146 research outputs found

    Navigating the tensions of integrating lived experience in participatory healthcare design

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    Despite growing interest in participatory approaches to healthcare design, the integration of people's lived experience-direct, first-hand understanding of a certain condition, situation, or identity-remains a key challenge to meaningful participation. Through an interview study with 23 patients, designers, family caregivers, and healthcare professionals involved in participatory healthcare design initiatives, the authors identify underlying tensions associated with leveraging lived experiences in healthcare design and investigate how existing strategies for integrating lived experience relate to these tensions. In doing so, this research offers insights for practitioners regarding ways of strategically navigating tensions when integrating people's lived experience through design in complex healthcare contexts.info:eu-repo/semantics/acceptedVersio

    Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage

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    Enfermedad cardiovascular; Terapia celular; SecretomaMalaltia cardiovascular; Teràpia cel·lular; SecretomaCardiovascular disease; Cell therapy; SecretomeBackground Cell-based therapeutic strategies have been proposed as an alternative for brain repair after stroke, but their clinical application has been hampered by potential adverse effects in the long term. The present study was designed to test the effect of the secretome of endothelial progenitor cells (EPCs) from stroke patients (scCM) on in vitro human models of angiogenesis and vascular barrier. Methods Two different scCM batches were analysed by mass spectrometry and a proteome profiler. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used for designing angiogenesis studies (proliferation, migration, and tubulogenesis) or in vitro models of EC monolayer (confluent monolayer ECs—CMECs) and blood–brain barrier (BBB; brain-like ECs—BLECs). Cells were treated with scCM (5 μg/mL) or protein-free endothelial basal medium (scEBM—control). CMECs or BLECs were exposed (6 h) to oxygen–glucose deprivation (OGD) conditions (1% oxygen and glucose-free medium) or normoxia (control—5% oxygen, 1 g/L of glucose) and treated with scCM or scEBM during reoxygenation (24 h). Results The analysis of different scCM batches showed a good reproducibility in terms of protein yield and composition. scCM increased CD34+-EC proliferation, tubulogenesis, and migration compared to the control (scEBM). The proteomic analysis of scCM revealed the presence of growth factors and molecules modulating cell metabolism and inflammatory pathways. Further, scCM decreased the permeability of CMECs and upregulated the expression of the junctional proteins such as occludin, VE-cadherin, and ZO-1. Such effects were possibly mediated through the activation of the interferon pathway and a moderate downregulation of Wnt signalling. Furthermore, OGD increased the permeability of both CMECs and BLECs, while scCM prevented the OGD-induced vascular leakage in both models. These effects were possibly mediated through the upregulation of junctional proteins and the regulation of MAPK/VEGFR2 activity. Conclusion Our results suggest that scCM promotes angiogenesis and the maturation of newly formed vessels while restoring the BBB function in ischemic conditions. In conclusion, our results highlight the possibility of using EPC-secretome as a therapeutic alternative to promote brain angiogenesis and protect from ischemia-induced vascular leakage.This work has been supported under the Euronanomed 8th Joint Call-MAGGBRIS collaborative project by grants from the Spanish Ministry of Science and Innovation (PCIN-2017-090) the French national agency (ANR-ANR-17-ENM3-0005-01), the AC17/00004 grant from Instituto Carlos III (ISCIII) with FEDR funds, and the National Centre for Research and Development (NCBR 15/EuronanoMed/2018). A part of this study has been also funded in the frame of the NANOSTEM project, a Marie Skłodowska-Curie Innovative Training Network (ITN) by receiving grant from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 764958 and the Expression of Interest (EoI) for Collaborative Projects on Regenerative Medicine 2019 P-CMR[C]), and the programs 2017-SGR-1427 and 2017-SGR-765 from the Generalitat de Cataluny. Alba Grayston is supported by the fellowship FI17/00073 from ISCIII with FEDR funds. Miguel Garcia-Gabilondo is supported by the PERIS grant SLT017/20/000197 from Generalitat de Cataluny. The mass spectrometer of the Spectrométrie de Masse de l’Artois (SMART) facilities used in this study was funded by the European Regional Development Fund (ERDF), the Hauts-de-France regional council, and the Université d’Artois (France)

    When the lens is too wide: The political consequences of the visual dehumanization of refugees

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    Photojournalistic images shape our understanding of sociopolitical events. How humans are depicted in images may have far-reaching consequences for our attitudes towards them. Social psychology has shown how the visualization of an ‘identifiable victim effect’ can elicit empathic responses. However, images of identifiable victims in the media are the exception rather than the norm. In the context of the Syrian refugee crisis, the majority of images in Western media depicted refugees as large unidentifiable groups. While the effects of the visual depiction of single individuals are well-known, the ways in which the visual framing of large groups operates, and its social and political consequences, remain unknown. We here focus on the visual depiction of refugees to understand how exposure to the dominant visual framing used in the media, depicting them in large groups of faceless individuals, affects their dehumanization and sets off political consequences. To that end we brought together insights from social psychology, social sciences and the humanities to test a range of hypotheses using methods from social and political psychology in 10 studies with the participation of 3951 European citizens. Seeing images of large groups resulted in greater implicit dehumanization compared with images depicting refugees in small groups. Images of large groups are also explicitly rated as more dehumanizing, and when coupled with meta-data such as newspaper headlines, images continue to play a significant and independent role on how (de)humanizing we perceive such news coverage to be. Moreover, after viewing images of large groups, participants showed increased preference for more dominant and less trustworthy-looking political leaders and supported fewer pro-refugee policies and more anti-refugee policies. In terms of a mechanistic understanding of these effects, the extent to which participants felt pity for refugees depicted in large groups as opposed to small groups mediated the effect of visual framing on the choice of a more authoritarian-looking leader. What we see in the media and how it is shown not only has consequences for the ways in which we relate to other human beings and our behaviour towards them but, ultimately, for the functioning of our political systems

    A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model

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    Inflammatory bowel diseases (IBD) describe a group of complex intestinal disorders characterized by inflammation in the gastrointestinal tract. Current treatments for IBD include the use of anti-inflammatory drugs; furthermore, recombinant lactic acid bacteria have been used as a therapeutic vehicle for anti-inflammatory agents in IBD models. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines; however, its oral administration is limited because it is quickly degraded in the gastrointestinal tract and systemic treatments have led to undesirable side effects. In this study, an engineered invasive strain of Lactococcus (L.) lactis producing Fibronectin Binding Protein A (FnBPA+), from Staphylococcus aureus capable of delivering, directly inside eukaryotic cells, an eukaryotic DNA expression vector containing the ORF coding for IL-10 of Mus musculus (pValac:il-10) was developed and its functionality was evaluated using in vitro and in vivo assays. Functionality of the plasmid and the invasive strain was demonstrated by transfection and invasiveness assays using cell cultures and in vivo in mice by fluorescence microscopy. TNBS inoculated mice that received this novel strain showed lower damage scores in their large intestines (at both macroscopic and microscopic levels), lower microbial translocation to liver, and increased anti-inflammatory/pro-inflammatory cytokine ratios compared to mice that received L. lactis FnBPA+ without the pValac:il-10 plasmid. The effectiveness was demonstrated of this novel DNA delivery therapeutic strategy in the prevention of inflammation using a murine model of colitis.Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Zurita-Turk, Meritxell. Universidade Federal Do Minas Gerais; Brasil;Fil: Alvarenga Lima, Fernanda. Universidade Federal Do Minas Gerais; Brasil;Fil: Coelho Dos Santos, Janete. No especifíca;Fil: Leclercq, Sophie Yvette. No especifíca;Fil: Chatel, Jean-Marc. Institut National de la Recherche Agronomique; Francia;Fil: Azevedo, Vasco. Universidade Federal Do Minas Gerais; Brasil;Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Miyoshi, Anderson. Universidade Federal Do Minas Gerais; Brasil;Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento de Investigacion. Catedra de Metodologia de la Invest.cientifica; Argentin

    Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis

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    Background: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract. Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study. We previously presented the development of an invasive strain of Lactococcus lactis (L. lactis) producing Fibronectin Binding Protein A (FnBPA) which was capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) and diminish inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of intestinal inflammation. As a new therapeutic strategy against IBD, the aim of this work was to evaluate the therapeutic effect of two L. lactis strains (the same invasive strain evaluated previously and the wild-type strain) carrying the therapeutic pValac:il-10 plasmid in the prevention of inflammation in a dextran sodium sulphate (DSS)-induced mouse model. Results: Results obtained showed that not only delivery of the pValac:il-10 plasmid by the invasive strain L. lactis MG1363 FnBPA+, but also by the wild-type strain L. lactis MG1363, was effective at diminishing intestinal inflammation (lower inflammation scores and higher IL-10 levels in the intestinal tissues, accompanied by decrease of IL-6) in the DSS-induced IBD mouse model. Conclusions: Administration of both L. lactis strains carrying the pValac:il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.Fil: Zurita Turk, Meritxell. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Santos, Ana C. G.. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Pereira, Vanessa Bastos. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Cara, Denise C.. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Leclercq, Sophie Y.. Fundaçao Ezequiel Dias. Laboratório de Inovaçao Biotecnológica; BrasilFil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Azevedo, Vasco. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; BrasilFil: Chatel, Jean-Marc. Universidade Federal do Minas Gerais; BrasilFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Miyoshi, Anderson. Universidade Federal Do Minas Gerais. Instituto de Cs.biologicas; Brasi

