2,684 research outputs found
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A Service Evaluation of the use of Mealtime Advice Mats within an Adult Learning Disability Service
This study aimed to gather the views of residential support staff and multidisciplinary team members (MDT) in order to evaluate the effectiveness of the current mealtime advice mats. It aimed to use the information to plan improvements to the mats themselves or their provision. Methods: This service evaluation of a NHS Learning Disability team was granted approval by the local audit and development committee and registered so with City, University of London in partial fulfilment of an MSc in SLT. Consenting participants (42: 21 paid support staff, 21 MDT professionals) answered specifically created questionnaires. Areas explored included; frequency of mat use, adherence with mat guidelines, knowledge of the potential consequences of dysphagia and the format and design of the mats. The results were analysed using descriptive statistics and review of the free text comments. Results: Results indicated high levels of awareness of mealtime mats and reported use by support staff. The MDT had less awareness and reported reduced use of the mats by themselves and support staff. Support and MDT staff shared differing facilitators and barriers for adherence to mealtime mat guidelines. The current format was viewed positively with differing views on potential improvements e.g. increased picture recommended by MDT but not support staff. There was general awareness of many consequences of dysphagia but not all, with the MDT less aware. Conclusion: This study’s findings contribute to the limited literature on dysphagia recommendations for people with LD. Implications for service development, improvements to mats and future research avenues are discussed
Crystal structures of Burkholderia cenocepacia dihydropteroate synthase in the apo-form and complexed with the product 7,8-dihydropteroate
<p>Abstract</p> <p>Background</p> <p>The enzyme dihydropteroate synthase (DHPS) participates in the <it>de novo </it>synthesis of folate cofactors by catalyzing the formation of 7,8-dihydropteroate from condensation of <it>p</it>-aminobenzoic acid with 6-hydroxymethyl-7,8-dihydropteroate pyrophosphate. DHPS is absent from humans, who acquire folates from diet, and has been validated as an antimicrobial therapeutic target by chemical and genetic means. The bacterium <it>Burkholderia cenocepacia </it>is an opportunistic pathogen and an infective agent of cystic fibrosis patients. The organism is highly resistant to antibiotics and there is a recognized need for the identification of new drugs against <it>Burkholderia </it>and related Gram-negative pathogens. Our characterization of the DHPS active site and interactions with the enzyme product are designed to underpin early stage drug discovery.</p> <p>Results</p> <p>An efficient recombinant protein expression system for DHPS from <it>B. cenocepacia </it>(<it>Bc</it>DHPS) was prepared, the dimeric enzyme purified in high yield and crystallized. The structure of the apo-enzyme and the complex with the product 7,8-dihydropteroate have been determined to 2.35 Å and 1.95 Å resolution respectively in distinct orthorhombic crystal forms. The latter represents the first crystal structure of the DHPS-pterin product complex, reveals key interactions involved in ligand binding, and reinforces data generated by other structural studies. Comparisons with orthologues identify plasticity near the substrate-binding pocket and in particular a range of loop conformations that contribute to the architecture of the DHPS active site. These structural data provide a foundation for hit discovery. An intriguing observation, an artifact of the analysis, that of a potential sulfenamide bond within the ligand complex structure is mentioned.</p> <p>Conclusion</p> <p>Structural similarities between <it>Bc</it>DHPS and orthologues from other Gram-negative species are evident as expected on the basis of a high level of sequence identity. The presence of 7,8-dihydropteroate in the binding site provides details about ligand recognition by the enzyme and the different states of the enzyme allow us to visualize distinct conformational states of loops adjacent to the active site. Improved drugs to combat infections by <it>Burkholderia sp. </it>and related Gram-negative bacteria are sought and our study now provides templates to assist that process and allow us to discuss new ways of inhibiting DHPS.</p
