347 research outputs found

    Adipose-Derived Stem Cells in Crohn's Rectovaginal Fistula

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    Therapeutic options for recto-vaginal fistula in the setting of Crohn's disease are limited and many data are available in the literature. The manuscript describes the history of a patient who has been the pioneer of our Clinical Trials in treating this disease in fistulizing Crohn's disease environment. We believe it is the first time that a patient with this disease has been treated by adipose-derived stem cells in allogeneic form. The conclusion of our study with Mary is that the use of mesenchymal stem cells derived from adipose tissue is secure, either in autologous or allogeneic form. Furthermore, we have proved that if we use multi-dose and multiple applications on a patient, it does not produce any adverse effect, which confirms us the safety of using these cells in patients at least in the fistulizing Crohn's disease environment

    Using Regulatory and Epistatic Networks to Extend the Findings of a Genome Scan: Identifying the Gene Drivers of Pigmentation in Merino Sheep

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    Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino sheep, by analysing multiple data types using a systems approach. First, a case control analysis of 49,034 ovine SNP was performed which confirmed a multigenic basis for the condition. We combined these results with gene expression data from five tissue types analysed with a skin-specific microarray. Promoter sequence analysis of differentially expressed genes allowed us to reverse-engineer a regulatory network. Likewise, by testing two-loci models derived from all pair-wise comparisons across piebald-associated SNP, we generated an epistatic network. At the intersection of both networks, we identified thirteen genes with insulin-like growth factor binding protein 7 (IGFBP7), platelet-derived growth factor alpha (PDGFRA) and the tetraspanin platelet activator CD9 at the kernel of the intersection. Further, we report a number of differentially expressed genes in regions containing highly associated SNP including ATRN, DOCK7, FGFR1OP, GLI3, SILV and TBX15. The application of network theory facilitated co-analysis of genetic variation with gene expression, recapitulated aspects of the known molecular biology of skin pigmentation and provided insights into the transcription regulation and epistatic interactions involved in piebald Merino sheep

    Caracterización y cartografía fitoclimáticas del bosque nativo subantártico en la Isla Grande de Tierra del Fuego (Patagonia, Argentina)

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    Isla Grande de Tierra del Fuego is especially peculiar in phytoclimatic terms, situated as it is at an extreme southerly latitude, surrounded by large water masses and close to the great mass of Antarctic ice. Its main peculiarities in this sense are the coolness of its summers and a very narrow temperature range. As a result, the woodland landscapes in the parts with forest cover are dominated by microphyllous broadleaf physiognomies, both evergreen and deciduous, of the Nothofagus genus. This paper reports a more in-depth investigation of the hitherto little-known phytoclimatic conditions in that territory which included calibration and validation of a model of phytoclimatic suitability that addresses the principal plant physiognomic units and phytoclimatic mapping. It discusses the causes behind the presence of broadleaf formations in thermal conditions which in the northern hemisphere would allow only coniferous formations or no tree formations at all, and also the edaphic peculiarities that may explain the presence of a evergreen species like Nothofagus betuloides in subantarctic mixed forests.La Isla Grande de Tierra del Fuego presenta una muy marcada originalidad fitoclimática por su posición en latitudes muy australes, estar rodeada por grandes masas de agua y por su cercanía a la gran masa de hielo polar antártica. Esta originalidad se traduce en un escaso calor estival y una oscilación térmica muy reducida como principales peculiaridades, dando lugar en sus porciones arboladas a paisajes boscosos dominados por fisionomías planifolias de carácter micrófilo, tanto perennifolias como caducifolias del género Nothofagus. Este trabajo profundiza en las hasta hoy escasamente conocidas condiciones fitoclimáticas de este territorio, mediante la calibración y validación de un modelo de idoneidad fitoclimática respecto de las principales unidades fisionómicas de vegetación y el establecimiento de una cartografía fitoclimática. Se discuten las causas que provocan la existencia de formaciones planifolias en condiciones térmicas que darían lugar a formaciones aciculifolias o desarboladas en el hemisferio Norte, así como las particularidades edáficas que condicionan la presencia de la estrategia perennifolia representada por Nothofagus betuloides en los bosques mixtos subantárticos

    Colgajo de vasto lateral de pedículo distal para cobertura de lesiones complejas de rodilla

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    El tratamiento de las heridas complejas articulares se muestra siempre complicado, el abordaje razonable conjunto por traumatólogos y cirujanos plásticos mejora el resultado clínico, funcional y estético. Presentamos el caso de un paciente politraumatizado con pérdida de sustancia a nivel de la rodilla secundaria a artritis séptica, necrosis de patela y exposición de cóndilos femorales que fue tratado mediante colgajo muscular de vastus lateralis de pedículo distal. El vastus lateralis permite la cobertura eficiente de l articulación expuesta sin afectar la extensión de la rodilla y dejando mínima secuela estética.The treatment of the joint complex wounds is difficult. A good clinic, functional and aesthetic outcome is possible when multidisciplinary approach by orthopaedics and plastic surgeons is carried out. We report a case of a patient with multiple fractures who presents a severe loss of soft tissue at the knee. This lesion was due to a septic arthritis with patellar necrosis and condillar exposition. The treatment was made by a distally pedicled vastus lateralis muscular flap. This flap lets efficient coverage for the exposed joint as well as the integrity of the extensión knee function without aesthetic seque

    Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry

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    Purpose To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients. Methods For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model. Results Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment consid- ered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer–Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6). Conclusion In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit

    Robots nadadores tipo flagelo bacteriano de pequeñas dimensiones: desarrollo de prototipos y plataformas de prueba

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    [Resumen] Este artículo presenta las primeras experiencias de nuestro equipo de investigación en el desarrollo de robots nadadores tipo flagelo helicoidal de pequeñas dimensiones (de unos pocos centímetros) capaces de navegar en un fluido en condiciones de bajo número de Reynolds. Se presentan dos prototipos de robots que difieren entre sí principalmente en la forma de actuación: robot nadador con actuación magnética externa, cuyo desplazamiento es posible gracias a un imán permanente en rotación, y robot nadador autopropulsado, mediante un motor de pequeñas dimensiones. Se describen tanto los prototipos desarrollados como las plataformas de prueba asociadas, así como los primeros experimentos realizados. El principal objetivo es demostrar que la actuación de los robots funciona, mientras que la propulsión de los mismos es una cuestión más delicada que requiere de una profundización e investigación mayor.Junta de Extremadura; GR15178https://doi.org/10.17979/spudc.978849749808

    Exofucosylation of adipose mesenchymal stromal cells alters their secretome profile

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    Mesenchymal stromal cells (MSCs) constitute the cell type more frequently used in many regenerative medicine approaches due to their exclusive immunomodulatory properties, and they have been reported to mediate profound immunomodulatory effects in vivo. Nevertheless, MSCs do not express essential adhesion molecules actively involved in cell migration, a phenotypic feature that hampers their ability to home inflamed tissues following intravenous administration. In this study, we investigated whether modification by fucosylation of murine AdMSCs (mAdMSCs) creates Hematopoietic Cell E-/L-selectin Ligand, the E-selectin-binding CD44 glycoform. This cell surface glycan modification of CD44 has previously shown in preclinical studies to favor trafficking of mAdMSCs to inflamed or injured peripheral tissues. We analyzed the impact that exofucosylation could have in other innate phenotypic and functional properties of MSCs. Compared to unmodified counterparts, fucosylated mAdMSCs demonstrated higher in vitro migration, an altered secretome pattern, including increased expression and secretion of anti-inflammatory molecules, and a higher capacity to inhibit mitogenstimulated splenocyte proliferation under standard culture conditions. Together, these findings indicate that exofucosylation could represent a suitable cell engineering strategy, not only to facilitate the in vivo MSC colonization of damaged tissues after systemic administration, but also to convert MSCs in a more potent immunomodulatory/antiinflammatory cell therapy-based product for the treatment of a variety of autoimmune, inflammatory, and degenerative diseases

    The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer

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    Most colorectal cancer (CRC)-related deaths are due to liver metastases. PKCζ is a tumor suppressor in CRC with reduced expression in metastasis. Given the importance of microRNAs (miRNAs) in regulating cellular plasticity, we performed an unbiased screening and identified the miR-200 family as the most relevant miRNAs downregulated by PKCζ deficiency. The regulation of the intracellular levels of miR-200 by PKCζ is post-transcriptional and involves their secretion in extracellular vesicles. Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/ADAR2 axis regulates miR-200 secretion through RNA editing. Loss of this axis results in epithelial-to-mesenchymal transition (EMT) and increased liver metastases, which can be inhibited in vivo by blocking miR-200 release. Therefore, the PKCζ/ADAR2 axis is a critical regulator of CRC metastases through modulation of miR-200 levels.Research was supported by grants from the NIH ( R01DK108743 , R01CA172025 , and R01CA207177 to J.M.; R01CA192642 and R01CA218254 to M.T.D.-M.)
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