Assessment of haemophilic arthropathy through balance analysis: a promising tool

This is an Author's Accepted Manuscript of an article published in Xavier García-Massó, Yiyao Ye-Lin, Javier Garcia-Casado, Felipe Querol & Luis-Millan Gonzalez (2019) Assessment of haemophilic arthropathy through balance analysis: a promising tool, Computer Methods in Biomechanics and Biomedical Engineering, 22:4, 418-425, DOI: 10.1080/10255842.2018.1561877, available online at: http://doi.org/10.1080/10255842.2018.1561877.[EN] The purpose of this study was to develop a tool able to distinguish between subjects who have haemophilic arthropathy in lower limbs and those who do not by analyzing the centre of pressure displacement. The second objective was to assess the possible different responses of haemophiliacs and healthy subjects by creating a classifier that could distinguish between both groups. Fiftyfour haemophilic patients (28 with and 26 without arthropathy) and 23 healthy subjects took part voluntarily in the study. A force plate was used to measure postural stability. A total of 276 centre of pressure displacement parameters were calculated under different conditions: unipedal/bipedal balance with eyes open/closed. These parameters were used to design a Quadratic Discriminant Analysis classifier. The arthropathy versus non-arthropathy classifier had an overall accuracy of 97.5% when only 10 features were used in its design. Similarly, the haemophiliac versus nonhaemophiliac classifier had an overall accuracy of 97.2% when only 7 features were used. In conclusion, an objective haemophilic arthropathy in lower limbs evaluation system was developed by analyzing centre of pressure displacement signals. The haemophiliac vs. non-haemophiliac classifier designed was also able to corroborate the existing differences in postural control between haemophilic patients (with and without arthropathy) and healthy subjects.García-Massó, X.; Ye Lin, Y.; Garcia-Casado, J.; Querol -Fuentes, F.; Gonzalez, L. (2019). 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Pomegranate Extract Improves Maximal Performance of Trained Cyclists after an Exhausting Endurance Trial: A Randomised Controlled Trial

The efficacy of pomegranate (Punica granatum) extract (PE) for improving performance and post-exercise recovery in an active population was equivocal in previous studies. In this study, a randomised, double-blinded, placebo-controlled, balanced, cross-over trial with two arms was conducted. Eligibility criteria for participants were as follows: male, amateur cyclist, with a training routine of 2 to 4 sessions per week (at least one hour per session). The cyclists (n = 26) were divided into treatment (PE) and placebo (PLA) groups for a period of 15 days. After physical tests, the groups were exchanged after a 14-day washout period. Exercise tests consisted of endurance bouts (square-wave endurance exercise test followed by an incremental exercise test to exhaustion) and an eccentric exercise drill. The objective was to assess the efficacy of PE in performance outcomes and post-exercise muscular recovery and force restoration after a prolonged submaximal effort. Twenty-six participants were included for statistical analysis. There was a statistically significant difference in total time to exhaustion (TTE)(17.66–170.94 s, p < 0.02) and the time to reach ventilatory threshold 2 (VT2)(26.98–82.55 s, p < 0.001), with greater values for the PE compared to the PLA group. No significant results were obtained for force restoration in the isokinetic unilateral low limb test. PE, after a prolonged submaximal effort, may be effective in improving performance outcomes at maximal effort and might help to restore force in the damaged muscles.Actividad Física y Deport

The structure of Leptospira interrogans GAPDH sheds light into an immunoevasion factor that can target the anaphylatoxin C5a of innate immunity