    Crescimento de nascidos a termo com peso baixo e adequado nos dois primeiros anos de vida

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    OBJECTIVE: To assess the growth pattern of full term low and adequate birth weight infants during the first two years of life and to identify the determinants at the time of the greatest growth deceleration. METHODS: A prospective cohort study was conducted with 148 full term infants in five small towns of the state of Pernambuco, Northeastern Brazil. Newborns were recruited from maternities between January 1993 and January 1994 and their anthropometric measurements were taken at one, two, four, six, 12 and 24 months of life. Risk factors were analyzed using multivariable linear regression. RESULTS: The increment of mean weight-for-age and length-for-age were more evident for low birth weight when compared with adequate weight infants, especially during the first two months after birth. From this point onward it was observed a progressive mean growth deceleration in both indexes up to 12 months of life. All infants had similar weight and length growth patterns. However, adequate birth weight infants remained in an upper level. Socioeconomic variables explained 23% of variation for weight-for-age, followed by 4% for birth weight. Socioeconomic condition was also the factor mostly affecting length-for-age, explaining 28% of its variation, followed by birth weight, maternal height and diarrhea. CONCLUSIONS: The study results suggest that interventions aiming to adequate growth should focus on prenatal care and social and environmental factors during childhood as a way of ensuring full expression of the genetic potential of this population.OBJETIVO: Verificar o padrão de crescimento de crianças nascidas a termo com peso baixo e adequado nos primeiros dois anos de vida e identificar fatores determinantes no momento de desaceleração máxima do crescimento. MÉTODOS: Estudo de coorte prospectiva com 148 lactentes nascidos a termo, em cinco municípios do Estado de Pernambuco. Os recém-nascidos foram recrutados nas maternidades no período de janeiro de 1993 a janeiro de 1994 e tiveram as medidas antropométricas aferidas com um, dois, quatro, seis, 12 e 24 meses. Os fatores de risco foram avaliados por análise de regressão linear multivariada. RESULTADOS: Houve incremento na média dos índices peso/idade e comprimento/idade mais evidente nas crianças com baixo peso do que nas com peso adequado ao nascer, especialmente nos dois primeiros meses de vida. A partir desta idade, observou-se desaceleração progressiva do crescimento até os 12 meses. O padrão de crescimento pôndero-estatural foi semelhante entre todas as crianças. Contudo, as nascidas com peso adequado mantiveram peso e comprimento acima das nascidas com baixo peso. As variáveis socioeconômicas explicaram 23% da variação do índice peso/idade, e o peso ao nascer, 4%. A condição socioeconômica explicou 28% da variação do índice comprimento/idade, seguido do peso ao nascer, altura materna e ocorrência de diarréia. CONCLUSÕES: Intervenções visando ao crescimento adequado devem ser direcionadas à assistência pré-natal e aos fatores socioambientais durante a infância, como forma de garantir a expressão máxima do potencial genético neste grupo populacional

    Microencapsulation of Lactic Acid Bacteria Improves the Gastrointestinal Delivery and in situ Expression of Recombinant Fluorescent Protein

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    The microencapsulation process of bacteria has been used for many years, mainly in the food industry and, among the different matrixes used, sodium alginate stands out. This matrix forms a protective wall around the encapsulated bacterial culture, increasing its viability and protecting against environmental adversities, such as low pH, for example. The aim of the present study was to evaluate both in vitro and in vivo, the capacity of the encapsulation process to maintain viable lactic acid bacteria (LAB) strains for a longer period of time and to verify if they are able to reach further regions of mouse intestine. For this purpose, a recombinant strain of LAB (L. lactis ssp. cremoris MG1363) carrying the pExu vector encoding the fluorescence protein mCherry [L. lactis MG1363 (pExu:mCherry)] was constructed. The pExu was designed by our group and acts as a vector for DNA vaccines, enabling the host cell to produce the protein of interest. The functionality of the pExu:mCherry vector, was demonstrated in vitro by fluorescence microscopy and flow cytometry after transfection of eukaryotic cells. After this confirmation, the recombinant strain was submitted to encapsulation protocol with sodium alginate (1%). Non-encapsulated, as well as encapsulated strains were orally administered to C57BL/6 mice and the expression of mCherry protein was evaluated at different times (0–168 h) in different bowel portions. Confocal microscopy showed that the expression of mCherry was higher in animals who received the encapsulated strain in all portions of intestine analyzed. These results were confirmed by qRT-PCR assay. Therefore, this is the first study comparing encapsulated and non-encapsulated L. lactis bacteria for mucosal DNA delivery applications. Our results showed that the microencapsulation process is an effective method to improve DNA delivery, ensuring a greater number of viable bacteria are able to reach different sections of the bowel

    EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

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    AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

    Mapping genomic loci implicates genes and synaptic biology in schizophrenia

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    Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies
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