24 research outputs found

    Leiomyosarcoma of the Cephalic Vein

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    A 78-year-old man presented with a mass on his right forearm. A 5 x 4 x 3 cm3 mass was excised en bloc with extensions along the course of the cephalic vein and its tributaries. Histological analysis revealed the mass to be a high-grade leiomyosarcoma arising within the cephalic vein. The tumour was controlled locally and distally until the patient died 10 months later, from an unrelated illness. This is the first reported case of a venous leiomyosarcoma of the cephalic vein

    'Special K' and a loss of cell-to-cell adhesion in proximal tubule-derived epithelial cells: modulation of the adherens junction complex by ketamine

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    Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention

    Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing

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    OBJECTIVES: To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing. PATIENTS AND METHODS: Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre randomised, double-blind, placebo-controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12-month disease re-assessment (imaging/biochemical/histological), and 12-month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion(s) on multi-parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length. RESULTS: Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve-month disease progression rate was 43.3%. Assessable 12-month treatment adherence in non-progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug-attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms. CONCLUSION: Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers

    The retrospective analysis of Antarctic tracking data project

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    The Retrospective Analysis of Antarctic Tracking Data (RAATD) is a Scientific Committee for Antarctic Research project led jointly by the Expert Groups on Birds and Marine Mammals and Antarctic Biodiversity Informatics, and endorsed by the Commission for the Conservation of Antarctic Marine Living Resources. RAATD consolidated tracking data for multiple species of Antarctic meso- and top-predators to identify Areas of Ecological Significance. These datasets and accompanying syntheses provide a greater understanding of fundamental ecosystem processes in the Southern Ocean, support modelling of predator distributions under future climate scenarios and create inputs that can be incorporated into decision making processes by management authorities. In this data paper, we present the compiled tracking data from research groups that have worked in the Antarctic since the 1990s. The data are publicly available through biodiversity.aq and the Ocean Biogeographic Information System. The archive includes tracking data from over 70 contributors across 12 national Antarctic programs, and includes data from 17 predator species, 4060 individual animals, and over 2.9 million observed locations

    The retrospective analysis of Antarctic tracking data project

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    The Retrospective Analysis of Antarctic Tracking Data (RAATD) is a Scientific Committee for Antarctic Research project led jointly by the Expert Groups on Birds and Marine Mammals and Antarctic Biodiversity Informatics, and endorsed by the Commission for the Conservation of Antarctic Marine Living Resources. RAATD consolidated tracking data for multiple species of Antarctic meso- and top-predators to identify Areas of Ecological Significance. These datasets and accompanying syntheses provide a greater understanding of fundamental ecosystem processes in the Southern Ocean, support modelling of predator distributions under future climate scenarios and create inputs that can be incorporated into decision making processes by management authorities. In this data paper, we present the compiled tracking data from research groups that have worked in the Antarctic since the 1990s. The data are publicly available through biodiversity.aq and the Ocean Biogeographic Information System. The archive includes tracking data from over 70 contributors across 12 national Antarctic programs, and includes data from 17 predator species, 4060 individual animals, and over 2.9 million observed locations.Supplementary Figure S1: Filtered location data (black) and tag deployment locations (red) for each species. Maps are Lambert Azimuthal projections extending from 90° S to 20° S.Supplementary Table S1: Names and coordinates of the major study sites in the Southern Ocean and on the Antarctic Continent where tracking devices were deployed on the selected species (indicated by their 4-letter codes in the last column).Online Table 1: Description of fields (column names) in the metadata and data files.Supranational committees and organisations including the Scientific Committee on Antarctic Research Life Science Group and BirdLife International. National institutions and foundations, including but not limited to Argentina (Dirección Nacional del Antártico), Australia (Australian Antarctic program; Australian Research Council; Sea World Research and Rescue Foundation Inc., IMOS is a national collaborative research infrastructure, supported by the Australian Government and operated by a consortium of institutions as an unincorporated joint venture, with the University of Tasmania as Lead Agent), Belgium (Belgian Science Policy Office, EU Lifewatch ERIC), Brazil (Brazilian Antarctic Programme; Brazilian National Research Council (CNPq/MCTI) and CAPES), France (Agence Nationale de la Recherche; Centre National d’Etudes Spatiales; Centre National de la Recherche Scientifique; the French Foundation for Research on Biodiversity (FRB; www.fondationbiodiversite.fr) in the context of the CESAB project “RAATD”; Fondation Total; Institut Paul-Emile Victor; Programme Zone Atelier de Recherches sur l’Environnement Antarctique et Subantarctique; Terres Australes et Antarctiques Françaises), Germany (Deutsche Forschungsgemeinschaft, Hanse-Wissenschaftskolleg - Institute for Advanced Study), Italy (Italian National Antarctic Research Program; Ministry for Education University and Research), Japan (Japanese Antarctic Research Expedition; JSPS Kakenhi grant), Monaco (Fondation Prince Albert II de Monaco), New Zealand (Ministry for Primary Industries - BRAG; Pew Charitable Trusts), Norway (Norwegian Antarctic Research Expeditions; Norwegian Research Council), Portugal (Foundation for Science and Technology), South Africa (Department of Environmental Affairs; National Research Foundation; South African National Antarctic Programme), UK (Darwin Plus; Ecosystems Programme at the British Antarctic Survey; Natural Environment Research Council; WWF), and USA (U.S. AMLR Program of NOAA Fisheries; US Office of Polar Programs).http://www.nature.com/sdataam2021Mammal Research Institut

    Introduction of an enhanced recovery protocol for radical cystectomy

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    Objective: To describe and assess an enhanced recovery protocol (ERP) for the peri-operative management of patients undergoing radical cystectomy (RC), which was started at our institution on 1 October 2005, as RC is associated with increased morbidity and longer inpatient stays than other major urological procedures. Patients and methods: An ERP was introduced in our institution that focused on reduced bowel preparation, and standardized feeding and analgesic regimens. In all, 112 consecutive patients were compared, i.e. 56 before implementing the ERP and 56 since introducing the ERP. The primary outcome measures were duration of total inpatient stay and interval from surgery to discharge, and the morbidity and mortality. Data were analysed retrospectively from cancer network and hospital records. Results: The demographics of the two groups showed no significant difference in age, gender distribution, American Society of Anesthesiologists grade, or type of urinary diversion. Re-admission, mortality and morbidity rates showed no statistically significant difference between the groups. The median (interquartile range) duration of hospital stay was 17 (15-23) days in the no-ERP group, and 13 (11-17) days in the ERP group (significantly different, P < 0.001, Wilcoxon rank-sum test). The median duration of recovery after RC was 15 (13-21) days in the no-ERP group and 12 (10-15) days in the ERP group (significantly different, P = 0.001, Wilcoxon rank-sum test). Conclusion: The introduction of an ERP was associated with significantly reduced hospital stay, with no deleterious effect on morbidity or mortality.4 page(s
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