Leptospirosis is a neglected worldwide zoonosis involving farm animals and domestic pets caused by the Gram-negative spirochete Leptospira interrogans. This bacterium deploys a variety of immune evasive mechanisms, some of them targeted at the complement system of the host’s innate immunity. In this work, we have solved the X-ray crystallographic structure of L. interrogans glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to 2.37-Å resolution, a glycolytic enzyme that has been shown to exhibit moonlighting functions that potentiate infectivity and immune evasion in various pathogenic organisms. Besides, we have characterized the enzyme’s kinetic parameters toward the cognate substrates and have proven that the two natural products anacardic acid and curcumin are able to inhibit L. interrogans GAPDH at micromolar concentration through a noncompetitive inhibition modality. Furthermore, we have established that L. interrogans GAPDH can interact with the anaphylatoxin C5a of human innate immunity in vitro using bio-layer interferometry and a short-range cross-linking reagent that tethers free thiol groups in protein complexes. To shed light into the interaction between L. interrogans GAPDH and C5a, we have also carried out cross-link guided protein-protein docking. These results suggest that L. interrogans could be placed in the growing list of bacterial pathogens that exploit glycolytic enzymes as extracellular immune evasive factors. Analysis of the docking results indicates a low affinity interaction that is consistent with previous evidence, including known binding modes of other α-helical proteins with GAPDH. These findings allow us to propose L. interrogans GAPDH as a potential immune evasive factor targeting the complement system

The case of a southern European glacier disappearing under recent warming that survived Roman and Medieval warm periods

Mountain glaciers have generally experienced an accelerated retreat over the last three decades as a rapid response to current global warming. However, the response to previous warm periods in the Holocene is not well-described for glaciers of the of southern Europe mountain ranges, such as the Pyrenees. The situation during the Medieval Climate Anomaly (900-1300 CE) is particularly relevant since it is not certain whether the glaciers just experienced significant ice loss or whether they actually disappeared. We present here the first chronological study of a glacier located in the Central Pyrenees (N Spain), the Monte Perdido Glacier (MPG), carried out by different radiochronological techniques and their comparison with geochemical proxies with neighboring paleoclimate records. The result of the chronological model proves that the glacier endured during the Roman Period and the Medieval Climate Anomaly. The lack of ice from last 600 years indicates that the ice formed during the Little Ice Age has melted away. The analyses of the content of several metals of anthropogenic origin, such as Zn, Se, Cd, Hg, Pb, appear in low amounts in MPG ice, which further supports our age model in which the record from the industrial period is lost. This study confirms the exceptional warming of the last decades in the context of last two millennia. We demonstrate that we are facing an unprecedented retreat of the 55 Pyrenean glaciers which survival is compromised beyond a few decades

Rapid changes of dust geochemistry in the Saharan Air Layer linked to sources and meteorology

Based at Izaña Observatory (∼2400 m a.s.l. in Tenerife), we performed 1-h resolution measurements of elemental composition of dust in the Saharan Air Layer (SAL) and studied the variability of the ratios of these elements to aluminium (elemental ratios). In a period (∼1 week) of continuous dust presence (50–200 μg/m3), we observed rapid variations of dust composition; some elemental ratios changed by a factor 2 in a few (5–8) hours. The lowest variability (Normalized Variability Range, %) was found for Si/Al (9%) and Fe/Al (9%), followed by the ratios of K, Ti, Mg, Mn, Ca and Sr to Al (20–80%), and the highest for S/Al, Na/Al and Cl/Al (110–160%) and a number of trace metals (Cr, Cu, Ni, Zn, Zr) and Br (>200%). This variability was induced by the alternating impacts of three of the large North African dust sources: NE Algeria (rich in evaporite minerals bearing Ca, S, Sr, K and Mg and in illite mineral), Western Sahara to Bechar region (containing Na, S and Cl rich Yermosol soils) and SW Sahara – Western Sahel (rich in illite and hematite). We traced the variability in large-scale meteorology using the so-called North African Dipole Intensity (NAFDI: strength of the subtropical Saharan high -Morocco-to the monsoon tropical low -Nigeria-). The mobilization of dust from the different sources was associated with westward propagating Harmattan pulses linked to the change of phase of NAFDI (- to +), the associated westward shifts of the Saharan Heat Low and convective monsoon inflow. We found a correlation between dust composition in the SAL and NAFDI: moderate NAFDI values (0 to +2.5) were associated with Ca, K, Na, Mg and S rich dust linked to dust sources in NE Algeria, whereas higher NAFDI values (+2.5 to +4) were linked to Fe rich dust (Ca, Na and S depleted) linked to dust sources in SW Sahara – Western Sahel. The results of this study also show that some trace elements (Br, Cr, Ni, Zn and Zr) are influenced by industrial emissions into North Africa.This study was performed within the project VARDUST-SAL (PGC 2018-099166-B-I00), funded by the Ministry of Science, Research and Innovation of Spain, the Research State Agency of Spain and the European Regional Development Fund (ERDF)

