86 research outputs found
Aged lipid-laden microglia display impaired responses to stroke
Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worse neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables transient microglia depletion that is followed by microglia repopulation after treatment interruption, causing no known harm to mice. We tested whether this strategy restored microglia function and ameliorated stroke outcome in old mice. Cerebral ischemia/reperfusion induced innate immune responses in microglia highlighted by type I interferon and metabolic changes involving lipid droplet biogenesis. Old microglia accumulated lipids under steady state and displayed exacerbated innate immune responses to stroke. Microglia repopulation in old mice reduced lipid-laden microglia, and the cells exhibited reduced inflammatory responses to ischemia. Moreover, old mice with renewed microglia showed improved motor function 2 weeks after stroke. We conclude that lipid deposits in aged microglia impair the cellular responses to ischemia and worsen functional recovery in old mice.© 2022 The Authors. Published under the terms of the CC BY 4.0 license
Programa de Estudios interdisciplinarios sobre prácticas de lectura, escritura y oralidad en la educación y las culturas
El Programa tiene como principal objetivo el desarrollo de iniciativas cooperativas entre grupos de investigación para aportar a la construcción interdisciplinaria y la difusión del conocimiento sobre las prácticas de lectura, escritura y oralidad y la enseñanza de estas prácticas en los niveles inicial, primario, secundario y universitario, desde abordajes propios de la psicología educacional, la psicolingüística, la sociolingüística y los estudios de literacidad.Facultad de Humanidades y Ciencias de la Educació
La Recerca en Conservació des de la Visió del Conservador-Restaurador
Setmana de la Ciència, Barcelona, 7 i 8 de novembre de 2013La secció de Conservació-Restauració de la Facultat de Belles Arts organitza unes jornades amb l'objectiu de difondre les investigacions al voltant de temes de gran interès per als professionals del sector. La Recerca en Conservació-Restauració ha estat vinculada normalment a les ciències afi ns i els seus plantejaments presenten una visió des d’aquestes branques de les Ciències. Però des de fa anys, els Conservadors-Restauradors desenvolupem una Recerca, també amb majúscules, des dels nostres coneixements i necessitats. Els plantejaments científi cs hi són ben presents, i afegim a més, un punt de vista pràctic que afavoreix el desenvolupament de la nostra disciplina.
Des de la Secció de Conservació-Restauració de la Facultat de Belles Arts de la Universitat de Barcelona volem difondre les investigacions que duem a terme, moltes de les quals s’han materialitzat en diferents tesis doctorals. Aquests treballs són una mostra més de les preocupacions individuals i de les necessitats de la conservació del Patrimoni Històrico-Artístic
Probiotic Bacteria Produce Conjugated Linoleic Acid Locally in the Gut That Targets Macrophage PPAR γ to Suppress Colitis
Inflammatory bowel disease (IBD) therapies are modestly successful and associated with significant side effects. Thus, the investigation of novel approaches to prevent colitis is important. Probiotic bacteria can produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anti-inflammatory effects. This study aimed to investigate the cellular and molecular mechanisms underlying the anti-inflammatory efficacy of probiotic bacteria using a mouse model of colitis. The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in a mouse model of DSS colitis. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen, blood and colonic lamina propria cells were phenotypically and functionally characterized. Fecal samples and colonic contents were collected to determine the effect of VSL#3 and CLA on gut microbial diversity and CLA production. CLA and VSL#3 treatment ameliorated colitis and decreased colonic bacterial diversity, a finding that correlated with decreased gut pathology. Colonic CLA concentrations were increased in response to probiotic bacterial treatment, but without systemic distribution in blood. VSL#3 and CLA decreased macrophage accumulation in the MLN of mice with DSS colitis. The loss of PPAR γ in myeloid cells abrogated the protective effect of probiotic bacteria and CLA in mice with DSS colitis. Probiotic bacteria modulate gut microbial diversity and favor local production of CLA in the colon that targets myeloid cell PPAR γ to suppress colitis
The role of emotions on consumers’ satisfaction within the fitness context
Previous studies have suggested that consumption-related emotions are important to understand post-purchase
