El codo flotante en el niño: opciones terapéuticas y complicaciones

La fractura simultánea ipsilateral del húmero y de uno o ambos huesos del antebrazo, llamada también "codo flotante", es una entidad poco frecuente, siendo escasa la literatura al respecto. En este artículo se describe nuestra experiencia con este tipo de lesiones en el paciente pediátrico, así como sus complicaciones asociadas y las distintas opciones de tratamiento. El tratamiento del codo flotante es actualmente controvertido en cuanto a su indicación y la técnica quirúrgica a emplear. También existe controversia con respecto a la mayor incidencia de complicaciones en este tipo de lesiones.Simultaneous ipsilateral fracture of the humerus and one or both bones of the forearm, also called "floating elbow" is a rare entity, with little literature. This article describes our experience with this type of injury in the pediatric patient and their associated complications and treatment options. The floating elbow treatment is currently controversial in terms of indications and surgical technique to use. There is also controversy over the increased incidence of complications in this type of injury

Serum metabolomics tells the story of disease degree in a fish enteritis model

Comunicación presentada en la 19th International Conference on Diseases of Fish and Shellfish, celebrada en Oporto (Portugal) del 9 al 12 de septiembre de 2019.[Introduction]: In animal production, enteritis is responsible for serious economic losses, being intestinal parasitism a major stress factor leading to malnutrition and lowered performance and production efficiency. The intestinal myxozoan parasite Enteromyxum leei dwells between gut epithelial cells and causes severe desquamative enteritis in gilthead sea bream (Sparus aurata) that impairs nutrient absorption causing anorexia, cachexia, growth impairment, reduced marketability and increased mortality. This study aimed to outline the gut failure produced in this fish-parasite model using a multifaceted approach and to find and validate serum non-lethal markers of gut barrier dysfunction.[Methodology]: Intestinal integrity was studied in parasitized and non-parasitized fish by immunohistochemistry with specific markers for cellular adhesion (E-cadherin) and tight junctions (Tjp-1 and Cldn3) and by functional studies of permeability (oral administration of FITC-dextran) and electrophysiology (Ussing chambers). Serum samples from parasitized and non-parasitized fish were analyzed using non-targeted metabolomics and some significantly altered metabolites were selected to be validated using commercial kits.[Results]: The expression of the tight junction proteins Tjp-1 and Cldn3 was significantly lower in parasitized fish along all the intestine, while no differences were found in E-cadherin labeling. Some parasitized fish showed a significant increase in paracellular uptake measured by FITC-dextran detection in serum. Electrophysiology studies showed a decrease in transepithelial resistance in infected animals, which showed a diarrheic profile when compared to the normal absorptive profile of the control animals. Serum metabolomics revealed 3702 ions, from which the differential expression of 20 identified compounds significantly separated control from infected groups in multivariate analyses (PLS-DA), and even separated groups by intensity of infection. Of these compounds, inosine and creatine were identified as relevant and tested with commercial kits in serum samples.[Conclusion]: This study demonstrates the loss of barrier function induced by the enteric parasite E. leei and underlines key markers to differentiate control and infected fish. The untargeted serum metabolomics approach did not reveal specific effects by the parasite, but more a profile typical of absorption dysfunction and anorexia, which are, of course, part of the disease signs.Funding: ParaFishControl H2020 project (634429), Aquaexcel2020 (652831, TNA AE10004-INTEBREAM), AGL2013-48560-R

TDR-LAB 2.0: Improved TDR software for soil water content and electrical conductivity measurements

Trabajo presentado en las XI Jornadas de Investigación en la Zona No Saturada del Suelo celebradas en Lugo del 6 al 8 de noviembre de 2013.[ES]: La técnica de Reflectometría de Dominio Temporal (TDR) permite estimar la humedad (θ) y la conductividad eléctrica aparente del suelo (σa). Esta comunicación presenta una nueva versión del programa TDR-Lab para la medida de θ y σa. El TDR-Lab 2.0 es compatible con tres ecómetros TDR diferentes y puede conectarse a multiplexores SDMX50 (Campbell Sci). Puede estimar θ y σa por métodos gráficos y numéricos y incluye nuevas aplicaciones para la medida de niveles de agua, potencial mátrico o conductividad eléctrica de la solución del suelo. Está disponible en una versión ligera que trabaja con ficheros XML y una versión completa que centraliza los datos en una base SQL. Una robusta interface de importación-exportación de datos permite comunicar ambas versiones.[EN]: Time Domain Reflectometry (TDR) is a widely used technique that allows real time estimation of soil volumetric water content (θ), and bulk electrical conductivity (σa). This work presents an enhanced release of TDR-Lab, software which controls instrumentation for measurements of θ and σa. TDR-Lab 2.0 supports three different TDR equipments and can be connected to a multiplexing system (SDMX50, Campbell Sci). Graphical or numerical methods can be used for the estimation of θ and σa. Additional features to carry out water-surface-level measurements such as matric potential and soil solution electrical conductivity are also available. A little and a full release, for field and laboratory applications have been developed. The light version works with XML-files instead of the SQL database engine of the extended TDRLab. A robust import/export graphical user interface facilitates transferring projects between the centralized SQL database and XML files.This research was supported by the Ministerio de Educación y Ciencia of Spain (grant AGL2010-22050-C03-02) and DGA- Obra social La Caixa (Grants: 2012/ GA LC 074).Peer reviewe

Spanish Cell Therapy Network (TerCel) : 15 years of successful collaborative translational research

In the current article we summarize the 15-year experience of the Spanish Cell Therapy Network (TerCel), a successful collaborative public initiative funded by the Spanish government for the support of nationwide translational research in this important area. Thirty-two research groups organized in three programs devoted to cardiovascular, neurodegenerative and immune-inflammatory diseases, respectively, currently form the network. Each program has three working packages focused on basic science, pre-clinical studies and clinical application. TerCel has contributed during this period to boost the translational research in cell therapy in Spain, setting up a network of Good Manufacturing Practice-certified cell manufacturing facilities- and increasing the number of translational research projects, publications, patents and clinical trials of the participating groups, especially those in collaboration. TerCel pays particular attention to the public-private collaboration, which, for instance, has led to the development of the first allogeneic cell therapy product approved by the European Medicines Agency, Darvadstrocel. The current collaborative work is focused on the development of multicenter phase 2 and 3 trials that could translate these therapies to clinical practice for the benefit of patients

Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer

Background: Wnt factors control cell differentiation through semi-independent molecular cascades known as the beta-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood. Results: Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring ROR2 promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic. Conclusions: Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control

Producción CientíficaThe mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214-1 and CC214-2. In vitro studies confirmed the superior ability of CC214-1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214-1 was more efficient in inhibiting na€ıve T cell activation and the expression of Tcell activation markers. In addition, CC214-1 induced specific tolerance against alloantigens, while preserving anti-cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214-2 significantly improved mice survival and decreased GvHD-induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214-1 on T lymphocytes and illustrates the role of CC214-2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.Gerencia Regional de Salud de Castilla y León (Proyecto GRS 726/A13

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

Objective Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. Design Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. Results Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. Conclusions p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis

A first-principles approach to electrical transport in atomic-scale nanostructures

We present a first-principles numerical implementation of Landauer formalism for electrical transport in nanostructures characterized down to the atomic level. The novelty and interest of our method lies essentially on two facts. First of all, it makes use of the versatile Gaussian98 code, which is widely used within the quantum chemistry community. Secondly, it incorporates the semi-infinite electrodes in a very generic and efficient way by means of Bethe lattices. We name this method the Gaussian Embedded Cluster Method (GECM). In order to make contact with other proposed implementations, we illustrate our technique by calculating the conductance in some well-studied systems such as metallic (Al and Au) nanocontacts and C-atom chains connected to metallic (Al and Au) electrodes. In the case of Al nanocontacts the conductance turns out to be quite dependent on the detailed atomic arrangement. On the contrary, the conductance in Au nanocontacts presents quite universal features. In the case of C chains, where the self-consistency guarantees the local charge transfer and the correct alignment of the molecular and electrode levels, we find that the conductance oscillates with the number of atoms in the chain regardless of the type of electrode. However, for short chains and Al electrodes the even-odd periodicity is reversed at equilibrium bond distances.Comment: 14 pages, two-column format, submitted to PR