69 research outputs found

    Stimulation of executive functions in school-age children

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    El neurodesarrollo puede verse afectado por múltiples situaciones de riesgo que comprometen la salud de la población infantil lo que puede tener un impacto en todo el ciclo vital. En este contexto, la prevención es un objetivo fundamental. El objetivo de este trabajo fue comprobar la eficacia de un programa de entrenamiento en funciones ejecutivas (PEFEN) en niños/as de educación infantil (5 años). Participaron 40 niños divididos en dos grupos (tratamiento y control), que fueron evaluados antes y después de la intervención. Los/as niños/as completaron el Cuestionario de Madurez Neuropsicológica Infantil (CUMANIN) y los padres la Evaluación Conductual de la Función Ejecutiva-Versión Infantil (BRIEF-P). El programa PEFEN está diseñado para estimular tres componentes de las funciones ejecutivas: la memoria de trabajo, la inhibición y la flexibilidad. El programa se imparte en el aula por los docentes de los/as niños/as, tiene una duración de 3 meses e incluye dos tipos de actividades diferentes (una de entrenamiento cognitivo y otra de mindfulness) que se presentan con una dificultad creciente. Los resultados ponen de manifiesto diferencias estadísticamente significativas entre los grupos en las escalas de psicomotricidad, estructuración espacial y visopercepción del CUMANIN y en la escala de control emocional del BRIEF-P, indicando un mejor rendimiento neuropsicológico en la segunda evaluación en los/as niños/as que participaron en el programa. Estos resultados permiten afirmar que es posible entrenar las funciones ejecutivas en niños/as de corta edad y que puede hacerse con programas que están integrados en el propio curriculum educativo.Neurodevelopment can be affected by multiple risk situations that compromise the health of the child population and can have an impact throughout the life cycle. In this context, prevention is a fundamental objective. The aim of this study was to test the efficacy of an executive function training programme (PEFEN) in children in early childhood education (5 years old). Forty children participated, divided into two groups (treatment and control), who were evaluated before and after the intervention. Children completed the Child Neuropsychological Maturity Questionnaire (CUMANIN) and parents completed the Behavioural Assessment of Executive Function-Child Version (BRIEF-P). The PEFEN programme is designed to stimulate three components of executive functions: working memory, inhibition and flexibility. The programme is delivered in the classroom by the children’s teachers, lasts 3 months and includes two different types of activities (one cognitive training and the other mindfulness) that are presented with increasing difficulty. The results show statistically significant differences between the groups in the psychomotor, spatial structuring and visuoperception scales of the CUMANIN and in the emotional control scale of the BRIEF-P, indicating a better neuropsychological performance in the second evaluation in the children who participated in the programme. These results allow us to affirm that it is possible to train executive functions in young children and that this can be done with programmes that are integrated into the educational curriculum itself

    Tracking the antibody immunome in sporadic colorectal cancer by using antigen self-assembled protein arrays

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    © 2021 by the authors.Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) “Una manera de hacer Europa” and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. CNPq-National Council for Scientific and Technological Development (Brazil) (306258/2019-6) and FAPERJ-Foundation for Research Support of Rio de Janeiro State for the financial support (E-26/201.670/2017 and 210.379/2018). M. González-González is supported by MINECOPTA2019-017870-I.A. Landeira-Viñuela is supported by VIII Centenario-USAL PhD Program. P.J.-V. is supported by JCYL PhD Program and scholarship JCYL-EDU/601/2020. P.D. and E.B. are supported by a JCYL-EDU/346/2013 Ph.D. scholarship

    PiRNA-associated proteins and retrotransposons are differentially expressed in murine testis and ovary of aryl hydrocarbon receptor deficient mice