The Antimicrobials Anacardic Acid and Curcumin Are Not-Competitive Inhibitors of Gram-Positive Bacterial Pathogenic Glyceraldehyde-3-Phosphate Dehydrogenase by a Mechanism Unrelated to Human C5a Anaphylatoxin Binding

The ubiquitous and highly abundant glycolytic enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pivotal for the energy and carbon metabolism of most organisms, including human pathogenic bacteria. For bacteria that depend mostly on glycolysis for survival, GAPDH is an attractive target for inhibitor discovery. The availability of high-resolution structures of GAPDH from various pathogenic bacteria is central to the discovery of new antibacterial compounds. We have determined the X-ray crystal structures of two new GAPDH enzymes from Gram-positive bacterial pathogens, Streptococcus pyogenes and Clostridium perfringens. These two structures, and the recent structure of Atopobium vaginae GAPDH, reveal details in the active site that can be exploited for the design of novel inhibitors based on naturally occurring molecules. Two such molecules, anacardic acid and curcumin, have been found to counter bacterial infection in clinical settings, although the cellular targets responsible for their antimicrobial properties remain unknown. We show that both anacardic acid and curcumin inhibit GAPDH from two bacterial pathogens through uncompetitive and non-competitive mechanisms, suggesting GAPDH as a relevant pharmaceutical target for antibacterial development. Inhibition of GAPDH by anacardic acid and curcumin seems to be unrelated to the immune evasion function of pathogenic bacterial GAPDH, since neither natural compound interfere with binding to the human C5a anaphylatoxin

The Sant Pau Initiative on Neurodegeneration (SPIN) cohort : A data set for biomarker discovery and validation in neurodegenerative disorders

Altres ajuts: The SPIN cohort has received funding from CIBERNED; Instituto de Salud Carlos III; jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa"; Generalitat de Catalunya; Fundació "La Marató TV3" Fundació Bancària Obra Social La Caixa; Fundación BBVA; Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica (FUNDELA); Global Brain Health Institute; Fundació Catalana Síndrome de Down; and Fundació Víctor Grífols i Lucas. These funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.The SPIN (Sant Pau Initiative on Neurodegeneration) cohort is a multimodal biomarker platform designed for neurodegenerative disease research following an integrative approach. Participants of the SPIN cohort provide informed consent to donate blood and cerebrospinal fluid samples, receive detailed neurological and neuropsychological evaluations, and undergo a structural 3T brain MRI scan. A subset also undergoes other functional or imaging studies (video-polysomnogram, 18 F-fluorodeoxyglucose PET, amyloid PET, Tau PET). Participants are followed annually for a minimum of 4 years, with repeated cerebrospinal fluid collection and imaging studies performed every other year, and brain donation is encouraged. The integration of clinical, neuropsychological, genetic, biochemical, imaging, and neuropathological information and the harmonization of protocols under the same umbrella allows the discovery and validation of key biomarkers across several neurodegenerative diseases. We describe our particular 10-year experience and how different research projects were unified under an umbrella biomarker program, which might be of help to other research teams pursuing similar approaches

Cultural Heritage in Europe: A commitment for socioeconomic change from managing our past II

