Inhibition of extracellular matrix assembly induces the expression of osteogenic markers in skeletal muscle cells by a BMP-2 independent mechanism

<p>Abstract</p> <p>Background</p> <p>The conversion of one cell type into another has been suggested to be, at the molecular level, the consequence of change(s) in the expression level of key developmental genes. Myoblasts have the ability to differentiate either to skeletal muscle or osteogenic lineage depending of external stimuli. Extracellular matrix (ECM) has been shown to be essential for skeletal muscle differentiation, through its direct interaction with myoblasts' cell receptors. We attempt to address if ECM also plays a role in the osteogenic differentiation of skeletal muscle cells.</p> <p>Results</p> <p>Inhibition of proteoglycan sulfation by sodium chlorate in myoblast cultures strongly affects ECM synthesis and deposition and induces the expression of the osteogenic lineage markers alkaline phosphatase (ALP) and osteocalcin in mononuclear cells. Induction of ALP by sodium chlorate does not affect the expression of specific muscle determination transcription factors, such as MyoD and Myf-5, in the same cells. The osteogenic transcription factor Cbfa-1 expression is also unaffected. Induction of ALP is not inhibited by a soluble form of BMP receptor IA. This suggests that the deviation of the myogenic pathway of C2C12 myoblasts into the osteogenic lineage by inhibitors of proteoglycan sulfation is BMP-2 independent. The increase of osteogenic markers expression can be totally prevented by an exogenous ECM. Interestingly, a similar BMP-2-independent ALP activity induction can be observed in myoblasts cultured on an ECM previously synthesized by BMP-2 treated myoblasts. Under <it>in vivo </it>conditions of increased ECM turn-over and deposition, as in the <it>mdx </it>dystrophic muscle and during skeletal muscle regeneration, an induction and relocalization of ALP is observed in a subpopulation of skeletal muscle fibers, whereas in normal skeletal muscle, ALP expression is restricted to blood vessels and some endomysial mononuclear cells.</p> <p>Conclusion</p> <p>These results suggest that signals arising from the ECM induce the expression of osteogenic markers in muscle cells by a mechanism independent of BMP-2 and without affecting the expression of key muscle or osteogenic determination genes. An induction and relocalization of ALP is also observed in <it>mdx </it>and regenerating skeletal muscles, <it>in vivo </it>conditions of increased muscle ECM deposition or turnover.</p

Implantes angulados en la rehabilitación parcial de sectores posteriores en maxilares atróficos

