Gender variability in electromyographic activity, in vivo behaviour of the human gastrocnemius and mechanical capacity during the take-off phase of a countermovement jump

PURPOSE: The purpose of this study was to analyse gender differences in neuromuscular behaviour of the gastrocnemius and vastus lateralis during the take-off phase of a countermovement jump (CMJ), using direct measures (ground reaction forces, muscle activity and dynamic ultrasound). METHODS: Sixty-four young adults (aged 18-25 years) participated voluntarily in this study, 35 men and 29 women. The firing of the trigger allowed obtainment of data collection vertical ground reaction forces (GRF), surface electromyography activity (sEMG) and dynamic ultrasound gastrocnemius of both legs. RESULTS: Statistically significant gender differences were observed in the jump performance, which appear to be based on differences in muscle architecture and the electrical activation of the gastrocnemius muscles and vastus lateralis. So while men developed greater peak power, velocity take-offs and jump heights, jump kinetics compared to women, women also required a higher electrical activity to develop lower power values. Additionally, the men had higher values pennation angles and muscle thickness than women. CONCLUSION: Men show higher performance of the jump test than women, due to significant statistical differences in the values of muscle architecture (pennation angle and thickness muscle), lower Neural Efficiency Index and a higher amount of sEMG activity per second during the take-off phase of a CMJ.Actividad Física y Deport

Variabilidad dentro del Registro Nacional multicéntrico en Vigilancia Activa; cuestionario a urólogos

Introducción: Nuestro objetivo principal es describir la utilización actual en España de la vigilancia activa (VA) identificando áreas de potencial mejora. Métodos: Un cuestionario generado en AEU/PIEM/2014/0001 (NCT02865330) fue remitido a todos los investigadores asociados (IA) durante los meses de enero-marzo del 2016. Incluía 7 dominios diferentes cubriendo diferentes aspectos en VA. Resultados: Treinta y tres de cuarenta y un IA respondieron el cuestionario. La VA es principalmente controlada por los Servicios de Urología (87,9%). Hubo una gran heterogeneidad en las clásicas variables clínico-patológicas como criterios de selección. La densidad de antígeno prostático específico (PSAd) solo se usaba en el 36,4% IA. La RMmp era claramente infrautilizada como estadificación inicial (6%). Solo el 27,3% reconocía un alto nivel de experiencia en RMmp de sus colegas radiólogos. Con relación a la biopsia de confirmación, la mayoría de los centros utilizaban la vía transrectal y solo 2/33 la vía transperineal/software de fusión. La mitad de los IA entrevistados pasaron a tratamiento activo ante progresión patológica a Gleason 7 (3 + 4). No existió consenso en cuanto a cuándo pasar a estrategia de observación. Conclusiones: El estudio demostró la infrautilización del consentimiento informado y de los cuestionarios de calidad de vida. El PSAd no se incluía como elemento decisor en la estrategia inicial en la mayoría. Se plasmó una desconfianza en la experiencia de los urólogos con la RMmp y una infrautilización de la vía transperineal, así como la no existencia de consenso en los protocolos de seguimiento y en los criterios de tratamiento activo., confirmando la necesidad de estudios prospectivos analizando el papel de la RMmp y los biomarcadores. Background: Our main objective was to report the current use of active surveillance in Spain and to identify areas for potential improvement. Methods: A questionnaire generated by the Platform for Multicentre Studies of the Spanish Urology Association (AEU/PIEM/2014/0001, NCT02865330) was sent to all associate researchers from January to March 2016. The questionnaire included 7 domains covering various aspects of active surveillance. Results: Thirty-three of the 41 associate researchers responded to the questionnaire. Active surveillance is mainly controlled by the urology departments (87.9%). There was considerable heterogeneity in the classical clinical-pathological variables as selection criteria. Only 36.4% of the associate researchers used prostate-specific antigen density (PSAd). Multiparametric magnetic resonance imaging (mpMRI) was clearly underused as initial staging (6%). Only 27.3% of the researchers stated that their radiology colleagues had a high level of experience in mpMRI. In terms of the confirmation biopsy, most of the centres used the transrectal pathway, and only 2 out of 33 used the transperineal pathway or fusion software. Half of the researchers interviewed applied active treatment when faced with disease progression to Gleason 7 (3+4). There was no consensus on when to transition to an observation strategy. Conclusions: The study showed the underutilisation of informed consent and quality-of-life questionnaires. PSAd was not included as a decisive element in the initial strategy for most researchers. There was a lack of confidence in the urologists’ mpMRI experience and an underutilisation of the transperineal pathway. There was also no consensus on the follow-up protocols and active treatment criteria, confirming the need for prospective studies to analyse the role of mpMRI and biomarkers

Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene Cluster Codeletion.

Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in GBM is CDKN2A gene loss, located close to the cluster of type I IFN genes at Ch9p21. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic and immunostimulatory properties that has been proposed for the treatment of GBM. We have analyzed the CDKN2A-IFN I gene cluster in 1018 glioma tumors and evaluated the NDV oncolytic e ect in six GBM CSCs ex vivo and in a mouse model. Our results indicate that more than 50% of GBM patients have some IFN deletion. Moreover, GBM susceptibility to NDV is dependent on the loss of the type I IFN. Infection of GBM with an NDV-expressing influenza virus NS1 protein can overcome the resistance to oncolysis by NDV of type I-competent cells. These results highlight the potential of using NDV vectors in antitumor therapies.post-print3309 K

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

Background Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. Methods We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. Results We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. Conclusions Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.post-print1360 K

About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants

RAD51D mutations have been recently identified in breast (BC) and ovarian cancer (OC) families. Although an etiological role in OC appears to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish BC/OC families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families and 129 patients without family history but with early-onset BC or OC or metachronous BC and OC. Mutation detection was performed with high-resolution melting, denaturing high-performance liquid chromatography or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del cosegregated in the family with one early-onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow-up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family

Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance

Background: Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months. Methods: Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA =10 ng/mL, cT1c-T2a, Grade group 1, =2 cores, and =5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group =2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher’s exact test, as appropriate established differences between groups of reclassification. Results: A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume. Conclusions: Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management