reactions. This study examines the relationship between fitness consumers’ emotions and overall satisfaction. After an
initial step of free-thought listing and content validity, followed by a pre-test, a survey was conducted among consumers
of five different fitness centers (n=786). The questionnaire included measures to assess positive and negative emotions,
as well as overall satisfaction with the fitness center. The results gathered through a structural equation model provide
evidence that negative emotion experienced by consumers impacts negatively overall satisfaction, while positive emotion
have a positive effect on overall satisfaction. These findings suggest managerial implications, such as the need to collect
consumers’ perceptions of both tangible and intangible aspects of the services, listen costumers’ opinions in a regular
basis, and provide regular training to staff members, in order to identify the triggers of positive emotions and contribute
to increased levels of overall satisfaction. Guidelines for future research within the fitness context are also suggested.Estudos precedentes sugerem
que as emoções relacionadas com o consumo são importantes para compreender as reações dos consumidores após a
compra. Este estudo analisa a relação entre as emoções dos consumidores de fitness e satisfação global. Depois de uma
etapa inicial de listagem de pensamento-livre e validade de conteúdo, seguido de um pré-teste, foi realizada uma pesquisa
entre os consumidores de cinco centros de fitness diferentes (n = 786). O questionário incluiu medidas para avaliar as
emoções positivas e negativas, bem como a satisfação global com o centro de fitness. Os resultados obtidos através de
um modelo de equações estruturais forneceram evidências de que as emoções negativas vivenciadas pelos consumidores
impactam negativamente a satisfação global, enquanto as emoções positivas têm um efeito positivo sobre a satisfação
global. Estes resultados sugerem implicações para os gestores, tais como a necessidade de recolher informação sobre a
perceção dos consumidores dos aspetos tangíveis e intangíveis dos serviços, ouvir regularmente as opiniões dos consumidores
e facultar formação regular aos colaboradores. Isto permitirá identificar os aspetos que desencadeiam emoções
positivas e contribuir para o aumento dos níveis de satisfação global. Orientações para futuras pesquisas no contexto de
fitness também são sugeridas.Sin financiación0.185 SJR (2015) Q3, 1090/1779 Medicine (miscellaneous); Q4, 177/229 Health (social science), 112/128 Sports scienceUE
Immunoregulatory Mechanisms Underlying Prevention of Colitis-Associated Colorectal Cancer by Probiotic Bacteria
Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer. Probiotic bacteria produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anticarcinogenic effects. This study aimed to investigate the cellular and molecular mechanisms underlying the efficacy of probiotic bacteria in mouse models of cancer. Methodology/Principal Findings: The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in mouse models of inflammation-driven colorectal cancer. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen and colonic lamina propria lymphocytes (LPL) were phenotypically and functionally characterized. Mice treated with CLA or VSL#3 recovered faster from the acute inflammatory phase of disease and had lower disease severity in the chronic, tumor-bearing phase of disease. Adenoma and adenocarcinoma formation was also diminished by both treatments. VSL#3 increased the mRNA expression of TNF-a, angiostatin and PPAR c whereas CLA decreased COX-2 levels. Moreover, VSL#3-treated mice had increased IL-17 expression in MLN CD4+ T cells and accumulation of Treg LPL and memory CD4+ T cells. Conclusions/Significance: Both CLA and VSL#3 suppressed colon carcinogenesis, although VSL#3 showed greater anticarcinogeni
Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)
PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020
Computational Modeling-Based Discovery of Novel Classes of Anti-Inflammatory Drugs That Target Lanthionine Synthetase C-Like Protein 2
Background: Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the eukaryotic lanthionine synthetase component C-Like protein family involved in signal transduction and insulin sensitization. Recently, LANCL2 is a target for the binding and signaling of abscisic acid (ABA), a plant hormone with anti-diabetic and anti-inflammatory effects. Methodology/Principal Findings: The goal of this study was to determine the role of LANCL2 as a potential therapeutic target for developing novel drugs and nutraceuticals against inflammatory diseases. Previously, we performed homology modeling to construct a three-dimensional structure of LANCL2 using the crystal structure of lanthionine synthetase component C-like protein 1 (LANCL1) as a template. Using this model, structure-based virtual screening was performed using compounds from NCI (National Cancer Institute) Diversity Set II, ChemBridge, ZINC natural products, and FDAapproved drugs databases. Several potential ligands were identified using molecular docking. In order to validate the antiinflammatory efficacy of the top ranked compound (NSC61610) in the NCI Diversity Set II, a series of in vitro and pre-clinical efficacy studies were performed using a mouse model of dextran sodium sulfate (DSS)-induced colitis. Our findings showed that the lead compound, NSC61610, activated peroxisome proliferator-activated receptor gamma in a LANCL2- and adenylate cyclase/cAMP dependent manner in vitro and ameliorated experimental colitis by down-modulating colonic inflammatory gene expression and favoring regulatory T cell responses
Identification of new molecular targets for PET imaging of the microglial anti-inflammatory activation state
Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess the efficacy of therapies aimed to reduce the tissue damaging activities of microglia and/or to promote the protective potential of these cells, suitable pre-clinical and clinical tools for the in vivo analysis of microglia activities and dynamics are required. The aim of this work was to identify new translational markers of the anti-inflammatory / protective state of microglia for the development of novel PET tracers. Methods: New translational markers of the anti-inflammatory/protective activation state of microglia were selected by bioinformatic approaches and were in vitro and ex vivo validated by qPCR and immunohistochemistry in rodent and human samples. Once a viable marker was identified, a novel PET tracer was developed. This tracer was subsequently confirmed by autoradiography experiments in murine and human brain tissues. Results: Here we provide evidence that P2RY12 expression increases in murine and human microglia following exposure to anti-inflammatory stimuli, and that its expression is modulated in the reparative phase of experimental and clinical stroke. We then synthesized a novel carbon-11 labeled tracer targeting P2RY12, showing increased binding in brain sections of mice treated with IL4, and low binding to brain sections of a murine stroke model and of a stroke patient. Conclusion: This study provides new translational targets for PET tracers for the anti-inflammatory/protective activation state of microglia and shows the potential of a rationale-based approach. It therefore paves the way for the development of novel non-invasive methodologies aimed to monitor the success of therapeutic approaches in various neurological diseases
Effects on short term outcome of non-invasive ventilation use in the emergency department to treat patients with acute heart failure: A propensity score-based analysis of the EAHFE Registry
Objective: To assess the effects of non-invasive ventilation (NIV) in emergency department (ED) patients with acute heart failure (AHF) on short term outcomes.
Methods: Patients from the EAHFE Registry (a multicenter, observational, multipurpose, cohort-designed database including consecutive AHF patients in 41 Spanish EDs) were grouped based on NIV treatment (NIV+ and NIV–groups). Using propensity score (PS) methodology, we identified two subgroups of patients matched by 38 covariates and compared regarding 30-day survival (primary outcome). Interaction was investigated for age, sex, ischemic cardiomyopathy, chronic obstructive pulmonary disease, AHF precipitated by an acute coronary syndrome (ACS), AHF classified as hypertensive or acute pulmonary edema (APE), and systolic blood pressure (SBP). Secondary outcomes were intensive care unit (ICU) admission; mechanical ventilation; in-hospital, 3-day and 7-day mortality; and prolonged hospitalization (>7 days).
Results: Of 11, 152 patients from the EAHFE (age (SD): 80 (10) years; 55.5% women), 718 (6.4%) were NIV+ and had a higher 30-day mortality (HR = 2.229; 95%CI = 1.861–2.670) (p 85 years, p < 0.001), AHF associated with ACS (p = 0.045), and SBP < 100 mmHg (p < 0.001). No significant differences were found in the secondary endpoints except for more prolonged hospitalizations in NIV+ patients (OR = 1.445; 95%CI = 1.122–1.862) (p = 0.004).
Conclusion: The use of NIV to treat AHF in ED is not associated with improved mortality outcomes and should be cautious in old patients and those with ACS and hypotension
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