Introducción: Tras la pérdida dental se producen una serie de cambios anatómicos que dificultan rehabilitación de los sectores posteriores en maxilares atróficos. Actualmente tenemos diferentes alternativas quirúrgicas para solventar estos problemas, como pueden ser las técnicas de elevación de seno maxilar, tanto con técnicas convencionales como con el empleo de osteotomos o las técnicas M.I.A.M.B.E. Otras alternativas pueden ser el empleo de injertos óseos, las rehabilitaciones con cantiléver distales, el empleo de implantes cortos, la colocación de implantes en localizaciones especiales o el empleo de implantes angulados. Estos últimos parecen presentar ventajas sobre las otras alternativas terapéuticas, pero tenemos poco información en la literatura sobre su empleo para la rehabilitación parcial de los sectores posteriores en maxilares atróficos. Objetivos: Analizar la tasa de supervivencia, la pérdida ósea alrededor de los implantes angulados y los posibles factores que pudiesen influir en dicha pérdida ósea se realizó este estudio retrospectivo. Material y metodología: En este estudio retrospectivo se recogieron 21 pacientes que portaron 27 rehabilitaciones parciales maxilares soportadas mediante 70 implantes dentales (33 angulados y 37 rectos o axiales), realizándose un seguimiento de todos los casos durante dos años con un intervalo de tres meses.. Las mediciones de la pérdida ósea alrededor de los implantes se realizó mediante radiografías periapicales digitales. Resultado: La angulación media de los implantes angulados fue de 32,8º. La diferencia en el margen óseo de los implantes angulados tras dos años de carga fue -0,3286 mm (SD=1,054) y en los colocados axialmente -0,7199 mm (SD=0,885), no encontrado diferencias estadísticamente significativas (p=0,096).No se registraron fracasos de los implantes, por lo que la supervivencia de los implantes angulados y rectos fue del 100%. En el análisis de la posible influencia de distintos factores en la diferencia del margen óseo, solo encontramos diferencias estadísticamente significativas según el momento de la carga de los implantes y el tipo de prótesis provisional empleada. Conclusiones: Las rehabilitaciones parciales de los sectores posteriores maxilares atróficos mediante el empleo combinado de implantes angulados y axiales a las fuerzas oclusales presentan la misma seguridad que los casos en los que colocamos los implantes de forma vertical con respecto al plano oclusal.Introduction: After tooth loss, a series of anatomical changes of the alveolar ridge may difficult the rehabilitation of edentulous posterior areas. Currently there are various surgical approaches to solve these problems, such as the techniques of maxillary sinus lift, both conventional and with the use of osteotomes or techniques MIAMBE. Other alternatives may be the use of bone grafts, rehabilitations with distal cantilever, the use of short implants, implant placement in special locations or use of tilted implants. The latter seem to have advantages over other therapeutic alternatives, but we have little information in the literature on their use for the partial rehabilitation of the atrophic posterior maxilla. Objectives: To analyze the survival rate, bone loss around angled implants and the factors that could influence bone loss. Material and methods: In this retrospective study, 21 patients who carried 27 partial restorations supported by 70 maxillary dental implants (33 and 37 angled straight or axial) were included. All cases were followed for two years with an interval of three months recall. Digital periapical radiographs were used to measure bone loss around implants. Result: The average angle of the tilted implants was 32,8º. The difference in bone margin on the tilted implants after two years of loading was -0.3286 mm (SD = 1.054) and the axially placed -0.7199 mm (SD = 0.885). No statistically significant difference was found (p = 0.096). No implant failures were recorded, so that the survival of straight and angled implants was 100%. In analyzing the influence that several factors may have on the difference of the bone margin, statistically significant differences were only found according to the time of loading and the type of provisional prosthesis used. Conclusions: Partial rehabilitation of the maxillary posterior atrophic area through the combined use of tilted and axial implants presents the same survival rate than cases in which implants were placed vertically with respect to the occlusal plane

Virtual Teaching Approach for the Analysis and Planning of Wireless Communications Systems

One of the most important aspects in the field of engineering education is practical training. Very clear examples of this are the laboratories for training in design, development and measurement of electronic systems. However, in other areas of engineering, as for example in the case of communications, where the main objective is the systems analysis and planning, analytical solutions, if is possible, either to the simulation through approaches and algorithms are typically used. We have developed a set of tools for improving the knowledge and skills in wireless communications systems planning, for students of telecommunications engineering of the “Universidad Politécnica de Madrid”. These tools are of relatively simple use, and they are designed with the intention of a gradual process in learning through the establishment of various educational objective levels. In this paper are presented some of these tools developed and also there is realized an analysis of student assessment in the use of such solutions

Latent tuberculosis infection screening in healthcare workers in four large hospitals in Santiago, Chile

