64 research outputs found

    Graduate Keynote. Golf Grip Force Evaluation in Individuals with and without Hand Arthritis Using a New Wearable Sensor Technology

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    BACKGROUND Hand osteoarthritis (H-OA) is the most common type of osteoarthritis largely affecting individuals over 45. H-OA involves pain, loss of grip strength and limiting participation in recreational activities such as golf. Currently, a number of ‘arthritic’ grips are designed using joint protection principles to ‘reduce hand forces and tight gripping’. However, no comprehensive examinations in their effectiveness have been conducted. HYPOTHESIS The purpose of this study is to systematically analyse the hand forces produced from various golf grips and arthritis grips at the distal-phalanges of the hand-grip interface in individuals with and without hand arthritis using new wearable sensor technology. METHODS The finger forces in the hand were measured using Pressure Profiles FingerTPS system for participant’s bottom gripping hand thumb, index, middle and ring fingers. The participants performed 3 golf shots using a real ball on artificial turf with 12, mid-iron clubs fitted with various types of standard and arthritis grips. RESULTS Preliminary results of 4 healthy participants demonstrated that serrated style golf grips designed for players with arthritis produced some of the highest forces. Also, players with larger hand length measures produce higher forces in smaller diameter grips and small hand length measures in larger diameter grips. DISCUSSION These preliminary results demonstrate the possibility that ‘arthritic’ golf grips are not appropriately designed for the given user along with the potential relationship between grip geometry and hand size to finger forces. In better understanding the mechanics of arthritis and its relation to sports, the design of more advanced sporting equipment can be developed

    Mapping auroral activity with Twitter

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    Twitter is a popular, publicly-accessible, social media service that has proven useful in mapping large-scale events in real-time. In this study, for the first time, the use of Twitter as a measure of auroral activity is investigated. Peaks in the number of aurora-related tweets are found to frequently coincide with geomagnetic disturbances (detection rate of 91%). Additionally, the number of daily aurora-related tweets is found to strongly correlate with several auroral strength proxies (ravg ≈ 0.7). An examination is made of the bias for location and time of day within Twitter data, and a first order correction of these effects is presented. Overall, the results suggest that Twitter can provide both specific details about an individual aurora and accurate real-time indication of when, and even from where, an aurora is visible

    Quantitative chemometric phenotyping of three-dimensional liver organoids by Raman spectral imaging

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    Confocal Raman spectral imaging (RSI) enables high-content, label-free visualization of a wide range of molecules in biological specimens without sample preparation. However, reliable quantification of the deconvoluted spectra is needed. Here we develop an integrated bioanalytical methodology, qRamanomics, to qualify RSI as a tissue phantom calibrated tool for quantitative spatial chemotyping of major classes of biomolecules. Next, we apply qRamanomics to fixed 3D liver organoids generated from stem-cell-derived or primary hepatocytes to assess specimen variation and maturity. We then demonstrate the utility of qRamanomics for identifying biomolecular response signatures from a panel of liver-altering drugs, probing drug-induced compositional changes in 3D organoids followed by in situ monitoring of drug metabolism and accumulation. Quantitative chemometric phenotyping constitutes an important step in developing quantitative label-free interrogation of 3D biological specimens

    New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians

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    Multiple in vivo test guidelines focusing on the estrogen, androgen, thyroid, and steroidogenesis pathways have been developed and validated for mammals, amphibians, or fish. However, these tests are resource-intensive and often use a large number of laboratory animals. Developing alternatives for in vivo tests is consistent with the replacement, reduction, and refinement principles for animal welfare considerations, which are supported by increasing mandates to move toward an “animal-free” testing paradigm worldwide. New approach methodologies (NAMs) hold great promise to identify molecular, cellular, and tissue changes that can be used to predict effects reliably and more efficiently at the individual level (and potentially on populations) while reducing the number of animals used in (eco)toxicological testing for endocrine disruption. In a collaborative effort, experts from government, academia, and industry met in 2020 to discuss the current challenges of testing for endocrine activity assessment for fish and amphibians. Continuing this cross-sector initiative, our review focuses on the current state of the science regarding the use of NAMs to identify chemical-induced endocrine effects. The present study highlights the challenges of using NAMs for safety assessment and what work is needed to reduce their uncertainties and increase their acceptance in regulatory processes. We have reviewed the current NAMs available for endocrine activity assessment including in silico, in vitro, and eleutheroembryo models. New approach methodologies can be integrated as part of a weight-of-evidence approach for hazard or risk assessment using the adverse outcome pathway framework. The development and utilization of NAMs not only allows for replacement, reduction, and refinement of animal testing but can also provide robust and fit-for-purpose methods to identify chemicals acting via endocrine mechanisms.publishedVersio

    Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

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    This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

    The read-across hypothesis and environmental risk assessment of pharmaceuticals

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    This article is made available through the Brunel Open Access Publishing Fund. Copyright © 2013 American Chemical Society.Pharmaceuticals in the environment have received increased attention over the past decade, as they are ubiquitous in rivers and waterways. Concentrations are in sub-ng to low μg/L, well below acute toxic levels, but there are uncertainties regarding the effects of chronic exposures and there is a need to prioritise which pharmaceuticals may be of concern. The read-across hypothesis stipulates that a drug will have an effect in non-target organisms only if the molecular targets such as receptors and enzymes have been conserved, resulting in a (specific) pharmacological effect only if plasma concentrations are similar to human therapeutic concentrations. If this holds true for different classes of pharmaceuticals, it should be possible to predict the potential environmental impact from information obtained during the drug development process. This paper critically reviews the evidence for read-across, and finds that few studies include plasma concentrations and mode of action based effects. Thus, despite a large number of apparently relevant papers and a general acceptance of the hypothesis, there is an absence of documented evidence. There is a need for large-scale studies to generate robust data for testing the read-across hypothesis and developing predictive models, the only feasible approach to protecting the environment.BBSRC Industrial Partnership Award BB/ I00646X/1 and BBSRC Industrial CASE Partnership Studentship BB/I53257X/1 with AstraZeneca Safety Health and Environment Research Programme

    Enrichment of Echinacea angustifolia with Bauer Alkylamide 11 and Bauer Ketone 23 Increased Anti-inflammatory Potential through Interference with COX-2 Enzyme Activity

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    Bauer alkylamide 11 and Bauer ketone 23 were previously found to be partially responsible forEchinacea angustifolia anti-inflammatory properties. This study further tested their importance using the inhibition of prostaglandin E2 (PGE2) and nitric oxide (NO) production by RAW264.7 mouse macrophages in the absence and presence of lipopolysaccharide (LPS) and E. angustifolia extracts, phytochemical enriched fractions, or pure synthesized standards. Molecular targets were probed using microarray, qRT-PCR, Western blot, and enzyme assays. Fractions with these phytochemicals were more potent inhibitors of LPS-induced PGE2 production than E. angustifolia extracts. Microarray did not detect changes in transcripts with phytochemical treatments; however, qRT-PCR showed a decrease in TNF-α and an increase of iNOS transcripts. LPS-induced COX-2 protein was increased by an E. angustifolia fraction containing Bauer ketone 23 and by pure phytochemical. COX-2 activity was decreased with all treatments. The phytochemical inhibition of PGE2 production byEchinacea may be due to the direct targeting of COX-2 enzyme
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