Acute study of dose-dependent effects of (-)-epicatechin on vascular function in healthy male volunteers: a randomized controlled trial

BACKGROUND & AIMS There is convincing clinical evidence to suggest that flavanol-containing foods/beverages are capable of inducing improvements in human vascular function. However, whilst (-)-epicatechin has been tested for efficacy, a full dose-dependency has yet to be established, particularly at doses below 1 mg/kg BW. The current study examined the dose-dependent effects of (-)-epicatechin on human vascular function with concurrent measurement of plasma (-)-epicatechin metabolites and levels of circulating nitrite and nitrate species, NOx. METHODS An acute, double-blind, placebo-controlled, crossover intervention trial was conducted in 20 healthy males with 4 treatment arms: water-based (-)-epicatechin (0.1, 0.5 and 1.0 mg/kg BW) and a water only as control. Vascular function was assessed by flow-mediated dilatation (FMD) measured at the brachial artery, laser Doppler imaging with iontophoresis (LDI) at the subcutaneous capillaries of the forearm (response to Ach and SNP) and peripheral blood pressure (BP) at baseline, 1, 2, 4 and 6 h post-intervention. Plasma analysis of epicatechin metabolites was conducted by LC-MS and circulating plasma of nitrite and nitrate species were performed using an HPLC-based system (ENO-30). RESULTS Significant increases in % FMD were found to occur at 1 and 2 h following intake of 1 mg/kg BW, and at 2 h for the 0.5 mg/kg BW intake. There were no significant changes in LDI or BP at any time-points or intake levels. Increases in FMD over the 6 h timeframe were closely paralleled by the appearance of total plasma (-)-epicatechin metabolites. Non-significant changes in circulating NOx was observed. CONCLUSIONS Our data add further evidence that (-)-epicatechin is a causal vasoactive molecule within flavanol-containing foods/beverages. In addition, we show for the first time that intake levels as low as 0.5 mg/kg BW are capable of inducing acute improvements in vascular function (FMD) in healthy volunteers

Towards more replicable content analysis for learning analytics

Content analysis (CA) is a method frequently used in the learning sciences and so increasingly applied in learning analytics (LA). Despite this ubiquity, CA is a subtle method, with many complexities and decision points affecting the outcomes it generates. Although appearing to be a neutral quantitative approach, coding CA constructs requires an attention to decision making and context that aligns it with a more subjective, qualitative interpretation of data. Despite these challenges, we increasingly see the labels in CA-derived datasets used as training sets for machine learning (ML) methods in LA. However, the scarcity of widely shareable datasets means research groups usually work independently to generate la- belled data, with few attempts made to compare practice and results across groups. A risk is emerging that different groups are coding constructs in different ways, leading to results that will not prove replicable. We report on two replication studies using a previously reported construct. A failure to achieve high inter-rater reliability suggests that coding of this scheme is not currently replicable across different research groups. We point to potential dangers in this result for those who would use ML to automate the detection of various educationally relevant constructs in LA

Caracterización clínico-patológica, genotipificación viral y heterogeneidad genética como determinantes de riesgo en COVID-19: Diseño del estudio y hallazgos iniciales: Clinical-pathological characterization, viral genotipification and genetic heterogeneity as risk determinants in COVID-19: Study design and initial findings

Introduction: The objective of the study is to describe the clinical, pathological, virological and genetic characteristics ofthe immune response of patients diagnosed with SARS-CoV-2 infection and its relationship with the unfavorable courseof the disease. Methods: Descriptive, relational, longitudinal and retrospective study based on the review of medicalrecords, taking post-mortem tru-cut biopsies of the lung and liver, taking blood samples and naso-oropharyngeal swabor endotracheal tube aspirate. In the first phase, the biopsies will be processed and studied with conventional andimmunohistochemical histology in the Pathological Anatomy service of the Carlos Seguín Escobedo National Hospitalin Arequipa, Peru. Results: Advanced mean age, male sex, and the presence of comorbidities were predominant indeceased patients. Lung biopsies showed predominantly the exudative and partially proliferative phases of diffuseand focal alveolar damage, associated primarily with intraalveolar macrophage hyperplasia with accumulation withinthe alveolar space-resembling desquamative pneumonia, as well as atypical binucleated intraalveolar pneumocytes,with eosinophilic nucleoli (similar to virocytes) in some cases. In the vast majority of cases, intravascular fibrin depositsassociated with the accumulation of inflammatory cells composed of neutrophils and monocytes, representingmicrothrombosis, were observed. Liver biopsies showed predominantly macrovesicular steatosis and in twocases microvesicular steatosis was observed. Additionally, varying degrees of necrosis and mild portal and lobularinflammation were observed. Conclusion: The clinical and pathological findings in this first report are consistent withprevious publications and confirm the pattern of diffuse alveolar damage associated with aggregates of intraalveolarmacrophages and microthrombosis; confirms in addition, macro and microvesicular hepatocytic steatosis, togetherwith variable degrees of necrosis.Introducción: El objetivo del estudio es describir las características clínicas, patológicas, virológicas y genéticas de larespuesta inmune de los pacientes diagnosticados con infección por SARS-CoV-2 y su relación con el curso desfavorablede la enfermedad. Métodos: Estudio descriptivo, relacional, longitudinal y retrospectivo basado en la revisión dehistorias clínicas, toma de biopsias tru-cut post-mortem de pulmón e hígado, toma de muestras de sangre e hisopadonaso-orofaríngeo o de aspirado del tubo endotraqueal. En la primera fase las biopsias serán procesadas y estudiadascon histología convencional e inmunohistoquímica en el servicio de Anatomía Patológica del hospital NacionalCarlos Seguín Escobedo de Arequipa, Perú. Resultados: La edad media avanzada, el sexo masculino y la presencia decomorbilidades fue predominante en los pacientes fallecidos. Las biopsias pulmonares mostraron predominantementelas fases exudativa y parcialmente proliferativa del daño alveolar difuso y focal, asociada principalmente a unahiperplasia de macrófagos intraalveolares con acumulación dentro del espacio alveolar, semejando una neumoníadescamativa, así como neumocitos intraalveolares binucleados y atípicos, con nucléolos eosinofílicos (semejante avirocitos) en algunos casos. En la gran mayoría de casos se observaron depósitos de fibrina intravascular asociadaal acúmulo de células inflamatorias compuestas por neutrófilos y monocitos, representando microtrombosis. Lasbiopsias de hígado mostraron esteatosis predominantemente macrovesicular y en dos casos se observó esteatosismicrovesicular. Adicionalmente, se observaron diversos grados de necrosis e inflamación portal y lobular. Conclusión:Los hallazgos clínicos y patológicos en este primer reporte son consistentes con publicaciones previas y confirmanel patrón de daño alveolar difuso asociado a agregados de macrofagos intraalveolares y microtrombosis; ademasesteatosis macro y microvesicular hepatocitica, junto a grados variables de necrosis