Diseño web, apoyo RRSS: Empresa Jansá Cultura y Tecnología https://appcultura.comEl proyecto formará en el Patrimonio Cultural existente en la Unión Europea desde su gestión. Supone actividades como: 1. Conocer los bienes culturales desde la visión crítica de los procesos de patrimonialización hasta la catalogación e inventario. 2 Planificar su financiación, legislación o la ordenación urbanística y territorial. 3. Controlar las acciones ilícitas que pueden deteriorarlos, así como la venta o la transmisión de estos bienes. 4. Plantear su socialización desde la interpretación y la difusión en ámbitos formales e informales, desde estrategias de turismo, tecnológicas o de redes sociales, así como realizar procesos participativos, de implicación de la sociedad civil y organizaciones interesadas en la toma de decisiones sobre su tratamiento. 5. Ser capaces de evaluar a corto, largo y medio plazo y desde múltiples perspectivas, incluida la del impacto socioeconómico. De la importancia del tema habla por si sola la declaración del Parlamento Europeo para la celebración del Año 2018 y que reproducimos (http://www.consilium.europa.eu/es/press/press-releases/2017/02/09-cultural-heritage/): " Año Europeo del Patrimonio Cultural en 2018: celebración de la diversidad y la riqueza de nuestro patrimonio europeo, cuyos objetivos son: - Promover la diversidad cultural, el diálogo intercultural y la cohesión social; - Poner de relieve la contribución económica del patrimonio cultural a los sectores cultural y de la creación, en particular a las pequeñas y medianas empresas, y al desarrollo local y regional; - Hacer hincapié en el papel del patrimonio cultural en las relaciones exteriores de la UE, por ejemplo, en la prevención de conflictos, la reconciliación tras estos y la reconstrucción del patrimonio cultural destruido " Abordar estos temas requiere una formación transdisciplinar, que aporta el equipo de docentes de la Universidad Complutense de Madrid y de la Universidad Politécnica de Madrid pertenecientes a las siguientes áreas de conocimiento: historia, historia del arte, geografía, arqueología, economía, sociología, psicología, derecho, arquitectura, ingeniería de las telecomunicaciones y de caminos, canales y puertos. A ellos se le suma una trayectoria de cerca de 30 años en los temas referidos, siendo nuestros centros pioneros en España para impartir esa formación y sin lugar a dudas innovadores en la transversalidad con la que las hemos impulsado en nuestras distintas facultades y escuelas, donde no existe el área de conocimiento como tal. Participamos miembros de varios grupos de investigación, como el de Gestión del Patrimonio Cultural, Patrimonio Turismo y Desarrollo o Paisajes Culturales. Destacan responsabilidades y docencias en Másteres como el de Conservación y Restauración en Patrimonio Arquitectónico, de la UPM o el de Museos y Patrimonio Histórico Artístico de la UCM, lineas de doctorado en Turismo y Desarrollo, asignaturas de grado y posgrados como Patrimonio Urbano, Paisaje Cultural y Ordenación Territorial o la gestión del patrimonio arqueológico. Así mismo la mayoría de nosotros hemos sido evaluados positivamente por el programa Docentia, y hemos participado y dirigido otros proyectos de innovación como el que se encuentra en los antecedentes a este sobre Patrimonio Cultural en CIU y el del decanato de la Fac. Geografía e Historia de Living Unilab sobre APs y ecosistemas de aprendizaje. Iniciativas con las que continuaremos participando. Pero, sin lugar a dudas, ha sido el Máster Interuniversitario Patrimonio Cultural en el S.XXI: Gestión e investigación, un motor de arranque para iniciativas conjuntas entre este equipo, a través del Campus de Excelencia Internacional, y es justo este año cuando se pone en marcha y podremos allí explorar gran parte de nuestras innovaciones recogidas en este proyecto. A estos esfuerzos se suma el alumnado: 13 estudiantes de grados y posgrados comprometidxs con la oportunidad que nos ofrece el pasado. No hay mejor aval para nuestra propuesta.The Educational Innovation Project “Cultural Heritage in Europe: a commitment for socioeconomic change from managing our past” of the Complutense University of Madrid together with the Technical University of Madrid, took advantage of the celebration of the European Year of Cultural Heritage 2018 to open new paths of transversal and multidisciplinary knowledge in the field of Cultural Heritage by applying a type of classroom teaching that would allow students to offer projects that could have an impact on society and contribute to meeting the objectives set by the European Commission for this year's celebration. From a European perspective, the project has completed a triple aspect: researcher, education and public service when working and disseminating Cultural Heritage among the population of Madrid and Europe. The work has been done on disciplines as diverse as Architecture, History, Civil Engineering, Geography, Tourism, etc. to compose from the different subjects involved a speech that will contribute to this field.Depto. de Prehistoria, Historia Antigua y ArqueologíaFac. de Geografía e HistoriaFALSEAyuntamiento de Madrid/Foro de Empresas por Madridsubmitte