Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response

Biomarcadores; Disfunción endotelial; Células progenitorasBiomarcadors; Disfunció endotelial; Cèl·lules progenitoresBiomarkers; Endothelial dysfunction; Progenitor cellsBackground: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b−) and activated (CD31+CD42b−CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH.This research was funded by grants PI12/00510, PI15/00582 and PI18/00960 from the Institute of Health Carlos III (ISCiii), Spain, co-funded by the European Union (ERDF/ESF); the Catalan Society of Respiratory Medicine (SOCAP); and the Fundación Contra la Hipertensión Pulmonar (FCHP). OTC is the former recipient of a Marie Curie Post-Doctoral Fellowship Award BIOTRACK-IDIBAPS, and the current recipient of a Miguel Servet contract from ISCiii (CP17/00114)

Novel Multi-Feature Bag-of-Words Descriptor via Subspace Random Projection for Efficient Human-Action Recognition

Human-action recognition through local spatio-temporal features have been widely applied because of their simplicity and its reasonable computational complexity. The most common method to represent such features is the well-known Bag-of-Words approach, which turns a Multiple-Instance Learning problem into a supervised learning one, which can be addressed by a standard classifier. In this paper, a learning framework for human-action recognition that follows the previous strategy is presented. First, spatio-temporal features are detected. Second, they are described by HOG-HOF descriptors, and then represented by a Bag of Words approach to create a feature vector representation. The resulting high dimensional features are reduced by means of a subspace-random-projection technique that is able to retain almost all the original information. Lastly, the reduced feature vectors are delivered to a classifier called Citation K-Nearest Neighborhood, especially adapted to Multiple-Instance Learning frameworks. Excellent results have been obtained, outperforming other state-of-the art approaches in a public database

Modelo integrado para la formación en tecnologías de fabricación para estudiantes de grado en el ámbito de la ingeniería industrial: caso práctico.

Caso práctico integración en fabricaciónDepartamento de Ciencias de los Materiales e Ingeniería Metalúrgica, Expresión Gráfica en la Ingeniería, Ingeniería Cartográfica, Geodesia y Fotogrametría, Ingeniería Mecánica e Ingeniería de los Procesos de Fabricació

Assessment of Tremor Severity in Patients with Essential Tremor Using Smartwatches

[Abstract] This paper presents a classification model for the automatic quantification of tremor severity in patients with essential tremor (ET). The system is based on the signals measured by two commercial smartwatches that the patients wear on their wrist and ankle. The smartwatches register acceleration and angular velocity in these body segments. A set of nine tremor features were used to train the classification algorithm. The proposed algorithm is based on a C4.5 decision tree classifier. It is able to assess rest and kinetic (postural or action) tremor. The method was evaluated using data collected from thirty-four patients with ET. The algorithm classifies the severity of tremor in five levels 0-4 corresponding to those in the Fahn-Tolosa-Marin tremor rating scale with a 94% accuracy. The method can be implemented in a networked platform for the remote monitoring and assessment of movement disorders such as ET or Parkinson’s disease.Ministerio de Economía, Industria u Competitividad; RTC-2015-3967-1Ministerio de Economía, Industria u Competitividad; DPI2015-68664-C4-1-RMinisterio de Economía, Industria u Competitividad; RTC-2015-4327-

An experience in integrated knowledge about Manufacturing Technologies for Students of the Grades of Industrial Engineering

Caso práctico integración en fabricaciónDepartamento de Ciencias de los Materiales e Ingeniería Metalúrgica, Expresión Gráfica en la Ingeniería, Ingeniería Cartográfica, Geodesia y Fotogrametría, Ingeniería Mecánica e Ingeniería de los Procesos de Fabricació

The role of snow in scavenging aerosol particles: A physical-chemical characterization