Indexación: Web of Science; Scielo.Introducción: Se desconoce en la actualidad cuál es la real prevalencia de infección tuberculosa latente en el personal de salud en Chile; sin embargo, este grupo ha sido descrito como con mayor riesgo de desarrollar tuberculosis activa que la población general. Objetivo: Determinar la prevalencia de infección tuberculosa latente en funcionarios de la salud en diferentes áreas laborales de riesgo. Metodología: Estudio de corte transversal, descriptivo, realizado en funcionarios pertenecientes a laboratorios clínicos o áreas de atención broncopulmonar de cuatro hospitales de la Región Metropolitana en quienes se hizo test de Quantiferon TB Gold®In tube(QFT). Resultados: Se evidenció infección tuberculosa latente en 20 de las 76 (26,3%) personas estudiadas. En aquellos funcionarios que referían antecedente de contacto en el pasado en la comunidad con enfermos de tuberculosis, la positividad del test llegó a 62,5%; en aquellos que pertenecían al Programa Nacional de Control de la Tuberculosis, a 50% y en los que realizaban toma de esputo inducido, baciloscopias o cultivo de micobacterias, a 38%. La proporción de individuos con QFT positivo fue significativamente menor en aquellos funcionarios que no tenían estos antecedentes (15,7%, p = 0,03). Se encontró además una mayor proporción de infección tuberculosa latente a mayor edad del individuo estudiado. Conclusión: La infección tuberculosa latente medida por QFT resultó altamente prevalente en el personal de la salud incluido en el presente estudio. Es necesario seguir profundizando en los posibles escenarios de implementación y limitaciones del uso de esta nueva herramienta diagnóstica, haciendo énfasis en el personal de la salud de mayor riesgo y menor edad.Background: It is currently unknown which is the prevalence of latent tuberculosis infection in healthcare workers in Chile, but this group has been described as at higher risk of developing active tuberculosis than general population. Objectives: To determine the prevalence of latent tuberculosis infection in a sample of healthcare workers from at risk areas. Methodology: A cross-sectional, descriptive study, conducted in health care workers from clinical laboratories or respiratory care areas in four hospitals in Santiago. Latent tuberculosis infection detection was determined by Quantiferon® TB Gold In Tube testing (QFT). Results: QFT resulted positive in 20 of 76 (26.3%) of the individuals tested. Test positivity reached 62.5% among the personnel that reported history of past TB contact in the community, 50% among the personnel who belonged to the national tuberculosis control program and 38% among those doing induced sputum, acid fast smear or mycobacterial cultures. The proportion of individuals with positive QFT was significantly lower in those personnel who had no such risk factors (15.7%, p = 0.03). The proportion of latent tuberculosis infection also increased in direct relation to the age of the subject. Conclusion: Latent tuberculosis infection as detected by QFT testing was highly prevalent in healthcare workers included in the present study. Further exploring the limitations and possible scenarios for this new diagnostic tool is needed, with emphasis on health personnel at higher-risk and younger individuals.http://www.scielo.cl/pdf/rci/v31n3/art02.pd

ECTS and Methodological Experiences in Telecommunications Systems Engineering for the Adjustment to European Space for Higher Education

In this paper we present a summary of the actions in educational innovation perform in the subjects of 3th year of Technical Engineering in Telecommunication Systems, as well as the results and conclusions obtained. These activities has been carry out in the frame of a Educational Innovation Project granted by the “Universidad Politécnica de Madrid” in the process in implementing the European Higher Education Area, and to improve the education quality. The main activities and developed materials are around the organization and coordination of the subjects, and on the utilization of methodologies and educational tools centred on the learning. Besides the academic results and the comparison with other subjects there will be included the opinions of pupils and teachers

Hyperhidrosis in sleep disorders – A narrative review of mechanisms and clinical significance

Funding Information: Grant Fondecyt 1211443 Publisher Copyright: © 2022 European Sleep Research Society.Hyperhidrosis is characterized by excessive sweating beyond thermoregulatory needs that affects patients' quality of life. It results from an excessive stimulation of eccrine sweat glands in the skin by the sympathetic nervous system. Hyperhidrosis may be primary or secondary to an underlying cause. Nocturnal hyperhidrosis is associated with different sleep disorders, such as obstructive sleep apnea, insomnia, restless legs syndrome/periodic limb movement during sleep and narcolepsy. The major cause of the hyperhidrosis is sympathetic overactivity and, in the case of narcolepsy type 1, orexin deficiency may also contribute. In this narrative review, we will provide an outline of the possible mechanisms underlying sudomotor dysfunction and the resulting nocturnal hyperhidrosis in these different sleep disorders and explore its clinical relevance.Peer reviewe

