Early diagnosis of frailty: Technological and non-intrusive devices for clinical detection

This work analyses different concepts for frailty diagnosis based on affordable standard technology such as smartphones or wearable devices. The goal is to provide ideas that go beyond classical diagnostic tools such as magnetic resonance imaging or tomography, thus changing the paradigm; enabling the detection of frailty without expensive facilities, in an ecological way for both patients and medical staff and even with continuous monitoring. Fried's five-point phenotype model of frailty along with a model based on trials and several classical physical tests were used for device classification. This work provides a starting point for future researchers who will have to try to bridge the gap separating elderly people from technology and medical tests in order to provide feasible, accurate and affordable tools for frailty monitoring for a wide range of users.This work was sponsored by the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (ERDF) across projects RTC-2017-6321-1 AEI/FEDER, UE, TEC2016-76021-C2-2-R AEI/FEDER, UE and PID2019-107270RB-C21/AEI/10.13039/501100011033, UE

C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation

C3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns of glomerular inflammation and C3 deposition caused by complement dysregulation. Here we report the identification of a familial C3G-associated genomic mutation in the gene complement factor H–related 1 (CFHR1), which encodes FHR1. The mutation resulted in the duplication of the N-terminal short consensus repeats (SCRs) that are conserved in FHR2 and FHR5. We determined that native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes, the formation of which is likely mediated by the conserved N-terminal domain. In mutant FHR1, duplication of the N-terminal domain resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidity for the FHR1 ligands C3b, iC3b, and C3dg and enhanced competition with complement factor H (FH) in surface plasmon resonance (SPR) studies and hemolytic assays. These data revealed that FHR1, FHR2, and FHR5 organize a combinatorial repertoire of oligomeric complexes and demonstrated that changes in FHR oligomerization influence the regulation of complement activation. In summary, our identification and characterization of a unique CFHR1 mutation provides insights into the biology of the FHRs and contributes to our understanding of the pathogenic mechanisms underlying C3G

Insights into hemolytic uremic syndrome: Segregation of three independent predisposition factors in a large, multiple affected pedigree

Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome (aHUS, MIM 235400), suggesting that the disease develops as a consequence of the inefficient protection of the renal endothelium from damage by the complement system. Incomplete penetrance of the disease in individuals carrying these mutations is, however, relatively frequent. Here, we report the identification of a large, multiple affected aHUS pedigree in which there is independent segregation of three different aHUS risk factors: a MCP missense mutation (c.-598C > T; Pro165Ser) that decreases MCP expression on the cell surface, a dinucleotide insertion in the coding sequence of factor I (c.-1610insAT) that introduces a premature stop codon in the factor I protein, and the MCPggaac SNP haplotype block that was previously shown to decrease the transcription activity from the MCP promoter. Interestingly, individuals affected by aHUS in the pedigree are only those who have inherited the three aHUS risk factors. These data show an additive effect for mutations in MCP and factor I and provide definitive support to the conclusion that aHUS results from a defective protection of cellular surfaces from complement activation. Furthermore, they help to explain the incomplete penetrance of the disease, illustrating that concurrence of multiple hits in complement regulatory proteins may be necessary to significantly impair host tissue protection and to confer susceptibility to aHUS. © 2005 Elsevier Ltd. All rights reserved.These studies were performed with funds provided by the Ministerio de Educación y Cultura (SAF2002-01085 and SAF03-03485) and from the Fondo de Investigaciones Sanitarias (C03/05; G03/054; G03/011, FIS 03/0621 and FIS 01/A046)Peer Reviewe

Akats-korronteen mugaketa MMC bihurgailudun VSC-HVDC sistemetan

Goi-tentsioko korronte zuzeneko (ingelesez, High Voltage Direct Current HVDC) garraio-sistemak gero eta garrantzitsuagoak dira sistema elektrikoan, onura ekonomiko eta teknikoak direla eta. Hala ere, akatsen bat gertatzen denean, korrontea eteteak oraindik ere erronka izaten jarraitzen du HVDC sareetan. Desiragarriak ez diren korronteak eteteko, korronte zuzeneko etengailuak erabil daitezke, baina horien gaitasuna mugatua da. Egoera hala izanik, akats-korronteen mugagailuak (ingelesez, Fault Current Limiter FCL) dira proposamenik egokiena akats-korronteak maneiagarriagoak diren balioetara txikitzeko; hartara, sistema elektrikoaren garraio-ahalmena handitu daiteke, ekipamendua aldatu beharrik gabe. Sarean aldez aurretik legokeen ekipamendua gai izango litzateke korronte berriak kudeatzeko eta sistema era eraginkorrean babesteko FCLen erabilpenaz. Artikulu honetan, FCL tresnen ezaugarri orokorrak eta sailkapena aurkezten dira. Ondoren, egoera solidoko FCLa erabili da maila anizkoitzeko bihurgailudun (ingelesez, Modular Multilevel Converter MMC) VSC-HVDC (ingelesez, Voltage Source Converter) sistema batean, eta horren jokaera azaltzen da simulazio bidez.