A highly specific Escherichia coli qPCR and its comparison with existing methods for environmental waters
The presence of Escherichia coli in environmental waters is considered as evidence of faecal contamination and is therefore commonly used as an indicator in both water quality and food safety analysis. The long period of time between sample collection and obtaining results from existing culture based methods means that contamination events may already impact public health by the time they are detected. The adoption of molecular based methods for E. coli could significantly reduce the time to detection. A new quantitative real-time PCR (qPCR) assay was developed to detect the ybbW gene sequence, which was found to be 100% exclusive and inclusive (specific and sensitive) for E. coli and directly compared for its ability to quantify E. coli in environmental waters against colony counts, quantitative real-time NASBA (qNASBA) targeting clpB and qPCR targeting uidA. Of the 87 E. coli strains tested, 100% were found to be ybbW positive, 94.2% were culture positive, 100% were clpB positive and 98.9% were uidA positive. The qPCR assays had a linear range of quantification over several orders of magnitude, and had high amplification efficiencies when using single isolates as a template. This compared favourably with qNASBA which showed poor linearity and amplification efficiency. When the assays were applied to environmental water samples, qNASBA was unable to reliably quantify E. coli while both qPCR assays were capable of predicting E. coli concentrations in environmental waters. This study highlights the inability of qNASBA targeting mRNA to quantify E. coli in environmental waters, and presents the first E. coli qPCR assay with 100% target exclusivity. The application of a highly exclusive and inclusive qPCR assay has the potential to allow water quality managers to reliably and rapidly detect and quantify E. coli and therefore take appropriate measures to reduce the risk to public health posed by faecal contamination
Oleophobic composite films based on multi-layer graphitic scaffolding
A new oleophobic composite material synthesised by utilising plasma-exfoliated multi-layered graphitic (MLG) material as scaffolding is presented herein. The composite consisted of a polyelectrolyte/fluorosurfactant complex derived from polydiallyldimethylammonium chloride (PDDA) and sodium perfluorooctanoate (PFO) and was used to prepare free-standing MLG composite films
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A roadmap for pyrodiversity science
Abstract:
Background:
Contemporary and projected shifts in global fire regimes highlight the importance of understanding how fire affects ecosystem function and biodiversity across taxa and geographies. Pyrodiversity, or heterogeneity in fire history, is often an important driver of biodiversity, though it has been largely overlooked until relatively recently. In this paper, we synthesise previous research to develop a theoretical framework on pyrodiversity–biodiversity relationships and propose future research and conservation management directions.
Theoretical Framework:
Pyrodiversity may affect biodiversity by diversifying available ecological niches, stabilising community networks and/or supporting diverse species pools available for post‐fire colonisation. Further, pyrodiversity's effects on biodiversity vary across different spatial, temporal and organismal scales depending on the mobility and other life history traits of the organisms in question and may be mediated by regional eco‐evolutionary factors such as historical fire regimes. Developing a generalisable understanding of pyrodiversity effects on biodiversity has been challenging, in part because pyrodiversity can be quantified in various ways.
Applying the Pyrodiversity Concept:
Exclusion of Indigenous fire stewardship, fire suppression, increased unplanned ignitions and climate change have led to dramatic shifts in fire regimes globally. Such shifts include departures from historic levels of pyrodiversity and add to existing challenges to biodiversity conservation in fire‐prone landscapes. Managers navigating these challenges can be aided by targeted research into observed contemporary pyrodiversity–biodiversity relationships as well as knowledge of historical reference conditions informed by both Indigenous and local ecological knowledge and western science.
Future Research Directions:
Several promising avenues exist for the advancement of pyrodiversity science to further both theoretical and practical goals. These lines of investigation include but are not limited to (1) testing the increasing variety of pyrodiversity metrics and analytical approaches; (2) assessing the spatial and temporal scale‐dependence of pyrodiversity's influence; (3) reconstructing historical pyrodiversity patterns and developing methods for predicting and/or promoting future pyrodiversity; and (4) expanding the focus of pyrodiversity science beyond biodiversity to better understand its influence on ecosystem function and processes more broadly
The Grizzly, October 8, 2015
Regional Threat Prompts Increased Safety Measures • Students Help Teach English to Cleaning Staff • U-Imagine Resources Help Entrepreneurs get Started • Not Your Ordinary Librarian: Interview with Ursinus\u27 New Instructional Technology Librarian • Fighting for Ophelia Hosts Biannual Kindness Week • UC Students Use Spanish Outside the Classroom • Hungry for a Good Discussion • An Honor and Opportunity • Opinions: Another Home: Studying Abroad; New Film Black Mass Rates 6 / 10 • Volleyball Eyes Turnaround in Second Half of Season • Making Strides • Football Looks to Bounce Back Strong After Bye Weekhttps://digitalcommons.ursinus.edu/grizzlynews/1673/thumbnail.jp
Six-Minute Walk Test Performance in Persons With Multiple Sclerosis While Using Passive or Powered Ankle-Foot Orthoses
Objective
To determine whether a powered ankle-foot orthosis (AFO) that provides dorsiflexor and plantar flexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS). Design
Short-term intervention. Setting
University research laboratory. Participants
Participants (N=16) with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive AFO. Interventions
Three 6-minute walk tests (6MWTs), 1 per footwear condition: shoes (no AFO), prescribed passive AFO, and portable powered AFO (PPAFO). Assistive devices were worn on the impaired limb. Main Outcome Measures
Distance walked and metabolic cost of transport were recorded during each 6MWT and compared between footwear conditions. Results
Each participant completed all three 6MWTs within the experimental design. PPAFO use resulted in a shorter 6MWT distance than did a passive AFO or shoe use. No differences were observed in metabolic cost of transport between footwear conditions. Conclusions
The current embodiment of this PPAFO did not improve endurance walking performance during the 6MWT in a sample of participants with gait impairment due to MS. Further research is required to determine whether expanded training or modified design of this powered orthosis can be effective in improving endurance walking performance in persons with gait impairment due to MS
Connecting Neuroinflammation and Neurodegeneration in Multiple Sclerosis: Are Oligodendrocyte Precursor Cells a Nexus of Disease?
The pathology in neurodegenerative diseases is often accompanied by inflammation. It is well-known that many cells within the central nervous system (CNS) also contribute to ongoing neuroinflammation, which can promote neurodegeneration. Multiple sclerosis (MS) is both an inflammatory and neurodegenerative disease in which there is a complex interplay between resident CNS cells to mediate myelin and axonal damage, and this communication network can vary depending on the subtype and chronicity of disease. Oligodendrocytes, the myelinating cell of the CNS, and their precursors, oligodendrocyte precursor cells (OPCs), are often thought of as the targets of autoimmune pathology during MS and in several animal models of MS; however, there is emerging evidence that OPCs actively contribute to inflammation that directly and indirectly contributes to neurodegeneration. Here we discuss several contributors to MS disease progression starting with lesion pathology and murine models amenable to studying particular aspects of disease. We then review how OPCs themselves can play an active role in promoting neuroinflammation and neurodegeneration, and how other resident CNS cells including microglia, astrocytes, and neurons can impact OPC function. Further, we outline the very complex and pleiotropic role(s) of several inflammatory cytokines and other secreted factors classically described as solely deleterious during MS and its animal models, but in fact, have many neuroprotective functions and promote a return to homeostasis, in part via modulation of OPC function. Finally, since MS affects patients from the onset of disease throughout their lifespan, we discuss the impact of aging on OPC function and CNS recovery. It is becoming clear that OPCs are not simply a bystander during MS progression and uncovering the active roles they play during different stages of disease will help uncover potential new avenues for therapeutic intervention
Adenosine 2A receptor and TIM3 suppress cytolytic killing of tumor cells via cytoskeletal polarization
Tumors generate an immune-suppressive environment that prevents effective killing of tumor cells by CD8(+) cytotoxic T cells (CTL). It remains largely unclear upon which cell type and at which stage of the anti-tumor response mediators of suppression act. We have combined an in vivo tumor model with a matching in vitro reconstruction of the tumor microenvironment based on tumor spheroids to identify suppressors of anti-tumor immunity that directly act on interaction between CTL and tumor cells and to determine mechanisms of action. An adenosine 2A receptor antagonist, as enhanced by blockade of TIM3, slowed tumor growth in vivo. Engagement of the adenosine 2A receptor and TIM3 reduced tumor cell killing in spheroids, impaired CTL cytoskeletal polarization ex vivo and in vitro and inhibited CTL infiltration into tumors and spheroids. With this role in CTL killing, blocking A(2A)R and TIM3 may complement therapies that enhance T cell priming, e.g. anti-PD-1 and anti-CTLA-4
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