[EN] The below cloud scavenging of aerosols by snow has been analysed in León (NW Spain). Six snow events were registered over the course of one year of study. Ultrafine and accumulation aerosol particles were measured using a scanning mobility particle sizer spectrometer, while hydrometeors were characterized using a disdrometer. Furthermore, the chemical composition of the melted snow-water samples (soluble and insoluble fractions) was analysed. The scavenging coefficient (λ) showed a great variability among events. An effective washing of particles was observed during the first 30 min of snowfall. The mean change in the scavenging efficiency (%ΔC) of particle number concentration (PNC) and λ coefficient during this time interval were: i) nucleation mode: 36.3 % and 3.02 · 10−4 s−1; ii) Aitken mode: 30.4 % and 2.37 · 10−4 s−1 and iii) accumulation mode: 22.4 % and 1.77 · 10−4 s−1. The range of particle sizes that is less efficiently scavenged by snowfall was observed between 400 and 600 nm. When analyzing the whole snow event, an increase of PNC was observed. Two possible explanations underlie this behaviour: it could be caused by changes in air masses or by the resuspension of aerosol particles scavenged by snowflakes upon reaching the ground. A clear relationship was observed between Ca2+, SO42− and NO3− concentrations of aerosol particles before the snow event and the concentrations registered in the melted snow-water. The largest and smallest changes in aerosol number concentrations were caused by snowflakes of 3 and 6 mm in diameter, respectively. The particle size distributions (PSD) were fitted to log-normal distributions and the parameters were compared before and after snowfall.S

Diseño de una plataforma para analizar el efecto de la estimulación mecánica aferente en el temblor de pacientes con temblor esencial

[Resumen] Este documento describe una plataforma para analizar los efectos de la estimulación mecánica aferente en pacientes con Temblor Esencial (TE). El temblor esencial es una enfermedad caracterizada por provocar temblor bilateral, cinético y postural en antebrazos y manos del paciente. El propósito de la plataforma descrita es esclarecer el papel que juegan determinadas estructuras cerebrales en la génesis del temblor. Para ello se utilizan estimuladores piezoeléctricos capaces de generar una vibración mecánica controlada que estimule los corpúsculos de Paccini del paciente, así como sensores inerciales encargados de monitorizar los efectos que tiene esta estimulación en el temblor de los pacientes. El protocolo propuesto para seguir en los ensayos experimentales, así como el análisis de datos posterior son descritos también en este documento.Ministerio de Economía y Competitividad; DPI2015-72638-EX

La estimulación mecánica aferente no reduce sistemáticamente el temblor de pacientes con temblor esencial

[ES] El temblor esencial (ET) es una uno de los desórdenes motrices más prevalentes en adultos, con tratamientos poco efectivos en la mitad de los casos. En este documento, estudiamos si la estimulación mecánica aferente puede reducir el temblor en pacientes de ET al estimular selectivamente las vías aferentes. Para ello, hemos diseñado una plataforma que permite estimular la mano y el antebrazo del paciente utilizando actuadores piezoeléctricos mientras monitorizamos el temblor mediante sensores inerciales. Hemos analizado el efecto de cuatro estrategias de estimulación, incluyendo estimulación a frecuencia constante y variable, en 18 pacientes de ET. A pesar de que no existe una clara respuesta a la vibración ante las diferentes estrategias, en la mayoría de los casos (50-72%) la estimulación mecánica se asocia a un aumento en la amplitud del temblor. Por el contrario, el temblor se reduce entre el 5 y el 12% de los pacientes. Sin embargo, estos resultados son difíciles de interpretar debido a la variabilidad intrínseca del temblor: durante ensayos de la misma duración, el temblor varió significativamente en el 67% de los pacientes (aumentando en el 45% y disminuyendo en el 22%). Por tanto, la estimulación mecánica de la extremidad no tiene un efecto sistemático en el temblor propio del Temblor Esencial.[EN] In spite of being one of the major causes of disability, Essential Tremor (ET) is not effectively handled in 50% of cases. We have hypothesised that tremor in ET could be reduced by recruiting afferent pathways through mechanical stimulation. We have designed a platform to stimulate the forearm and hand of the patient with piezoelectric actuators while the tremor is measured using inertial sensors. We have studied the effect of four different stimulation strategies in 18 ET patients, each stimulation strategy was characterized by the frequency of the vibration. Although the response to stimulation was very heterogeneous across patients and strategies, the majority of patients increased their tremor (between 50% and 72%, depending on the strategy), while a very reduced proportion (between 5 and 22%) of patients decreased their tremor amplitude. However, we considered that these results were difficult to explain because the high variability of the tremor that we have assessed: during equally long trials without stimulation, tremor increased significantly in 45% of patients and decreased in 22% of them. Therefore, we claim that mechanical vibration does not have a consistent and homogenous effect on ET tremor.Lora Millán, J.; López Blanco, R.; Gallego, J.; González De La Aleja, J.; Rocon, E. (2019). La estimulación mecánica aferente no reduce sistemáticamente el temblor de pacientes con temblor esencial. En 11º Simposio CEA de Bioingeniería. Editorial Universitat Politècnica de València. 179-189. https://doi.org/10.4995/CEABioIng.2019.10047OCS17918