Mutations in proteins of the Alternative Pathway of Complement and the Pathogenesis of Atypical Hemolytic Uremic Syndrome

10 páginas, 5 figuras, 1 tabla -- PAGS nros. 171-180Atypical hemolytic uremic syndrome is associated with mutations in the complement proteins factor H, factor I, factor B, C3, or membrane cofactor protein in about 50% of patients. The evolution and prognosis of the disease in patients carrying mutations in factor H is particularly poor, and renal transplantation most often fails because of recurrence of the disease in the graft. The risk of rapid loss of renal function in patients with functional mutations in factor H requires that effective treatment be initiated as soon as possible, but identification of these patients relies on genetic studies that are time consuming. We describe a case in which an in vitro hemolytic assay proved useful for rapidly assessing factor H dysfunction and for testing whether this dysfunction could be corrected with fresh frozen plasma. In the context of this case, we summarize recent advances in understanding the molecular mechanisms contributing to atypical hemolytic uremic syndrome, including descriptions of DNA- and protein-based analysis. We conclude that functional analysis of factor H should help rationalize the plasma treatment of patients with atypical hemolytic uremic syndromeThis work was funded by the Spanish Ministerio de Sanidad y Consumo (grants FIS 03/0621 and 06/0625 to P.S.C.) and the Spanish Ministerio de Educación y Cultura (grant SAF2005-00913 to S.R.C.)Peer reviewe

Characterization of complement factor H–related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome

8 Tables. 7 Figures. The online version of this article contains a data supplement.The factor H–related protein family (CFHR) is a group of minor plasma proteins genetically and structurally related to complement factor H (fH). Notably, deficiency of CFHR1/CFHR3 associates with protection against age-related macular degeneration and with the presence of anti-fH autoantibodies in atypical hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to analyze the CFHR proteins in plasma samples from controls, patients with aHUS, and patients with type II membranoproliferative glomerulonephritis. Here, we report on the identification of persons carrying novel deficiencies of CFHR1, CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies, suggesting that generation of these antibodies is specifically related to CFHR1 deficiency. We also report the characterization of a novel CFHR1 polymorphism, resulting from a gene conversion event between CFH and CFHR1, which strongly associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity to fH, may compete with fH, decreasing protection of cellular surfaces against complement damage. In summary, our comprehensive analyses of the CFHR proteins have improved our understanding of these proteins and provided further insights into aHUS pathogenesis.Sheila Pinto for excellent technical assistance and Prof Peter F. Zipfel (Hans-Knöll Institute, Jena, Germany) and Dr Jennifer McRae (St Vincent’s Health, Melbourne, Australia) for providing us with polyclonal antibodies recognizing CFHR proteins. We also thank Dr Marie Agnes Dragon-Durey (Hôpital Georges Pompidou, Paris, France) for the reference sample containing fH autoantibodies.Peer reviewe

Con-tacto : aprendiendo con nuevos amigos

El objetivo principal de este proyecto es observar y explorar el entorno inmediato identificando las características y propiedades más significativas de los elementos que lo conforman y estableciendo relaciones entre ellos. Otros objetivos son contribuir a un mayor conocimiento del trabajo que se realiza en las Casas de Niños; adecuar los centros a las Nuevas Tecnologías en el trabajo con los niños y niñas; mostrar los recursos naturales y comunitarios de la zona de Lozoya y contribuir al desarrollo de la capacidad de observación y escucha de los pequeños. En cuanto a la metodología, a través de un cuento se narra la historia de un ruiseñor que viene de muy lejos y se queda a vivir aquí. Se desarrollan técnicas nuevas para expresar pensamientos y emociones y las aulas se llenan de personajes distintos a los habituales que cuentan historias y ayudan a aprender. Las actividades realizadas son Cuentacuentos en las aulas, exposiciones fotográficas de pájaros que viven en la zona, salidas al campo, una obra de teatro y la Jornada de Puertas Abiertas en la que se entregará a cada niño un ejemplar del cuento. El juego está presente en el proceso de aprendizaje enmarcado en un espacio y un ambiente cálido y motivador con materiales conocidos y otros nuevos. El educador ha tenido una actitud de escucha, de observación durante las actividades y ha sido consciente de la fragilidad del alumnado y de la necesidad de estar pendiente de cada uno. En general, la evaluación es positiva y las visitas en el aula han diversificado las nuevas tecnologías y todos han aprendido a ser más respetuosos y tolerantes.Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Ordenación AcadémicaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES