91 research outputs found

    Definition of masks related to psychovisual features for video quality assessment

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    Video Quality Assessment needs to correspond to human perception. Pixel-based metrics (PSNR or MSE) fail in many circumstances for not taking into account the spatio-temporal property of human's visual perception. In this paper we propose a new pixel-weighted method to improve video quality metrics for artifacts evaluation. The method applies a psychovisual model based on motion, level of detail, pixel location and the appearance of human faces, which approximate the quality to the human eye's response. Subjective tests were developed to adjust the psychovisual model for demonstrating the noticeable improvement of an algorithm when weighting the pixels according to the factors analyzed instead of treating them equally. The analysis developed demonstrates the necessity of models adapted to the specific visualization of contents and the model presents an advance in quality to be applied over sequences when a determined artifact is analyzed

    Clinical behavior of children with infantile cerebral palsy after ozone therapy

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    Objective. The aim of this study was to determine the usefulness of ozone therapy in the treatment of Infantile Cerebral Palsy (ICP). Patients and methods. A non-controlled clinical assay was made in the Ozone Research Center (CIO), Havana, Cuba from January 2013 to January 2014. The sample was constituted by patients remitted to pediatrics consultation of CIO, to whom inclusion and exclusion criteria were applied. The study group involved 45 patients, from 1 month of birth to 8 years, with cerebral palsy of hypoxic-ischemic cause. The evaluation criteria were: evolution of the motor disorder according to the Gross Motor Function Classification System (GMFCS) scale, modification of muscle tone (Ashworth modified scale) and response to treatment (O?Brien modified scale). The way of administration was rectal insufflation; concentrations between 15, 20, 25 and 30 mg/L were used, volumes varied according to age, making calculation of the dose of ozone according to kilograms of weight. Cycles of 20 sessions, every 3 months were indicated, until completing 4 in 16 months. Patients were clinically evaluated, according to the scales used, before and after each cycle. Results and Discussion. The best answer to treatment was obtained in the group aged ? 4 years. The variables analyzed showed a significant improvement when the ozone treatment concluded. With respect to the evolution of the motor disorder, in 65 % of cases it improved. In the group of children below 4 years, the response was better in relation to the muscle tone. Response to treatment, according to the relatives? criteria, was of 70 % of the children with marked improvement in the tone and muscle function. Conclusions. The greatest percentage of patients improved in the evolution of the motor disorder; when the Manual Ability Classification System (MACS) scale was applied, more than half the patients showed an improvement. A high percentage of children get a satisfactory result regarding muscle tone and motor function. No side effects were present in any of the cases during the study

    Does Extended Interval Dosing Natalizumab Preserve Effectiveness in Multiple Sclerosis? A 7 Year-Retrospective Observational Study

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    The extended interval dosing (EID) of natalizumab has been suggested to be associated with a reduced risk of progressive multifocal leukoencephalopathy (PML) and short-term preservation of efficacy but its long-term effectiveness remain unknown. We aimed to determine the long-term effectiveness and safety of natalizumab in an EID setting in a cohort of patients with multiple sclerosis (MS) treated for more than 7 years. We conducted an observational retrospective cohort study, including 39 (34 female, 5 male) patients with clinically definite relapsing-MS, initially treated with standard interval dosing (SID) of natalizumab (mean time 54 months [SD29]) who were then switched to EID, every 8 weeks (mean time 76 months [SD13]). The main outcome measures included the following: i) annualized relapse rate (ARR), ii) radiological activity, iii) disability progression, and iv) NEDA-3 no evidence of disease activity index. EID preserved ARR, radiological activity, and prevented disability worsening during follow-up. The proportion of patients maintaining their NEDA-3 status after 24, 48, and 72 months of natalizumab administration in EID was 94%, 73%, and 70%, respectively. Stratified analysis according to history of drug therapy showed that the EID of natalizumab was slightly more effective in naïve patients than in those previously treated with other immunosuppressive drugs. No cases of PML or other severe adverse reactions were reported. In conclusion, long-term therapy with natalizumab in an EID setting following an SID regimen maintained its disease-modifying activity, and was safe and well tolerated for over 7 years. These encouraging observational results need to be confirmed in controlled clinical trials.FUNDING: This study was supported by IDIVAL (NVAL 16/11)

    Small Molecules as Toll-like Receptor 4 Modulators Drug and In-House Computational Repurposing

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    The innate immunity toll-like receptor 4 (TLR4) system is a receptor of paramount importance as a therapeutic target. Virtual screening following a “computer-aided drug repurposing” approach was applied to the discovery of novel TLR4 modulators with a non-lipopolysaccharide-like structure. We screened almost 29,000 approved drugs and drug-like molecules from commercial, public, and in-house academia chemical libraries and, after biological assays, identified several compounds with TLR4 antagonist activity. Our computational protocol showed to be a robust approach for the identification of hits with drug-like scaffolds as possible inhibitors of the TLR4 innate immune pathways. Our collaborative work broadens the chemical diversity for inspiration of new classes of TLR4 modulators.This work was financially supported by the Spanish Ministry for Science and Innovation (grants CTQ2014-57141-R, CTQ2017-88353-R, and PID2020-113588RB-I00 for S.M.S.; grants BES-2012-053653 for L.P.R., BES-2015-071588 for J.G.C. and PID2021-124983OB-I00 for J.C.M.), the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (MINECO/FEDER; SAF2016-75988-R), and the Community of Madrid (S-2010/BMD-2332) for M.F

    Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis

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    Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRα;RXRβ-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging

    Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro

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    Vascular calcification (VC), an unpredictable pathophysiological process and critical event in patients with cardiovascular diseases (CVDs), is the leading cause of morbi-mortality and disability in chronic kidney disease (CKD) patients worldwide. Currently, no diagnostic method is available for identifying patients at risk of VC development; the pathology is detected when the process is irreversible. Extracellular vesicles (EVs) from endothelial cells might promote VC. Therefore, their evaluation and characterization could be useful for designing new diagnostic tools. The aim of the present study is to investigate whether microvesicles (MVs) from endothelial cells damaged by uremic toxin and indoxyl sulfate (IS) could induce calcification in human vascular smooth muscle cells (VMSCs). Besides, we have also analyzed the molecular mechanisms by which these endothelial MVs can promote VC development. Endothelial damage has been evaluated according to the percentage of senescence in endothelial cells, differential microRNAs in endothelial cells, and the amount of MVs released per cell. To identify the role of MVs in VC, VSMCs were treated with MVs from IS-treated endothelial cells. Calcium, inflammatory gene expression, and procalcification mediator levels in VSMCs were determined. IS-treated endothelial cells underwent senescence and exhibited modulated microRNA expression and an increase in the release of MVs. VSMCs exposed to these MVs modulated the expression of pro-inflammatory genes and some mediators involved in calcification progression. MVs produced by IS-treated endothelial cells promoted calcification in VSMCs.Instituto de Salud Carlos IIISociedad Española de NefrologíaUniversidad de AlcaláGrupo SantanderUniversity fo California San Dieg

    Microbial aetiology of healthcare associated pneumonia in Spain: a prospective, multicentre, case-control study

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    Introduction: Healthcare-associated pneumonia (HCAP) is actually considered a subgroup of hospital-acquired pneumonia due to the reported high risk of multidrug-resistant pathogens in the USA. Therefore, current American Thoracic Society/Infectious Diseases Society of America guidelines suggest a nosocomial antibiotic treatment for HCAP. Unfortunately, the scientific evidence supporting this is contradictory. Methods: We conducted a prospective multicentre case-control study in Spain, comparing clinical presentation, outcomes and microbial aetiology of HCAP and community-acquired pneumonia (CAP) patients matched by age (±10 years), gender and period of admission (±10 weeks). Results: 476 patients (238 cases, 238 controls) were recruited for 2 years from June 2008. HCAP cases showed significantly more comorbidities (including dysphagia), higher frequency of previous antibiotic use in the preceding month, higher pneumonia severity score and worse clinical status (Charslon and Barthel scores). While microbial aetiology did not differ between the two groups (HCAP and CAP: Streptococcus pneumoniae: 51% vs 55%; viruses: 22% vs 12%; Legionella: 4% vs 9%; Gram-negative bacilli: 5% vs 4%; Pseudomonas aeruginosa: 4% vs 1%), HCAP patients showed worse mortality rates (1-month: HCAP, 12%; CAP 5%; 1-year: HCAP, 24%; CAP, 9%), length of hospital stay (9 vs 7 days), 1-month treatment failure (5.5% vs 1.5%) and readmission rate (18% vs 11%) (p<0.05, each). Conclusions: Despite a similar clinical presentation, HCAP was more severe due to patients' conditions (comorbidities) and showed worse clinical outcomes. Microbial aetiology of HCAP did not differ from CAP indicating that it is not related to increased mortality and in Spain most HCAP patients do not need nosocomial antibiotic coverage

    Construcción de un diccionario didáctico digital para la mejora del aprendizaje del latín y estudio preliminar de su extensión a otras lenguas

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    Los objetivos de este proyecto son la creación de una versión digital, disponible en línea y en abierto, de un diccionario basado en un modelo inédito lexicográfico y cognitivo y el estudio preliminar de su generalización a otras lenguas. La eficacia didáctica del modelo de diccionario ha sido probada en este curso académico experimentalmente para la enseñanza presencial del latín utilizando una versión en papel. La idea es construir una versión digital para que el alumno pueda utilizarlo tanto para el trabajo en el aula como para el trabajo personal y estudiar si es viable su aplicación general al estudio de otras lenguas, especialmente de las lenguas modernas. El diccionario en formato digital proporcionaría, frente al papel, tres ventajas significativas: (1) aumentar su accesibilidad lo que facilitaría su uso en cualquier momento y lugar, (2) ayudar al alumno con dificultades a nivelarse puesto que podría usarlo para repetir los ejercicios de aprendizaje tantas veces como lo necesite, y, (3), servir de base para llevar a cabo acciones educativas basadas en la autoformación en línea que faciliten y fomenten el aprendizaje del latín en particular y de otras lenguas si el resultado del estudio preliminar es positivo respecto a su generalización
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