A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis

The aim of this study was to identify new genetic variants associated with the severity of ankylosing spondylitis (AS). We sequenced the exome of eight patients diagnosed with AS, selected on the basis of the severity of their clinical parameters. We identified 27 variants in exons and regulatory regions. The contribution of candidate variants found to AS severity was validated by genotyping two Spanish cohorts consisting of 180 cases/300 controls and 419 cases/656 controls. Relationships of SNPs and clinical variables with the Bath Ankylosing Spondylitis Disease Activity and Functional Indices BASDAI and BASFI were analyzed. BASFI was standardized by adjusting for the duration of the disease since the appearance of the first symptoms. Refining the analysis of SNPs in the two cohorts, we found that the rs4819554 minor allele G in the promoter of the IL17RA gene was associated with AS (p<0.005). This variant was also associated with the BASFI score. Classifying AS patients by the severity of their functional status with respect to BASFI/disease duration of the 60th, 65th, 70th and 75th percentiles, we found the association increased from p60 to p75 (cohort 1: p<0.05 to p<0.01; cohort 2: p<0.01 to p<0.005). Our findings indicate a genetic role for the IL17/ILRA axis in the development of severe forms of AS

Identification of Epigenetic Interactions between MicroRNA-30c-5p and DNA Methyltransferases in Neuropathic Pain

Neuropathic pain is a prevalent and severe chronic syndrome, often refractory to treatment, whose development and maintenance may involve epigenetic mechanisms. We previously demonstrated a causal relationship between miR-30c-5p upregulation in nociception-related neural structures and neuropathic pain in rats subjected to sciatic nerve injury. Furthermore, a short course of an miR-30c-5p inhibitor administered into the cisterna magna exerts long-lasting antiallodynic effects via a TGF-?1-mediated mechanism. Herein, we show that miR-30c-5p inhibition leads to global DNA hyper-methylation of neurons in the lumbar dorsal root ganglia and spinal dorsal horn in rats subjected to sciatic nerve injury. Specifically, the inhibition of miR-30-5p significantly increased the expression of the novo DNA methyltransferases DNMT3a and DNMT3b in those structures. Furthermore, we identified the mechanism and found that miR-30c-5p targets the mRNAs of DNMT3a and DNMT3b. Quantitative methylation analysis revealed that the promoter region of the antiallodynic cytokine TGF-?1 was hypomethylated in the spinal dorsal horn of nerve-injured rats treated with the miR-30c-5p inhibitor, while the promoter of Nfyc, the host gene of miR-30c-5p, was hypermethylated. These results are consistent with long-term protection against neuropathic pain development after nerve injury. Altogether, our results highlight the key role of miR-30c-5p in the epigenetic mechanisms' underlying neuropathic pain and provide the basis for miR-30c-5p as a therapeutic target.Funding: This work was supported by: Grant SAF2016-77732-R funded by MCIN/AEI/10.13039/ 501100011033 and by “ERDF A way of making Europe”; Grant PID2019-104398RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (NVAL17/23). R.F. was the recipient of a pre-doctoral fellowship of the Foundation Tatiana Pérez de Guzmán el Bueno. Acknowledgments: We acknowledge the excellent technical assistance of Nieves García Iglesias