336 research outputs found

    Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice.

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    Amyotrophic lateral sclerosis (ALS) is a progressive motor neuronal disorder characterized by neuronal degeneration and currently no effective cure is available to stop or delay the disease from progression. Transplantation of murine glial-restricted precursors (mGRPs) is an attractive strategy to modulate ALS development and advancements such as the use of immune modulators could potentially extend graft survival and function. Using a well-established ALS transgenic mouse model (SOD1G93A), we tested mGRPs in combination with the immune modulators synthetic PreImplantation Factor (sPIF), Tacrolimus (Tac), and Costimulatory Blockade (CB). We report that transplantation of mGRPs into the cisterna magna did not result in increased mice survival. The addition of immunomodulatory regimes again did not increase mice lifespan but improved motor functions and sPIF was superior compared to other immune modulators. Immune modulators did not affect mGRPs engraftment significantly but reduced pro-inflammatory cytokine production. Finally, sPIF and CB reduced the number of microglial cells and prevented neuronal number loss. Given the safety profile and a neuroprotective potential of sPIF, we envision its clinical application in near future

    Integrating agriculture and health research for development: LCIRAH as an interdisciplinary programme to address a global challenge

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    The multiple burdens of persistent undernutrition and micronutrient deficiencies, along with the rapidly growing rates of overweight, obesity, and associated chronic diseases, are major challenges globally. The role of agriculture and the food system in meeting these challenges is very poorly understood. Achieving food security and addressing malnutrition in all its forms, a Sustainable Development Goal, requires an understanding of how changing food systems affect health outcomes and the development of new tools to design and evaluate interventions. An interinstitutional programme to address this interdisciplinary research challenge is described. Over the past seven years, the Leverhulme Centre for Integrative Research on Agriculture and Health has built a portfolio of successful and innovative research, trained a new cadre of interdisciplinary researchers in “Agri‐Health,” and built an international research community with a particular focus on strengthening research capacity in low‐ and middle‐income countries. The evolution of this programme is described, and key factors contributing to its success are discussed that may be of general value in designing interdisciplinary research programmes directed at supporting global development goals

    Synthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth.

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    Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality and spontaneous PTB is a major contributor. The preceding inflammation/infection contributes not only to spontaneous PTB but is associated with neonatal morbidities including impaired brain development. Therefore, control of exaggerated immune response during pregnancy is an attractive strategy. A potential candidate is synthetic PreImplantation Factor (sPIF) as sPIF prevents inflammatory induced fetal loss and has neuroprotective properties. Here, we tested maternal sPIF prophylaxis in pregnant mice subjected to a lipopolysaccharides (LPS) insult, which results in PTB. Additionally, we evaluated sPIF effects in placental and microglial cell lines. Maternal sPIF application reduced the LPS induced PTB rate significantly. Consequently, sPIF reduced microglial activation (Iba-1 positive cells) and preserved neuronal migration (Cux-2 positive cells) in fetal brains. In fetal brain lysates sPIF decreased IL-6 and INFγ concentrations. In-vitro, sPIF reduced Iba1 and TNFα expression in microglial cells and reduced the expression of pro-apoptotic (Bad and Bax) and inflammatory (IL-6 and NLRP4) genes in placental cell lines. Together, maternal sPIF prophylaxis prevents PTB in part by controlling exaggerated immune response. Given the sPIF`FDA Fast Track approval in non-pregnant subjects, we envision sPIF therapy in pregnancy

    Exploring the impact of dementia friendly ward environments on the provision of care: A qualitative thematic analysis

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    Dementia-friendly wards are recent developments to improve care for patients with dementia in acute hospitals. This qualitative study used focus groups to understand the impact of dementia friendly ward environments on nurses experiences of caring for acutely unwell patients with dementia. Qualified nurses and health care assistants working in an acute NHS Trust in England discussed their perceptions and experiences of working in a dementia-friendly ward environment. Four themes developed from the thematic analysis: (1) ‘It doesn’t look like a hospital’: A changed environment, (2) ‘More options to provide person-centred care’: No one size fits all, (3) ‘Before you could not see the patients’: A constant nurse presence and (4) ‘The ward remains the same’: Resistance to change. Recommendations and implementations for practice are discussed

    Measurements of π±\pi^\pm, K±^\pm, p and pˉ\bar{\textrm{p}} spectra in proton-proton interactions at 20, 31, 40, 80 and 158 GeV/c with the NA61/SHINE spectrometer at the CERN SPS

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    Measurements of inclusive spectra and mean multiplicities of π±\pi^\pm, K±^\pm, p and pˉ\bar{\textrm{p}} produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158 GeV/c (s=\sqrt{s} = 6.3, 7.7, 8.8, 12.3 and 17.3 GeV, respectively) were performed at the CERN Super Proton Synchrotron using the large acceptance NA61/SHINE hadron spectrometer. Spectra are presented as function of rapidity and transverse momentum and are compared to predictions of current models. The measurements serve as the baseline in the NA61/SHINE study of the properties of the onset of deconfinement and search for the critical point of strongly interacting matter

    Pion emission from the T2K replica target: method, results and application

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    The T2K long-baseline neutrino oscillation experiment in Japan needs precise predictions of the initial neutrino flux. The highest precision can be reached based on detailed measurements of hadron emission from the same target as used by T2K exposed to a proton beam of the same kinetic energy of 30 GeV. The corresponding data were recorded in 2007-2010 by the NA61/SHINE experiment at the CERN SPS using a replica of the T2K graphite target. In this paper details of the experiment, data taking, data analysis method and results from the 2007 pilot run are presented. Furthermore, the application of the NA61/SHINE measurements to the predictions of the T2K initial neutrino flux is described and discussed.Comment: updated version as published by NIM

    Measurement of Production Properties of Positively Charged Kaons in Proton-Carbon Interactions at 31 GeV/c

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    Spectra of positively charged kaons in p+C interactions at 31 GeV/c were measured with the NA61/SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2007 with a graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections and charged pion spectra were already measured using the same set of data. These new measurements in combination with the published ones are required to improve predictions of the neutrino flux for the T2K long baseline neutrino oscillation experiment in Japan. In particular, the knowledge of kaon production is crucial for precisely predicting the intrinsic electron neutrino component and the high energy tail of the T2K beam. The results are presented as a function of laboratory momentum in 2 intervals of the laboratory polar angle covering the range from 20 up to 240 mrad. The kaon spectra are compared with predictions of several hadron production models. Using the published pion results and the new kaon data, the K+/\pi+ ratios are computed.Comment: 10 pages, 11 figure
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