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Bedfordshire, United Kingdom

Piletska E.V.,Cranfield University | Stavroulakis G.,Cranfield University | Larcombe L.D.,Cranfield University | Whitcombe M.J.,Cranfield University | And 4 more authors.
Biomacromolecules | Year: 2011

Here we present the first molecular imprinted polymer (MIP) that is able to attenuate the biofilm formation of the opportunistic human pathogen Pseudomonas aeruginosa through specific sequestration of its signal molecule N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-AHL). The MIP was rationally designed using computational modeling, and its capacity and specificity and that of a corresponding blank polymer toward signal molecule of P. aeruginosa (3-oxo-C12-AHL) and its analogue were tested. The biofilm formation in the presence of polymers and without polymers was studied using scanning confocal laser microscopy. Staining with crystal violet dye was used for the quantification of the biofilm formation. A significant reduction of the biofilm growth was observed in the presence of MIP (>80%), which was superior to that of the resin prepared without template, which showed a reduction of 40% in comparison with biofilm, which was grown without polymer addition. It was shown that 3-oxo-C12-AHL-specific MIP prevented the development of quorum-sensing-controlled phenotypes (in this case, biofilm formation) from being up-regulated. The developed MIP could be considered as a new tool for the elimination of life-threatening infections in a multitude of practical applications; it could, for example, be grafted on the surface of medical devices such as catheters and lenses, be a component of paints, or be used as a wound adsorbent. © 2011 American Chemical Society.

Thway K.,Royal Marsden Hospital | Nicholson A.G.,UK National Heart and Lung Institute | Lawson K.,UK National Heart and Lung Institute | Gonzalez D.,Molecular Diagnostics | And 8 more authors.
American Journal of Surgical Pathology | Year: 2011

We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distinctive histomorphologic features and characterized by a recurrent fusion gene, that appear to represent a distinct tumor entity at this site. The patients [7 female, 3 male; aged 27 to 67 y (mean, 45 y)] presented with local or systemic symptoms (n=5), symptoms from cerebral metastasis (1), or incidentally (2). Follow-up of 6 patients showed that 1 with brain metastasis died shortly after primary tumor resection, 1 developed a renal metastasis but is alive and well, and 4 are disease free after 1 to 15 years. All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 8 and ranged from 1.5 to 4 cm. Microscopically, they were lobulated and composed of cords of polygonal, spindle, or stellate cells within myxoid stroma, morphologically reminiscent of extraskeletal myxoid chondrosarcoma. Four cases showed no or minimal atypia, 6 showed focal pleomorphism, and 5 had necrosis. Mitotic indices varied, with most tumors not exceeding 5/10 high-power fields. Tumors were immunoreactive for only vimentin and weakly focal for epithelial membrane antigen. Of 9 tumors, 7 were shown to harbor a specific EWSR1-CREB1 fusion by reverse transcription-polymerase chain reaction and direct sequencing, with 7 of 10 showing EWSR1 rearrangement by fluorescence in situ hybridization. This gene fusion has been described previously in 2 histologically and behaviorally different sarcomas: clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas; however, this is a novel finding in tumors with the morphology we describe and that occur in the pulmonary region. © 2011 Lippincott Williams & Wilkins.

Piletska E.V.,Cranfield University | Stavroulakis G.,Cranfield University | Karim K.,Cranfield University | Whitcombe M.J.,Cranfield University | And 5 more authors.
Biomacromolecules | Year: 2010

A first attempt to attenuate the quorum sensing (QS) of a marine heterotroph microorganism, Vibrio fischeri, using signal molecule-sequestering polymers (SSPs) is presented. A set of rationally designed polymers with affinity toward a signal molecule of V. fischeri, N-(β-ketocaproyl)-l- homoserine lactone (3-oxo-C6-AHL) was produced. It is reported that computationally designed polymers could sequester a signal molecule of V. fischeri and prevent QS-controlled phenotypes (in this case, bioluminescence) from being up-regulated. It was proven that the attenuation of bioluminescence of V. fischeri was due to sequestration of the signal molecule by specific polymers and not due to the toxicity of polymer or nonspecific depletion of nutrients. The ability to disrupt the bacterial communication using easy to synthesize and chemically inert polymers could provide a new concept for the development of pharmaceuticals and susceptible device coatings such as catheters. © 2010 American Chemical Society.

Smart L.M.,Royal Infirmary | Buchan M.,Derby Teaching Hospitals | Cropper A.J.,Derby Teaching Hospitals | Cross P.A.,Queen Elizabeth Hospital | And 3 more authors.
Cytopathology | Year: 2016

Produced by the British Association for Cytopathology October 2015. Copyright © 2016 John Wiley & Sons Ltd.

Marikar D.,Bedford Hospital | Reynolds S.,Stoke Mandeville Hospital | Moghraby O.S.,Child and Adolescent Mental Health Services CAMHS
Archives of Disease in Childhood: Education and Practice Edition | Year: 2016

We present a review of the Junior MARSIPAN (Management of Really Sick Patients with Anorexia Nervosa) guideline, which provides paediatricians with a framework for managing Anorexia Nervosa in the inpatient setting.

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