Improving Cognitive Visual-Motor Abilities in Individuals with Down Syndrome

Down syndrome causes a reduction in cognitive abilities, with visual-motor skills being particularly affected. In this work, we have focused on this skill in order to stimulate better learning. The proposal relies on stimulating the cognitive visual-motor skills of individuals with Down Syndrome (DS) using exercises with a gestural interaction platform based on the KINECT sensor named TANGO:H, the goal being to improve them. To validate the proposal, an experimental single-case study method was designed using two groups: a control group and an experimental one, with similar cognitive ages. Didactic exercises were provided to the experimental group using visual cognitive stimulation. These exercises were created on the TANGO:H Designer, a platform that was designed for gestural interaction using the KINECT sensor. As a result, TANGO:H allows for visual-motor cognitive stimulation through the movement of hands, arms, feet and head. The “Illinois Test of Psycholinguistic Abilities (ITPA)” was applied to both groups as a pre-test and post-test in its four reference sections: visual comprehension, visual-motor sequential memory, visual association, and visual integration. Two checks were made, one using the longitudinal comparison of the pre-test/post-test of the experimental group, and another that relied on comparing the difference of the means of the pre-test/post-test. We also used an observational methodology for the working sessions from the experimental group. Although the statistical results do not show significant differences between the two groups, the results of the observations exhibited an improvement in visual-motor cognitive skills

Spirometry and respiratory oscillometry: Feasibility and concordance in schoolchildren with asthma

Producción CientíficaObjective:The purpose of this study was to describe the feasibility of respiratory oscillometry (RO) in schoolchildren with asthma, and the concordance of its results with those of spirometry, to determine its clinical usefulness. Methods:RO and spirometry were performed in 154 children (6 to 14-year-old) with asthma, following strict quality criteria for the tests. Their feasibility (probability of valid test, time of execution, number of maneuvers needed to achieve a valid test, and perceived difficulty) was compared. The factors that influence feasibility were analyzed with multivariate methods. FEV1, FEV1/FVC, FVC and FEF25-75 for spirometry, and R5, AX and R5-19 for RO, were converted into z-scores and their concordance was investigated through intraclass correlation coefficients (ICC) and kappa indices for normal/abnormal values. Results:There were no differences in the probability of obtaining a valid RO or spirometry (83.1% vs. 81.8%, p = 0.868). RO required a lower number of maneuvers [mean (SD) 4.2 (1.8) versus 6.0 (1.6), p < 0.001] and less execution time [5.1 (2.7) versus 7.6 (2.4) minutes, p < 0.001], and patients considered it less difficult. Age increased the probability of obtaining valid RO and spirometry. The concordance of results between RO and spirometry was low, and only between zFEV1 and zAX could it be considered moderate (ICC = 0.412, kappa = 0.427). Conclusion:RO and spirometry are feasible in children with asthma. RO has some practical advantages, but the concordance of its results with spirometry is low.Junta de Castilla y León (Gerencia Regional de Salud - Grant/Award Number: 2191/A/2020

Fecal Metabolome and Bacterial Composition in Severe Obesity:Impact of Diet and Bariatric Surgery

The aim of this study was to monitor the impact of a preoperative low-calorie diet and bariatric surgery on the bacterial gut microbiota composition and functionality in severe obesity and to compare sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB). The study also aimed to incorporate big data analysis for the omics results and machine learning by a Lasso-based analysis to detect the potential markers for excess weight loss. Forty patients who underwent bariatric surgery were recruited (14 underwent SG, and 26 underwent RYGB). Each participant contributed 4 fecal samples (baseline, post-diet, 1 month after surgery and 3 months after surgery). The bacterial composition was determined by 16S rDNA massive sequencing using MiSeq (Illumina). Metabolic signatures associated to fecal concentrations of short-chain fatty acids, amino acids, biogenic amines, gamma-aminobutyric acid and ammonium were determined by gas and liquid chromatography. Orange 3 software was employed to correlate the variables, and a Lasso analysis was employed to predict the weight loss at the baseline samples. A correlation between Bacillota (formerly Firmicutes) abundance and excess weight was observed only for the highest body mass indexes. The low-calorie diet had little impact on composition and targeted metabolic activity. RYGB had a deeper impact on bacterial composition and putrefactive metabolism than SG, although the excess weight loss was comparable in the two groups. Significantly higher ammonium concentrations were detected in the feces of the RYGB group. We detected individual signatures of composition and functionality, rather than a gut microbiota characteristic of severe obesity, with opposing tendencies for almost all measured variables in the two surgical approaches. The gut microbiota of the baseline samples was not useful for predicting excess weight loss after the bariatric process

Impacto de la cirugía bariátrica en la microbiota intestinal y el metaboloma fecal

Resumen del trabajo presentado a la 14ª Reunión de la Red Española de Bacterias Lácticas (RedBAl), celebrada de forma telemática del 8 al 10 de Septiembre de 2021.Introducción: El tratamiento de la obesidad severa mediante cirugía bariátrica presenta la mejor relación efectividad/coste, siendo el sleeve gástrico (SG) y el bypass gástrico (BPG) las técnicas laparoscópicas más utilizadas. El BPG está recomendado en pacientes con mayor exceso de peso (IMC>50). Aunque se han descrito alteraciones en la microbiota intestinal (MI) en relación con la obesidad, existen pocos estudios en obesidad severa en los que se haya caracterizado este ecosistema y el metaboloma fecal. Objetivos: Evaluar el impacto de la dieta pre-operatoria y la técnica de cirugía bariátrica sobre la MI y el metaboloma fecal en obesidad severa. Sujetos y métodos: Se incluyeron 40 pacientes de cirugía bariátrica (14 SG y 26 BPG), se recogió información clínica de interés, así como muestras de heces a cuatro tiempos: 1)-basal, 2)-tras dieta preoperatoria, 3)-al mes y 4)- a los tres meses de la cirugía. Se determinó la composición de la MI mediante secuenciación del gen ARNr 16S y la concentración fecal de varios metabolitos (ácidos grasos de cadena corta-AGCC, aminoácidos y aminas biógenas-AB) mediante cromatografía de gases y líquida. Resultados: Se han detectado diferencias significativas en la composición de la MI de la muestra basal de los pacientes de BPG y de SG y cambios estadísticamente significativos en la composición de la MI y en el metaboloma fecal entre las cuatro muestras, existiendo un mayor impacto en el BPG. En el caso del patrón fecal de AGCC, ambas cirugías disminuyeron la concentración de los AGCC mayoritarios, aunque no hubo diferencias significativas entre ambas. La concentración fecal de aminoácidos transcurridos tres meses desde la operación fue en general inferior en el grupo de pacientes sometidos a BPG, mientras que la concentración de AB fue superior en comparación con los individuos operados mediante SG. Conclusiones: Los pacientes con obesidad severa e IMC>50 tienen una MI diferente, con mayor abundancia de Firmicutes. La cirugía bariátrica y la dieta preoperatoria asociada modifican la composición de la MI y el perfil de metabolitos fecales, siendo estos cambios más profundos cuando se utiliza la técnica de BPG, probablemente por la alteración anatómica del tránsito intestinal

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074

Implementación en la UCM del Grado en Estudios Europeos / Bachelor in European Studies en el marco de la alianza europea de universidades UNA EUROPA

El presente proyecto de innovación ha tenido por objetivo la implementación en la Universidad Complutense de Madrid del Nuevo Grado en Estudios Europeos / Bachelor of European Studies (BAES) creado en el marco de la nueva alianza europea de universidades UNA EUROPA integrada por la Universidad Complutense de Madrid, la Universidad de la Sorbona (París – I), Universidad Libre de Berlín, Universidad de Bolonia, Universidad Jaguelónica de Cracovia, Universidad de Helsinki, Universidad Católica de Lovaina, y Universidad de Edimburgo

Informe final del escaneo de horizonte sobre futuras especies exóticas invasoras en España

73 p.La introducción de especies exóticas invasoras (EEI) es una de las principales causas de la pérdida de biodiversidad a nivel global, que provoca grandes costes socioeconómicos. Sin embargo, el número de nuevas introducciones continúa creciendo año tras año. Por lo tanto, urge identificar posibles futuras EEI con el objetivo de diseñar e implementar medidas que prevengan y mitiguen los efectos negativos de su introducción. Así, el objetivo de este estudio es prospectar qué especies exóticas no establecidas en España podrían llegar fácilmente en los próximos 10 años, establecerse y causar importantes impactos ecológicos. Para ello, se ha realizado un escaneo de horizonte, siguiendo la metodología establecida en trabajos previos, siendo el primero para el conjunto de las especies exóticas invasoras en España. Se añadieron en el análisis especies que no son autóctonas de España, incluyendo los archipiélagos de Canarias y Baleares, y que no están establecidas en España. Un total de 39 científicos, expertos en distintos grupos taxonómicos y ecosistemas, ha evaluado 933 especies. Con el objetivo de analizar el acuerdo entre las evaluaciones individuales de los expertos y su consistencia, se llevaron a cabo dos análisis de fiabilidad complementarios, cuyos resultados se discuten en este informe. Como resultado del escaneo, se obtuvo una lista priorizada de 105 especies (46 con riesgo muy alto y 59 con riesgo alto). La mayoría de estas especies (84,8%), sin embargo, no están incluidas actualmente en el Catálogo Español de Especies Exóticas Invasoras. Por lo tanto, se recomienda la realización de un análisis de riesgo más detallado de estas especies y, si se confirma el riesgo alto, la solicitud de su incorporación en dicho catálogo o en el Listado de especies alóctonas susceptibles de competir con las especies silvestres autóctonas, alterar su pureza genética o los equilibrios ecológicos. Del mismo modo, se propone la realización de escaneos de horizonte específicos para los archipiélagos de Canarias y Baleares, ya que muchas de las especies autóctonas de la Península no lo son de las islas y podrían tener un gran impacto si allí se introdujeran. Este informe también analiza la afinidad taxonómica (i.e. filo) y funcional (i.e. productor primario, depredador, omnívoro, herbívoro o filtrador) de las especies de la lista priorizada, su origen geográfico y las principales vías de introducción. Por último, discute los mecanismos de impacto de dichas especies.Ministerio de Ciencia e Innovació

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES) : comprehensive genetic analysis by next-generation sequencing of 480 patients

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues