Effects of an eccentric training protocol using gliding discs on balance and lower body strength in healthy adults

Impaired balance and lower body weakness are the main causes of falls, which are considered to be the major cause of fractures and head injuries in the elderly and are recognised as a serious health problem. The aim of this study is to observe the effect of eccentric training, introducing new technologies (gliding discs), on body composition, lower body strength, balance and quality of life. A quasi-experimental study was carried out with 56 healthy participants who were divided into an experimental group (n = 31) who underwent the protocol consisting of 12 training sessions and a control group (n = 25) who did not undergo the training. Before and after the intervention, all participants underwent a measurement of body composition, the SJ jump, balance with accelerometry and quality of life with the Short Form 12 Health Survey. In the experimental group, statistically significant improvements were found in the variables balance and lower body strength. The application of this training protocol improves lower body strength and the ability to control balance in the adult population

Inhibition of eukaryotic cell-free protein synthesis by thionins from wheat endosperm

Thionins are polypeptide toxins of about 5000 molecular weight, present in the endosperms of many Gramineae, which modify membrane permeability and inhibit macromolecular synthesis in cultured mammalian cells. Evidence is presented that they inhibit in vitro protein synthesis at micromolar concentrations in cell-free systems derived from wheat germ or from rabbit reticulocytes. Inhibition seems to occur by direct binding of mRNA by the toxin, as judged by the ability of thionins to mediate retention of RNA in nitrocellulose filters and by the dependence of inhibitory concentrations on the amount of exogenous RNA added to the wheat-germ translation system. Commercial preparations of wheat-germ have been found to include some endosperm contamination (up to 15%), which may result in at least partially inhibitory concentrations of the toxin in the cell-free extracts

Sistema tegumentario de la vicuña (v. vicugna)

Samples of different cutaneous areas of mature vicuñas (V. vicugna) were studied microscopically. Thickness of skin, annexed glands and pileous follicles were considered. Follicular groups were of variable siza according to area and contained a greater quantity of follicles in back skin than the flanks. There were also main and secondary follicles within the follicular groupsSe estudiaron al microscopio óptico muestras de diferentes zonas cutáneas de vicuñas adultas (V. vicugna), previamente procesadas mediante diferentes técnicas. Se tuvieron en cuenta características diferenciales entre las distintas zonas tales como espesor de la piel, abundancia de las glándulas anexas y folículos pilosos, y fundamentalmente distribución de estos últimos y a su disposición en grupos foliculares. Estas agrupaciones resultaron de tamaño variable según la zona considerada. Se apreció que estos grupos contenían mayor número de folículos en la piel del dorso y de los flancos. En muchos casos se destacaron en estas agrupaciones folículos principales y secundario

A myxoid fibrotic reaction pattern is associated with metastatic risk in cutaneous squamous cell carcinoma

Metastasis; Fibrosis; Cutaneous squamous cell carcinomaMetástasis; Fibrosis; Carcinoma cutáneo de células escamosasMetàstasi; Fibrosi; Carcinoma cutani de cèl·lules escamosesAlthough desmoplasia has been associated with poor prognoses in cutaneous squamous cell carcinoma, little attention has been paid to the patterns of fibrosis. This study aimed to examine the different stromal fibrotic patterns as markers of metastatic risk. We performed a multicenter retrospective study that included 102 cutaneous squamous cell carcinomas (52 non-metastatic and 50 metastatic carcinomas). Clinical and histopa-thological data were registered. The fibrotic reaction pattern was classified as mature, intermediate or immature depending on the presence of keloid-like collagen and myxoid stroma. The immature pattern (areas characterized by myxoid changes with no inflammation) was observed in 18 samples and its presence was significantly associated with immuno-suppression, budding, desmoplasia, perineural invasion, anatomic level, tumoural depth and metastatic risk in the multivariate analysis. Our findings suggest that the presence of an immature myxoid fibrotic pattern, which can be easily identified by routine hematoxylin-eosin staining, is strongly associated with metastatic risk.This work has been supported by grant PI15/00236 from Fondo de Investigación Sanitaria (FIS), Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Ministerio de Sanidad, and the ‘‘Xarxa de Bancs de Tumours”

The expression levels of prolyl oligopeptidase responds not only to neuroinflammation but also to systemic inflammation upon liver failure in rat models and cirrhotic patients

Abstract Background Liver failure in experimental animals or in human cirrhosis elicits neuroinflammation. Prolyl oligopeptidase (PREP) has been implicated in neuroinflammatory events in neurodegenerative diseases: PREP protein levels are increased in brain glial cells upon neuroinflammatory insults, but the circulating PREP activity levels are decreased in multiple sclerosis patients in a process probably mediated by bioactive peptides. In this work, we studied the variation of PREP levels upon liver failure and correlated it with several inflammatory markers to conclude on the relation of PREP with systemic and/or neuroinflammation. Methods PREP enzymatic activity and protein levels measured with immunological techniques were determined in the brain and plasma of rats with portacaval shunt (PCS) and after treatment with ibuprofen. Those results were compared with the levels of PREP measured in plasma from cirrhotic patients with or without minimal hepatic encephalopathy (MHE). Levels of several pro-inflammatory cytokines and those of NO/cGMP homeostasis metabolites were measured in PCS rats and cirrhotic patients to conclude on the role of PREP in inflammation. Results In PCA rats, we found that PREP levels are significantly increased in the hippocampus, striatum and cerebellum, that in the cerebellum the PREP increase was significantly found in the extracellular space and that the levels were restored to those measured in control rats after administration of an anti-inflammatory agent, ibuprofen. In cirrhotic patients, circulatory PREP activity was found to correlate to systemic and neuroinflammatory markers and had a negative correlation with the severity of the disease, although no clear relation to MHE. Conclusions These results support the idea that PREP levels could be used as indicators of cirrhosis severity in humans, and using other markers, it might contribute to assessing the level of neuroinflammation in those patients. This work reports, for the first time, that PREP is secreted to the extracellular space in the cerebellum most probably due to glial activation and supports the role of the peptidase in the inflammatory response

