366 research outputs found

    The microRNA-29 family in cartilage homeostasis and osteoarthritis

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    MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

    Do specialty registrars change their attitudes, intentions and behaviour towards reporting incidents following a patient safety course?

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    <p>Abstract</p> <p>Background</p> <p>Reporting incidents can contribute to safer health care, as an awareness of the weaknesses of a system could be considered as a starting point for improvements. It is believed that patient safety education for specialty registrars could improve their attitudes, intentions and behaviour towards incident reporting. The objective of this study was to examine the effect of a two-day patient safety course on the attitudes, intentions and behaviour concerning the voluntary reporting of incidents by specialty registrars.</p> <p>Methods</p> <p>A patient safety course was designed to increase specialty registrars' knowledge, attitudes and skills in order to recognize and cope with unintended events and unsafe situations at an early stage. Data were collected through an 11-item questionnaire before, immediately after and six months after the course was given.</p> <p>Results</p> <p>The response rate at all three points in time assessed was 100% (n = 33). There were significant changes in incident reporting attitudes and intentions immediately after the course, as well as during follow-up. However, no significant changes were found in incident reporting behaviour.</p> <p>Conclusions</p> <p>It is shown that patient safety education can have long-term positive effects on attitudes towards reporting incidents and the intentions of registrars. However, further efforts need to be undertaken to induce a real change in behaviour.</p

    FReD: the Floral Reflectance Database - a web portal for analyses of flower colour

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    Background: Flower colour is of great importance in various fields relating to floral biology and pollinator behaviour. However, subjective human judgements of flower colour may be inaccurate and are irrelevant to the ecology and vision of the flower's pollinators. For precise, detailed information about the colours of flowers, a full reflectance spectrum for the flower of interest should be used rather than relying on such human assessments. Methodology/Principal Findings: The Floral Reflectance Database (FReD) has been developed to make an extensive collection of such data available to researchers. It is freely available at http://www.reflectance.co.uk. The database allows users to download spectral reflectance data for flower species collected from all over the world. These could, for example, be used in modelling interactions between pollinator vision and plant signals, or analyses of flower colours in various habitats. The database contains functions for calculating flower colour loci according to widely-used models of bee colour space, reflectance graphs of the spectra and an option to search for flowers with similar colours in bee colour space. Conclusions/Significance: The Floral Reflectance Database is a valuable new tool for researchers interested in the colours of flowers and their association with pollinator colour vision, containing raw spectral reflectance data for a large number of flower species

    Preventing delayed diagnosis of cancer: clinicians' views on main problems and solutions.

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    Background Delayed diagnosis is a major contributing factor to the UK’s lower cancer survival compared to many European countries. In the UK, there is a significant national variation in early cancer diagnosis. Healthcare providers can offer an insight into local priorities for timely cancer diagnosis. In this study, we aimed to identify the main problems and solutions relating to delay cancer diagnosis according to cancer care clinicians. Methods We developed and implemented a new priority-setting approach called PRIORITIZE and invited North West London cancer care clinicians to identify and prioritize main causes for and solutions to delayed diagnosis of cancer care. Results Clinicians identified a number of concrete problems and solutions relating to delayed diagnosis of cancer. Raising public awareness, patient education as well as better access to specialist care and diagnostic testing were seen as the highest priorities. The identified suggestions focused mostly on the delays during referrals from primary to secondary care. Conclusions Clinician-identified priorities for reducing delays in diagnoses of cancer covered wide dimensions of care. Many suggestions are implementable and affordable. PRIORITIZE is a timely, informative and scalable priority-setting approach and could be implemented as a routine preventative system for determining patient safety issues by frontline staff

    Early influences on cardiovascular and renal development

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    The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

    Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

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    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
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