883 research outputs found

    A systematic review and meta-analysis of enzyme replacement therapy in late-onset Pompe Disease

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    Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD). Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed. Results: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases. Conclusion: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102

    Emerging insights and lessons for the future

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    This concluding chapter summarises the key findings of the ‘Pathways’ transformative knowledge network (TKN), its contributions to the ‘sustainability transformations’ literature and the lessons and implications for internationally networked, transdisciplinary research projects in the future. It revisits the theoretical anchors and methodological anchors introduced in Chapters 2–4, and draws on insights from the TKN from individual hubs in each of these areas, pointing to experiences both during the project and after its formal conclusion. It discusses the approaches used to foster cross-learning and evaluation in the project, and describes the single-, double- and triple-loop learning that this enabled. The chapter provides a deeper understanding of ‘transformative pathways to sustainability’ and the role that science and research can play in fostering them, not only through formal research outputs but also the tacit and experiential knowledge and the relationships that they can foster. The chapter closes by offering lessons and recommendations for researchers, funders, policy-makers, managers and practitioners with an interest in enhancing the contribution of social science and transdisciplinary research to the transformative agenda of the Sustainable Development Goals.Fil: Ely, Adrian. University of Sussex; Reino UnidoFil: Marin, Anabel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; Argentina. Universidad Nacional de San Martin. Escuela de Economia y Negocios. Centro de Investigaciones Para la Transformacion.; ArgentinaFil: Marshall, Fiona. University of Sussex; Reino UnidoFil: Apgar, Marina. No especifĂ­ca;Fil: Eakin, Hallie. Arizona State University; Estados UnidosFil: Pereira, Laura. No especifĂ­ca;Fil: Charli Joseph, Lakshmi. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: Siquieros Garcia, Mario. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: Yang, Lichao. No especifĂ­ca;Fil: Chengo, Victoria. No especifĂ­ca;Fil: Abrol, Dinesh. No especifĂ­ca;Fil: Kushwaha, Pravin. No especifĂ­ca;Fil: Hackett, Edward. No especifĂ­ca;Fil: Navarrete, David Manuel. No especifĂ­ca;Fil: Mehrotra, Ritu Priya. No especifĂ­ca;Fil: Atela, Joanes. No especifĂ­ca;Fil: Mbeva, Kennedy. No especifĂ­ca;Fil: Onyango, Joel. No especifĂ­ca;Fil: Olsson, Per. No especifĂ­ca

    Ion conducting and paramagnetic d-PCL(530)/siloxane-based biohybrids doped with Mn 2+ ions

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    Amorphous α,ω-hidroxylpoly(Δ-caprolactone) (PCL(530))/siloxane ormolytes doped with manganese perchlorate (Mn(ClO4)2) (d-PCL(530)/siloxanenMn(ClO4)2) with n = 20, 50, and 100), thermally stable up to at least 200 ÂșC, were synthesized by the sol-gel method. Ionic conductivity values up to 4.8×10−8 and 2.0×10−6 S cm−1 at about 25 and 100 ÂșC, respectively, where obtained for n = 20. FT-IR data demonstrated that the hydrogen bonding interactions present in the non-doped d-PCL(530)/siloxane host hybrid matrix were significantly influenced by the inclusion of Mn(ClO4)2 which promoted the formation of more oxyethylene/urethane and urethane/urethane aggregates. In addition, the Mn2+ ions bonded to all the “free” C=O groups of the urethane cross-links and to some of the “free” ester groups of the amorphous PCL(530) chains. In the electrolytes, the ClO4 − ions were found “free” and bonded to the Mn2+ ions along a bidentate configuration. The magnitude of the electron paramagnetic resonance (EPR) hyperfine constant of the analyzed samples (A ≈ 90×10-4 cm−1 ) suggested that the bonding between Mn2+ ions and the surrounding ligands is moderately ionic. The synthetized d-PCL(530)/siloxanenMn(ClO4)2 biohybrids have potential application in paramagnetic, photoelectrochemical and electrochromic devices.This work was supported by Fundacao para a Ciencia e a Tecnologia (FCT) and Feder (contracts PTDC/CTM-BPC/112774/2009, PEst-OE/QUI/UI0616/2014 and PEst-C/QUI/UI0686/2013) and COST Action MP1202 "Rational design of hybrid organic-inorganic interfaces". R.F.P.P. acknowledges FCT for a grant (SFRH/BPD/87759/2012). M.M.S. acknowledges CNPq (PVE grant 406617/2013-9), for a mobility grant. The financial support of the Brazilian agencies Capes and CNPq are gratefully acknowledged. Research was partially financed by the CeRTEV, Center for Research, Technology and Education in Vitreous Materials, FAPESP 2013/07793-6.info:eu-repo/semantics/publishedVersio

    Public transport equity in Shenyang: Using structural equation modelling

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    In China, with the rapid development of urbanisation, the contradiction between supply and demand has become increasingly severe, particularly in large and medium-sized cities. Improving public transport equity can help to reduce the social exclusion of lower-income and socially vulnerable groups in relation to the urban transport system, and guarantee that public transport systems are given priority in terms of development. Using the concept of transport-related social equity, this study aims to explore the effects of public transport equity in relation to the quality of public transport, public participation, and public transport-related policy using Shenyang as a case study. Data are analysed using Structural Equation Model (SEM). Our findings show that the three latent variables of accessibility, affordability, and social impacts can be seen as representing the main characteristics of public transport equity; while improvements in public transport quality, public participation, and public transport-related polices play a significant role in reducing public transport inequity. Moreover, the findings indicate that public participation has direct, significant, positive influences on public transport quality and public transport-related policies. In terms of policy implications, we suggest that policies designed to improve public transport service quality, extend public transport fare concessions, and promote public participation in the public transport policy decision-making process should be given priority in the next round of urban comprehensive planning in order to reduce public transport-related social inequity in Shenyang and China more generally

    Vascular collagen type-IV in hypertension and cerebral small vessel disease

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    Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats. We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer's pathology (N=52; 21F/31M, age 82.8±6.95 years). We also studied archive tissue from young (age range 6.2-8.3 years) and older (17.0-22.7 years) primates ( ) and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10-12 months). Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (ρ: -0.427, =0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD ( <0.017), including age as a covariate and either clinical hypertension ( <0.030) or neuropathological SVD diagnosis ( <0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals ( =0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV. Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV
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