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    Previous studies suggested that the aryl hydrocarbon receptor (AhR) contributes to mice reproduction and fertility. However, the mechanisms involved remain mostly unknown. Retrotransposon silencing by Piwi-interacting RNAs (piRNAs) is essential for germ cell maturation and, remarkably, AhR has been identified as a regulator of murine B1-SINE retrotransposons. Here, using littermate AhR+/+ and AhR-/- mice, we report that AhR regulates the general course of spermatogenesis and oogenesis by a mechanism likely to be associated with piRNA-associated proteins, piRNAs and retrotransposons. piRNA-associated proteins MVH and Miwi are upregulated in leptotene to pachytene spermatocytes with a more precocious timing in AhR-/- than in AhR+/+ testes. piRNAs and transcripts from B1-SINE, LINE-1 and IAP retrotransposons increased at these meiotic stages in AhR-null testes. Moreover, B1-SINE transcripts colocalize with MVH and Miwi in leptonema and pachynema spermatocytes. Unexpectedly, AhR-/- males have increased sperm counts, higher sperm functionality and enhanced fertility than AhR+/+ mice. In contrast, piRNA-associated proteins and B1-SINE and IAP-derived transcripts are reduced in adult AhR-/- ovaries. Accordingly, AhR-null female mice have lower numbers of follicles when compared with AhR+/+ mice. Thus, AhR deficiency differentially affects testis and ovary development possibly by a process involving piRNA-associated proteins, piRNAs and transposable elements.Trabajo financiado por: Ministerio de Ciencia e Innovación. Ayuda BFU2011-22678 para Pedro María Fernández Salguero Ministerio de Economía y Competitividad. Ayuda SAF2014-51813-R para Pedro María Fernández Salguero Junta de Extremadura. Ayuda GR15008, para Pedro María Fernández Salguero Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III y Ministerio de Economía y Competitividad (RD12/0036/0032). Trabajos de laboratorio de Pedro María Fernández Salguero Ministerio de Economía y Competitividad. Ayuda AGL2013-43211-R, para Fernando Juan Peña Vega Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III. Ayuda para Eva María Rico Leo Ministerio de Economía y Competitividad. Ayuda para Francisco Javier González Rico Junta de Extremadura. Ayuda para Eva María Barrasa Ardila Ministerio de Educación, Cultura y Deportes. Beca de Formación de Personal de Investigación, para Nuria Moreno Marín Ministerio de Educación, Cultura y Deportes. Beca FPU13/03991, de Formación de Profesorado Universitario, para Patricia Martín Muñoz Ministerio de Economía y Competitividad. Beca Juan de la Cierva IJCI-2014-21671, para Cristina Ortega Ferrusola Ministerio de Economía y Competitividad, Beca BFU2014-59307-R, para Alberto M. Pendás y Elena Llano Cuadro MEIONet, Junta de Castilla y León y el Programa de Fondeos FEDER, de la Unión EuropeapeerReviewe

    Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

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    Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival

    Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer

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    Sporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/β-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/β-catenin signaling that also has undefined β-catenin-independent actions. Here we report for the first time that a proportion of DKK-1 locates within the nucleus of healthy small intestine and colon mucosa, and of CRC cells at specific chromatin sites of active transcription. Moreover, we show that DKK-1 regulates several cancer-related genes including the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and Ral-binding protein 1-associated Eps domain-containing 2 (REPS2), which are involved in detoxification of chemotherapeutic agents. Nuclear DKK-1 expression is lost along CRC progression; however, it remains high in a subset (15%) of CRC patients (n = 699) and associates with decreased progression-free survival (PFS) after chemotherapy administration and overall survival (OS) [adjusted HR, 1.65; 95% confidence interval (CI), 1.23-2.21; P = 0.002)]. Overexpression of ALDH1A1 and REPS2 associates with nuclear DKK-1 expression in tumors and correlates with decreased OS (P = 0.001 and 0.014) and PFS. In summary, our findings demonstrate a novel location of DKK-1 within the cell nucleus and support a role of nuclear DKK-1 as a predictive biomarker of chemoresistance in colorectal cancer

    Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

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    Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival. (C) 2021 The Authors. Published by Elsevier Ltd
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