Regulation of DMD pathology by an ankyrin-encoded miRNA

<p>Abstract</p> <p>Background</p> <p>Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting from the production of a nonfunctional dystrophin protein. MicroRNA (miRNA) are small 21- to 24-nucleotide RNA that can regulate both individual genes and entire cell signaling pathways. Previously, we identified several mRNA, both muscle-enriched and inflammation-induced, that are dysregulated in the skeletal muscles of DMD patients. One particularly muscle-enriched miRNA, miR-486, is significantly downregulated in dystrophin-deficient mouse and human skeletal muscles. miR-486 is embedded within the <it>ANKYRIN1(ANK1) </it>gene locus, which is transcribed as either a long (erythroid-enriched) or a short (heart muscle- and skeletal muscle-enriched) isoform, depending on the cell and tissue types.</p> <p>Results</p> <p>Inhibition of miR-486 in normal muscle myoblasts results in inhibited migration and failure to repair a wound in primary myoblast cell cultures. Conversely, overexpression of miR-486 in primary myoblast cell cultures results in increased proliferation with no changes in cellular apoptosis. Using bioinformatics and miRNA reporter assays, we have identified platelet-derived growth factor receptor β, along with several other downstream targets of the phosphatase and tensin homolog deleted on chromosome 10/AKT (PTEN/AKT) pathway, as being modulated by miR-486. The generation of muscle-specific transgenic mice that overexpress miR-486 revealed that miR-486 alters the cell cycle kinetics of regenerated myofibers <it>in vivo</it>, as these mice had impaired muscle regeneration.</p> <p>Conclusions</p> <p>These studies demonstrate a link for miR-486 as a regulator of the PTEN/AKT pathway in dystrophin-deficient muscle and an important factor in the regulation of DMD muscle pathology.</p

Straight and tilted implants for supporting screw-retained full-arch dental prostheses in atrophic maxillae : a 2-year prospective study

To evaluate, over a 2-year period, the treatment outcomes for maxillary full-arch fixed dental prostheses (FDPs) supported by a combination of both tilted and axially-placed implants and to compare the marginal bone loss (MBL) and implant survival rates (SR) between tilted and axial implants. A retrospective study has been carried out. Thirty-two patients (16 males and 16 females) treated with maxillary full-arch FDPs were included in this retrospective study. A total of 187 implants were inserted to rehabilitate the fully edentulous maxillary arches: 36% of them were tilted (T group, n = 68) and the remaining 64% were axially placed (A group, n = 119). From the total, 28% of the implants (n=53) were immediately loaded with screw-retained provisional acrylic restorations, whereas 72% underwent conventional delayed prosthetic loading 6 months post-operatively. Definitive restorations were hybrid implant prostheses (metal framework covered with high-density acrylic resin) and metal-ceramic screw-retained implant prostheses, and were placed 6 months after surgery. Such definitive restorations were checked for proper function and aesthetics every three months for two years. Peri-implant marginal bone levels were assessed by digital radiographs immediately after surgery and MBL was assessed at definitive implant loading (baseline) and 2 years afterwards. The 2-year implant SR were 100% for axially placed implants and 98.5% for tilted implants. No significant differences were found amongst the A and T implant groups. Marginal bone loss measured at 2 years after definitive prosthetic loading was of -0.73 ± 0.72 mm (maximum MBL of 1.43 mm) for axially positioned implants vs. ?0.51 ± 0.92 mm for tilted implants (maximum bone 1.45 mm). Differences in MBL were statistically significant when comparing immediately and delayed loaded implants. Based on the results of this retrospective clinical study, full-arch fixed prostheses supported by a combination of both tilted and axially placed implants may be considered a predictable and viable treatment modality for the prosthetic rehabilitation of the completely edentulous maxilla

ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to chemotherapy in lung cancer

The survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. In the last decade, several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown. In this study, we performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure. In addition, we studied at the protein level the expression of these genes in cancer samples and performed functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development. Remarkably, we found that 20% of lung cancer patients show ARID2 protein loss, partially explained by the presence of ARID2 mutations. In addition, we showed that ARID2 deficiency provokes profound chromatin structural changes altering cell transcriptional programs, which bolsters the proliferative and metastatic potential of the cells both in vitro and in vivo. Moreover, we demonstrated that ARID2 deficiency impairs DNA repair, enhancing the sensitivity of the cells to DNA-damaging agents. Our findings support that ARID2 is a bona fide tumor suppressor gene in lung cancer that may be exploited therapeutically.Financial Support: I. V. is supported by SAF2012-31627 and SAF2016-76758-R grants from the Spanish Ministerio de Economía y Competitividad (MINECO), by a Fundación Ramón Areces grant and by ERC2014-StG637904 grant from the European Research Council. I. V has been awardee of the Programa Ramón y Cajal (MINECO, Spain). T. M has been awardee of the Ayudas para la contratación de investigadores predoctorales (MINECO, Spain). B. M is awardee of the Ayudas para la formación de profesorado universitario (FPU, Ministerio de Educación y Formación Profesional, Spain). PC laboratory is supported by grant SAF-2015-63638R (MINECO/FEDER, UE); by Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) and by Asociación Española Contra el Cáncer (AECC), grant GCB141423113. BC has been supported by a Retos Jóvenes Investigadores grant SAF2015-73364-JIN (AEI/FEDER, UE) and a grant from Fundación Francisco Cobos. P. S. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001152), the UK Medical Research Council (FC001152). HUCA/IUOPA which is jointly financed by Servicio de Salud del Principado de Asturias, Instituto de Salud Carlos III and Fundación Bancaria Cajastur. This research was funded in part by the Wellcome Trust [FC001152]

La investigación en la Universidad

[Actas de:] "La Universidad española a examen: Jornadas sobre la Investigación en la Universidad" (25 y 26 de febrero de 1999: Universidad Carlos III de Madrid)Con motivo del X aniversario de la Universidad Carlos III de Madrid, el Instituto Antonio de Nebrija de Estudios sobre la Universidad organizó durante los días 25 y 26 de febrero de 1999 un encuentro titulado La universidad española a examen: Jornadas sobre investigación en la Universidad. En el encuentro celebrado participaron representantes de distintos ámbitos científicos, con el fin de ofrecer una visión más completa del panorama actual de la investigación en la Universidad, dejando constancia de las opiniones de la empresa, las universidades, las instituciones políticas, los organismos públicos de investigación. Este libro recoge sus resultados.Prólogo / Carmen Merino. -- Programa. -- Presentación / Gregorio Peces-Barba. -- La Investigación en la Universidad. Una opinion / César Nombela. -- Los Institutos Universitarios como estructuras organizativas de la investigación / José Manuel González Ros. -- Valoración de la investigación en la universidad española / Pedro Ramos Castellanos. -- Universidad e investigación. Por la diversidad y la rebeldía / Juan Urrutia. -- La universidad española, una fuente de tecnología necesaria para la empresa / Juan Mulet Meliá. -- Relaciones universidad y empresa. Una aportación empresarial / Ángel Martínez Román. -- Algunas reflexiones sobre el III Plan Regional de Investigación Científica e Innovación Tecnológica / Enrique Otero. -- Centros de Apoyo a la Investigación (CAI) / Juan Carlos Prieto Villapún. -- Infraestructuras científicas necesarias en la Comunidad de Madrid / Rodolfo Miranda. -- Importancia de los recursos humanos en relación con la I+D en Universidades / José Luis Sotelo. -- Investigación y Universidad / Alfonso Ruiz Miguel. -- Sobre el actual sistema de financiación de I+D / José Ramón Casar Corredera. -- Universidad e investigación: Hacia unas nuevas referencias en el contexto del Sistema Ciencia-Tecnología-Sociedad / Francisco Marcellán. -- Políticas de I+D en la Comunidad de Madrid / Francisco Rubia Vila. -- Perspectivas del Nuevo Plan Nacional de I+D / Javier Pascual Casado. -- Primer debate. Moderador Enrique Villalba. -- Segundo debate. Moderadora Adela Mora. -- Tercer debate. Moderador Francisco Marcellán. -- Clausura / Francisco Marcellán. -- Epílogo / Clara Eugenia Garcí