Características de la práctica físico-deportiva del alumnado con discapacidad de la Universitat de València

En la actualidad, la actividad físico-deportiva es fundamental para las personas con discapacidad debido a los múltiples beneficios físicos, psicológicos y sociales que aporta (Patel y Greydanus, 2010; Slater y Meade, 2004). Estudiar las características de la práctica físico-deportiva de este colectivo puede ser útil para poder desarrollar estrategias y programas que mejoren y aumenten dicha práctica (Bragaru,van Wilgen, Geertzen, Ruijs, Dijsktra y Dekker, 2013). Pese a ello, apenas existen estudios de carácter cuantitativo sobre el tema. De acuerdo con las carencias señaladas, el objetivo de este trabajo es identificar la cuantía de la práctica físico-deportiva del alumnado con discapacidad de la Universitat de València (UV), así como algunas características y pautas relacionadas con la misma. La muestra se compuso de 138 alumnos y alumnas con discapacidad de la UV (64 hombres y 74 mujeres), lo que supone un 13,3% de la presencia de este colectivo en la UV. Podemos decir que el nivel de práctica físico-deportiva del alumnado con discapacidad de la UV es elevado. Los resultados ponen de manifiesto que predomina la práctica recreativa frente a la competitiva y la práctica individual sobre la práctica en equipo. Por lo que respecta a la frecuencia, encontramos que un alto porcentaje del alumnado practica actividad físico-deportiva con mucha regularidad. Como se observa en la tabla 2, casi el 50% de los estudiantes practican tres veces o más por semana, siendo el grupo más numeroso, seguido de un 37,8% que practican entre una y dos veces por semana

Economía, desigualdad y bienestar en la España reciente

La idea de crecimiento económico se ha conciliado tradicionalmente con la de progreso social. En los años de transición democrática, el crecimiento económico llevaba a mejores condiciones de vida, más oportunidades, salarios más altos, pero este emparejamiento está roto en la actualidad. Entre las consecuencias de la reciente crisis financiera está el aumento de la dualización social, empujada por el aumento de la pobreza y la desigualdad en España. La gran contención de los salarios, junto al crecimiento del desempleo, ha derivado en un aumento de necesidades sociales en la población, así como en una preocupante vulnerabilidad de la infancia, manifiesta, por ejemplo en el crecimiento de la pobreza infantil. En este contexto se hace necesario revisar los retos a los que se enfrenta nuestro país: un enorme paro estructural, la dualización social y el aumento de la población en riesgo de pobreza o exclusión. Los mecanismos habituales de asistencia no han logrado contener la caída de ingresos en las familias durante la recesión, provocando un crecimiento de la desigualdad. La discusión acerca de la intervención del Estado en la redistribución de la riqueza así como más prestaciones sigue suscitando debate entre los expertos. El objetivo de este trabajo es conocer la situación actual y previa a la recesión en términos de bienestar y crecimiento económico, para lo cual se analizarán diversas estadísticas elaboradas por el INE

Green tea catechin inhibits fatty acid synthase without stimulating carnitine Palmitoyltransferase-1 or inducing weight loss in experimental animals

Background: The enzyme fatty acid synthase (FASN) is highly expressed in many human carcinomas and its inhibition is cytotoxic to human cancer cells. The use of FASN inhibitors has been limited until now by anorexia and weight loss, which is associated with the stimulation of fatty acid oxidation. Materials and Methods: The in vitro effect of (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism enzymes, on apoptosis and on cell signalling was evaluated. In vivo, the effect of EGCG on animal body weight was addressed. Results: EGCG inhibited FASN activity, induced apoptosis and caused a marked decrease of human epidermal growth factor receptor 2 (HER2), phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular (signal)-regulated kinase (ERK) 1/2 proteins, in breast cancer cells. EGCG did not induce a stimulatory effect on CPT-1 activity in vitro (84% of control), or on animal body weight in vivo (99% of control). Conclusion: EGCG is a FASN inhibitor with anticancer activity which does not exhibit cross-activation of fatty acid oxidation and does not induce weight loss, suggesting its potential use as an anticancer drug

Nintedanib plus letrozole in early breast cancer: A phase 0/I pharmacodynamic, pharmacokinetic, and safety clinical trial of combined FGFR1 and aromatase inhibition

The combined use of a FGFR1 blocker and aromatase inhibitors is appealing for treating breast cancer patients with FGFR1 amplification. However, no pharmacodynamic studies have addressed the effects of this combined target modulation. We conducted a phase 0/I clinical trial in an adjuvant setting, with the goal of obtaining pharmacodynamic proof of the effects of combined aromatase and FGFR1 inhibition and to establish the RP2D for nintedanib combined with letrozole. Patients and methods: Women with early-stage luminal breast cancer were eligible for enrollment in the study. Dose level 1 was nintedanib (150 mg/bid) plus letrozole (2.5 mg/day) administered for a single 28-day cycle (DLT assessment period), followed by a classic 3 + 3 schedule. FGF23 and 17-B-estradiol levels were determined on days 0 and 15; pharmacokinetic parameters were assessed on days 1 and 28. Patients were allowed to continue treatment for 6 cycles. The primary study endpoint was a demonstration of FGFR1 modulation (defined as a 25% increase in the plasma FGF23 level). Results: A total of 19 patients were enrolled in the study (10 in the expansion cohort following dose escalation). At the RP2D (nintedanib 200 mg/bid plus letrozole 2.5 mg/day), we observed a 55% mean increase in the plasma FGF23 level, and 81.2% of the patients had no detectable level of 17-B-estradiol in their plasma (87.5% of the patients treated with letrozole alone). Nintedanib and letrozole displayed a pharmacokinetic interaction that led to three- and twofold increases in their respective plasma concentrations. Most G3 toxic events (5 out of 6: 2 diarrhea and 3 hypertransaminasemia) occurred subsequent to the DLT assessment period. Conclusion: Combined treatment with nintedanib (200 mg/bid) plus letrozole (2.5 mg/day) effectively suppressed FGFR1 and aromatase activity, and these respective doses can be used as starting doses in any subsequent trials. However, drug-drug interactions may produce tolerability issues when these drugs are co-administered for an extended time period (e.g., 6 months). Patients enrolled in future trials with these drugs should be carefully monitored for their FGF23 levels and signs of toxicity, and those findings should guide individualized treatment decisionsMQF is a recipient of the following grants: AES - PI16/00354 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF) and B2017/BMD3733 - Call for Coordinated Research Groups from Madrid Region - Madrid Regional Government - ERDF funds. RC is a recipient of the following grants: AES PI17/01865 and PIE15/00068 by the ISCIII and co-funded by the European Regional Development Fund (ERDF). This study was partially funded by Boehringer-Ingelheim. CRIS Contra el Cancer Foundation contributed with a generous donation to this stud

Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer

Purpose: Triple-negative breast cancer (TNBC) is characterized by large heterogeneity and relative lack of available targeted therapies. To find therapeutic strategies for distinct patients with TNBC, several approaches have been used for TNBC clustering, including recently immune and phosphoproteomic patterns. Based on 70-kDa ribosomal protein S6 kinase (P70S6K)-TNBC clustering, the current study explores the immune profiling in TNBC tumors. Methods: Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated in human TNBC tumor samples. Furthermore, immunohistochemistry staining for CD8, CD4, Foxp3, and CD20 was performed in tissue microarrays (TMA) sections. Results: Histological analysis showed decreased sTILs, CD20+ cells, and CD8+/CD4+ ratio in high phosphorylated P70S6K (p-P70S6K) tumors. Moreover, p-P70S6K score was directly correlated with CD4+ and Foxp3+ T cells, while it was inversely correlated with CD8+/CD4+ and CD8+/Foxp3+ ratios. Conclusion: sTIL infiltration and lymphocyte profiling vary in the context of hyperactivation of P70S6K in TNBC tumorsThe project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 893597. RC is a recipient of the ISCIII grants: PI17/01865 and PI20/01458. MQF is a recipient of the following Grants: AES-PI19/00454 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF) and B2017/BMD3733 (Immunothercan-CM)—Call for Coordinated Research Groups from Madrid Region—Madrid Regional Government—ERDF funds. The study was also funded by CRIS Contra el Cancer Foundatio

Selective activity over a constitutively active RET-variant of the oral multikinase inhibitor dovitinib: results of the CNIO-BR002 phase I-trial

Background: given our preclinical data showing synergy between dovitinib and paclitaxel in preclinical models we conducted this phase I trial aiming to define the recommended phase II-dose (RP2D) on the basis of toxicity and pharmacodynamic criteria while searching for genetic variants that could sensitize patients to the regimen under study. Patients and methods: a 3+3 escalation schedule was adopted. Seriated FGF23 and dovitinib and paclitaxel pharmacokinetic profiles were determined along a single-agent dovitinib 'priming-phase' followed by a dovitinib + paclitaxel combination phase. RECIST 1.1 criteria and NCI CTCAE V.4.0 were used. In fresh pre-treatment tumor biopsy samples, FGFR1, 2 and 3 amplifications were revealed by FISH probes; 32 missense variants were genotyped in tumors and peripheral blood mononuclear cells with Taqman genotyping assays (FGFR1-3 and RET). Constructs encoding for wild-type and variant genes associated with clinical benefit were transfected into HEK-293 cells for preclinical experiments checking constitutive activation and dovitinib sensitivity of the variants. Results: twelve patients were recruited in three dose-levels. At level 1B (200 mg dovitinib 5-days-on/2-days-off plus 60 mg/m 2-week of paclitaxel) more than 50% FGF23 upregulation was observed and no dose-limiting-toxicities (DLTs) occurred. The most frequent toxicities were asthenia, neutropenia, nausea/vomiting and transaminitis. Two patients with progressive disease prior to trial inclusion achieved prolonged disease stabilization. Both had the germline variant G2071A in the RET gene, which led to constitutive activation of the protein product and Y-905 phosphorylation, both in transfectants and in patients with the alteration. This variant was sensitive to dovitinib; in addition both patients experienced progression upon medication withdrawal. Conclusions: level 1B was the RP2D as it provided adequate pharmacodynamic exposure to dovitinib. The G2071A germline variant act as a genetic modifier that renders different tumors sensitive to dovitinib

Características de la práctica físico-deportiva del alumnado con discapacidad de la Universitat de València

En la actualidad, la actividad físico-deportiva es fundamental para las personas con discapacidad debido a los múltiples beneficios físicos, psicológicos y sociales que aporta (Patel y Greydanus, 2010; Slater y Meade, 2004). Estudiar las características de la práctica físico-deportiva de este colectivo puede ser útil para poder desarrollar estrategias y programas que mejoren y aumenten dicha práctica (Bragaru, van Wilgen, Geertzen, Ruijs, Dijsktra y Dekker, 2013). Pese a ello, apenas existen estudios de carácter cuantitativo sobre el tema. Objetivo: De acuerdo con las carencias señaladas, el objetivo de este trabajo es identificar la cuantía de la práctica físico-deportiva del alumnado con discapacidad de la Universitat de València (UV), así como algunas características y pautas relacionadas con la misma.Currently, physical and sports activity is essential for people with disabilities due to the multiple physical, psychological and social benefits it provides (Patel and Greydanus, 2010; Slater and Meade, 2004). Studying the characteristics of the physical-sporting practice of this group can be useful to develop strategies and programs that improve and increase this practice (Bragaru, van Wilgen, Geertzen, Ruijs, Dijsktra and Dekker, 2013). Despite this, there are hardly any quantitative studies on the subject. Objective: According to the indicated deficiencies, the objective of this work is to identify the amount of physical-sporting practice of disabled students of the University of Valencia (UV), as well as some characteristics and guidelines related to it.peerReviewe

Selection of extreme phenotypes: the role of clinical observation in translational research

Systematic collection of phenotypes and their correlation with molecular data has been proposed as a useful method to advance in the study of disease. Although some databases for animal species are being developed, progress in humans is slow, probably due to the multifactorial origin of many human diseases and to the intricacy of accurately classifying phenotypes, among other factors. An alternative approach has been to identify and to study individuals or families with very characteristic, clinically relevant phenotypes. This strategy has shown increased efficiency to identify the molecular features underlying such phenotypes. While on most occasions the subjects selected for these studies presented harmful phenotypes, a few studies have been performed in individuals with very favourable phenotypes. The consistent results achieved suggest that it seems logical to further develop this strategy as a methodology to study human disease, including cancer. The identification and the study with high-throughput techniques of individuals showing a markedly decreased risk of developing cancer or of cancer patients presenting either an unusually favourable prognosis or striking responses following a specific treatment, might be promising ways to maximize the yield of this approach and to reveal the molecular causes that explain those phenotypes and thus highlight useful therapeutic targets. This manuscript reviews the current status of selection of extreme phenotypes in cancer research and provides directions for future development of this methodology

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.Instituto de Salud Carlos II