Fast-slow partially hyperbolic systems versus Freidlin-Wentzell random systems

We consider a simple class of fast-slow partially hyperbolic dynamical systems and show that the (properly rescaled) behaviour of the slow variable is very close to a Friedlin--Wentzell type random system for times that are rather long, but much shorter than the metastability scale. Also, we show the possibility of a "sink" with all the Lyapunov exponents positive, a phenomenon that turns out to be related to the lack of absolutely continuity of the central foliation.Comment: To appear in Journal of Statistical Physic

Anchoring of proteins to lactic acid bacteria

The anchoring of proteins to the cell surface of lactic acid bacteria (LAB) using genetic techniques is an exciting and emerging research area that holds great promise for a wide variety of biotechnological applications. This paper reviews five different types of anchoring domains that have been explored for their efficiency in attaching hybrid proteins to the cell membrane or cell wall of LAB. The most exploited anchoring regions are those with the LPXTG box that bind the proteins in a covalent way to the cell wall. In recent years, two new modes of cell wall protein anchoring have been studied and these may provide new approaches in surface display. The important progress that is being made with cell surface display of chimaeric proteins in the areas of vaccine development and enzyme- or whole-cell immobilisation is highlighted.

Hospitalization budget impact during the COVID-19 pandemic in Spain

To Mrs. Anne Murray for her support to translate the manuscript. This article is part of the doctoral thesis of Laura Álvarez as part of the Doctoral Program in Pharmacy, Granada University (Spain).Objectives: The aim was to determine the direct impact of the COVID-19 pandemic on Spain’s health budget. Methods: Budget impact analyses based on retrospective data from patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) admitted to a Spanish hospital between February 26 and May 21, 2020. Direct medical costs from the perspective of the hospital were calculated. We analyzed diagnostic tests, drugs, medical and nursing care, and isolation ward and ICU stays for three cohorts: patients seen in the emergency room only, hospitalized patients who tested positive for SARS-CoV-2, and patients who tested negative. Results: The impact on the hospital’s budget for the 3 months was calculated at €15,633,180, 97.4% of which was related to health care and hospitalization. ICU stays accounted for 5.3% of the total costs. The mean cost per patient was €10,744. The main costs were staffing costs (10,131 to 11,357 €/patient for physicians and 10,274 to 11,215 €/patient for nurses). Scenario analysis showed that the range of hospital expenditure was between €14,693,256 and €16,524,924. The median impact of the pandemic on the Spanish health budget in the sensitivity analysis using bootstrapped individual data was €9357 million (interquartile range [IQR], 9071 to 9689) for the conservative scenario (113,588 hospital admissions and 11,664 ICU admissions) and €10,385 million (IQR, 110,030 to 10,758) for the worst-case scenario (including suspected cases). Conclusion: The impact of COVID-19 on the Spanish public health budget (12.3% of total public health expenditure) is greater than multiple sclerosis, cancer and diabetes cost

Global attractor and asymptotic dynamics in the Kuramoto model for coupled noisy phase oscillators

We study the dynamics of the large N limit of the Kuramoto model of coupled phase oscillators, subject to white noise. We introduce the notion of shadow inertial manifold and we prove their existence for this model, supporting the fact that the long term dynamics of this model is finite dimensional. Following this, we prove that the global attractor of this model takes one of two forms. When coupling strength is below a critical value, the global attractor is a single equilibrium point corresponding to an incoherent state. Conversely, when coupling strength is beyond this critical value, the global attractor is a two-dimensional disk composed of radial trajectories connecting a saddle equilibrium (the incoherent state) to an invariant closed curve of locally stable equilibria (partially synchronized state). Our analysis hinges, on the one hand, upon sharp existence and uniqueness results and their consequence for the existence of a global attractor, and, on the other hand, on the study of the dynamics in the vicinity of the incoherent and synchronized equilibria. We prove in particular non-linear stability of each synchronized equilibrium, and normal hyperbolicity of the set of such equilibria. We explore mathematically and numerically several properties of the global attractor, in particular we discuss the limit of this attractor as noise intensity decreases to zero.Comment: revised version, 28 pages, 4 figure

Seguimiento de la cubierta vegetal en la península ibérica a partir de sensores de nueva generación y su interrelación con variables climáticas

Ponencia presentada en: XIII Congreso de la Asociación Española de Teledetección celebrado en Calatayud del 23 al 26 septiembre 2009.[ES]El objetivo principal del proyecto DULCINEA ha sido el desarrollo de una metodología multi-sensor para estimar parámetros biofísicos de la cubierta vegetal. La metodología desarrollada ha proporcionado estimaciones precisas de variables biofísicas de la vegetación (FVC, LAI) que han mostrado ser adecuadas para observar las variaciones inter- e intra-anuales de la cubierta en la Península Ibérica durante un periodo de 9 años (2000-2008). Los parámetros biofísicos obtenidos han permitido evaluar la vulnerabilidad de la vegetación ante condiciones ambientales extremas a nivel de la Península Ibérica. Un paso previo ha consistido en la elaboración de mapas detallados de parámetros climáticos y tipos de cubierta dominantes en la zona. Los modelos estadísticos aplicados han evidenciado una correlación significativa entre las variables biofísicas extraídas y algunas variables meteorológicas e índices de sequía operacionales. Esta interrelación es muy dependiente del tipo de cubierta y de las características climáticas de cada región. Se han encontrado correlaciones entre las anomalías de la cobertura vegetal y el SPI especialmente significativas para el caso de las regiones más secas, con valores típicos de R2 entre 0.4 y 0.7 durante los meses de Mayo y Junio.[EN]The main objective of the DULCINEA project is to provide coherent estimates of bio-physical variables such as fractional vegetation cover (FVC) and leaf area index (LAI) at regional to global scales. One of the goals of the project is to assess the potential of derived biophysical variables in the field of drought conditions monitoring. The aim was to analyse the vulnerability of natural ecosystems against the effects of climate fluctuations like drought and extreme events in the Iberian Peninsula, from the inter-correlation between the retrieved parameters and drought indices such as the Standardized Precipitation Index (SPI). The climatic disturbances affected both the growing season and the total amount of vegetation. Strong correlations have been found between SPI and satellitederived vegetation products, which are particularly significant in semi-arid regions.Este trabajo se enmarca en el proyecto DULCINEA (CGL2005-04202) y ha contado además con el soporte del proyecto ÁRTEMIS (CGL2008-00381)

PLR (Plastic Lithium Rechargeable) Batteries Using Nanoscale Materials: A Convenient Electrical Energy Power for the Future?

This communication describes the synthesis of: (i) non toxic and low cost nanocrystalline electrode materials which can be advantageously prepared at low temperature; (ii) highly conductive electrolyte membranes formed by the nano-encapsulation within a poly (acrylonitrile)-based polymer matrix of a solution of LiPF6 in organic solvants. The performances of rechargeable PLR (Plastic Lithium Rechargeable) batteries using the above mentioned components are presented

PpiA, a Surface PPIase of the Cyclophilin Family in Lactococcus lactis

Background: Protein folding in the envelope is a crucial limiting step of protein export and secretion. In order to better understand this process in Lactococcus lactis, a lactic acid bacterium, genes encoding putative exported folding factors like Peptidyl Prolyl Isomerases (PPIases) were searched for in lactococcal genomes. Results: In L. lactis, a new putative membrane PPIase of the cyclophilin subfamily, PpiA, was identified and characterized. ppiA gene was found to be constitutively expressed under normal and stress (heat shock, H2O2) conditions. Under normal conditions, PpiA protein was synthesized and released from intact cells by an exogenously added protease, showing that it was exposed at the cell surface. No obvious phenotype could be associated to a ppiA mutant strain under several laboratory conditions including stress conditions, except a very low sensitivity to H2O2. Induction of a ppiA copy provided in trans had no effect i) on the thermosensitivity of an mutant strain deficient for the lactococcal surface protease HtrA and ii) on the secretion and stability on four exported proteins (a highly degraded hybrid protein and three heterologous secreted proteins) in an otherwise wild-type strain background. However, a recombinant soluble form of PpiA that had been produced and secreted in L. lactis and purified from a culture supernatant displayed both PPIase and chaperone activities. Conclusions: Although L. lactis PpiA, a protein produced and exposed at the cell surface under normal conditions, displaye