342 research outputs found

    Remotely Supported Prehospital Ultrasound : Real-time Communication for Diagnosis in Remote and Rural Communities

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    Acknowledgments The research team would like to thank all of our volunteers and reviewers for their time and efforts during this study. The research was funded by Highlands & Islands Enterprise, UK Technology Strategy Boardā€™s Space and Life Sciences Catapult, University of Aberdeenā€™s dot.rural Digital Economy Hub and TAQA Bratani.Publisher PD

    Physiological and Pathophysiological Implications of Synaptic Tau

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    Tauopathies encompass a broad range of neurodegenerative diseases featuring extensive neuronal death and cognitive decline. However, research over the past 30 years has failed to significantly advance our understanding of how tau causes dementia, limiting the design of rational therapeutics. It has become evident that we need to expand our understanding of tau in physiology, in order to delineate how tau may contribute to pathology. This review discusses recent evidence that has uncovered a novel aspect of tau function, based on its previously uncharacterized localization to the synapse. Here, multiple streams of evidence support a critical role for synaptic tau in the regulation of synapse physiology. In particular, long-term depression, a form of synaptic weakening, is dependent on the presence of tau in hippocampal neurons. The regulation of tau by specific phosphorylation events downstream of GSK-3Ī² activation appears to be integral to this signaling role. We also describe how the regulation of synapse physiology by tau and its phosphorylation may inform our understanding of tauopathies and comorbid diseases. This work should provide a platform for future tau biology research in addition to therapeutic design.</jats:p

    The effectiveness of ultrasound in the detection of fractures in adults with suspected upper or lower limb injury : a systematic review and subgroup meta-analysis

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    The study was unfunded. LEā€™s involvement in this study was funded through the SatCare project which received financial support from the European Space Agency.Peer reviewedPublisher PD

    Epigallocatechin Gallate Modulates Microglia Phenotype to Suppress Pro-Inflammatory Signalling Cues and Inhibit Phagocytosis

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    Microglia are crucial players in the pathogenesis of late onset Alzheimerā€™s Disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, to promote Amyloid Ī² (AĪ²) clearance, disrupt plaque formation, or to dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids, such as the flavan 3-ols, are of interest due to their antioxidant, metal chelating, signalling and anti-inflammatory potential. Primary microglia were treated with a series of structurally related flavanol 3-ols to assess effects on phagocytosis, cytokine release and transcriptional responses by RNA sequencing. Data indicated that the extent of hydroxylation and the presence of the galloyl moiety were strong determinants of flavan 3-ol activity. Epigallocatechin gallate (EGCG) was the most effective flavan-3-ol tested and strongly inhibited phagocytosis of AĪ² independent of any metal chelating properties, suggesting a more direct modulation of microglia responsiveness. EGCG was broadly anti-inflammatory, reducing cytokine release and downregulating transcription, particularly of components of the microglia extracellular matrix such as MMP3 and SerpinB2. Collectively, this brings new insight into the actions of flavonoids on microglial responsiveness with potential implications for the therapeutic use of EGCG and structurally related flavanol-3-ols in AD

    Plasma microRNA levels following resection of metastatic melanoma

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    Melanoma remains the leading cause of skin cancerā€“related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples. Principal component analysis detected underlying patterns of miR expression between pre- vs postsurgical patients. Group A contained 3 of 4 patients with stage IV disease (pre- and postsurgical samples) and 2 patients with stage III disease (postsurgical samples only). The corresponding preoperative samples to both individuals with stage III disease were contained in group B along with 1 individual with stage IV disease (pre- and postsurgical samples). Group A was distinguished from group B by statistically significant analysis of variance changes in miR expression ( P < .0001). This analysis revealed that group A vs group B had downregulation of let-7b-5p, miR-520f, miR-720, miR-4454, miR-21-5p, miR-22-3p, miR-151a-3p, miR-378e, and miR-1283 and upregulation of miR-126-3p, miR-223-3p, miR-451a, let-7a-5p, let-7g-5p, miR-15b-5p, miR-16-5p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-26a-5p, miR-106a-5p, miR-17-5p, miR-130a-3p, miR-142-3p, miR-150-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, and miR-1976. Changes in miR expression were not readily evident in individuals with distant metastatic disease (stage IV) as these individuals may have prolonged inflammatory responses. Thus, inflammatory-driven miRs coinciding with tumor-derived miRs can blunt anticipated changes in expression profiles following surgical resection

    Remotely supported prehospital ultrasound : a feasibility study of real-time image transmission and expert guidance to aid diagnosis in remote and rural communities

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    ACKNOWLEDGEMENTS The project was supported by ultrasound manufacturers Philips Healthcare (UK), BK Medical (Peabody, MA; part of Analogic Ultrasound Group), and Tactical Wireless (Aylesbury, UK) who provided loan equipment and technical support. The authors would also like to thank the Scottish Ambulance Service for their support, staff and vehicles; the NHS staff who took part as experts; and the volunteers who participated in the scanning. FUNDING This research was supported by Highlands & Islands Enterprise, the UK Technology Strategy Boardā€™s Space and Life Sciences Catapult, the University of Aberdeenā€™s dot.rural Digital Economy Hub and by TAQA Bratani.Peer reviewedPostprin

    Combining transcranial ultrasound with intelligent communication methods to enhance the remote assessment and management of stroke patients : framework for a technology demonstrator

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    With over 150,000 strokes in the United Kingdom every year, and more than 1ā€‰million living survivors, stroke is the third most common cause of death and the leading cause of severe physical disability among adults. A major challenge in administering timely treatment is determining whether the stroke is due to vascular blockage (ischaemic) or haemorrhage. For patients with ischaemic stroke, thrombolysis (i.e. pharmacological 'clot-busting') can improve outcomes when delivered swiftly after onset, and current National Health Service Quality Improvement Scotland guidelines are for thrombolytic therapy to be provided to at least 80ā€‰per cent of eligible patients within 60ā€‰min of arrival at hospital. Thrombolysis in haemorrhagic stroke could severely compound the brain damage, so administration of thrombolytic therapy currently requires near-immediate care in a hospital, rapid consultation with a physician and access to imaging services (X-ray computed tomography or magnetic resonance imaging) and intensive care services. This is near impossible in remote and rural areas, and stroke mortality rates in Scotland are 50ā€‰per cent higher than in London. We here describe our current project developing a technology demonstrator with ultrasound imaging linked to an intelligent, multi-channel communication device - connecting to multiple 2G/3G/4G networks and/or satellites - in order to stream live ultrasound images, video and two-way audio streams to hospital-based specialists who can guide and advise ambulance clinicians regarding diagnosis. With portable ultrasound machines located in ambulances or general practices, use of such technology is not confined to stroke, although this is our current focus. Ultrasound assessment is useful in many other immediate care situations, suggesting potential wider applicability for this remote support system. Although our research programme is driven by rural need, the ideas are potentially applicable to urban areas where access to imaging and definitive treatment can be restricted by a range of operational factors

    Rotation-driven prolate-to-oblate shape phase transition in 190W: A projected shell model study

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    A shape phase transition is demonstrated to occur in 190W by applying the Projected Shell Model, which goes beyond the usual mean-field approximation. Rotation alignment of neutrons in the high-j, i_{13/2} orbital drives the yrast sequence of the system, changing suddenly from prolate to oblate shape at angular momentum 10ā„\hbar. We propose observables to test the picture.Comment: 9 pages, 3 figures, accepted for publication in Phys. Lett.
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