360 research outputs found

    Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.

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    Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T-cell phenotype. Adipose-derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4+ T-cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T-cells and B-cells in horses with ERU were similar to normal horses. However, CD4+ T-cells from horses with ERU expressed higher amounts of IFNγ indicating a pro-inflammatory Th1 phenotype. When co-incubated with MSCs, activated CD4+ T-cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell-cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4+ T-cell activation phenotype through a combination of cell-cell contact and prostaglandin signaling

    Energy relaxation pathways between light-matter states revealed by coherent two-dimensional spectroscopy

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    Coupling matter excitations to electromagnetic modes inside nano-scale optical resonators leads to the formation of hybrid light-matter states, so-called polaritons, allowing the controlled manipulation of material properties. Here, we investigate the photo-induced dynamics of a prototypical strongly-coupled molecular exciton-microcavity system using broadband two-dimensional Fourier transform spectroscopy and unravel the mechanistic details of its ultrafast photo-induced dynamics. We find evidence for a direct energy relaxation pathway from the upper to the lower polariton state that initially bypasses the excitonic manifold of states, which is often assumed to act as an intermediate energy reservoir, under certain experimental conditions. This observation provides new insight into polariton photophysics and could potentially aid the development of applications that rely on controlling the energy relaxation mechanism, such as in solar energy harvesting, manipulating chemical reactivity, the creation of Bose–Einstein condensates and quantum computing

    Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

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    Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108

    Calcium supplementation and risk of dementia in women with cerebrovascular disease

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    OBJECTIVE: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. METHODS: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70–92 years. At baseline in 2000–2001, and at follow-up in 2005–2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01–4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54–12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36–33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28–6.96, p = 0.011), but not in groups without these conditions. CONCLUSIONS: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed

    Low Cerebrospinal Fluid A beta(42) and A beta(40) are Related to White Matter Lesions in Cognitively Normal Elderly

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    Background: Low cerebrospinal fluid (CSF) levels of Aβ42 may be the earliest manifestation of Alzheimer’s disease (AD). Knowledge on how CSF Aβ interacts with different brain pathologies early in the disease process is limited. We examined how CSF Aβ markers relate to brain atrophy and white matter lesions (WMLs) in octogenarians with and without dementia to explore the earliest pathogenetic pathways of AD in the oldest old. // Objective: To study CSF amyloid biomarkers in relation to brain atrophy and WMLs in 85-year-olds with and without dementia. // Methods: 53 octogenarians took part in neuropsychiatric examinations and underwent both a lumbar puncture and a brain CT scan. CSF levels of Aβ42 and Aβ40 were examined in relation to cerebral atrophy and WMLs. Dementia was diagnosed. // Results: In 85-year-olds without dementia, lower levels of both CSF Aβ42 and CSF Aβ40 were associated with WMLs. CSF Aβ42 also correlated with measures of central atrophy, but not with cortical atrophy. In participants with dementia, lower CSF levels of Aβ42 were related to frontal, temporal, and parietal cortical atrophy but not to WMLs. // Conclusions: Our findings may suggest that there is an interrelationship between Aβ and subcortical WMLs in older persons without dementia. After onset of dementia, low CSF Aβ42, probably representing amyloid deposition in plaques, is associated with cortical atrophy. WMLs may be an earlier manifestation of Aβ deposition than cortical degeneration

    Statistical analysis of the sampling design: FishPi case study on the biological sampling of the European hake fishery

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    FishPi is a pilot project financed through an European grant (MARE/2014/19) aiming to strengthen regional coordination in the area of fisheries data collection. This project includes four case studies, one of which aims at analyzing alternative sampling plans for fisheries operating on Northern & Southern hake stocks. The case study analyzes a variety of sampling design scenarios, from Simple Random Sampling to combinations of stratified sampling designs (by country, by port, by quarter…), using anonymised landings data from logbooks and sales notes (2013-2014). The results were compared regarding bias and precision to evaluate the best approach. The most precise estimates of total catch were obtained in scenarios stratified by port and, secondly, by port and country and by port and quarter. The general conclusion was that regional sampling designs stratified by port provided improved precision in this fishery. Apart from statistical considerations, this conclusion was also discussed under other points of view to give a feasibility perspective showing that coverage by country, and also by domain (stock), would be compromised if regional design is simply based on statistical analyses. Efficiency and precision of sampling were found to be highly sensitive to the sampling assumptions and in general countries with smaller contributions to overall landings of hake would see their sampling plans reduced, compromising other requirements for advice such as those related to other stocks or local management measures established by National governments. Hence further analyses are being considered that integrate biometrics, cost-benefit aspects, and concurrent or single-stock sampling strategies

    The International criteria for reporting study Quality for Sudden Cardiac Arrest/Death tool: IQ-SCAD

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    Background Studies reporting on the incidence of sudden cardiac arrest and/or death (SCA/D) in athletes commonly lack methodological and reporting rigour, which has implications for screening and preventative policy in sport. To date, there are no tools designed for assessing study quality in studies investigating the incidence of SCA/D in athletes. Methods and Results The International criteria for reporting study Quality for Sudden Cardiac Arrest/Death tool (IQ-SCA/D) was developed following a Delphi process. Sixteen international experts in sports cardiology were identified and invited. Experts voted on each domain with subsequent moderated discussion for successive rounds until consensus was reached for a final tool. Inter-observer agreement between a novice, intermediate and expert observer was then assessed from the scoring of 22 relevant studies using weighted and unweighted Kappa analyses. The final IQ-SCA/D tool comprises 8 domains with a summated score out of a possible 22. Studies are categorised as low, intermediate and high quality with summated IQ-SCA/D scores of ≤11, 12-16 and ≥17 respectively. Inter-rater agreement was ‘substantial’ between all three observers for summated IQ-SCA/D scores and study categorisation. Conclusions The IQ-SCA/D is an expert consensus tool for assessing the study quality of research reporting the incidence of SCA/D in athletes. This tool may be used to assist researchers, reviewers, journal editors, and readers in contextualising the methodological quality of different studies with varying athlete SCA/D incidence estimates. Importantly, the IQ-SCA/D also provides an expert-informed framework to support and guide appropriate design and reporting practices in future SCA/D incidence trials

    Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice

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    Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2- macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Numbers R56DE020097 (SW) and F32DE026366 (JR

    Report of the Working Group on Commercial Catches (WGCATCH)

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    The Working Group on Commercial Catches (WGCATCH), chaired by Hans Gerritsen (Ireland) and Nuno Prista (Sweden), met in Lisbon, Portugal, 9–13 November 2015. WGCATCH is responsible for documenting national fishery sampling schemes, establishing best practice and guidelines on sampling and estimation procedures, and providing advice on other uses of fishery data. The meeting was attended by 30 participants from 15 countries. The group addressed a large number of terms of reference and the meeting was con-ducted through presentations, discussions and analysis of questionnaires. The main terms of reference were addressed in subgroups. The report is structured directly along the terms of reference and the main outcomes are listed below. Data collection schemes for small-scale fisheries WGCATCH provided descriptions of national small-scale fisheries through question-naires. An overview was obtained on the current data collection methods. Two major approaches were identified - census (e.g., sales, logbooks) and sampling methods (e.g., catch surveys) - and their main pros and cons were discussed. In most cases, specific sampling approaches are needed for these fisheries. The group developed a work plan to establish good-practice guidelines. Analysis of case studies of commercial fishery sampling designs and estimation Case studies of sampling designs and estimation involving megrim in divisions 7-8 were presented. A common theme is that issues with practical implementation of prob-ability-based sampling remain. WGCATCH summarized the main issues and provided a set of possible solutions. The group also provided guidance on dealing with previous data collected under métier-based sampling designs. Simulation models to investigate survey designs Several simulation studies were presented, most of them outlining the work of fishPi project (funded under MARE/2014/19) in evaluating regional sampling designs. A crit-ical review was carried out and WGCATCH produced general considerations and guidelines. WGCATCH recommends that these are taken into account when analysing the results of simulations of regional sampling design at RCM level. The affect of the landing obligation on catch sampling opportunities The affects on sampling and data quality of the current implementation of the landing obligation in the Baltic were reviewed. The group found that refusal rates for observer trips have increased to nearly 100% in at least one country, while in many other coun-tries on-board observer programmes did not suffer noticeable changes. WGCATCH established that the catches below the minimum size cannot be accurately estimated by sampling the landings below the minimum size because an unknown proportion of the catches may be discarded. The group also reiterated that it is important that the logbooks distinguish landings below and above the minimum size. Publication on statistically sound sampling schemes WGCATCH drafted detailed plans to produce a peer-reviewed paper in 2016. The pa-per will provide a synthesis of the evolution of sampling design towards best practice, illustrated with a number of concise case studies. Estimation procedures in the Regional Database (RDB) The work of WKRDB 2015 presented alongside existing and planned estimation pro-cedures in the RDB. Current work by Norway on a software package that will allow design-based estimation and optimization for stock assessment purposes was also pre-sented. The advantages of ensuring compatibility of this new software with the devel-opments currently planned for RDB-FishFrame are underscored. Repository of resources relevant to catch sampling WGCATCH initiated a repository with key resources; putting them into context with brief descriptions or review of each report, paper, book, website, software package etc. The intention is for this repository to be made available online by ICES. Sampling of incidental bycatches WGCATCH agreed to start routine documentation of sampling practices for bycatches of protected, endangered and threatened species (PETS) and rare fish species as well as routine evaluation of the limitations of current methods for collection and analysis. Training course on Design and Analysis of Statistical Sound catch sampling pro-grammes WGCATCH considered continuous training and expertise on sampling design, estima-tion and simulation to be the basis for successful implementation of statistical sound catch sampling programs. A new ICES Training Course in Design and Analysis of Sta-tistical Sound will take place at ICES HQ in Copenhagen, 12–16 September 2016. WGCATCH recommends that RCMs promote the attendance of these meetings among all MS involved

    International Criteria for Reporting Study Quality for Sudden Cardiac Arrest/Death Tool

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    Background Studies reporting on the incidence of sudden cardiac arrest and/or death (SCA/D) in athletes commonly lack methodological and reporting rigor, which has implications for screening and preventative policy in sport. To date, there are no tools designed for assessing study quality in studies investigating the incidence of SCA/D in athletes. Methods and Results The International Criteria for Reporting Study Quality for Sudden Cardiac Arrest/Death tool (IQ‐SCA/D) was developed following a Delphi process. Sixteen international experts in sports cardiology were identified and invited. Experts voted on each domain with subsequent moderated discussion for successive rounds until consensus was reached for a final tool. Interobserver agreement between a novice, intermediate, and expert observer was then assessed from the scoring of 22 relevant studies using weighted and unweighted κ analyses. The final IQ‐SCA/D tool comprises 8 domains with a summated score of a possible 22. Studies are categorized as low, intermediate, and high quality with summated IQ‐SCA/D scores of ≤11, 12 to 16, and ≥17, respectively. Interrater agreement was “substantial” between all 3 observers for summated IQ‐SCA/D scores and study categorization. Conclusions The IQ‐SCA/D is an expert consensus tool for assessing the study quality of research reporting the incidence of SCA/D in athletes. This tool may be used to assist researchers, reviewers, journal editors, and readers in contextualizing the methodological quality of different studies with varying athlete SCA/D incidence estimates. Importantly, the IQ‐SCA/D also provides an expert‐informed framework to support and guide appropriate design and reporting practices in future SCA/D incidence trials
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