650 research outputs found

    Visualisation of flow fields in the web platform

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    Visualization of vector fields plays an important role in research activities nowadays. Web applications allow a fast, multi-platform and multi-device access to data, which results in the need of optimized applications to be implemented in both high and low-performance devices. The computation of trajectories usually repeats calculations due to the fact that several points might lie over the same trajectory. This paper presents a new methodology to calculate point trajectories over a highly-dense and uniformly-distributed grid of points in which the trajectories are forced to lie over the points in the grid. Its advantages rely on a highly parallel computing implementation and in the reduction of the computational effort to calculate the stream paths since unnecessary calculations are avoided by reusing data through iterations. As case study, the visualization of oceanic streams in the web platform is presented and analyzed, using WebGL as the parallel computing architecture and the rendering engine

    Características metodológicas de las evaluaciones de tecnologías sanitarias elaboradas en Perú, 2019-2021

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    Background: Limitations have been reported to comply with good methodological practices in the development of health technology assessments (HTA). Therefore, the objective of the present study was to describe the methodological characteristics of the HTAs carried out in Peru, between 2019-2021. Methods: Descriptive study. We are looking for Peruvian institutions that prepare HTAs whose reports are accessible to the public. We collected the total number of HTAs produced by these institutions per year, and we collected the characteristics of the HTAs produced during the 2019-2021 period. Results: Three Peruvian institutions developed at least three public HTAs between 2019-2021: The Institute for the Evaluation of Technologies in Health and Research (IETSI) (n=142), the Unit for the Analysis and Generation of Evidence in Public Health (UNAGESP) (n=60), and the National Institute of Neoplastic Diseases (INEN) (n=40). The HTAs of UNAGESP did not reach a decision, while 35.9% of those of IETSI and 70.0% of those of INEN concluded in favor of the evaluated technology. All STDs explained the methodology used and performed systematic searches. However, few presented the risk of bias assessment of the included studies (17.4%), the certainty of the evidence (4.6%), or the benefits and harms per outcome (14.4%). None of the HTAs carried out cost studies or made explicit the methodology used to reach the decision. Conclusions: The HTAs evaluated presented favorable methodological aspects and certain shortcomings (in topics such as the report in the evaluation of risk of bias and certainty of the evidence, presentation of benefits and harms by outcome, and explanation of the methodology used to make decisions).Introducción: Se han reportado limitaciones para cumplir con buenas prácticas metodológicas en el desarrollo de evaluaciones de tecnologías sanitarias (ETS). Por ello, el objetivo del presente estudio fue describir las características metodológicas de las ETS elaboradas en Perú, entre 2019-2021. Métodos: Estudio descriptivo. Buscamos las instituciones peruanas que elaboren ETS cuyos informes sean accesibles al público. Recolectamos el número total de ETS que elaboraron estas instituciones por año, y recolectamos las características de las ETS elaboradas durante el periodo 2019-2021. Resultados: Tres instituciones peruanas elaboraron al menos tres ETS públicas entre 2019-2021: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) (n=142), la Unidad de Análisis y Generación de Evidencias en Salud Pública (UNAGESP) (n=60), y el Instituto Nacional de Enfermedades Neoplásicas (INEN) (n=40). Las ETS de UNAGESP no brindaron una decisión, mientras que 35,9% de las de IETSI y 70,0% de las de INEN concluyeron a favor de la tecnología evaluada. Todas las ETS explicaron la metodología usada y realizaron búsquedas sistemáticas. Sin embargo, pocas presentaron la evaluación de riesgo de sesgo de los estudios incluidos (17,4%), la certeza de la evidencia (4,6%), o los beneficios y daños por desenlace (14,4%). Ninguna ETS realizó estudios de costos ni explicitó la metodología usada para llegar a la decisión. Conclusiones: Las ETS evaluadas presentaron aspectos metodológicos favorables y ciertas falencias (en temas como el reporte en la evaluación de riesgo de sesgo y certeza de la evidencia, presentación de beneficios y daños por desenlace, y explicitación de la metodología usada para tomar decisiones)

    Genetic and environmental factors related to the development of myopic maculopathy in Spanish patients

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    High myopia and the subsequent degenerative changes of the retina, choroid, and sclera, known as myopic maculopathy (MM), are a serious visual problem in many Asian countries, and are beginning to be so in the south of Europe, especially in the Mediterranean. It is therefore necessary to carry out genetic and environmental studies to determine the possible causes of this disease. This study aims to verify if the genetic factors that have been most related to Asian populations are also associated in two Spanish cohorts. Eight SNPs from six genes (PAX6,SCO2,CCDC102B,BLID,chromosome 15q14, andCOL8A1) along with demographic, ophthalmic and environmental factors were analysed in two cohorts from a total of 365 highly myopic subjects and 177 control subjects. The genetic analysis showed thatCOL8A1SNP rs13095226 was associated with the development of choroidal neovascularization (CNV) and also seems to play an important role in the increase of axial length. The SNP rs634990 ofchromosome 15q14also showed a significant association with MM, although this was lost after the Bonferroni correction. Additional demographic and environmental factors, namely age, sex, smoking status, and pregnancy history, were also found to be associated with MM and CNV in this population

    Sex Hormone Receptor Expression in Craniopharyngiomas and Association with Tumor Aggressiveness Characteristics

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    Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life. Previous studies have reported that CPs express sex hormone receptors, including estrogen and progesterone receptors. Here, we systematically analyzed estrogen receptor α (ERα) and progesterone receptor (PR) expression by immunohistochemistry in a well-characterized series of patients with CP (n = 41) and analyzed their potential association with tumor aggressiveness features. A substantial proportion of CPs displayed a marked expression of PR. However, most CPs expressed low levels of ERα. No major association between PR and ERα expression and clinical aggressiveness features was observed in CPs. Additionally, in our series, β-catenin accumulation was not related to tumor recurrence. View Full-TextThis work was supported by grants from the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI16/00175 to A.S-M. and D.A.C.) and the Sistema Andaluz de Salud (A-0006-2017 and A-0055-2018 to A.S-M, RC-0006-2018 to D.A.C.)

    Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

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    BACKGROUND Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.The authors thank the Centro Nacional de Investigaciones Cardiovasculares (CNIC) Viral Vectors Unit for producing the adeno-associated virus serotype 9. Confocal experiments were conducted at the CNIC Microscopy and Dynamic Imaging Unit. The authors thank the CNIC Bioinformatics Unit for generating the in silico homology modeling simulations, F-function analysis, and helpful discussions. The authors also thank the Centro de Supercomputación de Galicia for the use of the Finis Terrae III supercomputer to perform molecular dynamics studies. The CNIC was supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). This work was supported by the National heart, Lung and Blood Institute under National Institutes of Health (NIH) grant R01HL163943; the La Caixa Banking Foundation project code HR18-00304 (grant LCF/PR/HR19/52160013); grants PI-FIS-2020, PI20/01220, PI-FIS-2023, and PI23/01039 from the Instituto de Salud Carlos III and cofunded by the Fondo Europeo de Desarrollo Regional (FEDER) and the European Union, respectively; grants PID2020-116935RB-I00 and BFU2016-75144-R funded by MICIU/AEI/10.13039/501100011033; the Fundación La Marató de TV3 (736/C/2020) amb el suport de la Fundació La Marató de TV3; the CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (grant CB16/11/00458); the European Union’s Horizon 2020 grant agreement GA-965286; and the Program S2022/BMD7229-CM ARCADIACM funded by the Comunidad de Madrid to J. Jalife; grant PID2021-126423OB-C22 (to M. Martín-Martínez) funded by MICIU/AEI/10.13039/501100011033; and European Regional Development Fund (ERDF) grant PID2022-137214OB-C22 (to M. Gutierrez-Rodríguez) funded by MICIU/AEI/10.13039/501100011033. The imaging studies were performed in the TRIMA@CNIC (Infraestructura de Imagen Traslacional Avanzada del CNIC) node of the ICTS ReDIB (Infraestructuras Científicas y Técnicas Singulares: Red Distribuida de Imagen Biomédica) grant ICTS-2018- 04-CNIC-16 funded by MICIU/AEI/10.13039/501100011033 and ERDF, and project EQC2018-005070-P funded by MICIU/AEI/10.13039/501100011033 and FEDER. A.I. Moreno-Manuel holds an formación profesional universitaria (FPU) contract (FPU20/01569) from the Ministerio de Universidades. J.M. Ruiz Robles holds an FPU contract (FPU22/03253) from the Ministerio de Universidades. L.K. Gutiérrez holds an FPI contract (PRE2018-083530) from the Ministerio de Economía y Competitividad de España cofunded by the Fondo Social Europeo, attached to project SEV-2015-0505-18-2. I. Martínez-Carrascoso holds a PFIS (Contratos predoctorales de formación en investigación en salud) contract (FI21/00243) funded by Instituto de Salud Carlos III and the Fondo Social Europeo Plus cofunded by the European Union. M.L. Vera-Pedrosa held contract PEJD-2019-PRE/BMD15982 funded by the Consejería de Educación e Investigación de la Comunidad de Madrid y Fondo Social Europeo.S

    Risk factors associated with methicillin-resistant Staphylococcus aureus skin and soft tissue infections in hospitalized patients in Colombia

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    Q2Q160-66Pacientes hospitalizadosObjectives: Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) represent a major clinical problem in Colombia. The aim of this study was to evaluate the risk factors associated with MRSA SSTI in Colombia. Methods: A multicenter cohort study with nested case–control design was performed. Patients with an SSTI with at least 48 h of inpatient care were included. Patients with an MRSA SSTI were considered the case group and patients with either a non-MRSA SSTI or with an Methicillin-susceptible S. aureus (MSSA) SSTI were the control groups. A multivariate logistic regression approach was used to evaluate risk factors associated with MRSA SSTI with two different statistical models. Results: A total 1134 patients were included. Cultures were positive for 498 patients, of which 52% (n = 259) were Staphylococcus aureus. MRSA was confirmed in 68.3% of the S. aureus cultures. In the first model, independent risk factors for MRSA SSTI were identified as the presence of abscess (P<0.0001), cellulitis (P = 0.0007), age 18–44 years (P = 0.001), and previous outpatient treatment in the previous index visit (P = 0.003); surgical site infection was a protective factor (P = 0.008). In the second model, the main risk factor found was previous outpatient treatment in the previous index visit (P = 0.013). Conclusions: Community-acquired SSTIs in Colombia are commonly caused by MRSA. Therefore, clinicians should consider MRSA when designing the initial empirical treatment for purulent SSTI in Colombia, although there seems to be low awareness of this fact
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