137 research outputs found

    International scientific consensus on medical plantar pressure measurement devices: technical requirements and performance

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    Background. Since 2006, the Italian National Institute of Health (ISS) has been conducting independent scientific activities to standardize the technical assessment of plantar pressure measurement devices (PMDs). Material and methods. On the basis of the ISS results, in 2010 the Pedobarographic Group of the International Foot and Ankle Biomechanics community (i-FAB-PG) promoted a consensus activity about the main technical requirements for the appropriate use of PMDs. The activity relied on a moodle- based on-line forum, documents exchange, discussions, reviews, meetings and a final sur - vey. Results. The participation of clinical and technical researchers, users, and manufactur - ers, contributed to the delivery of the hereby reported recommendations which specifically regard Medical PMDs in the form of platforms. Conclusions. The i-FAB-PG community reached overall agreement on the recommendations, with a few minor objections which are reported and commented in the document. Relevance. The present document, the highest result achievable within a small scientific community, will hopefully represent the starting point of the wider process of establishing official international guidelines or standards, within scientific communities and standardization organizations

    Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry

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    Alveolar soft-part sarcoma; Immune checkpoint; ImmunotherapySarcoma alveolar de partes blandas; Puntos de control inmunológico; InmunoterapiaSarcoma alveolar de parts toves; Punts de control immunològic; ImmunoteràpiaBackground Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. Materials and methods Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. Results Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. Conclusions This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.DSM is a recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155). The authors thank SELNET project. SELNET has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 825806

    Caracterización de complicaciones por otitis media aguda en el Hospital Clínico de la Pontificia Universidad Católica de Chile

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    Introducción: las complicaciones por otitis media aguda tienen una incidencia menor a un 1%. Aun así, se describe en literatura una mortalidad de un 5%. Actualmente existe escasa evidencia sobre estas complicaciones en nuestra realidad local. Objetivo: describir las de complicaciones de otitis media aguda según tipo, sexo, síntomas de ingreso, exámenes solicitados y tratamiento. Material y Métodos: estudio descriptivo retrospectivo de revisión de fichas clínicas que incluyó pacientes que ingresaron al Hospital Clínico de la Pontificia Universidad Católica de Chile con diagnóstico de otitis media aguda entre el 1 enero de 2000 hasta el 30 de julio de 2022. Resultados: se obtuvieron 71 pacientes ingresados por complicación de otitis media aguda. La edad media fue de 26,79 años, con 46 mujeres y 25 hombres. Se observaron complicaciones extracraneales, intracraneales y complicaciones simultáneas. Las complicaciones más frecuentes fueron la laberintitis y mastoiditis sin reportar casos de mortalidad. Discusión: actualmente existe escasa información sobre complicaciones de otitis media aguda y su epidemiología a nivel local.  Las complicaciones extracraneales fueron más frecuentes: de ellas, la laberintitis y la mastoiditis agudas. El diagnóstico es clínico con apoyo de exámenes tanto de laboratorio, audiovestibulares e imágenes. Con respecto al tratamiento quirúrgico, se debe evaluar caso a caso y debe incluir miringotomía con o sin instalación de tubo de ventilación y mastoidectomía en casos refractarios. Es importante la sospecha y la derivación precoz

    ErbB3-ErbB2 Complexes as a Therapeutic Target in a Subset of Wild-type BRAF/NRAS Cutaneous Melanomas.

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    The treatment options remain limited for patients with melanoma who are wild-type for both BRAF and NRAS (WT/WT). We demonstrate that a subgroup of WT/WT melanomas display high basal phosphorylation of ErbB3 that is associated with autocrine production of the ErbB3 ligand neuregulin-1 (NRG1). In WT/WT melanoma cells displaying high levels of phospho-ErbB3, knockdown of NRG1 reduced cell viability and was associated with decreased phosphorylation of ErbB3, its coreceptor ErbB2, and its downstream target, AKT. Similar effects were observed by targeting ErbB3 with either siRNAs or the neutralizing ErbB3 monoclonal antibodies huHER3-8 and NG33. In addition, pertuzumab-mediated inhibition of ErbB2 heterodimerization decreased AKT phosphorylation, cell growth in vitro, and xenograft growth in vivo. Pertuzumab also potentiated the effects of MEK inhibitor on WT/WT melanoma growth in vitro and in vivo. These findings demonstrate that targeting ErbB3-ErbB2 signaling in a cohort of WT/WT melanomas leads to tumor growth reduction. Together, these studies support the rationale to target the NRG1-ErbB3-ErbB2 axis as a novel treatment strategy in a subset of cutaneous melanomas

    Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

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    "© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

    Una combinación nueva en Erica (Ericaceae).

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    [EN] A new nomenclatural status and combination is proposed for Erica cinerea var. numidica. New data about the morphology, chorology and ecology of this taxon are given.[ES] Una combinación nueva en Erica (Ericaceae).- Se propone un nuevo estatus y combinación nomenclatural para Erica cinerea var. numidica. Se aportan nuevos datos sobre la morfología, corología y ecología de este taxón.This work has been supported by “Ajuts a grups de recerca consolidats: 2005SGR00344 and 2009SGR0439, Generalitat de Catalunya” and "Proyectos Intramurales de Incorporación del CSIC: 2009930I161".Peer reviewe

    The complementary roles of dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose PET/CT for imaging of carotid atherosclerosis

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    Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and [supersript 18]F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473)

    Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis : Fundamentals Of Care for UveitiS (FOCUS) Initiative

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    Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

    A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential

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    Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 1015 cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals

    SOX10 requirement for melanoma tumor growth is due, in part, to immune-mediated effects

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    Developmental factors may regulate the expression of immune modulatory proteins in cancer, linking embryonic development and cancer cell immune evasion. This is particularly relevant in melanoma because immune checkpoint inhibitors are commonly used in the clinic. SRY-box transcription factor 10 (SOX10) mediates neural crest development and is required for melanoma cell growth. In this study, we investigate immune-related targets of SOX10 and observe positive regulation of herpesvirus entry mediator (HVEM) and carcinoembryonic-antigen cell-adhesion molecule 1 (CEACAM1). Sox10 knockout reduces tumor growth in vivo, and this effect is exacerbated in immune-competent models. Modulation of CEACAM1 expression but not HVEM elicits modest effects on tumor growth. Importantly, Sox10 knockout effects on tumor growth are dependent, in part, on CD8+ T cells. Extending this analysis to samples from patients with cutaneous melanoma, we observe a negative correlation with SOX10 and immune-related pathways. These data demonstrate a role for SOX10 in regulating immune checkpoint protein expression and anti-tumor immunity in melanoma
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