Retrato robot del perfil geográfico de la delincuencia juvenil. Un análisis de la movilidad criminal en la ciudad de Albacete

En la actualidad todas las disciplinas que abordan el estudio de la delincuencia reconocen que la comprensión del fenómeno delictivo mejora si se tiene en cuenta el componente espacial o geográfico. Los ambientes han mostrado poseer ciertas características que fomentan o facilitan el delito, y los delincuentes gravitan en torno a aquellos ambientes vulnerables o lucrativos. En este sentido, gran parte de la literatura científica enmarcada en la categoría de criminología ambiental se ha consagrado a estudiar la existencia de patrones en el desplazamiento de los delincuentes en la búsqueda de objetivos. Un hallazgo compartido por la mayoría de investigaciones es que, por lo general, los individuos responden al principio del mínimo esfuerzo y se desplazan distancias relativamente cortas para cometer delitos. No obstante, se han documentado que dicha distancia es dependiente de otros factores como la naturaleza del hecho delictivo, la franja horaria, la relación víctima-victimario, el valor del bien deseado, etc. En el caso de la delincuencia juvenil, la evidencia empírica apunta a una menor movilidad criminal que en el caso de los adultos. A pesar de ello, en España no se ha realizado estudios que apoyen esta afirmación. Por ello, el objetivo de presente trabajo se dirige a conocer si los viajes sirven a algún propósito útil para los delincuentes juveniles, es decir, que les mueve a desplazarse. Para tratar de dar respuesta a esta pregunta, se ha analizado la relación entre distancia de decaimiento y algunas características del delito. Los resultados obtenidos han evidenciado que, por lo general, los delincuentes juveniles cometen los delitos en un entorno cercano, durante el desarrollo de otras actividades cotidianas no delictivas. Así, parecería confirmarse la idea de que el delito surge más bien como una oportunidad, en medio de las actividades normales de los jóvenes, en dónde existe algún elemento que funciona como precipitador de la conducta delictiva.Este trabajo se ha realizado con una ayuda del Plan Nacional I+D+i del Ministerio de Economía y Competitividad, “Análisis criminológico de la justicia penal en España. Una profundización sobre el proceso de producción de datos oficiales y sobre la eficacia del sistema de justicia” (DER2011-28769)

Nintedanib decreases muscle fibrosis and improves muscle function in a murine model of dystrophinopathy

Duchenne muscle dystrophy (DMD) is a genetic disorder characterized by progressive skeletal muscle weakness. Dystrophin deficiency induces instability of the sarcolemma during muscle contraction that leads to muscle necrosis and replacement of muscle by fibro-adipose tissue. Several therapies have been developed to counteract the fibrotic process. We report the effects of nintedanib, a tyrosine kinase inhibitor, in the mdx murine model of DMD. Nintedanib reduced proliferation and migration of human fibroblasts in vitro and decreased the expression of fibrotic genes such as COL1A1, COL3A1, FN1, TGFB1, and PDGFA. We treated seven mdx mice with 60 mg/kg/day nintedanib for 1 month. Electrophysiological studies showed an increase in the amplitude of the motor action potentials and an improvement of the morphology of motor unit potentials in the animals treated. Histological studies demonstrated a significant reduction of the fibrotic areas present in the skeletal muscles. Analysis of mRNA expression from muscles of treated mice showed a reduction in Col1a1, Col3a1, Tgfb1, and Pdgfa. Western blot showed a reduction in the expression of collagen I in skeletal muscles. In conclusion, nintedanib reduced the fibrotic process in a murine model of dystrophinopathy after 1 month of treatment, suggesting its potential use as a therapeutic drug in DMD patients.España, Ministerio de Economía y Competitividad BFU2016-74975-PEspaña, Instituto Ramón y Cajal PI13/0134

Proteasome inhibitors reduce thrombospondin-1 release in human dysferlin-deficient myotubes

Altres ajuts: This project has been funded by projects from the Fundación Isabel Gemio to II, EG and JDM and by Fundación Ramón Areces (CIVP18A3903) to NdL.Dysferlinopathies are a group of muscle disorders causing muscle weakness and absence or low levels of dysferlin, a type-II transmembrane protein and the causative gene of these dystrophies. Dysferlin is implicated in vesicle fusion, trafficking, and membrane repair. Muscle biopsy of patients with dysferlinopathy is characterized by the presence of inflammatory infiltrates. Studies in the muscle of both human and mouse models of dysferlinopathy suggest dysferlin deficient muscle plays a role in this inflammation by releasing thrombospondin-1. It has also been reported that vitamin D3 treatment enhances dysferlin expression. The ubiquitin-proteasome system recognizes and removes proteins that fail to fold or assemble properly and previous studies suggest that its inhibition could have a therapeutic effect in muscle dystrophies. Here we assessed whether inhibition of the ubiquitin proteasome system prevented degradation of dysferlin in immortalized myoblasts from a patients with two missense mutations in exon 44. To assess proteasome inhibition we treated dysferlin deficient myotubes with EB1089, a vitamin D3 analog, oprozomib and ixazomib. Western blot was performed to analyze the effect of these treatments on the recovery of dysferlin and myogenin expression. TSP-1 was quantified using the enzyme-linked immunosorbent assay to analyze the effect of these drugs on its release. A membrane repair assay was designed to assess the ability of treated myotubes to recover after membrane injury and fusion index was also measured with the different treatments. Data were analyzed using a one-way ANOVA test followed by Tukey post hoc test and analysis of variance. A p ≤ 0.05 was considered statistically significant. Treatment with proteasome inhibitors and EB1089 resulted in a trend towards an increase in dysferlin and myogenin expression. Furthermore, EB1089 and proteasome inhibitors reduced the release of TSP-1 in myotubes. However, no effect was observed on the repair of muscle membrane after injury. Our findings indicate that the ubiquitin-proteasome system might not be the main mechanism of mutant dysferlin degradation. However, its inhibition could help to improve muscle inflammation by reducing TSP-1 release. The online version contains supplementary material available at 10.1186/s12891-020-03756-7

Máster de Enfermedades Tropicales en las Redes Sociales: creación y uso de materiales audiovisuales, gestión de contenidos y difusión dentro del EEES.

Memoria ID-255. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2013-2014

Gluten Assessment in Beers: Comparison by Different Commercial ELISA Kits and Evaluation of NIR Analysis as a Complementary Technique

Traditionally, beers are made with gluten-containing cereals. It is crucial to have rapid analytical methodologies that allow gluten content control of the beers for celiac consumers. We assess the content of gluten in 65 conventional and 41 gluten-free labeled beers commercialized in Europe and compare the results in a subgroup of 71 beers with three ELISA kits. This research allows gathering information on the potential complementary utility of NIR analysis applied to gluten analysis of gluten-free beers in terms of time saving. Results obtained with the ELISA technique identified competitive R5 to be the most sensitive in detecting the prolamins, by eliciting a higher number of beers containing gluten above 20 mg/kg. The gluten content in conventional beers tested increased with the presence of wheat as raw material and with the use of ale-type yeasts. By using competitive R5, 3 out of the 41 gluten-free labeled beers appeared to contain gluten above 20 mg/kg, and conversely, 15 out of 65 of the conventional beers showed a gluten content below this threshold. According to our approaches, NIR did not achieve a suitable correlation with ELISA results, neither for gluten quantification nor for discrimination, and therefore, it cannot be proposed as a complementary technique.This research was funded by the Associació SMAP—Celíacs Catalunya. The GLUTEN3S research group is supported by a grant (GIU 18/78) from the University of the Basque Country, UPV/EHU

Gestión de contenidos, creación de materiales audiovisuales, incorporación del aula educativa multimedia, difusión y redes sociales dentro del Máster de Enfermedades Tropicales dentro del EEES

Memoria ID-0183. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Nintedanib Reduces Muscle Fibrosis and Improves Muscle Function of the Alpha-Sarcoglycan-Deficient Mice

Sarcoglycanopathies are a group of recessive limb-girdle muscular dystrophies, characterized by progressive muscle weakness. Sarcoglycan deficiency produces instability of the sarcolemma during muscle contraction, leading to continuous muscle fiber injury eventually producing fiber loss and replacement by fibro-adipose tissue. Therapeutic strategies aiming to reduce fibro-adipose expansion could be effective in muscular dystrophies. We report the positive effect of nintedanib in a murine model of alpha-sarcoglycanopathy. We treated 14 Sgca mice, six weeks old, with nintedanib 50 mg/kg every 12 h for 10 weeks and compared muscle function and histology with 14 Sgca mice treated with vehicle and six wild-type littermate mice. Muscle function was assessed using a treadmill and grip strength. A cardiac evaluation was performed by echocardiography and histological study. Structural analysis of the muscles, including a detailed study of the fibrotic and inflammatory processes, was performed using conventional staining and immunofluorescence. In addition, proteomics and transcriptomics studies were carried out. Nintedanib was well tolerated by the animals treated, although we observed weight loss. Sgca mice treated with nintedanib covered a longer distance on the treadmill, compared with non-treated Sgca mice, and showed higher strength in the grip test. Moreover, nintedanib improved the muscle architecture of treated mice, reducing the degenerative area and the fibrotic reaction that was associated with a reversion of the cytokine expression profile. Nintedanib improved muscle function and muscle architecture by reducing muscle fibrosis and degeneration and reverting the chronic inflammatory environment suggesting that it could be a useful therapy for patients with alpha-sarcoglycanopathy

Accelerometer Cut-Points for Physical Activity Assessment in Adults with Mild to Moderate Huntington’s Disease: A Cross-Sectional Multicentre Study

Accelerometers can estimate the intensity, frequency, and duration of physical activity in healthy adults. Although thresholds to distinguish varying levels of activity intensity using the Actigraph wGT3X-B have been established for the general population, their accuracy for Huntington’s disease (HD) is unknown. We aimed to define and cross-validate accelerometer cut-points for different walking speeds in adults with mild to moderate HD. A cross-sectional, multicentre, case-control, observational study was conducted with a convenience sample of 13 symptomatic ambulatory HD participants. The accelerometer was placed around the right hip, and a heart monitor was fitted around the chest to monitor heart rate variability. Participants walked on a treadmill at three speeds with light, moderate and vigorous intensities. Correlation and receiver operation curve analyses were performed between the accelerometer magnitude vector with relative oxygen and heart rate. Optimal cut-points for walking speeds of 3.2 km/h were ≤2852; 5.2 km/h: >2852 to ≤4117, and in increments until their maximum velocity: >4117. Our results support the application of the disease-specific cut-points for quantifying physical activity in patients with mild to moderate HD and promoting healthy lifestyle interventions.The project leading to these results has received funding from “La Caixa” Foundation (ID100010434), under agreement FUI1-PI008

Identification of serum microRNAs as potential biomarkers in Pompe disease

Altres ajuts: This study was supported by a grant from Sanofi-Genzyme (GZ-2015-11342) to Dr. Gallardo and has been registered in Clinicaltrials.gov (identifier NCT03045042).This study was supported by a grant from Sanofi-Genzyme (GZ-2015-11342) to Dr. Gallardo and has been registered in Clinicaltrials.gov (identifier NCT03045042).To analyze the microRNA profile in serum of patients with Adult Onset Pompe disease (AOPD). We analyzed the expression of 185 microRNAs in serum of 15 AOPD patients and five controls using microRNA PCR Panels. The expression levels of microRNAs that were deregulated were further studied in 35 AOPD patients and 10 controls using Real-Time PCR. Additionally, the skeletal muscle expression of microRNAs which showed significant increase levels in serum samples was also studied. Correlations between microRNA serum levels and muscle function test, spirometry, and quantitative muscle MRI were performed (these data correspond to the study NCT01914536 at ClinicalTrials.gov). We identified 14 microRNAs that showed different expression levels in serum samples of AOPD patients compared to controls. We validated these results in a larger cohort of patients and we found increased levels of three microRNAs, the so called dystromirs: miR-1-3p, miR-133a-3p, and miR-206. These microRNAs are involved in muscle regeneration and the expression of these was increased in patients' muscle biopsies. Significant correlations between microRNA levels and muscle function test were found. Serum expression levels of dystromirs may represent additional biomarkers for the follow-up of AOPD patients

Platelet Derived Growth Factor-AA Correlates With Muscle Function Tests and Quantitative Muscle Magnetic Resonance in Dystrophinopathies

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials.Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI.Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- β1 (TGF-β1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies.Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases