1,495 research outputs found

    The use of in-situ deployments to examine the success of water quality mitigation measures on a watercress farm

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    Watercress has long been believed to affect macroinvertebrate communities in chalk streams. Harvesting and washing watercress damages plant tissues and releases isothiocyanates which are potential toxicants to Gammarus pulex (L.). This study examined whether impacts on G. pulex of watercress farm factory wash water could be mitigated by treating via recirculation through the watercress beds

    Screening of the transcriptional regulatory regions of vascular endothelial growth factor receptor 2 (VEGFR2) in amyotrophic lateral sclerosis

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    Background Vascular endothelial growth factor (VEGF) has neurotrophic activity which is mediated by its main agonist receptor, VEGFR2. Dysregulation of VEGF causes motor neurone degeneration in a mouse model of amyotrophic lateral sclerosis (ALS), and expression of VEGFR2 is reduced in motor neurones and spinal cord of patients with ALS. Methods We have screened the promoter region and 4 exonic regions of functional significance of the VEGFR2 gene in a UK population of patients with ALS, for mutations and polymorphisms that may affect expression or function of this VEGF receptor. Results No mutations were identified in the VEGFR2 gene. We found no association between polymorphisms in the regulatory regions of the VEGFR2 gene and ALS. Conclusion Mechanisms other than genetic variation may downregulate expression or function of the VEGFR2 receptor in patients with ALS

    Can astrocytes be a target for precision medicine?

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    Astrocytes are the most abundant non-neural cell type residing within the central nervous system (CNS) displaying tremendous heterogeneity depending on their location. Once believed to be ‘passive support cells for electrically active neurons’, astrocytes are now recognised to play an active role in brain homeostasis by forming connections with the surrounding neurons, microglia and endothelial cells. Most importantly, they provide an optimum microenvironment for functional neurons through regulation of the blood brain barrier, energy supply and removal of debris and toxic waste. Their dysfunction has been identified as a potential contributing factor for several neurodegenerative disorders, from Alzheimer’s Disease to Amyotrophic Lateral Sclerosis. In this chapter, we will explore the implications of astrocyte dysfunction in neurodegenerative diseases and how these cells can be used as therapeutic targets in precision medicine

    Disrupted glycosylation of lipids and proteins is a cause of neurodegeneration

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    Glycosyltransferases represent a large family of enzymes that catalyse the biosynthesis of oligosaccharides, polysaccharides, and glycoconjugates. A number of studies have implicated glycosyltransferases in the pathogenesis of neurodegenerative diseases but differentiating cause from effect has been difficult. We have recently discovered that mutations proximal to the substrate binding site of glycosyltransferase 8 domain containing 1 (GLT8D1) are associated with familial amyotrophic lateral sclerosis (ALS). We demonstrated that ALS-associated mutations reduce activity of the enzyme suggesting a loss-of-function mechanism that is an attractive therapeutic target. Our work is the first evidence that isolated dysfunction of a glycosyltransferase is sufficient to cause a neurodegenerative disease, but connection between neurodegeneration and genetic variation within glycosyltransferases is not new. Previous studies have identified associations between mutations in UGT8 and sporadic ALS, and between ST6GAL1 mutations and conversion of mild cognitive impairment into clinical Alzheimer’s disease. In this review we consider potential mechanisms connecting glycosyltransferase dysfunction to neurodegeneration. The most prominent candidates are ganglioside synthesis and impaired addition of O-linked β-N-acetylglucosamine (O-GlcNAc) groups to proteins important for axonal and synaptic function. Special consideration is given to examples where genetic mutations within glycosyltransferases are associated with neurodegeneration in recognition of the fact that these changes are likely to be upstream causes present from birth

    The use of laser scanning as a method for measuring stairways following an accident

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    Copyright: 2015 Survey Review Ltd.MORE OpenChoice: Open Access ArticleStairs present significant potential for harm to their users. A fall on stairs, particularly in descent, often leads to serious injury or even death. The authors have been involved in the investigation of many workplace stair accidents. Proper forensic investigation into the cause of a stair accident has often found the incident to be wholly or partly caused by poor stair design. In order to establish the relationship between the stair design and a given fall, an onsite survey has to be conducted, determining the rises and goings along with other key dimensions. The Health and Safety Laboratory (HSL), Buxton, UK, regularly undertake this type of survey using a digital inclinometer, a steel rule and a tape measure. Laser scanning is an emerging technique that is now accessible to the surveyor to complement or replace traditional approaches. The laser scanner and associated software produces a dense point survey in 3D, allowing dimensional analysis of the features. The authors used both traditional and laser scanning techniques to study the scenes of two fatal stair falls. The analysis presented allows the suitability of laser scanning for stair-fall investigation to be considered. Identification and classification of errors are needed in order to consider if the error is acceptable or can be mitigated. Laser scanners are impressive instruments providing data from which can be used to create a virtual 3D environment that can be used to reconstruct and explain an event and contributing factors. The use of both survey methods currently provides the investigator with complimentary data that allows accurate measurements to be presented in the context of the three-dimensional environment.European Social Fund (ESF

    “Anything that makes life’s journey better.” Exploring the use of digital technology by people living with motor neurone disease

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    Our aim was to explore the attitudes of those living with motor neuron disease towards digital technology. Postal and online questionnaires surveyed 83 people with MND (pwMND) and 54 friends and family members (fMND). Five pwMND and five fMND underwent semi-structured interviews. 82% of pwMND and 87% of fMND use technology every day with iPads and laptops being the devices most commonly used. pwMND used technology to help them continue to participate in everyday activities such as socialising, entertainment and accessing the internet. The internet provided peer support and information about MND but information could be distressing or unreliable. Participants preferred information from professionals and official organisations. Participants were generally supportive of using of technology to access medical care. Barriers to technology, such as lack of digital literacy skills and upper limb dysfunction, and potential solutions were identified. More challenging barriers included language and cognitive difficulties, and the fear of becoming dependent on technology. Addressing the barriers identified in this research could help pwMND access technology. However, as healthcare delivery becomes more reliant on digital technology, care should be taken to ensure that those who are unable or unwilling to use technology continue to have their needs met in alternative ways

    412: PEG-filigrastim post-chemotherapy to mobilise PBSC in paediatric oncology patients

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    Clinical aspects of motor neurone disease

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    © 2016. Motor neurone disease (MND) is a disabling and ultimately fatal disease of the motor system, with few effective treatments. Considerable heterogeneity is observed in the clinical motor features of MND, with extra-motor manifestations now also recognized as part of the condition. Diagnosis remains clinical, with appropriate investigations to exclude mimics. The multidisciplinary team approach is at the centre of holistic management of patients and families and can improve survival and quality of life. Although the disease remains incurable, survival benefit has been observed with the use of non-invasive ventilation and riluzole. Recent identification of genetic causes of MND, particularly the . C9orf72 hexanucleotide repeat expansion, adds to the expanding knowledge on aetiology and pathogenesis. However, the challenge of elucidating the underlying causes and establishing effective disease-modifying therapies continues through active research. We review MND, focusing on clinical features, diagnosis and management
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