation and proper termination of the first sORF translation in front of the stem are required for shunt-mediated translation of a reporter ORF placed downstream of the RTSV leader. The base pairing that forms the basal helix is required for shunting, but its sequence can be varied. Shunt efficiency in RTSV is lower than in RTBV. But in addition to shunting the RTSV leader sequence allows relatively efficient linear ribosome migration, which also contributes to translation initiation downstream of the leader. We conclude that RTSV and RTBV have developed a similar, sORF-dependent shunt mechanism possibly to adapt to the host translation system and/or coordinate their life cycles. Given that sORF-dependent shunting also operates in a pararetrovirus Cauliflower mosaic virus and likely in other pararetroviruses that possess a conserved shunt configuration in their leaders it is tempting to propose that RTSV may have acquired shunt cis-elements from RTBV during their co-existence

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

Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2

Recent evidence established that the cell envelope of Mycobacterium tuberculosis, the bacillus causing tuberculosis (TB), is coated by an α-glucan-containing capsule that has been implicated in persistence in a mouse infection model. As one of three known metabolic routes to α-glucan in mycobacteria, the cytoplasmic GlgE-pathway converts trehalose to α(1 → 4),α(1 → 6)-linked glucan in 4 steps. Whether individual reaction steps, catalyzed by trehalose synthase TreS, maltokinase Pep2, and glycosyltransferases GlgE and GlgB, occur independently or in a coordinated fashion is not known. Here, we report the crystal structure of M. tuberculosis TreS, and show by small-angle X-ray scattering and analytical ultracentrifugation that TreS forms tetramers in solution. Together with Pep2, TreS forms a hetero-octameric complex, and we demonstrate that complex formation markedly accelerates maltokinase activity of Pep2. Thus, complex formation may act as part of a regulatory mechanism of the GlgE pathway, which overall must avoid accumulation of toxic pathway intermediates, such as maltose-1-phosphate, and optimize the use of scarce nutrients

Symptoms of pelvic floor dysfunction are poorly correlated with findings on clinical examination and dynamic MR imaging of the pelvic floor

Contains fulltext : 81433.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The aim of the study was to determine whether patients' symptoms agree with findings on clinical examination and dynamic MR imaging of the pelvic floor. METHODS: Symptoms of pelvic organ dysfunction were measured with the use of three validated questionnaires. The domain scores were compared with POP-Q and dynamic MR imaging measurements. The Spearman's rank correlation coefficient (r(s)) was used to assess agreement. RESULTS: Only the domain score genital prolapse was significantly correlated in the positive direction with the degree of pelvic organ prolapse as assessed by POP-Q and dynamic MR imaging (r(s) = 0.64 and 0.27, respectively), whereas the domain score urinary incontinence was inversely correlated (r(s) = -0.32 and -0.35, respectively). CONCLUSIONS: The sensation or visualization of a bulge in the vagina was the only symptom which correlated positively with the degree of pelvic organ prolapse, and clinical examination and dynamic MR imaging showed similar correlation in this respect

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