Non-circular motion evidences in the circumnuclear region of M100 (NGC 4321)

We analyse new integral field spectroscopy of the inner region (central 2.5 kpc) of the spiral galaxy NGC 4321 to study the peculiar kinematics of this region. Fourier analysis of the velocity residuals obtained by subtracting an axisymmetric rotation model from the $\rm H\alpha$ velocity field, indicates that the distortions are {\em global} features generated by an $m=2$ perturbation of the gravitational potential which can be explained by the nuclear bar. This bar has been previously observed in the near-infrared but not in the optical continuum dominated by star formation. We detect the optical counterpart of this bar in the 2D distribution of the old stellar population (inferred from the equivalent width map of the stellar absorption lines). We apply the Tremaine--Weinberg method to the stellar velocity field to calculate the pattern speed of the inner bar, obtaining a value of $\Omega_b$=160$\pm70\rm km s^{-1} kpc^{-1}$. This value is considerably la rger than the one obtained when a simple bar model is considered. However the uncertainties in the pattern speed determination prevent us to give support to alternative scenarios.Comment: 11 pages, 11 figures, accepted for publication in MNRA

Improving knowledge management through the support of image examination and data annotation using DICOM structured reporting

[EN] An important effort has been invested on improving the image diagnosis process in different medical areas using information technologies. The field of medical imaging involves two main data types: medical imaging and reports. Developments based on the DICOM standard have demonstrated to be a convenient and widespread solution among the medical community. The main objective of this work is to design a Web application prototype that will be able to improve diagnosis and follow-on of breast cancer patients. It is based on TRENCADIS middleware, which provides a knowledge-oriented storage model composed by federated repositories of DICOM image studies and DICOM-SR medical reports. The full structure and contents of the diagnosis reports are used as metadata for indexing images. The TRENCADIS infrastructure takes full advantage of Grid technologies by deploying multi-resource grid services that enable multiple views (reports schemes) of the knowledge database. The paper presents a real deployment of such Web application prototype in the Dr. Peset Hospital providing radiologists with a tool to create, store and search diagnostic reports based on breast cancer explorations (mammography, magnetic resonance, ultrasound, pre-surgery biopsy and post-surgery biopsy), improving support for diagnostics decisions. A technical details for use cases (outlining enhanced multi-resource grid services communication and processing steps) and interactions between actors and the deployed prototype are described. As a result, information is more structured, the logic is clearer, network messages have been reduced and, in general, the system is more resistant to failures.The authors wish to thank the financial support received from The Spanish Ministry of Education and Science to develop the project "CodeCloud", with reference TIN2010-17804.Salavert Torres, J.; Segrelles Quilis, JD.; Blanquer Espert, I.; Hernández García, V. (2012). Improving knowledge management through the support of image examination and data annotation using DICOM structured reporting. Journal of Biomedical Informatics. 45(6):1066-1074. https://doi.org/10.1016/j.jbi.2012.07.004S1066107445

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRAS(Q61)-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRAS(Q61) mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRAS(Q61)-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib. Targeted therapeutic options for NRAS-mutant melanoma are limited. Here, the authors show that under metabolic stress NRAS-mutant melanoma cells activate a BRAF-dependent glycolysis pathway for survival, leading to improve efficacy of sorafenib when combined with glycolysis inhibitors

HTLV infection in HCV-antibody positive patients in Spain.

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis or adult T cell leukemia at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers. The presence of anti-HTLV antibodies was examined in 3,838 consecutive individuals with reactive HCV serology attended during the last 3 years at 13 hospitals distributed across the Spanish geography. Overall 71% were male, and the median age was 41 years old. Foreigners represented 9% of the study population. A total of 50 individuals (1.3%) were seroreactive for HTLV, being 30 confirmed as HTLV-2 and 2 as HTLV-1 (0.12%). The remaining 18 had indeterminate Western blot patterns. Most individuals with HTLV-2 and HTLV indeterminate serology were human immunodeficiency virus positive, former injection drug users, and native Spaniards. In contrast, the two HTLV-1 infections were found in men coming from Brazil and the Dominican Republic, respectively. In summary, the overall prevalence of HTLV infection in individuals living in Spain seropositive for HCV is 1.3%, more than 10-fold greater than in general outclinics in Spain. However, immigrants from HTLV-1 endemic regions and former injection drug users with HTLV-2 infection are by far the major contributory groups in HCV patients. Therefore, testing for HTLV in newly diagnosed HCV individuals would not contribute much to improve late HTLV diagnosis in Spain

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a−/− mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling